We describe a case of a healthy 5-year-old Caucasian boy who presented acute left knee and left elbow swelling accompanied by pain. He denied trauma or other symptoms; 2 weeks earlier, however, he had suffered an upper respiratory tract infection without fever. Laboratory tests (complete blood cell count, hepatorenal function, serum electrolytes, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), autoantibodies ANA, ENA, anti-dsDNA, mycoplasma serology) were within normal limits and ultrasound examination of the affected joints revealed mild joint effusion. The child was treated with nonsteroidal anti-inflammatory drugs (NSDAIs) for 10 days with clinical resolution. One year later, he presented swelling of the left knee which had been ongoing for 2 months, persisting despite NSDAIs treatment. Ultrasound examination showed the presence of a Baker’s cyst and joint effusion in the suprapatellar recess. Juvenile Idiopathic Arthritis (JIA) was diagnosed and intra-articular steroid injection of the knee was performed. Three months later, the child was admitted to our hospital owing to the persistence of the knee swelling. Ultrasound and Magnetic Resonance Imaging (MRI) of the affected joint (Fig. ) confirmed the presence of a voluminous Baker’s cyst, but showed the resolution of the joint effusion in the suprapatellar recess. Laboratory tests, including autoimmunity, were negative. Physical examination revealed the presence of some skin lesions: non-tender mobile skin-colored papules localized in the gluteal and umbilical regions, plaques in the right lumbar region, nodular lesions in the left lumbar, left scapular, left anterior and medial femoral regions (Fig. ). The child’s parents reported that the first skin lesions had appeared 2 years earlier, when connective tissue nevus had been diagnosed. Owing to the increase in size and number of the lesions a skin biopsy was performed: histopathological examination revealed the presence of a perivascular chronic inflammatory infiltrate in the superficial dermis and interstitial mucine deposition in the reticular dermis (Fig. ). The clinical features and histopathological findings allowed us to diagnose CMI.
Currently our patient has been on follow-up for the last 3 years. Cutaneous manifestations remained almost stable during this period, however he experienced sporadic episodes of knee swelling and pain which resolved with NSAIDs.


A 35-year-old woman with VHL who underwent total pancreatectomy and right nephrectomy for pancreatic SCN and renal cell carcinoma (RCC), respectively, had postoperative follow-up examinations performed every 6 months []. At the 4th year follow-up examination, 12-mm and 15-mm tumors in the liver segment VIII and VI, respectively, were detected as hyper-enhanced mass in the early phase by contrast-enhanced computed tomography (CT) scan (Fig. a, b). Gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed arterially hyper-enhanced lesions in the liver, which were the same as the findings of the CT scan (Fig. c, d), showing iso-enhancement in the portal phase and hypo-enhancement in the delayed phase compared with the liver parenchyma. The liver tumors were radiographically diagnosed as metachronous metastases of pancreatic SCN or RCC. Partial resections of the liver were performed 53 months after the initial surgery. Contrast-enhanced intraoperative ultrasonography (CE-IOUS) using Sonazoid (gaseous perflubutane) showed early enhanced hyperechoic tumors in the liver, whereas intraoperative indocyanine green (ICG) fluorography showed no liver tumor. In the intraoperative macroscopic findings, the liver tumors were obscure. In microscopical observations, the tumors were confined in portal regions without invasion into the hepatic parenchyma, which consisted of microcysts lined by cuboidal epithelial cells with clear cytoplasm containing large amounts of glycogen that were stained by periodic acid Schiff with abolishment by diastase. Furthermore, immunohistochemically, the tumor was positive for pan-cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), cytokeratin (CK) 7, CK18, CK19, epidermal growth factor receptor (EGFR), inhibin α, laminin, type IV collagen, neuron specific enolase (NSE), and mucin (MUC) 6, but negative for CK20, CA125, S-100, CD10, CA19-9, paired-box gene (PAX) 8, vimentin, CD56, MUC1, MUC2, and MUC5AC. These immunohistochemical findings were similar to those of the primary pancreatic SCN, but differed from the RCC resected previously (Fig. ). Thus, the tumors were pathologically diagnosed as liver metastases of the pancreatic SCN, synonymous with serous cystadenocarcinoma in the World Health Organization (WHO) Classification of Tumours of the pancreas [].
After the second surgery, the patient had follow-up examinations performed every 6 months again. At the first follow-up examination, one and two tumors located in the liver segment III and VIII, respectively, were detected by contrast-enhanced CT and Gd-EOB-DTPA-enhanced MRI (Fig. ). Compared to the contrast-enhanced CT scan, the Gd-EOB-DTPA-enhanced MRI more clearly showed the tumors of segment VIII (Fig. a, c), as in the previous examination. On the other hand, the tumor of segment III was clearly detected by the contrast-enhanced CT, though undetectable in the Gd-EOB-DTPA-enhanced MRI (Fig. b, d). Liver metastases of SCN were radiologically suspected. Since it was a short period since the hepatectomy, radiological follow-up examinations were additionally performed every three months to observe changes in the number and size of the tumors. No increase in the number of the tumors was seen in the radiological examinations after 6 months. Thus, the liver tumors were considered to have a surgical indication. Anterior segmentectomy and partial resection of segment III were performed 66 months after the initial surgery and 13 months after the second, respectively. Findings of CE-IOUS using Sonazoid and intraoperative ICG fluorography were similar to those in the second surgery. Pathologically, the resected tumors again showed morphological and immunohistochemical features similar to the primary pancreatic SCN, hence these tumors were pathologically diagnosed as multiple metachronous liver metastases of pancreatic SCN, synonymous with serous cystadenocarcinoma (Fig. ). Although the radiological findings of CT/MRI in the tumor of segment III were different from those in the tumors of segment VIII, no histopathological findings suggesting a difference in the radiological findings were observed.
Since then, radiological follow-up examinations have been continuously performed. The patient has remained disease-free without any recurrence after the third operation for 6.5 years until the recent last follow-up.


A 38-year-old male known to have 22q11.2DS presented with recurrent vertigo lasting for hours and fluctuating tinnitus in the left ear. He had a history of neonatal seizure, hypocalcemia due to hypoparathyroidism, and intellectual disability, and underwent cardiac surgery due to congenital heart disease (tetralogy of Fallot) at 15 years of age. On examination, the patient showed characteristic facial features of 22q11.2DS such as hypertelorism, a short and broad nose, and a deeply grooved philtrum. There was no spontaneous nystagmus between vertigo attacks, and bedside head impulse and bithermal caloric tests were normal. The pure tone audiogram (PTA) demonstrated sensorineural hearing loss (SNHL) in the left ear (). Computed tomography (CT) imaging of the temporal bone revealed bilateral widening of the vestibules, soft tissue densities in the middle ear, and decreased mastoid air cells (). The patient was diagnosed with Ménière's disease, and treated with a low-salt diet and diuretics. The vertigo attacks resolved, and follow-up PTA revealed mild improvement of SNHL in the left ear ().
Five years after his initial presentation, the patient developed recurrent vertigo, hearing loss, and tinnitus in the left ear again. A physical examination demonstrated spontaneous left-beating nystagmus with downbeat components that increased during left eccentric gaze. Bithermal caloric tests were normal, and video head impulse tests showed normal vestibulo-ocular reflex (VOR) gains for all six semicircular canals (SCCs). PTA revealed profound SNHL in the left ear (). Treatment with diuretics, betahistine, and intratympanic steroid injection to the left ear failed to attenuate the vertigo attacks. A 1-month follow-up PTA revealed additional hearing loss in the right ear without improvement of the left SNHL (). The patient received an intravenous steroid injection followed by a tapering dose of oral steroids, resulting in a gradual reduction of the frequency of vertigo attacks. At the 1-year follow-up PTA, there was improvement of hearing loss in both ears, particularly in the right ear (). Since the vertigo attacks recurred after stopping diuretics, the patient was maintained on combination therapy with betahistine and diuretics. During a 3-year follow-up period, he remained symptom-free despite the persistence of left SNHL (). At the latest follow-up, the patient underwent delayed 3T magnetic resonance imaging (MRI; MAGNETOM Vida, Siemens, Erlangen, Germany) using a 64-channel array head coil, 4 h after intravenous gadolinium (12 ml of gadoterate meglumine, Dotarem; Guerbet, Aulnay-sous-Bois, France) to evaluate the presence of endolymphatic hydrops (EH) (). We performed the 3D fluid-attenuated inversion recovery (3D-FLAIR) images with the following parameters; field of view (FOV): 160 × 160 mm, repetition time (RT): 7,000 ms, echo time (ET): 303 ms, inversion time (IT): 2,050 ms, matrix size: 256 × 230, flip angle: 120°, number of excitation (NES): 2, and scan time of 6 min 39 s. Axial 3D-FLAIR revealed cochlear EH with dilation of the scala media in the left ear (), but no cochlear enhancement or vestibular EH.


A 12-years-old male student with unremarkable medical and surgical history was referred to our otorhinolaryngology clinic on July 2020 at Princess Basma Hospital in Jordan. He presented with his parents complaining from a sudden onset aphonia for 3 days duration. According to his parents, the patient has normal physical, social, cognitive and emotional developmental milestones. There was no history of upper respiratory tract infection, laryngeal trauma, fever, or cough. Patient is not on any medical treatment with unremarkable family history. They insisted that he suddenly had this problem following diving in swimming pool.
Clinically, the patient was afebrile with stable vital signs. He was conscious, alert, and following commands precisely, and examination of his ears, nose and throat were unremarkable. A flexible fiberoptic laryngoscopy under local anesthesia was performed by an otorhinolaryngology consultant. The larynx showed a mobile bilateral vocal cord with complete Aphonia (). There were no polyps, nodules, or compressive masses over the vocal cords. Phycological and neurological consultations were requested.
Based on overall assessment, patient was diagnosed with psychogenic aphonia, and his condition was discussed with his parents, speech therapist and psychologist. Following 3 weeks of intensive speech therapy sessions, patient showed significant improvement in his voice, and his treatment was continued for a total of 5 weeks. Patient was followed clinically for 6 months with no recurrence of previous symptoms.


In December 2019, a 60-year-old man was admitted to the Second Hospital of Nanjing due to persistent lung shadow for 2 years, but without any clinical symptoms. He had received the allograft kidney transplant because of chronic renal failure since 2011. The regular pre-transplant screening reports ever excluded TB or cancer for both the donor and the receipt. Afterwards, the renal function of the patient maintained stable with the combination drug therapy, which was composed of mycophenolate mofetil (500 mg/250 mg per day), cyclosporine (75 mg twice per day), prednisone (5 mg once per day), phoebus, Bailing capsule and valsartan. In December 2017, during the follow-up examination in the kidney transplant hospital, the chest CT found speckle and stripe shadows in the posterior segment of the right upper lobe (Fig. A), and a nodule in the anterior segment of right lower lobe with small cavity shadow inside (Fig. B). Both T-SPOT and purified protein derivative (PPD) tests were positive for Mycobacterium tuberculosis (MTB) infection, but detection of MTB from the sputum samples through smear microscopy, culture and real-time PCR was negative. Then, the empirical anti-TB therapy was started. Whereas, this treatment was terminated after 2 weeks since the patient family worried about indefinite diagnosis of TB and side effects.
At admission, physical examination revealed that respiratory, cardiovascular, abdominal and neurological characteristics were normal. Complete blood count test, C-reaction protein, erythrocyte sedimentation rate, coagulation (D-Dimer), tumor markers, liver and renal function tests were negative. As before, T-SPOT test was positive, but smear microscopy, culture and real-time PCR for MTB were still negative.
Remarkably, chest CT found some changes compared with 2 years ago. In the posterior segment of the right upper lobe, a soft tissue density mass shadow with spiculate boundary appeared (Fig. C). Also, the nodule in the right lower lobe became bigger (Fig. D). According to those radiological findings, the possibility of lung cancer in the upper lobe was considered. 18F-fluorodesoxyglucose positron-emission tomography (FDG-PET) CT found that FDG intake increased in both the pulmonary consolidation lesions, with SUVmax 8.2 in the right upper lobe and SUVmax 1.9 in the right lower lobe, respectively (Fig. ). Meanwhile, there was no obvious abnormality for the remaining part of lung, mediastinal lymph nodes, liver and kidney. Taken together, adenocarcinoma was probably considered. A CT-guided percutaneous transthoracic needle biopsy was then operated, and the pathological result confirmed lung adenocarcinoma in the right upper lobe.
The video-assisted thoracoscopic surgery (VATS) right upper lobectomy, wedge resection of right lower lobe and lymphadenectomy were operated. The pathological results revealed that both lobes had invasive adenocarcinoma but with different histological subtypes, according to the predominant pattern of the neoplastic cell growth, which was mainly acinar type and solid type for the upper lobe and lower lobe, respectively (Fig. A and B). To our interest, we observed caseous necrosis along with acinar type adenocarcinoma in the right upper lobe (Fig. A). Acid-fast staining for the surgical tissue samples detected MTB in the field (Fig. ). Real-time PCR was also positive for MTB. Therefore, we could make a definite diagnosis that smear-negative TB and adenocarcinoma co-existed in the right upper lobe.
According to TNM classification criteria, the adenocarcinoma in the right lobe was diagnosed with Stage IA, no chemotherapy or radiotherapy was taken further after surgical resection. Since TB infection was complicated in the right upper lobe, anti-TB treatment was still necessary. However, the challenge for TB treatment was how to avoid potential renal toxicity of anti-TB drugs. Considered that the KTR has been taking anti-rejection medication, rifampicin was firstly excluded because it would affect the expression of cytochrome P450 3A4 in the liver and in the small intestine and interfere with the metabolism of anti-rejection drugs []. Similarly, pyrazinamide was also excluded as it would lead to hyperuricemia and influence the renal function. The final anti-TB regimen for this patient was isoniazid (0.3 mg, QD, ethambutol (0.75 mg, QD) and moxifloxacin (0.4 mg, QD). After two-week treatment in hospital, the patient was discharged for continuous anti-TB treatment for 9 months in total.
In March 2021, at 6-month follow-up after drug withdrawal, the patient kept healthy without any uncomfortable symptoms. The normal tests for MTB and tumor were all negative, and the renal function was normal.


The patient was a 72-year-old woman with a past medical history of chronic cough with expectoration of thick sputum. She had been treated several times with antibiotics for chronic bronchitis. The patient did not have any history of childhood respiratory infections, tobacco smoking, aspiration pneumonia episodes, or neuromuscular disease. She was admitted to our facility because of fever, productive cough, wheezing, dyspnea, and hypoxemia with the diagnosis of lower respiratory tract infection. Pulmonary consultation was done to evaluate the patient for the management of chronic cough and dyspnea. Physical examination revealed pulmonary cachexia, bilateral coarse crackles, and wheezing. Digital clubbing was prominent in both hands. Fungal cultures and acid-fast bacilli smear were negative. Sputum cultures were positive for Pseudomonas aeruginosa and the patient was treated with broad-spectrum antibiotics. A chest CT scan was performed which revealed significantly enlarged trachea, bronchi, and bronchioles with mucoid impaction in distal airways (Figure ). The coronal tracheal diameter was measured to be 32 mm. Her most recent PFTs were in 2016 which showed moderate obstructive lung disease with a forced expiratory volume in one second (FEV1) of 60% and an FEV1:FVC ratio of 71%. These features are consistent with recurrent pulmonary infection, leading to bronchiectasis and mucoid impaction due to MKS.


This is a 70-year-old man with a past medical history of hypertension, hepatitis C infection, Barrett’s esophagus, a Zenker’s diverticulum, and severe AS, who presented to the emergency room (ER) complaining of new-onset melena and dyspnea. The patient reported melena starting one week prior to admission, but it was intermittently occurring for two months prior. The patient also reported progressive worsening of epigastric pain and nausea but no vomiting during this time. Furthermore, the patient had dyspnea and chest discomfort for two months, with associated dizziness. He denied any change in bowel habits, hematemesis, or bleeding from another site. He was admitted six months prior with the same complaints when a transthoracic echocardiogram (TTE) was performed and showed a normal left ventricular ejection fraction (LVEF) of 55%-60% and evidence of severe AS with an aortic valve area of 0.7 cm2, mean gradient 52 mmHg, and a peak aortic velocity of 4.4 m/s. At that time, an esophagogastroduodenoscopy (EGD) was completed which demonstrated Barrett's esophagus with high-grade dysplasia. Moreover, there was evidence of gastritis and a non-bleeding gastric ulcer with a clean base, which was biopsied, and it was negative for dysplasia or malignancy, as well as for Helicobacter pylori infection. Therefore, the patient was started on proton pump inhibitor (PPI) therapy.
On admission, the physical examination was significant for a grade III systolic ejection murmur in the right second intercostal space. The remainder of the physical exam was unremarkable including the abdominal exam. Laboratory studies were significant for microcytic anemia; serum hemoglobin 5.9 g/dL, hematocrit 20.6%, and mean corpuscular volume (MCV) 76.3 fL. White blood cells (WBC) and platelet counts were within normal limits. The basic metabolic profile was unremarkable, while the liver function test showed a slightly elevated aspartate aminotransferase (AST) to 53 IU/L, but was otherwise normal. Lipase, urinalysis, and coagulation profile were all within normal limits.
In the ER, the patient was given two units of packed red blood cells and was started on intravenous PPI. An EGD was repeated which showed three non-bleeding duodenal angioectasias (Figure ), which were treated with electrical cauterization. A colonoscopy was recommended but the patient refused. Subsequently, the patient underwent a balloon valvuloplasty for his severe symptomatic AS. He was not deemed to be a candidate for surgical aortic valve replacement (AVR) given his social status of being homeless and was also not a candidate for trans-catheter aortic valve replacement (TAVR) as he would not be able to be started on dual anti-platelet therapy (DAPT) given his active GI bleeding.
Upon discharge, the patient was admitted again multiple times with recurrent melena, dizziness, and acute blood loss anemia requiring blood transfusions. An EGD with push enteroscopy was repeated twice, which showed multiple duodenal and jejunal angiodysplastic lesions (Figure ), which were treated with argon plasma coagulation. The patient was also evaluated by the cardiology service as an outpatient, and he underwent TAVR subsequently when his GI bleeding stopped. Aspirin was changed to Plavix accordingly, and the patient was continued on PPI. The patient has been doing well since the TAVR procedure, with no recurrent episodes of GI bleeding or anemia. The follow-up TTE after the TAVR showed a normal LVEF of 55%-60% and no evidence of AS (aortic valve area 2.2 cm2, mean gradient 11 mmHg, and a peak aortic velocity of 2.3 m/s).


The patient was a 70-year-old female with no past medical history who presented with complaints of abdominal pain of three weeks' duration and one episode of hematemesis in the past week. At the emergency department, the patient underwent a CT scan of the abdomen, which exhibited a large, 8 x 6 x 6-cm abdominal mass arising from the stomach and extending to the lesser sac and central crus of the diaphragm with bilateral retroperitoneal lymphadenopathy (Figure ). Admission labs were remarkable for a hemoglobin of 11.8 g/dl (normal range: 13.5-17.5), hematocrit of 34.6% (normal range: 41-53), alkaline phosphatase of 109 U/L (normal range: 34-104), and a sodium of 129 mEq/L (normal range: 135-145). Gastroenterology was consulted, and they performed an esophagogastroduodenoscopy (EGD), which revealed a large excavated, ulcerated, and partially necrotic mass on the lesser curvature of the proximal gastric body (Figure ).
Histopathological analysis of tissue biopsied during EGD revealed gastric oxyntic mucosa with infiltrating mixed poorly differentiated adenocarcinoma (Figure ) and neuroendocrine carcinoma (Figure ). The uninvolved mucosa exhibited chronic gastritis with focal intestinal metaplasia. Immunostaining showed that the adenocarcinoma was diffusely and strongly positive for pancytokeratin (Figure ), while the neuroendocrine component showed weaker dot-like staining (Figure ).
The adenocarcinoma was positive for CDX2 while the neuroendocrine component was positive for synaptophysin and chromogranin (Figure ). Immunostains for CD45 and Helicobacter pylori were negative. Alcian blue and periodic acid-Schiff staining highlighted many goblet cells. CT scans of the chest and abdomen were performed two weeks later, which revealed bilateral pulmonary embolism, as well an interval increase in the size of the gastric mass now to 7 x 12 x 7 cm with new liver metastasis and moderate ascites (Figure ). MRI of the head was performed, which showed no intracranial pathology. The patient was determined to be a poor surgical candidate for resection due to advanced disease and was subsequently transitioned to hospice care.


A 76-year-old Japanese man with diabetes and hypertension presented with left lower quadrant abdominal and medial femoral pain for the previous 10 days. He was diagnosed with a left common iliac aneurysm by the consultant who referred him to our hospital. He denied any gastrointestinal symptoms before admission. He had no known allergies and was prescribed angiotensin II receptor blocker for hypertension and insulin for diabetes; however, he had discontinued these medications two months before hospitalization based on his own judgment.
He was alert (Glasgow Coma Scale 15), and his vital signs were as follows: body temperature, 38.2 °C; blood pressure, 117/54 mmHg; heart rate, 67 beats/min; respiratory rate, 14 breaths/min; and oxygen saturation, 98 % on ambient air. Physical examination indicated mild tenderness on the left lower abdomen. The findings from other examinations, including the palpation of bilateral dorsalis pedis arteries, were normal.
The laboratory findings were as follows: albumin, 3.0 g/dL; alanine transferase, 11 U/L; aspartate aminotransferase, 15 U/L; lactate dehydrogenase, 139 U/L; creatine kinase, 30 U/L; lactate, 7.7 mg/dL; blood urea nitrogen, 17 mg/dL; creatinine, 0.94 mg/dL; C-reactive protein, 5.15 mg/dL; blood glucose, 155 mg/dL; hemoglobin A1c (HbA1c), 6.9 %; white blood cell count, 6400/μL with 68.7 % neutrophils; hemoglobin, 8.8 g/dL; and platelet count, 22.2 × 104/μL.
Abdominal computed tomography (CT) showed a 27 × 32 mm sized saccular pseudoaneurysm surrounded by inflammation in the left common iliac artery (; A, C). The inflammation affected the inferior mesenteric artery and the left ureter (A), which caused left hydronephrosis (B).
Two sets of aerobic and anaerobic blood cultures (BacT/Alert FAN plus, bioMérieux, Marcy I’Etoile, France) obtained at admission turned positive within 21 h. Gram staining showed Gram-positive rods (A), which were quickly and accurately identified as L. monocytogenes, using the matrix-assisted laser desorption ionization (MALDI) biotyper Sepsityper kit® (Bruker Daltonik GmbH, Bremen, Germany) with a high score value (2.03) and the Verigene® system (Luminex, Austin, Texas, USA), within 24 h of obtaining the blood cultures. Isolates grew on 5% sheep blood agar (Nihon Becton-Dickinson, Tokyo, Japan), following 24 h incubation at 5% CO2 and 37 °C and exhibited a narrow zone of beta-hemolysis (B). The E-test® (bioMérieux, Marcy I’Etoile, France) suggested minimum inhibitory concentrations (MICs) of 0.19, 0.125, and 0.064 μg/mL for penicillin, ampicillin, and sulfamethoxazole/trimethoprim, respectively, which indicated susceptibility, according to the Clinical and Laboratory Standards Institute (CLSI) document (M100-Ed30) (; C, D) []. There was no evidence of infective endocarditis, as evaluated by transthoracic and transesophageal echocardiography or bacterial meningitis, as observed from the cerebrospinal fluid examination on day 2. In addition, the stool culture obtained during admission was negative for L. monocytogenes.
The patient was diagnosed with an infected aneurysm caused by L. monocytogenes and treated with 2 g of intravenous ampicillin every 6 h. He became apyrexial without any massive rupture of the infected aneurysm, because of the administration of the appropriate antibiotic; his blood pressure was well controlled with an intravenous antihypertensive calcium channel blocker. Blood cultures from samples obtained on day 6 were negative for L. monocytogenes. Therefore, surgical debridement, followed by in-situ Y-graft (Japan Lifeline Co., Ltd., Tokyo, Japan) placement with revascularization including the inferior mesenteric artery and omental implantation, was performed on day 8. The resected specimen culture was negative for L. monocytogenes, which could be attributed to the intensive antibiotic therapy before the surgery. Postoperative CT on day 16 indicated that all the anastomoses were patent without any complications (). After three weeks, the antibiotic therapy was changed from intravenous ampicillin to oral amoxicillin and the patient was discharged on day 23. Oral amoxicillin was discontinued on day 85, when all anastomoses remained patent without left hydronephrosis in the follow-up CT, and the patient has remained disease-free without recurrence ().


The study reports the case of a 99-year-old man (body mass = 55 kg; height = 160 cm; thigh circumference: right = 34 cm, left = 35 cm), with severe muscle mass deterioration and knee osteoarthritis, accompanied by muscle and joint pain that affected his muscle strength and function. Despite encountering great difficulty, he was able to walk, sit down and stand up with only the assistance of a walking stick; other simple activities of daily living, such as bathing and dressing, required the help of a family member. Following medical guidance, he made continuous use of medications for muscle-joint pain (Ultracet: tramadol hydrochloride 37.5 mg, paracetamol 325 mg; Tandrilax: caffeine 30 mg, carisoprodol 125 mg, diclofenac sodium 50 mg, paracetamol 300 mg) and anxiety (Bromazepan 3 mg). In addition to pharmacological treatment, he performed 3 weekly physical therapy sessions to relieve pain and reduce joint stiffness. He did not present any other acute or chronic diseases. The study was approved by the Institution's ethics committee and the participant and family members were informed of all benefits and risks of the study before signing an institutionally approved informed consent form.
We assessed the cross-sectional area (CSA) and muscle thickness (MT) of the vastus lateralis (VL) muscle, functional performance and quality of life {The World Health Organization Quality of Life Questionnaires [WHOQOL-bref (The WHOQOL Group, ) and WHOQOL-OLD (Power et al., )] and The Western Ontario and McMaster Universities Questionnaire (Bellamy et al., ) [WOMAC]}, before (Pre) the training period and after 12 (Mid) and 24 (Post) training sessions (). At each of these time points, 2 assessments were performed on two different days at the same time of day and the average between the two was presented. The participant was instructed to maintain his eating routine and abstain from stressful activities for at least 72 h before each evaluation day (Newton et al., ; Damas et al., ).
The CSA of the VL was evaluated using an ultrasound device (US) (Lixandrao et al., ). Images were acquired using mode B ultrasound, with a linear probe configured at 7.5 MHz (Samsung, MySono U6, Brazil), and applying transmission gel to ensure acoustic coupling with minimal epidermal compression. The skin was marked at the point corresponding to 50% of the total length of the right femur (SENIAM, ); from this point, successive markings were made transversely, both medially and laterally, at 2 cm intervals, to guide the displacement of the probe in the sagittal plane (). Sequential images of the right VL were recorded every 2 cm, starting at the most medial skin mark (over the rectus femoris muscle), and moving in the mid-lateral direction. An investigator, blinded to the timepoints, then opened the captured images in PowerPoint (Microsoft, USA), rotated them manually and organized them to reconstruct the complete view of the cross section of the VL. The complete image was then opened on the Image J software and the “polygonal” tool was used to calculate the CSA. MT was evaluated at the same time and place of acquisition of the CSA images, but with the probe oriented longitudinally to the muscular belly. The “straight” tool of the Image J software (Erskine et al., ) was used to measure the vertical distance between the deep aponeurosis and the superficial muscle aponeurosis at the right and left margins of the image and the mean value was recorded. Two US images were evaluated following this same procedure and the average between them was presented as the final MT value. The CV of the CSA and MT measures were 4.25 and 2.96%, respectively.
Following US imaging, a personalized blood pressure cuff (175 × 94 mm) with a pressure gauge (Missouri, São Paulo, Brazil) was fixed in the proximal region of his right thigh and a vascular doppler probe (DV-600; Martec, Ribeirão Preto, Brazil) was placed over his tibial artery. For the determination of blood pressure of complete vascular occlusion at rest, the cuff was inflated until the moment when the auscultatory pulse of the tibial artery was interrupted (Libardi et al., ). The procedure was repeated for the left leg. The cuff pressure necessary for complete blood flow restriction was 170 mmHg for the right leg and 150 mmHg for the left leg. Cuff pressure to be used during exercise was established at 50% of these values.
The functional performance was measured through “Timed Up and Go” (TUG) test with the aid of a force platform (AccuGait, AMTI, USA). The participant's wheelchair was positioned–and secured–so that his feet were placed on the platform (). He started the test sitting with his back on the chair, arms positioned on the side arms and feet on the force platform until the start command. After the command, the participant was instructed to get up as quickly as possible using the armrests of the chair, then walk–with external assistance–a distance of 3 m, return, and sit again with the back against the seat (Miotto et al., ). The first trial was a familiarization session and the second trial always served as the test session. Balance Clinic software (AMTI, USA) was used to compute the total time to complete the task. The TUG time was also divided into two components: (1) time spent atop the force plate at the beginning and ending of the test, which can approximately reflect the time used to get up and sit back on the chair, and (2) time spent off the force plate, i.e., time in which no forces are being applied to the platform, and thus, can approximately reflect the walking portion of the test. The CV's for the full TUG test, the time spent on the platform and time spent off the platform were of 5.98, 6.86, and 7.26%, respectively.
Three questionnaires were applied to assess possible impacts of the intervention on the participants quality of life (QoL): WHOQOL-bref, WHOQOL-OLD and WOMAC. The first one is a short form QoL assessment composed by one general QoL item, one general health item, and 24 items that cover four specific domains: physical health, psychological, social relationships and environment (The WHOQOL Group, ). The WHOQOL-OLD is a supplementary module which contains six facets considered especially relevant to older adults: (1) “sensory abilities” (2) “autonomy,” which refers to the ability to live independently and make his own decisions; (3) “past, present, and future activities,” related to accomplishments in life; (4) “social participation”; (5) “death and dying,” related to concerns and fear of dying; and, (6) “Intimacy” (Power et al., ). The WOMAC questionnaire is composed of three dimensions (pain, stiffness, and physical function) and is used to assess clinically relevant changes in health related QoL as a result of an intervention for people with OA (Bellamy et al., ). Scores for WHOQOL-bref and WHOQOL-OLD are scaled from 0 to 100 in a positive direction (i.e., higher scores denote higher QoL) while scores for WOMAC are scaled from 0 to 100 in a negative direction. The CV's for the global scores of WHOQOL-bref, WHOQOL-OLD, and WOMAC were of 2.97, 9.00, and 3.36%, respectively.
Training sessions were held three times per week, for a total of 24 sessions. The RT-BFR consisted of a unilateral free-weight knee extension exercise (). The participant was instructed to sit upright on a knee extension chair, with his lower back supported by the chair back, and then was instructed to perform the exercise with the largest range of motion possible to achieve without pain. He started the protocol with a warm-up of 10 repetitions without overload; then he performed three sets of 10–15 maximum repetitions using ankle weights strapped around his shin with a blood flow restriction (described below). A 1-min interval was allowed between sets. If the participant performed less than 10 repetitions in the first set, the load was readjusted to achieve at least 10 repetitions in the next; if 15 repetitions (or more) were performed in each of the three sets, the load adjustment was performed in the next session. In the first session of training, only the limb weight was used; by the last session, load was progressed to a 4 kg ankle weight. After performing the training with one leg, it was repeated with the other. The starting leg was switched every session. Blood flow was partially restricted unilaterally during sets and intervals using a cuff (175 × 94 mm; Missouri, Brazil) with a pressure gauge positioned in the proximal region of the thigh. Training pressure was established at 50% of the pressure of complete vascular occlusion (right leg: 85 mmHg; left leg: 75 mmHg) and was readjusted throughout the protocol so that the relative occlusion was maintained (Patterson et al., ).
From the tests (T), a coefficient of variation (CV) was computed for each outcome as:
where TE is the typical error of measurement and SD is the standard deviation of the difference between the two tests T (j = 1, 2) made on time point i (i = Pre; Mid; Post). Thus, the CV is an alternative form of presenting the TE, expressed as a percentage of the subject's mean score (Hopkins, ). It has been suggested that 1.5–2 times the typical error (TE) of measurement can be used as a threshold for deciding if a real change in outcome has occurred (Hopkins, ). Therefore, we evaluated percentage changes and compare with two times the CV as the cut point for significance.


An otherwise healthy two-year-old boy presented with an eight-day history of high-grade fevers up to 105F associated with vomiting, poor enteral intake, and abdominal pain. His mother reported that two weeks prior, the patient was playing with his family member who was sick with a cough and then he developed similar symptoms. The patient was treated with ibuprofen and his fever subsided, but then complained of a burning sensation with urination. He was prescribed amoxicillin for urinary tract infection and completed three days of a seven-day course. Two days later, the fever and cough returned prompting a visit to the emergency room where the patient was found to be influenza A positive and subsequently sent home with supportive management. Following discharge, he experienced refractory daily fevers between 101F and 105F, intermittent vomiting and coughing with post-tussive emesis. The patient was subsequently admitted to the hospital due to dehydration and abdominal pain.
During hospitalization the patient was febrile to 103F and was tachycardic, averaging 140-160 BPM. Laboratory results were remarkable for leukocytosis of 23,500 cells per microliter with bandemia of 29,000 cells per microliter, elevated c-reactive protein of 5.32mg/dL and procalcitonin that was 4.8ng/mL. Chest x-ray, blood-urine cultures, and urinalysis were all negative.
An ultrasound study of the abdomen was unable to localize any pathologies, including pyelonephritis (Figure ). CT of the abdomen and pelvis showed large volume ascites with patchy peritoneal enhancement towards the abdominopelvic junction. Hypodense fluid was seen throughout the large bowel; there was a dilated ascending colon with pneumatosis intestinalis, possible bowel ischemia. An oblong rim-enhancing collection was noted within the abdominopelvic junction. There was also moderate volume right-sided perinephric fluid (Figure ).
The patient was started on intravenous vancomycin and piperacillin-tazobactam and taken to the operating room for an exploratory laparotomy. Upon entering the peritoneum, clear ascites was encountered. The ascending colon was found to be intact with no pneumatosis or perforation. The appendix was noted to be hyperemic with no perforation; therefore, an appendectomy was performed. An abscess was noted tracking from the retroperitoneum with inflamed Gerota’s fascia and retroperitoneal portion of the duodenum. No perforation or pneumatosis was noted in the duodenum. A biopsy of Gerota’s fascia and culture from the abscess was sent to the laboratory. The abdomen was washed out with warm crystalloid solution. A temporary abdominal closure was performed and the patient was taken to pediatric ICU intubated and on a mechanical ventilator. On post-operative day four, the patient was taken back to operating room for a second look, further wash out, and abdominal closure.
Cultures from abscess grew methicillin-resistant Staphylococcus aureus. Repeat urinalysis and blood cultures showed no growth. Ultrasound of the hips showed no indicators of septic hip. Further workup with voiding cystourethrogram showed no evidence of vesicoureteral reflux during the filling or voiding phase. Parenteral nutrition was initiated. Patient was extubated on post-operative day five. Leukocytosis trended down. A peripherally inserted central catheter line was placed and the patient was discharged to a rehabilitation facility on hospital day 16 with ceftaroline and metronidazole.


Patient 1 (II-6, family 1) is a 12-year-old boy, product of full-term normal pregnancy with a birth weight of 3.2 kg. The parents are first cousins. All siblings are healthy. Delayed motor and speech development were noted during infancy. He was able to sit with support but not independently and able to roll over from side to side but unable to crawl. He had no meaningful verbal output, but remained alert, interactive with normal vision and hearing. At 14 months of age, and following a mild gastroenteritis, he presented with lethargy, somnolence, abnormal dystonic posturing of the upper limbs, and rapid breathing. He was found to have acute encephalopathy with severe lactic acidosis that required vigorous intravenous hydration and bicarbonate therapy in intensive care. At 20 months of age, he had a similar episode but less severe. Following these episodes, his condition has remained static with almost no further progress in his milestones. Brain magnetic resonance imaging (MRI) revealed bilateral symmetrical basal ganglia T2 hyperintensity with diffusion restriction seen in the caudate and the lentiform nuclei. At the most recent physical examination, his growth parameters are below third percentile for age. He is wheelchair bound, has prominent central hypotonia, and dystonic posturing when he attempts to reach for objects. He has no expressive language but remains alert and interactive. Investigations showed high serum lactate on two occasions at 6.9 mmol/L and 5.1 mmol/L (normal range, 0.7-2.1 mmol/L). Urine organic acid reveled slight elevation of 3-hydroxybutyric acid, acetoacetic acid, and lactic acid. Enzymatic activities of pyruvate dehydrogenase, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase in fibroblasts were normal. Mitochondrial respiratory chain studies in fibroblasts revealed a slightly decreased citrate synthase activity but otherwise normal (data not shown).


Patient 2 (II-2, family 2) is a 21-year-old male, product of a full-term normal pregnancy with a birth weight of 3.0 kg. His parents are healthy second cousin. At 7 months of age, he developed acute symptoms of lethargy, somnolence, and abnormal dystonic posturing of the upper limbs with rapid breathing associated with severe lactic acidosis. He was managed in intensive care with vigorous hydration and bicarbonate therapy. At 2 years of age, he was able to sit without support and started to walk with assistance but with some dystonic movements. His speech was delayed but had normal vision and hearing. He continued to have recurrent metabolic crises and later developed seizures that were controlled with antiepileptic medications. Current examination revealed growth parameters below third percentile for age. He has prominent central hypotonia and dystonic posturing of neck and both upper and lower extremities. Serum lactate was mildly elevated on two occasions at 2.2 and 3.4 mmol/L (normal range 0.7-2.1 mmol/L) with subsequent normal levels. Brain MRI at age of four, showed slight atrophy of the posterior parts of the putamena bilaterally in conjunction with signal abnormalities both on the T1- and the T2-weighted images. Magnetic resonance spectroscopy (MRS) showed a slight decrease in the creatine peak with respect to the choline in conjunction with small amount of lactate. With these findings, a genetic mitochondrial disease was suspected including Leigh's disease. Mitochondrial DNA (mtDNA) and SLC19A3 sequencing for biotin-responsive basal ganglia disease (BBGD; OMIM 607483) were unremarkable. Muscle biopsy revealed minimal thickening of capillaries in the majority of fascicles. Oxidative enzymes showed a slight accentuation of mitochondria with a subsarcolemmal localization. There was no evidence of cytochrome c oxidase deficiency, storage, or structural abnormalities in any muscle fibers, although a minimal increase in oxidative enzyme reactivity in the smooth muscles and vessels was noted. At the age of 17 years, he underwent deep brain stimulation (DBS) at the globus pallidus internus bilaterally following which, he showed significant improvement in his dystonic posturing, balance, and motor function enabling him to get out of wheelchair and use four-wheel walker instead.


Patient 3 (II-2, family 3) (only limited clinical information is available) is a 21-year-old male born normally with a birth weight of 2.5 kg. He is the older sibling of patient 4. At the age of 10 months, he was found to have developmental delay with central and peripheral hypotonia. He was not able to sit without support, stand, or walk. Dystonic movements and posturing of the upper extremities were noted at times. At the age of 6 years, his mother reported improvement in developmental skills. The patient was able to stand without support, take one to two steps, crawl slowly, and feed himself. He was able to say baba, mama, and comprehend simple commands. At age seven, he started walking with unsteady gait. His hearing and vision have remained normal. At the age of 19 years, he attended the school with acceptable performance.


Patient 4 (II-8, family 3) is a 10-year-old girl, product of full-term caesarian section delivery due to failure to progress and fetal distress. Birth weight was 2 kg with good APGAR score. At the age of 9 months, she presented with history of floppiness and frequent staring spells lasting for few seconds. No abnormal movements of the extremities were reported. She had no head control and was not able to sit. On examination, her growth parameters were below third percentile. She had prominent central hypotonia with dystonic posturing. Lactic acid level ranged from normal value of 1.4 to mildly elevated level of 4.2 mmol/L. Acylcarnitine profile and plasma amino acids were normal apart from mildly elevated alanine. Urine organic acids revealed elevated lactate. electroencephalogram (EEG) was normal. Brain MRI at age of 13 months was normal. At the age of three, her mother reported improvement in the development. The patient was able to stand without support, take one to two steps, crawl slowly, and feed herself. She was able to say baba, mama, and comprehend simple commands. At the age of 6 years, she showed further improvement in motor skills as she started walking with unsteady gait and mild dystonia.


Patient 5 (II-9, family 3) (only limited clinical information is available) is a 5-year-old female and the younger sibling of patients 3 and 4. She is a product of full-term lower segment caesarian section (LSCS) delivery due to large size of 4 kg, secondary to maternal gestational diabetes. At 6 months of age, she was noted to have central and peripheral hypotonia associated with failure to thrive. Her growth parameters are below third percentile for age. She is bed bound and fed via nasogastric tube. She has dystonic posturing with abnormal movements of the upper extremities. She has required several hospital admissions due to feeding problems with frequent vomiting, choking, difficulty in breathing, recurrent fever associated with seizures, and aspiration pneumonia.


Patient 6 (II-2, family 4) is a 4-year-old girl, born normally with a birth weight of 2.9 kg. She had normal acquisition of milestones during infancy. At 14 months of age, she presented with fever, severe lethargy, somnolence, and abnormal dystonic posturing of the upper limbs with rapid breathing. She was found to have acute encephalopathy, severe lactic acidosis, and hyperammonemia requiring intensive care management. This was followed by loss of her motor milestones with dystonic posturing of the neck and upper extremities. Her growth parameters including head circumference were normal. No dysmorphic facial features were noted. Head and neck, chest, cardiovascular, and abdominal examination were unremarkable. Central nervous system (CNS) examination revealed central hypotonia with intermittent dystonic movement of the arms, trunk, and lower extremities. MRI of the brain of T2/FLAIR showed high signal at lateral aspect of both putamen mainly posteriorly. She had no further episodes of metabolic decompensation and her latest serum lactate level was normal.


A 76-year-old woman with a four-month history of chronic myelomonocytic leukemia (CMML) being treated with Azacitidine presented to the emergency department with a chief complaint of a non-productive cough for one month. She endorsed 10 days of recurrent fevers, pleuritic chest pain, and night sweats. She also reported a 10 lb weight loss which she had attributed to a decreased appetite from chemotherapy. She denied any recent travel history but did mention that her husband was treated for latent TB 10 years prior.
On the initial examination, the patient was tachycardic, afebrile, and otherwise hemodynamically stable. Other than a mild leukocytosis to 12.5 k/µL, laboratory examinations were unremarkable. A chest CT scan revealed a new lobulated opacity of the right upper lobe as well as new mediastinal, supraclavicular, and upper abdominal lymphadenopathy (Figure ). This was as compared to CT imaging performed at the time of her initial CMML diagnosis four months earlier.
The patient was admitted and empirically started on vancomycin and meropenem for hospital-acquired pneumonia. Given her history of TB exposure, current immunosuppression, and the radiologic findings, a high suspicion for TB remained. However, early in her hospitalization, three acid-fast bacilli (AFB) smears with nucleic-acid amplification testing (NAAT-PCR) for Mycobacterium tuberculosis were negative. Throughout the hospital course and despite treatment with broad-spectrum antibiotics the patient continued to have a persistent fever with an oral temperature maximum of 38.7 °C and at least one reading of 37.9 °C or higher daily during the first eight days of admission. This prompted further infectious diseases work-up, with a particular focus on fungal infections which might have mimicked the presentation of TB. Such examinations included serum galactomannan, beta-D-glucan, cryptococcal antigen, urinary Legionella, Blastomyces, and Histoplasma antigens, all of which were negative. A QuantiFERON Gold (IFN-gamma release assay) was positive. Given the patient’s continued symptoms, negative infectious diseases work-up, and unresponsiveness to antibiotic therapy, TB was still suspected. The patient continued to have only scant sputum production despite induction attempts; therefore, a bronchoscopy was planned in order to obtain bronchoalveolar lavage (BAL) in hopes of better targeting her therapies. BAL from the patient’s right upper lobe tested negative for fungal antigens and were culture-negative for bacteria or fungi. The AFB smear and PCR from the BAL were also negative, but formal BAL TB cultures were ordered.


A 9-year-old female patient had been suffering from sciatica in her left leg for 6 months. Aside from the disabling pain in her left leg, she suffered from dysesthesia. Upon neurological examination, she had a mild paresis distal in her left leg and a positive straight leg raise test at 30 degrees. Apart from her father undergoing lumbar discectomy at 11 years old and her parental grandfather having rheumatoid arthritis, no other diseases have been reported in the family. Magnetic resonance imaging revealed a paramedian disk herniation at L5-S1 on the left side (Fig. ). She was firstly managed conservatively with physical therapy and pain relieving medications. Because of progressive symptoms, she received an epidural steroid injection which did not show sufficient efficacy. Eventually, she also developed a contracture in her left foot and was referred to the neurosurgery department. Because of the preferences of her parents, she was referred to a neurosurgeon with expertise in endoscopic spine surgery. Preoperative clinical outcomes are shown in Table .


A 50-year-old female was referred to a surgical clinic with troublesome recurrent abdominal pain for few months, few episodes of which had culminated in acute hospital admission. The pain was spasmodic in nature and associated with vomiting. She also described rectal bleeding and diarrhoea on a few occasions. Her history included a laparoscopy for diagnosis and treatment of pelvic endometriosis. She also underwent endometrial ablation for menorrhagia a few years ago.
Her abdomen was soft and non-tender, with no obvious masses or organomegaly. Her lab workup did not show any abnormality, she had normal hemoglobin (Hb) of 136 g/L (115-165 g/L), urea 5.5 mmol/L (2.5-7.8 mmol/L), and creatinine 65 µmol/L (45-84 µmol/L). Her faecal analysis was also unremarkable. She underwent a contrast-enhanced CT scan abdomen/pelvis, which did not show any abnormality. Also, a full colonoscopy was carried out, which did not show any anomaly.
Her MRI abdomen demonstrated an area of abnormal perienteric thickening in the distal ileum raising the possibility of either a Meckel's diverticulum or endometrial deposit. It was followed up by a small bowel MRI which remained equivocal, however, suggested that if thickened small bowel was just a tortuous small bowel loop (Figure ).
The patient also underwent a Technetium-99m (99mTc) nuclear medicine Meckel's scan, which interestingly showed an area of tracer uptake and suggested the possibility of Meckel's diverticulum (Figure ).
After a complete set of investigations, the patient underwent diagnostic laparoscopy, which demonstrated a distal small bowel mesenteric lesion causing kinking of the small bowel. Upon release, a chocolate-colored fluid was noted from the lesion. The involved small bowel was resected, and a side to side anastomosis was fashioned. The small bowel was thoroughly looked for the presence of Meckel's diverticulum, which was not present. Histology results were consistent with an endometrial deposit of the small bowel, and no other abnormality was found (Figure ).
Post-operatively, the patient has made a good recovery and remains symptoms-free to date.


An 11-year-old girl was admitted to the Emergency Department of Pediatric Medical Center with fever (39°C), coughing, tachypnea (38 times per minute), low oxygen saturation (93% in room air), and decreased level of consciousness (LOC). Glasgow Coma Scale (GCS) was 13 and lower extremities rashes were found in her physical examination. Also, results of the blood test on admission time revealed leukocytosis and increased level of C-reactive protein (CRP) (). The patient was transferred to the pediatric intensive care unit (PICU) and nasopharyngeal swab and stool sample analysis by reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 infection and, therefore, drug treatment for the COVID-19 was started according to the Iranian pediatric protocol, including hydroxychloroquine (5 mg/kg/dose), lopinavir /ritonavir (230 mg/m2/dose), ceftriaxone (75 mg/kg/dose), and vancomycin (10 mg/kg/dose) (). Because of persistent fever and tachycardia, pediatric cardiology consultation was requested and done on the 3rd day of hospitalization showing left ventricular ejection fraction (LVEF) of 64%, mild mitral regurgitation (MR), trivial tricuspid regurgitation (TR), trivial pulmonary insufficiency (PI), and a large mobile mass in the left atrium (LA) with attachment to the posterior leaflet of the mitral valve (). Hence, she became a candidate for emergency surgical intervention and cardiac surgery was performed on the 5th day. Intraoperative observations revealed a large thrombus in the LA with necrosis of the posterior leaflet of the mitral valve. Left atrium thrombus was resected completely and the mitral valve was repaired. Her clinical conditions improved following surgery and the results of postoperative echocardiography showed a normal heart function. She was discharged in good health condition after 10 days of hospitalization with negative RT-PCR for COVID-19.


An 7-year-old girl was referred to the Emergency Department of Pediatric Medical Center with fever (38.2°C), tachypnea (36 times per minute), lower extremities rashes, abdominal pain, and bilious vomiting. She had no significant past medical history, but she had close contact with a COVID-19 patient. In physical examination, tachycardia, and low blood pressure were observed, and thus, she was transferred to the PICU for respiratory support by continuous positive airway pressure (CPAP) along with pharmacotherapy. Leukocytosis with increased CRP and erythrocyte sedimentation rate (ESR) were found in blood test () and nasopharyngeal swab analysis by RT-PCR confirmed COVID-19. According to the cardiorespiratory and gastrointestinal symptoms and laboratory results, early diagnosis of COVID-19-induced multisystem inflammatory syndrome in children (MIS-C) was made and pharmaceutical treatment, including hydroxychloroquine (5 mg/kg/dose), lopinavir/ritonavir (230 mg/m2/dose), intravenous immunoglobulin (IVIG /2 gr/kg), methylprednisolone (30 mg/kg), and enoxaparin (2 mg/kg per 12 h) was started. Pediatric cardiology consultation was requested because of cardiomegaly and pulmonary edema in her chest X-ray and transthoracic echocardiography showed LVEF of 69% with better LV systolic function, minimal pericardial effusion, mild TR, trivial PI, and a large mobile mass in the LA (). Consequently, she underwent cardiac surgery on the 6th day of hospitalization and intraoperative observations revealed multiple large thrombi in LA and right atrium (RA) with necrosis of posterior leaflet of the mitral valve. Intracardiac thrombi were removed completely and the mitral valve was repaired. Second echocardiography after surgery showed normal heart function and she was discharged from hospital after 2 weeks in good health condition with negative COVID-19 test. In the histopathological assessment, fibrin clot, fibrinoid necrosis, and surface thrombus with dense neutrophilic infiltration were found in the necrotic tissue of posterior leaflet of the mitral valve ().


An 8-year-old girl was referred to the Emergency Department of Pediatric Medical Center with fever (38.2°C), tachycardia (PR 135), and tachypnea (40 times per min). Past medical history of the patient revealed that she had undergone orthopedic surgery a couple of weeks ago because of car accident injures. In her blood test, leukocytosis, increased CRP, and a remarkable rise in D-dimer were found and RT.PCR test for COVID-19 was positive (). Primary diagnosis of pulmonary thromboembolism (PTE) was made and pharmaceutical treatment, including hydroxychloroquine (5 mg/kg/dose), methylprednisolone (30 mg/kg), enoxaparin (2 mg/kg per 12 h), lopinavir /ritonavir (230 mg/m2/dose) was started. On the 2nd day of hospitalization, echocardiography was performed showing LVEF of 68%, mild LA and LV enlargement, trivial TR, trivial PI, and multiple homogenous masses in the LV and right side of the heart as well as clot strands in the main pulmonary artery (MPA) (). Therefore, she underwent emergency cardiac surgery on the 3rd day and multiple thrombi were resected from the cardiac chambers with the repair of the tricuspid valve. Also, blood clots were removed successfully from the MPA through thrombectomy. She was admitted to the PICU and pediatric ward and was discharged from the hospital after 2 weeks. Second echocardiography indicated normal cardiovascular function and she was discharged from the hospital in good health condition after 15 days with a negative test for COVID-19.
Pathological assessment of specimens in three children showed no fungal and bacterial infection and also SARS-CoV-2 RNA was not detected in the thrombi.


A 75-year-old female patient with a left renal mass and bone metastases was referred to our institution. A biopsy of the left renal mass was performed, and pathological analysis revealed collecting duct carcinoma (CDC) (PAX8+, Vimentin+, and CD10-) () []. Based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the prognostic risk was determined to be intermediate (<1 year since the diagnosis). Nivolumab and ipilimumab were administered four times every three weeks; then, nivolumab monotherapy was administered every two weeks for maintenance. After completion of two cycles of the combination immunotherapy, computed tomography (CT) revealed a slight enlargement of the primary tumor and bone metastases but showed no change during the two additional cycles of the combination therapy or the nivolumab monotherapy (). The best response achieved was stable disease (SD) lasting 23 months.


A 79-year-old female patient had a right renal tumor and multiple metastases to the lungs and lymph nodes. Pathological analysis of a biopsy specimen of the right renal mass revealed CDC (CK19+, PAX8+, and CD10-) () []. Based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, her risk level was determined to be poor (neutrophilia, anemia, and duration < 1 year after diagnosis). Combination immunotherapy with nivolumab and ipilimumab was administered, and after two cycles, computed tomography (CT) revealed new bilateral lung lesions. After two additional cycles, all the tumors shrank markedly (). However, the immunotherapy was unable to be continued due to rheumatoid arthritis development, an adverse event associated with the therapy. The best response achieved was a partial response (PR). The patient was followed up without treatment after four cycles of the combination therapy. After eight months, nivolumab was resumed because the lung metastases showed slight growth. Thereafter, SD continued for six months, indicating that the immunotherapy was able to suppress progression for 17 months.


A 77-year-old Caucasian male with a past medical history of MG presented to the emergency room (ER) with complaints of dysphagia for one week. The patient was first diagnosed with MG five years ago and has been maintained on prednisone 7.5-milligram tablet daily and pyridostigmine 60-milligram tablet six times daily. The dysphagia was associated with non-specific arthralgia, intermittent fevers, chills, and fatigue. The remaining review of systems is negative. He is compliant with medications. He received the first and second doses of Moderna COVID-19 vaccine approximately five and one weeks prior to presentation. In the ER, vitals were notable for tachypnea (20 breaths per minute), tachycardia (110 beats per minute), and hypoxia (Pox 91% on room air). An electrocardiogram showed sinus tachycardia. Chest x-ray was negative for any infiltrates, effusions, or consolidations. Labs were significant for acute renal failure (due to poor oral intake). The septic workup was negative. He was admitted to the neuro floor with MG exacerbation. He was started on pyridostigmine 60 milligrams every four hours, prednisone 7.5 milligrams daily, and intravenous (IV) immunoglobulin (Ig) 35 grams daily for five days. His acute renal failure resolved with adequate IV hydration. Over the next few days, the patient's oxygen requirement normalized, but the dysphagia persisted. On day six of admission, he acutely decompensated with another crisis of MG manifested by lethargy and flaccidity. An arterial blood gas analysis (ABG) confirmed acute hypercapnic respiratory failure for which the patient was intubated and transferred to the medical intensive care unit (MICU). He was started on prednisone 10 mg (which was gradually increased in 48-hour intervals to 40 mg), another two IVIg were given on days 9 and 10. Serial negative inspiratory force (NIF) readings were obtained, with improvement from -20 to more than -40 and subsequent successful extubation. The MG crisis was attributed to the second dose of the Moderna COVID-19 vaccine.


A 76-year-old male presented to our hospital complaining of dyspnea on exertion and substernal chest pain radiating to the left arm that was relieved by nitroglycerine and rest. He had documented coronary artery disease with percutaneous coronary intervention (PCI) to the right coronary artery (RCA) and ramus intermedius (RI) done more than five years prior to presentation. Other medical history consisted of hypertension, dyslipidemia, chronic obstructive pulmonary disease, obstructive sleep apnea, and hepatitis C. He had a 40 pack-year smoking history but no illicit drug use history. Family history was negative for heart disease.
Physical exam showed an obese male with normal vital signs. He had a regular heart rate and rhythm without any murmur or jugular venous distension. Lungs were clear to auscultation and no evidence of peripheral edema or pulse deficit was noted in the extremities. The rest of the physical examination was largely unremarkable.
Electrocardiogram (EKG) showed normal sinus rhythm with new T-wave inversions in anterolateral leads (Figure ). Troponin I peaked at 40.2 ng/ml. He was given aspirin 325 mg and was started on a heparin drip. Bedside echocardiogram showed an ejection fraction of 40%-45% and moderate apical hypokinesis. A left heart catheterization was performed urgently showing in-stent thrombosis of a prior RI stent and an accidental finding of anomalous LAD originating from RSV instead of the left coronary cusp (Figures , ). The patient subsequently underwent PCI of RI with a 2.5 x 38 mm drug-eluting stent (Figure ). Non-obstructive disease was noted in other vessels. His postoperative course was uneventful and he was discharged on appropriate guideline-directed medical therapy.


A previously healthy four-year-old African American female presented to the emergency department (ED) with a one-day history of persistent fever, malaise, anorexia, and headache. On physical exam, she was found to be in no acute distress. She was tachycardic with a temperature of 39.5°C and had mild pharyngeal erythema. An initial rapid strep test returned negative and a COVID-19 nasopharyngeal swab was obtained because the patient endorsed recent exposure, but the results were delayed. Urinalysis revealed pyuria leading to the initial diagnosis of a urinary tract infection (UTI), and she was discharged on cephalexin. A chest radiograph was taken at this time that revealed bronchiolitic changes consistent with COVID-19, but no specific treatment such as inhaled corticosteroids or remdesivir was administered due to the absence of any respiratory symptoms. Two days later, the patient returned to the ED with persistent high fever (38.7°C), new-onset mild vague abdominal pain, diarrhea (without nausea or vomiting), dark urine, and bilateral conjunctivitis. Repeat urinalysis showed persistent pyuria, but the urine culture from the previous visit showed no growth, and cephalexin was discontinued. Her COVID-19 polymerase chain reaction (PCR) test from the prior visit returned positive, and a repeat chest radiograph continued to show bronchiolitic changes though she did not have any clinical symptoms such as dyspnea or cough. Complete blood count (CBC) and comprehensive metabolic panel (CMP) revealed mild anemia (hemoglobin, Hgb 10.3 g/dL, hematocrit, Hct 30.4%) and thrombocytopenia (127,000/mcL) without leukocytosis or electrolyte abnormalities. A coagulation panel revealed normal prothrombin time (PT) and INR but elevated partial thromboplastin time (PTT) (40.5 s), fibrinogen (588 mg/dL), and D-dimer (1.81 mcg/mL). Inflammatory markers, other than ferritin, were elevated with an erythrocyte sedimentation rate (ESR) 50 mm/h and C-reactive protein (CRP) 16.28 mg/dL indicating a categorically high cardiovascular risk. Troponin-I levels were within normal limits, but both brain natriuretic peptide (BNP) and procalcitonin were elevated at 245 pg/mL and 3.15 ng/mL, respectively. Collectively, these labs suggested a diagnosis of acute COVID-19 with MIS-C features, though markers are not exclusive. Notably, a repeat PCR test on this date returned negative, but the patient was positive for IgG antibodies.
Acetaminophen, ibuprofen, and fluids were administered in the ED, but the patient remained tachycardic and her blood pressure dropped from 98/70 to 87/49 mmHg. Ceftriaxone was initiated for suspected sepsis and she was admitted to the floor. However, the patient remained hypotensive prompting the administration of fluid boluses and the replacement of ceftriaxone with more broad-spectrum antibiotics cefepime and vancomycin. When the patient showed increased work of breathing and signs of respiratory failure, she was transferred to the pediatric ICU where a norepinephrine drip was maintained. A chest radiograph showed new bilateral haziness and airspace opacities, and she was placed on bilevel positive airway pressure.
Due to the novelty and complexity of the case, a multidisciplinary team was consulted and involved throughout treatment in accordance with MIS-C treatment recommendations []. She was given intravenous immune globulin (IVIG) and methylprednisolone, and an echocardiogram was ordered revealing mild left atrial dilation with normal biventricular size and systolic function. Infectious disease specialists recommended close monitoring of inflammatory markers, and hematology-oncology specialists recommended subcutaneous enoxaparin sodium.
On day two of hospitalization, her abdominal pain worsened prompting an abdominal ultrasound that revealed a small amount of free fluid and a slightly edematous gallbladder. The patient also developed right hip pain, and an ultrasound revealed trace effusion. A subsequent increase in ESR (55 mm/h) and CRP (20 mg/dL) suggested an increase in overall inflammation due to her condition. Likewise, her previously normal troponin-I increased to 0.08 ng/mL, and BNP rose to 1433 pg/mL. Over the next day, these lab values remained elevated, and additional labs reflected a neutrophil-predominant increase in white blood cells from 7,200 to 11,000/mcL and increased D-dimer of 3.15 mcg/mL. Her systolic blood pressures remained in the 80s and she became progressively more tachycardic and tachypneic with breakthrough fevers.
By day four of hospitalization, the abdominal pain had become more severe and localized to her right lower quadrant. The CBC now showed leukocytosis (white blood cell count, WBC 19,600/mcL) with 80% neutrophils and 12% band neutrophils and a critical drop in Hgb (6.7 g/dL) and Hct (19.9%). Coags were in range, and she was transfused appropriately. Chest radiograph showed left lower lobe consolidation consistent with atelectasis, and an abdominal ultrasound was repeated and showed a fluid-filled, noncompressible appendix dilated up to 7 mm, suspicious for acute appendicitis (Figure ). The ultrasound also revealed debris in the urinary bladder, clinically correlating her pyuria with her initially diagnosed UTI. Enoxaparin sodium was held, and laparoscopic appendectomy was performed without complication. The retrocecal appendix appeared grossly normal with minimal induration or neovascularity, but the patient had significant ascites and ileus, presumably secondary to COVID-19. The intact appendix was sent to pathology in formalin and measured 5.4 cm long and 0.6 cm in diameter without a distinct rupture site. Microscopic analysis with hematoxylin and eosin stain revealed purple-pink serosa and congested vasculature, and sectioning revealed a patent lumen with dark red fluid and a wall thickness averaging 0.2 cm.
Following her appendectomy bilevel positive airway pressure (BiPAP) was continued, and a repeat chest radiograph revealed increased left lower lobe consolidation with small possible pleural effusion on the right. Antibiotics were discontinued due to negative urine and sputum culture. Post-operatively, WBCs returned to normal (10,000/mcL) and Hgb and Hct remained stable at 10.4 g/dL and 32.4%, respectively. CRP, BNP, and troponin-I remained elevated (15 mg/dL, 751 pg/mL, and 0.06 ng/mL).
On hospitalization day 5, a repeat ultrasound of the right hip revealed decreased trace joint effusion with new synovial thickening but no drainable fluid collection. Chest radiograph continued to show persistent hazy opacities with possible bilateral pleural effusion. The patient remained hemodynamically stable without pressor support and was transferred back to the floor with the continuation of steroids and IVIG.
The patient continued to feel better and on hospitalization day 6 troponin-I normalized (0.05 ng/mL). On hospitalization day 7, BNP peaked at 1564 pg/mL before dropping to 141 pg/mL the following day. An echocardiogram revealed normal systolic function, a trivial rim of pericardial fluid, and very mild left atrial dilation.
Over the next two days, a neutrophil-predominant leukocytosis returned (21,500 and 15,600/mcL) and Hgb and Hct decreased to critical values (6.4 g/dL and 19.7%). D-dimer was elevated (14.05 vs. 6.93 mcg/mL the previous day), and a chest radiograph was performed revealing improved aeration of lung bases without indications of a new pathology. Due to concern of blood loss at the surgical site, an abdominal ultrasound was performed suggesting the presence of a hematoma overlying the bladder amidst a moderate amount of free fluid. At this time, enoxaparin sodium was stopped, and on hospitalization day 9 Hgb and Hct increased to 10.1 g/dL and 30.7%. The patient continued to have pain and guarding of her lower abdomen prompted concern for expansion of the suprapubic hematoma. On hospitalization day 11, ultrasound findings revealed a mild decrease in overall size, and lab values improved.
Over hospitalization days 10-14, the patient continued to improve clinically. D-dimer, ferritin, CRP, and BNP remained elevated but stable (7.83 mcg/mL; 387 ng/mL; 1.1 mg/dL; and 270 pg/mL), and leukocytes, PT, and PTT normalized. The patient was discharged home with oral steroids for two weeks and was advised to follow up with rheumatology and cardiology. At follow-up, her only complaint was nonspecific abdominal pain. Repeat abdominal imaging was not performed, but repeat labs showed that her Hgb was improving, now up to 11.1 g/dL, along with a declining ferritin level of 217 ng/mL, with her CRP and D-dimer levels now returning to normal. Cardiology confirmed that a subsequent echocardiogram was normal, and rheumatology’s only further recommendations were to hold all vaccines for three to four months and live vaccines for 11 months since her illness.


The patient was a 45-year-old male born in Pakistan who had resided in Portugal for 7 years. He had a history of grade 3 obesity, with no other known personal history or usual pharmacological therapy.
The patient sought emergency care for fever, dry cough, dyspnea, chest pain, dysgeusia, headache and myalgia with 4 days of evolution. In the summary neurological examination at admission, there were no reported changes. In the evaluation of the respiratory system, tachypnea and pulmonary auscultation with bilateral rough vesicular murmur, without other adventitious sounds, were noted. The remainder of the objective examination showed no changes.
Of the complementary diagnostic tests performed at admission, there was a slight increase in inflammatory parameters and in arterial blood gases under an inspired oxygen fraction (FiO2) of 21%, with type 1 respiratory failure (), and extensive predominant bilateral, peripheral and basal opacities on chest teleradiography. After a positive reverse-transcription real-time polymerase chain reaction (RT-PCR) test for SARS-CoV-2 (nasal and oropharyngeal exudate) and negative tests for influenza A and B, Streptococcus pneumoniae and Legionella pneumophila, a diagnosis of pneumonia by SARS-CoV-2 infection was established.
Over the first 48 hours, progressive worsening of fatigue, dyspnea and type 1 respiratory failure, requiring an increase in supplemental oxygen therapy, were observed. Due to the lack of improvement, noninvasive mechanical ventilation was initiated; however, due to poor adherence, high-flow oxygen therapy was initiated through a nasal cannula, without a response to therapy.
In this context, the patient was admitted to the intensive care unit (ICU), level III, where he underwent sedoanalgesia and orotracheal intubation with connection to invasive mechanical ventilation.
On the eleventh day of hospitalization, treatment with remdesivir, dexamethasone, enoxaparin and empirical antibiotic therapy with amoxicillin/clavulanic acid and azithromycin, administered on suspicion of bacterial overinfection, was continued. During this period, sustained fever was observed, with a weak response to antipyretic therapy, with improvements in inflammatory parameters after the third day of hospitalization in the ICU ().
To exclude any concomitant infectious etiology, intravenous devices were replaced, and blood cultures, cultures of the tip of the central catheter and bronchial secretions, urinalysis, urine culture and transthoracic echocardiography were performed. Among the cultures, the blood culture yielded the only positive result, i.e., Klebsiella pneumoniae, which is sensitive to amoxicillin/clavulanic acid, which the patient was already receiving. The summary echocardiogram did not reveal valve changes suggestive of endocarditis, but the patient presented hypokinesia of the lateral wall and left ventricular apex, as well as poor biventricular function. A slight increase in troponins (1.8ng/mL) and ST-segment depression in leads I and aVL were confirmed, suggesting the existence of acute coronary syndrome or septic cardiomyopathy.
Other noninfectious causes of febrile symptoms in the critically ill patient were excluded, including treatment with neuroleptics or altered thyroid function.
Notably, there was a need for inotropic support with dobutamine in the ventilatory weaning phase as well as noninvasive ventilatory support after orotracheal extubation, which occurred on the fifteenth day of hospitalization.
On the sixteenth day of hospitalization (nineteenth day of confirmed disease), there was an episode of altered state of consciousness, conjugated deviation of the gaze to the right and myoclonus of the face and thoracic region to the left followed by a generalized tonic-clonic seizure crisis, which ceased after midazolam therapy. The hypothesis that the seizure occurred in the context of a hypoxic-ischemic event was excluded because the patient remained normotensive, there was never a perievent or hypoxemia, serum lactate level was normal, and diuresis remained preserved. Any ionic or glycemic disorders that could explain the inaugural seizure episode were excluded.
In the post-critical period, there was an absence of eye opening, no verbal response, failure to localize to pain (coma scale of Glasgow 7), and persistent left hemiparesis grade 3 out of 5. Due to the need for airway protection, the patient was sedated, subjected to orotracheal intubation and started on anticonvulsant therapy.
In the process of diagnosis of the convulsive episode, after cranial computed tomography confirmed no changes, the patient was subjected to lumbar puncture, with turbid CSF output and mild proteinorrachia but without pleocytosis and with normal opening pressure. In the CSF, neurotropic virus and venereal disease research laboratory (VDRL), acid-alcohol resistant bacteria tests and an RT-PCR test for SARS-CoV-2 were requested, and samples were collected for culture (). Electroencephalography was performed 1 hour after propofol suspension and under fentanyl, with a single record and total duration of 13 minutes; the findings indicated no changes ().
After confirmation of a positive RT-PCR test for SARS-CoV-2 RNA in the CSF, without CSF pleiocytosis, the hypothesis of bacterial but nonviral meningitis was excluded, considering the hypothesis of encephalitis. Magnetic resonance imaging (MRI) performed on the seventeenth day of hospitalization showed multiple image artifacts associated patient movement during the procedure, suggesting the need to repeat the examination.
After discontinuation of sedoanalgesia, a change in consciousness was observed, with a Glasgow coma scale score of 14, persistent left hemiparesis with muscle strength grade 4 in 5 and an absence of involuntary movements, allowing safe orotracheal extubation in 24 hours. Given the favorable clinical outcome, brain biopsy was excluded. On the twenty-first day of hospitalization, the patient was transferred to the ward.
The patient maintained apyrexia without altered state of consciousness. No new episodes of involuntary movements were observed, and on the twenty-sixth day of hospitalization, he underwent a reassessment MRI, which revealed no pathological changes. As he maintained a favorable clinical evolution, the patient was discharged on the thirty-first day of hospitalization without antiepileptic drugs and with an appointment for follow-up with the internal medicine department.


A 35-year-old male with no significant past medical history presented to an outside hospital with fever to 38.9 C, altered mental status, headache, and chest pain. EKG showed normal sinus rhythm with diffuse ST segment depression in leads II, aVF, and V3–V6. He was found to have leukocytosis with a white blood cell (WBC) count of 55.45 × 109/L (normal range: 4.2 to 9.1 × 109/L), thrombocytopenia with a platelet count of 102 × 109/L (150 to 330 × 109/L), and hemoglobin of 15.7 g/dL (13.7 to 17.5 g/dL). The leukocyte differential count revealed marked eosinophilia with an absolute eosinophil count of 16.64 × 109/L (0.0 to 0.5 × 109/L), representing 30% of the total WBC count. The remainder of the differential was significant for 44% neutrophils, 5% lymphocytes, 4% monocytes, 2% basophils, and 13% blasts (). A transthoracic echocardiogram showed a low normal systolic function with an estimated left ventricular ejection fraction of approximately 55% and concern for a left ventricular (LV) apical thrombus versus endomyocardial fibrosis. He subsequently underwent cardiac magnetic resonance imaging (MRI) which revealed large areas of subendocardial and midmyocardial delayed enhancement most prominent in the LV apex, suggestive of eosinophilic myocarditis, and confirmed the LV apical thrombus. A left heart catheterization revealed no evidence of coronary artery disease. He was transferred to our institution for further care.
Bone marrow aspirate and biopsy showed acute myeloid leukemia, minimally differentiated, with prominent eosinophilia and 28% blasts (). Flow cytometry on the aspirate specimen revealed a prominent and discrete low side scatter, dim CD45 blast gate comprising approximately 30% of total events, expressing CD34 (partial, 50%), CD33, CD38, HLA-DR, CD7 (bright), CD123, and CD71, while negative for cytoplasmic TdT, myeloperoxidase (MPO), and all other lymphoid and monocytic markers (25 additional antigens tested). Bone marrow core biopsy was hypercellular (95%) with abundant immature mononuclear blast forms and eosinophils present. Immunohistochemistry was negative for CD34, CD117, MPO, TdT, and PAX5.
Chromosome analysis and fluorescence in situ hybridization (FISH) analysis were performed using standard cytogenetic methods by the Cytogenetics Laboratory at the University of Rochester Medical Center. Twenty metaphase spreads were analyzed, and no clonal aberrations were detected. FISH analysis was performed on 200 interphase nuclei and revealed a normal pattern for each of the following probes: PDGFRA (4q12), PDGFRB, BCR/ABL1, RUNX1T1/RUNX1, KMT2A, and CBFB. Additional FISH analysis performed at a reference laboratory found no evidence of JAK2 and FGFR1 rearrangements. Taken together, cytogenetic analysis did not detect any recurrent gene rearrangements associated with eosinophilic myeloid neoplasms.
Mutation analysis was performed using next-generation sequencing on the Illumina (San Diego CA) MiSeqDx after library preparation using the Illumina TruSight Myeloid Sequencing Panel. Data analysis was performed using the Illumina MiSeq Reporter and VariantStudio programs, as well as custom software. Analysis revealed a pathogenic mutation in plant homeodomain finger 6 (PFH6) with VAF of 13%. The PHF6 mutation c.684_705delinsCCC causes a shift in the reading frame and premature termination of translation (p.His229ProfsTer44), thus deemed pathogenic as a chain-terminating mutation. Additionally, a mutation was found in ZRSR2 with VAF 73%. The ZRSR2 mutation c.1332_1343dup is an in-frame duplication of 4 amino acids (p.Ser445_Arg448dup). It has been reported in the gnomAD exomes database at about 0.2% and is likely not pathogenic.
Therapy was initiated with intravenous methylprednisolone 125 mg daily for 3 days followed by oral prednisone 1 mg/kg for 4 days. His symptoms improved, and his peripheral blood blast count was reduced to 1%, while the absolute peripheral blood eosinophil count was reduced to 10.6 × 109/L. This was followed by standard chemotherapy for AML with cytarabine (100 mg/m2 by intravenous continuous infusion on days 1–7) and idarubicin (12 mg/m2 intravenously on days 1–3). His day 14 bone marrow biopsy was hypocellular and consistent with chemotherapy-induced ablation, with no morphologic evidence of leukemia. A postinduction biopsy on day 39 was consistent with complete remission with complete hematologic recovery. He had one cycle of consolidative high-dose cytarabine followed by matched sibling donor allogeneic stem cell transplantation. He is in a sustained complete remission at the time of this report, with no evidence of relapse at 6 months after initial diagnosis.


A 44-year-old male presented to the emergency department with worsening periumbilical pain and bilious vomiting for four days. He did not have a fever, diarrhea, or gastrointestinal bleed, and his past medical history was unremarkable. He was neither an alcoholic nor a smoker. There was no history of inherited thrombophilic disorders in any of the family members. On examination, the patient had tachycardia and tachypnea. Abdominal examination showed a distended gaseous abdomen with mild diffuse tenderness. X-ray abdomen erect revealed dilated bowel loops with multiple air-fluid levels. His blood sugar, amylase, renal, and liver function tests were normal. Contrast-enhanced CT (CECT) abdomen showed stricture in proximal jejunum with dilated edematous proximal jejunal loops and thrombosis of portomesenteric confluence with extension into the superior mesenteric vein (SMV), and that was replaced by multiple collaterals (Figure ). The patient underwent an emergency laparotomy. Intraoperatively, we saw a narrowed segment of jejunum with proximal dilatation. Around 12 cm of jejunum was resected, and jejuno-jejunal anastomosis was done. The gross specimen showed critical stricture with dilated proximal bowel (Figure ). The postoperative period was uneventful. The patient was started on oral liquid diet and gradually accelerated to a solid diet. Histology of the resected specimen showed thrombosed blood vessels and nonspecific inflammation (Figure ). The patient was evaluated for inherited thrombophilia, and the reports of which were unyielding. He was started on an oral anticoagulant and is presently doing well on follow-up.


A 39-year-old man presented to our institution with abdominal pain, intermittent episodes of low-grade fever, yellowness of his eyes, and loss of appetite for two weeks. In addition to intermittent itching, he also reported a four-kilogram weight loss over the course of six months. He denied any dysuria, hematuria, skin lesions, or neurological deficits.
His past medical history was significant for an appendectomy as a child. He denied active use of alcohol or tobacco. He worked as an administrator for a non-governmental organization and was able to perform all his activities of daily living. His father and mother were alive and doing well, with no significant health issues. He denied using prescribed, herbal, or over-the-counter medications. He denied any significant travel history outside his work area.
On examination, he was cachectic, with mild pallor and jaundice. He had a blood pressure of 118/74 mmHg, pulse rate of 108 beats per minute, and temperature of 36.6°C. He had bilateral inguinal lymphadenopathy with skin excoriation marks. His left testicle was tender on palpation, but no urethral discharge or penile lesions were appreciated. His abdomen was scaphoid, with a mildly enlarged tender liver. A Lanz incision scar was present. He had no stigmata of chronic liver disease. His lower extremities appeared normal with no edema.
No neurological deficits were appreciated on his exam and his gait was normal.
The routine laboratory tests performed revealed an elevated white cell count of 16 x 106/L and hemoglobin of 8.4 g/dL (normocytic, normochromic with normal mean corpuscular volume [MCV]). His initial ferritin measured 1512 ng/mL, serum iron of 5.24 umol/L, and transferrin of 1.84 g/L suggestive of anemia of inflammation. His inflammatory markers were elevated with an erythrocyte sedimentation rate (ESR) of 55 mm/Hr, and a C-reactive protein (CRP) of 171 mg/dL. Liver function test revealed an elevated alkaline phosphatase of 408 U/L, gamma-glutamyltransferase (GGT) of 281 U/L, and direct hyperbilirubinemia of 103 umol/L with normal transaminases. His electrolytes including his creatinine were normal.
Hepatitis A, B, and C serology were negative. Blood cultures and urine cultures were also reported as negative. A rheumatoid factor was positive with negative anti-citrullinated peptide (anti-CCP), anti-nuclear, anti-smooth muscle, anti-mitochondrial and antineutrophil antibodies (C and P). A liver autoimmune panel was also negative. Complement and immunoglobulin levels were within normal ranges. Serum electrophoresis was negative for monoclonal gammopathy. Lactate dehydrogenase (LDH) and IgG4 subclass antibodies were within normal limits. We did not perform a serum QuantiFERON.
A testicular ultrasound done was reported as normal with incidental finding of right inguinal lymphadenopathy. An abdominal CT scan showed mild splenomegaly with mild bilateral hydroureteronephrosis with retroperitoneal fat stranding suggestive of early retroperitoneal fibrosis (Figure ). An ultrasound of the liver showed a gall bladder that was of normal size and wall thickness, no dilatation of the intrahepatic bile ducts, and no calculi. A follow-up FibroScan showed no fibrosis. An MRI of the liver was also reported as normal. A liver biopsy showed mild non-alcoholic hepatitis, but no fibrosis.
A diagnosis of idiopathic RPF was made based on his clinical and radiological findings. He was started on treatment with corticosteroids (prednisone 60 mg/day) with marked improvement in his symptoms within 72 hours. Corticosteroids were gradually tapered off over a six-month period. Follow-up laboratory testing done at two months showed decreasing inflammatory markers (CRP 55 mg/dL and ESR 29 mm/Hr) and resolving cholestasis (alkaline phosphatase [ALP] 127 U/L and GGT 100). At six months, a repeat CT scan showed resolution of the hydroureteronephrosis and the RPF (Figure ), and his liver function and hemoglobin had returned to baseline.


A 74-year-old man was referred to our department for advanced esophageal cancer, which initially presented with dyspepsia. Serum CA19-9 levels were elevated (724.89 U/ml). Upper gastrointestinal endoscopy revealed a type 2 tumor on the posterior wall of the mid-thoracic esophagus, approximately 29–32 cm from the incisor (Fig. a). Histopathologic analysis of the mucosal biopsy revealed adenocarcinoma. Contrast-enhanced computed tomography showed circumferential wall thickening in the mid-thoracic esophagus without enlarged lymph nodes and distant metastasis (Fig. b, c). Positron emission tomography–computed tomography showed accumulation in the primary tumor, but no evidence of lymph node or distant metastasis (Fig. d). Accordingly, a clinical stage of cT3N0M0 was established, thereby, requiring subtotal esophagectomy with lymph node dissection. The postoperative course was uneventful. Histopathologic analysis revealed a 50 × 40 mm moderately differentiated adenocarcinoma with invasion in the thoracic duct (pT4a) and lymph node metastasis at #108(1/4), #109R(1/3), and #109L(1/3) (pN2). These postoperative findings warranted the revision of the diagnosis and stage to moderately differentiated adenocarcinoma pT4apN2pM0 (pStage III) (Figs. and a).
Immunostaining revealed the increased diffuse expression of CA19-9 in the main tumor and all three metastatic lymph nodes, suggesting that it was a CA19-9-producing tumor. Moreover, it was also positive for (1) MUC5AC, epithelial-type mucus core proteins of the gastric gland fossa and (2) MUC6, a glandular-type mucus core protein present in the pyloric and cardiac glands (Fig. c, d). Furthermore, histopathologically, no ectopic gastric mucosa was found in the background mucosa. The absence of Barrett's epithelium and ectopic gastric mucosa in the mid-thoracic region led us to speculate that the tumor originated from the esophageal cardia. Three months postoperatively, the patient showed no recurrence and is undergoing outpatient observation.


A 59-year-old woman without previous history of psychiatric or neurological disease admitted herself to the emergency department of our university hospital with existential fears regarding her state of unemployment. Due to massive anxiety, a structured conversation with the patient was only feasible after anxiolytic treatment with lorazepam. During the clinical examination, it became apparent that the patient's fears were elicited by delusional ideas. The patient claimed that thoughts had been inserted into her head and were being controlled by someone else. Moreover, she reported ideas of audible thoughts. An organic schizophrenia-like disorder was assumed as the most likely diagnosis, and the patient was transferred from the emergency department to the Department of Psychiatry, Social Psychiatry, and Psychotherapy of our clinic. The patient claimed that her mother had been diagnosed with Alzheimer's disease at the age of 50 years and had died at the age of 65 years. Other family members had not been afflicted with neurological or psychiatric disease.
Laboratory investigations revealed a mild hypothyreosis due to status post hemithyroidectomy; hence, levothyroxine was substituted. Moreover, hyponatremia was identified and sodium chloride tablets were administered. Additionally, the patient was advised to reduce drinking tap water, of which she was consuming up to 4 liters per day. No abnormalities were detected in the complete blood count. Deficiencies of folic acid, vitamin B12, and ceruloplasmin as well as infection with human immunodeficiency virus, Borrelia burgdorferi, and Treponema pallidum could also be excluded.
After completion of the laboratory investigations, we initiated an antipsychotic treatment with risperidone. However, delusional ideas persisted despite treatment with risperidone. Due to sleep disturbances, we commenced a treatment with chlorprothixene, while risperidone was discontinued.
Further neurological examination revealed dysdiadochokinesis (predominantly of the left hand), mild hyperkinetic movements (particularly restlessness), bradykinesia in the finger-tapping test, and a broad-based gait. Rigidity, tremor, or postural instability was not present. In the meantime, the patient became increasingly disoriented to time and space and exhibited long-term memory deficits accompanied by episodes of fear, agitation, and perseverations, indicative of cognitive impairment. Cognitive function was assessed using the Consortium to Establish a Registry on Alzheimer's Disease neuropsychological assessment battery (CERAD+), which detected deficits in recognition of verbal content, a severe impairment of visuospatial abilities, a reduction in semantic and phonological word fluency, and a decreased cognitive flexibility (the latter was additionally evidenced in the Trail Making B test). Furthermore, we performed the Mini-Mental State Examination (MMST) and the frontal assessment battery (FAB) where the patient scored 22 out of 30 points and 10 out of 18 points, respectively, indicating reductions in mental flexibility, motor programming, environmental autonomy, and inhibitory control. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV Axis II Personality Disorders (SCID-II) showed no evidence of a personality disorder, while participation in the Beck Depression Inventory II (BDI-II) was refused by the patient., Due to clinically predominant executive dysfunction and the described psychopathological symptoms, we considered bv-FTD as the most likely diagnosis.
However, the neurological symptoms displayed by our patient could not sufficiently be explained by bv-FTD; therefore, an electroencephalogram was performed, which demonstrated a physiological alpha rhythm without signs of epileptiform potentials. Magnetic resonance imaging (MRI) revealed generalized cerebral atrophy with putaminal accentuation (putaminal rim sign), a hyperintensity at the lateral margin of the putamen, and ventriculomegaly (Figure ). A lumbar puncture with examination of CSF parameters including tau and beta-amyloid protein was unremarkable. Furthermore, intrathecal immunoglobulin synthesis and the presence of autoimmune encephalitis antibodies and protein 14–3–3 in CSF were excluded. Altogether, we suspected neurodegeneration as the underlying cause of all of the patient's symptoms including movement disturbances, symptoms of dementia, and psychiatric features.
To differentiate neurodegenerative disease patterns, cerebral glucose metabolism was investigated by 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) which revealed global cerebral glucose hypometabolism. Glucose uptake was particularly low in the striatum, frontal inferior cortex (opercular part), cingulum, precuneus, hippocampus, and amygdala when compared to a control group of corresponding age. In contrast, glucose hypermetabolism could be observed in the occipital lobe (Figure ). Such a glucose metabolism pattern was evaluated unusual in pure dementia and pointed to a neurodegenerative disease with primary involvement of the basal ganglia. Of note, glucose hypometabolism in the striatum has been observed in atypical Parkinson syndromes, especially in progressive supranuclear palsy (PSP), neuroacanthocytosis syndromes, and HD. This consideration led to genetic testing in order to determine the number of CAG repeats in the HTT gene. People with fewer than 29 CAG repeats never develop HD, while the presence of 39 or more CAG repeats inevitably leads to the development of HD., In our patient, genetic testing revealed 42 CAG repeats in the HTT gene, confirming the diagnosis of HD.
Over the course of inpatient care, the patient required support from the nursing staff for virtually all activities of daily living, including personal hygiene. Moreover, she was severely disoriented in both space and time. Therefore, the patient was assigned a legal guardian. Following discharge from our clinic, the patient was admitted to a residential home for patients with chronic psychiatric and neurological diseases.