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Tuberculosis_Dataset

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PMC4900050_01

Male

An 18-year-old male presented to his family physician approximately 45 minutes after sustaining an injury to his right shoulder. He was tackled by another player while playing football. He noted a "pop" at his right sternoclavicular joint (SCJ), and resultant difficulty moving the right arm secondary to pain and a reproducible popping sensation of the clavicle. He denied numbness or tingling, shortness of breath, neck pain, jaw pain, or facial swelling, but noted mild difficulty swallowing. The patient's past medical history was unremarkable. On physical examination, there was asymmetric swelling at the right SCJ. His skin was intact. Range of motion and strength was limited by pain. Tenderness to palpation was present at the right SCJ, and shoulder motion produced a palpable clavicular "clunk." The neurovascular exam of the right upper extremity was unremarkable. The patient's arm was placed in a sling, and an emergent CT scan was obtained after x-rays revealed an asymmetry of the SC joints (Fig. 1). The patient's arm was placed in a sling, and an emergent CT scan was then obtained (Figure 2, Figure 3). The orthopedic team on call was notified. Given the patient's stable examination, he was discharged home with a referral to the shoulder and elbow clinic for management. He was seen the following day in the shoulder clinic. His exam was unchanged. His diagnosis was posterior sternoclavicular fracture-dislocation, with fracture through the medial clavicular physis (Salter-Harris I). Risks and benefits of surgical reduction and stabilization were discussed with the patient and his father. They elected to proceed with surgery. Arrangements were made with a vascular surgeon for assistance if needed. The patient was taken to the operating room one week after injury for open reduction and internal fixation. Following routine preoperative procedure, the patient was carefully positioned in the supine attitude with a rolled towel between the shoulder blades. Under general anesthesia, and after administration of 2 grams of Ancef, a 5-cm necklace incision was made overlying the medial clavicle onto the manubrium. Meticulous dissection and hemostasis then followed to expose the periosteum on the clavicle. The two heads of the sternocleidomastoid were identified and protected throughout the case. The epiphysis was noted to be still attached to the articular disk and in appropriate orientation with the manubrium; however, the medial clavicle had dislocated posteriorly through the physis (Figure 4, Figure 5). Following debridement, the clavicle was atraumatically reduced using a point-to-point clamp. The medial clavicle was then sewn back to the epiphysis with transosseous and transepiphyseal #2 FiberWire sutures (Arthrex, Naples, FL), with excellent stability achieved to the repair (Figure 6, Figure 7). The periosteum was oversewn, and this was reefed back to the surrounding sternoclavicular ligament and articular disk medially. Excellent fixation was achieved. The shoulder was taken through a full range of motion, and no motion was appreciated at the fracture site. The wound was copiously irrigated and closed in layers. The arm was put into an UltraSling. The patient was observed overnight and discharged one day after surgery. The right shoulder was kept immobilized in a sling for four weeks to allow for fracture healing. Elbow and wrist range-of-motion and grip exercises for the hand were started immediately after surgery without restriction. At his two-week postoperative followup, the patient reported resolution of his dysphagia and was relatively painfree. His incision was healing appropriately, without evidence of infection or complication. He was instructed to continue with sling wear, removing it frequently for Codman, elbow, wrist, and hand exercises. He was not allowed to participate in contact sports for 6 months. A postoperative CT scan demonstrated near-anatomic reduction of the SCJ fracture-dislocation (Figure 8, Figure 9).

ct, computed tomography, mri, magnetic resonance imaging, scj, sternoclavicular joint

PMC3716243_01

Male

A 55 year old north Indian male patient presented with history of painless progressive jaundice for 6 months and few episodes of intermittent fever for 3 months. There was loss of appetite and weight loss of 5 kg over the previous 6 months. There was no history of hematemesis or malaena. The patient did not drink alcohol, was a non smoker, and nondiabetic. His performance status was 80% on Karnoffsky scale. On clinical examination, the patient was deeply jaundiced with pallor; no lymph nodes were palpable. He had mild hepatomegaly with palpable gallbladder. Blood parameters were as follows: Hemoglobin 8.9 g%, total bilirubin 18.4 mg/dl (conjugated12.4, unconjugated 6.0), alkaline phosphatase 850, aspartate aminotransferase 110, alanine aminotransferase 85. Viral markers for hepatitis were nonreactive. Serology for HIV I and II was nonreactive. Ultrasonography showed dilated proximal (CBD) with dilated intrahepatic biliary radicles and soft tissue shadow in lower end of CBD. There were multiple echogenic shadows in proximal CBD. Endoscopic retrograde cholangio pancreatogram (ERCP) revealed a stricture at the lower end of CBD, biliary stenting was not possible through the tight stricture. Magnetic resonance cholangio pancreaticogram (MRCP) showed soft tissue lesion in the terminal end of CBD suggestive of cholangiocarcinoma. Guided FNA from the lesion for cytological evidence was not carried out. Surgical resection for lower end CBD stricture was planned and a pylorus preserving pancreaticoduodectomy (PPD) was successfully carried out. Intraoperative findings did not suggest any metastasis or stigma of tuberculosis. Postoperative recovery was complicated by minor pancreatic leakage and wound infection. Oral feeding (fluids) was resumed on third postoperative day and the patient was able to eat normal diet by 7th postoperative day. Within 2 weeks, the pancreatic leakage dried up and abdominal drains were removed. Histopathology revealed granulomatous inflammation at lower end of CBD and periampullary region along with granulomatous lymphadenitis, both consistent with tuberculosis. The patient was started on antitubercular medication (four drug regime of INH, rifampicin, pyrazinamide, and ethambutol) without significant adverse effects. He had a steady recovery - his serum alkaline phosphatase and bilirubin level reaching normal values by 8th postoperative week. The patient is on follow up for the last 7 months, has gained weight and doing well.

bile ducts, obstructive jaundice, tuberculosis

PMC8519353_01

Female

The diagnosis of chronic insomnia was made with clinical interviews according to the American Academy of Sleep Medicine International Classification of Sleep Disorders, Third Edition (ICSD-3). The inclusion criteria were as follows: (1) 18 to 75 years old. (2) In compliance with the diagnostic criteria for chronic insomnia in ICSD-3. (3) In compliance with the TCM diagnostic criteria for insomnia, TCM syndrome of dysregulated coordination between the heart and the kidney. (4) Consistent administration of sedative-hypnotic drugs for more than 3 months before entering the study or not taking such drugs. (5) A total score higher than five on the Pittsburgh Sleep Quality Index (PSQI) questionnaire. (6) Patients voluntarily participated in the study and signed informed consent forms. All subjects who wanted to participate were given an outpatient interview to determine whether they met the inclusion criteria. The interviews were conducted by experienced clinicians in the form of semistructured interview questionnaires. The interview questionnaire included the cause of insomnia, the onset process, the main sleep complaints at the current time, the treatment process, the state before going to bed, the sleep-wake cycle, other sleep-related symptoms, mental states, and daytime symptoms. Individuals on stable doses of sedative-hypnotic medications were allowed to remain on them during the study. In addition, all subjects completed a one-week sleep diary to establish sleep patterns before the clinical interview. The exclusion criteria were as follows: (1) severe hepatic or renal function damage, haematological disease, respiratory disease, or diagnosis of one or more mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). (2) semistructured interviews determined that subjects had sleep disorders other than chronic insomnia. (3) Infectious diseases such as infectious hepatitis, tuberculosis, AIDS and syphilis. (4) Severe digestive system diseases or severe malnutrition. (5) Pregnant or lactating. (6) Severe trauma with no cure or other contraindications to acupuncture, such as allergic constitution or severe dermatosis. (7) An Apnoea-Hypopnea Index >10 or periodic limb movements index during sleep associated with >15 arousals per hour on diagnostic PSG. (8) Participation in other clinical trials in the last 3 months. The acupuncturist had received a master's degree in acupuncture and tui na, had a doctor qualification certificate, and had more than 3 years of acupuncture clinical work experience. All the research assistants received 3 days of training before the start of the study. Subjects in the acupuncture group were placed in a supine position. The acupuncturist selected two acupoints, HT 7 and KI 7. These acupoints were selected based on a previous systematic review and our clinical experience summary and because the use of only two points can streamline the treatment and alleviate patient pain. The needles used were disposable, sterile, stainless-steel acupuncture needles with a length of 40 mm and a diameter of 0.25 mm (Andy, Guizhou, China). The acupuncturist treated each acupoint bilaterally, and the depth of insertion was 10-20 mm. The acupuncturist selected the depth according to the subject's body type (high, short, fat and thin). After penetration, the acupuncturist lifted and twisted the needles to induce the subject's sensation of "De qi", and the needle was left for 20 minutes. "De qi" refers to manipulation of the needle by the acupuncturist (extract, intercalate, twist, and rotate) after the needle has been inserted into the acupoints to a certain depth so that the acupoints can be induced by the meridians. The patient has a conscious response, such as soreness, numbness, or tenderness. According to TCM, this is the key to the curative effect of acupuncture. In our study, different types of acupuncture treatments will be compared. One is ordinary acupuncture, and the other is related to the positive results in previous clinical studies. Subjects in the sham acupuncture group were treated with shallow needling of sham acupoints. Due to its convenience, this control group setting method has been widely used in acupuncture clinical research, especially for the purpose of exploring acupoint-specific effects among the Chinese population. Sham HT 7 was 2 cun ( 40 mm) lateral to HT 7, and sham KI 7 was 2 cun ( 40 mm) lateral to KI 7 (Figure 1). The purpose of choosing the sham points in this way is explained in previous similar clinical studies; this approach avoids the true acupoints and meridian routes. Choosing sham points close to the true acupoints was conducive to blinding. The acupuncturist took the sham points on both sides and performed needling at a depth of 2-4 mm, sufficient only to penetrate the skin. The acupuncturist did not manipulate the needles and did not cause "De qi". The parameters of the acupuncture needles were identical to those used in the acupuncture group. Subjects in the two groups received the same treatment, which included 3 times a week for a total of 10 treatments. Each subject experienced screening, treatment, and a follow-up period of approximately 8 weeks, and the treatment phase lasted approximately 3.5 weeks. All subjects were treated equally to prevent them from perceiving differences. They were told about the methods of acupuncture as follows: Pittsburgh Sleep Quality Index (PSQI): The PSQI contains 19 self-assessed items and 5 other-rated items. The self-assessed items evaluate duration of sleep, sleep onset latency, sleep efficiency, sleep disturbance, need for medications to sleep, daytime dysfunction, and overall sleep quality. The total score is 0-21. A higher score indicates a worse quality of sleep. The PSQI is widely used to evaluate sleep dysfunction, and it is more inclined to evaluate the subject's sleep state during the workday. A total score >5 indicates that the subjects have poor sleep quality and has significance for clinical treatment. The Chinese version of the PSQI has high reliability and validity for the Chinese population and has been used as an effective tool for sleep screening in clinical and scientific research. This study evaluated the PSQI at baseline, posttreatment, one-week follow-up and one-month follow-up. Insomnia Severity Scale (ISI): The ISI mainly evaluates the nature and severity of insomnia and its impact on daytime function. The scale consists of 7 evaluation items, and the total score ranges from 0-28 points. A higher score indicates more severe insomnia. The ISI is mainly used to screen for insomnia and to evaluate treatment effects in clinical research. A total score of 8-14 indicates subclinical insomnia, and a total score >14 indicates clinically significant insomnia. A reduction in the ISI score by 8 points or more reflects a significant treatment effect in clinical evaluations. ISI has good reliability and validity. The Chinese version has high reliability and validity for evaluating insomnia among the Chinese population. This study evaluated ISI at baseline, posttreatment, one-week follow-up and one-month follow-up. Polysomnography (PSG): PSG was used as the objective sleep evaluation index. The PSG (NIHON KOHDEN, Japan) used in this study was composed of multiple quantitative parameters. The collection indicators included electroencephalogram (EEG), mentalis electromyography (EMG), bilateral electrooculography (ECoG), oral/nasal airflow, and bilateral anterior tibial EMG. In this study, PSG was used for two consecutive nights to eliminate the "first night effect". PSG monitoring started from the usual bedtime to the next morning, and a total of 8.0 hours were recorded. The efficacy evaluation of this study was based on EEG. The sleep stages and parameters were manually scored based on the American Academy of Sleep Medicine Manual for the Scoring of Sleep and Associated Events. The objective sleep evaluation parameters used in this study included the following: total sleep duration (TST); sleep onset latency (lights out to first epoch of any sleep, SOL); REM sleep latency (REM-sl); wake after sleep onset (WASO, SOL minus TST); sleep efficiency (SE, TST/total recording time x 100%); arousal index (Arl; number of arousals x60/TST); and percent time in each stage (length of each sleep stage/TSTx100%). In this study, during the screening period and at posttreatment, two consecutive monitorings were performed, but only the second result for each timepoint was used as the efficacy evaluation index. Beck Anxiety Inventory (BAI): The BAI was developed by Beck et al in 1988 and contains a total of 21 anxiety symptom items. It has been used as an evaluation index to evaluate the anxiety state of the subject within the past week. Higher scores correspond to more serious anxiety. Generally, BAI>=45 is used as the criterion to indicate anxiety. The scale is simple in content, easy to administer, and easily understood. The Chinese version has good reliability and validity and is commonly used for the evaluation of anxiety symptoms in China. This study evaluated it at baseline and posttreatment. Beck Depression Inventory (BDI): The BDI was developed by Beck et al according to the diagnostic criteria for depression in the DSM-IV. Beck et al formulated the first version of the BDI in 1961 and restructured it for the second version, which is now generally used. The BDI has a total of 21 self-evaluated depression-related items that can evaluate depression in the past 7 days. The higher the total score, the more severe the depression. A total score of 0-13 indicates no depression, 14-19 indicates mild depression, and 29-63 indicates severe depression. The Chinese version of the BDI has good validity and reliability. This study evaluated it at baseline and posttreatment. Fatigue Severity Scale (FSS): FSS was proposed and formulated by Krupp et al in 1989. The FSS scale is simple and clear. It consists of only 9 self-evaluation items. Subjects scored themselves on the corresponding symptoms. Higher total scores indicate more fatigue. Studies have shown that the FSS score of patients with insomnia is higher than 5.5, which means that there is a high level of daytime fatigue among patients with insomnia. The Chinese version of the FSS has good validity and reliability. This study evaluated the FSS at baseline and posttreatment. Epworth Sleepiness Scale (ESS): The ESS is a relatively simple and internationally recognized sleepiness assessment scale. It has a total score of 24 points. The higher the score is, the more severe the daytime sleepiness. This scale is generally used to screen and evaluate the hypopnea status of patients with obstructive sleep apnoea-hypopnea syndrome (OSAHS), but studies have shown that the ESS scale can be used to screen and diagnose other sleep disorders. The Chinese version of the ESS has good validity and reliability. This study used the ESS to assess the daytime sleepiness of subjects at baseline and posttreatment. Two types of safety assessments were performed: evaluation of changes in routine blood tests, liver function, and kidney function after the 10 intervention sessions and records of adverse events during the entire study. The record of adverse events in this study was conducted using the Adverse Event Record Form. Subjects were required to fill in the list of adverse events during the study, including the time point, severity, measures taken, whether the event was related to the treatment and prognosis. During the assessment phase, researchers assessed the possible relationship between adverse events and the study treatment, as well as medications taken concurrently. Adverse events include all adverse reactions that are definitely related to treatment, most likely related to treatment, and likely related to treatment. The required sample size was estimated based on the change in PSQI scores. According to previous research by our team, sham acupuncture can reduce the PSQI to 14.76 after 10 interventions, with an SD of 3.35. This study hypothesized that acupuncture at HT 7 and KI 7 for insomnia would reduce the PSQI by 2.70 points more than sham acupuncture. According to the needs of this study, we made alpha=0.05 and 1-beta=0.90, according to the formula: A two-sided test was performed. Through the query, =1.96, =1.282, and calculated n=33.32 34. In addition, considering the loss factor (according to a 20% loss rate), the final sample size was 41 subjects in each group, for 82 subjects in total. Specialized statisticians who were independent of the research group generated 82 random numbers in SPSS 25.0 and then arranged these numbers in order from small to large. Numbers 1-41 were artificially specified as the acupuncture group, and 42-82 were specified as the sham acupuncture group. The random numbers are reproducible (random seed number: 20190520). Subjects entered the acupuncture group or the sham acupuncture group according to randomly assigned numbers at a ratio of 1:1 after signing the informed consent form. The random number and treatment plan corresponding to each subject were printed on a card and stored in an opaque envelope. Each subject who signed the informed consent form was given an envelope with their name, which was handed over to the acupuncturist during the treatment. The acupuncturist checked the envelope and removed the treatment card to view the treatment plan. During the study, the generation of the random numbers list, subject recruitment, acupuncture treatment, outcome measure assessment and follow-up were performed independently by different researchers. Only the outside assistant and the acupuncturist were aware of the allocation. Participants and other relevant researchers were blinded to the allocation. The statistics and analysis of all data were performed by two analytical researchers independent of the trial. Intention-to-treat (ITT) was used as the evaluation method to evaluate the results of the study. Statistical analysis of the data was performed using SPSS 25.0. The measurement data conformed to a normal distribution, and homogeneous variances were determined using the mean +- standard deviation to describe the central tendency and the degree of dispersion. The primary outcome assessments were analysed using a mixed-effect model for repeated measures (MMRM) with patients as a random-effect factor, treatment group, age, gender, time and comorbidities as the fixed variable, patients as the random variable, random effects including intercept, baseline as a covariable, age*group, gender*group, time*group and comorbidities*group as interaction effect using a first-order ante dependence covariance matrix. The comparison between groups used the independent sample t test, and the comparison of multiple time points within groups used repeated measurement data combined with multivariate variance analysis. For measurement data that did not conform to the normal distribution, the median, minimum, and maximum were given. The between-group comparisons used the Mann-Whitney U-test, and the within-group comparisons used the Friedman (F) test. Enumeration data were expressed as frequency and composition rate. For binary or multicategory nonranked data, comparisons between groups were performed by the chi2 test. If the data were ranked as ordinal data, the comparison between groups was performed by the Mann-Whitney U-test. All statistical analyses used two-sided tests, and P values of <=.05 were considered statistically significant.

acupuncture, chronic insomnia, randomized clinical trial, sleep and comorbid symptoms

PMC4352732_01

Male

A 44-year-old male with the past medical history of essential hypertension and tuberculosis presented to the emergency room (ER) with the complaints of high grade fever, fatigue, and shortness of breath. According to patient, he developed high grade fever 1 week ago that was accompanied by myalgias, frontal headache, and generalized weakness. Fever was followed by shortness of breath and exercise intolerance which started 3 days ago and worsened with time. History was positive for mild paroxysmal nocturnal dyspnea and orthopnea though he denied any chest pain, palpitations, cough, or syncope. He also had frequent light headedness and got 1 episode of coffee ground emesis after which he was brought to ER. There was no history of blood in stools or urine. The patient denied any history of diabetes, ischemic heart disease, or hyperlipidemia. The patient was only taking HCTZ for hypertension and did not have any allergies. He was an active smoker with a history of one pack of cigarettes daily but denied use of alcohol or illicit drugs. The family history was positive for myocardial infarction in father at the age of 77. The patient did have a history of recent sick contact with one of his brothers who had dengue fever 3 weeks ago. Review of patient's past medical records indicated that patient had dengue fever 1 year ago for which he was admitted on the floor but fever got resolved on its own with no complications. At that time patient developed vague chest discomfort for which EKG was done which showed widespread T wave inversions. Cardiac enzymes were mildly elevated and echocardiography showed normal wall thickness and ejection fraction of 58%. Taking into account above findings, a tentative diagnosis of mild dengue myocarditis was made. CXR was normal and patient was discharged. Endomyocardial biopsy and cardiac MRI were not done as the patient had mild myocarditis with normal myocardial functions. Follow-up CXR, Echo, and EKGs were normal and patient remained healthy other than having slight fatigue. In ER patient was lethargic and seemed anxious due to generalised body aches and headache. On physical examination, vital signs were as follows: blood pressure of 89/52 mmHg, temperature of 103 F, heart rate of 116/min, and respiratory rate of 19. Chest examination revealed reduced breath sounds at lung bases bilaterally with scattered fine crackles in both lungs; no rhonchi or wheeze was heard. Examination of heart was remarkable for normal S1 and S2 with no murmur or clicks; an S3 gallop sound was audible. There was no pallor, scleral icterus, cyanosis, clubbing, or peripheral edema. The rest of the physical examination was unremarkable. Patient was suspected to have dengue shock syndrome and was immediately admitted on floor and resuscitated with IV fluids. Antiemetics and Tylenol was also given. Routine EKG was done which showed sinus rhythm and frequent premature ventricular contractions (PVC) with no ST or T wave ischemic changes (Figure 1). CXR showed bilateral interstitial edema, cardiomegaly, and pleural effusion in both lungs (Figure 2). The X-ray findings were suggestive of acute congestive heart failure. Elevated BNP (1040) supported the X-ray findings His haematological investigations revealed slight thrombocytopenia (127000), leucopenia (3100), and haemoglobin of 12. Cardiac enzymes were initially slightly elevated but remained stable over the course of hospital stay (Table 1). Urgent transthoracic echocardiography was done which showed ejection fraction of 10% and left ventricle dilation without focal wall motion defect and or focal thinning (Figure 3). Cardiac catheterization revealed EF of 13% and normal coronary arteries (Figure 4). Patient was started on dobutamine infusion along with ACEIs, spironolactone, and Lasix. Blood cultures, ESR, hepatitis panel, thyroid profile, and urine drug screen were all within normal limits. Malarial antigen test and typhoid serology were also negative. Anti-dengue IGM by ELISA was negative at the time of admission but was positive for IGG antibodies at that time. Repeat testing on day 3 showed positive IGM antibodies for dengue. The diagnosis was confirmed with reverse transcriptase polymerised chain reaction (RT-PCR) which was positive for dengue virus serotype 3 (DEN-3). In view of above clinical scenario with positive dengue serology, history of myocarditis during primary dengue infection 1 year ago, and echocardiographic findings, diagnosis of dengue virus induced dilated cardiomyopathy (DCM) was made. Fulminant myocarditis with acute myocardial failure was ruled out as cardiac enzymes were almost normal in the setting of dilated cardiac chambers on Echo. Patient condition worsened gradually and he developed acute hypoxic respiratory failure for which he was intubated on day 4. Patent developed severe thrombocytopenia and despite platelet transfusions he developed massive lower GI bleed leading to refractory shock. Patient was transfused 2 units of PRBC and platelets, but despite aggressive resuscitation and intensive care, patient died on day 5.

PMC8123922_01

Female

Of course, xenophobia in the news and online needn't translate into in-person acts of racism. But while it needn't, such acts were perpetuated in local communities. Multiple Asian Americans' stories made the news, exposing the ways in which these people were made victims of racist attacks after the COVID-19 outbreak. One woman described a stranger shouting, "Get out of here. Go back to China. I don't want none of your swine flu here," in one week, and then being threatened by a man wanting to shoot her the next (Escobar). A man on a bus in Boston muttered about "diseased Chinese people" when a woman nearby sneezed into her sleeve" (Escobar). Children have also been targeted, as Devin Cabanilla's children were while at Costco. A sample vendor told Cabanilla's "Korean wife and mixed-race son to 'get away' from the samples, questioning whether they had come from China" (Escobar). A thirteen-year-old described tensions at school when her middle-school classmates started calling her "corona" and asked if she and her Asian American peers ate dogs (Escobar). And such incidents weren't confined to the United States. In Australia, some parents refused to let Asian doctors treat their kids (Escobar). In Canada, 10,000 people signed a petition asking a local school district to track down and isolate Chinese-Canadian kids after the Lunar New Year (Escobar). In London, a man was attacked by a mob of four people who punched and kicked him to the point that he was told he may need facial reconstructive surgery (Haynes). In the U.S. and elsewhere, at school, at work, and in public, the COVID-19 outbreak was followed by acts of racism that harmed members of already marginalized communities. None of this should be particularly surprising, as this is hardly the first time that some Americans have responded in these sorts of ways. In 1853, during the yellow fever epidemic, European immigrants were stigmatized since they were said to be more vulnerable to disease, to the point that the epidemic was nicknamed "The Strangers' Disease" (Carrigan).16 In the plague of 1899, health officials in Hawaii quarantined "Chinatown" first:a home to Chinese, Japanese, and Native Hawaiian residents:responding to the belief that Asians "were more susceptible to the bubonic plague than Europeans" (Mohr). A common public perception was that white people were protected from infection, with at least one local newspaper giving credence to this belief when it reported that the plague "was not dangerous to whites 'who were honest and cleanly" (Mohr).17 In an attempt to sanitize communal spaces with controlled fires, Chinatown was accidentally burned down in January of the following year. In 1924, the bubonic plague prompted Los Angeles officials to quarantine and guard Mexican-American neighborhoods, including those where there was not disease outbreak (Deverell). Officials expressed their hope that "all of that area where Mexicans live [be put] in sanitary condition" and urged that "a great deal of that area ... ought to be condemned and destroyed" (Deverell). This destruction ensued, in the name of sanitation, and the government refused to pay any compensation since the destroyed properties:houses, business, infrastructure, and the like:were construed as public health nuisances (Deverell). During more recent outbreaks, too, like those of SARS and Ebola, xenophobia was part of the public chaos. The SARS outbreak saw similar repercussions to those we enumerated earlier. A cartoon illustrated during that time features an open Chinese food takeout container with "SARS" written on it, and bearing the caption, "Bad Chinese Take-Out" (Shoichet). Claire Jean Kim discusses this phenomenon in her work, identifying the way in which "tropes of Chinese cruelty, transgressiveness, backwardness, and recklessness," took the media by storm during the SARS crisis. The public imagination turned against Chinese communities in 2003, just as it did in the early days of the COVID-19 pandemic. What's more, Kim also highlights the way that animal activists in particular "mobilized ethnocentric and anti-Chinese feeling among some part of the public" in a string of anti-cruelty campaigns in San Francisco. Though those activists certainly weren't trying to depict Chinese people as backward, callous, or uncivilized, the activists nevertheless did that by singling out practices at Chinese markets instead of far more heinous problems at American factory farms. We haven't told the full story of the economic and cultural importance of wet markets. We obviously haven't given a comprehensive account of pandemics and racist social responses. Still, even this brief sketch should be enough to make it plausible that abolishing wet markets would have significant consequences for many poor people; it also makes it clear that the United States is home to a long and complex history of majority groups linking disease outbreak to the presence of perceived foreigners at home. Importantly, this history includes a trend of blaming foreign food systems for pandemic outbreak, and our contemporary situation is one in which blame on food systems was cast in explicitly racist and xenophobic ways. What's more, while there are plenty of reasons to object to the wildlife trade and the forms of animal agriculture that support wet markets, humans generally cause animals less suffering in those systems than they do in conventional intensive systems. The conclusion of all this seems to be that activists' arguments against wet markets fit into a pattern of targeting and stereotyping institutions that support vulnerable populations. This pattern, we submit, was and is xenophobic, and on top of that, is unlikely to leave animals better off on net. Granted, there may be times and circumstances in which it is appropriate for animal activists to highlight links between COVID-19 and culturally important foodways. At a time of great fear and unrest, however, this involved participating in a xenophobic trend of blaming Chinese culture and citizens for a problem that is obviously caused by a complex set of factors, and which manifested itself in expressions of hatred for, and frustration with, Chinese people generally. So, if activists should avoid taking a non-trivial risk of leaving their beneficiaries seriously worse off due to their efforts when, in running that risk, they would be acting in ways that are morally objectionable for independent reasons, then activists shouldn't have run arguments against wet markets.18

activism, animal advocacy, covid-19, factory farms, wet markets

PMC10333629_01

Female

A 49-year-old woman (160 cm tall, weighing 50 kg), with histories of depression and adjustment disorder, was injured in a collision accident with a train, and was rushed to our hospital in a state of cardiopulmonary arrest and with her left leg amputated by the trauma. After arriving at the hospital, she was immediately intubated and ventilated, and resuscitation was continued. She was diagnosed as being in cardiac arrest due to hemorrhagic shock, and emergency thoracotomy and aortic occlusion were performed. Her heartbeat resumed within approximately 20 min, following massive fluid infusion and blood transfusion. Subsequently, the aortic occlusion was converted to percutaneous aortic blockade and the chest was closed, and transection of the right hip and angioembolization of the right superior gluteal artery were performed. She was extubated on the ninth hospitalization day and was given 1 L/min of oxygen by nasal inhalation to maintain SpO2 at above 97%. Blood laboratory test results at this time revealed a prothrombin time-international normalized ratio of 1.09, activated partial thromboplastin time of 25.5 s, fibrinogen level of 238 mg/dL, antithrombin-III (AT-III) of 107.9%, and elevated D-dimer level of 23.59 microg/mL. Thoracoabdominal X-rays showed fractures at Th10, 11, and L3-5, and magnetic resonance imaging showed findings of spinal cord injury at the Th7-11 levels. Along with other treatments, as required, perioperative deep vein thrombosis (DVT) prophylaxis was applied, in the form of withholding of anticoagulation, application of elastic stockings to the lower extremities and intermittent pneumatic compression, without performing lower extremity vascular echocardiography. The patient was scheduled for debridement on the 11th day after right hip dissection surgery, and heparin was to be started thereafter. For debridement, anesthesia was induced with propofol at a target concentration of 2.0 mug/mL, along with remifentanil 0.2 mug/kg/min, followed by rocuronium 50 mg. Anesthesia maintenance was performed with propofol at a target concentration of 1.5-2 microg/mL and remifentanil 0.1-0.2 microg/kg/min, with rocuronium, as needed, for muscle relaxation. Phenylephrine was administered as needed to maintain blood pressure. Intraoperatively, the patient was monitored using standard monitoring techniques, including direct measurement of arterial pressure, electrocardiography, SpO2, and bispectral index. Blood gas analysis showed a partial pressure of arterial oxygen (PaO2) of 121.3 mmHg and a partial pressure of arterial carbon dioxide (PaCO2) of 38.5 mmHg at a fraction of inspiratory oxygen (FiO2) of 0.5 at the start of surgery. Approximately 1 h after the start of surgery, her SpO2 decreased suddenly from 98% to the 60% level, heart rate increased (from 77 to 94 bpm), and blood pressure decreased (from 78/52 to 64/45 mmHg). End-tidal carbon dioxide tension (EtCO2) also decreased (from 33 to 25 mmHg) at the same instant. Although her blood pressure increased with the administration of a vasopressor, poor oxygenation persisted and EtCO2 remained low (19 mmHg). Blood gas analysis performed at this time showed a PaO2 of 53.9 mmHg and PaCO2 of 49.9 mmHg at an FiO2 of 1.0. Based on these findings, we suspected the development of PTE and performed transthoracic echocardiography (TTE). Evaluation revealed pressure overload in the right ventricle. Then, TEE was performed, which revealed a thrombus in the right pulmonary artery (Figure 1). After consulting with a cardiovascular surgeon, venoarterial extracorporeal membrane oxygenation (VA-ECMO) with femoral artery pumping and femoral vein debridement was performed. Following VA-ECMO initiation, her oxygenation improved and hemodynamics stabilized. Since the patient had recently undergone traumatic amputation of her lower leg and there were wounds all over her body, thrombolytic therapy was not administered since it could have increased the risk of bleeding and infection. Contrast-enhanced computed tomography (CT) was performed, which revealed a thrombus in the pulmonary artery (Figure 2). The next day, thrombectomy was performed under an open chest. No anticoagulation was used preoperatively, and the activated clotting time remained between 150 and 180 s while on VA-ECMO. After pulmonary artery thrombectomy, an organic thrombus was also found at the inferior vena cava side of the right atrium, and a dark red to partly white thrombus was observed in the right pulmonary artery (Figure 3). The patient's post-thrombectomy course was uneventful, with the maintenance of hemodynamics and oxygenation. Postoperatively, the patient was admitted to the intensive care unit under sedation and intubation and was extubated on the third postoperative day. Thereafter, she had a good course with no recurrence of PTE. She had no neurological complications.

transesophageal echocardiography, debridement, general anesthesia, pulmonary thromboembolism, venoarterial extracorporeal membrane oxygenation

PMC7731515_01

Male

We present a 68-year-old Caucasian male who reported left leg weakness during his intake interview at a local hospital. The patient had been experiencing leg weakness for one week. He was admitted to the hospital due to his complaint of leg weakness and fever. After three days, he was discharged from the hospital with the impression of a viral infection. Subsequently, the patient's symptoms worsened. He returned to the hospital one week later and was readmitted due to his inability to walk and left side and left arm weakness. The patient is married and living with his wife. He is a former ETOH abuser and former tobacco user (20 packs/year), and stated that he is currently a nondrinker and nonsmoker. The patient has worked for several years as a tugboat operator. The patient did not report any family medical history or known drug allergies. The patient reported a history of Hepatitis C, diabetes mellitus type 2, gastroesophageal reflux, aortic stenosis, and primary liver cancer metastasized to the right suprarenal gland. The patient had an aortic valve replacement one year ago, adrenalectomy (right), and chemoembolization about two years ago. The patient was alert, awake, and oriented times 3 to person, place, and time. The patient did not display signs of acute distress. Temperature: 36.9oC; blood pressure: 139/58 mmHg; heart rate: 83 bpm; respiratory rate: 19 rpm; O2 saturation 98%. Normocephalic atraumatic; mucous membranes moist; extraocular muscles intact; pupils equally round and reactive to light, with accommodation bilaterally; no jugular venous distention. Clear to auscultation. S1/ S2, holosystolic murmur at apex radiating to the axilla 3/6; no rubs, gallops. Soft, nontender, nondistended. No edema; pedal pulses +; + Janeway lesions on the right palm. No joint swelling or deformity. Venous stasis changes. AAOx3; Hand dominance: right. Normal. Short term/long term: intact. 2 to 12 intact. Normal: light touch, pin prick, position, vibration, temperature. Normal: bulk, tone. The patient showed no asterixis, no dystonia, no fasciculation, no myoclonus, no tremor. 2/5, UE Right: 5/5 1/5, LE Right: 5/5 Absent nystagmus. Doll's eyes, corneal reflex, gag reflex. 1+ B/L UE and LE No response (right, left). Not tested The patient exhibited focal weakness, gait disorder. The patient denied bladder incontinence, bowel incontinence, change in LOC, confusion, dizziness, headache, lightheaded, numbness, seizure, slurred speech, spinning sensation, fainting, unable to speak, vision change, and generalized weakness. White count 14 mg/dl, H and H 11 mg/dl, 35 mg/dl, platelet count 61 mg/dl. Creatinine 1.16mg/dl, potassium 3.7Eq/l, alk phos 143U/I, Mg 2.3 mEq/dl, Ca 8.2mE/dl, Pho 1.9 mE/dl. PT/INR: 17/1.6 sec; PTT: 31.5 sec. Total bilirubin 2.1 mg/dl H; total protein 5.7 mg/dl; AST 39 U/L, ALT 39 U/L. Negative. NSR. Negative. Intracranial hemorrhage, not aneurysm. 2.8 x 3 cm right parietal parenchymal hemorrhage; right parietal and left parietal subarachnoid hemorrhage. Technique throughout the carotid arterial system bilaterally showed calcified plaque at the carotid bulbs with no flow-limiting stenosis. Mildly echogenic liver (possibly secondary to fatty infiltration); prominent portal vein. (This raised the consideration of early portal hypertension. It was suggested to correlate further with clinical findings.) Transesophageal echocardiography (below) (Note. Image of mitral valve vegetation as shown on TEE from najms.org.) The initial findings led to an impression of metastatic disease. After further evaluation and testing (including blood and urine cultures), the patient was given a definitive diagnosis of infective endocarditis. It is important to note that the subsequent testing revealed two significant findings that suggested infective endocarditis by Duke criteria. (Major Duke criteria: positive blood culture tested two times, Gram-positive cocci in pairs as Streptococcus, and vegetation on the mitral valve noted on the 2D echo 10 mm; Minor Duke criteria: Murmur, systolic murmur on the apex MR, and hemorrhagic stroke.) The patient suffered acute hemorrhagic CVA secondary to septic cardioembolism. Administration of vancomycin empirically. Blood culture taken twice. Picc line for long-term IV ABX, 6 weeks. Reevaluate for possible mitral valve surgery. Preliminary impression for the patient was a large intraparenchymal hemorrhage likely secondary to metastatic disease since the patient had a history of hepatic cancer versus coagulopathy thrombocytopenia. During day 1 and 2 of treatment, the patient's MRI showed sizeable dominant hemorrhage in the right posterior parietal lobe demonstrating peripheral enhancement-which can be seen in metastatic disease but can also be due to the subacute phase of hemorrhage/ischemia. The findings showed large intraparenchymal hemorrhage, likely secondary to septic emboli. These findings contributed to the impression of metastatic disease, but other conditions were considered possible. The care providers discussed differential diagnoses for amyloidosis (less likely because the bleeding area), an aneurysm, AV malformation, and Traumatic Brain Injury (TBI); however, the patient did not report any trauma. Approximately day 4, the care providers suspected IE. On day 4 of treatment, an echocardiogram was ordered. An annular calcification in the mitral valve was observed as was mild thickening and normal leaflet separation and possible, mobile vegetation measuring 10 mm x 26 mm. The transmitral velocity was within normal range. There was moderate regurgitation and no evidence of stenosis. After reviewing the additional findings, an Infectious Disease (ID) inter-consult was completed. Blood and urine cultures were taken. The blood culture was positive for Gram-positive cocci (Enterococcus faecalis). TTE and TEE confirmed mitral valve vegetation. The definitive diagnosis was determined as bacterial endocarditis (2 major Duke criteria) with septic embolic and hemorrhagic bleeding. The management of the condition was focused on continuing patient treatment with vancomycin, ceftriaxone, and ampicillin/ sulbactam (Unasyn); IV for 6 weeks. The patient was discharged from the facility with close follow-up by the ID internist (infection disease specialist), a cardiologist, and a cardiothoracic surgeon. Mitral valve replacement was not needed. However, it was recommended to continue monitoring the bacteremia to assess the need for possible heart surgery and removal of the prosthetic valve. Complications of IE include cardiac, neurologic, renal, musculoskeletal; and complications related to systemic infection, such as embolization, metastatic infection, and mycotic aneurysm. These complications can co-occur and can be considered based on pathogenesis; such as cerebral infarct (embolic), heart valve destruction (the local spread of infection), vertebral osteomyelitis (metastatic infection), and glomerulonephritis (immune-mediated damage). It has been researched and described that IE should be considered a possible etiology if the patient displays symptoms of systemic arterial embolization. The likelihood of IE is increased in patients with cerebral and systemic arterial embolization. Echocardiography is central to the diagnosis and management of patients with IE. Evidence of an oscillating intracardiac mass or vegetation, an annular abscess, prosthetic valve partial dehiscence, and new valvular regurgitation are significant criteria in the diagnosis of IE. Definitive diagnosis of IE can be made based on clinical manifestations, blood cultures, and echocardiography. Additional evaluations for patients with suspected IE include electrocardiography, chest radiography, and other radiographic imaging targeting clinical manifestations. During an intake interview, it is essential to assess a patient with a prosthetic heart device, a history of surgeries, or recent dental procedures. It is imperative to highlight cerebral and systemic arterial embolization as related complications of IE. Echocardiography should be performed directly in patients suspected of IE (Class I; Level of Evidence A). At least three sets of blood cultures obtained from different venipuncture sites should be obtained, with the first and last samples drawn at least one hour apart. (Class I; Level of Evidence A). TEE should be performed if initial TTE images are negative, or inadequate in patients for whom there is an ongoing suspicion for IE, or when there is a concern for intracardiac complications in patients with an initial positive TTE (Class I; Level of Evidence B). If there is high suspicion of IE despite initial negative TEE, then repeat TEE is recommended in 3 to 5 days, or sooner if clinical findings change (Class I; Level of Evidence B). Repeat TEE after initial positive TEE if clinical features suggest a new development of intracardiac complications (Class I; Level of Evidence B). It is fundamental to obtain at least two sets of blood cultures every 24 to 48 hours until the bloodstream infection has cleared (Class IIa; Level of Evidence C). If operative tissue cultures are positive, then an entire antimicrobial course is indicated after valve surgery (Class IIa; Level of Evidence B). The risk of embolization in the setting of native valve endocarditis is 13 to 44 percent, and in many cases embolization occurs before a diagnosis of IE has been established. Among patients with IE, risk factors for embolization include vegetation size >10 mm; vegetation mobility; vegetation location on the anterior mitral leaflet; prior embolization; and infection with Staphylococcus aureus, Streptococcus bovis, or fungus. In a multicenter study of 384 patients with definitive IE (75 percent with native valve endocarditis), S. aureus and S. bovis were predictors of total embolic events, while vegetation length >10 mm and severe vegetation mobility were significant predictors of embolic events after initiation of antibiotic therapy. It is clear that the incidence of septic emboli in the setting of infected endocarditis depends on the size of the vegetation and the type of infective microorganism. Early valve surgery in left-sided NVE (during initial hospitalization and before completion of a full course of antibiotics) is indicated in patients with IE who present with valve dysfunction resulting in symptoms or signs of heart failure (Class I; Level of Evidence B). Early surgery should be considered, particularly in patients with IE caused by fungi or highly-resistant organisms; such as vancomycin-resistant Enterococcus or multidrug-resistant Gramnegative bacilli (Class I; Level of Evidence B). Early surgery is indicated in patients with IE complicated by heart block, annular or aortic abscess, or destructive penetrating lesions (Class I; Level of Evidence B). Early surgery is indicated with evidence of persistent infection after the start of appropriate antimicrobial therapy (Class I; Level of Evidence B). Early surgery is reasonable in patients who present with recurrent emboli and persistent or enlarging vegetations despite appropriate antibiotic therapy (Class IIa; Level of Evidence B). Early surgery is rational in patients with severe valve regurgitation and mobile vegetations >10 mm (Class IIa; Level of Evidence B). Early surgery may be considered in patients with mobile vegetations >10 mm, particularly when involving the anterior leaflet of the mitral valve and other relative indications for surgery (Class IIb; Level of Evidence C). Valve surgery may be considered without delay in IE patients with stroke or subclinical cerebral emboli and residual vegetation if imaging studies have excluded intracranial hemorrhage and if neurological damage is not severe (Class IIb; Level of Evidence B). In patients with major ischemic stroke or intracranial hemorrhage, it is recommended to delay valve surgery for at least four weeks (Class IIa; Level of Evidence B).

bacteremia, emboli, endocarditis, hemorrhage, infective, intraparenchymal, septic

PMC9992531_01

Male

Our case is a 12-year-old boy who was transferred to the Bambino Gesu Children's Hospital from another hospital in March 2022, for the management and treatment of severe neurological symptoms. The symptoms began 10 days after asymptomatic SARS-CoV-2 infection. SARS-CoV-2 infection was diagnosed by a nasopharyngeal swab polymerase chain reaction (PCR) test, which was performed after exposition to the virus. Notable neurological symptoms included irritability, headache, and difficulty in urinating. At 2 days after the onset of symptoms, the patient presented with fever, paraplegia, and loss of sensitivity from the T1 level. His medical history included growth retardation, genetic disorder, community-acquired pneumonia, and angioedema. The individual had been administered all the mandatory vaccines in Italy. However, the SARS-CoV-2 vaccine was not administered. Upon admission to the hospital, the child was alert and interactive. There was no cranial nerve dysfunction. Lower tendon reflexes and superficial abdominal reflexes were absent. Loss of sensitivity from the T1 level and paraplegia was observed. Dysmetria of the extremities was not present. The patient presented with bladder overdistention and fever. The cardiorespiratory system was not involved, and O2 saturation was 100% in room air, with stable and autonomous hemodynamics. At the onset of symptoms, a computed tomography (CT) scan of the brain was performed to exclude neurosurgical emergencies. Brain and spinal cord MRI with contrast revealed "signal alterations corresponding to the pons, the right middle cerebellar peduncle, and the subcortical white substance of the frontal lobes; the alterations at the right middle cerebellar peduncle and pons enhanced after gadolinium" (Figures 1, 2); and "signal alterations from C4 to the conus medullaris, with contrast impregnation at D1 and conus medullaris level" (Figure 3). These images were compatible with that of ADEM with spinal cord involvement. The CSF testing excluded infections, and the result was compatible with an immune-mediated disease (51 mg/dl proteins, 59/mm3 white blood cells, and 6/mm3 red blood cells). CSF and blood cultures were negative. Band autoantibodies were not detected in the CSF liquor and blood samples, which were anti-MOG-negative and anti-AQP4-negative (measured by enzyme-linked immunosorbent assay). Laboratory tests of blood samples excluded autoimmunity, infections, and immune deficiencies. In particular, antinuclear antibodies (ANA), extractable nuclear antigens (ENA), anti-smooth muscle antibodies (ASMA), anti-parietal cell antibodies (APCA), endomysial antibodies (EMA IgA), anti-liver-kidney microsome antibodies (LKM), antibodies to double-stranded DNA (Anti Ds-DNA), anti-neutrophil cytoplasmic antibodies (c-ANCA and p-ANCA), anti-cardiolipin antibodies, anti-beta-2-glycoprotein antibodies, and anti-citrullinated protein antibodies (anti-CCP) were negative. Mycobacterium tuberculosis DNA was not isolated; the nasopharyngeal swab was negative for respiratory viruses. Laboratory tests of blood samples were negative for other infections; in particular, cytomegalovirus (CMV), hepatitis B (antibodies positive for vaccination), hepatitis A (antibodies positive for vaccination), hepatitis C, Treponema pallidum, human immunodeficiency virus (HIV), and saccharomyces cerevisiae, were tested. Lymphocyte subpopulations were normal. Electroencephalography (EEG) was normal. The cardiological evaluation did not reveal any problems. Neurophysiological studies revealed normal visual evoked potentials (VEPs), whereas somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were altered. High-dose steroids (30 mg/kg/day for 3 days) and intravenous immunoglobulin (IVIG; 2 g/kg/day) were administered to the patient without any clinical improvement. The patient received five cycles of plasma exchange therapy, after the parental declaration of informed consent, followed by off-label rituximab infusion (weekly infusion for 4 weeks) as reported in recent pediatric severe cases of ADEM. The patient showed partial clinical improvement along with important radiological improvement. After the initial therapy with steroids and IVIG, no improvement was observed. Subsequently, plasma exchange therapy and rituximab infusion led to an important improvement that was documented in the brain and spinal cord MRI without contrast, performed 3 months later. At the spinal cord level, a reduction in alteration was observed (Figure 4), and no alterations were observed in the brain (Figures 5, 6). Clinically, the patient reported urinary complications of the neurogenic bladder. Unfortunately, paraplegia persisted, and the patient continued motor physiotherapy.

covid-19, acute disseminated encephalopathy, children, complications, neurological complications

PMC6451814_01

Male

A boy who was 13 years old presented to the emergency room with pain and difficulty in walking after a break (sudden deceleration) during a football match. The patient's height and weight were 1.62 m and 59 kg, respectively. Physical examination indicated pain when trying to fully extend either knees, bilateral pain on palpation, swelling over the anterior tibial tuberosity, joint effusion, and inability to walk. Ligament manoeuvres were negative (bilateral Lachman test). This patient has a previous history of Osgood-Schlatter disease in both knees. He suffered from anterior knee pain the year before. This pain forced him to stop sport activities and to undergo different treatments. He was treated with resting from contact-sport activities, physical therapy, and as a last resort, some injections (he was treated in a different hospital, and the patient cannot specify which drug was administered). Anteroposterior and lateral radiographs of both knees evidenced a bilateral tibial tuberosity avulsion fracture (Figure 1). The fractures of both knees were classified as Ogden type IIIA in the left knee and type IB in the right knee. Surgical treatment was proposed (open reduction and internal fixation with screws), and the patient underwent surgery 24 hours after the trauma. Under spinal anesthesia and in a supine position, an anterior approach was performed in both knees. Intravenous tranexamic acid was used in this case to avoid the use of bilateral tourniquet. After dissection and haematoma drainage, we cleaned the fracture site and reduced the distal fragment fracture under radiological control (Figure 2). The left knee (Ogden type IIIA) was internally fixed with 2 cannulated screws of 4.5 mm with a washer (Asniss III, Stryker, Selzach, Switzerland). The right one (type IB) was fixed with one cannulated screw and a washer. We reinforce fixation of both patellar tendons with one suture anchor (Iconix 2.3 mm, Stryker, Mahwah, NJ, USA) (Figure 3). On the basis of the patient's weight, type of fracture, and bilateral occurrence, immobilization was indicated for 3 weeks using a bilateral knee brace. Physical therapy was started with passive range of motion (ROM) exercises, and after a 3-week-period, loading and quadriceps strengthening exercises were allowed. At 8 weeks, full loading and active ROM exercises were performed. At 12 weeks after surgery, the patient had already achieved full ROM (0 -140 ) and regained bilateral knee extension strength. Approximately 20 weeks after the surgery, the patient was able to perform physical activities without limitations at the same level as before the injury. Return to play was allowed at 6 months postoperative. A nonsymptomatic hypertrophic scar was developed, but the patient has no limitations during sport activities. By now, there has been no need for hardware removal (Figure 4).

PMC4213402_01

Male

A 21-year-old Nepalese man was brought to our emergency room (ER) after a witnessed generalized tonic clonic seizure (GTCS), lasting for few minutes and aborted spontaneously. The patient was previously healthy with no history of seizures. There were no recent respiratory symptoms or fever. His vaccination status is unknown. He was fully alert and afebrile with no meningeal signs or focal neurological deficits upon ER arrival. A second GTCS in ER with longer duration prompted treatment with Lorazepam and Fosphenytoin. The patient became subsequently febrile and confused. He desaturated, became hypotensive, and required intubation and ICU admission. The initial EEG showed diffuse generalized slowing with no epileptiform discharges, but a repeat EEG performed on the second day of admission as the patient failed to regain consciousness revealed recurrent focal seizures of independent bihemispheric origin fulfilling the criteria of nonconvulsive SE (Figure 1). CT head, brain MRI, and cerebrospinal fluid (CSF) analysis were unrevealing. The CSF showed WBC count of two cells/mL, protein of 0.4 g/L, and glucose of 4.4 mmol/L (compared to 5.5 mmol/L serum glucose). CSF cytology, viral screen including herpes, TB PCR and culture, Gram stain, and fungal and bacterial cultures were all negative. Chest X-ray, followed by chest CT scan showed a left upper lobe consolidation (Figure 2). H1N1 infection was confirmed by PCR on bronchoalveolar lavage material. Otherwise, BUN/Creatinine, liver profile, electrolytes, thyroid function tests, RF, ANA, ANCA, HIV serology, and initial blood cultures were unrevealing. Despite aggressive treatment with successive infusions of Midazolam, Propofol and Thiopental, and multiple high doses antiepileptic medications including different combinations of Levetiracetam, Sodium Valproate, Phenytoin, Phenobarbital, and Topiramate, the electrographic seizures recurred at every attempt to reduce the intravenous sedative drugs. The patient was also treated with Oseltamivir. His hospital course was later complicated with septic shock and associated severe hypotension with multiorgan failure, resulting in cardiopulmonary arrest and death two weeks from his initial presentation.

PMC8235959_01

Male

A previously healthy 17-year-old Caucasian male patient, with no family history of known rheumatic diseases, was observed in the emergency department with a history of fever, dry cough, and pleuritic chest pain for the past 24 h. Chest X-ray revealed an hypotransparency on the left inferior lobe, and antibiotic therapy was initiated, based on the suspicion of community-acquired pneumonia. Five days later, the symptoms worsened, with the onset of conjunctival hyperemia, odynophagia, asthenia, anorexia, and nocturnal diaphoresis. In the emergency department, his weight was 70 kg (had decreased 4 kg compared to two months earlier), and physical examination revealed an axillar temperature of 37.6 C, bilateral bulbar conjunctival hyperemia, and bibasal decreased breath sounds. He was normotensive, and there was no identifiable organomegaly or adenopathy. Laboratory testing revealed hemoglobin 12.3 g/dL (MCV 80 fL, RDW 12.4%), lymphopenia (950/muL), increased DHL (498 U/L), and increased inflammatory markers (reactive C-protein 106.5 mg/L and erythrocyte sedimentation rate 71 mm/h). Chest X-ray exposed multiple nodular hypotransparent lesions scattered by both the lungs, and a CT scan showed parenchymal nodular areas with internal cavitation (Figures 1(a) and 1(b)). Faced with the possibility of a necrotizing pneumonia, he was admitted in the pediatric department and started empirical therapy with ceftriaxone and vancomycin. However, fever persisted, and eight days later, he started complaining of diffuse abdominal pain. A new thoracoabdominal CT scan presented worsening pulmonary lesions and an enlarged spleen (13 cm larger diameter), with marked heterogenicity. Renal function was normal (plasma creatinine 0.8 mg/dL, urea 25 mg/dL), and urinalysis presented a protein count of 25 mg/dL, with 10-25 erythrocytes per high resolution field. He underwent a bronchofibroscopy, which showed a lesion in the left portion of the carina and whose biopsy revealed a necrotizing inflammatory process. An autoimmune workup showed a positive C-ANCA (1/640) and anti-PR3 (2250 UQ) with negative antinuclear antibodies (ANAs), anti-double-stranded DNA (dsDNA), and antimyeloperoxidase (MPO) and a normal immunoglobulin and complement assessment. Considering a systemic ANCA-positive vasculitis, he started prednisolone 60 mg/day. Due to an extensive popliteal deep venous thrombosis and a superficial femoral thrombosis, anticoagulation therapy was also instituted. Five days later, an acute pulmonary thromboembolism and a splenic infarction were diagnosed, leading to intravenous methylprednisolone pulses (1 g for 3 days) and immunoglobulin perfusion (2 cycles of 0.4 g/kg, 5 days). To exclude pulmonary tuberculosis, a cultural and PCR search for BK was carried out. After negative results, rituximab was initiated (375 mg/m2/week, 4 weeks). Pneumocystis jirovecii prophylaxis with cotrimoxazole was also introduced. An episode of macroscopic hematuria was also noticed that resolved after 24 h. Cardiac evaluation revealed a noncircumferential pericardial effusion, without hemodynamic compromise. Ophthalmologic and ear-nose-throat (ENT) evaluations were normal. During outpatient follow-up, an angio-CT scan revealed complete resolution of pulmonary thromboembolism and nearly complete resolution of cavitated granulomas 4 months after onset of the disease (Figures 1(c) and 1(d)), and at this moment, clinical remission was achieved. The anticoagulation treatment was suspended after 9 months, with a progressive tapering of oral glucocorticoid and suspension after 12 months. He underwent maintenance therapy with rituximab every 6 months during the first 2 years. Despite hypogammaglobulinemia (minimum of 496 mg/dL), no infections or complications were reported, and immunoglobulin replacement therapy was not required. During the 43 months of follow-up, there is a reference to mild sinusitis symptoms with no further complaints. Pulmonary function tests and renal function remained normal. Regular analytical monitoring demonstrated normalization of ESR and a progressive decrease of C-ANCA titers.

PMC3040432_01

Male

A 64-year-old man, weighing 47 kg and having a height of 154 cm, was scheduled for a pericardiectomy for treatment of constrictive pericarditis. When he was hospitalized with a two-week history of aggravating dyspnea, he had been placed on outpatient follow-up for pulmonary tuberculosis, previously diagnosed with dyspnea on exertion and pleural effusion. His past medical history included diabetes mellitus diagnosed 20 years ago and stent insertion in the left anterior descending (LAD) coronary artery eight years ago. Preoperative ECG revealed left atrial enlargement, and ST depression and flat T-wave on lead II, III and V4-6. Chest radiograph showed pulmonary edema and bilateral pleural effusion. Coronary computerized tomography demonstrated that the LAD stent was intact, but there was >50% narrowing of the left circumflex coronary artery, and pericardial thickening with adhesion to the right atrial and left ventricular lateral walls. Echocardiography showed a left ventricular ejection fraction of 73%, and mild pulmonary hypertension with a systolic right ventricular pressure of 38 mmHg. An hour before surgery, premedication was done with IM morphine 3 mg. On arrival, continuous monitoring of ECG lead II and V5 was initiated, and the radial artery cannulation was done under local anesthesia for pressure monitoring. Vital signs before induction of anesthesia were HR 85/min, ABP 108/68 mmHg, and SpO2 98%. Anesthesia was induced with IV midazolam 3 mg and ketamine 20 mg. Rocuronium 50 mg was administered to facilitate endobronchial intubation with a 35 Fr left-sided double-lumen tube. After intubation, lungs were ventilated with a tidal volume of 8-10 ml/kg, adjusted to maintain end-tidal CO2 within 33-38 mmHg. Anesthesia was maintained with 1.0-1.5% sevoflurane in 60% oxygen in air and continuous infusion of remifentanil at 0.1-0.3microg/kg/min. After induction of anesthesia, the patient was turned to the head-down position with the head rotated leftward by approximately 60 to facilitate internal jugular catheterization. An 18-G puncture needle was inserted at the conjoined site of both bellies of the SCM, and was advanced toward the ipsilateral nipple until free regurgitation of venous, non-pulsatile blood flow was observed. During the first attempt, the puncture needle had to be withdrawn, as the J-tipped guide wire could be advanced <10 cm. After 5 min of manual compression, jugular venous puncture was retried in the same manner, and non-pulsatile, free-regurgitant blood flow was again obtained. In the second attempt, the J-tipped guide wire was inserted into the vessel without significant resistance, even though it was initially difficult to advance the wire and the puncture needle had to be withdrawn a few millimeters to obtain free regurgitant blood flow. Then, a 7-Fr double-lumen central venous catheter (Arrow Gard Blue, Arrow International, Inc., USA) was inserted using the Seldinger method and was suture-fixed at 16 cm in the skin after confirming free inflow of fluid. At the end of procedure, the guide wire withdrawn showed no deformations. Central venous pressure (CVP) was measured to be 20 mmHg with the patient in a supine position and thereafter was maintained within 30-40 mmHg in the right semi-lateral decubitus position at approximately 30 during one-lung ventilation for surgery. Such a high CVP was considered to be related to the constrictive pericarditis, as the pressure measurement was less than the mean arterial pressure of the radial artery (80-85 mmHg) and the waveform was flat without pulsations, being affected by right-side one-ling ventilation and surgical manipulation of the heart. During the catheterization, vital signs were stable with HR 83/min, BP 90-100/65-68 mmHg, and SpO2 99-100%. Arterial blood gas analysis was done after induction of anesthesia and revealed pH 7.486, PaO2 331 mmHg, and PaCO2 36.2 mmHg with FiO2 0.6. Approximately 50 minutes after the surgery began, the pressure waveform from the central venous catheter changed abruptly into what was seemingly an arterial waveform, with a mean pressure of 61 mmHg, almost same to the mean arterial pressure of 62 mmHg (Fig. 1). Simultaneously, blood regurgitated through the fluid line connected to the central venous catheter. Even though about 300 ml of fluid had already been administered, no hematoma or edema was shown in the puncture site. Arterial blood gas measurement was done on blood withdrawn from the central venous catheter, indicating a PaO2 of 438.7 mmHg with a FiO2 of 0.6, confirming that it was arterial blood. Furthermore, the catheter was apparent in the aortic arch on TEE (Fig. 2). Fluid infusion was immediately stopped, and the catheter was removed when the surgery was completed. After confirming that there was no bleeding or developing hematoma in the puncture site with >15 min of compression, the double-lumen tube was replaced with a single-lumen endotracheal tube. Thereafter, the patient was transferred to the intensive care unit with the endotracheal tube in situ. Extubation was done after seven days of mechanical ventilatory care for tachypnea and CO2 retention, and the patient was transferred to the general ward without central venous catheter-related complications on the 10th postoperative day.

arterial insertion, central venous catheterization, intraoperative complication

PMC9198831_01

Female

A 35-year-old woman was admitted in October 2021 with a history of low back pain for the past year, which worsened over the past 2 weeks, and the patient complained of radiating pain in the left lower limb. The patient was treated at another hospital 2 weeks ago, where MRI, CT, and x-ray showed T11-L1 bone destruction. She was diagnosed with thoracic spine tuberculosis and the details of the diagnosis were not mentioned. Then she was treated with isoniazid, rifampin, and ethambutol. The laboratory examination revealed white blood cell count (WBC) 2.10x 109 /L, erythrocyte sedimentation rate (ESR) 38 mm/h, C-reactive protein (CRP) 10.7 mg/L, interleukin-6 (IL-6) 0.35 pg/ml, and D-dimer 1.88 mg/L FEU. The patient tested positive for tuberculosis infection, as assessed by a T cell spot test. Chest CT showed scattered grain-like nodules in both lungs, suggesting pulmonary tuberculosis. CT of thoracic and lumbar spine revealed bone destruction of T11-L1, which was obvious in T12, mild reduction in the height of the vertebral body and narrowing of T11-12 intervertebral space, with a cold paravertebral abscess on both sides (Figure 1). These results were consistent with spinal tuberculosis. Consequently, the initial diagnosis was spinal tuberculosis with a cold abscess (T11-L1). Further, an ultrasound revealed an abnormal echo in the left paracolonic groove, which was associated with a cold abscess. Consequently, the patient was subjected to ultrasound-guided percutaneous catheter drainage on 15th October 2021 and 600 ml of pus was drained. After 16 days of drainage, the patient complained of severe chest and back pain. An electrocardiogram (ECG) was performed and it showed no any abnormal finding. The laboratory examination revealed WBC 3.40 x 109 /L, ESR 47 mm/h, CRP 17.4 mg/L, IL-6 37.5 pg/ml, PCT 0.07 ng/ml, and D-dimer 1.89 mg/L FEU. Re-examination of the thoracic and lumbar spine using enhanced MRI revealed bone destruction in T11-L1 and a massive mixed density shadow was observed in the front, wherein blood flow showed low signal on T1WI and T2WI, primarily owing to flow void effect. Obvious enhancement was observed after the lesion was enhanced (Figure 2), which was indicative of a thoracic aortic pseudoaneurysm. Consequently, it was recommended that endovascular aneurysm repair must be performed immediately, however, only bone graft fusion and internal fixation were performed, owing to the patient's personal reasons, and vertebral biopsy revealed a negative result in the acid-fast staining and the culture was positive for M. tuberculosis. Further, the patient developed pain and numbness in the left thigh after 10 days of the procedure. The laboratory examination revealed WBC 4.80 x 109 /L, ESR 26 mm/h, CRP 14.4 mg/L, IL-6 9.49 pg/ml, and D-dimer 10.42 mg/L FEU.A CT scan revealed enlargement of pseudoaneurysm (Figure 3). Following this, the patient underwent endovascular aneurysm repair. Digital subtraction angiography was performed with the patient under general anesthesia, which revealed an approximate 10 mm breach on the lower portion of the descending aorta, and the orifice of the pseudoaneurysm to be 20 mm away from the lower part of the celiac trunk. The stent graft (Medtronic Inc., 25 mm in diameter and 70 mm in length) was positioned well and correctly and repeated angiography confirmed a complete closure of the mass, a smooth blood flow in the aorta, and a firmly fixed stent on the aortic wall without distortion and displacement; no peripheral leakage of the contrast agent was observed. The surgery was successful and the patient continued to receive isoniazid (0.3 g/day), rifampin (0.45 g/day), and ethambutol (0.75 g/day) during the follow-up. The patient's symptoms gradually disappeared, and she was discharged. After 3 months' follow-up, repeated CT showed a firmly fixed stent on the aortic wall without distortion and displacement and a smooth blood flow in the aorta, and the pseudoaneurysm was basically absorbed without recurrence. Because the follow-up was outpatient, no laboratory examinations were done (Figure 4).

case report, endovascular repair, endovascular stent-graft, spinal tuberculosis, thoracic aortic pseudoaneurysm

PMC6150561_01

Male

A 12-year-old male child was referred to our hospital with a 6-year history of repeated attacks of chest infection. He received several courses of antibiotics and was also investigated for pulmonary tuberculosis because of persistent lung infiltrates on his chest x-ray. All investigations for tuberculosis were negative, but despite this he was treated empirically with antituberculous drugs for 6 months without improvement. At our hospital, he had a CT scan of the chest, which showed multiple cysts of variable sizes affecting the right upper lobe of the lung (Figure 1) as well as a cystic swelling in the posterior mediastinum. He underwent a diagnostic right thoracotomy. The right upper lobe was found to be firm in consistency and contained adhesions to the inner chest wall. These adhesions were released and there were multiple cysts in the right upper lobe of variable sizes (Figure 2). There was no consent for a lobectomy, so it was decided to take a large biopsy, including one of these cysts. Exploration of the posterior mediastinum revealed a cyst of about 3X2 centimeter in size overlaying the esophagus. The cyst was dissected using both sharp and blunt dissection. It was found to be adherent to the esophageal wall. The cyst was separated from the esophageal wall and excised totally. Postoperatively, the patient did well and was discharged home on the tenth postoperative day. Histopathology of the lung biopsy showed large areas of fibrosis with cystic formations of varying sizes filled with mucus and macrophages, lined by cuboidal or columnar epithelium and rarely metaplastic squamous epithelium. There was chronic inflammatory cell infiltrate in some areas with formation of lymphoid follicles, but no epithelioid or giant cell granulomas. The esophageal cyst showed a wall composed of smooth muscles with the presence of ganglion cells and lined by ciliated columnar epithelium, but no cartilage. These features are consistent with CCAM in association with an EDC. The patient was followed up in the outpatient clinic and the condition was explained to the father who agreed to a lobectomy. The patient subsequently underwent right upper lobectomy.

CT-scan of the chest showing multiple cysts of variable sizes in the right upper lobe.

PMC4531542_01

Female

A 44-year-old woman was admitted to the hospital because of nausea, vomiting and paraplegia of both lower extremities. She was diagnosed as HIV positive in June, 2000, when she presented with retinal necrosis caused by the varicella zoster virus. Subsequently, she was started on zidovudine, lamivudine, and indinavir at a baseline CD4 positive T lymphocyte count of 16/muL, a CD8 positive T lymphocyte count of 86/muL and a HIV-RNA of 1,129,768 copies/mL. Subsequently, medication was changed to lamivudine, stavudine, lopinavir/ritonavir in April, 2002 due to leukopenia caused by the zidovudine. She remained on this medication for 8 months, prior to December 2002, when she stopped the medication 10 days before admission due to the symptoms mentioned above. In January 2000, the patient was diagnosed with chronic viral hepatitis B. She had no history of hypertension, tuberculosis or DM, and no medication other than antiretroviral drugs had been taken. On admission, the patient complained of general weakness, nausea, vomiting and paralysis of both lower extremities. However, she did not present fever, chills, abdominal pain, constipation or diarrhea. The patient's blood pressure was 110/80 mmHg, pulse rate 80/min, respiration rate 25/min, temperature 36 C. She had a chronically ill-looking appearance and an alert mental status. Conjunctivae were not pale, sclerae were not icteric and cervical lymph nodes were not palpable. On chest auscultation, breathing sounds were clear in both lungs; her heartbeat was regular without murmur. The Abdomen was soft and flat without tenderness, and bowel sounds were normoactive. The liver and spleen were not palpable and no palpable abdominal mass was found by physical examination. Muscle strength of both legs had decreased to GII, and there were no deep tendon reflexes (DTRs). Neither CVA tenderness nor pitting edema of the extremities was apparent. A laboratory examination showed a WBC of 6,920/mm2 (neutrophils 58.8%, lymphocytes 29.1%, monocytes 6.9%, eosinophils 1.3%), a Hb of 14.7 mg/dL, a hematocrit of 42.3%, and a platelet count of 159,000/mm3. Blood chemistry revealed; calcium 9.5 mg/dL, inorganic P 0.4 mg/dL, uric acid 14 mg/dL, ALP 71 IU/L, amylase 48 IU/L, lipase 111 IU/L, BUN 6.8 mg/dL, Creatinine 0.8 mg/dL, total protein 7.0 g/dL, albumin 4.7 g/dL, AST/ALT 71/60 IU/L, total bilirubin 2.7 mg/dL, direct bilirubin 1.7 mg/dL, Na/K/Cl/tCO2 135/3.1/95/8 mEq/L, total cholesterol 252 mg/dL, TG 305 mg/dL, HDL-cholesterol 16 mg/dL, LDL cholesterol 157 mg/dL, lactate 10.8 mmol/L (normal 0.5-1.6 mmol/L), and creatinine kinase 3 IU/L. Immunochemistry showed positive HBeAg, HBV DNA 1,321 pg/mL, AFP 10.61 IU/mL (normal 0-7 IU/mL), and CEA 0.566 ng/mL (normal 0-5 ng/mL). The CD4 positive T lymphocyte count was 117/muL, the CD8 positive lymphocyte count 687/muL, and a HIV-RNA level of 133,000 copies/mL. Her pregnancy test was negative, as were blood, urine and stool culture. A cerebrospinal fluid examination performed to rule out a central nervous system infection showed no significant findings, and neither did brain MRI (Figure 1). A contrast CT scan of the abdomen, performed to rule out intra-abdominal malignancy, showed only a hepatic cyst (Figure 2). Arterial blood gas analysis (ABGA) revealed a pH of 7.291, pCO2 12.6 mmHg, pO2 142.1 mmHg, SaO2 99%, and BE-ECF 20.6. Accordingly, a diagnosis of lactic acidosis was made. Intravenous sodium bicarbonate infusion and conservative treatment were immediately initiated and antiretroviral drugs were stopped. The symptoms of nausea and vomiting subsided on the third day of treatment and from the tenth day, her paraplegia of both legs also started to improve. ABGA results and lactate levels gradually normalized (Table 1) and on the 11th day, ABGA showed pH 7.474, pCO2 39.9 mmHg, pO2 79 mmHg, SaO2 96.3%, BE-ECF +5.8, and lactate 2.9 mmol/L. The patient was discharged on the 14th day without any signs of lactic acidosis. At the time of discharge, total bilirubin had decreased to 1.3 mg/dL. After discharge, antiretroviral medications were resumed in the order:- of lamivudine, efavirenz, and lopinavir/ritonavir; none of the previous symptoms recurred. Two months after discharge, her serum lactate level was 4.8 mmol/L. The patient is still on antiretroviral therapy and is being followed up on an outpatient basis.

PMC7430075_01

Male

A 39-year-old man presented with worsening shortness of breath. The patient had a past medical history significant for follicular lymphoma (diagnosed 3 years ago) for which he had completed chemotherapy. He had a relapse of follicular lymphoma, which continued to progress despite chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP); eventually received an allogenic stem-cell transplant 1 year ago. The posttransplant course was complicated by graft-versus-host disease of the gastrointestinal tract and skin, cytomegalovirus viremia, BK virus-associated hemorrhagic cystitis, varicella-zoster dermatitis, polymicrobial blood stream infections, and hypogammaglobinemia. He was being treated with oral budesonide, ruxolitinib, and tacrolimus for graft-versus-host disease. The patient was a former smoker with 5 pack-year smoking history with no other primary lung diseases such as chronic obstructive pulmonary disease, bronchiectasis, emphysema, or pulmonary fibrosis. His pulmonary function test showed a normal spirometry and lung volumes with mildly reduced DLCO (carbon monoxide diffusing capacity). One month prior to this presentation, computed tomography (CT) scan of his chest showed multifocal pulmonary nodules suggesting invasive fungal infection. The patient was started on AmBisome and isuvaconazole and scheduled for bronchoscopy with TBB. Multiple TBB were performed in the lateral-basal segment of the right lower lobe of the lung. The procedure was performed without any complications, but no infectious etiology was identified, and the patient was discharged. When he presented again to the hospital with worsening shortness of breath, a repeat chest CT was ordered, which in comparison with the CT scan 1 month ago, showed variably changed pulmonary opacities, with new/increased areas of more focal consolidation the right upper lobe (Figure 1A) and left lower lobe (Figure 1B), and with decreased nodular and ground glass opacities elsewhere in the lungs. We repeated the bronchoscopy with TBB:obtaining a total of 7 biopsies from the lateral-basal segment of the left lower lobe of the lung. Chest X-ray (CXR) obtained 35 minutes after the procedure was negative for pneumothorax (Figure 2). Twenty-two hours postprocedure, the patient complained of acute onset of left-sided pleuritic chest pain. CXR revealed a small apical pneumothorax that remained unchanged on serial CXR evaluations and the patient was discharged home. A follow-up CXR performed the following day on an outpatient basis revealed a worsening pneumothorax (Figure 3) and the patient was re-admitted for further management. A 12-French pigtail chest tube was placed under ultrasound guidance that led to the resolution of pneumothorax. The patient was discharged home after a hospital stay of 4 days.

delayed complication, iatrogenic, pneumothorax, transbronchial biopsy

PMC2822252_01

Male

A 32-yr-old Korean male patient was admitted to Inha University Hospital, Incheon, Korea due to dyspnea and right chest pain for 1 day. On physical examination, the breath sound in the right lung fields was decreased without shifting of the maximal point of the cardiac impulse. He had a history of the right pneumothorax one and a half years ago, which was treated with tube thoracostomy. He had no history of pulmonary or bronchial tuberculosis before this admission. He was a smoker. The posteroanterior chest radiograph revealed increased radiolucency along with overinflated lung parenchyma and sparse vasculature in the upper half of the right lung. Also note v-shaped branching opacity was in the right parahilar area. Pneumothorax was associated in the right lower pleural cavity (Fig. 1). A 32 Fr chest tube was inserted into the right pleural cavity. The chest CT taken in the state of full expansion of the right lung after tube thoracostomy showed a branching soft tissue density in the region of the posterior segment of the right upper lobe. The orifice of the posterior segmental bronchus was visualized but the orifice of the subsegmental branch of the posterior segmental bronchus could not be visualized separate from the origin (Fig. 2). There were no endobronchial lesions in the bronchial tree on the bronchoscope and each orifice of the segmental bronchi of the right lung was seen normal. His forced expiratory volume at 1-sec (FEV1) was 3.49 L (91%) and forced vital capacity (FVC) was 4.57 L (100%). Perfusion lung scan showed a perfusion defect in the right upper lobe. Exploratory thoracotomy was done via muscle sparing vertical thoracotomy skin incision. There was a localized emphysematous change in the posterior segmental area of the right upper lobe with the apical pleural adhesion and the remaining lungs were normal. Right upper lobectomy was successfully undertaken. The pathological findings of the resected right upper lobe showed overinflation of the posterior segment. There were no obstructed lesions of the orifices of the three segmental bronchi of the right upper lobe. However, one of the subsegmental branch of the posterior segmental bronchus was obstructed and there was a 2.5x1.5x1.5 cm sized cystic mass containing brownish mucus material at the distal portion of the obstructed subsegmental bronchus. The cystic mass was not connected with other bronchial trees. Microscopically the distal air spaces of the atretic segmental bronchus showed overinflation only. However the foci of the subpleural bullae in the overinflated segment were observed (Fig. 3). His postoperative course was uneventful. He was discharged on the post-operative 7th day. He has been well 1.6 yr after the operation.

Chest CT scan shows a branching soft tissue density in the region of the posterior segment of the right upper lobe with marked decrease in attenuation and vascularity. The subsegmental branch of the posterior segmental bronchus could not be traced distal to this (arrow) posterior segmental bronchus.

PMC7424389_01

Female

A 65-year-old female presented to our clinic with a 2-year history of worsening bilateral pulsatile tinnitus. She described "humming" in both ears, in time with her heartbeat, which had become very difficult to ignore, to the point of being debilitating. She had no history of hearing loss. She denied autophony, hearing her eyeballs move, dizziness on straining, or any other symptoms pointing to a diagnosis of SSCD syndrome. Her past medical history was significant for hypothyroidism, overactive bladder, hypertension, chronic back pain, and a remote history of thrombocytopenia. She also reported being diagnosed with multiple vascular lesions in the head and neck, and some of these had been surgically removed during childhood, including one superficial and posterior to the right ear. Her medications included levothyroxine, gabapentin, hydromorphone, oxybutynin, and omeprazole. A complete blood cell count was ordered, showing no anemia or thrombocytopenia. Audiometry showed no hearing loss. Neurological and head-and-neck examination were normal. Her tympanic membranes appeared normal bilaterally. Pressurization of the neck bilaterally did not alleviate the intensity of the tinnitus. Her symptoms were ameliorated with rotation of the neck to the left. No murmurs or bruits were heard on auscultation. The patient underwent contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scans (Figure 1) as part of the workup for her symptoms. The CT scan showed multiple, bilateral, enlarged, venous malformations in the neck and posterior to the ears (Figures 1(a) and 1(c)). The T2-weighted MRI (Figures 1(b) and 1(d)) scan showed similar findings. Notably, some of these dilated venous channels contained phleboliths, often seen in low-flow venous malformations. No intracranial or auricular malformations were seen. Magnetic resonance angiography (MRA) was also performed (not shown), revealing 2 small (<5 mm) incidental aneurysms in the paraophthalmic internal carotid artery, which were thought to not be causing any symptoms.

PMC9527840_01

Female

A 19-year-old female presented to the outpatient department with the presence of a single, progressively growing, firm, diffuse swelling over the right preauricular region. There has been progressive trismus for eight months which developed insidiously over the past four months. The patient had been on self-prescribed systemic antibiotics for a week with no clinical improvement. The swelling measured 6 cm x 5 cm in the greatest dimension extending anteroposteriorly from the tragal pointer to a line perpendicular to the lateral canthus of the eye and superoinferiorly from the root of the helix to the inferior border of the mandible [Figure 1a and b] with no cutaneous sinuses. The throbbing and intermittent pain got aggravated on mastication. The swelling had raised temperature and tenderness on palpation. The cervical lymph nodes were not palpable clinically. Detailed medical history and systemic and intraoral examination were unremarkable. The provisional diagnosis of acute exacerbation of chronic arthritis was made. Orthopantomogram revealed an osteolytic lesion of the right mandibular condyle with loss of corticomedullary architecture, multiple cloaca, and sequestrum. T2W1 magnetic resonance imaging of the head demonstrated a hyperintense area over the right masseteric region extending up to the lateral pterygoid muscle with osteolytic configurational changes of the right mandibular condyle [Figure 2a]. Computed tomogram (CT) of the head revealed an osteolytic lesion in the right condyle measuring 6 cm x 4 cm x 2.3 cm, suggestive of suppurative osteomyelitis [Figure 2b and c]. Raised leukocyte, erythrocyte sedimentation rate, and C-reactive protein count were suggestive of underlying chronic infection. Based on the above findings, a diagnosis of septic arthritis, TBO condyle, and juvenile idiopathic arthritis was made. Mantoux test showed a negative reaction. Chest radiograph [Figure 3] and high-resolution computed tomography of the thorax were unremarkable. Three sputum specimens and fine-needle aspiration cytology (FNAC) of the swelling were found to be smear and culture negative. Considering the aetiology to be infectious, the patient was subjected to surgical exploration requiring decortication of bone (sequestrectomy) resulting in medullary destruction and cortical perforation followed by placement of corrugated rubber drain [Figure 4a-e]. Histopathology report of the resected specimen revealed extensive inflammatory infiltrate, focal areas of bone necrosis, caseation granuloma, and lymphocytic infiltration with Langerhans' giant cell. This made us to suspect the presence of tuberculous granuloma which is a consistent finding in a diagnosis of TBO [Figure 4f]. A polymerase chain reaction (PCR) of the curetted material showed positivity for TB bacilli. The patient was prescribed intravenous antibiotics (amoxicillin with clavulanic acid and metronidazole) for 1 week along with a multidrug antitubercular regimen comprising isoniazid (600 mg), rifampicin (450 mg), pyrazinamide (1500 mg), and ethambutol (1200 mg) for 6 months. The patient was advised of monthly follow-up [Figure 5a and b]. The outcome was satisfactory showing regeneration of bone at nine months, the surgical site healed completely, and CT (head) demonstrated a healthy remnant bone structure [Figure 6a-c].

condylectomy, extrapulmonary tuberculosis, mandibular condyle, preauricular region, tubercular osteomyelitis

PMC9393733_01

Female

Our patient is a 59-year-old woman with a history of hypertension and hyperglycemia for more than 15 years without previous history of alcohol consumption or smoking nor history of liver disease. She presented with intermittent fever without obvious inducement for 3 weeks (specific time points in Figure 1) with the highest temperature of 39 , accompanied by jaundice, occasional nausea, vomiting, and slight discomfort in the right upper abdomen. Biochemical examination revealed glutamic-pyruvate transaminase (ALT) levels of 198 U/L, glutamic-oxaloacetic transaminase (AST) 131 U/L, total bilirubin (TBil) 68 mumol/L, and direct bilirubin (DBil) 35.1 mumol/L. Blood routine examination revealed no obvious abnormalities. CT of the chest and abdomen showed no obvious active lesions in both lungs but gallbladder enlargement and dilatation of intrahepatic and extrahepatic bile ducts, common bile duct, and main pancreatic duct. MRI of the abdomen showed low biliary obstruction, and the obstruction level was located on the ampulla. Considering the possibility of inflammatory lesions, local hospitals gave anti-infection, fluid rehydration, liver protection, and other symptomatic treatment, but no obvious relief of symptoms. Abdominal color ultrasound was performed at the general surgery department of our hospital on 19 October 2020. It showed that there is a mass in the ampullary region with dilation of intrahepatic and extrahepatic bile ducts and main pancreatic duct. Moreover, enlargement of the gallbladder was also shown. No obvious abnormality was observed in the liver. CT of pancreatic vascular reconstruction showed a mass in the ampulla, surrounded by enlarged lymph nodes, and was considered malignant. The intrahepatic and extrahepatic bile ducts and pancreatic ducts were dilated, the gallbladder was enlarged, and no obvious abnormalities of the liver and retroperitoneal lymph nodes were observed (Figures 2A, D). Tumor marker AFP was 5.00 ng/ml (normal range 0-10 ng/ml) (Table 1). The pathological result of EUS-FNA was moderately to poorly differentiated ampullary adenocarcinoma (Figure 3A); the immunohistochemistry (IHC) of EUS-FNA was AFP (+) (Figure 3B). After the patient was admitted to the hospital, the patient was evaluated with an Eastern Cooperative Oncology Group (ECOG) score result of 1. Physical examination revealed yellow skin and yellow sclera. The patient and family had no previous medical history of chronic viral hepatitis, bowel polyps, and inflammatory bowel disease (IBD). The patient underwent pancreaticoduodenectomy on 30 October 2020. Intraoperative exploration showed that there were no free ascites or metastatic nodules in the abdominal cavity, the liver had a normal size with cholestasis-like changes, and the gallbladder was swollen. A mass with a size of about 3 cm * 3 cm could be reached in the ampulla, and the texture was hard. Postoperative pathology (pancreaticoduodenectomy specimen) (Figure 3C) showed that the duodenal papilla had a poorly differentiated adenocarcinoma, the size of the mass was 4 cm * 2.5 cm * 1.2 cm, and the cancer tissue penetrated the duodenal muscle wall and invaded the pancreatic tissue. There is no definite cancer tissue invasion in the common bile duct. Vascular cancer embolus and perineural invasion can be seen. No cancer remains at the gastric margin, small intestinal margin, common bile duct margin, broken end margin of the pancreas, peripheral margin of the pancreas, and hook process margin of the pancreas. Cancer metastasis was found in 1/6 lymph nodes around the pancreas, and no cancer metastasis was found in 3 lymph nodes around the stomach, 1 lymph node around the intestine, and 2 lymph nodes around the common bile duct. Another 3 lymph nodes were sent, and no cancer metastasis was found. Pathological stage was IIIA (T4, N1, cM0); IHC: cancer cell expression CK(+), S100(-), Her2(Sto)(++), COX2(+), VEGFR2(-), EGFR(++), Ki67(about 60%+), P16(focal +), CD56(-), PD-1(-), PD-L1(SP142)(the tumor cells -, interstitial immune cells about 5%+), MLH1(+), MSH2(+), MSH6(+), PMS2(+), c-Met(+), CgA(-); AFP (+) (Figure 3D). One month after surgery, CT and MRI scan showed multiple hepatic masses (Figures 2B, C) and retroperitoneal enlarged lymph nodes (Figures 2E, F), which were considered metastases. The patient refused to accept gene testing and targeted therapy, so one cycle of XELOX 3-week regimen chemotherapy was performed according to National Comprehensive Cancer Network (NCCN) guidelines for CRC. After one cycle of chemotherapy, tumor marker AFP rose from 300 to 1,931.90 ng/ml (Table 1). In order to clarify the nature of the liver lesions, liver biopsy was performed. Microscopic observation showed that the tumor cells were distributed in plate shape, and abundant blood sinus structures were seen, adenocarcinoma area and hepatoid differentiation area coexist, polygonal tumor cells with larger volume and eosinophilic cytoplasm can be seen in the hepatoid differentiation area (Figure 4A). Liver biopsy pathology showed adenocarcinoma, poorly differentiated; IHC showed cancer cell expression Hept1 (-), CK19 (+++), CK7 (-), CDX-2 (focal +), Ki67 (70%+), CK20 (-), Villin (+++), Syn (focal +), CgA (focal +), CD56 (focal +); AFP (+), GPC-3 (+) (Figures 4B, C). Combining the abnormal increase of serum AFP, microscopic pathological morphology and IHC features of tissue samples from presurgical EUS-FNS, surgery, and liver biopsy, this is a rare case of HAC of the duodenum with liver metastasis. However, the disease progressed rapidly, and the patient died within 1 month after biopsy. The survival time was only 161 days. Patients and their families hope that the information they provide can help clinicians have a deeper understanding of this kind of diseases, thus helping more patients.

alpha- fetoprotein (afp), hepatic metastases, hepatoid adenocarcinoma, hepatoid adenocarcinoma of the duodenum, immunohistochemical

PMC9043811_02

Female

Neurodevelopment was normal. She graduated from college and worked as a teacher before retirement at 60-years-old. There was no history of psychiatric symptoms or family history of psychiatric disorders or dementia. A graphical timeline with the most relevant symptoms is shown in Figure 1. Her present illness started with panic attacks at age 78, consisting of abrupt surges of intense emotional discomfort accompanied by abdominal distress (i.e., heartburn), shortness of breathing, chest discomfort (i.e., chest tightness), feelings of choking, and fear of dying or being seriously ill. The episodes, lasting around 1 h, were recurrent (3-4 per day) and were triggered by situations, such as waiting in line or seeing traffic. Flupentixol-Melitracen (21 mg/day) was prescribed but caused nervousness and hand trembling. The frequency of symptoms decreased with Sertraline (50 mg/day) and Mirtazapine (15 mg/day). At the end of that year, she developed parkinsonism (bradykinesia, hands tremble, hypophonia, and hypomimia), reported fluctuations in arousal (described as lethargic episodes), two episodes of syncope, marked constipation, and subjective decline in language and memory. At the age of 80, cognitive decline and parkinsonism became prominent. Structural magnetic resonance image (MRI) showed diffuse brain atrophy with no vascular injury, leading to a misdiagnosis of possible Alzheimer's Disease treated with Donepezil. She ceased this medication because of heartburn and physical discomfort, to which rivastigmine transdermal patches were prescribed. After a few months, she was re-admitted due to increased parkinsonism and was again misdiagnosed, but with Parkinson's Disease. Levodopa + Benserazide was prescribed, causing significant improvement of tremor and hypomimia for less than one year. During the 2 years before index admission, bradykinesia, hypophonia, and cognitive decline (in language and memory) gradually worsened. Panic attacks continued at a lower frequency (1 episode per day, 1 h each), and postprandial hypotension episodes (systolic blood pressure drop of 40 mmHg after eating) were also evidenced.

case report, dementia with lewy bodies, neuropsychiatric symptoms, panic attacks, prodromal dementia with lewy bodies

PMC9448882_01

Female

A 69-year-old woman consulted a hospital with a chief complaint of 7 days of fever, 4 days of blurry vision, and 4 h of glossolalia. She had a history of untreated diabetes mellitus and tuberculosis, which was cured 50 years ago. She had no other medical history and was not an alcohol drinker or a smoker. On admission, her initial vital signs included a body temperature of 38.2 C, a heart rate of 118 beats/min, a blood pressure of 128/60 mmHg, a respiratory rate of 20 breaths/min, and oxygen saturation of 98%. She was experiencing clouding of consciousness and was not able to cooperate with physical examination. After opening her eyelid, a mild conjunctival and corneal edema was found. Massive fibrinous exudation showed at the margin of the pupil with no pupillary light reflex in the right eye. There was percussion pain in the hepatic region and tenderness in the right upper quadrant of the abdomen. There was no hepatosplenomegaly. Meningeal irritation signs were suspected to be positive. Laboratory test results revealed a white blood cell count of 17.5 x 109/L, with a neutrophil predominance of 89.8%, and a platelet count of 128 x 109/L. The concentration of C-reactive protein (CRP) was 204.87 mg/L, and the procalcitonin (PCT) level was 14.82 ng/L. Arterial blood gas results were as follows (on 6 L/min oxygen via nasal cannula): a pH of 7.40, PaCO2 of 15 mmHg, PaO2 of 96 mmHg, HCO3 of 9.4 mmol/L, and lactic acid of 1.9 mmol/L. The coagulation profile showed an international normalized ratio of 1.47, an activated partial thromboplastin time of 38.9 s, and a prothrombin time of 14.9 s. Liver function test results were as follows: aspartate aminotransferase of 33.8 U/L; alanine aminotransferase of 33 U/L; lactate dehydrogenase of 303.86 IU/L; total bilirubin of 10.55 micromol/L; and direct bilirubin of 6.04 micromol/L. The fasting blood sugar level was 14.5 mmol/L, and HbA1C was 13.3%. A urine full report showed proteinuria (++) with 1.3 pus cells per high power field. Creatinine was 87 micromol/L, and urea was 8 mmol/L. Peripheral blood cultures were collected twice. Further imaging examinations were performed. An ultrasound scan (US) revealed a mixed echogenic mass containing solid and cystic components in the right lobe of her liver, measuring 5.0 x 3.9 cm in size. An abdominal CT scan showed a single low-density focus in the right lobe of the liver (45 mm x 38 mm), which demonstrated a possible liver abscess (Figure 1). No other intra-abdominal pathologies such as gallstones were observed on these imaging examinations. In order to detect intraocular diseases, an ocular ultrasound was performed. It revealed lens clouding in both eyes and vitreous clouding in both eyes (excluding blood or pus accumulation in the vitreous of the right eye), excluding partial retinal detachment in the right eye. Because of her 4-h delirium before admission, meningitis was considered. A head CT scan and a lumbar puncture were necessary. However, there were no remarkable findings according to the head CT result. Puncture examination showed that the intracranial pressure was 150 mm H2O. The cerebrospinal fluid (CSF) appeared yellow and purulent (Figure 2), revealing a 580,000 x 106/microL white blood cell count with a multinucleated cells percentage of 98%, protein above 15 g/L, and glucose less than 1.1 mmol/L. The CSF was also submitted for Gram staining and bacterial culture. The patient was preliminarily diagnosed with a primary liver abscess, endogenous endophthalmitis, and meningitis. Ultrasound-guided percutaneous catheter drainage (PCD) of the liver abscess was immediately performed, with a continuous drainage of 110-ml yellow pus. Specimens were retained for culture. Meropenem was given intravenously as an empirical treatment. The patient was given 0.1 ml of vancomycin (10 g/L) and 0.1 ml of ceftazidime (20 g/L) were by intravitreal injection. On the third day after admission, the oxygenation index reduced to 180, and the self-cleaning ability of the airway was poor. A tracheotomy was performed, and mechanical ventilation was started at once. Both blood and drainage fluid cultures grew K. pneumoniae with a high mucosal phenotype, which was sensitive to all the tested antibiotics. A string test showed a positive result (string >=5 mm). The cerebrospinal fluid culture showed gram-negative bacteria. With the completion of the assays, the ocular disease was diagnosed as endophthalmitis complicated by a liver abscess caused by hypervirulent K. pneumoniae. Ceftazidime was used alone for intravitreal injection. In conclusion, the patient had a liver abscess as the primary focus of infection with migratory infection of the eye and meninges. The pathogen was considered to be hypervirulent K. pneumoniae (hvKP) according to the results of the drug sensitivity test, clinical manifestations, and the string test (+). The patient was finally diagnosed with a K. pneumoniae liver abscess, purulent meningitis, and endogenous K. pneumoniae endophthalmitis in the right eye. Meropenem was continued to control the bloodstream infection. After 15 days of treatment, her body temperature became normal, and the rechecked blood routine, CRP, and PCT had normalized. A lumbar puncture and an abdominal CT were performed as part of reexamination. The CSF appeared transparent (Figure 2), revealing a 34 x 106/microl white blood cell count with a multinucleated cells percentage of 5%, protein of 3 g/L, and glucose of 6.1 mmol/L. CT showed a low-density shadow (15 mm x 21 mm) that was much smaller than the earlier one in the right lobe of her liver. She was successfully weaned from the ventilator with an oxygenation index of beyond 300 and was catheterized with oxygen at the tracheotomy site. She opened her eyes spontaneously but was not able to cooperate with the physical examination. Therefore, the eyesight of her right eye could not be evaluated. She had stable vital signs with a heart rate of 94 beats/min, blood pressure of 132/75 mmHg, and oxygen saturation of 100%. The anti-infective therapy was changed from meropenem to ceftazidime and lasted for 2 weeks. The patient was discharged with an improved condition and was followed up for long-term outcomes. However, during follow-up, she developed complications due to severe pneumonia and eventually died in a local hospital.

klebsiella pneumoniae liver abscess, diabetes mellitus, endophthalmitis, hypervirulent klebsiella pneumoniae, meningitis

PMC9426857_01

Male

An 11-year-old male castrated 5.7-kg domestic shorthair cat presented to the internal medicine service after experiencing two seizures (believed to be tonic-clonic). The medical record information prior to this presentation is limited. The patient was feline immunodeficiency virus (FIV) positive and had been seen at the referring veterinarian 3 months prior with a presenting complaint of fever and ataxia. Pulmonary nodules were identified on thoracic radiographs at that time. A diagnosis of systemic blastomycosis was made based on fine-needle aspiration (FNA) of an enlarged popliteal lymph node. A Blastomyces urine antigen enzyme immunoassay (Blastomyces quantitative antigen EIA; MiraVista Diagnostics; range of quantification 0.2-14.7 ng/ml) was performed and was highly positive (above the limit of quantification). The clinical signs and lung nodules had improved with treatment (itraconazole and amphotericin B; dose regimen unknown). The reported tonic-clonic seizures occurred after the most recent antifungal treatment had been administered. At presentation, no abnormalities were noted on physical and neurologic examination. On MRI of the brain, three separate intra-axial lesions were identified (Figure 1). A round 0.8-cm diameter nodule was associated with the ventral aspect of the left temporal lobe. This lesion was iso-to-slightly hypointense to gray matter, with a hyperintense rim on T2-weighted and T2-FLAIR images, was slightly hypointense on T1-weighted images, did not show evidence of susceptibility artifact on T2*-weighted images, and was strongly homogeneously contrast enhancing. There was moderate indistinct perilesional T2 hyperintensity, consistent with perilesional edema. A second well-circumscribed 0.4-cm diameter T2 hypointense and T1 isointense lesion was associated with the right cerebellar hemisphere and exhibited moderate ring enhancement following contrast medium administration. A third 0.2-cm diameter ring-enhancing lesion was noted in the cerebellar vermis, not seen on precontrast images. There was no evidence of perilesional edema associated with the cerebellar lesions. There was no evidence of meningeal enhancement or any abnormalities of the ventricular system, skull, nasal cavity, paranasal sinuses, tympanic bullae, orbits, ocular structures, and soft tissues of the head and cranial neck including regional lymph nodes. A cisternal cerebrospinal fluid (CSF) tap was obtained and yielded a diagnosis of probably iatrogenic hemorrhage without other cytologic abnormalities. A Blastomyces urine antigen EIA was moderately positive (3.04 ng/ml). Corticosteroid treatment was initiated (prednisolone 5-mg/head PO q 24 h x 3 days, 2.5-mg/head PO q 24 h x 3 days, and 1.25-mg/head PO q 24 h x 3 days) for treatment of perilesional edema and to help manage the inflammatory effects caused by fungal die-off. The patient was also started on phenobarbital (2.5-mg/kg PO BID of 20-mg/ml suspension), levetiracetam (20-mg/kg PO of 100-mg/ml suspension q 8 h), and fluconazole (50-mg/head PO q 12 h). Amphotericin B was discontinued. Phenobarbital was discontinued the following day due to the patient being very lethargic. The cat showed improvement over the next months and was considered clinically normal aside from an occasional cough and unrelated chronic gingivitis 2 months after the MRI examination (5 months after initial diagnosis). The previously seen pulmonary abnormalities had resolved. There was no recurrence of seizures, and no other neurologic abnormalities were reported. A Blastomyces urine antigen EIA was greatly improved but still mildly positive (0.73 ng/ml). The patient remained neurologically normal. Levetiracetam was gradually tapered from 5 to 8 months after the initial diagnosis without recurrence of seizure activity. A Blastomyces urine antigen EIA was still mildly positive after 7 and 9 months. Fluconazole was discontinued 15 months after the initial diagnosis (12 months after the first MRI examination) based on 2 consecutive negative Blastomyces urine antigen EIA tests. The cat represented 3 years later (4 years and 7 months after initial diagnosis) to the emergency service for a 24-h history of circling to the right and behavior changes. On neurologic examination, the patient was circling to the right and had a bilaterally absent menace response. Possible hyperesthesia of the head was also noted. Neurolocalization was to the right forebrain. Thoracic radiographs did not reveal any significant abnormalities. Magnetic resonance imaging was repeated. There was a new finding of an 1.2 x 1.4 cm ovoid mass in the right temporal lobe (Figure 2) which was predominantly T2 and T1 isointense to gray matter with a small centrally located T2 hyperintense and T1 hypointense focus which did not suppress on T2-FLAIR. The lesion was hypointense on both DWI and ADC maps. There was marked perilesional T2 and FLAIR hyperintensity following the white matter tracts of the right cerebral hemisphere with a moderate to marked mass effect characterized by compression of the right lateral ventricle, leftward midline shift, and caudal transtentorial and foramen magnum herniations. Following contrast medium administration, the mass displayed marked heterogeneous contrast enhancement. Mild focal pachymeningeal contrast enhancement was identified adjacent to the lesion. An 0.2-cm diameter well-defined T1, T2, and T2-FLAIR hypointense ovoid nodule was observed in the region of the previously seen cerebellar hemispheric lesion and was decreased in size. This lesion was associated with a susceptibility artifact on T2*-weighted images and had mild rim contrast enhancement. The lesion within the cerebellar vermis was no longer visible. An incidental small amount of fluid was noted within the bilateral tympanic bulla. The remaining structures of the head and cranial neck remained normal. The patient received a tapering dosing regimen of prednisolone (5-mg/head PO q 24 h x 3 days, 2.5-mg/head PO q 24 h x 3 days, and 1.25-mg/head PO q 24 h x 3 days). Fluconazole treatment was resumed empirically (50-mg/head PO q 12 h) while awaiting urine antigen testing results. A repeat Blastomyces urine EIA test was positive (4.24 ng/ml), and fluconazole treatment was continued. The patient improved, and the client reported the cat as being back to normal 5 weeks after the second MRI examination. On neurologic examination at that time, menace response was noted in both eyes. The pupillary light responses were decreased. Additional findings during this visit included weight loss, hypoalbuminemia, anemia, a soft heart murmur, and an irregular heartbeat. The patient represented for a work-up of these new problems to the internal medicine service 2 weeks later and at that point was diagnosed with large cell gastrointestinal (GI) lymphoma. Chemotherapy was started and initially well-tolerated. The owners did not report a recurrence of neurologic abnormalities, and the physical examinations performed by the oncology service over the next weeks did not reveal any obvious neurologic abnormalities. A full neurologic exam was not performed. Urine blastomycosis antigen tests were also not repeated during that time due to the inability to acquire sufficient urine samples. The patient started declining 2 months after the diagnosis of GI lymphoma and was euthanized 3 months later. An autopsy was not performed. The overall survival time after the initial diagnosis of systemic blastomycosis was 5 years.

blastomyces dermatitidis, brain, central nervous system, encephalitis, feline, fungal, magnetic resonance imaging

PMC2774484_01

Female

A 74-year-old woman with a history of gastric cancer presented with a chief complaint of lower back pain. Subjective lower back pain emerged approximately 4 months prior to her visit to our institute. On admission, deep tendon reflexes in both legs (patella tendon reflex (PTR) and Achilles tendon reflex (ATR)) were found to be decreased and hypoaesthesia was identified in the left L4 sensory region. Muscle weakness was observed in the left tibialis anterior muscle according to the manual muscle test (MMT), with a score of 4. Mild perianal hypoesthesia was observed. Neurologically, cauda equina syndrome and radiculopathy at and below the L4 level were identified. Regarding magnetic resonance imaging (MRI), T1-weighted imaging showed overall signal hypointensity for both L3 and L4 vertebral bodies, although T2-weighted imaging showed signal hyperintensity presumably indicating abundant abscess accumulation in the disc space, a lesion suspected to be epidural abscess in the spinal canal, and marked compression of the dural sac (Figure 1(a)). Contrast-enhanced computed tomography (CT) showed multiple abscess formation around vertebral bodies with calcification inside (Figure 1(b)). The preoperative diagnosis was infectious spondylitis (TB or pyogenic). Surgery was started with the patient in the lateral position under local anaesthesia. According to the PN manoeuvre, percutaneous puncture was performed into the L3/4 intervertebral disc. A sheath was inserted into the disc space to aspirate 30 mL of abscess, and lower back pain reduced immediately thereafter. Curettage was performed while checking anteroposterior and lateral views on an X-ray image intensifier. Finally, an epidural tube as the in-tube and a drainage tube of 3 mm diameter as the out-tube were indwelled in the disc space and the operation was completed. Continuous irrigation was then started. On postoperative day 3, Mycobacterium tuberculosis was detected as Gaffky grade 2. M. tuberculosis infection was also confirmed by tuberculosis-polymerase chain reaction (TB-PCR). Irrigation was thus continued until postoperative day 16 using a washing solution of 200 mL saline containing 1000 mg streptomycin each day. Multidrug antituberculous therapy was started using pyramide (900 mg/d), isoniazid (300 mg/d), rifampicin (300 mg/d), and ethambutol (500 mg/d). Immediately after the completion of irrigation, the patient wore a lumbar brace and started rehabilitation of walking and muscle strength of the legs. Histology showed typical TB tissue with central caseous necrosis, surrounded by epithelioid cells and Langhans-type giant cells. Severe lower back pain also resolved almost completely by 1-2 weeks postoperatively. MRI at 3 months postoperatively showed a clear tendency toward recovery of normal signal intensity in the L3 and L4 vertebral bodies on T1-weighted imaging, while most of the abscess with high signal intensity had disappeared from T2-weighted imaging. Good improvements were seen in both diagnostic imaging and clinical symptoms, with no tendency toward recurrence in blood biochemistry. All antituberculous agents were therefore discontinued at 7 months postoperatively. On MRI at 18 months postoperatively, signal intensity in vertebral bodies had completely recovered on T1-weighted imaging. No signal hyperintense regions were apparent in the disc space or epidurally to suggest abscess recurrence on T2-weighted imaging (Figure 1(c)). In addition, plain radiography indicated complete bone union at 30 months postoperatively (Figure 1(d)). At present, 7 years and 6 months after surgery, follow-up has shown good condition with no relapse of symptoms.

PMC2774484_02

Female

A 64-year-old woman was referred to our hospital with lower back pain and a history of surgery for leg varicose veins. Lower back pain had emerged about 3.5 months prior to her visit to our institute, with gradual worsening. The patient complained that lower back pain had never improved since onset and had been exacerbated by even slight exercise such as standing and walking. Regarding MRI, T1-weighted imaging showed overall signal hypointensity in both L2 and L3 vertebral bodies, whereas T2-weighted imaging showed signal hyperintensity presumably indicating abscess accumulation in the disc space extending to inside the L2 vertebral body. Subsequent gadolinium-enhanced imaging showed diffuse contrast in both L2 and L3 vertebral bodies and rim enhancement around the abscess in the right psoas muscle (Figure 2(a)). CT showed a destructive change in the L2 vertebral endplate, and cavitations >=10 mm in diameter were found in vertebral bodies (Figure 2(c)). Preoperative diagnosis was infectious spondylitis (TB or pyogenic). Surgery was performed similar to that described for Case 1. A sheath was inserted into the L2/3 disc space to allow curettage of infected disc tissue. Finally, a 3 mm diameter in-tube and a 5 mm diameter drainage tube as the out-tube were indwelled in the disc space and the operation was completed. Continuous irrigation was started. Histology on postoperative day 9 showed epithelioid cells centred around caseous necrosis, and QuantiFERON TB-2G showed strongly positive results. TB spondylitis was therefore finally diagnosed. Irrigation was performed until postoperative day 12 using only 250 mL of saline each day. Multidrug antituberculous therapy was started using isoniazid (300 mg/d), rifampicin (450 mg/d) and ethambutol (750 mg/d). After completion of irrigation, the patient wore a lumbar brace and started rehabilitation, mainly for walking. Strong lower back pain also disappeared by about 1-2 weeks postoperatively. MRI at 3 months postoperatively showed recovery to normal signal intensity from signal hypointensity in the L2 and L3 vertebral bodies, except for the cavity area on T1-weighted imaging. On T2-weighted imaging, part of the signal hyperintense area remained, but was restricted to the disc space and vertebral bodies, with disappearance of abscess in the right iliopsoas muscle (Figure 2(b)). By 6 months postoperatively, diagnostic imaging showed good improvement, as did clinical symptoms. There was no evidence of recurrence from blood biochemistry. Administration of all antituberculous agents was thus discontinued at 6 months postoperatively. At 12 months, signal intensity in L2 and L3 vertebral bodies had normalized on T1-weighted imaging. No signal hyperintense regions were seen in the disc space, inside vertebral bodies or in the psoas muscle on T2-weighted imaging. By 6 months postoperatively, CT showed repair of the L2 vertebral body cavity and bone remodelling, and the cavities was clearly reduced. At 12 months postoperatively, the cavity was completely repaired and disappeared (Figure 2(d)). At the time of writing, although complete bone union has not been achieved, follow-up shows good condition without relapse of symptoms at 24 months postoperatively.

PMC3420725_01

Female

A 26-year-old previously healthy Japanese female presented with nine days of myalgias, subjective fevers, and soaking night sweats. Four days prior, she developed multiple erythematous nodules on her face, chest, abdomen, and upper and lower extremities bilaterally. She complained of sore throat, nonproductive cough, painless oral ulcers, hand swelling, Raynaud's phenomenon, erythroderma, and abdominal bloating. She denied illicit or prescribed drug use, drug allergies, alcohol, or tobacco. She emigrated from Japan at age eight and received a BCG vaccination as a child. She reported recent travel to Europe and was sexually active with one partner. On physical examination, the patient was normotensive and afebrile. There was a tender right submandibular node and diffuse swelling of the hands without synovitis. Multiple 2-3 cm tender, erythematous, subcutaneous nodules were present over the face, chest, abdomen, and upper and lower extremities bilaterally (Figures 1(a) and 1(b)). She subsequently developed a fever of 39.5 Celsius. Initial laboratory tests included a hematocrit of 30.9%, an LDH of 329 iu/L, a positive Coombs antibody assay, an erythrocyte sedimentation rate of 58 mm/hr Westergren, a c-reactive protein of 182 mg/L (normal <6.3 mg/L), and a prolonged partial thromboplastin time of 38.7 sec (normal 20.9-33.6). Histochemical staining of the skin biopsy did not reveal organisms. A CT scan of the chest revealed interlobular septal and bronchial wall thickening of multiple lobes and patchy ground glass opacities suggestive of pulmonary edema or atypical or viral pneumonia. Further laboratory testing revealed an antinuclear antibody titer >640, speckled with positive anti-Smith and anti-Sm/RNP antibody assays. Complement levels and urinalysis were normal. A tuberculin skin test was positive to 14 mm at 48 hours. A quantiferon gold assay was indeterminate. A skin biopsy from her left thigh showed a relatively sparse interstitial inflammatory infiltrate composed of neutrophils, lymphocytes, and histiocytes. In addition, there were some foci of leukocytoclastic vasculitis. Neutrophils were also found in the subcutaneous tissue. The patient was treated with prednisone 40 mg and hydroxychloroquine 400 mg daily with a dramatic response. Dapsone was later added in an effort to taper the prednisone. She was also treated for latent tuberculosis with four months of rifampin.

PMC9133549_01

Male

A 39-year-old male patient was admitted to the Department of Emergency Medicine, the Second Hospital of Shanxi Medical University on May 12th, 2020, due to chief complaints of fever for more than 10 days and disturbance of consciousness accompanied by convulsions for 2 days. The patient developed intermittent fever before May 1st, 2020 (the specific time was unknown), the highest temperature was ~37.5 C, accompanied by chest tightness. The conditions were unresponsive to self-administered oral anti-inflammatory drugs. Diarrhea occurred on May 7th, and the conditions gradually deteriorated. On May 10th, the temperature elevated to 39 C, accompanied by headache, confusion, and inability to answer questions correctly. The patient had a history of intermittent "low fever" for 7-8 years. Due to his suspected "rheumatoid arthritis," the patient had taken oral medications (Chinese patent medicines and hormones, but the specific details were unknown) irregularly for many years. The patient had been married for 10 years without children. His wife was in good health and claimed that her reproductive system examination showed no abnormalities. When admission, the patient was admitted to the ICU of the Department of Neurology for further diagnosis and treatment. Physical examinations on admission showed the body temperature at 40 C, pulse at 120 beats/min, respiration rate at 20 times/min, blood pressure at 120/70 mmHg, blood oxygen saturation at 96%, and assisted ventilation. Nervous system examinations indicated moderate coma. The pupils were equal in size and roundness with a diameter of ~0.3 cm, and the light reflex was normal. His muscular tone of four limbs slightly increased. Meningeal irritation signs were positive, and bilateral pathological signs were negative. The patient was uncooperative with the rest physical examinations. Related biochemical and imaging examinations were also tested. Emergency blood gas analysis showed pH at 7.457, PCO2 at 28.9 mmHg, and PO2 at 97.7 mmHg. Routine blood test showed WBC counts at 12.34 x 109/L, RBC counts at 4.30 x 1012/L, hemoglobin concentration at 118.0 g/L, platelet counts at 258.00 x 109/L, and C-reactive protein at 277.20 mg/L. Head CT did not reveal any obvious abnormalities, while chest CT showed mild pneumonia of the lower lobes. Initial treatments included ice blanket and ice cap for physical cooling, empirical antiviral and antibacterial therapies, intravenous administration of gamma-globulin to improve immunity, elimination of autoimmune antibodies, rehydration, and other symptomatic and supportive treatment. At 23:18 of that night, the patient manifested sudden convulsions of the four limbs, loss of consciousness, lockjaw, and ocular gaze to the left. After intravenous injection of 10 mg diazepam, ocular gaze, limb stiffness, and convulsion stopped, but strong limb struggling occurred. Propofol was then administered for sedation purpose, followed by tracheal intubation, tracheotomy, and assisted ventilation. Subsequently, propofol combined with midazolam, meanwhile, antiviral, antibacterial, physical cooling, fluid rehydration, and other therapies were provided, but the temperature still elevated intermittently, up to 41 C. Relevant laboratory examinations were completed: Blood coagulation series showed prothrombin time control at 13.50 S, prothrombin time measurement at 12.7 S, D-dimer at 1,892 ng/ml. Procalcitonin was tested at 3.53 ng/ml. ESR was at 120.00 mm/h. IgG was at 15.70 g/L, IgA was <0.0667 g/L, IgM at 0.53 g/L. Mycobacterium tuberculosis antibody test and sputum acid-fast bacillus smear showed negative. Blood biochemistry showed Urea at 7.62 mmol/L, creatinine at 75.43 mumol/L, potassium at 3.83 mmol/L, sodium at 143.00 mmol/L, chlorine at 112.00 mmol/L, creatine kinase isoenzyme MB at 0.42 ng/mL, myoglobin at 103.02 ng/mL, hypersensitive troponin at 0.02 ng/mL, B-type natriuretic peptide at 38.38 pg/ml, ALT at 23.10 U/L, AST at 48.20 U/L, albumin at 24.20 g/L, and LDL at 2.43 mmol/L. Thyroid function showed Serum T3 3.75 pmol/L, serum free T4 12.71 pmol/L, highly sensitive serum TSH 0.76 mIU/L; 8. Folic acid 21.08 nmol/L, vitamin B12 252.00 pmol/L. CSF examination showed high pressure, WBC counts at 680 x 106/L, microscopic multinuclear cells at 81%, microscopic lymphocytes at 19%, RBC counts 170 x 106/L, gamma-globulin test (+), glucose at 0.69 mmol/L (2.2-3.9), chlorine at 124 mmol/L, and CSF proteins at 3.28 g/L (0.08-0.43). CSF virus series (human cytomegalovirus and EB virus) and ink staining (Cryptococcus and Mycobacterium tuberculosis) showed negative. CSF immunoglobulin showed IgG at 1250.00 mg/L, IgA at 0.91 mg/L, and IgM at 4.37 mg/L. Autoimmune encephalitis autoantibody, paraneoplastic syndrome autoantibody, and central nervous system demyeling antibody of CSF and blood were tested. The results of CSF were positive/weakly positive, while the blood results were all negative (Figures 1, 2). The CSF and blood samples of the patient were also sent for PACEseq metagenomic next-generation sequencing (mNGS) detection (Hugobiotech, Beijing, China). L. monocytogenes was identified in both CSF and blood, with the specific sequence number of 1,629 and 8, respectively (Figure 3). Based on the patient's symptoms, extra information was added according to the inquiry into the medical history of family members. The patient usually did not pay much attention to oral hygiene. He brushed teeth irregularly, and often ate food directly out of the refrigerator. He felt oral discomfort 2 days before disease onset. The patient had repeatedly instilled tobramycin eye drops due to eye discomfort, and often squeezed multiple acne on the face by himself. The past medication history included the use of a large amount of oral drugs for the treatment of rheumatoid arthritis, without seeking formal medical treatments, instead, he often searched the Internet for medicines on his own and orally administered more than 10 drugs (including non-steroidal hormonal anti-inflammatory drugs). Therefore, this patient had a history of ingesting unclean food and facial infection, as well as the use of multiple drugs including glucocorticoids. This could lead to a weakened and compromised immunity, causing L. monocytogenes invasion into the central nervous system. The patient was finally diagnosed as Listeria meningoencephalitis with secondary epilepsy and status epilepticus, bilateral pneumonia, and perhaps rheumatoid arthritis. Thus, adjusted treatments including ampicillin and rifampicin in combination with meropenem, linezolid, and acyclovir were given. Anti-epileptic therapy, dehydration to reduce cerebral edema, and intravenous infusion of globulin symptomatic and supportive treatments were also provided. After 10 days of treatments, the patient symptoms partially improved. The consciousness gradually regained. Seizures did not recur. His temperature gradually decreased. However, the patient's responsiveness was unsatisfactory. In the meantime, new problems emerged. Despite temperature decline, low fever persisted for a long time, fluctuating at 37.5-38.0 C, and ESR continued to be around 110 mm/h. Neurological examination showed suspicious paralysis of limbs and ophthalmoplegia: despite the consciousness, the patient was unable to speak due to tracheotomy or follow the sound, both eyes was able to move leftward, but the left eye outreached poorly, both pupils was equal in size and roundness with a diameter of 0.3 cm, light reflex was normal, muscle tone of the upper limbs slightly increased, while muscle tone of the lower limbs was basically normal, there was no voluntary movement of the four limbs even under strong stimulation, and bilateral pathological signs were negative. During treatment, the patient developed severe anemia, which met the indication for blood transfusion, unfortunately, repeated blood matching failed. On May 25th, 500 mg methylprednisolone pulse therapy was added. On the next day, the patient's symptoms significantly relieved. Both hands could raise off the bed, and muscle contraction of both lower limbs was observed. During the following more than 10 days of treatments (the protocol was the same as above), the patient's symptoms gradually improved. The temperature decreased to normal. The patient regained consciousness and was able to speak. His muscle tone of four limbs reached level 4, and ophthalmoplegia gradually alleviated. Repeated examinations of CSF routine and biochemistry gradually returned normal. ESR gradually decreased to normal level. On June 28th, mNGS result reported the number of specific sequences of L. monocytogenes decreased to 136. Subsequent re-examinations of MRI (T1, T2, FLAIR, DWI, ADC) showed bilateral frontal and parietal cortex necrosis and meningoencephalitis (Figure 4). The patient was instructed to strengthen rehabilitation training. Reexamination of the CSF on July 12th reported mononuclear cell proliferation, L. monocytogenes, and autoimmune antibody (-). Since the follow-up to present, small oral dose of hormone was regularly administered, and the disease has not recurred.

cns demyelinating diseases, complicated or secondary autoimmune encephalitis, metagenomic next-generation sequencing, pathogen detection, severe listeria encephalitis

PMC5629883_01

Female

A 41/2-year-old female child presented with fever for 11/2 months and cough for 5 months. There was no contact with a patient suffering from TB. A general practitioner had treated her with anti-TB therapy (ATT) for 2-3 months in view of positive Mantoux test. On examination, weight was 16 kg, and height was 98 cm. Both upper limb pulses were not felt and lower limb pulses were low volume. Blood pressure in the upper limbs could not be recorded and in the left lower limb was 122/80 mmHg. Systemic examination was normal. Chest X-ray showed bilateral collapse consolidation with prominent aortic knuckle. Hemoglobin was 10.1 g/dl, white blood cell (WBC) count was 15,100/cumm (70% polymorphs, 29% lymphocytes), erythrocyte sedimentation rate (ESR) of 17 mm at the end of 1 h. Mantoux test was negative and sputum smear did not show any acid-fast Bacilli. HIV ELISA was negative. TB Gold test was also negative. Echocardiography showed dilated ascending and descending aorta including abdominal aorta with hyperechoic intima, suggestive of aortoarteritis. Computed tomography angiography of the aorta showed aneurysmal dilatation of ascending aorta, arch and descending thoracic and suprarenal abdominal aorta with bilateral blocked subclavian artery. There was a small caliber infrarenal abdominal aorta. A bronchoalveolar lavage could not be done due to poor cardiac condition. She was started on four drugs of ATT and subsequently detected to have hypertension, for which she was started on methyldopa and nifedipine. Oral prednisolone was started at 1 mg/kg/day. An opinion of interventional radiologist was taken, and it was found to be not amenable to dilatation. She is on regular follow-up.

aortoarteritis, children, tuberculosis

PMC6462151_02

Male

We report a 27 year old man, 10 pack-years smoker, with a one-month history of dry cough, shortness of breath and general status's deterioration. A lung X ray showed bilateral alveolar opacities (Figure 1). Blood gases analysis in ambient air showed a pO2 of 57 mmHg, a pCO2 of 38.6 mmHg, a HCO3- of 29.2 mmHg. Because of the considerable deterioration in his respiratory condition and the need for high oxygen flow, he was referred to intensive care unit (ICU) with the diagnosis of an acute respiratory failure (ARF). Chest computed tomography (CT) showed diffuse ground-glass opacities (Figure 2A, Figure 2B) and mediastinal lymphadenopathies. All microbiological infectious investigations, especially tuberculosis, were negative. He had hypergammaglobulinemia of 21.9 g/l. Other immunological tests were otherwise negative. Transthoracic echocardiography was performed finding a hyperkinetic left ventricle, a small dilation of right ventricle with PAPs 48 mmHg and an intrapulmonary shunt revealed by contrast test. The bronchial endoscopy showed an inflammatory bronchial tree and the bronchoalveolar lavage (BAL) concluded to lymphocytic alveolitis with a ratio CD4 (helper T cells) over CD8 (suppressor T cells) (CD4/CD8) of 0.5. The bronchial biopsies showed inflammatory bronchial mucosa without any specificities. Despite the absence of Koch's bacillus in sputum analysis, we decided to begin a trial anti-tuberculosis treatment because of the severity of lung involvement added to high endemicity of tuberculosis in our country. Two weeks later, the patient presented an allergic skin reaction. As no recovery's signs were noted, we decided to stop the treatment. Corticosteroids were initiated considering idiopathic diffuse infiltrating pneumonitis. Unfortunately, the patient did not show any improvement and the chest scan performed after 27 days of treatment showed worsening interstitial infiltrates and fibrosis. Clinically, he required high flow oxygen (14 l/mn) alternating with non invasive ventilation sessions. Histological examination of the open lung's biopsy then performed showed diffuse lung parenchyma damage. It was altered by a mutilating fibrosis that was widening the alveolar septa. This fibrosis contained an abundant inflammatory infiltrate made of lymphocytes, plasmocytes and fewer neutrophils and eosinophils. Epithelioid and giant cell granulomas were also observed without either caseous or fibrinoid necrosis. This mutilating fibrosis induced an enlargement of some alveoli resulting in the formation of a honeycomb aspect. Fibroblastic foci were also noticed. Some alveoli contained hyaline membranes that were sometimes incorporated in the septa. There were no mineral particles observed with polarized light (Figure 3). Regarding these features, the diagnosis of usual interstitial pneumonia (UIP) associated to lesions of sarcoidosis or berylliosis with aspects suggestive of an acute exacerbation was retained. Since sarcoidosis was not very likely according to CD4/CD8 ratio in BAL, we investigated risk factors for chronic beryllium disease, particularly occupation's patient history. He was working as glassblower in an artistic glass factory since six months. Further to our request, occupational department's experts inspected the workplace and confirmed beryllium existence in compounds of colored glass. After confirmation of CBD, steroids were maintained and oxygen requirement slowly decreased. The patient was finally discharged at home after 55 days steroid treatment with long term oxygen therapy (2 l/minute). Pulmonary function tests at discharge showed a severe restrictive impairement. Steroid doses were slowly decreased and stopped after 10 months. A pre-transplant assessment was also made. One year after discharge, the patient felt somewhat better and pulmonary function tests showed a slight improvement. The CT scan performed found a partial regression of lung consolidations and ground glass opacities, but increase of distortion signs, cavities appearance of which one filled by aspergilloma. He received oral voriconazole 200 mg per day during 3 months. After a two-year period from the date of CBD diagnosis, the patient was again admitted in ICU for ARF. An enhanced CT scan performed showed further deterioration of pulmonary parenchyma (Figure 2C, Figure 2D) and pulmonary embolism with fatal issue.

lung toxicity, chronic beryllium disease, glassblower, interstitial pneumonia

CT scan (lung windowing): a & b) bilateral lung consolidations and ground glass opacities with bronchial distortion; c & d) CT scan at 2 years: partial regression of lung consolidations and ground glass opacities and increase of distortion signs and cavities appearance.

PMC5810523_01

Male

Seven years ago, a 50-year-old Chinese male with cough and expectoration (black phlegm) for about 2 weeks, sometimes accompanied with bloody sputum and breathlessness, was admitted to our hospital. These symptoms developed without apparent cause and in the absence of problems such as chest pain and/or distress, fever, nausea, or vomiting. A computed tomography (CT) scan of his chest showed a rough-edged shadow measuring nearly 32x22x10 mm in the right upper lobe of his lung, as shown in Figure 1 (A: before surgery; B: after surgery). The patient acknowledged several chronic disorders, including a 10-year history of bronchitis and emphysema, and was a smoker with a 30-pack-year history. The patient had no family history of lung cancer. There was no obvious abnormality noted in his system review. The results of a peripheral blood count, baseline serum chemistry screening, and urinalysis were normal on admission, and tumor biomarker tests and a purified protein derivative test for tuberculosis were also negative. A rough-edged shadow of his right upper lobe was once again seen on an enhanced CT scan of his chest, although a CT scan of his abdomen, magnetic resonance imaging of his brain, and a bone scan were all normal. His right bronchial tree also appeared normal on bronchoscopic examination, with no indication of malignancy in the biopsy and washings procured. A right-sided upper lobectomy and systematic mediastinal lymphadenectomy were performed. A tumor of his right upper lobe, roughly 3 cm in diameter, was evident at surgery, without puckering of visceral pleura. Microscopic sections showed the following findings: there were many large, multi-core, and bizarre giant cells, without special arrangement; cytoplasm was moderate to abundant, dense, and eosinophilic; nucleus was pleomorphic and phylloid; and the tumor cells appeared to have lost adhesion, and to be separated and embedded in a fibrous myxoid stroma. Histopathologic examination revealed the tumor cells were positively reactive to cytokeratin (CK) and vimentin, while immunostaining for chromogranin A (CgA) and synaptophysin (Syn) was negative, as shown in Figure 2. Diagnostically, vimentin is the major cytoskeletal component of mesenchymal cells and is often used as a marker of mesenchymally derived cells or cells undergoing an epithelial-to-mesenchymal transition during metastatic progression. Here, it was used as a sarcoma tumor marker to identify mesenchyme. Syn is often combined with CgA as a specific marker to identify tumors arising from neural and neuroendocrine tissues, such as neuroblastoma, carcinoid, and small-cell carcinoma. Therefore, the above findings supported the diagnosis of a GCCL. The detection of bronchial stump and mediastinal lymph nodes was negative, and it indicated that there was no lymph node metastasis in this patient. Since 2 months after surgery, the patient was treated with combined chemotherapy using gemcitabine (1,000 mg/m2 on days 1 and 8) and cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles, and then whole-body radiography examinations were carried out every year in a local hospital. He was still alive 7 years after surgery, free from disease progression. Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. Until now, the therapeutic result of this case is satisfactory. With the development of high-throughput sequencing technology, more and more genomes have been successfully sequenced. Recently, in order to explore the molecular structure of this tumor, mutations of 295 tumor-related driver genes were detected by a high-throughput sequencing test (Burning Rock Biotechnology Inc., Guangzhou, People's Republic of China). All the 295 genes are listed in Table S1. We analyzed normal and tumor tissues of this patient, after ruling out genetic variations; nine tumor-related somatic mutations were confirmed, of which six were missense variants and three were synonymous variants. The high-throughput screening results of the patient are shown in Table S2. The six missense mutations included KRAS, KMT2D, TP53, SETD2, TET2, and MAP3K. As a hotspot mutation, KRAS gene mutation on chromosome 12, exon 2 p.G12D, with a mutant abundance of about 26.7%, indicated the tumor may be sensitive to MEK inhibitor and CDK 4/6 inhibitor like trametinib and abemaciclib. TP53 gene mutation on chromosome 17, exon 7 p.R249K, with a mutant abundance of about 8.30%, indicated the tumor cell may be sensitive to some novel compound that can reverse the TP53 mutation like APR-246. For the other four somatic mutations, including KMT2D, SETD2, TET2, and MAP3K, there was no sufficient evidence to show their correlation with target drugs known so far in clinical use.

gene mutation, giant-cell carcinoma of the lung, high-throughput sequencing

PMC8110271_01

Female

Y village and two villages less than 2 km away accounted for approximately 50% of the total cases in Shijiazhuang. These villages are all located within 10 kilometres of Shijiazhuang Zhengding airport. Most young people in the villages prefer the city and migrate to work, leaving behind most of the elderly individuals, women and children. As of January 18, most of the confirmed cases in Shijiazhuang were farmers. The average age of the patients was 45 years old, and 27% of the patients were over 60 years old. The number of female cases was 1.5 times the number of male cases, and there were nearly 70 confirmed cases in primary and secondary school students. Geographical conditions contribute to the high concentration of the population. Since the villages are not far away from each other, their residents have close contact with each other. One of the important activities is going to the market. According to contact tracing efforts, on January 1, 2021, 13 individuals with confirmed infection from nearby villages went to the market at Y village, as villagers from other towns often drive to the market in their private cars. In addition to going to the market, an important activity for housewives is attending wedding banquets. Women represented a high proportion of the confirmed cases because they participate in more social activities than men do. In wedding ceremonies, women in the village act as drummers and play various musical instruments. There is a local custom of holding weddings at the end of the year. A total of 124 confirmed cases participated in a wedding banquet in Shijiazhuang that lasted from the end of 2020 to the beginning of 2021. A 44-year-old woman from Y village participated in three wedding banquets in just four days from December 30, 2020, to January 2, 2021. In addition, religious activities can easily lead to the spread of the pandemic. Before the outbreak of the pandemic, some people had gathered at the home of a family in the village for religious activities, which, like other gatherings, easily facilitated the spread of the pandemic. Most of the villagers said that since the domestic pandemic was basically under control in the summer of 2020, they relaxed their vigilance. This is reflected in the increase in party activities and the decision not to wear masks during hot weather. People treat cough and headache as minor diseases and may not go to the hospital. Moreover, rural residents' low awareness of medical treatment, poor medical habits and insufficient access to high-quality medical resources are important reasons for the outbreak. Rural primary medical institutions play an important role as gatekeepers, as do village clinics and township health centres, which are superior management units. The current public information of the Hebei epidemiological survey indicates that at least 62 people came to such medical institutions for treatment and medicine due to obvious symptoms, such as cough, headache and fever, but they did not arouse due vigilance. In reality, due to their limited conditions, rural primary clinics have no ability to diagnose patients. However, their main role should be to find suspected patients in time and report them to the hospital. The village's prevention and control logic has failed in this case. Primary medical institutions do not play a "sentinel" role in the actual diagnosis and treatment process. The direct causes of the logic failure of village pandemic prevention and control are traffic, culture, wedding banquets, geographical location, and population structure. These factors can be catalysts that intensify the spread of the pandemic in Y village. For example, convenient transportation and geographical location contribute to the quick spread of the pandemic. The gathering of people, for example, at the market and wedding banquets, further increases the number of people infected. Regarding the population structure, young people go out to work, leaving behind the elderly individuals, women and children, who generally lack information sources and have little understanding of the pandemic.

covid-19, challenges, health system, public health crisis, rural area

PMC8110271_02

Unknown

The indirect causes of the logic failure of village pandemic prevention and control are the inadequately equipped teams in the rural pandemic prevention system. For example, village-barefoot doctors are growing older and gradually withdrawing from front-line health work. Young college graduates are unwilling to stay in the countryside, and there is a shortage of talent in rural areas. In 2018, doctors aged 60 or older represented more than a quarter of rural doctors in China and even 80% in some townships, and only 5% of rural doctors were under 35 years old. Moreover, the phenomena of low medical history, low professional title and low professional level are common among village healthcare personnel. In 2018, only 15% of personnel had a bachelor's degree or above. Rural doctors account for more than 1/3 of the grassroots medical staff, and they are the main force of rural grassroots health prevention and control by virtue of their familiarity with villagers. However, it is undeniable that elderly grassroots medical workers offer little support for the prevention and control of infectious diseases. Elderly individuals are susceptible to COVID-19, and the probability of cross infection is high in the process of door-to-door service. Second, elderly village doctors find it difficult to operate the many new information technologies for prevention and control, which reflects the deep weakness of the rural public health system. The prevention and control of the pandemic ultimately needs the establishment of a multidimensional and deep governance system. In the post-pandemic era, the reconstruction of multiple prevention and control strategies and promotion of the modernization of public healthcare governance are important to address many risks in the future. It is suggested to reform the medical service supply system in rural areas, improve the emergency response mechanism for major public health events and strengthen health publicity and education. During the outbreak of a major pandemic, the efficient and orderly operation of medical emergency treatment systems is very important to improve the admission rate and reduce the infection rate and mortality. Primary medical institutions, as basic public health services in China, are responsible for the reporting and management of infectious diseases and public health emergencies. Therefore, it is necessary to consolidate the "gatekeeper" role of primary medical institutions. In the case of major public health emergencies, the hierarchical diagnosis and treatment system should be enforced, the medical order should be optimized, and hierarchical, separate treatment should be implemented. Therefore, it is necessary to increase investment and strengthen the construction of primary medical institutions. First, in the construction of primary medical institutions, pre-screening triage and fever clinics are necessary to undertake the functions of disease screening and patient classification management during health emergencies. Second, the use of electronic health records and the grid management of residents' health and the cooperation between the community and pandemic prevention and control institutions can support community pandemic prevention and control. Second, it is important to strengthen the public health function of medical institutions, promote the linkage of prevention control treatment and develop synergistic effects. Medical institutions themselves are also an integral part of the disease prevention and control system. They are responsible for the monitoring, reporting, emergency treatment of infectious diseases and public health issues, and prevention and control of infectious diseases in their responsible areas. Unfortunately, these public health functions have not been strictly defined at the legal level and have not been emphasized in the reform of public hospitals. The awareness of infectious disease prevention and control of medical institutions and clinicians needs to be strengthened; moreover, the medical service system and the public health system lack regular joint working mechanisms. Therefore, the public health function of the medical service system should be strengthened and supplemented by incentive mechanisms. Moreover, it is necessary to improve the communication and coordination mechanism within the public health system, realize information exchange and sharing, and build the working mode of medical prevention integration. For the prevention and control of infectious diseases and public health emergencies, the sequence of prevention, control, and treatment is formed, involving information sharing, personnel training, emergency drills, and scientific research cooperation, to develop synergistic effects. First the unitary management pattern should be eliminated and replaced with a mechanism for public, social and market participation. In the past four decades, social forces have developed unprecedentedly and played an increasingly important role in the social and economic life in China. However, the existing emergency management mechanism is designed based on the concept of an omnipotent government, and emergency management mainly depends on the actions of the government and relevant departments. In practice, due to the poor participation mechanism, economic and social organizations and the public cannot effectively cooperate with the government but play a limited role. Therefore, the unitary management pattern must be replaced by a social governance mechanism for major public health emergencies to enable the participation of the market, society and citizens. The public, society and market participation mechanism should be established for support during major public health emergencies. It integrates vertical social integration with horizontal social cooperation under the guidance of the government. In the whole chain of emergency management, a pattern of interaction among the government, the market and society should form a mutually complementary and efficient coordination under the guidance of the government. In the prevention and control of a pandemic, mass prevention and treatment measures represent an innovative mechanism of social participation. After the pandemic crisis, these measures need to be further refined and improved to become an important part of the emergency mechanism for major public health emergencies.,2 Second, a modern emergency material reserve system needs to be built. For example, in January 2021, citizens of Tonghua City, Jilin Province, reported on major media and network platforms that the closed management was caught off guard, daily necessities and food were seriously lacking, basic life could not be guaranteed, and hotlines were inaccessible. In response to the query, at a press conference held on the morning of January 24th, Vice Mayor Jiang Haiyan of Tonghua City apologized on behalf of the municipal party committee and the municipal government for the inconvenience caused by the untimely distribution of people's living materials. This highlights the importance of addressing the shortcomings of the existing classification, establishing special reserves for various departments and scientifically determining the demand for reserve materials by category, scale and structure based on big data technology and comprehensive risk analysis. Utilizing the unified national emergency material procurement and supply system, integrating all special reserve resources, stocking emergency supplies in central locations, and improving and guaranteeing the operational efficiency of the material reserve system are important steps. First, it is strongly suggested to build a national health education system and advance emergency management. The key to dealing with major public health emergencies is prevention. Emergency management is the most economical and effective method to build a national health education system and improve national health literacy. Health education has long been one of the important contents of public health services in China, but in practice, it is often a mere formality. Government investment should be increased and adequate funding be guaranteed to support the organizational system of health education institutions and provide health education to the whole population, and health education should be integrated into schools at all levels. Starting from childhood, health education should be strengthened for primary and secondary school students. Second, the prevention and control of major infectious diseases and emergency education should be strengthened, and publicity and education work should be normalized. In recent years, the focus of health education has gradually shifted from early infectious disease prevention and control to chronic disease prevention and health management. The pandemic represents a tragic warning: major infectious diseases have not left the stage of history. In particular, urbanization, ageing and globalization have made infectious diseases more active, and their return is inevitable. It is important to start from the source, strengthen publicity and education, improve awareness of protection, and change individuals' behaviour. Therefore, routine propaganda and education should pay equal attention to the prevention and control of major infectious diseases, chronic diseases and health management. In addition, emergency education on major infectious diseases should be strengthened to improve people's health literacy in emergencies.

covid-19, challenges, health system, public health crisis, rural area

PMC5633164_01

Male

Our patient is a 24-year old caucasian male diagnosed with SLE and associated antiphospholipid syndrome (APS) in 2001 at the age of 9. Initial symptoms were arthralgia, livedo reticularis and a decrease in complement. In 2005 he developed a class 4a glomerulonephritis. He was treated with prednisolone and cyclophosphamide as induction therapy and with azathioprine as maintenance treatment. Azathioprin was later changed to mycophenolate mofetil (MMF). His renal function normalized with an estimated glomerular filtration rate (eGFr) of 71 ml/min but permanent albuminuria of 2-3g/24 h. The diagnosis of APS was made in 2009 based on deep vein thrombosis, positive lupus anticoagulant >150 s (<42 s), elevated beta2-glycoprotein IgM 51 103 units/l (<20 units/l) and beta2-glycoprotein IgG 75 103 units/l (<20 units/l) and an increased APTT of 138 s (25-38 s) and he was therefore treated with warfarin (INR 2.0-3.5). In spite of the heavy immunosuppressive treatment, his SLE worsened. In 2008, he was seen in our department for the first time due to an increased cough, dyspnea and hemoptysis. He was in a physical good shape playing football in spite of his kidney and lung symptoms even when his haemoptysis worsened. A high-resolution computed tomography (HRCT) showed lobular ground glass attenuation compatible with alveolar bleeding (Fig. 1), confirmed by a bronchoscopy showing hemorrhagic lavage fluid and hemosiderin-laden macrophages (Fig. 2). Culture was without mycobacteria or other microorganisms. During the DAH episode he had low C3c 5.5 mumol/l (6.7-13.4 mumol/l), thrombocytopenia 84 109/l (145-350 109/l), low hemoglobin 6.8 mmol/l (8.3-10.5 mmol/l) and a hematocrite of 0.37 (0.40-0.50). The findings were interpreted as an activation of his SLE and the mycophenolate dosage was increased. Due to recurrent haemoptysis, RTX was added to his treatment. As induction therapy, 1g of RTX was administered twice two weeks apart. His condition improved rapidly. Forced expiratory volume in 1 second (FEV1) increased from 2.47L to 2.93L and forced vital capacity (FVC) increased from 2.72L to 3.28L. His haemoptysis decreased significantly. HRCT show significantly regression in ground glass attenuation (Fig. 3). However, after 3 months, the dyspnea and haemoptysis returned and he again required RTX followed by continuous RTX 1g initially once a year. Due to recurrent and increasing hemoptysis after two years of treatment, the intervals were shortened to 6 months between each series of RTX. During the 8 years with DAH, the patient was only hospitalized once due to a pulmonary infection. He has never been hospitalized due to DAH and has never needed mechanical ventilation. His current treatment consists of prednisolone 10 mg x 1, mycophenolate mofetil 500 mg x 3, hydroxychloroquin 200 mg x 1 and 1 g of RTX every 4 months.

High-resolution computed tomography (HRCT) showing lobular ground-glass opacities and in some areas interlobular septal thickening superimposed on ground-glass opacity (crazy paving pattern) compatible with alveolar bleeding.

PMC10498687_01

Female

A 33-year-old female presented with vague upper abdominal pain and dyspeptic symptoms for 2 months. She was otherwise well with no fever, constitutional symptoms, loss of appetite or loss of weight and was normoglycaemic. Her previous medical and surgical histories were unremarkable. She had no known allergies and her drug and psychosocial history was unremarkable. Her basic biochemistry, including liver enzymes were within normal limits. Her erythrocyte sedimentation rate was 13 mm in the first hour. She was investigated with a gastroduodenoscopy and an abdominal ultrasonography as her symptoms did not resolve with a trial of proton pump inhibitors. Her abdominal ultrasonography revealed a rounded 2.5 x 2.4 cm lesion in the head of the pancreas with low echogenic areas. Magnetic resonance imaging scans revealed a well-demarcated exophytic lesion with multiple T2 high signals and small cystic areas in the anterior superior part of the head of the pancreas measuring 23 x 20 x 28 mm (Figure 1). Following a multidisciplinary team discussion, a decision was made to perform a laparotomy followed by enucleation of the lesion, or Whipple procedure. The diagnosis was a pancreatic cystic neoplasm. An endoscopic ultrasound was not performed due to nonavailability. The CA 19-9 was within normal limits. She underwent a midline laparotomy and was found to have a well-defined exophytic firm to hard mass attached by a stalk to the upper border of the pancreatic head to the left of the hepatoduodenal ligament. The hepatic artery was densely adherent to the posterior surface of the mass. The mass was excised with a cuff of pancreatic tissue while carefully preserving the hepatic artery. Frozen section was not performed due to nonavailability in our institution. The postoperative period was uneventful. The histology revealed granulomatous inflammation of a lymph node with caseation which was pathognomonic of tuberculosis (Figure 2). Unfortunately, specimen for TB culture was not sent as the diagnosis of TB was not suspected during surgery. Even though Zeihl-Neelsen staining was not performed on the specimen, TB PCR was performed in aspirated fluid of the surgical specimen, and it was positive. Chest X-ray was done following the diagnosis but was normal. She was started on category 1 anti-tuberculosis therapy, that is, quadruple anti-microbial therapy for 2 months followed by dual therapy with rifampicin and isoniazid for 4 months according to the local guidelines of management of extra-pulmonary TB. At a follow up of 6 months, she was asymptomatic and further imaging was not performed.

pancreatic neoplasm, pancreatic tuberculosis

PMC7644338_01

Female

A 70-year-old ethnically Chinese female presented via the Emergency Department with a 2-week history of shortness of breath, productive cough, and confusion. A chest radiograph showed focal consolidation, and she was treated with antibiotics for community-acquired pneumonia and delirium. By day seven, her confusion had resolved. As part of the investigative work-up of her confusion, she received a CT head which showed a left frontal extra-axial lesion with patchy calcification (Figure 1). An outpatient MRI brain a month later demonstrated pachymeningeal and leptomeningeal enhancement bifrontally, with more marked changes on the left with underlying vasogenic oedema, and inflammatory opacification of the paranasal sinuses (Figure 2). She was subsequently admitted to the neurology ward for further assessment. She reported a one year exacerbation in the intensity of her chronic left frontal headache which she has had since her 30 s. They were described as a left frontal ache with migrainous features of nausea and photophobia, with no raised pressure features. She also described a reduced sense of smell and taste for 20 years which transiently improves on receiving prednisolone for exacerbation of asthma. There were no systemic features of arthralgia, weight loss, fevers, rash, or haemoptysis. Past medical history included childhood asthma, allergic contact dermatitis, and hypertension. Medication history included steroid and salbutamol inhalers, enalapril, and paracetamol. She was born in Singapore and has been a resident in the UK for 40 years. Neurological examination was normal with no nuchal rigidity, ophthalmic abnormalities, or cranial nerve signs. Further investigations revealed a chronically raised ESR (35-63 mm/h) for the past eight years with a normal CRP. She also had a chronically raised serum total IgE (137 kU/L) with a normal eosinophil count. Serum ANA, ANCA, rheumatoid factor, double-stranded DNA, anti-Ro, La, Sm, RNP, Jo1, and Scl-70 were negative. She had a serum IgA kappa paraprotein band of 14 g/L with normal serum-free light-chain ratio, beta2-microglobulin, renal function, calcium, and albumin levels. Serum IgG subclasses including IgG4 were normal. Serum fungal and cerebrospinal fluid (CSF) tuberculosis cultures were negative. Two sets of CSF examination showed normal cell count, protein and glucose levels, negative PCR for herpes simplex, varicella zoster and enteroviruses, and no neoplastic cells. CT chest, abdomen, and pelvis were normal. CT sinus showed chronic rhinosinusitis, and an olfactory cleft biopsy showed inflammatory mucosal changes with no evidence of IgG4-related disease or vasculitis. Bone marrow biopsy showed 10% plasma cells on trephine biopsy and 7% plasma cells on aspirate, and borderline between monoclonal gammopathy of uncertain significance (MGUS) and myeloma. MRI whole body showed diffuse osteopenia but no active myelomatous lesions. Serial MRI brains over two years showed a slow progression in the left frontal convexity pachymeningeal and leptomeningeal thickening and enhancement and bifrontal gliosis. She underwent an open left frontal meningeal biopsy two years into her initial presentation. Histopathological examination revealed a meningothelial neoplasm with a mitotic count of <4/10 high power fields and a low Ki67 labelling index (Figure 3). It also showed the presence of necrobiotic granulomata associated with elastotic degeneration. This was interpreted as an en-plaque meningioma (the WHO, 2016; Grade I) with associated granulomatous and fibroblastic reaction. Immunohistochemistry showed no tumoural expression of GFAP, CD34, STAT6, SMA, Desmin, MUC4, Cam5.2, or MNF116. Bacterial, fungal, and mycobacterial stains were negative. It was discussed with the patient that she has a benign slow-growing growth within the meninges which occupies much of her left frontal lobe area and it would be difficult to safely remove the whole plaque. She remains under conservative management with serial radiological and clinical monitoring. If the meningeal areas were to grow more as a globular lump with associated symptoms, targeted resection or other forms of localised treatment may be considered.

PMC5965009_01

Male

A 56-year-old male patient with coronary artery disease (CAD) and hypertension was referred with exertional dyspnea (NYHA II). Past medical history revealed that he had coarctation which was surgically corrected with a 16 mm x 20 mm Dacron tube graft at 21 years of age. On examination, his right upper limb blood pressure was 180/90 mmHg. The femoral pulses were faint. Radial femoral delay was apparent and blood pressure gradient of 30 mmHg was noted between upper and lower extremities. Chest X-ray revealed rib notching. Echocardiography showed a significant narrowing in the descending aorta just distal to subclavian artery inside the tube graft with peak gradient of 38 mmHg and mean gradient of 16 mmHg with diastolic spillage. There was concentric left ventricular hypertrophy with good systolic function. Contrast-enhanced computed tomography revealed severe stenosis at the proximal and distal anastomosis of the Dacron tube graft [Figures 1 and 2]. A decision was made to proceed with staged coronary angiography and later CoA stenting. Coronary angiogram revealed mid left anterior descending artery and diagonal disease which were stented. Two weeks later, the patient went for CoA stenting. Under general anesthesia, a 7F sheath was placed in the left femoral artery and a 6F sheath in the right radial artery. The coarctation site was crossed with 0.035 cm x 150 cm Terumo guidewire and 6F multipurpose catheter. Simultaneous recording from the ascending aorta and descending aorta revealed a peak-to-peak gradient of 54 mmHg. Ascending aorta angiogram [Figure 3] showed severe coarctation at the sites of proximal and distal anastomosis (6 mm each) of the tubed conduit and normal head and neck branches. The conduit length was 20 mm and diameter 14 mm. A 0.035 cm x 260 cm Amplatz super stiff wire was placed in the right subclavian artery for stability and a 14F Check Flo-Cook long sheath was placed over the wire. A 39-mm Cheatham platinum (CP)-covered stent (NuMed Inc., Hopkinton, New York, USA) was mounted to 14 mm x 40 mm BIB balloon to BIB catheter. Stent position was confirmed using aortic arch angiogram through the right radial artery approach. The stent was deployed inside the Dacron graft with right ventricular pacing at 170 bpm. Poststent implantation, the gradient dropped to 11 mmHg. The covered stent was postdilated with a 16 mm x 45 mm BIB balloon twice with good flaring of the proximal and distal ends of stent. Postballoon, dilatation revealed still further drop in gradient to 8 mmHg. Final angiogram [Figure 4] confirmed the good stent position and absence of any extravasation or tear. The measurements at proximal and distal coarctation sites were 14 mm each. The patient had uneventful recovery and discharged home the next day. Currently, the patient is asymptomatic and weaning off all antihypertensive medications.

covered stenting, recoarctation of the aorta, tube graft

PMC5412738_01

Male

A 67-year-old male patient (height 165 cm; body weight 88 kg), without previous cardiological history, was admitted to our emergency room for paroxysmal nocturnal dyspnea. The patient had reduction of functional capability and dyspnea (New York Heart Association functional class III) in the preceding months. He was on chronic therapy with enalapril for systemic hypertension. Electrocardiogram on admission showed atrial fibrillation with ventricular rate response of 100 beats/min, right bundle branch block and diffuse repolarization abnormalities. Physical examination revealed a 2/6 L holosystolic murmur over the aortic area, a fixed split of the second heartbeat and mild signs of pulmonary congestion. Transthoracic echocardiography showed normal size of the left ventricle, which was hypertrophic and with normal ejection fraction. Color-Doppler evaluation revealed left to right shunt in the basal portion of the interatrial septum without the involvement of the interventricular septum [Figure 1] and moderate mitral valve regurgitation. Right atrium was dilated, right ventricle was hypertrophic and mildly dilated (telediastolic diameter 49 mm) with moderate to severe tricuspid regurgitation. Systolic pulmonary artery pressure was 40 mmHg. Chest X-ray showed posterior bilateral pleural effusion, diffuse thickening of the interstitial peribronchial vascular tissue and enlargement of the cardiac shadow. For further evaluation, a transesophageal echocardiography was performed, confirming an atrial septal defect, ostium primum type, with left-to-right shunt [Figure 2]. Mitral valve appeared dysmorphic, fibrocalcific (compatible with a cleft of mitral valve's anterior leaflet) with moderate regurgitation. Subsequently, coronary angiography revealed no coronary artery disease. The patient underwent surgical closure with autologous pericardium patch (intraoperative measurement of the defect was 1,9 x 3 cm, localized in the caudal portion of the septum). During surgery, the patient developed complete atrioventricular block requiring permanent epicardial pacemaker implantation. Postoperative transthoracic echocardiography showed no residual atrial communication, with a slight reduction of the right sections dimensions and mild mitral regurgitation.

congenital heart disease, echocardiography, mitral cleft, ostium primum

PMC7968547_01

Female

A 63-year-old woman came to our hospital complaining of recurrent upper abdominal fullness discomfort for almost 10 years. She experienced exacerbation of intermittent nausea, vomiting with chyme (5 mL), heartburn, acid regurgitation, and eructation for 6 months. No history of hypertension, diabetes mellitus, or coronary heart disease was noted. Upon physical examination, a 5 x 4 cm mass with a hard texture and poor mobility was observed in the upper abdomen. Routine blood and tumor marker test results were within normal range. Abdomen computed tomography (CT, Figure 1A) showed a 32 mm x 22 mm soft tissue mass shadow with homogeneous density in the descending duodenum, which was protruding into the duodenal lumen. Moreover, thickening of the adjacent intestinal wall was noted. Upper abdomen magnetic resonance imaging (MRI, Figure 1B) revealed a significant thickening of the wall of the duodenal bulb and descending duodenum. The wall thickness was 1.1 cm. The signals were slightly low in T 1-weighted images and slightly high in T 2-weighted images. Endoscopic ultrasonography (Figure 1C and D) demonstrated that there was a protrusion in the duodenal bulb of about 26 x 18 mm in size with a clear boundary, smooth surface, and irregular shape and the base being about 17 mm, color signals abound. Neoplasm resection of duodenum was performed, and we found a mass measuring about 25 x 30 x 10 mm located in the descending duodenum. It was soft, brittle, and mobile with a clear boundary. The pathological result (Figure 2) of the mass revealed multiple Brunner's glands with tubes, fibers, and smooth muscle diffuse distribution. No dysplasia was noted on the epithelium. It was diagnosed as Brunner's gland adenoma of the duodenum. The patient was discharged from the hospital a week after recovery. To date, no relapse has occurred.

brunner’s glands, adenoma, benign tumor, duodenum

PMC7792877_01

Male

A 40-year-old male with loss of consciousness was referred to neurology ward (AL-Zahra Hospital) after controlling for the elevation of creatine phosphokinase (CPK) (4050 U/L) and creatine (Cr) levels (4.9 mg/dL) due to rhabdomyolysis and acute renal failure in nephrology department. Hemodialysis approach was performed for him. In neurology service, he complained paresthesia in the upper limb, myalgia, cramp, and weakness in the lower limb without fasciculation. He worked in a battery manufacturing company and had no past medical and drug history or drug abuser. On physical examination, tenderness and swelling in the right limb were detected. Given neurologic examination, the patient could not walk without aid, and generalized atrophy was seen without fasciculation. Force of muscle in upper limb both in proximal and distal was 5/5, in lower limb of the proximal part in the right side 1/5 and in left side 3/5, and in distal part was 0/5. Deep tendon reflex (DTR) was +2 in upper limb, +1 in left knee, 0 in left Achilles, and 0 in right knee and Achilles. Babinski was negative; stock sensory loss, abnormal position, and vibration sense in lower limb were detected. Laboratory data showed CPK (1315 unit/L), lactate dehydrogenase (LDH) (1550 unit/L), increased levels of liver enzymes (aspartate aminotransferase: 75 unit/L, alanine aminotransferase; 88 unit/L), gamma-glutamyl transferase level (152 unit/L and minimally elevated blood urea nitrogen (41 mg/dL), Cr (1.8 mg/dL), and thyroid-stimulating hormone (21.4 mu/l). Vasculitis test and ganglioside antibodies panel, cerebrospinal fluid (CSF) analysis, Brucella antibodies, hepatitis B surface antigen, hepatitis C virus Ab, and HIV Ab were all normal. Moreover, the urine toxin screen test for morphine was positive (only one time) and in second and third time was negative. BLL (6 months before this symptom) was 75 mug/dL, and it was rechecked again after hemodialysis in hospital, and the BLL in three separate times was 30, 10, and 12 mug/dL. In addition, mild polychromasia, hypochrome, and anisocytosis in blood smear were reported. CBC analysis showed that elevated level of leukocytosis (white blood cell: 15,800/mm3 and anemia (red blood cell: 3.50Mil/mm3, Hb: 10.6 g/dL, Hct32.6%) was reported. Electrophysiological test revealed a severe acute-subacute polyradiculoneuropathy with nonirritative proximal myopathy in lower limbs, without any evidence of compression neuropathy pattern. Magnetic resonance imaging (MRI) showed hyperintensity in the anterior and posterior compartment in both thighs (right > left) and also in paraspinal muscles in short-tau inversion recovery [Figure 1]. Thereafter, magnetic resonance neurography (MRN) was ordered, which showed multilobulated collection in the right gluteus muscle and right femur neck osteomyelitis; however, lumbosacral nerve roots were normal [Figure 2]. Normal Doppler sonography of limb and abdomen and pelvic sonography for rule out of deep venous thrombosis were performed which no evidence was found. First, with suspicious of autoimmune neuropathy, treatment was started with intravenous immunoglobulin (IVIG), but due to lack of efficacy and having allergy to drug, it was stopped. After, the first evaluation, with suspicious of nondiabetic polyradiculoneuropathy, the patient was treated with corticosteroids and due to MRN findings was referred to infectious service. After taking antibiotics without efficacy, corticosteroid regimen was stopped, and the patient was discharged. Three months later, he was admitted again in our neurology ward. On neurological examination, he was wheelchair-bound, like before generalized atrophy was seen but without fasciculation. Force of muscles decreased as 3 months ago, and DTR was absent in both upper and lower limbs. Again, vasculitis test and CSF analysis were normal. The normal level of myositis-specific antibodies panel was measured. Erythrocyte sedimentation rate, C-reactive protein, and tuberculosis antibodies were normal. Hemoglobin levels were measured 12, 11, 10.3, and 9.7 g/dL in different times. In new electromyography finding, a severe subacute lumbosacral polyradiculoneuropathy with proximal myopathy in the lower limb and paraspinal muscle was reported. Plasma exchanged was started without efficacy. In second lumbosacral MRI with Gadolinium enhancement of paraspinal muscles was reported [Figure 3]. In MRI of hip and thigh, hyperintensity in proximal muscles, particularly in the right side with avascular necrosis in the right femur neck, was noticed [Figure 4]. In addition, hyperintensity in anterior and posterior muscles in leg MRI was presented [Figure 5]. With these results, it was decided to take the patient to muscle biopsy, confirming the diagnosis. In muscle biopsy, severe necrosis was displayed, and in left sural nerve biopsy, a mild wall thickening in vessels without infiltration with no evidence of vasculitis was shown [Figure 6]. All paraclinical tests for acute polyradiculoneuropathy such as ganglioside antibodies panel, CSF analysis, and vasculitis test and also for necrotizing myopathy such as myositis-specific antibodies panel were performed, and we did not find any etiology except increased BLL (30 mug/dl). In retrograde examination, blue line in gum of the teeth was detected [Figure 7], and the patient was referred to poisoning specialist, and penicillamine (500 mg q8h) with pyridoxine (50 mg daily) for 8 months was started for him. Penicillamine is the only accessible drug for lead intoxication in Iran. After treatment, the BLL reached to 20 mug/d. In follow-up examination, the force of muscles in the proximal part of the lower limb was mildly improved (+3/5 in both sides), but the force of distal muscles was not improved (0/5). Finally, the patient was advised to monthly follow-up of BLL and neurologic exams.

case report, lead poisoning, muscle, necrosis, penicillamine, rhabdomyolysis

PMC2913650_01

Male

A 32-year-old married male, graduate, with stable premorbid personality traits, without any genetic loading, non-addict, normotensive, non-diabetic developed aberrant behaviour for the first time. This led to irregularities and inattentiveness at work, increasing global withdrawal, emotional aloofness, irritable and impulsive outbursts, neglect of personal hygiene and personal care, delusion of reference, fragmentary persecutory delusion, impaired judgement and insight for illness. The altered behaviour persisted for more than 6 months when he suddenly developed profound psychomotor retardation, inability to speak, tremulousness while walking and held anything that he came in contact with. He did not communicate any depressive symptom. His condition progressed to complete immobility with abnormal postures and mutism, and he needed assisted feeding. Response to strong noxious stimuli were absent although spontaneous movements were present. Although he slept most of the time, he nevertheless looked alert with his eyes chasing objects during the waking phase. There was no history of fever, lymphadenopathy or diarrhoea. No history of head injury, seizure or ear discharge was reported. He was diagnosed as a case of functional catatonia and was referred to our centre. General examination was within normal limits. There was no cutaneous lesion, oral thrush, hepatosplenomegaly or lymphadenopathy. Pulmonary tuberculosis was not evident both on clinical and radiological examination. Higher function examination revealed an extreme degree of hypokinesia, mutism and catalepsy for more than 30 seconds. He looked conscious, vigilant with positive eye-tracking movements, and loss of apparent condition-avoidance response. Orientation, attention, concentration, memory and judgement could not be commented upon due to mutism. His affect was blunt without weeping or laughing spells (no pseudobulbar pattern). Cerebellar signs could not be tested; mild motor ataxia was present. There was no sensory-motor deficit but bladder and bowel incontinence was present. A syndromic diagnosis of catatonia was made. The patient was subjected to a battery of investigations. Routine blood and urine examination, hepatic and renal function tests were within normal limits except mild iron deficiency anaemia; serum B12 and HbAIC levels were within the normal range. The optic fundus was normal. CSF pressure and biochemical parameters were normal and the VDRL test was negative. X-ray chest and USG abdomen were normal. CT scan revealed a single non-enhancing hypodense lesion in the left frontal cortex and mild cerebral atrophy for his age (Fig 1). After 7 days of hospitalization, the patient revealed positive grasp, rooting and glabellar tap reflexes, and right hemiparesis (grade III). At that point, considering the focal cerebral damage, he was categorized as a case of akinetic mutism. The patient was found to be positive for HIV-1 and -2, which was confirmed by the Western blot test. The total leucocyte count was 4990 cells/cmm, lymphocytes were 16%, the absolute lymphocyte count was 800 cells/cmm. The absolute CD3+ T lymphocyte count was 528 cells/cmm. The absolute CD4+ T helper cell count was 339 cells/cmm (normal range 337-1690 cells/cmm). Analysis was done using the flowcytometry method. MRI, done after 5 days of CT scan, revealed multiple, confluent, non-enhancing, discrete, asymmetric, subcortical white matter lesions, maximum in the frontoparieto-occipital and cerebellar regions without mass effect (Figs 2-5). Ante-mortem brain biopsy was not feasible. A final diagnosis of PML in AIDS was made for inducing the state of akinetic mutism.

aids, pml, akinetic mutism, catatonia

PMC5301086_01

Male

The patient was a 53-year-old man in good health without any major illnesses. He claimed that in a recent car accident, which had occurred 3 days before he reported to the clinic, his right eye was hit by a suddenly inflating airbag. In addition to severe pain, he suffered from a sudden-onset loss of vision. Based on the patient's description, his car was involved in a full frontal collision with a roadside sign as he was making a left turn. He was not wearing his seatbelt and was driving at a speed of 50 km/h. The first clinical examination revealed that his right eye was not perceptive to light. The visual acuity of his left eye was 0.8. The intraocular pressure (IOP) of his right and left eye was 12 and 15 mm Hg, respectively. Slit lamp examination revealed that the anterior segment was largely normal and did not exhibit corneal or scleral laceration. Dilated fundus examination revealed that his right eye had massive subretinal hemorrhage around the optic disc with macular involvement in addition to vitreous hemorrhage, while his left eye was normal. Although the resolution was poor due to vitreous hemorrhage, optical coherence tomography (OCT) revealed a hint of macular edema with subretinal fluid with a central retinal thickness of 436 mum (Fig. 1). After a week of observation, the right eye still had no perception to light. Therefore, the patient was advised to have an intravitreal injection of 0.3 mL sulfur hexafluoride (SF6) in the right eye. The patient agreed, and the injection was administered with him in the prone position. Four days after the injection, vision in the right eye had improved. The patient could recognize hand motion within a distance of 60 cm. The IOP was 12 mm Hg. Dilated fundus examination revealed significantly reduced subretinal macular hemorrhage, which was pushed to the periphery of the retina. It was also observed that the location of the choroidal rupture was on the superior and the temporal side of the macula. OCT results suggested that the macular edema had significantly reduced, and the central retinal thickness had decreased to 278 mum, but it still contained some subretinal fluid. Since the intraocular gas had nearly disappeared, it was subsequently recommended that the patient receive a second intravitreal injection of 0.3 mL SF6 in the right eye. One week after the injection, visual acuity of the right eye had improved to 0.03, but the subretinal hemorrhage and the vitreous hemorrhage conditions had not improved at all (Fig. 2), while the central retinal thickness had slightly increased to 319 mum. Since it was possible that a secondary choroidal neovascularization (CNV) had occurred, after fully informing the patient of the potential benefits and risks, we scheduled the patient for immediate intravitreal injection of 1.25 mg/0.05 mL bevacizumab in the right eye. Three weeks after the injection, the corrected visual acuity of the right eye had improved to 0.4, with only small amounts of residual subretinal hemorrhage at the superior, inferior, and nasal side of the eye. Vitreous hemorrhage had almost entirely disappeared as well. Fundus examination revealed a visible scar caused by the choroidal rupture. OCT results showed a complete absence of subretinal fluid, and the central retinal thickness had decreased to 210 mum. The location of the choroidal rupture was observed on fluorescein angiography, and dye leakage was not observed during the early or late phase (Fig. 3).

airbags, choroidal rupture, intravitreal bevacizumab, intravitreal sulfur hexafluoride

PMC7086868_01

Male

A 16-year-old adolescent was admitted to Princess Margaret Hospital, Hong Kong with high swinging fever up to 39.9 C for 5 days. He developed profuse diarrhoea with passage of greenish, watery, loose stools 1 day before admission. He also complained of dry cough, myalgia and general malaise. There was no running nose, chills, rigor, headache or shortness of breath. He resided in a housing estate (Amoy Garden) where a massive outbreak of SARS had occurred. There was no travel history or history of contact with SARS patients. General examination showed a febrile lethargic child with mild dehydration (ca. 5%). Examination of the abdomen showed mild epigastric tenderness but no organomegaly and bowel sounds were normal. There was no respiratory distress. Examination of the other systems was unremarkable. A chest X-ray film revealed right upper zone infiltrates (Fig. 1a). He was administered intravenous cefotaxime and oral clarithromycin to cover the usual organisms associated with community acquired pneumonia. Isolation in a negative pressure room was instituted in view of the epidemiological link to a SARS outbreak. His fever persisted after admission and a maximum temperature of 40 C was recorded on day 6 from onset of illness. He refused oral intake as he vomited after every meal. A pulse-temperature deficit resembling that of typhoid fever was noted on the observation chart (Fig. 2). On day 6 from onset of fever, intravenous ceftriaxone, the empiric treatment of choice for typhoid fever in our locality, was administered in place of cefotaxime. Ribavirin was commenced for suspected SARS in view of the lack of clinical response to the initial antibiotic regimen. His general condition did not improve and he continued to run a high swinging fever with malaise, epigastric pain, and persistent vomiting and diarrhoea. On day 8, intravenous hydrocortisone was instituted because of radiographic progression of the right upper lobe consolidation (Fig. 1b). Fever subsided 1 day after the initiation of hydrocortisone therapy and his general condition as well as the gastrointestinal symptoms improved rapidly. Radiological resolution was more gradual. Steroids were continued in the form of oral prednisolone after 4 days of intravenous hydrocortisone therapy and tailed off over 10 days. Ribavirin was given for a total of 10 days. Ceftriaxone and clarithromycin were discontinued after 7 days. He was kept under isolation and discharged on day 21 after onset of fever. The initial total white cell count was 4.4x109/l (reference range 4.0-10.0x109/l) with absolute neutrophil and lymphocyte counts of 3.2x109/l (reference range 2.0-7.0x109/l) and 0.9x109/l (reference range 1.0-3.0x109/l) respectively. The lowest lymphocyte count was 0.6x109/l which occurred on day 13. The initial platelet count was 132x109/l (reference range 150-600x109/l). Reactive thrombocytosis up to 635x109/l was noted on day 21. Haemoglobin level and the clotting profile were normal. C-reactive protein, erythrocyte sedimentation rate, creatine kinase and lactate dehydrogenase levels were not elevated. Alanine aminotransferase level was elevated to 472 IU/l (reference range 1-40 IU/l) on day 13. Total bilirubin was elevated up to 37 micromol/l (reference range 4-20 micromol/l) on day 15. No bacteria were recovered from stool and blood cultures. Widal serology was negative. Viral culture and reverse transcriptase polymerase chain reaction (RT-PCR) assay targeting severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were performed on nasopharyngeal aspirates, stool and urine samples. RT-PCR was positive in nasopharyngeal aspirates collected on days 5 and 12. RT-PCR was also positive in stool samples collected on days 8, 15, 19, 21 and 22. Viral culture was negative. Cold agglutinin titre was not raised and anti-mycoplasma IgM was negative. Paired acute and convalescent serum samples showed a rise in SARS-CoV titre (<25 on day 2, 25 on day 32, and 400 on day 118). No increase in antibody titres to influenza A and B, parainfluenza virus types 1, 2 and 3, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae and Chlamydia pneumoniae were demonstrated in convalescent serum samples.

PMC8551576_01

Female

A girl aged 12 years was hospitalized after eight months of unsuccessful treatment for disseminated pulmonary rifampin resistant tuberculosis (RR-TB) to determine further treatment tactics. A household contact with the father, who was ill with TB since 2016, was established; drug susceptibility data were absent. The girl was diagnosed with TB in December 2018 at the referral to a health facility with complaints of high temperature (39 S), expectoration, and weakness. Plain chest X-ray revealed infiltrative changes with cavities in the upper lobe of the left lung with multiple dissemination foci into both lungs. Ziehl-Neelsen sputum smear microscopy result was positive. The Xpert MTB/RIF assay determined resistance to rifampin. Chemotherapy was administered as follows: AmZELfx - three months; ZELfxEto - five months. The treatment outcome: a positive sputum smear result by microscopy, lack of positive X-ray dynamics. The BACTEC MGIT-960 detected growth of mycobacteria in culture. Multidrug resistance (MDR) of M. tuberculosis was established with the following spectrum: isoniazid, rifampin, ethambutol, pyrazinamide, ethionamide, levofloxacin, moxifloxacin, para-aminosalicylic acid (HREZEtoLfxMfxPAS). Susceptibility to amikacin, capreomycin, cycloserine, linezolid, bedaquiline (AmCmCsLzdBdq) was preserved. Chest computed tomography (CT) showed the presentations of disseminated pulmonary TB (Fig. 1). Considering the prior treatment failure due to drug resistance and severity of the disease, we used a personalized chemotherapy regimen (AmCsLzdBdq) adapted to the specific case. The chemotherapy regimen contained bedaquiline, which was a new drug with age restrictions for that moment: age 18 years or above. We obtained an informed consent for bedaquiline use from the patient's father. Amikacin was withdrawn after three months due to the toxic reaction (sensorineural hearing loss), and the treatment was continued with CsLzdBdq. We used three courses of bedaquiline due to life-saving considerations. Sputum conversion was observed after one month. Chest CT after 18 months of treatment showed significant resolution of infiltrates and dissemination foci in S 1, 2 of the left lung, cavity closure (Fig. 2). We did not observe cardiotoxic effects of the prolonged use of bedaquiline (the QTs interval did not change during the whole treatment course).

bedaquiline, children, mdr-tb, pulmonary tb, treatment

A fragment of the chest CT image before bedaquiline-containing chemotherapy: the areas of lung tissue consolidation with cavities in the upper lobe of the left lung. Multiple centrilobular foci, blending in some parts, in both lungs.

PMC8551576_01

Female

A girl aged 12 years was hospitalized after eight months of unsuccessful treatment for disseminated pulmonary rifampin resistant tuberculosis (RR-TB) to determine further treatment tactics. A household contact with the father, who was ill with TB since 2016, was established; drug susceptibility data were absent. The girl was diagnosed with TB in December 2018 at the referral to a health facility with complaints of high temperature (39 S), expectoration, and weakness. Plain chest X-ray revealed infiltrative changes with cavities in the upper lobe of the left lung with multiple dissemination foci into both lungs. Ziehl-Neelsen sputum smear microscopy result was positive. The Xpert MTB/RIF assay determined resistance to rifampin. Chemotherapy was administered as follows: AmZELfx - three months; ZELfxEto - five months. The treatment outcome: a positive sputum smear result by microscopy, lack of positive X-ray dynamics. The BACTEC MGIT-960 detected growth of mycobacteria in culture. Multidrug resistance (MDR) of M. tuberculosis was established with the following spectrum: isoniazid, rifampin, ethambutol, pyrazinamide, ethionamide, levofloxacin, moxifloxacin, para-aminosalicylic acid (HREZEtoLfxMfxPAS). Susceptibility to amikacin, capreomycin, cycloserine, linezolid, bedaquiline (AmCmCsLzdBdq) was preserved. Chest computed tomography (CT) showed the presentations of disseminated pulmonary TB (Fig. 1). Considering the prior treatment failure due to drug resistance and severity of the disease, we used a personalized chemotherapy regimen (AmCsLzdBdq) adapted to the specific case. The chemotherapy regimen contained bedaquiline, which was a new drug with age restrictions for that moment: age 18 years or above. We obtained an informed consent for bedaquiline use from the patient's father. Amikacin was withdrawn after three months due to the toxic reaction (sensorineural hearing loss), and the treatment was continued with CsLzdBdq. We used three courses of bedaquiline due to life-saving considerations. Sputum conversion was observed after one month. Chest CT after 18 months of treatment showed significant resolution of infiltrates and dissemination foci in S 1, 2 of the left lung, cavity closure (Fig. 2). We did not observe cardiotoxic effects of the prolonged use of bedaquiline (the QTs interval did not change during the whole treatment course).

bedaquiline, children, mdr-tb, pulmonary tb, treatment

A fragment of the chest CT image after 18-month bedaquiline-containing chemotherapy: residual changes after disseminated pulmonary TB in the form of single small solid foci in both lungs.

PMC10147527_01

Female

A 38-year-old woman was admitted to our emergency gynecologic unit referring amenorrhea lasting 9 weeks, inconstant pelvic pain, and vaginal bleeding that started 2 days earlier. She had three previous deliveries, all performed by at-term CS: the first one in 2004 for a twin pregnancy, and the other two in 2009 and 2011. All CS occurred successfully and without any complications. Her family and personal histories were negative for any disease. General physical examination was unremarkable and vital signs were within normal limits, with a heart rate of 90 bpm and a blood pressure of 105/60 mmHg. The abdomen was treatable by superficial palpation and painful on the deep one at the hypogastric site. The uterus had a pasty consistency, and the cervix was closed; no adnexal tenderness or pelvic swelling during the bimanual visit was appreciable; the speculum examination did not show blood loss from the uterine cervix. TVUS was carried out showing a uterus with a higher size (longitudinal diameter = 96 mm; latero-lateral diameter = 61 mm; and antero-posterior diameter = 48 mm). Uterine adnexa were regular in location and size with the presence of corpus luteum in the left ovary of 25 mm x 20 mm. No free fluid in Douglas' pouch was detected. In the cervico-isthmic site, inside the thickness of the uterine wall, a GS of 16 mm (corresponding to six gestational weeks) was detected with no embryonic echoes suggestive of heartbeat (Figure 1). The dosage of beta-human chorionic gonadotropin (beta-hCG) was 12,770 mU/mL, lower than the normal range for nine gestational weeks, ranging from 22,075 to 227,000 mU/mL. Considering the following findings: implantation on the site of previous cesarean wounds, stop of GS growth at six gestational weeks, absence of embryonic heartbeat on TVUS, and lower beta-hCG values, a diagnosis of CSP was done. First, spinal anesthesia was carried out, and the patient was placed in a gynecological position with a sterile operating field. Cleaning and disinfection of the surgical site were done. By a transvaginal way, after visualizing the cervix and putting the tenacula, we started the procedure by performing bladder retraction, considering the multiple previous CS. A 2-cm horizontal incision was made in the anterior cervix about 1 cm beneath the estimated vaginocervical fold, and the bladder was retracted using a swab on a stick. The uterus was pulled towards the contralateral side of the intended ligature, to allow for ample working space and visualization of the vessel bundle. Thus, permanent bilateral ligature of the cervical branch of the uterine artery was performed using a synthetic absorbable thread (Vicryl, CT2, 2-0, Ethicon, Johnson & Johnson, Spreitenbach, Switzerland). An eight-distal loop-shaped stitch on each side of the late absorbable thread was applied, under the guidance of the index finger placed in the cervical canal and lower uterine segment, allowing the uterine artery pulsation. The whole procedure was then repeated with the contralateral vessel bundle (Figure 2). The anterior vaginal wall and anterior cervical lip were reunited with a few interrupted stitches. A progressive dilation of the cervix up to 10 Hegar dilatators was carried out. A Foerster ring forceps was inserted into the cervico-isthmic cavity, and the entire GS was identified under ultrasound guidance and pulled out. Blood loss was negligible owing to the previous uterine ligation. Curettage of the uterine cavity ended the procedure. Finally, an utero-vaginal package was inserted. The patient was kept under observation, and the postoperative course was uneventful. Slight blood loss was observed after removing the package the following day. On the third day, beta-hCG was 223 mU/mL, and the patient was discharged following a TVUS control that showed a regular uterus, with normal endometrial thickness and cervix, absence of intrauterine blood clots or necrotic areas, and no free fluid in the Douglas pouch. The trophism of the cervix was found to be regular at follow-up. A week after discharge, the blood test was normal and beta-hCG values were 89 mU/mL. Four weeks later, beta-hCG was unremarkable and menstruation resumed regularly. One year later, she delivered a healthy female newborn by elective and uneventful CS.

PMC8325462_02

Male

A 40-year-old man presented with sudden-onset left-sided chest pain of two days duration. The pain was severe, pleuritic in nature and relieved by non-steroidal anti-inflammatory drugs (NSAIDS). There was a history of self-limited intermittent dry cough over the preceding 3 months and occasional exertional dyspnea. The patient gave a history of recurrent upper respiratory tract infections (URTIs) and a single episode of pneumonia in childhood. There was also a history of URTIs and bronchitis in adulthood for which he was prescribed brief courses of various antibiotics once or twice a year in recent years. Chest radiographs done during these more recent episodes were clear. There was no prior history of previous diagnosis of pulmonary tuberculosis (TB). He had a 10-year history of smoking which stopped 10 years prior to presentation. Physical examination revealed a respiratory rate of 20 cycles per minute, oxygen saturation of 98% on room air and vesicular breath sounds with reduced air entry at the bases. The remainder of the vital signs and physical examination were normal. Full blood count showed a total white blood cell count of 4.4x109/L (ref 4.0-11.0 x109 /L) with relative neutropenia and eosinophilia. Other parameters of the full blood count were within normal limits. Erythrocyte sedimentation rate (ESR) was 13 mm in the first hour and the HIV I and II screen was non-reactive. Chest radiograph and computed tomography (CT) scan are shown in Figure 1. A 12-lead electrocardiogram and cardiac troponins showed no evidence of myocardial ischemia or infarction. A 2D echocardiogram showed no regional wall motion abnormalities. D-dimer was within normal limits and angiography of pulmonary vessels showed no filling defect. Flexible bronchoscopy with bronchoalveolar lavage (BAL) showed a hyperemic and inflamed trachea down to the left main bronchus, lingula and left lower lobe with some patchy hyperemic spots. The right bronchopulmonary tree was unremarkable. Routine bacterial culture of BAL fluid revealed no growth and cytology showed features suggestive of chronic inflammation. He was placed on oral moxifloxacin 400mg daily and azithromycin 500mg daily was added to patient s regimen a few days later. The chest pain improved with antibiotic therapy and the patient was discharged home to complete a 10-day course of oral antibiotics. Acid-fast bacilli (AFB) smear performed on bronchoalveolar fluid became available after discharge and was positive. The patient was placed empirically on rifampicin, isoniazid, pyrazinamide, ethambutol (RHZE) and pyridoxine for presumed pulmonary TB while awaiting drug susceptibility testing. A few weeks after the commencement of RHZE, the report of the culture of the BAL fluid indicated the isolation of Mycobacterium chelonae subspecie abscessus and Mycobacterium immunogenum. No susceptibility data were made available. Anti-TB therapy was stopped and the patient was placed on Azithromycin and Rifampicin, which he took for about 10 months. He had a repeat bronchoscopy with BAL about 2 months after his initial presentation; all bacterial and mycobacterial cultures and cytology were negative and there were no abnormal findings on bronchoscopy. A chest X-Ray and CT scan at the end of therapy, almost a year after initial presentation showed no abnormality (Figure 2).

non-tuberculous mycobacteria, case report, immunocompetent, pneumonia, tuberculosis

PMC4584436_01

Male

A 28-year-old Indian male with chronic weakness, loss of appetite, and a pulsatile mass in the abdomen was referred to our department for radiological evaluation. The patient was normotensive, non-smoker, non-diabetic, and was admitted for alteration of his general state, including weight loss, dizziness, and mild fever (38 C) for past 1 month. Laboratory evaluation evidenced elevated white cell count [20,000 per cubic mm (normal 3000-11,000)] and C-reactive protein (CRP). Tuberculin skin test was positive. Blood culture result was negative for Staphylococcus and Streptococcus species, Salmonella, Gram-negative bacteria, such as Escherichia coli, Klebsiella, and Pseudomonas mycobacterium, and fungi, such as C. albicans and Aspergillus. The patient had no history of tuberculosis or any previous intravascular procedure. Abdominal ultrasound (USG) showed mild hepatosplenomegaly and multiple significantly enlarged, heterogeneous, necrotic, conglomerate retroperitoneal lymph nodes including periportal and peripancreatic nodes. Color flow Doppler examination demonstrated multiple variable-sized aneurysms of abdominal aorta with pulsatile flow in the center and thrombus at the periphery. A CT angiography of whole abdomen was performed and the images were evaluated using multiplanar reconstruction and 3D volume rendering techniques. The CT angiography revealed multiple saccular aneurysms with thin irregular walls, arising from the abdominal aorta [Figures 1 and 2]. Two aneurysms were seen, one at suprarenal aorta and measuring 5.2 x 2.5 cm and the other involving infrarenal abdominal aorta and measuring 4.5 x 4 cm. One of the aneurysms was causing near-total compression of right renal artery, resulting in chronic renal parenchymal changes secondary to ischemia [Figure 3]. Multiple enlarged (largest 2.8 cm in short-axis dimension) para-aortic lymph nodes were identified in the vicinity of the aneurysms showing evidence of internal necrosis [Figure 4]. No evidence of any abnormally enhancing mass lesion or bowel wall thickening could be identified. Screening of thorax for aneurysms was unremarkable. A USG-guided core biopsy of the retroperitoneal (pre-para aortic) lymph node was performed. The lymph node biopsy revealed central caseous necrotic material with epithelioid cells and macrophages consistent with tubercular etiology [Figure 5]. Based on the biopsy results, a presumptive diagnosis of tubercular aneurysm was made, and the patient was put on anti-tubercular treatment and advised surgical management of abdominal aortic aneurysms. On follow-up, the patient responded well to the anti-tubercular drug therapy, as there was reduction in the size of the retroperitoneal lymph nodes including pre-para aortic and peripancreatic nodes, as compared to previous pre-treatment scans. Post anti-tuberculosis treatment, the patient was advised open surgical/endovascular stenting procedures.

abdominal aorta, multidetector computerized tomography, mycotic aneurysm, systemic tuberculosis

PMC4614336_01

Female

A 13-year-old Bahraini girl initially presented to a private hospital with a two day history of agitation and new onset of severe continuous bitemporal headache associated with slurring of speech. She had no history of fever, trauma, drug intake or migraine. She had no other past medical history of significance. Her birth and developmental histories were normal. She always performed well in school. Her mother had a long history of a generalized seizure disorder, which was controlled with medication. Her other family members were healthy. She was investigated for a possible cranial lesion and/or seizure, with a brain CT scan and an electroencephalogram (EEG) performed, both of which were normal. The following day she reported both vague auditory and visual hallucinations as well as fatigue. She was seen by a psychiatrist and prescribed antipsychotics for psychosis. Over the following few days, her condition worsened with a new onset of generalized tonic clonic seizures lasting for two minutes. She then presented to the emergency department at our hospital and required pediatric intensive care unit admission for monitoring and further work up. Upon examination, she was afebrile. Her blood pressure, heart rate and saturation were within normal limits. She was opening her eyes spontaneously and obeying simple commands with occasional inappropriate speech. Her Glasgow Coma Scale was 13. Her pupils were constricted bilaterally with sluggish reaction to light. Fundoscopy was normal. Her muscle tone was decreased with generalized diminished deep tendon reflexes. Her plantar responses were equivocal. Her gait was normal. She had no signs of incoordination. Other systems examination were unremarkable. She developed further seizures with shallow breathing, for which she was intubated and started on midazolam infusion, intravenous phenytoin and phenobarbitone. Her EEG showed generalized delta rhythm with sharply contoured waves over the left frontotemporal region. Valproic acid, levetiracetam and clonazepam were all needed for seizure control. She was worked up for causes of neuropsychiatric diseases such as infectious and autoimmune encephalitis with extensive laboratory investigations including complete blood counts, ANA, anti-dsDNA, C3, C4, serum copper, ceruloplasmin, urine porphobilinogen and all were normal pending the result of anti-NMDAR-Ab. Her serological tests for herpes, influenza, EBV, CMV and RSV were negative except for mycoplasma IgM. She was started empirically on IV acyclovir and ceftriaxone along with oral clarithromycin. She received 1 g/kg/dose of intravenous immunoglobulins (IVIG) once daily for two days. Cerebrospinal fluid (CSF) analysis showed pleocytosis with WBC count of 60 cells/high power field (normal 0-5 cells/high power field) and 96% lymphocytes (normal 60-70% lymphocytes) with normal glucose and protein concentrations. CSF oligoclonal bands were negative. Polymerase chain reaction (PCR) analysis of the CSF for enterovirus, CMV, herpes, EBV and mycoplasma was negative. The antibiotics were discontinued when her blood and CSF cultures returned negative. Acyclovir was then discontinued upon obtaining negative PCR viral study of her CSF. Her brain and entire spine magnetic resonance imaging (MRI) scans showed a non-sectoral lesion that was of a high signal intensity in both tbl2 and FLAIR involving the grey and white matter of the left cerebellar hemisphere with no spinal involvement, suggestive of ADEM and less likely of an infectious process (Fig. 1). Having excluded infection and presuming "autoimmune etiology" we proceeded with an empiric trial of steroids and intravenous pulse methyl prednisolone 30 mg/kg/dose every six hours for five days which was given followed by maintenance with oral prednisolone. Anti-NMDAR-Ab assay from CSF, IgG isotype result was 1:16 (reference value 1:1). It was obtained by qualitative indirect immunofluorescence testing done at Bioscientia Institut fur Medizinische Diagnostik (Ingelheim am Rhein, Germany). The result was obtained three weeks after admission. Anti-NMDAR-Abs were not identified in her serum. High anti-NMDAR-Abs confirmed our suspicion of anti-NMDAR-Ab encephalitis. She was extubated around that time and noted to be in a catatonic state; mute, with reduced level of communication and poor appetite for food with periods of occasional agitation. She was responsive to pain, turning in bed with dystonic posturing, some choreoathetoid movements of the limbs and facial grimacing. She was accordingly started on trihexyphenidyl for dystonia and haloperidol for chorea and periodic agitation. Despite ongoing physiotherapy over a period of four weeks, she developed spasticity in her lower limbs for which baclofen was added. Her dystonia and choreoathetosis did not improve; accordingly she was given five sessions of plasmapheresis over ten days. A repeat MRI scan of her brain and entire spine showed complete resolution of the signal abnormality in the left cerebellar hemisphere with no spinal involvement (Fig. 2). She developed paralytic ileus with abdominal distension and was investigated with repeated ultrasound and CT scans of her abdomen, but neither showed any evidence of a tumor. Her family refused a follow up CSF study for anti-NMDAR-Abs. A multidisciplinary team approach was needed. During the acute stage of the disease, the intensivists' role was focusing on patient stabilization and intubation together with the neurologists for seizure control. Other specialist roles were involved in managing complications and rehabilitation including psychiatrists, physiotherapists, occupational therapists, speech therapists and nutritionists. Each specialists' individualized evaluation and recommendations were obtained regularly as well as a general consensus on patient care. Over the following two months, she showed signs of improvement with seizure control, decreased spasticity and improved speech. She continued to have occasional choreoathetoid movements. Her Modified Rankin Scale scored 4 (moderately severe disability, unable to attend to own bodily needs without assistance, and unable to walk unassisted). Anticonvulsants were weaned off over the following six months. She was followed up in the outpatient clinic and noted to improve remarkably with disappearance of the extrapyramidal symptoms, regaining normal functional mobility with good recall and fluent speech. Her Modified Rankin score reduced to stage 1 (no significant disability, able to carry out all usual activities, despite some symptoms) in one year and reached stage 0 (no symptoms) in two years time. She continued to have no evidence of malignancies.

acute disseminated encephalomyelitis (adem), anti-n-methyl-d-aspartate receptor antibody (anti-nmdar-ab), central nervous system (cns), encephalitis

PMC3960813_01

Male

A 62-year-old male patient, resident of West Bengal, was suffering from cough and chest pain for the last 6 months. He underwent initial management in a local hospital. He was a non-smoker and non-alcoholic. He had no history of fever, hematemesis, malena, diarrhea, headache, or body ache. He had not suffered from diseases like tuberculosis, asthma, chronic obstructive pulmonary disease (COPD), or gastroesophageal reflux disease (GERD). He was not taking any drugs at that time. Initial clinical evaluation in the local hospital revealed that the patient had moderate pallor, cachexia but no lymphadenopathy. Auscultation of chest showed bilateral normal breath sounds, Chest radiograph showed a small left-sided pleural effusion. Routine hematological investigations detected pancytopenia with hemoglobin level of 7.7 g/dl. Erythrocyte Sedimentation Rate was 100 mm/h. Mantoux test for tuberculosis was negative. Sputum culture for acid-fast bacilli (AFB) was negative. Ziehl-Neelsen stain of the sputum smears was also negative for AFB. The patient was prescribed antitussives and analgesics, but no significant improvement occurred. He was then referred to our hospital for further management. After examining the patient, we obtained another chest radiograph that confirmed the presence of a small left-sided pleural effusion [Figure 1]. Known causes of pleural effusion like heart failure, pneumonia, tuberculosis, or carcinoma of lung were absent in this patient. He did not have any symptoms of arthritis, which is commonly found in autoimmune diseases. Therefore, the cause of pleural effusion remained unexplained. On thorough examination, a mild splenomegaly was detected. To detect the cause of splenomegaly, serum bilirubin, liver enzymes, and prothrombin time were estimated which were within normal limits. HBsAg, anti-HCV and anti-HIV antibodies were negative by ELISA technique. Widal test for enteric fever and test for malaria antigens were negative. Total serum protein estimation was done, which was found to be within normal limits. However, the albumin/globulin ratio was reversed, being 0.2. Napier's aldehyde test was then performed which is based on the principle of hypergammaglobulinemia, that occurs in VL. About 1 ml of patient's serum was mixed well with a drop of 40% formalin, shaken and kept at room temperature. Opacification and solidification of serum was seen after 10 min signifying a positive result. Subsequently, bone-marrow aspiration was undertaken, which showed both intracellular and extracellular amastigote forms of L. donovani. Slight excess of plasma cells was also noted [Figure 2]. The patient was treated with IV Sodium Stibogluconate with prompt clinical and laboratory improvement. Chest radiograph was done after 1 month, which showed resolution of preceding pleural effusion [Figure 3]. He was on follow-up for another 6 months, which was uneventful.

immunocompetent patient, pleural effusion, visceral leishmaniasis

PMC8861510_01

Female

A 61-year-old woman presented to our department with a 3-week history of progressive bilateral weakness of her lower limbs. She had severe walking impairment with associated dizziness, headache, nausea, and vomiting. Although in good spirits, she reported anorexia, insomnia, and urinary and fecal incontinence, with a recent 5-kg weight loss. The patient denied a history of hypertensive disease, diabetes mellitus, and infectious diseases, such as hepatitis and tuberculosis. She also denied a history of respiratory symptoms such as fever, dyspnea, cough, and sputum. She had no food or drug allergies and no familial genetic disorders. She denied tobacco or alcohol use and had no history of surgery or trauma. On the first admission, the patient's vital signs were stable, body temperature was normal (37.0 C), blood pressure was 153/92 mmHg, heart rate was 86 beats per minute, and the breath sounds and respiratory rate were normal. Her speech was initially fluent. Her pupils were equal in size, 3-mm diameter, and reacted appropriately to light. No apparent ocular muscle weakness was present, although she had horizontal nystagmus. There was no facial muscle weakness, and her tongue extension was centered. The muscle strength of both upper limbs was normal. Kernig's sign was negative. At the presentation, the examination was notable for movement disorders having grade -1 muscle strength in both her lower limbs, with active tendon reflexes. The swelling was observed in her left lower limb. The Babinski and Chaddock reflexes were positive bilaterally. There was a profound sensory disturbance with hypoesthesia at the T6 level and below with reduced vibration sense. The bilateral finger-nose and rapidly alternating tests were normal when testing for cerebellar dysfunction, but she could not perform the bilateral heel-knee-shin test. On the 2nd day after admission, the patient developed severe chest pain with intermittent nausea and vomiting, chest tightness, and dyspnea. After the blood test and imaging results were available, she was diagnosed with PE. During hospitalization, about 2 weeks after the admission, the patient developed a progressively worsening speech disturbance. The patient can understand others but is not fluent in her speech. Before discharge, that patient was in poor condition. She was indifferent to answering any questions. Her vital signs and other physical examinations were the same as her admission. The patient tested arterial oxygen saturation at the time of the dyspnea and chest pain, indicating a partial oxygen pressure of 63 mmHg. The D-dimer blood level was elevated, 11.26 mug/ml (normal range: 0-1 mug/ml). The cerebrospinal fluid (CSF) was yellow with elevated pressure, >400 mmH2O. CSF examination showed elevated protein level 30.81 g/l (normal range: 0.15-0.45 g/l), but low levels of glucose, 1.6 mmol/l (normal range: 2.3-4.1 mmol/l), and chloride, 110 mmol/l (normal range: 119-129 mmol/l). Moreover, for the white cell count (WBC-BF: 34.00 x 106/l), 96.0% of the content comprised lymphocytes and 4.0% monocytes; however, the red blood cell count was 0/L. Brain 3T MRI [ Figure 1A (1-4)] showed lesions in the corpus callosum and the left lateral periventricular area. Combined with the MR spectroscopy results, the lesions were considered tumors. Spectroscopic metabolite analysis at the corpus callosum lesion showed a low N-acetyl aspartate peak and increased choline. Cervical-spine MRI [ Figure 1B (1-2)] showed high-intensity signaling in the spinal cord at the C2-C7 vertebra levels and abnormal enhancement in the spinal cord at the C5-T4 vertebrae. Positron emission tomography-computed whole-body imaging showed limited hypermetabolic foci in the corpus callosum and diffused metabolic increases in the spinal cord cervicothoracic and lumbosacral regions, which were suggestive of malignancy. No hypermetabolic changes were observed in other organs, including the lungs. Ultrasound scanning of the lower extremities suggested the presence of thrombosis in the left common femoral vein and bilateral intermuscular veins (acute stage, complete type). A pulmonary computed tomography angiogram ( Figures 2A, B ) showed multiple bilateral pulmonary-artery embolisms. Biopsy showed that the pathological diagnosis was grade IV glioblastoma with necrosis not otherwise specified. Immunohistochemistry staining ( Figure 3 ) results were CD20(-), CD3(-), CD79a (-), PAX-5(-), LCA (-), Ki-67(>40%), GFAP (+), Olig-2(+), ATRX (+), MAP2(+), P53(+30%), IDH1R132H mutation (-), MGMT (+30%), MBP (-), NeuN (-), Syn (+), vimentin (+), nestin (+), CD56(+), H3K27me3(+), and H3K27M mutation (+). According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System, this case lacked molecular test results; there was insufficient evidence to classify this case as a distinct disease entity. The biopsy tissues were obtained from the corpus callosum, and the lesions are shown in brain MRI (in Figure 1 , lesions marked with arrows). The family and patient decided that palliative care was the best option for the brain and spinal cord gliomas because she felt severely unwell and had non-operable multicentric midline GBM lesions. The patient developed deep vein thrombosis (VTE) and PE during hospitalization. Therefore, she was administered rivaroxaban 15 mg orally twice daily for the first 3 weeks. After the follow-up, we learned that the patient gradually became unconscious at home, and his respiratory and cardiac functions gradually worsened. The patient died 42 days after hospital discharge. The time from symptom onset to death was approximately 3 months.

h3k27m-mutant glioblastoma, brain glioblastoma, case report, multicentric glioblastoma, pulmonary embolism, spinal glioblastoma

PMC7609909_01

Female

A 52-year-old woman was admitted with intermittent headache lasting for 5 months. The patient's headache gradually worsened 1 week before admission, and vomiting occurred 2 days before hospitalization. Physical examination revealed normal findings. The patient had a history of hypertension and hyperlipidemia. No abnormality was found in the laboratory test results, which included blood routine examination, C-reactive protein, and erythrocyte sedimentation rate measurement. The serum tuberculosis antibody, toxoplasma antibody, and tumor markers were all negative. Serologic tests revealed positive results of the T. pallidum particle agglutination (TPPA) and toluidine red unheated serum test (TRUST), with a TRUST titer of 1:64. The human immunodeficiency virus (HIV) test was negative. Cerebrospinal fluid (CSF) examination was not performed. The patient denied any history related to venereal diseases, and the skin mucous membrane was free of rash and erythema. Conventional MR, proton MR spectroscopy, and perfusion MRI were carried out in the patient. All MR images were obtained using a 3.0 T clinical MR scanner (Discovery MR750, General Electric Healthcare, Milwaukee, WI, United States) with an eight-channel head coil. The conventional MRI sequences and parameters were as follows: axial T2-weighted imaging [repetition time (TR)/echo time (TE) = 5,200/90 ms, matrix = 512 x 512, field of view (FOV) = 24 cm, thickness = 5 mm, gap = 1.5 mm], axial T1-weighted imaging (TR/TE 1,750/25 ms, matrix = 320 x 256, FOV = 24 cm, thickness = 5 mm, gap = 1.5 mm), and diffusion-weighted imaging (TR/TE = 3,000/10 ms, matrix = 160 x 160, FOV = 24 cm, thickness = 5 mm, gap = 1.5 mm, b-value = 0, 1,000). Axial, sagittal, and coronal T1-weighted images after injection of gadolinium contrast agent (0.1 mmol/kg) were acquired. Perfusion imaging was performed by using a three-dimensional pseudo-continuous arterial spin labeling (ASL) technique with the specific imaging parameters: TR/TE = 4,600/10 ms, PLD = 1,525 ms, matrix = 128 x 128, FOV = 24 cm, thickness = 4 mm. ASL images were transferred to the workstation (ADW4.6, General Electric Healthcare) for post-processing and analyzed using FuncTool software (General Electric Healthcare) with the quantitative perfusion cerebral blood flow (CBF) map. Proton MR spectroscopy was obtained using a single-voxel point-resolved spectroscopy sequence (TR = 1,500 ms, TE = 35 ms). A volume of interest of 2 x 2 x 2 cm3 was selected from the lesion identified on the T2-weighted imaging sequence, and saturation bands were placed around the voxel. The process of shimming and water suppression was completed by the automatic pre-scanning program, making the bandwidth <7 and water suppression >97%. The MR machine's individual configuration software was applied to complete the correction of the baseline, identification of each compound, and analysis of peak value and ratio of each compound. MRI (Figures 1A-C) revealed multiple nodules with evident perilesional edema in the right temporal lobe, which was characterized by hypointensity on T1-weighted images, mostly hyperintensity on T2-weighted images, and slight hyperintensity on diffusion-weighted imaging. Contrast-enhanced T1-weighted images (Figures 1D-F) showed significant enhancement of the nodules and adjacent meninges ("dural tail"). In addition, the right ventricle was compressed and the middle line structure was skewed to the left. Single-voxel MR spectroscopy with an echo time of 35 ms (Figures 2A,B) revealed a slightly increased choline (Cho) peak and a slight decrease in the peaks of creatine (Cr) and N-acetylaspartate (NAA). The Cho/Cr and Cho/NAA ratio over the lesion was 1.24 and 0.932, respectively. A peak rising between 0.9 and 1.3 ppm represented the lipid/lactate. Perfusion MRI (Figure 2C) suggested that regional CBF in the nodule area was lower than that of the contralateral normal regions, with the highest relative CBF value of 0.84 in the lesion area, while the edema area around the lesion presented less perfusion. Merely based on the clinical manifestations, laboratory results, and conventional MR images, the diagnosis of inflammatory granuloma should be first suspected, while a differential diagnosis including neoplastic lesions such as meningiomas and brain metastasis should also be considered. However, the findings of advanced techniques such as MR spectroscopy and MR perfusion provide more clues in diagnosing inflammatory granuloma and have effectively ruled out meningioma and brain metastasis. Considering the evident mass effect of the lesion, the patient underwent surgical resection of the nodules. During the surgery, multiple solid nodules were seen protruding from the dura of the temporal lobe into the adjacent cerebral cortex and had an unclear boundary, hard and brittle texture, and general blood supply. Severe edema in the brain tissue of the right temporal lobe was also observed. Post-operative pathology (Figure 3) revealed granulation tissue with ischemic necrosis surrounded by multinucleated giant cells, plasmacytes, and lymphocytes. Based on the above findings, the clinical diagnosis of cerebral syphilitic gumma was made. Penicillin treatment (18 million U/day) was given for 2 weeks after the operation, and the patient's symptoms were relieved gradually. On the seventh day post-op, the patient was examined with non-contrast computed tomography (CT). The post-op CT (Figure 1G) showed no nodules, and a certain amount of hypodense edematous zone could be found on the right temporal lobe. After 6 months, the patient's headache disappeared completely.

mr perfusion, mr spectroscopy cerebral syphilitic gumma, brain tumor, cerebral syphilitic gumma, magnetic resonance imaging

PMC3203977_01

Male

We report the case of a 24-year-old man who presented progressive precordial pain and dyspnea that had worsened in the last six months prior to the consultation with no previous history of arterial hypertension, dyslipidemia, smoking habits, or infectious diseases, such as syphilis or immunodeficiency syndrome. The physical examination showed no signs of congenital syndromes and revealed only severe systolic murmur in the aortic focus. Preoperative examinations were conducted as routine. Laboratory tests as well as the chest radiograph were unchanged. The electrocardiogram showed sinus rhythm, incomplete right bundle branch block and moderate left ventricular hypertrophy. The echocardiogram revealed aortic stenosis caused by a thickened aortic valve, which determined a gradient of 65 mmHg, left ventricular ejection fraction of 0.63, ascending aortic diameter of 30 mm, and systolic and diastolic diameters of 32 and 48 mm, respectively. Then, we proposed the surgery for aortic valve replacement. The procedure was performed by median sternotomy. After the pericardiotomy, we noticed an uncommon aspect of the ascending aorta, with an irregular surface and thinned dilated areas with soft superficial texture (Figure 1). Aortic cannulation was performed above and medial to the innominate artery, and right atrial cannulation was performed through the right atrial appendage. A left ventricular vent was placed via the right superior pulmonary vein. After total heparinization, cardiopulmonary bypass was then established, the aorta was cross-clamped and a transverse aortotomy was performed. The internal aspect of the vessel was thickened, with multiple focal cavities of different sizes corresponding to the external dilatations; no thrombi were found (Figure 2). Antegrade cold blood cardioplegic solution was infused every twenty minutes. The three thickened aortic leaflets, as well as the anterolateral convexity and anteromedial concavity of the aorta were excised, leaving the posterior one third, macroscopically normal, to serve as support tissue to the vascular prosthesis that would be placed. Samples were submitted for histological study, and the procedure was completed. The prosthesis implanted was a mechanical no. 21; a Dacron tube prosthesis (no. 24) was positioned in replacement of the ascending aorta above the coronary ostia. De-airing was performed through a catheter placed in the tube; the aortic cross-clamp was removed. As the heartbeats became effective, the cardiopulmonary bypass was ended, and the surgery was finalized as usual. The patient was sent to the intensive care unit, where he remained for one day. He was then discharged by the tenth day in good health. He recovered and has lived until the present moment without complications. The histopathological findings were ascending aorta with areas of intimal fibrosis with dystrophic calcification consistent with arteriosclerosis. Areas of medial cystic degeneration with saccular dilations were observed to be diffusely distributed; inflammation was absent (Figure 3-A,B,C). The aortic leaflets were fibrous with myxomatous degeneration and dystrophic calcification. The loss of smooth muscle cells was markedly important, as was the deposition of extracellular matrix following the degeneration. Angiotomography of the aorta was performed post-operatively and showed no other injuries in the aorta. Furthermore, the prosthetic graft in the ascending aorta and the mechanic valve prosthesis in the aortic position were properly positioned (Figure 4). Some laboratory tests were performed in order to try to identify infectious diseases, such as syphilis and HIV, and autoimmune diseases, such as vasculitis, with no positive results.

PMC2822302_02

Male

Patient 3 was a 22-yr-old man who had suffered from tuberculosis, lymphadenitis, hepatitis, enteric fever, meningitis, and Behcet's disease since he was 6 yr old. The following bacterial species were isolated: group B Salmonella spp. in his blood, liver biopsy and stool; coagulase negative Staphylococcus in bile; and Enterococcus in urine.

PMC8088537_01

Male

A 25-year-old male with known case of disseminated tuberculosis (TB), hepatitis C, and human immunodeficiency virus (HIV) presented with a progressive paraparesis and loss of sphincter control (T8 level) of 2 months duration. He had already been on antitubercular therapy for the prior 8 months and had been taking antiretroviral therapy medication for HIV since 2018, although on an irregular basis.

intradural extramedullary, spine, tuberculosis

PMC9728212_01

Male

In a 44-year-old male who recently immigrated from Bosnia-Herzegovina to Austria, computed tomography for an episode of acute pancreatitis revealed pancreatic pseudocysts, mild ascites and peritonitis. Due to proven alcohol abuse and furthermore unremarkable medical history no further investigation was forced, and the patient was discharged from the Department of Surgery after conservative therapy. About six months later, he was readmitted to the Department of Internal Medicine due to abdominal pain and massive ascites. Surprisingly, paracentesis (8,000 ml) produced morphological chylous ascites (Fig. 1) with triglyceride levels of 1,999 mg/dl. Further investigation revealed regular liver (serum) and pancreatic (serum and ascites) enzymes, and was unremarkable for malignancy or bacterial and fungal infection. Technetium scintigraphy excluded leaks of the lymphatic system as a consequence of pancreatitis. Despite discharge after clinical stabilisation, he had to be re-admitted six weeks later, presenting with massive weight gain (19 kg) and deterioration of his general condition. Another paracentesis revealed chylous ascites (16,000 ml) without further hints regarding microbial or cytologic diagnosis. Measurement of hepatic venous pressure gradient (HVPG: 4 mmHg) excluded idiopathic portal hypertension for any reason. Thereafter, screening for debatable parasite infestation revealed positive IgG for S. stercoralis and negative results for Trichinella, Ascaris, Toxocara, Taenia solium, Echinococcus and Fasciola serology. Tests for human immunodeficiency virus (HIV), mycobacterium tuberculosis, human T-cell lymphotropic virus (HTLV), and stool microscopy for parasites were negative. Exposure to the pathogen may have taken place while the patient was working and sleeping at construction sites with poor sanitation in Bosnia-Herzegovina, a work environment for migrants from all over the world, as detailed history revealed. History and clinical examination were negative for any skin rashes. Before treatment initiation with ivermectin (0.23 mg/kg BW per os/qd, i.e. 21 mg), another paracentesis had to be performed as the patient deteriorated again, with dyspnoea. As chylous ascites was still present, a sample was sent to the Institute of Specific Prophylaxis and Tropical Medicine at the Medical University of Vienna, questioning whether S. stercoralis might be detectable in ascites as well, which finally could be proven only by PCR revealing strongyloides DNA, whereas repeated stool tests remained negative. After treatment, neither ascites nor general condition showed clinical improvement on follow-up visits. Thus, a second cycle of Ivermectin was initiated, but this time on two occasions, 2 weeks apart . After this the patient improved significantly, with a gain in appetite and stabilisation of body weight within the next visits. A last paracentesis revealed chylous fluid, however, without detectable strongyloides DNA. Diuretic treatment was reduced consecutively, and finally completely withdrawn, without recurrence of ascites.

strongyloides stercoralis, strongyloidiasis, chylous ascites, immigration, ivermectin

PMC4802090_01

Unknown

Tuberculosis (TB) cases are on the rise more so in developing countries. According to and), TB is foremost among diseases that cause mortality worldwide. The statistics indicate that 8.6 million people were infected with this disease in 2012 and the death due to the disease was about 8.6 million of which about a quarter were people who had been diagnosed positive for HIV. Many of these deaths could have been averted through treatment. Among the cases worldwide, South East Asia tops the list with 29% followed by Africa (27%), and Western Pacific regions (19%). The two largest populated nations of the world also recorded high incidence of TB cases with India accounting for 26% and China registering 12%. The incidence of TB cases is significantly lower in developed countries. Coinfection of TB with HIV is on the rise. According to the Global TB Report 2013, among those who were infected with TB in 2012, HIV positive persons constituted about 13% off the total number. Further cause for worry is the emergence of multi-drug resistant TB cases worldwide estimated to be 450,000 for the same year with about 170,000 deaths being attributed to it. Although the incidence of TB infection and death due to the disease is higher among men than women, it is among the top three causes of death for women. Of the 8.6 million new cases of TB globally in 2012, a third of them were women. Coinfection with HIV was responsible for the death of 160,000 of the 450,000 women who died of TB in 2012. Children under 15 years old represented 6% of TB cases worldwide and 8% of the mortality among HIV negative TB cases were children. According to), TB can have detrimental effect on the economic situations of individuals and nations as most active cases of TB occur in persons between the ages of 19 and 49. It is during this phase of their lives that people are actively involved in their career and contribute towards a nation's Gross Domestic Product (GDP). Table 3 describes the patients according to category of cases. Majority of them were new cases (87.5%), 3 of them were treatment after interruption, there was 1 case each (2.5%) for relapse and treatment failure.

PMC6661416_01

Female

An 8-year old female presented for evaluation in February 2003 after several months of syncopal and near syncopal episodes. Her past history was only remarkable for a severe respiratory infection at an age of 6 years. She was diagnosed with idiopathic pulmonary arterial hypertension and no cause of pulmonary vascular disease has been identified throughout her life (Table 1). Table 2 lists the medications that were being used for long-term outpatient care and the medications that were used for acute vasodilator testing at the time of her hemodynamic evaluations. She consistently showed a marked decrease in mean pulmonary arterial pressure (mPAP) while breathing 20 parts per million (ppm) inhaled nitric oxide (iNO). The response occurs within 30-60 seconds as illustrated in Fig. 1 by the MPAP and abrupt change in the intensity of the second heart sound by acoustic cardiography. She presented before the Sitbon criterion was published to identify patients that might respond favorably to calcium channel blocker (CCB) therapy. She was initially treated as an outpatient with medications that target the nitric oxide pathway of signal transduction, including sildenafil and intermittent transdermal nitroglycerin. Due to her history of syncope, iNO was approved for short-term emergency treatment by the Institutional Review Board of the University of Utah and an investigator sponsored Investigational New Drug application with the United States Food and Drug Administration. A delivery system was provided by Pulmonox and a source of nitric oxide was provided by SensorMedics, a subsidiary of VIASYS Healthcare. She had no subsequent episodes of syncope. However, she could only be treated with iNO transiently for periods of 10-15 minutes a few times a day. Her mPAP progressively increased with this treatment strategy. She had little or no acute pulmonary vasodilator response to sildenafil or nitroglycerin during subsequent hemodynamic evaluations. Fig. 2 illustrates that sildenafil and tadalafil did not even prolong the pulmonary vasodilatory effect of iNO. Her mPAP decreased when she was treated acutely with intravenous diltiazem during her second hemodynamic evaluation. Thereafter, sildenafil and nitroglycerin were discontinued and amlodipine has been the mainstay of her outpatient therapy. Fig. 3 illustrates the impact of long-term outpatient therapy on her baseline ratio of pulmonary to systemic vascular resistance (Rp:Rs) over time. Treatment with amlodipine therapy has been associated with a decrease in mPAP, Rp and Rp:Rs; however, these measurements have not decreased to levels that are readily achieved with iNO. The dose of amlodipine has been limited by severe gingival hyperplasia. An increase in mPAP was observed while she was entering puberty at 12 years of age. She also experienced an adverse reaction to minocycline at 13-14 years of age with an increase in anti-nuclear antibody and an increase in serum transaminases. A four-month trial of nighttime iNO was approved by the Institutional Review Board of the University of Utah and a modified investigator sponsored Investigational New Drug application with the United States Food and Drug Administration. A delivery system and a source of nitric oxide were provided by INO Therapeutics. This trial was completed without complications. We did not have a delivery system or funding to continue treatment at home long-term. She was too young to be enrolled in clinical trials with iNO using an investigational outpatient delivery system. She had no decrease in mPAP when treated acutely with l-arginine. Riociguat was added to her outpatient regimen after an oral dose acutely decreased her mPAP. However, the dose of riociguat has been limited due to severe pain associated with gastroesophageal reflux despite treatment with multiple antacids. Of note, she developed severe exertional dyspnea and near syncope when a specialty pharmacy instructed her to stop amlodipine after starting riociguat. Her symptoms improved when the amlodipine was resumed. She had a limited acute response to epoprostenol and has not been treated with a prostacyclin analog as an outpatient. She has not been treated with an endothelin receptor antagonist.

calcium channel blocker, guanylate cyclase, nitric oxide, nitric oxide synthase, pulmonary hypertension, vasodilator testing, calcium channel blocker(s), ccb, inhaled nitric oxide, ino, mean pulmonary arterial pressure, mpap, parts per million, ppm

PMC8995639_01

Male

A 65-year-old male patient presented our clinic with a 4-year history of recalcitrant skin lesions. He was being treated as presumptive clinical diagnosis as verruca vulgaris with multiple topical therapies, including creams containing 5-fluorouracil, salicylate, retinoids, 40% urea, and cryotherapy. Despite the medical interventions, the lesion has been growing steadily. At the first visit, a well-demarcated, hyperkeratotic verrucous plaque on the thenar region of his left hand was observed. The plaque had a surface area of 10 cm2 and was extending dorsally over the first interdigital fold (Fig. 1a). Except for the plaque, the patient's physical examination was unremarkable. On further questioning, the patient revealed that he had cared for a cow for a month for the religious "Feast of Sacrifice" 5 years ago. Due to the lesion's unresponsiveness to conventional verruca therapies, a tuberculin skin test (TST), a skin biopsy for histological examination, polymerase chain reaction, and culture were performed. Histological sections showed epidermal hyperplasia and dermal noncaseous granulomas (Fig. 2a). TST resulted in 12-mm induration (Fig. 2b). The culture and polymerase chain reaction test results were positive for M. bovis. Based on clinical and laboratory findings, TBVC was diagnosed. Further diagnostic procedures revealed no other systemic involvement. Due to the patient's objection to therapy with a multiple drug regimen, an intralesional BCG injection was planned. A suspension from freeze-dried powder containing attenuated bacilli of M. bovis (prepared from a BCG culture [OncoTice ]) was prepared according to the manufacturer's instructions. 12.5 mg powderized BCG was diluted in 50 mL serum physiologic to obtain a suspension containing 0.4-1.6 x 107 CFU/mL. A total volume of 2,083 mL BCG was injected into a 10 cm2-plaque intralesionally (0.2 mL per cm2). The injected dose was calculated according to the ratio of one dose of OncoTice to the mean urothelium surface area of an adult male without prostatic symptoms, which is 50 mL-240 cm2. On the third day after the injection, an inflammatory reaction was observed. The plaque became edematous, erythematous (Fig. 3-f1). The patient had a fever of 38 C concurrently, which continued for one and a half day and was reduced with cold compresses. On the 10th day, erythema and edema were regressed, and the lesional area began to desquamate (Fig. 3-i1). On the 18th day, suppurative foci on the hand dorsum emerged and were drained by puncturing (Fig. 3-l1). Finally, on the 40th day, signs of acute inflammation were subsided without leaving any scars, and the lesional area shrank from 10 cm2 to 2.0 cm2 (Fig. 3-o1) (Fig. 1b). After that, the patient had to relocate to another city and was lost to our follow-up.

bacillus calmette-guérin, immunotherapy, tuberculosis verrucosa cutis

PMC4369642_01

Male

A 23-year-old male, previously healthy, was admitted to the emergency room following a cerebral gunshot wound, at close range, from a hand gun. On admission, the patient presented with a Glasgow Coma Score (GCS) of 14 (E4 + M6 + V4), obeyed commands, had normal pupil responses and extremity movement, yet was agitated and restless. Respiratory and circulatory parameters were stable. The entrance was located just behind the right ear, no exit wound was visible. Subsequently, the patient was sedated, intubated, and a full body CT-scan was performed, revealing no extracranial injuries. A CT-scan of the head revealed several bone fragments in the right temporal lobe below the entrance of the bullet (Figure 1A), which progressed through the brain with a bihemispheric central and transventricular trajectory. Along the route, intraparenchymal- and subarachnoid-hemorrhages were present (Figure 1B). The patient underwent wound revision and monitoring neurosurgery, receiving a Licox brain tissue oximetry device (PBtO2; Integra LifeSciences, Plainsboro, NJ, USA), an intracerebral microdialysis catheter (CMA70, Microdialysis AB, Stockholm, Sweden), an intracranial pressure (ICP) device (Codman DePuy Synthes, Johnson & Johnson Medical, New Brunswick, NJ, USA), and an extra-ventricular drain (Medtronic, Minneapolis, MN, USA). The patient was transferred to the neuro-intensive care unit for further treatment. During the following day, the patient deteriorated with an increased ICP, increased intracerebral lactate:pyruvate ratio (LPR), and increased serum levels of the biomarker S100B (Figure 2). This prompted an increase in administration of sedatives (propofol and midazolam), iterative doses of hypertonic saline, and infusion of pentobarbiturates. Despite this, the ICP remained elevated. The neurosurgeon on call decided to perform a hemicraniectomy in order to improve the intracranial conditions. Following the procedure, the ICP returned to normal levels (<20 mmHg), although the LPR remained high (>40) (Figure 2). The post-operative CT-scan revealed hypodense areas, indicating edema or that the tissue was at risk for ischemia, primarily in the cerebral areas supplied by the posterior circulation (Figure 3). On day 7 post-trauma, the patient deteriorated further, with increasing LPR and S100B levels, yet normal cerebral oxygenation (PBtO2 >15mm Hg), hence not indicating ischemia, though perhaps an ongoing mitochondrial dysfunction with a metabolic crisis. This lead to the initiation of hyperbaric oxygen (HBO) treatment (75 min, 2.8 bar with two air-brakes, followed by a stage-wise decompression during 40 min), which had an imminent, and stabilizing, effect on the LPR (Figures 2 and 4). The ICP remained normal (<20 mmHg) throughout the HBO treatment period. The PBtO2 was not monitored during the HBO, because of technical issues, but showed a sustained increase to levels above 20 mmHg after the completed hyperbaric treatment, allowing the decrease of fraction of inspired oxygen (FiO2) (Figure 5). The secondary increase of S100B stopped, and was followed by a steady decline (Figure 2). The focal LPR is measured using the microdialysis technique, which is compatible to use inside the hyperbaric chamber. However, the measured levels may not be completely reliable during the compression and decompression phases, since the speed of perfusion is influenced by the surrounding pressure changes. The patient received two further HBO treatments, same type and duration, on day 8 and day 10 post-trauma. In order to visualize the changes before and after HBO treatment, Figure 4 shows LPR, PBtO2, and ICP during the 3 days of HBO treatment. The LPR has the highest level after the HBO treatment, which is a single sample, and thus presumably false. Following this peak, there is a sustained period of lower LPR samples. Day 16 after injury, the patient was provided with a tracheostomy. A MRI on day 16 showed bilateral temporal damage with cytotoxic edema along the trajectory, yet no ischemic injury or permanent damage to the frontal lobes (Figure 6). Neurophysiological examination on day 27 revealed signs of bilateral cortical blindness (no visually evoked potentials detected), no signs of brain stem damage (normal brainstem auditory evoked potentials, BAEP), and no irregularities on the electromyogram (EMG). The patient himself was not aware of being blind. On day 36, the patient was discharged from NICU to an intermediate neurosurgical ward. The patient started physiotherapy and at day 38 after injury, he was able to move with support. At discharge from the neurosurgical clinic, the patient was still blind and had cognitive deficits yet had regained almost all motoric functions and could walk a shorter distance without support. Six months after trauma, the patient is still dependent on medical staff in order to move, as well as suffering from cortical blindness and cognitive shortfall. It has been shown that patients with low GCS at admission, unresponsive pupils, bihemispheric transventricular injury, and subarachnoid hemorrhage usually have a poor outcome after cerebral gunshot wounds. This penetrating brain injury was treated as a severe traumatic brain injury (TBI) (GCS3-8). At our department, patients suffering from severe TBI are mechanically ventilated, and sedated with morphine, midazolam, and/or propofol. If mass lesions are present, they are evacuated as deemed appropriate. Mean arterial pressure (MAP) is measured intra-arterially. Cerebral perfusion pressure (CPP) is calculated as MAP-ICP with the transducers placed at mid-lateral ventricular level. The patients are treated in 30 sitting position. ICP is targeted at <20 mmHg and CPP is targeted at 50-70 mmHg. Targets are achieved with intravenous infusions, vasopressors, osmotic therapy, and intermittent CSF drainage from ventricular catheters, ventilation, temperature control, and decompressive craniotomy, if needed. Patients are normoventilated (pCO2 approx. 4.5 kPa). Blood glucose is targeted at 4-8 mmol/L and hemoglobin is targeted at >90 g/L. Temperature is regulated at 37 C with paracetamol or external wrapping cooling systems. If ICP could not be regulated with the previously described techniques, sodium thiopental is infused, limited by burst suppression and monitored with continuous electroencephalography (EEG). Mild hypothermia (35-36 C) is used for high refractory ICP. Intracerebral microdialysis is performed routinely in patients suffering from severe traumatic brain injuries. Increasing LPR >40 indicates tissue ischemia or mitochondrial dysfunction. We routinely obtain serum samples of the biomarker S100B every 12 h and recognize secondary peaks as a negative prognostic indicator. Hyperbaric treatment seemed already in the mid-1970s to improve outcome in patients suffering from TBI presenting mid-brain symptoms, especially during 1.5-2.0 bar for 40 min. Recent studies by Rockswold and co-workers have shown beneficial effect by using hyperbaric treatment with significantly improved markers of oxidative metabolism, reduced intracranial hypertension, and improvement in markers of cerebral toxicity as well as a significant reduction in mortality and improved favorable outcome. In the present case report, we present a patient with relatively high GCS and normal pupil response at admission, despite a gunshot wound with a detrimental bihemispheric trajectory. The patient developed an increasing LPR, indicating local tissue damage due to ischemia or mitochondrial dysfunction, and was thus treated with 2.8 bar HBO. The intracranial conditions of the patient improved, and the patient survived despite unfavorable odds. The current setting presents a higher pressure than reported by the Rockswold group. This regimen was chosen as a rescue measure of "last resort," facing the uncontrolled increase in LPR, because of presumed cerebral mitochondrial dysfunction. An increased FIO2 was tested, but failed to improve cerebral metabolic conditions (Figure 5). The patient's vital and metabolic parameters were thoroughly monitored during the HBO procedure, and the pressure would be lowered if any adverse effects had been detected. Despite the success achieved in this particular case, we do not recommend this regimen as a standard HBO procedure in severe TBI cases. More studies are necessary to determine the optimal dose regimen and to individualize the treatment. The graphs presented are exported using the LabPilot software (Microdialysis AB, Stockholm, Sweden).

human, hyperbaric oxygen, microdialysis, multi-modal monitoring, penetrating brain injury

PMC8222916_01

Female

A 26-year-old pregnant woman was admitted owing to cough for 11 days, fever for 6 days and dyspnea for 2 days at 15 weeks of gestation. She presented with a dry cough 11 days prior to admission, accompanied by profound fatigue and night sweats. After treatment with Chinese patent medicine, the symptoms were temporarily resolved. High fever occurred 6 days prior, with a peak temperature of 39.3 C, accompanied by cough with white sputum. There was no clinical response to symptomatic treatment administered. Her previous symptoms aggravated 2 days prior, with a peak temperature of 40.1 C, along with dyspnea and altered sensorium. There were no chills, loss of consciousness, hemoptysis, or colporrhagia. Chest X-ray showed diffuse bilateral infiltration and nested polymerase chain reaction (PCR) for M. tuberculosis complex in sputum was positive, which was performed in the Maternal and Child Health Hospital. She was then transferred to the medical intensive care unit (MICU) of the Third Affiliated Hospital of Sun Yat-Sen University for isolation and further treatment. The patient had a past history of Evans syndrome (ES) for 4 years. She regularly took oral corticosteroids (prednisone 20-45mg/day) and had normal hemoglobin and platelet counts. She had no disorders related to the other organs and was a non-smoker. She had no past history of M. tuberculosis infection and any recent travel, tick bites, or poultry contact. Her pregnancy duration was uneventful to date. On admission to the MICU (day 1), her vital signs were as follows: body temperature, 37.0 C, pulse rate, 120 beats/min, respiratory rate, 40 breaths/min, blood pressure, 140/68 mmHg, and oxygen saturation, 95.0% with breathing 15 L/min of oxygen by venture mask. She was drowsy and appeared to be acutely ill. The diminished breath sounds and wet rales in both lungs were heard on auscultation. There was no audible murmur on cardiac auscultation. Tenderness, hepatomegaly and splenomegaly were not detected. The patient had no neck stiffness. No rash was observed. Laboratory data upon admission revealed a white blood cell (WBC) count of 13.86 x 109/L with an elevated neutrophil ratio of 94.0% and normal eosinophil ratio, hemoglobin of 101 g/L, and platelet count of 73 x 109/L. The concentration of C-reactive protein (CRP) and procalcitonin was 222.0mg/L and 3.29ng/mL, respectively. The erythrocyte sedimentation rate (ESR) was 47 mm/h. Albumin was 20.8g/L. Globulin was 21.8g/L. Triglyceride level was 1.3 mmol/L. Her lactic dehydrogenase (LDH) level was 568 U/L. The uric acid concentration was 429 micromol/L. Electrolytes, creatinine, aspartate aminotransferase, alanine aminotransferase, total bilirubin and direct bilirubin levels were within normal limits. Even with continuous nasal high flow oxygen therapy, arterial blood gas analysis showed a pH of 7.44, PO2 of 71.0 mmHg, PCO2 of 38 mmHg, oxygenation index of 87.6, and lactate level of 1.0 mmol/L. Coagulation tests demonstrated prothrombin time of 13.7 s, prothrombin activity of 95%, and fibrinogen 5.0 g/L. Serology for respiratory viruses (adenovirus, influenza A virus, influenza B virus, parainfluenza, and respiratory syncytial virus) as well as bacteriological assays (Mycoplasma pneumoniae, Chlamydia pneumonia, and Legionella) were all negative. Tests for cytomegalovirus, Epstein Barr virus, Toxoplasma, rubella virus, herpes simplex virus, HIV, hepatitis A, B, C, and E viruses, dengue virus, malaria, Leptospira, and scrub typhus were also negative. Cryptococcal antigen was negative. The galactomannan and beta-D-glucan tests were both negative. The interferon-gamma release assay was indeterminate. Peripheral blood culture was negative. However, the sputum smear sample was positive for acid-fast bacilli. All the indicators were negative for routine laboratory screening (anti-nuclear antibody, anti-extractable nuclear antigen antibody, and anti-neutrophilic cytoplasmic antibody, et al) for autoimmune diseases. Coombs test was negative (The detailed immunological profile was shown in Supplementary File 1 ). The counts of CD3, CD4, and CD8 T lymphocytes in blood were 520/mm3, 208/mm3 and 284/mm3 respectively, with a decreased CD4/CD8 ratio of 0.73. After admission, a lumbar puncture showed no abnormalities. There was no evidence in cytology and biochemistry of cerebrospinal fluid supporting the existence of tuberculous meningitis. Chest computed tomography (CT) revealed diffuse infiltration and patchy shadows in both lungs and bilateral pleural effusion ( Figures 1A, B ). Abdominal CT revealed splenomegaly but showed no peritonitis and seroperitoneum. After admission, the patient was initially administered with non-invasive positive pressure ventilation, anti-tuberculosis therapy (ATT), and a low dose of methylprednisolone (40 mg qd intravenous infusion). The details of ATT were isoniazid (0.8 g qd intravenous infusion), rifampin (0.4 g qd orally), ethambutol (0.75 g qd orally), pyrazinamide (0.5 g TID orally) and moxifloxacin (0.4 g qd intravenous infusion). However, the patient's condition deteriorated rapidly with high fever, acute respiratory distress syndrome (ARDS), pancytopenia, and hyperferritinemia on day 3. The patient was treated with tracheal intubation and mechanical ventilation. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) identified 926 of 225958 DNA sequence reads and 195 of 491668 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 of 125859 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens (Methods, quality control and detailed results of mNGS were shown in Supplementary File 2 ). Bone marrow smears showed increased macrophage activity with hemophagocytosis without evidence of leukemia or lymphoma. And there was no evidence of M. tuberculosis in bone marrow ( Figure 2A ). Additional blood tests showed hyperferritinemia (6649 ng/mL, normal range 10-291 ng/mL), low NK cell activity (13.08%, normal value: >=15.1%, tested by flow cytometry) and elevated soluble CD25 levels (5730 pg/mL, normal value: <2400 pg/mL, tested by ELISA). Genetic testing for primary HLH was negative (Detailed result of genetic testing was shown in Supplementary File 3 ). As the embryo died on day 5, she underwent a medical abortion, and caseating tuberculous granulomas were found in the placenta ( Figure 3 ). Clinical laboratory tests and imaging were performed by the department of laboratory and image center of the Third Affiliated Hospital of Sun Yat-sen University, respectively. mNGS, NK cell activity, level of soluble CD25 and genetic testing for primary HLH were performed and reported by Guangzhou Kingmed Medical Test Center Co., Ltd. At the most severe moment, the patient was assessed with an acute physiology and chronic health evaluation (APACHE) II score of 32, sepsis related organ failure assessment (SOFA) score of 14, Marshall score of 14 and mortality risk of 85.3%. Following consultation with a multidisciplinary team, a diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy of higher dose of methylprednisolone (80 mg bid intravenous infusion) combined with immunoglobulin (20 g qd intravenous infusion, days 2-10) and plasma exchange (2000 mL each time on days 4 and 8) was administered. The patient responded well to the treatment, with marked improvement in fever and cytopenia ( Figures 4A, B ). She failed to respond to transfusion of platelet initially, then platelet count began to increase spontaneously after combined therapeutic strategy. Elevation of eosinophil ratio was not noted during the treatment. Along with the resolution of hypofibrinogenemia and hyperferritinemia ( Figure 4C ), the concentrations of CRP and interleukin (IL)-6 decreased continuously ( Figure 4D ). The second bone marrow aspiration showed no hemophagocytosis ( Figure 2B ). Her condition improved daily, along with the increase in oxygenation index and improvement in chest CT gradually ( Figures 1C-F ); she was withdrawn from the ventilator on day 10 and was discharged on day 19. Two weeks later, pleural fluid culture revealed M. tuberculosis and was confirmed by Xpert. Based on the clinical data, the patient was finally diagnosed with disseminated TB-associated HLH, severe pneumonia, type I respiratory failure, severe ARDS, medical abortion, and ES. The patient was in good condition during the follow-up. Two months after discharge, the standard four-drug ATT was changed to a two-drug continuation phase with isoniazid and rifampin. Methylprednisolone was reduced to 12 mg qd orally. No significant abnormalities were found in WBC, hemoglobin, platelet count, CRP, ESR, LDH, ferritin, and uric acid in the serum.

evans syndrome, case report, corticosteroid, hemophagocytic lymphohistiocytosis, tuberculosis

PMC6915030_01

Female

A 9-year-old Caucasian female presented to the West Virginia University otolaryngology clinic with the chief complaint of gradually increasing swelling of her upper and lower lips which started 4 months prior. The lip swelling was reported to be very distressing to the child and her parents. Prior to presentation at the otolaryngology clinic, the patient was seen by a pediatric dentist, periodontist, and allergist. The patient had a history of excessive thumb sucking, wearing nail polish, and playing with homemade slime containing glue, saline, shaving cream, and glitter. The patient had a history of mild eczematous skin lesions and vague rhinitis including nasal congestion, occasional postnasal drainage, varying complaints of headaches, and occasional conjunctival pruritus. Seasonal symptoms were worse in spring time, with the pollens of trees, grasses, and weeds possibly playing a role. There was no contributory family history, medication history, or history of allergy to food, drugs, or cosmetics. The patient did not have any contributory past medical or surgical history. Physical examination revealed a symmetrically enlarged, erythematous upper lip with erythematous and edematous maxillary anterior gingiva, particularly on the right side (Figures 1 and 2). The allergist also noted mild fissures in the lip area, as well as evidence of cheilitis. The patient was prescribed mupirocin ointment for the perioral areas where the cheilitis was present in order to clear any superficial infection. This treatment likely resolved these issues prior to patient presentation at the otolaryngology clinic. The suggested differential diagnosis was Crohn's disease, sarcoidosis, tuberculosis, angioedema, and orofacial granulomatosis. Routine laboratory tests (basic metabolic panel, complete blood count with differential, erythrocyte sedimentation rate, hepatic function panel, HAV antibody, HCV antibody, HBV envelope antibody and antigen, C-reactive protein, immunoglobulin panel, C4 complement, C3 complement, glomerular basement membrane antibodies, and cytoplasmic neutrophil antibodies) were performed and were reported to be within normal limits. No clinical signs or symptoms of gastrointestinal disease were present. A right upper lip incisional biopsy was performed. Submucosal lymphohistiocytic infiltrate with loose perivascular granulomas were found. The underlying salivary gland tissue was prominent with lymphocytic infiltrate with occasional germinal center formation. Acid-fast bacilli were not seen on a concentrated smear. The patient's history, physical examination, blood and serum tests, and pathology results led to a diagnosis of OFG of the upper and lower lip with maxillary gingival hyperplasia. The patient was treated with azithromycin pulses for one month. This treatment consisted of 500 milligrams once daily for 3 days, followed by 4 days of no medication. This regimen was followed for a total of 4 weeks as previously described by De et al. in an effort to avoid corticosteroids given the parents' concern for corticosteroid side effects. The patient saw improvement of symptoms following this treatment. However, after using a lip gloss containing glitter, she experienced an exacerbation of her oral swelling and returned to the clinic. Given the perceived treatment failure, the patient was subsequently treated with 40 milligrams once daily of prednisone for 2 weeks. The patient reported marked improvement following oral steroid administration. Once again, however, the patient experienced an exacerbation of her OFG following swimming. She was treated again with the same regimen of oral steroids. In addition, she avoided foods containing benzoates as well as products containing glitter, both of which seemed to be triggers for her OFG. The patient experienced noticeable improvement in her gingival hyperplasia and lip swelling following the treatment with oral steroids and behavioral modifications.

PMC10069495_01

Female

A 45-year-old female patient was admitted to the First Affiliated Hospital of Guangxi Medical University for a sore throat lasting for 20 days on September 8, 2022. She was a teacher and had no underlying diseases. Computed tomography (CT) examination showed a space-occupying lesion. The primary lesion had not yet been determined, and the patient was admitted to our hospital. The contrast-enhanced chest CT examination showed mixed nodules in the anterior segment of the right upper lobe, inflammation of posterior segment, and middle of the right upper lobe and inferior lingual segment of left upper lobe, and mediastinal space-occupying lesions and multiple lymphadenopathy (Figure 1). The mediastinal space-occupying lesion was suspected to be a tumor, so ultrasound-guided mediastinal mass puncture was performed in the daytime operating room of our hospital. On admission, the patient's laboratory results were as follows: hemoglobin (HGB) was 106.60g/L, the CD4+ lymphocyte count was 549/microL, the serum high sensitivity C-reactive protein levels were 2.65mg/L (normal 0-1mg/L), serum albumin was 37.6g/L (normal 40-55g/L), glycoprotein antigen 199 54.0U/mL (normal 0-37U/mL), serum glycosylated HGB was normal, and beta-(1,3)-D-glucan (BDG) and galactomannan (GM) were negative. Liver and renal functions were normal. The human immunodeficiency virus antibody test was negative. The patient's mediastinal lesion was located near the main trachea, and infection was not ruled out, and EBUS-TBNA was performed. EBUS-TBNA showed an extratracheal pressure stenosis and unspecified echo mass at the 4-6 o'clock position in the 5cm trachea under the glottis (Figure 2). The patient's mediastinal mass tissue was sent for mNGS (KingMed Diagnostics, Nanning, China). DNA extraction was performed with the JianShi universal DNA/RNA extraction kit, and subsequently an Illumina Next 550 sequencer was used for a single-end 76-base pair sequencing strategy. A DNA library was constructed, and subsequently Burrows-Wheeler Aligner (BWA) software and the NCBI database were used for analysis. Within 24 h after receipt of the sample, the mNGS results reported Aspergillus fumigatus infection. The mNGS detected 301 sequences that could be mapped to Aspergillus fumigatus in a total of 28,759,120 sequences, and the coverage was 0.12%, making up 97.80% of the total microbe sequences (Figure 3). Tissue from EBUS-TBNA mass puncture tissue was sent for pathological examination, and 5 days after receipt of the sample, the histopathological results showed large number of neutrophil cell infiltrations and Aspergillus hyphae (Figure 4), and periodic acid-Schiff (PAS) staining of specimens was positive. Microscopic examination of EBUS-TBNA mass tissue cytological smear showed no cancer cells. Fourteen days after receipt of the sample, the EBUS-TBNA tissue fungi culture (the culture media medium was CHROMagar medium) suggested growth of Aspergillus fumigatus, and bacterial culture showed no bacteria growth. No fungi sequences were found in mNGS of the bronchoalveolar lavage (BAL) fluid. BAL-BDG and -GM were negative. Subsequently, the histopathology of ultrasound-guided mediastinal mass puncture tissue results also showed inflammatory cell infiltration and Aspergillus hyphae (Figure 4). PAS staining of specimens was positive, and the mass was considered aspergillosis with suppuration. Considering that the patient had eating disorder, gastroscopy was performed. An esophageal mass with stenosis was found, and gastroscopic biopsy of the esophageal submucosal mass tissue revealed esophageal aspergillosis. The patient was diagnosed as having mediastinal abscess with Aspergillus fumigatus infection and treated with voriconazole (0.2 g, IV infusion, q.d.) beginning September 13. Her symptoms improved, and she was discharged on September 18 on continued oral voriconazole (0.2 g, twice a day) antifungal therapy. One month after discharge, the patient was followed up by telephone. The patient was generally in good condition, and the liver and kidney functions and blood routine tests were normal. The patient is still being followed-up.

aspergillus fumigatus, case report, diagnosis, mediastinal abscess, metagenomic next-generation sequencing

Contrast-enhanced chest CT of the patient on September 1, 2022. Space-occupying lesion of anterior upper mediastinum is shown. A low-density necrosis area can be seen on enhanced scan, which is separated from the surrounding esophagus. (A) Lung view.

PMC3952391_01

Male

The present case report is about a 31-year old male patient who presented to our medical center with a productive cough, hemoptysis and chest pain for a month. He had a history of pulmonary tuberculosis (TB) twice over the last 10 years. In the first episode, he was treated with the World Health Organization category (CAT) I standard regimen including: Isoniazid (H), Rifampin (R), Pyrazinamide (Z) and Ethambutol (E) for 6 months (2HRZE/4HR). In the second episode, a CAT II regimen including streptomycin in the 1st 2 months (2HRZES/1HREZ/5HRE) was prescribed for 8 months. His treatment was successful, however one year after completion of the second therapy, he presented with respiratory symptoms to our hospital. His vital signs were within the normal limits. On physical examination, he was pale and afebrile with generalized wheezing and bilateral bronchial rhonchi. Laboratory studies revealed the following values: Total white blood cell (WBC) count: 103,600 cells/ul with 5% neutrophils, 14% mature monocytes, 11% lymphocyte and more than 20% immature nucleated cells of myeloid lineage some with monocytoid morphology; hemoglobin 5.8 g/dl; platelets 233,000 cells/ul and erythrocyte sedimentation rate 125 mm/h. All other biochemical tests were unremarkable. Chest X-ray and spiral computed tomography scan of the thorax showed a cavitary lesion in the right upper lobe surrounding diffuse infiltrates with pleural thickening. There were also some areas of nodular infiltrate demonstrating a " tree-in-bud" appearance in left lung [Figure 1]. A sputum smear was positive for acid-fast bacilli, so anti-TB regimen (CAT I) was initiated, culture and drug susceptibility testing were initiated. In addition, bone marrow biopsy was performed and AML - M4 was diagnosed by histopathological examination, based on published criteria. Chemotherapy agents consisting Danurubicin 70 mg/q12h plus Cytarabine 1600 mg/q12h were started. The patient was transferred to the intensive care unit due to fever and severe neutropenia (WBC 880 cells/ul) on the 6th day of chemotherapy and Meropenem 1 g/q8 h, Vancomycin 1 g/q12h and Itraconazole 100 mg/daily were initiated. The polymerase chain reaction (PCR) of deoxyribonucleic acid collected from sputum sample of patient (based on IS6110 primer) was negative for Mycobacterium tuberculosis complex. The Mycobacterium identification was performed by PCR-restriction fragment length polymorphism (RFLP) polymorphism analysis and subsequently M. branderi was isolated from the sputum of the patient. A 440 bp fragment of hsp65 gene was first amplified (based on TB11, TB12 primer) and then the PCR product digested using BstEII and HaeIII restriction endonucleases. The obtained digested pattern (BstEII; 235,211 bp: HaeIII; 130,106,80,41,37 bp) was compared with the standard strains published on database [Figure 2]. To further confirm the identification of M. branderi pure colonies were isolated at 25 C and 45 C within 3 weeks of incubation. Differentiation of M. branderi from Mycobacterium celatum was done based on phenotypic characteristic of colonies and pigment production. The colonies of M. branderi had not produced pigment. The susceptibility testing observed for the clinical isolate included resistance to Isoniazid and Rifampin. The anti-TB drugs were stopped and treatment was modified to Clarithromycin 500 mg/q12 h, Ciprofloxacin 500 mg/q12h and Doxycycline 100 mg/q12 h. This combination regimen was well tolerated and the patient's symptoms resolved. After 1 month of treatment, sputum smear and culture conversion was reported. Following discharge from hospital, mycobacterial treatment was continued for 12 months and our patient remained smear negative and free of pulmonary symptoms in follow-up appointments.

acute myelogenous leukemia, mycobacterium branderi, pcr-restriction fragment length polymorphism

PMC10081889_01

Male

A 37-year-old male with a medical history of nephrolithiasis, latent tuberculosis, and a 20+ pack-year smoking history initially presented in February 2021 with complaints of hematuria, right flank pain, and new onset clot passage. A renal and bladder ultrasound was then done which showed numerous irregular cysts in the right kidney, a normal left kidney, a heterogeneous mass in the bladder, and clot passage. A cystoscopy was performed which visualized the clot but detected no cancerous lesions or stones. Cytology from the bladder washing was negative. Urine cultures and an acid-fast bacteria stain were negative. A CT chest, abdomen, and pelvis with contrast was performed which demonstrated perinephric stranding, marked hydronephrosis, and marked thinning of the right renal parenchyma (Figure 1(a)). A nuclear medicine renal scan indicated impaired right kidney function (33%) with preserved left kidney function (67%). These findings were consistent with right-sided XGP, but a formal diagnosis could not be made without the pathology of a specimen. Given the normal creatinine and preserved left renal function, a simple right nephrectomy was recommended. The patient declined the operation and was discharged against medical advice. He returned to the ER two months later with similar complaints as before of right flank pain, dysuria, and hematuria. He was able to find relief with over-the-counter nonsteroidal anti-inflammatory drugs and agreed to undergo a nephrectomy. A CT abdomen/pelvis showed significant progression of the right XGP as well as a new infiltrative process of the right renal pelvis with possible right renal vein thrombosis (Figure 1(b)). The patient underwent an open right radical nephrectomy to treat the extensive XGP during this hospital admission. Pathology of the specimen showed UC with squamous differentiation in a background of XGP. Specimen margins were negative for invasive carcinoma without evidence of tumor in regional lymph nodes. A CT abdomen/pelvis two months later in September 2021, however, was significant for multiple new poorly defined hepatic hypodensities with concern for metastatic disease versus abscesses related to disseminated infection (Figure 1(c)). The patient also later endorsed the onset of bone pain. CT-guided liver biopsy was ordered which confirmed metastatic UC. However, nuclear medicine bone scan and CT chest with contrast were negative for osseous metastasis and thoracic lesions or lymphadenopathy, respectively. The patient was then evaluated by medical oncology and was started on gemcitabine and cisplatin (GC) palliative chemotherapy given the progression to metastatic disease. Within one week of chemotherapy induction, the patient required hospital admission to treat sepsis secondary to mucositis. Following discharge, he was able to resume his chemotherapy regimen. A CT chest, abdomen, and pelvis performed after the third cycle of GC demonstrated interval reduction in the size of liver lesions without any appreciable change in abdominal lymphadenopathy. Given the patient's ongoing clinical response, the decision was made to complete 6 cycles of platinum-based chemotherapy. He was eventually treated with avelumab maintenance. Despite this, the patient had rapid disease progression. Given his overall critical status and poor prognosis, the decision was made to transition patient to hospice, and he eventually passed away due to the disease.

PMC4435753_01

Male

A 55-year-old male, with multiple myeloma, was admitted with a fever up to 38.5 C and cervical lymph node enlargement 70 days after an allogeneic HSCT from an unrelated donor with human leukocyte antigen DQB1 mismatch (9/10 matched), for early progression after an autologous HSCT. After reduced intensity conditioning with fludarabine (40 mg/m2 4 days), melphalan (70 mg/m2 1 day), and thymoglobulin (2.5 mg/kg 3 days), he received a T-cell-replete peripheral blood allograft containing 5.7 x 106 CD34+ cells/kg. Graft-versus-host disease prophylaxis consisted of tacrolimus (from day 1) and methotrexate (on days +1, +3, and +6). He received acyclovir as anti-infective prophylaxis and was isolated in a HEPA filtered room during the severe neutropenia period. The patient denied previous exposure or infection by M. tuberculosis. Bacillus Calmette-Guerin vaccination status was unknown and tuberculin skin test (TST) is not routinely performed to HSCT candidates at our hospital. At admission, a contrast-enhanced computed tomography (CT) showed right laterocervical lymph node enlargement (Figure 1A) and a high-resolution chest CT revealed old pulmonary scar lesions in the right upper lobe but no signs of active infection (Figure 1B). Quantitative polymerase chain reaction (qPCR) in the peripheral blood-detected epstein-barr viral (EBV) replication (820 copies/mL) and a first cervical biopsy was not diagnostic. Tacrolimus taper was started, and the patient was discharged afebrile with oral antibiotherapy. On day +90, fever was noted again, and the biopsy wound presented purulent suppuration (Figure 2), which was sent for culture. EBV replication was no more detected during the follow-up. Histologic exam of a second biopsy showed caseating granulomas (Figure 3). PCR analysis of the lymph node demonstrated the presence of M. tuberculosis consensus sequences, which was confirmed by microbiological cultures isolating M. tuberculosis complex. Combined treatment with rifampicin, isoniazid, and pyrazinamide was initiated with a quick recovery of all infectious symptoms. Antituberculosis therapy was maintained for 9 months with a complete resolution of tuberculosis (TB).

haematopoietic stem cell transplantation, lymph node tuberculosis

(B) Highresolution chest CT revealed old pulmonary scar lesions with pleural thickening in the right upper lobe.

PMC7525059_01

Male

A 45-year-old man presented at the emergency department of our tertiary teaching hospital with a septic arthritis of the left hip. Four weeks before presentation the hip became painful. Since then the pain worsened and the patient became febrile. He did not suffer from night sweats. The patient had no significant medical history. He originated from former Yugoslavia, where he spent the holidays once or twice a year. His occupation was supervisor in a metal recycling company in the harbour of Rotterdam. On physical examination the hip was mildly swollen and painful at palpation. Laboratory investigation showed an increased C reactive protein (CRP) of 234 mg l-1 (normal <10) with a normal leukocyte count. Magnetic resonance imaging (MRI) of the hip was performed, which showed a high-intensity signal and a lot of intra-articular fluid at the swollen side of the hip. With an ultrasound guided biopsy synovial fluid was aspirated and sent to the microbiology department. The working hypothesis was an ordinary septic arthritis. However, a gram stain of the synovial fluid did not show any micro-organisms. Antibiotic treatment was started immediately with intravenous cefuroxime and one dose of gentamicin, according to local antibiotic guidelines. After starting antibiotic treatment the fever and increased CRP persisted. Therefore, a chest radiograph was taken, which showed bilateral, perihilar infiltrates consisting of several small nodules. A chest computed tomography (CT) showed perihilar diffuse nodular infiltrates (Fig. 1). With a differential diagnosis of pulmonary and extrapulmonary tuberculosis, the hip synovial fluid was stained with auramine-rhodamine and then acid-fast bacilli could be visualized. Next, GeneXpert MTB/Rif (Cepheid, Sunnyvale, CA, USA), a molecular test based on nucleic acid amplification, confirmed M. tuberculosis complex in the sample from the synovial fluid. The normal aerobic and anaerobic cultures were negative. The mycobacterial culture, using our BD BACTEC MGIT 960 mycobacteria culture system (BD Diagnostics, Sparks, MD, USA) was negative after 6 weeks of culture. Given the positive GeneXpert and no history of pre-treatment, it was decided to extend the culture period for another 6 weeks. After a total of 75 days of culture, the mycobacterial culture became positive (Fig. 2). In order to differentiate within the M. tuberculosis complex we used the GenoType MTBC molecular genetic assay (HAIN Lifescience, Nehren, Germany) and identified the strain as an M. microti . Additionally, the GenoType MTBDRplus (HAIN Lifescience) was performed in order to identify molecular genetic resistance towards isoniazid (INH) and rifampicin (RMP). This hybridization assay showed no mutations in the rpoB gene (associated with RMP susceptibility) and no mutations in the katG or inhA genes (associated with INH susceptibility). The sputum of the patient was also tested for mycobacteria, but turned out to be negative by auramine-rhodamine staining, GeneXpert and (mycobacterial) culture. Eventually, broncho-alveolar lavage was performed, but with the previous three tests M. microti could not be detected. The M. microti infection was treated with INH, RMP, pyrazinamide and ethambutol according to the World Health Organization recommended dosage. Initially the patient recovered and the fever and pain in the hip disappeared. Therefore, the pyrazinamide and ethambutol were discontinued after 2 months. However, shortly thereafter the former complaints reoccurred and the pyrazinamide and ethambutol were restarted. A CT scan of the hip revealed bone destruction at the anterior side and multiple abscesses in the adjacent muscles (Fig. 3). A radiological drainage of these abscesses was performed. Therapeutic drug monitoring of RMP and INH showed that drug levels of both drugs were subtherapeutic. Hereafter, the dose of INH was increased to 900 mg per day and RMP to 1800 mg per day. Shortly after this treatment modification the patient got complaints of polyneuropathy. Therefore, the INH was discontinued. The other drugs were continued and eventually, the patient improved clinically.

mycobacterium microti, extrapulmonary tuberculosis, mycobacterium tuberculosis complex

Chest computed tomography, showing perihilar consolidations at both sides with underlying bronchiectasis. In the periphery of the lungs smaller nodular infiltrates are visible. These are indicated by the arrows.

PMC3417363_01

Female

In this review we aim to give a contribution to the understanding of relevant aspects of Bcc bacteria-mediated respiratory infections in CF patients, based on the epidemiological surveys carried out by our research group of a case-study population that has been routinely followed for the past 16 years at the CF Treatment Center of Santa Maria Hospital (HSM), in Lisbon. This CF population comprises a total of 124 patients, of which 58% are children (up to 18 years old) and 42% are adults (Figure 1). In the CF pediatric population 54% are female and 46% are male, while in the CF adult population 58% are females and 42% males. Bcc bacteria have been isolated from 41 of these patients, belonging to both the adult (n = 12) and pediatric (n = 29) populations. The age at the time of the first Bcc isolation varied between a few months of life and 28 years old, with an estimated mean age of 10 years. Studies involving the use of B. cenocepacia isolates collected from CF patients at HSM were approved by the ethics committee of the Hospital, and the anonymity of the patients is preserved. The CF subpopulation is represented by a collection of 506 Bcc clinical isolates and clonal variants that were gathered during our 16-year collaboration with the HSM CF Center. This collection includes serial isolates recovered from persistently colonized patients from the early to late stages of infection. According to this routine, sputum samples are obtained from CF patients every 2-3 months, during periodic consultations to monitor their clinical status, or more often for patients showing clinical deterioration (Cunha et al.,). The systematic molecular analysis of the 506 isolates revealed that the most prevalent Bcc species recovered from the sputa of the 41 Bcc-infected patients are B. cepacia and B. cenocepacia (Figure 2A). While B. cepacia is not a predominant Bcc species among the CF population characterized worldwide (Mahenthiralingam and Vandamme,), detailed molecular analysis unveiled an exceptionally high incidence of B. cepacia at the HSM CF Center from 2003 to 2005 (Figure 2B), with isolates being retrieved from 11 out of 13 Bcc-infected patients (Cunha et al.,). This abnormal prevalence of B. cepacia was associated with two B. cepacia clones that were indistinguishable from two strains isolated from contaminated non-sterile saline solutions for nasal application, detected during routine market surveillance by the Portuguese Medicines and Health Products Authority, INFARMED (Cunha et al.,). After this contamination was detected, the number of B. cepacia isolates identified at HSM gradually declined over the following years, although still remaining significantly high due to persistent colonization of the living patients (Figure 2B). Interestingly, 2005 coincides with a peak in the number of CF patients with newly detected Bcc infections (Figure 2C). Although transmission of Bcc bacteria is considered an important factor in the colonization of CF patients, other primary sources of infection must be taken into account in CF centers where the recommended control measures are followed, as is the case of the CF center at HSM. It is likely that the environment might act as a reservoir for novel Bcc infections (Pallud et al.,; LiPuma et al.,; Vanlaere et al.,), and attention should be given to continuous monitoring of medication for microbial contaminations. Indeed, Bcc bacteria are resistant to multiple antimicrobials and to diverse growth inhibitors that can even be used as carbon sources (Coenye and Vandamme,). Since these bacteria also have minimal nutritional requirements, they are able to grow in aqueous products, including disinfectants (Oie and Kamiya,; Ghazal et al.,). Contamination of albuterol and sulbutamol nebulization solutions (Balkhy et al.,; Ghazal et al.,), nebulizers (Hutchinson et al.,), mouthwash (Matrician et al.,), nasal sprays (Dolan et al.,), and ultrasound gel (Jacobson et al.,) have resulted in outbreaks of nosocomial infections by Bcc bacteria. Therefore, the surveillance of unexplained outbreaks of less common pathogens is essential; in particular, those involving poorly represented species, like B. cepacia, especially in patients with underlying lung disease and increased risk such as CF patients. In addition to B. cenocepacia and B. cepacia, four other Bcc species have been isolated from the HSM CF population: B. dolosa, B. contaminans, B. stabilis, and B. multivorans (Cunha et al.,, unpublished results; Figures 2A,B,D). Because the taxonomy of Bcc bacteria evolved significantly in the last few years, with the description of eight novel species (Vanlaere et al.,), we have re-examined the species identification of several isolates from our collection. We paid special attention to isolates that were classified as B. cepacia with recA-RFLP profile K (Cunha et al.,), since this taxon was recently shown to comprise at least two novel species (Vanlaere et al.,), and the multilocus sequence typing (MLST) analysis revealed that several of those isolates now belong to the B. contaminans species. Co-infection with two or three different Bcc species was also observed in nine patients, mainly involving B. cenocepacia and B. cepacia, and in a smaller percentage with B. cenocepacia and B. contaminans, with B. cenocepacia, B. stabilis, and B. multivorans, or with B. cenocepacia and B. dolosa (Figure 2D). Although there is a generalized idea that B. cenocepacia is associated with greater morbidity and mortality in CF patients (Speert,; Mahenthiralingam et al.,), epidemiological surveys show that all of the species above are associated with poor clinical outcome, including the cepacia syndrome, and give rise to chronic and transient infections (Cunha et al.,; Drevinek and Mahenthiralingam,). In fact, it is not clear why strains of different Bcc species differ in their persistence, epidemiology, and pathogenic potential in CF, or why the same strain can be associated with very different clinical outcomes. It probably depends on factors that are inherent to each individual patient, on co-colonization by other pathogens and on other still unidentified factors.

burkholderia cenocepacia, burkholderia cepacia complex, chronic respiratory infection, clonal variation, cystic fibrosis, genome-wide expression, long-term colonization

PMC7201821_01

Female

A 69-year-old female complained of intermittent right leg radicular pain in the past two years and which became worse with numbness in the recent four days. Moreover, the patient also had severe intermittent claudication, and the claudication distance was only about 20 meters. The decreased muscle force of the right quadriceps femoris and extensor hallucis longus and hypesthesia in the bilateral dorsal foot skin were found through physical examination. The Lasegue sign of the right leg was positive, and the bilateral Babinski signs were negative. The flexion and extension lateral lumbar radiographs showed segmental dynamic instability at L2-3 and L3-4 (Figure 1(a)). Sagittal computed tomography (CT) showed multilevel disc degeneration, severe osteophyte at L4-5, and L3 spondylolisthesis relative to upper and lower vertebra (Figure 1(b)). Magnetic resonance imaging (MRI) revealed serious central stenosis at L3-4 and lumbar disc herniation and right lateral recess stenosis at L4-5 (Figure 1(c)). White blood cell (WBC) count and blood chemistry, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were all unremarkable during hospitalization. Laminectomy of L4 and right-sided hemilaminectomy of L5 were performed to decompress the right L4, L5 nerve root, and dural sac. Discectomy and intervertebral fusion were done in L3-4 and L4-5 levels, and bilateral facet joint fusion of L2-3 was performed due to segmental dynamic instability of L2-3. L2 to L5 were fixed by rigid instruments (DePuy Synthes, West Chester, PA, USA). The right leg pain visual analogue scale (VAS) had decreased significantly the first day after surgery. Celecoxib was given to relieve low back pain. The patient was discharged home after she was able to walk independently without difficulties with a Boston brace (ten days after the surgery). The postoperative and one-month follow-up's lumbar radiographs showed no abnormal findings (Figure 2). Two months after the surgery, however, the patient returned to our department with serious throbbing low back pain. The physical examination did not reveal any dysfunction of lumbar and sacral nerves. The surgical wound had healed completely. And there was a little percussion pain over the spinous process of upper instrumented vertebrae. The blood laboratory test was indicative of bacterial infection, WBC count 7.5*109/L, neutrophile granulocyte percentage (NEU) 87.9%, ESR 16 mm/h, CRP 87.25 mg/L, and procalcitonin (PCT) 0.049 mug/L. Although the location of the infection and pathogenic bacteria were unclear, the empirical antibiotic vancomycin was prescribed after vein blood culture. However, the blood culture did not show any bacteria growth a few days later. The spondylodiscitis signal of adjacent segment in lumbar MRI further confirmed our hypothesis of infection of the lumbar spine (Figure 3(b)). The low back pain was relieved by vancomycin anti-infective therapy and celecoxib. After 5 weeks intravenous vancomycin anti-infective treatment, the patient was discharged home and we advised our patient to proceed with orally administered cefdinir. The blood laboratory tests were done periodically, and the main inflammatory index changing curves are shown in Figure 4. Within 20 days after the last review, the patient presented again with exacerbation of throbbing low back pain. The blood laboratory test suggested that the spondylodiscitis in L1-2 was uncontrolled, WBC count 10.1*109/L, NEU percentage 89.9%, ESR 30 mm/h, CRP 38.40 mg/L, and PCT 0.047 mug/L. Vancomycin and cefoperazone were combined to cover both Gram-positive cocci and Gram-negative bacilli, and oral metronidazole was used to cover the anaerobe as well. Moreover, the radiographic images revealed serious spondylodiscitis and bony endplate destruction at the adjacent L1-2 segment (Figure 5). The combined anti-infective therapy continued for a week, and the serious low back pain relieved quickly with blood inflammatory indexes dropping significantly. Single intravenous cefoperazone was used sustainably, and radiographic examinations were taken to observe the destructive extent of L1-2 segmental spondylodiscitis. The patient needed to keep strictly on her bed to avoid infective space collapse. After five-week continuous anti-infective therapy, the main blood inflammatory indexes dropped to the normal level (Figure 6), with slight residual symptom. However, the spondylodiscitis and bony endplate destruction at the L1-2 space had little changes (Figure 7). The patient then underwent posterior intervertebral debridement and posterior superior iliac crest autograft implant at the L1-2 space; the initial pedicle screws in L2 were taken out for high temperature sterilization and reimplanted. And the upper instrumented level was extended to L1 (Figures 8(a) and 8(b)). The wound drainage was pulled out after continuous negative bacterial culture of drainage liquid. The patient had satisfactory symptom relief and significant inflammatory indexes decreased (Figure 6). The debrided tissues from L1-2 did not show tumor, tuberculosis, and fungal infection through pathologic examination, and the bacterial culture did not show any bacteria growth. The patient was able to walk independently with the Boston brace (one week after revision surgery). The intravenous cefoperazone was used sustainably for four weeks after the second surgery, and then the patient was discharged. The patient came back to the out-patient department for review every two weeks. The inflammatory indexes almost dropped to normal (Figure 6). The six-week follow-up's CT scan showed that the destructive space was closed to fusion (Figure 8(c)). The patient did not complain of obvious symptoms any more.

PMC9849371_01

Female

A 42-year-old woman with a history of B-LBL was admitted to the Institute of Hematology and Blood Diseases Hospital, Tianjin, China, because of persistent dyspnea. In May 2019, the patient was evaluated at another hospital for recurrent pain in her right hip, which had begun 6 months earlier and gradually worsened with no obvious predisposing causes. PET-CT scans revealed multiple high-density nodules in both the kidneys, left acetabulum, left ilium, bilateral tibia, and right fibula as well as intense FDG uptake by these nodules. Immunohistochemical (IHC) analysis of a left kidney biopsy specimen indicated positivity for CD10, TdT, CD79a, Pax-5, CD43, c-myc (20%), and Ki-67 (90%) and negativity for CD3, CD20, CD5, CD23, Bcl-2, Bcl-6, MUM1, and CyclinD1. Neither bone marrow smear nor flow cytometry revealed any abnormal lymphocytes, and bone marrow biopsy revealed active proliferation of the hematopoietic tissue. Cytogenetic analysis revealed an abnormal karyotype: 46,XX,t(1,19)(q23;p13),-4,+mar[18]/46,XX(2). Gene fusion analysis showed positivity for E2A/PBX1. These findings led to the diagnosis of B-LBL with E2A/PBX1. The patient had received two cycles of induction chemotherapy with a combination of cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyper-CVAD A), methotrexate, and cytarabine (hyper-CVAD B). Bone marrow examination revealed 10% blasts, while PET-CT revealed no intense FDG uptake. Subsequently, the patient received vindesine, daunorubicin, cyclophosphamide, pegaspargase, prednisone (VDCLP), cyclophosphamide, cytarabine, 6-mercaptopurine (CAM), vindesine, cyclophosphamide, idarubicin, dexamethasone (VICD). Every bone marrow smear after each chemotherapy showed CR, while E2A/PBX1 was undetectable, 3.68% and 0.22% as determined via polymerase chain reaction, respectively. The patient remained well for 3 months. In May 2020, bone marrow smear revealed 47% lymphoblasts, while the rate of E2A/PBX1 rearrangement was 45.55%. Lymphoblasts accounted for 4.96% of the marrow cellularity, as determined using flow cytometry. These results suggested a diagnosis of B-ALL with E2A/PBX1 expression. Treatment with orally administered 6-mercaptopurine and prednisone was initiated to relieve the tumor burden. In June 2020, the patient underwent allo-HSCT from a matched, sibling donor after a conditioning regimen with cyclophosphamide, fludarabine, idarubicin, and antithymocyte globulin and total body irradiation. Early post-transplantation complications included mild diarrhea and mucositis. The bone marrow smear indicated CR, no E2A/PBX1 amplification, and full donor chimerism. PET-CT revealed that the treatment was effective and that the CR of the disease was achieved, with a Deauville score of 1 point. In September 2020, the patient complained of left breast pain that had begun 1 week earlier. Breast ultrasound showed multiple nodules in the left breast, while IHC of a left breast biopsy specimen indicated extramedullary recurrence of B-ALL after transplantation. Neither bone marrow aspirate nor flow cytometry showed any abnormal blasts, while E2A/PBX1 was undetectable. PET-CT revealed progressive disease, with a maximum standard uptake value (SUVmax) of 23.0 and a Deauville score of 5 points ( Figure 1A ). Then, the administration of decitabine, fludarabine, cytarabine, and granulocyte colony-stimulating factor was initiated. Acute graft-versus-host-disease of the skin occurred after donor lymphocyte infusion. Eventually, the breast nodules decreased in size, and PET-CT revealed PR of the disease, with a Deauville score of 4 points. In November 2020, the patient underwent donor-derived anti-CD19 CAR T-cell infusion after a conditioning regimen with fludarabine and cyclophosphamide. The sequence of CD19 CAR consists of an anti-CD19 single-chain antibody fragment (FMC63), CD28 transmembrane domain, 4-1BB, CD3zeta, T2A autocleavage sequences, and endodomain-deleted EGFR (tEGFR). Four days later, the patient had a recurrent high fever with a temperature of 40 C, along with lethargy and vomiting. Based on a previous study, a grade-2 cytokine release syndrome (CRS) was identified. These clinical issues improved after providing supportive care with antibiotics (meropenem and caspofungin) and dexamethasone. Meanwhile, no clear etiological evidence with next-generation sequencing (NGS) or blood culture was obtained. The patient achieved CR and was negative for minimal residual disease on the 14th day after CAR T-cell therapy and remained well for 5 months. In May 2021, the patient complained of chest pain that worsened when the patient breathed in or lay flat. Electrocardiogram (ECG) and myocardial enzyme levels were normal. Echocardiography (Echo) revealed massive pericardial effusion with rapid progression to cardiac tamponade. Ultrasound-guided pericardiocentesis, which was performed to alleviate the clinical symptoms and drain the excess fluid around the heart, revealed the presence of a hemorrhagic and exudative liquid. Multiple diagnostic tests for pericardial effusion, including bacterial gram staining, bacterial culture, fungal culture, acid fast bacteria staining, tuberculosis (TB) antibody examination, biopsy, and NGS, were performed. The results of all the above mentioned tests were negative. Flow cytometry of pericardial effusion and bone marrow aspirate did not reveal any tumor cells or CAR T cells. However, quantitative real-time polymerase chain reaction (qPCR) revealed that the copy number of CAR DNA per microgram of genome was 1.92 x 101. The results of additional laboratory tests, including those of cytokines, are shown in Table 1 . Given that some cytokines of the pericardial fluid were notably increased, CRS was considered as the possible cause of pericardial effusion. The pericardial effusion was gradually reduced and removed after immunosuppressive therapy with methylprednisolone and rucotinib. Bone marrow aspirate and PET-CT showed CR, with a Deauville score of 1 point. On presentation to our hospital (November 2021), the patient complained of dyspnea and fatigue that had begun 2 weeks earlier. The patient's medical history included hypertension. However, the patient did not need to take medications on a regular basis to control it under the guidance of a cardiologist. Immunosuppressive therapy with rucotinib and dexamethasone and preventive fungal treatment with orally administered posaconazole were continued. There were no known drug allergies. The patient lived with her husband and one child in rural China. The patient had previously worked as a farmer and did not smoke or drink. On examination, the patient's temperature was 36.6 C, her heart rate was 104 beats per minute, blood pressure was 94/68 mmHg, respiratory rate was 25 breaths per minute, and oxygen saturation was 93% while the patient breathed ambient air. Severe edema of the limbs was identified, while the results of the remaining examinations were normal. The copy number of cytomegalovirus (CMV) was 8,953 per milliliter (reference range: <1,000). Other laboratory test results are shown in Table 2 . ECG revealed changes in the ST segment, and Echo revealed that the left ventricular ejection fraction (LVEF) had decreased to 49%. The level of serum cytokines was significantly increased ( Figure 2A ). Chest CT revealed interstitial inflammation of both lungs. The patient received diuretic, albumin infusion, antiviral with ganciclovir, and supportive treatments. As part of CAR T-cell therapy, tocilizumab was administered to control elevated serum cytokine levels. Clinical symptoms were slightly improved within 1 week of admission. Notably, the level of cardiac troponin I (cTNI) was elevated prior to the administration of tocilizumab. On the 12th day after presentation, PET-CT of the body and head was performed, which showed cardiac involvement and abnormal uptake in the liver ( Figures 1B, C ). Bone marrow aspirate and cytogenetic analysis were normal, while flow cytometry revealed lymphoblasts that accounted for 0.15% of the marrow cellularity. E2A/PBX1 rearrangement was also positive. The results of CAR T cells are shown in Figure 2B . A cardiac mass biopsy was needed to achieve the pathological diagnosis but was not performed due to the patient's poor physical condition. Owing to her poor physical condition, the patient was finally administered a reduced intensity chemotherapy with cyclophosphamide, vindesine, and prednisolone (VCP). Nevertheless, on the third day of chemotherapy, her blood pressure and oxygen saturation suddenly dropped to 61/29 mmHg and 76%, respectively. Along with a heart rate of 170 beats per minute, moist rales could be heard at the base of the left lung. ECG revealed tachycardia, ST-segment depression, and inverted T waves in the V2-6 leads. Although timely first-aid measures were provided, the patient could not be rescued and was eventually discharged from the hospital. The clinical course of the patient is shown in Figure 3 .

b cell acute lymphoblastic leukemia, b cell lymphoblastic lymphoma, allogeneic hematopoietic stem cell transplantation, cardiac involvement, chimeric antigen receptor t cells

PMC6542496_01

Male

A 77-year-old man presented with depressive mood, asthenia, anorexia and weight loss of 20 kg. He also had a 1-month history of an enlarging and non-painful breast lump (Fig. 1). He did not have fever, night sweats, cough or breathlessness. He denied trauma or contact with tuberculosis. Physical examination revealed a firm and elastic mass in the internal quadrants of the left breast with well-defined contours, about 6 cm in diameter. Local temperature was normal and the overlying skin and nipple were intact. There was no evident neck or axillary palpable adenopathy. Laboratory tests showed a white blood cell count within normal limits, haemoglobin of 12.1 g/dl and C-reactive protein of 5.42 mg/dl; all other blood chemistry results were within normal limits. Radiography showed no obvious lesions (Fig. 2). Mammary ultrasound revealed in the inner quadrants of the left breast a thick-walled cystic formation measuring 69x20 mm, with detritus in the region of greatest slope. Fine needle aspiration cytology (FNAC) of a white fluid revealed a necrotic background with granulomas without neoplastic cells. Polymerase chain reaction (PCR) and acid-fast bacilli stain of the aspirate were both positive for tuberculosis. Computed tomography (CT) of the thorax showed a liquid collection in the left anterior thoracic wall, measuring 31x80 mm, associated with irregularity and discontinuity of the 4th left costal cartilage, with a fistulous tract that crossed the cartilage into a small locus posterior to the left internal mammary artery; in the upper left lobe there was a cavitated nodule measuring 22 mm, compatible with an active tuberculous process (Figs. 3 and 4). Positron emission tomography (PET) showed a possible nodule in the left upper lobe and bilateral mediastinum-hilar adenopathy, with increased uptake of FDG-F18 (Fig. 5). Peripheral uptake of FDG-F18 was noted as well in a hypodense mass in the left anterior thoracic wall. An interferon-gamma release assay (IGRA) was positive and HIV serology was negative. A sputum smear was positive for acid-fast bacilli (AFB) which was also positive by Ziehl-Neelsen staining. Sputum culture was positive for Mycobacterium tuberculosis complex that was sensitive to all tested drugs. The final diagnosis was pulmonary tuberculosis (PT) with a tuberculous mass in the left anterior chest wall, as a result of direct extension from underlying pleural and pulmonary disease. Quadruple therapy with anti-tuberculosis drugs was started: isoniazid (300 mg), rifampicin (450 mg), ethambutol (800 mg) and pyrazinamide (1500 mg). The mass did not improve with medical treatment and so was drained. The patient was discharged home following 26 days in hospital after he had improved clinically, gained weight, and three sputum smears were negative.

tuberculosis, breast lump, geriatric medicine, infectious disease

Computed tomography (CT) of the thorax showing pulmonary tuberculosis lesions.

PMC9549793_01

Female

A 24-year-old patient, gravida 1, at 40 weeks gestation by LMP, was brought to the emergency department by her family complaining of abdominal pain for 12 hours and active vaginal bleeding. She had no significant past medical history and never had antenatal care during pregnancy. She does not smoke or use drugs except antiemetics and analgesics (Navidoxine and Paracetamol). The patient had no significant personal or family history of congenital anomalies. She also denies a previous history of surgical operations, dilation and curettage, and abortions. Initially, the patient felt mild uterine contractions, minimal vaginal bleeding, and lower abdominal pain at night. The patient's condition deteriorated in the morning, and she was brought to the hospital. The patient denies a trail of labor with misoprostol or oxytocin at home or another hospital. On examination, she was pale and distressed, with a blood pressure of 70/40 mm Hg and a maternal tachycardia of 120 bpm. The uterus was tender to palpation, with no contractions noted. The patient was hemodynamically unstable. An ultrasound scan showed a fetus with no heartbeat in a transverse position. The location of the placenta could not be identified due to much free fluid in the abdominal cavity. Vaginal examination revealed a 3 cm dilated cervix with 50% effacement and active vaginal bleeding. Due to the emergency, we could not perform a detailed fetal ultrasound. The hemoglobin level at arrival was 5.4 g/dl. The patient was rushed to the operating room for an emergent operation due to suspicion of uterine rupture or placental abruption. The patient had immediate laparotomy under general anesthesia through a Pfannenstiel incision. At surgical exploration, massive hemoperitoneum was evident. A dead fresh female infant weighing 3140 grams with lethal skeletal dysplasia was found extruded in the abdominal cavity and was extracted with no need for a hysterotomy incision (Figure 1). There was marked frontal bossing with large anterior and posterior fontanelles. The nasal bridge was flat, and the ears were low set. The limbs and fingers were remarkably short, proximally and distally, with redundant skin. There was a narrow thorax with a protuberant abdomen. Based on these findings, a Type 1 Thanatophoric dysplasia diagnosis was made (Figure 2). The fetal head and abdominal circumferences were 40 cm and 55 cm, respectively. After the evacuation of the hemoperitoneum, a rupture of the uterus from the fundus anteriorly to the lower segment down to the cervix was observed (Figure 3). There was no uterine anomaly in this case, and the location of the placenta was anteriorly in the uterine fundus. The bladder was intact. The uterine defect was repaired with a continuous double-layer closure with a 1-0 vicryl absorbable suture. After obtaining hemostasis, layers were closed anatomically. The total estimated blood loss was 3000 mL; the patient was transfused with three units of red cell pack and three units of fresh frozen plasma. The patient was discharged on the fourth postoperative day with a hemoglobin level of 9.6 g/dl in good condition. After one week of follow-up, the patient was advised to use a contraceptive method for two years and prompt antenatal care for subsequent pregnancies.

primagravida, thanatophoric dysplasia, antenatal care, case report, uterine rupture

PMC10203512_01

Male

A 54-year-old male presented to our hospital because of upper abdominal pain. The patient weighed 65 kg, his height was 167 cm, and the standard liver volume (SLV) was 1231 mL, which was calculated based on the Urata formula. Laboratory examination ( Table 1 ) showed alpha fetoprotein (AFP) >60500 ng/mL, total bilirubin (TBil) 20.4 mumol/L, direct bilirubin (DBil) 7.1 mumol/L, alanine transaminase (ALT) 69 U/L, and hepatitis B surface antigen (HBsAg) (+). Abdominal enhanced computed tomography (CT) indicated liver cirrhosis, a 14.9 cm x 11.8 cm mass located in the right liver and a 1.5 cm x 1.0 cm mass located in the left liver both with heterogeneous rapid enhancement of the mass in the arterial phase ( Figure 1A ). The patient was diagnosed with chronic hepatitis B from childhood and had regular antiviral therapy while finding the masses in the liver. The clinical diagnosis was HCC with BCLC-B stage. According to the BCLC strategy, transarterial chemoembolization (TACE) and a combination of the targeted drug (lenvatinib, 8 mg once a day) and ICIs (camrelizumab, 200 mg every three weeks) were performed ( Figure 1F ). After two courses of TACE and five cycles of immunotherapy, abdominal enhanced CT showed that the range of enhancement was significantly smaller than before. Although the diameter of the lesion was slightly smaller, the lesion reached partial response (PR; i.e., >30% decrease in the sum of diameters of viable (enhancing) target lesions) according to modified Response Evaluation Criteria Solid Tumours (mRECIST). Laboratory examination before the surgery showed AFP 167.0 ng/mL, TBil 14.6 mumol/L, DBil 5.9 mumol/L, aspartic transaminase (AST) 41 U/L, and ALT 37 U/L. The volume of FLR was 475 mL, as calculated by abdominal CT ( Figure 1B ). An insufficient FLR could be linked to a high risk of postoperative liver failure after first-stage resection. After having obtained the consent of the patient and his family, the first stage of ALPPS and resection of the left lesion by laparoscopy was performed three months after the first course of TACE. A postoperative liver function test (LFT) indicated TBil 13.3 mumol/L, DBil 5.5 mumol/L, and ALT 303 U/L. Liver function improved after liver protection therapy. Twenty-one days after the first-stage surgery, abdominal CT indicated that the FLR increased to 576 mL ( Figure 1C ), and the rate of FLR/SLV was 46.8%, which could meet the needs of the body. The second stage of ALPPS was completed, and the TBil, DBil and ALT were 30.6 mumol/L, 13.3 mumol/L and 182 U/L, respectively, on the first day after surgery. Changes in liver function are shown in Figure 1E . The FLR was 708 mL ( Figure 1D ), and the patient was discharged 7 days after second-stage ALPPS. A pathology report demonstrated a mass in the left liver with moderately differentiated HCC and a mass in the right liver with extensive haemorrhage and necrosis and no clear residual tumour cells, which reached pathological complete response (pCR). The systemic therapy was restored two months after ALPPS with the same regimen as before in the follow-up clinic. The follow-up examination showed no recurrence on imaging and sufficient FLR on that day.

associating liver partition and portal vein ligation for staged hepatectomy, future liver remnant, immune checkpoint inhibitors, immunotherapy, unresectable hepatocellular carcinoma

PMC10203512_02

Male

A 48-year-old male was admitted to our hospital due to a palpable mass in the right upper abdomen. The patient weighed 60 kg with a height of 178 cm, and the SLV was 1217 mL. Laboratory examination ( Table 2 ) revealed TBil 12.2 mumol/L, DBil 5.8 mumol/L, alkaline phosphatase (ALP) 1016 U/L, gamma gamma-glutamyl transpeptidase (gamma-GGT) 671 U/L, HBV-DNA 735780 IU/L, and HBsAg (+). AFP was at the normal level. Abdominal enhanced CT showed a 16.2 cm x 11.2 cm mass situated in the right liver with inhomogeneous enhancement of the mass in the arterial phase and multiple intrahepatic metastatic lesions ( Figure 2A ). In addition, the patient was administered interferon therapy when diagnosed with HBV. According to the BCLC-B stage, stereotactic therapy for HCC was performed (i.e., TACE combined with 8 mg lenvatinib once a day and 200 mg camrelizumab every three weeks, Figure 2F ). Abdominal CT showed that the diameter of the lesion was reduced from 16.2 cm to 9.7 cm ( Figure 2B ) after three courses of TACE and ten cycles of camrelizumab. LFT was almost normal, except ALP 261 U/L and gamma-GGT 120 U/L. The first stage of ALPPS was performed with laparoscopy after obtaining the consent of the patient and his family. LFT suggested TBil 12.5 mumol/L, DBil 5.6 mumol/L, and ALT 163 U/L on the first day after surgery. One month after the first-stage surgery, the volume of FLR was 473 mL, which was more hypertrophic than the baseline volume of FLR (356 mL) ( Figure 2C ). The rate of FLR/SLV was 38.9%, and the patient received right hepatectomy plus right caudate-leaf resection by laparotomy. Changes in liver function are shown in Figure 2E . The pathology report suggested moderately differentiated hepatocellular carcinoma with satellite nodules. Systemic therapy was restored one week after second-stage ALPPS. Re-examination of CT one month after second-stage ALPPS indicated sufficient FLR ( Figure 2D ).

associating liver partition and portal vein ligation for staged hepatectomy, future liver remnant, immune checkpoint inhibitors, immunotherapy, unresectable hepatocellular carcinoma

PMC3897989_01

Male

A 65-year-old male was admitted to our hospital complaining of jaundice, pruritus, mild right upper abdominal pain and darkening urine. Past medical history revealed atrial fibrillation and the patient was on intermittent aspirin therapy. And the family history was negative. Physical examination revealed icteric sclera and skin, mild upper abdominal tenderness, arythmia, irregular heart sound and pulse deficit. The laboratory test data at admission showed that the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (gamma-GT), total bilirubin (TBil) and direct bilirubin (DBil) were elevated to 79 U/L (5-45 U/L), 51 U/L (5-35 U/L), 540 U/L (30-110 U/L), 197 U/L (7-50 U/L), 408 mumol/L(0-20.5 mumol/L) and 283.7 mumol/L (0-6.8 mumol/L), respectively. Serum IgG and IgM were 3,180 mg/dL (694-1620 mg/dL) and 344 mg/dL (60-263 mg/dL), respectively. The titer of antinuclear antibody (ANA) was 1:320. Screening for antoimmune diseases revealed that the patient was positive for antimitochondrial antibody (AMA), anti-AMA-M2 and anti-Ro antibody. Common tumor markers and viral markers were all negative. Both computed tomography (CT) and magnetic resonance image (MRI) revealed diffusive enlargement of the pancreas, capsuled by an armorlike low-density rim and enhanced homogenously (Figure 1). Other abnormalities included significant dilation of intra- and extra-hepatic bile duct, diffusive thickening of the gallbladder wall and atrophy of the right kidney. Endoscopic retrograde cholangio-pancreatography (ERCP) was conducted, revealing similar findings with CT and MRI. No sign of malignancy was observed. Test of tumor markers from the bile showed CEA of 66.89 ng/mL (0-5 ng/mL) and CA199 larger than 4000 U/mL (<37.0 U/mL), but examinations of exfoliated cells proved negative for three consecutive times. The biliary culture was positive for ESBL-producing Klebsiella pneumoniae. Infection was suspected and meropenem (0.5 g per 8 hours) was administered. Based on the biochemical evidence of cholestasis from the elevation of ALP, gamma-GT and TBil, and the presence of AMA, the patient was clinically diagnosed with PBC and UDCA (250 mg, three times per day) was initiated immediately after nasobiliary drainage, which partially improved the patient's liver function (Figure 2). Since the patient was also suspected of suffering from AIP, the following examinations were conducted. IgG4 was measured and turned out to be 44.36 g/L (0.03-2 g/L). CT-guided pancreatic biopsy was performed, and histopathological evaluation showed dense lymphoplasmacytic infiltration and fibrosis. IgG4+ plasma cell was stained and counted to be as high as 95 per high-power field (HPF) (Figure 3). ECT of salivary gland was normal. So the diagnosis of type I AIP was confirmed in accordance with the diagnostic criteria. Steroid therapy with intravenous methylprednisolone (MEP) (40 mg per day) was administered promptly. Serum ALP, gamma-GP, TBil and DBil just before steroid therapy were 376 U/L, 38 U/L, 404.9 mumol/L and 289.2 mumol/L, respectively, and one week later were 243 U/L, 47 U/L, 47 U/L, 206.1 mumol/L and 167.1 mumol/L, respectively. Then we stepped down the steroid therapy with oral MEP 32 mg daily, yet the serum liver enzymes and bilirubin bounced up. So we increased the dose to 32 mg in the morning and 16 mg in the afternoon. And then the laboratory values improved. A repeat MRI showed remarkable reduction of the pancreas. 40 days after treatment, the IgG and IgM returned back into the normal range. The serum levels of ALP, gamma-GP, TBil and DBil were 135 U/L, 134 U/L, 82.8 mumol/L and 54.9 mumol/L, respectively. The patient was discharged and followed up at the clinic with MEP tapered off weekly by 5 mg. The clinical course is depicted in Figure 2. About 40 days after discharge, the patient developed red maculopapules on his right chest with prickling-like pain, worsened with erosion and blisters. The patient was diagnosed with herpes zoster and treated with acyclovir (500 mg twice a day) for 9 days. Unfortunately for the patient, a chest X-ray later showed multiple nodules in the right lung. Chest CT displayed multiple patchy shadows with cavity. CT-guided lung biopsy showed neutrophil aggregation and fibrous effusion within the alveoli. The patient was diagnosed with pulmonary abscess and was treated effectively with moxifloxacin (Figure 1). Given the immunosuppressed status of the patient, thymosin was injected twice a week to restore the immune function. The liver function and immunological indices of the patient were normal during the subsequent one-year follow-up period.

CT and MRI scan of the patient. Chest CT (H) showed a large patchy shadow in the right lower lobe.

PMC6295306_01

Female

We report the case of a 25-year-old woman (164cm, 84kg, G2 P1). She was referred to the tertiary care level delivery unit of Farhat Hached University Hospital for a scheduled c-section at 37 weeks of gestation. The medical history of the parturient notes a hypertrophic cardiomyopathy diagnosed at the age of 12 in a context of a repeated shortness of breath. She has been put under bisprolol 2.5 mg/day. The evolution of the illness was marked by the occurrence of two episodes of syncope at the age of twenty. The rhythmologic exploration has highlighted severe and paroxysmal ventricular rhythm disorders indicating the placement of a double room implantable cardioverter defibrillator (ICD). Afterwards, the evolution was uneventful. The current pregnancy was spontaneous and well followed by the obstetrician and the cardiologist (monthly consultation). No cardiovascular or obstetric complication was noted. Bisprolol dose was doubled throughout the pregnancy. The patient presented for an elective cesarean section at 39 SA. Clinical examination showed 86 heartbeats per minute, blood pressure of 110/80 mm Hg and a respiratory rate of 18 cycles/min. A transthoracic ultrasonography showed an asymmetrically overdeveloped left ventricle (LV), an inter ventricular septum at 28 mm, a Left ventricular ejection fraction of 80%, an intra LV gradient of 10 mm Hg, a disorder of the compliance of the LV with high filling pressures of the LV, a non-dilated left atrium, and not distended right cavities with normal systolic function of the right ventricle (Figure 1). Anesthetic examination shows a good venous capital and no evidence for oral intubation difficulty. The patient was sent on the eve of the caesarean section to her cardiologist who decided the deactivation of the defibrillator given the risk of inadvertent activation during the scheduled surgery. In the operating room, the patient received invasive monitoring of her blood pressure, her electrocardiogram, her pulse oxygen saturation measurement and her expired CO2 pressure. The venous infusion during the surgery was established with a 16 G peripheral branule in the back of the left hand prefilled with 500ml of saline. The patient had a rachi-analgesia at the level of L4 - L5 with 200mug of morphine. The induction was with a rapid sequence with 3 mg/kg propofol, 1 mg/kg of suxamethonium and 0.5mug/kg of remifentanil. Oral intubation was performed without incident. The anesthesia was performed by of sevoflurane and of remifentanil at a dose of 0.05g/kg/min. An antibiotic prophylaxis with 2g of Cefazolin was administered after the clamping of the umbilical cord. Ten minutes after the anesthetic induction occurred the fetal extraction of a female newborn of 2900 g weight and an Apgar score of 8/9/10. Five IU of oxytocin were slowly intravenously injected then, followed after the delivery by a dose of 20 IU of oxytocin for 4 hours. During the surgery the hemodynamic parameters were stable (no heart arhythmia) authorizing the awakening and extubation of the patient on the operating table. The patient was transferred in the resuscitation care unit. She received a multimodal analgesia. The ICD has been reactivated 6 hours after the end of the intervention. Postoperative outcomes were simple: in particular, no cardiac rhythm disorder, or heart failure. The patient was released 3 days after her delivery. She was referred to her cardiologist for a further adjustment of her drugs.

pregnancy, anesthesia, implantable cardioverter-defibrillator

PMC9273825_01

Female

A 28-year-old young female patient came to our hospital for the treatment. She had a 3-year medical history of chest pain on the right side. A CT scan outside the hospital found a mass in her lungs 7 days ago. The admission CT showed that there was a prominent mass on the right posterior upper chest wall invading the adjacent vertebral body but the boundary between the lesion and the surrounding tissues was relatively clear (Figures 1A,B). The laboratory examination did not reveal any specific findings. After completing other examinations, the clinician surgically removed the tumor. During the operation, it was observed that there was a tumor of about 8 * 7 * 5 cm on the right posterior chest wall at the position of the 1-4 posterior ribs. The cut surface of the tumor was fish-like, and it possesses a tough texture, poor mobility, and abundant blood supply, thus destroying the right posterior rib. The specimens were thereafter fixed in 4% neutral buffered formaldehyde and then embedded in paraffin, sectioned routinely, stained with HE, and observed under a microscope. The specific experimental procedures were carried out in strict accordance with the instructions, and the control was established routinely. We used fluorescence in situ hybridization to detect the status of EWSR-1 and FUS genes in the tumor tissues. According to the previously reported protocol, EWSR-1 and FUS fragmentation probes were used for FISH. If more than 10% of the 100 cells analyzed show rearrangements, the tumor sample was considered as positive. The tumor was evaluated and scored by two independent investigators. After clinical resection, a gray-yellow gray-brown foliated mass with a size of 8 x 7 x 5 cm was sent for the pathological evaluation. The surface of the mass appeared to be enveloped. The cut surface was grayish-yellow-white, solid, and tough, with mucinous degeneration in some specific areas (Figure 2). The boundary of the entire tumor was still clear. The tumor cells were abundant, and the morphology was relatively uniform. They were arranged in single, nested, cord-like, or sheet-like arrangements in the vitreous collagen interstitial, showed infiltrating growth, and the local bone tissue invasion can be seen. The stroma was composed of a large number of collagen fibers with obvious hyaline degeneration and occasional mucus-like areas. The tumor cells showed diverse morphologies and were spindle-shaped, short spindle-shaped, or irregular-shaped epithelioid cells. The tumor cell nuclei were oval, round, or polygonal, with sparse cytoplasm and rare mitotic images. A part of the area of the tumor showed that broad hyalinized collagen areas and mucinous degeneration-like areas were alternately arranged. In the peripheral part of the tumor, the cells were spindle-shaped and arranged in the bundles, exhibited fibromatosis-like images, and migrated with epithelial-like cells. Fatty changes could be seen locally in some specific areas (Figure 3). We did an immunohistochemical test for the tumor tissues, the immunohistochemical examination of the tumor showed positivity for Vimentin, MUC4, and CD99, while the other tumor markers such as CK, EMA, Calretinin (CR), WT1, D2-40, CD34, STAT6, CD99, beta-catenin, S100, SMA, Desmin and SATB2 were negatively expressed, and Ki67 index as proliferation marker was about 10% (Figures 4A,B, (A) MUC4 expression in colon glands (positive control), (B) MUC4 expression in tumors). The FISH analysis uses FUS and EWSR1 dual-color lysis probe to detect and analyze paraffin sections. For the EWSR1 lysis probe, among 200 different tumor cells, about 40% of the cells showed one fusion (red/green) signal and one or two red cleavage signals per nucleus. FISH results suggested that there was a non-interchangeable translocation involving the EWSR1 gene. On the contrary, for FUS fragmentation probes, the tumor cells showed 3-10 fusion (red/green) signals per nucleus. However, none of these were tested to determine their genetic partners or fusion breakpoints (Figures 4C,D). Thereafter, we further used the next-generation sequencing technology based on targeted deep sequencing to detect the potential RNA sequence of this case specimen, the RNA sequencing was performed on an Illumina NextSeq platform. We found that there was presence of EWSR1-CREB3L1 fusion, which was composed of exon 9 of EWSR1 and exon 6 of CREB3L1. However, there were no abnormal changes observed in the FUS gene.

ewsr1, fish, immunohistochemistry, sclerosing epithelioid fibrosarcoma, soft tissue sarcoma

PMC4275023_01

Male

A 47 year old South Asian male teacher presented to our institute in June 2012 with a diagnosis made elsewhere of accelerated hypertension and acute left ventricular failure following a recent anterior wall myocardial infarction. He was admitted to hospital for further cardiac management, and a nephrology consultation was sought for renal insufficiency (serum creatinine 1.9 mg/dl). The presence of an active urinary sediment (urine albumin 3+ by dipstick and microscopic hematuria) necessitated a renal biopsy which showed IgA nephropathy ( Figure 1) with an Oxford Pathological score of M1E0S1T1, 5/10 glomerular sclerosis and 30% IF/TA with hypertensive changes in blood vessels ( Figure 2). The patient was initiated on olmesartan 20 mg/day and prednisolone 50 mg/day and a follow up for management of proteinuria was advised. He presented again 7 months later with swelling pain and erythema of the right clavicle that had been present for 2 months. He was evaluated for these complaints at another centre before presentation to ours and was diagnosed with synovitis of the medial end of the right clavicle. Ultrasound guided aspiration of fluid from the swelling and analysis of bacterial cultures in an external laboratory did not reveal any organism. The patient was subsequently treated with non steroidal anti inflammatory drugs and prednisolone for 1 week. Physical examination following admission at our centre revealed a normal body mass index (BMI) and vitals with an otherwise unremarkable systemic examination. Local examination of the right clavicle revealed a swelling of 2x3 cm with erythema, induration, warmth and tenderness with a firm consistency. The skin did not show discharging sinuses. Laboratory investigations revealed the following: white blood cells (WBC) count 12,400 cells/mm 3 with predominant polymorphonuclear cells, platelet count 290,000/mm 3, erythrocyte sedimentation rate (ESR) 93 mm/hr, urea 42 mg/dl and serum creatinine 1.5 mg/dl. Liver function tests revealed: serum glutamic oxaloacetic transaminase (SGOT) 69 IU, serum glutamic-pyruvic transaminase (SGPT) 44 IU, alanine aminotransferase (ALP) 130 kU, total protein 7.3 g/dl serum albumin 3.3 g/dl. Serology for HIV, hepatitis B and the venereal disease laboratory test (VDRL) were negative, anti-streptococcal antibody (ASO) was titre-negative, and C3 and C4 levels were within the normal range. Urine analysis showed 1+ albumin by dipstick, and microscopic examination of the urine showed 6-8 WBC/high power field (hpf), 2-3 epithelial cells/hpf, 4-6 RBCs/hpf and occasional granular casts. Sonography of the abdomen showed bilateral normal sized kidneys with increased echogenicity and maintained corticomedullary differentiation. Ultrasound guided aspirate of the pus from the right clavicle was cultured using BacT Alert 120 (bioMerieux, France) which showed Gram-negative and oxidase-positive rods. This suggested the presence of P. aeruginosa that was found to be sensitive to cefoperazone and sulbactam, using Vitek Compact II (bioMerieux, France). Repeated staining for Acid Fast Bacilli was negative. Tuberculosis (TB) PCR analysis and staining for fungal elements were negative. CT scan of the clavicle showed cortical and subcortical irregularity with soft tissue swelling of the medial end of right clavicle suggestive of osteomyelitis. Curettage and lavage of the site was followed by a gentamicin impregnated dressing (Septocoll E, Biomet Deutschland GmbH, Berlin), and histopathological examination of the sequestrum revealed non-caseating granulomas surrounded by many neutrophils, lymphocytes and plasma cells, suggestive of chronic osteomyelitis. The patient was begun on intravenous cefoperazone and sulbactum 1.5 g BD as per the sensitivity report for a period over 3 weeks.

PMC8053605_01

Male

A 77-year-old man was admitted to the Affiliated Hospital of Nantong University in November 2018 with a >1-month history of repeated fever, with night sweats and weight loss. Laboratory results showed thrombocytopenia and liver function reports showed increased lactate dehydrogenase and decreased albumin levels. A hepatitis B surface antigen test was positive, serum IgG levels were low, peripheral blood EBV-DNA was 2885 viral copies/mL (reference range, 0-1000 viral copies/mL), VCA IgG antibodies showed 170 U/mL (reference range, 0-20 U/mL) and EBNA IgG antibodies were 119U/mL (reference range, 0-5 U/mL). Lymphocyte subset analyses showed decreased lymphocyte, total T lymphocyte, helper T cell, and cytotoxic T cell counts. No obvious abnormality was detected by bone marrow puncture. Positron emission tomography (PET)/computed tomography (CT) showed increased 18F-fluorodeoxyglucose (FDG) uptake in multiple masses, including extensive lymphadenopathy in the neck, chest, abdomen, pelvic cavity, and inguinal region, with evident splenomegaly and nodular lesions, some of which showed slightly higher FDG standardized uptake values (SUVmax; approximately 10, short diameter <2 cm). In addition, an intestinal mass (measuring 5.8x4.5x3.7 cm) revealed a notably higher FDG SUVmax of 20.5. Core needle aspiration cytology of the left axillary nodule performed the unnormal lymph node architecture with a infiltrate of atypical lymphoid proliferation, predominantly composed of medium-sized T cells with a clear cytoplasm, occasional eosinophils, immunoblasts, and proliferation of high endothelial venules. Immunohistochemistry showed these neoplastic T cells were positive for CD3, PD-1, CD10, Bcl-6, CD4, CD8, CD5, CD21 (expansion of the follicular dendritic cell meshwork +), Ki67 (30%+), and negativity for CD56, CD20, CXCL13, and Epstein-Barr-encoded RNA (EBER), with partial loss of CD7. T cell receptor gene rearrangement was positive but no clonal IgH gene rearrangement was detected (Figure 1). The patient was diagnosed with AITL, with a prognostic index for T-cell lymphoma (PIT) score of 3. Before treatment, he suddenly developed severe abdominal pain, and abdominal CT showed gastrointestinal perforation. He therefore underwent emergency surgery, and pathological examination showed an ulcerative mass on the ileum. Immunohistochemical staining revealed that the diffuse infiltration of these abnormal medium-to-large-sized lymphocytes with prominent nucleoli was predominantly positive for Bcl-6, MUM1, CD20, CD21, CD10, EBER (>200/high-power field), and Ki67 (80%+), but negative for CD3, PD-1, CD8, CD4, CD5, CD7, and CXCL13 (Figure 2). He was subsequently diagnosed with EBV-positive DLBCL (stage IV, group B). The International Prognostic Index (IPI) was 4, indicating high risk. The patient had a history of tuberculosis for 40 years and had undergone a left upper lobe resection 7 months prior with postoperative pathology of the lung tissue suggesting carcinoma in situ. Considering his complex illness and inferior performance status, the patient was administered six cycles of R2-miniCHOP (lenalidomide 25 mg by oral administration on days 1-10, rituximab 600 mg on day 0, cyclophosphamide 600 mg on day 1, doxorubicin liposome 20 mg on day 1, vinorelbine 30 mg on day 1, and prednisone 30 mg on days 1-5), with no serious adverse events during treatment. His symptoms subsequently improved, with weight gain. PET/CT scan demonstrated decreased FDG uptake in many parts of the body compared with before treatment (Figure 3). The patient was then treated with lenalidomide (10 mg/day on days 1-21, every 28 days) as maintenance therapy and remained in sustained remission for more than 20 months.

epstein–barr virus, angioimmunoblastic t-cell lymphoma, diffuse large b-cell lymphoma, discordant lymphoma, lenalidomide, positron emission tomography/computed tomography

PMC5420064_01

Male

A 13-year-old football player with a 1-year history of recurrent palpitations during exercise despite beta-blocker therapy attended our Paediatric Arrhythmia Clinic. An initial electrophysiology study diagnosed typical slow-fast AVNRT. Despite an aggressive radiofrequency ablation procedure including lesions in the low, middle, and superior aspects of the triangle of Koch as well as in the coronary sinus, we could not induce any junctional response. After a conventional right-sided procedure, there was no modification in the tachycardia characteristics or in the slow pathway conduction (including tachycardia induction, cycle length, and slow pathway refractory period). A decision was made to attempt a left-sided procedure. A steerable decapolar electrode catheter was placed in the coronary sinus, and the His position was again identified on the anterior septum. The transseptal puncture was performed using the usual technique under fluoroscopy guidance without complications, followed by heparin administration. A deflectable catheter with a 4-mm tip was introduced into the left atrium, and the septal aspect of the mitral valve was mapped. A balanced atrioventricular signal with multicomponent atrial electrograms and low amplitude potentials was identified in the posteroseptal aspect of the mitral annulus, 3 mm above the coronary sinus (Figure 1). This left site clearly corresponded with the usual target for a conventional right-sided procedure (Figure 2, Figure 3). At this point, a single radiofrequency application resulted in an immediate accelerated junctional response with stable retrograde ventriculoatrial conduction. This application also resulted in temperatures of 55 -60 and was continued for 60 seconds. After this ablation, AVNRT was not inducible despite aggressive atrial stimulation on isoprenaline. The procedure was terminated without complications, and the patient did not show recurrence of palpitations afterward.

avnrt ablation, left-septal ablation, pediatric electrophysiology, slow pathway ablation, transeptal ablation

PMC9421219_01

Unknown

We carried out a retrospective chart review of patients in the respiratory care unit (RCU) at Jackson Memorial hospital in Miami, Florida. Inclusion criteria included: patients older than 18 years old, concomitant diagnosis of HIV and active TB, receiving DTG and RBN, and undergoing measurement of DTG and RBN plasma concentrations. Furthermore, the adherence of these medications is high as these patients were evaluated in the inpatient setting where administration of medications is monitored by clinicians. On admission to RCU, the patients are started on a TB regimen and undergo PK sampling 2 weeks after the regimen is established. When changes are made to the TB medications, or HIV medications are added, a repeat sampling is done. Blood sampling is done when fasting. DTG: Samples are drawn at the end of dosing interval to assess trough plasma concentration (Cmin) and at 2 and 6 h to assess peak (Cmax) concentration. The typical DTG peak and trough concentrations are approximately 3.3 mcg/mL and 0.80 mcg/mL, respectively. However, we do agree that there is an acceptable range and trough concentrations that may be higher than the in vitro protein-adjusted IC90 for wild-type virus. RBN: Samples are drawn at 3 and 7 h to assess peak plasma concentration (Cmax) to capture either early or delayed absorption. Expected concentrations are 0.45-0.9 mcg/mL. Blood samples were sent to the Infectious Disease Pharmacokinetics Lab at the University of Florida in Gainesville, Florida. Phoenix WinNonlin v.8.0 (Certara USA, Inc., Princeton, NJ, USA) was used to perform the non-compartmental analysis and calculate the area under the concentration-time curve (AUC) for DTG and RBN. The area under the concentration-time curve for the dosing interval (AUC0-tau) and 24-h period (AUC0-24) were calculated. AUC0-tau and AUC0-24 were extrapolated from the elimination phase captured during the PK sampling of each drug. If the elimination phase was not captured during that time, the AUC0-last sample was reported instead. Tables 1 and 2 shows the calculated AUCs for DTG and RBN. In addition to therapeutic drug monitoring (TDM), patients underwent blood collection for evaluation of CD4+ cells and viral loads. Our study was approved by the institutional review board, University of Miami, Jackson Memorial Hospital; number: 20191069. This is a retrospective study with chart review for data collection; no written informed consent was required by the institution.

hiv, dolutegravir, rifabutin, tuberculosis

PMC6010612_02

Female

Her family history revealed that she was born from non-consanguineous parents. Her father, a smoker affected with a chronic cough and bronchorrhea with chronic bouts of bronchitis and sibilance, died at the age of 36 from respiratory distress. Four male siblings also died from respiratory distress at the age of 7 days, 3 months, 2 years and 6 years, respectively. A 10-year-old brother was healthy, while a 5-year-old sister was affected with chronic respiratory symptoms (patient 2) and an 11-year-old sister presented with joint and skin symptoms (patient 3). Her mother was suffering from ankylosing spondyloarthritis (ASA). The genealogical tree is shown in Fig. 1. At admission, physical examination of the index case described a 151-cm-tall girl weighing 49 kg, 37 C of body temperature, 92 heart beats/min, 100/60 mm Hg of blood pressure, 38 breaths/min of respiratory rate, absence of cyanosis, no nail clubbing, a cambered and tympanic chest to percussion, wheezing in the tops, and crackles at lung bases. Chest X-ray showed bronchiectasis. Thoracic computed tomography (CT) confirmed cystic right bronchiectasis of the middle and lingular lobes (Fig. 2a). A functional respiratory assessment (FRA) showed a mixed and diffuse ventilation defect with moderate obstruction, more severe in the small airways. Blood count detailed 6.6 G/L leucocytes, 3.66 G/L neutrophils, 116 g/L hemoglobin and 362 G/L platelets. A normal sweat test (<50 mmoL/L) excluded the diagnosis of cystic fibrosis. HIV serology was negative, immunoglobulin quantitation was within the normal ranges (IgM: 0.75 g/L, IgA: 3.19 g/L, IgG: 15.32 g/L). Tuberculosis and aspergillar superinfection were also excluded. Serum protein electrophoresis, performed as a first-line of investigation, showed no alpha-1 globulin peak. Serum AAT quantitative analysis was performed by an immunoturbidimetric test adapted on a multiparametric analyser Konelab 60* (Thermo Fisher Scientific, Cergy Pontoise, France) and revealed undetectable levels (AAT <0.1 g/L). AAT elastase inhibitory activity (EIA), assessed through a kinetic spectrophotometric method, was drastically decreased (3849 Inhibitory Units/L, with 17,500-31,500 IU/L as reference values), in accordance with the very low level of serum AAT. AAT phenotyping, carried out by isoelectrofocusing electrophoresis (IEF) using ready-to-use agarose gels with immunological detection, revealed a profile without any band, consistent with a very low circulating level of AAT. PI*S and PI*Z-allele-screening by dot blot PCR was negative so a further search for rare variants, by genotyping of the whole coding sequence of SERPINA1 gene by Next Generation Sequencing (NGS), was advised. Genotyping results, according to usual nomenclature, were as follows: a c.775A>T homozygous mutation in exon III of SERPINA1 was characterized. The expected consequence is the generation of a truncated protein with premature stop codon p.(Lys259*), leading to an inactive protein. This Null mutation was previously identified by Zorzetto et al. and recorded as Q0cairo. An additional homozygous c.638T>C sequence variation was also identified, corresponding to a frequently observed variant p.(Val213Ala); this variant was associated with the Q0cairo described by Zorzetto et al. The same homozygous genotype was identified for patients 2 and 3. The Q0cairo mutation was also detected, in heterozygosis, for the maternal DNA, along with the heterozygous point mutations characterizing the PI*M2 allele, which is generally considered to be without physiological or clinical impact. Nevertheless, an increase in PI*M2 allele frequency has been reported in Tunisian asthmatic patients. The biochemical and genetic results of the four family members are summarized in Table 1. The clinical history of the index case revealed recurrent episodes of cough, bronchial congestion and dyspnea from the age of 3 months. At the age of 8, she developed a bronchorrhea with chronic wheezing and bronchial exacerbations. Moreover, she presented with several episodes of bronchial super-infection that required hospitalization. Bronchoconstriction was chronic with severe exacerbations in autumn/winter that required salbutamol nebulization at home in addition to a bronchodilator, inhaled corticosteroid, leukotriene antagonists and annual influenza vaccination. The patient developed two episodes of right pneumothorax: the first was treated with two thoracic drains, the second was more severe and spread to bilateral sides respecting apexes after a broncho-pleural fistula and a cystic bronchiectasis complication. Intermittent neutropenia was revealed by blood counting.

alpha-1 antitrypsin deficiency, bronchiectasis, null mutation, panniculitis, serpina1 genotyping

PMC9039281_01

Male

A 54-year-old man was admitted to the Department of Intensive Care Medicine of the First Affiliated Hospital, Sun Yat-sen University, on June 30th, 2021, due to headache and fatigue for 2 days. The patient developed a headache on June 28th, 2021, without obvious inducement, and gradually had drowsiness, accompanied by fatigue, anorexia, and occasional cough, which could not be relieved after rest. No other abnormal symptoms were detected. The patient had a history of hypertension and gout for more than 10 years. He since had been diagnosed with sepsis and multiple organ failure in the ICU of a local hospital due to fever with upper abdominal pain. Metagenomic next-generation sequencing (mNGS) of blood on May 8th showed negative. After treatment of mepem 1 g every 6 h (Q6H), the patient was cured and was discharged 2 months ago. He did not take immunosuppressive drugs regularly for a long time and had no history of exposure to poisons, chemical agents, or animals. Personal and family histories were unremarkable. Physical examination on admission showed body temperature of 36.0 C, pulse at 94 beats/min, respiratory rate of 14 breaths/min, blood pressure at 69/37 mmHg, drowsiness, chemosis, coarse breath sounds, and a small number of moist rales heard in both lower lungs. Cardio abdominal physical examination was unremarkable. Extremities were moderate edema. The movement of both upper limbs was good, and the movement of both lower limbs was limited. Auxiliary examination was also performed. Blood gas analysis showed metabolic acidosis, pH of 7.25, BE -16 mmol/L, and oxygenation >300. Elevated infection indicators analysis showed CRP of 234.75 mg/L, PCT of 5.06 ng/mL, and WBC of 41.84 x 109/L. The patient was detected with mild anemia (RBC of 3.26 x 1012/L and Hb 93 g/L), prolonged coagulation time (APTT of 58.2 s), renal insufficiency (urea of 19.5 mmol/L and CREA 357 mumol/L), and acute heart failure (TnT-T of 0.130 ng/mL and NT-proBNP of 20813.0 pg/mL). In addition, the patient had elevated liver metabolic total bilirubin (TBIL of 79.6 mumol/L) and predominantly elevated direct bilirubin (DBIL of 55.9 mumol/L). Immunosuppressive status revealed a lower immunoglobulin M (0.49 g/L) and immunoglobulin G (7.37 g/L), B lymphocytes (CD3-CD19 +) % of 0.48%, B lymphocytes (CD3-CD19 +) count of 2.41 cells/mul, regulatory T-cells (Treg) of 18.75%, interleukin 6 of 1508.65 pg/mL, and interleukin of 10 5.57 pg/mL. Bacteriology, mycology, and tuberculosis tests of blood, sputum, urine, and stool showed no pathogens. HIV, syphilis, and Hepatitis virus tests were negative. Radiography of the pulmonary showed worsening infiltrate (Figure 1). Septic shock was considered. The patient was given Sulperazone 3 g, Q8H for anti-infection, fluid infusion, correction of acidosis, acid suppression, stomach protection, and prothrombin complex supplement on June 30th. After 7-day treatment, the infection indicators were significantly lower than before, with PCT of 1.19 ng/mL, CRP of 49.41 mg/L, WBC of 8.08 x 109/L, NEUT of 6.94 x 109/L. The conditions were under control. On July 7th, the patient had a sudden light coma with repeated generalized tonic-clonic seizures, with the most extended duration lasting for about 90 s. He was transferred to the neurological ICU for treatment with a GCS score of 5. Twenty-four-hour bedside quantitative EEG monitoring was immediately performed, which showed simultaneous epileptic discharges in both cerebral hemispheres during convulsive seizures. Sodium valproate 1,200 mg QD (from July 7th to July 10th), and Oxcarbazepine 300 mg Q12H combined Levetiracetam 1 g Q12H (from July 9th to August 16th) were then used. The epilepsy did not recur. On July 8th, a lumbar puncture was performed to measure the initial pressure of 210 cmH2O and the final pressure of 135 cmH2O. CSF was collected and submitted for examination. Biochemical combination of CSF revealed glucose of 3.0 mmol/L, CSF chloride (Cl) of 131 mmol/L, CSF protein (PROT) of 734.7 mg/L, synchronous blood glucose of 5.9 mmol/L, and blood chloride of 117 mmol/L. Samples were also sent for PACEseq mNGS (Hugobiotech, Beijing, China). QIAamp DNA Micro Kit (QIAGEN, Germany) was used for DNA extraction, and the libraries were then constructed using QIAseq Ultralow Input Library Kit for Illumina (QIAGEN, Germany). The quality of libraries was assessed by Qubit (Thermo Fisher) and Agilent 2100 Bioanalyzer (Agilent Technologies). The qualified DNA libraries were finally sequenced on Nextseq 550 platform (Illumina). Adapter, short, low-quality, and low-complexity reads were removed from the raw data. The human DNA was filtered out by mapping to human reference database (hg38). The remaining reads were finally aligned to the Microbial Genome Databases (http://ftp.ncbi.nlm.nih.gov/genomes/). B19V DNA (2 specific reads) in CSF was detected. Polymerase chain reaction (PCR) was then performed using B19V Q-PCR Detection Kit (ZJ Bio-Tech, Shanghai, China) and confirmed the mNGS results. CSF cytology showed a lymphocyte-monocyte reaction pattern. CSF routine, bacterial culture, autoimmune encephalitis antibody detection, and oligoclonal bands (OB) were unremarkable. Determination of CSF B19V DNA on July 9th showed 1.0 x 10 copies/mL. B19V caused encephalitis was considered. After transfer, the patient's pneumonia was gradually aggravated, with type I respiratory failure and oxygenation index <200 on July 11th. Chest radiography showed inflammatory infiltration in bilateral lungs with bilateral pleural effusion. Brain plain MRI + enhancement MRI + DWI showed only scattered ischemic lesions in bilateral cerebral hemispheres. Echocardiography and color Doppler ultrasound of liver, gallbladder, pancreas, and spleen were unremarkable. Determination of B19V DNA in blood on July 11st showed 2.96 x 105 copies/mL; B19V DNA and Enterococcus faecium was detected by PACEseq mNGS on July 13th, with the specific reads number of 1,430 and 22, respectively. Blood B19V IgM was negative, and IgG was positive. The reexamination of EEG on July 14th showed no epileptic discharges. Determination of B19V DNA in pleural fluid on July 15th showed the DNA determination of 1.36 x 105 copies/mL; mNGS detected B19V in BALF on July 15th, with the specific reads number of 11, Corynebacterium striatum, with the particular reads number of 250, Acinetobacter baumannii, with the particular reads number of 17, Enterococcus faecium, with the specific reads number of 13, Staphylococcus aureus, with the particular reads number of 11, Pseudomonas aeruginosa, with the particular reads number of 11. In addition to the symptoms of the central nervous system, the patient's anemia was progressively aggravated. After multiple blood transfusions and platelet therapy, the lowest hemoglobin was 58 g/L on August 8th, the proportion of reticulocytes was 0.0026, the reticulocyte count was 0.0089 x 1012/L, the lowest platelet count was 60 x 109/L, red blood cells and platelets were inhibited, and red blood cell morphology examination showed shrinkage and acanthocytes. The patient was finally diagnosed with encephalitis caused by B19V, secondary epilepsy, severe anemia, and bilateral pneumonia. The patient was given mepem 1 g, Q8H on July 10th, and then switched to vancomycin 1 g, Q12H on July 18th, intravenous gamma globulin 0.4 g/Kg body weight for 5 days from July 15th for symptomatic treatment of heart failure, renal failure, and other symptoms of organ damage. The patient did not have any more seizures. He gradually became conscious, opened and closed his eyes when instructed, made eye contact when called, GCS score increased to 10 points, oxygenation index was more significant than 300, and anemia was improved. On July 20th, reexamination showed the proportion of reticulocytes was 0.0702, and reticulocyte count was 0.2078 x 1012/L. On July 27th, reexamination showed that blood B19V DNA was <1,000 copies/ml. The number of mNGS specific reads and viral DNA quantification in the different specimens are showed in Table 1, while mNGS outcomes belong to the patient are showed in Figure 2. Afterment treatment, the patient had clear consciousness and could simply communicate with his family. He was finally discharged on August 16th. There was no sequelae or relapse of this patient after 4-month follow-up. The patient could take care of himself and communicate with his family normally. The timeline of this case was shown in Figure 3.

case report, human parvovirus b19, immunosuppressed, mngs, multiple organ dysfunction

PMC9109271_01

Male

A 57-year-old male patient presented with fever, general malaise, weight loss, and chronic right flank pain. He first noticed a cutaneous discharge at the right lower quadrant 3 weeks ago. His medical history included extracorporeal shock wave lithotripsy of the right kidney years ago and recurrent urinary tract infection. Laboratory studies revealed leukocytosis (14.26/mL, range 4-10/mL) and elevated C-reactive protein level (43.02 mg/L, range 0-5 mg/L). Serum creatinine level was within a normal range (95 micromol/L, range 62-106 micromol/L). Urinalysis was normal and urine culture was negative. A 1 cm cutaneous opening with yellowish discharge was seen at the right lower quadrant. Real-time polymerase chain reaction (PCR) of the urine and pus were negative for Mycobacterium tuberculosis. A chest X ray appeared normal. Plain abdominal radiography demonstrated a small right kidney shadow with compacted stones (Figure 1). A 4-phase low-dose computed tomographic (CT) urography was indicated. Pre-contrast images revealed an atrophic and deformed right kidney with multiple nephrolithiasis, parenchymal calcification, multifocal fat deposits throughout the renal parenchyma, and perirenal fat stranding (Figure 2). Gas was not evident. On serial contrast images, the renal parenchyma was completely destroyed and the pyelocalyceal system was unrecognizable. A loss of differentiation between the anterior renal parenchyma and second portion of the duodenum was also appreciated, suggesting an adhesion. Renal function was not seen in the delayed excretory phases, implying a severely impaired kidney function. The right ureter was dilated (# 10 mm) with wall thickening and intraluminal hyper-attenuation compared to the contralateral normal counterpart (Figure 3). Hydronephrosis and perirenal abscess were not observed in all phases. A 7.5 cm x 6 cm x 3.5 cm fluid collection was found at the right lower quadrant, confined within the right iliac muscle. The collection had a thick enhanced wall and a 1 cm cutaneous opening. The right ureter was found to empty at the medial margin of the collection, indicating a chronic ureteral iliac muscle fistula. The "run-off" ureter was not seen on any delayed phases even with the patient was on prone position. The adjacent bony and vascular structures appeared normal. Other abnormality was a left kidney stone. A CT fistulography was consequently performed which demonstrated a complex fistula from the intramuscular collection, connecting with the distal ureter upward to the right pyelocalyceal system and communicating with the adjacent duodenum (Figure 4), corresponding to stage III according to Malek and Elder classification. There was no evidence of nephrobronchial fistula. XGP was highly suspected. Surgical exploration through a midline incision confirmed the presence of a pyeloduodenal and a ureteromuscular fistula. Right total nephrectomy, abscess evacuation, and fistula closure were performed. Escherichia coli and Streptococcus viridans were isolated on pus culture. Pathological examination of the resected kidney confirmed diffuse XGP. Microscopically, the lesion had three distinct zones centered by a calyx. The inner zone consisted of leukocytes, lymphocytes, plasma cells, histiocytes or macrophages, and necrosis. The middle zone consisted of granulation tissues surrounded by hemorrhage. The classic feature was the presence of lipid-laden foamy macrophages (xanthoma cells) that gave a yellow color to the tissue. The outer zone consisted of giant cells, cholesterol clefts, and fibrous tissues. In addition, various degrees of renal tubular atrophy and tubular dilatation were also observed (Figure 5). At immunohistochemistry, the lesion was positive for CD68 and vimentin, and negative for smooth muscle actin (SMA), desmin, and epithelial markers (Figure 6). Michaelis-Gutmann bodies were not evident; therefore, malakoplakia was excluded. The patient was discharged uneventfully after 10 days and was sent home on oral antibiotics. He has been doing well without recurrent fistula or abscess during 15-month follow-up.

pyelonephritis, fat deposit, fistula

PMC8414578_01

Male

A 28-year-old male patient had a dry cough, chest tightness after exercise, and shortness of breath for 1 week. He took oral cephalosporin for 3 days without any efficiency, and his symptoms got worse. On admission, leukoplakia in the mouth, little wet rales at the bottom of both lungs, and multiple swollen lymph nodes were found on clinical examination. His temperature was 37.6 C. His blood test results showed that the white blood cell count was 6.52*109/L, with an elevation in neutrophil ratio of 72.7%, high level of C-reactive protein (CRP) at 166 mg/L and serum amyloid protein A at 130 mg/L, low level of oxygen partial pressure at 87.5 mmHg and albumin at 30.3 g/L. Blood culture, antibody tests of Legionella pneumophila, Streptococcus pneumoniae, and Mycoplasma pneumoniae, and PCR-based detection of SARS-CoV-2 were negative. Cryptococcal capsular antigen, 1-3-beta-D glucan detection, aspergillus galactomannan detection, and interferon-gamma release assays were negative. The viral load of HIV-RNA was 84,100 IU/ml. CD4+ T-cell count was 11 cells/mul. CT of the lung revealed multifocal bilateral ground-glass opacities (Figure 1). According to the clinical diagnosis of PCP, the patient was treated with four pills of sulfamethoxazole-trimethoprim (sulfamethoxazole 1.2 g, trimethoprim 240 mg) three times a day. After treatment for 2 days (on day 3), the symptoms of the patient were more severe, and his temperature got to 39.9 C. We performed a bronchoscopy on the patient, and it showed bronchial mucosa hyperemia and bronchial inflammatory changes. Nucleated cell counts of bronchoalveolar lavage (BAL) were 20 * 106/L. Cryptococcal antigen, 1-3-beta-D glucan detection, and culture of BAL were negative. Hexamine silver staining of P. jiroveci and PCR-based detection of cytomegalovirus and Mycobacterium tuberculosis were also negative. In addition, next-generation sequencing technologies (NGS) of BAL were carried out, the BAL was sent to a laboratory, and DNA was extracted for whole genomic sequencing, purified, and sonicated to a size of 100-150 bp. The DNA libraries were constructed followed by end repair, joint connection, no bias PCR amplification, and sequenced using the MGlseq-2000 platform after quality control. High-quality sequencing data were generated by removing low-quality reads. After removing human sequences, the remaining sequencing data were aligned to the bacterial, viral, fungal, and protozoan databases. After treatment for 5 days (on day 6), CT of the lung revealed that it was worse than before (Figure 2). Results of NGS reported 205,658 unique reads of P. jirovecii, with coverage of identified genes 1.70% and 115 unique reads of T. whipplei, with coverage of identified genes 1.00% in BAL. The P. jirovecii-specific SYBR Green quantitative real-time PCR (qPCR) assay targeting a 301 bp fragment using a CFX96 Real-Time System was performed. The forward primer (pH207 5-ACAAATCGGACTAGGATATAGCTGGT-3) and the reverse primer pAZ102-E were used to detect the mtLSUrRNA gene, and the copy number of P. jiroveci was 4,787.36 copies/ml. For specific T. whipplei qPCR, the specimen was tested by using Twhi3F (5-TTGTGTATTTGGTATTAGATGAAACAG-3), Twhi3R (5-CCCTACAATATGAAACAGCCTTTG-3) primer pair, and the specific TaqMan probe Twhi3 (6-FAM-GGGATAGAGCAGGAGGTGTCTGTCTGG-TAMRA). When the specimen was positive in this assay, the result was confirmed by a second qPCR by using Twhi2F (5-TGAGGATGTATCTGTGTATGGGACA-3) andTwhi2R (5-TCCTGTTACAAGCAGTACAAAACAAA-3) primer set, and the Twhi2 probe (6-FAM-GAGAGATGGGGTGCAGGACAGGG-TAMRA). The copy number of T. whipplei was 11,717.3 copies/ml. Considering the progressed condition of the patient, meropenem 1 g q8h and caspofungin 70 mg per day were added for treating the infections of T. whipplei and P. jirovecii. Methylprednisolone 40 mg BID was added due to the severe symptoms. On day 12, there was a clinical improvement, and CT of the lungs showed obviously better than before (Figure 3), and the patient was discharged on day 16.

hiv, ngs, pneumocystis pneumonia, tropheryma whipplei, case report

PMC7077940_01

Female

A 21-year-old woman visited the outpatient orthodontic clinic of Okayama University Hospital with the chief complaint of a protruding maxillary right central incisor. She desired nonsurgical treatment with invisible appliance. Front and profile facial photographs showed a symmetrical face, convex profile and protruded and incompetent lips (Fig 1). Mentalis muscle strain was seen, and a slightly gummy smile was observed. An intraoral examination revealed an excessive 8.0-mm overjet (OJ), with Angle Class III molar relationships on both sides and bilateral congenitally missing mandibular canines. A Class II division 1 incisor relationship, with anterior open bite (AOB) and tongue thrusting habit was observed. She had no family history of the same open bite condition. Anterior mild crowding was also observed in maxillary and mandibular arches. The upper dental midline almost coincided with the facial midline; however, the lower dental midline was shifted 1.0 mm toward left. Panoramic radiograph confirmed the absence of mandibular canines on both sides, and two midline supernumerary teeth were detected at the maxillary central incisors region (Fig 1K). Cone-beam computed tomography showed no pathological problems in the root structure of maxillary central incisors on either side (Figs 1L to 1M). The patient reported clicking sounds in the temporomandibular joint without pain during maximum opening on the right side. The interincisal distance on maximum opening was 44 mm. In comparison to the Japanese female norms, cephalometric evaluation showed a mild skeletal Class II jaw relationship (ANB = 4.5 ; SNA = 83.0 ; SNB = 78.5 ). Although her lower facial height ratio was normal (N-Me = 125.5 mm; Me-PP = 71.5 mm), with normal mandibular plane angle (FMA = 29.0 ) (Fig. 1J, Table 1), a decreased overbite of -1.0 mm was observed, since she had two distinct upper occlusal planes. The maxillary incisor angle was increased (U1-SN = 114.0 ), and the mandibular incisor angle was slightly reduced (L1-Mp = 87.5 ). The lower lip was slightly protruded against the aesthetic E-line (upper = 0.0 mm; lower = +2.5 mm). Given the above findings, the patient was diagnosed with a mild skeletal Class II jaw-base relationship; increased OJ, due to the bilateral congenitally missing mandibular canines; and Angle Class III malocclusion with AOB. The primary treatment objectives were to correct the increased OJ with substitution of the mandibular canines by the first premolars, and the AOB without extruding the maxillary and mandibular incisors; create lip sealing and improve facial aesthetics. Additional objectives included Class III molar correction and establishment of functional occlusion. Based on the primary objectives, extraction of the maxillary first premolars was considered to correct the OJ. The use of temporary anchorage devices (TADs) was also planned to control the vertical relationship of maxillary molars. Another conservative approach involves maxillary molar distalization using TADs, and extraction of the maxillary third molars. However, this option increases the risk of AOB, since vertical control is difficult. After a thorough discussion of these options, the patient agreed with the premolar extraction treatment plan, with lingual brackets in the maxillary arch and labial brackets in the mandibular arch. After extraction of two supernumerary teeth, a transpalatal arch was inserted in the maxillary arch (Figs 2A - 2D). Two TADs were also implanted at the buccal side of the maxillary molar region of both sides, to control the vertical relationship of posterior teeth. Four weeks after implantation, a 0.018-in preadjusted Edgewise appliance (iPass , Dentaurum, Pforzheim, Germany) was placed, with sectional 0.016 x 0.022-in NiTi wires in the maxillary posterior segment. Two months after leveling and alignment, 0.016 x 0.022-in stainless steel (SS) archwire was installed to initiate the vertical anchorage control of the maxillary molars, using an elastomeric chain from the TADs to the segmental wires (Figs 2E - 2H). After 4 months of molar intrusion and bilateral maxillary first premolars extraction, the maxillary lingual brackets (STb , Ormco, Glendora, CA, USA) by indirect bonding system and the mandibular labial brackets (iPass , Dentaurum, Pforzheim, Germany) by direct bonding system were placed, then the alignment was initiated by inserting 0.014-in NiTi wires in both arches (Figs 2I - 2P).The wire size was increased to 0.016 x 0.022-in NiTi. For space closure and anterior teeth retraction of the maxillary arch, a loop mechanic with 0.017 x 0.025-in SS was used (Figs 2Q - 2T). Detailing and finishing were achieved using 0.016 x 0.022-in beta-titanium-molybdenum wire in both arches (Figs 2U - 2X). After 35 months of active treatment, a circumferential double retainer with a tongue crib in the maxillary arch and a lingual bonded retainer in the maxillary and mandibular arches were used as retention appliances. Compared to the pretreatment photographs, the posttreatment photographs showed retraction of the upper and lower lips, which subsequently improved the patient's facial profile and the relief of lip incompetence (Figs 3A-3I). Although the missing mandibular canines were substituted by mandibular first premolars, well-aligned arches and good interdigitation were achieved, with Angle Class I molar relation (Figs 3A-3I). By means of the extraction of maxillary first premolars and retraction of maxillary anterior teeth, an ideal overjet of 2.0 mm and an overbite of 2.0 mm were also achieved (Table 1). The posttreatment panoramic radiograph showed acceptable root parallelism, with no significant root resorption, except for slight apical root resorption of the maxillary right second premolar (Fig 3K). Superimposition of the pre- and posttreatment cephalometric tracings showed that the maxillary and mandibular incisors inclination was normalized (Fig 4). The mild skeletal Class II relationship was improved due to the slight reduction in the SNA angle (Table 1). The vertical dimension was maintained after orthodontic treatment. In the evaluation using a jaw movement recording system with six degrees of freedom (Gnathohexagraph System, version 1.31; Ono Sokki, Kanagawa, Japan), a smooth increase in the condylar movement was observed during protrusive or lateral excursion (Fig 5, Table 2).The interincisal distance on maximum opening without pain was maintained at 45 mm. Good facial aesthetics and acceptable occlusion were maintained after 29 months of retention (Figs 6 and 7). Occlusal force and occlusal contact area were also increased, compared with before treatment (Table 3). The patient was satisfied with treatment results.

PMC3016730_03

Female

N.M., a 49-year-old female, was admitted with acute abdominal pain, fever, leukocytosis and thickened gallbladder containing stones on ultrasound. The gallbladder was found to be inflamed and edematous at time of surgery. Dissection within the triangle of Calot demonstrated venous structures between the later confirmed cystic duct and artery (Figure 3). Cholecystectomy proceeded uneventfully. Early in our experience with laparoscopic cholecystectomy, the presence of small tubular structures within the triangle of Calot became evident as being necessarily divided to proceed with the dissection. Among these was a structure that presented as a bridge between the cystic artery and duct; the division of which, unless controlled, resulted in insignificant but annoying bleeding. It quickly became a standard part of the procedure to clip or cauterize this ves sel during the dissection. Its color and non-pulsatile bleeding when divided, indicated that this was a vein, ostensibly unnamed. Further experience established the presence of other veins consistently present within the triangle. It was subsequently determined that these venous channels were named as the cystic veins and their courses documented in early textbooks of anatomy.

PMC5149636_01

Female

A 37-year-old female was admitted with new onset of shortness of breath. On physical examination she was dyspnoeic, heart rate was 110 beats/min, and blood pressure was 80/50 mmHg with a pulsus paradoxus of 22 mmHg. Neck veins were distended; heart sounds were distant; no pericardial friction rub was heard; dullness was found on both lung bases. Chest X-ray revealed bilateral pleural effusions and severe cardiomegaly. On electrocardiogram (ECG), low voltage and widespread ST segment elevations were found. Echocardiography demonstrated a large pericardial effusion (Figures 1(a) and 1(b)) with collapse of the right atrium and ventricle as well as classical hemodynamic changes, typical of tamponade. On emergent pericardiocentesis, 770 cc of hemorrhagic fluid was aspirated. Cultures of the fluid were sterile, and neither acid fast bacilli nor malignant cells were found. On chemical analysis of the pericardial fluid a low glucose level of 3 mg% (normal: 60-80 mg%), a high LDH level of 6644 mg% (normal: usually <400 mg%), and 300 eosinophils/mL (17%, no normal values but probably <1%) were found. Pharyngeal and rectal cultures were negative for enteroviruses; serological tests for cytomegalic virus, Epstein Barr virus, Q-fever, and mycoplasma were negative; rheumatoid factor, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, and thyroid function tests were within normal limits. Computed tomography (CT) of the chest and abdomen was normal except for pericardial and bilateral pleural effusions and left lower lobe atelectasis (Figure 1(c)). Neither pericardial nor pleural calcifications or masses were seen. Benign pericarditis was suspected and the patient was treated with ibuprofen and colchicine for 16 weeks. Three months later, the patient had recurrent dyspnea and clinical signs of cardiac tamponade and a large pericardial effusion was found on echocardiography. On repeat pericardiocentesis 1200 cc of sterile hemorrhagic fluid was aspirated. Tests for acid fast bacilli were again negative and on cytologic examination only reactive mesothelial cells were seen. Chemical characteristics of the pericardial fluid were similar to the previous analysis. Since the patient immigrated to Israel from Ethiopia where TB is endemic and since she had hemorrhagic pericardial effusions with very low glucose levels and in the absence of a response to anti-inflammatory drugs, TB pericarditis was highly suspected and empiric antituberculous therapy was added to colchicine and prednisone. However, pericardial fluid reaccumulated during the following 4 weeks. An exploratory thoracoscopy and a pericardial window operation were performed and a pericardial biopsy was taken which showed large polygonal tumor cells with prominent nuclei and cytoplasmic vacuoles on Hematoxylin and Eosin staining. Cytokeratin and Calretinin staining were strongly positive in tumor cells, consistent with primary malignant mesothelioma. Subtotal pericardiectomy was performed. Tumor foci were also detected on histological examination of mediastinal fat (Figures 2(a), 2(b), and 2(c)). Since the pericardium was the only tissue originating from mesothelial cells in which malignant cells were found, a diagnosis of primary malignant pericardial mesothelioma (PMPM) was made. The patient denied any known contact with asbestos. The patient was asymptomatic for a couple of months but on followup echocardiograms progressive encasement of the heart in tumor tissue was evident. Despite chemotherapy, a year later, the patient died.

PMC3085497_01

Male

A 49-year-old farm laborer was referred to our hospital with complete heart block, incidentally discovered when he presented with persistent left sciatica despite analgesic treatment. No personal or familial history except a smoking habit was reported. The sciatica did not require immediate surgical management according to the physicians' assessment after a spinal magnetic resonance imaging. Electrocardiogram (Figure 1) revealed complete atrioventricular block associated with atrial tachycardia. Thus, this patient was sent to our intensive care unit for cardiac investigation. Clinical history revealed New York Heart Association (NYHA) class II dyspnea, associated with clinical signs of global heart failure. Chest radiography demonstrated cardiomegaly and bilateral hilar overload. Transthoracic echocardiography (Figure 2(a), see Movie 1 Supplementary Material available online at doi:10.1155/2011/740928) revealed extensive localized thickening of the right ventricle, right atrium, interatrial septum, and basal to mid interventricular septum associated with a pericardial effusion. The infiltration extended around the root of the pulmonary artery and aorta (Figure 2(b), Movie 2). Left ventricular systolic function was slightly impaired (ejection fraction = 54%). Analysis of tissue Doppler indices showed elevated left ventricular filling pressures (E/E' ratio = 16.4). Blood sample tests found an isolated inflammatory syndrome: C-Reactive Protein raised to 50 mg/L. Nt-proBNP increased to 1150 pg/mL (N < 125 pg/mL). Serological tests for a bacterial, fungal, or immunological (including anti-nuclear antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor) cause were negative. QuantiFERON-TB Gold test was negative, and the angiotensin-converting enzyme level was normal. Cardiovascular magnetic resonance (CMR) imaging was performed to localize and characterize the nature of the tissue thickening. Four-chamber (Figure 3(c), Movie 3), apical short-axis, and long-axis (Movie 4) cine images were performed using steady-state free precession (SSFP) cine sequences. The right ventricular wall was akinetic, with preservation of apical contractility. Short-axis dark-blood T2-weighted (Figures 3(a) and 3(b)) sequences confirmed concentric thickening and oedema of the right ventricle. First-pass perfusion (Figure 3(d), Movie 5) showed enhancement of the right ventricular and interventricular septum infiltration consistent with an active inflammatory process. Delayed enhancement CMR (Figures 3(e) and 3(f)) sequences demonstrated widespread and heterogeneous enhancement of the right ventricle. Combined (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) was performed to look for primary malignant lesion (Figure 4) showing moderate FDG uptake involving mainly the right heart chambers of the heart. This whole body exam did not detect any extracardiac locations of FDG uptake. The patient was treated with diuretics, angiotensin-converting enzyme inhibitors, spironolactone, amiodarone, and adequate anticoagulation (INR 2.0-3.0) with warfarin associated with steroid therapy (prednisolone 1 mg/kg/day). Right ventricular myocardial biopsy and implantation of a dual-chamber epicardial pacemaker were performed via a sternal thoracotomy. Hematoxylin-eosin-saffron stained sections of the tissue sample showed a granulomatous reaction consisting of nodular cellular infiltrates (histiocytes associated with lymphocytic elements) with an abundant fibrotic reaction (Figures 5(a) and 5(b)). Immunohistochemistry revealed a prevalence of T lymphocytes (CD3 positive; Figure 5(c)) mixed with B lymphocytes (CD20 positive), histiocytes (CD68 positive; Figure 5(d)) and a few plasma cells (CD138 positive). Neither giant cells nor epithelioid cells were observed, thus rejecting the diagnoses of giant cell myocarditis and cardiac sarcoidosis. Vessels were not specifically concerned with the cellular infiltrates, so that a diagnosis of vasculitis was also excluded. Congo red and hematoxylin-eosin stained sections did not show amyloid deposits. Nested/reverse transcription-PCR did not detect any genomes of enterovirus, adenovirus, parvovirus B19, or human herpes virus type 6. At followup twelve months later, the patient described NYHA class II dyspnea, with no clinical signs of heart failure. Echocardiography revealed persistent myocardial infiltration, although the pericardial effusion had resolved. The patient remained pacemaker dependent with underlying complete heart block, which is probably the consequence of infiltration of the cardiac conduction system with granulomatous tissue. Nt-proBNP had decreased to 550 pg/mL.

PMC9927030_01

Male

A 35-year-old Asian male presented to the hospital with a syncopal episode while he was walking home from a restaurant. He had two glasses of wine that evening but had been feeling dizzy and lightheaded in recent weeks. He did not have any significant past medical history and was not on any regular medication. He denied any palpitations, chest pain, or shortness of breath. He could not recall the syncopal episode fully and was found at the roadside by bystanders. On arrival at the hospital, his electrocardiogram (ECG) showed normal sinus rhythm (NSR) with right axis deviation (RAD) and right bundle branch block (RBBB) (Figure 1). He had sustained facial and hand injuries. Most blood tests including troponin T, creatinine kinase, HbA1c, immune screening tests such as complement levels, rheumatoid factor, proteinase 3 antibody, myeloperoxidase antibody, myocardial antibody, and cardiolipin antibody, thyroid function tests, creatinine kinase were within normal limits. Viral screening for human immunodeficiency virus, hepatitis, and COVID-19 was negative. The erythrocyte sedimentation rate was mildly elevated at 14 mm/hour (Normal range: 1-10 mm/hr). Computerized tomography (CT) scan of the head and face showed a small fracture to the superior maxillary wall with overlying soft tissue swelling without any intracranial pathology. CT pulmonary angiogram showed florid centrilobular nodular opacification affecting the right upper and middle lobes, hilar lymphadenopathy, and anterior abdominal lymphadenopathy suggestive of possible tuberculosis (Figure 2). Following further investigation and respiratory input, it was felt tuberculosis was highly unlikely. He was commenced on bisoprolol 2.5 mg once daily. Echocardiography showed normal biventricular function with an estimated left ventricular ejection fraction (LVEF) of 55% and no regional wall motion abnormalities (Videos 1-2). Cardiovascular magnetic resonance imaging (CMR) showed normal biventricular function, mild atrial dilatation, and extensive, crescent-shaped, subepicardial late gadolinium enhancement seen in basal to apical inferior, basal to apical lateral, and mid to apical anterior segments (Figures 3-5). The patient was offered an implantable cardioverter defibrillator (ICD) for secondary prevention. The patient was discussed in a multidisciplinary team meeting (MDT) for subcutaneous versus transvenous ICD and had subcutaneous ICD screening which was normal. A transvenous ICD was implanted following a multidisciplinary team meeting. Chest radiography post-ICD implantation showed satisfactory leads positioning (Figure 5). Post-implantation device checks were satisfactory, and the patient was discharged home on bisoprolol 2.5 mg once daily with outpatient cardiology follow-up in the device clinic.

arrhythmogenic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (arvc/d), cardiac magnetic resonanced imaging, cardioinhibitory syncope, emergency echocardiography, implantable cardioverter-defibrillator (icd), life-threatening arrhythmia, prevention of syncope, right bundle branch block, ventricular dysrhythmia

PMC4501556_01

Female

A healthy 34 year old woman presented to medical attention after experiencing several days of moderately severe pleuritic chest pain without other respiratory or constitutional symptoms. She was Ecuadorian where she lived until the age of 5 and had not recently been, worked at a local supermarket (although not in food handling capacity) and had moderate persistent asthma well controlled on combination long acting beta-agonist and medium dose inhaled corticosteroid. Contrast CT scan of the chest demonstrated several bilateral pulmonary nodules without infiltrate, adenopathy or effusion. The largest was 1.5 x 1.5 cm in the left upper lobe with cavitation (Fig. 1). Active tuberculosis was ruled out. Blood cultures were negative and transthoracic echocardiogram did not demonstrate valvular vegetations. Nonspecific inflammatory markers were elevated: C-rp 61 mg/L (normal range: 0-3) and ESR 28 MM/h (normal range: 0-22) and ANA was positive with titer 1:80; however, ANCA were within the normal range. She did not have a leukocytosis (WBC 8300/uL). Serologic evaluation for fungal disease was negative. She had a mild transaminitis with alanine aminotransferase > aspartate aminotransferase and imaging of the liver via ultrasound and CT scan revealed steatosis without discrete lesions. Expectorated sputum grew Mycobacterium avium complex; however the clinical scenario seemed largely incompatible. Airway examination on bronchoscopy and bronchoalveolar lavage were also unrevealing. The patient underwent a surgical biopsy of the left upper lobe nodule - our leading diagnostic consideration of which at the time was seronegative pulmonary vasculitis. Pathology did not show granuloma, malignancy or AFB; rather, was an abscess (Fig. 3). Culture of the material grew Fusobacterium necrophorum. Notably, she had no upper respiratory symptoms, neck pain, febrile illness or dental work around the time of this presentation. On further detailed questioning she recalled a sore throat 5 months prior without fever, and enjoyed several months of good health in the intervening time. CT of sinus/neck were normal and in fact, on repeat chest CT several weeks later lung nodules contralateral to biopsy and prior to any therapy were smaller in size (Fig. 2). We elected to treat with ertapenem for 6 weeks and CT scan after therapy showed resolution of all dominant nodules. Of note, chest pain resolved well prior to initiation of therapy and has not recurred.

fusobacterium necrophorum, lemierre's syndrome, pulmonary nodule

Rounded inferio-medial left lower lobe nodule present on CT on original CT scan.

PMC5173512_01

Male

A 40-year-old man who had been treated for recurrent oral candidiasis came to our hospital because of general malaise and progressive body weight loss, losing 10 kg in a half year. He was bisexual, having no habit of intravenous drug use. While he had no history of any sexually transmitted diseases, he had experienced herpes zoster 5 years before, but he had never taken any human immunodeficiency virus (HIV) antibody tests. At presentation, he had low grade fever, gum bleeding and tinglingness in the posterior cervical region. He complained of no particular respiratory and gastrointestinal symptoms. Physical examination revealed oral candidiasis, gingivitis and slight lymphadenopathy involving the cervical, submandibular, left postauricular and inguinal nodes (measuring 4-5 mm in diameter, without tenderness). The liver and spleen were not palpable. Folliculitis was seen on the trunk and extremities. An HIV screening test was positive and a Western blot test was done, and it proved to be positive. Blood examination results were as follows (Table 1); HIV-RNA 1,400,000 copies/mL, CD4 count 10/muL, slight pancytopenia, and hypergloburinemia were seen. The serum alkaline phosphatase (ALP) level and lactate dehydrogenase (LDH) level were slightly elevated. With an extremely low CD4 count and wasting syndrome, he was diagnosed as having AIDS. Therefore, a thorough examination regarding opportunistic infections and sexually transmitted diseases was done. Plasma (1->3) beta-D-glucan, cytomegalovirus antigenemia, HBs-antigen, hepatitis C virus (HCV) antibody, and Treponema pallidum latex agglutination test, and rapid plasma reagin test were negative. Blood, fecal, sputum, and urine cultures were done, but no particular microbes including bacteria, mycobacteria, fungi, and protozoa were detected. A computed tomography (CT) scan showed slight splenomegaly and lymph node swelling in the neck areas. Lymphadenopathy was not detected in the thorax or abdomen. No lung lesions were found in a CT scan. Brain MRI, esophagogastroduodenoscopy and total colonoscopy showed no abnormalities. Pneumocystis pneumonia (PCP) was not suspected, and sulfamethoxazole 800 mg/trimethoprim 160 mg was administered as PCP prophylaxis. Oral azithromycin 1,200 mg weekly was also started as prophylaxis for the MAC infection. At that time, no respiratory symptoms were observed, and mycobacterium was not detected in a smear. However, after four weeks of incubation mycobacterium was detected in a sputum culture, but polymerase chain reaction (PCR) tests for M. tuberculosis and MAC were negative. After the completion of fluconazole therapy for oral candidiasis, cART was started with abacavir, lamivudine and darunavir/ritonavir. On day 11 (of cART), fever, tender submental lymph node swelling and trismus developed. On day 18, his temperature rose to 40 C and cervical lymph node (LN) swelling became more conspicuous with severe tenderness (Fig. 1). The serum ALP level was 618 U/L and MAC-IRS was suspected. On day 28, we performed a biopsy of the submental lymph node. At this time, the CD4 count was 94/muL and the serum HIV-RNA level had declined to 1,700 copies/mL. The sampled lymph node had swollen to 2 cm in diameter and the surface of section was gray-white with focal yellowish area. Histologically, non-caseous granuloma was seen (Fig. 2a), and relatively thin bacilli were detected in Ziehl-Neelsen staining (Fig. 2b). Mycobacterium was isolated after 8.8 days in supplemented Middlebrook 7H9 broth liquid culture (BacT/ALERT(R) MP for mycobacterium, Biomerieux, USA) and after 11 days in 7H11 agar culture. In 2% Ogawa egg slant medium (Kyokuto Pharmaceutical Industrial, Tokyo, Japan), it was scotochromogenic with an intense yellow color in both light and dark conditions (Fig. 3). Therefore, the strain was thought to belong to the Runyon II group. DNA-DNA hybridization (DDH Mycobacteria(R) Kyokuto Pharmaceutical Industrial) was done, but there were no matches with any of the 18 mycobacterial species. To identify this isolate, sequence analyses were performed, targeting fragments of the 16S ribosomal RNA (16S rRNA, 269 bp), RNA polymerase B (rpoB, 315 bp), and heat shock protein 65 (hsp65, 401 bp) genes. In a 16S rRNA sequence, although this isolate best matched with M. simiae with 99.7% homology, it also matched several reference strains with more than 98.5% homology (M. lentiflavum, M. triplex, M. genavense, M. intermedium, M. scrofulaceum, M. kansasii and M. gastri). The sequence analysis showed a high homology rate with Mycobacterium sp. UN-152, (GeneBank accession no. AB547401) reported as M. shigaense; 100% in 16S rRNA, 100% in rpoB, and 94% in hsp65. This strain was thus identified to be M. shigaense. Later the strain was proven to grow at 25 C, 30 C and 37 C, but not at 42 C. A niacin test was negative. Table 2 shows the results of antimicrobial susceptibility tests (BrothMIC NTM(R); Kyokuto Pharmaceutical Industrial). Clarithromycin, ethanbutol and rifabutin seemed to be moderately susceptible, while the others were not susceptible. An antimycobacterial regimen was started on day 25 of cART. The regimen contained rifabutin (RBT) 150 mg, ethanbutol (EB) 750 mg, and clarithromycin (CAM) 800 mg. Isoniazid (INH) 300 mg was also added until the subspecies was identified. Soon after initiation of the regimens, the fever subsided, but lymph node enlargement continued. A subcutaneous abscess with a protruding erythematous lesion appeared on the sternum and grew to 5 cm in diameter within a week (Fig. 4). Drainage was performed, and again, mycobacterium was found in Ziehl-Neelsen stain, and it was later identified to be M. shigaense. Thus, the final diagnosis was immune reconstitution syndrome caused by the novel mycobacterium, M. shigaense. Though we could find mycobacterium in the biopsy or drainage specimens, it took over 4 months to correctly identify this strain. Meanwhile, INH was continued. The serum ALP level normalized at 12 weeks, HIV-RNA turned to negative at 16 weeks, and the CD4 count recovered to over 100/muL at 27 weeks after the initiation of cART (Fig. 5). Blood, urine and stool cultures for Mycobacterial were repeatedly done, but those were all negative. The skin lesions and lymphadenopathy all gradually improved, and the antimycobacterial regimen was stopped after 6 months. Since then, the patient has been followed up without any recurrence of NTM disease for more than a year.

PMC10232950_01

Male

In September 2010, this 67-year-old man presented with fever, productive cough, and vomiting for 1 week. This was associated with progressive weight loss, poor appetite, lethargy, and increasing confusion over the past 3 weeks. He did not have abdominal pain, chronic cough, night sweats, or altered bowel habit. There was no headache, palpitations, or diaphoresis. His past medical history included hypertension, hyperlipidemia, and right inguinal hernia, which was operated on 10 years ago. Chronic medications included amlodipine, lisinopril, and simvastatin. He was not on corticosteroids, diuretics, lithium, antacids, calcium, or vitamin D supplementation. Four weeks prior, he underwent saucerization of a right forearm abscess and received a course of antimicrobials. He did not consume alcohol or recreational drug. On examination, he was confused with a Glasgow Coma scale (GCS) of 14. He was febrile and hemodynamically unstable with blood pressure of 80/50 mmHg, heart rate of 80 beats per minute, and oxygen saturation of 99% on room air. He was clinically dehydrated. Cardiovascular, respiratory, and abdominal examination was unremarkable, with no focal neurological deficit or neck rigidity. He did not have any features of Cushing's syndrome, and there were no hyperpigmented skin creases or buccal mucosa. Initial investigations showed left upper lobe consolidation on chest radiograph and raised inflammatory markers. Computed tomography (CT) scan of the brain was unremarkable. Biochemical investigation revealed acute renal failure (creatinine at 407 micromol/L, from 84 micromol/L 3 weeks prior) and severe hypercalcemia of 3.55 mmol/L, which was deemed the likely cause of his altered sensorium. Intact parathyroid hormone (iPTH) was low at 0.81 pmol/L (reference: 1.3-7.6 pmol/L). Electrocardiogram revealed normal sinus rhythm with no shortened QTc interval. There was mild hyponatremia (serum sodium of 132 mmol/L) with normokalemia. The initial impression was pneumonia complicated by septic shock and acute renal failure and hypercalcemia secondary to underlying malignancy in view of his loss of weight. He was immediately initiated on intravenous (IV) 0.9% sodium chloride drip and IV antibiotics (piperacillin/tazobactam and azithromycin) for healthcare-associated pneumonia. Despite 4.5 L of IV fluids, he had refractory hypotension and was put on ionotropic support, followed by IV hydrocortisone of 100 mg every 8 h as per conventional treatment of septic shock. He was intubated for airway protection in view of dropping GCS. Subsequently, he underwent continuous renal replacement therapy (CRRT) with low-calcium dialysate for acute renal failure with pulmonary congestion and persistent hypercalcemia. After 5 days, his hemodynamics and renal function improved, and he was weaned off ionotropic support, hydrocortisone, and CRRT. Despite resolution of pneumonia and normalization of serum calcium, he remained persistently drowsy and febrile. Antimicrobial therapy was escalated to cover for presumptive meningoencephalitis with IV meropenem, vancomycin, and acyclovir. Magnetic resonance imaging (MRI) of his brain was unremarkable, and cerebrospinal fluid (CSF) study was negative for acid fast bacilli, fungal, bacteria, and neurotropic viruses, although electroencephalogram showed severe diffuse encephalopathy with no epileptiform activity. Although his fever resolved and overall condition improved, he remained confused when he was transferred out of the intensive care unit (ICU) on day 17 of admission. His calcium levels (corrected for albumin and ionized calcium) returned to normal after IV fluids, hydrocortisone, and CRRT. Ionized calcium was monitored in ICU during CRRT that can alter total serum calcium, as well as hypoalbuminuria and acid base disturbances. Ionized calcium level remained normal for 12 days after cessation of CRRT and hydrocortisone. However, after transfer out of ICU, hypercalcemia recurred with peak corrected calcium of 3.16 mmol/L on day 19 of admission ( Figure 1 ). He received IV NS hydration and IV pamidronate of 90 mg slow infusion on recurrence of hypercalcemia with little effect. Initial serum phosphate was high normal at 1.62 mmol/L (reference: 0.65-1.65 mmol/L), and he was vitamin D-insufficient (25-hydroxyvitamin D at 22.6 microg/L). Severe PTH-independent hypercalcemia is most commonly secondary to hypercalcemia of malignancy, and this was consistent with his history of weight loss. However, there was no evidence of malignancy on CT thorax, abdomen, pelvis, and MRI brain. His alkaline phosphatase (ALP) was normal at 58 U/L (reference: 32-103 U/L), which suggested the absence of bone lesions, and myeloma panel was negative. There was no mediastinal enlargement, lymphadenopathy, or hepatosplenomegaly suggesting sarcoidosis or lymphoma on imaging. The endotracheal aspirate and CSF studies were negative for tuberculosis and fungi. Immobilization can cause hypercalcemia in the presence of high bone turnover conditions, but there was no prolonged immobilization prior to admission nor elevated ALP suggesting Paget's disease of the bone or hyperthyroidism. Vitamin A level was sent and returned several weeks later, as low, at 0.2 mg/L (reference: 0.3-0.8 mg/L). Although his hypotension and hyponatremia had resolved, a short Synacthen test was performed the following morning, with a blunted response: baseline undetecable, <8 nmol/L; and peak serum cortisol, 12 nmol/L. Serum cortisol had not been assessed prior to hydrocortisone initiation in the ICU. Immediately, IV hydrocortisone of 50 mg every 8 h was reinitiated. Adrenocorticotropic hormone (ACTH) level was low at 3.2 ng/L (reference: 10-60 ng/L), consistent with secondary adrenal insufficiency. His other pituitary hormones were normal: free T4, 13.7 pmol/L; thyroid-stimulating hormone, 2.84 mIU/L; Insulin-like Growth Factor-1 (IGF-1), 62.6 ng/ml; prolactin, 141.8 mIU/L; and total testosterone, 15.4 nmol/L. His calcium level improved markedly after 3 days of IV hydrocortisone, and it was converted to oral hydrocortisone of 20 mg every 8 h and subsequently tailed down to 20 mg daily in divided doses. His altered mentation resolved more gradually, and, by 7 days, he made a complete recovery. On further questioning, he revealed that he previously consumed "Jamu" (traditional Malay medication) to improve vitality but had stopped 5 years prior to admission. "Jamu" are often made up from blends of herbal ingredients. As they are unregulated, they may contain unusually high amount of corticosteroids. There was no other exogenous steroid consumption or application. However, he was prescribed oral fluconazole of 200 mg twice daily for 4 weeks for his forearm abscess, as cultures showed "unspecified mould". He had been consuming this up till this admission. There was no history of previous head trauma, surgery, or radiotherapy. MRI pituitary gland was normal with no adenoma, stalk thickening, or loss of T2 bright spot suggesting lymphocytic hypophysitis. One year later, although all the other anterior pituitary hormones remained normal, serum cortisol remained low, at 15 nmol/L, whereas ACTH increased to 78.2 ng/L, suggesting recovery process of the hypothalamic-pituitary-adrenal (HPA) axis from chronic suppression with exogenous steroid. Serum aldosterone was normal at 17 ng/dl, with plasma renin activity at 4.5 ng/ml/h. Furthermore, previous CT imaging of his abdomen did not show any adrenal masses, hemorrhage, or atrophy. We established a final diagnosis of adrenal insufficiency secondary to HPA axis suppression from chronic traditional medication use, with Addisonian crisis and hypercalcemia precipitated by fluconazole use. Whereas his ACTH increased after the first year, his cortisol levels rose more gradually. After 8 years, glucocorticoid replacement was completely stopped. He has since been off steroids for 2 years, without any further recurrences of hypercalcemia, or Addisonian crisis since his initial presentation.

adrenal insufficiency, anti-fungal, azole, hemodialysis, hypercalcemia, hypothalamic-pituitary-adrenal axis, iatrogenic cushing’s

PMC5330040_01

Male

A 48-year-old Portuguese man, Caucasian, professional diver, working and living in Angola, with no significant medical history apart from several malaria episodes. Four days after completing a 3-day prophylactic medication scheme for paludisme (sulfadoxine 500 mg/pyrimethamine 25 mg - S-P), he presented a flu-like syndrome, aggravated with fever and a pruritic facial rash, that extended to the trunk [Figure 1 resumes the progression and presentation of disease]. He was started on amoxicillin plus clavulanic acid, metronidazole, dexamethasone, loratadine, and ibuprofen. In <24 h, developed a severe mucosal damage with odynophagia and dysphagia, extensive bullous lesions on the face and trunk and a fever of 40 C. He was admitted to a medical clinic in Luanda, stopped all the previous medication, initiated fluid therapy and the day after decided to fly to Lisbon and directly to our hospital. After evaluation by a multidisciplinary team (internal medicine and plastic surgery), a Lyell's syndrome was suspected, and he was admitted in our Burn Unit. On skin examination, he presented a generalized exanthema with purpuric macules, bullae and erosions, with epidermal detachment - a positive Nikolsky sign [Figures 2-4]. Around 70% of TBSA was involved, including head, neck, anterior and posterior trunk, arms, and genitals. The oral mucosae had edema, erythema, and blistering. Ruptured blisters formed hemorrhagic erosions resulting in dysphagia and inability to speak. Ocular involvement, with mild erythema and mucous purulent exudate was present. Vital signs were stable with an elevated body temperature of 39 C, there were no significant changes in the cardiac and pulmonary physical examination. There were no abnormalities detected on chest X-ray and electrocardiogram studies. Mortality scores, on admission were Simplified Acute Physiology Score II - 19; sequential organ failure assessment (SOFA) - 1. On admission, the severity-of-illness-score for TEN (SCORTEN), was 2 (12.2% of mortality). A skin biopsy, skin swabs, and blood culture were performed on admission. Femoral central venous catheter (CVC), radial arterial line, nasogastric tube, and urinary catheter were placed. The patient was monitored in the Burn Unit, started on fluids (Parkland formula), along with subcutaneous enoxaparin (40 mg/day); intravenous (IV) pantoprazole (40 mg/day) and morphine perfusion (0.05 mg/kg/h). Topical ophthalmic chloramphenicol and prednisolone every 8 h was instituted. He was followed-up daily by a plastic surgeon, an anesthesiologist, an ophthalmologist and a nurse team. On the 3rd day after admission, there was a deterioration of the level of consciousness, persistent fever and progression of the cutaneous and mucosal lesions to a TBSA of 80%, becoming more hemorrhagic. SOFA and SCORTEN aggravated to 4 (58.3% of mortality), which led us to initiate a 3-day course of IV immunoglobulin (IVIG) (1 g/kg/day). On the 1st day of IVIG, he developed a mild to moderate side-effect reaction, that subsided with supportive therapy. After the 3rd day of immunoglobulin therapy, the skin lesions began to heal and clinical state improved progressively. Since his admission, the patient was on spontaneous ventilation (FiO2 40-60% adjusted to keep oxygen-hemoglobin saturation above 94%), despite severe mucosal lesions he maintained protective airway reflexes, no signs of respiratory compromise on chest X-ray or arterial blood gas analysis and good respiratory dynamic. Care to avoid pressure sores and to obtain an adequate temperature and humidity state was taken, daily aseptic dressings with paraffin gauze and iodopovidone and weekly sessions of balneotherapy for mechanical debridement of necrotic areas were done. These were performed under sedoanalgesia with midazolam, fentanyl, propofol and ketamine, maintaining spontaneous breathing. No biologic or synthetic skin substitutes were needed. Hemorrhagic lesions led to coagulopathy requiring topical hemostasis, blood transfusion, and occasional plasma therapy. The skin biopsy evidenced epidermal necrosis with intense lymphocyte reaction and dermal-epidermal sloughing with preservation of the dermis, compatible with Lyell syndrome. Infection control and periodic surface and blood cultures of the regions affected were drawn whenever indicated. Due to persistent fever, empiric antibiotic therapy with piperacillin and tazobactam plus gentamicin was initiated and later redirected to a methicillin-sensitive Staphylococcus aureus, identified in blood and CVC culture, to which he completed 7 days of flucloxacilin. It was also isolated, on his 15th day of admission, an Escherichia coli in genital lesions swabs, to which he completed 7 days of cefuroxime. All other blood cultures, skin swabs and urine cultures were sterile. He presented progressive clinical improvement from the 5th day and epidermalization from the 10th day after admission at our Burn Unit. He was discharged to the plastic surgery ward on the 25th day. We verified total epidermalization of the affected areas, although with dyschromia and cutaneous hypersensibility with no residual mucosal or ophthalmic lesions [Figures 5-7]. TEN is a severe mucocutaneous exfoliative reaction. Stevens-Johnson syndrome (SJS) and TEN were considered part of erythema multiforme (EM) spectrum of disease. EM has a less severe presentation with <10% TSBA involved, minimal mucous involvement and typical symmetrical target-lesions. Nowadays, SJS and TEN (but not EM) are considered variants of the same pathologic process, differing only in the extent and severity of mucosal and/or cutaneous involvement. According to Chan et al., TEN is presents with involvement of at least two mucous membranes, loss of confluent sheets of epidermis exposing the dermis of at least 20% of TBSA, fever and a compatible skin biopsy (paucicelular infiltrates and widespread necrotic epidermis involving all layers). In Europe, TEN is indiscriminately classified as being present when more than 30% or 10% of the TBSA is involved whether it presents with or without spots, respectively. In the United States, SJS is defined as epidermal detachment >10% TBSA and TEN is defined as epidermal detachment >30% the TBSA while both SJS and TEN can have mucosal involvement. In between (TBSA 10-30%) there is overlapping of SJS and TEN. In 90% of cases, TEN is triggered by an idiosyncratic immune-allergic reaction related to a drug. More than 220 medications have been implicated, but only a few of them are most commonly involved [Table 1]. The incidence is higher in extremes of age, and there is a female/male ratio of 1.5:1. Recently, the EuroSCAR study estimated the risk of different drugs in SJS or TEN. Covering more than 100 million inhabitants in hospitals of five European countries, this study confirmed the risk related to anti-infective sulfonamides, allopurinol, carbamazepine, phenobarbital, phenytoin, and oxicam-nonsteroidal anti-inflammatory drugs. Among newer drugs, strong associations were reported for nevirapine and lamotrigine, and weaker associations for sertraline, pantoprazole, and tramadol. Plasmodium chloroquine-resistance increased TEN secondary to the association S-P, with a few fatal cases described in the literature. The possibility of TEN should always be taken into account when prescribing high-risk drugs. It is common understanding that this disease is the presentation of an unregulated immune reaction against epithelial cells; re-challenging an individual with the same drug can result in fast recurrence of SJS/TEN, pointing to an immunologic mechanism of sensitization and memory. Two pathogenic immune mechanisms are described: perforin-granzyme mediated cell apoptosis and Fas-FasL mediated cell apoptosis. Drug intake leads to accumulation of toxic metabolites or immunoallergic mechanisms, with reactive metabolites behaving as highly immunogenic haptens. These trigger cytokines release (such as tumor necrosis factor [TNF]-alpha, interleukin [IL]-10 and IL-6), with CD95 receptor activation (Fas) leading to massive apoptosis of keratinocyte and mucosal epithelial cells. The Fas-FasL pathway theory is based on a drug-mediated up-regulation, which triggers a downstream caspase cascade of apoptosis. IVIG is thought to inhibit this reaction, but its effectiveness as a treatment modality remains debated. Another accepted theory suggests that, in genetically predisposed individuals, drug metabolites accumulate in the epidermis and can induce an immunologic process similar to graft-versus-host disease. On the other hand, several immune-histological studies and blister fluid analysis, point to T lymphocytes as the main character in the pathogenesis of SJS/TEN. How a drug, in a given patient, regulates the function of these key players leading to SJS/TEN, is still debated. TEN usually develops 1-3 weeks after contact with a suspect drug with no consistent tests to conclusively prove the link. TEN is preceded by a prodromal phase (48-72 h) of a flu-like syndrome (fever, dysphagia, cough, gastrointestinal symptoms, myalgia). Later this can progress, although inconsistently, to systemic symptoms with low albumin, leukopenia, anemia and possibly disseminated intravascular coagulation (DIC). Mucosal and cutaneous lesions are characteristic. Mucosal lesions may be the first to appear, mainly involving the stratified squamous epithelium. Erosion and shedding of conjunctiva, respiratory, oral, pharyngeal, esophagus, urethral, anal, vaginal, and perineal mucosa can be found. However, oral, pharyngeal, conjunctiva and urethral surfaces are most frequently affected. Cutaneous lesions predominate in sun-exposed areas and usually begin symmetrically on the trunk. The scalp, legs, and the distal part of the arms (except palms and soles) are relatively spared. These lesions start as an acute macular erythematous rash with central blistering and target lesions with a dark red center and lighter red halo. Rapidly, they exhibit Nikolsky's sign (epidermal detachment by gentle lateral pressure on the skin). This detachment can become very extensive with a total epidermal loss in 24 h in severe cases. Diagnosis of TEN is largely clinical but has to be confirmed by skin biopsy histology. Histological studies reveal widespread necrotic epidermis involving all layers. To rule out autoimmune blistering diseases, direct immune fluorescence staining should be performed, and no immunoglobulin or complement deposition should be detected. Re-epithelialization is evident in 1-3 weeks, although fever may persist without culture proven infection. Other pathologies to include in the differential diagnosis of TEN are EM, impetigo, SJS, staphylococcal scalded skin syndrome, lupus erythematosus, pemphigus vulgaris, linear IgA dermatosis, bullous pemphigoid, cutaneous T-cell lymphoma, toxic shock syndrome, Kawasaki disease, graft versus host disease, and thermal or chemical burns. Only necrotic skin or detachable skin (Nikolsky +) should be included to evaluate the TBSA involved. The extension of involvement is a major prognostic factor. No randomized controlled trials or guidelines exist for TEN's treatment. Guidelines proposed by Avakian et al. in 1991 and revised in 2007 by Fromowitz et al. can be considered a starting point. These are built on a multidisciplinary approach, early diagnosis, withdrawal of suspected/causative drug(s), supportive care and definite therapies with three primary goals: hemodynamic stability, pain management, and infection control. The SCORTEN is now the most commonly used scoring system. Apart from evaluating the severity of the clinical picture, can aid in decision making. A score of 3 or more should be treated in an Intensive Care Unit if possible. Isolation, appropriate wound management, constant nurse control and the availability of technologically advanced devices, make the Burn Unit the most suitable place for the treatment of TEN patients according to several authors. Garcia-Doval et al. have shown that early culprit drug withdrawal and the shorter the half-life of the drug, the better the prognosis. After discontinuing unnecessary and suspect medications, first-line management is fluid and electrolyte replacement, acid-base, metabolic regulation and topical skin management. Fluid replacement should be started with crystalloids. The amount to be administered is controversial. Most authors use Parkland's formula and administrate Ringer's solution, as in burn patients. Others state that third space loss phenomenon and changes in vascular permeability are absent, contrary to burn patients, with less need for fluid-aggressive therapy. TEN patients present several nutrition management difficulties. Oropharyngeal lesions may cause difficulties in eating, drinking and enteral tube placement. High nutritional requirements due to an hypermetabolic response, appear to be related to TBSA affected. Nutrient absorption can be altered by gastrointestinal mucosa involvement. Some authors suggest avoiding nasogastric tube because of gastrointestinal mucosae potential involvement; however, this might be the only feeding alternative. Total parenteral nutrition should be started in patients without an enteral route. As for other critically ill patients, analgesia, prophylaxis for deep vein thrombosis and erosive gastric ulcer, daily physical therapy, prevention of pressure sores, and infections cannot be overemphasized. Periodic laboratory analysis and cultures, according to clinical context, should be collected. This is also valid for X-ray and gasometrical analysis to evaluate respiratory compromise. Antibiotic therapy should be guided by high suspicion of infection, microbiological cultures, and antibiogram, except when there is leukopenia. Invasive procedures should be reduced to a minimum and avoid affected areas. Topical wound care is essential in the treatment of TEN. The ideal wound dressing for re-epithelialization should preserve physiologic conditions, protecting the wound and allowing unrestricted movements. It must also be permeable, easy to apply, nontoxic, nonadherent, and low priced. Some authors suggest aggressive operative debridement, while others support a conservative approach since blistered skin acts as a natural biological dressing, which likely favors re-epithelialization. Whichever approach is chosen; the exposed dermis should be protected with some form of coverage. Detached epidermis should be removed under sedoanalgesia, avoiding general anesthesia and endotracheal intubation. When the dermis is intact, nonadhesive wound dressings are enough, assuring aseptic conditions and daily dressings. Exposed areas should be sterilized using chlorhexidine or silver nitrate 0.5%, and covered with paraffin gauze, biological materials, synthetic skin substitutes, or adsorbent skin dressings. Aquacel Ag was recently reported in TEN wound treatment, does not need daily changing and can remain in place for 3 days or until epithelialization is complete. According to some authors, it is cost effective, reduces wound infection, the frequency of dressing changes and pain levels. The use of sulfonamide-containing solutions is contraindicated due the possible implication in the pathophysiology of the syndrome and additionally, might delay re-epithelialization. The role of the immune system in TEN's pathophysiology inspired the administration of various agents with immunologic actions. Some institutions use systemic corticosteroids, immunosuppressives (cyclophosphamide, cyclosporine), anti-TNF-alpha agents, plasmapheresis, and human IVIG. Nevertheless, there is no consensus on treatment effects. Prompt withdrawal of the suspected drug is the first-line therapy and was, for many years, the only validated one to reduce mortality. Despite some success, corticosteroids and immunosuppressives are not considered as a standard treatment for TEN. Some authors consider there are risks of administering an immunosuppressant drug to an already immunosuppressed individual. Plasmapheresis is reported to lead to some success. Nevertheless, there is no agreement about the efficacy of this expensive treatment, its benefits are still unclear and there are series of nonresponding patients. N-acetylcysteine anti-oxidant effects, in high doses, might inhibit cytokines production and release, like TNF-alpha and IL-1, involved in TEN's physiopathology. IVIG is the most recent therapeutic approach to TEN, 24 proposed in 1998 by Viard et al. It's pharmacokinetics is based on blockage of CD95 cell-surface receptor (Fas) that induces keratinocyte apoptosis. IVIGs are obtained from plasma of blood donors, fractionated and purified until obtaining predominantly IgG (90-98%), traces of IgA, IgM, CD4, CD8, human leukocyte antigen molecules, and cytokines. IVIG dosage, however, is still unclear. Viard et al. indicated a protocol in which IVIG should be infused at doses of 0.7 g/kg daily for 4 days (total dose 2.8 g/kg) and with methylprednisolone 250 mg/6 h for the first 48 h. This protocol was modified successively by different authors. Despite the potential biases and although they are not directly comparable, most studies suggested a benefit, of high-dose IVIG, in TEN's mortality. Trent et al. conducted a systematic review from 1992 to 2006, to study the dose-response relationship. Despite the study limitations stated by the authors, results showed that within each 1 g/kg increase in IVIG dose, there was a statistically significant 4.2-fold increase in TEN patient survival. IVIG treatment is still not globally accepted. In Portugal, there are few cases in the literature and none comparing IVIG with other conservative therapies. About 40% of survivors of TEN have residual and potentially disabling lesions. After the acute period, skin and mucosal sequelae are unfortunately frequent with a threat to life or its quality. Sepsis is responsible for more than 50% of mortality, especially if it is associated with DIC. Common pathogens in TEN sepsis are S. aureus and Pseudomonas aeruginosa. Ocular involvement can lead to eyelid fusion, corneal ulcers, and subsequent blindness. Pulmonary sequelae range from chronic bronchitis, bronchiectasis, obliterans bronchiolitis, pneumonia or acute respiratory distress syndrome. These may dictate the need to invasive mechanical ventilation, which can be challenging in these patients. There might also be a reduction in diffusing capacity of the lung for carbon monoxide (DLCO) of 35-40% even in those who do not require mechanical ventilation. Other sequelae as dysphagia, diarrhea, esophagic stenosis or rupture, hepatitis, vaginal and ureteral stenosis, hair loss, nails dystrophy, hypo or hyperpigmentation can also be seen. There are several clinical and laboratory factors that influence adversely the prognosis. The TBSA involved, advanced age, significant comorbidities, delay in suspending the culprit drug, concomitant intake of multiple drugs, need for multiples transfusions and a long re-epithelialization time (more than 9 days). Neutropenia is the most consistent laboratory data to prognosis. Another important factor is more than 48 h delay in admission to an Intensive Care/Burn Unit.

immunoglobulin, lyell syndrome, malaria, sulfonamides, toxic epidermal necrolysis

PMC6180881_02

Male

A 39-year-old male presented with gradually increasing breast lumps on both sides for 1.5 years with no history of trauma. There was no past history of diabetes, hypertension, tuberculosis, pancreatitis, joint pains, fever or weight loss. On palpation, slightly tender subcutaneous masses measuring approximately 3 x 3 and 2 x 2 cm were noted in the left supra-areolar region and the right upper outer quadrant, respectively. Ultrasonography in the regions of the palpable abnormality (Figure 1) revealed an ill-defined, hyperechoic, subcutaneous mass with internal vascularity measuring 25 x 7 mm in the left supra-areolar region and another mass measuring 22 x 9 mm in the upper outer quadrant of the right breast [breast imaging-reporting and data system (BI-RADS) 4a]. Multiple subcentimetre lymph nodes with a few showing an attenuated hilum were seen in both the axillae (more on the left side) and the cervical regions. On mammography (Figure 2), an ill-defined, dense (compared with subcutaneous fat) mass was noted in the upper half of the left breast and upper outer quadrant of the right breast, with no evidence of calcification, architectural distortion or skin retraction (BI-RADS 4a). Contrast-enhanced dynamic MRI of the breasts (Figures 3 and 4) showed focal areas of marked fat stranding with overlying skin thickening measuring 29 x 24 and 13 x 8 mm superolateral to the left nipple and the right upper outer quadrant, respectively. These areas were markedly hyperintense on T 2 weighted fat-suppressed sequence. On contrast administration, the lesions showed heterogeneous enhancement and predominantly Type I kinetic enhancement curves. No evidence of restricted diffusion was noted bilaterally. Both the lesions had similar morphological and kinetic features. The lesions were characterized as BI-RADS 4. Since the imaging findings were inconclusive, histopathological evaluation was advised. Ultrasonography-guided core needle biopsy was performed on the larger lesion in the left breast. Histopathology (Figure 5) revealed fibrofatty tissue fragments infiltrated by lymphoplasmacytic cells arranged in a lobular and focally septal distribution. Few of the vessels showed sclerosis, intimal oedema and lymphocytic infiltration. Focally, the infiltrate revealed a few scattered, intermediate-sized, transformed lymphocytes/immunoblasts. There was no evidence of granulomatous or neoplastic pathology. On immunohistochemistry (CD2, CD5 and CD7), no loss of T-cell antigen was seen. Histopathological findings were suggestive of panniculitis, likely autoimmune related. Quantitative serum antinuclear antibody (ANA) analysis (IgG immunodot assay) was carried out and SS-A/Ro 60-kD, sp100, M2 recombinant and M2 native turned positive with values of 100, 33, 28 and 37 U ml-1, respectively. The ANA HEp-2 was positive at 1 : 40 titre and showed a fine speckled pattern. Anti-dsDNA antibody was negative. The leukocyte count, erythrocyte sedimentation rate, renal and hepatic function tests, urine analysis and serum amylase and lipase were within normal limits. Lupus mastitis or lupus panniculitis of male breast is a very uncommon condition that is a clinical and radiological mimicker of malignancy and in the absence of history of autoimmune disorder can lead to mismanagement of the disease as breast malignancy. The close clinical and radiological similarity of this condition with panniculitis-like T-cell lymphoma also adds to the diagnostic dilemma. However, histopathology, immunohistochemistry and serum markers for autoimmune disorders help in diagnosis. Lupus mastitis is an unusual, benign disease that is very uncommon in males. Imaging and clinical findings are non-specific as it mimics mastitis and malignancy. Timely diagnosis with histopathological and serum analysis is the key to management. Written informed consent for the case to be published (including images, case history and data) was obtained from the patient for publication of this case report, including accompanying images and is within the hospital records.

PMC5420920_01

Female

A 75-year-old woman with systemic lupus erythematosus was evaluated for two months of chronic, low back pain. She also reported subjective fevers, weight loss, and an initially necrotic, one-centimeter wound on her right calf that developed five months earlier. She had no history of trauma, paraspinal steroid injections, or past cardiac or spine surgery. Medications are significant for prednisone and hydroxychloroquine. On exam she was afebrile, with normal vitals, mild lumbar tenderness, normal strength, and intact reflexes in the lower extremities and without saddle anesthesia. Laboratory analysis showed normocytic anemia (hemoglobin 11.6 g/dL), normal white blood cells (5.4 x 109/L), normal platelets (175 x 109/L), hyponatremia (124 mmol/L), and elevated erythrocyte sedimentation rate (106 mm/hr) and C-reactive protein (117 mg/L). She had normal serum complement levels, a negative HIV, and an indeterminate QuantiFERON test. MRI with and without contrast of the thoracic and lumbar spine revealed multilevel discitis and prevertebral osteomyelitis at L1-2, L2-3, and L5-S1 (Figure 1). An abscess located in L5-S1 (Figure 1(a), white arrow) was aspirated. Culture of the abscess revealed polymorphonuclear cells without organisms on conventional and acid-fast bacilli staining. Bacterial and fungal microscopy of the abscess and blood cultures were obtained. Cryptococcal PCR, Coccidioides antibody, and Mycobacterium tuberculosis polymerase chain reaction were negative. The patient was started on empiric intravenous vancomycin and ertapenem. On day 12, M. chimaera was identified in the abscess aspirate by culture and sequencing. She was then transitioned to clarithromycin, rifampin, and ethambutol. A new biopsy of the calf wound was positive for M. chimaera. Surgical discectomy, debridement, and fusion were recommended; however, she deferred surgery and was discharged with a prolonged course of antimycobacterials.

PMC9902057_01

Female

A 60-year-old diabetic woman presented to the emergency department with lower-limb weakness and loss of sensation that had developed gradually over a year along with upper back pain. A history of trauma, tuberculosis, fever, weight loss, and bladder and bowel incontinence were all ruled out. There was no prior history of hospitalisation or medical treatment. The patient was fully conscious with a Glasgow coma score (GCS) of 15. Mild tenderness at the D4-D5 vertebral level with spastic paraplegia (power 0/5) with no upper extremity weakness and an exaggerated deep tendon reflex was noted on clinical examination. A further neurological examination revealed that pinprick and fine touch sensations were reduced below the level of D5, but posterior column sensations were intact. The magnetic resonance imaging (MRI) revealed a well-defined extradural, intensely enhancing right-sided ventrodorsal semicircular lesion causing severe spinal cord impingement (Figure 1) as well as a periaortic soft tissue mass (Figure 2). The lesion was found to have a ventral extension from D1-D5 and a dorsal extension from D2-D6. The CT aortogram revealed diffuse thickening and enhancement of the ascending aorta, aortic arch, and descending aorta, with periaortic mass measuring up to 13 mm (Figure 3). The proximal parts of the aortic arch vessels, bilateral renal arteries, and common iliac vessels were also thickened with luminal narrowing. A repeat clinical examination revealed a lower radial pulse intensity on the right upper limb compared to the left, with a systolic pressure difference of 20 mmHg. There was no tenderness or thickening of the bilateral superficial temporal arteries on palpation. Preoperative investigations revealed elevated erythrocyte sedimentation rate (ESR) (74 mm/hr) and C-reactive protein (2.9 mg/dl) with elevated neutrophils (88% on the differential blood count). Anti-dsDNA (18 IU/ml), anti-cardiolipin immunoglobulin G (IgG) (<2 U/ml), and rheumatoid factor (8.6 IU/ml) levels were normal. The rapid plasma reagin test was non-reactive, and anti-nuclear antibody results were negative. The viral markers (HIV, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV)) were also non-reactive. Based on large vessel vasculitis features on imaging and European League Against Rheumatism (EULAR) diagnostic criteria for TA, a probable diagnosis of TA leading to compressive thoracic myelopathy was made, and the patient was immediately scheduled for surgical decompression due to severe spinal cord compression. A biopsy of the lesion was performed after transpedicular decompression at the D4-D5 level, followed by decompressive laminectomy (D1-D6) and posterior fusion with transpedicular screws. Histopathological examination of the tissue revealed a dense chronic inflammatory infiltrate composed of foamy histocytes, lymphocytes, and plasma cells (Figure 4). The acid-fast bacilli stain was negative, and there was no evidence of necrosis. The probability of IgG4-related disease was also ruled out, as the immunohistochemistry staining of the biopsy specimen revealed <10% IgG4 plasma cells with absent storiform fibrosis and phlebitis. Because there was no improvement in the patient's neurological status in the immediate postoperative period, the patient was advised to undergo rehabilitation before being discharged from the hospital. To treat large vessel vasculitis caused by TA, the rheumatologist prescribed oral prednisolone 20 mg/day and mycophenolate mofetil 1500 mg/day. The immunotherapy was gradually tapered over six months, and a six-month follow-up MRI revealed a near-complete reduction in the extradural mass (Figure 5) as well as full neurological recovery (Power 5/5).

compressive myelopathy, decompressive laminectomy, immunotherapy, spastic paraplegia, takayasu arteritis

PMC8327681_01

Female

A 30-year-old female patient presented to the clinic with intermittent haemoptysis for the past 2 years. She was a lifetime non-smoker, had no significant organic or inorganic dust exposures, and had not recently travelled. She reported progressively worsening dyspnoea and a chronic non-productive cough. There were no constitutional symptoms or a history of tuberculosis. A review of her past medical history revealed that 2 years prior to consulting us, she presented to a different pulmonology unit following an episode of massive haemoptysis. Following extensive investigations, the only identifiable pathology was that of an enlarged right hilar lymph node. A biopsy of the lymph node was performed via a thoracotomy and revealed a hyalinising granuloma. The patient was lost to follow-up until her presentation to our unit. No abnormal signs were elicited on physical examination. In particular, we found no clinical signs suggestive of tuberculosis, sarcoidosis, or connective tissue disease. Spirometry showed mild restriction and a reduced diffusing capacity of the lung for carbon monoxide. A chest radiograph showed reduced volume of the right hemithorax and a right hilar mass-like opacity. Computed tomography found a prominent right bronchial arterial circulation with a distended bronchial artery, tortuous fifth to seventh intercostal arteries, and collateralisation of the pulmonary circulation. A right hilar soft tissue mass was found to be encasing the right pulmonary artery with resultant attenuation of the vessel (Fig. 1). Multifocal areas of ground-glass opacification were seen in the right upper and middle lobes with associated interlobular septal thickening consistent with pulmonary haemorrhage. The previous diagnosis of hyalinising granuloma was excluded after review of the radiology. Microbiological examination of expectorated sputum was negative for tuberculosis, and cytological evaluation was unrevealing. Serological studies for histoplasmosis, Aspergillus and connective tissue disease were negative. Serum angiotensin-converting enzyme, IgG4 and calcium were within normal limits. We proceeded to perform an endobronchial ultrasound with transbronchial fine-needle aspiration of the subcarinal component of the mass-like lesion. No endobronchial lesions were observed during the bronchoscopy, and all major and segmental airways were patent. The aspirate was evaluated by microscopic cytopathological examination, flow cytometry, mycology and mycobacterial culture. Cytopathological examination revealed a paucicellular aspirate with no evidence of malignancy or granulomatous disease, flow cytometry was normal, and microbiological culture examination was negative for tuberculosis and there was no growth on mycology culture. A diagnosis of idiopathic fibrosing mediastinitis was made following consensus by a multi-disciplinary team, and on the basis of highly suggestive radiology (a constrictive, fibrosing lesion of the right hilum and adjacent mediastinal structures) and the exclusion of competing differential diagnoses. Treatment with high-dose oral corticosteroids was initiated and the patient remains clinically stable without evidence of disease progression during follow-up care. She has had no further episodes of haemoptysis.

fibrosing mediastinitis, haemoptysis, idiopathic fibrosing mediastinitis

PMC7171659_02

Male

Case 2 is an 84-year-old man without remarkable medical history other than hyperlipidemia and prostatic hyperplasia. His chief complaint was cough, and an X-ray image showed an abnormal shadow on the upper mediastinum. A CT scan showed a 7.2 cm large mixed mass with a papillary solid component in the anterior mediastinum, and the trachea was compressed to the right and back. We could not confirm continuity with the thyroid; we found no lymph node metastases (Figure 3). A PET-CT showed accumulation in the upper mediastinal tumor (SUVmax = 46.32) and pale nodules in the left lower lobe (SUVmax = 5.23; Figure 3). Neck ultrasonography revealed multiple nodules reminiscent of an adenomatous goiter in both lobes with no malignant appearance (the mediastinal tumors could not be visualized, and their continuity with the thyroid was unclear). We performed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis of the mediastinal tumor, but found no tumor cells, and the tumor's origin remained unknown. In blood tests, the thyroid function was normal, but the thyroglobulin level rose to 2450 ng/mL. No other tumor markers were significant. We suspected that the mediastinal tumor originated from a thyroid cancer, and we decided to resect it. The patient underwent total thyroidectomy, central neck dissection, and mediastinal tumor resection with sternal incision. The mediastinal tumor adhered to the brachiocephalic artery and the right recurrent nerve on the right side, with the trachea and esophagus on the dorsal side and with the left recurrent laryngeal nerve on the left side. On the caudal side, a part of the thymus was resected together because the tumor also adhered to it. Pathological findings included a fibrotic capsule and marked internal necrosis. The pathological report suggested a papillary carcinoma because of the preponderance of papillary growth and the presence of a papillary carcinoma nucleus (nuclear groove; Figure 4). We found no evidence of continuity between the mediastinal tumor and the thyroid. In addition, we noticed a 9 mm nodule in the isthmus of the thyroid and a nuclear finding of papillary carcinoma. We considered the nodule to represent a metastasis to the thyroid. We found no lymph node metastases. The thyroglobulin level decreased to 25.7 ng/mL after surgery. Administration of 131-iodine (100 mCi) resulted in strong accumulation in the thyroid bed and weak accumulation in lung metastasis. Therefore, we plan to follow-up the RAI therapy.

PMC2984303_01

Male

A 25 year old left hand-dominant man presented with swelling and mild numbness of the left arm of three days duration. Just a day before the onset of the swelling, he carried a heavy television set to his house. He had a history of pleural tuberculosis which was successfully cured after anti-tuberculosis treatment. He denied any past history of surgery and intravenous drug use. No family history of a similar illness was detected. Clinical examination revealed few dilated veins in the arm and the upper left half of the chest, which became more prominent during Valsalva's manoeuvre. The left upper limb showed normal arterial pulses and there was no neurological deficit or bony injury. A Doppler ultrasonography confirmed thrombosis of the left subclavian/axillary vein. Other investigation results including x-rays of the left shoulder and chest, computerized tomography of the upper chest and complete blood count (CBC) were all normal. The coagulation profile revealed activated partial thromboplastin time (aPTT) and prothrombin time (PT) within normal range while the international normalized ratio (INR) was 1.0. The patient was treated as an outpatient with low molecular weight heparin (LMWH) for 6 days and then maintained on oral warfarin for 6 months. A Doppler imaging done after the third month of initiation of warfarin treatment revealed complete recanalization of the subclavian/axillary vein and development of collateral circulation. The patient was followed for three years without any apparent complications or relapse except a mild occasional pain on the affected limb.

deep vein thrombosis, paget-schroetter syndrome, axillary vein, subclavian vein

PMC7101478_01

Female

A 46-year-old woman presented with continuous abdominal pain for more than a month. There was no family history of gastrointestinal tumors. There was no sign of peritonitis, and no abnormal findings were detected from the laboratory studies performed at admission, such as serum electrocytes, TB-IFN, and the immune PHOMO check. The CT results were within normal limits (Fig.1). The EUS indicated a hypoechoic tumor with slightly heterogeneous internal echoes originating from the submucosal area located at the stomach antrum, measuring 1.3*1.0 cm with well-defined borders (Fig.2A BC). The tumor protruded into the cavity. Upon ESD, we could see a yellow oval tissue with a well-defined border that was similar to fat or pancreatic lesions (Fig.2D). Histopathologic analysis indicated an onion-skin-like concentric formation of the fibroblastic stroma and spindle cells with inflammatory cell infiltration, predominantly by numerous eosinophils (Fig.3A). Immunohistochemical examination showed that the cells were positive for CD34 (Fig.3B), Smooth Muscle Actin (SMA) (Fig.3C), and were negative for CD117 (Fig.3D), DOG-1 (Fig.3E), S100 (Fig.3F) and ALK (Fig.3G). The P53 labeling index was 1% (Fig.3H), whereas the Ki-67 labeling index was 5% in the spindle cells (Fig.3I). The histopathological and immunohistochemical findings were consistent with an IFP. By using an acid inhibitor and painkiller, the abdominal pain was not significantly improved, but was relieved after ESD. She is currently in clinical remission. Finally, we diagnosed the tumor as an IFP because the histopathological and immunohistochemical findings were the same. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Heisinki Declaration and has been approved by the Affiliated Hospital of Southwest Medical University review board. Informed consent: Informed consent has been obtained from patient included in this study.

endoscopy, immunocytochemistry, pathology, vanek’s tumor