A 11-year-old boy was admitted to our outpatient department on October 15, 2018, with chest tightness after exercise for 5 years, aggravated in half a month, and repeated hemorrhinia for 2 years. The patient had a history of syncope 1 year ago. His grandmother had a history of pulmonary hypertension. On admission examination, his heart rate was 78 beats/min, his blood pressure was 102/65 mm Hg, and his SpO2 was 96%. The heart sounds were regular, and no murmur was detected. No obvious abnormalities were observed in the rest of the physical examinations. Blood tests noted normal hemoglobin (146 g/L, normal 130–175), increased N-terminal pro-brain natriuretic peptide (NT-ProBNP, 643pg/ml, normal <125), increased total bilirubin (30 μmol/L, normal 3.4–21.1), increased direct bilirubin (10.1 μmol/L, normal < 6.8), increased indirect bilirubin (20.6 μmol/L, normal < 3.1–17.0), and increased alkaline phosphatase (324U/L, normal 45–125). Electrocardiograph (ECG) revealed a sinus rhythm, and right axis deviation reached + 132° (Fig. ). Transthoracic echocardiography revealed a right atrial dimension of 40 mm, a right ventricular dimension of 30 mm, a left atrial dimension of 28 mm, a left ventricular end-diastolic dimension of 43 mm, a left ventricular end-systolic dimension of 30 mm, a left ventricular ejection fraction of 73%, a tricuspid annular plane systolic excursion of 15 mm, a maximum tricuspid regurgitation velocity, and a pulmonary artery systolic pressure of 91 mm. Cardiac magnetic resonance revealed a enlargement of right atrium and right ventricle (Fig. ). Cardiopulmonary exercise test showed that the overall functional status of cardiopulmonary motor function, the effectiveness of oxygen uptake ventilation and nitrogen dioxide ventilation were significantly limited. Computed tomographic pulmonary angiography (CTPA) showed enlargement of right ventricle, dilatation of main pulmonary artery, changes of pulmonary hypertension, and diffuse small patches of light ground glass opacity in both lungs.
The patient underwent right cardiac catheterization, acute pulmonary vasodilator testing (AVT) and pulmonary angiography on October 29, 2018. Details are as follows: (1) Baseline blood pressure was 115/54/74 mm Hg, pulmonary arterial pressure (PAP) was 95/40/59 mm Hg, pulmonary artery wedge pressure was 8/7/6 mm Hg, cardiac output was 4.23L/min, cardiac index was 2.9L/min/m2, and pulmonary vascular resistance was 12.53 Wood U, (2) PAP was 109/32/60 mm Hg after inhalation of vantamivir (AVT negative), (3) Pulmonary angiography showed dilatation of left and right pulmonary arteries, no obvious stenosis, filling defect or occlusive lesions, no decrease or absence of distal segmental perfusion, and the perfusion velocity was acceptable.
Later, we used high-throughput gene sequencing technology to detect all exon genes for the patient. Genetic tests revealed that the patient carried a non-sense mutation of BMPR2, c. 1452G > A, which resulted in the termination of BMPR2 protein at 484 position and significantly affected the function of the protein (Table ). Mutation analysis of ACVRL1, ENG, and SMAD4 was normal.
According to the symptoms, signs and examination results, we diagnosed familial pulmonary arterial hypertension and suspected hereditary hemorrhagic telangiectasia. The patient was discharged from hospital on October 28, 2018, and was treated with ambrisentan 2.5 mg qd.
On November 26, 2018, the patient had a large amount of black stool. The stool was hard and normal in shape, and there was little blood on the surface. The patient had abdominal discomfort and no bleeding and ecchymosis on the skin. At 4 am on November 28, 2018, the patient woke up in sleep, followed by convulsion, characterized by sudden loss of consciousness, eyeball upturn, sudden generalized and ankylosing facial and extremity muscle convulsions, cyanosis of lips, incontinence of urine and feces, and self-remission after 30 seconds. The patient was immediately admitted to the emergency department. Blood tests noted decreased hemoglobin (62 g/L, normal 130–175), increased NT-ProBNP (1010pg/ml, normal < 125), increased creatine kinase (721U/L, normal 55–170), increased lactate dehydrogenase (247U/L, normal 135–225). Faecal occult blood test was positive. There were no significant changes in echocardiographic data. Short-range video electroencephalogram was normal. No obvious abnormalities were found in cranial magnetic resonance imaging and magnetic resonance angiography. We planned to have further gastrointestinal endoscopy, but the patient's family refused. Acute gastrointestinal bleeding and convulsions caused by acute ischemic-hypoxic encephalopathy were considered in the diagnosis. Therapeutically, omeprazole was given to inhibit gastric acid secretion, tranexamic acid and etamsylate were used to stop bleeding, and suspended red blood cells were infused. On December 2, 2018, hemoglobin was 104 g/L, and fecal occult blood test was negative. During the follow-up for the next month, the patient had no black stool, no hemorrhinia, and no significant changes in chest tightness.


The patient is a male, 60 years old with a height of 178 cm, and a weight of 77 kg. He was admitted to hospital for complaint of joint pain and limitation of motion for nearly 10 years. He had a history of ORIF surgery 10 years ago due to a fall injury-induced right distal humerus fracture.
Physical examination displayed that the right elbow joint was swollen, the pain was obvious during the activity, and the range of motion was limited (motion arc <30°, rotation range <30°). There was no evident obstacle in the right hand; the skin feeling in the right upper limb was reduced. The elbow joint function evaluation was poor (hospital for special surgery [HSS] score 15 points, Mayo score 55 points). Plain radiographs, computed tomography (CT) scan, and 3D reconstruction of the plates by Mimics 20.0 software (Materialise, Leuven, Belgium) revealed fracture lines, fracture displacement, and fixator breakage in the right distal humerus (Fig. ). The personalized TEA was decided after consultation and discussion. The process diagram of the preoperative and prosthesis design is shown in Figure .
The CT was scanned by Philips company's 256-row spiral CT (Philips, Amsterdam, Netherlands). The parameters are as follows: tube current 232 mA, tube voltage 120 kV, and scanning layer thickness 1 mm. After scanning, the CT data of the bilateral elbow joints in digital imaging and communications in medicine format was collected and imported into Mimics software (Materialise) for 3D reconstruction of the bilateral elbow joints, and the stereolithography (STL) format file was saved. The STL was a format of triangular mesh to represent the 3D CAD model.
The STL format file of the 3D right elbow joint model was imported into Magics software (Materialise). The model should be repaired without structural errors and moved to the appropriate position of workbench. The support structure must be generated to prepare for printing. At last, the adjusted STL file was exported to the SLA450 resin printer, and the patient's stereolithography resin elbow joint model was printed. The resin models prepared in this process could provide references for the osteotomy range and preoperative simulation.
The 3D printed hinge elbow joint prosthesis was designed according to the mirror image of the symmetrical humerus. The personalized elbow joint prosthesis was modeled on the blueprint of typical Coonrad–Morrey elbow prosthesis. According to the affected bone condition of the humerus and the residual bone morphology after osteotomy, the prosthesis stem's length and size were determined. For insurance purposes, we designed three “sleeves” with thicknesses of 4, 8, and 12 mm, which were used to compensate for the size deviation between the osteotomy and the prosthesis. The elbow joint prosthesis was fabricated with Ti6Al4V powder using electron beam melting techniques in an Arcam Q10 plus metal printer.
The resin model of the right elbow joint was used to simulate intraoperative osteotomy. The affected bone of the proximal ulna and the distal humerus was removed, then the 3D printed personalized prosthesis was implanted into the residual bone. The simulation process verified that the prosthesis matched well with bone.
The patient was taken the supine position after general anesthesia and disinfection. The medial incision of the right elbow was taken. First, the obsolete fixation device was removed, and the osteotomy was performed as simulated. The broken bone at the proximal end of the ulna, and the olecranon were cut according to the preoperative design; then the olecranon tip was removed. The elbow was flexed to separate the distal end of the humerus from the ulna. The middle part of the trochlea humerus was removed by the bone saw, and the medullary cavity of the humerus was opened. Then the T-handle was used to insert into the medullary cavity before testing the prosthesis. The prosthesis edge was just flush with the capitulum humerus and the articular surface of humeral supracondylar. The ulna was reamed along the long axis, the proximal ulna and the distal humerus were prepared, and the prosthesis was inserted into the ulnar and the humeral medullary cavity, respectively. The bolts were used to fix the prosthesis at both ends. The prosthesis was ensured that elbow joints could realize flexible extension and flexion, and the motion arc of the passive elbow joint was ensured to reach 140° nearly. Besides, to maintain the humerus’ integrity as much as possible, wire fixation was used to bound the large bone pieces at the distal end of the humerus. Finally, the intraoperative positioning showed that the prosthesis was in the correct position; the incision was closed layer by layer. (The surgical procedure is shown in Fig. )
The operation was completed successfully. It took 65 minutes from osteotomy to the installation of the personalized elbow prosthesis. The blood loss volume was 235 mL. Rehabilitation guidance was given in the following rehabilitation exercise. The elbow function was evaluated with Mayo and HSS function scores during the follow-up, as shown in Table . The motion ranges before and after surgery (36th months) of the right elbow are shown in Figure . The elbow joint motion range increased from 15-45° to 0-135°, and the rotation range reached 90°. The Mayo score was 95 points, and the HSS score was 90 points. The elbow joint plain radiographs at the 1st, 3rd, 6th, 12th, 24th, and 36th months after operation were reviewed. The plain radiographs of last time (36th months after operation) showed in Figure revealed that the prosthesis was in a good position and no sign of loosening. No complications such as fractures and dislocations around the joints were found. There was no symptom of nerve damage according to the physical examination. There was no sign of infection according to the laboratory test results of erythrocyte sedimentation rate and C-reactive protein. The patient was sufficient to complete the basic life activities such as washing, dressing, and eating.


A 65-year old male patient with atrial fibrillation conducted anterogradely through an AP, was hospitalized for catheter ablation. He presented recurring episodes of palpitations lasting minutes to hours every 2 to 3 weeks. The physical examination revealed a grade II apical systolic murmur and was otherwise normal, without any sign of left or right heart failure. The twelve-lead ECG showed sinus rhythm with a heart rate of 70 beats per minute, normal PR interval(160ms) with no delta wave. Echocardiography revealed a non-dilated left ventricle with a normal ejection fraction of 58%. Neither the 24-hour Holter ECG, nor the exercise stress test revealed presence of AP – the PR interval was normal and no delta wave was detected. Most probably AP has become latent due to chronic amiodarone treatment of 200 mg/d for several months.
The patient underwent an electrophysiological study under local anesthesia. During hospitalization, the ECG records in both atrial fibrillation and sinus rhythm revealed no AP (Figure A, B,). A catheter was placed in each of the: coronary sinus, right ventricle, high right atrium, and at the His bundle region. Programmed stimulation of the atria and ventricles was performed. A normal His-ventricle (HV) interval of 48 ms was documented without any sign of antegrade or retrograde conduction through an AP. After atropine injection repeated atrial and ventricular stimulation could not induce any reentrant tachycardia and the HV remained normal with antegrade and retrograde conduction through the nodal pathway. Atrial fibrillation was induced by aggressive atrial stimulation of 150 ms but it only resulted in narrow QRS and no conduction through an AP (Fig. ). As a result, we decided to inject adenosine boluses of 12, 18, and 36 mg followed by 10 cc of saline flush, with 3 to 5 beats conducted through a left lateral AP (Fig. ). Mapping could not be performed during the transient effect of adenosine. Since 5 mg of betablocker and 1 vial of Digoxin were injected but without any sign of AP, the AP was further mapped under continuous adenosine infusion of 1.5 mg/kg adenosine over 5 minutes. Under adenosine infusion the AP became apparent (Fig. ) and the mapping of the lateral mitral ring together with catheter ablation using the transseptal approach were possible. Only antegrade conduction through the AP was observed, without retrograde conduction. After 3 minutes of mapping, a good spot was found in the left lateral wall and catheter ablation was performed (Fig. ) with subsequent complete AV block due to adenosine (Fig. ). After the infusion was stopped the normal sinus rhythm resumed. Upon repeating the bolus of adenosine with complete AV block no sign of AP was detected (Fig. ). Programmed atrial and ventricular stimulation was performed without conduction through an AP.
In the follow-up, a catheter ablation of atrial fibrillation was also performed as the patient continued to present atrial fibrillation (AF) with narrow QRS.


Ms. A is a 26-year-old single unemployed woman referred to a tertiary Neuropsychiatry Unit for ongoing management of neuropsychiatric symptoms of SSADH deficiency. Delayed developmental milestones and seizures were noted from an early age. At 4 years of age, Ms. A was diagnosed with epilepsy and global developmental delay of unknown aetiology. No further work-up was conducted. She was treated with antiepileptic medication and early psychosocial intervention, attending specialised primary and secondary schools.
At 12 years of age, Ms. A was diagnosed with SSADH deficiency following the diagnosis of her younger brother with the same condition. Her diagnosis was confirmed via urinary organic acid quantification, with elevated 4-hydroxybutyric acid and 4,5-dihydroxy hexanoic lactone levels. Genotyping was not performed. Formal neuropsychological testing at the time revealed mild-to-moderate intellectual disability.
From age 14, Ms. A experienced significant functional decline with manifestation of worsening OCD symptoms. She displayed marked difficulties initiating tasks, obsessional slowness and hesitancy in her activities of daily living, particularly when toileting and eating resulting in incontinence and weight loss, driven by obsessional doubt (about whether she was eating correctly or too quickly, had lifted her leg the correct way to put on trousers), and fears that certain behaviours may result in harm to her mother or brother. She exhibited motor rituals, particularly regarding the placement of food utensils and the correct “cutting” of food, and stereotypies of her hands and face involving wiping and chewing. Mealtimes were particularly problematic: prefaced by 30 min of pacing, 30–45 min of ordering cutlery, and then 1–2 h of slow mastication, marked by frequent pauses, requiring prompting to continue. She denied intrusive internal imagery. There were no religious or sexual preoccupations, counting or cleaning behaviours. Delusions and hallucinations were not apparent. Ms. A also showed increasing agitation and anxiety. When 22-years-old, Ms. A was referred to the Neuropsychiatry Unit for assessment and symptomatic management of these symptoms. Her score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at initial assessment was 33, denoting extreme OCD (0–13 mild, 14–25 moderate, 26–34 moderate-severe OCD; 35–40 severe OCD) []. On mental state, she was well-groomed and politely-engaged. She had markedly reduced eye contact and a mild fine tremor of her upper limbs. Her speech was slow, had low tone and was mildly dystonic. Her vocalisations were slow, with long latency and were brief. Her affect was restricted yet congruent with her mood. There were no psychotic phenomena, yet she was preoccupied with internal cognitions of doubt and uncertainty. Neurological examination revealed mildly elevated tone, particularly on augmentation, with cogwheeling and hyperreflexia bilaterally. She demonstrated occasional orobuccal lip-sucking movements and athetoid movements of the trunk. She had reduced arm swing when walking, pedestal turning, with reduced foot clearance and stride length. Eye movements showed some saccadic intrusions into slow pursuit movements, and saccadic over-and under-shoot requiring multiple small corrections. Her only treatment at this time was lamotrigine 75 mg bd.
Neuroimaging revealed significant increased T2 signal in the pars interna and externa of the globi pallidi, substantiae nigrae and dentate nuclei bilaterally (Fig. ). Moderate volume loss was also evident involving primarily the frontal lobe white matter, deep grey matter nuclei, brainstem and cerebellum.
Ms. A commenced the serotonergic medication escitalopram, which was gradually up-titrated from 10 mg to 70 mg od. This moderately improved her obsessional slowness, psychomotor retardation and motor rituals. Spontaneity in initiating movements and complex activities remained problematic. Her Y-BOCS scale decreased to 24 over 18 months, and the duration of mealtimes halved.
Further attempts to optimise Ms. A’s residual OCD symptoms were made: the adjuncts risperidone 0.5 mg od, methylphenidate 5 mg od, mirtazapine 7.5 mg od were added cumulatively. These medications offered no benefit with her obsessive-compulsive phenomena. These were discontinued in turn due to worsening extrapyramidal side effects, agitation and social withdrawal, and hypersomnolence respectively. Conservative and non-pharmacologic therapies were also trialled to manage Ms. A’s OCD symptoms to improve her obsessional slowness and break compulsive rituals.
At age 25, Ms. A’s anxiety improved using lorazepam 1 mg bd. Shortly thereafter Ms. A commenced the dopaminergic pramipexole hydrochloride, up-titrated from 0.25 mg to 0.5 mg bd. This significantly improved her obsessional slowness, motor initiation and psychomotor speed, with a reduction in mealtime duration by a further 50%. Further attempts to increase the dose of pramipexole hydrochloride yielded increased initiation and volition, yet increased Ms. A’s anxiety and agitation. She continued with pramipexole hydrochloride 0.5 mg bd. Ms. A had significant functional improvement in undertaking her activities of daily living, increased social engagement and a markedly increased hedonic response.


A 79-year-old Japanese man was referred to our hospital for esophageal cancer. Gastrointestinal endoscopy revealed a 37-cm tumor starting at the incisors with Barrett’s esophagus (Fig. a) and multiple brownish mucous membranes from the lower to the upper body of the stomach (Fig. b). A biopsy of the esophageal tumor revealed a well-differentiated adenocarcinoma, whereas biopsy of the brownish mucous membranes in the stomach revealed MALT lymphoma. A large lymph node in the mesenteric membrane of the small intestine (Fig. a) was confirmed by a computed tomography scan. However, no accumulation of contrast agent was observed in the lymph node on positron emission tomography (PET) (Fig. b). All laboratory data were within the normal range: the carcinoembryonic antigen level was 2.7 ng/mL (normal range < 5.0 mg/dL), the cytokeratin 19 fragment level was 1.3 ng/mL (normal range < 3.5 mg/dL), the squamous cell carcinoma-associated antigen level was 1.4 ng/mL (normal range < 1.5 ng/dL), and anti-Hp antibody testing was negative. According to the Union for International Cancer Control Tumor–Node–Metastasis classification (8th edition), Barrett’s esophageal cancer was classified as cStage IA (cT1bN0M0). We elected to perform endoscopic submucosal dissection (ESD) as a first-line treatment option considering the balance of surgical risk and the presence of MALT. The pathological analysis of the ESD specimen revealed a well-differentiated adenocarcinoma pDMM, ly (+), v (−), HMX, VM0. Furthermore, gastrointestinal endoscopy revealed the presence of remnant tumor after the ESD (Fig. ). Therefore, we elected to perform radical surgery for Barrett’s esophageal cancer only as a second option.
Esophagectomy with two-field lymph node dissection and gastric conduit reconstruction via the posterior mediastinal route were performed. Since a large lymph node was located in the mesentery of the small intestine, both the lymph node and the small intestine were resected together. The operation time was 6 h and 18 min, with an estimated blood loss of 80 mL.
The resected tumor measured 30 × 20 mm in short-segment Barrett’s esophagus and contained a post-ESD scar (Fig. a). Pathologic analysis showed a well-differentiated adenocarcinoma with short-segment Barrett’s esophagus, 0-IIc, 30 × 20 mm, pT1a-SMM ly0 v0 N0 M0, and pStage0 according to the 8th edition of the UICC TNM staging system. This patient was diagnosed with MALT lymphoma of the cell component in the large abdominal lymph node (Fig. b). The MALT lymphoma did not invade the esophagus, but rather, it spread throughout the stomach, including the resected margin.
The patient’s postoperative course was uneventful. The patient resumed eating on postoperative day 7 and was discharged from the hospital on postoperative day 14. No additional treatment was administered for MALT. Thus far, with respect to the MALT lymphoma, no recurrent disease except that in the gastric tube has been observed.
According to the European Society of Medical Oncology guidelines for gastric MALT lymphoma [], the patient was classified as stage I based on the Lugano staging system. The patient was negative for anti-Hp antibody, and thus, we prioritized treatment for Barrett’s esophageal cancer over treatment for the MALT lymphoma. According to the “Practical Guidelines for Hematological Malignancies (2018) of the Japanese Society of Hematology,” radiotherapy is recommended as the initial treatment in patients with Hp-negative gastric MALT lymphoma based on category 2B evidence. Antibiotic treatment was also recommended in a previous report []. Since these evidence levels were low and because substantial time is required to obtain a therapeutic effect regardless of whether radiation therapy or antibiotic therapy is applied, we decided that esophageal cancer treatment should proceed.
Although FDG uptake during PET-CT is frequently observed in many MALT lymphomas with high-grade malignant potential [], this case did not show abnormal FDG uptake in the mesenteric lymph nodes or in other lesions. We removed the enlarged lymph nodes during the surgery for esophageal cancer and submitted the specimens for pathological examination. After consultation with a hematologist, we elected to prioritize esophageal cancer treatment.
Initially, we decided to perform ESD because Yu et al. reported that elderly patients who underwent esophagectomy had significantly lower cancer-related and 5-year overall survival (OS) rates than relatively younger patients []. However, pathological findings of ESD specimens revealed lymph node infiltration with possible positive horizontal margins. Moreover, post-ESD gastrointestinal endoscopy performed during follow-up detected residual tumor. Since Barrett’s esophageal cancer showed scar tissue-related stenosis after ESD, we could not perform additional ESD.
We believe that chemoradiation therapy may likely worsen the stenosis. Therefore, we considered surgery to be the best option in this case. We elected to perform radical esophagectomy as an additional treatment. For this elderly patient, it was important to determine which organ should be used for reconstruction after esophagectomy. Reconstruction using the colon or jejunum should be performed after total gastrectomy []. Actually, colonic or jejunal reconstruction may be associated with higher morbidity and mortality rates than a gastric conduit [–]. Shimada et al. [] reported that the use of a colon substitution in patients with remnant stomach was a significant independent risk factor for poor 5-year OS rates compared with gastric substitution. No reports have been published on residual MALT lymphoma at the resected margin of the stomach. Therefore, the prognosis of MALT lymphoma that remains on the gastric tube after esophagectomy is unknown. The patient experienced no complications and was discharged from the hospital on postoperative day 14.
Initially, we considered the MALT lymphoma to be a localized lesion in the stomach, but a pathologic analysis revealed that the lymphoma in the mesentery of the small intestine was actually metastases of the MALT lymphoma. In many cases, the MALT lymphoma is less likely to have a worse prognosis even if residual lymphoma cells are present []. Radiation therapy and chemotherapy have been reported to be treatments for MALT lymphoma, but a precise treatment has not yet been established. In this case, the swollen lymph nodes in the mesentery were removed during surgery, and no more obvious metastatic lymph nodes remained. Therefore, considering the patient’s age, the patient was followed-up without additional therapy.
Thieblemont et al. published data on a new prognostic factor for MALT lymphoma. Three individual factors with the greatest prognostic significance were age > 70 years, Ann Arbor stage III or IV, and an elevated lactate dehydrogenase (LDH) level. These factors allowed the three groups to be classified as follows: low, intermediate, and high risk (according to the presence of 0, 1, or > 2 of these factors, respectively). The 5-year OS rates in the low-, intermediate-, and high-risk groups were 98.7%, 93.1%, and 64.3%, respectively []. Since this case was classified as intermediate risk, the 5-year OS rates were estimated to be over 90%, which is considered to be much better than the OS rates estimated as a result of his esophageal cancer. In this case, we decided not to administer additional treatment for the MALT lymphoma and only intended to perform observations during follow-up. At 6 months after surgery, no recurrent esophageal cancer or MALT lymphoma was observed. Although the observation period was short, upfront esophageal cancer surgery without any postoperative complications was the preferred approach for this patient.
To our knowledge, based on a search for literature published between January 1983 and March 2020 in the Japan Medical Abstracts Society and PubMed databases using the key words esophageal cancer, gastric MALT lymphoma, and surgery, this is the first report of esophageal cancer with gastric MALT lymphoma. We believe that it is possible to use the stomach despite the presence of low-grade MALT lymphoma as a reconstructed esophagus in elderly patients. If the stomach with MALT lymphoma can be used as a reconstructed organ, the choice of surgery may be expanded, and postoperative complications can be reduced.


This case involved a 64-year-old female with a history of hypertension and paroxysmal atrial fibrillation who came to the hospital with complaints of yellow discoloration of her skin, intermittent fevers and a recent history of right upper quadrant pain with nausea. Her primary care provider sent her to the emergency room after basic lab work revealed a total bilirubin of 14.3. Of note, the patient was previously seen in the hospital six months prior for a skin rash on her extremities and abdomen that was biopsied and later described as psoriasiform dermatitis (Figure ). It was thought to be a drug reaction from a medication, but the rash still persisted after discontinuation. On this admission, a CT abdomen was ordered in the setting of painless jaundice and it revealed masses in the pancreatic head and neck with confluent disease encasing the periportal structures and was highly suspicious for malignancy (Figure ). Biopsy after the endoscopic ultrasound was consistent with pancreatic adenocarcinoma. The patient was evaluated by gastroenterology and she had a biliary sphincterotomy with stenting to assist with the hyperbilirubinemia secondary to the pancreatic obstruction. Oncology staged her disease and started her on modified FOLFIRINOX therapy and she was discharged for further treatment and follow-up.


A 66-year-old woman presented with abnormal genital bleeding. She was diagnosed with cervical cancer, and radical surgery could not be performed because of severe local invasion (stage IIIB; cT3bN1M0). Computed tomography (CT) for cancer staging incidentally revealed a pancreatic body tumor. The patient was referred to our hospital for further examination and treatment. After consulting with the gynecologist, we judged that it would take a long time to start treatment for cervical cancer if the pancreatic tumor was first examined closely and then resected. For this reason, the pancreatic tumor was inspected while performing radiation therapy for cervical cancer. She had no history of malignancies. Physical examination did not reveal any specific findings except for the abnormal genital bleeding. Tumor markers such as carcinoembryonic antigen (CEA) (5.1 ng/mL), carbohydrate antigen 19-9 (CA19-9) (749.8 U/mL), DUPAN-2 (320 U/mL), and Span-1 (69.0 U/mL) were elevated, while squamous cell carcinoma antigen and cancer antigen 125 were within normal range. Plain CT, contrast-enhanced CT, and gadolinium-ethoxybenzyl-diethylenetriamine pantaacetic acid (Gd-EOB-DPTA)-enhanced magnetic resonance imaging (MRI) revealed a 21-mm nodule in the pancreatic body that showed gradually intense enhancement, and a 20-mm calcification in the proximal side of the nodule (Fig. a–f). No enlarged lymph nodes or distant metastasis were evident. Magnetic resonance cholangiopancreatography showed main pancreatic duct (MPD) disruption and MPD dilation in the distal side of the disruption (Fig. a). Endoscopic retrograde cholangiopancreatography showed MPD disruption distal to the calcification. Endoscopic ultrasonography (EUS) demonstrated that there was a 21-mm hypoechoic lesion near the calcification, and invasion to the splenic vein was suspected (Fig. b, c). EUS-guided fine-needle aspiration cytology of the hypoechoic lesion revealed adenocarcinoma. Based on these findings, the patient was diagnosed with pancreatic cancer (stage IIA; cT3N0M0). The patient had been receiving radiotherapy for the cervical cancer for a month (external irradiation 50.4Gy/28Fr, intracavity irradiation 24Gy/4Fr) when distal pancreatectomy with D2 lymph node dissection was carried out. At the same time, splenectomy was also performed. The operating time was 236 min, and the blood loss volume was 60 mL. A macroscopic examination of the resected specimen showed a 20-mm hard mass in the pancreatic body and a 38-mm well-circumscribed nodule just distal to the mass (Figs. and ). A postoperative pathological examination revealed well-differentiated IDC in the nodule and confirmed perineural and anterior serosal invasion (Fig. a). There were no findings such as squamous cell components suggesting a relationship between pancreatic cancer and cervical cancer. In the hard mass, vitrified tissues with areas containing uniform tumor cells were found, presenting mild atypia, no lymphovascular invasion, and no infiltration to adjacent organs (Fig. b). In addition, calcification and ossification were also found in the vitrified tissues (Fig. c). Immunohistochemical staining revealed that uniform tumor cells from the hard mass were positive for β-catenin and CD10 (Fig. a, b), which were compatible with SPN. Additionally, the number of viable SPN cells was small, and the number of vitrified tissues was high. Furthermore, there was fibrosis with tissue destruction and exocrine parenchyma loss in pancreatic tissues distal to SPN. Coarse calcifications were thought to have been removed during cytohistologic preparation or eliminated by demineralization. The boundary between β-catenin-stained SPN cells and non-stained IDC cells was clear (Fig. ). Accordingly, the final pathological diagnosis was SPN combined with IDC of the pancreas. The pancreatic IDC was classified as stage IIB (pT3N1M0) according to the 8th edition of the International Union Against Cancer Tumor–Node–Metastasis classification. Postoperatively, the patient followed an uneventful course and no complications. Three weeks after surgery, the patient received adjuvant chemotherapy with S-1, an oral fluoropyrimidine, at a dose of 100 mg/day (60 mg per body surface area). However, 4 weeks after surgery, she complained of strong backache, and CEA and CA19-9 were elevated to 8.3 ng/mL and 7088.6 U/mL, respectively. MRI revealed multiple vertebral metastases despite no bone metastasis preoperatively. Although chemotherapy sessions were not interrupted, she died 8 weeks after surgery.


A 66-year-old right-handed female presented to the Emergency Department after her first generalised tonic–clonic seizure that had started while she was sitting watching television. Four months prior to this, the patient had experienced a single absence-like seizure episode described as a short period of staring without being able to speak. There was also a nine-month history of mild early morning headaches and intermittent anosmia. Her past medical history included choriocarcinoma in remission, coeliac disease, hiatus hernia, osteopaenia and allergic rhinitis. Examination of the head, neck and neurological system was normal. Full blood count, coagulation, liver function, urea and electrolytes were within normal ranges, except for a moderate hyponatraemia (122 mmol/L), low serum osmolality (263 mOsm/kg) and low urine osmolality (134 mOsm/kg), consistent with a syndrome of inappropriate antidiuretic hormone secretion (SIADH).
MRI scan of the head revealed a cystic mass extending from the left nasal cavity into the anterior cranial fossa, associated with vasogenic oedema at the base of both frontal lobes (Fig. ). There was minor midline shift to the right and minimal effacement of the anterior horn of the left lateral ventricle, but no evidence of hydrocephalus or haemorrhage. The patient was given dexamethasone for reversal of cerebral oedema and levetiracetam for seizure prophylaxis. Computed tomography (CT) scan of the thorax, abdomen and pelvis showed no evidence of disseminated malignancy (modified Kadish stage C, Dulguerov stage T4N0M0, Biller stage T3N0M0). The case was discussed in the neuro-oncology multi-disciplinary team meeting, and the decision was taken to offer an endoscopic-guided anterior skull base biopsy.
Histopathological analysis of the biopsy specimen showed respiratory epithelium with in situ neuroendocrine cell hyperplasia, which was in the form of cell nests composed of small cells containing uniform nuclei and small nucleoli, with interspersed fibrillary neuropil-like material (Fig. a, b). The cells stained with chromogranin and synaptophysin, and the neuropil-like material was positive for neurofilament (Fig. c–f). No neuroblastoma or neuroendocrine carcinoma were noted in the biopsy. The patient was offered radical resection by an image-guided bicoronal craniotomy and transnasal endoscopic approach. The lateral borders of tumour were dissected to the skull base and anterior and posterior bony borders were drilled down, before repair was made using a right nasoseptal flap. Tumour resection was then completed intracranially.
The specimens surgically resected from the left sinonasal cavity and from inside the anterior cranial fossa revealed a distinctly biphasic tumour, comprising an epithelial component of atypical cuboidal and ciliated columnar cells, and a neuroendocrine component of primitive-appearing small cells with scant cytoplasm and speckled nuclear chromatin (Fig. a–d).
The epithelial component was prominent within the sinonasal cavity, and formed glands, cords, cribriform structures and ill-defined sheets. The neuroendocrine component comprising small cells was interspersed with the glandular element. In the intracranial specimen, ill-defined and anastomosing sheets of both components were present. Brain tissue was identified and it is likely that cells with moderately abundant eosinophilic cytoplasm represented native neuronal cells rather than ganglionic differentiation within the tumour. No focal necrosis was seen, however, apoptotic nuclear fragments were present amongst tumour cells. There were, on average, two mitoses per ten high power fields.
Immunohistochemical analysis of the epithelial component showed strong cytokeratin CAM 5.2, AE1/AE3 and CK positivity (Fig. a). The small neuroendocrine cells showed patchy and variable intensity perinuclear staining at least focally. Epithelial membrane antigen stained the epithelial component and there was a diffuse, dot-like staining of the neuroendocrine cells. CD56, chromogranin, synaptophysin and calretinin stained the neuroendocrine cells but not the epithelial component (Fig. b–d). On S100 staining, there was a focal peripheral staining of some tumour groups in the intracranial component in a manner similar to that observed with sustentacular cells in ONB (Fig. e). There was no staining with p63 (Fig. f). The proliferation fraction was variable but low overall, and estimated to be less than 10%.
In summary, this was a biphasic tumour with epithelial and neuroendocrine components. Sinonasal teratocarcinosarcoma is a rare tumour that can arise in this site and shows a combination of epithelial, mesenchymal and neuroepithelial elements. This entity was not considered in the differential diagnosis due to the lack of heterologous epithelial elements including squamous cells and of a mesenchymal component with rhabdomyoblastic, cartilaginous, osteoblastic, smooth muscle or adipocytic differentiation []. Based on the morphology and immunophenotype, the following diagnoses were considered: combined neuroendocrine carcinoma and adenocarcinoma, ONB with divergent glandular differentiation, and mixed ONB and adenocarcinoma. The diagnosis of ONB was favoured over a neuroendocrine carcinoma due to the presence of neuropil-like material, S100 positive sustentacular cells focally within the tumour, positivity of the neuroendocrine component for calretinin and negativity for p63, location of the lesion arising out of the left olfactory groove, and the presence of neuroendocrine hyperplasia. The last feature has been described in ONB []. The distinction between co-incident adenocarcinoma and divergent glandular differentiation, both of which have been described in cases of ONB, was made on the basis of significant cellular atypia, ciliated cells, and irregular CK staining in the glandular component. Following these considerations, a final diagnosis of mixed ONB and adenocarcinoma was made.
The patient went on to receive adjuvant chemotherapy and radiotherapy. Post-treatment MRI head and whole-body positron emission tomography (PET)-CT showed no evidence of metastasis. However, 9 months after treatment, a soft mobile mass measuring 2 cm in the left neck level IIb/III was identified. Ultrasound of the neck revealed bilateral level IIb-IV nodes. Fine needle aspiration of the palpable left node was performed, which was highly cellular and contained malignant cells arranged both in groups and as a dispersed population. Some cells showed high nuclear-to-cytoplasmic ratio, whilst others contained moderate amounts of pale blue cytoplasm. In places the nuclei had speckled chromatin and showed evidence of moulding. Mucoid material with scattered macrophages and lymphoid cells were present in the background. This cytomorphology was considered consistent with metastatic spread of the primary tumour.
The patient underwent bilateral modified radical neck dissection and node clearance with a temporary tracheostomy for 1 year. Histological examination confirmed metastatic adenocarcinoma with occasional small areas of solid growth suggestive of neuroendocrine differentiation in 20 of 115 nodes. The patient received adjuvant radiotherapy for 6 weeks. Six month post-treatment whole-body PET-CT has shown no evidence of recurrent disease.


We present a 36-year-old male who was admitted to our department due to the gradual worsening of the left eye vision. Ophthalmologic evaluation of the patient’s retina showed no remarkable ﬁndings while ocular examination showed visual acuity 8/10 on the right eye and 1/10 on the left eye. The formal visual field testing, by using the standard Goldman perimetry study, revealed a left upper temporal quadrant deficit. Further neurological examination was normal. No endocrine dysfunction was identified preoperatively. Brain computed tomography (CT) scan revealed a sellar mass with sellar enlargement and dorsum sella erosion (Figure ). Further investigation with brain magnetic resonance imaging (MRI) demonstrated a 3 cm sellar mass, intensely and homogeneously enhancing after the intravenous (IV) administration of gadolinium, with suprasellar extension, inferior displacement of the infundibulum, and upward displacement of the optic chiasm and anterior communicating artery complex (Figures -).
The patient underwent a surgical operation via a transglabellar approach (Figures -). A highly vascularized tumor was recognized and total resection was achieved (Figures -). The excised surgical specimen was sent for histology (Figures -).
Histopathological examination of the tumor showed a cellular proliferation of stromal cells, interlaced by numerous thin-walled vessels, foam, and vacuolated histiocytes. No mitoses were identified. In histochemical and immunohistochemical stains, stromal cells were positive to vimentin and epidermal growth factor receptor (EGFR) and in limited locations, also positive in EMA and neuron-specific enolase (NSE) while negative in CK7, CK20, CK 5/6, glial fibrillary acidic protein (GFAP), pancytokeratin, CK34βΕ12, S-100, and α-inhibin. The cellular proliferation index ki67 was less than 1%. Differential diagnosis included angiomatous meningioma, angioblastic meningioma, transitional angioblastic, and angioblastomatous meningioma. The overall histological diagnosis was capillary hemangioblastoma (World Health Organization (WHO) Grade I).
Postoperatively, the patient had considerable improvement in his visual acuity and temporal quadrant deficit. Except for transient diabetes insipidus, the rest of the postoperative course was uneventful, including any endocrine dysfunction.
After the histological diagnosis, initially, VHL syndrome was excluded via further imaging studies, including ophthalmic ultrasonography, abdominal, cervical, thoracic, and lumbar MRI. Although imaging studies were negative for other tumors and there was no known family history, genetic screening was suggested to the patient for von Hippel-Lindau gene mutations. No residual tumor was recognized in the brain MRI six months after surgery and the genetic test was negative for VHL mutations (Figure ).


A 71 year old man with a medical history of alcohol abuse, diabetes mellitus, essential hypertension, and depression was admitted to the intensive care unit suffering from dyspnea, productive cough, hematemesis, and black colored stools. Physical examination revealed the patient in poor general condition; hypotensive with blood pressure 87/50 mm Hg, pulse 106 b.p.m, a temperature of 37.8 C and saturating 100% on 3 liters of oxygen. Laboratory tests showed hemoglobin 7.9 gram/deciliter (g/dl), leukocytes 7.9 kilo/microliter (k/uL), platelets 155 k/uL , sodium 129 mg/dL , potassium 3.4 millimole/liter (mmol/L) , BUN 22 mg/dL, creatinine 0.96 mg/dL, glucose 150 mg/dl, anion gap 25 mmol/L, lactic acid 5.3, ALT 44 units/liter (U/L), AST 74 U/L, total bilirubin 2.25 mg/dL, international normal ratio (INR) 1.6 and urine ketones negligible.
Blood pressure responded to intravenous (IV) hydration 30ml/kg. The patient was started on IV Rocephin,and azithromycin for pneumonia based on symptoms and chest XR showing right lower lung infiltrates. The patient has suspected bleeding from esophageal varices, an indication of heavy alcohol abuse. He was started on proton pump inhibitors and an octreotide drip was administered.
Esophagogastroduodenoscopy (EGD) revealed circumferential, diffuse, friable mucosa extending from the proximal esophagus to the distal esophagus with sharp demarcation at the esophagogastric junction (GEJ) ().
There were areas of black appearing esophageal mucosa in the distal esophagus. The gastric exam showed mild areas of erythema in the body but no Wischnewsky lesions, in other words gastric mucosal petechial hemorrhages. The duodenum revealed an area of semi-lunar ulceration in the bulb and several areas of ulceration/semi-circumferential with a black eschar-like appearance at the ulcerative base in the second and third part of the duodenum ().
Proton pump inhibitors continued, while octreotide drip was discontinued. Abdominal and pelvic CT with contrast was unremarkable for any thrombosis. It showed hepatic steatosis. The patient continued to improve on symptomatic management. One week later, a repeat EGD showed improving esophagitis and duodenum ulcers. Black discoloration of esophagus and duodenum was resolved. The patient continued to improve and was discharged.


An 84-year-old woman with a past medical history of hypertension, hyperlipidemia, heart failure with preserved ejection fraction (HFpEF), severe pulmonary hypertension (pulmonary arterial systolic pressure of 76 mmHg), and chronic pericardial effusion of unclear etiology presented to the ED with shortness of breath of sudden onset that had started at rest and had quickly become severe. She had a chronic large but hemodynamically stable pericardial effusion. An extensive workup for the etiology of her pericardial effusion had been stubbornly unrevealing. An elective pericardial window formation had previously been planned as she had been hemodynamically stable. During this admission, she was in moderate respiratory distress with sinus tachycardia to 105 beats/min, respiratory rate of 30 times/min, and oxygen saturation of 85% on room air. Physical examination revealed bilateral leg edema and jugular venous distension with muffled heart sounds. A bedside transthoracic echocardiogram (TTE) showed a new early diastolic RV collapse with a large pericardial effusion (Figure , Video ). The inferior vena cava was dilated at 29 mm (Figure ), was non-compressible, and had a blunted respirophasic motion (Video , Figures , ). She underwent an emergent pericardial window with the removal of 1.2 liters of serous fluid and adequate clinical improvement. She was followed up closely in the intensive care unit (ICU) postoperatively. Fluid studies and an intraoperative pericardial biopsy yet again failed to reveal any pathology. On hospital day two, she became hypotensive to 85/40 mmHg with altered mental status. She subsequently went into cardiogenic shock complicated by pulmonary edema and hypoxic respiratory failure requiring intubation, diuretics, and inotropes. RV systolic failure and severe right atrial dilation were confirmed by a repeat TTE (Video ). Over the next few days, there was worsening hemodynamic instability. Given her poor prognosis, the decision to transition her to comfort care was made by her family.


A 71-year-old male was referred to our outpatient department with rising prostate
specific antigen (PSA) levels (6.70 ng/ml, reference range:
0–4 ng/ml). His past medical history was relevant for
right lung cancer. His current medical history was relevant for arterial
hypertension, which was being treated with zofenopril, diabetes mellitus treated
with metformin and psoriatic arthritis under treatment with golimumab plus
methotrexate. His family history was negative for PCa and he did not report lower
urinary tract symptoms, hematuria or fever. Digital rectal examination of the
prostate revealed a focal area of fixed induration involving the right lobe. Urine
culture was negative and urinalysis did not reveal abnormal findings. PCa was
suspected. A 3-Tesla prostate multiparametric magnetic resonance imaging (MRI)
determined the presence of a 4 cm nodular lesion characterized by low signal
intensity on T2-weighted sequences and involved both the peripheral and transition
zone of the right lobe with extension to the peripheral zone of the mid basal left
lobe (A). Capsular irregularity,
suspicious for extracapsular extension, was also evident. ‘On
diffusion-weighted imaging the lesion was characterized by significant signal
restriction with low apparent diffusion coefficient (ADC) values (B & C).’ Dynamic contrast
enhanced images revealed diffuse enhancement post contrast (D). A Prostate Imaging Reporting
and Data System version 2 score of five was assigned to the lesion, indicating a
clinically significant PCa was highly likely to be present. The patient underwent
prostate biopsy. Target biopsies revealed aggregates of lymphocytes, plasma cells,
histiocytes and epithelioid cells around damaged glands, together with a
tubercle-like reaction with multinucleated giant cells, as well as a collection of
neutrophils and eosinophils. These aspects were compatible with GP (). Non target biopsies
demonstrated a marked and extensive chronic prostatitis coexisting with multiple
spots of acute prostatitis. The patient underwent observation and PSA spontaneously
decreased to 0.70 ng/ml at 6 months follow-up.


A 58-year-old male with a pertinent past medical history of dyslipidemia initially presented to the hospital due to acute shortness of breath and subjective fever for the past week. On presentation, he was swabbed for novel coronavirus, which resulted as positive. For the first five days, he was monitored on the regular medical floor for his oxygen requirements, which fluctuated between 2 and 3 liters on the nasal cannula. He was initiated on hydroxychloroquine and azithromycin for five days, and his progression of inflammatory markers was trending every 48 hours (Table ).
On the fifth day of admission, the patient’s oxygen requirement worsened to the point that he had to be transitioned to a non-rebreather mask on 15 liters. His other vital signs included a blood pressure of 130/75 mm Hg, respiratory rate of 22 breaths per minute, temperature of 99.4 degrees Celsius, and pulse oxygenation ranging from 90% to 94%. He was transferred to the critical care unit for closer monitoring. He was initiated on intravenous corticosteroids and interleukin (IL) 1 inhibitor anakinra. On the seventh day, he started complaining about paleness and cold left lower extremity as compared to the right side. On examination, there were no motor or sensory deficits; however, pulses were detectable only on Doppler ultrasound (Figure ). Urgent vascular surgery evaluation was conducted, and the bilateral arterial duplex was performed, which demonstrated normal arterial flow. The patient, however, was switched to therapeutic low molecular weight heparin (LMWH) given the high suspicion for prothrombotic state associated with cytokine release syndrome.
His oxygen requirements were successfully titrated down to 6 liters by the 10th day of hospitalization; however, he continued to complain about his left cold foot, which gradually progressed to develop cyanosis. The patient at this time was switched to intravenous heparin drip in consideration of unstable peripheral vascular disease. With no improvement noted in his cyanosis, CT angiogram was obtained, which demonstrated filling defects in the main left femoral artery suspicious of thrombus (Figure ). Decreased blood flow was also noted in the left popliteal, posterior tibial, peroneal, and anterior tibial arteries.
Heparin drip was continued and aspirin 81 milligrams was added in the regimen. Despite being on full anticoagulation, the patient was developing arterial thromboses, which prompted hematology evaluation for hypercoagulable screening. Peripheral smear was also performed, which did not reveal any schistocytes; the red blood cells, leukocytes, and platelets demonstrated normal features.
Extensive blood workup including genetic studies was obtained, which are summarized in Table . The mildly elevated anticardiolipin immunoglobulin M was considered secondary to inflammation and deemed non-specific. Ultimately, vascular surgery was performed, with angioplasty as limb salvage therapy in the femoral, popliteal, and tibial arteries. The re-vascularization was followed with below-the-ankle amputation of the necrotic dead tissue.


The patient, a 68 year old female UK resident, presented in April 2019 with a subcutaneous cystic lesion on the right palm containing thick yellowish-brown fluid. The patient recalled a penetrating injury approximately at the site of the lesion, involving a thorny plant whilst on vacation in Fiji three years previously, and indicated that the lump had developed over the six months preceding her presentation.
The cyst, which appeared encapsulated, was excised surgically in its entirety. Microscopic examination of fluid from the cyst revealed large amounts of filamentous fungal elements (A), some of which resembled toruloid mycelia (xylohyphae), and portions of which were conspicuously dematiaceous in appearance (B). Culture of cyst fluid yielded pure growth of fungus at 30 and 37 °C (C), with faster growth at the lower temperature. Fungal colonies on Sabouraud agar were flat with raised, floccose, folded or umbilicate centres. Colonies were velvety, olivaceous-grey to brown with dark greenish-grey colony reverse (D). Microscopic examination of tease mounts prepared from fungal growth in culture at 30 °C (E) revealed regular pale brown, septate hyphae and scant budding cells, which were oval to ellipsoidal, light olivaceous-green and measured 2.5 by 3.5 μm. Budding cells predominated in cultures maintained at 37 °C (F), and often had a short annellated zone. Since colonial and microscopic appearance of the organism was consistent with members of the genus Exophiala, for which we have previously developed an extensive mass spectral database [], the isolate was subjected to MALDI-TOF MS analyses. Mass spectral profiles matched those of Exophiala campbellii [] in the MRL database with reasonable MeanLogScores (2.012). Formal confirmation of identity was achieved through PCR amplification and sequencing of portions of the 28S rRNA gene and the internal transcribed spacer region 1 (ITS) performed exactly as described previously []. The sequences generated were 100% identical to those corresponding to the type strain of Exophiala campbellii, isolate NCPF 2274 (EMBL accession numbers for the current case MN091927 and MN091928). The isolate from the current case is stored in metabolically inactive form in the NCPF with the unique identifier NCPF 7936. Antifungal susceptibility testing was performed on isolate NCPF 7936 using CLSI methodologies []. Minimum inhibitory concentrations (in mg/L) for amphotericin B, itraconazole, posaconazole and voriconazole were 0.5, 0.25, 0.125 and 0.125, respectively. Further confirmation that E. campbellii was the etiological agent was obtained by pan-fungal PCR amplification and sequencing of fungal genomic DNA extracted directly from cyst fluid, which was performed exactly as described previously []. Pan-fungal PCR was positive with primers targeting both the 28S rRNA gene and ITS1, and sequences generated from both amplicons again matched those of E. campbellii in the public synchronized EMBL database (data not shown). Since the surgical team was confident that the cyst had been completely excised, antifungal therapy was not initiated post-operatively.


A term female baby weighing 2.96 kg was born to a 23-year-old primigravida mother at 38 weeks gestation by normal vaginal delivery. There was no significant antenatal illness and the parents were nonconsanguineous. Antenatal ultrasound was not done. The baby had an Apgar of 8/10 at 1' and 9/ 10 at 5'. She was born with a ruptured meningomyelocele at the lower thoracic vertebral level, without any dysmorphic features, a length of 48 cm, and a head circumference of 37 cm. The baby was hemodynamically stable without any movement of both lower limbs. Cardiovascular and respiratory systems were normal. MRI brain was done which showed rudimentary anterior falx cerebri with incompletely formed interhemispheric fissure, absence of septum pellucidum with agenesis of the corpus callosum, severe thinning of cerebrum without parieto-occipital lobe formation, dysplastic unfused thalamus, platybasia with horizontally placed clivus, posterior fossa appears smaller with dysplastic cerebellum and brainstem, and there is herniation of cerebellum and brainstem with widened foramen magnum (Figure ). MRI spine also was done which revealed thin and dysplastic spinal cord with tethering of cord noted at sixth thoracic vertebral level, spinal dysraphism with defective posterior elements at seventh cervical vertebral level through which neural elements are protruding into the sac, and this sac is seen continuous with bony spinal canal deformity which is hypointense in T1 weighted image and hyperintense in T2 weighted image and it extends from D6 to L2 level (Figure ).
The MRI findings were consistent with a case of semilobar HPE with Arnold Chiari type II malformation. The chromosomal analysis report was within normal limits. Parental counseling was done regarding the baby’s poor prognosis. The baby was released from the hospital as the parents did not want to continue further management.


A term male baby weighing 3.9 kg was born to a 38-year-old mother at 40 weeks gestation by normal vaginal delivery. He was born to a third-degree consanguineous parent without any significant antenatal illness. Antenatal ultrasound was not done. The baby had an Apgar of 8/10 at 1' and 9/10 at 5'. The baby developed poor feeding and lethargy on day 2 of life, evaluated for neonatal sepsis, and initial investigations for sepsis were within normal limits. MRI was done which showed monoventricle with rudimentary posterior interhemispheric fissure and incomplete falx cerebri. There is an absence of corpus callosum, cavum septum pellucidum, and anterior fossa midline structures, posterior fossa and both cerebellar hemispheres appear normal (Figure ).
The MRI features suggest that this is a semilobar type of HPE. The baby showed gradual improvement and was released from the hospital on day 7 of life.


A 23-year-old boy, brother of Case 2, with no history of toxic or drug exposure, started at age 14 with action tremor in the right arm. Three years later, at the age of 17, he consulted us for a worsening of the tremor and progression to all four limbs. He denied REM sleep behaviour disorder, hyposmia, depression or constipation. On physical examination the patient exhibited postural and action tremor in both arms, with an asymmetrical rest component, of greater amplitude in the right side; and rest tremor in both legs, of greater amplitude in the left side (Video ). He also had minimal dystonic posturing in his right arm and foot. As the patient underwent complementary studies, both an acute levodopa challenge and one-month 1000 mg/day trial were performed to look for a possible therapeutic agent and narrow down differential diagnosis, but tremor was neither responsive to this, nor to alcohol nor propranolol. 18F-DOPA-PET scan showed a normal striatal uptake. Olfactory function assessment proved normal. Other complementary studies were normal, including brain MRI, complete blood count, liver function tests, homocysteine, B12, folate, VDRL, thyroid screening, serum copper, 24-hour cupruria, ceruloplasmin, EKG and nerve conduction studies. Fragile-X pre-mutations and Charcot Marie Tooth type 1A mutations were also investigated due to his sibling’s phenotype and proved normal. Whole exome sequencing (WES) detected a heterozygous pathogenic variant in exon 7 of the Parkin gene at c.823C>T (p.Arg275Trp) and an unreported heterozygous variant in the acceptor splice site of intron 4 at c.535-2A>C, categorized as likely pathogenic by in silico parameters due to a very likely aberrant effect on splicing. The patient received trihexyphenidyl 5 mg TID with almost complete tremor resolution and sustained response for the last five years. He has neither developed additional parkinsonian features nor autonomic dysfunction.


A 65-year old woman began at the age of 20 with rest tremor in the right hand and subtle rigidity and bradykinesia in the right arm, which were non-progressive for more than ten years. Her family history revealed that her father suffered PD since the age of 60. When first seen by us at the age of 39, she presented a severe bilateral and symmetric rest, postural, and intention jerky tremor also involving the head but not her chin. She presented slight rigidity and bradykinesia. Brain MRI was normal, as well as 24-hour cupruria. Olfactory testing was normal, and dopaminergic imaging with 99mTc-TRODAT-1 revealed a mild bilateral reduction uptake, with a posterior to anterior gradient, predominantly on the right putamen. Tremor was unresponsive to neither 250 mg acute challenge with levodopa nor to sustained 1000 mg/day dose for more than one month. Trihexyphenidyl 5 mg TID resulted in a marked reduction of tremor. After ten years of use, she developed cognitive complaints that completely reverted with trihexyphenidyl withdrawal. The patient exhibited a remarkably mild motor compromise, with mildly more prominent bradykinesia in the left side of her body, consistent with the 99mTc-TRODAT-1 findings (Video ). The patient has remained on monotherapy with dopamine agonists for the last 20 years, currently with 3 mg of pramipexole. At the age of 65, with 45 years of disease duration, she has neither developed drug-induced dyskinesias nor wearing-off phenomena. Her condition has slightly progressed due to the development of freezing of gait. Sporadic attempts to reintroduce levodopa have showed no response in tremor or in the freezing of gait. WES detected a known heterozygous pathogenic variant in exon 2 of the Parkin gene at p.(Asn52Metfs*29) and a known heterozygous pathogenic variant in exon 7 at p.(Arg275Trp).


A 17-year-old boy who was 174-cm tall and weighed 65 kg admitted to the hospital due to abdominal pain since one day before admission. The pain was in the periumbilical area and right lower quadrant of the abdomen and started after an excessive exercise (boxing). The patient had no nausea, vomiting, but anorexia.
The patient was also a known case of G6PD deficiency since birth time. The G6PD deficiency test was conducted, and the result was deficient and confirmed the diagnosis. He had no hemolytic crisis, jaundice, and blood transfusion up-to-date. At first, in the hospital, before and after the operation, the patient and his family members did not give an appropriate history of growth hormone abuse, but gave a history of using growth hormone for growth problems and short stature under an endocrinologist follow-up from childhood; but after a precise history taking, we found that the patient had started illegally to use recombinant human growth hormone (a five mg injection under the skin) for bodybuilding and strength advantage from two month prior to surgery once a day at bed time (Norditropin FlexPro (somatropine) subcutaneous solution (5 mg/1.5 mL)). The patient had no delayed bone age, but had normal velocity growth. The patient had visited an endocrinologist 15 days prior to his admission to the hospital and was sent for a health check-up and also checking for insulin-like growth factor 1 (IGF 1) and a thyroid function test (TFT). TFT showed normal range T3, T4, and TSH as 1.51 nmol/ml, 9.1 g/dl, and 1.82 mIU/ml, retrospectively, and IGF 1 was 180.6 ng/ml (reference interval 75–850).
The patient had left wrist fracture 3 years before the current hospital admission, but no prior surgeries were found. Moreover, his grandparents and father received general anesthesia without recognized complications.
The patient's physical exam was normal except for right lower quadrant (RLQ) abdominal tenderness, rebound tenderness, and positive Rovsing's sign without any evidence of fever. Laboratory studies were unremarkable, and there was no evidence of active hemolysis. His hemoglobin (Hb) level was 14.1 g/dl; however, other hemolytic laboratory parameters were not evaluated because there was no history of G6PD deficiency-related sequelae such as hemolysis, jaundice, or blood transfusion. The patient was sent to the operation room with the impression of acute appendicitis for open appendectomy.
In the operation room, the patient's vital signs immediately before induction of anesthesia were as follows: pulse rate = 86 beat/minutes, blood pressure = 120/80 mm Hg, respiratory rate = 12 breaths/minutes, and axillary temperature = 36.7 degrees Celsius. In the supine position, under continuous electrocardiography, pulse oximetry, capnography, monitoring ETCO2, blood pressure monitoring, and temperature measurement (axillary), the patient underwent 3 min of denitrogenation with 100% oxygen through a facemask. Anesthesia was induced using midazolam (2 mg), thiopental sodium (200 mg), and isoflurane in oxygen using the Bain circuit. After confirming the loss of consciousness, atracurium (30 mg) and fentanyl (25 mcg) were administered, and then, endotracheal intubation was performed using a 7.5 mm tube (internal diameter) with an inflatable cuff. After applying the ventilator, ETCO2 was 34 mmHg. The patient received cefazoline 1 gr IV for one dose for antibiotic prophylaxis, and the operation started. Anesthesia was maintained with isoflurane in oxygen during operation.
At the end of the operation, about 45 minutes after starting the induction of anesthesia and starting surgery, while the patient was still intubated and going to be awake and having his own spontaneous respiration, he developed with (in order of occurrence) an increased heart rate to 124 beat/minutes (sinus tachycardia), increased body (axillary) temperature to about 41.7 degrees Celsius, gasping like respiration, increased ETCO2 to 153 mmHg, MMR, and then generalized body rigidity, so the malignant hyperthermia susceptibility was considered. Blood pressure was mildly elevated and was 140/80 mmHg. The color and volume of the perioperative urine was normal. Immediately, inhalational anesthetics were discontinued, and the Bain circuit and machine were exchanged to be replaced with an uncontaminated one; next, dantrolene rapid intravenous (IV) bolus (2.5 mg/kg) was given, and one vial of sodium bicarbonate was infused. An internal Foley catheter and nasogastric tube were inserted, and the bladder and the stomach were irrigated with cold saline, and the patient was hydrated with 1000 cc cold crystalloids for two times to reach the urine output of at least 2 cc/kg/hour. The patient was further cooled with a wet sponge applied to the surface of the body. About 30 minutes after administration of dantrolene and cooling measures, the heart rate was dramatically decreased to 80 beats/minutes, ETCO2 decreased from 153 to 35 mm Hg, and temperature decreased to 38.5°C (axillary), and cooling measures were stopped. The patient could not be extubated due to a low level of consciousness at the end of the operation, and was sent intubated to the surgical intensive care unit (ICU). In the ICU, dantrolene was continued at 1.0 mg/kg every 6 hours for 24 hours.
The patient had been in the hospital for twelve days; the first three nights were in the ICU for stabilization and, then, till the discharge day in the surgical ward. The patient was under close observation, and continuous monitoring of heart, blood pressure, temperature, and urine output was performed while checking for arterial blood gases (PH, partial pressure of carbon dioxide (PCO2), HCO3− and base excess in the extracellular fluid compartment (BEecf)), white blood cell count (WBC), Hb, platelet count, liver enzymes as aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin, alkaline phosphatase (AlK–P), albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), blood sugar (BS), electrolytes (Na+ and K+), calcium (Ca2+), CPK, creatine kinase-muscle/brain (CKMB), and lactate dehydrogenase (LDH) (Tables and ).
In this case, the urine output did not decrease, the urine color did not change, and urine analysis was considered to be normal. Reticulocyte and corrected reticulocyte count were 1.5% and 1%, respectively. A peripheral blood smear was taken and showed no fragmented red blood cells (RBCs), but mild leukocytosis (neutrophilia). Direct Combs and indirect Combs tests were both negative. Viral markers as hepatitis B surface (HBS) antigen-antibody, hepatitis C virus (HCV) antibody, and human immune-deficiency virus (HIV) antibody were negative by the enzyme-linked immunosorbent assay (ELISA) technique. C-reactive protein (CRP) and uric acid were checked and were in the normal range (0.7 and 3.3 mg/dl retrospectively). Troponin I was checked and was positive, so it was titrated and was 41.5 ng/l, and echocardiography was performed which revealed a normal ventricular function without residual pulmonary valve stenosis or pulmonary regurgitation. The antinuclear antibody (ANA) titer was 0.289 and was negative. Ceruloplasmin was 0.398 g/l and was in the normal range. Serum sodium, magnesium (Mg), prothrombin time (PT), partial thromboplastin time (PTT), the international normalized ratio (INR), hemoglobin (Hb), platelet (Plt), blood urea nitrogen (BUN), and creatinine (Cr) were all in the normal range.


A 59-year-old man presented to the ED due to decreased oral intake for a few days. His medical problems included hypertension, diabetes mellitus type II, hereditary hemochromatosis, hereditary elliptocytosis, and myelodysplastic syndrome. On further questioning, the patient mentioned that he had an episode of midsternal chest pressure earlier in the day and it lasted for a couple of hours. It was associated with shortness of breath, but he denied any palpitation or diaphoresis. The pain did not recur, and he was pain free in the ED.
On arrival, his blood pressure was 139/84 mmHg, heart rate was 72 beats per minute, temperature was 97.6°F, and respiratory rate of 18 per minute with an oxygen saturation of 97% on room air. Cardiac exam revealed regular rate and rhythm with normal S1 and S2. His lungs were clear to auscultation bilaterally. He had no cyanosis, clubbing, or lower extremity swelling.
Initial labs showed a sodium level of 134 mEq/L (135-145 mEq/L), potassium 4.2 mEq/L (3.8-5.1 mEq/L), blood urea nitrogen 21 mg/dL (9-26 mg/dL), serum creatinine 1.1 mg/dL (0.7-1.4 mg/dL), white blood cell count 7,700 per mm3 (4.4-10.7 K/mm3), hemoglobin 10.6 g/dL (13.5-17 g/dl), troponin I 12.30 ng/dL (0-0.05 ng/dL), creatine kinase-MB (CK-MB) 14.7 ng/mL (0.0-5.0 ng/ml), and creatine phosphokinase (CPK) 140 units/L (21-232 units/L). Electrocardiogram (EKG) showed ST segment elevations in the inferior leads with reciprocal ST depressions in the anterior leads (Figure ).
The patient was taken for emergent cardiac catheterization and it revealed a complete occlusion of the right coronary artery (RCA). He underwent a successful percutaneous intervention with a drug eluting stent to the RCA. After the procedure, the primary team noticed that the patient was confused and lethargic that was concerning for an acute stroke. Neurological exam, however, did not reveal any focal deficit. A CT head done three hours post procedure showed subarachnoid blood products involving the left and right parietal lobes as well as the occipital lobes with local sulcal effacement and gyral edema (Figure ). These findings were consistent with acute SAH. His antiplatelets were held and he was transferred to the ICU for strict blood pressure control. Due to these concerning findings, an MRI brain was performed 12 hours later which did not show SAH but did reveal multiple acute infarcts in the bilateral frontal lobes (Figure ). His antiplatelets were restarted. Stroke work up included an echocardiogram that did not reveal any patent foramen ovale or left atrial appendage thrombus and imaging of the carotid arteries that did not show any significant stenosis. He was diagnosed with an embolic stroke of unknown origin and sent home with a loop recorder.


A 68-year-old man with high fever and without any apparent cause was prescribed oral moxifloxacin in a community clinic. On day 5, his maximum body temperature reached to 41 °C with shivering, and so he visited the emergency department immediately. On laboratory examination, his white cell count was raised to 11.74*109/L and neutrophil percentage was 92.4%. The results of blood culture indicated Salmonella enteritidis (O9), while Widal test and Weil-Felix test were shown to be negative, which confirmed the diagnosis of Salmonella enteritidis sepsis. The patient was healthy before, and had no history of any other diseases, as well as smoking and drinking history. According to the results of antibiotic susceptibility test, piperacillin/tazobactam was prescribed. His temperature returned to normal after 2 days. He was discharged after maintenance of normal body temperature for 12 days, and was instructed to continue oral cefixime. On day 6 after discharge, he discontinued cefixime by himself and had fever (increased to 38.6 °C) accompanied with chills, fatigue, and night sweats. He also had paroxysmal pain in the left chest and back. He did not visit the hospital and took cefixime at home, and his body temperature was maintained constant at 37–38 °C. However, the patient was admitted after 24 days due to long-term low-grade fever and fatigue. He complained of slight back pain when inquired in detailed. His white cell count was 8.21*109/L and neutrophil percentage was 73.3%. C-reactive protein (CRP) was 45μg/ml, and erythrocyte sedimentation rate (ESR) was 55 mm/h. Blood cultures still indicated Salmonella enteritidis (O9). Spine MRI showed abnormal signal changes at T9-T10 vertebral bone and adjacent soft tissues, and the corresponding spinal cord was compressed. CT scan (Fig. ) showed infectious lesions. More specifically, bone destruction and sclerotic bone formation were observed, indicating that the course of spondylitis was not short. PET-CT revealed changes in T9-T10 vertebrae and intervertebral space, and formation of soft tissue masses adjacent to the vertebra, increased fluorodeoxyglucose (FDG) metabolism, and spinal tuberculosis was considered (Fig. ). Anti-mycobacterium tuberculosis antibody and T-spot test were shown to be negative. The final diagnosis confirmed it as thoracic spine infection. Intervertebral lesion debridement, partial rib resection, intervertebral bone fusion and pedicle screw internal fixation were performed. After surgery, the patient experienced a significant decrease in pain. Finally, histopathological results suggested inflammatory cell infiltration and tissue bacterial culture indicated Salmonella enteritidis (O9) (Fig. ). He underwent treatment with piperacillin/tazobactam for 2 weeks consecutively. His postoperative temperature and white cell count remained normal. Blood cultures were negative twice in a row, so he was discharged from the hospital. Ceftriaxone was prescribed for 3 weeks once a day after discharge. The patient was followed up for 4 months after discharge and showed a good prognosis. From postoperative imaging results after 4 months, intervertebral fusion was achieved in T9-T10 (Fig. ).


Patient 1 was a 40-year-old man who presented to the ED with mild left-sided chest pain. He had been seen nine days earlier due to fever and cough, and was diagnosed with COVID-19. However, during that visit, he had no shortness of breath, no significant decrease in oxygenation while ambulating, a normal sinus rhythm electrocardiogram (ECG) with no significant ST-segment changes, and was discharged home on precautions. Since his prior visit, he reported no immobility or significant change in daily activities, and he had no significant past medical history and took no medications. Repeat EKG demonstrated no ST-segment changes. The emergency physician caring for the patient was concerned that COVID-19 could be a risk factor for PE, and ordered a D-dimer, which was elevated at 4489 nanograms per milliliter (ng/mL) (reference range 0–499 ng/mL). Troponin and brain natriuretic peptide (BNP) levels were normal. A computed tomography angiogram (CTA) demonstrated bilateral pulmonary emboli and bilateral lower lobe ground-glass opacities consistent with COVID-19 pneumonia. He was discharged on a course of rivaroxaban.


Patient 2 was a 48-year-old man who presented with right-sided chest pain, which was sharp in character and pleuritic. He reported no accompanying dyspnea or worsening of the pain with exertion. His ECG demonstrated normal sinus rhythm without significant ST-segment changes. He reported a past medical history of gout, but was on neither prophylactic treatment nor active treatment for a flare in the months prior to presentation. He had been seen 14 days prior, during which he had presented with similar symptoms, but also with an accompanying fever and dyspnea. During that visit, he underwent a CTA which showed multifocal ground-glass infiltrates, consistent with COVID-19 infection, and was discharged home on isolation precautions.
During his return visit, he underwent D-dimer testing, which was elevated at 2183 ng/mL (reference range 0–499 ng/mL). A CTA demonstrated a right upper segmental PE, multiple subsegmental pulmonary emboli, and progression in the size of ground-glass infiltrates (which were not associated with vascular filling defects). He was briefly admitted to the medical service, and discharged after a two-day admission on a course of apixaban.


Patient 3 was a 47-year-old woman who presented with left-sided chest pain, which was pressure-like in character and non-pleuritic. She noted some worsening of her symptoms with exertion, but the pain was also present at rest. Her ECG showed sinus rhythm without significant ST-segment changes, and an initial troponin was negative (<0.01 ng/mL). She had been seen nine days previously, with cough and dyspnea, and had undergone an evaluation including ECG and chest radiograph, and discharged home on precautions with a presumptive diagnosis of COVID-19. This was confirmed on outpatient testing two days later.
Relative to her initial presentation, she reported that the chest pain she was experiencing was new, but the sensation of dyspnea and the frequency of her cough had lessened significantly. She reported no significant change in activity while at home, and reported no hormone use or other risk factors for PE. A D-dimer was drawn and elevated at 5821 ng/mL (ref: 0–499 ng/mL). CTA was performed and demonstrated emboli throughout the right upper segmental branch and bilateral lower lobe segmental and subsegmental branches. Due to her clot burden, she was admitted to the medical service and started on apixiban. An inpatient echocardiogram demonstrated no evidence to suggest cor pulmonale, and she was discharged after two days.


A 63-year-old male with end-stage renal disease (ESRD) presented to the emergency department with severe, bilateral lower-extremity pain with black necrotic ulcerations (). The symptoms began five weeks prior, and review of systems was negative for fevers or trauma. The patient was previously treated with antibiotics, prednisone, and oxycodone without improvement. Further evaluation via point-of-care ultrasound focusing on the necrotic areas revealed calcium deposits and shadowing (). Computed tomography confirmed soft tissue calcifications ().


A 72-year-old woman presented to the emergency department (ED) after she attended the hospital for a routine ophthalmology appointment and felt dyspnoeic. She had experienced one week of lethargy, feeling generally unwell and loss of taste, and one day of dyspnoea, palpitations, and diarrhoea. She did not complain of fevers, cough, or chest pain. She was entirely independent and had a history of hypertension, seasonal asthma, and glaucoma. On assessment she was tachypnoeic (32 breaths per minute) with increased work of breathing and had oxygen saturations of 90% on 15 litres of oxygen via a non-rebreather mask. She was in atrial fibrillation with a rapid ventricular response (125–170 beats per minute) and was hypotensive (87/62 millimetres of mercury [mmHg]).
Venous and arterial blood samples were taken and sent for analysis (). A chest radiograph (CXR) showed widespread bilateral infiltrates suspicious for COVID-19. A computed tomography pulmonary angiogram (CTPA) demonstrated extensive bilateral pulmonary emboli with no evidence of right heart strain and extensive, patchy ground-glass changes in keeping with COVID-19. She was given intravenous (IV) fluids, magnesium sulphate and verapamil which reduced her heart rate to 115 beats per minute, but she remained in atrial fibrillation and remained hypotensive (95/60 mmHg). She was chemically cardioverted with IV amiodarone although she remained hypotensive. She was given treatment dose tinzaparin before being switched to rivaroxaban. Her case was discussed with interventional radiology, cardiology, and intensive care regarding catheter-directed and systemic thrombolysis; a decision was made that thrombolysis was not appropriate due to the risk of pulmonary haemorrhage and that the persistent hypotension was likely related to verapamil therapy. A nasopharyngeal aspirate confirmed COVID-19 infection on reverse transcription-polymerase chain reaction (RT-PCR).


A 62-year-old man was brought into the ED by ambulance with three days of worsening dyspnoea, reduced appetite, myalgia, intermittent diarrhoea, abdominal cramping and one episode of vomiting, but no chest pain. He had experienced a fever three weeks previously and tested positive for COVID-19 before self-isolating and completing a course of azithromycin. He was previously independent and his only medical history was hypertension and hypercholesterolaemia. On assessment in the ambulance he had oxygen saturations of 52% on room air which improved to 88% on 15 litres of oxygen via a non-rebreather mask. In the ED he was tachypnoeic (24 breaths per minute), with saturations of 97% on 15 litres of oxygen. He was tachycardic (113 breaths per minute), normotensive (100/72 mmHg), and an electrocardiogram (ECG) showed sinus tachycardia with no evidence of right heart strain.
A CXR showed extensive, bilateral peripheral patchy opacification suspicious for COVID-19. A CTPA demonstrated bilateral acute pulmonary emboli with no features of right heart strain and extensive peripheral ground-glass and peri-lobular consolidation consistent with COVID-19. The patient was treated with treatment dose tinzaparin and high-flow oxygen. A nasopharyngeal aspirate confirmed COVID-19 infection RT-PCR.


A 78-year-old man was brought into the ED by ambulance with four days of fever, dry cough, lethargy, myalgia, coryza, dyspnoea and one episode of haemoptysis, but no chest pain. He had a history of benign prostate hyperplasia and hypercholesterolaemia, but was otherwise active and independent. On assessment with the ambulance service he was in respiratory distress and had oxygen saturations of 60% on room air. On assessment in the ED he had oxygen saturations of 88% on 15 litres of oxygen via a non-rebreather mask and tachypnoeic (35 breaths per minute). He was normotensive (120/94 mmHg) but had cool peripheries with a peripheral capillary refill time of five seconds. An ECG showed he was in atrial fibrillation with a rapid ventricular response (140 beats per minute) with ST depression in lateral leads and no evidence of right heart strain.
A CXR showed bilateral consolidation suspicious for COVID-19. A point-of-care echocardiogram showed reduced right ventricular free wall contractility. A CTPA showed multiple subsegmental pulmonary emboli throughout the right hemithorax and left lower lobe with evidence of right heart strain (right ventricle:left ventricle ratio >1:1) and extensive ground-glass changes. The patient was taken to the intensive care unit (ICU) due to progressive hypoxia where he was intubated and ventilated and treated with treatment dose tinzaparin. A nasopharyngeal aspirate confirmed COVID-19 infection RT-PCR.


A 63-year-old man presented with two weeks of myalgia, fever and lethargy, and three days of haemoptysis and pleuritic chest pain. He was independent with no comorbidities. He had normal observations and a normal examination. An ECG showed new right bundle branch block. A CXR showed bilateral peripheral areas of consolidation suspicious for COVID-19. A CTPA demonstrated bilateral pulmonary emboli with complete occlusion to the left lower lobar artery, a right sided pulmonary infarct, right heart strain (right ventricle:left ventricle ratio of 1.4:1), and patchy ground-glass shadowing suggestive of COVID-19. He was treated with treatment dose tinzaparin.


An HIV-negative 24-year-old Caucasian female born and raised in New Mexico presented with worsening bilateral lower extremity weakness and numbness. The patient had been previously diagnosed with coccidioidomycosis meningitis at age 16 years and was on daily antifungal medication. She denied any fever, chills, dysuria and upper extremity weakness. She had stopped taking her regular antifungal medication for the past year to "see what would happen." The decision to stop the antifungal was not due to adverse effects, but her hopeful curiosity for meningitis remission without continued treatment. Physical exam revealed 3/5 motor strength in both proximal and distal lower extremity bilaterally and cold and vibration sensory deficits starting distally and increasing proximally. Cerebrospinal fluid (CSF) was negative for malignancy. Moreover, CSF and serum complement fixed Ab were positive for coccidioidomycosis (1:128 titer and 1:16 titer, respectively), and IgM and IgG were both positive. Her thoracic MRI showed enhancing septations within the thecal sac in the thoracic region, resembling cystic arachnoid formations (Figure ).
Neurosurgery performed T8-L2 laminectomy for removal of arachnoid cysts (Figure ).
The pathology report from the biopsy of the arachnoiditis found chronic inflammation with coccidioidomycosis (Figures , ).
The patient later was discharged on fluconazole 800 mg PO daily and started rehab. On a return visit a month later, she endorsed mild improvement of all her neurological deficits. The patient is encouraged to continue rehab and medication adherence.


A 23-year-old man with acute severe aplastic anemia was allografted with 15.55 × 108 nucleated cells and 9.56 × 106 CD34-positive cells from a 5/10-HLA-matched related donor after conditioning with busulfan 6.4 mg/kg and cyclophosphamide 200 mg/kg. Prophylaxis for GVHD consisted of Cyclosporin A, short-term methotrexate, and anti-thymocyte globulin 10 mg/kg. Ruxolitinib and mycophenolate mofetil were used as immunosuppressive therapy afterward. He also received trimethoprim-sulfamethoxazole, acyclovir and voriconazole for continuous infection prophylaxis. Engraftments of neutrophils and platelets were documented on day +9 and day +8, respectively.
From day +44, the patient reported loose stools twice a day with fever (99–100.4°F). With regard to the foregoing rash (Grade I°), elevated liver enzyme and bloating, methylprednisolone (40 mg per 12 hours) and cyclosporine (5 mg/kg) were utilized for initial treatment of suspected aGVHD. He was discharged on +67 when symptoms were alleviated.
However, on day +69, the patient was re-admitted for worsen GI symptoms --green-watery diarrhea, abdominal cramps, bloating, nausea, vomiting, fever (99–100.4°F) and fatigue. The frequency and the amount of defecation increased to more than 10 times per day with a total volume of 1000 ml. His laboratory results were as follows: white blood cell count 6.61G/L (neutrophils 51.8%, lymphocytes 32.5%, monocytes 8.0%, and eosinophil 7.0%), hemoglobin 120 g/L, platelets 396 G/L, C-reactive protein 155.3 mg/L. Renal and hepatic function tests showed normal levels. The patient tested negative for cytomegalovirus and Epstein-Barr virus, human immunodeficiency virus, syphilis, and hepatitis B virus. Additionally, he lost around 10 kg over the past 2 months. He was initially suspected of aGVHD according to his former symptoms after HSCT. Nevertheless, on the first day of hospitalization, stool examination for ova and parasites showed Giardia trophozoites and cysts (Fig. , repeated 3 times). Upon further questioning, he revealed the consumption of relatively unsanitary food after HSCT.
Therefore, methylprednisolone was stopped and the patient was intravenously treated with a 7-day course of metronidazole (500 mg, tid.) which was well-tolerated. Notably, after treatment for only 2 days, G lamblia and white blood cells in stool turned negative, while red blood cells diminished promptly. Meanwhile, his GI symptoms remarkably alleviated during the treatment course. After being discharged from the hospital on day +83, the patient remained asymptomatic during further follow-up. (The timeline in Fig. summarized the main clinical events after allo-HSCT). The patient has provided informed consent for publication of the case.


The patient, a 69-year-old man, could not actively extend the left thumb interphalangeal (IP) joint approximately 10 days before presentation and was referred to our institution for an examination. The patient had experienced pain in the wrist joint since a long period. However, the patient did not participate in sports and had no recollection of any trauma and infection. His medical history included pyogenic spondylitis and autoimmune hepatitis, and he had been undergoing corticosteroid therapy (5 mg) for 1 year. Although inability of active extension of the left thumb and swelling in the snuff box were observed, there was no tenderness. Grip strength was 25 kg in the right hand and 11 kg in the left hand, right wrist extension and flexion were 65° each, and left wrist extension and flexion were 60° and 50°, respectively.
Plain X-rays revealed advanced stage SNAC in the left hand; supinated oblique view revealed an enlarged soft tissue shadow due to the growth of the dorsal ridge (). We diagnosed the patient with EPL tendon subcutaneous rupture due to SNAC.
We performed the surgery 10 weeks after the initial diagnosis, because the patient's general condition was not favorable due to pyogenic spondylitis. During the surgery, when the dorsal part of the wrist was opened, the EPL tendon was found to be absent. We noted scarring surrounding the snuff box, perforation of the joint capsule, and a cartilage defect in the capitate head. A proximal-type scaphoid nonunion was detected, and bone growth to the dorsal part of the dorsal ridge was observed (). The EPL tendon rupture was attributed to the bone growth. We performed scaphoid lunate advanced collapse (SLAC) reconstruction using a 4-corner fusion procedure described by Watson and Ballet [], replacing the missing EPL tendon with the extensor indicis proprius (EIP) tendon using Pulvertaft weave fashion (). A long thumb spica cast was used for the patient until week 3 following surgery, and a short thumb spica cast was used from week 4 to week 7. The cast was removed 7 weeks after surgery; however, active extension of the thumb again became impossible.
At 6 months after surgery, extension and flexion in the left wrist were 30° and 35°, respectively. The patient was unable to extend his thumb, improvement in the transferred tendon function could not be confirmed, and the transferred tendon was not palpable in the snuff box (). Accordingly, a tendon transfer using the palmaris longus (PL) tendon was planned based on a diagnosis of transferred EIP tendon rerupture. The transferred EIP tendon had reruptured in the dead space where the scaphoid bone was previously located (). The PL tendon and distal palmar aponeurosis were taken, according to the Camitz method [], and transferred to the EPL tendon using Pulvertaft weave fashion. A thumb spica cast was applied for 3 weeks. Although active extension of the left thumb was possible 1 year after the second surgery, a 20° extension lag persisted. Left hand grip strength was 21 kg, left thumb IP joint extension was 5°, and flexion was 75°. Disabilities of the Arm, Shoulder and Hand score was 29.3 points.


Our patient was a 77-year-old Azerbaijani man from Urmia, a city in northwestern Iran. He was admitted to our hospital following a scalp wound sustained in a car accident. The result of his initial clinical examination was normal, and his brain computed tomographic scan was negative for traumatic intracranial hemorrhage and skull fractures. Some of his lab results in admission were as follows: hemoglobin A1c 7.4%, blood sugar 265 mg/dl, high-density lipoprotein 35 mg/dl, low-density lipoprotein 71 mg/dl, cholesterol 142 mg/dl, and triglycerides 75 mg/dl. His medications included carvedilol 3.125 mg, Nitroglycerin 6.4 mg, aspirin 100 mg, Lantus insulin 10 units, and atorvastatin 40 mg. He had a history of type 2 diabetes, hypertension, and hyperlipidemia. He had atherosclerosis and had undergone angiography and stent implantation 12 years ago. He had a family history of diabetes, hypertension, and coronary artery disease. He is a smoker who smoked one pack per day. He denied addiction to any kind of drugs or alcohol. The patient was hospitalized with an extensive scalp wound and underwent reconstructive surgery for the scalp wound on April 20, 2019. The scalp wound became infected, and he developed scalp necrosis 4 days after the surgery (Fig. ). The patient received saline wound irrigation and wet-to-dry dressing twice per day. He had no improvement despite receiving conventional treatments, and he was referred to the wound management team. In the first step, necrotic tissues were removed by autolytic debridement, and the skull was exposed (Fig. ). Then, we used MDT for further debridement and disinfection of the wounds from bacterial infections as well as tending to increase granulated tissues on the wound. The edges of the wound were stimulated because of the larval secretion. This process helps maggots to immediately start their activity and increase their output. Sterile maggots for this case study were prepared in the Laboratory of Medicinal Flies in the Department of Medical Entomology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. The maggots were L1 larvae of Lucilia sericata (Diptera: Calliphoridae). The maggot therapy procedure included preparation of the wound, release of the larvae on the wound, and dressing and removing of larvae after 48 hours. Next, larval therapy may be done immediately after removing third-instar larvae or after some time gaps. The peripheral area of the wound was prepared with zinc oxide to prevent irritation that may be produced by secretions of larvae (Fig. ). After two treatments with larval therapy, all the necrotic tissues were totally removed, and granulation tissues appeared (Fig. ). After four treatments with MDT in 3 weeks, silver-containing dressing and NPWT were applied to the wound for 7 months in order to make granulation tissue grow faster and promote the healing process (Fig. ). AMG was used to accelerate epithelialization of the wound in the last month of treatment (Fig. ). The scalp wound recovered well and totally closed (Fig. ). The patient was discharged to home in good condition and is enjoying life with the healed wound (Fig. ). No adverse effects were reported during or after therapeutic intervention.