A 56-year-old man was admitted to the hospital 1 week after a left thyroid nodule was discovered during a physical examination. Color Doppler ultrasonography revealed a hypoechoic area approximately 1.2 × 0.8 cm in size in the central portion of the left thyroid gland. The area had unclear boundaries with the surrounding tissues, an irregular shape, aspect ratio imbalance, and fine sand calcification, and its TI-RADS grade was 4B. Fine needle aspiration cytology of the left thyroid nodule suggested papillary thyroid cancer. Preoperative thyroid function and serum calcium and phosphorus levels were within the normal range.
Surgical treatment was performed under general anesthesia on 14 June 2019. The patient was placed in the supine position and intubated under general anesthesia. The intubation process was smooth, and no abnormal secretions were found in the mouth, pharynx, or larynx. Shoulder pads were used to fully expose the neck. A low neck arc incision was made to separate the skin flaps and expose the thyroid glands. Using a 1-mL skin test syringe, nanocarbon suspension (H20041829; Chongqing LUMMY Pharmaceutical Co., Ltd., Congqing, China) was injected with a perpendicular orientation into the two upper and lower poles of the left thyroid gland to about 4 mm in depth. A total of 0.2 mL was slowly injected at each point, confirming the site before injection and avoiding injection into the blood vessels. The syringe was retrieved, and the injection point was pressed with gauze to prevent nanocarbon spillage from affecting the operation. Left thyroid gland lobectomy and left central lymph node dissection were performed 10 minutes after injecting the nanocarbon suspension. The operation area was then rinsed with warm saline to check that the trachea was intact. No bubbles were found in the operation area after checking with an artificial tympanic lung. No obvious diverticulum was found in the exposed trachea after the radical operation for left thyroid cancer, and no thyroglossal cyst or fistula was found after anterior laryngeal lymph node dissection. A drainage tube was placed in the operation area, and the incision was sutured layer by layer. The procedure was smooth. When the tracheal tube was retrieved, a large amount of carbon-containing secretions was found in the patient’s mouth, and the inflatable balloon surface of the tracheal tube was covered with these secretions ( and ). The secretions in the mouth were suctioned as much as possible with a sputum suction tube. The patient recovered smoothly and had no carbon-containing secretions after the operation. The drainage tube drained a small amount of reddish exudate and was removed on the second postoperative day. No fever, cough, sputum production, chest pain, hoarseness, or hypocalcemia-induced convulsions were noted after the operation. The serum calcium and parathormone levels were within the normal range. The patient was discharged on the third postoperative day. At the time of this writing, he was still undergoing follow-up without signs of discomfort.


Our patient is a 30-year-old female with a past medical history of von Willebrand’s disease, bipolar disorder, major depressive disorder, anxiety and opioid abuse who presented to our hospital for right-sided abdominal pain and blood per rectum. She experienced massive hematemesis in the emergency department with blood pressure 98/55 mmHg, heart rate 145 bpm and respiratory rate 18 breaths per minute. Hemoglobin and hematocrit levels were 3.2 g/dl and 9.5%, respectively, and lactate level was 7.0 mmol/l. She promptly received 4 units of packed red blood cells with improvement of vital signs. Initial computed tomography (CT) of the abdomen and pelvis was negative for intra-abdominal pathology. Therefore, she was taken for emergent endoscopy. Esophagogastroduodenoscopy revealed an ulcerative mass of the second portion of the duodenum with overall poor visualization secondary to bleeding; biopsies were taken. Concomitant flexible sigmoidoscopy revealed blood in the rectum with no other pathologic findings. Emergency CT angiogram was performed revealing active hemorrhage into the duodenum (). The patient was admitted to the surgical intensive care unit where she underwent placement of resuscitative lines. Hemoglobin and hematocrit levels were 3.9 g/dl and 10.1% despite initial resuscitation and the patient was further transfused 6 units packed red blood cells, 2 pools of cryoprecipitate, 4 pools of platelets and 5 units of plasma; 1 g of tranexamic acid was given every 8 hours for 2 days. Per hematology recommendations, von Willebran factor/factor VIII complex (Humate-P) and desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP) were administered. The patient underwent emergent mesenteric angiography by interventional radiology that revealed extensive vascular arcades at the second portion of the duodenum from the inferior pancreaticoduodenal artery without active extravasation (). The patient’s inappropriate response to multiple blood products necessitated emergent surgical exploration. Midline laparotomy revealed no gross hemoperitoneum. The hepatic flexure was mobilized and a Kocher maneuver was performed, revealing an ulcerative duodenal mass at the second portion of the duodenum. A longitudinal duodenotomy allowed for localization of an actively hemorrhaging mass 5 mm distal to the hepatopancreatic ampulla. The ampulla was cannulated with a pediatric feeding tube to mark its location during tumor resection. A wedge resection of the hemorrhagic duodenal mass was performed, including a small portion of nearby pancreatic head parenchyma. Hemostasis and preservation of bile flow through the ampulla was confirmed. The duodenotomy was hand-sewn in two layers transversely. A surgical drain was placed at the site of duodenal resection. The patient remained hypotensive and hypothermic, leading to a decision to institute damage control measures with temporary abdominal closure using a negative pressure wound therapy device. After further resuscitation and stabilization, the patient was brought back to the operating room 2 days later for planned re-exploration and definitive abdominal wall closure. Her postoperative recovery was complicated by a superficial incisional surgical-site infection that was treated successfully with drainage and a negative pressure wound therapy device, and she was discharged on hospital Day 22. Final surgical pathology revealed duodenal GIST measuring 2.5 × 2.0 × 1.4 cm with negative margins and no lymph nodes, corresponding to a pT2 tumor per the American Joint Committee on Cancer grading system. The GIST was mixed spindle and epitheliod type, CD117, CD34 and DOG 1 positive and CK7, AE1/AE3, synaptophysin and actin negative. The tumor had low mitotic rate, histologic Grade 1 with a Ki-67 index <5% and deemed low risk for recurrence. Due to the clinical and immunohistologic findings, observation without tyrosine kinase inhibitor therapy was the chosen management strategy. One-month follow-up was unremarkable and without symptoms of ongoing bleeding or recurrence.


A 60-year-old male with a background of hypertension, smoking, and no known drug allergies, was admitted in our hospital with an inferior STEMI. He remained haemodynamically stable (Killip 1) with normal blood pressure (140/80 mmHg) and heart rate without need of drug support. In the emergency department, heparin 5000 IU, ticagrelor 180 mg, and aspirin 250 mg were administered. While preparing him for urgent coronary angiography (CA), he experienced a ventricular fibrillation immediately treated with direct current (DC)-shock and followed by vomiting. The CA showed an occlusion of proximal right coronary artery which was successfully treated with thrombus aspiration and direct implantation of one drug-eluting stent (Ultimaster, Terumo Corporation) 3.5 × 20 mm (, Videos S1 and S2). After 45 min, back in the ICU, the patient reported chest pain with evidence of inferior ST-segment elevation. A new CA revealed an early acute intrastent thrombosis (ST, , Video S3), which was treated by wiring of the artery, thrombus aspiration followed by post-dilatation with 3.75 mm non-compliant (NC) balloon. He was then reloaded with ticagrelor 180 mg and an intracoronary bolus of GP2b3a inhibitors was administered. Intravascular ultrasound sonography (IVUS, OptiCross™ Boston Scientific) was performed, showing severe strut malapposition in the mid-portion of the stent (about 6–14 mm from the proximal edge) due to a partial stent crushing occurred after the post-dilatation with the NC balloon in the second procedure (, Video S4). Since the first guidewire wire could not gain the true stent lumen, the IVUS probe was placed between the vessel wall and the crushed stent (see ). In order to see the initial section of the crushed struts, the ‘live view’ was set. After several IVUS-guided attempts, a Sion Black wire (Asahi Intecc) successfully gained its way through nearly all the stent true lumen (, Video S5, see ). Subsequent post-dilatation with 1.0 balloon up to 4.25 NC balloon permitted a good final angiographic and IVUS result. (The total time from the beginning of the first CA to the end of the second coronary intervention procedure was 2 h and 40 min, see Timeline; see , Videos S6–S8; ) Four days later the patient was discharged asymptomatic with normal ejection fraction and at 1 year of follow-up he did not experience further events.


A 38-year-old man from Wuhan, the epicenter of the COVID-19 outbreak, presented with binaural hearing loss and tinnitus lasting for two months. He underwent endoscopic tympanometry on January 16; on the second postoperative day, he went outdoors and caught a cold. His body temperature was elevated to 38.1℃.
Laboratory examination revealed a normal percentage neutrophil count (75%, normal range: 40–75%) and a decreased percentage lymphocyte count (14.8%, normal range: 20–50%). Screening was negative for multiple respiratory pathogens including influenza A, influenza B, respiratory syncytial virus, adenovirus, human parainfluenza virus, mycoplasma pneumoniae, and chlamydia pneumoniae. The patient's sputum tested positive for 2019-nCoV in a real-time polymerase chain reaction assay.
On January 26, the patient developed a high fever and cough and was initiated on high-flow nasal cannula (HFNC) oxygen therapy. The fraction of inspired O2 (FiO2) was 80%, while the gas flow-rate was 20 L/min. The patient was continued on HFNC oxygen therapy from January 26 to February 4. On February 1, he suffered from chest tightness and palpitation. The arterial oxygen saturation (SpO2) could reach 90% after oxygen therapy. On February 5, he exhibited aggravated dyspnea and severe hypoxemia (SpO2 < 70%). He received non-invasive mechanical ventilation in the intensive care unit until February 10 with symptomatic relief. The initial FiO2 was 60%, while the gas flow-rate was 50 L/min. The modes used were pressure support ventilation and positive end-expiratory pressure with 1.18 KPa (12 cmH2O) and 0.98 KPa (10 cmH2O), respectively. Thereafter, the patient continued to receive HFNC oxygen therapy until the last follow-up CT scan.
The initial chest CT showed ground-glass opacities (GGO) in the left lower lobe (). Over the next 10 days, the lesions increased in extent and density and progressed to consolidation (). The clinical symptoms deteriorated, and acute respiratory distress syndrome was diagnosed. A follow-up CT scan revealed emphysema (, ). After 15 days of supportive treatment, chest CT showed an improvement in the pulmonary lesions, disappearance of the mediastinal emphysema, and appearance of a giant bulla in the left lung (, ). Eight days later, the final follow-up CT scan revealed a small pneumothorax and pleural effusion in the left thorax (, ).


A 23-year-old female was referred to our university-based hospital with generalized skin rash and oral ulcer for 6 weeks. The rash first appeared on the trunk and gradually progressed to involve all extremities as well as the face. There was no history of recent upper respiratory tract infection. She had no underlying skin disease or systemic disease and did not take any medication. She was treated with intravenous dexamethasone 20 mg daily, intravenous acyclovir, and oral azithromycin for 5 days by a local dermatologist without clinical improvement.
On examination, temperature was 37.3°C, pulse 92 beats per minute, blood pressure 130/70 mm Hg, and respiratory rate 20 breaths per minute. Dermatologic examination showed generalized scaly erythema with multiple foci of atypical targetoid lesions on the trunk and all extremities as well as the face. Bilateral conjunctival injection, scaly hemorrhagic crusted erosion on both upper and lower lips, as well as mild erosion on bilateral buccal mucosa and genital site were noted (Fig. ). Lymph nodes were impalpable. The remaining examinations were unremarkable.
A 4-mm punch biopsy was performed on a lesion of the chest. Routine histopathology demonstrated superficial perivascular infiltration (predominately consisting of lymphocytes and eosinophils), mild epidermal hyperplasia, basal vacuolization, exocytosis, scattered necrotic keratinocyte, as well as prominent melanophages (Fig. ). Direct immunofluorescence study showed intercellular deposition of IgG resembling chicken wire feature and linear basement membrane zone staining with IgG and C3 (Fig. ).
Blood samples for indirect immunofluorescence test disclosed circulating IgG autoantibodies directed against transitional epithelial cells of rat bladder. Anti-desmoglein 1 and anti-desmoglein 3 via the enzyme-linked immunosorbent assay technique were 47.97 U/mL and >200 U/mL (normal <20 U/mL), respectively. Anti-BP180 was >200 RU/mL (normal <20 RU/mL) and anti-BP230 was negative. Herpes simplex virus type 1 and 2 DNA, Venereal Disease Research Laboratory, Treponema pallidum hemagglutination assay, as well as Mycoplasma titer were all negative. We were unable to perform immunoblotting, but given the clinical, histopathologic, as well as direct and indirect immunofluorescence results, the diagnosis was consistent with PNP. Computed tomography with contrast of the chest and abdomen revealed a 6.7 × 5.5 cm, markedly enhancing oval-shaped structure at the left para-aortic region surrounded by dilated vessels. According to the computed tomographic findings, a provisional diagnosis of Castleman's disease (CD) was made.
The patient was treated with intravenous immunoglobulin (IVIG) 2 g/kg/day over 5 consecutive days and surgical removal of the tumor. The pathologic findings were compatible with hyaline-vascular type CD. Although there was substantial improvement in the truncal lesions 10 days after IVIG administration, the lesions on acral area and the oral lesions were refractory to treatment. Two weeks after the complete 5-day course of IVIG, the patient died as a result of Staphylococcus and Acinetobacter septicemia.


Example: 62-year-old male patient with a history of 11 years of CH. At first, the CH was right-sided, but years ago the location switched to the left side and has been chronic ever since. Until recently he took 720mg verapamil but this was no longer tolerated and he now treated every attack exclusively with triptan injections and oxygen. When he started the PBCS treatment he had two to four attacks at night, the main pain being located behind the left eye, radiating into the lower jaw. Already after the second PBCS therapy attack frequency was reduced to only one attack per night. Also, the pain decreased so that he did not need any acute medication anymore. After the third treatment. the CH changed to the right side. After three further treatments, he was completely pain-free for 3 months. Then, the CH started again. This time, after his previous positive experiences with the PBCS therapy, the patient was highly motivated to be treated again. Eighteen further treatments improved the frequency of attacks, also the intensity of pain, but overall the clinical result was not sufficiently satisfactory so that the treatment attempt was terminated without lasting success.


A 27-year-old male presented with multiple cervical and mediastinal lymphadenopathies. The excisional biopsy disclosed classical HL, nodular sclerosis subtype, characterized by architectural effacement by nodular collagenous bands, and a mixed-population inflammatory background including numerous eosinophils admixed with Hodgkin and Reed-Sternberg (HRS) cells. Computed tomography (CT) scan of chest and pelvis revealed lymphadenopathies in bilateral neck and superior mediastinum; multiple bone lesions in T1, 2, 12, and L4 vertebrae and right ischium. Whole-body positron emission tomography (PET) scan revealed multiple sites of bone and liver involvement. The diagnosis was classical HL, nodular sclerosis type, Ann Arbor stage IVEB (stage IV: diffuse or disseminated foci of involvement of one or more extralymphatic organs or tissues; E: extranodal organ involvement; B: presence of systemic symptoms like fever and loss of weight), with liver and bone metastasis. He experienced a short remission after 12 cycles of primary chemotherapy with ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and then relapsed in para-aortic lymph nodes. After ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) salvage chemotherapy, he received subsequent high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) chemotherapy conditioning and autologous peripheral blood stem cell transplantation. However, his disease relapsed 5 months thereafter. Subsequent chemotherapeutic regimens of vinorelbine + gemcitabine and DVIP (dexamethasone, etoposide, ifosfamide, and cisplatin) only achieved a limited period of partial clinical response. Re-biopsy of the chest wall soft-tissue mass confirmed classical HL with cluster of differentiation 30 (CD30) expression. BV was then administered, but after three cycles of treatment, rapid progression occurred (). The patient experienced a severe skin reaction to subsequent lenalidomide treatment. Immunotherapy with pembrolizumab was then initiated, and his disease responded well for 16 months () until the PET scan showed progression with recurrent bony involvement and relapse (). Because of the limited options for subsequent treatment and the patient being medically unfit for allogeneic stem cell transplantation, a combination of BV and pembrolizumab was initiated, and remission was achieved for > 15 months ().


A 42-year-old female (BMI, 27.4 kg/m2) presented with 2 years of left knee medial joint pain. Active range of motion (ROM) in the left knee was from 0 to 140 degrees with no extension lag. Preoperative Tegner scores, Lysholm scores and Knee Injury and Osteoarthritis Outcome (KOOS) scores are shown in . Preoperative radiographs of the left knee joint showed mild medial osteoarthritis (OA) of the knee and hip–knee–ankle (HKA) angle of 1.5-degree varus. 1.5-Tesla MRI was performed on unit (Toshiba, Kawasaki, Japan) was used with an extremity surface coil. Proton density images were obtained using the fast spin-echo technique. A modified magnetic resonance observation of cartilage repair tissue (MOCART) system was used for the quantitative evaluation of MRI findings of the cartilage injury [15–17]. MRI showed cartilage injury of the medial femoral condyle (MFC) and trochlea of the left knee ().
One-stage ACI using Reveille CP was performed under general anesthesia. The medial subvastus approach was used. Articular cartilage injury was shown in the trochlea (1.3 × 1.7 cm; Outerbridge classification, Grade III) and MFC (2.5 × 3.5 cm; Outerbridge classification: Grade III) (). We harvested the healthy cartilage (0.5 × 1.5 cm) in non-weight-bearing area of the lateral femoral condyle, and the microfracture was performed at a 4-mm power pick at the cartilage lesion (). Harvested cartilage fragments were loaded directly onto the Reveille CP (). The tissue was morselized in a sterile saline with the drill speed at 1500 rpm for 2 minutes (), and the chamber was plunged through a filtration apparatus to ensure that only the decanted, particulated cartilage remained (). The particulates were collected into the delivery device. The collected volume was measured using a syringe marked at every 0.1-ml increment (). The grafted cartilage particulates at the lesion were compressed, and the bone glue was applied over the particulated tissue (), followed by turning off of a tourniquet. The area of grafted cartilage was confirmed so that it did not fall off. Knee joints were immobilized for 4 weeks with a soft knee brace. A ROM exercise is started with a continuous passive motion device at 3 weeks after the surgery. Partial weight-bearing (30% body weight) was allowed at 4 weeks, and full weight-bearing permission was given from 8 weeks after the surgery.


As a control case, a 51-year-old female (BMI, 24.1 kg/m2) presented with 4.5 years of left knee medial joint pain. Preoperative Tegner scores, Lysholm scores and KOOS scores are shown in . Preoperative radiographs of the left knee joint showed mild medial osteoarthritis (OA) of the knee and hip–knee–ankle (HKA) angle of 1.3-degree varus. MRI showed cartilage injury at the MFC (). Approximately 0.5 g of the healthy cartilage was harvested from less weight-bearing regions of the intercondylar notch using arthroscopy. The specimen was sent to J-TEC for cartilage culture. At 4 weeks after the harvest, the microfracture was performed at a 4-mm power pick at the cartilage lesion, and the two-stage implantation of tissue-engineered cartilage-like tissue (JACC) was performed on the cartilage injury site (4.5 × 5.5 cm; Outerbridge classification, Grade III), and then the tissue implantation site was covered with periosteum taken from the tibia of the same patient (). Knee joints were immobilized for 4 weeks with a soft knee brace. A ROM exercise is started with a continuous passive motion device at 3 weeks after surgery. Partial weight-bearing (30% body weight) was allowed at 4 weeks, and full weight-bearing permission was given from 8 weeks after the surgery.
Postoperative ROM, Lysholm scores and KOOS scores between cases 1 and 2 are shown in . The ROM at 1 year after Reveille CP surgery was less than that of JACC. The Lysholm, pain and QOL scores of KOOS at 1 year after Reveille CP surgery were higher than these scores of JACC ().
MRI findings at 1 year after the surgery indicated signal intensity area in the grafted area for the patient with JACC (), whereas the patient who underwent Reveille CP exhibited greater thickness at the grafted area as compared to the surrounding healthy cartilage (). The MOCART score at 1 year after the Reveille CP surgery (60 points) was higher than that of JACC (50 points).


A 36-week-old 2950 g, 11-day-old baby boy was intubated following cardiopulmonary resuscitation performed upon respiratory arrest at birth. During his physical examination, he was intubated and tachycardic (150 bpm) with a poor general health condition. In the abdominal examination, the mass filling the right abdominal quadrant and descending into the pelvis was detected. In its ultrasonography (USG), in hepatic segments of 4a, 4b, 2.3; structurally hyperechoic patchy areas with punctate echoes and occasionally linear hypoechoic vascular structures with sharp borders and large nodular formations were observed. In addition, it was reported that the segment 4b localization showed an approximately 172x17 mm hyperechoic lesion with lobulated and smooth contours. Computed tomography (CT) demonstrated an extremely enlarged liver with its longest diameter being 182 mm. In the contrast-enhanced CT examination, multiple numbers of disseminated lesions which filled up left lobe segments 2, and 3 which are characterized by patchy areas of nodular formations with sharp borders were seen. However, in the arterial phase, peripheries of these lesions were intensely contrast- enhanced, and in portal and delayed venous phase contrast uptake gradually became more intense towards central regions of these lesions.
Levels of serum enzymes (AST 155 U/L, ALT 45.31, GGT 230.6 U/L,) and tumor markers (AFP >300 IU/Ml, CA 125: 112.3 U/ml, CEA 1.47 ng/ml, CA 19-9: 6.43 U/ml.) were as recorded.
The patient was operated with diagnoses of hepatoblastoma, infantile hepatic hemangioma, atypical giant hemangioma, and undersigned. Informed consent form was obtained from the family of the patient.
After proper application of antibacterial solution and draping of the surgical site, the abdomen was entered with an inverted T incision Hepatic tumoral mass with approximate dimensions of 15x10x20 cm was observed. The mass at first glance was seen to originate from the left lateral part of the liver and extended into the pelvis. The left lobe of the liver was liberated from its attachments and delivered out of the abdomen. The hilar region was made visible. Following cholecystectomy, the left hepatic artery (left HA) was found and dissected. It was observed that the left HA diameter was very enlarged. The right hepatic artery (right HA) and segment 4 artery were exposed. Segment 4 artery was found to originate from the left HA. The main portal vein was exposed. The left portal branch was dissected. The left portal branch was dissected from the umbilical fissure and the arterial branches of segments 4, 2, and 3 were revealed. The main arterial branches leading to segments 2 and 3 were ligated to protect segment 4. A nearly 50% decrease in the size of the avascularized mass was observed. Then, liver parenchyma was dissected with the help of CUSA (Cavitron ultrasonic surgical aspirator) and crushing clamp applied at a safe distance between the mass border and the parenchyma. Bile canaliculi and vascular structures were closed with a titanium clip. The left hepatic vein was dissected away from the area where it entered inferior vena cava over the vascular clamp and closed in two layers with 5/0 non-absorbable suture. The left lateral bile duct was exposed and ligated. The mass completely separated from the liver was taken out of the abdomen. After bleeding control, an absorbent drain was placed in the hilar region and the abdominal layers were closed.
After the operation, the patient was intubated and taken to the neonatal intensive care unit. For five days, his vital signs remained stable, so he was weaned from the mechanical ventilator. Any pathological finding was not detected in the control USG, so the absorbent drain in the abdomen was removed. The dressing of the surgical wound and follow-up of the patient was continued for ten days. Since any complication did not develop, the patient was discharged and followed up in the outpatient clinic.
The histopathological examination of the removed mass revealed a 10.5x7 cm mass lesion containing stroma-rich and diffusely sinusoidal vascular tissue compatible with infantile hepatic hemangioma which can be clearly differentiated from liver tissue.


A 32-year-old woman, gravida 2 para 2, presented to our institution with a history of progressively worsening abdominal pain over the past 2 months. She reported intermittent, suprapubic, and central abdominal pain with associated nausea, weight gain, abdominal distension, early satiety, constipation, and urinary frequency. Similar episodes of pain were diagnosed as Helicobacter pylori induced gastritis and treated unsuccessfully with proton-pump inhibitors. Tumor markers revealed elevated CA 125 (244.9) and CA 19-9 (76).
A computed tomography (CT) abdomen and pelvis were performed per discretion of the ordering emergency room physician, which revealed a large heterogeneous mass in the left adnexa measuring 19 × 17 × 10.4 cm, containing fat, calcification, and soft-tissue consistent with a teratoma [-, -]. However, there was a significant mass effect, mesenteric/omental stranding, and ascites concerning for malignant transformation and peritoneal carcinomatosis versus intraperitoneal rupture with resultant granulomatous peritonitis [ and ]. Further findings included a mature ovarian teratoma measuring 5.4 × 5.4 × 6.9 cm in the right adnexa [].
Although surgery was indicated, initial evaluation in the emergency department demonstrated severe hyponatremia (serum sodium of 116 mmol/L), and our patient was admitted for management in the MICU. Initially, her hyponatremia responded to fluid resuscitation (serum sodium 125 mmol/L) and she was transferred to the gynecology team for further work-up; however, she required readmission to the MICU for refractory hyponatremia (serum sodium 118 mmol/L). Her serum sodium corrected after management with fluid restriction and salt tablets, and she was transferred to gynecology for planned surgery. Pre-operative laboratories demonstrated serum sodium 130 mmol/L, plasma osmolality 240 mmol/L, urinary sodium 220 mWq/L, and urine osmolality 779 mEq/L. Other preoperative laboratories indicated normal adrenal and thyroid function.
Intraoperative findings confirmed bilateral ovarian masses and ascites; however, gross peritoneal carcinomatosis was not reported. Samples were then sent for surgical pathology following bilateral salpingo-oophorectomy, omentectomy, and pelvic lymph node dissections. Our patient’s sodium levels immediately increased to normal after surgery and continued to normalize as she was weaned off of fluids and salt tablets.
Macroscopic examination of the bilateral salpingo- oophorectomy specimen revealed a 21.5 × 17.5 × 8.5 cm focally disrupted, enlarged left ovary and an 8.0 × 6.0 × 5.5 cm cystic right ovary. The outer surface of the left ovary was remarkable for numerous adhesions with a 12.0 × 6.0 × 0.5 cm portion of omentum attached. Serial sectioning revealed numerous tan- white and tan-yellow solid and cystic areas admixed with hair, skin, and cartilaginous tissues. The outer surface of the right ovary was remarkable for a scant amount of adhesions. It was filled with yellow mucoid material including skin, cartilage, and teeth attached to the inner lining of the ovarian wall.
Microscopically, the left ovary revealed a solid tumor with areas of neurotubules and neuroepithelial rosettes [-] along with mature components including skin appendages, cartilages, and pancreatic and neural glial tissues [-]. The diagnosis of immature teratoma (Grade 2) was made based on the presence of neurotubules in two low-power fields as described previously.[ The right ovary, on the other hand, consisted of all mature components and, therefore, represented a mature cystic teratoma [-]. The nodules in the uterine serosa, rectal peritoneum, and omentum were composed of mature, predominantly gliomatosis admixed with adipose tissue [-], which occurs in about one-third of the cases with immature teratoma.[
The patient’s serum sodium returned to normal 24 h after surgery and stabilized at about 138 mEq/L. The final diagnosis was FIGO Stage 1A Grade 2 immature teratoma, and the patient started 4 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. Since her surgery, there has been no evidence of recurrent disease and her tumor markers have stabilized at normal levels. The patient has not shown symptoms or objective evidence of recurrent hyponatremia, as well.


A 15-year-old male was brought to the emergency department after sustaining a gunshot wound to the head. Non-contrast computed tomography (CT) scan of the head demonstrated a trajectory entering the right inferior temporal bone, entering the anterior portion of the middle cranial fossa, traversing the anterior right temporal lobe, entering the right orbital cavity, and exiting through the ethmoid sinus and ultimately the left orbital cavity. There was a right temporal tip contusion along the ballistics path, with associated extra-axial and subarachnoid hemorrhage (SAH). The Sylvian fissures were not involved in the ballistic trajectory [].
The patient was taken emergently to the operating room for a right-sided decompressive craniectomy and debridement of the right temporal region. The patient started to follow commands, was moving in all extremities, and was extubated by hospital day 3. He underwent repair of his ruptured left globe and persisted with complete vision loss in the right eye.
Initial CT angiogram (CTA) within 24 h of his admission showed no vascular injury; however, a repeat CTA was performed 5 days later for vascular surveillance for TICA, which showed interval development of a right middle cerebral artery (MCA) bifurcation aneurysm. The same scanner produced both CTAs with 420 slices at 0.6 mm thickness, including three dimensional reconstructions. A subsequent diagnostic cerebral angiogram (DCA) confirmed the presence of a 4 × 3 mm right MCA bifurcation aneurysm, and also identified a 2 mm right internal carotid artery (ICA) terminus aneurysm, as well as severe vasospasm of the proximal ICA and MCA vessels [].
The patient was taken to surgery for clipping of the right MCA and right ICA terminus TICAs. Direct clipping of the lacerations in the vessels was successful, although bypass was prepared for, depending on the intraoperative findings []. Due to the severe vasospasm, patient was treated with intracisternal papaverine. Sixty milligrams of papaverine diluted in 2cc of saline is injected into the intracisternal space over the affected vessels. Papaverine is a vasodilator which relaxes the smooth muscles of vessels. Adventitial dissection was performed allowing for better penetration of papaverine and removal of any possible sites of constriction.[] The surgical cavity is then irrigated and final hemostasis obtained.
The end-tidal CO2 was kept constant and cerebral blood flow (CBF) measurements were then obtained before and after performing the therapeutic maneuvers using the Charbel Micro-Flowprobe® (Transonic). Measurements were taken at the distal ICA just before the ICA terminus as well as the A1 and M1 segment arteries just after the ICA terminus. This instrument relies on transit-time ultrasound volume flowmetry to obtain blood flow measurements in mL/min. The measurements demonstrated improvement in flow after the therapeutic maneuvers [].
The patient returned to the intensive care unit. Repeat catheter angiogram was performed on hospital day 10 and confirmed that the two previously treated aneurysms were excluded from the circulation. Previously-identified vasospasm of the right supraclinoid ICA, M1, and A1 segments was improved. Two-month follow-up DCA demonstrated substantial improvement in the distal ICA caliber and improvement in the M1 irregularity. Several distal dilated vessels in the anterior temporal region were identified as suspicious for pseudoaneurysms, but have largely resolved on the 2-month catheter angiogram. Two weeks after the initial presentation, the patient was neurologically intact, with the exception of bilateral blindness related to the ballistics path, and was discharged to inpatient rehabilitation center.


A 56-year-old male presented with the 1-year onset of progressive dysphagia and 8 months of dysphonia. Notably, his neurological examination was intact. The barium swallow showed a narrowed esophageal lumen at the C4–C5 level []. X-ray and computed tomography studies revealed the classical “Ostrich beak” changes of the ossified ALL at the C4–C5 level; the disc spaces were preserved [ and ]. Utilizing an anterior cervical approach, the large beak-like osteophyte was removed, while preserving the anterior annulus; the extent and adequacy of resection was confirmed intraoperatively utilizing a lateral radiograph [ and ]. Postoperatively, he was discharged on anti- inflammatory medications for 10 days.


A 63-year-old male, with a history of diabetes (type 2), hypertension, hyperlipidemia, and cardiac disease, was quadriplegic after a traumatic hyperextension injury (e.g., due to a fall). He rendered immediately quadriplegic ASIA Grade “A” indicative of a complete C5 motor/sensory deficit. Radiological studies revealed cervical C3–C6 OPLL resulting in marked cervical cord compression; the T2- weighted MR images revealed a hyperintense intrinsic cord signal indicative of a spinal cord injury []. Within 18 h after the initial injury, the patient underwent a double- door expansive laminoplasty employing a Laminoplasty Basket (Ammtec, Tokyo, Japan); postoperatively, the patient improved to ASIA Grade “B.”[]
However, following the surgery, the patient developed a persistent small bowel ileus. When conventional therapy (e.g., gastric suction, laxatives, dimethicone, and dinoprost) failed to resolve the ileus over the first 3 postoperative days, the patient was given Kampo medications consisting of bukuryoin (TJ-69, Tsumura & Co., Tokyo, Japan) 7.5 g/day and hangekobokuto (TJ-16, Tsumura & Co.) 7.5 g/day []. The ileus improved in 2 days and resolved in 7 days []. Interestingly, when the ileus recurred after Kampo medications were later stopped, reinstitution of Kampo therapy again resolved the problem.


A 73-year-old male was referred to our hospital for gradually progressing right lower abdominal pain. His past history included prostate carcinoma with bone metastasis at 60 years of age, and type 2 diabetes mellitus diagnosed at 62 years of age with poor control of the hemoglobin A1c (HbA1c) level measuring 8.0%. Family history revealed that his siblings had type 2 diabetes mellitus and his uncle had gastric cancer. He had a personal history of social alcohol drinking of less than 60 g per day, and smoking of 25 cigarettes per day for 25 years but had quit for over 20 years. Current medications included bicalutamide for prostate carcinoma, metformin, glimepiride and sitagliptin for type 2 diabetes mellitus, and ramelteon, suvorexant, and zolpidem for insomnia.
The vital signs of the patient were stable. Right lower abdominal tenderness was noted without abdominal guarding or rebound tenderness. Laboratory data revealed abnormal liver enzyme levels, and serologic tests were negative for hepatitis B and C (Table ). Esophagogastroduodenoscopy and total colonoscopy revealed no abnormalities except for cecal diverticulum. Ultrasonography revealed a 5.5-cm tumor near the ileocecal junction, while contrast-enhanced computed tomography (CT), and positron emission tomography-CT showed multiple nodules with cystic lesions in the peritoneum, suggesting peritoneal dissemination in addition to the main tumor (Fig. ).
A diagnostic laparoscopy was performed, and a tumor extending from the right lateral abdominal wall with irregular focal protrusion was noted. Multiple brown-colored nodules on the greater omentum, one nodule on the small intestines, and one nodule on the anterior abdominal wall, sharing the same gross appearance, were also noted. Histological examination revealed tumor cells with a relatively abundant cytoplasm and a large area of hyperplasia in a palisading pattern (Fig. ). Small bile droplets were detected in the tumor cells by bile stain. Immunohistochemical staining showed that the tumor cells were positive for alpha methyl acyl coenzyme A racemase, cytokine (CK) 8, alpha-fetoprotein (AFP), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), and weakly positive for anti-hepatocyte, CK 18, heat shock protein 70, and glypican 3 (Fig. ). According to the abovementioned results, HCC of the abdominal wall with peritoneal seeding was diagnosed. Because no lesion of the mother liver was discovered by abdominal sonography, CT, or magnetic resonance imaging, a diagnosis of ectopic HCC was determined. Additional laboratory tests showed an elevated serum AFP level and PIVKA-II level, and liver biopsy revealed slight inflammatory infiltrates in the portal area with mild to moderate fibrosis and slight fatty change in liver cells.
The patient received 400 mg of sorafenib per day for ectopic HCC. Two months later, CT imaging showed a significant increase in the tumor size, and blood tests showed increased levels of serum AFP and PIVKA-II. During the follow-up, the tumor response was classified as progressive disease according to response evaluation criteria in solid tumors (RECIST) version 1.1 and modified RECIST (mRECIST). However, the patient showed strong willingness to continue the treatment. Four months later, hematochezia and grade 3 anemia were noticed, according to the categorization of common terminology criteria for adverse events (CTCAE) version 5.0. Contrast-enhanced abdominal CT for evaluation of gastrointestinal bleeding showed tumor progression in the small intestines, which was considered the cause of bloody stools and progressive anemia. However, since the patient refused further survey of the lesions, conservative treatment with blood transfusion was performed. In addition, the bleeding complication was also considered one of the adverse effects of sorafenib, by which the blockade of vascular endothelial growth factor caused endothelial disruption and consequent bleeding events. As a result, the dosage of sorafenib was modified to 200 mg per day. In spite of that, sorafenib was eventually ceased 7 months after the start of treatment because of persistent diarrhea and progressive anemia. One month after the cessation of sorafenib, the serum PIVKA-II level increased abruptly (Fig. ).
Afterward, the patient had persistent anemia with tarry stool and dizziness. In consequence, the cause of progressive anemia was suspected to be intestinal infiltration of ectopic HCC, rather than side effects of sorafenib. Because the patient refused further treatment for malignancy, he was transferred to hospice care and expired 1 year after diagnosis.


Our first report was of a 69-year-old male with a clinical diagnosis of HCC (BCLC stage B). His liver function was ALBI grade 1, so we considered TACE to be the most reasonable first therapy. However, his celiac artery was occluded from a previous surgical procedure. We then attempted to approach from the mesenteric artery, which was immediately impassable due to a thrombus. Thus, we performed direct hepatic artery puncture under ultrasonographic guidance and, although temporarily, we were able to control the disease with percutaneous lipiodol chemotherapy.


Our second case was an 81-year-old female with hepatitis C virus-related HCC (BCLC stage A). She had been transported by ambulance with emergent ruptured HCC. Her liver function was ALBI grade 1. In this case, her tumor-feeding artery diverged from the cystic artery; selective TACE would have been very difficult and she refused surgery. Therefore, we performed direct hepatic artery puncture, and after confirming insertion into the blood vessel with solenoid echo, we performed ethanol injection to destroy the feeding artery. This treatment successfully stopped tumor bleeding, and furthermore, tumor necrosis was obtained, as seen on an enhanced computed tomography image.


A 2-year-old girl was brought to the hospital due to an apparent disfigurement and bluish skin in the right periorbital region and a soft mass-like diffuse lesion on the scalp. The lesion was non-pulsatile and bluish, and the patient did not complain of pain. There was no relevant history, and she was delivered vaginally after a full-term pregnancy ().
Computed tomography confirmed vascular masses in the right periorbital, retrobulbar, and extracranial parietal regions. Doppler ultrasonography and magnetic resonance imaging (MRI) confirmed venous malformations in the aforementioned regions (). We suspected the presence of cranial holes facilitating the communication between the extracranial venous malformations and intracranial superior sagittal sinus, as observed on MRI. Therefore, we performed a transfemoral cerebral angiography (TFCA) to confirm the presence/absence of holes. Visualizing the right internal carotid artery via angiography revealed transdural and transcranial superficial drainage from the frontal cortical veins and from the superior ophthalmic veins. Therefore, we confirmed that subcutaneous venous malformations in the scalp communicated with the superior sagittal sinus and diagnosed the patient with SP.
After placing the patient in the supine position under general anesthesia, a plastic surgeon and neurosurgeon made an incision in the scalp on the left side. After confirming engorged veins in the subgaleal layer by performing a slight periosteal dissection of the scalp from the left to the right side, we ligated and excised the abnormal extracranial veins. Following which, we ligated and removed the veins draining into the superior sagittal sinus, through a relatively large cranial hole in the midline. The cranial hole was sealed with bone wax. We consequently created a subgaleal negative drainage and ended the surgery by suturing the wound ().
A radiology specialist performed four sessions of sclerotherapy on the patient under general anesthesia, after administering bleomycin via a butterfly needle after ultrasonography-guided needling for the right superior ophthalmic venous malformations and for SP in the right parietotemporal scalp region (). Follow-up ultrasonography and MRI showed marked improvements in venous malformations and SP.
In the postoperative course, the mass on the scalp greatly decreased in volume, and the abnormally communicating veins disappeared. We subsequently performed another excision and six sessions of sclerotherapy using bleomycin on the remaining venous malformations in the periorbital region. Currently, the patient is under observation for the duration of the follow-up period ().


Clinical history and physical examination findings
A 14-year-old adolescent male presented to the accident and emergency unit of the Tamale Teaching (TTH), with a painful, huge ulcerated and necrotic right leg tumor of an unspecified duration. The condition began as small palpable and painful swelling for which the family had different treatment modalities from the herbalists. However, while on the herbal treatments, the lesion kept increasing in size, until 1 day he saw an ulcer over the swelling. The ulcer also subsequently increased in size; thus, extending from the right knee to involving the entire leg. 2 months before the presentation at the TTH; he sought medical attention at the Zebilla District Hospital in the Upper East Region of Ghana, where he was referred to TTH for further management.
On examination, the patient was not pale, not jaundice, afebrile and hydration was satisfactory. He had a near circumferential (63.5 cm) fungating, nodular and necrotic right knee joint tumor that extends inferiorly to involve the entire leg. The tumor was soft to firm in consistency, pussy, and offensive. There was right inguinal lymphadenopathy (matted: 2.0 cm × 4.0 cm).


A 53-year-old woman was referred to the chest clinic with a 3-month history of expectoration of bronchial casts. She had been diagnosed with asthma 21 years previously and managed with Becotide and Ventolin inhalers. Her medical history included polycystic ovary syndrome, hirsutism, type 2 diabetes mellitus and obesity. Since the 1990s, she had had recurrent bouts of pericarditis with normal coronary angiogram and cardiac MRI findings. She was previously investigated for arthralgia, fatigue, bilateral anterior uveitis and oral ulcers with no genital involvement. Behçet’s disease had been suggested but investigations for this had been negative.
In the clinic, she reported occasional chest tightness and dyspnoea with no wheeze. She produced thick sputum, resembling casts, 10–12 times per day. She was a never smoker. Serological investigations including IgE, specific IgE for Aspergillus fumigatus and ANCA were unremarkable. Historical eosinophil counts were all within the normal range. Lung function tests showed a minimal obstructive defect: forced expiratory volume 1 second 2.13L (88.2%), forced vital capacity 2.89L (101.6% predicted) and forced expiratory ratio 67.2%, with normal lung volumes and gas transfer. Peak flow ranged from 350 to 400 L/min with minimal diurnal variation. Baseline computed tomography (CT) of the chest revealed moderate air trapping in keeping with small airway disease. Bronchoscopy was performed and showed no endobronchial lesions, secretions or abnormal airway inflammation. Routine endobronchial mucosal biopsies were taken for histopathology.
The patient was readmitted the day following bronchoscopy with cough, dyspnoea and pyrexia. Chest radiography showed evidence of right lower lobe consolidation (). Intravenous ciprofloxacin and metronidazole were commenced, followed by vancomycin and hydrocortisone. A bedside echocardiogram showed no significant biventricular dilatation or impairment. The patient deteriorated despite high flow oxygen and non-invasive ventilatory support, and required mechanical ventilation 6 days following admission.
Broncho-alveolar lavage cultures grew mixed respiratory flora. Respiratory viral PCR, an HIV screen and urinary legionella antibody were negative. There was delayed detection of Pneumocystis jirovecii (cycle 33) likely representing colonisation. Antibiotics were changed to meropenem and clarithromycin. Ventilation was difficult due to to fibrinous casts plugging her airways. Repeated bronchoscopies revealed thick tenacious casts that were removed with a biopsy forceps and large-volume saline flushes ( and ). There was no evidence of underlying airway injury or stenoses. Returned fluid appeared chylous in nature reflecting possible lymphatic pathology.
Nebulised acetylcysteine, saline and tissue plasminogen activator (TPA) were trialled. Human albumin solution was given experimentally to reduce fluid diffusion into the lungs. The patient persistently required high inspired concentrations of oxygen (80–100%), and was ventilated with low tidal volumes (4–5 ml/kg) and high levels of PEEP (up to 12 cm H2O). Despite conventional treatment, the patient had several peri-arrest episodes due to inadequate ventilation, and veno-venous ECMO (VV ECMO) was commenced on day 14.
Initially, the patient required twice daily bronchoscopic clearance of casts. Radiological embolization of the thoracic duct or surgical ligation was considered, but her clinical condition was too unstable for this to be performed safely. A fat-free enteral feed was commenced in the interim, and sedation changed from propofol to midazolam to reduce chyle production.
The patient’s respiratory status gradually improved with reduced need for airway clearance. A tracheostomy was performed on day 27 and she came off VV ECMO on day 32. She was sent back to our local centre with minimal oxygen requirements and pressure support. She was eventually weaned off the ventilator and decannulated after 45 days. She has been discharged and remains stable on a fat-free diet.


A 60-year-old man visited a local hospital for a physical examination in January
2015. His serum α-fetoprotein (AFP) was 2940.5 ng/mL (normal value <20 ng/mL).
His routine biochemistry results were as follows: creatinine (Cr) 51 mol/L
(reference value 40–106 mol/L), globulin 51.2 g/L (reference value 15–30 g/L), and
albumin 37.1 g/L (reference value 35–52 g/L). Routine blood test results were
normal. Hepatitis B virus (HBV) DNA was 2.85 × 103 (normal
value < 1.0 × 103). B-mode ultrasound suggested a space-occupying
right liver lesion of about 2.6 × 2.8 cm, with a clear boundary and uneven internal
echo. Liver magnetic resonance imaging (MRI) suggested that the T1 signal was
slightly low and the T2 signal was high in the V segment of the right lobe. After
enhancement, the arterial phase was obviously enhanced and contrast medium in the
portal phase was withdrawn, showing fast in and fast out (). The patient was therefore
clinically diagnosed with HCC and treated with radiofrequency ablation and tenofovir
disoproxil anti-HBV therapy. His serum AFP level fell to 140.8 ng/mL and his
globulin level to 45.1 g/L after therapy.
Liver MRI conducted in February 2016 showed mostly coagulative necrosis of the tumor
in segment V, but a 21-mm nodule in the lower inner margin was suspected to indicate
local relapse ()
and a 17-mm nodule in segment VI was believed to be a new lesion. The patient
received further radiofrequency ablation.
Positron emission tomography-computed tomography (PET-CT) in June 2017 revealed a
right hepatic focal mass with no evidence of increased 2-fluoro-2-deoxy-D-glucose
(FDG) metabolism, widespread bone destruction, and osteogenic changes. Some lesions
with abnormal FDG metabolism and multiple bone metastases were assessed. The patient
was then treated with sorafenib.
The patient was admitted to our Hematology Department in March 2018 with
a > 1-month history of fatigue and a pale complexion. Physical examination showed
stable vital signs, an Eastern Cooperative Oncology Group (ECOG) score of 4, a
numeric rating scale (NRS) score of 2 to 4, a clear mind, listless and anemic
appearance, multiple ecchymoses in the skin and mucosa throughout the body, no
yellowing of the skin or mucosa, no enlargement of superficial lymph nodes, coarse
breathing sounds and scattered wet rales in both lungs. His abdomen was soft and his
liver and spleen were unaffected. There was no tenderness or rebound pain in the
abdomen. Bowel sounds were active 5 to 7 times per minute, and there was edema in
both lower limbs. Auxiliary examination was conducted Routine blood tests showed a
white blood cell count of 5.7 × 109/L, hemoglobin level of 61 g/L,
platelet count of 120 × 109/L, and reticulocyte count of 3.6%. Routine
biochemistry showed Cr 56.9 mol/L, total protein 79.5 g/L, albumin 14.8 g/L, and
globulin 64.7 g/L. His serum AFP level was 0.3 ng/L and HBV DNA was < 30 IU/mL.
No mutations were detected. HBV surface antigen, E antigen, and core antibody were
positive. Chest CT showed infectious lesions in both lungs with bilateral pleural
effusion and pericardial effusion, and his sternum, cervical, and thoracic vertebrae
showed multiple rib fractures. Abdominal CT revealed two oval, uniform-density
nodules in his right liver; the larger nodule was about 3.34 × 4.11 cm, but no
increase in the lesion was obvious on the enhanced scan.
He had anemia, increased globulin level, and multiple rib fractures. We therefore
considered the possibility of plasma cell disease and the patient underwent
additional examinations. The results were as follows: immunoglobulin (Ig)
A < 0.0667 g/L, IgG 53.9 g/L, IgM 0.16 g/L, peripheral blood
β2-microglobulin 5.20 mg/L, and peripheral blood immunofixation
electrophoresis suggested abnormal monoclonal bands in IgG and κ. A bone marrow
smear () showed
decreased proliferation of granulocytes and erythroid cells. Mature red blood cells
were arranged like strings of beads, and the proportion of plasma cells to nucleated
cells was increased to 87.0%. Naive plasma cells were occasionally observed, with
dense, blue-gray, cytoplasm with nuclear offset and thick, dense, dark purplish-red
chromatin. Bone marrow biopsy showed clusters of plasma cells in the marrow puncture
tissues ().
Immunohistochemistry results showed CD3 (5%+), CD20 (3%+), CD117 (−), CD79α (2%+),
CD33 (−), CD34 (−), CD43 (15%+), CD14 (5%+), CD61 (2%+), CD235α (10%+), LCA (8%+),
MPO (20%+), HLA-DR (2%+), κ (+), λ (−), CD19 (−), CD56 (+), CD10 (+), CD38 (+)
(), CD138 (+)
(), CAM5.2 (−),
and CK (−). Bone marrow flow cytometry () showed CD38 (++), CD138 (++), and
small amounts of CD19 (+), CD56 (+), and CD20 (−). Igκ light chain restriction
expression was observed in about 45.0% of the plasma cells, suggesting the presence
of monoclonal plasma cells. The bone marrow karyotype was normal. The patient was
diagnosed with MM (IgG - κ DS IIIA). He received PCD chemotherapy (bortezomib 2.0
g/day on days 1, 4, 8, and 11 plus cyclophosphamide 0.3 g/day on days 1 to 4 plus
dexamethasone 20 mg/day on day 1 and 2, 4 and 5, 8 and 9, and 11 and 12) on 9 April
2018. The patients subsequently presented with bloody stools, decreased urine
volume, and chest wall skin ecchymosis. His platelet count declined progressively to
11 × 109/L, prothrombin time and activated partial thromboplastin
time were significantly prolonged, and his fibrinogen was significantly decreased.
The patient died on 23 April 2018 of MM complicated by disseminated intravascular
coagulation.
The study was approved by the Ethics Committee of Hangzhou Red Cross Hospital. The
patient provided written informed consent for the procedures and his relatives
provided consent for publication of this report.


A 42-year-old man with Stage V chronic kidney disease and CVID with hyperimmunoglobulin M was evaluated for PH during a hospital admission for acute right heart failure. He was diagnosed with CVID at 19 years old and was treated with intravenous immunoglobulin (IVIg) since age 38. An echocardiogram showed a severely dilated right ventricle (RV), RV hypertrophy, severe RV systolic dysfunction with an estimated RV systolic pressure (RVSP) of 73 mmHg. His brain natriuretic peptide (BNP) was 1789 pg/mL. Right heart catheterization (RHC) revealed RA pressure of 14 mmHg, mean PA pressure of 54 mmHg, pulmonary capillary wedge pressure (PCWP) of 8 mmHg with a Fick of cardiac output of 3.05 L/min/m2 and pulmonary vascular resistance (PVR) of 15 Woods Units. Chest computed tomography (CT) showed enlarged pulmonary arteries, ground glass opacities in the bilateral lower lobes, no findings of chronic thromboembolic disease (a). Pulmonary function testing (PFT) revealed mild restriction and severely reduced diffusion capacity (forced expiratory volume 2.6 L, 71% predicted; forced vital capacity 3.5 L, 76%; FEV1/FVC 75%; total lung capacity 4.8 L, 78% predicted; diffusing capacity for carbon monoxide 48% predicted). He started sildenafil and ambrisentan but developed worsening RV failure and renal failure prompting admission for dialysis and inhaled epoprostenol. He transitioned to IV epoprostenol therapy with improvement to mild RV systolic dysfunction and BNP normalized to 58 pg/nL.
Two years later, he developed worsening dyspnea, cough, and hypoxemia, with a chest CT showed multifocal pulmonary infiltrates. Spirometry was stable with worsening diffusion capacity (30% predicted). His echocardiogram showed RVSP 50 mmHg and mildly depressed RV systolic function. Lung biopsy revealed a complex pattern of follicular bronchiolitis/hyperplastic bronchus-associated lymphoid tissue, nonspecific interstitial pneumonitis (NSIP)-like, and lymphoid interstitial pneumonitis (LIP)-like areas, scattered histiocyte aggregates consistent with poorly formed granulomas, and occasional foci of bronchiolitis obliterans-organizing pneumonia (b). Significant fibrosis was also present. Elastin stains demonstrated advanced hypertensive remodeling of both arteries and veins, with intimal hyperplasia (frequently occlusive) and reduplication of the elastic laminae; arterial changes were equivalent to Heath-Edwards grade 3 (no plexiform lesions were present) (c and d). There were no findings of amyloid deposition on pathologic specimens. He was diagnosed with GL-ILD and started on corticosteroids with rapid improvement in hypoxemia and resolution of radiographic abnormalities. He continues on IV epoprostenol for PAH.


A 41-year-old woman with CVID diagnosed at age 27, on chronic IVIg, was admitted for dyspnea and exertional hypoxia. Six years prior to this presentation, she was found to have bronchiectasis, septal thickening, ground glass opacities, and nodular densities on chest CT (e). Lung biopsy revealed follicular bronchiolitis with occasional LIP-like areas, variable bronchiolectasis, a few histiocyte aggregates consistent with poorly formed granulomas, and foci of NSIP-like pattern, both cellular and fibrotic (f). Elastin stains showed mild to moderate arterial hypertensive remodeling, with occasional non-occlusive intimal proliferative lesions and variable reduplication of the elastic laminae, equivalent to Heath-Edwards early grade 2; small veins had frequent mild intimal proliferation (g and h). No evidence of amyloid involvement was seen on pathology. Echocardiogram showed normal RVSP and RV function. She was diagnosed with GL-ILD and treated with corticosteroids with clinical improvement. Spirometry improved to mild-moderate obstruction (FEV1 1.98 L, 64% predicted) and moderately reduced diffusion capacity (50% predicted) and was stable for several years. At the current presentation, she had a new dilated, hypertrophied RV with moderately depressed RV systolic function and estimated RVSP of 87 mmHg on echocardiogram with a BNP of 894 pg/nL. Her PFTs showed similar degree of obstruction with severely reduced diffusion capacity (DLCO 7.1 mL/mmHg/min, 29% predicted). Chest CT showed a dilated PA but was otherwise unchanged compared to prior CT scans. An RHC revealed RA pressure of 7 mmHg, mean PA pressure of 58 mmHg, PCWP of 9 mmHg with a Fick of cardiac output of 4.02 L/min/m2 and PVR of 9.2 Woods Units. Based on advanced pre-capillary PAH with stable, mild parenchymal lung disease, she was offered PAH-directed therapies. She declined parenteral prostacyclin therapy and is currently on tadalafil and ambrisentan, with improvement in clinical symptoms and normalization of BNP (39 pg/nL).


A 34-year-old woman was admitted to the emergency unit complaining of limb numbness and watery diarrhoea (8–10 bowel movements/day) which started 2 weeks earlier. The patient reported a weight loss of about 10 kg in the last 2 months in the absence of hyporexia. Her clinical history unravelled microcytic anaemia treated with oral iron replacement. Physical examination showed severe weakness of the limbs with a bilaterally positive Trousseau’s sign without cardiorespiratory abnormalities. Vital parameters were within the normal range. The abdomen was flat, without tenderness, while auscultation disclosed increased intestinal sounds. Her ECG showed a sinus rhythm with type 1 atrioventricular block, flat T waves associated with U waves and an elongated QTc interval (570 ms). Laboratory tests revealed severe electrolyte imbalance, with hyponatraemia (133 mmol/L), hypokalaemia (1.6 mmol/L), hypocalcaemia (ionised calcium of 0.9 mmol/L), hypophosphataemia (1.6 mg/dL) and hypomagnesaemia (1.4 mmol/L). Furthermore, the patient had hypochromic microcytic anaemia (haemoglobin of 85 g/L, with a mean cell volume of 68 fL and a mean cell haemoglobin of 20.6 pg), normal platelet count (297×10ˆ9/L), iron (serum iron 18 µg/dL; ferritin 2 ng/mL) and folate deficiency (2 ng/mL), as well as hypoproteinaemia and hypoalbuminaemia (total serum protein 4.4 g/dL; albumin 2.6 g/dL). Due to severe electrolyte imbalance, a conspicuous electrolyte replacement was rapidly administered, leading to a slight improvement in electrocardiographic abnormalities. The patient was then admitted to the internal medicine ward for adequate investigation and treatment. During the hospitalisation, the common causes of infectious diarrhoea were excluded by stool cultures, and the faecal occult blood test resulted negative. Both ultrasound and abdominal X-ray examinations were unremarkable. Liver function tests revealed a slight increase of transaminases, with alanine transaminase and aspartate transaminase values of 47 U/L and 60 U/L (n.v. 5-35 for both parameters), respectively. Based on the lack of fever, normal C reactive protein and the presence of non-bloody, watery diarrhoea, the patient was further evaluated with an upper endoscopy. The examination revealed stigmata of villous atrophy at the duodenal level (), where biopsies were taken from the bulb and the second portion. Histopathological analysis showed the presence of a severe villous atrophy (Marsh-Oberhüber grade 3c) () without any evidence of aberrant intraepithelial lymphocytes. Based on the histopathological result, we used enzyme-linked immunoassay to test IgA anti-TG2, which turned to be positive at low titre (23 U/mL, n.v. <10 U/mL). This result was associated with the positivity of IgA antiendomysial antibodies (1:80) revealed by indirect immunofluorescence. The genetic test showed human leucocyte antigen (HLA)-DQ2 positivity. Therefore, a firm diagnosis of CD was established and the patient started a gluten-free diet (GFD). Due to rapid improvement after gluten withdrawal, a course with steroid treatment was deemed not necessary. Since diarrhoea and paraesthesia showed significant improvement with complete regression in about a week, the patient was discharged in good health.


A 50-year-old male patient was admitted to our hospital with progressive dyspnea, cough, and cold sweats. He mentioned night sweating for a year and 15 kilograms weight loss. His medical history stated a human immunodeficiency virus (HIV) infection since 2003, with a double-sided pneumonia with Pneumocystis jirovecii (among other pathogens) at admittance, therefore diagnosed as acquired immunodeficiency syndrome (AIDS). Patient was treated with antiretroviral therapy with an undetectable viral load in 2012, but had stopped taking medication 1 year ago. He lived in a homeless shelter with his wife (who was also HIV positive); his children were accommodated elsewhere. There was no (intravenous) drug or alcohol use, and he had quit smoking 15 years ago. Physical examination on admission showed a non-acutely ill patient, tachypneic with an oxygen saturation of 88% on room air. His blood pressure was 130/80 mm Hg, heart rate 132 per minute, and temperature 38.2°C. Percussion of the lungs did not reveal any dullness, and at auscultation normal breath sounds were heard except for the left lower side. Other physical examination was unremarkable.
Relevant laboratory results on admission were hemoglobin 7.2 mmol/L, white blood cell count 6.6 × 109/L, platelets 214 × 109/L, and C-reactive protein (CRP) 64 mg/L. There was no renal or hepatic insufficiency. Immunology results were as follows: CD4: 0.039 × 109/L, CD8: 1.2 × 109/L, CD4/CD8 ratio: 0.033. A chest X-ray showed bilateral “cloudy” infiltrates.
The patient was treated according to the local sepsis protocol, with gentamicin 280 mg and amoxicillin/clavulanic acid 1200 mg intravenously in the emergency room. This was followed by cotrimoxazole (3 × 1920 mg) and prednisolone (2 × 40 mg) the next day for suspected PJP. Two days after admission, a bronchoscopy with bronchoalveolar lavage (BAL) was performed to confirm the diagnosis. Directly after this procedure, the patient became dyspneic, had low oxygen saturations (82%), and developed subcutaneous emphysema. Due to progressive respiratory insufficiency, endotracheal intubation and mechanical ventilation were necessary. Bronchoscopy-guided intubation was performed in the operating theater, which was uneventful. A computed tomography (CT) scan of the chest immediately after intubation showed subcutaneous and mediastinal emphysema without pneumothorax. Also, severe air bronchograms and bilateral infiltrations were seen. Patient was admitted to the intensive care unit (ICU) afterward.
During the (ventilatory) treatment on the ICU, the subcutaneous and mediastinal emphysema increased, resulting in swelling of the entire face, arms, and torso down to the scrotum (). Several bronchoscopies were performed to exclude tracheal injury that could have occurred during the BAL, but no injury was visualized. Despite efforts to treat patient with lung protective ventilation, using low tidal volumes and low airway pressures, the emphysema continued to increase. A new CT scan was performed 1 week after admission to the ICU, showing severe subcutaneous and mediastinal emphysema (). Treatment of the emphysema by skin incisions alone (“blow holes”) was considered but discarded due to the high HIV viral load (700,000 copies/mL) of the patient and the fear of viral spreading by blood spatters. Because of the severity and increase of the symptoms and no obvious tracheal injury (on subsequent bronchoscopies and CT scans), a search for other treatment options was performed. After elaborate consideration, it was decided to make two infraclavicular skin incisions and place VAC therapy on these incisions (ActiV.A.C., KCI Medical, –125 mm Hg; ). While the subcutaneous emphysema started to improve significantly, a gradual clinical improvement was seen in the first week. VAC therapy was ended 9 days after initiation. The subcutaneous emphysema continued to decrease after removal of the VAC therapy system.
During his stay on the ICU, inflammatory markers decreased together with the pulmonary infiltrations on the chest X-ray, implying adequate treatment of the PJP. Patient was extubated after 17 days of mechanical ventilation, with a significant ICU-acquired weakness. Furthermore, dysphonia was reported, possibly caused by emphysema of the larynx. The patient was discharged to the general ward 25 days after admission to the ICU. Antiretroviral medicine was restarted, and patient was finally discharged to a medical rehabilitation center for further recovery.


A 48-year-old, mixed-ethnicity woman arrived at our Unit with a complaint of a mass extruding from the vaginal orifice that was associated with bleeding and pain for a couple hour. The patient had brought the mass in a container. She denied any history of menstrual delay as well as use of medications. A previous ultrasound had revealed an endometrial nodule with a vascular pedicle measuring 20 × 12 cm2, suggestive of a polyp or submucous myoma. At the time of admission, the patient appeared calm without severe pain, but with abdominal tenderness. Speculum examination showed a closed cervix with a moderate amount of bleeding. The uterus was of a fibroelastic consistency and tender on examination. After the examination of the patient, the team dissected the extruded structure, thinking that it was a clot; however, it was found to be very hard. It was a long mass that was difficult to diagnose ().
Therefore, we subjected it to anatomopathological analysis which indicated that it was a myomatous lesion measuring 3.4 × 1.7 × 1.0 cm3. Microscopy revealed well-delimited nodular formation, formed by multidirectional bundles of spindle cells, and oval nuclei without atypia. It was diagnosed as a leiomyoma ().
The patient was treated with broad-spectrum antibiotic. Patient follow-up at 1 and 3 months was clinically and ecographically normal ().


A 32-year-old, seemingly healthy, man presented an acute syncope while practicing
physical activities, followed by hemiplegia on the right side, right labial
commissure deviation, and disorientation. At the emergency unit, his brain
computed tomography scan showed a intraparenchymal hematoma in the left basal
ganglia, measuring 3.8 × 3.1 × 2.8 cm, with edema in a small area that induced a contralateral deviation in the
midline structures. The patient was a former smoker who had stopped smoking for
a month, and therefore, at that time, was likely to have suffered a hemorrhagic
stroke. A cerebral arteriography further showed occlusion of the middle cerebral
artery. During clinical evaluation at the hospital, laboratory tests showed that
the patient was HIV1 positive. At the time, his CD4 count was 333 and his viral
load was 7792 copies/ml without any associated co-morbidity (hepatitis B and C,
cytomegalovirus, toxoplasmosis, and fluorescent treponemal antibody absorption
test results were found to be negative). Further, the patient started highly
active antiretroviral therapy during his hospitalization. Magnetic resonance
imaging of his brain showed an expansive lesion in the periventricular region
and in the internal capsule on the left side, with extension to the thalamus,
inferior to the cerebral peduncle, along with the corona radiate and a semi-oval
white center at the top left, measuring about 4.5 × 4.0 × 4.6 cm. The tumor mass presented a heterogeneous signal intensity on T1 and T2,
with a large amount of blood residue and hypo-intense signal on conducting
susceptibility-weighted imaging, with heterogeneous and irregular enhanced
contrast. Moreover, there was a central lesion area with a necrotic aspect,
without the contrast being enhanced or diffusion restriction being encountered
in the uppermost portion of the lesion. These findings suggested an associated
neoplasm in the same area where the hemorrhagic changes were found ().
The patient underwent a stereotactic biopsy of the supposed neoplasm 2 months
after his stroke, when he was diagnosed with an anaplastic astrocytoma. The
neoplasia could not be completely resected owing to its location. In addition to
the administration of antiviral drugs for HIV, the patient started chemotherapy
with temozolomide, and underwent five cycles of 30 Gy radiotherapy, leading a
normal life for a year.
At 1 year and 7 months following disease onset, the patient developed chronic
dorsalgia, which worsened after physical therapy. A magnetic resonance imaging
of the thoracic spine indicated a pathological fracture of the 9th thoracic
vertebral body, along with spinal cord compression. The patient underwent a
surgical procedure in order to decompress his spinal cord with laminectomy and
partial corpectomy, followed by pedicular screw stabilization. The biopsy of the
ninth thoracic vertebral body mass led to the diagnosis of glioblastoma
metastasis in this vertebral body. Moreover, a month prior to the spine surgery,
a mass was noted in the patient’s anterior neck tissue, which was also analyzed
via magnetic resonance imaging. Therefore, he was asked to
undergo a lymph node biopsy, which also showed glioblastoma metastasis ().
At 3 months after his first spine surgery, the patient reported acute anterior
thoracic and rib pain, despite a series of spine radiotherapy sessions, and in
addition to several chemotherapy cycles. The new thoracic spine magnetic
resonance imaging showed a recurrence of spinal cord compression on the same
site as before, with foramen stenosis resulting from the regrowth of the tumor
mass in the vertebral body. Subsequently, the patient underwent a new palliative
surgical procedure to decompress the spinal cord, along with the debridement of
the spine canal, as a result of which we managed to isolate his cancer cells
(). At that
time, a thoracic computed brain tomography scan showed multiple lytic lesions on
the ribs and the scapula, whereas the thoracic magnetic resonance imaging showed
extensive edema on the same sites, suggesting permeating lesions (secondary
implants). Towards the end of his life, the patient presented metastatic masses
in the cervical area (ribs, scapula, and neck) and in the spine, wherein an
extracranial tumor emerged from the first biopsy path, all of which were
compatible with the glioblastoma metastasis. After palliative spine surgery, the
patient developed liver insufficiency as well as pneumonia, and was thus treated
with antibiotics. After 2 weeks of palliative treatment, the patient died as a
consequence of his disease.
Representative sections of the patient’s stereotactic biopsy were stained with
hematoxylin and eosin; a small area with a diffuse and rich proliferation of
gemistocytic astrocytes could be observed (). Endothelial proliferation was
observed, after which single-labeled immunoperoxidase staining was performed
using standard procedures. For this purpose, the following primary antibodies
were used: monoclonal anti-glial fibrillary acidic protein (GFAP EP672Y, Cell
Marque; 1:500), mouse monoclonal anti-IDH-1R132H/DIA-H09 (Optistain; 1:300), and
monoclonal anti-Ki67 (SP6, Cell Marque; 1:5000). The immunohistochemistry showed
diffuse positivity for the glial fibrillary acidic protein, was IDH-1R132H
negative, and displayed a proliferation index of 8% (Ki–67) (–). In addition, the
diagnosis showed a grade III anaplastic astrocytoma (World Health Organization).
The vertebral body and the resections of the lymph nodes depicted the same
histology as that of diffuse gemistocytic astrocyte and cell pleomorphism.
However, in these samples, we could still identify necrosis. Again, the
diagnosis showed metastatic glioblastoma.
When the patient underwent a palliative spine surgery for decompression 2 years
after disease onset, his metastatic glioblastoma (met-GBM18) cells were
isolated, established, and characterized in our laboratory (). This study was approved by the
Clinical Research Ethics Committee of Instituto Estadual do Cérebro Paulo
Niemeyer (CAAE:90670018.4.0000.8110). The cells were cultured in Dulbecco’s
Modified Eagle Medium/Nutrient Mixture F-12, supplemented with 10% fetal bovine
serum, and maintained at 37°C in an atmosphere containing 95% air and 5%
CO2. For immunofluorescence, the met-GBM18 cells were cultured on
coverslips in 24-well plates as described previously. The cells were subsequently stained using standard procedures. In
summary, the following primary antibodies were used: polyclonal rabbit anti-GFAP
(Dako, Carpinteria, CA, USA; 1:200), polyclonal rabbit S100 (Dako; 1:400),
anti-SOX-2 (Cell Signaling Technology, Danvers, MA, USA; 1:400), monoclonal
mouse anti-Vimentin Clone V9 (Dako; 1:100), Anti-Nestin Antibody (Millipore,
Bedford, MA, USA; 1:200), and anti-HIV-1 p24 monoclonal mouse (NIH AIDS reagent
program, NIH, Bethesda, MD, USA; 1:1000). As a control for the nonspecific
binding of secondary antibodies, primary antibodies were omitted. The secondary
antibodies were goat anti-rabbit IgG or goat anti-mouse IgG, conjugated with
Alexa Fluor 488 (1:750). The nuclei were stained with
4′,6-diamidino-2-phenylindole (DAPI). In all cases, no reactivity was observed
when the primary antibody was absent. The cell preparations were mounted
directly on the ProLong® Gold Antifade reagent and visualized in a DMi8 advanced
fluorescence microscope (Leica Microsystems, Wetzlar, Germany).


A 67-year-old man with a past medical history of type 2 diabetes mellitus, hypertension, ischemic cardiomyopathy with left ventricular aneurysm and an ejection fraction of 15% presented to the emergency department (ED) with fever, cough and dyspnea for 4 days.
On presentation, he was febrile to 100.6 °F, hypertensive to 157/70 mm Hg and hypoxic with an oxygen saturation (SaO2) of 88% on ambient room air. His electrocardiogram (EKG) was unremarkable for any acute change. The chest X-ray revealed bilateral diffuse ground-glass opacities (GGOs) in lungs (). The pertinent laboratory findings are shown in .
The clinical symptoms, elevated inflammatory markers, PaO2/FiO2 < 300 and eventual positive nasal swab were consistent with COVID-19 pneumonia and mild ARDS. Patient was started on non-invasive positive pressure ventilation, with off-label tocilizumab 400 mg × 1, hydroxychloroquine 400 mg BID × day 1, then 400 mg for the next 4 days, and 400 mg azithromycin for 5 days. The patient was started on optimal home dose diuretic. The optimal heart regimen including valsartan-sacubitril 49 - 51 mg BID was held due to inconsistent reports of worsening of COVID-19 secondary to renin angiotensin aldosterone system medication. Initially statins were continued, but on day 4 were stopped given the worsening of primary transaminitis due to COVID-19 in the setting of statins. Despite management our patient died in the setting of COVID-19 ARDS causing respiratory failure.


A 6-year old boy was admitted to our clinic with the complaints of attention difficulties, hyperactivity, impulsivity and aggression to peers. His psychiatric evaluation and the parent-rated and teacher-rated scales both indicated an ADHD-combined type diagnosis. Conners’ Teacher Rating Scale Score (CTRS) on admission to clinic was 45 [] while the Turgay DSM-IV Disruptive Behavior Disorders Rating Scale parent form (T-DSM-IV-S) [] total score was 48 with a hyperactivity subscale score of 24 and an attention deficit subscale score of 24. His developmental history was reported to be normal. His medical history revealed that he had a streptococcal infection 14 months ago and subsequently had been diagnosed with ARF. As a symptom of ARF, he had Sydenham chorea and stiffness in hand joints but he did not have any cardiac or skin lesions. In his neurologic examination, Sydenham’s chorea was evident with mild unintentional movements in the neck and arms. Since the diagnosis of ARF and Sydenham chorea, patient was on haloperidol 1.5 mg/day, valproate 500 mg/day and 1.200.000 IU benzilpenisilin once in 3 weeks. He had no previous admission to child psychiatry, no history of seizures or any other medical conditions.
For the treatment of ADHD, osmotic-release oral system (OROS) MPH was planned to initiate and the patient was referred to pediatrics department. After the approval of medication by pediatrics department, OROS MPH was started in the dose of 18 mg/day. Three days after MPH treatment, patient was admitted to our clinic with the complaints of worsening of chorea. In his clinical evaluation, a marked increase in chorea symptoms was observed in arms. In addition, chorea symptoms were observed to emerge in legs, which were not present before MPH treatment. The Chorea Intensity Scale score was 12 on initial admission to clinic and increased to 27 after MPH treatment. Due to an exacerbation of chorea, MPH treatment was discontinued. At the 2-week-follow-up, patient’s chorea symptoms resolved back to the level before MPH treatment. At this follow-up, the chorea intensity scale score was found to be 11. After the discontinuation of MPH, no additional medication was initiated for 2 weeks. Thereafter, ATX was started in the dose of 10 mg/day (0.5 mg/kg/day). Ten days follow-up on ATX treatment revealed a mild improvement in ADHD symptoms with no worsening in chorea symptoms. The chorea intensity scale score was 9; while CTRS score was 40 and T-DSM-IV-S total score was 36, with a hyperactivity subscale score of 19 and an attention deficit subscale score of 17. ATX dose was gradually increased to 18 mg and 25 mg/day in 3 weeks. Patient was reported to have moderate improvement in ADHD symptoms and no worsening was reported in chorea. The chorea intensity scale score was 9; while CTRS score was 37 and T-DSM-IV-S total score was 28. shows the changes in Chorea Intensity Scale scores during MPH and ATX treatments.


A 78-year-old African-American male with a history of paroxysmal atrial fibrillation, syncope, hypertension, and HF with reduced ejection fraction of 30%–40% (diagnosed 2016) presented to the emergency department with increased exercise intolerance, episodic chest pressure, and shortness of breath. Other past medical history included stroke, chronic kidney disease, and small bowel obstruction. Home medications were rivaroxaban, beta blocker, statin, angiotensin-converting enzyme (ACE) inhibitor, and torsemide. The vital signs on arrival were normal. The physical examination was significant for a non-obese male with an irregular heartbeat, elevated jugular venous distention (6 cm above sternal angle), bilateral lower extremity edema, and inspiratory crackles. Cardiac auscultation did not reveal any extra heart sounds. Labs were significant for troponin I (TnI) of 0.27 ng/mL (normal < 0.03 ng/mL) and brain natriuretic peptide (BNP) of 389 pg/mL (normal < 100 pg/mL), both of which were higher than his known baselines (0.14 ng/mL and 300 pg/mL, respectively). Furthermore, chart review revealed a persistently elevated TnI (mean = 0.145 ng/mL) for approximately 10 years (5 years before his CHF diagnosis). All other labs, including kidney and liver function, hematology, and urine drug screen, were normal.
Chest X-ray revealed no acute cardiopulmonary abnormalities. Electrocardiogram () showed normal sinus rhythm with low voltage, but no signs of ischemia. The patient was admitted for management of non-ST elevation myocardial infarction (NSTEMI) and CHF exacerbation.
Transthoracic echocardiography (TTE) () revealed a progressive decline in left ventricular ejection fraction (LVEF) to 25%–35%. It was also significant for worsening diastolic dysfunction with E/A of 3.5 and medial E/E′ of 24, despite the patient’s adherence to medical management. The initial TTE done 3 years prior to this presentation showed LVEF 50%–55% and mild diastolic dysfunction with E/A 0.78. The repeat TTE done 1.5 years later revealed a decline in LVEF to 30%–40%.
Given the progressive decline in LVEF, a cardiac MRI (magnetic resonance imaging) was performed to rule out apical ventricular thrombi. The MRI revealed diffuse late gadolinium enhancement concerning for amyloidosis. Follow-up nuclear bone imaging () revealed increased cardiac uptake greater than bone, suggestive of grade III CA. Fat pad biopsy and mass spectrometry confirmed TTR amyloidosis. The patient was managed conservatively with diuretics, with significant improvement in symptoms, and was discharged with appropriate follow-up in place. Metoprolol was discontinued on discharge due to concerns of worsening the amyloidosis symptoms.


A 64-year-old Caucasian man presented with sudden vision loss from his left eye. He suffered from non-small-cell lung carcinoma and had been in treatment with durvalumab 1,125 mg every 3 weeks for the past 20 months. The patient had no signs of other systemic conditions and his arterial blood pressure was normal. Serologies for herpes viruses, human immunodeficiency virus, and T. pallidum were negative. He had no previous history of ophthalmic pathology. His best-corrected visual acuity (BCVA) was 20/20 in his right eye and counting fingers in his left eye. There were no pathological findings in the anterior segment examination. The fundoscopy showed papillitis, dot and blot hemorrhages, intraretinal hemorrhages, severe cystoid macular edema, and mild white sheathing in the macular vascular branches (Fig. ). Posterior optical coherence tomography (Swept Source OCT, TritonTM, TOPCON, Japan) confirmed the cystoid macular edema associated with hyperreflective material that might be fibrin, secondary to the severe retinal inflammation, as well as vitreous hyperreflective foci. Ultra-wide-field fundus fluorescein angiography (Optos®, Optomap®, UK) revealed tertiary branch phlebitis and vascular leakage (Fig. ). The patient was admitted and started on methylprednisolone bolus 500 mg/day for 3 days, followed by methylprednisolone 1 mg/kg/day for 1 week, and then tapered oral prednisone, starting from 30 mg/day, over 3 weeks. During his admission, the patient was seen daily. In as little as 24 h after being admitted, the patient referred an ongoing improvement of his visual symptoms, is BCVA was 20/50 by the time the treatment ended, and eventually evolved to 20/25 after 2 months follow-up. During this time, the posterior optical coherence tomography (Swept Source OCT, TritonTM, TOPCON, Japan) registered a gradual reduction of the macular edema (Fig. ) and the ultra-wide-field fundus fluorescein angiography (Optos®, Optomap®, UK) a resolution of the ocular vasculitis.
After a 1-year follow-up, the patient showed a complete resolution of this condition, showed no signs of vasculitis or other ocular findings, had no need for rescue treatment, and is currently still on durvalumab without other side effects being reported.


A 43-year-old man was hospitalized for chest tightness. He had developed recurrent chronic and intermittent melena 3 months before hospitalization, but these symptoms were not regarded as important. However, his symptoms subsequently worsened, developing into more frequent melena with new symptoms such as dizziness, nausea, and epigastric pain. The epigastric pain usually occurred with the bleeding, and it generally eased after the melena stopped. The patient had no history of taking any special drugs or having any infection before the onset of melena or chest tightness. We carefully reviewed his medical history and performed a complete medical examination. When he was young, he had often experienced large amounts of spontaneous bleeding from the nose and gingiva at a high frequency several times a year. Moreover, he had been previously diagnosed with severe anemia for which he received blood transfusions. His parents were in good health, and their marriage was non-consanguineous. Physical examination of the patient on admission revealed pale skin and epigastric tenderness. The main laboratory tests results were as follows: hemoglobin, 44 g/L; red blood cell count, 3.27 × 1012/L; platelet count, 147 × 109/L; fibrinogen, 2.026 g/L; prothrombin time, 12.2 seconds; and activated partial thromboplastin time, 12.2 seconds.
The patient was initially diagnosed with upper gastrointestinal bleeding and underwent gastroscopy, which revealed oozing of blood in the wall of the gastric antrum (). He underwent endoscopic hemostasis therapy with no complications. A proton pump inhibitor and somatostatin were administered postoperatively. The patient also received blood transfusions, and his condition gradually stabilized. No obvious lesions such as erosions or ulcerations were found by gastroscopy (). Because of the patient’s bleeding history, we considered that he may have had various blood diseases. Platelet aggregation assays revealed no aggregation with 2 μmol/L adenosine diphosphate or 2 μmol/L adrenaline, while a slightly weaker response to ristocetin was noted (23% (60S), 29% (180S), and 31% (300S)). Finally, flow cytometry revealed that the integrin αIIbβ3 concentration was 14% of normal, while the levels of the other glycoproteins were approximately normal. The patient was diagnosed with GT (type II). Genetic studies revealed a compound heterozygotic mutation in the ITGA2B gene, and the mutation bases were c.2333A>C and c.1750C>T.
Upon confirmation of the diagnosis, the patient was treated with a platelet transfusion to prevent surgical bleeding. The melena stopped and he was gradually transitioned to a normal diet. Soon afterward, he fully recovered and was discharged from the hospital. The patient was seen for follow-up visits once every 6 months after discharge. He underwent several endoscopic examinations, which showed no recurrence of the upper gastrointestinal bleeding.
The patient provided written informed consent for publication of this report. This was a retrospective case report; therefore, institutional review board approval was not required.


A 54-year-old man presented with a 10-year history of mechanical back pain, which became worse with activities and was reduced after bed rest. In the last 3 mo, his back pain had progressively increased and radiated into the left lower limb with numbness.
He had no relevant traumatic history.
Physical examination revealed a stiff lumbar spine with limited range of flexion, extension, and lateral bending. There were tenderness and percussion pain over the L4-L5 lumbar spine. Bilateral lower limb dermatomal sensation was normal, but he had decreased muscle strength (class IV) of the left hallux dorsal extensor. Lower extremity muscle tension, bilateral straight leg raising test, and strengthening test were all normal.
Laboratory data showed no infectious or inflammatory findings.
The initial plain radiographs revealed a decrease in height of the L4-L5 disc space. No instability was noted on the dynamic radiographs of flexion and extension of the lumbar spine (Figure and ). Magnetic resonance imaging (MRI) scans showed L3-S1 disc degeneration with associated low signal intensity and L4-L5 disc herniation (Figure and ).


A 9-year-old female domestic shorthair indoor-only cat was presented to the ophthalmology referral consultation at the Teaching Hospital of the Faculty of Veterinary Medicine, Lisbon University with a right globe lesion that had started 6 months ago. The cat had been undergoing long-term treatment for conjunctivitis by the referring veterinarian, and showed no improvement or change in the clinical appearance of the lesion. Oral and topical antibiotics and topical anti-inflammatory drugs, including steroids, had been prescribed. Complete physical examination revealed no other abnormalities.
On ophthalmic examination, the cat presented with an extensive elevated pink mass that covered two-thirds of the cornea of the right eye (OD) (). The left eye (OS) had no clinical signs of disease. In the OD the dazzle reflex was positive, the menace response was absent and palpebral closure was impossible owing to the presence of the mass, leading to lagophthalmos. The corneal reflex was decreased, probably due to changes of the termination of corneal nerves. In the OD, direct and indirect pupillary light reflexes were impossible to evaluate owing to the large mass and grey opacity in the remaining cornea that rendered visualisation of the pupil impossible. In the OS, menace response and all the remaining ocular reflexes were present. In the OS both direct and indirect pupillary light reflexes were present, as light could pass through the opaque cornea, so a functional retina in the right eye could be expected.
Schirmer tear test (Dina strips Schirmer-Plus; Luneau SAS) was 11 mm/min in the OD and 18 mm/min in the OS. Intraocular pressure measurement obtained by applanation tonometry (Tono-Pen XL; Medtronic Solan) following instillation of a topical anaesthetic (Oxibuprocaine, Anestocil; Laboratórios Edol) was 13 mmHg in the OD and 18 mmHg in the OS. The left cornea did not stain with fluorescein dye, while the right eye mass captured some stain.
Slit-lamp biomicroscopy (SL14 Kowa Company) of the OD allowed for better visualisation of the mass and showed no abnormalities in the OS. Two drops of a topical mydriatic drug corresponding to tropicamide in a 1% concentration (Tropicil Top; Laboratórios Edol) were applied in the OS. Indirect funduscopic examination (Heine Omega 180) was impossible to perform in the OD owing to the mass, but was normal in the OS.
The differential diagnoses for the OD mass included eosinophilic keratitis, chronic keratitis, traumatic injury, corneal foreign body and neoplasia.
Complete blood count (CBC) and serum chemistry analysis were within normal limits. Triple-view thoracic x-rays were obtained to rule out thoracic lesions. Although corneal surface cytology is an important complementary examination, it could not be performed in this patient without heavy sedation or general anaesthesia, and so surgical biopsy was considered the best option.
The patient was premedicated with methadone (Semfortan; Dechra Veterinary Products) at a dosage of 0.2 mg/kg body weight subcutaneously and anaesthetised with propofol at a dose of 5 mg/kg body weight intravenously (Propofol Lipuro; B Braun Medical). Endotracheal intubation was performed following topical anaesthesia of the larynx and volatile anaesthesia was maintained with isoflurane. On induction, cephalosporin (Cefazolina Labesfal; Labesfal – Laboratório Almiro) at a dosage of 22 mg/kg body weight was administered intravenously to prevent bacterial contamination of the surgical site and meloxicam (Meloxidyl; Ceva) at a dosage of 0.1 mg/kg body weight was given subcutaneously for the control of postoperative pain.
Periocular skin of the right eye was clipped and surgical asepsis was obtained with povidone–iodine 1:20 solution, followed by sterile saline. After completion of draping, a 5 mm lateral canthotomy was performed to increase corneal exposure. Surgery was performed using a surgical microscope, a Collibri forceps to grasp the mass and the corneal lamellae, and a disposable crescent blade was used to carefully dissect between collagen stromal layers. This task was difficult to accomplish because the mass was friable and difficult to grasp without tearing the tissue. An attempt was made to achieve a surgical-free margin, sparing as much corneal stroma as possible (–). The excised tissue was sent for histopathology.
Lateral canthotomy was routinely closed in two layers with 5-0 simple interrupted absorbable sutures (Surgycril; B Braun Medical).
Histopathology revealed that the tissue corresponded to a corneal SCC ().
Postoperatively, medical treatment consisted of oral meloxicam (Meloxidyl; Ceva) at a dosage of 0.05 mg/kg body weight for 4 days, and doxycycline (Ronaxan; Pfizer) at a dosage of 10 mg/kg body weight for 7 days postoperatively. Additionally, topical tobramycin drops (Tobrex; Edol) were applied every 4 h for 14 days in the OD, along with ganciclovir 0.15% in gel form (Virgan; Laboratoires Thea) every 4 h to prevent an eventual exacerbation of a latent feline herpesvirus infection, which is endemic in Portugal. An Elizabethan collar was advised to prevent self-mutilation of the surgical site. Ten days later, the canthotomy skin sutures were removed. The cornea healed with no complications, apart from a moderate superficial neovascularisation on the surgical site.
One month postoperatively, a fluorescein test was negative, the cornea had completely healed and topical mitomycin C adjuvant treatment was initiated. The drug was diluted in sterile water at a concentration of 0.04% (0.4 mg in 10 ml of sterile water), placed in commercial sterile dry tubes; three tubes were prepared – one for each treatment. Tubes were protected from light (covered with Vet Wrap) and kept at 4ºC. One drop was applied three times daily in the OD for a course of 15 days, followed by a 15-day interval with no other medication apart from artificial tear drops three times daily. Three treatment cycles were performed, one per month. The cytostatic agent was applied by the owner using chemotherapy gloves. There were no immunosuppressed owners or children at home and the cat was the sole pet and always kept indoors. There was no pruritus or signs of ocular discomfort throughout the treatment, and an Elizabethan collar was unnecessary.
No secondary side effects, either systemic or local, were observed with this topical chemotherapy. By the end of the chemotherapy protocol, CBC and biochemistry profiles were within normal limits. The patient was ophthalmically rechecked every 2 weeks and the cornea was clear throughout the treatment, showing no signs of inflammation, epiphora or ocular discharge. Fluorescein tests were negative. Over the course of treatment, the cornea regained transparency and decreased its neovascularisation (). During follow-up evaluations, every 2 months after the end of treatment, an almost clear cornea was appreciated, with slight neovascularisation and discrete scarring. Symblepharon of the dorsal bulbar conjunctiva to the third eyelid was present at 2 o’clock. There was no epiphora or ocular discharge, signs of inflammation, pruritus or ocular discomfort. Intraocular pressure was normal. There was no recurrence of the neoplasm at the 1-year follow-up.