We present the case of a 71-year-old self-employed, non-smoking German female patient scheduled to undergo a right TKA. Relevant past medical history included type 2 diabetes mellitus treated with insulin (HbA1c 43 mmol/mol), BMI of 35.5 kg/m2 (176 cm/ 110 kg), arterial hypertension (usual value 140/60 mmHg via right arm) and restless leg syndrome. Important self-medications were metformin, valsartan, hydrochlorothiazide, nebivolol, aspirin, lercanidipine hydrochloride, levodopa and benserazide hydrochloride. The patient’s history included a TKA on the right side in 2000, a traumatic dislocation in 2011 and a revision arthroplasty in 2012 due to instability. These operations were performed under general anaesthesia without complications.
In February 2018, the patient presented to our orthopaedic outpatient department because of increasing pain in the right knee joint. Examinations showed implant loosening and Staphylococcus epidermidis infection. Therefore, the patient was scheduled for a two-stage revision with implant removal and antibiotic-loaded spacer implantation. Antibiotic therapy was deliberately withheld in view of the patient’s stable, non-septic clinical parameters and to better evaluate potential antibiotic sensitivities following surgical removal of the infected prosthesis. For pain management, she received a prescription for celecoxib and metamizole per os (PO), as well as subcutaneous antithrombotic prophylaxis with enoxaparin sodium. The patient was advised to follow the rest/ice/compression/elevation (RICE) protocol during the time until surgery.
In the premedication visit, the patient was classified as ASA III (according to the American Society of Anaesthesiologists) with a metabolic equivalent of ≥4. An electrocardiogram (ECG) and current lab values (erythrocytes 7.0 mmol/l; Hb 7.0 mmol/l; Hk 0.32 l/l; CRP 5.7 mg/l; all others were without abnormalities) had already been determined. The patient showed no signs of cardiopulmonary decompensation such as dyspnoea, oedema or auscultatory abnormalities at the time. On the day of surgery, 5 mg oxazepam PO and the patient’s usual medication, except metformin, valsartan and hydrochlorothiazide, were administered. The patient was informed that she could eat until 6 h before surgery and drink clear liquids until 2 h before surgery. The procedure was performed under general anaesthesia with endotracheal intubation. The initial vital parameters were a blood pressure (BP) of 160/80 mmHg and a heart rate (HR) of 65 bpm. Anaesthesia induction was performed under standard monitoring (non-invasive BP, HR and pulse oximetry) in the following order: propofol (180 mg) intravenous (IV), sufentanil (20 μg) IV and rocuronium (50 mg) IV. Sevoflurane (target value of minimal alveolar concentration of 0.8–0.9) and sufentanil (10 μg as a single IV bolus at the incision site) were used to maintain anaesthesia.
Furthermore, 1 g of tranexamic acid IV and balanced electrolyte solution (2 l of Jonosteril, which includes sodium chloride, sodium acetate trihydrate, potassium acetate, magnesium acetate tetrahydrate, calcium acetate) was given during the entire surgery. After anaesthesia induction, BP was 95/55 mmHg, and BP measurement was performed every 3 minand documented every 5 min. Because of a fall in blood pressure, the patient received norepinephrine (20 ml/h at 3 μg/min via IV perfusion) for 20 min to increase the mean arterial pressure to 65 mmHg. This regimen was performed directly after anaesthesia induction and was stopped at when the mean arterial pressure reached 65 mmHg, which occurred after 28 min (after the initial surgical incision). Thereafter, the patient was stable without catecholamines.
After incision and preparation of the knee, the surgeon observed pronounced synovitis and intramedullary femoral and tibial periprosthetic infected membranes. A smear was collected, and the patient received cefuroxime at 1.5 g IV. During the tibial component removal, spontaneously resolving episodes of asystole were observed on 3-lead-ECG. The asystole events were observed twice over a maximum of 2 s and depended on the surgical manipulation. Before any intervention, the events ended spontaneously with complete removal, and no haemodynamic changes were observed. Because of the short action and no haemodynamic changes, as well as the observation of stable blood pressure, we checked the 3-lead-ECG to exclude an artefact due to the manipulation and the high sensibility of the derivation. The operation proceeded without abnormalities until 45 min after incision, and the surgeon began the intramedullary reaming. This procedure led to a seven-second asystole again and was associated with a fast fall in BP (42/18 mmHg), oxygen saturation (68%) and end-tidal CO2 (21 mmHg). We informed the surgeon and interrupted the intervention. Epinephrine was prepared but not injected because at the same time, the asystole vanished. There was a complete recovery of haemodynamic parameters (92/56 mmHg; 98%; 42 mmHg). The heart rate was 52 bpm. The patient received 0.5 mg of atropine IV to prevent reproducible asystole for the rest of the procedure. Catecholamines were not necessary because of increased BP. Other reasons for asystole were checked, without any indication of a reversible cause. It is possible that the manipulations (reaming) led to pain with a vasovagal reaction, but around these events, the patient had no signs of pain, such as hypertension or tachycardia. From the advent of asystole until the end of the surgery, the depth of anaesthesia was monitored by the bispectral index (BIS), with no evidence of low anaesthesia (BIS score of 42) after the last event. According to our standard operation procedure, BIS was not indicated for this surgery, but we wanted to ensure an adequate depth of anaesthesia while minimising sevoflurane anaesthetic administration due to the patient’s comorbidities until the end of operation.
Extubating was performed without any problems. The patient received metamizole (1 g) at the end of surgery to prevent postoperative pain. In the recovery room, the patient first received a 12-channel ECG, which was without any abnormalities. Laboratory tests and blood gas analysis (troponin, BNP, CK-MB, D-Dimers, electrolytes) were performed to exclude ischaemia, embolic events, infarction or changes in electrolytes as the reason for asystole. We performed a case conference with our cardiologists. The subsequent transthoracic echocardiography was also without any abnormalities according to the age of our patient. Non-invasive cardiovascular investigations, such as repeated 12-channel-ECG, 24-h Holter monitoring and ultrasound of extracranial vessels, were performed. These investigations revealed minor supraventricular ectopic activity but were otherwise unremarkable. The cardiologist assumed that the patient had a vagal reaction when bone manipulations were performed by the surgeon and advised atropine IV (without recommendation of a dose) for the following operations.
Six weeks later, the patient underwent scheduled spacer removal and TKA. The patient received atropine IV (1 mg) after induction of anaesthesia to reach a higher HR and underwent invasive BP measurement and BIS monitoring. As the surgeon manipulated the medullary cavity, the patient developed a self-limiting episode of bradycardia (40 bpm) lasting only 3 s. No other events were recorded during surgery or hospital stay.


A three-year-old male child was admitted to the pediatric ward of Dr. Ruth KM Pfau, Civil Hospital Karachi (CHK) with a one-year history of generalized weakness, loose motions, decreased appetite and intermittent fever not associated with rigors, chills or night sweats, an eight-month history of inability to walk and sit, polydipsia, polyurea, abdominal distention and loss of neck holding for 14 days. He had a previous history of hospitalization six months ago due to the same complaints. The patient was accompanied by his mother. He weighed 6 kg, is the 7th born child to his parents and was delivered at term to a 37-year-old G7P7 mother via normal vaginal delivery. The mother did not report any complications or illnesses during pregnancy. He cried immediately after birth, and there were no complications during or after birth. There is no consanguinity between mother and father. The child was vaccinated but was malnourished, with an unremarkable family history.
The patient also developed diarrhea which was bulky in consistency, green in color with seven episodes per day after every meal intake. Diarrhea was associated with abdominal distention and vomiting. The mother then started giving him a combination of trimethoprim-sulfamethoxazole, after which diarrhea subsided. The child developed neck holding at four years of age, he started sitting at eight months and started walking with support at 12 months of age. The child was first breastfed within three hours of delivery and was exclusively breastfed up to six months. Complimentary feeding was started after six months with pulses, mashed potatoes, porridge and chicken. Breastfeeding was continued up to two years. Currently, the child takes 1-2 feeds per day. The personal history revealed that the patient was sleeping normally, but the appetite was decreased. The mother also noticed a weight loss, altered bowel habits, and micturition was normal.
On examination (O/E), the patient was lying on the bed irritated, severely wasted and emaciated with visible bony deformities. Initial vitals included blood pressure (BP) 110/70 mmHg, a regular pulse of 90 beats/min, a respiratory rate of 20 breaths/min, and a low-grade fever of 100° F. The patient was anemic and dehydrated, while, there was no presence of edema, clubbing, cyanosis, and lymphadenopathy. On further examination, parietal and frontal bossing, rachitic rosary (Figure ), widening of wrists and knock knees (it's a valgus deformity in which legs curve inwards so that the feet are apart when the knees are touching) were found as well. On abdominal examination, it was soft, non-tender, distended with mild tenderness on both flank regions, with a centrally placed umbilicus. The liver was palpable three fingers below the right costal margin. Gut sounds were audible 3-4 sounds/min. All other systems were unremarkable.
The anthropometric measures of the child are as follows: weight = 6.5 kg, occipitofrontal circumference = 49.5 cm, height = 72.5 cm, mid-upper arm circumference = 8 cm, upper segment = 45 cm, lower segment = 27.5 cm, weight for height = 6.5/9 *100 = 72.2 (moderately low) and height for age = 72.5/94.6*100 = 76.6 (severely low).
On investigations performed, complete blood count (CBC) showed a hemoglobin (Hb) of 5.4 gm/dl, mean corpuscular volume (MCV) of 82 fl and a platelet count of 187,000/mL. The total leukocyte count (TLC) was 10.6 x 109/L, including 39% neutrophils and 48% lymphocytes. His inflammatory markers were raised with a C-reactive protein (CRP) of 23 mg/L [Normal (N) = 3] and an elevated erythrocyte sedimentation rate (ESR) of 115 mm/hr (N = 0-22) for men and (N = 0-29) for women. The clotting profile showed an international normalized ratio (INR) of 1.01, while prothrombin time (PT) was 10.6 seconds.
The urea creatinine electrolytes (UCE) were within normal range except decreased potassium levels of 2.8 mEq/L. The levels of calcium, magnesium and phosphate in blood were 15.1, 1.9 and 4 mg/dL, respectively. The blood culture showed a growth of Burkholderia species. The urinalysis showed a pH of 5.0, specific gravity of 1.025, with the presence of protein and blood. Additionally, numerous red cells were seen along with yeast and 4-6 pus cells per high power field (HPF). The urine culture showed growth of Candida species. The stool analysis showed that the stool was hard, acidic, brown in color with 1-2 pus cells per HPF. His vitamin D levels came out to be 54.29 ng/mL, and parathyroid levels were 8.36 pg/ml. Liver function tests showed a total bilirubin of 0.28 mg/dL, direct bilirubin of 0.21 mg/dL and levels of alkaline phosphate alanine aminotransferase were 368 and 3 units per liter, respectively.
The X-rays of the chest (Figure ), skull (Figure ) and femur (Figure ) are attached below. Additionally, ultrasound of kidney ureters and bladder (KUB) showed an incidental finding of bilateral renal calculi (right kidney at lower pole measuring 0.7 cm, in the left kidney at mid pole measuring 0.7 cm), along with bilateral grade 2 renal parenchymal changes. The urinary bladder was normal in thickness with no presence of focal mass, calculus or diverticulum.
Considering the diagnosis of OI, an ophthalmology review was done to look for lens dislocation and blue sclera, but neither was present in both eyes. However, the left eye showed a corneal thinning nasally, temporally and inferiorly.
During the hospital stay, the patient was intravenously given cefotaxime 220 mg, piperacillin-tazobactam 700 mg, and meropenem three times a day. Additionally, linezolid 70 mg was injected every eight hours, along with injections of bisphosphonate 7 mg for three days, amikacin 55 mg twice a day for 14 days and fluconazole 85 mg loading dose, 45 mg once a day for 10 days. The patient was also given a teaspoon of the combination (artemether and lumefantrine) once a day. Three pints of red blood cells were transfused as well, after which his Hb became 10.6 mg/dL. During the stay, the child had a prolonged course of fever with pancytopenia, which improved on injections of meropenem, amikacin, and fluconazole.


The patient was a 55-year-old male entrepreneur, who had been experiencing pain of moderate intensity in the mid third of his left thigh for approximately 6 days. He sought emergency care at a hospital in response to a sudden increase in the intensity of the pain combined with swelling at the site of pain. He had a history of smoking equating to approximately 37 pack years. He did not have any other comorbidities. On physical examination he was slightly pale, with tachycardia (120 bpm) and blood pressure at 100 x 70 mmHg. Physical examination by segments was unremarkable for the head and neck, thorax, and abdomen. Vascular examination of the right lower limb found normal auscultation and visual inspection results, with all pulses present and normal. The left lower limb was well-perfused, but there was ecchymosis and a pulsatile swelling between the mid and distal thirds of the thigh, in the anteromedial region ( a). Inspection of the left foot also revealed signs of distal microembolization ( b) and popliteal and distal pulses were absent.
Ultrasonography of the left thigh showed an aneurysmal dilatation of the SFA measuring 5.8 x 5.3 cm and with associated mural thrombi and perivascular accumulations compatible with a ruptured aneurysm ( ). Since angiotomography was not available at the service providing care, the decision was taken to perform emergency surgical treatment.
During the procedure, extensive hematoma was observed involving subcutaneous and muscle tissues in the anteromedial region of the thigh. Once this had been removed, the ruptured SFA aneurysm could be seen ( 3b). There were no obvious signs of active infection. Proximal and distal ligatures were performed and then the aneurysm was resected and samples collected for anatomopathological and microbiological analyses. Revascularization of the limb was then accomplished by interposition of the contralateral great saphenous vein in reverse, with end-to-side anastomosis – taking into consideration the diameter of the femoral artery and the significant destruction of its walls, as illustrated in c. The contralateral saphenous vein was used both because of the probability of associated damage to deep veins in the limb involved in rupture and because of the greater likelihood of injury during dissection, due to anatomic distortions. There were no intercurrent conditions during the procedure
The patient was prescribed prolonged, wide-spectrum antibiotic therapy until the results of the microbiological culture of the aneurysmal fragment were available, showing no evidence of growth of microorganisms. The anatomopathological analysis found true aneurysmal walls, with no specific abnormalities. Supplementary imaging exams did not identify any additional aneurysms or any evidence of valve vegetations suggestive of endocarditis.
At 1-month follow-up, the patient had palpable distal pulses and was free from pain or other problems.


A 19-year-old female with no significant past medical history was referred to the emergency department from her antenatal clinic for further evaluation of fever 102 F, headache, malaise, nausea, and vomiting of 4-days duration following mild sore throat. She was in her 28th week of gestation on presentation. Physical examination showed an obese and anxious-appearing lady in mild respiratory distress with gravid abdomen. She weighed 142 kilograms (kg) with a BMI of 44.3. Her blood pressure was 111/60 mmHg, respiratory rate 24, heart rate 111, temperature 101.8 F, and oxygen saturation 96% on 2 liters (L) nasal cannula oxygen. She had dry mucous membranes, with no oral thrush or ulcers. Her abdomen was gravid with focal areas of tenderness, bowel sounds were heard, and fetal movement was detected. Pulmonary and cardiovascular examinations were unremarkable.
Her initial laboratory tests were significant for white blood cell (WBC) count of 11.8 K/uL with 78% neutrophil predominance and lymphopenia (0.77 K/uL). Although she had no urinary symptoms, urinalysis showed bacteriuria, confirmed as group B streptococcus agalactiae (GBS) with cultures. Initial chest X-ray and liver enzymes on admission were unremarkable. She was started on intravenous fluids for suspected gastroenteritis and oral cephalexin for asymptomatic GBS infection. Stool studies for clostridium difficile, comprehensive panel, ova, and parasites were ordered which all returned negative. However, she continued to spike fever through the third day of hospitalization prompting expansion of antibiotic coverage to Vancomycin and Zosyn (). Liver transaminases which had been normal began to spike. Aspartate aminotransferase (AST) was 190, alanine aminotransferase (AST) was 135, and alkaline phosphatase was 110 while bilirubin remained normal. Serum Tylenol and hepatitis A, B, and C serologies were negative. Infectious Disease (ID) consultation was requested who recommended further infectious work-up with CMV, EBV, HIV, HSV, Rickettsia, and Leptospira serologies.
The patient continued to spike high grade fever reaching 103 F on day 4 of admission despite being on broad-spectrum antibiotics and negative infectious work-up including the aforementioned serologies. She also developed bloody diarrhea and acute kidney injury (AKI) prompting evaluation for possible Hemolytic Uremic Syndrome (HUS) and autoimmune diseases which all returned negative as well. Right upper quadrant ultrasound showed normal liver and gallbladder morphologies. Magnetic resonance imaging of the abdomen and pelvis without contrast showed diffuse T2 hyperintensity throughout the liver compatible with acute liver injury but was negative for any focal intra-abdominal or pelvic abscess.
One week into her hospitalization, her AST and ALT kept trending up reaching a peak of 1712 U/L and 845 U/L, respectively (), mildly elevated alkaline phosphatase 140, INR 1.6, normal total bilirubin, absolute lymphocyte count of 0.11 K/uL, persistently negative blood cultures, and serum creatinine increased to 2.9 mg/dL, all concerning for a disseminated process. She became increasingly lethargic, tachycardic, and tachypneic necessitating care in the intensive care unit. With uprising liver enzymes and negative extensive infectious and rheumatologic work-up including Hep A, B, C serologies and PCR, EBV, CMV, Parvovirus, Rickettsia, and Leptospiral serologies, as well as negative HSV 1 and 2 IgM and IgG antibodies, antinuclear, and anti-liver-kidney microsomal antibodies, normal cryoglobulins, ceruloplasmin, alpha 1 antitrypsin and serum copper levels, and largely unremarkable imaging and stool studies, a decision was made to proceed with a liver biopsy. At this time, empiric acyclovir was started while other antibiotics were discontinued per ID recommendations.
Within the first 24 hours of starting acyclovir, AST and ALT began to downtrend while fever and diarrhea improved (). Despite negative HSV-2 serologies, the PCR was reported on hospital day-8 with a very high viral load >100 million DNA copies/ml following which she reported a remote history of cold sores but denied a history of genital ulcers. A diagnosis of HSV hepatitis was made and she was transitioned to Val-acyclovir 1 gram three times daily to complete 14 days of therapy, then to resume acyclovir 400 mg three times daily until delivery to prevent recurrence. On the 12th day of hospitalization, she was discharged home without needing a biopsy anymore and with complete resolution of symptoms and improvement of liver enzymes and AKI; AST 72, ALT 208, alkaline phosphatase 150, total bilirubin 0.5 and creatinine 0.5. She remained symptom-free with complete normalization of creatinine and liver enzymes at outpatient follow-up two weeks after discharge. She was eventually delivered of a healthy baby boy via cesarean section at 38 weeks of gestation with no peripartum complications.


In June 2011, a 56-year-old male was referred to our department by head and neck surgeon in order to improve his upper denture retention and stability. The patient was diagnosed with a squamous cell carcinoma of the maxillary gingiva (T4N0M0) in May 2005 and underwent an extended left maxillectomy, an anterior and middle cranial base resection, a left ophthalmectomy, and a flap reconstruction using the rectus abdominis muscle were performed. On physical examination, a recessed deformation on the left side of his face could be seen because of the left ophthalmectomy. The function of the left levator palpebrae muscle was eliminated to the level of a slight elevation by using the frontal muscle. A metal plate was anchored to the inferior wall of orbit. The left ethmoid bone, inferior nasal turbinate, the maxilla, alisphenoid, medial and lateral pterygoid muscle were already excised during the mesh titanium plate reconstruction of the anterior wall from the maxillary orbital region. Intraorally, the left maxilla had been excised from the midline, with the rectus abdominis muscle flap sutured directly to the soft palate. The peripheral mucous membrane around the left upper lip was already scarred, without the oral vestibule, and the flap margin had moved along with the surrounding soft tissue. The 70 × 50 mm flap was sagging from its weight and was in contact with the mandibular molars, reducing the volume of the oral cavity unless dentures were worn. The maxilla was removed from the midline to the maxillary tuberosity, while the mandible was removed from the anterior border of the ramus to the coronoid process. Dead space was eliminated because the abdominal rectus muscle was placed from the anterior cranial base to the oral cavity during reconstruction (Fig. ). No expiratory leakage or food reflux was observed, and the rhinopharyngeal closure was maintained. Prior to performing surgery, there was no tumor recurrence or metastasis. The patient had a mouth opening of 43 mm, which we judged operable and then conducted the flap reduction and elevation under general anesthesia in Dec 2008. Informed consent was obtained from the patient’s parents prior to study initiation, and all procedures were performed in accordance with the Declaration of Helsinki.
Surgical reconstruction was performed as follows:An incision was made from the buccal side of the sutured edge (scar) in the abdominal rectus muscle flap (Fig. ). We can conduct a vestibular extension at the same time by incising this position. The adipose tissue was peeled from the buccal side to slightly beyond the skin flap center while maintaining approximately 5 mm thickness. The adipose tissue was reduced using a radio knife (8 g) (Fig. ). When we reduce fat tissue, we must avoid perforating of the skin. The skin was incised directly above the zygomatic bone, with tissue separation (avoiding exposure of the plate) to enable easy visibility of the zygomatic bone. Subsequently, the subcutaneous tissue was peeled from the zygomatic bone to the oral cavity for tunneling. Three mini QUICKANCHOR® (Depuy Mitek Surgical Products, Inc. Raynham, MA, USA) anchors were placed in the zygomatic bone, and anchor sutures were drawn through the subcutaneous tissue to lift the skin flap. A modeling compound was used to shape the margin of the celluloid splint (Fig. ). The advantage of flap suspension using Mitek anchors is the simple operability, less anchor positioning limitation, and easier length adjustment of the thread for suspension, which lead to easier fixation of soft tissue without slackness as well as clinically sufficient strength for fixation of ligament and tissue. On the other hand, less than 4 mm thickness of the cortical bone for suture anchor fixation causes insufficient fixation, therefore, determining placing position on the bone for fixation is necessary. Consequently, due to the versatility, the position that is considered optimal for stronger fixation and more efficient suspension can be selected as the anchor placing position, while the periosteum, corium, and scar tissue that are thought the most suitable for maintaining the strength can be chosen for the suture thread. Regarding the anchor placing position in this case, we determined 3 positions on the zygomatic bone and sutured flap corium taking into consideration a complete maxillectomy had been completed, which resulted in being able to lift the flap outward and upward.
Postoperatively, the color of the skin flap was normal without congestion or necrosis. The celluloid splint was removed 10 days after the surgery with no infection or necrosis observed in the skin flap. We can find only fat, scar tissue, not carcinoma in the reduced fat tissure. At 3 months postoperatively, epithelialization and scarring were observed on the border of the skin flap and buccal mucosa, with no wound opening. Next, a denture that was stabilized to the right residual teeth with a clasp made. This prosthesis had two double Akers cast clasps unilaterally to retain the prosthesis by the four remaining molars. The major connector used anteria paratal plate. The patient was quite satisfied to be able to masticate, form an alimentary bolus, and swallow without any teeth falling out. No re-sagging of the skin flap or wound infection was observed at 3 years postoperatively. Patient follow-up will be continued at our department (Fig. ).


A 64-year-old Caucasian man with a lifelong history of thrombocytopenia was found with elevated total protein of 10.3 g/dl, serum monoclonal spike of 3.5 g/dl, immunoglobulin G (IgG) of 5371 mg/dl, and free lambda light chains of 703 mg/dl with free kappa/lambda ratio of 0.08. Calcium and renal function were within normal limits. Hemoglobin was 16.6 g/dL, and platelet count was 33 × 103/μL. Skeletal survey was negative for any lytic lesions. Bone marrow examination showed adequate megakaryocytes with normal platelet morphology, and no dysmegakaryopoiesis or micromegakaryocytes were seen on the bone marrow. Erythrocytes and granulocytes were adequate in number without any significant abnormality.
The past medical history included essential hypertension and hypogonadism, but without neuropathy or dermatologic conditions. The diagnosis of thrombocytopenia stemmed from childhood and was accompanied by a penetrant family history of thrombocytopenia seen in his mother, maternal aunt, brother, and son. No genetic cause of the thrombocytopenia had been established, and questioning found no personal or family history of physical deformity, vision, hearing, or bleeding disorders. Laboratory review of his platelet count history ranged from 30 to 50 × 103/μL.
Repeat testing of hemoglobin was 17.9 g/dl with hematocrit of 55.6%. Peripheral blood examination showed normal appearing red and white blood cells, with erythrocytosis, and morphologically normal platelets that were decreased in number. Erythropoietin level was normal (12.2 mIU/mL), and molecular testing found no mutations in JAK2 V617F or BCR/ABL1 (p190 and p210). The erythrocytosis was attributed to use of testosterone supplementation for hypogonadism. A limited congenital thrombocytopenia testing panel was ordered and resulted negative for mutations in myeloproliferative leukemia protein (MPL), runt-related transcription factor 1 (RUNX1), myosin heavy chain 9 (MYH9), and Wiskott–Aldrich syndrome (WAS) gene mutations. Flow cytometry for platelet associated autoantibodies. Anti-glycoprotein IIb/IIIa antibodies, anti-glycoprotein Ib/Ix antibodies, and anti-glycoprotein CD36 antibodies were also negative.
After a period of monitoring, his serum IgG increased to 7063 mg/dl and monoclonal-spike to 5.4 g/dl. Albumin level was 2.7 g/dl, and beta-2 microglobulin level was 2.52 mg/dl. Repeat bone marrow biopsy showed 70% plasma cells with adequate megakaryocytes and normal platelet morphology, and he was diagnosed with International Staging System (ISS) stage II IgG lambda multiple myeloma. Treatment was now indicated, however complicated given his marked thrombocytopenia.
He started treatment with pulse doses of dexamethasone (40 mg daily for 4 days) with subsequent addition of bortezomib at 0.4 mg/m2 with slow escalation to full dose (1.3 mg/m2) by week 3. Oral cyclophosphamide (600 mg/weekly) was added to this regimen during cycle 2. After 5 cycles of CyBorD (cyclophosphamide, bortezomib, and dexamethasone), the patient had normalization of IgG levels and decrease in M-spike to 0.62 g/dl consistent with a partial response. He was referred for consolidative melphalan-conditioned autologous stem cell transplant.
Stem cell mobilization with granulocyte colony-stimulating factor (10 mcg/kg × 5 doses and plerixafor 24 mg × 1 dose) resulted in peak white blood cell count of 151 × 103/μL and stem cell yield of 105.6 × 106 CD34+/kg in a single session (the highest recorded at our institution that year). The patient proceeded to high-dose melphalan (200 mg/m2) followed by infusion of 45 × 106 CD34+/kg autologous stem cells. Despite a robust and quick neutrophil engraftment on day +9, the patient encountered marked nausea and a severe pruritic skin rash that started after engraftment and lasted for 1-2 months, resembling a graft versus host reaction. After engraftment, his platelet count peaked as high as 84 × 103/μL on D + 21 before slowly declining back to his baseline of about 30 × 103/cells 6 weeks after transplant. He continued to have stable disease after autologous transplant and started lenalidomide maintenance with aspirin prophylaxis.
At a subsequent follow-up visit after autologous transplant, a more comprehensive 21-gene-inherited thrombocytopenia panel was sent, and a heterogeneous mutation of ANKRD26 c.-128G>A in the 5′ untranslated region (5′ UTR) of chromosome 10 was identified. This was consistent with a diagnosis of ANKRD26-RT. The patient continues to have persistent thrombocytopenia in the range of 30–50 × 103 platelets. Given his significant family penetrance of thrombocytopenia, the patient and family were referred to genetic counseling for further evaluation.


A 34-year-old Caucasian male presented with the incidental finding of anemia during a preliminary evaluation for rheumatoid arthritis. The patient was asymptomatic with the exception of a three-month history of wrist and ankle joint pain. Past medical history was positive for only a three-year history of occasional spotty, painless rectal bleeding attributed to internal hemorrhoids. Physical exam findings were positive for mild extremity pallor and positive fecal occult blood test. Hematologic studies revealed a significant microcytic, hypochromic anemia with severe iron deficiency. Laboratory studies revealed no evidence of vitamin deficiency, hemolytic activity, hematuria, hypothyroidism, or clotting factor disorder. Erythrocyte sedimentation rate (ESR), rheumatoid factor, and cyclic citrullinated peptide 3 (CCP3) were elevated supporting the diagnosis of underlying rheumatoid arthritis. On further questioning, the patient revealed that he had been utilizing an average of 2000 mg of ibuprofen daily during the previous several months in an attempt to control his joint pain. He was evaluated for a potential upper gastrointestinal bleed with an esophagogastroduodenoscopy (EGD), which found no evidence of active bleeding. As the patient continued to have decreasing hemoglobin levels, he was evaluated for a lower gastrointestinal source of bleeding by colonoscopy, which revealed an 8 cm circumferential mass at the anal verge (Figure ).
Pathological evaluation of biopsy samples revealed a moderately differentiated invasive adenocarcinoma. The patient had no family history of colorectal cancer or major associated risk factors, such as obesity, smoking history, heavy alcohol use, diabetes mellitus type 2, or a history of inflammatory bowel disease. Following discharge, positron emission tomography (PET) scan showed extensive metastatic disease to multiple regional lymph nodes as well as multiple suspicious hepatic lesions and bilateral pulmonary nodules. Due to the poor prognosis, recommended treatment consisted of folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX-4) along with palliative radiation.


A previously healthy 52-year-old Samoan woman initially presented to her primary care provider with complaints of otalgia and swelling in the left side of her face for three weeks. She reported no facial weakness, trismus, dysphagia, odynophagia, dental pain, fevers, chills, weight loss, and fatigue. On initial physical exam, a 6 cm nontender, subcutaneous, cystic mass was palpated in the left parotid. The oral cavity showed no deformities or evidence of abnormalities. There was no lymphadenopathy of the anterior or posterior cervical chain, supraclavicular, or axillary lymph nodes. At that time, she was prescribed with antibiotics for presumed sialadenitis with no effect on her symptoms. On the next follow-up visit, she was referred to otolaryngology for further evaluation.
A neck and chest computer topography (CT) scan demonstrated two necrotic left parotid masses measuring 2.5 × 2.8 cm and 2.7 × 2.8 cm, respectively, multiple ipsilateral lymph nodes measuring up to 1.9 cm in diameter, and an asymmetrically enhancing left nasopharynx. A fine needle aspiration (FNA) of an involved local lymph node revealed a nonkeratinizing, undifferentiated carcinoma composed of pleomorphic cells positive for Epstein-Barr virus (EBV). The differential diagnosis based on FNA findings includes primary parotid carcinoma, lymphoepithelial carcinoma, or metastatic nasopharyngeal carcinoma. Blind biopsies of the nasopharynx were negative. PET/CT revealed hypermetabolic activity in the left parotid gland and several local nodes, highly suggestive of a primary parotid neoplasm. Excisional biopsy revealed a nonkeratinizing, undifferentiated carcinoma composed of pleomorphic cells, positive for Epstein-Barr virus (EBV). The results of subsequent excisional biopsy of the parotid gland masses were consistent with previous FNA findings.
The patient was staged as Stage IVa (cT3N2bM0) per AJCC 7th ed. Due to the extension of the parotid disease toward the main trunk of cranial nerve (CN) VII, there was a concern for postoperative CN VII palsy with surgical management. Surgery was therefore deferred, and definitive cisplatin-based concurrent/chemoradiation treatment was initiated. On first surveillance PET/CT, at 12 weeks postconcurrent chemoradiation treatment, she was found to have PET-avid hepatic and bone lesions (). A CT-guided portacaval lymph node biopsy confirmed a metastatic disease (). IHC staining of the portal cava lymph node demonstrated 100% PD-L1 expression. Next Generation Sequencing was negative for additional mutations. Pembrolizumab monotherapy resulted in a near complete resolution of her hepatic metastasis and complete metabolic resolution of the left parotid mass, cervical adenopathy, and skeletal lesions on PET/CT following four cycles (). Follow-up PET/CT scan found a progression of disease per RECIST v1.1 criteria after seven months of treatment.


A 45-year-old obese postmenopausal female with a history of coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, and chronic angina was brought to the Emergency Department midsummer after a motor vehicle accident (MVA) in which she was the restrained driver. While stationary, she was struck by another vehicle from behind at a high rate of speed with immediate airbag deployment. Though the patient did not lose consciousness at the scene and had self-extricated prior to EMS arrival, she requested hospital transport for further evaluation of chest, neck, and back pain. On initial evaluation, the patient complained of chest pain primarily across her left chest and shoulder in a seatbelt-type distribution, though she did also endorse some bilateral chest wall pain, diffuse midline neck pain, and low back pain.
In addition to her cardiac risk factors, her medical history was significant for anxiety, gastroesophageal reflux disease (GERD), migraines, and fibromyalgia. Her home medications included escitalopram, buspirone, pantoprazole, ranitidine, aspirin, clopidogrel, evolocumab, and isosorbide mononitrate. She had an extensive surgical history including a total abdominal hysterectomy, bilateral salpingo-oophorectomy, coronary artery bypass grafting (CABG), and placement of coronary stents. She denied current use of tobacco, alcohol, or illicit drugs. She had just been admitted to the hospital for unstable angina a few months prior, at which time cardiac catheterization was performed, demonstrating three patent bypass grafts: right internal mammary artery (RIMA) to left anterior descending artery (LAD), left internal mammary artery (LIMA) to obtuse marginal artery, and a saphenous vein graft from the proximal aorta to the proximal right coronary artery (RCA). One saphenous vein graft from the posterior descending artery (PDA) to the posterolateral ventricular artery segment was occluded, though this was not a new finding as it was first discovered to be occluded several years ago. Both previously placed drug-eluding stents in the second marginal and left circumflex arteries were widely patent. The catheterization also demonstrated severely diseased and diffusely calcified coronary arteries, with 95% occlusion in the proximal LAD and 100% occlusion in both the first marginal artery and the mid to distal RCA. Of note, her stenosis had worsened since her last catheterization one year earlier, which showed 70% occlusion in the mid-LAD, 90% occlusion in the distal LAD, and 90% occlusion in the mid to distal RCA. No intervention was performed during either catheterization procedure.
Physical exam revealed that the patient was in notable distress and had diffuse midline spinal and paraspinal tenderness, as well as chest wall tenderness. Her pulse was 100/minute, temperature 37.6°C, blood pressure 157/119 mmHg, respiratory rate 16 breaths/min, and SpO2 99% on room air. Chest radiographs and head computed tomography (CT) scans were unremarkable, and the aorta had a normal course and caliber on thorax CT scan. Electrocardiogram (EKG) was also unremarkable, without any ST depression or elevation, T wave inversions, or QTc prolongation noted. Laboratory workup revealed an elevated troponin-T level at 0.564 [normal <0.010]. The patient was not hyponatremic. Three hours later, her troponin-T level decreased to 0.459. BNP, CK, and lactate levels were not obtained.
Cardiac contusion secondary to blunt chest trauma from the MVA was suspected as the initial diagnosis. The patient was admitted to the acute cardiology service and underwent a transthoracic echocardiogram the following morning, which demonstrated reduced systolic function with an ejection fraction of 35%, diffuse areas of mid to apical hypokinesis, and hyperkinesis in the anterior and inferior basal segments (). Previous echocardiograms completed three months and one year prior to this episode did not show these abnormalities; those studies lacked wall motion abnormalities and demonstrated normal systolic function with ejection fractions of 60% and 65%, respectively. Thus, these new wall motion abnormalities and reduced systolic function in conjunction with elevated cardiac enzymes, a normal electrocardiogram, and the patient's clinical presentation were consistent with a diagnosis of stress-induced cardiomyopathy.
She was started on a beta blocker and discharged the next day. A follow-up echocardiogram four months later demonstrated return of systolic function with an improved ejection fraction of 55% and normal wall motion, indicating complete resolution.


A 30-year-old male presented in December 2017 to the emergency department complaining of abdominal pain, which started around 3 am, and the pain was characterized as sharp, epigastric, nonradiating, and 9/10 in intensity. He admitted drinking alcohol, used to drink 5-6 glasses of wine/cocktails a day, but claimed he stopped a week ago, and he denied smoking or another illicit drug use.
Laboratory exams on admission were significant for lactic acid 3.7 (0.7-2.0 mmol/L), lipase >3000IU/L (11-82 IU/L), WBC 33,300 mmcu (4,000-11,000mmcu), and glucose 147mg/dl (70-99mg/dl). Patient underwent CT abdomen that showed acute pancreatitis. The next day patient glucose increased to 502mg/dl, bicarbonate was 18mg/dl (21-31mg/dl), and anion gap was 14. Patient then was transferred to Intensive Care Unit (ICU) for insulin infusion and management of diabetic ketoacidosis (DKA). His hemoglobin A1c was 5.5%.
Repeat CT abdomen with contrast () was concerning for necrotizing pancreatitis. After few days he was switched to subcutaneous insulin glargine/aspart and transferred back to general medical floor. Because patient developed fever and had persistent leukocytosis, and he was started on meropenem. His conditioned improved and antibiotics were changed to oral doxycycline and levofloxacin; he was discharged on insulin glargine 20U at bedtime and correctional insulin.
Patient continued to follow up as an outpatient. His blood sugars were ranging between 80 and 200 and A1c at the office visit was 4% in April 2017. Glargine was decreased to 15U nightly and sliding scale with meals was continued. In June 2017 glargine was reduced by a primary care provider to 7U due to symptomatic hypoglycemia. In July 2017 at an endocrinologist's office, A1c was 6.4%, and he allegedly reported daily fasting blood sugars ranging between 70 and 200. Glargine then was stopped and patient was advised to continue taking correctional aspart insulin to administer 3U if glucose>150 ().
In December 2017, while the patient was off glargine, A1c worsened to 8%. Patient was only using aspart as indicated and blood sugars were rarely >200s. Glargine was reinstated 5U nightly and Humalog started 4U with meals with an instruction not to take it if glucose was <110. However, in April 2018, HbA1c was 8.3% and he had episodes of symptomatic hypoglycemia. After further investigation, patient disclosed that, to avoid extra expenses, he used veterinary U-40 insulin syringes for the prescribed U100 insulin that he was getting from his wife, who herself worked in a veterinarian clinic. Unfortunately, he stopped checking his sugars regularly and on the next appointment in October 2018, HbA1c was 14%. Patient was taking glargine 8U at bedtime and Humalog 4 U if glucose was <150 and 7 U if glucose was 250-350 ().


A 59-year-old healthy Japanese female with chronic rhinitis was taken to our emergency department due to a sudden and painless left periorbital swelling following forceful nose-blowing. Examination revealed a gross swelling of the left eye. There was painless palpable emphysema around her left eye; she had normal eyeball movement and visual activity. By ophthalmic consultation, the intraocular pressure was found to be slightly higher in her left eye (20 mmHg) compared to the right (13 mmHg). Noncontrast CT revealed orbital subcutaneous and subconjunctival emphysema and fracture of the median orbital wall of the left eye. Focal herniation of extraconal fat into the ethmoid air cells was noted (). Otherwise, her extraocular muscles, optic nerve, and globe were unremarkable. The patient was treated conservatively with prophylactic administration of oral cefdinir and ofloxacin eye ointment and referred to her nearest doctor for outpatient follow-up. The patient was instructed to not blow her nose and advised regarding symptoms requiring immediate review. By the next day, the orbital swelling and periorbital emphysema had partially resolved with normal intraocular pressure.


A 21-year-old male with a history of one episode of right orchitis well treated with antibiotics two years ago presented to the urology outpatient department with a painless swelling of the right hemiscrotum without any associated other symptoms. Local examination revealed a palpable firm right testicular mass with atrophy of the whole testis. The left testis was palpated in the scrotum and is of normal size with no suspicious mass. His laboratory findings including Germ Cell Tumour serum markers were within the normal range (Alpha-fetoprotein (AFP): 0,86 μg/L, Beta human chorionic gonadotrophin (β-HCG) < 0,5 mIU/mL, and lactate dehydrogenase (LDH): 241 UI/ml).
Scrotal ultrasound () demonstrated a suspicious solid well-defined mass within the right epididymis, measuring 21 x 14 mm. The mass was slightly heterogeneous with hyperechoic appearance and regular smooth contour. Distinct from the lesion, the right testis appeared smaller in size measuring 23 x 12 x 15 mm. Imaging of the contralateral scrotum revealed no anomaly. A radical right orchiectomy was performed via an inguinal incision. Recovery was uneventful. The surgical specimen consisted of the right testis measuring 3.5x2.5x1 cm in size and of the spermatic cord measuring 5 cm in length. Sectioning of the specimen () revealed a single well circumscribed nodular tissue with multiple foci of hemorrhage. Microscopic examination of the nodular tissue () showed an admixture of mature lobulated adipose tissue and numerous dilated and thicken walled blood vessels with no signs of malignancies such as germ cell atypia or intraepithelial germ cell neoplasm. Thus a diagnosis of paratesticular angiolipoma was made.


A 61-year-old woman was referred by another institution with a diagnosis of distal transverse colon invasive adenocarcinoma and resectable liver metastases. Her past medical history revealed type 2 diabetes mellitus, hypertension, and chronic kidney disease. No relevant family history was noted. The case was discussed at the multidisciplinary tumor board meeting, and the decision was taken for the patient to undergo surgery for the primary tumor and subsequently address the treatment of liver metastases. A laparoscopic-assisted transverse colectomy with primary anastomosis was performed with no intraoperative complications. On the fourth postoperative day, she developed tachypnea, fever, and leukocytosis. A CT scan of the chest and abdomen with contrast was carried out. This showed a right middle lobe opacification consistent with pneumonia. A small <5 cm localized pelvic collection was noted; otherwise, the intra-abdominal organs including the spleen were unremarkable (). Blood cultures were negative. Conservative treatment with intravenous ciprofloxacin was initiated. Her condition slowly improved. However, three days later, she developed severe metabolic acidosis due to acute renal failure. She was shifted to the ICU and underwent urgent hemodialysis. Four days after starting hemodialysis, she complained of acute left upper abdominal pain and developed hypovolemic shock.
Laboratory investigations showed normochromic normocytic anemia (hemoglobin 8.7 g/dL (12-17), white cell count 20.8 × 109/L (4-11), platelet count 517 × 109/L (150-400), blood urea nitrogen 12.9 mmol/L (2.7-7.2), and creatinine 342 μmol/L (53-97)). Liver function tests showed an albumin of 14 g/L (34-50), alkaline phosphatase of 225 μ/L (54-144), prothrombin time of 16.1 (9.6-12.6), partial thromboplastin time of 36 sec. (24.3-30.2), and international normalized ratio of 1.5 (0.8-1.2).
Blood gases revealed a pH of 7.15 (7.3-7.4), pCO2 of 27 mmHg (36-46), HCO3 of 18.5 mmol/L (21-28), lactate of 1.5 mmol/L (0.5-1), and anion gap of 24.2.
A CT scan of the abdomen and pelvis showed a large subcapsular splenic hematoma with gas formation. There was no evidence of bowel perforation or obstruction ().
An emergency laparotomy was performed, and this showed a ruptured splenic hematoma. Peritoneal lavage and splenectomy were performed. Histology showed a necrotic spleen with fibrin and focal fat necrosis with no evidence of malignancy.
The patient made a slow but uneventful recovery and was eventually transferred to the nephrology unit to continue treatment for renal failure.


An 80-year-old African-American male presented to the University of Michigan Hospital and Health Systems Comprehensive Wound Center for ongoing care of a painful right foot fifth digit wound. He first noticed the lesion after stubbing the digit 2 months prior. He presented to his primary care doctor 1 month after the injury and the lesion was diagnosed as a diabetic foot ulcer (DFU). The lesion improved minimally with local wound care. Due to stagnation of the suspected DFU the patient presented to the wound center for further care. Upon initial wound center presentation, a granulomatous mass was noted to the medial aspect of the right fifth digit (Fig. ). A biopsy of the lesion was subsequently scheduled. However, upon presenting to the biopsy procedure, the patient stated the granulomatous mass had sloughed off in his sock the week prior leaving only a small partial-thickness ulcer (Fig. ). The patient elected to defer the biopsy as his symptoms had improved. The patient continued regular monthly follow-up at the wound center with development of his wound into two painful papules.
The patient’s past medical history was significant for type 2 diabetes mellitus T2DM, hypertension, hyperlipidemia, asthma, and dementia. He denied a family history of skin lesions and cancer. He did not take any immunosuppressive medication. The patient was a lifelong non-smoker and denied alcohol and illicit drug use. He was married, heterosexual and monogamous. At the time of presentation his last recorded hemoglobin A1c was 6.1%. Clinical examination revealed palpable pedal pulses with triphasic flow to the bilateral dorsalis pedis artery and posterior tibialis artery. His right hallux toe pressure was 126 mmHg and his left hallux toe pressure was 184 mmHg. He had diminished protective sensation, 2 out of 4 sites bilaterally, as tested with 10-g 5.07 Semmes-Weinstein monofilament as per American Diabetes Association guidelines []. To the medial aspect of the patient’s right fifth digit were two firm, cyanotic appearing papules. The distal papule measured 0.5 cm in diameter and the proximal papule measured 0.7 cm in diameter (Fig. ). There were no clinical signs of infection noted to the right foot. As the lesion caused moderate discomfort and did not improve despite 2 months of local care at the wound center, a biopsy of the lesion was again recommended.
After obtaining written informed consent a #15 blade was used to perform a shave biopsy of both the right fifth digit proximal and distal papules. The two specimens were labeled appropriately and sent separately to the University of Michigan Hospital and Health Systems pathology laboratory for assessment. The pathology report identified the specimen obtained from the distal papule as the superficial aspect of a hemorrhagic vascular lesion. The specimen from the proximal papule was identified as Kaposi sarcoma, nodular stage, transected at the deep margin. Hematoxylin and eosin stain demonstrated dermal nodules with haphazard spindle cell proliferation of endothelial cells forming vascular spaces which is diagnostic of classic KS (Fig. ). The tumor cells showed diagnostic positive staining for HHV-8 (Fig. ).
After the resulting classic KS diagnosis, the patient was referred to the Surgical Oncology Clinic at the University of Michigan Hospital and Health Systems. He underwent a series of blood tests to assess for underlying immunosuppression including HIV testing and a complete blood count with platelet and differential. He was determined to be HIV seronegative without any other clinical findings of immunosuppression. His case was reviewed by the University of Michigan Sarcoma Medical Oncology Department as well as the Multidisciplinary Sarcoma Tumor Board. The consensus of the combined board was local therapy with radiation without surgical intervention. The patient underwent 30 Gy of radiation in 10 fractions directed to the right foot fifth digit. The patient tolerated radiotherapy well and upon finishing his course of therapy, the KS lesion to the right foot had completely resolved. Upon a 10 month follow-up from initiation of radiation, the patient was disease free.


A 33-year-old female sought evaluation in our Department of General Surgery with a 2-year history of sporadic abdominal pain that had become aggravated during the past week. The character of pain became sharp and frequent. The pain was localized to the left lower abdomen. There was no nausea and vomiting. There was no history of abdominal trauma. The patient had a congenital anomaly of the kidneys and uterus; there was no menstruation. The patient had undergone an appendectomy in the past. On physical examination, the patient was afebrile. The abdominal examination revealed pain and a mass in the left lower quadrant area upon palpation. The mass was approximately 4 × 5 cm in diameters and was not circumscribed. The patient had no rebound tenderness and muscle rigidity. Laboratory testing revealed the following: white blood cell count, 7.13 × 109/L; neutrophilic granulocytes, 76.8%; hemoglobin, 120 g/L; and platelet count, 322 × 109/L. Computed tomography (CT) revealed an intestinal stromal tumor () and pelvic kidneys (). Digestive tract radiography showed possible extraintestinal involvement (). An intestinal stromal tumor was diagnosed and an abdominal laparotomy was performed; however, the intestinal tract was normal and a mass was noted in the sigmoid flexure. The tumor exhibited exophytic growth without infiltration and was 6.0 × 5.0 × 3.0 cm in size. The tumor and colon (proximal and distal length, 10 cm; ~25 cm) were excised. A rapid frozen section pathologic examination revealed a solitary fibrous tumor (SFT). A colon anastomosis was performed and the patient had fully recovered 7-days post-operatively. The final diagnosis was an ectopic ovary with corpora lutea bleeding (). The patient recovered well after surgery and there were no post-operative complications. The patient was doing well at the 11-month follow-up visit. Written informed consent was obtained from the patient and The Third People's Hospital of Dalian had approved the study (NO. 2018-LW-001).


A 23-year-old male with a history of migraine headaches for over 10 years was studied. The headaches responded favorably to usual analgesic treatment and worsened with physical exercise.
The patient looked for medical attention due to sudden and intense headaches in the occipital region with no evident cause, whose characteristics differed from the previous ones. An emergency computed tomography (CT) scan was performed, revealing the presence of a right occipital intracerebral hematoma that required immediate hospitalization and treatment for a month until resolution of the clot. One year after being symptom-free, he began to experience a mild to moderate oppressive headache in the right temporal region, which improved with analgesics for approximately 15 days. After that, the oppressive headache restarted with more intense hemicrania, accompanied by fatigue, short episodes of altered consciousness, sweating, multiple instances of projectile vomiting, and blurred vision of the left eye. General physical and neurological exams did not show any positive data, nor was there evidence of triggering events, such as traumatic brain injury, hematologic disorders, previous surgeries, or infections of the central nervous system (CNS).
Mood changes, including permanent irritability, aggressiveness, anxiety, diminished ability to think or concentrate, and temporo-spatial time disorientation, appeared during the follow-up period and a second CT-scan was performed.
Laboratory tests included the following: hemoglobin 133 g/L; leucocytes 8.1 × 103, platelets 373 u/L. A coagulogram indicated the following: suitable platelets, bleeding time 1.30 s, coagulation time 8 min, prothrombin time 15.2 s (control 13 s ± 3), and activated thromboplastin time 30 s; glycemia 4.83 mmol/L; glutamic oxaloacetic transaminase (GOT) 42.51 U/L; glutamic oxaloacetic transaminase (GPT) 42.29 U/L; cholesterol 4.24 mmol/L; triglycerides 0.90 mmol/L; creatinin 82.81 μmol/L; uric acid 280 μmol/L; total protein 72.15 g/L; albumin 41.30 g/L; negative human immunodeficiency virus (HIV) and non-reactive Venereal Disease Research Laboratory (VDRL).
Urgent multislice tomography showed a laminar SDH in the right fronto-parietal region, a posterior interhemispheric fissure at the level of the tentorium, and ipsilateral occipital intracerebral hematoma (2.2 × 2.3 cm in axial section), with a volume of 7 mL. These lesions produced a slight mass effect on the neighboring structures, and the midline was displaced 0.5 cm ().
Both hematomas were reabsorbed gradually (), with satisfactory clinical evolution after a two-month follow-up period. shows the increased frontal subdural hematoma and its extension to parietal and frontal lobes. Angiography revealed ecstatic cortical veins, one of them with saccular dilatation adjacent to the IPH (). For this reason, we decided to perform cerebral angiography, which confirmed the dural arteriovenous fistula. It connected the artery, a branch of the external carotid artery, with cortical veins in the superior sagittal sinus drainage (). After endovascular therapy, the evolution of the patient was satisfactory ( and ). Two years later, no bleeding had appeared, and the subsequent angiographic studies were negative.


A 44-year-old Japanese male, an office worker, was transported to our emergency department with a complaint of temporary loss of consciousness. He had experienced fatigue for 3 years and had fallen easily in his daily life starting 2 months before admission. He was feverish and had a cough and phlegm for several days before admission. On the way to work, he felt drowsy and fell down the stairs of the train station, necessitating transport to our hospital by ambulance. The peripheral blood analysis noted mild elevation of white blood cells. The blood chemistry test disclosed mild elevation of C-reactive protein and mild liver dysfunction (). He was thin, i.e., his height was 174 cm and he weighed 52 kg (). Chest computed tomography (CT) showed severe infiltration in the upper posterior fields of both lungs as well as food debris in the esophagus. He was diagnosed as having aspiration pneumonia. His past medical history included diabetes mellitus that had been treated by a local doctor; glycated hemoglobin was approximately 7%. He had experienced ileus six times since age 30 years. He was not married. His father had died of dilated cardiomyopathy at the age of 70 and had also been thin. On the other hand, his mother was healthy but his maternal uncle was diabetic. His younger sister (Case 2) also had mild muscle weakness of the four extremities. Aspiration pneumonia was treated by intravenous administration of antibiotics under conditions of food-take restriction combined with temporary insulin infusion, and the respiratory symptoms subsided. On the neurological examinations after improvement of pneumonia, he presented with typical clinical manifestations of DM1 (), such as forehead balding, hatchet face with bilateral ptosis, nasal speech, mild muscle weakness of the four extremities, handgrip myotonia, and diffuse muscle atrophy. Electromyography performed to test the biceps brachii muscle and femoral quadriceps muscle on the left side revealed frequent myotonic discharges. Because DM1 was strongly suspected, we recommended that, after providing informed consent during genetic counseling, he undergo genetic testing for DM1 together with his younger sister. The number of CTG repeats in the DMPK gene was abnormally expanded to about 600 repeats in the elder brother and about 900 repeats in the younger sister, in contrast to those of healthy individuals who have 5 to 37 repeats (), thereby confirming the diagnosis of DM1 in these siblings ().


His younger sister was a 41-year-old woman, a housewife. She was obese according to the Japanese criteria (), i.e., she was 156 cm in height, weighing 69.6 kg (102 cm waist circumference and a 164.2 cm2 visceral fat area calculated employing abdominal CT). Slightly impaired fasting glucose levels had been pointed out on her medical check-ups since 3 years earlier, but she had never consulted a doctor. She had noted repeated falls and injuries for the past 5–6 years. She had married at the age of 37 and had undergone infertility treatment. When she was admitted for detailed examination to our hospital, she showed distal muscle weakness of the four extremities as described above, handgrip myotonia, and distal muscle atrophy, which were consistent with the characteristics of DM1. The laboratory data showed elevated fasting glucose with dyslipidemia, which met the Japanese criteria for metabolic syndrome (MetS) () (), and an oral glucose tolerance test using 75 gram glucose showed impaired glucose tolerance (IGT) (), followed by starting treatment with diet and exercise. Based on the presence of MetS, a sleep study was conducted using an apnomonitor Type 4 (SAS-2100, NIHON KOHDEN, Tokyo, Japan) () (, , ). The apnea-hypopnea index (AHI) was defined as the average number of apnea and hypopnea episodes per hour of recording time in bed. The younger sister's AHI was high at 55.9, which suggested that she had severe SAS, as defined by an AHI of 30 or more, though no snoring, apneic episodes, nocturnal dyspnea or signs of daytime somnolence were observed (, ). Her arterial blood gas (ABG) showed hypoxia accompanied by hypercapnia and her lung function test, using spirometry (CHESTAC-8900, Chest, Tokyo, Japan), revealed a decreased percent predicted vital capacity (VC) of 67.9% while Forced Expiratory Volume in 1 s (FEV1)/ Forced Vital Capacity (FVC) (Gaensler index) was adequate at 87.9% () ().
We then also analyzed the respiratory function of the elder brother (Case 1), although, like his sister, he had not complained of voluntary symptoms suggestive of SAS. His AHI examined using an apnomonitor Type 4 was 55.1 and his ABG showed CO2 retention without hypoxemia (). His percent predicted VC was decreased, at 51.9%, while the Gaensler index was sufficient at 93.9%, similar to his sister's values (). His aspiration pneumonia was regarded as possibly being due to DM1, which can cause expiratory muscle weakness. The indications for non-invasive positive pressure ventilation (NPPV) were assessed by an experienced pulmonologist. Based on chronic alveolar hypoventilation (patients with decreased percent predicted VC are at high risk), diurnal hypercapnia (PaCO2 ≥ 45 mmHg) according to the ABG, evidence of nocturnal hypoventilation on nocturnal pulse-oximetry, defined as SpO2 < 92% more than 4 times during the entire sleep time or >4% of the entire sleep time as well as AHI≥10 events/h, these two siblings were started on NPPV. The NPPV consisted of 6 cmH2O of inspiratory positive airway pressure, 4 cmH2O of expiratory positive airway pressure and a 12 bpm back-up rate in spontaneous/timed mode during sleep (, , –). These two siblings have been followed at outpatient care by the same pulmonologist and there has been no apparent worsening of symptoms since starting NPPV therapy. Both patients have shown good compliance. The ABG of the brother revealed slight elevation of PaCO2, that is, pH 7.4, PaCO2 51.5 mmHg, PaO2 76.9 mmHg, HC 28.5 mmol/l, BE 2.1 mmol/l, and SaO2 95%. Because the sister's arteries are very thin, making it difficult for us to determine her ABG, spirometry was performed 3 months after initiating NPPV therapy and revealed almost no interval changes as compared to the baseline data before starting NPPV, with the direct value of VC being 1.9 L, VC 68.3% pred, direct value of FVC 1.84 L, FVC 66.2% pred, direct value of FEV1 1.52 L, FEV1 59.4% pred, and FEV1% (Gaensler index; FEV1/FVC) 101.8%.
As to other complications, the brother showed negative results on brain magnetic resonance imaging (MRI), echocardiography, abdominal ultrasound and, except for the diabetes, on endocrinologic examinations (). The sister underwent brain MRI which showed localized white matter hyperintense lesions in the right temporal lobe, a common finding in DM1 (), which may have accounted for her hypoventilation (). Other studies including echocardiography, abdominal ultrasound, and endocrinological examinations yielded essentially normal results except for cataracts and IGT.


A 46-year-old male with a past medical history of hypertension presented to our trauma bay with complex injuries of the right nose and midface, which included an amputated nose, upper lip and right eyebrow approximately 40 minutes after an assault including numerous human bite wounds. His right ala, right sidewall, and right upper lip were entirely missing, with nasal airways on each side visible. The amputated specimens included nasal tissue which measured approximately 4.0 x 4.0 cm, the eyebrow 2.0 x 2.0 cm, and the upper lip 1.0 x 11.7 cm (Figure ). After rapid sequence intubation, assessment, and stabilization, the patient was taken to the operating room about one hour after the initial presentation for reattachment and wound reconstruction.
In the OR, the superior labial artery and a small outflow vein, which was likely part of the superior labial venous plexus, were identified and isolated from the lateral portion of the lip. However, the nasal segment contained no identifiable viable artery or vein. Therefore, the nasal and eyebrow portions were replanted similarly to full thickness skin grafts and the upper lip was replanted using microvascular techniques. The segments of each vessel were flushed with heparinized saline. Then, the superior labial artery was anastomosed using 9-0 nylon interrupted sutures, followed by anastomosis of the vein using 9-0 nylon. After three hours and 19 minutes of operating time, arterial blood flow was immediately apparent, but venous flow was not definitive. The wounds of the upper eyelid and right cheek were debrided and then closed.
To improve the chance of tissue survival, our patient was scheduled to receive hyperbaric oxygen treatment within 24 hours post-operation. However, the patient reported that his ears could not tolerate the pressure and therapy was postponed until otolaryngology could insert tubes at the bedside. Additionally, he was receiving 30 mg of enoxaparin daily to mitigate the chance of outflow venous thrombosis. The replaced nasal and eyebrow tissue and the microsurgically replanted upper lip appeared to have some minor ischemia at the lateral margins (particularly of the nasal tip) that would most likely require revision, but the majority of the three portions appeared healthy (Figure ).
Later that day, the patient reported upper extremity numbness. After a non-contrast CT showed no intracranial abnormality, he received 8.34 mg bolus of tPA followed by 75.1 mg of IV tPA over the course of an hour for possible ischemic stroke. Subsequent MRI showed a small acute left frontal cortical infarction. The next morning the patient reported chest discomfort and an EKG showed ST-segment elevation of inferior leads with elevated troponin peak of 132.2 due to myocardial infarction. The patient then underwent left heart catheterization that showed adequate flow and no need for further intervention. After these events, he received 30 mg of enoxaparin twice a day per protocol.
After tPA treatment, there was marked continuous sanguineous discharge from the replant sites and the eyebrow, nose, and upper lip began to appear increasingly dusky. Our patient was determined to be a high-risk candidate for immediate revision surgery and plans for secondary reconstruction were made. The patient returned six days later for facial wound debridement of necrotic wounds of the upper lip, nose, and right forehead with subsequent placement of Integra artificial dermis (Figure ). He subsequently underwent nose and upper lip advancement flaps to save oral competence. A month later, nasal reconstruction was undertaken with a left paramedian forehead flap and full-thickness skin graft to upper lip and nose. The second stage of reconstruction was done one month later including the second stage of the paramedian flap, ear cartilage graft to the nose, and full-thickness skin graft of the upper lip (Figure ). Subsequent reconstruction one month later included an Abbe flap from the lower lip to the upper lip and final revision of the forehead flap. Overall, our patient was satisfied with the cosmetic and functional outcome of his reconstruction four months after his final surgery (Figure ).


A 54-year-old Chinese man consulted a medical doctor with the complaint of recent painful neck and right upper limb without any clear causes. He had a medical history of left traumatic humeral fracture 10 years ago that did not significantly affect his recent daily life after surgery. The patient had no recent history of head or spinal trauma and did not take any related antiplatelet or anticoagulant drugs. In addition, the patient had no exposure to any toxic substances and no significant relevant family history. A clinical diagnosis of cervical spondylosis was originally considered based on X-rays of the cervical spine, and the patient received small needle-scalpel treatment for relieving pain relief, which was administered by a rural doctor. When no obvious improvement was observed 20 days later, the patient was admitted to our hospital for further diagnosis and treatment. The patient was experiencing progressive neurologic deterioration involving both upper and lower limbs. Upon neurological evaluation, he exhibited reduced response to light touch and pinprick, with a sensory level below the angle of the mandible. He had trouble during urination and significantly decreased muscle tension. He was subsequently incapable of antigravity power in his upper limbs (the left and right muscle strength was graded as 4/5 and 2/5, respectively) and had a significant loss of motor function in both lower extremities (the muscle strength was graded as 1/5). Urgent magnetic resonance imaging (MRI) of the cervical spine demonstrated a right spinal epidural hematoma located at the posterior spinal epidural space with severe cord compression and subcutaneous soft tissue hemorrhage, extending from the C2 to C7 spinal vertebral level (). Routine laboratory investigations indicated that renal and liver functions, serum potassium and coagulation index were normal. Given his progressive symptoms and MRI results, the diagnosis of cervical extradural hematoma was finally considered. The patient had received the ventilatory and adjunctive therapy, omeprazole, mannitol, and a high dose of steroids after the diagnosis of cervical extradural hematoma. Unfortunately, the patient refused urgent surgery; thus, he continued to progressively deteriorate and later died due to respiratory failure.


The presented case is a 68-year-old female patient with BMI 26, ASA score II, ECOG performance status 0, CR POSSUM operative severity score 6 with mortality prediction 1%, with hypothyroidism and high blood pressure, non-smoker, with a history of Billroth II gastric resection, cholecystectomy and choledochoduodenostomy. The patient exhibited suspected neoplastic lesion of the liver with negative CT guided biopsy. The workup included gastroscopy with chronic gastritis and subsequent colonoscopy with extensive benign polyp of lateral spreading tumor type 15 cm from the anal verge with size 30 × 25 × 25 mm and non-lifting phenomenon contraindicated for endoscopic treatment. A low anterior resection was carried out. The anastomosis was performed with a circular stapler approximately 10 cm from the anal verge. The only peroperative complication was bleeding from sacral excavation with a blood loss of approximately 800 ml. On the fourth postoperative day, septic shock with CT-confirmed inflammatory changes in small pelvis and peritoneal cavity effusion without a confirmed leak. Skin inflammation of the right groin and femoral region developed. Broad-spectrum antibiotics and surgical revision under general anesthesia with abdominal washing and diverting ileostomy was performed. Further intensive care required broad-spectrum antibiotics, the circulation was supported with small doses of norepinephrine. In the following course, general and local clinical conditions were still worsening with localized skin necrosis and maximum SOFA score 12 (Respiratory system +2, Nervous system +3, Cardiovascular system +3, Liver 0, Coagulation +3, Kidneys +1) with 80% mortality risk.
On the 8th postoperative day, severe necrotic tissue infection in the right groin and a presacral anastomotic leak were confirmed (). Endoscopy showed a 3 cm wide anastomotic dehiscence on the ventrolateral margin with a 5 cm long cavity and pelvic necrotic tissue (). Necrectomy of necrotic skin and soft tissue extending to right lower pelvis was carried out and drained with subsequently proven Enterococcus and Pseudomonas infection (). The leak was managed by EVAC with an extraluminal installation.
The technique consisted of sigmoidoscopic determination of the leak, measuring of the cavity, lavage and necrectomy and application of the foam using overtube. The negative pressure was set to 50–75 mmHg, subsequently to 100–125 mmHg. In the course of EVAC therapy, clinical status was rapidly improved. A total of 6 procedures were performed until there was a defect of 1 cm in diameter. The whole hospital stay took 40 days, the ICU stay 16 days.
Colonoscopy 3 months after surgery showed a healed anastomosis without remanent cavity, fistula or stenosis (). The skin defects were healed after 117 days, the ileostomy was restored 14 months after primary surgery. Within 3 years of follow-up, no rectal fistula, stenosis or continence impairment occurred. The liver lesion disappeared, thus suspected to be caused by ascending biliary infection following choledochoduodenostomy.


A previously healthy, athletic 16-year-old boy (body surface area 1.82 mm2) was transferred to our cardiac institution with a 9-day history of a sustained high fever complicated by diarrhea and abdominal pain. He had no history of allergic disease such as bronchial asthma, or known drug allergies. He had received oral cefdinir for a few days for suspected bacterial enterocolitis two weeks previously. His symptoms had been resistant to the antibiotics and antipyretic medications given in the prior tertiary center. Upon arrival at our center, he exhibited cardiogenic shock with a body temperature of 40.5°, heart rate 107 beats/min (irregular), systolic pressure 90, and diastolic pressure ranging from 30 to 75 mmHg (measured by oscillometric method, unstable), and respiratory rate 48/min. He was mostly conscious but occasionally stuporous. No jugular distension, limb edema, or skin rash was observed. His peripheral body was cold despite his body trunk being warm. On auscultation, he had regularly irregular muffled heart sounds without a significant murmur, and some rales bibasally. The electrocardiogram revealed tachycardia, sinus rhythm, right axis deviation, nonspecific ST-T change, and clockwise rotation (). His chest radiograph showed prominent pulmonary edema, accumulation of pleural effusion, and an enlarged cardiac shadow (). Echocardiography showed LV systolic dysfunction—LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) = 130/76 mL; LV ejection fraction (LVEF) 42%—a mildly thickened and echogenic LV wall, and a modest amount of pericardial effusion, without visible intraventricular thrombus (). Blood tests showed respiratory alkalosis, high concentration of markers of cardiac injury (troponin I 1843.6 pg/mL [upper limit of normal: 26.2 pg/mL]), heart failure (plasma brain natriuretic peptide 2671.1 pg/mL [18.4 pg/mL]), evidence of an inflammatory response (white blood cell count 8.5 × 103/μL with neutrophils 93% and eosinophils 1.5% and serum C-reactive protein 29 mg/dL), mild hepatic failure (aspartate aminotransferase 145 U/L [38 U/L] and alanine aminotransferase 100 U/L [44 U/L]), and almost unimpaired renal function (blood urea nitrogen 26 mg/dL [20 mg/dL] and creatinine 1.2 mg/dL [1.08 mg/dL]). The myeloperoxidase-anti-neutrophil cytoplasmic antibody was below the detectable range.
Despite inotropic support and fluid resuscitation, his systolic blood pressure suddenly fell to 80 mmHg in the middle of the initial evaluation. Based on the clinical diagnosis of cardiogenic shock, an Impella 2.5 was immediately inserted into the right femoral artery via a 12-Fr sheath, followed by a right-ventricular (RV) endomyocardial biopsy (EMB) via the right internal jugular. Intact coronary arteries were subsequently confirmed by coronary angiography. Chest radiography after Impella placement showed alleviated pulmonary edema () together with elevation of the mean arterial pressure from 51 to 72 mmHg, although the LVEF was decreased to 27% (; Supplementary ). Because of his high sustained fever, fluid resuscitation with extracellular fluid and blood products (approximately 6 L/day) was required to maintain the mean arterial pressure >55 mmHg. However, the mean pulmonary wedge pressure was mildly elevated (10–13 mmHg) without the patient displaying radiographic pulmonary edema.
Within 48 h after admission, eosinophilic myocarditis was diagnosed based on the histological findings (). Immunosuppressive therapy consisting of methylprednisolone 1000 mg/day for 3 days followed by prednisolone 1 mg/kg/day and azathioprine 2 mg/kg/day was commenced, which improved his LV systolic function in the short term (LVEF 47% by day 6) and decreased the body temperature, leading to hemodynamic stabilization. The doses of inotropes required to maintain stable hemodynamics during Impella use were decreased by day 4 (maximum dose of dobutamine was 2.2 μg/kg/min and of dopamine 1.5 μg/kg/min on days 1 and 2).
He was gradually, day by day, weaned from the Impella, decreasing from the P8 to P2 level without showing marked end-organ failure. The Impella was surgically removed on day 7, with his postremoval blood pressure at 120/70 mmHg and heart rate at 65 beats/min on with minimal inotropic support (dobutamine and dopamine, 3.0 μg/kg/min each) to avoid sudden hemodynamic deterioration immediately after removal of the MCS. He was extubated on day 8, followed by initiation of antiheart failure medications (e.g., angiotensin-converting-enzyme inhibitor and β-blocking agent) to prevent further remodeling. The follow-up EMB, performed 2 weeks after his admission, revealed improved infiltration of eosinophils and lymphocytes and some degree of fibrosis (Supplementary ). Azathioprine was tapered off, whereas prednisolone dose was gradually tapered to 30 mg/day. He was discharged from hospital 6 weeks after the admission without a major complication ().
Thallium-201 and iodine (I)-123 β-methyl-p-iodophenylpentadecanoic acid (BMIPP) dual-tracer myocardial scintigraphy 3 weeks after admission showed a patchy deficit of perfusion at the anterolateral wall and a discordantly larger deficit of fatty acid metabolism (perfusion-metabolism mismatch), suggesting regional myocardial damage with potential reversibility ().
Cardiac 1.5-T magnetic resonance imaging (CMR) 4 weeks after admission showed no high-intensity areas on T2-weighted imaging or late-gadolinium enhancement (LGE), but prolonged native T1 mapping at papillary muscle level, indicating myocardial edema (; Supplementary ).
At discharge from the hospital, follow-up chest radiography revealed diminishing cardiomegaly with no pulmonary congestion (). At the same time echocardiography showed recovery of contractility with LVEF 60% (). The patient was weaned off steroid therapy 5 months after the onset of his myocarditis and showed no evidence of recurrence in the subsequent 7 months.


A 77-year-old man was seen in the radiation oncology center at our hospital because of a persistently elevated serum level of prostate-specific antigen (PSA) in March 7, 2016. Ten years earlier, he was found to have a PSA level of 52.736 ng/ml at his annual physical examination. And pelvic MRI revealed an evidence of PCa. The reminder of the examination is unremarkable. Thus, a systematic transrectal ultrasound-guided biopsy in February 7, 2007 demonstrated bilateral focus of adenocarcinoma (Gleason score, 9 out of 10 [left side, grade 4 plus grade5]; 7 out of 10 [right side, grade 3 plus grade 4]). The patient was treated with radical prostatectomy (RP) because of the definite diagnosis on March 8, 2007. Surgical pathology showed no tumor invasion in the left and right seminal vesicles and deferens, and no metastasis was found in bilateral iliac lymph nodes, but with bladder neck invasion. So, the pretreatment clinical and postoperative pathologic features suggested that he fell into pT4N0M0 stage and the National Comprehensive Cancer Network high-risk group. Following surgery, the patient was regularly monitored serum level of PSA. And it decreased to 0.001 ng/ml 25 days after RP. However, 2 consecutive follow-up PSA values higher than 0.2 ng/ml approximately 2 months after RP. Casodex was then used as one of an adjuvant therapy at another institution at May 10, 2007, due to consideration of the BCR. During the next 9 years, he was treated with different endocrine agents because of unstable serum levels of PSA, which including leuprorelin, goserelin, flutamide. Nevertheless, the serum level of testosterone was maintained at castration level, but serum levels of PSA still elevated. Until February 22, 2016, the pelvic MRI showed a nodule in the prostate and should be further confirmed whether it was a local recurrence (Fig. ). After MDT discussion, the current diagnoses of this patient were:
Postoperative PCa, high risk;
CRPC;
local recurrence.
According to the absence of clear guidelines, treatment options at this stage are difficult to choose. Generally, there are several possible treatment options as follows:
continuous androgen-deprivation therapy (ADT);
secondary surgery;
salvage radiation therapy (SRT);
systemic treatment with docetaxel or other medicine, or
other treatments.
In our institution, PCa MDT was carried out for this patient, and then the SRT was suggested for the patients. Therefore, the patient underwent pelvic RT from March 10, 2016 to May 3, 2016 with a total dose of 200 cGy × 37 F = 7400 cGy. The target area was the prostate tumor bed area + local recurrence area. Each stage of field modification was based on diffusion images of the patient with MR, in order to minimize the doses of organs at risk, while maximizing the radiation doses of locally recurrent lesions. After 37 fractions of RT treatment, he underwent follow-up examinations every 3 months. The serum levels of PSA were all between 0 and 0.007 ng/ml, and serum levels of testosterone were between 41.9 and 188.7 ng/dl. After 1 year of RT, the pelvic MRI scan in June 26, 2017 showed no evidence of nodules in the prostate region and no enlarged lymph nodes were found in the pelvic cavity (Fig. ). And EPIC26 scale assessment revealed leak-free urine, good urine control, no defecation abnormalities or blood in the stool, no breast tenderness and breast enlargement significantly improved. The patient now has no adjuvant therapy, including endocrine therapy. Quality of life intact, and is still under follow-up, the specific course of disease and related treatment shown in Figure .


Our patient was a 41-year-old Japanese man who had had occasional discomfort in the right knee since elementary school. He had no pain at rest, but he experienced occasional pain when moving the knee. The pain had made it difficult for him to sit on his heels (Japanese seiza position) for the past year. Although he had undergone radiography and MRI examinations at several hospitals since childhood, no issues were reported; subsequently, he consulted our hospital.
At the time of his consultation, physical examination showed mild swelling and a loss of range of motion. The active range of motion of the knee was 30 degrees of extension and 120 degrees of flexion, improving to 10 degrees of extension when relaxed in a recumbent position. He had no instability of the knee. He had an intense fear of a sensation that something was caught in his knee joint. Blood test results were unremarkable. There was no tenderness at the femorotibial (FT) joint level. However, he complained of discomfort proximally, near the patellofemoral (PF) joint to the medial pouch. Careful palpation revealed an elastic soft tissue mass measuring about 3 cm. When his lower leg was hanging down while he was in a seated position, the blood vessels centered on this area became engorged.
X-rays showed no obvious findings. MRI showed a mass measuring about 40 × 12 × 15 mm (Fig. a, b, ovals). The mass was homogeneous with a low intensity on T1-weighted sequences and high intensity on T2-weighted sequences adjacent to the medial femoral condyle. The shape of the medial femoral condyle presented with a concavity in axial images, with irregular margins from the PF to the medial femoral condyle. There were no abnormal signals in the intraosseous tissue. Suspecting a hemangioma, we performed MRA of the patient’s leg. The results showed a hyperintense region on the medial side of the knee joint, consistent with that seen on an MRI scan (Fig. , circle). Moreover, another hyperintense region measuring about 2 cm was also observed near the lateral femoral condyle (Fig. , arrowhead) and was suspected to be an extra-articular hemangioma. All evidence suggested intermediate-type hemangioma.
We performed surgery with the patient under general anesthesia. When his lower leg was hanging down on an operating table, remarkable engorgement of the blood vessels was observed. Arthroscopic examination was performed to confirm the nature, location, and extent of the mass (Fig. ). The findings revealed a soft tissue mass that had grown from the PF to the medial pouch; the mass had spread from the medial epicondyle to the medial articular surface and was pinched by extension of the knee. The hyperintense region revealed by MRA was found at the lateral femoral condyle. There was no damage to the meniscus. A small incision to the lateral mass for subcutaneous access revealed a multilocular soft tissue mass measuring about 2 cm penetrating through the fascia of the vastus lateralis; the mass had the obvious appearance of a hemangioma. Because some of the engorged blood vessels were connected to the joint, we added an incision into the articular capsule. The mass infiltrated the synovial wall of the suprapatellar pouch; thus, the mass, measuring about 20 × 18 × 10 mm, was excised en bloc. On the basis of a report of synovial hemangioma occurring outside the knee joint [], our patient’s case was considered to be a synovial hemangioma of the intermediate type originating from the intra-articular synovia, which was connected from the intra-articular region to the extra-articular region. With regard to the medial mass, because of its very large size, we decided to perform open surgery and visually identified the mass. The size of the mass was about 40 × 16 × 7 mm, and it spanned from the medial epicondyle to the medial articular surface. A part of the mass was attached to the cortex of the medial femoral condyle. We detached the mass from the bone surface and excised it. Upon resection, the medial condyle was observed to be dimpled with the shape of a crater (Fig. ). The spread of the mass suggested a diffuse-type synovial hemangioma. Under direct observation, we performed complete hemostasis and sutured each layer. Histopathological diagnosis indicated a hemangioma originating from the synovial membrane or subsynovial connective tissue, as well as irregular arteriovenous connections (Fig. ). Ultimately, the diagnosis of this patient was a diffused intermediate-type synovial hemangioma. The patient became asymptomatic after surgery, with no recurrence for more than 4 years.


Patient 1, a 59 year-old male with no past medical history, presented with wrist pain. An x-ray study of the right wrist demonstrated advanced arthritis in his area of symptoms, but also extensive calcification of both radial and ulnar arteries (). Based on this finding, further discussion regarding the presence of peripheral vascular disease and cardiac disease was undertaken. The patient denied any personal history of symptoms or previous cardiac workup. It was suggested that the patient considers further evaluation including a CAC score. The scan identified a total coronary calcium score of 424 which indicates extensive plaque burden. Based upon age-adjusted population data, this patient is at a high risk of a future cardiac event.


Patient 2, a 60 year-old otherwise healthy man, presented with pain in his right wrist which developed acutely when lifting a heavy machine. The x-ray study demonstrated scapholunate widening and radiocarpal arthrosis in addition to significant calcification of his ulnar artery which is most clearly seen on the lateral radiograph (). Similar to Patient 1, additional history revealed no prior symptoms or workup for CAD. A CAC score of 174 was interpreted as evidence of moderate calcium plaque with possible areas of significant narrowing. All of the calcifications were found in the left anterior descending artery.


Patient 3, a 59 year-old male with a 37-year history of diabetes but no known cardiac disease, also presented with wrist pain prompting an x-ray demonstrating scapholunate advanced collapse as well as arterial calcification (). A CAC score of 1412 indicated significant coronary disease.


A 71-year-old female with a past medical history of bilateral ductal carcinoma in situ, hypertension, and recent bilateral knee replacement presented to the emergency department with worsening headaches, confusion, photophobia, fevers and fatigue. Initial vital signs were temperature of 38.4°C, heart rate of 123 beats/min, blood pressure 164/97 mmHg and oxygen saturation at 98% on room air. Physical exam revealed lethargy, irritability and nuchal rigidity. Workup demonstrated WBC of 11,400/μL, Hgb of 10.8 g/dl, platelets 347,000/μL. Head CT was unremarkable. Lumbar puncture showed elevated nucleated cells with neutrophilic predominance. She was started on empiric therapy with vancomycin, ceftriaxone, trimethoprim-sulfamethoxazole (TMP-SMX, or bactrim) to cover for Listeria (penicillin was listed as an allergy) and acyclovir. Cerebrospinal fluid (CSF), herpes simplex virus (HSV), polymerase chain reaction (PCR) and culture returned negative, thus vancomycin, acyclovir and bactrim were discontinued after three days. Ceftriaxone was continued to complete a seven-day course. At this point, patient’s presenting symptomatology was resolving.
On hospital day six, platelets dropped to 1,000/μL. With 1 unit of platelet transfusion, platelets increased to 73,000/μL, but down trended to zero. Figure illustrates the platelet count over the course of the patient's hospital stay. A peripheral blood smear showed zero platelets per high power field, with no noted schistocytes or platelet clumping. Immature platelet fraction was 30.7%, indicative of peripheral destruction with appropriate marrow response. Patient’s hemoglobin remained stable during her hospital course with no clinical evidence of bleeding. The patient received prophylactic heparin during hospitalization with a 4T score of 3, suggesting a low probability of heparin-induced thrombocytopenia. Vitamin B12 and copper were within normal limits. Given the timing and severity of thrombocytopenia after being on three antibiotics commonly associated (bactrim, vancomycin and ceftriaxone), DITP was suspected. Ceftriaxone was discontinued and she was started on dexamethasone 40 mg/day for four days. Platelets began to uptrend as can be seen in Figure . Platelet count at the time of discharge was 155,000/μL and 346,000/μL at a three-week follow-up. Post discharge, serum antibody testing returned positive for ceftriaxone-dependent platelet reactive IgG antibodies and negative for vancomycin and bactrim, further supporting the diagnosis of DITP secondary to ceftriaxone.


A 48-year-old Caucasian male with a past medical history of hypertension presented to the emergency department (ED) with epigastric abdominal pain, nausea, and vomiting. Vitals were stable. Lipase was elevated to over 600, alanine transaminase was 46, and aspartate transaminase was 41. All other labs were within normal limits. An abdominal computed tomography (CT) with contrast was done immediately, which demonstrated edema of the pancreas and peripancreatic collection of fluid, indicating acute pancreatitis (Figure ).
Per-oral (PO) pain medication was initiated, as there was difficulty in achieving intravenous (IV) access, so the patient was unable to receive IV fluids. Oral rehydration was encouraged. Due to the intractable uncontrolled pain, the patient was transferred. Upon transfer, the IV line was secured and fluids were started. However, due to the persistence of epigastric pain, a repeat CT abdomen without contrast was performed to ascertain whether the pancreatitis was worsening or if other differentials should be considered. On this CT, thrombosis of the hepatic vein and splenic vein was evident (Figure ).
The patient was started on a heparin drip while pancreatitis symptoms eventually dissipated with supportive treatment. The patient was transitioned to PO blood thinners and discharged with follow-up.


A 28-year-old man presented at our hospital after a fall from his bicycle. He complained of right shoulder pain and the inability to move his right arm. The patient had a history of right ACJ dislocation because of a fall from his bicycle seven months earlier (Fig. a). He had undergone a right ACJ reconstruction with a suture-button (Zimmer Biomet, Warsaw, IN) and a hook plate (HOYA Technosurgical, Shinjuku, Tokyo, Japan) at another hospital (Fig. b). The suture-button passed from the clavicle to the coracoid via a 4.5 mm drill hole. After ACJ reconstruction, the hook plate was removed four months ago while X-ray radiography image before the removal suggested widening of the suture hole (Fig. c).
At the time of the present visit, a deformity of the right distal clavicle and loss of range of the right shoulder motion were observed. There were no findings suggestive of nerve or vascular injury. X-ray radiography images revealed a right clavicle fracture at the suture hole (Fig. ). Due to significant dislocation of the clavicle, removal of a suture-button, open reduction and internal fixation were scheduled.
Intraoperative findings demonstrated a fracture through the suture hole and multiple drilling holes near the suture hole (Fig. ). After the end-button of the coracoid process was detected and gripped with forceps, the suture was cut and the suture-button removed. Thereafter, open reduction was performed, and internal fixation was completed with a plate (Stryker, Kalamazoo, MI) (Fig. ).


A was a 50 year old, admitted to psychiatric hospital under Section 38 of the UK Mental Health Act (which allows a court of law to send a patient to hospital for assessment and treatment before being sentenced) after she pleaded guilty to a charge of arson. She was brought to court by her landlord for deliberately setting fire to her home. At time of transfer to neuropsychiatry, she had neurological features typical of early stage HD including chorea and dystonia.
A was the main carer for her mother who had HD. Aged 27 yrs. she developed depression and anxiety becoming morbidly obese as she would comfort eat when anxious. A positive genetic test for HD at 43 yrs. triggered the first of many suicide attempts, suicide threats and episodes of self-harm. Several years later, events culminated with neighbours calling emergency services to put out a fire in her living room and she was arrested on suspicion of arson.
On admission A stated she would rather die than live with HD and was placed on close supervision as fire setting remained a risk. Increased physiotherapy input resulted in improved gait and posture through exercise and she enjoyed escorted community leave. A behavioural program using a token economy to address her aggression was implemented and home visits subsequently facilitated. Two years after admission there was an increase in levels of anger and frustration which the patient herself attributed to worsening mobility and falls. Cognitive decline with marked impulsivity was evident and she frequently required seclusion. Three years later she was discharged to a nursing home as she was no longer independently mobile and risk to self and others was therefore much reduced.