Table shows our review of the literature.
A 54-year-old Japanese woman presented with acute severe neck pain. The pain was of acute onset and had started 12 hours prior to her hospital visit. She had no significant medical history. Her vital signs were normal, with the exception of mild fever (37.5°C). She also had a limited range of motion during rotation of her neck and moderate pain and discomfort during swallowing. She had no oropharyngeal abnormalities, meningeal signs, and neurological abnormalities.
Laboratory data showed a slight elevation of C-reactive protein (0.29), an erythrocyte sedimentation rate of 16 mm/h, and a normal white blood cell count (4100/ul). Other laboratory findings were within normal limits. Plain radiographs of the cervical spine showed no apparent abnormality (Figure ). Owing to suspicion of emergent diseases, such as a retropharyngeal abscess, CT of the neck was performed. It revealed massive retropharyngeal calcification with its longest diameter (18 mm) in front of the C1-C2 vertebrae (Figure ). It was inhomogeneous and irregularly shaped with associated soft tissue swelling. Magnetic resonance imaging (MRI) showed markedly increased signal intensity on T2-weighted images and intermediate signal intensity on T1-weighted images at the anterior C1 to C5 level (Figure ). There were no findings of spondylitis, epidural abscess, or tumor.
Thus, the patient was diagnosed with acute calcific retropharyngeal tendinitis, and the condition was treated with a soft collar and non-steroidal anti-inflammatory drugs (NSAIDs). Two weeks later, the neck pain and dysphagia improved. At the one-month follow-up, she had a complete resolution of the symptoms. A follow-up CT showed residual marginal calcification, which was diminishing in size, suggesting an eggshell-like calcification (Figure ).


The 4-year-old boy was the third child of nonconsanguineous parents and was admitted to our ward in February 2019 for proteinuria and edema lasting 1 month. Both his parents and two older sisters were healthy and had normal stature, and his two brothers were stillborn of unknown cause. He was born at 34 weeks of gestation with a 1-kg birth weight and presented growth retardation. He had a short trunk with a height of 81 cm and a weight of 9.5 kg. The boy demonstrated subtle dysmorphology, with a triangular shape, a broad nasal bridge and a bulbous nasal tip. He had swollen eyelids, lumbar lordosis and a protruding abdomen (Fig. ). The shifting dullness was negative, and his bilateral lower limbs were swollen. In our department, the laboratory findings were as follows: lymphocytes, 0.5 × 109/L; urine protein, 3.67 g/d (0–0.15 g/d); urine protein/creatinine, 20.1 g/g (0–0.2 g/g); albumin, 9.8 g/L (40.0 g/L-55.0 g/L); cholesterol, 11.72 mmol/L (2.9 mmol/L-5.20 mmol/L); FT3, 0.73 pg/ml (2.00 pg/ml − 4.40 pg/ml); FT4, 0.58 ng/dl (0.93 ng/dl-1.70 ng/dl); and TSH, 10.85 μIU/ml (0.27 μIU/ml-4.20 μIU/ml). The flow cytometry results were as follows: CD3+, 137/μL; CD3 + CD4+, 79/μL; CD3 + CD8+, 7/μL; CD4+/CD8+, 1.54; CD3-CD19+, 405/μL; and CD3-CD16/CD56+, 176/μL. He had no hepatitis infection, and the markers of autoimmunity (ANA, ANCA, dsDNA) were negative. Skeletal X rays showed small iliac wings, small ossification centers of the capital femoral epiphyses, shallow dysplastic acetabular fossae and mildly flattened vertebrae (Fig. ). He was diagnosed with nephrotic syndrome and hypothyroidism, received 6 weeks of prednisone (17.5 mg/d) and pulse steroid therapy with 100 mg methyl prednisolone for 3 days, and was then started on a combined therapy of steroids and tacrolimus. However, his proteinuria did not improve. During hospitalization, he had influenza A, severe bacterial pneumonia and fungal infection. Because of his special phenotype and resistance to multiple immunosuppressants, a kidney biopsy and gene sequencing were performed. The specimen for LM included twenty-one glomeruli, seven of which exhibited global or focal sclerosis, and some glomeruli were poorly developed (Fig. ). The deposition of IgA, IgG, IgM, C1q, C3, and C4 by immunofluorescent study (IF) was negative. EM revealed a focal thickness of the GBM (500–2000 nm in thickness) without electron-dense deposits. The foot process of podocyte effacement was extensive, with some cytoplasmic processes infolding into the GBM (Fig. ). Whole exome sequencing showed novel compound heterozygous mutations in the SMARCAL1 gene (NM_001127207), []. Two mutations(c.2141 + 5G > A; c.2528 + 1G > A) were inherited from his parents (Fig. ). The c.2141 + 5G > A mutation was confirmed to create a novel splice donor site []. The c.2528 + 1G > A mutation was not observed in the gnomAD database. According to the ACMG guidelines [], the c.2528 + 1G > A mutation was classified as likely pathogenic. According to the clinical manifestations and pedigree analysis, we established the diagnosis of SIOD. Given the resistance to steroids and tacrolimus, we stopped these drugs gradually and only treated him with diuretics and angiotensin-converting enzyme inhibitors (ACEIs). After treatment, his edema disappeared gradually, and he was discharged 2 months later. We followed up until June 2019, and the boy did not have edema again and had normal renal function.


A 17-year-old Caucasian woman was referred by her own general practitioner to the department of adolescent psychiatry and addiction prevention for binge drinking and daily use of marijuana. The intake together with her parents showed that the patient already had a history of moderate depression and an eating disorder, anorectic of the purging type with moderate severity. No abnormalities were reported regarding appearance, behavior, eye contact, and rapport orientation and cognition [intelligence quotient (IQ) of 127]. However, she regularly suffered from suicidal thoughts and a low ability to experience pleasure. Though she had no concrete suicide plans, in gloomy periods she showed risky behavior, like crossing a busy road without looking. She usually performed well in school, despite occasional lags in attendance, which were compensated with short periods of active study. Her mother had a history of MDD.
At the department of adolescent psychiatry and addiction prevention, we classified the addiction behavior as mild. But we also established a comorbid psychiatric and substance-use disorder profile. Thus, we chose for an integrated treatment for comorbidity that has been found to be consistently superior (). Effective treatment for comorbid conditions combines different therapeutic modalities, i.e. psychotherapy [e.g. motivational interviewing (MI), cognitive behavioral therapy (CBT)], pharmacotherapy (e.g. antidepressants), and family therapy. Using combinations of different modalities typically increases therapeutic effect by exerting a synergistic impact on symptoms ().
With MI, the patient was motivated to choose a first education-related treatment goal. This was to prevent school dropout at all cost. We started CBT to control her marihuana and alcohol abuse and prevent school dropout. We added medication in order to try to stabilize her mood with fluoxetine, an SSRI, which might also modulate stress. The medication initially seemed to have some effect but after two months there was a sharp mood drop, increased suicidality and aggravation of eating disorder symptoms. Eventually she had a body mass index of 16 kg/m2. The eating problems were mapped and analysed by an eating disorder specialist. The latter used a problem-solving approach and focused on both directive counseling and emotional support. The eating disorder specialist also advised to choose a medication with low risks of weight gain. The psychiatrist changed the medication to citalopram.
Subsequently, the treatment team focused on teaching the patient how to cope with stressful situations and the associated anxiety. The stress appeared to be mainly caused by a feeling of lack of control. The patient turned out to have a high intelligence and learning ability, but also felt that she had no control over her learning process. She had not sufficiently developed social learning strategies in her early school years. In addition, there appeared to be an issue of individuation and separation problems. These problems got worse because it was almost impossible for her parents to let her develop in her own way due to the stress they had over her suicidal thoughts, drug use, and worsening physical condition due to bad eating habits. We decided on an additional family counseling approach to address these issues.
The integrated treatment modality approach proved effective. She developed a realistic idea of what caused her stress, how she reacted situationally and improved her awareness that she tends to have control over everything. Her parents were involved in helping her developing control coping skills and checking on achievements. Because of this insight, she succeeded in maintaining her diet less strictly and experimenting with behaving differently without alcohol or drugs. Her parents saw that she was doing better and were able to release her a bit more. This increased her sense of control and provided enough space to further discover what goals she wanted to achieve. In the process her mood and her ability to experience pleasure improved significantly. She successfully passed her school exams and proceeded to university.


A 15-year old Caucasian girl was referred by her own general practitioner after a suicide attempt with symptoms of sadness, anxiety, and obsessive–compulsive behavior. The intake was together with her parents. She was struggling in school, despite her very supportive family. No drug abuse or other psychiatric symptoms were found. She told the counselor she tried hard, but felt that she could not keep up in school; it was never good enough, no matter how hard she tried. The counselor estimated that the school level was appropriate for the level of intelligence of the patient.
She had periods when her self-esteem was very low. During these periods she spent hours on her appearance, focusing on her hair and makeup. Her hair fell out as a result of these sessions. She could not stop herself, and always ended with self-harm. This in turn lowered her self-esteem and increased the experienced stress. She was locked in a downward spiral. Gradually her mood disorder worsened and made her passive. She no longer wanted to go to school and meet friends, but passed hours in front of the mirror. She attempted to end her life.
We hypothesized on the basis of the girl's stress complaints that she felt school, parents, and friends expected too much of her. After a neuropsychological assessment the testing showed that she had a disharmonic intelligence profile with an IQ of approximately 80 (using the Wechsler Intelligence Scale For Children-III ()), inconsistent at all factor levels. We classified a mild intellectual developmental disorder in the conceptual and practical domain, which explained the structural struggle with the standard school curriculum instructions. We educated parents and school on how instructions might fit in better with her learning abilities and style. Her preferred method of learning new things was being shown how to do it, as opposed to having it explained to her. This led to significant stress reduction and positive school experiences. In the process her self-esteem improved, the experienced stress decreased, and her mood improved. CBT was adjusted to her learning style and was used to reduce her obsessive–compulsive behavior.


An otherwise healthy six-year-old male presented to the ED on day four of illness with fevers, sore throat, and dysuria with dark urine. The patient saw his primary care physician on day one of illness with a temperature of 101.4 degrees Fahrenheit (F) and was diagnosed with a nonspecific viral illness, but his symptoms continued to worsen despite supportive care. In the days following the office visit, he had temperatures to 102° F daily, and developed jaundice, a maculopapular rash, and an erythematous tongue with papules ( and ).
The patient presented at the ED without a fever in the setting of acetaminophen use at home (last dose unknown). History was obtained from the mother and patient, and they endorsed slight non-productive cough but otherwise denied associated symptoms. The patient was fully immunized and his past medical history was unremarkable. Initial ED exam revealed a well-appearing patient with temperature of 99.7° F, pulse 115 beats per minute, blood pressure 98/64 millimeters of mercury, respiratory rate 22 breaths per minute, oxygen saturation 97% on room air, and weight 19.7 kilograms. His head was atraumatic and normocephalic. However, his ear, nose, and throat exam revealed an erythematous tongue with flesh-colored papules (). His sclerae were icteric and injected without exudate, and the conjunctival injection spared the limbus (). No significant cervical lymphadenopathy was detected.
Cardiac auscultation revealed a regular rate and rhythm without murmurs, and the lungs were clear bilaterally. His abdomen was non-tender even to deep palpation. Skin exam was notable for diffuse jaundice and an erythematous maculopapular rash to the abdomen and face, sparing the palms and soles. He was awake and alert, following commands, and answering questions appropriately for his age.
Initial laboratory values were obtained for diagnosis. A complete blood count had a leukocytosis to 16.3 thousandths K/μL (normal range: 6.0–17.0 K/μL) with 86% neutrophils (35%–45%), and platelet count of 369 K/μL (210–490 K/μL). Total bilirubin was elevated at 5.4 milligrams per deciliter (mg/dL) (0.3–1.8 mg/dL), and conjugated bilirubin was 2.9 mg/dL (0.0–0.3 mg/dL). Hepatic panel revealed mild transaminitis (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, 59 units (U) per liter (L) (17–59U/L), 169 U/L (21–72U/L), and 425 U/L (150–380U/L), respectively. Urinalysis revealed trace protein, large bilirubin, no casts, 3–5 red blood cells with trace hemolysis, and 3–5 white blood cells. An initial pharyngeal rapid strep test was negative.
The patient was admitted to the pediatric ward for antibiotics and serial exams, pending abdominal imaging, autoimmune testing, additional labs, viral serologies, and culture results. A comprehensive right upper quadrant ultrasound showed a normal appearing gallbladder and no intrahepatic or extrahepatic biliary ductal dilatation to suggest biliary obstruction. The chest radiograph noted possible right basilar airspace disease. However, given the lack of sputum, respiratory complaints, increased oxygen support, and the associated physical exam findings, pneumonia was considered to be inconsistent with the presentation.
Erythrocyte sedimentation rate (ESR) was elevated at 113 millimeters per hour mm/hr (0–10mm/hr) and C-reactive protein (CRP) was elevated at 3.5 milligrams (mg)/dL (less than 1.0mg/dL), consistent with possible KD. Gamma-glutamyltransferase was elevated at 241U/L (15–73 U/L). Throat cultures, antistreptolysin O, hepatitis B surface antigen, hepatitis B core antibody, hepatitis A immunoglobulin (Ig) M, hepatitis C antibody, cytolomegalo virus IgG/IgM, toxoplasmosis IgG/IgM, monospot, blood cultures, and leptospirosis testing were negative, making infectious or post-infectious etiologies less likely.
On day seven of illness (hospital day four), the patient developed bilateral cervical lymphadenopathy up to one centimeter, and his bilateral bulbar conjunctival injection worsened. Despite being afebrile at ED presentation, he continued to spike fevers in the hospital (until the sixth day of illness and third hospital day), despite administration of ibuprofen. During his admission, the patient had an elevated ALT, low albumin, thrombocytosis, and elevated WBC, thus meeting at least three supplemental criteria for KD, making incomplete KD the likely diagnosis. The case was discussed with a remote KD specialist, and the next day the patient was transferred to the intensive care unit for IVIG infusion. An echocardiogram was within normal limits, although limited by inability to assess the full length of the coronary arteries. The patient was initiated on aspirin 81 mg daily. He was discharged on low-dose aspirin with plans to obtain repeat outpatient echocardiograms.
Two weeks after discharge, the patient was evaluated by a pediatric cardiologist. Desquamation of the hands and feet were noted (). Repeat formal echocardiogram was normal, without evidence of pericardial effusion or coronary dilation. Approximately two months after his illness, the majority of the patient’s symptoms had resolved and low-dose aspirin was discontinued. A repeat echocardiogram eight months after initial illness was normal, and a telephone follow-up at 10 months indicated that he continued to do well.


A 20-year-old previously healthy male originally presented to an urgent care center with a chief complaint of fever and rash. He was diagnosed with a viral upper respiratory infection and sent home with supportive care. Six days later, the patient presented to the emergency department (ED) with continued fever and rash. Vital signs included a temperature of 103.0˚ Fahrenheit, heart rate 115 beats per minute, blood pressure 93/54 millimeters of mercury, respiratory rate 24 breaths per minute, and an oxygen saturation of 91%. Physical examination revealed a diffuse, morbilliform rash across the trunk and extremities, sparing the face ( and ). There was no mucosal or ocular involvement. Chest radiograph revealed bilateral infiltrates consistent with multifocal pneumonia (). Labs included a normal leukocyte count (8300 units per liter [uL], reference range 4200–9100/uL) with an absolute lymphocyte count of 800/uL (reference range 1300–3600/uL). A C-reactive protein was elevated at 118.5 milligrams per liter (mg/L) (reference range 0–5 mg/L). A rapid strep test and an human immunodeficiency virus test were both negative, as was a respiratory viral panel. The patient required escalating amounts of supplemental oxygen during his ED course and was admitted to the intensive care unit (ICU). A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction test resulted positive on hospital day two. The patient remains hospitalized in the ICU on hospital day six.


A 26-year-old male patient presented to our institution with a painless enlargement of the left testicle that had been present for 1 month. Physical examination revealed a palpable mass within the testicle, routine blood and urine tests were normal, and serum AFP, β-HCG, and CEA were negative. Ultrasonography showed the diameter of the left testicle was increased but it had a normal shape and smooth surface. There was a 54 mm × 30 mm hyperechoic mass inside the testicle that had a regular shape and a distinct margin. The mass had a heterogeneous internal echotexture, with a central area of increased echogenicity accompanied by an acoustic shadow (Fig. A).
MR imaging was performed with a Philips Intera Achieva 1.5T Super conducting MR scanner and a phased array coil. Transverse T2-weighted images (repetition time [TR] 4500 ms, echo time [TE] 120 ms), transverse T1-weighted images (TR500 ms, TE 10 ms), transverse, coronal, and sagittal images with fat suppression using spectral attenuated inversion recovery (SPAIR) (TR3500 ms, TE 100 ms), and contrast-enhanced transverse, sagittal, and coronal images using a THRIVE sequence (TR 3.9 ms, TE 1.84 ms, thickness, 1.0 mm) were obtained with the following parameters: number of excitations (NEX) = 3, transverse images field of view (FOV) = 180 × 180, coronal and sagittal images FOV = 250 × 250, Gd-DTPA = 0.2 mmol/kg, flow rate = 2.0 mL/s.
MR imaging findings are shown in Figure B–E and G–J. The left testicle was enlarged. A round 48 mm × 45 mm × 43 mm mass was seen inside the testicle. The left testicle showed several hypointense areas on T1-weighted images, the signal intensity at the periphery was the same in both testicles, but the rest of the left testicle was hypointense on T2-weighted images.
T2-weighted images of the lesion showed a thin hypointense capsule. T1-weighted images of the lesion showed a hyperintense nodule on the cyst wall, which appeared hypointense on T2-weighted and SPAIR images. After Gd-DTPA injection, the lesion was not enhanced; however, the nodule was enhanced on THRIVE images. The lesion showed a small black ring on T2-weighted and SPAIR images, which was not enhanced on THRIVE images (Fig. J).


Patient 1 was a 61-year-old man who visited a local hospital 3 months prior due to chest distress. Chest fluoroscopy revealed a localized enlarged right lower edge, and he visited our hospital to seek a further diagnosis and treatment. An outpatient physical examination showed his body temperature was 36.5 °C, his pulse was 75 beats/minute, his blood pressure was 130/70 mm Hg, and his heart border was enlarged rightward. There was no other positive sign. An electrocardiogram revealed sinus rhythm with a ventricular rate of 80 beats/min and a regular heart rhythm. A 24-hour ambulatory electrocardiogram (AECG) revealed no supraventricular arrhythmia. Transthoracic echocardiography (IE33, PHILIPS, Netherlands) revealed a cystic mass 5.8 cm × 5.2 cm × 4.0 cm in size in the area of the right atrium (Fig. a); this mass was connected to the right atrium, and spontaneous angiography was observed within the mass. No thrombosis was seen in the mass, the tumor body compressed the right ventricle at diastole, and blood flow entering the right ventricle was not restricted. The left atrium and bilateral ventricles had normal structures, no abnormality was detected in the valve or ventricular wall activities, and the left ventricular ejection fraction was 73%. The patient was therefore diagnosed with RAA. Computed tomography (CT) angiography (CTA, Aquilion One, TOSHIBA, Japan) revealed a diverticular lesion in the right atrium area. Contrast agent filling was seen inside the lesion, and no external compressive structure was seen in the adjacent coronary artery (Fig. b and c). Magnetic resonance imaging (MRI, MAGNETOM Avanto 1.5T MRI, SIEMENS, Germany) also revealed diverticular changes in the right atrium area with a thin luminal wall (Fig. d). The patient had a 3-year history of hypertension, and his blood pressure was controlled at 120–140/70–90 mm Hg by orally administered antihypertensive drugs. The patient refused surgical treatment, so oral administration of warfarin anticoagulant therapy was prescribed, and the international normalized ratio of prothrombin time was maintained at 2.0 to 3.0.


Patient 2 was a 26-year-old man who visited our hospital due to the discovery of heart shadow enlargement during an orientation health check in another hospital 4 months prior. A physical examination revealed his body temperature was 36.7 °C, his pulse was 71 beats/minute, his blood pressure was 121/71 mm Hg, the heart border was enlarged bilaterally, and there was no detected cardiac murmur. ECG revealed type I atrial flutter with a ventricular rate of 77 beats/min, a regular heart rhythm, and that the cardiac electric axis was shifted leftward. Transthoracic ultrasonography (IE33, PHILIPS, Netherlands) revealed a cystic mass in the right auricle area (Fig. a) that was approximately 6.4 cm × 4.3 cm × 3.9 cm in size and was connected to the right atrium. No abnormality was observed in the bilateral ventricles or left atrial structure. Doppler ultrasonography revealed unrestricted bilateral ventricular blood filling at diastole. Transesophageal ultrasonography revealed dense spontaneous contrast agent stagnation inside the lesion, but no thrombosis was seen inside the lesion or in the left atrium. The patient was diagnosed with RAA. Chest CTA (Aquilion One, TOSHIBA, Japan) suggested that the right atrium was oval and protruded outside the cavity, and the contrast agent density inside the lesion was similar to that in the right atrium (Fig. b–d). The patient refused surgical treatment and was prescribed orally administered amiodarone and warfarin anticoagulant therapy. At present, the patient has been followed up for 4 months, and no clinical symptom has been observed.


A 54-year-old male was referred to local hospital with cough and expectoration in April 2018. Chest computed tomography (CT) revealed a mass in the left of the lung, with multiple mediastinal lymph node metastases (4L, 5 and 6 region). Endobronchial ultrasound-guided transbronchial needle aspiration result was consistent with adenocarcinoma. Staging evaluation in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) with CT, positron emission tomography- CT, and magnetic resonance imaging of the brain conformed stage IIIB (T3N2M0) according to the UICC 7th edition TNM classification. The patient was given concurrent chemotherapy, consisting of 500 mg/m2 pemetrexed and 75 mg/m2 cisplatin on day 1 every 3 weeks for 2 cycles, and definitive thoracic radiotherapy of volumetric modulated arc therapy (95%PGTV 60.2Gy in 28 fractions. 95%GTV 50.4Gy in 28 fractions). The isodose lines of radiation dose distribution are showed in Figure . A CT scan of the chest indicated a partial response. Grade I esophageal toxicity, Grade II gastrointestinal toxicity, Grade I dermatological toxicity and Grade I myelotoxicity (Common Terminology Criteria for Adverse Events Version 4.0; CTCAE v4.0) were the side effects of the concurrent chemoradiotherapy.
However, 2 months after completing concurrent chemoradiotherapy, he developed progressive disease with enlargement of right inguinal lymph node. Biopsy of the inguinal lymph node was consistent with adenocarcinoma and the patient was administered docetaxel 75 mg/m2 on day 1, carboplatin AUC 5 on day 2 plus bevacizumab 7.5 mg/kg on day 1 once every 3 weeks.
Eighteen days after 4 cycles, the patient presented a sudden onset of acute cough after drinking. Esophageal Barium meal revealed a TF. Gastroscopy showed an esophageal mucosa erosion to be 28 to 36 cm from the nostrils, in which a deep hole was observed (Fig. ). Then a jejunal feeding tube was placed for nutrition (Fig. ). Forty days after the placement, the patients suffered from lung infections by an unclosed TF and a covered esophageal stent was placed in the esophagus (Fig. ). The TF was managed with stents. Until now, 6 months after the event of TF, the patient was still in follow-up care without any complication related to the stent placement.


A 24-year-old otherwise healthy male patient had acquired extensive burn injuries at a gasoline fire and was admitted to the National Hospital of Burns, Hanoi (day 0). Physical examination showed extensive injuries involving 75% (with a deep injury proportion of 60%) of the total body surface including his face, scalp, chest, abdomen, back, and all extremities. The respiratory system was severely involved. The patient was treated with intravenous fluids, parenteral antibiotics and antifungal drugs, and topical silver sulfadiazine ointment. He underwent surgical measures for debridement and skin transplantation, mechanical ventilation, and dialysis. His hospital course was interspersed with multiple episodes of local and disseminated infections. Wound swab cultures were positive for Acinetobacter baumannii, Pseudomonas aeruginosa, and Candida tropicalis. Blood specimens were taken from the central venous catheter and peripheral veins for culture, and Stenotrophomonas maltophilia, C. tropicalis, A. baumannii, and P. aeruginosa were isolated at different time points. C. tropicalis fungemia was successfully treated with antifungal drugs as evident by the negative result of blood culture on day 38. However, the patient did not recover from septicemia caused by P. aeruginosa and multiple organ failure. The patient’s family insisted on discharge of the patient on day 58 after hospital admittance against urgent medical advice. He died several days after discharge due to multiple organ dysfunction. The anti-infectious management of the patient is depicted in .
A biopsy taken from the bottom of a burn ulcer on day 24 and stained with hematoxylin-eosin showed proliferating fibrous connective tissue, collagen fibers, fibrinoid necrosis, and newly formed blood vessels. There were abundant varicosities and yeast-like structures indicating fungal infection in the tissue and on the base of the ulcer ().
Cultures of the biopsy specimens yielded white colonies and many wide, crescent-shaped macroconidia characteristic of Fusarium on microscopic examination ().
The isolated strain was subjected to molecular analysis by sequencing the internal transcribed spacer (ITS) region and identified as F. solani (ITS sequence submitted to GenBank [MN066126]).
Susceptibility testing of the isolation was performed by agar disk diffusion procedure as described previously. The inhibition zones of amphotericin B and itraconazole were of 8 and 11 mm, respectively, while there was no zone of inhibition to fluconazole, voriconazole, and caspofungin, meaning that the isolation was resistant to all tested drugs.


A 29-year-old woman presented with abdominal pain, vomiting, and bloody diarrhea. Contrast-enhanced CT of the abdomen showed a partial bowel obstruction secondary to a large proximal colonic mass thought to be a primary tumor [Fig. ]. In addition, there was a large right hepatic mass suspicious for metastasis. Colonoscopy demonstrated a partially obstructing lesion at the hepatic flexure and biopsy showed moderately-to-poorly differentiated infiltrating adenocarcinoma without mucinous features. Further genetic testing showed loss of MLH1 and PMS2 with mutations in MLH1 and CDH1, suggestive of Lynch syndrome. The liver mass enlarged despite 5 cycles of chemotherapy with FOLFIRINOX. Three months after presentation, the patient underwent a right hepatic lobectomy (with preservation of the left triangular ligament), a cholecystectomy, and diverting ileostomy in preparation for a right hemicolectomy which occurred three months later. Two days later, she presented with deep vein thrombosis. She was placed on intravenous heparin and an IVC (inferior vena cava) filter was requested. During filter placement, there were large clots in the suprarenal IVC and narrowing of the superior aspect of the IVC above the hepatic vein inflow [Fig. ]. The filter was placed superior to the thrombus. Next day, the patient was found to be hypotensive with blood pressure of 80–90/50–60 mmHg, heart rate of 70–80 bpm, oliguria, and elevated liver enzymes [Fig. ]. Her hemoglobin remained stable. Given persistent hypotension requiring vasopressors, CT of the abdomen was obtained to evaluate for hemorrhage. The liver remnant had shifted into the space vacated by the right hepatic lobe and the IVC was severely narrowed at the point above the hepatic vein inflow associated with thrombus in the suprarenal IVC. There was concern that venous return was impaired by both the IVC narrowing and IVC clots, and thrombectomy was performed. Initial procedure included IVC thrombectomy using AngioVac (AngioDynamics, Inc., Queensbury, NY) with technical success. However, rethrombosis of the IVC occurred. Review of the imaging showed torsion of the IVC at the level of the subdiaphramatic vena cava near the confluence of the hepatic veins and the IVC causing thrombosis. The patient was retreated with thrombectomy with AngioVac followed by removal of the suprarenal IVC filter and subsequent stenting of the kinked area using a Z-stent measuring 25 × 50 mm (Cook, Inc., Bloomington, IN) [Fig. ]. Post-procedure, the patient’s blood pressure, liver enzymes, bilirubin, and creatinine returned to baseline levels. The patient was discharged 6 days later on oral rivaroxaban.


A 64-year-old woman was undergoing follow-up for primary aldosteronism at the Department of Internal Medicine of our hospital. The patient had hypertension, primary aldosteronism, and a goitrous tumor. The patient had last undergone follow-up computed tomography (CT) more than 10 years previously. However, in 2012, follow-up CT incidentally revealed a 7-mm cystic lesion in segment 8 of the liver. At that time, the cyst was considered benign and monitored regularly. Moreover, from 2012 to 2017, the cystic lesion kept increasing in size, reaching 17 mm. In 2017, CT also revealed a 13-mm mural nodule in the cyst wall (Fig. a–c); therefore, the patient was referred to our department for a possible malignant tumor. CT revealed that the proximal bile duct showed no abnormalities, such as dilation or stenosis, while the distal bile duct showed slight dilation, indicative of a mucin-producing biliary tumor. In addition, magnetic resonance imaging (T2-weighted imaging) revealed a 17-mm cystic lesion, with an internal signal intensity equivalent to that of water (Fig. a, b). Endoscopic ultrasonography revealed a 13-mm mural nodule in the cystic wall that was enhanced on contrast-enhanced ultrasonography (Fig. c). Laboratory measurements revealed normal level of liver enzymes. The carcinoembryonic antigen level was slightly elevated (5.3 ng/ml), but the levels of carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II were within the normal ranges.
We suspected a branch-type IPNB and thought that the presence of mural nodule suggested a potential of malignancy. However, the mass was small and diagnosis could not be made without performing biopsy. Several previous studies showed the usefulness of FDG-PET as a diagnostic tool to detect biliary malignancy []. However, considering the small tumor size, we considered CT, MRI, and contrast-enhanced ultrasonography were sufficient for the assessment of surgical indication. Thus, we have omitted FDG-PET from preoperative workup at this time.
Accordingly, surgical resection was planned for diagnosis and treatment. Because branch-type IPNB might show horizontal spread through the intrahepatic bile duct, we thought that anatomical resection of the liver was appropriate to obtain a sufficient surgical margin as much as possible. Accordingly, we performed laparoscopic anatomical resection of segment 8 of the liver via the extrahepatic Glissonean pedicle approach (Fig. a–c). After cystic plate cholecystectomy, the Glissonean pedicle of segment 8 was isolated and clamped by using a vascular clip (Fig. b). After confirming the ischemic demarcation line, the liver parenchyma was dissected along the marked line and the middle and right hepatic veins (Fig. c). During dissection, the Glissonean pedicle of segment 8 was ligated, clipped, and divided.
Macroscopic examination revealed that the cyst was 17 mm and located in S8; the mural nodule was 13 mm (Fig. a) and showed mucin production. The bile ducts of segment 8 were visualized in addition to cystic space (Fig. a), suggesting that the cystic tumor communicated directly with the lumen of the adjacent bile duct. The tumor was very close to the bile duct. On microscopic histopathological examination, the resected specimen showed papillary growth and fibrovascular cores in the nodular area, comprising high-grade atypical epithelial cells in the cystic wall. However, papillary projection did not invade the adjacent bile duct lumen. The tumor was composed of papillary and glandular components; the origin of the present tumor might have derived from a peribiliary gland, not the large bile ducts.
Immunohistochemical analysis showed that the tumor was positive for MUC1, MUC5AC, MUC6, CK7, and CK20 and negative for MUC2. The final pathology was an IPNB, high grade (Fig. b–d) that did not invade the bile duct epithelium. The ductal margin at bile duct resection stump was also negative on histopathological examination.
The patient had an uneventful recovery, with no postoperative complications, and discharged 12 days after surgery. Follow-up abdominal CT after surgery did not reveal any mass, with the patient being asymptomatic 30 months after the surgery.


A 39-year old male presented with pain and discomfort of the left thigh. One month prior to the admission, the patient complained of discomfortness with intermittent pain in his left thigh and went to a general practitioner. However, the pain did not subside. Six days before the admission, the patient felt sudden pain in the left thigh while walking fast, then he fell down and was unable to walk. He was brought to a private hospital in Yogyakarta and X-ray examination was performed, showing a fracture and soft tissue mass in the left proximal femur (). The surgeon decided to perform open reduction and internal fixation (ORIF). During the surgery, abnormal appearance of the bone and the surrounding tissue was found. Tissue samples were taken for histopathology examination and skeletal traction was performed instead of ORIF. The patient was then referred to our institute for further investigation.
Laboratory examination showed normal range of complete blood count, electrolytes, alkaline phosphatase (ALP), and also lactate dehydrogenase (LDH). There was no increased levels in other specific tumor marker examinations of other organs which showed no source of metastatic bone disease. Bone survey was performed and showed no sign of abnormality in other bones. Further, computerized tomography (CT) scan of the chest and abdomen were done and also showed no signs of metastasis in the regions. Magnetic resonance imaging (MRI) was done. It showed the presence of soft tissue lesion in the left proximal femur (subtrochanteric) with the size 12.2 × 9.8 × 13.8 cm, with expansion of the lesion to femoral head, femoral neck, trochanteric area and femoral shaft causing pathologic fracture of the left subtrochanter femur.
Histologic section showed mesenchymal tumors with increased cellularity, arranged in solid and alveolar fashion and infiltration to surrounding soft tissue (). Moreover, the tumor cells consisted of epithelioid cells, small to moderate in size. Eosinophilic cytoplasm was visible with caudated appearance and round to oval nuclei, while some spindle nuclei were found with irregular chromatin, and prominent nucleoli (). Numerous mitosis and a wide area of necrosis were present. Based on morphology, the tumor was assessed as epithelioid rhabdomyosarcoma with differential diagnosis of epithelioid sarcoma. Immunohistochemistry examination revealed vimentin () and CK positive expression (), while myogenin was negative (). Further immunostaining using CD34 () and HMB45 were also negative (). Thus, immunostaining profile was suitable as proximal epithelioid sarcoma, with the rhabdoid variant.
A radical resection was planned, and the patient was taken for surgical hip disarticulation. Following the surgery, adjuvant chemotherapy was done using Doxorubicin and Ifosfamide for 6 cycles. Then, the patient was referred to radiation oncology and underwent intensity-modulated radiation therapy at 6000 cGy to the left hip joint.
The patient had a slow yet uneventful postoperative recovery. On the most recent CT imaging of chest and abdomen done 1-year postoperatively, there was no evidence of metastasis. He returned to daily activities using a lower limb prosthesis and remained free of recurrence.


A 35-year-old man was hospitalized after a 10-year history of occipitocervical pain and limited mobility (Fig. ). Physical examination revealed mild tenderness in the back of the upper cervical vertebrae and limited mobility of the neck. The muscle strength of the limbs was grade 4, and there was slight loss of limb and trunk sensation. Excretory function was normal. Pathological reflexes were positive, and bilateral patellar tendon reflexes were hyperactive. Cervical anteroposterior and lateral plain radiography, cervical computed tomography (CT), and magnetic resonance imaging (MRI) revealed an occipitocervical junction deformity accompanied by spinal cord compression. Occipitocervical deformity was diagnosed. On the fifth day after admission, the patient underwent a corrective operation involving posterior reduction and occipitocervical fixation and fusion. The bone graft comprised both ilium and artificial bone.
The standard occipitocervical posterior midline approach was adopted to expose the posterior structures of the C0–C3 vertebrae. Care was taken to protect the vertebral artery and posterior vascular plexus. Intraoperative fluoroscopy revealed that the occipitocervical joint sequence was good, and the reduction was successful. Screw insertion was a three-step process. First, occipital screws were inserted in the mediolateral tubercle and the occipital protrusion of the occipital bone (total of three occipital screws) []. Second, pedicle screws were inserted bilaterally in C2 using the Harms and Melcher technique [], and lateral mass screws were inserted bilaterally in C3 using the Roy–Camille et al. technique []. Third, an additional spinous process screw (3.5 mm diameter, 20 mm long) was inserted vertically into C2 []. The depth and angle of its implantation was determined using the Goel and Kulkarni technique [], and the screw itself was chosen according to its length and diameter based on the patient’s appearance on preoperative CT scans. Following screw insertion, three rods were then connected from C0 to C3. An occipital screw was placed in the occipital protrusion and connected to the C2 spinous process screw. A high-speed drill was used to prepare the bone graft bed on the posterior structure of the occipitocervical joint. The graft comprised bone from the posterosuperior ilium and artificial bone.
The patient could walk with a neck brace on postoperative day 3 and continued wearing the neck brace for the next 3 months. No neurovascular complications or incision infection were observed during the 24-month follow-up. Postoperative radiography showed that the internal fixation remained stable. Successful fusion was confirmed 4 months after the operation. Postoperative MRI showed that the occipitocervical decompression was sufficient, and there was no obvious spinal cord compression. The muscle strength of the limbs was grade 5, and at the 24-month follow-up visit the patient’s sensation function had improved from its preoperative state (Fig. ).


A 62-year-old male, married, retired, with type 2 diabetes for more than 15 years, background to rheumatoid arthritis and myocardial revascularization, with no history of using alcohol or tobacco, without neuropathy, feeling pain in right foot which showed signs of dry necrosis in the plate and in the digital pulp of the third finger, and partial necrosis in the hallux reported. He Presented with distal pulses in the finger extremities, without fever, heartbeat of 80/min fc, and Pa 13 × 9 and was attended at the Diabetic Foot Treatment Center with diagnosis of type II diabetes and ischemic diabetic foot. He presented with progressive and painful necrotic plaques in the right hallux and 3rd right foot pod. The color of the feet was purple with fuming appearance. In terms of background, the patient reported treatment with a rheumatologist at the Hospital das Clínicas in São Paulo due to arthritis of the hands and coronary stent placement for 6 months at INCOR-SP. He was being medicated with prednisone, clopidogrel, and metformin.
After clinical evaluation, he was medicated with Cilostazol 50, and an arterial echo Doppler of the lower limbs was requested. This examination concluded that the arterial trunks had vascular patency with three-phase flow. There was a minor, noticeable improvement of the right toes after two months of treatment with Cilostazol but with worsening of the contralateral toes. There were fixed cyanosis and resting pain of the 3rd and 4th toes of the left foot. Even an intensive care treatment by photodynamic therapy (PDT) did not improve the condition of the diabetic foot []. After consulting his cardiologist to authorize the use of SC, this drug was administered at the daily dose of 50 mg. This treatment was maintained for 10 months, with remission of the endpoint ischemia. The patient reported feeling well, and PDT started to respond well. After 5 PDT sections, feet lesion healed and the patient regained his colored feet and reported no pain ().
One year after discharge, the patient returned again with lesion in his 1st left toe, ischemia in the 2nd right toe, with a necrotic plaque and ulcerated digital pulp, a lot of resting pain, and left lateral hallux ulcer. SC was once again administered, this time in doses of 50 mg every 12 hours (100 mg/day). After 3 months and 6 PDT sections, the 1st left toe had already healed, but the patient started to report hypoglycemia attacks. The use of Metformin and fasting was discontinued, as long as glucose levels were kept between 82 and 93 mg/dl, and SC was reduced again to 50 mg. The treatment of the 2nd finger, which was initially ulcerated, was finalized by PDT, and the patient was discharged.
During this relatively long period (more than two years), glycemia was obtained daily throughout several months, and average values are shown in . It is clear that SC allowed for a reduction and stabilization of glycemic values, with the extra benefit of having improved also the microvasculature, as indicated by the cure of the diabetic foot. It is also possible to note that there is an effect of the dose of SC, since during the 100 mg/day period, glycemia was significantly lower than in the other three periods in which the patient received a SC dose of 50 mg/day. However, as mentioned above, patient 1 under 100 mg/day of SC had an important hypoglycemic event, which was not observed at the 50 mg/day dose.


A 73-year-old male, medical doctor, widower for 2 years, lives in the house with his two children. He is a social ethicist, smoker for 40 years, and quitted smoking 18 years ago as a response for the diagnosis of pulmonary emphysema, asthma, and systemic arterial hypertension (SAH). 10 years ago, he was diagnosed with Type 2 diabetes mellitus and dyslipidemia. For the long-term asthmatic status, he uses formoterol fumarate dihydrate 200 mg with bisoprolol hemifumarate 1.25 mg daily (inhaled bronchial dilator) 1x daily; for systemic arterial hypertension, losartan and hydrochlorothiazide 50/12.5 mg (morning and afternoon); for dyslipidemia, rosuvastatin 20 mg, AAS 100 mg.
Two months after starting SC, the patient reported having an important hypoglycemic attack (glucose level of 27 mg/dl) (). 3 hours after starting this episode, this patient still presented dysarthria, mental confusion, and loss of consciousness and was hospitalized in the ICU with good recovery after glucose replacement. The use of SC was suspended during the hospitalization period, and the medication for diabetes was resumed. After dismissal from the hospital, SC was reintroduced at a dose of 25 mg 3 times per day, and postprandial glucose remained around 138 mg/dl, even when consuming sweets; sulfonylurea (gliclazide) has been discontinued and home glycemia ranged from 101 to 117 mg/dl. Six months after the episode, the patient showed stabilization of symptoms with normal blood pressure, 61 beats per minute, 95% O2.


A 36-year-old man, who was a chronic hepatitis C carrier presented at a local hospital after a motorcycle accident on November 28, 2017. First, resuscitation was performed and abdominal computed tomography (CT) revealed a liver injury. Then, he was transferred to our emergency department (ED) after resuscitation. At the ED, he presented a full Glasgow coma scale and his blood pressure was 118/82 mmHg, respiratory rate was 20 breaths/min, and pulse rate was 65 beats/min. Right upper abdominal tenderness was noted on physical examination, and blood tests revealed a white blood cell count of 9200/mm3, hemoglobin level of 13.4 gm%, serum aspartate aminotransferase level of 1165 U/L, and serum alanine aminotransferase level of 1173 U/L. On reviewing the abdomen computed tomography (CT) scan, a grade III liver injury was observed, in accordance with the American Association for the Surgery of Trauma–Organ Injury Scale for liver injury () []. The segment 7/8 of the liver showed a large intra-parenchymal hematoma, and there was no hemoperitoneum or contrast extravasation (). Thus, he was admitted to the intensive care unit (ICU) for NOM of the blunt liver injury. In the ICU, intermittent high fever up to 38.7 °C was observed, which lasted for three days, and chest radiography revealed right pleural effusion and some entrapped air over the right subphrenic space (). Then, repeat abdominal CT on the same day revealed a large abscess with rupture at the previously injured liver parenchyma with air and fluid accumulation around the perihepatic space (). Then, laparoscopic drainage of the ruptured liver abscess was performed immediately. During the surgery, the surgeon and the camera operator stood on the patient’s left side, with an assistant on the other side. Carbon dioxide pneumoperitoneum (12 mmHg) was established through an umbilical incision using Hasson technique, and a zero-degree-angled laparoscopy was introduced through an 11-mm port. Then, a 5 mm port for liver access was placed at the left lateral abdomen, and a third 5 mm port was placed at the right lateral abdomen to elevate the liver. By laparoscopy, the turbid bloody fluid and necrotic tissue around the injured liver could be drained well (). Approximately 250 mL of infective bloody fluid was drained and sent for culture. Finally, a chest tube was placed for drainage via the right-side port wound. After laparoscopic drainage, fever subsided and the abscess culture revealed the presence of Salmonella enterica, serogroup D. According to the sensitivity test, ertapenem (Merck Sharp & Dohme, France) 1 g QD intravenously was given for 11 days. He recovered well and was discharged on December 15, 2017. Follow-up abdominal CT performed 4 months later showed a well-healed liver injury and no residual abscess ().


A 48-year-old African-American woman with a history of hypertension presented with a right-sided neck mass of 10 years with intermittent purulent discharge. She additionally reported three years of unintentional weight loss, fatigue, anorexia, constipation, night sweats, and chills. On presentation, her vital signs were within normal limits. On physical examination, the woman had severe bitemporal wasting, skin pallor, and a large right-sided neck mass with sanguineous discharge (Figure ), but no lymphadenopathy. Cardiac and pulmonary examinations were normal; however, her abdomen was notable for hepatomegaly of approximately 18 cm and a palpable spleen. Initial laboratory investigations are presented in Table .
CT scan of the neck showed a 4-cm cystic mass abutting the posterior aspect of the superficial lobe of the right parotid gland with multiple calcifications within the right parotid gland (Figure ). Fine needle aspiration of the parotid mass revealed acinar cells of the salivary gland with focal atypia and severe inflammation suggestive of sialadenitis. While awaiting further workup, the patient left against medical advice.
Four days later, she was brought back to the hospital by her family after they found her confused. Upon this presentation, she was hypotensive, tachycardic and disoriented to place, time, and circumstances. CT scan of the head revealed no acute abnormalities. CT chest showed three right-sided pulmonary nodules and bilateral pleural effusions. Despite aggressive fluid resuscitation in the medical ICU, she remained hypotensive.
Investigations
Investigations were undertaken for hypotension. Serum chemistry was significant for a calcium level of 14.4 g/dL. Serum cortisol was 4.6 ug/dL (10-20 ug/dL) with no response to adrenocorticotropic hormone (ACTH) stimulation after 30 min (5.8 ug/dL) and one hour (6.9 ug/dL). Echocardiography showed a normal left ventricular ejection fraction and normal diastolic parameters. However, the estimated pulmonary artery systolic pressure was elevated at 50 mmHg with concomitant severe right ventricular dysfunction and right atrial enlargement.
Further workup showed normal serum and urine electrophoresis, negative HIV antibodies, anti-nuclear antibody, and anti-mitochondrial antibody. Parathyroid hormone level was normal at 58 pg/mL (ref: 10-65 pg/mL) and serum angiotensin converting enzyme (ACE) level was elevated at 141 U/L (ref: 8-52 U/L). Bone marrow biopsy showed hypercellular marrow, no atypical infiltrates or granuloma, and no abnormal clonal cells on flow cytometry. Core needle biopsy of the liver subsequently showed pale homogenous eosinophilic deposits in between hepatocellular and sinusoidal trabeculae, compatible with amyloid deposition (Figure ).
Differential diagnosis
Lymphoproliferative disease such as lymphoma, nonlymphoproliferative metastatic cancer, sarcoidosis, disseminated tuberculosis, and disseminated fungal infection were amongst the diagnostic possibilities considered.
Treatment
The patient was started on stress dose intravenous hydrocortisone with subsequent improvement in blood pressure. She was subsequently transitioned to oral hydrocortisone and discharged in stable condition with outpatient follow-up.
Outcome and follow-up
Two months after discharge, the patient presented with five days of shortness of breath and cough and was found to be hypoxic. Chest X-ray showed increased burden of lung nodules in addition to multifocal lung consolidation. Intubation was offered to the patient in the setting of worsening respiratory distress and increasing supplemental oxygen requirements, however, she declined and passed away on the night of admission.


A 26-year old African-American female, who was a JW with a history of sickle cell disease (SCD; hemoglobin SC), presented to the emergency room with a pain crisis involving the back, arms, legs, and chest. Her exam was normal except for pallor. Her hemoglobin (Hb) at admission was 7.7 g/dL; serum lactate dehydrogenase (LDH) was elevated at 6077 IU, serum haptoglobin was reduced at 24 mg/dl; serum bilirubin and liver enzymes were elevated. She was admitted for an acute pain crisis and treated with intravenous fluids and analgesics. Over the next 24 hours, she developed respiratory distress and was hypoxic. Chest X-ray showed opacities in bilateral lung fields (Figure ).
The patient was diagnosed as having ACS and was transferred to the intensive care unit (ICU) for further management. The patient’s respiratory status worsened and she was intubated and placed on invasive mechanical ventilation (assist control, with a tidal volume of 6 mL/kg ideal body weight). Her Hb and hematocrit (Hct) continued to decline with a nadir Hb of 3.1 g/dL. To minimize energy expenditure and oxygen consumption (VO2), the patient was deeply sedated and paralyzed with intravenous cisatracurium infusion. The patient was placed on 100% fraction of inspired oxygen (FiO2), to increase oxygen solubility in the blood and maximize partial pressure of oxygen (pO2) in her arterial blood and thereby help oxygen delivery (DO2) to the tissues. The FIO2 was lowered to 50% after 72 hours to prevent oxygen toxicity. While on 100% FIO2, the patient's pO2 was 150 mm Hg and O2 saturation was 100% on 100% FIO2. Though the risks of hyperoxia are well known, in this case, it was outweighed by the risk of cellular anoxia due to impaired oxygen delivery, resulting from a severely reduced Hb, which the hyperoxia aimed to correct. In addition, blood loss was minimized by avoiding daily blood draws and pediatric tubes for samples were used, when needed. The patient was administered erythropoietin to stimulate erythropoiesis in conjunction with vitamin B12, folate, multivitamin, and vitamin C. The patient was also loaded with intravenous (IV) iron and given leuprolide injection to prevent blood loss by suppressing menstrual bleeding. Erythropoietin was stopped after two weeks of daily administration. The paralytic drug was discontinued after 7 days. LDH and haptoglobin levels improved indicating resolution of hemolysis. After two weeks, her Hb and Hct began to show slow but steady improvement (Figure ), and her chest X-ray demonstrated improvement as well. She was eventually weaned off sedation and successfully extubated. At discharge after a 5-week hospitalization, her Hb and Hct had increased to 7.7 g/dL and 23.6%, respectively, and she was ambulating with normal oxygenation on room air.


Our patient was a 79-year-old female who presented with a six-month history of increased forgetfulness, muscle weakness, arm tremors, and changes in speech and penmanship. Her past medical history was significant for cerebellopontine angle vestibular schwannoma diagnosed four years ago and treated with CyberKnife therapy (Accuray Inc., Sunnyvale, CA) without complications or reoccurrence. After treatment, the patient did not develop any auditory deficits such as hearing loss or tinnitus consistent with persistent disease. Furthermore, she did not develop facial palsy following CyberKnife therapy. On physical examination, our patient was noted to be wheelchair-bound for locomotion. Mental status exam revealed moderate cognitive impairment with hesitation initiating speech/minimal speech, hypomania and hypophonia. Remaining neuro exam revealed facial asymmetry with voluntary movement, increased muscle rigidity, cogwheel rigidity, proximal muscle weakness in lower extremities (exemplified by difficulty getting from a sitting to a standing position), mild, bilateral upper extremity tremor, myoclonus and hesitation in gait initiation. MRI brain was conducted and revealed the ribbon-like signal hyperintensity of cerebral cortical gyri (cortical ribboning) in the parietal and occipital regions, known as the cortical ribbon sign, suggestive of CJD (Figure ).
Prior to presenting to our facility, this patient had been diagnosed with and treated for Parkinson's disease and trigeminal neuralgia without improvement. Due to the rapid progression of her disease, severity of her symptoms and failed treatment attempts over the last six months, we performed a diagnostic lumbar puncture to test for CJD. Cerebrospinal fluid (CSF) analysis at this time detected 14-3-3 proteins and the diagnosis of sCJD was made. Based on her clinical picture, it was determined that our patient had advanced stage sCJD. Therefore, she was admitted for close medical supervision and treatment. Our patient was only offered symptomatic management and supportive treatment due to the absence of standard therapy to date for advanced sCJD.


This case presents a 20-year-old German female patient diagnosed with a chronic wound infection caused by MFC following a traffic accident in Vietnam (see Fig. for a timeline). The patient was travelling through Vietnam when she was involved in a motorbike accident in February 2019. She was taken to the emergency department of a hospital in Hanoi where she presented with a large wound on the right leg. At the time of admission, she was complaining of severe pain in her back and right foreleg, as well as headache and nausea. The patient reported no other pre-existing medical conditions. Radiograph of the lower leg did not show any signs of fracture, and cranio-encephalic traumatic lesions were excluded in the cranial computed tomography (CT) scan. However, a lumbosacral spine CT scan revealed stable fractures of the thoracic vertebrae (T4 / 5). The patient underwent surgical debridement and suture of the leg wound the next day (see Fig. a for a representative photograph) and was treated with metronidazole and ceftriaxone over four days. She was discharged eight days after admission, transported to Germany and immediately admitted to a local hospital. At that time, her right lower leg was swollen, but lacked signs of surgical site infection. The patient was discharged three days afterwards, and dressing changes were subsequently performed in an outpatient-setting by her general practitioner and in local hospitals. Approximately five weeks after the accident, wound inflammation was observed for the first time, with redness and warmth around the suture site and dehiscent areas of the wound edges. However, no signs of systemic infection such as fever, increased leukocyte count, or C-reactive protein levels were apparent. Three days later, she was re-admitted to a local hospital with the diagnosis of wound infection. Surgeons described purulent exudate and a subcutaneous firm tumor measuring 2 × 4 cm in size (Fig. b) with spontaneous drainage (Fig. c). The patient was discharged, and oral antibiotic treatment with amoxicillin / clavulanic acid was continued for two weeks on suspicion of soft tissue infection. In the next follow-up presentation, two new lesions with serous drainage (Fig. d) were documented. Of note, several swabs failed to show growth of any pathogenic bacteria on standard microbiological examination. Magnetic resonance imaging (MRI) was performed, showing neither bone involvement, nor a remaining foreign body underlying the chronic infection. The patient was transferred to our university hospital where plastic surgical debridement was performed. On histopathological examination, chronic granulomatous purulent inflammation was documented. The lesion was covered by skin grafting and local flap surgery three days later, while intravenous antibiotic treatment with ampicillin / sulbactam was continued over ten days (Fig. e). However, the wound failed to heal, and persistent infected cutaneous lesions were noted on follow-up outpatient appointments (Fig. f). MFC could then be grown from a biopsy on Columbia agar on culture day two. Species identification via MALDI-TOF and subsequent genotypic identification using a DNA hybridization strip assay (GenoType Mycobacterium CM, Hain Lifescience / Bruker) [] was performed and Infectious Diseases specialist consultation was initiated. Minimal inhibitory concentration (MIC)-determination via broth microdilution revealed susceptibility to amikacin and fluoroquinolones, and intermediate sensitivity to imipenem, while the isolated strain exhibited resistance toward linezolid, doxycycline / minocycline, trimethoprim-sulfamethoxazole, clarithromycin, and cefoxitin (based on CLSI-breakpoints, M24-A2 2011). In addition, susceptibility testing for the second line antimycobacterial agents clofazimine, bedaquiline, and delamanid was performed (Table ). Though official clinical breakpoints for susceptibility testing of NTM for those agents have not been defined yet [, ], the results pointed towards resistance against delamanid and susceptibility for bedaquiline considering proposed European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Mycobacterium tuberculosis (version 10.0) and previous studies [].
The table lists Minimal inhibitory concentrations (MIC) of fourteen distinct antimicrobial substances tested on the clinical MFC isolate. Susceptibility was interpreted using CLSI breakpoints (M24-A2 2011), if available. S = sensitive; R = resistant; I = intermediate.
The patient was transferred to the Infectious Diseases department for further diagnostics and treatment. Due to persistent back pain and mild paresthesia in the peripheral extremities, a whole spine MRI was performed, which showed no sign of disseminated infection. In addition, chest radiograph and abdominal ultrasound did not reveal any abnormal findings and the patient tested negative for Human Immunodeficiency Virus (HIV)-infection. Based on the American Thoracic Society / Infectious Diseases Society of America (ATS / IDSA) guideline and susceptibility testing results, antibiotic therapy was initiated with amikacin (initially 10–15 mg / kg of body weight once a day, intravenously, subsequently adjusted to serum level), levofloxacin (500 mg once a day, orally), and imipenem / cilastatin (0.5 g / 0.5 g twice a day, intravenously) (Fig. g). Treatment was generally tolerated well, however, nausea occasionally required symptomatic antiemetic therapy. Also, the patient reported to feel dizzy when exposed to sunlight. After five weeks and upon clinical improvement as well as approval of health insurance coverage and written informed consent on off-label use, the treatment was changed to an oral regimen consisting of levofloxacin (500 mg once a day, orally) combined with bedaquiline used at doses that have been recommended for MDR TB [] (14 days of 400 mg once a day orally, followed by 200 mg three times per week). The patient could be discharged and was followed up as an outpatient in our Infectious Diseases clinic. Continuous clinical improvement was noted (Fig. h). Apart from persisting nausea, the patient did not report any notable treatment-related side-effects. Liver enzymes, renal function and blood count were regularly checked and remained unremarkable. Upon completion of four months of treatment the former wound showed persistent scarring without clinical or radiological signs of infection (Fig. i). Since then, the appearance of the scar has continuously improved (Fig. j, k) and five months after completion of therapy, which is 14 months after the initial traffic accident, there is no evidence of infection (Fig. l).


We report a case of a 59-year-old male hospitalized in May 2017 for nephrotic syndrome, discovered after systematic dipstick. The patient’s past medical history was primary APS with lupus anticoagulant confirmed at 12-week interval, discovered in June 2015 after a second pulmonary embolism. No criteria for SLE were present. His usual treatment was vitamin K antagonist therapy.
On admission, he presented edema of the lower limbs; normal blood pressure; creatininemia 1.7 mg/dl (150 μmol/l); albuminemia 25.9 g/l; albuminuria 4.7 g/g; microscopic hematuria; normal renal ultrasound; negative anti-nuclear antibodies; positive lupus anticoagulant; and anti-PLA2R titer of 1:320 on indirect immunofluorescence, confirmed later on ELISA. HIV, syphilis, HBV and HCV serologies and screening for malignancy were negative.
Due to the high recurrence risk of pulmonary embolism when stopping anticoagulation, we did not perform a biopsy and we treated the patient as an idiopathic MN with angiotensin-converting-enzyme inhibitor. Three months after the onset of nephrotic syndrome, antiphospholipid antibodies spontaneously became negative. No remission was observed at 6 months with angiotensin-converting-enzyme inhibitor treatment with albuminemia 38 g/l, albuminuria 6.4 g/g and persistent anti-PLA2R antibodies.
Consequently, kidney biopsy was performed showing both i) antiphospholipid syndrome chronic vascular nephropathy with asymmetric fibrous intimal hyperplasia and tubular thyroidization and ii) MN stage II with diffuse glomerular basement membrane thickening on light microscopy and “spikes” on silver stain, without cellular proliferation. Immunofluorescence microscopy revealed a diffuse granular pattern of C3 and immunoglobulin G (with IgG4 dominance) staining along the glomerular basement membrane (staining for IgA, IgM and C1q were negative). Immunohistochemistry revealed PLA2R in deposits (Fig. ).
A treatment with rituximab was started 6 months after the beginning of follow-up (2 infusions of 375 mg/m2 administered 1 week apart) with 9 months later a decrease in serum PLA2R antibody levels at a titer of 1:10 on indirect immunofluorescence and partial remission.


In compliance with SCARE criteria (Agha et al. []), this report is a case of a 26-year-old African female, who presented with massive haemoptysis, chest pain and persistent cough. The patient had been treated for pulmonary TB two years before and had Human Immunodeficiency Virus, which was being treated with antiretroviral drugs. The patient was acute-on-chronic ill looking and clinically wasted. She had mild respiratory distress with respiratory rate of 22 breaths per minute. Other vital signs were normal. Physical examination revealed pale sclera and palms, which were suggestive of anaemia. On chest examination, there were crepitations on the left upper lobe area with no murmurs audible to suggest the presence of the fistula. The baseline blood confirmed anaemia with haemoglobin of 5.1 g/dl and other bloodlines were normal. An International normalized ratio (INR), urea, electrolytes and creatinine were also normal. Resuscitation was undertaken while completing other investigations. Chest X-ray (CXR) was done, with posteroanterior (PA) and lateral views showing left upper zone opacification obscuring the left cardiac knob [A,B]. The left lower zone had an opacity obscuring the left cardiac border, suggestive of multilobar infection/vascular pathology. In subsequent computed tomography angiogram (CTA), there was a reverse “S” shaped outpouching contrast content structure from aortic arch lateral to the Left Subclavian Artery (LSA) origin with adjacent pleural density and surrounding the lung opacity. The features were suggestive of aneurysm, which complicated with aortobronchial fistula surrounded by haematoma [A–C]. The lingula segment of the left upper lobe had consolidative changes and there were also bilateral diffuse patchy scattering centrilobar opacities, which suggested an active pulmonary infection [A,B]. The patient was admitted to Intensive Care Unit (ICU) for optimization in preparation for surgery. Medical therapy in the form of antitussive, sedatives, antifibrinolytics and empirical antibiotics were provided. The patient did not require any security of the airway or mechanical ventilatory support. The patient underwent TEVAR two days after ICU admission. The procedure was done via general anaesthesia with invasive lines monitoring. The right femoral artery was exposed via oblique groin incision. The left common femoral artery was punctured with 5Fr sheath for angiographic access. The initial angiogram showed that the Left Common Carotid Artery (LCCA) had a common origin with brachiocephalic trunk [A]. At approximately 10 mm distal to the LSA, a focal aneurysm was noted on the proximal descending aorta, with 13 mm base. The appearance suggested a vascular aneurysm (A). There was no opacification of the pulmonary vasculature. Through the brachial artery approach, a vascular occlusion plug (Amplatzer) was deployed to the origin of the LSA to minimize the risk of the endoleaks. The TEVAR was performed via the right groin access, using Medtronic navion thoracic stentgraft with coverage of the LSA [B]. The completion angiography showed appropriate opacification of brachiocephalic trunk and its branches, including the LCCA. There was no flow into LSA. Fistula and aneurysm were excluded. Postoperative phase was uneventful. Within the same admission (after two weeks) the patient was taken for second stage of the operation, which involved apical-lower segmentectomy and apace-posterior segment debridement and pulmonary fistula repair. The approach was via muscle sparing posterolateral thoracotomy with the chest entered through the 5th intercostal space, over unresected 6th rib. Intra-pleural mobilization of the lung was undertaken with the use of both blunt and sharp dissections. A haematoma was identified within apical-lower segment. The apical part of apico-posterior segment was attached to the aorta at the fistula site, which on mobilization the two were separated without bleeding []. The fistulae site on both aorta and lung were biopsied for microbiological and histopathological studies. An oblique fissure was complete, with less dense adhesions, for which adhesionolysis was done. The interlobar artery was identified and its overlying pleura was opened and dissected. The apical lower segment artery was identified, dissected, suture ligated and divided. The vein draining the apical-lower segment was also dissected and controlled in similar manner. The bronchus to apical lower segment was dissected and clamped, and an anaesthetist was asked to insufflate the lung for delineation of segment. The GIA stapler was used to resect apical lower segment bronchus. The stump was immersed into saline and was not leaking. The apical part of apico-posterior segment adjacent to area of the fistula was necrotic. It was debrided and closed with continuous Prolene 4/0 suture without using a healthy or pleural tissue for buttressing, because the tract was too small and was thoroughly debrided. A tissue of the fistula stump on the aorta was sampled for microbiological and histopathological studies. The aortic fistula stump was approximated with interrupted Prolene 4/0 suture. A size 7.5 rigid bronchoscope was passed into the airway, the trachea and the carina looked normal. No fistula was visualized within airway. The operation was uneventful and the patient was discharged and reviewed after two weeks for general follow up and histopathology results. Hematoxylin and Eosin (H&E) sections [A,B] showed fibrous connective tissue with poorly formed granulomas while lung sections showed necrotizing granulomatous inflammation. The granulomas were composed of aggregates of epitheliod histiocytes with central caseating necrosis and Langhan-type giant cells. Acid-fast fast bacilli or fungi were not evident. Although acid-fast bacilli were not identified [C,D], mycobacterial infection was still favoured. Correlation with microbiological culture and susceptibility testing was advised. The patient was put on anti-tuberculous treatment for nine months, which she completed uneventfully. She is currently coming for follow-ups every three months to check for possible recurrence.


We present a case of severe AKI with rhabdomyolysis in a 49-year-old, experienced, competitive male trail runner (weight 66 kg, height 183 cm, body mass index 19.7 kg/m2, running 5-6 times/ week, training load 70-100 km/week) who presented six days after a 110-km trail race to the accident and emergency department. He participated in one of Europe’s toughest ultra-trail race, the Grossglockner Ultra-Trail, a 110-km trail race with 6.500 m positive climb and an average elevation higher than 2,000 m for at least half of the course, including technically difficult terrain and trails. He finished the race in a time of approximately 18 hours (overall winning time of 14:40:14 hr:c). Prior to the event, he was free of injury, otherwise fit and healthy, non-smoker, with no other past medical history of note. Blood tests approximately six months before the event showed a normal renal function (creatinine 1 mg/dL, glomerular filtration rate [GFR] >90 mL/min/1.73 m2). Immediately prior to the event, he ingested 500 mg of naproxen and 20 mg of esomeprazole. Throughout the race, he consumed little oral fluids (approximately 4 litres of fluids in total, during approximately 18 hours of running). There was no urination throughout the race. Immediately after crossing the finish line, he started to re-hydrate and increased his fluid intake ad libitum and shortly thereafter had one episode of chocolate brown urination. He felt fine, with some post-race fatigue and subsequently returned home. The following day he noticed some mild generalised swelling with oliguria, despite regular food and fluid intake. After two days, urination returned to normal, but the generalised oedema increased over the following days with a combined weight gain of approximately 10 kg. Subsequently, he felt generally tired and fatigued, and at this stage he presented to the local accident and emergency department six days post-event. Biochemically the diagnosis of severe AKI with rhabdomyolysis was made. Conservative measures with intravenous and oral fluid therapy were instigated, and renal replacement therapy was contemplated. However, his kidney function gradually improved, as well as elevated potassium levels, with conservative measures; therefore renal replacement therapy was not required. Further investigations included abdominal radiographs (due to abdominal extension), ultrasounds of both kidneys, urine analysis (dip stick and microscopic) and serial laboratory blood tests, as well as cardiac assessment, including ECG. Radiological imaging and cardiological assessment were unremarkable, as well as blood gas analysis, without signs of metabolic acidosis. The patient remained hospitalised for two weeks, and on discharge his renal function and clinical symptoms had improved considerably. Subsequent regular blood test demonstrated a gradual return of his creatinine levels after approximately six months. Estimated laboratory GFR remained reduced, with no evidence of microproteinuria (albumin-to-creatinine ratio) (Table ). At this point, he was allowed to return to gradual aerobic activity under close supervision of his sports physician.


The patient is a 47-year-old Caucasian man presenting to the emergency department with dysphagia. He states that about an hour after his dinner the previous night, he had production of thick mucus with inability to swallow. He slept well that night, but the next morning, he reported that he had difficulty swallowing both pills and liquids. He also admitted to some mild hoarseness.
The patient reports that he had a Wegener's flare about three months prior which involved paresthesias of the lower extremities, sinusitis, and leukocytoclastic vasculitis. He was treated with pulse dose steroids, rituximab, and prednisone. His prednisone had been titrated down to 20 mg twice a day at the time of presentation. He also stated that he had an endoscopy done 1 month prior due to dental erosions, where he was found to have evidence of esophageal candidiasis.
He denied any other symptoms including fever/chills, cough, hemoptysis, shortness of breath, sore throat, heartburn, chest pain, abdominal pain, hematuria, or upper and lower extremity weakness/numbness.
His past medical history included hyperlipidemia and granulomatosis with polyangiitis that was diagnosed 13 years ago. At that time, he presented with a sinus flare and was put into remission by Cytoxan. His GPA manifestations have included sinusitis, saddle-nose deformity, peripheral neuropathy, and skin lesions. He has never had pulmonary or renal involvement. He drinks alcohol socially. He denies smoking or illicit drug use. Surgical history and family history are noncontributory.
On arrival to the emergency room, patient was tachycardic at 128 beats/min and was slightly hypertensive at 144/86 mm Hg. On physical examination, he was a middle-age Caucasian man in no acute distress. He did have a rather Cushingoid appearance. Pupils were equally round and reactive to light. Oropharyngeal examination revealed oral thrush on his tongue without evidence of erythema or ulcers. Nasal turbinates were of normal appearance. Saddle-nose deformity was present (Figure ). There was no lymphadenopathy. Cardiovascular examination did not reveal any abnormal heart sounds. Lung sounds were clear. Abdomen was soft and nontender. Upon neurological examination, cranial nerves II-XII were intact. Motor and sensory examinations were intact. He had no dysdiadochokinesis or dysmetria. His gait was normal. Skin examination revealed livedo reticularis on his lower extremities with some healed crusted lesions (Figure ).
In the emergency department, electrocardiogram (EKG) revealed sinus tachycardia. Laboratories were largely unremarkable except a slight leukocytosis of 11.4 K/µL and albumin of 3.0 g/dL. Screening for mononucleosis was negative, and rapid Group A Strep screen was also negative. An esophagram was obtained which showed an irregular shaggy appearance of the esophagus. Due to the fact that he was on steroids, he was started on fluconazole for presumed esophageal candidiasis and admitted to the hospital. A pharyngogram was obtained which showed severe oropharyngeal dysphagia; however, these findings were not consistent with esophageal Candidiasis. Other etiologies for his dysphagia had to be entertained, including possible cranial nerve involvement of his Wegener's. A bedside laryngoscopy was performed which showed a slightly rotated larynx and abnormal vocal cord function. Neurologist was consulted who noted that the patient had an absent gag reflex. Computed tomography (CT) of the neck with IV contrast was gotten which was unremarkable Therefore, magnetic resonance imaging (MRI) of the head was ordered which revealed an acute left medullary infarct (Figures , , and ) as well as two acute lacunar infarcts involving the left centrum semiovale (Figure ). Lipid panel was abnormal with a total cholesterol of 239 mg/dL, LDL of 223 mg/dL, HLD of 33 mg/dL, and triglycerides of 290 mg/dL. His glycated hemoglobin (HbA1c) was 5.8%. Echocardiogram demonstrated normal ejection fraction, left ventricular hypertrophy, and normal left atrial chamber without thrombus. Due to his relatively young age and the fact that he had only one risk factor for stroke, we could not attribute his stroke to only hyperlipidemia. Other causes of stroke had to be evaluated including vasculitis or hypercoagulability. Computed tomography angiography (CTA) of the head was negative for vasculopathy. Anticardiolipin, lupus anticoagulant, and beta-2 glycoprotein were all negative. C-ANCA was positive at 1:40, and anti-PR3 was positive at 52.9 U/mL. P-ANCA was negative. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated at 45 mm/h and 2.2 mg/dL, respectively. A lumbar puncture was done which was negative for infection and only showed a mildly elevated CSF protein of 77 mg/dL.
The patient was started on aspirin in addition to high intensity statin which he was already on. Azathioprine was added by his rheumatologist, and his steroid taper was continued. Over the course of his hospital stay, he slowly had improvement of his dysphagia and hoarseness. A repeat pharyngogram still showed significant dysphagia, and the patient had to undergo percutaneous endoscopic gastrostomy tube (PEG) placement with tube feeds. Patient was discharged in stable condition with instructions to follow-up with his rheumatologist.


A 79-year-old Caucasian female presented to the emergency department with persistent shortness of breath and rapid irregular palpitations that had been ongoing for seven hours. She had a past medical history of coronary artery disease, severe aortic stenosis, essential hypertension, and dyslipidemia, and she had undergone an angioplasty without stents 13 years prior. A physical examination revealed an initial blood pressure of 71/50 mmHg [heart rate: 132 beats per minute (bpm)] that spontaneously increased to 107/61 mmHg (heart rate: 111 bpm) within five minutes, an irregularly irregular pulse, oxygen saturation of 95% on room air, variable S1 and S2 sounds with a 3/6 systolic ejection murmur in the left upper sternal region, and fine end-inspiratory pulmonary crackles at the bilateral bases. No peripheral edema was noted. A twelve-lead electrocardiogram revealed atrial fibrillation and rapid ventricular response at an average rate of 144 bpm. A portable chest X-ray showed increased pulmonary vasculature markings along with air bronchograms and subtle bilateral costophrenic angle obliteration. The patient’s laboratory workup upon admission is shown in . Intravenous heparin was started for anticoagulation. Given the clinical picture of pulmonary edema, urgent electrical cardioversion was delivered, resulting in restoration of sinus rhythm. A subsequent two-dimensional echocardiogram showed preserved left ventricular function (estimated ejection fraction: 55%–60%), moderate left ventricular hypertrophy, a severely dilated left atrium, and severe aortic and moderate mitral valve stenosis. Amiodarone was started with oral loading at a dose of 400 mg three times per day, beginning on the first day of admission.
On the fourth day following admission, the patient developed mild shortness of breath. A repeated chest X-ray showed a case of pulmonary congestion not significantly altered from the previous one. A repeated brain natriuretic peptide test showed the level was increased to 438 pg/ml. Her sodium (Na) was noted to have dropped from 134 meq/l to 126 meq/l. She was treated with a 40-mg dose of furosemide intravenously and her home regimen of hydrochlorothiazide (HCTZ), which had been discontinued upon admission, was resumed. This resulted in a subsequent improvement of her symptoms. The amiodarone was reduced to 400 mg daily; then, on hospitalization the fifth day, it was further reduced to 200 mg daily. On the sixth day, the patient began to complain of nausea, generalized weakness, headache, and blurred vision. A physical examination revealed a distended jugular vein, pulmonary rales, and the same systolic murmur noted previously. Peripheral edema remained absent. A computed tomogram of the head ruled out acute intracranial changes. Repeat serum Na level result was 124 meq/l, and HCTZ was discontinued. However, the patient’s Na level continued to drop throughout the next day (the seventh day) to 113 meq/l, reaching a nadir of 110 meq/l in less than 24 hours. Serum and urine osmolarities were 258 Osm/kg and 246 Osm/kg, respectively. Random urine Na, uric acid, and creatinine were tested (. The fractional excretions of Na and urate (FEurate) were 0.36% and 19.6%, respectively. At that point, syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was suspected. Other causes of hyponatremia, such as acute kidney injury, hypothyroidism, and adrenal insufficiency were ruled out (. The patient’s intake of fluid was restricted and, due to the severe hyponatremia, she was treated with two 15-mg doses of tolvaptan spaced 12 hours apart. Due to a lack of improvement initially, an additional single dose of 30 mg was administered on the following day (the eighth day). An increase in serum Na level by 15 meq/l was subsequently noted in the following 24 hours and due to concern for potential inadvertent complications from rapid correction, dextrose 5% water was infused at 100 ml/h for 24 hours and two doses of desmopressin 2 µg were administered intravenously six hours apart. The rise in serum Na was successfully halted and instead it dropped to a level of 120 meq/l on day 10. As it has been linked to SIADH in very rare case reports, the amiodarone was suspected to have been the offending agent and was discontinued on the ninth day. Instead, sotalol was initiated 48 hours later for the maintenance of sinus rhythm. Sodium chloride (NaCl) tablets (3 g/day) were added and her serum Na level gradually improved within a few days to 129 meq/l on day 13 and 135 meq/l on day 18 after discharge, respectively. The serum Na levels and administration times of potentially Na level-altering medications are depicted in .


A 44-year-old man was admitted to our clinic after falling while playing soccer. The initial complaint was severe right thigh pain with a visible deformity of the femur. In our initial evaluation, there were no associated injuries. We could neither establish an open wound nor neurologic deficits. His medical history revealed a right femoral shaft fracture caused in a traffic accident approximately 22 years ago, which had been treated with intramedullary nailing at a hospital in China. Anteroposterior and lateral radiographs obtained in the emergency room revealed a refracture of the right femoral shaft and a bent IM nail (Fig. ). The initial varus deformity of the nail was 60.1° in the coronal plane. We tried closed manual reduction of the fracture and bent nail with analgesics in the emergency room. After reduction, the varus deformity was decreased to 26.0° in the coronal plane (Fig. ).
Under general anesthesia, the patient was then placed in the left lateral decubitus position, and closed reduction of the fracture and bent IM nail was tried under C-arm image intensifier control. After the nail was straightened (Fig. ), the entry site of the nail at the greater trochanter was exposed through a 5 cm skin incision. The nail was extracted smoothly by the standard method and in one piece. After nail extraction, the reaming of the intramedullary canal was performed to a diameter of 13 mm. A new IM nail (12 mm × 380 mm) was inserted through the previous insertion site and fixed with locking screws (Fig. ). There were no postoperative complications and the patient was mobilized with partial-weight bearing assisted with a crutch on postoperative day two. One year after surgery, the fracture union was complete and the patient was pain-free (Fig. ). The range of motion in the hip and knee were normal.


A 27-year-old man, who had suffered a right femur diaphyseal fracture after a motorcycle accident and been treated with an IM nail at our centre three years before, presented again after falling down the stairs. The incident had resulted in a refracture of the femoral shaft with posterolateral bending of the nail. The valgus deformity of the nail was 16.1° in the coronal plane with an apex-posterior angulation of 34.8° in the sagittal plane (Fig. ). Removal of the nail and internal fixation were indicated.
The patient was placed in the left lateral decubitus position under general anesthesia. Initially, a closed manipulation of the bent nail was attempted under C-arm image intensifier control, but no difference in the valgus deformity was achieved. Intraoperatively, the skin was incised for a length of 15 cm above the bent part of the nail. Using a high-speed cutting burr, the apex part of the bent nail was progressively sectioned until the nail could be straightened. During this procedure, soft tissues were protected and permanently irrigated while any metal debris was carefully removed with the suction. Afterwards, the nail was extracted through the original incision at the hip. However, in the process of extracting the nail, the comminution of the fracture site was extended and had to be fixed with a cerclage wire. Then the femoral canal was reamed to 13 mm and a new nail (13 mm × 360 mm) was inserted (Fig. ). No complications occurred postoperatively. Six months after surgery, the fracture union was complete with sufficient callus formation around the fracture site (Fig. ).


A 13-year-old man presented with a 2-year history of multiple depressed skin lesions on his face. The lesions initially presented as asymptomatic erythematous patches which had gradually developed depressed centres over time. There was no history of trauma, ulceration, fever, cough, breathlessness, sensory loss, or intralesional steroid used to treat the lesions. Before presenting to our hospital, he had been diagnosed as lupus vulgaris in another hospital and had been given antituberculous therapy for 6 months. However, the skin lesions had gradually progressed during treatment. On physical examination, multiple erythematous plaques with a slightly atrophic appearance were seen on the patient's face (A and B). A full neurological examination was carried out, and the patient was found to have intact sensation. There was no palpable enlargement of peripheral nerves. Laboratory findings, including blood and urine routine examination, biochemistry investigations and antinuclear antibody test, were within normal limits. Purified protein derivative test proved to be negative, and a posterior-anterior chest X-ray revealed bilateral hilar lymphadenopathy. The skin biopsy showed dermal numerous compact epithelioid granulomas, surrounded by a collar of sparse lymphocytes with no evidence of acid-fast bacilli or fungi (C and D). There was no polarizable foreign material within the granulomas. We finally diagnosed the patient with atrophic cutaneous sarcoidosis. The patient was started on 0.5 mg/kg/day of prednisone (25 mg/day) and 6.0 mg/kg/day of hydroxychloroquine (300 mg/day). After 2 months, partially regression of the erythematous plaques and the bilateral hilar lymphadenopathy was achieved. Prednisone was tapered by 5 mg/month and was discontinued 4 months later. Then, oral administration of hydroxychloroquine was given for the consecutive 3 months. After 9 months of treatment, the patient presented an almost complete clinical response without bilateral hilar lymphadenopathy (E and F).


A 36-year-old female presented with dull aching pain in the left elbow for eight months. She noticed a progressive loss in the range of movements of her left elbow. One of her close relatives was on anti-tubercular treatment for pulmonary tuberculosis. She had a low-grade fever without cough, chills, rigor, night sweats, and loss of appetite or loss of weight. At the time of examination, there was fullness around the lateral aspect of the elbow, with synovial thickening around the radio-capitular joint. There was tenderness over radial head. The range of flexion was 70 degrees, and the supination and pronation were restricted to 30 degrees.
Hemogram showed a total leukocyte count of 12,000/mm3 with increased neutrophil count, hemoglobin of 12 g/dL, and hematocrit of 42%. Renal and liver function tests were all within normal limits. The erythrocyte sedimentation rate (ESR) was elevated to 70 mm per hour. The C-reactive protein was within normal limits. Mantoux test was positive. Sputum culture and GeneXpert® test (Cepheid, Sunnyvale, CA, USA) were negative. Fungal culture and real-time polymerase chain reaction were negative. Plain X-ray of the left elbow showed peri-articular osteoporosis with the destruction of the head and neck region of the proximal radius. Even though there was severe osteopenia, there was no destruction in the distal articular surface of the humerus and trochlea-humeral joint. Periosteal reaction was seen beyond the destruction in radius (Figures , ). MRI revealed 4.5 × 3.5 × 2 cm soft tissue lesion in the anterior part of the proximal radius. There was erosion of the anterior part of the head and neck of the radius. Periosteal reaction was seen around the neck. Effusion and synovial thickening were seen in the elbow joint. MRI features were suggestive of tuberculosis of the elbow (Figure , ).
With the above clinical features and investigations, our diagnosis was tuberculosis of the elbow. Pigmented villonodular synovitis, early synovial osteochondromatosis, and inflammatory arthritis were considered as the differential diagnosis.
An open biopsy was performed through a lateral approach. Grossly, there were multiple bits of bone and synovial tissue measuring 3 × 2 × 1 cm. Histopathology showed a collection of chronic inflammatory cells in the bone and soft tissues with histiocytes showing marked emperipolesis and foci of necrosis with palisaded granuloma (Figures , ). Immunohistochemistry of the histiocytes in the lesion showed positivity for S-100 protein (Figure ), confirming the diagnosis of solitary primary Rosai-Dorfman disease of the upper end of the radius.
Post-operatively the left upper limb was immobilized for about two weeks in a long arm slab. The patient was further followed up in the oncology department. She was treated with glucocorticoid and methotrexate. After 18 months, she is asymptomatic, even though there is a restriction of elbow movements. There is no evidence of recurrence.


A 28-year-old woman was admitted for severe preeclampsia at 33 + 4 weeks. It was her fifth pregnancy. None of her previous pregnancies had been complicated by preeclampsia. Her foetus presented with severe intrauterine growth restriction (estimated foetal weight < 3rd percentile).
Her initial physical examination was remarkable for hypertension and a dipstick proteinuria (2+). She had no neurological symptoms.
Initial laboratory investigations (Table ) revealed mild renal impairment, hyperleukocytosis, mild anemia without thrombocytopenia. Coagulation assays were unremarkable.
Two days after admission, at 33 + 6 weeks, she presented with epigastric pain and her foetus was bradycardic (80 beats per minute). An emergency Cesarean section was performed during which a large retroplacental hematoma was uncovered. She delivered a 1400 g healthy baby boy. Postpartum hemorrhage (1.2 L) occurred immediately prompting the administration of 3 L of crystalloid fluids, and 1 g of tranexamic acid. In order to prevent eclampsia, treatment with magnesium sulfate was initiated.
Due to severe preeclampsia and anuria following the Cesarean section, she was transferred to the intensive care unit (ICU) for monitoring.
Physical examination revealed no fever (37.7 °C), controlled blood pressure (138/84 mmHg under 4 g per hour of intravenous nicardipine) and no tachycardia (97 beats per minute). Neurologic examination was remarkable for drowsiness (Glasgow score = 13) with no evidence of focal neurological signs and normal osteotendinous reflexes. Epigastric pain was persistent.
Immediately after surgery, hemostasis disorders consistent with disseminated intravascular coagulation (DIC) appeared (Table ) with an International Society on Thrombosis and Hemostasis score of seven, prompting the administration of five units of red blood cells, three units of fresh frozen plasma, and 3 g of fibrinogen. At this point, prothrombin time fell to 46%, platelets and fibrinogen decreased to 23.000 and 1.92 g/L respectively, and D-dimer value was above 20.000 μg/L.
Signs of HELLP syndrome were present, as defined by severe cytolysis, thrombocytopenia and microangiopathic hemolytic anemia (Table ). ALF developed, as defined by grade 3 encephalopathy, and a MELD score of 32. Blood glucose test remained normal, but a peak lactate level of 7 mmol/L was observed on day 2. Simultaneously, an acute kidney injury (KDIGO stage 3) occurred (Table ) requiring hemodialysis (overload and anuria). Finally, empiric antibiotic therapy with tazocillin was started due to suspected sepsis with fever plateau at 38.5.
Four days following delivery, the patient was referred to our renal ICU due to suspected TTP. The neurological examination was unchanged with persistent drowsiness. A brain magnetic resonance imaging (MRI) was deemed normal. Abdominal MRI showed heterogeneous high signal intensity on T1 and T2-weighted images in the posterior right lobe of the liver suggestive of liver necrosis (Fig. a, b, c).
In the hypothesis of a coincident TTP, methylprednisolone (1 mg/kg) and daily TPE with 100% frozen plasma units were initiated. By the fourth TPE, liver function and platelet count were restored to normal values (Fig. d). TPE was thereafter gradually tapered off with a total of 11 sessions (8 daily sessions, then two sessions spaced 48 h apart and one last session 4 days later).
As part of the diagnostic work-up, ADAMTS13 activity was found to be undetectable, yet anti-ADAMTS13 auto-antibodies were not found. Corticosteroids were stopped as soon as ADAMTS13 auto-antibody negativity was obtained (total duration of 9 days). A kidney biopsy demonstrated severe acute tubular necrosis but no signs of cortical necrosis or TMA. Atypical hemolytic and uremic syndrome was excluded from renal biopsy and alternate complement pathway explorations, including genetic analysis (Table ). Acute fatty liver of pregnancy was ruled out given the presence of hemolysis, and the absence of hypoglycemia and hyperechogenicity on liver ultrasound. Antiphospholipid antibody syndrome was also ruled out.
ADAMTS13 activity rose to 17 and 24%, 4 and 7 days, respectively, after discontinuation of TPE. Genetic analysis of ADAMTS13 did not reveal any sequence variation. Both antibody-mediated TTP and congenital TTP were thus excluded. On hospital discharge (27 days after delivery) the patient had recovered complete liver and kidney function.