A 35-year-old female was admitted to our outpatients' clinic with a compliant of an eight-month history of right heel pain which had increased gradually in the past two months. The pain of the patient often occurred at night and it was not related with daily or sporting activities and most commonly felt at rest. Her symptoms started insidiously and she did not mention any trauma. She had been smoking 20 cigarettes per day for 10 years, and she did not suffer from any medical condition. Furthermore, no hereditary disease was found in the patient's family history.
Physical examination revealed no abnormal findings. Her blood tests were all normal, including all the inflammatory markers. The patient underwent plain radiograph examination and a 21-millimeter-diameter cystic lesion was observed in the long axis of the calcaneus. The magnetic resonance imaging (MRI) examination was applied for the confirmation and it showed 22 × 20 mm intraosseous cystic lesion at the posterior part of the calcaneus which revealed hypointense signal on T1-weighted images and hyperintense signal on T2-weighted images (). The contrast-enhanced MRI was not available for this patient.
Although the lesion was radiologically benign, extended curettage and iliac bone grafting were planned to exclude the malignancy risk that may be caused by smoking history. The operation was performed under spinal anesthesia. After bone grafting from the right ilium was completed, tourniquet was applied to the right thigh. A lateral approach to the calcaneus was used. After opening a 10 × 10 mm valve from the lateral aspect of the calcaneus, the cyst was excised and the cyst walls were debrided by burr. After preparation of the area, the cavity was filled with bone grafts.
Microscopic examination revealed compact hypercellular areas with spindle cells which show nuclear palisading around fibrillary process in some areas. There was no mitotic activity. Diffuse expression of S-100 protein was observed with immunohistochemical staining, and Ki-67 proliferation index was observed around 5% at the highest level ().
In the presence of these findings, histopathologic diagnosis of the patient was reported as intraosseous schwannoma. Postoperatively, short leg splint was applied until the sutures were removed (). Ankle function exercises were begun at the second week after surgery. After 4 weeks of nonweight-bearing, she completely recovered with no pain at the end of the 2nd month.


A 36-year-old Brazilian male patient was admitted to the hospital with a palpable lump in his right breast, located at the junction of the upper quadrants of the right breast (Fig. ). On physical examination, the lesion appeared firm with irregular margins. Axillary lymphadenopathy was negative and there were no palpable supraclavicular nodes. On breast imaging, ultrasonography showed a hypoechoic mass with partially defined contours measuring 4.0 × 3.0 cm, located at the upper region of the right pectoralis major muscle at the 12 o’clock position with muscle infiltration (Fig. ). Histological examination of core biopsy samples revealed a malignant tumor. Preoperative exams, such as X-rays and chest CT scan, abdominal US did not show any signs of disease. Radical mastectomy was then performed, due to pectoralis major muscle infiltration, consisting in removal of the breast along with the major and minor pectoralis muscles. Biopsy of the sentinel lymph node was performed. Gross examination revealed a solid tumor measuring 3.7 × 3.5 cm with a yellowish-tan cut surface and local foci of hemorrhage. Histopathology showed intravascular papillary proliferation of endothelial cells, spindle cell areas and necrosis, atypia and prominent mitotic figures, consistent with the diagnosis of high-grade angiosarcoma with areas of infiltration of the pectoralis major muscle (HE staining, magnification of 400×) (Fig. ). Histopathology also demonstrated a surgical specimen with clear margins, absence of angiolymphatic and perineural invasion, in addition to sentinel lymph node free of metastasis. Immunohistochemical study revealed a tumor positive for CD31 marker (Fig. ), confirming the vascular nature of the tumor. At the two-week follow-up of the surgical procedure, adequate wound healing was observed, without any evidence of the disease. The patient was transferred to the clinical oncology department, where he presented with severe headache and seizures after the second cycle of adjuvant chemotherapy with paclitaxel. Magnetic resonance imaging of the brain was ordered, revealing a right frontal parasagittal lesion, measuring 1.3 × 1.1 cm with a hemorrhagic component and perilesional edema, suggestive of brain metastasis. The disease progressed rapidly, culminating in the patient’s death at 20 days after the onset of neurological symptoms.


A 3-year-old Caucasian girl presented to the emergency room of a community hospital complaining of abdominal pain. After 3 hours, an abdominal X-ray showed a coin lithium battery (CR 2025) located in the fundus of her stomach (Fig. ); she was transferred to a referral pediatric hospital. After 6 hours, she developed massive hematemesis and severe hypovolemic shock. The indicated computed tomography (CT) scan was not done due to her severe hemodynamic instability, and the surgeon decided to perform esophagogastroscopy to directly diagnose and treat. She was then referred to the operating room. Urgent endoscopy was unsuccessful because of the large amount of blood and clots in her esophagus and in her stomach, which prevented the localization both of the bleeding site and of the coin battery. Consequently, an emergency laparotomy was attempted (8 hours after the presentation of symptoms), and the coin battery was manually identified in the gastric fundus. The surgeon then performed a gastrotomy to directly visualize the area of interest, remove the coin battery, and treat the presumable bleeding site. Despite removal of the coin battery from her stomach, and suturing of the burned area, the child still had hematemesis and hypovolemic shock. A Sengstaken–Blakemore tube was placed in order to stop further misunderstood esophageal bleeding sources along the transit area of the foreign body. She was then referred to our tertiary referral center, and directly to the operating room. Clinical conditions at admission were critical, multiple blood transfusions and high-dose vasopressors could not maintain her blood pressure. Endoscopy showed a massive bleeding localized in the medium esophagus (Fig. ). The Sengstaken tube was removed. To treat the massive esophageal hemorrhage, a 20 mm endoscopic dilation balloon (CRE PRO; Boston Scientific, EU) was inflated directly over the bleeding site. The partial reduction of the bleeding allowed an attempt at angiography, although there was a high clinical suspicion of AEF. Percutaneous cannulation of her left common femoral artery was attempted, followed by insertion of a 0.35 Bentson wire, advancement of a 5 Fr sheath, and insertion of a marker pigtail catheter. An aortogram was obtained in a left anterior oblique projection, and revealed extravasation of contrast, confirming the suspicion of an aortic rupture just above the diaphragmatic plane (Fig. ). The Bentson wire was retrieved, and an Amplatz Super Stiff™ wire (Boston Scientific, USA) was introduced. An 11 Fr sheath was then advanced over the wire and placed in her common femoral artery. Considering the life-threatening condition, an endovascular stent was released to stop the massive blood flow. A covered balloon-expandable stainless steel stent of 16 × 61 mm (Advanta™ V12; Atrium Medical Corporation, USA) was placed across the rupture in the thoracic aorta (Fig. ), and dilated up to 12 atm, which corresponds to a nominal pressure to avoid aortic wall injury. After the deflation of both balloons (endoscopic and angiographic), hemodynamic stability was achieved. A hemostatic endoscopic powder (Hemospray®; Cook Medical, Ireland) was sprayed directly on the residual bleeding sites, achieving complete hemostasis. During the entire procedure, our patient was given 2 units of packed red blood cells (estimated blood volume 1520 ml) []. The final angiogram revealed a resolution of the aortic leak, with a good expansion of the stent. She maintained hemodynamic stability, had palpable pedal pulse postoperatively, and was admitted to the intensive care unit, where her hematocrit level and hemodynamics remained stable. A CT angiography confirmed the correct placement of the aortic stent, and no evidence of leakage of contrast dye injected in the esophagus.
After 72 hours, the orotracheal tube was removed, and she started to breathe spontaneously again. After 1 week we endoscopically placed a nasoduodenal tube to start enteral feeding. Every 7 days, esophagogastroduodenoscopies (EGDs) were performed to follow the complete mucosal healing, and after 1 month, she started eating again, and was discharged home.
The 1-year endoscopic examination showed only complete re-epithelialization on the previous esophageal bleeding site (Fig. ). A 3-year follow-up was uneventful.
Four consecutive CT scans (one every 12 months) showed the correct position of the angiographic stent and no other pathologic signs.
Our patient is being followed-up by our cardiology team.


A 58-year-old Japanese woman was admitted to our hospital by ambulance because of a 1-week history of malaise, lumbago, and fever of unknown origin. She had no relevant medical history and no family history. She was a nonsmoker, but she had drunk about 60 to 80 g of alcohol per day for 30 years. Liver dysfunction had been noted for the past 10 years.
On admission, her height was 158 cm, weight 56.2 kg, and body temperature 39.5 °C. Her blood pressure was 101/60 mmHg. Her heart rate was 106 beats per minute. A physical examination showed no major abnormalities. She was alert but short of breath on exertion, with an arterial blood oxygen saturation of 94%, partial oxygen pressure of 72.0 mmHg, and partial carbon dioxide pressure of 27.2 mmHg. A chest radiograph showed no obvious signs suggesting pneumonia or pulmonary congestion. Electrocardiography showed sinus tachycardia and no other abnormalities. Plain computed tomography of the neck, chest, and abdomen and ultrasound of the abdomen revealed no significant abnormalities except for fatty change of the liver. Laboratory tests showed an elevated white blood cell count; elevated levels of serum liver enzymes, blood urea nitrogen, creatinine, uric acid, C-reactive protein (CRP), and serum brain natriuretic peptide; hypoproteinemia; and hypokalemia (Table ). Serum rheumatoid factor was negative. Urinalysis was positive for ketone bodies, but the urinary sediment showed no abnormalities. Cultures of blood, urine, and sputum were carried out on admission. Intravenous administration of sulbactam/ampicillin (SBT/ABPC) (9 g/day) was begun from the day of hospitalization.
On day 2, the patient remained febrile. The sputum culture showed no significant growth of pathogenic bacteria, and the urine culture was sterile. However, gram-negative rods were detected in the blood culture. Subsequent echocardiography revealed two vegetations, one of which was attached to the anterior leaflet of the MV and was approximately 4 × 1 mm in size (Fig. ). The other was attached to the chorda tendinea adjacent to the posterior papillary muscle, and its size was larger (10 × 2 mm) than that of the MV vegetation (Fig. ). Based on these findings, combined antibiotics including SBT/ABPC (9 g/day) and gentamycin (GM) (80 mg/day) were administered on day 2. Repeated blood cultures were also performed on days 2 and 3, and all culture sets were positive for gram-negative rods, which were proven to be pansensitive E. coli on day 6. Based on these findings, the patient was diagnosed with IE due to E. coli in accordance with the modified Duke criteria []. An ophthalmologist and dermatologist also examined her on day 6, but they observed no remarkable findings associated with IE. Contrast-enhanced computed tomography of the chest and abdomen on day 7 showed no remarkable findings; magnetic resonance imaging (MRI) and magnetic resonance angiography of the brain on day 8 also showed no abnormalities.
After antibiotic medication including SBT/ABPC and GM, the patient’s general condition improved. Her body temperature normalized on day 5, and her white blood cell count returned to a normal level (8600/mm3); her CRP level significantly decreased (5.09 mg/dL) on day 6. Blood culture analysis on day 7 and thereafter revealed no bacterial growth, but her CRP level remained mildly elevated (about 2.0 mg/dL). Echocardiography on day 14 showed a decrease in the size of the vegetations; those attached to the MV and chorda tendinea were 2 × 1 and 5 × 1 mm, respectively. However, the patient developed severe lumbago on day 20. Her white blood cell count was normal (5900/mm3), but her CRP level had increased to 3.1 mg/dL. MRI of the lumbar spine on day 21 revealed purulent spondylitis lesions in the L1 and L2 lumbar vertebrae. Intravenous meropenem (6 g/day) was substituted for SBT/ABPC and GM on day 21 despite the sterile blood culture. The patient’s clinical course was good thereafter; her lumbago improved. Transthoracic echocardiography on day 35 revealed complete resolution of the vegetations. On day 54, her CRP level decreased to 0.34 mg/dL. Administration of meropenem was terminated, and she was discharged from our hospital on day 56. After discharge, oral levofloxacin (500 mg/day) was administered for 2 months in accordance with the suggestions of orthopedic surgeons. Her CRP level normalized after 2 months. Both upper endoscopy and colonoscopy performed 3 months after discharge showed no abnormalities. MRI findings of the lumbar spine normalized after 7 months. She also stopped drinking alcohol for 12 months and remained well during that time.


The patient was a 78-year-old Chinese gentleman who presented with fever, cough, diarrhoea and vomiting, of 1 day duration. Significant comorbidities included ischaemic heart disease (IHD), chronic obstructive pulmonary disease (COPD), bronchiectasis, peptic ulcer disease, hypertension and hyperlipidaemia.
Other than bilateral crepitations in the lung, the physical examination was otherwise unremarkable. Initial investigations were significant for a mild leucocytosis, acute kidney injury and mild hypokalaemia (Table ). Chest and abdominal radiographs were unremarkable. Treatment was initiated for an infective exacerbation of bronchiectasis. Blood cultures and stool microbiology studies were sent off, and intravenous Co-amoxiclav and hydration were started.
Blood culture initially was reported as positive of gram negative rod. An ultrasound of abdomen was done. It showed no intra-abdominal abscess. Over the next few days, stool and blood cultures came back positive for non-typhoidal Salmonella species sensitive to ampicillin, ceftriaxone and cotrimoxazole. Salmonella serovar was not specified due to the hospital laboratory protocol. A computed tomography (CT) aortogram (Fig. ) was done to look for aortitis as our patient has significant atherosclerosis. It did not show aortitis; however, an enlarged (11–12 mm in diameter), fluid filled appendix with hyperenhancement of the wall, minimal adjacent fat stranding and small mesenteric nodes in the right iliac fossa, was found. This was consistent with acute inflammation of the appendix and likely reactive lymphadenopathy. There was no evidence of abscess or perforation. A surgical and radiological consult was obtained, both agreed that the findings were in keeping with acute appendicitis. The decision was made to proceed with conservative management in view of poor premorbid status and multiple comorbid conditions.
The patient completed 2 weeks of intravenous ceftriaxone. Repeat blood culture did not show persistent salmonella bacteraemia. Acute kidney injury resolved and the patient was discharged well.


A 53-year-old male denied past medical and trauma history presented to our hospital with blurred vision of his right eye for one week with floaters and obscured sensation over nasal visual field. Ocular examination showed a 120 degree retinal tear (from 7 to 11 o’clock) with large inverted rigid flap and retinal detachment from 6 to 12 o’clock with macula-off in his right eye (Fig. ). The grading of proliferative vitreoretinopathy (PVR) was “Grade C”. The BCVA of his right eye was only naming digit at his first presentation. Under the impression of GRT with retinal detachment, 23-gauge pars plana vitrectomy were performed using Constellation high speed vitrectomy system (Alcon Surgical, Fort Worth, TX, USA) and Topcon non-contact wide angle viewing system (Topcon Medical Inc. Livermore, CA, USA). During surgery, the temporal retina was noted to have a rolled and stiffened edge at the posterior aspect of the giant retinal tear (Fig. ). The vitreous was removed and tractions were relieved as much as possible, then perfluorocarbon liquids (PFCL) was injected to help unfolding the large inverted retinal flap (Fig. ). Three stainless steel retinal tacks were inserted along the posterior edge of the giant retinal tear using a modified Southerland intraocular forceps [] to help fixating the large inverted retinal flap (Fig. and ). Then, fluid-gas exchange, endolaser photocoagulation and intraocular silicone oil tamponade were performed as well (Fig. ). Initial reattachment of his right retina was achieved and his best corrected visual acuity improved to 0.3 of his right eye postoperatively. There was no recurrent retinal detachment during follow up period of 19 months (Figs. and ).


A 56-year-old Japanese woman presented with right-sided Bell’s palsy due to dysfunction of the facial nerve (VII) in October 2013. She had been diagnosed as having rheumatoid arthritis in August 2013 and treated with methotrexate orally. She had no relevant medical family history. Methotrexate was discontinued when she suffered from Bell’s palsy. Her condition improved following oral administration of 30 mg of prednisolone/day. Soon after prednisolone was discontinued in November 2013, methotrexate was resumed. In March 2014, she was admitted to a general hospital due to the appearance of bilateral floaters. Her best corrected visual acuity was 20/20 in her right eye and 20/25 in her left eye; an ophthalmological examination revealed bilateral granulomatous uveitis. Chest computed tomography (CT) revealed bilateral hilar lymphadenopathy and mediastinal lymph node swelling. Laboratory tests revealed elevated levels of serum angiotensin-converting enzyme (ACE) (35.0 IU/L; normal, 8.3–21.4 IU/L). She was histologically diagnosed as having sarcoidosis following skin and transbronchial lung biopsies. In February 2015, she developed dysphagia due to dysfunction of the vagus nerve (X), following which she was treated with 30 mg of prednisolone/day. Following an improvement in her symptoms, prednisolone dosage was tapered to 4 mg/day by August 2015. However, she experienced recurrence of nerve VII palsy in November 2015, despite continued treatment with 4 mg of prednisolone/day. In December 2015, magnetic resonance imaging (MRI) revealed brain parenchyma lesions (Fig. ), although no neurological symptoms, such as motor/sensory paralysis or paresthesia, were observed. In January 2016, she experienced recurrence of nerve X palsy, following which she was treated again with 30 mg of prednisolone/day. In May 2016 (prednisolone, 20 mg/day), she exhibited increased intraocular pressure (IOP) in her right eye and was referred to our hospital for treatment.
At the initial visit, her best corrected visual acuity was 20/20 in her right eye and 20/28 in her left eye. The IOP was 40 mmHg in her right and 14 mmHg in her left eye. There was no inflammation in the anterior chamber, although massive, diffuse vitreous opacities were observed in both eyes (Fig. ). Retinal periphlebitis and macular edema were detected using fluorescence angiography. In July 2016, she underwent trabeculectomy of her right eye, following which the right eye IOP decreased to 10 mmHg. No postoperative inflammation was observed. As a result, 20 mg of prednisolone/day was continued, and she experienced no worsening of brain parenchyma lesions or recurrence of cranial nerve palsy to date. The clinical course is presented in Fig. .


A 13-year-old female presented to pediatric otolaryngology clinic for follow-up of a left-sided tongue mass, first detected in 2015, which was recently getting bigger and causing dental problems and difficulties with chewing. The patient has a past medical history of NF2, with bilateral acoustic neuromas (also known as vestibular schwannomas), diagnosed more than 10 years ago. During this period, she underwent removal of a right optic nerve glioma and several neurofibromas of the skin. She also has a strong family history of NF2, with her father and two sisters also diagnosed with NF2.
Oral cavity examination revealed a well circumscribed mass on the left anterior tip of the tongue (). The mass was approximately 2.0 x 2.0 cm, nontender, and nonerythematous. Clinically, it appeared to be a tongue neural tumor associated with NF2.
Excisional biopsy of the tongue mass was performed under general anesthesia. The mass was removed with 2.0 mm margins around the lesion (). The postoperative period was uneventful. Gross examination of the specimen revealed a 1.7 x 1.4 x 0.5 cm nodule, which was serially sectioned to reveal multiple, well circumscribed white fibrous nodules ranging from 0.1 to 0.7 cm, with the largest nodule abutting the surgical margin.
Histopathological examination revealed a spindle cell tumor with multinodular growth pattern, resulting from interlacing fascicles of Schwann cells (plexiform growth) (). Most of the tumor consists of cellular areas (Antoni type A) with Verocay bodies, formed by palisading of nuclei and separated by cell processes of Schwann cells (). Immunohistochemical analysis revealed the tumor cells to be strongly positive for S-100 protein () and negative for smooth muscle actin (SMA). EMA highlighted perineural fibroblasts surrounding tumor nodules (). These morphologic features, along with the immunoprofile, are diagnostic of plexiform schwannoma.


A 51-year-old Bolivian male with a past medical history of long-standing rheumatoid arthritis which was treated with methotrexate and steroids 10 years prior to his presentation when he noticed an enlarged spleen. He was diagnosed with Felty’s syndrome and was treated with corticosteroids. Later, he was found to have a decreased white cell count which was treated with filgrastim. Several months before hospitalisation, the patient experienced increasing fatigue, night sweats and weight loss of 10 Ibs and was admitted to the hospital after developing nausea. There was no history of fever, joint pain or skin rash.
On physical examination, vital signs included a blood pressure of 126/77 mmHg, heart rate of 93 bpm, respiratory rate of 12/minutes and temperature of 36.5 °C. Abdominal examination revealed a flat abdomen with a total liver span of 10 cm and a splenomegaly of 15–16 cm below the left costal margin. There was no lymphadenopathy in the cervical, supraclavicular or axillary areas. Laboratory findings were significant for leukopenia (white blood cell 0.58 × 109/L), anaemia (Hgb 8.5 g/dL) and thrombocytopenia (platelets 54 × 109/L), i.e., a pancytopenia.
A computerised tomographic scan of the chest, abdomen and pelvis showed a massively enlarged spleen measuring 12.3 × 21.2 × 30.1 cm. There was a poorly defined mass in the spleen consistent with lymphomatous involvement. The liver was also enlarged measuring 18.2 × 20.2 × 21.5 cm. Bone marrow biopsy revealed small to intermediate sized T lymphocytes in an interstitial and intrasinusoidal distribution involving approximately 30% of the cellularity of a 98% cellular marrow and mild reticulin fibrosis; flow cytometry revealed T lymphocytes that were positive for CD3, CD7, CD2, CD45 and TCR-γδ and negative for CD5, CD4, CD8 and TCR-αβ. Chromosomal abnormalities were not detected. Based on these findings, a diagnosis of HSTCL was made.


A 26-year-old male patient with no remarkable medical and social history presented with a five-day history of a cough and fever. Before coming to our hospital, he went to a clinic and received amoxicillin, which resulted in no improvement of his symptoms. He visited another hospital three days before presenting to us and was hospitalized with a diagnosis of bacterial pneumonia. Although he received tazobactam/piperacillin, his clinical symptoms showed deterioration. Two days later, he was admitted to our hospital.
His vital signs were as follows: temperature, 38.1°C, heart rate of 112 beats/min, blood pressure of 98/60 mmHg, respiratory rate of 24 breaths/min, and saturation of peripheral oxygen of 94% with a reservoir mask of 6 L/min. On physical examination, weak respiratory sounds and coarse crackles were heard in the lower left chest.
His initial white blood cell count was 6,800/μL, hemoglobin was 14.0g/dL, platelet count was 133,000/μL, and C-reactive protein level was 34.30 mg/dL (). Arterial blood gas (reservoir mask of 6 L/min) showed that the pH was 7.44, PCO2 was 41.1 mmHg, PO2 was 69.2 mmHg, HCO3− was 27.2 mmol/l, and BE was 2.8 mmol/L. Among the viral and bacterial rapid tests performed, only the Mycoplasma antigen tested positive.
Chest radiography indicated an infiltrating shadow in left middle lung field and right lower lung field. A chest CT indicated lobar pneumonia in the lower left lobe and an infiltrating shadow in the left whole lung lobe and the lower right lobe (). Based on these findings, the patient was diagnosed with severe mycoplasma pneumonia.
Azithromycin 500 mg/day and prednisolone 30 mg/day were initiated. After admission, his respiratory condition worsened until a reservoir mask 15 L/min was required. We then changed the reservoir mask to a nasal high-flow oxygen (40 L/min, FiO2:0.8) and increased the prednisolone to 60 mg/day. In case of macrolide resistance, we additionally administrated minocycline 200 mg/day. On hospital day 4, the patient's respiratory status and inflammatory markers on laboratory findings improved. On hospital day 20, he was discharged.


A 47-year-old African American male with poorly controlled diabetes mellitus type 1 presented with lower back pain intensifying over several weeks. The patient was born and raised in Ohio but moved away to join the army. While in the military, he was stationed in Germany and Korea. He had moved to Arizona approximately a year prior. The patient had complaints of six months of progressively worse chronic nonproductive cough, night sweats, and significant weight loss. He denied fever, headaches, confusion, gait abnormalities, new joint pain, and skin rashes. Physical examination was grossly unremarkable. The white blood cell (WBC) count was 7,800/μL. Chest X-ray revealed bilateral hilar lymph nodes along with likely granuloma at the right middle lobe. Computed tomography of the chest revealed subcentimeter bilateral pulmonary nodules and middle mediastinal and right hilar lymphadenopathy. He underwent bronchoalveolar lavage with transbronchial lymph node biopsy. The pathology was consistent with granulomatous inflammation and fungal elements consistent with extensive coccidiosis. His cocci serology IDCF qualitative was positive, and the cocci IDCF titer was 8. His HIV test was negative. He was diagnosed with pulmonary coccidioidomycosis and started on oral fluconazole 400 mg daily.
The patient had returned to the Emergency Department complaining of worsening lower back pain over the past few weeks. He denied bowel or bladder incontinence and numbness. Physical examination revealed tenderness at the lower back. X-ray of the lumbosacral spine did not show osteomyelitis. Magnetic resonance imaging (MRI) of the lumbar spine without contrast revealed acute-to-subacute superior endplate compression deformity of the L3 vertebral body. Also noted was approximately 10–20% loss of the vertebral body height. No evidence of epidural abscess, spinal canal compromise, neural foraminal narrowing, or spinal cord compression was noted. CT-guided needle biopsy was performed confirming osteomyelitis due to C. immitis (Figures and ). Fluconazole was switched to itraconazole for better bone penetration. Unfortunately, the patient had significant weight gain and lower extremity swelling. Therefore, itraconazole was switched to posaconazole. He subsequently had gradual improvement of lower extremity swelling and weight loss. Subsequent MRI of the lumbar spine with and without contrast revealed T2 hyperintensity within the disc extending into the inferior endplate of L2 and superior endplate of L3. Findings were related to discitis and osteomyelitis. There was also a compression fracture of the superior endplate of L3 with approximately 50% height loss. Finally, there was a mass-like ventral epidural enhancement to the left of the midline with associated mass effect on the thecal sac related to developing an epidural abscess (). Neurosurgery was consulted, and the patient underwent L2-L3 laminectomy, L2-L4 posterior spinal fusion, and evacuation of the epidural abscess. The pathology report also confirmed to be positive for Coccidioides spherules (Figures and ). He underwent retreatment with intravenous liposomal amphotericin B (AmBisome) 5 mg/kg of ideal weight for several weeks along with continuing oral posaconazole for life. His repeat cocci IDCF titers decreased from 8 to 2. The patient denied axial pain or radicular pain. His spine remained stable, and he was neurologically intact.


An 85-year-old man visited our hospital for treatment of sustained ventricular tachycardia (VT), which caused an unstable hemodynamic state. His medical history was significant for acute myocardial infarction (AMI) 2 weeks prior, and a drug-eluting stent was implanted in the left main trunk. On admission, the patient was asymptomatic. His vital signs were as follows: blood pressure, 144/78 mm Hg; pulse rate, 80 beats/min; respiratory rate, 16 breaths/min. His oxygen saturation was 99% in room air, whereas his laboratory test showed the following results: sodium, 140 mmol/L; potassium, 4.5 mmol/L; creatine kinase, 28 U/L; creatine kinase-muscle/brain, 9 U/L. Electrocardiography showed sinus rhythm with T-wave inversions in the I, aVL, and V1-V6 leads. Chest radiography revealed mild widening of the cardiac silhouette and right pleural effusion (). After the admission, he presented with sustained VT. Intravenous amiodarone was administered and CPR was performed, but amiodarone was ineffective in terminating VT. Hence, emergency coronary angiography (CAG) was performed for suspected myocardial ischemia. Intra-aortic balloon pumping and percutaneous cardiopulmonary support were established before emergency CAG because of his unstable hemodynamic state. CAG revealed 90% stenosis at the middle segment of the left descending artery, thus, ad hoc percutaneous coronary intervention (PCI) was performed. During the PCI, his serum hemoglobin level decreased from 11.1 to 3.0 g/dL. Chest radiography revealed pleural effusion in the right lung, which was not present on admission. Noncontrast CT was performed after emergency PCI, which revealed right hemothorax without any chest wall fractures. A right chest tube was placed, and 1.8 L of pleural effusion was drained over 6 hours. Despite blood transfusion of 12 units of red blood cells and 12 units of fresh frozen plasma, his serum hemoglobin level decreased, suggesting persistent blood loss. To identify the source of the bleeding, contrast CT was performed, which revealed small anterior mediastinal hematoma and bloody pleural effusion (). Three-dimensional contrast CT demonstrated an extravasation at the branch of the right IMA (Figures and ). The patient's deteriorating hemodynamic condition precluded thoracotomy or embolization to stop the bleeding. He subsequently died on the next day of hospitalization.


A 62-year-old male with history of hypertension, coronary artery disease, and sick sinus syndrome presented to outpatient device check clinic to establish care for a pacemaker device. He underwent implantation of a dual-chamber pacemaker device (St. Jude Accent generator with Medtronic CapSure SP Novus atrial and ventricular leads) in 2002 for sick sinus syndrome and had a generator changeout in 2011. The lead model was not implicated in a recall to our knowledge and search. The patient had his last device check performed in March 2017, and no problems with the device function were reported at that time. The patient denied any trauma to the chest or upper extremities, chest pain, shortness of breath, palpitations, presyncope, or syncopal episodes. He denied any device-related complications in the past. The patient reported a recent visit to a popular theme park in the 1st week of August, where he enjoyed multiple high thrill rides including high-velocity roller coaster rides. On physical examination, he was afebrile with normal pulse, blood pressure, and respiratory rate. His left pectoral pacemaker implant site showed no erythema, swelling, warmth, drainage, or signs of erosion. Labs showed normal blood counts and normal renal and liver function. A 12-lead ECG showed normal sinus rhythm with a heart rate of 60 beats per minute and atrial pacing spikes with loss of capture (). Pacemaker device evaluation showed approximate remaining battery life of 9 years and programmed DDDR pacing mode. Heart rate histograms showed 54% atrial pacing and 15% ventricular pacing. The right ventricular lead showed normal sensing, impedance, and pacing threshold. The right atrial lead was noted to have unusually high impedance of 2175 ohms and no capture on testing at voltages as high as 7.5 mV. Lead impedance history clearly showed an abrupt increase in the atrial lead impedance in August, at the time patient had visited the theme park, from around 600 ohms to 1000 ohms and subsequently above 2000 ohms (). EGM showed atrial lead noise. A chest X-ray (CXR) was obtained which revealed an intact right ventricular lead and complete severance of the right atrial lead tip (Figures and ). The pacemaker was reprogrammed from DDDR to VVIR mode. After discussion and review with the patient, it was decided not to retrieve the fractured lead or insert a new atrial lead, due to his intrinsic sinus rhythm having taken over, no evidence of atrioventricular (AV) block, and no current requirement for pacing. It was decided to follow the patient clinically to see if he will require insertion of an atrial lead in future.


A 46-year-old male with a history of alcoholic liver cirrhosis complicated by small esophageal varices after banding and moderate ascites was awaiting liver transplant (MELD 24, Child-Pugh class B). He presented with a 3-day history of abdominal pain. He described the pain as sharp and located around the periumbilical area with notable suprapubic discomfort. He also reported associated symptoms of nausea, hematochezia, and general malaise. On further review of systems, he reported chills, increased fatigue, shortness of breath, lightheadedness, and decreased appetite 4 days prior to presentation. He reported compliance at home with a sodium-restricted diet and medications. Physical exam was significant for abdominal distension with positive fluid wave, generalized abdominal tenderness, and splenomegaly. Scant blood was noted on the rectal exam. Laboratory studies revealed stable hemoglobin of 12.4 g/dL, hematocrit of 36.8%, platelet of 83 K/UL, leukocytosis of 15.4 K/UL with 78% neutrophils and 16% bands, sodium of 130 mmol/L, ammonia of 83 Umol/L, ALT of 40 U/L, AST of 42 U/L, and alkaline phosphatase of 127 U/L. International normalized ratio (INR) was 2.02. Diagnostic paracentesis revealed serosanguinous fluid and ascitic fluid polymorphonuclear neutrophils (PMN) count of 686 cells/mm3, consistent with culture negative neutrocytic ascites. Blood cultures revealed no growth of organisms. The patient was started on intravenous (IV) ceftriaxone, IV pantoprazole infusion, and an IV bolus of octreotide followed by continuous infusion. He completed a 5-day course of IV ceftriaxone therapy.
The patient underwent an esophagogastroduodenoscopy (EGD) which showed ulcerations in the distal esophagus from prior banding of small esophageal varices and diffuse portal hypertensive gastropathy (). Mucosal edema and erythema with an area of oozing of blood were identified in the duodenum bulb and between proximally located duodenal folds with no specific identifiable lesion. These findings correlated with a diagnosis of portal hypertensive duodenopathy (). Colonoscopy was performed, and it showed no active bleeding. However, there were old blood clots in the terminal ileum in addition to mild inflammation in the terminal ileum near the ileocecal valve. Video capsule endoscopy was also performed, and it revealed no active bleeding. Because of the concern of the possible failure of the patient on medical therapy for portal hypertension while awaiting liver transplant, the patient was referred for evaluation by a transjugular intrahepatic portosystemic shunt (TIPS). The patient successfully underwent the TIPS procedure. Follow-up occurred one month later in clinic. At this time, the patient reported resolution of the hematochezia.


A 28-year-old male patient with Type II Rothmund-Thomson syndrome presented to his physician with an enlarged left supraclavicular (Virchow's) node. Due to his syndrome, he had a small build, areas of skin hyperpigmentation, early skin aging with actinic keratoses, sparse thin hair, abnormal skeletal development, and osteoporotic brittle bones with a history of 18 fractures. Previously, at age 25, a lesion at the base of the penis was excised which was diagnosed as Bowen's disease. At the time of presentation, a neck ultrasound confirmed an enlarged 1.8 cm left supraclavicular node which appeared to be avascular. A chest X-ray and abdominal ultrasound were performed at that time which were normal. An outpatient referral was made to a local surgeon.
Two months later, he presented to a community hospital with a three-week history of progressively worsening postprandial vomiting and upper abdominal pain. At that time, he was not tolerating any oral intake. A repeat ultrasound demonstrated a concerning mass on the left lateral aspect of the aorta. An esophagogastroduodenoscopy was done urgently, and a polyp was found in the 2nd part of the duodenum as well as an inflamed and friable obstructing lesion in the 3rd part of the duodenum. The scope could not be advanced beyond this point. Biopsies taken at the time of endoscopy revealed high grade invasive mucinous adenocarcinoma of the signet ring cell type with neuroendocrine features at the site of the obstructing lesion. The biopsies of the polyp demonstrated high grade intramucosal mucinous adenocarcinoma arising within a tubulovillous adenomatous polyp.
He was transferred to our institution to undergo further imaging and management. At that time, his functional status was poor. He had lost approximately 25 lbs and had an ECoG performance status of 3 to 4. On examination, a fullness in the epigastrium was noted. The CT scan demonstrated a large distal duodenal mass with extensive lymphadenopathy, as well as a nodule in the right upper lobe of the lung. Attempts to place a duodenal stent across the lesion were unsuccessful. He underwent palliative radiotherapy and subsequently underwent a laparotomy and gastrojejunostomy to bypass the obstructing lesion. The patient declined systemic chemotherapy and was treated with palliative intent, as per his goals of care, which allowed him to return home to be with his family.
He developed Herpes Zoster shortly after his discharge and was treated as an outpatient with oral antiviral therapy. Two months after his diagnosis of duodenal adenocarcinoma, he presented to the hospital with significant shortness of breath. Additional imaging was done which revealed multiple masses in the right lung, significantly increased mediastinal adenopathy compressing the pulmonary artery, postobstructive pneumonitis in the right lower lobe, and airspace disease suspicious for aspiration bilaterally. He progressively worsened despite supportive care and passed away shortly thereafter.


A 42-year-old female patient with past medical history of obesity and a bariatric surgery consults for a year of symptoms consisting in progressive bilateral exophthalmos, especially on the left side, associated with eye pain, bilateral hyaline rhinorrhea and headache, without a change in visual capacity. Upon consultation to the emergency room (day 0), a brain MRI was performed, with a nasopharynx-dependent mass invasion of the anterior cerebral fossa, orbit and maxillary and frontal sinuses finding (see -B). At first, it was diagnosed as an invasive nasopharyngeal tumor associated with cerebrospinal fluid (CSF) fistula, which was scheduled for surgical resection.
She was admitted for tumor resection through bifrontal craniotomy with transnasal endoscopic approach (day +69). On admission, the patient was stable, without motor or sensory deficits at the neurological physical exam. After tumor resection, the microbiological study of the lesion was performed, where KOH showed septated hyaline hyphae on day +71 and the culture was positive for Aspergillus flavus (day +75) (see -A). Pathological analysis reported invasion of all the nasal respiratory mucosa by a granulomatous inflammatory infiltrate, with a few foci of necrosis and extensive areas of fibrosis, giant cells and histiocytes had septated hyaline hyphae phagocytized. The bone fragments were surrounded by the same type of inflammatory infiltrate. The coloring of PAS and Gomori allowed identification of the typical hyphae of Aspergillus in the respiratory mucosa and bone tissue. The patient received amphotericin B 50 mg IV q 24 h from day 70 to day 75, and subsequently, after the identification of A. flavus, management was changed to voriconazole 200 mg PO q12hours during 6 months.
On day +74, multiple extension studies were performed, including a negative serum galactomannan (0.326), a negative HIV serology, normal immunoglobulin G 14.4 g/l, CD4: 660 cells/µl (normal), CD3:1042 cells/µl (normal), and a computed tomography scan (CT scan) of the thorax, where a right apical pulmonary nodule with frosted glass pattern was reported, suggestive of initial infection by Aspergillus. Afterward, bronchoscopy and bronchoalveolar lavage (BAL) were performed (day +76), with galactomannan in BAL reported positive (result: 0.718, positive: >0.5).
Laboratory tests, including complete blood count (CBC), kidney and liver function tests (LFT) were within normal limits during the hospitalization. Protein electrophoresis showed moderate decline in albumin.
During the post-operatory, the patient persisted with a cerebrospinal fluid fistula and received acetazolamide from day +78 to day +98. The remaining clinical course was uneventful, and patient was discharged on day +89 with full recovery and without recurrence.
A 76-year-old female patient with a history of hypothyroidism managed with levothyroxine 50 g/day and recurrent left eye chronic dacryocystitis by Methicillin-resistant S. aureus (MRSA) (day −27). Required reconstructive surgery of the left lacrimal pathway (day 0), where a lacrimal duct lesion extending to the adenoid region was found, and resection of the lacrimal duct bone was also performed. The pathology report showed lymphoplasmacytic severe chronic inflammatory infiltrate in soft tissue and fragments of bone with osteomyelitis, as well as a mass that revealed septate hyphae and some irregular, partially pigmented with occasional formation of conidial heads of Aspergillus in the microbiological examination (day +13). In the fungal culture, Aspergillus flavus was isolated (day +26); thus craniofacial invasive aspergillosis was diagnosed, and management with voriconazole 200 mg PO q12h was initiated on day +13 and continued for three months (day +103). Extension studies were performed on day +14, which reported a normal CBC, kidney function, and LFT, negative serum galactomannan (0.315), negative HIV, a brain MRI showing microangiopathic leukoencephalopathy without others abnormalities and a thorax CT scan that reported nonspecific thickening of interlobular septae. The patient's clinical course was adequate without recurrence of the disease.


A 38-year-old Japanese housewife who was a heavy smoker was admitted to our hospital because of upper respiratory distress that developed half a year prior to admission. She had no past medical history. On admission, her vital signs were normal. Physical examination showed hoarseness, stridor, wheezing, and orthopnoea, but no swelling of the tonsils, thyroid, or lymph nodes. A computed tomography of the neck revealed an enlarged tumor ().


A 74-year-old male presented to the emergency department with right-sided weakness and confusion and was found to have a left parietal intraparenchymal hemorrhage with cerebral edema and left-to-right midline shift on non-contrast computed tomography (CT) of the head. Increase in cerebral edema and expansion of the hematoma caused clinical neurological decline necessitating a left-sided hemicraniectomy with clot evacuation. A cranial ultrasound was performed two days after surgery to assess for progression of cerebral edema and intracranial hemorrhage. A transtemporal approach in axial plane was used to visualize intracranial structures through the craniectomy window ( and ). Physiological structures such as the falx cerebri, lateral ventricles, midbrain, mammillary bodies, choroid plexus, splenium of corpus callosum, thalami, and circle of Willis were visualized with incredible anatomical detail. Pathologies such as intracranial hemorrhage, focal ischemic areas, and vasogenic edema, as well as encephalomalacia, were identified with close correlation to the non-contrast head CT. The patient is currently recovering in the neurocritical care unit with supportive care.


We present two cases of cerebrovascular accidents. Case #1: A 24-year-old man presented with open fractures of the left femur and tibia after a motor vehicle collision. Within two hours, he developed left facio-bracial paresis. Although he arrived in the window period for thrombolysis, polytrauma precluded thrombolysis. His modified Rankin Scale (mRS) score at admission was five. Case #2: A 26-year-old man presented to the emergency department after eight hours with hemiplegia and global aphasia. His admission mRS score was four. Stroke workuprevealed hyperhomocysteinemia (>114 μmol/L).


A 55-year-old man with severe MR and middle scallop prolapse due to torn chordae underwent MVR. Preoperative LV ejection fraction, tricuspid annular plane systolic excursion and right ventricular fractional area change were 62%, 26 mm and 44%, respectively. MVR was performed with folding middle scallop and annuloplasty with a 30-mm Physio II annuloplasty ring (Edwards Lifesciences LLC, Irvine, CA, USA). MR was well controlled. Despite difficulty weaning from cardiopulmonary bypass and some persistent surgical bleeding, he was hemodynamically stabilized on admission to the ICU without evidence of SAM and LVOTO.
He became hemodynamically unstable on the first postoperative day, with parameters as follows: heart rate 87 beats/min (bpm), sinus rhythm, arterial pressure 80/48 mmHg, pulmonary artery pressure 28/20 mmHg, central venous pressure 17 mmHg, cardiac index 1.7 L/min/m2, right ventricular stroke work index (RVSWI) 1.6 g/m2/beat, and mixed venous oxygen saturation (SvO2) 54%.
Transthoracic echocardiography (TTE) was performed to investigate the cause of hemodynamic deterioration; however, adequate images could not be obtained. TEE was then performed and showed right ventricular (RV) dysfunction without SAM and LVOTO. We decided to increase the dose of inotrope (adrenaline) to improve RV function and the hemodynamics stabilized.
Severe hypotension developed on the second postoperative day. Hemodynamic parameters were as follows: heart rate 90 bpm, arterial pressure 50/42 mmHg, pulmonary artery pressure 28/20 mmHg, central venous pressure 13 mmHg, cardiac index 1.6 L/min/m2, RVSWI 2.4 g/m2/beat, and SvO2 48%. The ventilator settings were as follows: pressure assist-control ventilation, respiratory rate 14 breaths/min, peak inspiratory pressure 16 cmH2O, inspiration time 1.6 s, positive end-expiratory pressure 10 cmH2O, and fraction of inspiratory oxygen 0.6.
Although the dose of dopamine, dobutamine and adrenaline was greatly increased to 5.4 µg/kg/min, 5.4 µg/kg/min and 0.05 µg/kg/min, respectively, and intra-aortic balloon pumping was started, hemodynamic parameters did not show improvement. No pulmonary vasodilator was used because of avoiding hypotension.
Repeat TEE revealed the hyperdynamic left ventricle (LV) without any regional wall motion abnormality, as well as LVOTO and severe MR (vena contracta 8 mm) due to SAM (Fig. ; Additional file ). In addition, RV dysfunction was still presented. We immediately reduced the inotrope dose and started vasopressors (vasopressin 2 unit/h) with volume loading (acetate Ringer 500 mL and 5% albumin 250 mL). SAM, LVOTO, and MR rapidly resolved and hemodynamic parameters stabilized. However, when normal sinus rhythm converted into junctional rhythm, SAM, LVOTO and severe MR recurred and hemodynamic parameters again became unstable (Figs. , ; Additional files , , ). TEE showed that conversion from normal sinus rhythm into junctional rhythm worsened the severity of SAM, LVOTO, and MR. The electrocardiogram showed junctional rhythm alternating with sinus rhythm, repeated at short intervals. We found that the rhythm change had a significant effect on the emergence of SAM and hemodynamic deterioration. Temporary atrial pacing was used to stabilize the heart rhythm. After starting atrial pacing, the hemodynamics stabilized and SAM, LVOTO, and MR did not recur (Fig. ). He discharged from ICU on the 22nd postoperative day and from the hospital on the 43rd postoperative day.


Patient 2 is a 65-year-old African-American female, also depicted in Figure . She had an apparently normal perinatal and neonatal history, slow physical growth, and some learning difficulty in childhood. The patient began developing staring spells at approximately 6 years of age, which were eventually interpreted and treated as seizures. Pubertal development was apparently normal with menses starting at age 11. There was a report of heavy menses, and a hysterectomy was ultimately performed due to uterine fibroids. Her health history also included cataract removal in her mid-50s, tinnitus, brittle teeth, and a heart murmur.
The initial genetic evaluation was prompted by pain and numbness in the extremities at age 55 years. Imaging studies revealed spinal stenosis of T11-12 and some spinal cord impingement treated with surgical decompression of the spinal cord. Her stature was 146.7 cm (≤3rd centile), weight 91.2 kg (>97th centile), and head circumference 56.4 cm (60th centile). The arms were disproportionately short with more severe shortness of the humeri. There were no ventral elbow creases. Her fingers were short and distally tapered. Short lower extremities and brachydactyly of the toes were also present. Dysmorphic facial features are noted in Figure .
Health concerns included glaucoma, hypertension, and hypercholesterolemia. She continued to have increasing symptoms of stiffness and pain involving her back, groin, and knees causing limitations of her mobility.
Skeletal anomalies found during the first skeletal survey of Patient 2 at age 55 years were thought to be consistent with Robinow syndrome, as were her clinical features. However, this diagnosis was considered unlikely upon finding no molecular alteration by ROR2 mutation screening. The radiographic findings are illustrated in Figure .


A previously well four-and-a-half year-old boy presented with an upper respiratory tract infection, loss of appetite, fatigue and increasing breathlessness in the past 1 week before admission. There was no history of chest pain, cyanosis, joint pain or swelling. Predisposing factors, such as congenital cardiac disease, were excluded by review of the patient’s medical records. The patient received treatment in a primary care centre before being admitted to hospital. On examination, he was tachypnoeic and pale, with clammy extremities. His heart rate was 90 beats min−1, respiratory rate 30 breaths min−1, blood pressure 100/60 mmHg and temperature 37 °C. There was a mild face and lower limb oedema. On cardiac examination, there was decreased cardiac impulse on palpation. Heart sounds were muffled and no murmur was heard. His liver was palpable 3 cm below the costal angle. Pulses were palpable and equal in all four extremities. Laboratory examinations revealed a normal haemoglobin level of 132 g l−1 with a slightly increased white blood cell count (15 900 cells mm−3), whereas the platelet count was within normal limits (342 000 platelets mm−3). Unfortunately, cardiac markers such as troponin, creatinine kinase (CK) and its MB isoenzyme (CK-MB) were not tested due to limited resources. Chest X-ray showed cardiomegaly with congested lungs. Electrocardiography (ECG) revealed a sinus rhythm with a heart rate of 136 beats min−1. There was a normal P wave with slightly prolonged PR interval (>0.2 s). The QRS axis was normal and a possible left ventricular hypertrophy. There was no obvious ST change. Informed consent for patient management was taken by the clinician in the hospital before examination.


A 22-year-old male amateur basketball player with no relevant medical history was admitted to our hospital due to continuous severe lower back pain with radiating nerve pain and numbness from the hip to the posterior part of the left leg. Physical examination revealed paravertebral muscle spasm, diminished sensation at the lateral aspect of the sole of the left foot, diminished strength in plantar flexion on the left side, a weakened Achilles tendon reflex on the left side, and a positive straight-leg raise test (30 degrees) on the left side. Magnetic resonance imaging of the lower spine showed a herniated nucleus pulposus at the left L5-S1 level, and so the patient was diagnosed with left lumbar disc herniation at L5-S1.
Preoperative evaluation was normal. The patient opted to undergo surgical treatment with PEID after failure of conservative treatment. Tracheal intubation was facilitated via the administration of atracurium and penehyclidine. General anesthesia was induced with propofol and fentanyl, and was maintained with sevoflurane, fentanyl, and atracurium. The PEID was successfully completed within 40 min, with complete removal of the herniated disc, annuloplasty of the annulus fibrosus, and thorough decompression of the S1 nerve root. Intraoperatively, the patient was infused with 1,100 mL of Ringer’s lactate solution. Throughout the entire procedure, the urine volume was 400 mL, and the blood loss was less than 20 mL.
Extubation was performed when the patient was conscious, spontaneously breathing, and performing purposeful movements. The patient then suddenly began to respire forcefully. The heart rate was 130 beats/min, blood pressure was 155/90 mmHg, respiratory rate was 35 breaths/min, and SpO2 had decreased from 98 to 65%, followed by the production of 5 ml of pink frothy sputum. Chest auscultation performed by the anesthetist revealed tachycardia and dispersed moist rales bilaterally. Arterial blood gas analysis showed that the pH was 7.34, PaO2 was 71 mmHg, and PaCO2 was 40 mmHg. Electrocardiography indicated sinus tachycardia. NPPE was diagnosed. The airway was kept unobstructed, and oxygen was delivered at 5 L/min via mask ventilation. The infusion volume was limited. Dexamethasone was administered to relieve spasm, and 20 mg of furosemide was administered intravenously to treat pulmonary edema. The SpO2 improved and was maintained above 93%.
After stabilization with supportive treatment for about 60 min in the operating room, the patient was transferred to the orthopedic ward. Subsequent laboratory testing indicated an increased white cell count of 12.5 × 109/L, an elevated neutrophil percentage of 84%, and a hematocrit decrease from 45.3 to 40.7%. The D-dimer level was 1.0 ng/mL, while the other main laboratory parameters were within normal limits. Repeat arterial blood gas analysis indicated that the pH was 7.37, PaO2 was 95 mmHg, and PaCO2 was 48 mmHg with oxygenation via nasal catheterization. Compared with the normal chest radiograph preoperatively (Fig. ), the emergency chest radiograph showed bilateral infiltrates with opacities and nodules (Fig. ). Two hours later, chest computed tomography (CT) of a pulmonary window showed increased vascular diameter, a mosaic pattern of attenuation, and bilateral pleural effusion (Fig. ).
The patient was afebrile, and cefazolin was administered prophylactically. The oxygen requirement gradually decreased to room air, with the hematocrit remaining stable, and the vital signs remaining stable for the following 24 h. A chest radiograph obtained in the morning on postoperative day 1 still showed bilateral infiltrates with opacities and nodules; however, the severity of these was obviously decreased compared with the radiograph taken the previous evening (Fig. ). A chest radiograph taken in the afternoon on postoperative day 1 showed that the infiltrates had further decreased. In the evening on postoperative day 1, CT showed a marked decrease in bilateral pleural effusion (Fig. ). The vital signs were stable, without tachycardia, tachypnea, and/or hemoptysis. At 3 days postoperatively, radiography showed nearly complete resolution of the lung infiltrate (Fig. , ) and CT (Fig. ). The patient was discharged 3 days after spinal surgery, at which time he reported that he was satisfied with the whole therapeutic process, and had marked improvement of the symptoms in the back and left leg.
At 6 weeks postoperatively, the patient was examined in the outpatient department. The pulse oxygenation was 100% on room air, and there were no abnormal findings on chest auscultation, radiography (Fig. ), and CT (Fig. ).


A 42-year-old woman, who was admitted to the Department of Hematology, The Second Hospital of Hebei Medical University (Shijiazhuang, China) on May 6, 2016, presented with a one-month history of paleness and fatigue.
The patient was a farmer with a history of tuberculous pleurisy 24 years ago. The hematological analysis revealed the following: white blood cell count (WBC), 23.8 × 109/L; hemoglobin (Hb), 64 g/L; platelet count (PLT), 433 × 109/L. Bone marrow and peripheral blood smears identified the proliferation of lymphoblastic cells (87% of bone marrow nucleated cells). Karyotype analysis revealed a normal karyotype (46, XX) [20] (Fig. ). Immunophenotypic analysis by flow cytometry (FCM) revealed that blast cells accounted for 76.8%, which were positive for CD34, CD10, CD19, CD22 and HLA-DR, and negative for cIgM (Fig. ). Hence, the diagnosis of common B-cell acute lymphoblastic leukemia was confirmed.
The patient received a standard induction chemotherapy regimen with dexamethasone, vincristine, daunorubicin, cyclophosphamide and peg-L-asparaginase, and subsequently achieved partial remission. Merely 5% of lymphoblasts were observed in the bone marrow smear. After receiving the second induction chemotherapy with vincristine, cyclophosphamide, mitoxantrone, cytarabine and dexamethasone, the patient was discharged from the hospital (June 18, 2016).
On July 22, 2016, the patient was admitted to our hospital again for consolidation. The complete blood count revealed the following: WBC, 4.1 × 109/L; Hb, 82 g/L; PLT, 206 × 109/L. The bone marrow examination revealed 41% of lymphoblasts. Therefore, early relapse was diagnosed. After one cycle of CAM (CTX, Ara-c and 6-MP) and two cycles of MA (methotrexate and cytarabine), 26% of lymphoblasts was found in the bone marrow. The leukemia in the patient was relapsed and refractory. Therefore, CAR-T therapy was introduced to the patient.
After the patient provided consent, 100 mL of peripheral blood was collected to prepare the anti-CD19 CAR-T cells. The CAR-T cells were engineered by Hebei Senlangbio Technology Co., Ltd. (Shijiazhuang, China). The construct of CD19-CAR comprised of the following: anti-CD19 scFv (FMC63), the CD28 transmembrane domain, 4-1BB costimulatory, CD3zeta activation domains, T2A autocleavage sequences, and endodomain-truncated EGFR. Three lentivirus package systems were used (psPAX2, pMD2.G and pLenti-EF1-CAR19), and these were co-transfected with JetPRIME (Polyplus Transfection) in 293FT cells. The lymphodepleting chemotherapy with the FC regimen (30 mg/m2 of fludarabine, day − 4 to − 2; 30 mg/kg of cyclophosphamide, day − 3 to − 1) started on November 5, 2016 (day − 4). On day zero, the patient received an infusion of anti-CD19 CAR-T cells, which were transfected by the Senl-B19 lentiviral vector to express the anti-CD19 CARs, and expanded with IL-2 and IL-7. The total dose was 5.0 × 105 CAR-positive T-cells/Kg. Body temperature, C-reactive protein, CAR-T cell number in peripheral blood, the copy of CAR DNA, and leukemia cell level in the bone marrow were detected by FCM, as presented in Figs. and .
On the day of reinfusion of CAR-T cells, the patient developed fever with a temperature of 38.4 °C. The temperature was lowered by NSAIDs and returned to normal after a week. The fever regenerated on the 14th day after transfusion, and body temperature returned to normal after 3 days of piperacillin treatment. On December 2, 2016, the blood examination revealed the following: WBC, 3.2 × 109/L; Hb, 80 g/L; PLT, 354 × 109/L. On December 6, 2016 (day 28), no lymphoblast was found in the bone marrow smear. The minimal residual leukemia examined by FCM was also negative, since no CD19+CD34+ lymphocyte was found in the bone marrow.
The patient has a human leukocyte antigen (HLA)-full matched brother, who was willing to be a donor for the hematopoietic stem cell transplantation (HSCT). On December 11, 2016, the patient underwent allogeneic transplantation with granulocyte colony-stimulating factor mobilized bone marrow cells plus peripheral blood hematopoietic stem cells from the patient’s brother. The preconditioning regimen was myeloablative, including cytosine arabinoside (2 g/m2) on day − 9, busulfan (3.2 mg/kg/day) on day − 8, − 7 and − 6, cyclophosphamide (1.8 g/m2/day) on day − 5 and − 4, and semustine (250 mg/m2) on day − 3. The graft-versus-host disease (GVHD) prophylaxis was based on cyclosporine, mycophenolate mofetil (MMF), and a short course of methotrexate. Donor mononuclear cells of 8 × 108/Kg, including CD34 positive cells of 2.88 × 106/Kg, were transfused. Neutrophil and platelet engraftments were observed on day + 10, while a full-donor-chimerism of 97.5% was evidenced on day + 28.
On day + 28, the patient had a seizure, accompanied by thrombocytopenia. Then, red-cell fragments were found in the peripheral blood smear. Other important abnormal results included elevated levels of serum lactate dehydrogenase (LDH), positivity for proteinuria (240 mg/dL), and a negative Coombs test. All these led to the diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA). Cyclosporin A was discontinued, a high dose of methylprednisolone (10 mg/kg) was used and tapered, and therapeutic plasma exchange (TPE) was performed daily for the first week, and on every second day for the second week, followed by plasma infusion every 3 days for 2 weeks. On August 4, 2017, no sign of seizure was present, blood examination revealed a WBC of 9.9 × 109/L, a Hb of 77 g/L and a PLT 20 × 109/L. Furthermore, the bone marrow smear revealed no lymphoblasts, and the minimal residual disease (MRD) assayed by FCM was negative. The DNA chimerism revealed a full-donor type, and the patient was discharged from the hospital.


A 65-year-old man was referred to our hospital because of hyperproteinaemia, eosinophilia, anaemia, and proteinuria after a 2-week history of slight fever, fatigue, and malaise.
On admission, his mental status was normal, body temperature was 36.5 °C, pulse was 73 bpm and regular, and blood pressure was 118/75 mmHg. A physical examination revealed eruption and oedema in his lower extremities; however, no abnormal signs were observed in the lungs, heart, or abdomen. His lymph node and thyroid gland were not swollen. The laboratory findings on admission are summarized in Table . In brief, the eosinophil count was markedly increased (50%). The IgG and IgG4 levels were markedly increased (6380 and 2430 mg/dL, respectively). Urinalysis revealed massive proteinuria (3.5 g/day) with haematuria (5–10 per high-power field), and the β2-microglobulin level was 2863 ng/mL. Chest radiography revealed ground-glass opacities in the lower lung field. Chest computed tomography (CT) revealed bronchial wall thickening and ground-glass opacities in the right middle and lower lobes of the lung. Abdominal CT revealed bilateral renal enlargement.
A renal biopsy was performed. Light microscopy revealed 3 global scleroses and no crescent within the 9 glomeruli. In the interstitium, severe infiltration of plasma cells and eosinophils, with storiform fibrosis and infiltration of numerous IgG4-positive plasma cells (IgG4-/IgG-positive plasma cell ratio > 50%) were observed (Fig. a, b). In the functioning glomeruli, the GBM had a bubbling appearance with spikes but without significant mesangial cell or matrix proliferation (Fig. c). Direct fast scarlet staining was negative.
On immunofluorescence, the expression of IgG and complements was negative; however, IgA was positively expressed in a granular pattern along the GBM. An IgA subclass analysis revealed significant monoclonal deposition of IgA1-λ (Fig. ). We cut the frozen sections of renal biopsy specimens several times for other purposes such as immunostaining. Therefore, the last cut section was used for IgA subclass analysis, and there were few residual tissues and only an obliquely cut segment of the glomerulus remained. For this reason, we believe that it seemed that only a segment of the glomerulus stained with IgA1. Immunofluorescence staining for antibodies to M-type phospholipase A2 receptor (PLA2R) was negative (data not shown).
Electron microscopy revealed GBM thickening, widespread podocyte effacement, and irregular and small non-organized and non-Randall-type granular electron-dense deposits in the GBM (Fig. ) that were shaped like snow leopard spot-like pattern. On the basis of these findings, the diagnosis was IgA1-lambda-type non-Randall monoclonal immunoglobulin deposition disease associated with membranous features in a patient with IgG4-related TIN, according to the criteria for IgG4-RD []. Corticosteroid therapy was initiated with 3 days of 500 mg intravenous methyl-prednisolone, followed by 40 mg/day prednisolone. After the treatment, the oedema, eruption, and eosinophilia remarkably improved immediately. The serum creatinine level decreased to 1.0 mg/dL, and IgG and IgG4 levels decreased to within their normal ranges. However, massive proteinuria persisted.


A 29 year old woman with a previous history of migraine, mild asthma, congenital asymptomatic bicuspid aorta valve accidentally discovered during routine examination, missed abortion and anembryonic pregnancy was diagnosed with relapsing-remitting MS. She was treated with interferon beta1-b for five years, until it was decided to escalate the treatment due to new gadolinium enhancing MRI lesions and a sensory attack. The Expanded Disability Status Scale score was 2,0. Tests for tuberculosis, HIV, hepatitis B and C, routine blood and urine analyses, as well as respiratory examination and chest X-ray were negative. She had stopped smoking four years previously, and stopped using interferon beta 1b four months prior to the first alemtuzumab infusion because she wished to get pregnant.
The patient received standard premedication with 1000 mg methylprednisolone, 10 mg cetirizine, 1000 mg paracetamol and 400 mg acyclovir per day before each alemtuzumab infusion (12 mg per day). Prior to administration of alemtuzumab hypotension (70/35 mmHg) and bradycardia (45 beats per minute) was noticed and patient reported mild dizziness that improved after administration of Ringer’s acetate. A vasovagal reaction was suspected. For this reason, the alemtuzumab infusion was started at a low rate (12 ml/hour). Except mild headache that was treated with paracetamol and ibuprofen no infusion-associated reactions were observed the first day. Blood pressure and heart rate were normal during the alemtuzumab infusion.
At the end of the second alemtuzumab infusion, 24 h after the start of the first infusion, the patient developed chest pain on inspiration, shortness of breath, and cough. Four hours later she started coughing up bright red blood tinged sputum without clots. Body temperature, blood pressure, heart sounds and oxygen saturation were normal. Electrocardiogram showed sinus bradycardia at 48 beats/min. Auscultation revealed crepitations over the right lung, and chest x-ray showed corresponding shadowing. Platelet and leukocyte counts two hours after symptom onset were normal, and c-reactive protein was 26 mg/l (ref. < 5). Arterial blood gas analysis four hours after onset of haemoptysis was normal except for pO2 at the lower reference limit (11,0 kPa; ref. 11,0–14,4) and elevated lactate 1,3 mmol/l (ref.0,4-0,8). Haemoglobin fell from 12,0 g/dl (ref. 3, 7–15 g/dl) before the first infusion to 10,5 g/dl the day after onset of haemoptysis. Urinary analysis and serum creatinine remained normal.
Computed tomography (CT) pulmonary angiography performed shortly after onset of haemoptysis showed extensive bilateral upper and lower lobe opacities with centrilobular distribution and minimal (up to 5 mm) bilateral pleural effusions without evidence of pulmonary embolism (Fig. ). Interlobular septal thickening and dependent gradient were not present. The heart size was normal. At bronchoscopy performed 60 h after onset of haemoptysis the bronchoalveolar lavage (BAL) fluid was persistently macroscopically markedly bloody, without dilution on successive aliquots. There were no evidence of pathogenic bacteria, viruses, or atypical cells. Differential cell count of the BAL revealed 6% macrophages without hemosiderin inclusions on iron staining and 94% neutrophils indicating acute lung injury. Microscopy of BAL fluid showed many erythrocytes but counting in successive aliquots was not performed.
The patient remained stable from a respiratory point of view with normal vital parameters. No treatment for lung haemorrhage was given. Chest pain and haemoptysis resolved in two days. At discharge from hospital one week after onset of haemoptysis CT showed total resolution of pulmonary opacities and pleural effusions on the right side, and unchanged minimal amounts of pleural effusion on the left side. Her cough resolved after four weeks, and she has thereafter not experienced respiratory symptoms.
Alemtuzumab was discontinued after the second infusion. Her MS has remained clinically and radiologically stable, and new treatment has not been initiated because of prolonged lymphopenia (0,33 10*9/l 13 months after alemtuzumab infusions).


A 62-year-old Japanese male with SCA6 was admitted to our hospital due to exacerbation of ataxia. He developed diplopia and body sway in his 30s. These symptoms gradually progressed, and gait disturbance and dysarthria appeared in his 50s. At age 61 years, he was genetically diagnosed as SCA6. He could walk by himself with bilateral Lofstrand crutches, but had recently begun to fall frequently. He had a family history of SCA6 in his mother and 2 siblings. None of them could walk by themselves and were using a wheelchair. Clinical examination revealed truncal and limb ataxia, dysarthria, horizontal gaze-evoked nystagmus, and slight vertical misalignment (slight restriction of upper ocular movement of the left eyeball) in a neurological confrontation test. The misalignment was clearer for the upper-right gaze (Fig. ). He had no cognitive dysfunction, his fundus was normal and he had no low vision.


A 63-year-old Caucasian male presented with a one-week history of uncontrolled choreiform movements of his left upper extremity. As described by the patient, his left arm began “jerking uncontrollably out of nowhere” while working in his shed at home. Prior to this development, the patient stated he had one similar episode a year ago which lasted for two days and resolved spontaneously. He did not seek evaluation at that time. His past medical history consisted of uncontrolled insulin-dependent diabetes, hypertension, schizoaffective disorder, and polysubstance abuse in remission. He reported having diabetes mellitus for at least 10 years. Reviewing the medical records, his previous HbA1C readings ranged from 13.8% to 12.4% over a 12-month span prior to his admission. His average blood sugar readings over this time ranged from 300 to 350 mg/dl. BMI was 25.3 kg/m2. His home insulin regimen included 10 units of NovoLog three times a day with meals and Lantus 20 units every morning. He was not on any oral diabetic medications. The patient reported that he was not compliant with his home insulin medications. Notably for comparison, an MRI brain performed 5 months before for a fall did not reveal any abnormalities. He denied any recent medication changes, illnesses, or headaches. His ESR and CRP were elevated, and his initial glucose level was 339 mg/dl. HbA1C was 9.9% on the day of his admission. Vital signs were normal upon presentation, and physical exam was benign aside from the hemichorea movements of the left upper extremity. Our differential diagnosis included neoplastic disorders (metastatic brain disease and brain tumor), Huntington's disease, ischemic or hemorrhagic stroke, trauma, and drug or chemical toxicity (dopamine agonist or phenytoin). CT scan of the head showed areas of high density in the right lenticular nucleus and right caudate head. Subsequent precontrast MRI demonstrated T1 and T2 hyperintense abnormalities in the caudate nucleus portion of the right basal ganglia (). Postcontrast MRI of the brain showed no abnormal enhancement excluding the possibility of a mass lesion (). Diffusion-weighted MRI brain images did not reveal any abnormal restricted diffusion in the right basal ganglia which excluded ischemia (). All of these changes were consistent with the movement pattern he was displaying and with a diagnosis of CHBG. Other conditions that have been known to cause hyperintense imaging abnormalities on MRI such as this include various cellular respiratory toxins such as carbon monoxide, methanol, and cyanide. Leigh disease and hyperammonemia from chronic cirrhosis have also been known to cause this. Our patient did not have any history that would correlate with these alternative possibilities, and additionally, none of these alternatives have been known to present with hemichorea. Inpatient treatment consisted of restarting the patient's home insulin regimen with the addition of inpatient corrective coverage. This included Lantus 20 units every morning and 10 units of NovoLog 3 times a day with meals. The patient's symptoms eventually resolved with control of his blood sugar levels. Control was achieved over roughly 48 hours during which our patient's blood glucose levels dropped from an average of mid-300s to the 170–200 mg/dl range. The choreoathetosis progressed from continuous movements to intermittent and then finally to resolution.
Endocrinology was consulted for assistance with the patient's difficult glycemic control. During his posthospitalization outpatient course, our patient began to consistently adhere to his outpatient diabetic medications. Lantus was increased to 40 units every morning and NovoLog was increased 13 units 3 times a day with meals. His HbA1C 6 months after discharge had improved to 7.1%. There were no further occurrences of choreiform movements. This time course of events demonstrates how treatment of hyperglycemia can adequately treat and lead to complete resolution of hemichorea-hemiballismic movements in patients with CHBG. In this case, symptomatic improvement began being observed 48 hours after initiation of glucose control.


We present the case of a 56-year-old male, admitted to the emergency room with [TBI] secondary to a gunshot wound in the right posterior parietal area. At admission he was awake with 11 points in the Glasgow Coma Scale [GCS] (O4 V2 M5), right pupil 4 mm, left pupil 3 mm, both light reactive. The initial CT scan () showed the entry zone of the projectile almost in the midline, bi-parietal intracerebral hemorrhage that was predominant in the right side, with cerebral edema in both occipital lobes. Two hours after admission, he suffered neurological deterioration to 8 points in the GCS (O1 V2 M5) and required intensive care unit [ICU] medical treatment that include: intubation, mechanical ventilation, sedation and analgesia.
We decided to place a parenchimal intracranial pressure monitor in the right Kocher point. The initial intracranial pressure was 60 mmHg, that was persistent despite optimal medical treatment. The patient was taken to the operating room and a posterior bi-parietal decompressive craniectomy was performed. After the Dural opening the intracranial pressure diminished until 42 mmHg; at the end of the surgery the intracranial pressure was 10 mmHg ().
Postoperatively the patient was admitted to the ICU where he was under intensive neuroprotective treatment with intracranial pressures under 15 mmHg. The 24 h postsurgical CT scan showed an adequate surgical decompression and presence of basal cisterns (, ).
The patient was kept under sedation and analgesia with midazolam and propofol, maintaining a Richmond Analgesia-Sedation Score [RASS] -5, and the pupils returned to 2 mm, low reflective, he required vasopressor support (norepinephrine) to keep a mean arterial pressure between 90–100 mmHg. His diary urinary output was 1–1.2 ml/kg/h. At day 4 the sedatives were suspended to assess neurological response, however, six days after the surgery the patient underwent tracheostomy because the maximal Glasgow Coma Scale was 8 points; had diminished gag-reflex and developed nosocomial pneumonia. ICU discharged the patient to Neurosurgery service 12 days after, where he completed antibiotic treatment, started rehabilitation and physical therapy. At discharge of our service, at day 16 of hospitalization the patient was with 11 points in the GCS (O4, V1, M6), pupils were 3 mm both adequate light responsive, the surgical wound did not presented any complications, the strength in the 4 extremities was 4/5, reflexes ++, and sensibility was conserved in all of its modalities. Six months after the initial trauma the patient underwent cranioplasty with autologous bone graft.


Case 1: 65-year-old male, with a penetrating aortic ulcer (PAU) on the descending
thoracic aorta. On the CT angiography (), it seemed to start right after the origin of the left subclavian
artery, extending to the descending thoracic aorta, with a maximum diameter of
57 mm.
Patient was selected for endovascular treatment. The initial planning suggested
that the endoprosthesis could be anchored in Zone 3[ with the free flow zone over the left
subclavian artery.


Case 2: 67-year-old male, with a descending aorta aneurysm and distal involvement
of the aortic arch with a maximum diameter of 10.0 x 9.2 cm ().


Case 3: 75-year-old male, being followed-up by the Cardiology team for severe
aortic valve stenosis with an ejection fraction of 30% in New York Heart
Association (NYHA) functional class III ().


Case 4: 68-year-old male, with asymptomatic infrarenal abdominal aortic aneurysm
extending to the iliac arteries with maximum diameter of 67 mm ().


Case 5: 64-year-old male, 3 years follow-up for Stanford type B chronic aortic
dissection, with acute abdominal pain, undergoing surgical treatment ().


Case 6: 67-year-old female, Stanford type A chronic dissection, with acute
dyspnea and chest pain undergoing ascending aorta replacement ().


A 73-year-old Caucasian male with a biopsy-proven diagnosis of stage IV poorly differentiated adenocarcinoma of the lung, epidermal growth factor receptor mutation negative, anaplastic lymphoma kinase translocation negative, and PD-L1 tumor proportion score of 20% was started on carboplatin, pemetrexed, and pembrolizumab. The patient was receiving the chemotherapy regimen every three weeks and prior to initiating cycle two, he developed generalized weakness. On presentation, he expressed subjective progressive weakness of the lower extremities (LEs) greater than the upper extremities (UEs). The physical exam was significant for 3/5 motor strength and absent deep tendon reflexes in the bilateral upper extremities (UEs) and LEs. Given the clinical presentation, an irAE secondary to an IO agent was suspected, with a differential diagnosis that included Guillain-Barré syndrome (GBS) versus myasthenia gravis-like syndrome. Lumbar puncture revealed albuminocytological dissociation in the cerebrospinal fluid (CSF) of 68 g/L, which further supported AIDP. The paraneoplastic panel was negative. Infectious workup, including CSF cultures, cytogenetic studies, polymerase chain reaction (PCR) for herpes simplex virus, cytomegalovirus, and serum venereal disease research laboratory (VDRL) was also negative. Methylprednisolone, along with intravenous immunoglobulin (IVIG), were initiated. Despite five infusions of IVIG, the patient’s strength diminished to 2/5 in the bilateral UEs and LEs. IVIG treatments were stopped and plasmapheresis was initiated. On Day 8 of hospitalization, the patient was transferred to the intensive care unit (ICU) for worsening respiratory status, as indicated by the measured lowest negative inspiratory force (NIF) of -20 cm H2O and forced vital capacity (FVC) of 1.1 L. Fortunately, the patient’s respiratory status improved with plasmapheresis and high-dose corticosteroid treatments and he never required mechanical ventilation. The patient received a total of eight sessions of plasmapheresis with a gradual recovery of his motor function. At Day 25 of hospitalization, the patient’s strength in his right UE was 5/5, left UE 3/5, and bilateral LEs 3/5. He was discharged to an acute rehabilitation facility on low-dose prednisone with instructions to follow up in the outpatient department. Unfortunately, the patient was re-admitted one month after discharge with another irAE and was subsequently placed in hospice care.


An 81-year-old Caucasian male with a diagnosis of melanoma on the right anterior chest wall and a wide local excision was found to have a recurrence in the right lung four months after initial diagnosis. Pembrolizumab was initiated, however, treatment was switched to dabrafenib and trametinib once molecular studies confirmed positivity for the BRAF V600R mutation. Nine months after diagnosis, magnetic resonance imaging (MRI) of the brain with and without contrast revealed multiple metastatic lesions in the brain (Figures -), prompting the administration of the second cycle of pembrolizumab in addition to dabrafenib and trametinib. One month following the second cycle of pembrolizumab, the patient was admitted to the hospital with progressive weakness described as originating in the bilateral LEs and then spreading to his bilateral UEs. His neurological exam revealed a strength of 2/5 in the bilateral UEs and 0/5 in the bilateral LEs with areflexia and no bulbar muscle weakness. A lumbar puncture showed an albuminocytologic dissociation with elevated CSF protein (56 g/L), which supported our diagnosis of AIDP. Electromyography was consistent with motor and sensory neuropathy. Infectious workup revealed negative CSF cultures and VDRL. Antibodies to ganglioside GM1 for GBS were negative. He was promptly started on methylprednisolone and IVIG for five days. On Day 1 of treatment, he developed acute hypoxic respiratory failure, requiring mechanical ventilation. After five days of treatment without any clinical improvement, plasmapheresis was initiated. On Day 14 of hospitalization, he developed a generalized tonic-clonic seizure. A computed tomography (CT) scan of the brain without contrast revealed a hemorrhage within one of his metastatic lesions and associated vasogenic edema (Figure ). On the same day, care was withdrawn and the patient expired shortly after.


Fifty-four year-old man presented with a history of 3 months of severe shuffling gait, urinary incontinence, and difficulty managing finances and keeping track of appointments. On examination a soft voice, a delay in left shoulder shrug and mild cogwheel rigidity in the left arm were noticeable. A brain MRI revealed marked ventriculomegaly (calculated Evans index = 0.42) () (Figure ). A lumbar puncture with removal of 50 ml of cerebrospinal fluid (CSF) was performed. The CSF was clear and colorless with an opening pressure of 18 cmH20. After the spinal test, Mini-Mental State Examination scored improved from 23/30 to 29/30 and the patient subjectively experienced significant relief from his gait-related symptoms, showing a 10% of increase in his walking speed. INPH was diagnosed and a ventriculoperitoneal (VP) shunt was placed (Figure ). Cognitive impairment and urinary incontinence improved, but the parkinsonian features persisted. Then treatment with levodopa was added, and the patient experienced a sustained improvement. It was thought that PD coexisted with INPH. Five years later, he presented with acute headache and cognitive impairment. Shunt obstruction which necessitated surgical intervention was diagnosed. The VP shunt was replaced and these acute symptoms resolved.
After 7 years on levodopa treatment, the patient developed gait freezing and severe levodopa-induced dyskinesia. He was treated with various combinations of trihexyphenidyl, amantadine, pramipexole, and levodopa, up to a maximum tolerated dose (1,500 mg daily), with minimal benefit to his overall functions. At an outside institution, DBS surgery was not considered due to diagnostic and technical concerns; the latter were related to the ventriculomegaly that could complicate the accurate placement of the DBS leads.
At the age of 67, the patient was subsequently referred to our institution. Motor score following a levodopa challenge decreased from 45 to 28 on UPDRS III (40% improvement). The Unified Dyskinesia Rating Scale (UDysRS) was very high (128 out of a maximum of 196). A battery of neurocognitive tests showed no signs of cognitive impairment. After a long discussion with the patient and his family on the pro and cons of the surgery, we decided to carry out DBS because the patient was suffering from medically intractable parkinsonism. The patient underwent bilateral GPi-DBS. We chose the ventral GPi in order to suppress dyskinesia and because its more lateral position compared to the subthalamic nucleus reduces the risk of breaching the ventricle walls. We used MRI/CT fusion techniques for anatomical indirect targeting with a stereotactic CT frame. Anterior and posterior commissures were identified, and the AC-PC line was 40 mm (the usual length of the AC-PC line is measured between 19 and 32 mm). The coordinates for the right GPi were 27.38 mm lateral (X), 1.85 mm anterior (Y), and −8 mm inferior (Z) to the midpoint of the intercommisural AC-PC line (10.7° from mid-sagittal plane and 53.3° from axial plane). For the left GPi the coordinates were X: −25.35 mm, Y: 3.69 mm, and Z: −8.42 mm (11.7° from mid-sagittal plane and 67.3° from axial plane). The right burr-hole placement was shifted laterally to avoid the right VP shunt and the enlarged frontal horns of the lateral ventricles (please see Additional File : CT video). The number of microelectrode trajectories was reduced to only one. Intraoperative microelectrode recording (MER) identified the neuronal firing pattern of the GPi. Recordings were performed in steps of 0.5–1 mm, from 15 mm above the presumed target until 3 mm below the target. Microstimulation with trains of high-frecuency (200 Hz) and currents from 0.5 to 5 mA was performed in order to test for proximity of the internal capsule, without any noticeable twitching or contraction coincident with stimulation. Visual evoked responses were obtained by a stimulus of light delivered as a flash and the optic tract was identified at the base of both GPi. The GPi-DBS lead placement was confirmed on a postoperative CT scan (Figure ).
Two weeks after leads placement, monopolar stimulation of the left dorsal and right ventral contacts (1-/11-) at 3.2 V in the left GPi and 3.6 V in the right GPi with a frequency of 130 Hz and pulse duration of 90 ms led to the best clinical response. There was a 71% decrease in the UPDRS III score during the on-stimulation state (28 to 8). The patient's dyskinesias resolved dramatically with a UdysRS of 15 (88% improvement) during the on-stimulation condition. The observed motor benefits and the improvement of his daily activities have persisted 10 months after surgery. (Please see Additional File : movie shows the before/after surgery; medication-off/stimulation-on condition).
The subject gave written informed consent for the publication of this case report and video files in accordance with the Declaration of Helsinki.


A 50-year-old woman presented with an episode of hemoptysis. She also reported low grade fevers, night sweats and chest discomfort. Her past medical history was notable for allergic rhinitis/sinusitis and asthma, and she experienced recurring upper respiratory tract infections, sinusitis, and bronchitis approximately three times per year. Chest computed tomography imaging revealed left upper lobe consolidation with a central cavitary lesion, adjacent scattered consolidation, ground-glass opacities and tree-in-bud markings (Fig. ). She subsequently underwent bronchoscopy, and bronchoalveolar lavage grew Mycobacterium avium complex (MAC). Consequently, she underwent cavitary MAC treatment with rifampin, ethambutol, erythromycin, and intravenous amikacin with improvements in low-grade fever, night sweats, and chest discomfort.
Four months later, her symptoms returned, and chest imaging revealed a new right basilar lung infiltrate, with increased ground-glass and consolidative focal patchy disease, as well as bronchiectasis. Repeat bronchoscopy revealed a positive fungal culture for Aspergillus and she was subsequently started on voriconazole. Upon re-evaluation, the patient exhibited oral ulcers, purpuric skin lesions, and new onset peripheral neuropathy and was referred for an additional opinion.
Pertinent laboratory findings included a complete blood count with a total white cell count of 11,000 cells per microliter with marked hypereosinophilia at 5200 eosinophils per microliter. Erythrocyte sedimentation rate was elevated at 92 mm/hr., and C-reactive protein was elevated at 1.154 mg/dL (normal less than 0.4). Quantitative serum immunoglobulin E (IgE) was also elevated at 520 international units/mL (normal 0 to 11). Patient was negative for ANCA, hepatitis B or C, PR3 antibody and MPO antibody.
Pulmonary function testing demonstrated normal total lung capacity (TLC) and thoracic gas volume but an elevated residual volume at 2.93 L (154% of predicted) suggesting mild air trapping. Airflows were normal, with a forced expiratory volume in one second (FEV1) of 2.67 L (90% of predicted) and forced vital capacity (FVC) was 3.23 L (86% of predicted) with no significant bronchodilator response. Diffusing capacity of the lungs for carbon monoxide (DLCO) was mildly reduced at 20.97 or 77% of predicted, but when corrected for alveolar volume (VA), corrected to normal with a DLCO/VA of 4.59 or 86% of predicted. The VA was significantly less than the TLC, suggesting gas mal-distribution.
Repeat bronchoscopy was performed with transbronchial biopsies. Histopathology showed acute and chronic inflammation, scattered eosinophils (42 eosinophils per 60 × high power field), fresh hemorrhage and tissue eosinophilia most prominently in the bronchial wall and adjacent alveolated lung parenchyma. There was no evidence of granuloma formation or necrotizing vasculitis (Figs. , and ).
The constellation of compelling clinical, radiographic, laboratory, and pathologic findings believed to suggest GPA/EGPA overlap syndrome included a cavitary pulmonary lesion unresponsive to anti-microbial therapy, oral ulcers, purpuric skin lesions, peripheral neuropathy, long-standing asthma, chronic sinusitis, one or more episodes of alveolar hemorrhage, migratory pulmonary infiltrates on chest imaging, peripheral hypereosinophilia, a markedly elevated IgE level, elevated inflammatory markers and eosinophilic inflammation in the pulmonary parenchyma on histopathologic examination.
In addition to the very complex clinical picture most suggestive of EGPA/GPA overlap syndrome, there was compelling evidence for a concomitant aspergillus pulmonary infection, and the patient also met criteria for a diagnosis of allergic bronchopulmonary aspergillosis. There is a possibility that the aspergillus pulmonary infection may have complicated our patient’s clinical picture as it may have contributed to her pulmonary cavitation and sinusitis.
While the patient had been previously treated with oral corticosteroids and anti-fungal therapy for a prolonged period of time with little improvement, with the addition of anti-interleukin (IL)-5 therapy and cytotoxic therapy (azathioprine) to the oral corticosteroids and anti-fungal therapy, the patient had dramatic improvement in her disease manifestations.
Between 1986 and 2017, we identified 15 cases that described an overlap syndrome involving both GPA and EGPA (Table ). Patients ranged in age between 21 and 78. Of those whose sexes were identified, 80 % of cases described were female. All cases described involved the lungs, 60 % described sinus involvement, and over half had displayed renal involvement. An overwhelming majority of patients were positive for c-ANCA and demonstrated eosinophilia (peripheral or tissue involvement). A preponderance of the cases described were treated with systemic corticosteroids combined with cytotoxic/immunosuppressive agents.