A 34-year-old Japanese woman had a chief complaint of bilateral coxalgia. She visited the Department of Dermatology at our hospital at 17 years of age after developing yellow-brown papules on her neck, eyelids, and armpits at the age of 16 years. She was diagnosed as having xanthoma disseminatum, and she has been followed up by staff in the Departments of Dermatology and Internal Medicine since then. At the age of 33 years, she developed left coxalgia and visited our department for the first time. Her Japanese Orthopaedic Association (JOA) score of hip joint function was 56 points. Radiographs revealed slight narrowing of the joint space, which manifested as mild arthrosis, but we decided to perform a conservative course of observation. Her left coxalgia became aggravated, and she developed pain in her right hip joint that interfered with activities of daily living (ADLs). Thus, she was hospitalized for close examination and treatment at the age of 34 years.
Regarding her medical history, there was nothing in particular to note apart from xanthoma disseminatum and its complications. Concurrent diseases of xanthoma disseminatum included xanthomas in the hypophysis, respiratory tract mucosa, bulbar conjunctiva, and kidney peripheries, in addition to diabetes insipidus, chronic renal failure, and hypothyroidism. She had undergone tracheotomy at the age of 31 years because of respiratory tract constriction caused by a respiratory tract mucosal lesion. Xanthoma disseminatum had been controlled with orally administered prednisolone.
She experienced pain in both hip joints during walking and body movements, and she was able to walk continuously for approximately 15 minutes. Ranges of motion of both hip joints were restricted to 100°/100° in flexion and 10°/10° in abduction. The JOA scores were 48 in her right hip and 42 in her left hip.
Although plain radiographs revealed narrowing of the joint space, irregularity on the loading plane, and bone sclerosis in her left hip during the first examination, the joint spaces had disappeared in both hip joints by the time of admission, with deformation of the femoral heads, indicating progression of arthrosis. Numerous 5-mm radiolucent bands that resembled worm-eaten tracks were observed in the lower part of the femoral heads adjacent to the joint surface (Fig. a, b). A magnetic resonance imaging (MRI) scan revealed high-intensity areas—slightly higher than T1-weighted image intensity—along the joint capsules and synovial capsules that infiltrated the bone in a pattern resembling worm-eaten tracks. Short tau inversion recovery imaging scans showed high-intensity areas from the femoral head to the neck in both femurs—particularly in the left femur—suggesting bone marrow edema (Fig. a, b).
Since hip arthrosis progressed rapidly in both hips 1 year after the first examination, we suspected hip arthrosis caused by xanthoma disseminatum. Total hip arthroplasty (THA) was performed on her left hip first because she had more severe pain on the left side. THA was performed on her right hip 9 months later.
A posterolateral approach was used in both hip joint operations, and AMS cups and Perfix 910 stems (both cementless) (Kyocera, Osaka, Japan) were used as implants. The intraarticular pressure was high on both sides, and yellow tumorous lesions bulged from the joint capsule upon incision. The tumorous lesion was excised as much as possible after osteotomy of the femoral neck. Multiple yellow, tumorous lesions in the neck of the femoral heads were dissected with an obscure boundary to the joint capsule. When the femoral head was cut longitudinally, yellow, tumorous lesions infiltrated in patterns of worm-eaten tracks, as observed by radiographic and MRI scans (Fig. a, b).
Various inflammatory cells, including xanthoma cells, infiltrated the bone, and Touton-type multinucleated giant cells were observed. Mitosis—observed sporadically in the tumor cells—was normal (Fig. a, b). Macroscopic bone defects showed corresponding histological findings, and intraosseous and intraarticular lesions of xanthoma disseminatum were diagnosed.
At the time of the last observation (4 years after THA of our patient’s right hip joint and 4 years and 9 months after THA of her left hip joint), the JOA scores were 88 in both joints, and there was no disturbance of ADLs. Plain radiographs showed no deflection of the implants, and her postoperative course was satisfactory (Fig. a, b).


Three years ago, an 11-year-old girl presented to the hospital with pain in the right jaw after becoming aware of a mass in her right cheek. After detailed examination, the patient was diagnosed with ASPS with primary tumor in the right cheek and multiple lung metastases, and chemotherapeutic treatment was initiated. After receiving 1 cycle of VAC therapy (vincristine [2 mg], actinomycin D [0.045 mg/kg], and cyclophosphamide [1.2 g/m2]), the patient developed grade 4 neutropenia. After this treatment, the patient received 1 cycle of the treatment regimen prescribed for rhabdomyosarcoma (vincristine [2 mg], pirarubicin [60 mg/m2], cyclophosphamide [1.2 g/m2], cisplatin [20 mg/m2]) and 1 cycle of ifosfamide (1800 mg/m2), etoposide (100 mg/m2), actinomycin D (0.045 mg/kg), and vincristine (2 mg); however, the development of severe neutropenia made it difficult to continue administration of these drugs. The patient was then treated with oral administration of 800 mg/day of pazopanib for 1 year, and clinical benefit was achieved. Upon stabilization of the disease, oral administration of pazopanib was discontinued; however, 1 year later, fluorodeoxyglucose accumulation was observed in the right front of the skull (maximum standardized uptake value [SUV-max], 2.8) (Fig. a) and in the left breast (SUV-max, 2.4) (Fig. b) using fluorodeoxyglucose-positron emission tomography/computed tomography.
An elastic, soft tumor, approximately 3 cm in size, was palpated in the lower lateral region of the left breast. Ultrasonography revealed a hypoechoic, internally heterogeneous mass measuring 22.4 × 16.2 × 21.1 mm with a rich blood supply (Fig. a, b), while magnetic resonance imaging showed a 3-cm sized tumor that was larger than the one found on prior imaging (Fig. c). Examination of a core-needle biopsy specimen from the same site showed proliferating tumor cells with abundant foamy cytoplasm, clear nucleoli, and oval nuclei (Fig. a, b). The tumor cells tested positive for AE1/AE3, CAM 5.2, vimentin, S-100, α-actin, desmin, and HMB 45. The specimen showed negative periodic acid–Schiff (PAS) staining after diastase digestion (Fig. a, b); furthermore, the specimen then tested positive for transcription factor E3, resulting in a pathological diagnosis of ASPS (Fig. c). Based on the above information, we established a diagnosis of ASPS with left mammary, lung, and cranial metastases. Due to chemoresistance, surgical excision was selected as the mode of treatment; resection of the cranial bone showing metastasis was performed first and partial mastectomy of the left breast was performed in two stages. The mammary tumor was 25 mm in size, and the cut surface was solid with a reddish gray color (Fig. a, b). Histological findings similar to those of the needle biopsy specimen were also obtained in the final pathological diagnosis and resection margins were negative. Postoperative conditions were good, and we are currently monitoring the patient through regular follow-ups (visual palpation every 3 months and semi-annual mammary gland ultrasonography).


A 64-year old female with unresectable ovarian carcinoma underwent resection of the seeding nodule of ovarian carcinoma and created a loop ileostomy in the right lower part of the abdomen due to direct invasion of the carcinoma to the terminal ileum. During the formation of the loop ileostomy, the ileum penetrated the rectus abdominis muscle; the ileum was fixed to the anterior sheath of the rectus abdominis muscle with 8–10 stitches. Furthermore, the ileum and skin were also fixed with 12 stitches. There was no fixation between the peritoneum and the mesentery of the ileum. The patient subsequently underwent chemotherapy. Prolapse of the ileostomy appeared approximately 17 months after the operation, and it continued to progressively worsen. Repositioning of the prolapse was especially difficult, as bleeding occurred from the mucosa of the prolapsed intestine, and there were edematous and ischemic changes of tip of prolapsed intestine. Thus, we decided to perform the operation. The patient’s Performance Status was three and the general state was gradually getting worse. Pethidine hydrochloride (17.5 mg) was administered intravenously to obtain pain relief just before the operation. No heavy sedative was prescribed for the patient and, while conscious, the patient remained lucid throughout the operation.
The prolapsed intestinal tract with the Alice forceps was cut in accordance with the axis that intersected perpendicular to the mesentery by GIATM 60-4.8 (COVIDIEN, Dublin, IRL) (Fig a and b). It was separated so that the height of the intestinal tract that remained might be set 4–5 cm from the skin. Next, the isolated intestinal tract was separated using the same device in the direction of the minor axis (Fig. c). The interrupted suture was carried out to reinforce the part at which the stapler overlapped using absorbable sutures, and the operation was completed (Fig. d). The postoperative progress was good, and the chemotherapy was continued. The patient’s general state got worse gradually, and her treatment became a plan of best supportive care. Nineteen months after the first time operation, the general state got even worse and she died. After revision of the prolapse, there were no further troubles with the ileostomy.


A 46-year-old man presented with otorrhea, itching, and a foreign body sensation in his right ear. Otoscopic examination revealed a soft reddish protruding lesion at the posterosuperior portion of the entry to the right external auditory canal (). Computed tomography of the temporal bone showed a dense, protruding soft tissue lesion of the skin overlying the cartilage of the external auditory canal, but there was no evidence of the mastoid or middle ear lesions (). A tissue biopsy showed granulation tissue. Treatment with ointment containing gentamicin sulfate was ineffective. The skin lesion was endaurally resected; pathologic examination showed luminal structures in the middle to deep layer of the epidermis and inflammatory granulation below pseudoepitheliomatous hyperplasia (Figures and ). The walls of the luminal structures consisted of inner luminal secretory cells and outer myoepithelial cells (). These inner luminal secretory cells showed apical decapitation secretion.
The patient was diagnosed with an apocrine adenoma and pseudoepitheliomatous hyperplasia with inflammatory granulation. After surgery, otorrhea due to slight inflammatory granulation was prolonged. Therefore, additional resection of the posterosuperior portion of the ear auditory canal entry, including the cartilage over the bone, was conducted. The skin defect of the posterosuperior portion of the auditory canal was reconstructed using a postauricular island pedicle skin flap. The otorrhea and inflammation resolved. Three years after surgery, there has been no evidence of recurrence.


A 47-years-old woman with diabetes mellitus presented to our department with severe abdominal pain and fever. The local hospital’s computed tomography showed massive mural thrombosis in the thoracic and abdominal aorta from the level of the diaphragmatic muscle to the superior mesenteric artery (Fig. ). The spleen had a large area of infarction complicated by portal venous thrombosis. This patient underwent amputation three years ago due to extensive thrombosis of the left upper extremity artery. Further examination in our hospital showed thrombosis in the portal vein, the superior mesenteric vein and the splenic vein. Laboratory examination showed the following: prothrombin time 10.9 s, D-Dimer 1.030 μg/mL, C-reactive protein > 200 mg/mL, erythrocyte sedimentation rate 99 mm/h, NH3 73.5 μmol/L. Rheumatic immune tests, liver function, kidney function and electrolytes were normal, except for an albumin of 25.6 g/L.
Preoperative preparation and intraoperative procedures were carefully performed to improve the success rate and to reduce the risk of thrombus shedding during intervention. The catheter and guide wire was placed in the mesenteric artery and left renal artery via left femoral artery puncture, so that balloon angioplasty or stent implantation could be performed immediately once those branch vessels were blocked by shedding thrombus. Written informed consent was obtained from the patient for the use of RFS and the right femoral artery was incised to implant the RSF. The aortic thrombus was successfully compressed and fixed without thrombosis during intervention (Fig. a, b). A transjugular intrahepatic portosystemic stent shunt (TIPSS) procedure was conducted and a thrombolytic catheter was inserted in the portal vein for thrombolysis (Fig. a, b). Urokinase 100,000 units (Lizhu pharmaceutical Co., Ltd., Guangdong, China) was dissolved in 50 ml of normal saline, and given by microinfusion pump every 8 h. Warfarin sodium tablets 3.75 mg (Qilu pharmaceutical, Shangdong, China) were taken orally once a day after the procedure. In addition, 1000 units of heparin sodium (Fengyuan pharmaceutical co., Ltd., Anhui, China) and 0.6 mg of octreotide (Chinese medicine & pharmaceutical co., Ltd., China) were dissolved in 50 ml of normal saline and given by microinfusion pump every 12 h. Omeprazole 40 mg (Changchun Fuchun Pharmaceutical Co., Ltd., Changchun, China) and levofloxacin 0.6 mg (Yangzijiang Pharmaceutical Group Co., Ltd., Jiangshu, China) were administrated intravenously once a day.
Relief of the patient’s abdominal pain was evident 3 days after the interventional procedure, and pain resolved completely after 15 days. Angiography showed that the abdominal aortic thrombus was mostly dissolved, with only a few residual thrombi. A 12 F sheath was introduced through the guide wire and the RSF was retrieved (Fig. c, d). Catheter angiography confirmed an recovery of portal vein thrombosis via indwelling catheter. Portal vein thrombosis almost completely disappeared and the patient was discharged after 16 days (Fig. c). She received oral warfarin sodium 100 mg per day for anticoagulation with an international normalized ratio of 2–3. One month later, the bilateral renal artery, superior mesenteric artery, lower extremity artery and portal vein were well visualized, without thrombosis. The upper abdominal aorta was normal with a small amount of residual thrombus. The patient appears normal and no complications have occurred after 14 months.


History and examination
A 42-year-old male with a history of right eye visual field abnormalities presented with recent visual disturbances of the right eye and intermittent headaches. The visual disturbances were described as intermittent spots of blurriness. Initial MRI with contrast showed an oval-shaped lesion within or abutting the right optic chiasm. The lesion demonstrated intrinsic T1 hyperintensity (Figure ), as well as susceptibility and increased T2 and fluid-attenuated inversion recovery (FLAIR) signal. In the subsequent months, the patient complained of worsening visual changes that included the left eye as well. Visual acuity was graded 20/30 OD, 20/20 OS, and visual field testing revealed a very small scotoma in the left lower quadrant of the right eye. Pupils were equal, round, and reactive to light. Color vision was within normal limits with 14 out of 14 color plates correctly named in each eye. A dilated funduscopic exam revealed the discs to be sharp and pink with a cup to disc ratio of 0.1 OD, 0.2 OS and no optic nerve pallor on either side. Extra-ocular motility was intact bilaterally. At this time, the patient was referred to our services and was diagnosed as a possible CM, with a differential diagnosis, including craniopharyngioma, meningioma, and arteriovenous malformation (AVM). Due to the eloquent location of the lesion and the risk of visual loss, observation was chosen over surgery. Two months after presentation to the clinic, the patient visited the emergency department due to headaches and further visual changes in the inferior fields of both eyes, citing increased blurriness specifically. Visual acuity worsened to 20/40 OD, with no visual field cuts and no papilledema bilaterally. The patient was started on corticosteroids. Repeat MRI showed an expansion of the right optic chiasm/nerve lesion with increased T1 hyperintensity compatible with acute hemorrhage (Figure ). The lesion extended posteriorly and laterally to abut the right uncus and right cerebral peduncle. Visual field deficits were present in about three-quarters of his vision in both eyes, including the left temporal field and the right inferior nasal field (Figure ). After discussing therapeutic strategies with the patient, the decision was made to operate because subsequent bleeding could have caused irreversible blindness in both eyes.
Operation
Under general anesthesia, the senior author (EMD) performed a right pterional craniotomy for the resection of the right optic nerve and chiasm CM. Brain relaxation was performed by draining cerebrospinal fluid from the cisterns, making the opening of the Sylvian fissure unnecessary. The right optic nerve was identified microscopically and followed back to the chiasm, which showed purplish discoloration with hemosiderin staining. Discoloration was distributed along the superomedial aspect of the optic nerve on the right side and the posterior aspect of the optic chiasm. The CM was microdissected from the surface of the optic nerve without incising the nerve itself. The middle portion of the CM was densely adherent to the vasculature of the optic chiasm and nerve. Cauterization of the residual portion of the CM was completed, preserving the vasculature in order to reduce the likelihood of an ischemic event. Frozen and permanent specimens were sent to pathology. The frozen section returned as abnormal vessel and hematoma. Surgically, there was GTR; however, subsequent radiographic imaging provided evidence that the resection may have been subtotal (see discussion). Craniotomy closure occurred by the replacement of the bone flap and the reapproximation of the myocutaneous flap.
Postoperative course
There were no immediate complications following the procedure. The permanent specimen returned as CM and three weeks postoperatively, the patient had regained approximately half of the vision that was lost and continued to improve (Figure ). MRI 12 months postoperatively showed no sign of recurrence (Figure ). Over two years after surgery, the patient had resumed all preoperative activities and reported significant visual recovery, with headaches occurring only once weekly. Thirty-two months after resection, MRI showed a small slightly lobulated area of T1 hyperintense material within the postoperative cavity along the right aspect of the optic chiasm (Figure ). This finding was new as compared to prior imaging and suggested that minimal recurrence in this location should be considered. Upon follow-up with ophthalmology, visual field deficits were stable. MRI at 39 months postresection showed previously seen small amounts of T1 hyperintensity in the central and right aspect of the optic chiasm with significantly decreased conspicuity (Figure ). Only a trace amount of T1 hyperintensity remained at the right aspect of the optic chiasm, suggesting the 32-month postop scan may have demonstrated a trace amount of subacute hemorrhage in the area suspected of being residual CM. During ophthalmological follow-up at three years, the patient mentioned having difficulty reading and more consistently occurring headaches since his office visit six months prior. Headaches were reported to be different than past migraines. When compared to older visual field testing, there was a worsening of deficits in the left eye but within the standard deviation. Visual acuity remained stable at 20/30 OD, 20/20 OS. The suspected residual CM will be followed with serial imaging and visual field tests with the possibility of additional surgical resection in the case of visual deterioration.


A 37-year-old female was assessed for a slowly growing right cervical mass. The mass was an asymptomatic nodule at the beginning but gave rise to neck and right upper limb pain 3–4 months later. The patient showed a swollen right upper limb with complete loss of motor function but preserved sensory function. Contrast-enhanced computed tomography (CECT) (Figure ) revealed a soft tissue mass in tight contact with the right trapezius muscle, containing a central dysmorphic calcification. The mass is enhancing as the adjacent muscles with poor delineation with the trapezius as seen on axial (C) and sagittal (F) contrast-enhanced CT images (arrows). Shortly after, the lesion was surgically removed. Almost two years later, a control CECT (Figure ) showed a large contrast-enhanced mass containing multiple scattered calcifications (A–E, arrows), extending into the paravertebral muscles (F, long arrow), towards the spinal canal and the foramina, with multifocal epidural invasion, compression of the spinal cord and nerve roots (F, short arrows) and elsewhere, thrombosis of the superior vena cava (G, arrow), all consistent with an extensive tumor recurrence. Unfortunately, the multiple recurrences were unsuccessfully managed by repeated surgery, radiotherapy and chemotherapy. Histopathology (Figure ) showed typical features of ossifying fibromyxoid tumor (OFMT) with bony component.


An 85-year-old woman with type 2 diabetes mellitus presented to the emergency department of our hospital with coma and shock. She had not visited any hospital previously, had never been examined for complications of diabetes, and had never consumed any medications before. On admission, her vital signs were as follows: consciousness, Glasgow Coma Scale score 3/15 (E1V1M1); blood pressure, 80/40 mm Hg; pulse rate, 130 bpm; and temperature, 37.3°C. Laboratory analysis revealed neutropenia (neutrophils count, 640/µL) and elevated C-reactive protein level to 12.73 mg/dL. The levels of blood glucose and hemoglobin (Hb)A1c were 237 mg/dL and 12.1%, respectively. Blood and urine cultures showed the presence of Escherichia coli. CT of the abdomen and pelvis without contrast revealed diffuse gas collection within the urinary bladder wall (Figures , , ), which is a typical sign of EC caused by gas-forming bacteria., The patient was intensively treated with a broad-spectrum antibiotic meropenem hydrate and a vasopressor, and was put on respirator and catheterized; however, she died within 2 days due to circulatory failure. Based on literature review, including our study, from 2016 to 2018 in Japan, the mortality rate of EC is 26% (Table ). This study may provide a new insight into this disease.


The patient was a Japanese 72-year-old man, who had been diagnosed with atypical chronic myeloid leukemia (aCML) in 2014. He was an ex-smoker who did not regularly consume alcohol. In September 2015, treatment with oral cytarabine ocfosfate hydrate was initiated. After four cycles, he developed pneumonia, and treatment was terminated in February 2016. In April 2016, although he had no complaints, his serum C-reactive protein level was found to have re-increased to 4.6 mg/dL, and a chest X-ray and high-resolution computed tomography (HRCT) revealed scattered small nodular shadows and patchy consolidation (Figure A,B). The radiological findings did not improve despite the administration of antibiotics and antifungal drugs.
We performed bronchoscopy in May 2016. Bronchoalveolar lavage performed in the right upper lobe recovered 90 mL of 150 mL (60%) with 1.3 × 105/mL cells (neutrophils: 26%, lymphocytes: 36%, eosinophils: 1%, and macrophages: 37%). The histological examination of a specimen obtained from the right upper lobe via transbronchial lung biopsy revealed findings consistent with OP (Figure A). On immunofluorescence testing, the patient's antinuclear antibody titer was <40, and no other autoantibodies, including anti-SS-A, anti-aminoacyl tRNA synthetase antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibody, were detected. We diagnosed the patient with secondary OP associated with aCML. Treatment with prednisolone (30 mg, daily) was initiated, which resulted in the improvement of the laboratory and radiological findings, and the dose of prednisolone was then gradually tapered (Figure ). In September 2016, the patient developed general fatigue while under treatment with prednisolone (17.5 mg, daily). Chest CT revealed diffuse ground-glass opacities (GGOs). We considered the possibility of a recurrence of OP, and therefore increased the dose of prednisolone to 30 mg, daily; however, the patient's condition did not improve.
The patient was admitted to our hospital due to dyspnea on effort in November 2016. On admission, a physical examination revealed the following findings: respiratory rate, 15 breaths per minute; heart rate, 80 beats per minute; blood pressure, 106/60 mm Hg; and body temperature, 37.3°C. Chest auscultation revealed no abnormalities.
The laboratory tests performed on admission included an arterial blood gas analysis under ambient air, which showed the following findings: partial pressure of oxygen, 60.3 Torr; partial pressure of carbon dioxide, 30.4 Torr; and pH, 7.446. A blood analysis revealed the following findings: white blood cell count, 41 900/μL (neutrophil, 88.0%; lymphocytes, 5.0%; monocytes, 2.0%; promyelocytes, 1.0%; and myelocytes, 3.0%; metacytes, 1.0%); hemoglobin, 7.8 g/dL; platelet count, 34.2 × 104/μL; lactate dehydrogenase, 564 IU/L, Krebs von den Lugen-6, 2826 U/mL; and carcinoembryonic antigen, 15.6 ng/mL. The patient was negative for β-D glucan and cytomegalovirus antigen. HRCT showed diffuse GGOs in both lung fields (Figure C,D).
On the following day, we performed bronchoscopy with bronchoalveolar lavage in the right middle lobe. The bronchoalveolar lavage fluid showed a light milky appearance (Figure B) and was periodic acid-Schiff (PAS)-positive. Transbronchial lung biopsy revealed the precipitation of dense, homogenous, eosinophilic material, which had a fine granular appearance, and which filled the alveoli (Figure C); however, no evidence of OP was found. Based on these findings, he was diagnosed with PAP. Although the granulocyte/macrophage colony-stimulating factor autoantibody level was not measured, the diagnosis of sPAP was confirmed by compatible radiological findings and a pre-existing diagnosis of aCML.,
He gradually developed respiratory failure with the progression of PAP; whole-lung lavage was subsequently performed. Unfortunately, the patient died of acute enteritis within 1 month of whole-lung lavage.


Female patient, aged 57 years, BMI=23, was planned to undergo elective thyroidectomy, due to multinodular goiter. Her medical history included arterial hypertension, controlled with beta blocker and angiotensin receptors II antagonist. The patient has satisfactory physical status with no symptoms from cardiac and respiratory systems (no dyspnoea or coughing, no smoking history, asthma or COPD, >4 METS). No other concerns were raised regarding her family or previous anaesthetic history (she had received general anaesthesia 10 years ago for appendectomy without complications). Physical examination and laboratory testing did not reveal any findings and the patient had no prognostic factors of difficult airway management (Mallampati classification: II, thyromental distance > 6 cm, interincisional gap> 4 cm, and cervical spine extension > 90°). Chest X-ray was normal, regarding lung parenchyma but with slightly enlarged cardiac silhouette. This finding, in conjunction with Q waves, seen on ECG, made further cardiologic consultation necessary. However, no signs of cardiac disease were revealed, either by clinical examination, or by transthoracic ultrasound performed. The patient was scheduled for the operation a few days later and discharged home with the appropriate recommendations for medications and preoperative fasting.
On the day of operation, after establishment of the basic monitoring and intravenous line, anaesthesia was induced with midazolam 2 mg, Fentanyl 3 μg/Kg, and Propofol 2.5 mg/Kg and muscle relaxation was achieved with Cisatracurium 0.2 mg/Kg. Mask ventilation was difficult but pretty adequate. During first attempt of intubation, direct laryngoscopy resulted in a Cormarck=Lehane III and despite the use of elastic bougie was unsuccessful without passing the vocal cords. An LMA # 4 was inserted and a more experienced anaesthetist was called. At that time SpO2 was dropped to 95% with FiO2=1 with controlled ventilation with MV= 3.5 L/Min and adequate capnometry. After several minutes of ventilation with LMA and as SpO2 was 99% intubation was reattempted with the use of C-mac videolaryngoscope (Karl Stortz® Tuttlingen, Germany) and an elastic bougie. Second attempt was successful, as laryngoscopic view was significantly improved (Cormarck-Lehane: IIa), without any suspicion of airway trauma. A 7.5 mm neural integrity monitor (NIM) electromyogram (EMG) tracheal tube (Comepa®, Bagnolet, France) was used for intubation. Attention was paid for the proper placement of the tube (the silver color-coded contact band placed between the vocal cords). Anaesthesia was then maintained with desflurane 1 MAC in air/oxygen with FiO2=0.5.
Despite adequate ventilation (MV=5 L/min, Vt=480, RR=11, PEEP=3, and EtCO2=38mmHg) a sudden drop in SpO2 was observed during the next 2 minutes after intubation. SpO2 dropped at 75% with FiO2=1, with a concomitant hypotension (75/40 mmHg) and tachycardia (95bpm). Respiratory monitoring showed only slightly elevated Peak Inspiratory Pressure (28cmΗ2O). Since this incident happened before commencement of the operation, surgical drapes were removed and the patient was manually ventilated. During manual ventilation, it was observed that positive ventilation led to greater SpO2 drop, while stopping ventilation with open airway pressure release valve and FiO2=1 (apnoeic oxygenation), resulting in improvement of SpO2 (85-87%). Chest auscultation revealed excessively reduced sounds in the right hemithorax. Based on these clinical findings, the suspicion of tension pneumothorax was raised. A thoracic surgeon was immediately called, along with bed-side X-ray. The thoracic surgeon performed emergency insertion of a 14G venous cannula to the 2nd intercostal space at midclavicular line with immediate drainage of bubbles and haemorrhagic fluid and improvement of hemodynamics (BP: 95 mmHg, HR: 88 bpm) and SpO2: 92%. Chest X-ray confirmed the diagnosis of pneumothorax (). A thoracostomy tube was inserted with further improvement of oxygenation and drainage of 100 ml haemorrhagic fluid. The operation was postponed and the patient was transferred to the CT-suite, under sedation and controlled ventilation. CT scan revealed haemothorax and pneumothorax to the right hemithorax (), perihepatic fluid collection, and fluid in the Morison's pouch. Moreover, the diagnosis of multiple bullae was posed. The patient returned to the Postanesthesia Care Unit under sedation. ABG analysis was satisfactory (pH=7.35, PO2=123 mmHg with FiO2=0.5, and pCO2=38 mmHg). Hence, recovery from sedation and extubation was decided, which was uneventful. The patient was discharged a few days later. After investigation for pulmonary cystic disease, the patient underwent two stages of bilateral thoracotomy for partial parietal pleurectomy, lung apicectomy, and bullectomy, during the next few months (). One year later she underwent total thyroidectomy for multinodular goiter without any perioperative complications.


A 17-year-old girl presented to the surgical department with dull aching poorly localized left hypochondrial pain for two years, the patient had no other associated symptoms. The patient had history of blunt abdominal trauma to the upper abdomen two years before presentation to which she attributed her symptom.


A 62-year-old man of Bangladeshi origin was brought to the emergency department with lethargy and fever. Over the previous 2 weeks, he had developed a productive cough and weight loss. His past medical history included ulcerative colitis (diagnosed in 1999), which was quiescent on surveillance colonoscopy 2 days prior to admission. A suspicious rectal lesion was, however, biopsied. He had coronary artery bypass grafting in 1999, type 2 diabetes, hypertension, hyperlipidaemia and chronic hepatitis B. His medication included prednisolone, 10 mg daily (which he had been taking for 15 years), azathioprine 150 mg daily, Asacol (mesalazine) 2 mg daily, tenofovir and allopurinol 100 mg daily. His family acknowledged he had been taking prednisolone at greater than the prescribed dose for approximately 2 months prior to admission.
The patient was born in Sylhet, Bangladesh, and had moved to the UK aged 14. 6 months previous to the admission, he had travelled back to Sylhet for a 1 month family visit. He had not been unwell during the trip or until presentation. There was no unusual exposure history. There was no other significant or relevant travel history during his lifetime.
On examination he had a temperature of 34.8 °C, a non-tender erythematous left calf overlying a saphenous vein harvest site. His haemoglobin was 116 g l−1, white cell count 6.2x109 per litre and C-reactive protein 138 mg l−1. Initial management included empirical intravenous flucloxacillin 1 g four times daily for presumed cellulitis. A lower limb ultrasound excluded deep vein thromboses, and a computed tomography scan of chest, abdomen and pelvis demonstrated a rectal mass and a right basal pneumonia. Antibiotics were changed to intravenous benzylpenicillin 1.2 g four times daily and oral clarithromycin 500 mg twice daily.
Over the initial week, his condition deteriorated with fever to 40 °C, rising C-reactive protein and erythema spreading up the left leg to the scrotum, abdomen, left flank and right leg. The skin became tender and warm to touch. Dermatologists reviewed the skin on day 6 (). A differential diagnosis of multifocal cellulitis, panniculitis or migratory thrombophlebitis, in the context of possible malignancy was made. The patient developed a tender, swollen right testicle. An ultrasound showed epididymo-orchitis. Empirical treatment with oral ciprofloxacin 500 mg twice daily and oral doxycycline 100 mg twice daily was added.
The infectious diseases team suggested changing the benzylpenicillin to intravenous ceftriaxone 2 g daily, and adding oral linezolid 600 mg twice daily and intravenous amikacin 1.2 g once daily. Vasculitic, auto-immune and sexual health (HIV, chlamydia, gonorrhoea) screens and mycoplasma serology were negative. A trans-thoracic echocardiogram showed no signs of endocarditis. Blood cultures were negative.
On day 12, the patient was transferred to critical care for ventilation and noradrenaline (dose titrated to blood pressure within the standard critical care range of 6–13 µg min−1) for septic shock, considered secondary to cellulitis. He remained febrile at 40 °C and had developed a coagulopathy and bloody diarrhoea. His antibiotics were changed to meropenem 1 g three times daily and linezolid 600 mg twice daily. Plastic surgeons and urologists did not suspect necrotizing fasciitis.
The erythema spread to his flanks. No papules, nodules or umbilicated lesions were noted. In view of the diagnostic uncertainty, a skin biopsy was performed on day 15. A rectal biopsy showed CMV inclusion bodies and the plasma CMV DNA viral load was 15 304 copies ml−1. Intravenous ganciclovir 375 mg twice daily was initiated on day 19 to treat suspected disseminated CMV disease with evidence of colitis, epididymo-orchitis and panniculitis. CMV DNA was detected in skin, urine and throat samples.
Due to worsening leucopenia and thrombocytopenia, the ganciclovir was changed to foscarnet 4.5 g three times daily. Fluconazole 400 mg daily was added empirically on day 27 given the lack of clinical improvement, due to the presence of Candida albicans in the urine on day 24. The skin biopsy was reported on day 28 as showing septal/lobar panniculitis. To exclude necrotizing fasciitis, a scrotal incision was performed, which was sterile. Examination of the rectum showed no inflammation.
The fluconazole was switched to micafungin 100 mg daily on day 31, due to the growth of Candida glabrata from urine culture on day 30. Following a methenamine silver stain, the histopathologists reported the first skin biopsy as showing small, round yeasts of 3–5 microns within well-circumscribed areas of inflammation in the dermis and subcutaneous fat (). A skin biopsy was repeated the same day with samples sent for microbiological and fungal culture and molecular testing. On day 34, the pan-fungal PCR confirmed DNA from H. capsulatum. The micafungin was changed to AmBisome (amphotericin B) 320 mg daily.
A bone marrow biopsy was performed on day 33, which showed pancytopenia with increased macrophage activity, without evidence of malignancy, acid-fast bacilli or fungi. Ferritin and triglyceride levels were raised (47 798 µg l−1 and 2.45 mmol l−1, respectively) supporting a diagnosis of HLH. Immunosuppression was considered, but due to the patient's extremely poor clinical condition was not given. The bone marrow culture subsequently grew H. capsulatum. The patient continued to deteriorate and died on day 36 of admission.


A 67-year-old man presented to the clinic for follow-up of celiac disease and microscopic colitis diagnosed five years prior. He complained of six to seven large, loose bowel movements daily starting 10 months prior to this visit. His symptoms began soon after a prior admission for acute coronary syndrome requiring percutaneous coronary artery intervention. Review of systems was negative for dark stools, hematochezia, and abdominal pain. He denied any upper gastrointestinal symptoms, and he was adherent to a strict gluten-free diet. His last upper and lower endoscopies were five years prior to presentation, both of which were normal examinations. Biopsies were consistent with celiac disease and microscopic (lymphocytic) colitis.
The patient was started on aspirin and ticagrelor after his coronary artery stent placement 10 months prior. Additionally, he was on lisinopril and atorvastatin.
Physical examination was unremarkable. Laboratory workup, including a complete blood count (CBC) and comprehensive metabolic panel (CMP), was also unremarkable. Further testing revealed a negative Clostridium difficile polymerase chain reaction (PCR), negative stool studies for Giardia, and a negative enzyme-linked immunosorbent assay (ELISA) test for immunoglobulin A (IgA) tissue transglutaminase antibodies. The patient continued to have diarrhea despite multiple trials of different interventions, including budesonide, cholestyramine, atropine/diphenoxylate, and bismuth. Subsequently, a course of rifaximin for possible small intestinal bacterial overgrowth was tried, which yielded no change in symptoms.
The possibility of ticagrelor being the offending agent was considered, as the onset of diarrhea corresponded with the time of initiation of treatment. The patient’s ticagrelor medication was replaced with clopidogrel, and his diarrhea completely resolved within one week. The patient had no complaints at his one-month follow-up visit, and he reported one to two well-formed stools per day.


A previously healthy 36 year old female of Thai descent presented to the emergency department with a 4 day history of worsening dyspnea and a nonproductive cough. She also reported fevers, chills, and myalgias, for which she had taken both acetaminophen and ibuprofen without relief. The patient had moved to Hawaii in 2013, but had lived until then in her native Thailand. She had not traveled since then, had no sick contacts, no history of tuberculosis or hematologic disease, no unusual occupational exposures, and was not immunocompromised. She was in a monogamous sexual relationship.
Upon initial presentation, the patient maintained oxygen saturation over 90% on room air but was tachypneic to > 50 breaths per minute and tachycardic, with signs of accessory muscle use and increased work of breathing. Chest radiograph performed in the emergency department revealed increased interstitial markings and alveolar airspace disease. Non-contrast computed tomography (CT) of the chest demonstrated diffuse smooth interlobular septal thickening, with superimposed areas of ground glass attenuation and peribronchial airspace consolidation (Fig. ). These nonspecific but significant findings were concerning for acute respiratory distress syndrome (ARDS) and other noncardiogenic causes of pulmonary edema, PAP, atypical infectious processes such as Pneumocystis jirovecii pneumonia, alveolar hemorrhage, or drug-induced lung disease.
Lab abnormalities included microcytic anemia, elevated lactate (2.9 mmol/L, with subsequent 5 h trend to 3.9 mmol/L), mildly elevated procalcitonin (1.91 ng/mL), and lactate dehydrogenase (LDH) of 286 u/L. HIV – 1 + 2 antigen + antibody assay was negative. After volume administration and initial doses of azithromycin and ceftriaxone, the patient was admitted to the intensive care unit. An arterial blood gas drawn shortly after her arrival showed a pH of 7.41, pCO2 24, and pO2 63 on FiO2 0.40. Oxygenation worsened despite empiric antimicrobial therapy, requiring intubation and mechanical ventilation for progressive hypoxic respiratory failure on the first hospital day. Diagnostic bronchoscopy with bronchoalveolar lavage (BAL) was performed; cell count and differential of lavage fluid showed granular amorphous debris with few macrophages and neutrophils. Wright-Giemsa and acid-fast stains of the lavage material were not consistent with Pneumocystis or tuberculous pneumonia, respectively; subsequent Periodic Acid-Schiff staining of the amorphous granular material was positive, consistent with PAP (Fig. ). No findings concerning for hematologic malignancy were seen on peripheral blood smear, lowering suspicion for underlying malignancy. Anti-GM-CSF autoantibody assay was sent and eventually returned positive with a concentration of 7.9mcg/mL, consistent with autoimmune PAP; however, this result was not available for 21 days and thus not useful for clinical decision-making.
WLL was considered, as this is the treatment of choice in symptomatic PAP [, , ]. However, oxygenation transiently worsens during WLL; when this occurs, salvage methods such as ECMO are typically employed []. This patient’s oxygenation was tenuous and ECMO is unavailable in this geographically remote location, so an alternative treatment regimen was devised. The patient was initially treated empirically with aerosolized GM-CSF (dose 250mcg), administered in-line with the endotracheal tube circuit, for two days while awaiting BAL results, but experienced no clinical improvement. Following confirmation of the PAP diagnosis but before anti-GM-CSF antibody results were available, subcutaneous (SQ) GM-CSF (also at 250mcg) was initiated []. This yielded a decrease in LDH measurements and improvement in oxygenation such that the patient was successfully extubated on the fourth day of SQ GM-CSF therapy [–]. However, she continued to require supplemental oxygen at 4 l per minute at rest and remained profoundly dyspneic. In the days following extubation, her LDH also began to rise, from 381 u/L on her first day of SQ GM-CSF to 536 u/L five days later.
Following discussions with colleagues in a large academic center, the patient was offered and elected to undergo sequential lobar lavage of the anatomic lobes most severely affected on CT in order to expedite clearance of the alveolar space. During each treatment session, the patient was intubated under general (total intravenous) anesthesia without neuromuscular blockade. An Olympus P-180 videobronchoscope was introduced through the endotracheal tube and wedged into each compatible segmental or subsegmental airway of the lobe being treated. Each anatomic region was lavaged with warmed normal saline solution in increments of 50-60 mL until the return was clear (Fig. ). The right upper lobe (most radiographically abnormal) was lavaged first and required 1500 mL to return partially-cleared. One week later, the left upper lobe and lingula were lavaged with 4000 mL; an additional week later, segments of the right middle and lower lobes were lavaged with 3500 mL of saline solution. Over the course of three sessions, lavage return was consistently > 85% of instilled fluid.
After each lobar lavage, the patient experienced stepwise improvement in her symptoms, oxygen requirement, and tachypnea. LDH also decreased immediately following her right upper lobe lavage, from 536 u/L to 404 u/L. Repeat imaging showed improvement not only in the areas lavaged, but also in the contralateral lung. The day after her second lobar lavage, she had no oxygen requirement at rest, and denied any shortness of breath even with moderate exertion, although she required 3 l by nasal cannula to maintain saturation > 90% when walking. LDH continued to decrease, to 253 u/L. The patient was discharged shortly thereafter with home oxygen for exertion, and completed a total four week course of SQ GM-CSF. The third lavage was performed on an outpatient basis.
One month after discharge, the patient no longer required supplemental oxygen. Nine months after discharge, surveillance imaging of the lungs showed great improvement in previously visualized ground-glass opacities, with only small areas of residual disease. The patient has not required repeat therapy with either GM-CSF or lavage, and at the time of writing is asymptomatic, with preserved FEV1, FVC, and DLCO.


A 55-year-old female patient presented to our intensive care unit (ICU) after laparoscopic gastric bypass surgery. She had underlying morbid obesity, with a body mass index of 53.6 kg/m2, hypertension and clinically probable obstructive sleep apnoea. Intra-operatively, the surgery was protracted to about eight hours due to technical difficulties. Due to her underlying comorbidities and prolonged surgery, she was admitted to the ICU for post-operative observation and remained intubated. Following extubation on post-operative day 2, she developed persistent tachycardia and hypoxemic respiratory failure and was commenced on noninvasive ventilation (NIV). A few hours later, she developed epigastric pain. An anastomotic leak was suspected, which was confirmed by endoscopic findings. Subsequently, urgent surgical repair of the leak was carried out. She recovered over a course of 5 days after the re-surgery and was discharged to the ward.


Patient 1: The first patient was a 78-year-old African male who first presented to his local hospital with constitutional symptoms and abdominal distension, which progressed over a four-month period. He was later referred to us for further management. This was his first-ever consultation and admission to any medical facility. There was no past surgical or medical history of note and no history of illicit drug use. However he was an occasional drinker and a smoker with a three-pack year history. He had no family history of note.
Physical examination revealed skin hyperpigmentation, lower abdominal mass and features of severe tricuspid regurgitation with right heart failure. The rest of his clinical examination was unremarkable. Carcinoid syndrome with CHD was suspected during routine transthoracic echocardiographic assessment, and his images are shown in .
His biochemical laboratory results revealed a markedly elevated serum 5-hydroxyindoleacetic acid (HIAA), which was more than 10 times the upper limit of normal. An octreotide scan was positive for the primary lesion localised around the periprostatic area. Additional blood results revealed normal renal and hepatic function. His full blood count revealed features in keeping with anaemia of chronic diseases. The prostate-specific antigen level was mildly elevated. Chest radiography revealed a mildly increased cardiothoracic ratio and hyperinflated lungs. Unfortunately, the patient refused further hospital management, including surgery, and died a year later.


Patient 2: The second patient was a 32-year-old male of Indian descent who presented with a two-month history of abdominal pain, weight loss and diarrhoea. He had no significant past medical, surgical, family or occupational history. Patient 2: The second patient was a 32-year-old male of Indian descent who presented with a two-month history of abdominal pain, weight loss and diarrhoea. He had no significant past medical, surgical, family or occupational history.
His clinical examination revealed features of right heart failure with severe tricuspid and moderate pulmonary valve regurgitation. The rest of his examination was unremarkable. Chest radiography revealed a mildly increased cardiothoracic ratio and an electrocardiogram revealed sinus rhythm. Blood results revealed mild pre-renal dysfunction, anaemia of chronic disease, normal liver function test and normal comprehensive metabolic panel. Further biochemical results revealed an elevated 5-HIAA level and prior to referral, his private practitioner had already commenced medical therapy, which included octreotide.
Two weeks later the patient was referred for a specialist’s opinion and further management. His echocardiographic and computed tomographic images are presented in and , respectively. His symptoms improved dramatically on medical therapy and he was subsequently referred to the surgical team, where an elective tricuspid valve replacement (TVR) was successfully performed six months later. His intra-operative and postoperative periods were uneventful, and his symptoms continued to improve on subsequent follow-up visits.


A 56-year-old female patient with an overall healthy oral state visited the clinic for implant placement after the removal of a retained right mandibular 1st molar (tooth 46) root (Figures and ). After local anesthesia, the dental root was separated using a high-speed handpiece and #558 bur, followed by careful atraumatic extraction using an elevator. After drilling into the interradicular septum using only a 4 mm diameter trephine bur to obtain autologous bone, a 10 mm long and 5 mm diameter implant (AnyOne, Megagen Implant Co., Seoul, Korea) was inserted 1 mm deeper than the height of the buccolingual alveolar ridge. The gap between the inserted fixture and extraction socket was about 4 mm in both the buccolingual and mesiodistal directions (). The gap between the extraction socket and implant was filled with autologous particulate bone obtained by grinding the bone core made by the trephine bur (). After equipping it with a cylinder-type healing abutment (), a silicone cap was fabricated as described earlier and then placed over the healing abutment because it was easily stretched using the pincettes (). Except for the force that exerted light pressure on the soft tissues around the extraction socket, the installed silicone cap showed no movement (). Thus, without making an incision or using sutures and a barrier membrane, the extraction socket was sealed using only autologous bone and a silicone cap. The silicone cap is seen as a radiopacity on a radiograph ().
The patient was instructed to be careful not to dislodge the cap with their tongue, masticatory movements, or by brushing. The patient was advised to rinse with a 0.1% chlorhexidine digluconate solution (Hexomedine solution, Bukwang Pharm. Co., Seoul, Korea) twice daily for 2 weeks. Additionally, the patient was prescribed with antibiotics (Augmentin 625 mg, Ilsung Pharm. Co., Seoul, Korea) three times a day for 7 days. On clinical images taken at 2 weeks postinsertion, plaque bacteria were observed adhering to the healing abutment, but not the silicon cap, with only slight discoloration (). The cap also did not create a foreign body reaction or cause pain to the patient. Although the surrounding gingival margin was temporally suppressed by compression due to the silicon cap, healthy soft tissue regenerated, completely sealing the extraction socket (). At 2 months after the removal of the cap, the suppressed soft tissue had healed completely (). A final prosthesis was provided at 6 months after implant insertion, and healthy attached gingiva formed around the final prosthesis (), showing integration with the surrounding gingival margin, including the mucogingival junction (MGJ) line (). Furthermore, regenerated bone tissue was observed on the radiograph (). A radiograph taken at 22 months postoperatively also showed a well-maintained alveolar bone height ().


A 42-year-old male patient was admitted for a retained dental root and root apex lesion at tooth 16 and required an implant prosthesis for an extracted tooth 17 (). Computed tomography () revealed that the retained bone height was insufficient due to the large root apex lesion of tooth 16. After atraumatic extraction of tooth 16, bone-added osteotome sinus floor elevation (BAOSFE) was performed using allogenic bone (SureOss, Osstem Implant Co., Seoul, Korea) to enhance the primary fixation of the implant. This BAOSFE procedure was performed using a drill and osteotome according to Summers' original technique []. A 13 mm long and 6 mm diameter implant (AnyOne, Megagen Implant Co., Seoul, Korea) was then immediately inserted with insertion torque exceeding 40 N cm (); the implant was inserted 1 mm deeper than the height of the alveolar ridge of the extraction socket. After collecting 10 cm3 of peripheral blood, platelet-rich fibrin (PRF) was prepared using a centrifuge (MF550, Hanil Science Industrial Co., Incheon, Korea). After application of the cylinder-type healing abutment, the gap in the extraction socket was filled with allograft material (SureOss, Osstem Implant Co., Seoul, Korea) up to the height of the alveolar ridge of the extraction socket, followed by filling with the PRF membrane up to the height of the soft tissue in the extraction socket (). Due to gingival tearing during extraction, two interrupted nonabsorbable sutures (Dafilon 5-0, B. Braun, Melsungen, Germany) were inserted. After fabricating a silicone cap as described earlier, it was placed over the healing abutment (Figures and ). Using a flapless technique, a nonsubmerged 13 mm long and 5 mm diameter implant (AnyOne, Megagen Implant Co., Seoul, Korea) was inserted into the region of tooth 17, where the ridge had healed, accompanied by BAOSFE to enhance the primary fixation of the implant.
At 2 weeks postinsertion, the cleanly maintained silicone cap and sutures were removed (); the extraction socket showed satisfactory healing, with soft tissue formation (). The final prosthesis was applied 8 months postoperatively. The soft tissue initially suppressed by the silicone cap was restored, and a well-formed attached gingiva was observed (). In addition, stable bone tissue was observed around the inserted implant neck, and increased vertical alveolar bone was observed under the implant (). Clinical and radiographic evaluation at 2 years postoperatively revealed a healthy gingival margin and satisfactory stability (Figures and ).


We present the case of a 70 year old male who had an elective right inguinal hernia repair. He reported a longstanding history of a right inguinal lump which had been causing increasing discomfort over the previous 12 months. His past medical history included an emergency laparoscopic cholecystectomy 5 years prior, as well as atrial fibrillation. On examination, the patient had a mildly tender right inguinoscrotal hernia. Despite being tender, the hernia was reducible and there were no overlying skin changes. Abdominal and testicular examinations were otherwise unremarkable.
Open right inguinal hernia repair was performed using a modified Kugel technique. Intraoperative findings validated clinical examination and a large indirect hernia was reduced. Upon reduction, the hernia sac was found to have multiple 5 mm foreign bodies embedded into the wall. On closer inspection these foreign bodies were macroscopically consistent with gallstones (see , ). The hernia sac and foreign bodies were sent to the pathologist who confirmed the foreign bodies to be cholesterol gallstones.
The immediate post-operative recovery was uneventful and the patient was discharged home the following day. He was reviewed four weeks later in the outpatient surgical clinic where he reported a good recovery.


A 39-year-old female was brought to our emergency room by a private vehicle after being shot. An evaluation revealed a wound at the lower left back and at the mons pubis. Exploratory laparotomy and resection of the sigmoid colon, left ovary, and fallopian tube with a colostomy was performed. Postoperative deep venous thrombosis prophylaxis in the form of enoxaparin, 30 mg every 12 hours, was given and then changed to heparin, 5,000 units subcutaneously every eight hours, due to worsening renal function. The patient did well until postoperative day 4 when she complained of increased abdominal pain out of proportion to the clinical findings. Her symptoms worsened the following day. A computed tomography (CT) scan of the abdomen and pelvis was obtained, the results of which were consistent with postoperative ileus and raising concerns for right colon ischemia.
The patient was managed conservatively, and bedside drainage of the superficial wound infection was done on postoperative day 6 with improvement in abdominal pain. On the following day, a repeat CT of the abdomen and pelvis raised more concerns for bowel ischemia; however, the patient refused reexploration (Figure ).
A computed tomography angiogram (CTA) of the chest was obtained for worsening pulmonary symptoms on postoperative day 8 and was consistent with lower lobe pneumonia.
Feculent drainage around the stoma was noticed on postoperative day 9, and an exploratory laparotomy was performed with resection of multiple small bowel ischemic loops, cholecystectomy, and right hemicolectomy. The rest of the small bowel appeared dusky and friable. After multiple visits to the operating room, she was left with only a few inches of the proximal jejunum. A CTA of the abdomen was done on postoperative day 13 from her initial surgery and was consistent with a superior mesenteric artery occlusion (Figure ).
Admission platelet count was 281, down to 82 on postoperative day 11 when she tested positive for heparin-induced antibodies. The pre-test probability for HIT score was high (2 for thrombocytopenia, 1 for timing, 2 for thrombosis, 2 for no other cause = 7). The heparin was stopped and argatroban was used. The patient did survive her injury and was referred to a small bowel transplant center.


A woman in her late 60s was transferred in July 2012 from her local hospital because of anemia of at least one and a half year duration. She had no relevant family history, but had been treated for diabetes type 2 and hypertension for decades and paroxysmal atrial fibrillation for a few years. She had suffered from recurrent urinary tract infections, several times with fever and once with verified urosepsis. A concrement had been removed from her right ureter a few months ago.
Her history of anemia started gradually with fatigue in 2010-11. Her hemoglobin (Hb) level was 8.9 g/dL in February 2011, as compared to 13.4 at the last known previous assessment in 2008. She had received an erythrocyte transfusion at her local hospital without any transfusion reaction or other problems, and she had already suffered several exacerbations of anemia during febrile infections. There was no history of acrocyanosis or Raynaud phenomena.
On admission, she was in good general condition and did not present any pathological findings by physical examination. In particular, there was no acrocyanosis, lymphadenopathy, or splenomegaly. Chest radiography and abdominal ultrasonography were unremarkable. Hb was 8.2 g/dL, leukocytes 7.8 × 109/L with normal differential count, platelets 263 × 109/L, mean corpuscular volume (MCV) 99 fL, reticulocytes 88 × 109/L, and C-reactive protein (CRP) 11 mg/L. Serum levels of iron, transferrin, cobalamin, and folic acid as well as transferrin saturation were within the reference range, however, with elevated ferritin at 1257 μg/L. Genetic screening for hemochromatosis showed no HFE gene abnormalities. Concentrations of electrolytes, calcium, creatinine, and liver transaminases were normal. Lactate dehydrogenase (LDH) was elevated at 544 U/L, bilirubin elevated at 43 μmol/L, while haptoglobin was undetectable (less than 0.1 g/L). Her urine was negative for hemoglobin and protein. Serum albumin was 41 g/L with normal immunoglobulin levels (IgG 7.0 g/L, IgA 3.2 g/L, and IgM 0.69 g/L). Serum electrophoresis identified a small spike of monoclonal IgAλ. Free λ chains in serum were slightly elevated at 53 mg/L, however, with a κ/λ ratio within the reference range. The direct antiglobulin test (DAT) was strongly positive for C3d and negative for IgG, IgM, and IgA. CA titer at 4°C was 128. Serum erythropoietin was slightly elevated at 36 IU/L.
Based on these findings, she was diagnosed with CA-mediated AIHA. With a chronic course, no signs of malignancy so far, and no recent specific infection, this AIHA was further classified as primary CAD. A bone marrow trephine biopsy showed erythroid hyperplasia and small lymphocytic infiltrates interpreted as lymphoplasmacytic lymphoma (LPL). Flow cytometry in bone marrow aspirate revealed two small, clonal populations: one of B-lymphocytes that displayed a κ phenotype and the other one of λ positive plasma cells.
The further development in Hb and IgA levels is shown in . During the next couple of years, Hb ranged from 9.0 to 10.0 g/dL; she had only mild fatigue and no transfusion requirement. Management consisted of regular follow-up, avoidance of cold exposure, and prompt antibiotic therapy in case of febrile bacterial infection but no CAD-directed pharmacological therapy. By 2014, a second bone marrow biopsy showed erythroid hyperplasia and lymphoid infiltrates, now interpreted as probable CAD-associated LPD []. Flow cytometry in bone marrow aspirate again demonstrated 2 pathological clones of κ positive B-lymphocytes (approximately 5%) and λ positive plasma cells (0.7%), respectively.
Her condition remained stable until late spring 2016, when she deteriorated. Her fatigue worsened, her atrial fibrillation relapsed more frequently, and her Hb level declined to 8.5 g/dL. The reticulocyte count was now elevated at 191 × 109/L, LDH was 303 U/L, bilirubin 96 μmol/L, haptoglobin <0.1 g/L, while IgA had increased to 12.5 g/L and CA titer to 512. The DAT findings were unchanged. We decided to give her rituximab monotherapy [], four weekly doses of 375 mg/m2, which she received from August 2016. Hb rose to 12.5 g/dL by December 2016, while bilirubin and LDH normalized. Unexpectedly, however, her IgA level continued to increase from 12.5 g/L immediately before rituximab treatment to 19.6 g/L by January 2017.
From June 2017, Hb started again to decline and IgA continued to increase. In January 2018, she experienced severe lumbar pain after having removed snow from her courtyard, which can be heavy work in Norway. One month later, Hb was 9.5 g/dL, while the absolute reticulocyte count was 153 × 109/L and the levels of LDH, bilirubin, and haptoglobin had not changed significantly. The IgA level was 24.5 g/L and β2-microglobulin 3.5 mg/L. A new trephine biopsy showed hypercellular bone marrow affected by 20% infiltration of monoclonal, λ positive plasma cells, and some small lymphocytic infiltrates. A CT scan showed osteolytic lesions of the skull but no relevant pathological findings in her spine, pelvis, or femora. She was diagnosed with development of MM.
In February 2018, a local visiting hematologist initiated a cycle of melphalan and prednisolone. During the next couple of weeks, Hb declined further to 8.0 g/dL, however, without any neutropenia or thrombocytopenia. Concomitantly, a rise in bilirubin and LDH was observed, and she was diagnosed with an exacerbation of CAD. Melphalan and prednisolone were discontinued after the first cycle.
Hoping to induce remission of both MM and CAD, we decided in March 2018 to offer her bortezomib-based therapy [] with the addition of dexamethasone and rituximab [, , ]. She received four cycles at four weeks' interval of bortezomib (1.3 mg/m2 weekly for 3 weeks), rituximab (375 mg/m2 once per treatment cycle), and dexamethasone (20 mg on days 1, 2, 8, 9, 15, and 16). She tolerated this combination well; her Hb level increased from 8.0 g/dL to 13.6 g/dL following the first cycle and reached 14.4 g/dL after the second one. Bilirubin and LDH normalized within a couple of weeks, and reticulocyte count declined to the normal range (65 × 109/L). IgA had declined to 3.8 g/L by the start of the second cycle. Her back pain improved. Ten weeks after start of therapy, Hb was 13.2 g/L, bilirubin 7 μmol/L, LDH 247 U/L, haptoglobin 0.24 g/L, and CA titer 64. IgA remained in plateau at 3.9 g/L, while serum electrophoresis did not show any monoclonal spike. DAT was still positive for C3d.
The lymphoma pathologist in our group (U.R.) did a centralized, parallel review of all three bone marrow samples based on extensive experience with CAD-associated bone marrow pathology []. The 2012 biopsy shows, in addition to erythroid hyperplasia, intraparenchymatous, κ positive B-cell infiltrates consistent with CAD-associated LPD. There are scattered κ positive plasma cells, more of them near the lymphocytic infiltrates, and one distinct infiltrate of λ positive plasma cells. In the 2014 biopsy, the picture has not changed significantly. The trephine biopsy from February 2018 shows an IgAλ positive plasma cell population that has expanded, but IgMκ positive B-cell infiltrates can still be seen. In retrospect, therefore, all three biopsies show two clones; and in the 2018 sample, the CAD-associated IgMκ plasma cell population seems “hidden” among the expanding, myeloma-associated IgAλ plasma cells ().


A 46 years old woman was referred to our facility for surgical therapy of an enlarging metastatic gastrointestinal stromal tumour involving the liver. This is on the background of partial gastrectomy for a “benign” tumour in Germany in 1994, which was believed to be the primary. Staging computed tomography scan revealed a grossly enlarged right hepatic lobe secondary to multiple metastases. Two lesions measured 23 cm × 18 cm (oblique axial dimension) and 23 cm × 25 cm × 24 cm (anteroposterior dimension), respectively. The huge tumour led to compression of IVC, right portal and hepatic veins (). The patient’s laboratory studies were within normal except for anaemia (Hb 100). She received neoadjuvant therapy of imatinib, to which the tumour responded with significant size shrinkage.
She proceeded to undergo an extended right liver resection using cardiopulmonary bypass (CPB) and autotransfusion with intraoperative cell salvage (ICS). Induction of anaesthesia was uncomplicated, followed by placement of lines and a transoesophageal echocardiogram (TOE) probe. On rotational thromboelastometry (ROTEM), maximal clot firmness on FIBTEM was indicative of low fibrinogen (A5 value at 4 mm; A10 value at 4 mm; A20 value at 5 mm). Intraoperatively, a massive tumour of right liver lobe (17 kg) was discovered (). The TOE during early dissection phase was consistent with severe IVC compression and pressure overload on RA/RV suggesting that CPB – instead of veno-venous extracorporeal membrane oxygenation – was necessary to complete the surgery. She was heparinised (20,000 U) to reach activated coagulation time (ACT) of 602 before establishment of CPB. During tumour resection, large volume of fluid and blood products [6 U of packed red blood cells (PRBC), 6 U of fresh frozen plasma (FFP)] was infused to replace intra-abdominal losses. Bleeding from liver edges was controlled adequately with local haemostatic agent (Floseal, Baxter, US). High dose vasopressor support was instituted soon after commencing CPB and early resection – initially with noradrenaline (8 mg/100 ml at 10–50 ml/h) and then vasopressin (2.4 units/h). Eventually, the liver tumour was successfully resected and delivered.
The rates of noradrenaline and vasopressin were running at 50–75 ml/h (16 mg/100 ml) and 6 units/h towards the end of CPB, respectively. Steroids were given and, at this time, there was adequate flow on CPB with no evidence of clot. The patient was then weaned from CBP with good cardiac function. CPB time was 2 h 15 min. A total of 300 mg protamine sulphate was administered for heparin reversal prior to decannulation. Even though her coagulation profile including ACT and ROTEM was acceptable, the haemorrhage was refractory to protamine and blood components. She continued to demand a relatively high dose of vasopressors, although the demand was decreasing over time. Total blood products consumed at that stage were 18 U PRBC, 17 U FFP, 17 U of cryoprecipitate apheresis (equivalent to 34 U of cryoprecipitate derived from whole blood), 3 U pooled platelets and 2500 U prothrombinex. A joint decision among the surgeon, anaesthetist and haematologist was made to administer rFVIIa (90 ) of rFVIIa (NovoSeven, Novo Nordisk, Denmark) approximately 1-h post-CPB in an attempt to arrest the bleeding. The pH was 6.808 and temperature was 35.3 °C at time of administration.
Ten minutes following administration of rFVIIa, the patient became haemodynamically unstable secondary to right ventricular failure and went into cardiac arrest. Intraoperative TOE demonstrated extensive thrombi within the right atrium, right ventricle and bilateral pulmonary arteries (). Heparin was readministered to achieve an ACT of >999 s, CPB was emergently resumed and internal cardiac massage was performed. Right atriotomy and pulmonary atriotomy were attempted successfully to evacuate the aforementioned thrombi. Despite the clearance of right atrium, repeat TOE showed formation of thrombus in left ventricle and aortic arch. There was also noticeable intra-coronary venous thrombosis. The prothrombotic state resulted in eventual propagation of clot into venous drainage line of CPB machine and no flow could be established due to the blocked venous cannulae (SVC and IVC).The treatment was ultimately withdrawn and the patient died soon on the table. Following this event, Therapeutic Goods Aministration (TGA) was notified of the suspected adverse drug reaction.


A 56-year-old female was referred to our department from another facility in the patient’s area for a rapidly progressing tumor in the gallbladder and liver area. The patient reported several-month right upper quadrant pain and 4-kg weight loss over the past year. There was no laboratory sign of obstructive jaundice at the day of admission. Preoperative CT and MR scan (Figs. and ) of the liver was performed, and the patient was diagnosed with a tumor in the gallbladder area with a relatively massive infiltration of the S5 and S6 liver segments and extensive regions of necrosis. Given the potentially resectable lesion according to preoperative imaging, exploratory laparotomy was indicated to attempt radical resection. During the exploration, a voluminous tumor was found attached to the peritoneum. Intraoperative ultrasound was performed and revealed a tumor originating from the gallbladder bed area and reaching up to the area of the hepatic hilum and extensive involvement of the hepatoduodenal ligament by the tumor through the lymph nodes. The tumor was classified as inoperable due to this finding. But during the exploration, however, a rupture of the fragile tumor occurred with massive eruption of the necrotic mass and the gallbladder content into the abdominal cavity, accompanied by bleeding of the liver parenchyma. We decided that the condition could only be managed by attempting modified resection. We performed cholecystectomy and non-anatomical resection of hepatic segments S5 and S6 and partial resection of S4 without lymphadenectomy as a debulking operation (Fig. ). The course of hospitalization was uncomplicated, and the patient was discharged to home care on postoperative day 9. Histologically, the tumor was confirmed as MINEN of gallbladder (Figs. , , and ), and its non-neuroendocrine component had the character of moderately differentiated tubular gall bladder adenocarcinoma, while the neuroendocrine component had the appearance of small cell carcinoma and was dominant, accounting for more than 65% of the viable tumor. The neuroendocrine component contained extensive necrosis, with mitotic index 64/10 HPF and a proliferation index of 70% (Fig. ). It was therefore obvious that the prognosis and the subsequent biological behavior would be influenced in particular by the neuroendocrine carcinoma component. Six weeks after the discharge, the patient underwent a follow-up CT scan prior to the initiation of systemic therapy, which revealed a large recurrence of the disease at the resection surface of the liver accompanied by hilar lymphadenopathy. The patient was started on systemic therapy with etoposide and carboplatin in combination with somatostatin analogues with very good radiological effect. We use this regimen as a standard in patients with MINEN of gastrointestinal tract with dominant neuroendocrine component, even with no somatostatin receptors staining available. Now the patient is almost a year after being diagnosed with a tumor, after completion of 6 cycles of adjuvant chemotherapy (carboplatin + etoposide) in combination with biological therapy, the long-acting somatostatin analogues. The patient is in good clinical condition, and while a recently performed PET/MRI scan revealed a hepatic lesion and hilar lymphadenopathy in full regression, there was a spread of small peritoneal and pleural metastases, with a solitary metastasis in Th9. The condition was evaluated as disease progression stage according to RECIST criteria, the patient remains in the follow-up care, and it is now 13 months after surgery (Figs. , , and ).


An 18-year-old woman with CF was considered as a candidate for bilateral LT. Her respiratory failure had advanced, so that a supplemental oxygen therapy and night-time non-invasive ventilation were initiated. Bilateral pneumothoraxes with subcutaneous emphysema were detected on an elective control in March 2015. At that time, her FEV1 had decreased to 1.35 L (34% of predicted). She was referred to the respiratory department where her ventilatory failure acutely progressed. After a short resuscitation she was connected to ventilator and subsequently to extracorporeal membrane oxygenation (ECMO). She was listed for a Scandinavian emergency LT. S. apiospermum was detected in fungal culture of the tracheal aspirate with susceptibility testing showing minimal inhibitory concentrations of: voriconazole 0.125mg/L, itraconazole 6mg/L, posaconazole 6mg/L and amphotericin B 12mg/L. After five days on ECMO, she underwent a bilateral LT (defined as day 0). Pseudomonas aeruginosa and S. apiospermum colonizations were detected in the extracted native lungs. The peri-operative course was complicated by pseudomonas septicemia which was treated with intravenous (IV) tazobactam/piperacillin, tobramycin, and oral ciprofloxacin with a good clinical outcome. IV caspofungin was started postoperatively for antifungal prophylaxis with a single loading dose of 70mg, followed by 50mg daily for 17 days.
Her baseline immunosuppression regimen consisted of tacrolimus, mycophenolate mofetil, and prednisolone. Prophylactic valganciclovir, azithromycin, trimethoprim/sulfamethoxazole and nebulized colistin and amphotericin B were initiated.
The first postoperative bronchoscopy at day 30 postoperatively revealed normal anastomotic healing process and otherwise unremarkable endobronchial findings. Bacterial and fungal cultures of bronchoalveolar lavage (BAL) were negative. Histological acute minimal rejection (A1B1) was detected in transbronchial lung biopsy (TBB). The patient was not treated with additional corticosteroids considering her good clinical condition and previous infections and colonizations.
At the second control visit 60 days postoperatively, she presented with upper back pain that radiated to the left leg. Symmetric, painful, palpable, and slightly pigmented nodules with small ulcerations had appeared on both legs (). The surgical wound had started to secrete. She had no fever. Her C-reactive protein was 31 mg/l, erythrocyte sedimentation rate 58 mm/h and leukocyte level 9.8 E9/l. Systemic fungal infection was suspected, and IV voriconazole was initiated at 300mg twice a day for 24 hours and at 200mg twice a day thereafter. At that time, her immunosuppression consisted of prednisolone, tacrolimus and mycophenolate mofetil. The latter was discontinued due to suspicion of systemic infection. Control bronchoscopy with TBB revealed no histological signs of rejection. In the following days, she developed neurological symptoms: headache, nausea, vertigo and her right side of the mouth was slightly dropped. Also, her left leg was numb, and the muscular strength was decreased. Computerized tomography showed no infiltrates in the lung parenchyma but there were small subcutaneous collections under the sternotomy. Brain magnetic resonance imaging (MRI) revealed multiple ring-enhancing lesions with perifocal oedema compatible with abscesses (a and b). Spine MRI showed oedema and multiple abscesses as well in cervical and thoracic spinal cord (c). Subsequently, the histopathological findings from initial skin nodule revealed septal panniculitis with fungal culture and nucleic acid test positive for S. apiospermum. S. apiospermum was also cultured from BAL fluid and the surgical wound secretion. Multiple blood cultures were taken with no signs of fungemia. We refrained from CNS biopsy due to consisted cultural findings matching with radiological appearance.
Neurological symptoms vanished gradually, and the patient was discharged from the hospital after three weeks of treatment. Intravenous voriconazole was continued at home for ten months. Miltefosine was combined to the therapy one month after initiation of voriconazole but it was discontinued after two days due to nausea, interactions with tacrolimus and on the other hand good clinical response to voriconazole. MRIs and clinical status were controlled every one to four months. After ten months of intravenous administration voriconazole was switched to oral tablets with a dose of 300mg twice daily. Therapeutic serum levels were confirmed by repeated measurements (target therapeutic limits 2–5.5mg/l). At a control visit in June 2018 three years after LT and 35 months of treatment, the voriconazole treatment was terminated. After the discontinuation of antifungal treatment, the patient has visited our clinic for two controls with no signs of fungal re-infection. The last visit was in January 2019, nearly four years after the LT and eight months after the termination of voriconazole. She was symptomless with preserved lung allograft function: Her FEV1 was 2.7 L (77% predicted). Brain MRI revealed only few residual lesions (d), which had been stable and inactive for months.


A 45-year-old male with a previous history of tympanoplasty and functional endoscopic sinus surgery with septoplasty 10 years earlier presented to the ear, nose, and throat (ENT) clinic with several months of left moderate-to-severe otalgia and a sensation of ear blockage in his left ear accompanied by ipsilateral hearing loss. He gave a history of multiple failed ear wax removal in his left ear that had been performed at several ENT clinics, despite the use of alkaline ear drops.
On examination, the patient was comfortable and afebrile, and his vital signs were stable. Otoscopic examination of the left ear revealed impacted left ear wax covering the tympanic membrane, which could not be assessed. Otoscopic examination of the right ear also demonstrated mild ear wax, and the tympanic membrane was unremarkable. Oropharynx examination was unremarkable, the lymph nodes of the neck were not palpable, and all cranial nerves were intact upon examination. Nasal endoscopy revealed no pathologies. Ear wax removal under suction was attempted and failed. Another trial of removal after using alkaline ear drops for several days was also attempted but was unsuccessful. However, the surgeon became suspicious that the patient had KO rather than impacted ear wax because the wax was thick, had the appearance of keratin plugs, and was hard to remove after several attempts, despite the use of ear alkaline drops.
Blood test results of the patient were within normal limits. The patient was planned for microscope-guided examination of the ears under general anesthesia. The examination revealed that the left ear was full of wax that was accumulating in the skin and contained a thick keratinous plug that had dilated the external auditory canal (EAC) with pockets and bone remodeling. Furthermore, the patient ear canal was circumferentially distended with a normal annulus. The tympanic membrane became visible and was intact. The keratinous plug was removed, and a diagnosis of KO was established (). An ear pack was draped with antibiotics and placed in the left ear. The patient was extubated, shifted to the ward without any complications, and discharged the same evening with the ear pack, which was removed after 3 weeks in the outpatient clinic. The patient was started on ciprofloxacin ear drops and analgesia for 1 week.
In the follow-up, the ear pack was removed, his hearing returned to normal level, and the pain disappeared. Pathological analysis of the removed plug revealed acellular lamellated keratin flakes and keratinous material (Figures and ), which confirmed our diagnosis.


A 73-year-old Caucasian woman with a past medical history (PMHx) of esophageal dysmotility, gastroesophageal reflux disease (GERD), lymphocytic colitis, chronic obstructive pulmonary disease (COPD), essential hypertension (HTN), hyperlipidemia (HLD), neuropathy, and depression presented with substernal pleuritic chest pain and lightheadedness that began 2 hours after an uncomplicated outpatient upper and lower endoscopy. She did not have any known allergies. Her family history was significant for myocardial infarction (MI) in her father and cerebrovascular accident in her mother. She was married with two children, retired, previously worked for an advertising agency, and resided in New York City. She smoked one pack of cigarettes per day for 30 years and quit in 2001. She drank two alcoholic drinks per night. Medications taken prior to admission, during hospitalization, and after discharge included a 10 mg oxybutynin extended-release oral tablet once daily for urinary symptoms, a 40 mg omeprazole oral tablet once daily for GERD, a 10 mg amlodipine oral tablet once daily for HTN, a 300 mg bupropion extended-release oral tablet once daily for depression, a 20 mg escitalopram oral tablet once daily for depression, a 100 mg topiramate oral tablet once daily for neuropathy, a 50 mg tramadol oral tablet as needed every 4 hours for pain, and a 135 mg fenofibric acid delayed-release oral tablet once daily for HLD. Prior to presentation, the patient had undergone three endoscopies, after which her postprocedure course was uncomplicated. Upper and/or lower endoscopies were done on March 11, 2013, May 29, 2014, and December 3, 2015, for epigastric abdominal pain, periumbilical abdominal pain, and chronic diarrhea, respectively.
Biopsies were taken throughout the esophagus, stomach, duodenum, jejunum, ileum, and colon. The upper endoscopy and lower endoscopy took 5 and 25 minutes to complete, respectively.
In the emergency room, her vital signs were as follows: afebrile (36.8 °C), heart rate of 101 beats/min, blood pressure of 116/59 mmHg, respiratory rate of 16 breaths/min, and oxygen saturation of 93% on room air. She was a well-appearing woman, alert, and in no acute distress. She was well hydrated and well nourished. Her skin color, texture, and turgor were all normal without any suspicious rashes or lesions. Her head was normocephalic and atraumatic without any masses, lesions, or tenderness. Her eye examination included anicteric sclera with pupils that were equally round and reactive to light and with intact extraocular movements. Her ear, nose, and throat examination were all normal. Her neck was supple without any adenopathy. Her thyroid was of normal size and symmetric without any bruits. Her lungs were clear to auscultation without any wheezing, rhonchi, or rales. Her heart sounds included a regular rhythm and rate without murmurs, rubs, or gallops. Her abdominal examination revealed a soft, nontender abdomen, normoactive bowel sounds, and was nonsignificant for masses or organomegaly. Her extremities did not show any deformities, edema, skin discoloration, clubbing, or cyanosis and had good capillary refill. No joint swelling, deformity, or tenderness was observed. Her peripheral pulses were normal. The patient was alert and oriented to person, place, and time. Her speech was fluent with appropriate repetition and comprehension. Cranial nerves II–XII were intact without any deficits. Her gait was normal and steady. Her sensation (light touch, pinprick, position sense, and vibration sense) was grossly intact. Her reflexes were 2+ and symmetric at the biceps, triceps, knees, and ankles. She had no pronator drift of outstretched arms; her muscle bulk and tone were normal; and she had full strength bilaterally.
Initial laboratory studies revealed a hemoglobin level of 11.5 g/dl (normal range for females, 12.0 to 15.0 g/dl), which was the patient’s baseline hemoglobin; a troponin I level of 8 ng/ml (normal range, 0 to 0.4 ng/ml); and a B-type natriuretic peptide level of 2900 pg/ml (normal range, up to 100 mg/L). Other laboratory findings, including electrolytes, liver function tests, renal function tests, complete blood count, serology, and urinalysis, were all within normal limits.
An initial ECG was notable for T-wave inversions in the anterolateral leads and submillimeter ST elevations in the V4–V6 precordial leads, concerning for ACS (Fig. ). A bedside transthoracic echocardiogram (TTE) revealed apical hypokinesis (Fig. ), and computed tomography of the chest, abdomen, and pelvis did not reveal pulmonary emboli or acute abdominal processes. Left heart catheterization demonstrated nonobstructive CAD with a left ventriculogram of 45% and diffuse wall hypokinesis, consistent with a diagnosis of takotsubo cardiomyopathy, thought to be precipitated by the patient’s recent upper and lower endoscopic procedures (Fig. a and b). The patient’s angina resolved after the procedure, and repeat ECG revealed less marked ST depressions and resolved ST elevations (Fig. ). She was discharged home on hospital day 7. She did not require any further intervention or medical management.
The patient did well after discharge. After nine months post-discharge, she was admitted for worsening lower extremity edema. The TTE at the time was significant for a high left ventricular outflow tract (LVOT) gradient (peak LVOT gradients of 42 mmHg at rest and 122 mm Hg with Valsalva maneuver). Her ejection fraction (normal range, 55–70%) at the time was 81%, and pertinent results of TTE included fibrocalcific changes of the aortic valve with mildly reduced opening; moderate mitral annular calcification; systolic anterior motion of the anterior mitral valve leaflet; and normal functioning of the left atrium, right ventricle, tricuspid valve, and pulmonic valve. She was discharged with instructions on avoiding diuresis and beginning initiation of metoprolol (6.25 mg every 6 hours) for negative inotropy and to decrease systolic anterior motion.


An 18-year-old female was diagnosed with CVID at age six. As previously described in Chen et al. she, her mother, and younger brother were found to have a heterozygous pathogenic variant in NFKB2 that results in an autosomal dominant form of CVID (). She developed autoimmune manifestations, including acquired central adrenal insufficiency, alopecia universalis, vitiligo, and nail dystrophy. Her infectious history was significant for both bacterial and viral respiratory infections, recurrent herpes simplex of the lips and surrounding perioral skin, and chronic candidal onychomycosis. Adrenal insufficiency was treated with maintenance doses of hydrocortisone and stress dose adjustments during times of illness. Early-onset hypogammaglobulinemia required lifelong gammaglobulin replacement to prevent recurrent sinopulmonary infections. Recurrent herpes simplex infection was controlled with chronic suppressive oral valacyclovir therapy. A Luminex-based assay of the patient's plasma [1:100 dilution, as described by Ding et al. ()] identified the presence of autoantibodies against interferon-α (IFN-α) and interferon-ω (IFN-ω) (). Next, patient plasma was incubated with control peripheral blood mononuclear cells and STAT1 phosphorylation was measured by flow cytometry after incubation in unstimulated or stimulated conditions as described by Burbelo et al. (). The patient's plasma demonstrated neutralizing anti-IFN-α and IFN-ω antibodies which inhibited STAT1-phosphorylation in control cells, whereas control and parental plasma did not lead to inhibition (). The affected sibling's plasma also demonstrated neutralizing anti-IFN-α antibodies, and partial blockade of IFN-ω signaling.
At 16 years of age, the patient required intensive care hospitalization for decompensated septic shock of unknown etiology requiring vasopressor support. Prior to the hospitalization she had become non-compliant with medications, including gammaglobulin replacement. She developed acute renal injury, electrolyte disturbances, and adrenal crisis secondary to sepsis of unknown etiology which required stress dosing of steroids and electrolyte replacement. During this time, hypomagnesemia resulted in torsades de pointes and prolonged QT syndrome. Her persistent renal injury required chronic daily oral electrolyte replacement to prevent recurrence of arrhythmias.
Two years later, the patient presented to the emergency department with a month-long history of progressive, painful, vegetative facial lesions. The lesions initially developed periorally, similar to prior herpes simplex outbreaks. Despite increasing valacyclovir to treatment dosing, the lesions became purulent and continued to spread, involving the nose and right cheek. She was treated for presumed bacterial cellulitis with oral cefdinir. When a bacterial culture reportedly grew group B streptococcus, cefdinir was transitioned to oral clindamycin. Valacyclovir was discontinued as the lesions did not improve while on the medication. She reported tactile fevers and chills with continued progression of the vegetative lesions despite antibiotic treatment.
Upon hospitalization, laboratory evaluation identified leukocytosis (neutrophils 7,000 cells/μl; lymphocytes 7,900 cells/μl) and elevated C-reactive protein (11.6 mg/dL; normal range 0–1.5 mg/dL). Natural killer (NK) cell expression of CD107a was reduced, and NK cell functional assays demonstrated reduced cytotoxicity (Cincinnati Children's Diagnostic Immunology Laboratory). Her cutaneous exam revealed exophytic, thick, yellow-brown plaques involving the bilateral nares, right oral commissure, and adjacent medial cheek. The plaques were exudative and distorted the nasal architecture (). A wound swab from the medial cheek was positive for HSV by polymerase chain reaction (PCR) assay. Other bacterial or viral infections often seen in immunodeficient patients, including varicella zoster and cytomegalovirus (CMV), were ruled out. The patient's systemic symptoms raised concern for HSV viremia, and a HSV peripheral blood PCR was positive. She did not have any neurological symptoms or meningeal signs; thus, HSV meningitis or encephalitis were not suspected. HSV type-1 was isolated from tissue culture of affected skin on the medial cheek; pathology demonstrated spongiosis and mixed granulomatous dermal infiltration with fat necrosis. Intravenous foscarnet therapy resulted in rapid improvement of her cutaneous eruption, including the associated pain, and systemic symptoms (). Slower, continued resolution occurred over several weeks (). The patient had recurrence of HSV vegetans and HSV viremia 3 months later. On this second occasion, early identification of HSV as the source of skin infection led to expedited hospitalization and early initiation of antiviral therapy. She had a significantly shorter hospital course with transition to oral valacyclovir at discharge when HSV culture demonstrated susceptibility to acyclovir.


A 71-year-old woman with a history of hypertension, hyperlipemia, and angina was admitted to our Department of Neurology for tinnitus in the head. On physical examination, bilateral hearing impairment was found. The cerebral magnetic resonance imaging (MRI) detected signal changes consisted with multiple cerebral infarctions and bilateral demyelination in the centrum semiovale. And the cerebral MRA detected atherosclerotic cerebral arteries and bilateral stenosis of the middle cerebral arteries (Fig. a, b). For further diagnosis, the patient underwent DSA subsequently. The total amount of iopamidol (Bracco Imaging Italia S.r.L.) administered during the procedure was 110 ml. The DSA showed that the patient had bilateral embryonic posterior cerebral arteries, 40% stenosis of the left middle cerebral artery and tortuous vertebral arteries bilaterally. There was no obvious calcification of the aortic arch; angiography of the arch using 25 ml iopamidol was performed only once. Ten minutes after the aortic arch angiography, the patient experienced mild headache. The pain was bearable, and the patient could cooperate during the remainder of the procedure. The DSA was completed 20 min later. No haemorrhage or vasospasm was detected during the procedure. The headache was continuous, and the patient suffered nausea and vomiting. The immediate physical examination showed no obvious abnormal sign. The patient was treated with 8 mg ramosetron and 10 mg dexamethasone. After 20 min of observation, the symptoms were relieved. Her cerebral CT scan at the time was normal (Fig. a, b, c). Two hours later, the patient manifested dizziness with nausea and vomiting and was treated with 8 mg ondansetron and 20 mg diphenhydramine. Meanwhile, compound sodium chloride injection was used to facilitate the elimination of the contrast agent. The treatment alleviated her symptoms. Four hours after the procedure, the patient re-experienced dizziness; thus 5 mg dexamethasone was administered but resulted in no alleviation until after 11 h wherein dizziness was relived but her blood pressure was 183/92 mmHg. The patient was drowsy but could answer questions correctly. The pupil were symmetric and reactive, and limb movements were preserved. To manage hypertension, 30 mg nimodipine tablets were used. Fourteen hours after the procedure, the patient fell asleep, but at 17 h, respiratory failure progressed and oxygen saturation dropped to 88%. The patient was in a coma state, with sighing respiration. Anisocoria with non-reactive pupils developed, limb drop test was positive along with flexor plantar and Babinski sign was negative. Therefore, cerebral hernia was considered. The patient was treated with 20% mannitol, nikethamide, lobeline and diprophylline, and was transferred to the intensive care unit for further treatment after cardio-pulmonary resuscitation, endotracheal intubation and mechanical ventilation. Two days after the procedure, cerebral CT scan indicated diffuse cerebral oedema, loss of grey-white differentiation, effacement of the cerebral sulci and decrease in cerebrospinal fluid space (Fig. d, e, f). The patient was treated with dehydration, mechanical ventilation, and anti-infectious agent, but the diffuse cerebral oedema did not improve. Nine days after the procedure, the third cerebral CT scan showed that the cerebral oedema had become much more severe, the ventricles had disappeared and there was hyperdense signal in the subarachnoid space, which was considered to be indicative of a pseudo-subarachnoid haemorrhage due to the severe cerebral oedema [] (Fig. g, h, i). Fifteen days after the procedure, the cerebral CT scan detected unrelieved diffuse cerebral oedema, and the hyperdense signal in the subarachnoid space persisted (Fig. j, k, l). None of these cerebral CT scans showed intracerebral haemorrhage or infarct in this patient. The patient remained in a continuous deep coma state, and the brainstem reflexes had disappeared; she died 56 days after that sudden deterioration.


A 43-year-old woman presented with a chief concern of painless swelling in the right cheek, which she had first noticed two years ago. On examination, we noted a 1 cm x 1 cm painless, firm mass in the patient’s right cheek area (Figure ).
The rest of the examination revealed no pathologic alterations in the head and neck area. Ultrasonography showed a round tumor under the skin, outside of the buccinator muscle and around the anterior edge of the masseter muscle. Furthermore, this tumor was separated from the main parotid gland (Figure ).
The patient underwent fine-needle aspiration cytology and was diagnosed with a pleomorphic adenoma originating from an accessory parotid gland. After we discussed the risks of the procedure and the possibility of avoiding a scar with the patient, she provided informed consent to undergo surgery via a transoral approach. Transoral excision of the tumor was performed with assistance from an endoscopy for improved visualization (Figure ). Frozen section was not performed in view of preoperative benign cytology report as well as no perioperative clinical suspicion. No intraoperative complications were encountered such as excessive bleeding. Postoperatively, the patient had minimal parotid swelling which was treated conservatively. Post surgery histopathology showed a benign pleomorphic adenoma. We monitored the patient via follow-up for eight months and found no postoperative complications, including pain, facial or auricular nerve weakness, salivary fistula, infection, tumor recurrence, Frey’s syndrome or depression deformity (Figure ).