A 47-year-old female with a past medical history significant for severe bilateral inguinal hidradenitis suppurativa and Crohn’s disease presented for the evaluation of a clinically symptomatic terminal ileal stricture. Preoperatively, she was taking Humira® (adalimumab; AbbVie, Inc.) injections every other week, and while this did not appear to impact her stricture symptoms, her inguinal hidradenitis suppurativa remained in remission with this treatment. After evaluation and discussion, the patient underwent a laparoscopy, during which she was found to have grossly normal large and small bowel, with the exception of a 20 cm segment of grossly narrowed, hyper-vascularized terminal ileum, which was partially obscured by creeping fat, and minimally dilated ileum proximal to the obstruction. A laparoscopic ileocectomy with primary anastomosis was performed. The patient tolerated the procedure without complication, was extubated in the operating room, and was transferred to the surgical floor following recovery. Pathology demonstrated both active and chronic Crohn’s disease with significant obstruction of the ileal lumen.
On the first postoperative day, the patient’s hematocrit began to drop, and that evening, her systolic blood pressure dropped to 100 mmHg. On examination, her abdomen was moderately distended. The patient was transfused a single unit of packed red blood cells and returned emergently to the operating room for a presumed diagnosis of active hemorrhage. Exploration was performed through a limited midline incision. Upon entering the abdominal cavity, a large volume of clotted and hemolyzed blood was encountered and removed. The abdomen was irrigated and explored in a systematic fashion to identify any source of the hemorrhage. We found no surgical source of the bleeding, noting diffuse, low-rate bleeding from areas of prior surgical dissection, including the right lower quadrant peritoneum and divided peritoneal edges. We also noted diffuse, low-rate oozing from areas where no surgical manipulation had been performed, including both fallopian tubes and the peritoneum overlying the hepatic flexure mesentery.
As there was no role for electrocautery or suture ligation, we irrigated with warm normal saline, packed with laparotomy pads, and transfused two units of fresh frozen plasma (FFP) while warming the patient. The packing was removed, and little bleeding was now identified. Several sheets of SURGICEL and SURGICEL powder (Ethicon US, LLC, Cincinnati, OH) were placed over areas of the most active diffuse bleeding. Intraoperative blood tests failed to identify any coagulation abnormalities or evidence of disseminated intravascular coagulopathy.
The patient was extubated and transferred to the intensive care unit. Her subsequent recovery was rapid and unremarkable, with no further evidence of bleeding. She was discharged from the hospital nine days after her initial surgery.
Less than 24 hours after hospital discharge, the patient’s husband brought her to the emergency department, stating that following dinner, she suddenly began “acting and talking strangely,” after which he witnessed her suffering a seizure. Soon after presenting, the patient had a second grand mal seizure in the emergency department. A non-contrast head CT was unremarkable. The patient was admitted, treated with standard anti-seizure medications, and suffered no more seizures, recovering rapidly (including a return to normal, oriented, appropriate mental status). MRI of the brain the next day (Figure ) identified white matter demyelination sites, which were confirmed by neurology to be the likely source of her new-onset seizures.


A 7-year-old girl was admitted to our hospital on May 16, 2019 with chief complaints of pale complexion persisting for 1 year and a cough for 20 days. She presented cough, purulent sputum, occasional chest pain, and the prophylactic use of voriconazole. She was previously diagnosed with IDA at the local hospital because of dizziness and complaints of abdominal pain at presentation on April 2018. On Feb 25, 2019 she was diagnosed with IPH at our hospital based on the manifestation of diffuse fine granular shadows in both lungs on chest computed tomography (CT), the presence of hemosiderin-laden macrophages in the gastric juice, aggravation of her pale complexion, apathy, poor appetite, occasional emesis of gastric contents without bile and blood, absence of hematuria, and presence of black stool (Fig. a). From then on, uninterrupted doses of corticosteroids (methylprednisolone, 2 mg/kg·day for 20 days, then 1.54 mg/kg·day for 2 months) were administered. Prior to admission, the CT showed diffuse granular shadows in both lungs and round nodular high-density shadows in the right lung on May 2nd, 2019 (Fig. b).The patient is the second child of a healthy couple, and her 16-year-old sister was healthy.
Physical examination revealed a blood pressure of 111/68 mmHg, a respiratory rate of 31 beats/min, a pulse of 100 beats/min and a weight of 31.5 kg. Pale complexion and a fat round face appearance were noted. The patient had a paroxysmal continuous cough, mild coarse breath sounds on auscultation, the liver located 2 cm below the ribs, and the spleen not palpable below the costal region. Moist rales, wheezing, hemoptysis, chest pain, and dyspnea were absent. Neurological examinations revealed no apparent abnormalities. There was no rash, no clubbed fingers, and no bruises on the lips and extremities.
Laboratory investigations revealed a white blood cell count of 20.62 × 109/L (reference range, 4–10 × 109/L), platelet count of 310 × 109/L (reference range, 100–400 × 109/L), hemoglobin level of 152 g/L (reference range, 110–155 g/L), mean erythrocyte volume of 85.3 fL (reference range, 75–92 fL), average hemoglobin content of 25.4 pg (reference range, 26–31 pg), and reticulocyte 1.36% (reference range, 0.5–1.5%). IgG, IgA and IgM were 5.40 g/L, 0.81 g/L and 1.87 g/L, respectively. The right lung contained scattered, circular lesions, and the boundaries were clear on chest CT performed on the day of admission (Fig. c, d). Bone marrow biopsy revealed active erythroid hyperplasia, primarily in the late juvenile erythrocytes, and the central globus pallidus of some mature erythrocytes was enlarged, which was consistent with the myelogram of iron- deficiency anemia (Fig. a). The anti-tuberculous antibody test, enzyme-linked immunospot assay, tuberculin test, HIV Ig, ANA, P-ANCA, C-ANCA, MPO + PR3, ESR and anti-GBM were negative. Viral nasopharyngeal swab tests, test for Mycoplasma pneumonia RNA in the sputum, antibody tests for Mycoplasma pneumonia and Chlamydia pneumonia, 16S rRNA screening for the presence of gram-positive and gram-negative bacteria, and multiple blood cultures (e.g. for the detection of L form bacteria, anaerobic bacteria, fungus etc.) were negative.
For further pathogen analysis, fiberoptic bronchoscopy was performed on the third day of admission. The lymphocyte, neutrophil, and macrophage counts in the bronchoalveolar lavage fluid (BALF) were approximately 3, 2, and 95%, respectively. Eosinophils were absent. Multiple erythrocytes and large numbers of hemosiderin-laden macrophages were observed (Fig. b). The BALF culture was negative. Next-generation sequencing (NGS) (BGISEQ-50) was performed to detect the presence of pathogens in the BALF. The sequencing results were compared to the sequences of pathogens in the four Microbial Genome Databases, including 3446 species of bacteria, 206 species of fungi, 4152 viruses, and 140 species of parasites. A 96% match was found with the reference sequence of N. abscessus.
Sulbactam and cefoperazone were used intravenously. The galactomannan test and (1, 3) β-D glucan test suggested fungal infection, and oral voriconazole was administered as antibacterial and antifungal treatment at the second day after admission. However, no improvement was noted. The lesion in the inferior lobe of right lung was better, cavity formation was observed, new lesions appeared in the left lung, and bilateral pleural thickening was observed (Fig. e, f) on May 29, 2019 (14th day of admission). After N. abscessus infection was diagnosed on May 21, 2019, linezolid with a dose of 0.04 g/kg·day was administered (Fig. ). Finally, the patient was discharged on June 3nd, 2019.
Chest radiography performed at 1, 15 and 21 months after discharge (Fig. ) indicated significant improvement of the pulmonary lesions compared to that at the time of admission with a small dose of methylprednisolone (0.25 mg/kg·day). Oral linezolid with a dose of 0.03 g/kg·day for 7 days was discontinued one week after discharge. The patient’s symptoms and pulmonary lesions had recovered, and the IPH appeared to be well-controlled (Fig. g, h).


Seventy-year-old man with a past medical history of alcoholism, overweight (Body Mass Index of 28.9 kg/m2) and T2D for more than 10 years, well-controlled with a combination of dipeptidyl peptidase-4 inhibitor, biguanide and sulfonylurea (last known HbA1c 7.8%; average blood glucose levels of 162 mg/dL), with no previous episodes of DKA.
He presented to the emergency department with epigastric pain and vomiting for 3 days. The day before, he had been prescribed empagliflozin for hyperglycemia. At admission, he was alert and oriented, with dehydrated skin and mucous membranes. The blood pressure was 136/90 mmHg with a pulse of 116 bpm. He was febrile (tympanic temperature −38 °C) and had tachypnea. Cardiac and pulmonary auscultation was clear. There was diffuse abdominal tenderness but with no signs of peritoneal irritation. Urinary output was >0.5 mL/kg/h.
Labs showed normal renal function and no electrolyte abnormalities. Amylase (253 U/L) and lipase (493 U/L) were elevated. There was also hyperglycemia (188 mg/dL), ketonemia (6.6 mmol/L) and metabolic acidemia with an increased anion gap (AG)—pH 7.28; pCO2 22 mmHg; HCO3− 10.3 mEq/L; lactate 2.0 mmol/L; AG 26 mmol/L—which worsened despite aggressive intravenous fluid replacement. Other causes of metabolic acidosis with an increased AG were excluded (renal insufficiency lactic acidosis and intoxication either by methanol, ethylene glycol or salicylates) and the diagnosis of SGLT2 Inhibitor-Associated Euglycemic DKA was assumed, aggravated in the context of an acute pancreatitis and decreased carbohydrate intake. Normal saline with dextrose and intravenous continuous insulin perfusion were started, alongside vital signs, hourly blood glucose, serum ketones and potassium were monitored. Afterwards, he was admitted to the surgical ward, with daily Internal Medicine evaluation, under a basal-bolus insulin regimen, with a favorable clinical evolution. After hospital discharge, the patient remained on basal-bolus insulin therapy, and was also referred to a specialized diabetes mellitus consultation for follow-up.


A 43-year-old female patient (para 9 with her last delivery two months prior) known hypertensive for 10 years presented to our department with gastrointestinal bleeding in the form of hematemesis, multiple episodes of melena, and hematochezia for one week. She also complained of weight loss and non-radiating and self-relieving epigastric pain not associated with positional changes. The patient was then assessed for causes of pseudoaneurysm formation, which primarily includes pancreatitis and cholecystitis. However, no significant abdominal tenderness, palpable abdominal mass, jaundice, flank tenderness, and increase in serum lipase and amylase were observed. The only significant findings included laboratory studies showing mild anemia with a hemoglobin of 9.6 g/dL, hematocrit of 29.5%, mean corpuscular hemoglobin (MCH) of 26.7, and red blood cells of 3.6 × 10^12/L, for which she was transfused two units of blood and started on injectable Vitamin K (10 mg, once daily), injectable tranexamic acid (500 mg, TDS), and omeprazole infusion (40 mg, once daily). After two days, her hemoglobin levels of 12.4 g/d, hematocrit of 37.5%, MCH of 26.7, and red blood cells 4.64 × 10^12/L. Meanwhile, mesenteric CT angiography also showed multiple splanchnic pseudoaneurysms involving the celiac axis trifurcation, gastroduodenal artery, superior/inferior pancreaticoduodenal artery, and jejunoileal branch of the superior mesenteric artery, and a large partially thrombosed pseudoaneurysm arising from superior pancreaticoduodenal branch causing a significant mass effect on the second part of duodenum as seen in Figure .
Based on such findings, coiling and embolization of the corresponding arteries were planed. Accordingly, the right common femoral artery was used as the access route with a retrograde 5-Fr catheter, which provided access to the celiac trunk and then into the gastroduodenal artery using a 4-Fr C2 and microcatheter. The large aneurysm in the gastroduodenal artery was identified and crossed. Multiple other small aneurysms with secondary aterio-venous malformations were also observed. The whole flow circuit (retrograde and anterograde) to the large aneurysm was packed with multiple coils, with the aneurysm sack also being coiled can be seen in Figure .
The second aneurysm in the pancreaticoduodenal artery was accessed after multiple attempts, showing multiple coils of variable sizes blocking the aneurysm sack and its retro- and anterograde flow evident from Figure .
As seen in Figure repeat angiography revealed good outcomes, with no retrograde or anterograde filling of aneurysm and immediate complications having been observed.
Postoperative care included augmentin administration (1 mg, intravenous; two doses) with positional changes to prevent any hematoma formation. The patient was advised to keep her head tilted on 45-degree angle. She was observed for one more day for any hematoma formation or bleeding prior to discharge.


We present a two-year-old female with no past medical history who was transferred from an outside facility after 15 episodes of projectile emesis which progressed from a clear to a coffee-ground color. According to the mother, the patient was afebrile at home with no sick contacts, no rash, no recent travel, no pets in the house, no diarrhea, or constipation. However, she complained of nausea and her mother noted significant fatigue and lethargy. Her last bowel movement was two nights prior to arrival. The patient was unable to articulate her own symptoms due to diffuse and sharp pain located in her abdomen. She lived at home with her mom, dad, and three dogs. She had no known drug allergies.
On examination, the patient was visibly in acute distress. She was pale, uncomfortable, and restless in bed with continual abdominal guarding. On palpation, her abdomen was hard, distended, and diffusely tender with severity being highest in the right lower quadrant. Her vitals revealed sinus tachycardia at a regular rate of 176 beats per minute, blood pressure 96/71 mmHg, respiratory rate 25 breaths per minute, temperature at 100.6°F (orally), and oxygen saturation at 98% on room air.
The patient’s laboratory studies were remarkable for a white blood cell count of 11.62 × 109 cells/L, sodium at 133 meq/L, potassium at 5.4 meq/L, and bicarbonate at 16 mmol/L with an anion gap of 10 meq/L. Ultrasound of the abdomen showed free fluid throughout the abdomen with several thickened bowel wall loops, no evidence of intussusception, and no visualization of the appendix. The patient was then rushed for a computed tomography (CT) of the abdomen without contrast which showed abnormal dilatation of mid-to-distal small bowel loops with no clear point of transition (Figures , ) suggesting a possible small bowel obstruction or perforated appendicitis; however, the appendix was still unable to be visualized. There was no evidence of bowel perforation.
The diagnosis of small bowel obstruction was clear from the patient’s acute presentation and imaging. However, the cause of obstruction remained unclear (Figure ). Specifically, imaging had ruled out intussusception and the appendix was unable to be visualized (Figure ). Therefore, the decision was made to perform a stat diagnostic laparoscopy with a possible conversion to laparotomy.
The patient was taken to the operating room where a diagnostic laparoscopy with conversion to laparotomy was performed. There was a 25 cm segment of necrotic ileum identified. Upon further inspection, there was an absence of the mesentery for the distal three-fourths of the small bowel. There was an obvious strangulated internal hernia causing the obstructive ischemia of the aforementioned segment of the bowel. The necrotic section of the bowel was removed and an end-to-end anastomosis was created between the two ends of the bowel. Attention was then turned to the appendix which was subsequently resected and removed. The patient was kept overnight for observation and was discharged with a targeted oral antibiotic course the following day due to an unremarkable post-operative course.


The proband marked III-7 (Fig. ), a 45-year-old pre-menopausal woman and her elder sister, a 51-year-old premenopausal woman marked III-6 (Fig. ), presented with abnormal vaginal bleeding. Pathological examination revealed endometrioid adenocarcinoma and imaging examination revealed that the disease was confined to the endometrial cavity. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. Her niece marked IV-5 (Fig. ), a 28-year-old woman, was diagnosed with endometrial carcinoma and received 500 mg medroxyprogesterone acetate daily for 3 months to preserve fertility. However, the disease progressed and the aforementioned staging operations were performed for the niece. Histological examination revealed carcinosarcoma with lymph node metastasis. She received chemoradiation therapy with cisplatin-ifosfamide. All three women were healthy without evidence of relapse for over 4 years.
Their family history revealed a typical clustering of cancer. Five first- and second-degree relatives had also died of colon, pancreatic, or uterine cancer and four other relatives had also developed stomach, colon, or uterine cancer (Fig. ). Ten of her relatives were diagnosed with Lynch syndrome-associated cancers across four generations. Therefore, this family meets the Amsterdam II criteria.
Immunohistochemical analysis of MMR protein was performed in biopsy specimens of patients. MLH1 and PMS2 expression were negative in the proband shown and her niece, indicating the loss of these proteins (Fig. a). Furthermore, MLH1, MSH2, MSH6, and PMS2 were deficient in the proband’s elder sister (Fig. b). To identify Lynch syndrome, MLH1 (reference sequence: NM 000249) and MSH2 (reference sequence: NM 000251) variants were evaluated using genomic DNA from peripheral blood of the proband. Polymerase chain reaction (PCR) amplification and Sanger sequencing were performed for genetic analysis (Seoul clinical laboratories, ABI veriti for PCR amplification, ABI 3500DX for Sanger sequencing). A c.1367delC variant was detected in MLH1 (Fig. ); however, no variant was detected in MSH2. We performed genetic analyses for the MLH1 variant among the proband’s relatives and III-2, III-6, IV-5, and IV-11 displayed the same MLH1 variant (Fig. ).


Herein we report a case of a polystigmatized 3 year-old boy, who was born by cesarean section in the 37th week of gestational age of a risk pregnancy, marked by oligohydramnios and growth retardation with a birth weight of 2680 g, length of 45 cm and Apgar score 8 of 10. During the first weeks of pregnancy the mother was taking oral hormonal contraceptive Dienorette (Laboratorios Leon Farma S.A., ESP), and reported also occasional alcohol and tobacco use. Following birth, the proband had numerous visible anomalies, such as thoracic left convex scoliosis, microretrognathia, cleft of both soft and hard palate, blue sclerae, bilateral clinodactyly of the 5th finger, single transverse palmar crease, bilateral talipes equinovarus, and simple incomplete syndactyly of the second and third toes. The talipes equinovarus and the cleft palate were surgically corrected at the age of 2 and 11 months, respectively. Other clinical features included horizontal nystagmus, hypermetropy, strabism, hypotonia with hypotonic quadriparesis and acral hypertonus, mild dyspnea, gastroesophageal reflux, hydronephrosis, and obstipated stool often with blood admixture. The patient was reported of having subclinical hypothyreosis, impaired cholesterol metabolism and hypoproteinemia with mildly decreased levels of total cholesterol, HDL cholesterol and apolipoproteins A and B. At the age of 2, speech and walking still absented, and patient showed signs of delayed psychomotor and mental development. At the age of 3, the proband was diagnosed with hypsarrhythmia and he developed epileptic seizures with eyelid myoclonia and infantile spasms. The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25 mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation.
Following the identification of the possible molecular cause of the symptoms (described below), the patient underwent further examinations such as electroencephalography (EEG) and magnetic resonance imaging (MRI) that confirmed the suspected diagnosis of PVNH7. Native and sleep EEG showed a severely pathological graph with encephalopathic character similar to Lennox-Gastaut syndrome. In the native EEG, slow basal activity in the delta range with poor regional differentiation and very frequent spike-wave complexes with slow frequency of 3 Hz and very high amplitude were observed, predominantly on the left side (mainly generalized). In the sleep EEG, transients were undetectable and epileptic activity was increased with no changes in the feature and localization. MRI confirmed the occurrence of supratentorial bilateral subependymal nodular to laminar lesions of cortex signal indicating the grey matter heterotopia with the width of 11 mm. In addition, numerous lesions showing nodular character located paraventricularly, in the central white matter and in corona radiata were observed. MRI revealed also thickened cortex bilaterally suggesting polymicrogyria without the signal changes, as well as hypoplasia of optic nerves and chiasma bilaterally. The unaffected parents reported no family history of known inherited diseases, abortions or developmental anomalies, except of the proband's older brother, who presented with hypotonia, blue sclerae, hydronephrosis, bilateral palmar crease (that was found also in their father), and bilateral talipes equinovarus. Supplementary Table S1 overviews the proband‘s complete symptomatology, together with the phenotype of his brother and the previously reported cases of PVNH7, while some of the external phenotypic features of the presently reported patient are visible on Figure .
Cytogenetic testing of the proband's genome revealed neither chromosomal aberrations nor numeric abnormalities. No pathogenic or likely pathogenic genomic imbalances on submicroscopic level were identified using array comparative genomic hybridisation. Whole-exome sequencing was then performed using DNA samples belonging to the proband, his brother and both his parents (details on the methodology can be found in Supplementary File 1). Conventional top-down strategy, that is, the phenotype and inheritance-pattern driven variant filtration and prioritization was complicated because of the then undiagnosed core feature of nodular heterotopia, slightly overlapping symptomatology of the brothers and the resulting ambiguity in inheritance-pattern. Therefore, we opted for the opposite approach, that is, the bottom-up strategy based on the identification and listing of all the proband's variants evidenced by ClinVar as pathogenic and likely pathogenic with subsequent manual searching for those consistent with proband's clinical manifestations, population data, and segregation patterns of the suspected variants and the partial phenotypes in the family. None of these analyses was performed due to research and all presented findings were results of the routine process of molecular diagnostics, therefore no ethics committee approval was needed.
In the patient's data set we identified a highly suspected heterozygous single nucleotide variant in the NEDD4L gene, NM_001144967.2(NEDD4L):c.2677G>A;p.Glu893Lys that was reported to be associated with PVNH7. This variant was not present in any other analysed family member suggesting a likely de novo origin, although we were not able to rule out genetic mosaicism in one of the parents. With regard to PVHN7, c.2677G>A (p.Glu893Lys) variant was classified either as “pathogenic” by 4 individual submissions in ClinVar database or as a “variant of uncertain significance” by single submitter (ClinVarID_225191). Human Gene Mutation Database classified it as a “disease causing mutation” (CM1613945), based on primary literature reports. Despite being present in dbSNP (rs879255597), the variant had no known frequency data at the time of the preparation of this manuscript (Build 154, Released on April 21, 2020), suggesting very low population frequency. According to the classification criteria of the American College of Medical Genetics and Genomics,[ the variant can be classified as “pathogenic” since it fulfils 2 strong and 1 moderate evidence: same amino acid substitution was described previously as pathogenic independently of the nucleotide sequence; de novo variant was present in a patient without a family history of the disease; and variant absent or was present at very low frequency in controls, in our case represented by the major population studies evidenced by dbSNP.


A 16-year-old Indonesian boy with fever and cough, and a history of close contact with a confirmed case COVID-19 patient was admitted to the emergency department in our hospital. From anamnesis, there was no comorbidity (e.g. hypertension, diabetes mellitus, autoimmune disease, or malignancy). Vital signs and oxygen saturation were in normal ranges. Laboratory, radiology, and nasopharyngeal swab polymerase chain reaction (PCR) tests were conducted and the results were positive for COVID-19 with CT values of RdrP: 28.05, E: 27.08. Laboratory examination showed leucocytes of 3720 cells/μL, platelet 241,000 cells/μL, lymphocytes 10%, monocytes 13%, neutrophil-to-lymphocyte ratio (NLR) 7.1, absolute lymphocyte count (ALC) 780 μL, d-dimer 269 ng/mL, quantitative C-reactive protein (CRP) < 5 mg/L, prothrombin time 13.1 sec, the international normalized ratio (INR) 0.96, and partial thromboplastin of time 23.7. The posteroanterior (PA) chest X-ray showed no radiological abnormalities in the heart and lungs (Fig. A). Computed tomography (CT) scan of the chest at the time also showed no visible acute lung inflammation, lung mass, or mediastinal tumour (Fig. B). The patient was treated with azithromycin, N-acetyl cysteine, paracetamol, and other supporting medications such as zinc, vitamin D3, vitamin C, and curcumin.
After several days of the treatment, the patient showed clinical improvement. On day 13, the patient had a nasopharyngeal swab PCR examination with a positive result of CT values of RdrP: 33.79, E: 33.77. On day 15 of the treatment, the patient suddenly had a high fever accompanied by severe and throbbing headaches, flatulence, nausea and vomiting, abdominal pain, numbness of arms, tingling and immobility of legs, and oxygen saturation of 93%.
The patient was then subjected to additional drugs, such as meropenem, dexamethasone, remdesivir, low-molecular weight heparin (LMWH) for five days, ondansetron, omeprazole, and supplements (e.g. vitamin C, zinc, and vitamin D3). Laboratory examination showed leucocytes of 12,220 cells/μL, platelet 260,000 cell/μL, monocytes 12%, NLR 17.72, lymphocytes 4.4%, d-dimer 16,180 ng/mL, quantitative CRP 26.4 mg/L, activated partial thromboplastin time (APTT) 19.9 sec, potassium 3.2, and aspartate aminotransferase (AST) of 51 U/L. Radiology examination showed no radiological abnormalities both in the heart and lungs (Fig. A). CT scan of the chest showed solitary ground-glass opacity nodules on S6 left lung (Fig. B). We consulted a neurologist, and the patient was then given additional peripheral neuropathy vitamin therapy such as methylcobalamin and vitamin B1 for five days. Furthermore, the patient was also given oxygen therapy and he felt better after that.
On day 20 of the treatment, the clinical symptoms reduced. The patient was able to move the limbs again and the tingling sensation reduced. The d-dimer value of 460 ng/mL, quantitative CRP of 6.1 mg/L, lymphocytes 13%, platelet 284,000 cell/μL and the other parameters were within normal ranges, although the PCR result was still positive. At the end of the third week, the patient was discharged from the hospital. The patient's PCR result was negative. The laboratory and radiology results had also improved.


A 69-year-old male patient was referred to our pain management clinic with a chief complaint of severe pain in both upper extremities. When he was 49 years old, he had a severe traffic accident and was rushed to the hospital. After examination, he was diagnosed with cervical ossification of the posterior longitudinal ligament, for which he had no relevant medical history. He underwent a C3–C6 laminoplasty immediately post-injury. However, his complete bilateral lower extremity paralysis and incomplete upper limb paralysis, as well as his severe upper limb pain symptoms persisted and he was diagnosed with C4 SCI (American Spinal Injury Association Impairment Scale A) []. He was prescribed various medications including antiepileptics, antidepressants, and weak opioids, those analgesics did not sufficiently relieve his pain. He underwent rehabilitation once a week to prevent joint contractures.
On presentation to our institution, his spontaneous, sharp electrical intermittent pain lasted between several minutes to half an hour and recurred in both upper extremities multiple times daily. The pain severely interrupted the patient’s sleep and quality of life (QOL), with a maximum pain score of 10 and a minimum of 7 on the numerical rating scale (NRS; 0–10). Although he maintained spontaneous breathing, he required maximum assistance with activities of daily living such as feeding and cleaning himself. He had paresthesia in C5–Th3 and sensory paralysis below T4. Manual muscle testing of the bilateral biceps and deltoid muscles revealed scores of 2–3/5, and his lower extremities showed complete paralysis. Muscle atrophy and edematous change were observed in his bilateral upper extremities. Magnetic resonance imaging (MRI) of the cervical spinal cord revealed a high-intensity lesion in the C3–C4 spinal cord (Fig. ). Although a T1 transforaminal epidural block reduced his pain to NRS 4, the effect was temporary. Therefore, his pain was considered an at-level SCI neuropathic pain, entailing both peripheral and central neuropathic pain. This patient was deemed a good candidate for SCS; therefore, we opted to perform an SCS surgical trial and implantation, and two 8-electrode epidural trial leads (Vectris™ SureScan™ MRI percutaneous leads, Medtronic Inc., Minneapolis, MN, USA) were implanted. Epidural access was obtained at the T6/7 interlaminar space. We had planned to position the tip of the leads at the target cervical dorsal column to obtain paresthesia in the painful region; however, the lead tips were placed at T1 because of epidural space adhesions at the cervical level (Fig. ). We tried sub-perception SCS stimulation (1-kHz frequency, 90-μs pulse width) as a trial stimulation for 7 days, and the patient experienced > 50% pain improvement (NRS range, 3–5). Hence, he underwent permanent implantation of a pulse generator (Intellis, Medtronic Inc., Minneapolis, MN, USA) in a subcutaneous pocket in the left abdominal region. One month after implantation, the patient’s pain intensity further improved to an average NRS of 3. His sleep and QOL significantly improved. At a 12-month follow-up, the patient did not report any increase in pain. Figure shows the patient’s progress in terms of pain scores and sleep quality.


The first patient was a man aged 25 years who has a history of RRP since he was 6 months old. Patients' first visit was complaints of shortness of breath. The complaint was preceded by a hoarse voice since 5 months ago. Endoscopic examination of the larynx showed a mass of laryngeal papillomas that filled the larynx so that the airway became narrow. Patients diagnosed with pediatric laryngeal papilloma type and upper airway obstruction. Patients undergo tracheotomy and proceed with microscopic laryngeal surgery to clear the papilloma mass.
Patients undergo papilloma cleansing surgery every 2 to 4 months. The patients who live outside the city and far from the health center that capable of performing laryngeal surgery cause patients to repeatedly experience upper airway obstruction so that they undergo a repeated tracheotomy. It was obtained a history by one of the patient that has undergone tracheotomy 4 times due to repeated upper airway obstruction. Until the age of 25 years, patients have undergone surgery 88 times already. The frequency of surgery does not decrease even though the patient has reached adulthood. Papilloma of the trachea began to spread to the bronchi since the age of 12 years so that the tracheocele was maintained from 1992 until now.
Repeated surgery causes stenosis in the larynx () so that the tracheocele is maintained. Another benefit of maintaining tracheoculosis is that it facilitates bronchoscopy when cleaning papillomas in the trachea-bronchi. A final endoscopic examination shows papilloma implantation in the trachea to the proximal right main bronchi (). HPV virus examination by the PCR method showed that the presence of HPV type 11 infection in patients with papilloma preparations ().
Histopathological examination of papilloma tissue was revealed the squamous epithelium coated with papilloma with moderate dysplasia and epithelium that appeared to be koilocytosis (). CT-scan of the cervical-thoracic thoracic () shows laryngeal narrowing due to papilloma mass and in the thorax papilloma growths are found in the trachea to the carina and nodules are found in the right lung parenchyma.


The second patient was a female aged 9 years old who has suffered from RRP since she was 6 months old. A history of surgery that has been undertaken was four times. Patients do not control on time so that the papilloma mass fills the larynx and becomes short of breath. At the age of 3, the patient has a tracheotomy. A final endoscopic examination showed papillomas growing on the trachea so that the tracheal cannula was maintained to date to keep the upper airway patent ().


A 33-year-old Chinese female patient presented to our department with facial and lower limbs edema for over 1 month. Over 1 month before admission, her serum creatinine was 61 μmol/L (normal range 44-133). Ten days ago, her serum creatinine elevated (125 μmol/L), with 24-h urinary protein 3.36 g (normal range 0-0.15), and urinary red blood cell 30-40/high power field (HPF) (normal range 0-3), serum albumin 14 g/L (normal range 40-55). Complete blood count showed low levels of platelet (84 × 109/L, normal range 125-350), white cell count (1.98 × 109/L, normal range 3.5-9.5), and hemoglobin (100 g/L). Her antinuclear antibodies were 1:10000 (normal range1:< 100), C3 was 0.134 g/L (normal range 0.6-1.5), C4 was 0.044 g/L (normal range 0.12-0.36), anti-dsDNA antibody (ELISA) > 800 IU/ml (normal range < 100), anti-Smith antibody 82 (normal range < 25). She was then diagnosed with SLE []. Renal ultrasonography showed normal kidney size and cortical thickness with increased echogenicity in the renal parenchymal.
Four days ago, her serum albumin was 11.6 g/L, with 24-h urinary protein 1.28 g/300 ml, urinary red blood cell 0-2/HPF, serum creatinine 179 μmol/L. Her hemoglobin was 113 g/L and platelet 161 × 109/L, which increased possibly due to extracellular dehydration from nephrotic syndrome. She had been on intravenous methylprednisolone of 40 mg due to renal and hematological involvement, subcutaneous injection of low molecular weight heparin at 3075AXaIU, and diuretics since. One day before admission, her hemoglobin was 65 g/L, platelet 79 × 109/L, and her urine full of red blood cells under HPF. She had no other medical history to report. The next day she was transferred to our department through an ambulance.
On admission, the patient was restless but responded correctly. Physical examination revealed pallor and relatively unstable vital signs (blood pressure, 149/85 mmHg; pulse, 130 beats/min, T 36.5 °C). Inspection revealed scattered ecchymosis due to anticoagulant injections on the abdomen. Abdominal palpation showed involuntary guarding and rigidity. Left flank tenderness on deep palpation was noted. Due to general weakness and frailty, it is hard for the patient to recall when the pain started creeping up. Initial investigations revealed a hemoglobin level of 42 g/L. Serum creatinine peaked at 296.2 μmol/L. Coagulation test was relatively normal except for high d-dimer level of 1.25 mg/L (normal range < 0.24 mg/L). Bedside abdominal ultrasonography showed a large left peri-renal fluid collection. There was no history of abdominal trauma. Therefore, spontaneous perirenal hemorrhage was highly suspected. A subsequent non-contrast abdominopelvic CT scan demonstrated subcapsular and perirenal hematoma of the left kidney (Fig. a). Emergency renal arteriography identified active extravasation of contrast media from a distant branch of the left renal artery (Fig. c). Furthermore, selective transcatheter embolization effectively obliterated the bleeding spot (Fig. d). With red blood cell transfusion and closely monitoring of hemoglobin, there was no sign of active bleeding. As the bleeding stopped, the patient continued 40 mg of methylprednisolone daily since admission for major organ involvement. Four days after admission, contrast-enhanced abdominopelvic CT confirmed renal parenchymal laceration (Fig. b).
Three days after admission, she manifested a sustained fever and cognitive defects. Her blood urea nitrogen was 63.99 mmol/L (normal range 1.8-7.1), and supportive hemodialysis was initiated in case of uremia encephalopathy. Except for lumbosacral decubitus ulcer infection, there were no signs of infection involving other systems. Neurologic examination reported no focal signs. Non-contract head CT was normal. Magnetic resonance imaging revealed slightly widened sulci and fissures of bilateral cerebral hemispheres. Since she could not cooperate, the cerebrospinal fluid test was postponed. Despite aggressive antibiotic therapy, headache and fever of over 38.5 °C persisted. As lupus encephalopathy was highly possible, she was administered three rounds of three-day intravenous pulses of methylprednisolone of 500 mg (since day six), followed by 40 mg methylprednisolone daily. She regained consciousness, and her fever resolved utterly after the pulse methylprednisolone. Renal replacement therapy was suspended after five times.
Due to her lumbosacral decubitus ulcer infection, a renal biopsy was unable to be performed. As she manifested as nephrotic syndrome with less prominent hematuria, lupus membranous nephropathy was highly suspected. After three pulses of methylprednisolone, she maintained 40 mg of methylprednisolone daily and two intravenous cyclophosphamide boluses (on day 34 and day 57 since admission, cumulative doses of 0.4 g). Her renal function gradually improved. One month after admission, her serum creatinine was restored to 46.3 μmol/, and urine volume increased to 2300 ml/d. Six weeks after admission, her albumin maintained a low level of 21 g/L, and cyclosporine 50 mg twice daily was added (Fig. ).
Thrombocytopenia had occurred since disease onset and did not improve after two rounds of intravenous pulses of methylprednisolone (Fig. ). On day sixteen after admission, her platelet count reached the lowest level of 31 × 109/L. Bone marrow aspiration smears showed normal thrombopoiesis. Antiplatelet antibody testing was negative. Lupus anticoagulant was absent. The anticardiolipin antibody of IgM and IgG isotype in serum was < 2.00 and < 12.0 PL-IgM-U/ml, respectively, within the normal range; and anti-β2-glycoprotein 1 antibody of IgG and IgM isotype in serum was 6.50 and 2.99RU/ml, respectively, within the normal range. Her lactate dehydrogenase was 956 IU/L (normal range 100-240), absolute reticulocyte percentage 6.15% (normal range 1.0-2.5), mean corpuscular volume (MCV) 83.4 femtoliters (normal range 82-100), international normalized ratio (INR) 0.84. Moreover, there were schistocytes observed on the peripheral blood smear. Her PLASMIC score was 6 points (hemolysis, no active cancer in the preceding year, no history of solid organ or hematopoietic stem cell transplant, MCV < 90 femtoliters, INR < 1.5, creatinine< 177 μmol/L), indicating moderate/high risk for thrombotic microangiopathy (TMA). Plasma exchange was recommended under this condition. Meanwhile, waiting for ADAMTS13 results, the patient received five times plasma exchange. Later results reported that complement factor H, anti-factor H autoantibodies were within a normal range, and ADAMTS13 activity was 75%. Six weeks after admission, the patient’s platelet level finally reached 125 × 109/L (Fig. ).
The following recovery was uneventful, and 2 months after admission, she was discharged and with regular follow-up. Ten months after discharge, her prednisone was gradually tapered down to 5 mg daily, with cyclophosphamide 50 mg every other day fortnightly (cumulative dose of 6.8 g), and cyclosporin stopped 5 months after discharge. Her latest laboratory results were as follows: anti-dsDNA (ELISA) < 100 IU/ml, C3 0.875 g/L, C4 0.236 g/L, hemoglobin 109 g/L, platelet count 157 × 109/L, serum creatinine 64 μmol/L, and albumin 37 g/L, urine protein +, urine red blood cell 0-1/HPF. Serologic measures and disease activity indices manifested her clinical remission.


A 67-year-old man presented to Accident and Emergency with a 1-day history large volumes of bright red per rectal bleeding. He denied any previous episodes. The patient had no previous surgical history, no history of gastrointestinal disturbance, and no change in bowel habit, weight loss, lethargy, abdominal pain or any infective symptoms. He had a background of insulin-dependent diabetes, hypertension, ischaemic heart disease and asthma. At time of initial surgical assessment, he had a systolic blood pressure of 103 mm Hg and a heart rate of 93 bpm. Abdominal examination did not identify any specific abnormalities and per rectal examination demonstrated fresh blood on the glove. The initial haemoglobin level was 158 mg/dl.
During initial surgical assessment, the patient identified that he was a practicing Jehovah’s Witness and would not accept blood products, even if that would result in a poor outcome, including death. The patient was therefore resuscitated intravenously with crystalloids as per his expressed wishes and underwent a CT angiogram to investigate the cause of the bleeding. CT scan demonstrated active bleeding in the caecum/appendix with an obvious blush noted ().
Despite an 18-hour period of conservative management, the patient continued to active bleed. Following discussion with the consultant surgeon, the consultant interventional radiologist and the patient, it was decided to proceed to a mesenteric angiogram to specifically identify and treat the area of bleeding. The patient’s beliefs as a Jehovah’s witness and his decision to refuse blood products did factor in this decision. Although he was stable, it was felt that it would be best to avoid a large operation, such a right hemicolectomy which may be required to control the bleeding operatively. Without the option of blood products, the morbidity and mortality from such a procedure could be much higher.
At angiogram, the superior mesenteric artery (SMA) was successfully cannulated, and the patient was found to have active extravasation from the appendiceal artery (). This was successfully controlled with a 3 mm coil.
Due to the embolization of an end artery, the high possibility of ischaemia of the appendix was a concern and the patient was closely monitored for signs of rebleeding and peritonism. He was also prophylactically placed on IV antibiotics per trust guidelines for intra-abdominal pathology. After 72 hours of conservative management, he exhibited signs of local peritonism in the right iliac fossa and a rising white cell count and the decision was made to proceed with operative management. A laparoscopic appendicecetomy was performed, and he was found to have an inflamed appendix with blue discoloration indicating ischemia (). No perforation or other abnormalities throughout the examined bowel were identified. Final histology demonstrated partial distal infarction, healthy viable base and no sign of neoplasm. The patient had an unremarkable recovery following his operation and was discharged after 2 days.


An 8-year-old previously healthy boy was referred to the pediatric rheumatology center of Kerman University, in Southeast of Iran, for left side lower extremity gait disturbance and limping. This condition had appeared three weeks prior to his visit and he did not have any history of trauma or vigorous activity. However, he had experienced mild respiratory tract infection including low-grade fever and cough approximately one week before refusing to walk. During this time, he had visited an orthopedist. However, his condition was not diagnosed in that visit. Finally, he was referred to our clinic for more evaluations. At the time of his first visit, the patient did not have a fever. We performed a complete and systematic examination. He had an antalgic gait at his left side due to difficulty in weight bearing. His physical examination revealed pain and limitation in flexion, internal and external rotational movements of left hip with a positive FABER Test. There was not any evidence of other contributing factors and red flags, including organomegaly, lymphadenopathy, skin lesions, and neurological deficits. His laboratory evaluations revealed a White Blood Cell (WBC) count of 9109 /L with an Absolute Neutrophil Count (ANC) of 3.2 109 /L and an Absolute Lymphocyte Count (ALC) of 109 /L, a platelet count of 312,000/µL, and a hemoglobin of 15.5 g/dl. The Erythrocyte Sediment Rate (ESR) and C-Reactive Protein (CRP) were 3mm/h and 3.5 mg/L, respectively (Table ). Considering the preceding symptoms of fever and cough, a serological investigation for both IgM and IgG of SARS-CoV-2 infection was performed. The tests indicated a high IgM level of 3.4 (with a 1.1 cut off) in the first test, and a high IgG level of 3.8 (with a 1.1 cut off) in the second test, which was performed one week later. Detection of SARS-CoV-2 antibodies was performed using SARS-CoV-2 immunoglobulin M (IgM) ELISA kits (Pishtaz Teb, Iran, ) and SARS-CoV-2 IgG ELISA kits (Pishtaz Teb, Iran ) according to the manufacturer’s protocol (Specificity: 97.30 %; Sensitivity: 79.40 %) []. The nasopharyngeal swab for coronavirus Polymerase Chain Reaction (PCR) assay was not tested due to latency evaluation from preceding symptoms and patient’s parents refusal. There was not any evidence of marked joint space widening, reactive bone and fatty changes and other pathologic findings in his hip X-Ray. In addition, his chest radiography was normal. He underwent hip joints ultrasound study with a result of 7mm effusion in left side. Finally, Magnetic Resonance Imaging (MRI) showed a moderate joint effusion at his left hip articulation and a minimal joint effusion at his right hip joint (Fig. ). Treatment was administered by skin traction and Naproxen 250 mg twice a day. The patient consequently recovered approximately one week later without any issues with either hip movement restriction or gait pattern and mobility.


A 6-year-old girl, who had experienced a high-grade fever for two days approximately one week prior to her visit, was referred to our outpatient Clinic due to her left side lower extremity limp. She complained of polyartheralgia in several joints including both knees and wrists with a predominant left lower limb pain in groin region and knee. She was born from a consanguineous marriage from a repeat cesarean section with a birth weight of 2.7 Kg. She had a history of right side hydronephrosis, which had gradually improved. The patient also had a history of limping three years ago, which had led to her hospitalization and aspiration of the right hip joint fluid. She had been unsuccessfully treated for septic arthritis by an orthopedic surgeon. Her mother is a nurse, who had been working in a secondary hospital facility for COVID-19 patients. At the time visit, the patient was thoroughly examined; she did not have fever and her vital signs were within the normal range. She could not bear weight on her lower left limb and had an antalgic gait. During examination, she showed no evidence of muscle involvement, but she had some limitations in the range of movements of her left hip joint and scant tenderness in both wrists. Despite the hip joint involvement, she did not have any compensatory gait pattern, any other limitations such as knee flexion, or any remarkable foot and ankle positioning. Her laboratory evaluation were as followings: WBC: 9.68109 /L (Neutrophils = 5.69 109 /L & Lymphocyte = 10 9 /L), platelet count: 511,000/µL, Hemoglobin: 11.9 g/dl, ESR = 39mm/h and CRP = 12 mg/L. She also tested positive for Coronavirus using PCR analysis. Serological investigation for both IgM and IgG of SARS-CoV-2 infection revealed a mild increase in IgM level to 1.2 (with a 1.1 cut off) without increasing the IgG level [] (Table ). Further hip X-Ray was normal. The hip ultrasound showed evidence of mild joint effusion in both hip joints especially in the anterior part of her left side (Fig. ). This patient was also diagnosed with post coronavirus reactive arthritis, and successfully treated with Ibuprofen 40 mg/kg/day administered in three doses during the day. She completely recovered and her laboratory and ultrasound findings became normal after 4 days. Her follow up at least for 45 days later did not show any subsequent signs or sequels.


A 48-year-old male has been suffering from prominent right eye, right conjunctiva congestion, swelling and abnormal intracranial noise for 40 days after trauma. The digital subtraction angiography (DSA) revealed the presence of right carotid cavernous fistula (CCF) (). After the temporary occlusion of the right ICA by compression, the anterior communicating artery was not immediately visualized (), and the posterior communicating artery was also not visualized during the vertebral artery angiography (). In addition, the patient could not tolerate the temporary right internal carotid compression test (<2 min) and suffered syncope. If Onyx was used for embolization, a filling balloon needs to be used to temporally occlude the fistula, which would prevent the Onyx from filtrating into the internal artery. However, the filling balloon would block the blood flow of the internal artery, and the blocking time would last for more than 2 min, which may lead to cerebral ischemia. Therefore, Onyx embolization was not suitable for this patient due to lack of good compensation. Simple coil embolization was chosen, because the patient could not afford the high cost. Larger coils were preferred to reduce the number of coil usage. During the operation, double microcatheters were placed, and the first five coils were smoothly filled (). When the 6th coil was filled, the fistula could not be completely filled, although the attempt to adjust the coil was made. Hence, the 6th coil was withdrawn. Due to the withdrawal of the 6th coil, the originally filled five coils were filled closely toward the fistula. The right ICA showed complete occlusion of the fistula and patency of the parent artery (). After 6 months, the DSA revealed no recanalization of the fistula (). After 7 years of follow-up, no symptoms of recanalization occurred. Therefore, the good outcome of this patient suggests that this procedure is feasible for treating the dCCF by simple coil embolization of the fistula.


A 51-year-old male subject was referred to our institution after the onset of frequent headaches, abnormal vascular bruit, and the absence of vision in the right eye. The preoperative DSA revealed the existence of right CCF (). However, after identifying the location of the fistula, one microcatheter was preset into the depth of the fistula (). Then, a large coil was used to form a basket, and support the microcatheter (). Accordingly, another microcatheter was placed in the shallow part of the fistula, and the coils were filled into this region through the microcatheter (), until the fistula was occluded (). The angiography without subtraction () and 5s-3D angiography () revealed that these coils remained stable, and tightly covered the fistula. Furthermore, these were dense in the shallowness of the fistula, and loose in the depth of the fistula. At 18 months after the operation, the DSA revealed no recanalization of the fistula, the excellent reconstruction of the parent vessel (), and the stable shape of the coils ().


A 55-year-old male subject presented with abnormal vascular bruit after trauma. The DSA revealed a right CCF (), and this was successfully occluded through the above treatment using only three coils (). At 3 months after the operation, the DSA revealed a pseudoaneurysm as a result of the compression of coils, but there was no recanalization of the fistula (). At 1 year after the operation, the DSA revealed the enlargement of the pseudoaneurysm as a result of the further compression of coils. However, no recanalization of the fistula was observed (). At 2 years after the operation, the DSA showed that the pseudoaneurysm became much smaller than the earlier size, and the fistula was still occluded ().


A 22-year-old male patient presented to the Emergency Department
with a 2-day history of haemoptysis (~100 mL) and dysphagia. He
had vital signs within the normal range, was haemodynamically
stable and had no stigmata of any chronic medical conditions. A
respiratory examination revealed decreased air entry in the right
middle and lower zones. The chest radiograph showed a well
circumscribed dense homogeneous opacity in the mid to lower
zones of the right hemithorax and a small left lower zone cavity with
a water-lily sign and obliteration of the left hemi-diaphragm .
He was suspected to have bilateral pulmonary hydatid cysts, with a
complicated left cyst.
Contrast computed tomography (CT) chest scan revealed multiple
cysts in both lungs (left side-complicated) and spleen consistent
with hydatid disease. The right lower zone (RLZ) cyst measured
94 × 110 mm (axial), 149 mm (long) and the left lower lobe cyst was
collapsed and measured about 48 mm. The spleen had a 127 mm
cystic lesion with a normal looking liver .
The patient was commenced on intravenous co-amoxiclav and oral
albendazole and had subsequent cessation of haemoptysis and then
referral for surgical management of the pulmonary and abdominal
cystic lesions. He subsequently had an elective right thoracotomy and
cystectomy with air leak closure without capitonnage at 6 weeks post
presentation.
The operation revealed a large hydatid cyst that ruptured upon
efforts to enucleate it. The membranes were delivered, major air leaks
were closed with 3/0 prolene sutures and the cavity was left without
capitonnage being performed. Routine chest closure was done with 2
drains placed and secured. The postoperative intensive care unit (ICU)
and ward stay were uneventful, and the patient was discharged 6 days
postoperatively with chest radiography that showed a small cavity in
the RLZ.
The patient presented again to the emergency department 8 days
after discharge with another episode of significant haemoptysis. The
repeat chest radiograph showed a small cavity in the right hemithorax
with a fluid level suggestive of the cystectomy space and a near normal looking left hemithorax . He was admitted and had medical
management of haemoptysis. He then experienced another episode
of massive haemoptysis, this time with airway compromise evidenced
by CO2
retention on the arterial blood gas (ABG). The repeat chest
radiography showed expansion of the right-sided cavity and a left
lower zone opacity. At this time, the working diagnosis was bleeding
on the operated side and aspiration to the left chest. Bronchoscopy
at this time showed blood in both main bronchi. Emergency right
thoracotomy was then performed where few air leaks were closed and
the cavity was capitonnaged. There was no obvious blood noted within
the cystectomy cavity though minimal blood remained in the pleural
cavity. The patient was extubated after routine drain placement and
chest closure.
He developed another significant bout of haemoptysis which
required reintubation 24 hours later. A post intubation chest
radiograph showed significant pleural collection and a chest drain was
placed to drain the space. An urgent CT chest scan showed a small
left lower lobe cavity with surrounding necrotic features, left pleural
collection with a collapsed and consolidated left lower lobe. The left
splenic cyst was noted to be intact .
Emergency bronchoscopy and left thoracotomy were performed
on the patient. Bronchoscopy showed a significant blood clot in the
left main bronchus and clear right main bronchus. Left thoracotomy
revealed a complicated cyst in the left lower lobe with significant
consolidation of the left lower lobe and the cavity was noted to be
small with foul smelling blood clots. A pulsatile bleeding vessel noted
within the cavity wall was ligated with 3/0 vicryl and the cavity was
capitonnaged. After routine placement of two chest drains, chest
closure was followed by an uneventful ICU stay
He recuperated well in the ward and was discharged home after
5 days and no further episode of haemoptysis was reported. The
latest chest radiograph is shown in . The patient is currently
doing well clinically and is scheduled for yearly review with a chest
radiograph to exclude recurrence. He was also referred to our general
surgical team to manage his splenic cyst.


A 55-year-old female was referred to the pulmonology outpatient
department with a history of a persistent productive cough of
‘pink’ sputum for the preceding 12 months. During this time, she
also developed progressively worsening dyspnoea and had grade 3
dyspnoea on the modified Medical Research Council scale at the
time of presentation to the clinic. No other respiratory symptoms
such as wheezing or chest pain were reported and she did not have
any constitutional symptoms of fever, night sweats or weight loss.
She had no history of any childhood respiratory illnesses nor did
she have any history of previous tuberculosis. The patient never
smoked and maintained sober habits. Her family history was non-contributory, and she was employed as a domestic worker with no
significant exposures that she could recall. She had hypertension and
was on chronic medication that included spironolactone, furosemide,
amlodipine, aspirin, simvastatin and oestrogen replacement therapy.
She previously underwent hysterectomy for abnormal uterine bleeding
and no malignancy was detected at the time.
She was treated with a 7-day course of amoxicillin-clavulanic acid
for supposed community-acquired pneumonia at a local hospital prior
to referral. Sputum for microscopy, culture and sensitivity during
this time did not yield any pathogens. The result of a tuberculosis
GeneXpert test was negative, but Mycobacterium tuberculosis culture
or investigations for atypical pathogens were not done. Blood tests
showed a white cell count of 7.3 × 109
/L, haemoglobin level of
13.6 g/dL, platelet count of 267 × 109
/L, C-reactive protein level of
21 mg/L and she tested negative for HIV. Although a chest radiograph
performed at the local hospital was described as revealing ‘extensive
opacification of the left lung’, the image was not presented at the clinic
and thus could not be reviewed. In view of her poor response to
treatment and blood results that were not in keeping with infection,
she was referred to us for further evaluation
On clinical examination, she was obese with a body mass index
of 48.24 kg/m²
. Her blood pressure was 120/80 mmHg, pulse rate
was 72 beats per minute (bpm), respiratory rate was 15 breaths
per minute and oxygen saturation was 93% measured by pulse
oximetry while breathing room air at rest. Arterial blood gas testing
was not performed. On respiratory examination, her trachea was
centrally situated, but she had dullness to percussion and bronchial
breathing of the whole of the left hemithorax, while she had normal
percussion and vesicular breath sounds on the right. The rest of the
clinical examination was within normal limits. A chest X-ray image
at the time of initial assessment revealed complete opacification
of the left lung with associated air bronchogrammes noted in the
left perihilar region .
Chest computed tomography analysis
confirmed dense consolidation of the left lung with no evidence
of atelectasis or pleural effusion .
In view of the clinical
problem of a non-resolving pneumonia, the differential diagnoses
included atypical pneumonia, non-tuberculous mycobacterial
disease, primary lymphoma of the lung and slow-growing primary
lung neoplasms. Flexible bronchoscopy was therefore performed to
obtain respiratory specimens for further analysis. Inspection of the
tracheobronchial tree revealed an excessive amount of watery sputum
in the airways in keeping with bronchorrhea. Bronchoalveolar lavage
specimens from the left upper lobe were sent for microscopy, culture
and polymerase chain reaction (PCR) tests for Mycobacterium
tuberculosis, Pneumocystis jirovecii, Mycoplasma pneumoniae and
Chlamydia pneumoniae. All PCR tests were negative. Flow cytometry
of bronchoalveolar lavage fluid found a normal ratio of CD4:CD8
cells, in keeping with a reactive T-cell response. Transbronchial lung
biopsies, however, revealed tumour tissue with the appearance of
a well-differentiated mucus-secreting adenocarcinoma with lepidic
features .
Immunohistochemical staining for cytokeratin 7
(CK7), thyroid transcription factor-1 (TTF-1) and napsin A were
positive, while staining for CK20 was negative. A final diagnosis
of invasive mucinous adenocarcinoma (previously known as
bronchioloalveolar carcinoma) was therefore established.


A 14-year-old girl underwent anatomical spinal reconstruction using notch-free, pre-bent rods (Fig. ); the MT Cobb angle was 63° (T7–L2), and the TK angle was 9° (T5–T12). The apex of the scoliosis was at T10. Postoperative radiographs obtained 1 week after surgery showed that the MT scoliosis and TK angles were 9° and 28°, respectively. The apex of the TK was at T6.


A 52-year-old woman presented to our clinic with regular tachycardia of 140 beats per minute, as revealed by a portable electrocardiogram (ECG). Although she had been diagnosed with Ebstein anomaly as a child, she did not undergo corrective surgery owing to the absence of any symptoms of heart failure, cyanosis, worsening exercise capacity, and progressive right-ventricular (RV) dilatation. A 12-lead ECG performed during sinus rhythm revealed a right bundle branch block with a normal PR interval and no evidence of ventricular pre-excitation. Echocardiography showed severe right-atrial (RA) dilatation and severe tricuspid regurgitation caused by apical displacement of the posterior and medial leaflets. Left-ventricular systolic function was normal.
An electrophysiological study was performed, and orthodromic atrioventricular re-entrant tachycardia (AVRT) was repeatedly induced because of a right-sided accessory pathway. The CARTOSOUND system, intracardiac echo facilitating full mapping integration of the CARTO3 3D electroanatomic mapping system (version 6.0, Biosense Webster, Inc, Diamond Bar, CA), was used for anatomic mapping. Apical displacement of the posterior and medial leaflets of the tricuspid valve was apparent. Using this information, the site of the functional tricuspid valve annulus, which was defined as the area surrounded by the sites of attachment of the leaflets of the tricuspid valve, was manually tagged.
Subsequently, a high-density activation map of both the RA and the RV was generated, using a PentaRay catheter (Biosense Webster, Inc.) during AVRT. This system allows for the visualization of the time phase difference with a lower threshold of total activation time as potential conduction block areas. Therefore, the activation map revealed the electrical atrioventricular (AV) groove (true tricuspid valve annulus, solid white line in ) and an overt gap between the true tricuspid valve and the functional tricuspid valve annulus (atrialized right ventricle [ARV]) (;
, view video online). In this patient, although both atrial and ventricular electrograms were recorded at the true tricuspid valve, the single ventricular electrogram was recorded at the functional tricuspid valve annulus. Therefore, the functional tricuspid valve was in the RV and was not the “true tricuspid valve.”
Furthermore, an accessory pathway was apparently located at the posterior aspect of the true tricuspid valve (; and
, view videos online). An ablation catheter (ThermoCool SmartTouch SF; Biosense Webster, Inc) that was passed through a steerable sheath (AgilisTM NxT; Abbott Medical, Inc, Minneapolis, MN) and placed at the visualized accessory pathway showed continuous ventruculoatrial (VA) potentials. The first radiofrequency application with an output of 30 W was successful in terminating the AVRT and eliminating conduction across the accessory pathway, 2.8 seconds after initiation (average temperature: 27°C, average contact force: 6 g) ().


A 17-year-old male presented to our emergency department (ED) with severe headache, nausea, emesis and fever for 1 day. Medical history was notable for chronic headache for 1 year eventually attributed to a large frontotemporal arachnoid cyst with mass effect. He underwent left temporal craniotomy for open fenestration of the arachnoid cyst 25 days prior to this presentation. He had a mild headache postoperatively, attributed to aseptic meningitis, that improved with steroids. No drains were left postoperatively. He was discharged on postoperative day (POD) 3 with steroid taper for 10 days. Overall, he continued to have intermittent headache that were not severe enough to seek medical attention until this presentation.
In ED, his work-up revealed positive influenza B PCR, unremarkable CBC, C-reactive protein 51 mg L−1 (normal≤9.9 mg L−1) and erythrocyte sedimentation rate 25 mm h−1 (normal ≤15 mm h−1). Head CT scan showed stable postoperative findings. He was admitted for supportive care but noted to have progressively worsening left temporal swelling at the craniotomy site that was diagnosed as a CSF leak from displaced dural graft secondary to persistent emesis. On the third day of admission, he underwent repeat craniotomy, revealing a defect in the dura that was repaired with a new graft and dural sealant. Although there were no findings suggestive of infection, a surveillance wound culture was obtained from soft tissue surrounding the craniotomy flap. Postoperatively, his symptoms improved except for mild headaches and he was discharged on POD 1 after a stable brain MRI.
The soft tissue swab was inoculated to 5 % sheep blood agar (BBL catalogue no. 221261), Chocolate agar (BBL catalogue no. 221267), and MacConkey agar (BBL catalogue no. 221270). The Gram stain prepared from the tissue swab showed no polymorphonuclear cells or organisms on the slide. The incubation conditions for the primary culture plates and subcultures were 5 % CO2 atmosphere at 35°C. Light growth of pinpoint Gram-negative coccoid colonies appeared at 48 hours, with poor growth at 72 hours. After 96 hours incubation, pale salmon-coloured colonies grew on 5 % sheep blood agar and chocolate agar. These were tested for identification and susceptibilities using the NC68 panel (Beckman Coulter catalogue no. B1017-422) on the MicroScan WalkAway 96 Plus System (Beckman Coulter), but there was insufficient growth on the panel for identification or susceptibility results due to the organism’s fastidious, slow-growing properties on culture. A Gram-negative identification card (bioMérieux Vitek 2 GN card, catalogue no. 21341) was set up on the VITEK 2 system (bioMérieux) and was identified with 98 % confidence. shows the minimum inhibitory concentration (MIC) and susceptibility for the tested antibiotics. Susceptibility testing was done utilizing Etest (bioMérieux) strips. Susceptibility results were interpreted according to the Clinical and Laboratory Standards Institute []; the organism was susceptible to both levofloxacin and meropenem.
The patient was called back to the ED on POD 5 when the organism was identified on soft tissue culture; susceptibility testing was pending at that point. He reported mild photophobia and intermittent headache since the dural repair. His exam did not show signs of meningismus or nuchal rigidity. CSF studies revealed WBC 231/mm3 (normal 0–5/mm3), 51 % neutrophils, 47 % lymphocytes, 2 % monohistiocytes, RBC 16/mm3 (normal 0/mm3), protein 77 mg dl−1 (normal 15–45 mg dl−1), glucose 41 mg dl−1 (normal 40–70 mg dl−1) and a negative Gram stain. Given the abnormal CSF profile, differential diagnosis included bacterial and aseptic meningitis. In the case of aseptic meningitis, the growth of from the soft tissue sample would be attributed to specimen contamination or soft tissue infection. He received intravenous (IV) meropenem 2 grams every 8 hours for possible bacterial meningitis with sp. and dexamethasone for possible aseptic meningitis while CSF cultures were pending. He showed rapid improvement. After his blood and CSF cultures were negative for 48 hours; he was diagnosed with aseptic meningitis and soft tissue infection with . He was discharged on oral levofloxacin 750 mg daily for 6 days and a steroid taper for 7 days. CSF bacterial cultures and 16s rRNA PCR and sequencing, for suspicion of sp. infection as described below, failed to identify a pathogen. The CSF sample volume for culture was more than 1 ml, the incubation conditions were 5–10 % CO2 atmosphere at 35°C and the culture was held for 10 days.
Two days after completion of antibiotics and steroid course (POD 15), he presented to the ED again with severe headache, nausea, emesis, neck pain, photophobia and fever for 1 day. He had nuchal rigidity without other signs of meningismus. Repeat CSF analysis showed WBC 8720/mm3, 76 % neutrophils, 4 % lymphocytes, 20 % monohistiocytes, RBC 8/mm2, protein 213 mg dl−1, glucose 22 mg dl−1. Complete blood count was notable for WBC 30×103 µl−1 with 77 % neutrophils. Brain MRI and MRV with contrast showed generalized leptomeningeal enhancement including ventricles. He was re-admitted and started on IV meropenem 2 grams every 8 hours and empiric vancomycin 15 mg/kg/dose every 8 hours. His repeat CSF culture was negative. Again, the CSF specimen was >1 ml in volume with the same incubation conditions and duration as described above. Vancomycin was discontinued after 48 hours of negative CSF culture, while meropenem was continued pending further testing given the higher suspicion for sp. infection. CSF bacterial 16s rRNA PCR and sequencing identified sp. consistent with bacterial meningitis. In both instances, the previous and current CSF testing, 16S rRNA amplicon sequencing was performed with universal primers (5F TTGRAGAGTTTGATYMTGGCT and 531R GTATTACCGCGGCKGCTG) using cycle sequencing described before []. Percent identity was 99.8 % (339/440) to strain B_MAR_18_176 (GenBank: MN396262.1)
The patient’s symptoms resolved within a week of antibiotic therapy, and he was discharged with meropenem 2 g IV every 8 hours and oral dexamethasone taper for 4 weeks. He was followed weekly in the outpatient clinic with complete resolution of all his symptoms including headache.


A 78-year-old Hispanic male with a past medical history of ischemic cardiomyopathy and end-stage renal disease presented to the emergency department (ED) with signs and symptoms of volume overload after missing his hemodialysis session. The patient complained of shortness of breath, paroxysmal nocturnal dyspnea, orthopnea, and dyspnea on exertion for the last three days before admission. He had a known history of true apical aneurysm confirmed on computerized tomography angiography. The patient was on chronic anticoagulation regimen for questionable apical thrombus on transthoracic echocardiography (TTE). Upon initial presentation to the ED, the patient complained of worsening shortness of breath, and was found to have fine bibasilar lung crackles, no jugular venous distention, and normal heart sounds on physical examination. Electrocardiogram (ECG) was performed and showed normal sinus rhythm with poor R-wave progression. No significant changes were found on ECG when compared with previous studies. Chest X-ray showed findings suggestive of early pulmonary vascular congestion. Initial troponin was mildly elevated at 0.046 ng/mL which subsequently trended down after an urgent hemodialysis session along with improvement in the patient’s breathing status.
A TTE was obtained which demonstrated a 2.2 × 2.3 cm globular structure in left ventricular apex with an abnormal appearance of the apical lateral segment (Figure ).
Doppler pattern was suggestive of either canalization of the apical mass or hypertrabeculation presenting as an unusual variation of LVNC with focal involvement of the left ventricular myocardium. Perflutren-enhanced images demonstrated heavy trabeculation in the left ventricular apex and apical lateral segment (Figure ).
Cardiac magnetic resonance imaging confirmed the diagnosis of LVNC. Anticoagulation was continued by the team to reduce the thromboembolic risk associated with LVNC.


A 65-year-old male with frequent episodes of abdominal pain and fever was referred to the University of Occupational and Environmental Hospital. Approximately seven years before the consult, the patient experienced abdominal pain and high-grade fever, lasting for a few days and spontaneously resolving without treatment. Similar attacks were noted once every two months, but he did not seek medical care because the symptoms were tolerable and spontaneously relieved within a few days. During the first visit, the patient presented with a fever of approximately 38°C, abdominal pain, watery diarrhea, and constipation. His blood test results revealed a white blood cell count of 11640/μL, serum C-reactive protein (CRP) level of 14.7 mg/dL, and erythrocyte sedimentation rate of 59 mm/h. These findings suggested ongoing inflammation. He was diagnosed with FMF based on the Livneh criteria []. Exon 10 mutations were not found, but P369S and R408Q were present. Subsequently, he was treated with colchicine (0.75 mg/day) for three years. However, the FMF attacks persisted. Thus, prednisolone (30 mg/day) was added to his treatment. The FMF attacks were slightly relieved, and the dose of prednisolone was gradually increased. However, the patient began exhibiting symptoms of depressed mood, anxiety, insomnia, fatigue, and decreased motivation. Prednisolone was tapered off due to prednisolone-induced depression. However, his depressive mood and restlessness worsened and were accompanied by agitation and suicidal thoughts. He attempted suicide via hanging, failed, and was admitted to the psychiatry ward at our university hospital. He was considered to be in a major depression secondary to a medical condition given in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition. His 17-item version of the Hamilton Assessment Scale for Depression (HAM-D) score was 22 points on admission. Escitalopram (10 mg/day) was added to the colchicine regimen and increased to 20 mg/day. His psychiatric symptoms drastically improved, and the HAM-D score decreased to seven points three weeks after escitalopram treatment. In addition, he also tested negative for CRP, and the fever and abdominal pain attacks completely disappeared. Since then, his physical FMF symptoms and accompanying depressive symptoms have not relapsed with escitalopram and colchicine. Written informed consent was obtained from the patient for this case report (Figure ).


A 49-year-old female patient was diagnosed with a thyroid nodule on routine neck ultrasound; she had no family history of thyroid cancer. Laboratory tests showed euthyroidism. Neck ultrasound revealed partly cystic and hypoechoic nodules in both thyroid lobes, the largest of which was 10 x 8 x 15 mm in the right lobe. No enlarged neck lymph nodes were identified.
Ultrasound-guided FNA was performed and interpreted as suspicious for papillary thyroid carcinoma, and a total thyroidectomy was undertaken. The thyroid gland was received intact. Serial sectioning revealed multiple nodules. The tumor was identified in the right lobe, measuring 0.3x0.2x0.1cm. Microscopic examination revealed classic papillary thyroid microcarcinoma in multi-nodular goiter ().
The patient was discharged after a week and scheduled for close follow-up.
Five months later, the patient presented with odynophagia. Physical examination showed a left neck mass, which on the ultrasound examination consisted of an enlarged rounded cortically thickened left level II lymph node measuring 1.5 x 2.5 cm, likely metastatic, with few smaller yet pathological left level Ib and II lymph nodes. Ultrasound-guided lymph node FNA was done. The smears showed cells with reniform nuclei and abundant eosinophilic cytoplasm. The nuclei displayed prominent grooving but no nuclear pseudoinclusions (). Many eosinophils were seen in the background. These cells were positive for CD68 and CD1a (1D) and negative for S100, ERG, and TTF1.
The diagnosis was consistent with Langerhans cell histiocytosis. Subsequently, a chest CT scan was performed and revealed small pulmonary nodules and cysts affecting both lungs, primarily seen in the lower lobes, likely due to pulmonary Langerhans cell histiocytosis (). After three months, the Chest CT scan showed unchanged bilateral pulmonary nodules with no mediastinal or axillary lymphadenopathy, and the bone scan revealed nonspecific lytic lesions within the proximal right femoral shaft. The patient was asked to stop smoking, and she was scheduled for a regular follow up CT scan every three months.


A 69-year-old male presented a left thyroid nodule diagnosed on FNA cytology as papillary thyroid carcinoma. During investigations, the patient was found to have multiple bone lytic lesions. Biopsies of the lumbar vertebra and left clavicle showed Langerhans cell histiocytosis. The patient underwent total thyroidectomy with left cervical lymph node dissection. Sectioning of the specimen revealed two lesions in the right thyroid lobe measuring 3.7 X 3.5 X 2.5 cm and 0.7 X 0.7 X 0.5 cm and a single lesion in the left thyroid lobe measuring 1 X 0.7 X 0.7 cm.
Additionally, the left thyroid lobe showed a goitrous nodule measuring 3.7 X 3.5 X 2.5cm. The microscopic examination concluded a multifocal classical papillary carcinoma confined to the thyroid gland with no extra-capsular extension neither lymph node involvement. However, four lymph nodes showed morphologic features of focal involvement by Langerhans cell histiocytosis. Immunohistochemical stains have confirmed these features. The Langerhans cells were positive for CD1a and negative for TTF-1. The thyroid gland was extensively examined without any morphological evidence of Langerhans cell histiocytosis involvement.
Four years later, the patient presented with anemia leukocytosis, and bone marrow biopsy showed marrow involvement by Langerhans cell histiocytosis (). The estimated degree of involvement was 40% with associated secondary myelofibrosis.


A 66-year-old black male was admitted complaining of an unexplained weight loss of 30 kg, front neck lump, purpuric lesions over the trunk and limbs, and proximal weakness over the past year. The laboratory workup was consistent with hepatic dysfunction with mild elevation of the hepatic enzymes, renal failure (creatinine clearance of 40 mL/min) with mild proteinuria, normocytic and normochromic anemia, and thrombocytopenia. Serum protein electrophoresis showed hypoalbuminemia and no abnormality in the gamma-globulin zone. The thyroid function was normal. Serologic testing for HIV and syphilis were negative. The rheumatoid factor and antinuclear antibody were within normal limits. The initial working diagnosis was systemic vasculitis, and the patient was empirically prescribed prednisone without clinical response. After two weeks of hospitalization, the patient started with intermittent abdominal pain and hemodynamic instability. He was transferred to the intensive care unit (ICU) due to severe hypotension. Unfortunately, the outcome was unfavorable, and he died after five days, despite the advanced cardiac and respiratory life support. An autopsy was performed with the consent of the family.


The patient was a 72-year-old female with a previous medical history of myocardial infarction, hypertension, and type 2 diabetes who presented to the emergency department (ED) after being found unresponsive at home. Per report, she was last known well the previous day when she spoke to her friend. Her friend called her on the day of presentation, and she did not answer. The police were contacted and found her unconscious in her home. On arrival to the ED, the patient had a GCS score of 9. An emergent head computed tomography (CT) was obtained, which showed significant IVH with casted ventricles (Figure ). CT angiography (CTA) was performed, which showed a left-sided A2-3 junction aneurysm measuring 3.3 x 2.2 millimeters.
The patient was emergently transferred to the intensive care unit (ICU) where a Kocher’s point right EVD was placed using the IRRAflow system. The irrigation rate was started at 40 mL/hour. The following morning, the patient was taken for coil embolization of the aneurysm, which went without complication (Figure ). On hospital day 2, the patient had significant elevation of intracranial pressure (ICP) > 30 mmHg for which a left-sided EVD catheter was placed. Due to supply limitations, a standard EVD catheter was used. Unfortunately, by the following day, the left-sided EVD catheter had become clotted and stopped draining. The decision was made to leave it in place as it was still transducing good ICP waveforms and as current imaging suggested that the ventricular systems were not in communication (Figure ).
Over the subsequent days of hospitalization, the patient was noted to have multiple examination changes including asymmetry in upper extremity strength and a left gaze deviation. As part of our institutional protocol for aneurysmal subarachnoid hemorrhage, daily transcranial Dopplers are performed. However, this patient had poor temporal windows, making this modality unhelpful. As such, the patient was taken for multiple angiograms, which demonstrated diffuse vasospasm. During each angiogram, verapamil was administered to treat the vasospasm. In addition, continuous electroencephalogram (EEG) was carried out to rule out seizures. No seizures were seen.
By hospital day 6, it was clear based upon the head imaging that the ventricle containing the IRRAflow catheter had superior clearance of the hemorrhage (Figure ). It was decided that a left-sided IRRAflow would be placed to aid ventricular drainage on the left side. Placement went without issue. The following day, intraventricular alteplase (tissue plasminogen activator [tPA]) was started through the right-sided EVD. We followed our typical protocol of clamping of the system for one hour following administration. Irrigation was then continued following the one-hour clamp.
Over the subsequent 24-hour period, there was significant drainage through the bilateral EVD systems as the previously clotted left EVD was replaced with a working IRRAflow. The total 24-hour blood-tinged drainage neared 500 mL. Serial images demonstrated a decrease in clot burden and ventricular caliber as a result (Figure ). From a medical standpoint, the patient was unable to be weaned off the ventilator, and on hospital day 15 the patient underwent tracheostomy and PEG (percutaneous endoscopic gastrostomy) tube placement at the request of the family who still wanted to pursue aggressive care despite the patient’s poor neurological status.
Despite good drainage through the bilateral IRRAflow EVD system, the patient failed several EVD clamp trials to determine shunt dependency. The right-sided EVD was pulled, and the left-sided system was used for testing as this ventricle was persistently enlarged. On hospital day 23, the patient underwent a left ventriculoperitoneal shunt placement given the increased caliber of the left-sided ventricular system. At this time, the ventricular system had been completely cleared of blood (Figure ).
After shunt placement, the patient was sent to the intermediate level care unit for ventilator weaning. The rest of the patient’s hospitalization was long and complicated by multiple pneumonias and a pulmonary embolus. The neurologic status of the patient never improved, and the patient was minimally responsive despite maximal neurosurgical management. After multiple family discussions, the family elected for comfort measures only and the patient expired after five months of hospitalization.


Our patient is a 49-year-old man originally admitted to the psychiatry service after presenting with psychotic symptoms associated with hostility and anger. The psychiatry service admitted the patient and initiated a regimen of haloperidol and valproic acid. He continued to remain psychotic with delusions despite increases in haloperidol; therefore, he was switched to lithium and clozapine due to treatment-resistant schizophrenia. Clozapine was initially started at 50 mg orally at bedtime, increased to 75 mg, and finally to 100 mg within a few weeks of initiation. The patient began spiking fevers, which peaked at 104.4°F, approximately four weeks after being initiated on clozapine, and he developed tachycardia with a heart rate of 125 beats/minute. The persistent fevers led to management by a medicine inpatient service for further evaluation of the presumed systemic inflammatory response syndrome due to noninfectious etiology. Blood cultures and other blood work were unremarkable, making it difficult to determine the source of his fever. Chest X-ray did not reveal any consolidation, and urinalysis was negative. As there was no suspicion of an infectious source for the fever, broad-spectrum antibiotics that had been initiated were discontinued. Clozapine was also discontinued; yet, he remained periodically febrile. The patient denied any symptoms associated with acute coronary syndrome. The cardiac markers were 0.08 ng/mL upon admission; however, his troponin, C-reactive protein (CRP), and brain natriuretic peptide (BNP) levels subsequently elevated to 4.03 ng/mL, 24.1 mg/dL, and 366 pg/mL, respectively. His eosinophil count was normal, peaking at 4.9%. Other workups for myocarditis including a respiratory viral panel and common viral serum antibody tests for coxsackievirus, Epstein-Barr virus, adenovirus, parvovirus, and cytomegalovirus were negative. His eosinophil count was also unremarkable.
Upon physical examination, an S3 gallop was appreciated at the cardiac apex. Electrocardiography (Figure ) initially showed sinus tachycardia, and echocardiography showed a dilated left ventricle with an ejection fraction of 30-35% (Figure ) and pericardial effusion (Figure ). A widened E-point septal separation (EPSS) was also found on echocardiography, which correlated with left ventricle dysfunction (Figure ). The patient was transferred to the cardiac care unit for management of acute heart failure with reduced ejection fraction with differential at that point, including CIM. He was started on guideline-directed medical therapy for acute heart failure, including diuresis with furosemide. His fever subsided eventually after discontinuation of clozapine, and he was medically optimized.


A 73-year-old male retiree after a 45-year career as a television broadcasting technician with no previous difficulties with balance, vision, or hearing presented to our unit with complaints of acute vertigo and imbalance when getting out of bed over a number of days 2 months prior. These were the first such episodes in his life. His past history included acute myocardial infarction, type 1 diabetes, congenital nystagmus (CN), farsightedness, and astigmatism, though he was otherwise healthy and remained an active member of a string-instrument band. The patient denied having any symptoms affecting his hearing.
He reported to the emergency department during the acute phase due to an inability to stand, after which he continued to present instability and imbalance over 1 month, even with mild movements. His instability and imbalance were less intense on presentation to our unit, although his condition continued to prevent him from going out alone and from driving. The patient was examined by an ear, nose, and throat specialist (without specific diagnosis, treated with betahistine) and a neurologist. A magnetic resonance imaging scan of the brain and inner ear revealed no abnormalities. During his first visit, his dizziness handicap inventory (DHI) was 30.
A clinical examination and videonystagmography (VNG) was performed to test his eye movement (Interacoustics VN415). With the patient looking at the center, a high-frequency horizontal nystagmus (3–4 beats/s) was observed, with no well-defined or even alternating fast phase initially and pseudopendular left beating afterwards; the nystagmus changed direction when the patient looked to the right, becoming more pendular. Gaze to the left showed a much less evident irregular pseudopendular left beating nystagmus (). The nystagmus prevented reliable assessment of vestibular function through a battery of clinical (spontaneous nystagmus, head shaking, vibration-induced nystagmus, HIT) and VNG tests. A Romberg test revealed increased static body sway without falling. His gait was wide-based, he was unsteady and had difficulty maintaining balance; these symptoms worsened with head movements.
The first HIMP protocol () was performed without selecting the check box “Spontaneous Nystagmus” (SN not selected) (). Calibration of eye movements took abnormally long, though measurement was possible (). We experienced great difficulty in generating bilateral horizontal VOR and fast, high-velocity compensatory eye movements were recorded, with impulses mainly to the right [80% refixation saccades, 53% of which were overt, with a PR score of 52% ()] and only some slower saccades to the left (6% covert) (), with a mean VOR gain of 0.21 to the right and 0.37 to the left. Vertical VOR showed mean gain values of 0.61 for the right (R) anterior semicircular canal (SCC) [lower than normal age-range values ()] with 100% of saccades identified as overt (PR score, 45%) (). The mean VOR gain of the left (L) anterior SCC was within the normal range, with 31% covert saccades (PR score, 22%); mean VOR gain values for both posterior SCCs were within normal limits and no saccades were detected in these channels.
Cervical vestibular-evoked myogenic potentials (cVEMPs) were normal (). Computerized dynamic posturography (CDP) showed a vestibular pattern with visual dysfunction, average stability of 63%, hip-strategy movements, and center-of-gravity alignment displaced forward with falls in conditions 5 and 6 ().
Pure tone audiometry evidenced bilateral sensorineural hearing loss (SNHL). The loss was mild at high frequencies in the right ear and mild to moderate in the middle-to-high frequency range for the left ear, compatible with presbycusis ().
On his first visit to our unit (2 months after onset of symptoms), the patient was initially diagnosed with acute vestibular syndrome (AVS), probably due to a right superior vestibular neuritis with incomplete compensation of the vestibular deficit.
The patient underwent a customized vestibular rehabilitation program in our unit and in his home, including exercises for gaze stabilization, VOR adaptation, habituation acquisition, and balance (). VOR adaptation also included the following: passive and then active lateral head impulses to both sides with vHIT monitoring (, ) and effective pitch-up and pitch-down head impulses. The patient was also instructed to perform these exercises in the home and carry out a range of activities in different environments to recover activities of daily living.
As shown in , the patient had follow-up visits at 1, 2, 4, and 6 months, including DHI and physical examination. HIMP and SHIMP tests were performed during all visits (except at month 4) in the same conditions as the 1st visit. In contrast, SN was selected at months 2 and 6, thus allowing comparison of the VOR in the two vHIT conditions. We performed a CDP at months 2 and 6, a temporal bone CT scan at month 4, and a VNG at month 6 of follow-up. Time series records for vHIT recording of all six canals vHIT recording timeseries are included as together with the impulse rejection/aceptance rate (–).
The patient reported significant improvement at 1 month of follow-up, with less imbalance, though he continued to refrain from leaving the home and driving (DHI: 6). At month 2, he reported “leading a normal life” (DHI: 0), although he was still unable to drive comfortably and sometimes had difficulties climbing stairs. HIMP test results for both lateral SCCs performed at 1 and 2 months of follow-up and with calibration are shown in , together with those from the first visit (to allow for comparison along follow-up). We recorded mean VOR gain values for lateral impulses to the left of 0.32 at month 1 and 0.34 at month 2, and 0.45 and 0.34, respectively, for impulses to the right. Rapid saccadic compensatory eye movements were observed during both visits, showing similar unilateral patterns not identified as refixation saccades by vHIT with impulses to the left; with impulses to the right, only 10% of overt saccades were identified at the 1st month and 9% at the 2nd (80% on first visit). Mean VOR gain of the R anterior SCC at 1 month of follow-up improved from 0.61 (first visit) to 0.68 (normal age-range values), with 15% overt saccades (100% on the initial visit) (); at month 2, the mean gain was 0.72 with no presence of saccades (). At month 1 and 2, mean VOR gain in both posterior and in the L anterior SCCs were within the normal range for the patient's age, and no refixation saccades were found (data not shown in ).
SHIMP testing protocols carried out at months 1 and 2 showed a mean VOR gain of 0.27 and 0.26 with impulses to the right and 0.3 and 0.27, respectively, to the left (), with a small number of anticompensatory saccades observed only at 1 month of follow-up, with impulses to the left.
At 2 months of follow-up, lateral HIMP trials (SN selected) () showed similar mean VOR gain values (0.3 to the left and 0.31 to the right) as with SN not selected (), with 5% of refixation overt saccades identified to the left and 30% to the right. Each vertical SCC showed a mean VOR gain that was within the normal values for the patient's age () (), without refixation saccades. SHIMP trials at 2 months of follow-up () also revealed similar mean VOR gain values (0.29 to the left and 0.28 to the right) in both vHIT conditions (), without anticompensatory saccades.
CDP at 2 months was normal (average maximum stability, 82%).
At 4 months of follow-up the patient was asymptomatic and had recovered the ability to drive and climb stairs (DHI: 0). Balance and an ear CT scan were normal. Customized maintenance exercises were advised if needed ().
At 6 months the patient was “leading a normal life with occasional slight difficulty walking in the dark at home” (DHI: 2). Balance and CDP were both normal. VNG showed CN with the same features as before. Lateral HIMP test results resembled those at month 2, with slightly higher HIMP-assessed mean VOR gain values with lateral impulses to the right in both vHIT conditions (). Vertical HIMP trials also showed mean VOR gains that were within the normal age-based range (). SHIMP mean VOR gain values were also similar to those at month 2 in both vHIT conditions (), with some anticompensatory saccades upon impulses to the right (SN selected).
The patient adhered closely to the prescribed treatment and tolerated the treatments delivered at the clinic well. His self-report and subjective and objective outcome measures indicated appreciable improvement during follow-up ().