A 3-year-old girl was referred to the pediatrician with hepatomegaly and developmental delay. The girl was the first child of consanguineous marriage in an Iranian family. She was delivered following a normal and term pregnancy with a birth weight of 2.95 kg, and height of 47 cm. No hypoglycemia was noted in the perinatal period and the postnatal transition.
At the age of 1, she developed abdominal distension. However, abdominal ultrasound has been reported as unremarkable. During childhood, she frequently experienced morning nausea, vomiting, and lethargy.
At the age of 2, she was referred to our center because of developmental delay. Biochemical lab tests revealed high hepatic transaminases (ALT 375 U/L, AST 495 U/L), mild neutropenia (750 per microliter), microcytic hypochromic anemia (hemoglobin of 10.3 g/dl and hematocrit of 34.1 %, mean corpuscular volume of 73.81 fl., and low mean corpuscular hemoglobin 25.54 pg), as well as high triglyceride (498 mg/dl), and cholesterol (268 mg/dl).
A abdominal ultrasound revealed hepatomegaly with mild diffuse heterogeneous echogenicity of the liver parenchyma. A liver biopsy was performed, which revealed cirrhosis with severe swelling of the hepatocytes with clear cytoplasm. Portal tracts showed very mild lymphocytic infiltration (Fig. ). According to clinical findings and liver biopsy, a hepatic form of GSD was suspected, so treatment with frequent feeds was initiated. Nevertheless, hepatic transaminase elevation persisted and ketosis with hyperlactatemia were developed. Therefore, at the age of 3, an aggressive regimen with uncooked cornstarch (5 times per day) and protein (2.5 g/kg/day) was initiated. After the diet therapy, her morning vomiting, and lethargy improved, and hepatic enzyme (ALT 80 U/L, AST 86 U/L) were decreased, but her cholesterol level increased (313 mg/dl).
Targeted gene sequencing (TGS) with a custom-targeted Ion AmpliSeq panel was performed. The panel included 7219 amplicons covering 450 genes associated with Inborn Metabolic Diseases consisting of glycogen storage disorders genes with hepatic involvement. Sanger sequencing validated identified the variants, using an ABI Prism 3500 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). Analyses were done using an Ion Torrent 540 chip (Life Technologies, Guilford, CT, South San Francisco, CA). The human genome 19 was used as the reference. Polyphen2, SIFT, and Mutation Taster were used for in silico analysis, GERP and Phastcons scores were used to evaluate the conservation of the variants. The population frequency of each variation was evaluated, using data from the gnomAD database. ACMG guidelines were used for variant interpretation []. The sequence variants were described according to the Human Genome Variation Society Nomenclature []. Interestingly, TGS findings showed that the patient carried two novel variants, which consisted of a homozygous variant c.1127-2 A > G (p.?) in exon 12, a homozygous missense variant c.2840 A > G (p.Gln947Arg) in exon 28 of the PHKB gene. In silico analysis revealed that the novel variant, c.1127-2 A > G (p.?) is pathogenic, which would have possibly damaged the splice site, and two other ones are variants of uncertain significance (VUS). However, samples from the parents were not available for the zygosity determination of these novel variants. It should be mentioned that both parents were asymptomatic.


The patient was an 87-year-old man who had presented with hypercalcemia at a health check 3 years before, resulting in parathyroid adenoma found by 99mTc-MIBI scintigraphy. He was prescribed bisphosphonate and regularly followed. During follow-up, he was also diagnosed with VMCs based on findings of multiple small hypodense lesions in the liver as observed on plain computed tomography (Fig. A). Two months prior to his death, he was hospitalized for a hypercalcemia crisis presenting dehydration, hypercalcemia (serum calcium, 15.9 mg/dL), and renal dysfunction (serum creatinine, 2.7 mg/dL). Hypercalcemia was improved by intravenous rehydration and synthetic calcitonin administration, although renal dysfunction remained. During hospitalization, he repeatedly suffered from aspiration pneumonitis and pseudomembranous colitis, each of which was improved by antibiotic administration. Ten days prior to his death, he developed septic fever. Ochrobactrum anthropic was detected in both blood and central venous catheter cultures. The central venous catheter was removed and meropenem was administered; however, his fever continued and he died. An autopsy was performed 18 hours after his death. Grossly, a large number of small lesions consisting of nodules and cysts were observed in the liver (Fig. B). They were considered VMCs; therefore, culture tests were not performed. Microscopically, the lesions presented as acute purulent cholangitis with numerous microabscesses accompanied with VMCs (Fig. C). In some microabscesses, gram-negative rods were observed (Fig. D), especially in the hepatic portal area, and in the common bile duct, which indicated that pathogenic bacteria had ascended from the bowel. Initially, we suspected the bacteria of Ochrobactrum anthropic, which were detected in both blood and central venous catheter cultures 10 days before death. However, if that was the case, the bacteria should have infected via blood vessels, which was inconsistent with the microscopic findings. Therefore, we conducted 16S rRNA gene sequencing using the postmortem FFPE tissues.
Detailed methodology is provided in the supplemental material. We selected FFPE liver tissue showing acute cholangitis with abundant gram-negative rods in microabscesses. For the negative control, 2 noninfectious FFPE liver tissues, obtained from 2 different autopsy cases, were used. All samples underwent FFPE processing after approximately 1 month of fixation with 20% buffered formalin. Three sets of primer pairs for the 16S rRNA gene with different amplicon sizes were used: 357F/518R, 8F/518R, and 8F/1492R. To assess the human DNA preservation status in the FFPE tissues, a human β-globin primer pair was used. Amplicon from PCR with 357F/518R primer pair appeared as a faint band in this case and as faint bands with a slightly larger size in the 2 negative control cases (Fig. , top panel). DNA sequencing of this case revealed the Pseudomonas genus was the most likely causative bacteria, as determined by the NCBI BLAST database (). Among them, P. aeruginosa was suspected to be the prime pathogen, with 85% similarity to the amplified 100-bp band. Meanwhile, sequences from the negative control cases showed a very weak matching to the various genera, and was considered to be nonspecifically amplified DNA. PCR products using both primer pairs, 8F/518R and 8F/1492R, showed no bands (Fig. , middle panels), which suggested DNA fragmentation in postmortem FFPE samples, and also implied no contamination by fresh bacteria during the FFPE processing. PCR products using human β-globin primers for a 110-bp PCR product showed positive bands for all postmortem cases (Fig. , bottom panel).
To further confirm P. aeruginosa, we performed P. aeruginosa-specific DNA amplification followed by sequencing and immunohistochemical staining. PCR products using the primer pair for a 72-bp amplicon of the oprL gene showed a clear band for only this case (Fig. A). The resultant sequence revealed 100% concordance with P. aeruginosa. Immunohistochemistry for anti-Pseudomonas antibody (ab68538, rabbit polyclonal, 1:1000 dilution; Abcam, Cambridge, UK) showed distinctly positive results for rod-shaped bacteria in the microabscess (Fig. B).


A 52-year-old Indian man presented with a two-year history of non-specific central chest pain. His pain started gradually and had been increasing in severity. It started to interrupt his daily activities. The pain was not related to exercise, meals, or respiration. His pain was not relieved by simple analgesics. The patient reported no history of trauma. The pain was not associated with cough, fever, anorexia, or weight loss. Otherwise, the patient was healthy and his past medical history is unremarkable.
On examination, his vital signs were within the normal limits. Examination of the chest revealed central tenderness over the sternum. Lung auscultation revealed normal vesicular breathing throughout both lung fields with no added sounds. Cardiac sounds were normal. The frontal chest radiograph showed clear lung fields. A 12-lead electrocardiograph demonstrated a normal sinus rhythm. In light of these findings, the patient was diagnosed as having costochondritis. He was prescribed non-steroidal anti-inflammatory agents and was given a follow-up appointment.
After two weeks, the patient presented again with no improvement in his pain. However, erythematous changes over the sternum were observed. Routine laboratory investigation, including hematological, liver, renal function tests, and inflammatory markers were within normal limits. Considering the recent changes and the long history of pain, the patient was referred to have a computed tomography scan of the chest.
The computed tomography scan revealed extensive destructive lesions in the sternal bone, suggestive of the diagnosis of sternal osteomyelitis (Figure ). Subsequently, a specimen was obtained from the sternum for culture and histopathological examinations. The biopsy revealed the growth of Mycobacterium tuberculosis.
Considering these findings, the patient was referred to the infectious disease team for management. He was commenced on anti-tubercular medications, including rifampin, isoniazid, pyrazinamide, and ethambutol, for 12 months. The patient was followed-up with frequently during the course of treatment and improvement in his symptoms was evident. After the completion of the treatment course, the patient had a complete resolution of his symptoms.


A six-year-old boy presented to the pediatric ward with left-sided hemiparesis and facial nerve weakness of one month's duration. It was examined with blood and biochemical investigations including MRI brain with contrast. The MRI showed multiple well-defined focal lesions bilaterally in the parietal region, predominantly on the right side. Other investigations were normal. The findings of MRI brain and spinal cord were suggestive of MS and the child was treated with methylprednisolone followed by oral prednisolone. Subsequently, the patient experienced numerous relapses with multiple episodes of limb weakness and facial nerve weakness. MRI brain and spinal cord was repeated during each episode and showed multiple new lesions, which had not been found in previous studies. The pattern of clinical and neuroradiological features was compatible with MS (as per the International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders). During relapses, the child was treated with methylprednisolone. Figures , show multiple hyperintense white matter lesions on T2-weighted MRI, which were supportive of a diagnosis of MS.
Subsequently, the patient was treated once with intravenous interferon due to frequent relapses and increased severity. However, owing to the side effects of the drug (fever with chills and headache), it was discontinued. During the latest episode at 13 years of age, he was admitted following an episode of right-sided hemiparesis, visual impairment, difficulty in walking and swallowing for three weeks, and fever for one day. It was managed as a relapse of MS and bacterial infection as the child had a high fever with high inflammatory markers. He was treated with intravenous methylprednisolone and intravenous antibiotics. Following the commencement of treatment, he improved gradually. He was discharged with oral prednisolone, and his physiotherapy and occupational therapy were continued. The patient is currently being followed up at the multidisciplinary clinic.


A 28-year-old, active-duty military male with relapsed, refractory, metastatic, malignant, giant-cell-rich, primary bone sarcoma presented to the Emergency Department (ED) by cardiology instruction for evaluation of a large pericardial effusion with possible early tamponade physiology that was identified on an outpatient transthoracic echocardiogram (TTE). The echocardiogram was performed to further evaluate findings from a positron emission tomography (PET) scan completed three days prior that demonstrated findings concerning for cardiac metastasis to the interventricular septum with extension into the right ventricular outflow tract, along with an interval increase in the size of a pericardial effusion when compared to a PET scan from five months prior (Figure ). At the time of initial evaluation in the ED, the patient was asymptomatic from a cardiopulmonary standpoint, specifically denying chest pain or dyspnea, though endorsing chronic superficial abdominal tenderness in multiple abdominal regions. Vital signs were normal and physical examination was significant only for mild epigastric and right upper quadrant tenderness. An ECG was obtained that demonstrated sinus rhythm, low voltage, and anteroseptal myocardial injury (Figure ).
In the setting of ST-segment elevation, additional concern was raised by the discovery of hypokinesis of the septal myocardium on bedside echocardiogram, though it should be noted that this area of myocardium was being impinged upon by a 47 mm × 23 mm mass in the interventricular septum (Figure ).
However, given the lack of cardiopulmonary symptoms, the patient was treated conservatively with serial ECGs and cardiac enzymes. Initial troponin was 0.14 ng/mL (99th percentile for assay being 0.03 ng/mL) with stable values on repeat assays performed at six-hour intervals. The patient was then admitted to the Coronary Care Unit and monitored closely for signs of cardiac tamponade (i.e., pulsus paradoxus). He subsequently required pericardiocentesis for a large pericardial effusion concerning for tamponade physiology based on mitral inflow velocities. Based on cytology with negative infectious labs, the effusion was deemed secondary to his malignancy. Following a seven-day hospitalization and extensive multidisciplinary discussions with the patient and his family regarding the prognosis, the patient elected to forgo any further cardiac imaging and was discharged home with hospice, where he died shortly after discharge.


A 57-year-old male with hypertension and diabetes presented to an outside hospital with rigors and fatigue in February 2021. His past medical history was notable for a prolonged hospitalization with COVID-19 in November of 2020. Prior to that admission, he had had a good performance status and was not known to have any intrinsic liver disease. Unfortunately, he had developed severe COVID-19 pneumonia, respiratory failure, and had received a tracheostomy due to an inability to wean off the ventilator. His course was further complicated by a right atrial and right ventricular thrombus with pulmonary embolisms. He was managed with a percutaneous endoscopic gastrostomy (PEG) tube and was discharged from a skilled nursing facility three months after the admission. He was not known to have complicated biliary disease. He had not experienced any previous episodes of cholangitis, pancreatitis, or obstructive jaundice. His imaging during his hospitalization did not identify any liver disease.
He was brought back to a medical facility one month after his discharge. He was found to have a fever of 38.3 °C, tachycardia, and hypotension. His initial blood work showed leukocytosis with a WBC count of 19 x 109/L, alkaline phosphatase of 870 U/L (normal range: 30-135 U/L), alanine aminotransferase (ALT) of 77 U/L (normal range: 10-55 U/L), and bilirubin of 1.3 mg/dL. His ultrasound showed cholelithiasis and a dilated common bile duct (CBD) (9 mm). An echogenic focus consistent with a stone was noted in the distal CBD on ultrasound. Repeat COVID-19 polymerase chain reaction (PCR) testing was negative twice. He was diagnosed with cholangitis and was resuscitated with 5 L of crystalloids and broad-spectrum antibiotic coverage. He progressed to septic shock and was stabilized on norepinephrine with improvement in his serum lactate. He was transferred to our institution for a higher level of care and consideration of performing an endoscopic retrograde cholangiopancreatography (ERCP). His CT scan upon arrival showed a moderately distended gallbladder. There was mild gallbladder wall thickening and pericholecystic fluid consistent with acute cholecystitis. In line with the ultrasound findings, several tiny stones in the distal CBD were found (Figure ). His anticoagulation was held for 24 hours prior to his ERCP.
ERCP confirmed a distal linear filling defect within the lower CBD (Figure ). Interestingly, there was CBD dilation without intrahepatic duct dilation (Figure ). A sphincterotomy and balloon sphincteroplasty were performed. The linear bile duct stone in the shape of a bile duct cast was extracted using balloon sweep. There was mild oozing from his sphincterotomy, and hence his bile duct was stented given the need for the resumption of anticoagulation. A bile duct aspirate grew Staphylococcus epidermidis. After the procedure, his condition was found to be good with improvement in his liver enzymes. His antibiotics were deescalated to oral medications and his diet was advanced. His acute cholecystitis was managed with antibiotics. General surgery reviewed his case and offered an outpatient cholecystectomy.
A repeat outpatient ERCP was performed for stent removal. During this exam, his stents and further bile duct casts were removed. However, the second ERCP was indicative of significant intrahepatic ductal disease (Figure ). He was evaluated by hepatology and diagnosed with SSC-CIP. Primary sclerosing cholangitis, congestive hepatopathy, and other causes of secondary sclerosing cholangitis were excluded.


A 24-year-old male patient, who was previously healthy, presented to the Hamad General Hospital complaining of progressive left-sided pleuritic chest pain lasting for a few weeks. He noticed two large lumps in front of his chest, precisely at the same site of the pain slowly increasing in size over four months. He experienced a loss of appetite and weight of eight kilograms over the same duration. The patient denied any history of cough, shortness of breath, fever, or night sweats. He was a lifelong non-smoker, with no contact with sick people and no recent travel, with unremarkable family history.
On examination, he was afebrile, maintaining normal oxygen saturation on ambient air. There were two anterior chest wall masses: the first above the left second rib, measuring 7 × 7 cm, and the second over the left costal margin measuring 10 × 10 cm. The covering skin of both masses appeared normal with no draining sinus or tract. The lumps were mobile, cold, non-pulsatile, and not tender. Chest auscultation and examination of other relevant systems were unremarkable.
His laboratory investigations showed hemoglobin of 11.4 g/dL, C-reactive protein of 65 mg/L, positive Quantiferon TB gold plus, and normal kidney and liver function tests ().
A chest x-ray showed airspace opacity noted in the left perihilar region (). Chest computed tomography (CT) showed two lenticular-shaped collections noted in the left anterior chest wall. One is noted along the internal surface of the left third rib measures 19 × 53 mm causing bone destruction. The other one is in the subcutaneous tissue measures 60 × 33 mm, with an enlarged left hilar lymph node showing peripheral enhancement and central hypodense necrotic area ( A, B) with associated underlying third rib destruction (). Ultrasound examination of the lesion in the lower chest wall showed well defined hypoechoic area, with varying degrees of internal heterogeneity ().
The patient failed to produce any sputum even after induction. The acid-fast bacilli smear (AFB) of the aspirated fluid from the chest wall swelling was negative, but the Polymerase Chain Reaction (PCR) was positive. The aspirated fluid culture grew a pan-sensitive Mycobacterium Tuberculosis Complex (MTB). We diagnosed him with primary chest wall tuberculosis and therefore started on first-line anti-tuberculosis medications. The patient traveled back to Nepal and lost follow up with us.


A 54-year-old male patient developed myoclonic jerks in the left shoulder 4 years after alloHSCT for B-cell chronic lymphocytic leukemia (B-CLL, for details see Table ). Post-transplant complications had included mild and transient acute GvHD of the skin starting 4 months after alloHSCT. Due to incomplete donor chimerism he had received 3 donor lymphocyte infusions (DLIs) on days 174, 210 and 314 leading to conversion to complete donor chimerism and durable hematological remission. The neurological examination revealed intermittent brachial dystonic seizures on the left side of his body (see Supplementary Information ). Neuropsychologic testing uncovered mild cognitive impairments in the areas of perceptual-motor skills, learning, and memory. The standard laboratory examination showed a known impaired kidney function and a slightly elevated creatine kinase. Brain MRI displayed no acute evidence of vascular or inflammatory/infectious pathology, particularly no imaging signs of encephalitis. Active neoplasia was ruled out by 18F-fluorodeoxyglucose PET/CT. Standard electroencephalography was normal. Detailed laboratory studies showed a decreased Vitamin D level (10.4 ng/ml, reference range: 20–50 ng/ml). Cerebrospinal fluid (CSF) analysis demonstrated a marginal pleocytosis (5 cells/µl, reference range < 5/µl) with detection of activated lymphocytes. CNS malignancy was ruled out by CSF cytology and FACS analysis. Moreover, a mild blood-CSF-barrier dysfunction (Q-albumin 9.9, protein 677 mg/l) and marginally positive oligoclonal bands (type 2a) without intrathecal immunoglobulin synthesis in Reiber graphs were found. Autoimmune encephalitis antibodies against the voltage-gated potassium channel associated LGI-1 protein with a serum titer of 1:40 and antineuronal antibodies against the GABA-synthesizing enzyme GAD with a serum titer of 1:1600 were detected (Fig. A,C), leading to the diagnosis of antibody-mediated immune encephalitis. After methylprednisolone (1 g/day for 5 days) and five cycles of immunoadsorption a therapy with the anti-CD20 antibody rituximab was established. In addition, an antiepileptic combination medication with valproic acid and levetiracetam was initiated. This therapy resulted in a significant reduction of motor and cognitive impairments, which remained stable in the long-term follow-up of 33 months under semi-annual rituximab infusion, allowing to discontinue valproic acid treatment.


A 65-year-old female patient was referred to our neurological department due to progressive left-sided choreatiform movement disorder, hemiparesis on the right, and visual loss on both eyes starting one month earlier. Onset of neurological symptoms was on day 201 after alloHSCT for high risk myelodysplastic/myeloproliferative syndrome. Post-transplant complications had included mild and transient acute GvHD of the skin at four months and delayed engraftment failure which was successfully treated by a T-cell-depleted stem cell boost five months after alloHSCT (for details see Table ). Presentation at the neurological department was 1 month after treatment of zoster ophthalmicus with intravenous acyclovir for three weeks which entirely cured the skin lesions. Central nervous system zoster reactivation or other infections (CMV, HSV, EBV, borreliosis, and lues) as a possible reason for the neurological symptoms could be excluded by unremarkable cerebrospinal fluid analysis. Brain MRI revealed long-segment increased T2-weighted signal of the optic nerve in the middle portion and infratentorial periependymal lesions (Fig. A,B) both with contrast enhancement. Spinal cord MRI demonstrated a high signal T2-lesion involving five vertebral segments suggestive of extensive cervical myelitis (Fig. C,D) and one additional lower cervical lateral lesion (Fig. C). Comprehensive autoimmune laboratory testing resulted in positive MOG-IgG with a serum titer of 1:30 (Fig. B). Diagnosis of MOG-IgG associated encephalomyelitis was made, and the patient was treated with methylprednisolone (500 mg/day for 5 days) followed by five cycles of immunoadsorption, tapered oral steroids, and rituximab every six months. Motoric complaints remitted completely, the visual acuity recovered successively, and no new neurologic deterioration occurred during 31 months of follow-up under regularly administered rituximab treatment. However, after the fifth course of rituximab, full donor chimerism was suddenly and completely lost, and the patient was again diagnosed with myelodysplastic/myeloproliferative syndrome, albeit in an earlier stage. The regular neurological treatment was therefore changed to high-dose immunoglobulins.


A 63-year-old female patient was admitted to our hospital because of rapidly progressive leg accentuated atrophic tetraparesis and paresthesia almost one year after alloHSCT for high risk myelodysplastic syndrome (for details see Table ). Post-transplant complications had included transient neuropathic complaints by day 12 which recovered spontaneously, severe acute GvHD of the skin by day 31 and moderate GvHD of the gut by day 49, both transient. An atypical hemolytic uremic syndrome was diagnosed 3 months after alloHSCT and successfully treated with plasmapheresis and eculizumab. A simultaneously observed tetraparesis with electrophysiological identification of an axonal polyneuropathy was interpreted as critical illness polyneuropathy. Almost 1 year after alloHSCT progressive leg weakness with loss of walking ability and increasing numbness of all limbs over two months led to a detailed neurological examination. Nerve conduction studies revealed a severe axonal polyneuropathy with a significant deterioration compared to the previous measurement. Because of subjective and objective xerophthalmia and positive SSA(Ro)-autoantibodies a minor salivary gland biopsy was performed and uncovered a sialadenitis with more than one focus per 4 mm2 (Fig. D), but no fibrotic areas as seen in chronic GvHD-related dry eye disease. Hence, chronic inflammatory polyneuropathy associated with Sjögren’s syndrome was diagnosed. Since then, with the exception of a single interruption due to a severe infection, she received monthly intravenous immunoglobulin treatment, whereby clinical symptoms and electrophysiological measurements improved. The polyneuropathy was stable at last follow-up, 29 months after initiation of immunoglobulin treatment.
At onset of the neurological complaints, all patients had 100% donor chimerism for peripheral blood mononuclear cells (PBMCs), CD19+ B cells, CD4+ and CD8+ T cells, except for patient 1, who had 95% chimerism for CD19+ B cells (Table ).


A 58-year-old man underwent laparoscopic radical resection of sigmoid carcinoma and ileostomy in the local hospital in June 2017. After the operation, he underwent intermittent chemotherapy six times. His physical condition recovered, and the re-examination showed no tumor recurrence. The patient was expected to undergo ileostomy takedown in the local hospital in June 2018 and April 2019, respectively, but the operation was not performed because of the COA, which was found by colonoscopy. The patient was admitted to the Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China in May 2019. To address the difficult and complicated post-surgery problems of this cancer patient, the medical team conducted a comprehensive and careful related examination and disease evaluation. The abdominal enhanced computed tomography (CT) showed postoperative changes of sigmoid carcinoma. The intestinal lumen above the anastomotic stoma was narrow and adhered to the anterior sacral fascia. The stoma was unobstructed after the right lower abdominal fistulation (Fig. a). Further barium enema examination suggested that the anastomotic stoma in rectum is completely closed and separated (Fig. b). Blind ends were present on both sides of the sigmoid colon and the rectum, and the bilateral blind ends were approximately 3.0 cm apart. The laboratory examination of the patients showed that there was no obvious abnormality in the general hemogram and no significant change in the level of tumor markers. Physical examination showed no obvious discomfort.
Despite the presence of COA with anastomotic separation, the examination results indicated that the blind end of the anastomotic site grew well. No obvious defect was found in the surrounding tissue. At the same time, the additional surgical operation would bring more trauma. Therefore, after speaking with the patient and his family, we planned to perform endoscopic operation on the patient to treat his disease. If endoscopic surgery cannot solve the problem, then surgery can be performed immediately or postponed as an alternative.
After the improvement of the preoperative examination, along with adequate preoperative communication and informed consent of patients, endoscopic surgery was proposed. In endoscopic surgery (Fig. ), we first observed the two blind ends of the anastomotic stoma through colonoscopy. On the one hand, the COA can be seen at about 8 cm through the anus side of colonoscopy. The closure line showed a fine line scar, and the intestinal wall at the blind end was soft. On the other hand, the colonoscope entered through the ileostomy side to reach the rectal segment. The front of the blind end of the bowel was found to also be truncated and closed with a white linear scar, and a titanium clip was placed at the proximal blind end. The intestinal wall of this blind end was also soft when touched. Second, the distance between the blind ends of both sides of the intestine was 3–4 cm, as measured by fluoroscopy at different positions. Subsequently, the colonoscope re-entered through the anal side. The hook knife (KDL-620LR; Olympus Optical) was used to slowly cut through the scar tissue layer by layer in the center of the blind end of the intestinal canal, and the yellow adipose tissue became visible. The direction of incision was determined to be parallel to the direction of the titanium clip at the proximal blind end, as shown by repeated fluoroscopic observation. The adipose tissue was carefully cut open, and the proximal intestinal muscular layer was still not visible after 4 cm of advance. Third, EUS-FNA (19 Ga, 1.10 mm; Boston Scientific) puncture needle was used to puncture along the direction of the titanium clip under fluoroscopy, and a small amount of contrast agent was injected to observe the flow direction and the visualization of the intestinal canal. The intestine was visualized after the needle touched the titanium clip, and a yellow zebra guide wire was placed after the needle entered the proximal intestine. Finally, colonoscopy was performed through one side of ileostomy to confirm that the guide wire was located in the proximal intestine tube. The dilation tube and balloon (M00558430; Boston Scientific) were inserted over the guide wire, and the incised bowel was gradually dilated to 12 mm under fluoroscopy. Subsequently, a 60 mm * 20 mm self-expandable full-coated metal stent (Cook Medical, Bloomington, IN, USA) was placed over the guide wire to bridge both sides of the intestine, thereby achieving the repair of anastomotic closure with separation through the endoscopic operation. After completion of the operation, the patency of the stent was checked, no bleeding was found on the wound surface, and the anal canal was retained. Compared with the “drastic” surgical operation, this endoscopic surgery solved the intractable problem of COA with anastomotic separation with a more delicate and subtle operation and with minimal trauma. Endoscopic stent removal was performed on the patient 10 days later. The continuity of the bowel was observed intraoperatively, and an anal tube was placed in the proximal part of the anastomosis to observe the postoperative recovery.
One month later, stenosis was observed at the original anastomotic recanalization site during endoscopic examination, and scar-like hyperplasia was observed in the surrounding tissues. We successfully leaped over the narrow segment through inserting a new self-expandable full-coated metal stent of the same specification, and the stent expanded smoothly (Fig. ). After 1 week, the patient underwent stent removal and came to our hospital for follow-up and reexamination for several times after discharge. The anastomotic stenosis of the patient was gradually relieved. At 1 year after the endoscopic recanalization procedure for COA with anastomotic separation, the patient came to our hospital in June 2020 for ileostomy takedown. No related complications occurred during and after the operation. No obvious abnormality was found in the relevant post-operation laboratory and imaging examinations.
The follow-up situation at 3 months after discharge was as follows. The patient returned to a normal diet from a fluid diet and achieved normal exhaust and defecation. The results of colonoscopy showed that the anastomotic stoma healed well, and no obvious stenosis was found. At the same time, biopsy and pathological examination were carried out on the new tissue of the original anastomotic closure with anastomotic separation. The pathological results indicated that this site was normal intestinal mucosal tissue (Fig. ). Further endoscopic ultrasonography also confirmed the growth of normal intestinal mucosal tissues at the original anastomotic recanalization site (Fig. ).


A 14-year-old adolescent male belonging to central India presented to our tertiary care health facility in central India with a history of persistent headache for 2 weeks, projectile vomiting for 5 days, neck stiffness for 5 days, and a single episode of generalized tonic-clonic seizure (GTCS) lasting for 10 minutes. Papilledema was present. Systemic examination showed right-sided hemiparesis (power 2/5) with exaggerated deep tendon reflexes and a positive Babinski sign suggestive of an intracranial space-occupying lesion (SOL).
After initial stabilization, brain magnetic resonance imaging (MRI) revealed a heterogeneously enhancing mass (6.2 × 5.2 × 4 cm), located in the left lateral ventricle extending diffusely into the ipsilateral parietooccipital region with perilesional edema with a midline shift of 6 mm (Fig. ). There were no signs of spinal cord involvement. Magnetic resonance (MR) spectroscopy showed reduced N-acetyl-aspartate (NAA) and increased choline, with a lactate peak suggestive of a malignant mass.
Gross total excision of the tumor was achieved with coagulation of the choroid plexus. Intraoperative findings revealed a soft, cystic, necrotic, and highly vascular tumor with intraventricular extension. Histopathological examination revealed crowded and branched papillae merging to form sheets of tumor cells disrupted by areas of necrosis with tumor cells exhibiting nuclear pleomorphism (multilobulated, multinucleated hyperchromatic nuclei). Mitoses were readily identified (15–20/10 hpf). Surrounding brain parenchyma infiltration was also noted (Fig. ). Immunohistochemistry showed tumor cells expressing cytokeratin (focal) and P53 (diffuse) but did not express synaptophysin, glial fibrillary acidic protein (GFAP), or epithelial membrane antigen (EMA). Also, MIB-1 nuclear labeling was increased markedly, with the index being approximately 40% in areas of highest proliferative activity. Hence, a diagnosis of choroid plexus carcinoma (CPC) was rendered.
The patient’s postoperative recovery was satisfactory with improved power (5/5 on the right side) and resolution of all symptoms. The patient was planned for adjuvant radiotherapy. He received 59 Gy of cranial radiation in 33 fractions using intensity-modulated radiation therapy (IMRT). Follow-up imaging after 3 months showed no residual neoplastic lesion with no metastatic lesion elsewhere on CNS imaging (Fig. ). The further management plan includes close follow-up for the next 6 months with neuroimaging again 1 year postsurgery.


The first case involves a 5-year-old Caucasian girl who was initially admitted to our clinic for behavioural disorder. She had a history of not following rules, both within and outside the family setting, and had no understanding or sense of dangers. She was unable to focus on tasks and to maintain attention on the activity on hand, interrupting these activities (e.g. playing) and tasks before completion. She refused to stop manifesting crises of anger, crying and hetero-aggressive behaviour. These behaviours occurred at home and at school, impairing relationships with peers and parents. She had an irregular sleep pattern, with frequent awakenings and primary nocturnal enuresis (5 times/week).
At 6 years of age, the girl was diagnosed with oppositional defiant disorder and treated with risperidone 1 mg/day. Three months later, her parents noticed poor clinical benefits and some side effects: hyperphagia, weight gain (8 kg), hyperprolactinaemia (42.63 ng/ml) and increasing frequency of enuresis (7 time/week). At age 7 years, we switched medication from risperidone to aripiprazole, starting with 2.5 mg/day and increasing the dose up to 5 mg/day within 2 weeks. Four weeks later, she showed improvements in her behavioural symptoms, decrease in hyperprolactinaemia and disappearance of enuresis.


The second case involves a young Caucasian boy, aged 7 years, who had been diagnosed elsewhere with generalized epilepsy secondary to a perinatal hypoxic-ischemic event, intellectual disability and early-onset psychosis. Since then, he had been treated with risperidone 1.50 mg/day, oxcarbazepine 750 mg/day and biperidene hydrochloride 100 mg/day. Soon after starting this treatment regimen, he developed daily distal tremors in the upper limbs exacerbated by emotional stress and became nonresponsive to anticholinergic treatment. At 9 years of age, nocturnal enuresis, 4 nights/week, reappeared. At 11 years of age, since the above treatment was ineffective, the proband was admitted for clinical assessment to our department where we stopped risperidone and replaced it with aripiprazole through a slow titration from 2.5 to 15 mg/day. After 1 month of treatment with the new therapeutic regimen, self-injuries and aggression decreased and bedwetting disappeared.
Both patients do not have a family history of enuresis. Moreover, urine examinations and routine biochemistry were normal.


A 16-year-old male of Caribbean descent without medical history presented with febrile neck stiffness, stupor, brisk reflexes, and no respiratory symptom, after 8 days of fever. Serum inflammatory studies showed elevated white blood cell count (12.6 G/L), elevated C-reactive protein (250 mg/L), procalcitonin (86 μg/L), and interleukin-6 (15.6 pg/mL, normal <8.5 pg/mL) levels. Hematology data showed initial thrombopenia (76 G/L), elevated fibrinogen (4.8 g/l), and D-dimer (1,357 ng/mL) levels. CSF analysis after receiving one cefotaxime injection favored bacterial meningitis with purulent fluid (1,566 cells/μl, 76% neutrophils), low glucose level (27 mg/dL), and elevated protein level (500 mg/dL). CSF Gram staining revealed both Gram-positive cocci and Gram-negative bacilli, without possible further identification; culture was sterile. CSF meningitis/encephalitis PCR panel and SARS-CoV-2 PCR were negative. Nasopharyngeal PCR was positive for SARS-CoV-2. Blood culture was positive for F. necrophorum and Streptococcus constellatus. Brain MRI revealed vasculitis of the Circle of Willis, with vessel wall enhancement and stenosis of the left internal carotid artery, middle cerebral artery (MCA), and anterior cerebral artery, associated with sphenoid sinusitis (). The association of a sphenoid sinusitis with anaerobic germ and an intracranial arteritis, but without initial cervical or cerebral vein involvement, oriented toward a diagnosis of atypical LS, prompting antimicrobial treatment, stroke prevention, and venous thrombosis prevention. Antimicrobial management associated an intravenous combined antibiotic drug course adapted to microbiological findings and meningeal and bone diffusion (cefotaxime, metronidazole, and levofloxacin) with endoscopic sphenoidotomy achieving good drainage. Stroke prevention combined anti-inflammatory (dexamethasone pulse course) and antithrombotic (aspirin) treatments, associated with careful maintenance of hemodynamic homeostasis. The patient had daily echocardiography and transcranial Doppler assessments to adjust blood volume and blood pressure, in order to maintain adequate cerebral perfusion. Venous thrombosis prevention relied on prophylactic dose enoxaparin treatment. While still in the pediatric intensive care unit, the patient presented with sudden right hemiplegia and aphasia 9 days after admission. MRI confirmed recent arterial ischemic stroke in the left MCA territory, severe and bilateral vasculitis, and left ophthalmic vein thrombosis (). Despite anti-inflammatory and antithrombotic treatment intensification with high-dose methylprednisolone pulse course, tocilizumab (anti-IL-6 receptor), remdesivir, and full-dose enoxaparin, clinical situation deteriorated, and the patient became comatose with severe brainstem dysfunction. While intubated, the patient had systematic standard chest X-Rays and arterial blood gases; all were normal. Intracranial pressure monitoring revealed intractable intracranial hypertension and the patient died 17 days after admission.


A 15-year-old female presented to hospital to a tertiary care emergency department with a history of malaise, dry cough, strawberry tongue, rash and jaundice. COVID19 was confirmed by detection of two SARS-CoV-2 viral genes using polymerase chain reaction. Her complete blood count, electrolytes, coagulation profile and blood gas were normal. C-reactive protein and ferritin were mildly elevated at 25.7 mg/L and 302 μg/L, respectively. She had a mild hepatitis with alanine aminotransferase 142 U/L, aspartate aminotransferase 87 U/L, alkaline phosphate 405 U/L, total bilirubin 92.6 μmol/L. She was admitted to hospital with a presumptive diagnosis of atypical KD and treated with intravenous immunoglobulin (IVIg) and Aspirin. Her inpatient electrocardiogram and echocardiogram were normal.
Blood was drawn for inflammation/endothelial injury profiling after the patient's COVID-19 status was confirmed, but IVIg had already been administered approximately 48 h earlier. Thus, analyte measurements must be evaluated in the context of this immune modulator (see below). Nonetheless, we measured 59 inflammation- and endothelium-related analytes using multiplexed biomarker immunoassay kits or enzyme-linked immunosorbent assay (ELISA). As only one COVID-19 pediatric patient was admitted to our hospital, we compared the measured analyte values from this COVID-19 case patient to analyte reference ranges that we obtained from a cohort of 20 pediatric healthy control subjects [median 15 years of age (IQR 8)].
The analyte data from the COVID-19 patient and the 20 healthy control subjects were first visualized with a nonlinear dimensionality reduction on the full data matrix using the t-distributed stochastic nearest neighbor (t-SNE) embedding algorithm () (). t-SNE assumes that the “optimal” representation of the data lies on a manifold with complex geometry, but low dimension, embedded in the full dimensional space of the raw data. Based on analyte measurements, the COVID-19 case patient is a clear outlier with respect to her inflammation and endothelial injury profile.
We then generated confidence intervals (CIs) for the expected value of each analyte using the plasma measurements from the 20 healthy pediatric controls. The plasma values for each analyte were not normally distributed, so we computed 99.9% (95%, Bonferonni corrected for comparison across 59 plasma analytes) CIs via the bias corrected and accelerated bootstrap. Plasma analyte values in the COVID-19 case patient that were outside the CIs for healthy control subjects were therefore considered significant (p < 0.05, corrected; ). We found significant elevations in 21 inflammation and endothelial analyte markers, while 1 endothelial glycocalyx degradation marker (heparan sulfate) was significantly depressed ().
After 3 days of observation, and partial resolution of her symptoms, our COVID-19 case patient was discharged home on Aspirin (3 mg/kg/day). Follow-up appointments at 2- and 6-weeks post-discharge revealed resolving hepatitis and both electrocardiograms and echocardiograms were normal with no evidence of coronary aneurysm. The aspirin was discontinued at the 6-week follow-up appointment.


A 46-year-old female presented to the primary care outpatient clinic with excruciating back pain radiating down to the lower extremities bilaterally along the inner calves. The patient presented to the office four weeks prior for back pain and was diagnosed with sciatica. She was prescribed tizanidine and tramadol to help alleviate her symptoms. Her past medical history was notable for chronic low back pain due to osteoarthritis diagnosed in 2017. She originally attributed her worsening pain to recently starting a new job where she was responsible for lifting a significant amount of weight, however, she reported that her back pain continued to worsen and described the pain as different from the previous pain. Additionally, the patient reported new onset urinary incontinence, numbness, and tingling in her inner thighs and calves. She reported that tramadol and tizanidine relieved her symptoms in the beginning, however, stopped providing any relief. The pain was described as constant and unrelieved by position or specific motions. She described the pain as sharp and tingling in nature. She reported the pain severity as a 9/10 at rest and after walking or movement, a 10/10.
Past medical history was significant for type 2 diabetes diagnosed in January 2020, essential hypertension diagnosed in July 2017, chronic back pain and osteoarthritis of the lumbar spine diagnosed in 2017, and iron-deficiency anemia diagnosed in August 2017. The patient had a cholecystectomy in 2015 without complications. The patient reports compliance with her medications: ergocalciferol (vitamin D2) 1,250 mcg capsule po once weekly, esomeprazole magnesium 40 mg po, losartan 100 mg tablet po daily, gabapentin 300 mg po daily, and ozempic 0.5 mg subcutaneous pen injection once weekly. Family history is significant for several family members having malignancy as illustrated below in Table .
At arrival the patient was afebrile (98.4℉) and hypertensive (161/80), with a regular heart rate of 91, respiratory rate of 18, and oxygen saturation of 100%. Physical exam revealed a healthy-appearing, well-nourished patient in significant pain. Musculoskeletal exam revealed pain along the lumbosacral spine with all range of motion (ROM), pain with movement and reduced ROM by 80% (great difficulty with getting out of chair). Neurological exam was significant for sensory deficits along the inner thigh. Considering the new onset urinary symptoms and change in intensity and description of pain from prior encounters an urgent MRI was ordered, the imaging results are displayed in Figure .
The patient was called and informed of her diagnoses and was instructed to immediately report to the nearest ED. Upon arrival to the ED, lab work and CT scan without contrast were ordered and neurosurgery was consulted (Table ). CT scan confirmed a gently lobulated soft tissue mass arising from the right psoas muscle extending into right L3 neural foramen resulting in CES. The CT scan also determined that unlike the infiltrative changes seen in the recent MRI, there was no definitive destructive osteoblastic or osteolytic changes evident.
Neurosurgery confirmed the diagnosis of CES and performed a laminectomy of L3. Additionally the tumor was removed and sent to pathology. Upon removal the tumor was described to be a very hemorrhagic, soft, and rubbery tissue that was highly attached to the dura. The biopsy was sent to pathology and the patient was discharged postoperative day one. Biopsy results confirmed the presence of a plasma cell neoplasm with the pathology report shown in Table below. The differential diagnosis for the patient remained plasmacytoma versus multiple myeloma.
Three days after discharge the patient followed up at her primary care office, where she reported a significant improvement in her symptoms. The patient’s back pain had improved drastically with only minimal residual urinary incontinence. Additional testing was ordered by medical oncology to assess for any additional neoplasms. After thorough evaluation no additional masses were found, kidney function remained adequate, and baseline anemia unchanged. Therefore, the final diagnosis of a plasmacytoma was confirmed.


We present the case of a 71-year-old man with a past medical history of coronary artery disease, remote history of three-vessel coronary artery bypass graft surgery (LIMA-LAD [left internal mammary artery-left anterior descending artery], SVG-PDA [saphenous vein graft to the posterior descending artery, SVG-OM [SVG to the obtuse marginal branch of the circumflex]), ischemic cardiomyopathy, hypertension, hyperlipidemia, and paroxysmal atrial fibrillation. He presented to the hospital following four weeks of progressive weakness, shortness of breath, and a syncopal episode. His vitals revealed a blood pressure of 110/64 mg Hg, pulse of 70 bpm, respiratory rate of 12 breaths per minute, and SaO2 100% on 4 liters supplemental oxygen by nasal cannula. On physical examination, he was cachectic and chronically ill in appearance, with peripheral cyanosis, pallor, and elevated jugular venous pressure. There was a mid to late peaking systolic ejection murmur at the base that was 3/6 in intensity and radiated to the carotid arteries. His carotid pulse was weak but not delayed.
Echocardiography demonstrated severe LV systolic dysfunction, LVEF of 20-25%, and reduced stroke volume (Doppler LVOT [left ventricular outflow tract] stroke volume of 30 mL and stroke volume index of 19.6 mL/m2). The aortic valve was thickened and appeared calcified (Figure ).
The peak aortic valve velocity was 2.05 m/sec and the mean gradient was 9 mmHg. The calculated AVA by the continuity equation was 0.8 cm2 (indexed valve area of 0.5 cm/m2). During infusion of low-dose dobutamine, the LVOT Doppler stroke volume increased to 33 mL and the calculated aortic valve area (AVA) did not change (Table ).
The LVOT stroke volume then declined at higher doses, that is, a biphasic response suggestive of myocardial viability but not meeting standard criteria for flow reserve []. Two-dimensional images at peak stress demonstrated the areas of new distal septal, apical, apical lateral, and mid to distal inferior wall akinesis, concerning for LAD territory ischemia. CT angiogram of the head and neck showed extensive stenosis involving the right innominate artery, left common carotid artery, right common carotid artery, right internal carotid artery, and bilateral subclavian arteries extending to the axillary arteries (Figure ).
Coronary angiography revealed patent LIMA-LAD, SVG-OM1 (SVG to the first OM), and SVG-rPDA (SVG to the right PDA) grafts, but severe stenosis of the proximal left subclavian artery (70 mmHg gradient) proximal to the LIMA takeoff (Figures , ).
Therefore, it was speculated that left subclavian arterial stenosis was a significant contributor to the LAD territory ischemia. A multidisciplinary team of cardiologists, interventional cardiologists, and vascular surgeons placed a 7-mm Dacron® bypass graft from the left common carotid artery to the left subclavian artery distal to the stenosis, reperfusing the LAD territory myocardium. This required intra-aortic balloon pump support and the patient remained on dobutamine post-operatively.
Repeat DSE five days following the bypass surgery demonstrated a higher LVOT stroke volume and AVA (48 mL and 1.1 cm2, respectively) on dobutamine 7.5 mcg/kg/min than present pre-operatively and a progressive, proportional rise in LVOT stroke volume and AVA (62 mL and 1.3 cm2, respectively) with increasing doses of dobutamine (up to 20 mcg/kg/min) (Table ). This confirmed the diagnosis of AV pseudo stenosis. The projected valve area calculation showed an AVA of >3.0 cm2 at a flow of 250 mL/sec (Figure ).
The patient was weaned off dobutamine and showed remarkable improvement in his symptoms. Patient was discharged to cardiac rehabilitation.


A 78-year-old male with a past medical history of chronic kidney disease, coronary artery disease, atrial fibrillation, congestive heart failure, and obesity presented to his local rural medical center with chief complaints of worsening abdominal pain, bilious vomiting, and lethargy. He was discharged one week prior with an upper gastrointestinal bleed due to a 2 cm duodenal ulcer and was discharged with pantoprazole and sucralfate. However, over the next week, he became unable to walk no more than 15 feet without experiencing excruciating abdominal pain localized to his periumbilical region. During his initial presentation to the emergency department, his abdominal examination demonstrated right lower quadrant tenderness. His emergency department laboratory results were noncontributory. Computed tomography (CT) without contrast showed air in the intrahepatic bile ducts and a radiodense mass in the distal terminal ileum consistent with a stone. There was also proximal dilation of small bowel consistent with obstruction (Figures , ).
On the subsequent day, he underwent exploratory laparotomy to remove the gallstone. A midline laparotomy incision was made in the periumbilical region. Sharp dissection was used to carry it down to the level of the peritoneum. Large dilated small bowel loops were immediately encountered, and they were followed to the impacted gallstone which was noted 6 cm proximal to the ileocecal valve. This was elevated into the wound and the stone was easily dislodged from its impacted site. The site where it was lodged was noted to have ecchymosis on the bowel wall with inflammation, but no evidence of perforation or necrosis was noted. Additionally, there was some inflammation in the surrounding mesentery in this region. The gallstone was milked back approximately 20 cm into the dilated proximal portion of the small intestines.
At this point, a Meckel’s diverticulum was encountered which had a large broad base and a long stalk (Figure ). The gallstone was positioned to be contained within the Meckel’s diverticulum and a thoracoadbominal-55 blue load stapler was used to transect the Meckel’s diverticulum with the gallstone in a horizontal fashion. After this, the staple line was oversewn with 4-0 silk sutures leaving a patent ileal lumen (Figure ). The gallstone was then retrieved (Figure ). Some of the bowel content were milked back into the stomach and removed via nasogastric suction. There was no spillage or contamination from the Meckel’s diverticulectomy. It was decided to withhold cholecystectomy and closure of the fistula due to age and comorbidities.
He was admitted to the intensive care unit where he remained intubated until post-operative day one. Post-operative complications included ileus and acute-on-chronic renal failure, which were managed using intravenous fluids and nasogastric tube placement, respectively. After a few more days of conservative ileus resolution, the nasogastric tube was removed, his renal function improved, and his diet was advanced to solids. He was subsequently discharged after a 10-day hospital stay with complete resolution of his initial symptoms. Five years thereafter, he remains free of abdominal pain and has not experienced any other bouts of gallstone ileus.


A 22-year-old Bangladeshi gentleman with no significant past medical history, presented to emergency department with neck pain and stiffness of three days duration associated with low grade fever. There was no history of headache, photophobia, convulsion or vomiting. The patient didn’t report any history of trauma. He worked as a shepherd.
He was admitted to medical ward for further evaluation and management. On arrival, he appeared comfortable but complained of neck pain and spasm. His vitals signs on admission were; Temperature: 36.9° c, Pulse rate:74/min, Blood pressure:124/90 mmHg, Respiratory rate:21/min.
Findings on physical examination were significant for limitation in neck flexion with no neurological deficit. Other system examination were unremarkable. Initial blood investigation revealed elevation of liver enzymes with high level of C-reactive protein (CRP), mycobacterium tuberculosis PCR test was negative, Brucella serology using enzyme-linked immunosorbent assay was positive for IgG and IgM with a positive agglutination titer of 1/ 1280, blood cultures grew gram negative coccobacilli, lumbar puncture revealed normal cerebrospinal fluid cytology with negative culture . The patient was evaluated with a brain computed tomography scan (CT) which was unremarkable, regrettably the trans thoracic echocardiogram was not performed .
Given his clinical presentation, prior history of exposure to sheeps and a positive brucella serology test, he was diagnosed as a case of acute brucellosis. The patient was started on doxycycline and aminoglycoside on the second day of admission. In view of persisting neck pain Magnetic Resonance Imaging (MRI) of cervical spine was done which showed a small anterior extradural collection at C5/C6 levels extending more to the right side with mild mass effect (). The patient condition was discussed with spine surgeon to evaluate the need for surgical intervention. It was decided to proceed with evacuation of the epidural collection. Exploration showed thickening of posterior longitudinal ligament with abnormal tissue attached to it. Tissue culture was taken which revel no growth, histopathological examination of tissue samples showed nonspecific inflammatory process with nonspecific granuloma.
Patient showed significant clinical improvement after the surgical evacuation with reduction of inflammatory markers (CRP decreased from 51 to 20), liver function test was not normalized but shows significant retrogression, patient discharged home in a good general condition on oral doxycycline and rifampicin to be continued for a minimum period of 6 weeks, after he receive six days in hospital gentamycin therapy.


A 70-year-old man developed sudden onset severe central chest pain lasting in total 2 h. Cardiovascular risk factors included only hypertension and the patient had a history of mild haemophilia B and chronic obstructive pulmonary disease (COPD). He presented to our institute some hours later, where a 12-lead electrocardiogram demonstrated T wave inversion in leads III and V1-V6 () and hs-TnI was mildly elevated (120 ng/L, normal < 14 ng/L), therefore a NSTE-ACS was diagnosed. Blood pressure was 160/90 mmHg. Baseline Factor IX activity was 24.9% (), activated Partial Thromboplastin Time [aPTT] was 37.9 s and international normalized ratio (INR) 0.98 (INR is normal and aPTT is prolonged in haemophilia patients). Haemogram and biochemical parameters were all within normal ranges.
As we adopted an early intervention strategy, the patient was referred to haematology for consultation and joined management. The patient was loaded with dual antiplatelet therapy (aspirin and clopidogrel), b-blocker and lansoprazole. The coronary angiogram was performed the next day and periprocedural intravenous unfractionated heparin (UFH) was used, guided by the ACT (activated clotting time) levels. Although ACT is prolonged in patients with haemophilia, replacement of the deficient FVIII or FIX suppress this phenomenon. Despite this, ACT remains a useful point-of-care test in order to monitor coagulation during PCI and to guide unfractionated heparin (UFH) treatment. Recombinant factor IX (with a periprocedural level target of >80%) was also administered (). Given the baseline level (24.9%), the patient received 5000 units of recombinant factor IX (Benefix, Pfizer, Philadelelphia, PA, USA) intravenously two hours before coronary angiography (CAG). CAG was performed using the left radial artery access and demonstrated unobstructed right and left circumflex coronary arteries. The left anterior descending artery (LAD) had proximally a severe non-calcified lesion causing 99% stenosis (A). The culprit lesion was treated with a 2.75 mm × 18 mm zotarolimus eluting stent and post-dilated with a non-compliant balloon 3.0 mm × 15 mm at 18 atm with a good final angiographic result (B). Three hours later, the TR BAND® Radial Compression Device was removed and neither bleeding nor haematoma was observed. The patient had an uneventful recovery and was discharged the following day with recommendation for DAPT (aspirin and clopidogrel) for 1 month. He continued to receive prophylaxis therapy with regular administration of FIX concentrates to keep trough levels around ≥30% while on DAPT (). He was completely asymptomatic in a follow-up appointment one month later, with preserved left ventricular systolic function on transthoracic echocardiography.


A 45-year-old premenopausal woman with no identified comorbidities noticed a right breast mass in late 2016, which was subsequently evaluated and ruled out as a cyst by a medical doctor during consultation. At that time, she weighed 54 kg with a body mass index (BMI) of 22.5 kg/m2.
In May 2017, she was treated for a skin ulceration in the cyst region of her right breast at a hospital near her home in Ohio, USA. The cyst was drained and found to be infected with Staphylococcus aureus. She also displayed a palpable nodule near the skin lesion. A bilateral mammogram on May 4, 2017 identified a 1.6-cm mass in the right medial breast with skin tethering. Bilateral breast ultrasound identified masses in both breasts and an enlarged right axillary lymph node. A punch biopsy of the skin lesion was performed on May 11, 2017, which demonstrated a grade 3 invasive ductal carcinoma involving the dermis, epidermis, and dermal lymphatic spaces. ER and PR were strongly positive (> 95%), and HER2 was negative on immunohistochemistry (1+). The patient received antibiotics for her infection and was offered conventional chemotherapy, which she refused because of the chemotherapy’s potential for side effects and toxicity. In March 2018, following clinical and radiological confirmation of disease progression, she received radiotherapy at the University of California, Los Angeles for local disease control. Subsequent evaluation in June 2018 using whole-body (18F)-FDG-PET-computed tomography (PET-CT) scan identified widespread metastatic disease. FDG-avid lymphadenopathy (LAP) was detected in the lower-left neck and supraclavicular region. Locally advanced breast cancer was suggested based on the findings of a large ulcerative lesion with intense hypermetabolism in irregular soft tissue thickening involving the medial aspect of both breasts. Involvement of the right adjacent pectoral musculature and direct invasion of the sternum were the areas of concern. The possibility of superimposed inflammatory/infectious processes (including osteomyelitis of the sternum) and postradiation changes were also considered. Numerous other FDG-avid lesions in both breasts and soft tissues of the chest wall were suspected to be metastases and/or multifocal primary lesions. Multiple FDG-avid pulmonary (and possibly pleural) metastases and extensive metastatic LAP were also detected. Multiple FDG-avid metastatic liver lesions and portacaval adenopathy were identified in the abdomen and pelvis, along with multifocal osseous metastases in the axial and appendicular skeleton. In July 2018, a new ultrasound-guided core biopsy was performed on the left breast axillary, which further documented widespread metastatic disease. Evidence of grade 2 invasive mammary carcinoma (ER (+), PR (+), and HER2 (-)) with mixed ductal and lobular features was consistent with her initial biopsy from May 2017. A follow-up CT scan in August 2018 confirmed significant and wide interval progression of metastatic disease at multiple pre-identified sites. An interval increase in the size of the pericardial effusion caused narrowing of both atria, particularly the left atria. Following this dismal report, the patient underwent echocardiography to assess tamponade physiology, which was reported to correlate with the PET-CT scan findings. Pericardiocentesis was performed with subsequent drainage of 360-mL of serosanguinous fluid. The patient was subsequently considered ineligible for further conventional therapy due to her advanced end-stage disease, poor performance status (Eastern Cooperative Oncology Group [ECOG] score: 3), and advanced respiratory symptoms. She obtained a second opinion and was informed that her expected prognosis was less than one month. The patient sought other treatment options and was ultimately admitted to the ChemoThermia Oncology Center, Istanbul, Turkey on November 5, 2018. Upon admission, her weight was 38 kg (BMI: 18.1 kg/m2). Poor performance status (ECOG score: 3) and a recent worsening respiratory tract infection were also noted. She underwent an objective clinical evaluation and documentation of her status, which included magnetic resonance imaging (MRI) of the brain with contrast, whole-body FDG-PET CT, and a detailed laboratory assessment (Figures -). The MRI revealed an 8-mm malignant lesion in the left occipital lobe. The FDG-PET/CT scan reconfirmed widespread metastatic disease with progression when compared to her prior scan. Laboratory results showed normal kidney function, a slight elevation in the liver enzyme level, and high C-reactive protein level of 119 mg/mL. Tumor markers were elevated with carcinoembryonic antigen and cancer antigen 15-3 of 45.6 ng/mL and 527 U/mL, respectively.
Whole-body (18F)-FDG-PET-CT scan performed before treatment on November 5, 2018 showed widespread multiple metastatic lesions in the lungs, mediastinum, liver, abdomen, and bones (Figure , Video ).
Following this detailed physical, biochemical, and radiological evaluation confirming widespread end-stage disease with a poor prognosis (< 1 month), the patient received counseling regarding potential side effects and complications of treatment. After providing written informed consent, the patient started treatment at our clinic on November 7, 2018.
Metabolically supported chemotherapy
Premedication consisted of 45.5 mg of pheniramine maleate, 0.25 mg of palonosetron hydrochloride, and regular insulin (Humulin® R) in doses ranging between 5 and 10 IU to attain mild hypoglycemia, defined as blood glucose levels of approximately 50 - 60 mg/dL (in accordance with MSCT protocols) [-]. The patient received 17 treatment sessions in each session after 14-hour fasting. The patient’s blood glucose levels were measured by finger stick testing upon admission, and her blood glucose was titrated to the targeted pretreatment mildly hypoglycemic level with insulin administration. The attending physician and nurse closely monitored the patient’s blood glucose levels and assessed her for clinical symptoms of hypoglycemia. Her fasting blood glucose levels upon admission ranged between 67 and 88 mg/dL, whereas her achieved pretreatment blood glucose ranged between 51 and 58 mg/dL. A chemotherapy regimen comprised of gemcitabine (600 mg/m2), carboplatin area under the curve 2, and paclitaxel (60 mg/m2) was initiated upon reaching the targeted blood glucose level. This drug combination was delivered on the first and eighth day of a 21-day cycle. Concurrent with this treatment, 4 mg of zoledronic acid was delivered every 28 days to treat the metastatic bone lesions.
Ketogenic diet, hyperthermia, and hyperbaric oxygen therapy
The patient was advised to adopt a diet that was high in fat and significantly limited in carbohydrates, modeling a KD. She and her caregiver were informed in detail about which foods to include and which foods should be strictly avoided. She was directed to modify familiar meals by eliminating grains and reducing sugars and dense starches while simultaneously incorporating more fats. Given that her cancer was ER +, she was advised to limit high-fat dairy products, which are contraindicated in estrogen-sensitive cancers. At each visit, an assessment of the patient’s blood glucose levels and review of the caregiver’s food records offered evidence of the patient’s ongoing compliance with KD principles, and further refinements to the dietary plan were made at each visit. Together with every MSCT treatment, the patient also received local HT and HBOT: two sessions of each - one of each on the same day as MSCT and one of each on the day following MSCT.
For each 60-minute HT session, an OncoTherm EHY-3010 HT device (OncoTherm, Troisdorf, Germany) was used to gradually increase the temperature of the tumoral region. The OncoTherm device uses modulated electrohyperthermia technology to selectively increase metabolic pressure on tumor tissue without negatively affecting the normal surrounding tissues, including the skin. A 30 × 40-cm mobile electrode was used for HT sessions and was placed starting from the supraclavicular region and covering the thoracic region and the upper abdomen, including the liver, targeting both the primary tumor and the supraclavicular, thoracic, and liver metastatic lesions. The objective of HT was twofold: (1) to obtain a tumoral tissue temperature greater than 43°C at the tumor site, as this temperature is reported to be cytotoxic, and (2) to increase blood circulation to the tumoral region which, in turn, is expected to improve chemotherapy drug delivery. The device used indirect temperature estimations based on the energy applied: indirect heat estimation for this patient’s local HT sessions ranged from 44.1°C to 45.6°C.
For each 60-minute HBOT session, a Quamvis320® hyperbaric oxygen chamber (OxyHealth, Santa Fe Springs, CA, USA) was used. This is a soft-walled chamber with a 32-inch diameter when inflated. The chamber was pressurized using a clean air compressor that filters air to 0.01 µm and a 10 L/min O2 concentrator to produce an operating pressure of 1.5 atmospheres absolute.
The patient’s treatment protocol comprising of MSCT, KD, HT, and HBOT was started together with infusional antibiotics on November 7, 2018. On November 9, she was hospitalized with respiratory complaints. On November 10, following the worsening of her respiratory function as evidenced by low blood oxygen saturation levels of 50% - 60%, she was intubated for effective medical support and transferred to the intensive care unit. Upon admission to the intensive care unit, her rectal swab culture was positive for vancomycin-resistant Enterococcus. Following the routine hospital protocol, she was moved to isolation within the intensive care unit, and her treatment was adjusted accordingly. She received mechanical ventilatory support for five days, along with infusional supportive care and antibiotic therapy. She was extubated on November 15 and transferred from the intensive care unit to the internal medicine ward where her infusional supportive care and antibiotic therapy were continued for an additional five days. The patient was discharged from inpatient hospital care on November 19 with stable vital signs and an oxygen saturation of 98% at room air. Her treatment was resumed as an outpatient at our clinic on the same day. After completing her fourth treatment cycle, a treatment response evaluation PET-CT scan was performed on January 16, 2019. Her PET-CT scan revealed the following findings: no pathologic FDG uptake at the head and neck; FDG uptake at both supraclavicular areas within physiological limits; 14-mm hypermetabolic LAP (standardized uptake value (SUV): 4 - 5) at the left axilla, and no mass lesion with FDG uptake in the left and right breast parenchymal areas. The thorax scan, when compared to her prior scan, revealed fewer and smaller nodules without FDG uptake. Free pleural fluid covering 3 cm on the right and 2.5 cm on the left was observed. In the mediastinal and hilar regions, no lymph nodes with pathologic FDG uptake were evident. The previously identified nodules in the liver parenchyma were again evident in the abdominal scan, with a significant reduction in metabolic activity and size, with the largest nodule measuring 3.2 cm at segment 8 (SUV: 3-4). Sclerotic changes without FDG uptake were observed in the skeletal system scan. In summary, the scan documented a treatment response at all sites. Low-density FDG uptake at nodules in the liver and a left axillary LAP indicated a partial response at these sites with a complete response to treatment at all other lesions (Figure , Video ).
Following the PET-CT scan on January 16, 2019, the patient continued with the same treatment protocol for an additional five cycles of treatment. A follow-up PET-CT scan and contrast MRI of the brain were performed on April 25, 2019, for treatment response evaluation. When compared to the January scan, the April scan revealed that the multiple nodules in the liver no longer displayed malignant FDG uptake. Similarly, the hypermetabolic activity previously observed in the left axillary LAP was no longer evident. The April MRI scan of the brain showed a complete response to treatment with no evidence of an 8-mm malignant lesion previously documented in the pretreatment MRI dated November 2018. In summary, the scan reports from April indicated a complete response to treatment for all lesions with no evidence of active disease (Figures -, Video ).
After treatment and before returning home to Ohio, the patient was advised to continue the KD, along with previously prescribed medications (metformin, doxycycline, meloxicam, capecitabine, rivaroxaban) and dietary supplements (medicinal mushrooms, curcumin, quercetin, alpha-lipoic acid, selenium, milk thistle, resveratrol) as follow-up maintenance therapy. To date (two years), she has continued with the recommended maintenance protocol in Ohio. Routine follow-up scans (PET/CT and MRI) and laboratory tests were performed and assessed by a local medical oncologist with some gaps due to limitations imposed by COVID-19. Her most recent follow-up PET/CT scan and laboratory tests were performed in March 2021 and indicated stability with no evidence of recurrent disease. The patient’s quality of life improved, and she was able to resume meaningful full-time work beginning May 1, 2019.


A previously healthy 14 year old male adolescent of mixed Turkish and German ethnicity presented at our emergency ward with headache, fever up to 39.9 °C, and vomiting since three days. Asymptomatic SARS CoV-2 RNA detection via PCR three months earlier was reported. Moreover, he suffered from decreased appetite, sore throat, and pain during swallowing. In addition, he complained about sleepiness and photophobia. On admission, he was febrile (38.6 °C) and showed tachycardia (130/min), the clinical examination revealed enlarged tonsils and deep-red inflamed pharynx, both eyes demonstrated slight, non-suppurative conjunctivitis. Pulmonary auscultation was normal, also no exanthema on the whole dermis was noted. Blood tests revealed elevated inflammatory markers paralleled by an activated coagulatory system and high cardiac injury biomarkers indicating participation of the myocardium ().
Echocardiographic evaluation showed normal heart function, coronary arteries, and valves ().
A small pericardial effusion was revealed () and electrocardiogram (ECG) showed no abnormalities.
The patient was started on i.v. antibiotics for presumed bacterial infection with consecutive clinical deterioration. After exclusion of acute viral and bacterial infection (), positive SARS CoV-2 IgG was retrieved, encountering asymptomatic Covid-19 earlier. Therefore, and after reviewing all clinical and laboratory data, diagnosis of PIMS-TS was made. Consecutively, an immunomodulatory therapy using immunoglobulin G (i.v.) was given, according to Kawasaki disease guidelines. As the patient’s weight was 73 kg, concerns about hyperviscosity after administration of 2 gr/kg BW in one dose were raised. Therefore, we decided to administer 2 gr/kg BW immunoglobulin G on two consecutive days (1 gr/kg BW each day) with good tolerability. The patient also received—in concordance to the Kawasaki disease treatment protocol—high dose acetylsalicylic acid. Twenty-four hours after administration of the second dose, the patient was afebrile and his clinical status improved. Acetylsalicylic acid dose was reduced to 5 mg/kg BW once daily, echocardiographic control some days later revealed resolution of the aforementioned pericardial effusion. Antibiotic therapy was ended after five days, and the patient was discharged from hospital on day 13. At follow-up two weeks later, he remained asymptomatic and in good condition.


A 17-year-old female adolescent of German ethnicity with prior good health conditions presented to our hospital with two days of history of itching exanthema beginning at the arms and feet, spreading secondarily over the whole body. She complained about ocular globe pain and swelling around the eyes. The patient also reported being unwell and experiencing fever chills and sweats. In addition, she complained of shortness of breath and pain in the neck. Following an uncomplicated infection of the upper respiratory tract, she was tested positive for SARS CoV-2 via PCR four weeks ago. At that time, recovery was fast, experiencing no complications. On admission, she presented in slightly decreased general condition, showing erythematous, non-scaling, itching exanthema on the whole body with predilection sites at the back, palms, and face. Auscultation of lungs and heart was unremarkable, transcutaneous oxygen saturation was 98%. Pharyngeal inspection demonstrated inflamed oral mucosa. Bilateral non-suppurative conjunctivitis was present, no enlarged lymph nodes could be detected. Neurological examination was unremarkable. Blood tests showed elevated levels for CRP, ferritin, D-Dimer, soluble Interferon 2-receptor (). Viral and bacterial detection tests, except for SARS CoV-2 antibodies, were negative (). Echocardiography demonstrated reduced left ventricular function and pericardial effusion along with elevated myocardial injury biomarkers ( and ) ( and ).
ECG resulted unremarkable. Given the combination of typical symptoms, PIMS-TS were diagnosed and consecutively a therapy with i.v. immunoglobulins G and high-dose acetylsalicylic acid was started. Due to concerns of hyperviscosity after administration of immunoglobulin G at a dose of 2 gr/kg BW in one dose, a division of immunoglobulin G dose to 1 gr/kg BW on two consecutive days was undertaken, as the girl’s weight was 76 kg. This therapy was well tolerated. Twenty-four hours after administration of the second dose, the young woman was afebrile and in good condition. Elevated inflammation markers improved after being afebrile (), echocardiographic follow-up also demonstrated improved cardiac function and diminished pericardial effusion (). The patient was discharged on day 7 with dramatically improved general condition. Echocardiographic control two weeks later showed normalization of cardiac function.


A previously healthy seven-year-old German girl presented to our hospital with fever up to 39.8 °C, headache, and belly pain for three days. She complained of sore throat, pain during swallowing and shortness of breath on exertion. She vomited repeatedly, oral ingestion of fluids and food was markedly reduced. Four weeks ago, she was tested positively for SARS-CoV-2, being only mildly affected with temporary loss of smell. Her parents were also tested positive at that time. On admission, the girl presented with reduced general condition, her body temperature was 39.5 °C, showing red, cracked lips, a scant erythematous rash on the back and reddened pharynx. A slight bilateral non-suppurative conjunctivitis was also noted. Her heart rate at rest counted 140 beats/min. The patient also showed elevated respiratory frequency with a transcutaneous oxygen saturation of 95%. No enlarged lymph nodes could be detected and no peripheral edema was noted. Neurological examination was unremarkable. Blood test revealed elevated inflammatory markers () with no evidence of bacterial infection (). After four weeks of being tested positive for SARS CoV-2 by PCR, the test was still positive with a cycle threshold (ct) value of 34.8, possibly indicating not being contagious anymore (). Therefore, therapy with remdesivir was not initiated. High titer of SARS CoV-2 IgG was also detected, suggesting immunity against SARS CoV-2. Echocardiography showed reduced left ventricular function, accentuated coronary arteries close to the outlet, but no aneurysm and a scant pericardial effusion () ().
ECG demonstrated no abnormalities. After excluding bacterial infection and COVID -19, the diagnosis of PIMS-TS was established and immunoglobulins (2 gr/kg BW in two divided doses administered twenty-four hours apart) were given with respect to diminished left ventricular function and hyperviscosity. High-dose acetylsalicylic acid p.o. was also added. The therapy was well tolerated, twenty-four hours after the second dose, she remained afebrile and her general condition improved. After decline of fever, acetylsalicylic acid dose was reduced to 5 mg/kg BW/day. Follow-up of inflammatory and cardiac markers showed improved values (), echocardiographic assessment after therapy revealed normalized left ventricular function and coronary outlets with no pathological findings (). The patient was discharged on day 9 in good clinical condition. Follow-up some days later revealed no further complications.
Incidence of SARS CoV-2 and PIMS-TS
summarizes the general characteristics of PIMS-TS patients.
We estimated incidence rates per year applying the Wilson method []. The incidence rate, for those under 18 years of age, of SARS CoV-2 positivity and of PIMS-TS among all SARS CoV-2 positive tested children for our administrative district (Ostallgäu) and our urban district (city of Kaufbeuren) are presented ().
The total number of inhabitants on 31 December 2020 in the whole region was 217.425, of which 32.697 under 18 years of age []. During a period of 50 weeks (week 12 in 2020 to week 8 in 2021), 570 SARS CoV-2 positive cases under 18 years tested by PCR were reported to the local health authority. During this period, three PIMS-TS patients were encountered during 15 weeks, equivalent to an incidence rate of 1.8% per year for SARS-CoV-2 positivity (95% CI: 1.7% to 2.0%) and among them 1.7% per year (95% CI: 0.9% to 3.1%) for PIMS-TS, after extrapolation to one complete year (SARS-CoV-2 positivity 593 cases, PIMS-TS cases 10 cases).


The patient was a 66-year-old man with a past medical history of end-stage renal disease with an arteriovenous fistula placed five years prior in the left arm for dialysis, hypertension, and diabetes who presented with one-week history of non-bloody diarrhea, vomiting, and fever. On physical examination, the patient was tachycardic and tachypneic. The patient’s initial laboratory results were significant for a leukocytosis of 23,000/µL with elevated inflammatory markers including a D-dimer of 4,700 ng/mL, a C-reactive protein of 382 mg/L, and a procalcitonin of 25.26 ng/mL. An initial chest radiograph was significant for a widened mediastinum with a lucent region alongside the thoracic aorta (Figure ). Computed tomography showed a 1.4 cm aneurysmal out-pouching of the proximal descending thoracic aorta along with inflammatory changes and gas bubbles in the periaortic soft tissues extending from the aortic arch to the mid descending thoracic aorta diagnostic of emphysematous aortitis (Figures -). There was also a large, loculated, left-sided pleural effusion with atelectasis of the left lower lobe initially concerning for empyema, but likely reactive as thoracentesis revealed polymorphonuclear lymphocytes with negative bacterial cultures.
Blood cultures revealed Clostridium subterminale bacteremia. The patient was worked up to determine the primary source of bacterial infection. Since Clostridial infection can be associated with pathology in the gastrointestinal tract, the patient underwent colonoscopy and esophagogastroduodenoscopy, which were both negative. Abdominal CT also showed no evidence of gastrointestinal lesion or malignancy. Echocardiography, performed to exclude seeding from endocarditis, was also negative. The patient urgently underwent ascending aorta and distal arch reconstruction with a left carotid-subclavian bypass. Unfortunately, despite multiple revisions of the aortic graft, broad-spectrum antibiotics, and vasopressor support, the patient succumbed to cardiac arrest from multi-organ failure due to septic shock. Post-mortem aortic tissue cultures were positive for C. innocuum.


A 14-year-old boy of Malian nationality accompanied by his parents presented at IOTA, Bamako, Mali, with a painless swelling of the upper right eyelid, which had been gradually increasing for approximately 3 months. Visual acuity was logMAR 0.10 and 0.00 in the right and left eye, respectively. External examination revealed a right orbito-palpebral mass, pushing the globe slightly downward and inward (Fig. a). Slit lamp examination of the anterior segment and fundus was normal in both the eyes; intraocular pressure was 13 mmHg on both eyes. Computed tomography revealed a mass of the right lacrimal gland with low tissue density and heterogeneity that was enhanced by iodine contrast. The right palpebral mass measured 29 × 13 mm (Fig. b).
Total excision of the mass was performed by transpalpebral orbitotomy. Pathological examination revealed an inflammatory granulomatous infiltrate of the lacrimal gland consisting of lymphocytes, eosinophils, giant cells, epithelioid cell, histiocytes and calcified schistosome eggs with terminal spine (Fig. ).
We questioned the patient and his parents regarding a possible history of schistosomiasis. The patient revealed that he has been experiencing terminal hematuria for at least 3 months. Urine examination revealed eggs of S. haematobium. An abdominopelvic ultrasound found irregular thickening of the bladder wall with cystitis and homogeneous splenomegaly. No other ectopic locations of the eggs were found. Praziquantel 40 mg/kg was administered to the patient. The hematuria stopped after 1 week. The dose of the prescribed medication was renewed 1 month later. After 3 years of follow-up, no recurrence was noted (Fig. ).


A 7-year-old boy presented to our hospital complaining of torticollis, neck pain, and right-side hemiplegia that occurred after a seat-belt injury sustained during a car accident 1 day previous. Clinical examination showed tenderness and limited neck rotation. Neurological examination showed motor weakness on the right side (right upper extremity, muscle power grade 0/5; right lower extremity, 2–3/5; and left upper and lower extremities, 5/5) and no sensation of pain and temperature on the left side. Plain radiographs (Fig. A and B) revealed anteriorly displaced transverse dens fracture along with ossiculum terminale, increased atlanto-dental interval (ADI) of 4.5 mm, asymmetric distance between the lateral masses of C1, anteriorly displaced and rotated right lateral mass of C1 to the left side, and increased anterior soft tissue swelling that indicated a retropharyngeal hematoma. Sagittal and coronal reconstructed computed tomography (CT) scans (Fig. C and D) showed the same findings more clearly. Axial CT scans (Fig. E and F) revealed unilateral facet subluxation with increased ADI of 4.5 mm, indicating type II AARS. Sagittal and coronal magnetic resonance imaging (MRI) (Fig. A and B) revealed retropharyngeal hematoma and transverse dens fracture. Right parasagittal and axial MRI (Fig. C and D) revealed intramedullary hemorrhage that occupied about 35% of the right side of the C3–4 spinal cord. However, no bony injuries were identified at C3–4 or the subaxial spine. An evaluation and consideration of neurologic abnormalities and radiologic findings resulted in diagnosis of Brown-Sequard syndrome at C3–4. Axial MRI (Fig. E and F) revealed rupture of the TAL at the same right side of the C1 lateral mass, which was type 1B TAL injury (Dickman classification).[
On admission, the patient's body weight was 22 kg, and he received methylprednisolone for SCIWORA of Brown-Sequard syndrome at C3–4. An infusion of methylprednisolone 500 mg for 3 hours was repeated for 5 days according to recommendation from physicians of the departments of pediatrics and neurology. At the same time, continuous traction was applied using a halter with 1-kg of weight. The weight was gradually increased to 3-kg over a period of 2 weeks, but he failed to achieve successful reduction. Therefore, manual reduction was attempted with the patient under general anesthesia, and reduction was finally achieved. The patient wore a custom-made Minerva brace for 6 weeks. The motor weakness and sensory abnormality gradually improved after methylprednisolone treatment (right upper extremity, muscle power grade 3/5; right lower extremity, 4–5/5). One month after closed reduction, follow-up CT (Fig. A and B) scans showed successful reduction of anteriorly displaced transverse dens fracture along with ossiculum terminale, decreased ADI of 3 mm, and correction of type II AARS. Seven months after closed reduction, follow-up plain radiographs (Fig. C and D) revealed corrected type II AARS that was well maintained and normalization of ADI to 2 mm. The reduced transverse dens fracture along with an ossiculum terminale was well maintained but still not united. The motor grade was slightly improved to the right upper extremity 3–4/5 and the right lower extremity 4–5/5. Furthermore, pain and temperature sensation on the left side were returned to normal. Compared to his initial findings, the patient's torticollis and limited neck rotation were corrected with a normal neck posture (Fig. E and F). After attending another hospital for further rehabilitation, the patient was no longer followed.


43-year-old female patient who had surgery for right breast cancer in 2015 and underwent a right mastectomy followed by 5 sessions of radiotherapy and 6 sessions of chemotherapy stopped in August 2016, and on hormonal therapy (Tamoxifen 1cp/d), presented to our department of maxillofacial surgery in November 2020 for left parotid swelling that had been progressing for 3 months. The patient was reported to our department by a regional referral hospital.
The clinical examination revealed a parotid mass of 4 cm long axis with skin that appeared to be normal in appearance, firm on palpation, painless, mobile to the superficial and deep plane, without facial palsy, with moderate trismus and mobile high homolateral jugulo-carotid cervical adenopathy with no visible inflammatory signs, an examination of the orifice of the Stenon's duct shows no inflammation or bloody outflow, and otoscopic examination finds no signs of invasion of the external ear duct.
Facial MRI revealed a slightly limited tissue process in the left parotid gland with polylobed contours in the T1 isosignal and T2 isosignal, which was heterogeneously enhanced after injection of the contrast agent [], with thickening and infiltration of the opposite soft tissues in contact with the medial pterygoid muscle and the external jugular vein, without any damage to the mandibular bone at the complimentary scan.
The extension survey did not reveal any distant metastasis. The patient underwent exotic parotidectomy with extemporaneous examination revealing carcinoma, followed by full parotidectomy with facial nerve preservation and homolateral supra-digastric adenectomy []. Surgical intervention was performed by our chief of maxillofacial department who has 15 years of operative experience.
The anatomopathological outcome of the specimen concluded at parotid Ewing's sarcoma with the positivity of CD99, cytokeratin AE1AE3, and synaptophysin. The patient was sent to oncology for adjuvant radiotherapy then was followed after her discharge in the outpatient department by a rhythm of twice a month for two first months and then once per month for a year.


A 53 year old Iranian man without any past medical history presented to the emergency department with symptoms of severe headache and bizarre behavior. Symptom onset occurred 2 weeks before admission; the first symptoms were fever and myalgia. The fever lasted 3 days, and then cough and dyspnea appeared. With the progression of dyspnea, the patient experienced some episodes of severe generalized headache. The headache became progressively worse, and on the day of his admission, he exhibited bizarre behavior. For example, he undressed, removing his shirt and trousers, in front of his family and also tried to urinate in the room. Due to the appearance of dysarthria that morning and other problems, he was admitted to the emergency department. He had no specific family or social history. On physical exam, except for dysarthria, he had normal vital signs, no sign of hypoxia, and normal neurological exam. The patient was alert and oriented to time, place, and person. No neck stiffness, Kernig’s sign, or Brudzinski’s sign was detected.
Routine laboratory tests and chest and brain computed tomography (CT) were performed. Laboratory test results are summarized in Table . Chest CT revealed bilateral peripheral ground-glass opacities suggestive of COVID-19 infection (Fig. ).
Due to normal brain CT results, brain magnetic resonance imaging (MRI) was performed to evaluate the cause of dysarthria and bizarre behavior (Fig. ). The brain MRI results were normal.
Based on the respiratory problem and positive polymerase chain reaction (PCR) test for COVID-19, the patient was treated with hydroxychloroquine (200 mg twice daily for 5 days). After 2 days, dysarthria and abnormal behavior were resolved completely. The patient was discharged on day 4, with resolution of respiratory and neurological signs and symptoms.


A 69-year-old male with a past medical history of hypertension and coronary artery disease with remote stenting presented with chest pain and abdominal pain for the past week as well as associated orthopnea. On arrival, the patient had a blood pressure of 86/48 mmHg and a heart rate of 104 bpm; he was afebrile and did not require supplemental oxygen. Electrocardiogram (ECG) showed sinus rhythm with a left bundle branch block and premature ventricular complexes (Figure ).
Physical exam revealed jugular venous distention but no obvious murmur or rubs. Laboratory results were significant for a leukocytosis of 19,000 cells/mm3, elevated C-reactive protein of 25.1 mg/dL, and an elevated erythrocyte sedimentation rate of > 130 mm/hr. Chest X-ray showed an enlarged cardiac silhouette and bibasilar atelectasis but no obvious effusion (Figure ).
Computed Tomography showed a large pericardial effusion with moderate pleural effusion but otherwise no intra-abdominal pathology (Figure ). Bedside transthoracic echocardiography confirmed a large pericardial effusion with tamponade physiology. The patient was emergently taken for pericardiocentesis and 500 cc of straw-colored fluid was aspirated with resulting hemodynamic stability of the patient.
Analysis of the pericardial fluid revealed 2565 nucleated cells (95% neutrophils), glucose of 52 giving a fluid-to-serum glucose ratio of 0.5, and <2000 red blood cells (RBC). Culture of the aspirated fluid grew methicillin-sensitive Staphylococcus aureus (MSSA). Interestingly, all blood cultures remained negative and the patient had no history of chest trauma or previous intrathoracic procedures.
The patient had a persistent leukocytosis and again was persistently hypotensive. A transesophageal echocardiogram showed preserved ejection fraction, no valve vegetations concerning for endocarditis, and a reduction in the pericardial effusion with evidence of fibrin products (Figure ).
It was decided to take the patient's sternotomy and mediastinal washout. Direct examination of the mediastinum revealed extensive inflammation and adhesions of the pericardium and aorta with purulent effusion (Figure ). Intra-operative cultures also grew MSSA. Biopsy of the pericardium was consistent with fibrosis, chronic inflammation, and fibrinopurulent debris. Cytology was negative for malignancy. The patient was treated with four weeks of intravenous cefazolin from the date of the pericardial washout. The patient required multiple washouts to achieve sterility of the pericardial space.


An 84-year-old woman was referred to our hospital for treatment of a primary RP tumour. At the age of 52, the patient underwent complete resection of a mass, approximately 3 cm at RP in 1991. The pathological diagnosis was LMS. Twenty-four years after the primary resection, metachronous recurrences occurred within the soft tissues, which were repeatedly resected. The recurrence sites were as follows: psoas muscle, latissimus dorsi muscle, deltoid muscle, and chest wall. As the tumours within the soft tissues felt stiff upon palpation, these tumours were easily detected by the patient. Ten recurrences occurred in the extremities, two in the retroperitoneum and three in the back. The chest wall was also involved twice, but both were completely resected. In 2015, multiple liver metastases were identified. Computed tomography(CT) showed that the tumour was located in segments 4, 5, 6, and 8. The whole tumour was enhanced in the early phase, and the enhancement was prolonged in the late phase (A–C). Ethoxybenzyl-magnetic resonance imaging(EOB-MRI) revealed that the tumours showed a high signal intensity on T2WI and a low signal intensity on T1WI (A and B). S4 subsegmentectomy and partial resection of sections 5,6, and 8, and cholecystectomy were performed. The operation time was 338 min, while intraoperative bleeding was measured in 400 ml. Gross examination revealed tumors with a fleshly and white-gray appearance and haemorrhagic foci (). Microscopically, the neoplastic cells appeared elongated with abundant cytoplasm and centrally located nuclei containing blunt-ended nucleoli resembling cigars (). Pathological examination revealed LMS metastasis. In 2017, liver metastasis recurred, and partial resection of segments 3 and 4 was performed (A). The patient was pathologically diagnosed with LMS metastases. In 2019, the patient underwent liver resection for the third time for segment 8 recurrence and survived with no signs of recurrence 1 year after the last surgery (B). Long-term survival of 29 years was achieved after undergoing over 20 surgical resections. All procedures used in this study were approved by the ethics committee of our institution. Written informed consent was obtained from the patient for the publication of this case report and accompanying images