A fifteen year old male presented to the Emergency Department (ED) at Cork University Hospital (CUH), a level one trauma centre serving the southeast of Ireland, after being crushed under the front wheel of a tractor on a farm. There was no significant past medical or surgical history.
Initial management followed standard Advanced Trauma Life Support (ATLS) protocol [], and Orthopaedic Association Audit standards for Trauma (BOAST) guidelines for pelvic fracture [].
On admission Glasgow Coma Scale (GCS) was 10, the patient was intubated by the Emergency team after deterioration of his concousness level. We applied a chest tube after we had done needle decompression for left side tension pneumothorax. He underwent emergency embolization of the internal iliac artery. He responded well and the haemodynamic stability was achieved. On examination the left leg was noted to be internally rotated. Dorsalis pedis pulses were preserved bilaterally. Plain films demonstrated fractures of the left sacrum and iliac bone, a locked symphysis pubis () and fracture of the distal left femur. Computed tomography (CT) scan of the pelvis () demonstrated multiple fractures; displaced fracture of the left iliac bone, commuted left sacral ala fracture, minimally displaced right-sided sacral ala fracture with plastic deformation of the posterior crescent fracture configuration which was not fully extended through the iliac wing, and complete rupture of the pubic symphysis with LSP. CT scan of the lumbosacral spine (), showed a complete burst fracture of the L3 and L4 vertebral bodies and minimally displaced transverse process fractures of the right L1-L4 vertebrae. The surgical treatment for this young patient was a challenge. The patient was haemodynamically unstable on admission. We arranged a selective coil embolisation of the internal iliac artery by using multiple 6 mm pushable Azur CX coils () to stop the bleeding after failure of all measurements of resuscitation.
A multidisciplinary team (MDT) including National Spine Injuries Unit and pelvic trauma specialist were consulted and the patient was transferred to the National Spine Injuries Unit, Mater Misericordae Hospital Dublin for definitive management.
The decision for a closed reduction to unlock the LSP by using the external fixator (Hoffman 2) as a lever arm for reduction was made as the best option for a skeletally immature haemodynamically unstable patient. The Illiosacral Joint (ISJ) was fixated with two illiosacral cannulated screws.
The patient was in the supine position on the orthopaedic table. An external fixator was applied to the pelvis and used as a lever arm for closed reduction of the LSP. This involved applying an anterior and lateral pulling force directly on the pubic bone via the external fixator with a simultaneous external rotation force applied on the left iliac wing (). The bilateral SIJ fracture was fixed with two fully threaded cannulated screws () using the method described by Routt et al. []. The distal femur was fixed with external fixators (). The patient's position was then changed to prone for posterior spinal stabilisation L1 to L5 with two rods and ten pedicular screws ().
Post-operative management included analgesia, thromboembolic prevention commenced 48 h post operatively with subcutaneous enoxaparin, bed rest for 48 h with 30 degrees inclination. The post-operative period was uneventful. We allowed partial weight bearing for eight weeks. We removed the external fixator after eight weeks from the initial surgery after clinical and radiological confirmation of fractures healing by plain radiograph (, ).
After one year from the initial injury the patient was fully weight bearing with no limping. We assessed his quality of life and mobility by SF-12 an SF-32 outcome scores []. His SF-12 was 42 and SF-32 was 97. His updated radiographs are illustrated in ().


A 13-year-old girl presented with right lower leg pain, which she had been experiencing for the past 2 months. Plain radiographs showed a well-circumscribed lesion with a partially calcified nidus (A,B). CT showed a well-defined oval nidus with low attenuation (C–E). Therefore, she was diagnosed with osteoid osteoma.
The operation was performed under general anesthesia with the patient lying in the supine position with a tourniquet. The nidus was identified using fluoroscopy. Then, two guide pins were inserted into the center of the lesion under fluoroscopic guidance. A 7.3-mm cannulated drill bit was used to drill into the cortex, and a hole was created for entry of the arthroscope (F,G). One portal was used as the viewing portal for the arthroscope, and the other was used as the working portal for the instrument (H). Arthroscopic findings showed a mineralized nidus lesion (I). The nidus was excised for biopsy, and removal was performed using a curette and arthroscopic burr (J). Postoperative CT revealed the complete resection of the nidus (L–N), and the diagnosis of osteoid osteoma was confirmed by histological examination.
Partial weight bearing with crutches was allowed for the first 3 weeks. The patient’s symptoms resolved completely after the operation, and she was pain-free at the 1-month follow-up. She returned to sporting activities at 2 months and showed good functional scores (Lysholm score: 81, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score: 0).


A 19-year-old man visited our clinic with right lower leg pain, which he had been experiencing for the past 1 month. Physical examination revealed a limping gait. Plain radiographs and CT images revealed a radiolucent center with surrounding reactive sclerosis on the posteromedial aspect of the tibial shaft ().
Exact targeting of the medulloscope is needed for intramedullary lesions because of the small range of motion of the instrument due to cortical canal hardness. Therefore, we created a guide device using three-dimensional (3D) printing to target localized lesions on the posterior side of the tibia (A,B). In the operating room, we easily accessed the nidus using this targeting guide and removed the nidus using medulloscopy (C–F) with minimal incisions (G). Postoperative CT showed complete resection of the nidus (I,K).
After surgery, the patient’s leg was immobilized using a splint for the first 3 weeks to prevent possible pathologic fracture from the medulloscopy canal. Partial weight bearing with a single crutch was allowed for the next 3 weeks. At 3 months after surgery, CT showed good union of the cortex of the canal area, and the patient returned to sporting activities with good functional scores (Lysholm score: 94, WOMAC score: 0).


A 42-year-old female patient was referred to the Oral and Maxillofacial Surgery team, with an indication for orthognathic surgery. During anamnesis, she reported a history of chronic sinusitis, which triggered headaches, facial pain, constant episodes of rhinorrhea, and breathing difficulties. The patient also reported having undergone treatment with an otorhinolaryngologist for six years. During this period, several antibiotic prescriptions and nasal endoscopy exams were performed (Fig. A,B), however, with no results. On tomographic examination, bilateral opacification of the maxillary sinuses was found (Fig. C,D). Therefore, an endodontic assessment of the maxillary teeth was requested, which found no signs of pulp involvement. Orthognathic surgery planning was employed, as it was a chronic clinical condition, and the patient had an indication for this surgical procedure. Thus, during the intraoperative period, after Lefort I downfracture, the presence of dark and foamy masses was found, which occupied a quarter of the maxillary sinuses, bilaterally (Fig. ). In addition, a mucus-like soft tissue was observed on both floors of these paranasal sinuses (Fig. A). Based on the findings, the hypotheses of fungal balls and mucous retention cysts were considered. Progress was made with total curettage of the maxillary sinuses.
The collected material was sent for histopathological analysis, which confirmed the diagnosis of fungal balls (predominantly Aspergillus sp) (Fig. B,C) and mucous retention cysts. After the surgical procedure, the patient obtained a significant improvement in her breathing capacity, in addition to the reduction of sinus symptoms, and was subsequently referred to an infectologist and an otorhinolaryngologist for assessment and additional treatment. After a 1-month follow-up post-surgery, the patient developed an epiphora. With this, she was referred to the ophthalmologist, who opted for Dacryocystorhinostomy, with ductal clearance by a possible fungal ball. The patient used Itraconazole 200mg daily for 07 months and is in the postoperative period of 02 years, with significant regression of clinical and imaging signs and symptoms (Fig. D,E).


A 57-year-old man underwent posterior sectionectomy for a hepatic tumor of maximum diameter 10 cm that protruded from segment 6 into the retroperitoneum (Figs. and ). Histological examination of the primary tumor showed a simple nodular lesion with extranodular growth, and moderately to poorly differentiated HCC. The tumor had formed a capsule. Infiltration of the capsule and portal vein invasion (vp1) were noted. No intrahepatic or regional lymph node metastasis was observed. Surgical margins were negative. The pathological stage was III according to the staging system of the Liver Cancer Study Group of Japan [].
After 6 months with watchful waiting, follow-up computed tomography (CT) revealed multiple nodules suspected of indicating peritoneal dissemination (Fig. ). The patient had dyslipidemia but no liver disease, and was taking no medication. The liver was impalpable, and there was no obvious abdominal tenderness or rebound pain. Laboratory data showed a white blood cell count of 2.75 × 109 /L with normal differential counts and a C-reactive protein concentration of 0.5 mg/L. Concentrations of hepatobiliary enzymes were within normal limits, whereas those of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were high at 1,480 ng/mL and 970 mAU/mL, respectively; these had tended to increase since the original operation. CT and magnetic resonance imaging (MRI) showed only four nodules in the abdominal cavity, the doubling times of which were rapid at 22 days. No other metastases were detected by these imaging studies.
On the basis of these findings, we diagnosed peritoneal dissemination of HCC after hepatectomy. Because of their rapid growth and apparent resectability, surgical resection was carried out. ICG (0.5 mg/kg) was injected intravenously 2 days before the procedure and the peritoneal nodules identified by their brightness in the operative field using an ICG near-infrared fluorescence imaging system (PDE™, Hamamatsu Photonics K.K., Hamamatsu, Japan). A total of eight lesions were thus identified and resected, including some that had not been identified by preoperative imaging studies (Fig. ). However, there were no ICG signals on the surface of the remnant liver. The peritoneal cancer index (PCI) was 6 (right upper; the maximum tumor was 28 mm and the score 2, right flank; 14 mm and 2, epigastrium; 2 mm and 1, central; 2 mm and 1, respectively), and the completeness of cytoreduction (CC) score was 0. Histopathological examination of five of the eight resected lesions showed proliferating cancer cells, with some scattered small pseudo-glandular structures (Fig. ). We diagnosed peritoneal dissemination of HCC based on the pathological findings and their similarity to those of the original HCC. We concluded that the recurrences were likely attributable to exposure of the tumor to the serosa at the time of the original operation. Additionally, three of the four resected lesions that had not been detected by preoperative imaging studies were found to consist of nonspecific fibrous tissue.
The postoperative course was smooth and the patient was discharged soon after surgery. Two months later, follow-up CT revealed further peritoneal dissemination that had not been detected by imaging studies performed preoperatively or intraoperative investigation. For these reasons, the patient was commenced on lenvatinib. Thereafter, the patient’s condition was stable and no new lesions were identified in the subsequent 10 months, during which there was a progressive decrease in concentrations of tumor markers.


A 77-year-old man with a significant medical history of hyperlipidemia and hypertension had presented with a 3-day history of new-onset pain, swelling behind his right knee, and distal edema. The patient had undergone right knee replacement 8 years before this presentation. He had not undergone any imaging studies since his knee replacement. Hence, the aneurysm size before COVID-19 was unavailable. Computed tomography angiography (CTA) of the right leg demonstrated a 7.5 × 7.2-cm popliteal artery aneurysm with no evidence of rupture, leak, or distal embolization. Clinically, the patient had a visibly pulsatile mass behind his right knee, with worsening pedal edema and palpable pedal pulses. The inability to bend his knee to >90° owing to the increasing pressure causing pain had been noted just 3 days before presentation. The pain was significantly relieved with full extension. He had no evidence of deep vein thrombosis found by the CTA or foot drop clinically. A nasopharyngeal swab for SARS-Cov-2 RNA test was positive. The patient had no respiratory symptoms or fever. The laboratory test results were all normal, except for elevated C-reactive protein (CRP) and D-dimer levels and a slightly diminished platelet count (). Treatment was undertaken using conscious sedation. Contralateral femoral access was obtained, and the aneurysm was excluded using a 8-mm × 250-mm Viabahn stent (W.L. Gore, Flagstaff, Ariz) placed through a 7F sheath (). The next day, the patient continued to have palpable pedal pulses with no pulsation over the popliteal aneurysm, and he was discharged home with a prescription for apixaban 5 mg twice daily. At the 1-month follow-up examination, his knee pain had resolved, and duplex imaging studies had demonstrated aneurysm thrombosis with graft patency. The size of the aneurysm was stable compared with previous computed tomography images. At 6 months after treatment, the patient's symptoms had resolved, and he was able to flex his knee to the status before his initial presentation. The patient also noted that he has fewer visible varicose veins compared with previously.


A 71-year-old man with a medical history of hypertension and hypothyroidism had presented with a 2-hour history of severe right hand pain. The patient underwent CTA, which demonstrated an axillary artery occlusion with ground-glass opacification in the lungs. Clinically, the patient had no radial or brachial pulses in his right arm, and pallor, hypoesthesia, and coolness of the right arm were present. The patient had had no fever or respiratory symptoms but had had an oxygen saturation of 88% on room air. A nasopharyngeal swab for SARS-CoV-2 RNA test was positive. The patient underwent an emergency right upper extremity angiography, which demonstrated an acute axillary artery thrombosis (, A). The lesion was crossed with a spider filter (Medtronic Inc, Minneapolis, Minn) and treated with AngioJet (Boston Scientific, Marlborough, Mass) mechanical thrombectomy. Repeat angiography demonstrated minimal residual thrombus, which was managed with a self-expanding stent (, B). No evidence of vascular compression at the thoracic outlet was noted during provocative maneuvers. The patient developed a palpable radial pulse with resolution of pain. The patient was given oral steroids and apixaban. He was discharged on the fourth postoperative day once he no longer required supplemental oxygen. At his 1-month follow-up examination, he had had continued arterial patency and no new thrombotic events.


A 35-year-old African American male with a medical history significant for asthma, active smoking (12-pack-year smoking history), pulmonary hypertension, and sickle cell disease presented to the hospital with complaints of productive cough and chest discomfort of five days duration. He also provided a history of associated fever and anorexia. Physical exam revealed tachycardia, pallor, and decreased airway entry in the right lung base. He had a baseline hemoglobin level of 8-9 g/dl. Investigations showed leukocytosis, reticulocytosis, and severe anemia. Chest X-ray showed bilateral infiltrates and a small right-sided pleural effusion. Shortly after admission, the patient’s condition deteriorated, and he developed acute respiratory distress. Arterial blood gas (ABG) PO2 was 58 mmHg on room air. Pan-cultures were obtained, and he was managed with oxygen, intravenous fluids (IVF), and empiric broad-spectrum intravenous antibiotics. His condition worsened, and repeat ABG while on 100% oxygen showed PO2 of 35 mmHg, after which he was transferred to the Medical Intensive Care Unit (MICU) and subsequently intubated for hypoxic respiratory failure. In the MICU, the patient’s hospital course progressively worsened with the development of adult respiratory distress syndrome. Computed tomography (CT) of the chest was done after intubation, and it showed opacification of the lung parenchyma most prominently in the mid to lower lung fields posteriorly (Figure ).
The primary managing team initially transfused the patient with two units of packed red blood cells without significant clinical response. Due to the patient’s non-response, the hematology team was consulted, and their recommendation was to initiate an exchange blood transfusion. The patient received one complete course of exchange blood transfusion with no significant change in his clinical condition. His pan-cultures remained negative. With the continued deterioration of his clinical condition, the decision was made to initiate a second course of exchange blood transfusion. Upon completing the second course of exchange transfusion, his clinical condition markedly improved, and he remained stable. He was ultimately discharged home to follow up with the outpatient SCD clinic.


A 7-year-old boy treated for two months with valproic acid because of epilepsy was admitted to the Department of Paediatrics and Gastroenterology, Medical University in Lublin for epigastric pain and vomiting. On admission, the serum amylase activity was 982 U/L (reference value up to 118 U/L) and lipase activity of 1523 U/L (reference value up to 51 U/L) was found. The abdominal ultrasound showed a slightly swollen pancreas with decreased echogenicity. The serum valproate level was within therapeutic limits.


A 4-year-old girl with Smith–Lemli–Opitz syndrome was admitted to the Department of Paediatrics and Gastroenterology, Medical University in Lublin due to abdominal pain. She was treated with valproate due to epilepsy. The dose of drug had been increased two weeks earlier to achieve better control of seizure events. On admission, the serum amylase activity was 234 U/L and the lipase activity was 495 U/L. Abdominal ultrasonography did not reveal any abnormalities. The serum valproate level was within therapeutic range. According to the neurologist’s recommendation, valproic acid was switched to levetiracetam. However, due to the lack of a sufficient antiepileptic effect of this therapy, after six months of first AP episode in our patient, valproic acid was reintroduced. After two months, the girl was admitted to our department again because of abdominal pain. Highly increased activity in the serum amylase (1936 U/L) and lipase (2433 U/L) was stated. The pancreas image in the ultrasound examination was unchanged.


A 15-year-old boy treated with valproic acid for several years due to epilepsy was admitted to the Department of Paediatrics and Gastroenterology, Medical University in Lublin because of abdominal pain. Two weeks before admission to our department, the dose of the antiepileptic drug had been increased to improve seizure control. On admission, the activity of the serum amylase was 562 U/L, and lipase, 1362 U/L. The initial abdominal ultrasound examination did not reveal any abnormalities. The level of valproic acid in the serum was within the therapeutic range. Although the typical treatment (diet zero, painkillers for the first few days) was introduced, the patient’s condition did not improve. The laboratory results showed an increase in inflammatory markers and the progressive increase in pancreatic enzymes in the serum. The computer tomography (CT) scans performed on the fourth day of hospitalization revealed two foci of necrosis in the pancreas. Intensive treatment was applied, including broad-spectrum antibiotic (meropenem) and total parenteral nutrition achieving the resolution of AP symptoms within one week. In the fourth week of hospitalization, CT scans showed a normal image of the pancreas and the laboratory results revealed normal activity of pancreatic enzymes.


A 17-year-old boy with epilepsy was admitted to the Department of Paediatrics and Gastroenterology, Medical University of Lublin because of abdominal pain. For two years, the patient had several modifications of antiepileptic therapy due to insufficient efficacy and/or poor tolerability of the drug. Two months before admission to our department, the boy started valproic acid therapy. In the laboratory results, amylase activity was 232 U/L and lipase activity was 534 U/L. The abdominal ultrasound examination showed heterogeneous echogenicity of the pancreas.
In all patients, the typical treatment of acute pancreatitis was applied, previous antiepileptic treatment was changed to levetiracetam or anti-epileptic drugs instead of valproate, achieving the resolution of symptoms and the normalization of pancreatic enzymes. Except for patient 3, who was re-treated with valproic acid, no relapse of acute pancreatitis was observed in the patients described.


A 31-year-old woman was admitted to the emergency department with worsening dyspnoea. She begun to feel dyspnoea on effort 10 days prior and 4 days before admission, the symptom worsened accompanied by a non-productive cough on deep breathing. However, she had no subjective symptoms of palpitations, no underlying cardiac disease, and was not receiving any regulation medication or consuming supplements. Upon initial examination, the patient was alert, oriented, and afebrile, with a blood pressure of 137/78 mmHg, tachycardia of 244 beats/min, and tachypnoea of 36 breaths/min. Cardiovascular auscultation revealed cardiac gallop rhythm and bilateral crackles. Electrocardiogram revealed three or more distinctive P-wave morphologies, plus tachycardia with a heart rate of 184 beats/min (Fig. a). The P-wave morphologies were different from the normal sinus P-wave morphology in the previous electrocardiogram performed 5 years earlier (Additional file ), suggesting multifocal atrial tachycardia (MAT). Chest radiography revealed cardiomegaly with pulmonary congestion (Fig. b), and echocardiography revealed left ventricular dilatation and generalized severe hypokinesis with an ejection fraction of 20%, suggesting DCM. Further, laboratory tests revealed elevated levels of aspartate aminotransferase (84 U/L, reference: 13–30 U/L), alanine aminotransferase (80 U/L, reference: 7–23 U/L), total bilirubin (3.0 mg/dL, reference: 0.4–1.5 mg/dL), cardiac troponin I (35.6 pg/mL, reference: < 26.2 pg/mL), and brain natriuretic peptide (1,524.4 pg/mL, reference: < 18.4 pg/mL). Tachycardia persisted despite intravenous administration of adenosine triphosphate, verapamil, and landiolol, and multiple cardioversion attempts were ineffective. The patient rapidly progressed to cardiogenic shock and respiratory decompensation, necessitating transfer to the intensive care unit, intubation, and inotropic support. She received infusions of noradrenaline (0.04 µg/kg/min), dobutamine (2 µg/kg/min), and milrinone (0.125 µg/kg/min). Mildly elevated circulating cardiac enzymes were noted and acute coronary syndrome was suspected. However, urgent coronary angiography was unremarkable and an intra-aortic balloon pump (IABP) was inserted. Amiodarone was started for refractory tachyarrhythmia. The intravenous dose was started with 125 mg administered over 10 min, followed by an infusion of 0.8 mg/min for 6 h, and then a maintenance infusion of 0.4 mg/min for the next 18 h. A subsequent oral dose was started at 400 mg/day and gradually reduced to 200 mg/day. Incessant tachyarrhythmia finally reverted to sinus rhythm and resulted in a significant heart rate reduction. Administration of a vasopressin V2-receptor antagonist (tolvaptan 15 mg/day) with loop diuretics (azosemide 30 mg/day) was initiated to ameliorate congestion. In addition, anticoagulation with intravenous heparin (19,200 units/day) was initiated to prevent intracardiac thrombus formation, and low-dose pimobendane (1.25 mg twice daily) was used to enhance left ventricular systolic function. She remained hemodynamically stable with support from the IABP and was progressively weaned from the vasoactive agents. After confirming the patient’s condition to be euvolemia, anti-failure therapy was started at extremely low doses (enalapril, spironolactone, and carvedilol), which were carefully and gradually increased based on the patient’s tolerance (Fig. ). IABP was weaned on day 7. After confirming that there was no re-exacerbation of HF following the introduction of anti-failure medication, the patient was weaned from the ventilator and transferred to the general ward on day 11.
Diagnostic endomyocardial biopsy (EMB) was performed on day 8. Photomicrograph revealed moderate myocyte hypertrophy with moderate interstitial fibrosis and a few interstitial inflammatory infiltrates without associated myocyte necrosis (Fig. ). The counts of CD3 + T-lymphocytes and CD68 + macrophages were 2.2 and 23.9 cells/mm2, respectively; this corresponded to 6.2 leucocytes/mm2, including up to 4 monocytes/mm2, which did not fulfill the proposed immunohistochemical criteria for myocarditis (≥ 14 leucocytes/mm2, including up to 4 monocytes/mm2 and CD3 + T-lymphocytes ≥ 7 cells/mm2) by World Heart Federation and European Society of Cardiology. Furthermore, late gadolinium-enhanced cardiac magnetic resonance imaging showed no abnormalities, indicating the absence of myocardial necrosis, supporting this notion.In addition, a workup for the unexplained tachycardia was performed. We performed thyroid function tests using stored blood samples obtained on admission day 1 through day 7 (Table ). Strikingly, thyroid studies using pre-amiodarone treatment sera on admission demonstrated undetectable thyroid-stimulating hormone (TSH) levels (reference: 0.35–4.94 mIU/L), and markedly elevated free T3 and T4 (> 30 pg/mL, reference: 1.71–3.71 pg/mL; 3.81 ng/dL, reference: 0.7–1.48 ng/dL, respectively), strongly suggesting thyrotoxicosis.
In consultation with an endocrinologist, a thorough physical examination revealed mild exophthalmos and thyromegaly, which could not be recognised during the initial physical examination. Graves' disease (GD) was suspected as a cause of the thyrotoxicosis. In addition, antibodies to thyrotropin receptor (TRAb) (11.5 IU/L, reference: 0–2.0 IU/L), and thyroid-stimulating antibodies (TSAb) (651%, reference: 0–120%) were detected, further supporting this notion (Table ). After a careful interview, the subject revealed about a two-week history of diarrhoea and nausea before admission, suggesting preceding gastroenteritis. The patient fulfilled the Japan Thyroid Association diagnostic criteria for TS. Notably, we recognized that amiodarone treatment had unexpectedly controlled TS (Fig. ). Her clinical status improved during her hospitalization. However, the patient’s thyroid hormone levels began to increase on day 14, suggesting the escape phenomenon. Thiamazole (10 mg/day) was started on day 31. As the patient was a staff nurse of our hospital, she was permitted and wished to continue her hospitalization and rehabilitation. Thus, she was finally discharged on day 40, when serial echocardiography showed significant improvements in the left ventricular systolic function and reverse remodeling (Fig. ; Additional files , , , ). The patient subsequently received treatment at our outpatient clinic to establish clinical euthyroidism. She remained clinically stable during a 2-month follow-up, and the results of thyroid function tests were as follows: undetectable TSH, free T3 (4.38 pg/mL), free T4 (1.35 ng/dL), TRAb (5.1 IU/L), and TSAb (245%).
Ultimately, total thyroidectomy was performed because she wished to become pregnant. The resected thyroid gland was markedly enlarged and weighed 122 g. Thyroid pathology was consistent with GD. The postoperative course was uneventful. Full recovery of the LVSD was observed at the 6-month follow-up. Even after subsequent tapering and discontinuation of beta-blockers, she remained clinically stable at the 48-month follow-up.


A 54-year-old male with a history of chronic obstructive pulmonary disease had reported worsening dyspnea and productive cough for one week. He was found to be hypoxic and then intubated due to ongoing respiratory distress, despite high flow ventilation. A computed tomography (CT) of the chest showed diffuse, patchy ground-glass opacities throughout bilateral lungs. He was started on broad-spectrum antibiotics and placed on airway pressure release ventilation (APRV). He improved from a respiratory perspective and was extubated on hospital day four, however, due to worsening respiratory distress and hypoxia he was reintubated on hospital day nine. Over the next 36 hours, the patient was hypoxemic despite increasing P high settings on APRV and 100% fraction of inspired oxygen (FiO2) and the decision was made to start V-V ECMO.
Under ultrasound guidance, a 17-French return cannula (Bio-Medicus, Minneapolis, MN, USA) was percutaneously inserted into the right internal jugular vein (IJ) via Seldinger technique, with tip of cannula at the junction of superior vena cava (SVC) and right atrium. Next, a 21-French Bio-Medicus drainage cannula was placed in the right common femoral vein via Seldinger technique, with the tip in the inferior vena cava (IVC). The patient tolerated cannulation without any complication. A chest radiograph confirmed appropriate placement of IJ catheter (Figure ).
Shortly after, during placement of the arterial line, the patient went into pulseless electrical activity (PEA) and cardiopulmonary resuscitation (CPR) was initiated. A bedside echocardiogram revealed a large pericardial effusion demonstrating tamponade physiology (Video ).
After an emergent bedside pericardiocentesis, with 60cc of blood drained, the patient remained in PEA. A 17-French cannula was inserted through the left common femoral artery into the aorta and the patient was converted to V-A ECMO. Once the V-A ECMO circuit was started, CPR was ceased, and the patient maintained acceptable hemodynamics. He underwent an emergent median sternotomy, the pericardial sac was incised with cautery, and approximately one liter of dark blood was evacuated from the pericardial sac. There was immediate relief of tamponade and improvement of hemodynamics. On inspection, a clear injury to the right atrium at the junction of the IVC was identified and subsequently repaired. The patient was weaned off ECMO on postoperative day 12 and he underwent tracheostomy on postoperative day 17. The patient was eventually discharged to a vent facility one month later.


A 48-year-old male patient was admitted with shortness of breath, fever, generalized malaise and worsening productive cough starting a week prior to admission. The patient’s past medical history was significant for chronic obstructive pulmonary disease, history of renal transplant in 2001, hypertension, diabetes mellitus, obesity, gout, and obstructive sleep apnea. His past surgical history was significant for amputation of the left fourth and fifth toes, and right nephrectomy in 2019. His immunosuppressive regimen consisted of mycophenolate mofetil 500 mg twice daily and prednisone 5 mg per day. He denied any exposure to pets.
On physical examination, the patient's weight was 123 kg with a BMI of 34.4, temperature 99.2 °F, blood pressure 116/56 mm/hg, heart rate 91 beats/minute. Oxygen (O2) saturation was 60% in room air. He was alert and oriented on arrival. Cardiac exam revealed regular heart sounds without murmurs. On lung exam, there were bibasilar crackles. The rest of his physical exam was normal.
White blood cell count was 7.7x10^3/µL ( 4-10.5^3/µL), 29% lymphocytes. Creatinine was 6.6 mg/dL (0.5-1.2 mg/dL) with a glomerular filtration rate (GFR) of 11 mL/min/1.73 m2 and serum glucose 151 mg/dL (range 65-109 mg/dL). His COVID-19 reverse transcription polymerase chain reaction (RT-PCR) test from nasopharyngeal swab was positive. Chest X-ray showed bilateral diffuse consolidations.
The patient was initially placed on a 100% non-rebreathing mask and later on a high flow O2 nasal cannula. The patient remained hypoxemic and developed respiratory failure. He was intubated and required mechanical ventilator support. The patient was also initiated on continuous renal replacement therapy. He was started on intravenous ceftriaxone 1 gm and oral azithromycin as well as a course of hydroxychloroquine 400 mg twice daily followed by 400 mg once daily. In addition, he was given intravenous methylprednisolone 100 mg daily. The patient completed five days of treatment of intravenous ceftriaxone and oral azithromycin with an improvement of radiologic findings. After a week, the patient started developing fevers up to 103 °F. Chest X-ray showed an increase in lung infiltrates (Figure ).
Intravenous cefepime 1 gm loading followed by 500 mg next day was given. The patient remained intubated, seemed to be clinically deteriorating, and continued to be febrile, and therefore, intravenous azithromycin 500 mg was given. The sputum sample sent 12 days after intubation grew B. bronchiseptica; blood cultures remained negative. The patient became afebrile and was extubated within 24 hours after starting intravenous azithromycin. Intravenous cefepime was stopped and intravenous piperacillin/tazobactam 2.25 gm every eight hours was started and the patient continued with intravenous azithromycin. The organism was resistant to cefepime, intermediately sensitive to ceftazidime, and sensitive to levofloxacin, trimethoprim-sulfamethoxazole, tigecycline, gentamicin, tobramycin, meropenem, and piperacillin/tazobactam. Due to the rapid response to azithromycin leading to extubation, a decision was made to discontinue piperacillin/tazobactam and to continue with azithromycin. The patient continued to improve clinically and remained afebrile. Treatment continued with intravenous azithromycin for a total of 10 days. Chest X-ray two weeks post-discharge showed pulmonary vascular congestion, left lung atelectasis, and resolution of his lung infiltrates (Figure ). Two months after discharge, the patient was doing well clinically but required intermittent renal replacement therapy.


Approval and written informed consent for publication of this report were obtained from the patient.
A 76-year-old female (height, 155 cm; weight, 59.6 kg) had chronic heart failure with severe mitral regurgitation (MR), mild tricuspid regurgitation (TR), and chronical atrial fibrillation. Her comorbidities included hypertension and old cerebral infarction at the right medulla oblongata. A preoperative transthoracic echocardiogram (TTE) showed a left ventricular ejection fraction of 62% and no left ventricular wall asynergy. Mitral valve repair, tricuspid annuloplasty, maze procedure, and left atrial appendage closure were scheduled. The surgical risk calculated by the Society of Thoracic Surgeons score (STS score) was 2.23% and that calculated by the European System for Cardiac Operative Risk Evaluation (EURO score) was 2.52%.
On arrival at the operating room, we inserted an arterial line into the right radial artery to monitor hemodynamics. And we also monitored bilateral regional cerebral oxygen saturation (rSO2) by using INVOSTM and the bispectal index (BIS) value to assess the patient’s depth of sedation. Anesthesia was induced using remimazolam at 6 mg/kg/h, remifentanil at 0.25 μg/kg/min, and rocuronium at 0.85 mg/kg. The patient did not complain of pain at the infusion site during administration of remimazolam. Remimazolam was adjusted by 1 mg/kg/h after loss of consciousness (LoC). The time from administration of remimazolam to LoC was 130 s. We inserted central venous and pulmonary artery catheters from the right internal jugular vein as well as a probe for monitoring transesophageal echocardiography (TEE) after intubation. During induction, the patient’s mean blood pressure (BP) decreased by more than 50%, from 137 to 54 mmHg, and 5 mg of ephedrine was administered three times to maintain mean BP over 65 mmHg. rSO2 was decreased within 10% from the baseline value regardless of hypotension during induction. The BIS value ranged from 31 to 42 in the period of induction (Fig. ). Remimazolam was adjusted by 0.6–1.0 mg/kg/h according to the BIS value until the end of the surgery, and the depth of sedation was stable when the BIS value ranged from 30 to 50, even in the period of undergoing CPB. We did not induce hypothermia, and body temperature was maintained at 35–36 °C during CPB.
Surgical procedures were completed successfully. While left ventricular function was preserved after CPB, oxygenation status deteriorated after CPB. PaO2/FiO2 ratio (P/F ratio) decreased to 104 mmHg from 250 mmHg before CPB. Although we repeated sputum suction and recruitment maneuvers, P/F ratio was not improved (136 mmHg) at discharge from the operating room. TEE showed trivial MR remaining after mitral valve repair and systolic function was preserved. At the end of the surgery, the intraoperative dose of fentanyl was 17 μg/kg. Intraoperative infusion volume was 1300 ml and we transfused 280 ml of red blood cells and 720 ml of fresh frozen plasma. Bleeding volume was 360 ml, and water balance was + 1570 ml in total. Total operation time was 365 min, total anesthesia time was 474 min, and CPB time was 252 min.
We transferred the patient from the operating room to the intensive care unit (ICU). Administration of remimazolam was stopped after arriving at the ICU. A chest X-ray and ultrasonography showed mild pleural effusion and atelectasis in the right lung field. We did not antagonize remimazolam with flumazenil because of the poor oxygenation. Dexmedetomidine was administered until her oxygenation improved sufficiently for extubation. The patient showed a nodding response about 90 min after arriving at the ICU. The tracheal tube was removed 220 min later when the P/F ratio was 248 mmHg. We confirmed that there was no intraoperative awareness or recall and that there were no serious complications associated with the use of remimazolam throughout the perioperative period. The patient was moved to the general ward on postoperative day (POD) 1. The patient had disorientation and delirium on POD 6, but magnetic resonance imaging (MRI) showed no new lesion of cerebral infarction. The patient showed a motor and sensory disorder in her left lower limb on POD 10 and she was diagnosed with right cerebral infarction. She was discharged on POD 41 and transferred to another hospital to continue rehabilitation.


Patient A was a 49-year-old divorced man, father of two children, with an elementary educational background and low socio-economic status. He was the owner of two small bars. Family members with problematic use of substances included patient’s father (alcohol), uncle (alcohol), two brothers (alcohol, opioids, and stimulants), and previous partner (alcohol). The age of onset for alcohol consumption was 13. At the age of 16, patient used stimulants (cocaine) and cannabis for the first time. The age of onset for using opioids (heroin), hallucinogens (Lysergic acid diethylamide, LSD), and other stimulants (amphetamine) was 19. From the age of 20 until the age of 38, patient A underwent eight in/outpatient treatments for substance use disorders at a different hospital in Barcelona, Hospital Sant Pau. Treatment at this hospital included individual psychotherapy, group therapy, and pharmacotherapy (disulfiram, anxiolytics, and antipsychotic medication). Patient A maintained abstinence during treatments only, followed by alcohol abuse after treatment discharges.
At the age of 38, patient A received treatment for liver cirrhosis at Hospital Clinic of Barcelona, and he was derived then to the Addictive Behaviors Unit from the same hospital. Patient had a first appointment with a clinical psychologist but abandoned the treatment soon after. Between the age of 38 and 42, it is unknown whether the patient received treatment at a different hospital, either at public or private settings. At the age of 42, patient A had an overdose as a result of a combination of several substances: alcohol, stimulants, hallucinogens, and antipsychotic medication. After discharge from the intensive care unit for addressing the overdose episode, patient had a continuous pattern of alcohol use. At 46, patient A was administered two inpatient-based treatments for alcoholic hepatitis at Hospital Clinic of Barcelona. He had a 9-day abstinence period between these treatments for alcoholic hepatitis, followed by alcohol abuse after the second treatment discharge. Patient was again directed to the Addictive Behaviors Unit at the same hospital. At the second appointment with the clinical psychologist, patient A reported several motives to cease substance misuse: a hazardous pattern of substance use, severe alcohol withdrawal syndrome, numerous failed attempts to maintain abstinence over a prolonged period of time, severe alcohol craving, alcohol tolerance [patient A was consuming 26 standard drink units (SDU)/day at the time of the appointment at the age of 46], alongside using other illicit substances and tobacco on an occasional basis. A SDU is a single consumption of 10 g of ethanol (the standard quantity of wine or beer and half the standard quantity of liquor; ). In addition to substance misuse, patient A reported psycho-social and economic concerns (divorce, family substance abuse, and unemployment).
Patient A was assessed by different professionals at the Addictive Behaviors Unit (clinical psychologist and psychiatrist). Patient A fulfilled the criteria for antisocial personality disorder. In addition, the outcomes of the assessments indicated severe alcohol use disorder, moderate tobacco use disorder, moderate stimulant use disorder (cocaine), mild cannabis use disorder, mild sedative, hypnotic, or anxiolytic use disorder (as a result of continuous use of benzodiazepine-based medication) according to the Diagnostic and Statistical Manual of Mental Disorders (). As patient A experienced numerous relapses after treatment discharges and even had a continuous alcohol consumption pattern during outpatient-based treatment, he was considered “resistant to TAU.”
Patient underwent a detoxification program on an inpatient basis with clonazepam. Then pharmacotherapy included disulfiram, anxiolytic and gabapentin medication on an outpatient basis (disulfiram and anxiolytic medication from 46 to 49 years and gabapentin for several months at the age of 49). The psychological treatment followed a multidisciplinary protocol, including cognitive-behavioral, motivational, and third-wave therapeutic approaches at an individual and group level. Urine analyses were collected tri-weekly. From the age of 46 until 49, while under TAU at the Addictive Behaviors Unit, patient A was admitted to several therapeutic communities in Barcelona but abandoned after a maximum of 3–4 weeks. Despite the efforts from a multidisciplinary approach, patient A had a maximum of 4 weeks of abstinence each time there was an attempt to cease substance use, from 46 until the age of 49 as self-reported the patient and confirmed by urine analyses. He experienced several relapses mainly with alcohol, and occasionally with cocaine and cannabis. Overall, patient A had a continuous and hazardous pattern of alcohol consumption and occasional use of illicit substances from the age of 16 until 49.
At the age of 49, patient A was introduced to the VR-CET program as part of a larger clinical trial [the ethical code number of the clinical trial is 0377 (HCB/2017/0377) and the approval date was 09/2017]. Until that moment, patient A had never experienced a VR-based psychological treatment. At the moment of his inclusion in the study, patient A was under outpatient treatment at the Addictive Behaviors Unit, receiving medication and psychological treatment as detailed in the TAU at the Addictive Behaviors Unit. A month before the first appointment with the clinician-scientist from the University of Barcelona, patient A used alcohol, tobacco, cannabis, and cocaine. The entire VR-CET protocol lasted for 5 weeks, with two assessment sessions (pre-and post-VR-CET and six VR-CET booster sessions). Then, patient A abandoned the treatment received at the Addictive Behaviors Unit. represents a visual overview (VA) of the patient’s relevant current and past clinical data.
Given the complexity of patient A’s psychological status and medical concerns, in addition to the fact that he had an unfavorable response to previous therapies, we aimed at contributing to the educational, scientific, and clinical practice communities by illustrating a novel therapeutic approach and highlighting the clinical potential of technologies like virtual reality and eye-tracking in addressing the underlying mechanisms of AUD.


Case 1 was a 70-year-old male smoker with a history of chronic obstructive pulmonary disease, atrial flutter, and mitral regurgitation. He presented to the emergency room on 25 October 2019 with a right pneumothorax. A chest drain was inserted with satisfactory lung expansion. Computed tomography (CT) showed right pneumothorax on a background of pulmonary emphysema (Fig. ). Air leak persisted and he was not considered a surgical candidate due to poor lung function, as spirometry three years previously showed a forced expiratory volume in 1 sec (FEV1) of only 0.92 L (34% predicted) and FEV1 to forced vital capacity (FVC) ratio was 0.42. On Day 26, bronchoscopy was performed and balloon occlusion of the right upper lobe (RUL) resulted in immediate cessation of the air leak. Sequential occlusion of individual segmental bronchi of the right upper lobe failed to stop the air leak. Therefore, each of the three segmental bronchi had one EBV inserted, after which air leak stopped immediately. Compared to the pre-procedural chest radiograph (CXR) (Fig. ), the post-procedural CXR (Fig. ) showed near-complete collapse of the RUL, with pneumothorax still present in the right upper zone, but not in the right lower zone. However, the patient developed sudden increase in shortness of breath 20 h after EBV insertion with clinical feature of tension pneumothorax. CXR showed that the RUL collapse was maintained but there was a large right pneumothorax over both upper and lower zones (Fig. ). The old chest drain was replaced by a 20-F chest drain with improved clinical condition and the CXR showed satisfactory lung expansion (Fig. ). There was PAL that was treated with autologous blood patch five days later. Air leak stopped two days afterwards and the chest drain was removed the next day. The EBVs were removed six weeks after its insertion without complication.


Case 2 was a 56-year-old male heavy smoker with no history of prior medical illness. He presented to the emergency room on 11 December 2016 with sudden onset of shortness of breath. CXR showed a right pneumothorax. A chest drain was inserted with satisfactory lung re-expansion, but with continued air leak. A CT on Day 7 showed diffuse emphysematous changes with large bullae in both lungs (Fig. ). He was not considered a surgical candidate in view of the perceived poor lung function as suggested by the CT findings. On Day 25, bronchoscopy was performed with the intention of stopping the air leak by inserting EBVs. Balloon occlusion of the right upper lobe resulted in similar findings to Case 1, so EBVs were inserted into each of the RUL segmental bronchi. Air leak stopped immediately. CXR taken 1 h later (Fig. ) when compared to the pre-procedural CXR (Fig. ) showed significant collapse of the right upper lobe. However, the patient developed sudden increase in shortness of breath 12 h after EBV insertion. CXR showed no new findings on the right side but a new pneumothorax on the left side (Fig. ), for which a 24-F chest drain was inserted (Fig. ). Subsequently, he suffered from hospital-acquired pneumonia necessitating removal of the EBVs with recurrence of air leak on the right side. Air leak persisted on both sides. The patient was treated conservatively, and the left PAL stopped spontaneously after three months with the left chest drain removed on 13 April 2017. Air leak on the right side finally stopped following five applications of minocycline chemical pleurodesis, and the right chest drain was removed on 1 June 2017.


A 29-year-old man was admitted to hospital with a high fever and left chest pain. He was born with a low birth weight and had a history of post-natal oxygen therapy. In addition to this, he had a history of tetralogy of Fallot (TOF) with pulmonary valve atresia and major aortopulmonary collateral arteries and underwent several operations in early childhood to address these anomalies. He was not immunocompromised and was a non-smoker. Multiple bullae and low attenuation area in both lungs had been pointed out since early childhood. Chest computed tomography (CT) performed a year before admission showed the lung bullae without intrabullous fluid in both the lower lung lobes (Fig. ). On admission, laboratory tests showed increased inflammatory markers (white blood cells count: 11,640/μL, C-reactive protein: 12.3 mg/dL). Chest radiography revealed intrabullous fluid in the lower part of the left lung (Fig. ). Chest CT showed two bullae with intrabullous fluid in both the lower lobes and centrilobular small nodular shadow in the right upper lobe and left lower one, and there was low attenuation area in both the lung lobes (Fig. ). The patient's symptoms and intrabullous fluid did not improve despite treatment with ampicillin/sulbactam. Culture of bronchial washing specimen from the right upper lobe bronchus and left lower lobe one was negative for bacteria but positive for acid-fast bacilli. Polymerase chain reaction and culture revealed M. intracellulare. Percutaneous drainage from the bulla with intrabullous fluid on the left lower lobe was performed and a drainage tube was inserted. Purulent fluid was drained and found to contain mainly lymphocytes. Findings on culture of this fluid were the same as those of the bronchial washing specimen. There were no fungal isolates. Therefore, we diagnosed infected left lung bulla associated with M. intracellulare. He was treated with rifampicin, clarithromycin, ethambutol, and intermittent amikacin in accordance with the American Thoracic Society/Infectious Diseases Society of America recommendations for severe MAC lung disease []. The drainage tube on the left side was removed when fluid was no longer draining. His fever and chest pain gradually improved. Inflammatory markers also decreased to normal range. Intermittent amikacin therapy was completed in three months, and other triple therapy was continued for two years. During the course of treatment, we confirmed the negative finding of sputum for M. intracellulare four months after starting treatment. Imaging at the end of the treatment revealed that the intrabullous fluid in both the lung bullae disappeared and wall thickness of both bullae reduced (Fig. ). Based on these findings, a diagnosis of multiple infected lung bullae associated with M. intracellulare was made. In addition to this, small nodular shadow in the right middle lobe and left lower lobe also disappeared. There has been no recurrence to date.


A today 25-year old woman with a complex 3-year history of cardiomyopathy following viral myocarditis underwent successful orthotopic heart transplantation at our institution.
Six months prior to transplantation, she was listed in a prioritized status (Eurotransplant “HU” high urgent) but heart failure symptoms worsened with refractory signs of cardiogenic shock despite increased inotropic support. INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile was at level 2. Left ventricular assist device (LVAD, HeartWare, HeartWare Inc.) was implanted in April 2017, i.e. 6 months before transplantation. During the initial postoperative period, the patient developed treatment-refractory right heart failure. Weaning of inotropic agents was again unsuccessful and led to massive dizziness, arrhythmia, and impaired flow of the LVAD. The patient was again placed in the highest priority status (Eurotransplant “HU” high urgent) for a heart transplant while staying hospitalized in the ICU. Inotropic support before transplantation was maintained with Dobutamine (3.2 µg/kg/min) and Milrinone (0.5 µg/kg/min). LVAD flow remained around 3.8–4.1 l/min.
At the time of admission for transplantation, the patient had well-controlled pulmonary pressure (18/13 mm Hg) and low PVR (95 Dynes.s.cm-5). ABO status was compatible (B-/B-), cytomegalovirus mismatched (CMV −/+). The initial HLA antibody results of this mother were reported as being positive for Class I (Luminex Screen solid-phase arrays) specified for HLA B13, B41, B44, B45, B47, B49, B50, B60, B62, B71, B72, B76, and in a weaker expression for HLA B51, B54, B55, B56, B59, B63, B78. No preformed antibodies were cytotoxic. No C1q binding ability could be detected before transplant. The prospective donor-specific crossmatch was negative.
The donor was a 51-year old woman with a history of moderate alcohol consumption and chronic pancreatitis who was transferred to the emergency department of another hospital after the intentional ingestion of Methanol. Despite vasopressor support with noradrenaline, continuous hemodialysis, and therapy directed towards the preservation of neuronal function the donor’s condition had evolved to brain death four days after admission. Echocardiography revealed normal heart function and diameters. Cardiac catheterization ruled out coronary artery disease, and the ECG was unremarkable.
The heart transplantation was uneventful with an allograft ischemic time of 287 minutes. The LVAD was explanted. Pathological findings of the native heart confirmed interstitial fibrosis and mild hypertrophy consistent with the etiology of dilated postmyocarditic heart disease. The patient received induction therapy with cumulative 2 mg/kg body weight (120 mg) of anti-thymocyte globulin (ATG) and triple-maintenance immunosuppression therapy with Cyclosporine (switched to Tacrolimus on POD 9), Mycophenolate Mofetil, and Prednisone. The retrospective HLA crossmatch was negative; the retrospective amount of HLA mismatch was HLA-A/B/C/DR/DQ: 0/2/-/2/2. The initial postoperative course was uncomplicated, and the patient was extubated 48 hours after surgery.
On postoperative day (POD) 5, a decrease in myocardial function was noticed on transthoracic echocardiographic (TTE) follow up (FU). Pulsed-wave tissue Doppler imaging (PW-TDI) revealed a reduction of the radial and longitudinal systolic peak velocities (Sm) from 10/9 cm/s to 6/8 cm/s as signs for potential rejection (). At this time point, the patient was already off inotropic support. The ECG remained unchanged (). Right ventricular (RV) biopsy was performed. Histology revealed no cellular rejection (Level 0R of the International Society for Heart and Lung Transplantation criteria, IHSLT), but acute pathologic antibody-mediated rejection (pAMR grade 1 (I+), i.e. positive immunohistochemical staining with normal biopsy history.
We administered 60 mg of ATG, two infusions with low-dose intravenous immunoglobulin (1mg/kg body weight each), combined with steroid pulse therapy. No plasmapheresis was performed. At this time point, the expression of the donor-specific HLA Class 1 IgG against B44 had increased and C1q binding ability could be detected for non-donor specific B45 with a possible crossmatch. Six hours after RV biopsy, the patient presented signs of hemorrhagic shock. Computer tomography revealed acute retroperitoneal bleeding as a complication of the femoral puncture and the patient had to undergo emergent surgical decompression. Transfusion of 2 units of ABO-compatible packed red blood cells was necessary. The postoperative course was satisfying, with an echocardiogram showing ongoing improvement in cardiac function (PW-TDI Sm 10/9 cm/s). Ongoing tests on donor-specific HLA-IgG-antibodies revealed increased activity against B44, and increased complement binding activity of these antibodies was detected for the first time on POD 11. The patient was transferred to the transplantation unit of our institution on POD 12. Four cycles of plasmapheresis were performed. Two more doses of 60 mg ATG were administered when a slight decrease in myocardial function was again observed on POD 13. Despite a first remission in the histological stains on POD 21 (pAMR grade 0 in second RV biopsy), the patient presented persistent atrial arrhythmias (atrial flutter with varying A-V conduction) as well as non-sustained ventricular tachycardia (nsVT).
A first CMR was performed on a Philips Ingenia 3.0 Tesla Scanner one month after transplantation (). The exam revealed concentric left ventricular (LV) hypertrophy with moderately impaired biventricular function in line with prior TTE findings. Multiple cystic structures were found in the septal, mediolateral, and anterior parts of the LV with a crescent-shaped course ranging from the cavum through the myocardium to the epicardium. Late Gadolinium Enhancement (LGE) demonstrated high signal intensity of the described cystic lesions indicating fibrotic replacement. There was no evidence of regional myocardial edema in the T2-weighted images outside the above areas. Myocardial relaxation times were slightly increased (T1 native 1,389 ms; normal range 1,098–1,354 ms at 3 Tesla. T2 52 ms; normal range 35–51 ms at 3 Tesla).
RV biopsy four weeks after transplant revealed ongoing AMR (pAMR grade 2) with T-cell infiltrates and cell destruction including the vessels. Three more cycles of plasmapheresis, three doses of ATG, and steroid pulse therapy were administered. Five days later, a single dose of Rituximab was given to the patient.
In the 6-week FU, CMR LV-function had increased to about 50–55%. The cystic structures in the LV remained unchanged. Corresponding T2 images were strongly hyperintense and the LGE pattern was suspicious for mitochondrial cardiomyopathy. Electron microscopy of the biopsy specimens was performed. Ultrastructural findings revealed the presence of intracellular fat droplets, a high amount of fibrous tissue, and degenerative products (). The morphology of mitochondria was found to be normal. The high amount of fatty-fibrous tissue in the right ventricle raised the suspicion of Arrhythmogenic right ventricular cardiomyopathy (ARVC) or another specific underlying cardiac disease of the donor.
A genetic study of donor DNA was initiated. Next-generation sequencing with Illumina TruSight™ Cardio Sequencing Kit (Illumina, San Diego, CA, USA) including 174 potential genes for Cardiomyopathies was performed. A detailed list of investigated genes can be found in the .
Sequencing revealed two genetic variants in the coding gene for Titin with uncertain impact on the pathogenesis of ARVC, i.e. classification 3 in the American College of Medical Genetics and Genomics (ACMG) guidelines (). No other specific findings, i.e. no genetic variants explaining either the persistent rejection or the cystic changes could be detected.
FU TTE found levels of Sm to remain on a relatively low level despite the treatment efforts (10/8 cm/s for radial and longitudinal values respectively). Expression of the donor-specific HLA Class 1 antibodies against B44 was still detectable at week seven after transplant. Steroid pulse therapy, three more cycles of plasmapheresis (without additional ATG) plus increased dosages of mycophenolate mofetil (4g/d) were administered. Under this regimen, the patient finally attained and maintained remission. RV biopsy at week eight after transplant showed no signs of cellular or antibody-mediated rejection (ISHLT level 0R, pAMR grade 0). Despite the high frequency of intravenous steroids and the required changes in the immunosuppressive regimen, the transplant course was uneventful regarding infection. The patient’s tacrolimus levels were maintained at around 12–14 ng/ml.
Before discharge CMR before discharge showed normal T1 values as compared to the previous examinations as a possible sign of remission. No change in the intramyocardial cysts was found. A wearable cardioverter defibrillator (LifeVest, ZOLL, Pittsburgh, PA, USA) was put on to prevent cardiac arrest due to heart rhythm disturbances. The patient was discharged ten weeks after transplantation to a cardiovascular rehabilitation center. TTE, lab, and clinical state remained stable, and the patient was in a very satisfying condition when seen in the outpatient department for regular clinical, biochemical, and echocardiographic FU. RV biopsy FU exams showed no pathology for cellular or humoral rejection. At the time of writing this report, 32 months after transplant have elapsed and the patient is in a stable clinical state. CMR 32 months FU shows cardiac function to remain stable. However, measures of extracellular volume remain slightly elevated (ECV 33%, cutoff 30%) indicating diffuse fibrosis of the myocardium (). The described postoperative course is summarized as a Timeline in .


A 62-year-old man fell from a height of 4 m on March 26, 2020. He did not have any history of neurological, psychological, or genetic disorders. He complained of severe low back pain. When he visited the emergency department, he did not complain of muscle weakness or decreased sensation in both lower extremities. Physical examination confirmed no neurological deficit caused by the spinal cord injury. Recent compression fractures at T11, 12, and L1 and narrowing of the left T11 neural foramina were observed in the T-L junction on MRI. Therefore, surgery for posterior fusion of T10–L2 was performed on March 31. The patient's general condition improved, and he was transferred to the rehabilitation department on April 14 for active rehabilitation treatment.
With increasing abdominal pressure, for example, when standing up or coughing, an approximately 15- × 15-cm marked protrusion on the left flank following the T11 dermatome was observed (Fig. ). No palpable mass, pain, tenderness, or rebound tenderness was observed. Previously, he was in a bedridden state, so he did not notice such symptoms. The patient complained of hypoesthesia confined to the left T11 dermatome, and some gastrointestinal symptoms such as abdominal discomfort and dyspepsia.
Abdominal hernia was ruled out because no defects were found in the musculofascial layers of the abdominal wall in the initial abdominal CT scan. In addition, hematoma and ascites were not detected in the CT scan. Therefore, the cause of the abdominal protrusion was considered to be a pseudohernia. To confirm this, 3 tests were performed. To quantitatively analyze muscle activity, US and sEMG were used to demonstrate muscle weakness and needle EMG to demonstrate denervation.
First, the thicknesses of the 3 layers of abdominal muscles were measured using US (Fig. ). Measurements were performed in the area with the most severe herniation and on the opposite side. A 2-step test was conducted as follows: first, while the patient was resting in the supine position and, second, while the patient blew the positive expiratory pressure (PEP) device (Threshold PEP, Philips, Monroeville, PA) constantly at 20% strength of the measured maximal expiratory pressure (MEP) in the standing position. The MEP was assessed in a standardized manner using a desktop spirometer (Pony FX, Cosmed, Rome, Italy) to assess the strength of the respiratory muscles. Each stage was repeated 3 times, and the average value was obtained. The thicknesses of the 3 muscle layers, namely the external oblique (EO), internal oblique (IO), and transverse abdominis (TrA), were measured.
Second, the activities of the abdominal muscles were measured using sEMG by attaching electrodes to 8 channels at the same time, on both rectus abdominis (RA), both EO, both IO/TrA muscles, and the most severe herniation area and opposite side. Conductive adhesive hydrogel snap electrodes (Covidien 533 foam electrodes, Covidien: 710 Medtronic Parkway, Minneapolis, MN, USA) were used for sEMG. The electrode was composed of a 1-cm-sized circular conductive area. The electrodes were placed parallel to the muscle fiber orientation, and the distance between the centers of each electrode was 2 cm. The electrode recording RA muscle activity was attached 2 cm lateral to the umbilicus. The electrode recording the EO muscle activity was attached laterally to the RA and directly above the anterior superior iliac crest, halfway between the crest and the ribs at a slightly oblique angle, and the electrode recording the IO/TrA muscle activity was attached 2 cm medially and below the anterior superior iliac spine (Fig. ).[ Muscle activity was measured using the BTS-FREEEMG 1000 device (BTS Bioengineering, Milan, Italy) with a sampling frequency of 1 kHz, and the band-pass was filtered at 20 to 500 Hz.
The activities of the muscles while the patient blew the PEP device at 20% intensity of the MEP were compared. The percentage of the reference voluntary contraction (% RVC) was calculated for normalization by using the muscle activity during the blowing at the MEP. The % RVC of each muscle was determined using the following equation:
The root mean square (RMS) of each muscle was analyzed at 3 seconds in the middle of the 5-second blowing. After 3 repeated measurements, the maximum RMS value within 20% of the mean RMS value was selected. This process was conducted in a standing position, with a break of at least 3 minutes between each measurement. The results are shown in Table .
Third, a US-guided needle EMG was performed to confirm the presence of denervation potential. Under US guidance, the EMG needle was inserted in the bilateral IO muscle, and the insertional activity, resting potential, and motor unit potential during volition were measured.
The patient wore an elastic binder during activities to prevent protrusion of the abdominal wall. In addition, he had been training his abdominal muscles through McGill exercise and breathing exercises using abdominal muscles, such as with a PEP device.
After the study, the patient was discharged. It was supposed to check the progress of recovery in out-patient department, but the patient did not come for personal reasons.
As it is a case report with written informed consent, our institutional review board does not require formal ethical approval. Written consent was obtained from the patient for publication of this case report.


A 46-year-old woman complained of visual and gait disturbances and increasing headaches that had started some days earlier. Physical examination revealed a hemianopia to the right and restricted orientation to time without additional neurological deficits. A first magnetic resonance imaging (MRI) was performed, which revealed a large contrast-enhancing lesion within the left occipital lobe (Fig. ). The patient was transferred to the department of neurosurgery at our university hospital. After interdisciplinary discussion in the neuro-oncological board, tumor resection was indicated and performed by use of intraoperative neuronavigation without any additional deficits. Neuropathological examination confirmed an unmethylated but isocitrate dehydrogenase 1 (IDH1) R132H-mutated glioblastoma with a high proliferation rate (MIB‑1: 15–20% immunopositive tumor cells). Combined radiotherapy and chemotherapy with adjuvant temozolomide (TMZ) (EORTC/-NCIC trial protocol []) was indicated according to our institutional guidelines. Subsequently, the patient developed steroid-induced psychosis and tapering of steroids along with pentoxifylline and boswellia treatment was recommended. At this time MRI showed significant contrast-enhancement and perilesional edema and dexamethasone was prescribed (Fig. ). The patient recovered clinically and follow-up MRI displayed partial recovery of brain edema (Fig. ). After discontinuation of steroids, the patient redeveloped symptoms of depression and MRI showed recurrence of brain edema. At this stage steroids were readministered while continuing with the intensified TMZ chemotherapy. After completion of the second cycle, the patient complained of mild hemiparesis graded as 4/5 on the medical research council (MRC) scale for muscle strength, hemiparesthesia, and constant fatigue. At this point in time MRI showed persisting signs of edema and contrast-enhancement suspicious of tumor progression (Fig. ).
The indication for reoperation was established at the weekly interdisciplinary neuro-oncological board meeting. Intraoperatively, abundant tissue necrosis was detectable most likely resembling radiation necrosis; however, temporomesially above the tentorium signs of vital tumor were also detectable. Surgery again went well without postoperative deficit. The patient had clinically stable disease for 6 months, before MRI revealed signs of progressive disease. The patient quickly deteriorated clinically and finally succumbed to the disease 16 months after first symptoms had occurred.


A previously healthy 30 years old man, with no medical history, was admitted to the emergency room after a car accident: rollover by his car.
The physical examination on his admission was as follows: hearts rate of 145 beats/minute, blood pressure of 80/30 mmHg, with no signs of external bleeding, medullar trauma or limb fracture, the respiratory rate was 25 cycles/min, and pulse oximetry 75% on ambient air, 85% on high concentration mask with ronchis on the right side. The Glasgow Coma Scale GCS was 10/15 (eyes opening response 2/4, verbal response 3/5, and motor response 4/5) with contracted pupils, and no localization signs.
At this moment a decision to put the patient on mechanical ventilation was taking with inspiratory fraction of oxygen at 100%, tidal volume og 6 mL/kg and pression end expiratory pressure at 3mBar, with pulse oximetry at 93%.
The complete blood count showed the following: hemoglobin 12 g/dl, platelets 350000/mL, prothrombin time 80%, fibrinogen 3.5 g/l, white blood cells 7500/mL, eosinphils 55%, normal renal function : creatinine 0.8 mg/dl, urea 0.30 g/L.
After hemodynamic stabilization by fluid restitution with 500 mL of saline serum, and introduction of norepinephrine 1 mg/h, the full-body computerized tomography CT scan was performed, and it showed no internal bleeding, pneumothorax or medullar trauma, and showed on the thoracic level where it showed a well limited rounded formation of regular contours containing a hydro-aeric level related to a ruptured hydatid cyst ().
After ruling out the possibility of a hemorrhagic, hypovolemic shock, the diagnosis of anaphylactic shock due to post-traumatic rupture of hydatid cyst was maintained, norepinephrine was switched with epinephrine with a dose of 2 mg/h, and we gave him 500 mg of hydrocortisone with improvement in the hemodynamic state.
The patient was admitted to the operating room the next day for cyst removal by open thoracotomy ().
In the postoperative period, Albendazole was started with a dose of 400 mg/day.
The evolution was favorable; he was extubated in the immediate post-operative period and referred to the thoracic department.


A 56-year-old Caucasian male with no significant past medical history presented with an 18-month history of intermittent sharp shooting-type right-sided chest pain. The pain was aggravated by arm movement and radiated to the anteromedial aspect of the right pectoral region. The patient denied any other symptomatology. Physical examination was unremarkable. In particular, no upper or lower limb motor or sensory deficit was detected. Routine laboratory evaluation (full blood count C-reactive protein, erythrocyte sedimentation rate) and a chest X-ray were normal.
A magnetic resonance imaging (MRI) scan of the brain was normal. A spinal MRI scan was carried out for further assessment. At the T1 vertebral level, a 9-mm T1 isointense, T2 heterogeneously hyperintense, homogenously enhancing intradural extramedullary mass with an intramedullary component was detected. The lesion involved the right posterolateral aspect of the spinal cord and exhibited a posterior exophytic component. The mass displayed no broad-based dural component, cystic or hemorrhagic features, flow voids, calcifications, or spinal cord expansion (Figures -).
At the T1/T2 vertebral level, two additional 9- and 5-mm intradural lesions with both an intra- and extramedullary components were noted. These lesions demonstrated similar MRI characteristics to the lesion at the T1 level. The smaller left-sided lesion projected along the course of nerve roots in the posterolateral aspect of the cord, whereas the larger right-sided lesion indented the cord. There was no evidence of cord compression (Figures -).
As there were no red flag features (focal neurological deficit or radiological cord compression), a conservative management approach was adopted and future annual MRI follow-up was planned. Two years later, the patient presented with significant neuropathic chest pain refractory to analgesics. A spinal MRI scan showed a 2-mm increase in the size of the spinal lesions with associated spinal cord edema. As a consequence, laminectomy and tumor excision was carried out. Intra-operatively, multiple separate intradural lesions with intramedullary extension were identified corresponding to the filing detected on MRI. The vast majority of lesions were resected, with only a small remnant left to avoid iatrogenic spinal cord injury.
Histopathological evaluation of the excised tumor showed biphasic architecture with areas of densely compacted spindle cells with pronounced nuclear palisading, whereas other areas demonstrated less cellularly dense architecture. No mitotic activity was seen. Features were consistent with Antoni A and B growth patterns of schwannoma (Figures -).
Early (10 days) post-operative MRI imaging revealed near-complete resection of the multiple spinal schwannomas (Figures -).
Six months post-operatively, the pain resolved completely. Spinal MRI imaging showed no tumor residuum or recurrence.


A 72-year-old man with a history of squamous cell carcinoma of the oropharynx (treated 10 years prior with radical resection of the oropharyngeal lesion, chemotherapy, and local radiation) and recent hospital admission for immune thrombocytopenic purpura (treated with high-dose steroids) presented from an outside hospital for Ear Nose and Throat (ENT) evaluation of a non-healing buccal ulcer present for three weeks. He also reported worsening odynophagia and 20-pound weight loss over two months that prompted his family to bring him to the outside hospital for evaluation. At the outside hospital, the patient was hypoxic, with oxygen saturation in the high 80s in room air, and a chest x-ray revealed a right lower lung opacity, suggestive of pneumonia. He was started on empiric antibiotic therapy with vancomycin and piperacillin/tazobactam for presumed healthcare-associated pneumonia. Given his past medical history and reported weight loss, the buccal lesion was suspicious of recurrent malignancy, and he was transferred to our hospital for further workup.
At the time of transfer, the patient was afebrile (98.8 degrees Fahrenheit) with a blood pressure of 108/64 mmHg, heart rate of 82, respiratory rate of 18, and oxygen saturation of 100% on non-rebreather face mask at 80% fraction of inspired oxygen (FiO2). Physical examination revealed a cachectic man with oral thrush, a small area of erythema with central ulceration on the posterior left buccal mucosa and diminished lung sounds on the right. Labs demonstrated a white blood cell count of 9.5 x 10^3/µl, hemoglobin of 11.2 g/dL, and platelets of 72 x 10^3/µl (baseline unknown). Chest x-ray demonstrated right middle and lower lobe opacities, suggestive of hospital-acquired pneumonia versus aspiration pneumonia given the odynophagia, or metastatic disease from recurrent oral cancer (Figure ). Vancomycin and piperacillin/tazobactam were continued and nystatin was started to treat the oral thrush. A modified barium swallow examination performed under fluoroscopic guidance determined the patient had severe dysphagia and recommended that the patient receive nothing by mouth. Gastroenterology was consulted for placement of a percutaneous endoscopic gastrostomy (PEG) tube. ENT planned to biopsy the left buccal mucosa to confirm the suspicion of recurrent oral cancer.
Over the next few days of admission, the patient developed low-grade fevers and acute hypoxic respiratory failure with multiple episodes of desaturation to the high 80s despite being on 3L nasal cannula. He ultimately required high flow oxygen and subsequent bilevel positive airway pressure machine (BiPAP). Repeat chest x-ray showed increased bilateral lung opacities suggestive of pleural effusions despite broad-spectrum antibiotic therapy (Figure ).
Given the patient’s worsening respiratory status, piperacillin/tazobactam was discontinued and antibiotics were broadened to include meropenem and azithromycin, in addition to the vancomycin. Blood cultures drawn on admission showed no growth to date. Due to worsening clinical status, repeat blood cultures were sent, as well as sputum culture, respiratory pathogen panel, cytomegalovirus (CMV) and herpes simplex virus 1 and 2 antibodies (HSV1, HSV2). Buccal mucosa biopsy was deferred for several days pending stabilization of the patient’s respiratory status. A transthoracic echocardiogram was obtained to assess cardiac function in the setting of hypoxia and revealed an ejection fraction of 65% and moderate pericardial effusion without cardiac tamponade physiology. A CT chest without contrast revealed a multifocal pneumonia and a spiculated nodule in the right middle lobe (Figure ).
On hospital day seven, the result of an esophagogastroduodenoscopy conducted for dysphagia evaluation at the outside hospital prior to transfer was obtained. The report mentioned a non-bleeding esophageal ulcer and biopsy of the lesion was positive for cytomegalovirus inclusions with a negative HSV1 stain. Later, both CMV immunoglobulin M (IgM) and immunoglobulin G (IgG) serologies came back positive with a CMV Quantitative DNA polymerase chain reaction (PCR) of 4,549 IU/mL (7824.28 copies/mL). HIV screen was negative.
Vancomycin and azithromycin were discontinued. The patient was started on ganciclovir and continued on meropenem. Subsequently, his respiratory status began to improve. He was weaned off of BiPAP and high flow oxygen, saturating at 95 to 100% on 6L nasal cannula that continued to be titrated down. On day 11 of admission, ENT performed a bedside biopsy of the left buccal lesion and GI placed a PEG tube for nutrition. The intravenous ganciclovir was switched to valganciclovir to be administered via the PEG tube. Final pathology of the buccal ulcer revealed intracellular features consistent with herpes simplex virus and was positive for HSV1 and HSV2 immuno-stains (Figures , ).
Meropenem was discontinued after a 10-day course and he was switched from valganciclovir to intravenous valacyclovir on hospital day 15. The patient’s white blood cell count remained within normal limits and blood cultures showed no growth throughout the duration of the admission. Repeat chest x-ray after four days of antiviral medication demonstrated improvement of the bilateral consolidations (Figure ). On hospital day 16, the patient was deemed stable for transfer back to the outside hospital for continued care.
The patient was transferred back to the outside hospital upon stabilization of his respiratory status and completion of the buccal ulcer biopsy for continuation of care. The patient and his family were unable to be reached for one-month and six-month follow-ups after the transfer. As a result, an update on the patient’s clinical course after transfer could not be obtained.


A 56-year-old male was diagnosed with κ light chain MM in 2014 for which he received five lines of therapy including proteasome inhibitors and immunomodulatory drugs (). Disease involvement of CNS and spinal cord was discovered in 2017 and was characterized by impaired right vision, limited neck mobility, and detection of monoclonal plasma cells on CSF analysis. The patient then received another three lines of therapy, but the CNS/spine lesions were refractory to treatment including combinations of daratumumab, cytarabine, methotrexate, dexamethasone, cis-platinum, etoposide, and cyclophosphamide. He was then enrolled in a clinical trial of BCMA-CART therapy against MM (NCT03196414, currently recruiting, ). Immediately prior to CART treatment, the patient was confirmed to have stage I refractory CNS-MM according to the Revised International Staging System for multiple myeloma (R-ISS). The baseline findings at study enrollment included visual impairment, bilateral paraplegia, bladder and bowel incontinence, an elevated κ/λ ratio on CSF analysis (), and a MRI result showing a leptomeningeal lesion of 6.8 × 5.8 mm () and several other small abnormalities of the right occipital lobe and thoracolumbar spine. Subjectively, the patient complained of lower back stiffness and lower extremity weakness and indicated no history of cognitive disorder or seizure. A bilateral bone marrow biopsy immediately before CART treatment indicated no marrow disease, suggesting the patient had isolated CNS-MM.
On our phase I trial, the patient received one intravenous infusion of 5 × 107/kg autologous BCMA-CART cells per body weight without prior lymphodepletion (). Lymphodepleting chemotherapy was not administered due to the concerns of his lymphopenia (absolute lymphocyte count at study enrollment: 0.25 ×109/L) and an increased risk of neurotoxicity (). Six hours after the infusion, he developed fever and hypotension (). The patient’s neurological status was monitored daily in a similar way to the CD19 CART criteria (). Two days later, the patient complained of headache but remained awake and alert. On day 4, the patient developed lethargy and obtundation (responded slowly and hesitantly to verbal stimuli), and chemosis and stiff neck were also observed. His neurological symptoms further progressed on day 9 manifested as stupor, aphasia (could not give any verbal response), pupil asymmetry and loss of light reflex (left: 3 mm, normal reflex; right: 5 mm, no reflex), assessed as grade 4 neurotoxic events. To further evaluate these neurological findings, a CSF analysis was performed. The results revealed that interleukin-6 (IL-6, ) had increased from 10 pg/L measured before CART treatment to 5,000 pg/L accompanied by slight increases in interferon γ, IL-2, and IL-10 (). Other significant results included pleocytosis and high levels of lactate dehydrogenase (LDH) and protein (). Furthermore, a contemporaneous CAR transgene analysis showed a significant number of CART cells in his CSF on day 9 post-infusion (). Taken together, these results indicated that the neurological symptoms were probably caused by the CSF CART cells. The patient therefore received intravenous methylprednisolone (40 mg, single dose) and mannitol, and the neurological symptoms improved gradually. Tocilizumab was not used considering that it does not penetrate the BBB and because its use was not warranted in the absence of systemic symptoms (). By day 13, lethargy disappeared, and pupils returned to normal. Interestingly, dramatic levels of IL-6 continued to be detected in his CSF at various time points. Therefore, he received intrathecal dexamethasone (5 mg) on day 15 and day 18 which was followed by a significant drop in the CSF IL-6 level. By day 24, the patient exhibited a normal mental status with rapid and accurate responses to verbal questions. A favorable response of the disease was observed indicated by a reduction of more than 50% of the leptomeningeal lesion by MRI on day 30 (), disappearance of monoclonal plasma cells and a normal κ/λ ratio in his CSF on day 23 (), which was assessed as a partial response per International Myeloma Working Group (IMWG) criteria (). The patient indicated regaining of his urinary continence and had slight improvements of lower limb movement at month 1 and month 3 follow-ups. His clinical response persisted through 5.5 months.


The patient was a 33-year-old Iranian/Persian woman with a history of bilateral multifocal papillary thyroid carcinoma and left-sided cervical lymphadenopathy. She underwent a total thyroidectomy and treated with iodine 131 at a dose of 150 ml 3 years ago. Subsequently, she gradually was developed weakness, lethargy, facial swelling (moon face), and abdominal obesity. The patient's weight was increased from 70 to 113 kg over 3 years, and nutrition counseling did not control her weight gain. The patient was referred to Shahid Beheshti Hospital in Kashan, Iran. She was completed a consent form. The patient did not have a family history of thyroid disease or a malignancy. She was living in Kashan and was not an addict or a smoker. The patient was taking Levothyroxine (100 μg daily), Sertraline (100 mg bidaily), Propranolol (20 mg bidaily), and Respridone (1 mg bidaily). The patient did not have a history of steroid use. The patient experienced irregular menstrual cycles with intervals of 90 days and the duration of each cycle equal to 4 days. She had low-volume bleeding, and over time, the intervals between her menstrual cycles were increased. Eventually, the menstrual cycle was interrupted, and the patient was developed secondary amenorrhea. She was experienced mood swings, depression, and aggression during this period that did not improve despite treatment. Her blood pressure was 150/50, and her Body mass index (BMI) was 42. Hirsutism was observed on her face, breast, and around the navel. Purple striae on the abdomen, dryness all over the skin, multiple ecchymoses on the leg (easy bruising), a and muscle strength of 4/5 on both lower limbs were evident.
Firstly, laboratory tests, including Thyroid-stimulating Hormone (TSH), Follicle-stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin, Estradiol, urine-free cortisol (24 hours), and overnight dexamethasone were requested for the patient (Table ). The screening tests of Cushing's syndrome were positive; therefore, the low-dose dexamethasone test was performed to confirm the diagnosis. The patient was treated for two days with 0.5 mg dexamethasone every 6 hours, and the cortisol level (8 AM) was above 50 nmol/L [].
The cortisol level was 463 nmol/L; therefore, Cushing's syndrome was proposed for the patient. The ACTH level was measured to differentiate Cushing's syndrome from Cushing's disease. It was below 5 pg/ml, and the disease was considered as ACTH-independent Cushing's syndrome. An adrenal mass was observed in a computerized tomography (CT) scan of the adrenal gland (Fig ). The patient underwent laparoscopic right adrenalectomy and was removed a mass with 3.5 cm in diameter and weighing 18 g. Pathologic evaluation was suggested the benign adrenal adenoma. The mass was a fatty tissue without necrosis and hemorrhage. During 6 days after surgery, the patient was treated with an injection of 100 mg daily hydrocortisone. She was treated with oral prednisolone (5 mg daily) after discharge.
After 4 months, most of the symptoms of Cushing's syndrome, including weight gain, menstrual irregularities, hirsutism, and abdominal striae were partially cured. The patient's blood pressure, electrolytes, and TSH levels were normal, while she was receiving prednisolone and levothyroxine 100 micrograms per day. No mass was observed on a CT scan of the patient's abdomen after three months; therefore, the surgery was successful.


A 72-year-old male presented to our emergency department with complaints of worsening chronic diarrhea. The patient had a past medical history of delusional disorder and intermittent chronic diarrhea for the past two years. Surgical history was significant for resection of rectal mass two weeks earlier, which was performed at another institute before the presentation, pathology of which was consistent with villous adenoma. He had no known drug allergy and denied cigarette smoking, recreational drug use, or alcohol use. He also denied any recent travel. The review of the system was otherwise negative. On examination, the patient’s vital signs were within normal limits. Physical signs of dehydration were present; otherwise, the physical exam was unremarkable.
Laboratory tests were significant for hyponatremia (sodium of 116 mEq/L), hypokalemia (potassium of 2.9 mEq/L), low serum chloride level (52 mEq/L), azotemia (blood urea nitrogen level of 167 mg/dL), elevated creatinine (5 mg/dL), increased anion gap (38 mmoles/L) and elevated blood osmolality (321 mOsm/kg). The stool workup was negative for any infectious cause. Stool osmotic gap consistent with secretory <50 mOsm/kg. Celiac panel and stool occult blood were negative. Erythrocyte sedimentation rate was normal (12 mm/hr). Computerized tomography (CT) scan of the abdomen showed diffuse eccentric rectal wall thickening prominent on the right lateral rectal wall, which was concerning for neoplasm for which patient underwent colonoscopy, which revealed an infiltrative non-obstructing large mass in the recto-sigmoid colon. The mass was circumferential and measured 14 cm in length, extending 2 cms from the anal verge to 16 cms from the anal verge (Figure ).
The pathology result was consistent with tubulovillous adenoma (Figure ). The patient was referred for colorectal surgery and successfully underwent laparoscopic abdominoperineal resection (APR) and loop ileostomy. The surgical specimen pathology report was consistent with tubulovillous adenoma with patchy high-grade dysplasia with no invasion signs. Given the pathology showing villous adenoma, electrolyte abnormalities likely due to secretory diarrhea, and the presence of acute kidney injury, the diagnosis of McKittrick-Wheelock syndrome was made.


A 65-year-old woman with a medical history of hypertension, fibromyalgia, and COVID-19 infection one-month prior came to the emergency department with complaints of a progressively worsening headache and persistent emesis for one week. The headache was described as frontal and retro-orbital. She also noted symptoms of nausea, vomiting, photophobia, and phonophobia. She endorsed continued malaise and cough associated with her previous COVID-19 diagnosis; however, her disease course was mild and limited to those symptoms. Initial neurological examination was unremarkable. She underwent a CT scan of the brain, which revealed an 8 mm sellar/suprasellar high-density lesion with possible mass effect on the optic chiasm (Figure ). She was administered a single 10 mg dose of Decadron, and further imaging was ordered. MRI of the brain demonstrated a 14 mm heterogeneously enhancing sellar/suprasellar lesion with intrinsic high T1 signal areas and diffusion restriction, suggesting recent hemorrhage (Figure ). An initial endocrinology workup was unremarkable for cortisol (1.6 ug/dL), thyroid-stimulating hormone (TSH: 3.28 uU/mL), and T4 (1.2 ng/dL). She had mildly elevated follicle-stimulating hormone (FSH: 30.8 mU/mL); however, luteinizing hormone (LH: 8.1 mU/mL) was not elevated as would be expected given her postmenopausal status. This finding was attributed to pituitary dysfunction. The patient had no evidence of diabetes insipidus. The endocrinology team started her on hydrocortisone three times daily. Over the course of her stay, the patient denied any other neurological symptoms and reported that her headache had significantly improved.
Approximately one month after discharge, the patient returned to the hospital for follow-up endocrinology laboratory measurements and imaging. She noted continued improvement of her symptoms and resolution of her headache. At this time, an MRI brain showed the interval evolution of an intrapituitary hemorrhage, which drastically decreased in size and showed both subacute and chronic blood products with a new size of 8 mm x 4 mm (Figure ). Neurosurgery reviewed the images and noted the absence of a clear underlying pituitary tumor. Endocrinology reported normal prolactin levels (8.7 ng/mL) and adrenocorticotropin hormone (ACTH: 14.7 pg/mL). The patient had a slightly low LH (2.0 mU/mL) and FSH (6.0 mU/mL), both of which should be elevated due to menopause. The patient’s cortisol also remained low even while taking hydrocortisone. Thyroid hormones decreased while TSH was normal (T4: 3.3 ng/dL, Free T4: 0.4 ng/dL, TSH: 1.93 uU/mL). The patient was started on levothyroxine for central hypothyroidism. Endocrinology scheduled an additional follow-up for ACTH stimulation tests and urine studies due to hypernatremia (Na+: 149 mEq/L after fasting and water restriction). Neurosurgery scheduled a third MRI follow-up in six months (May 2021) to recheck for underlying neuropathology; however, at this time, the only precipitating factor and known association in this patient is a COVID-19 infection.


A 45-year-old female presented with complaints of swelling over the right lateral aspect of neck for the last 10 years associated with mild pain over the swelling. Occasionally, the patient also complained of difficulty in breathing and restricted opening of her mouth. She did not complain of any difficulty in swallowing. There was no history of any previous infection like fever, tooth ache or trauma or any other medical condition. Initially, the swelling was small in size and gradually progressed to a size of 10 × 12 cm, extending 4 cm below the lower border of mandible to upper border of clavicle, medial border being 4 cm lateral to midline and lateral border extending up to posterior triangle. On examination, the patient was pale and the swelling was measured to be of size 10 × 12 cm over the right lateral aspect of neck, which did not move on deglutition, was soft and cystic in nature, mobile, non-tender, no local rise in temperature, lateral border of the swelling was extending up to the posterior triangle, and medial border and superior border could not be made out, whereas the inferior border extended up to the clavicle. There was no discharge, redness, sinus from swelling and the overlying skin appeared normal. On intraoral examination, no abnormal findings were noted. Multiple palpable lymph nodes in the cervical region were noted. The nerve supply seemed to be in order.
The baseline investigations for complete blood count, routine urine test and renal function test were reported within normal limits. Ultrasonography of the neck revealed a large cystic swelling of size 13 × 9 × 8 cm (419 cc volume) on the right cervical region extending from the level of hyoid bone to clavicle, with external echoes, no vascularity and no calcification. Carotid vessels were pushed medially in inferior aspect and posteriorly in superior aspect. Multiple enlarged nodes in the cervical region were present with the largest measuring 1.2 cm. The impression was reported as an infected cyst/abscess in right cervical region. A magnetic resonance imaging (MRI) of neck was also performed, which showed a well-defined cystic lesion 13 × 8 × 8 cm extending from level of mandible to right supraclavicular fossa, displacing larynx and trachea to left, carotid vessel displaced medially. The impression was reported as a second branchial cyst or lymphatic cyst.
The plan for this patient was excision biopsy as there was uncertainty in the diagnosis as well as prognosis with a horizontal incision 3 cm below the mandible (Risdon’s incision). This involved complete removal of vesicles in order to prevent any further recurrences, although the risk of complications like scar and disfigurement significantly rises []. The excision was done under general anaesthesia and the tissue sample sent for evaluation. The biopsy specimen measured about 14 × 9 × 8 cm with irregular borders and soft in consistency.
Post-operative period was uneventful. There was no neurological impairment. Patient was on antibiotics, analgesics and proton pump inhibitors. Biopsy report confirmed the diagnosis as lymphangioma. It had clusters of lymphoid tissue, large underdeveloped lymphatic channels with unorganized smooth muscle cells in its walls surrounded by connective tissue. It also contained vascular spaces lined by epithelial cells, which were thickened in some places [].