A 60-year-old man presented to the emergency department with chest pain lasting for 2 days. Electrocardiography revealed ST-segment elevation in leads V1–V4 as well as elevated levels of serum troponin T (5.68 ng/mL; normal range, <0.14 ng/mL) and a creatine kinase-myocardial band (33.73 U/L; normal range, <25 U/L), indicating AMI. Routine blood tests showed a mildly increased erythrocyte level (6.05 × 109/L; normal range, 3.5–9.5 × 109/L) and a significantly increased leukocyte level (20.56 × 109/L; normal range, 3.5–9.5 × 109/L) and platelet count (643 × 109/L; normal range, 100–300 × 109/L). However, his hemoglobin level was normal (171 g/L; normal range, 130–175 g/L) (). Emergency coronary angiography showed total obstruction of the middle of the left anterior descending coronary artery (). Therefore, leukocyte elevation was initially considered to be caused by stress after myocardial ischemia. After receiving 300 mg aspirin and 180 mg ticagrelor, a stent was successfully placed, and antiplatelet therapy with oral aspirin (100 mg per day) and ticagrelor (90 mg twice daily) was administered. He had no conventional risk factors for cardiovascular disease. Twelve days later, the patient suddenly developed dizziness, diplopia, and visual distortion. Cerebral computed tomography (CT) revealed a hemorrhagic infarction in the right parieto-occipital lobe (). The craniocervical CT angiogram (CTA) was normal. Blood routine test indicated mildly increased levels of hematocrit (55.4%; normal range, 40–50%), leukocytes (12.12 × 109/L; normal range, 3.5–9.5 × 109/L), and hemoglobin (183 g/L; normal range, 130–175 g/L) and significantly increased platelet count (1,128 × 109/L; normal range, 100–300 × 109/L). A blood electrolyte test showed an elevated potassium concentration (5.9 mmol/L; normal range, 3.5–5.5 mmol/L), and intravenous calcium gluconate was used to reduce blood potassium. However, in the next few days, blood routine examinations showed significantly increased levels of erythrocytes, hemoglobin, hematocrit, and leukocyte and platelet count (). Thus, bone marrow biopsy was performed, which demonstrated the proliferation of all three cell lineages. Bone marrow aspirate smears revealed active hyperplasia of bone marrow, and the ratio of G/E (granulocytes to erythrocytes) was 1.65. The proportion of granulocyte was increased, accounting for 56%, and granulocytes account for 34%. There were > 200 megakaryocytes. There were no common risk factors of atherosclerotic vascular diseases for the patient, including smoking, hypertension, diabetes, hyperuricemia, hyperhomocysteinemia, hyperlipidemia, and atrial fibrillation, etc.
Since hematocrit and hemoglobin levels were significantly increased and bone marrow biopsy showed proliferation of all three lineage cells, PV was strongly suspected. Gene testing confirmed a positive JAK2 mutation. The patient refused venous exsanguination. Patients with thrombosis aged >60 years should be treated with either hydroxyurea or interferon for descending cell therapy. He was then treated with hydroxyurea (500 mg) twice daily and interferon (30 μg) once daily. Since the patient was still required to take antiplatelet drugs to prevent thrombosis and myocardial and cerebral infarctions, the patient was only administered ticagrelor every 12 h. After 3 months of treatment, his blood routine returned to normal.


A 44-year-old woman with hemoptysis, hematuria, and epistaxis, and positive for PR3 antibodies, was scheduled to be hospitalized for renal and nasal biopsies. However, because the patient's respiratory status worsened, tracheal intubation with ventilator support was necessary. Although two days of steroid pulse therapy (1 g/day methylprednisolone) was started, her respiratory status did not improve within 2 days, and the patient required ventilator support with nearly 100% oxygen. Therefore, the patient was transferred to the ICU at our hospital with a suspected diagnosis of new-onset DAH with AAV (). On admission to the ICU, her oxygen partial pressure was 67.8 mmHg and her carbon dioxide partial pressure was 46.3 mmHg while on 100% oxygen and positive end-expiratory pressure. Laboratory tests revealed the following: PR3 antibody titer, 28.2 IU/mL; white blood cell count, 16,100/μL; hemoglobin, 6.1 g/dL; platelet count, 187,000/μL; albumin, 2.1 g/dL; blood urea nitrogen, 23.7 mg/dL; creatinine, 0.44 mg/dL; aspartate aminotransferase, 34 U/L; alanine aminotransferase, 19 U/L; lactate dehydrogenase, 779 U/L; total bilirubin, 1.1 mg/dL; creatinine phosphokinase, 657 U/L; C-reactive protein, 9.67 mg/dL; prothrombin time, 70.5%; activated partial thromboplastin time, 23.6 s; as well as hematuria and proteinuria.
Anticoagulant-free VV-ECMO was initially started using a heparin-coated circuit and it was planned to introduce anticoagulant gradually. However, bowel bleeding occurred on day 2 of admission. Because a colonoscopy showed multiple ulcers, an anticoagulant was not used for almost the entire duration of VV-ECMO. An anticoagulant (nafamostat) was trialed on day 9, but it needed to be stopped due to recurrent bowel bleeding.
To treat AAV, the patient was given a steroid pulse for 1 day followed by 1.0 mg/kg/day of prednisolone, and daily plasma exchange (7 times in 8 days). Additionally, 500 mg of cyclophosphamide was infused on day 6 (). After starting VV-ECMO support, oxygen partial pressure was maintained more than 150 mmHg by VV-ECMO with 100% oxygen gas and 3.5–4.0 L/min flow. On day 11, bilateral diffuse infiltration shadow by DAH was decreased on chest X-ray, after checking more than 250 mmHg of P/F ratio with clamping ECMO oxygen gas (no oxygen), VV-ECMO was withdrawn. On day 12, P/F ratio showed more than 400 mmHg, therefore, ventilator support was stopped and the patient was extubated. Only one VV-ECMO circuit could be completed without anticoagulant within a 10-day course without circuit exchange. However, deep vein thrombosis in the inferior vena cava (IVC) was diagnosed by computed tomography on day 12, which required IVC filtration management for 17 days, afterwards there was no recurrence of thrombus.
The patient was transferred from the ICU to a general ward on day 13, and discharged from hospital on day 51, after four infusions of cyclophosphamide (500 mg) by every two weeks. After a total of six infusions of cyclophosphamide, AAV was relapsed and the patient was prescribed rituximab (500 mg) by every two weeks, started 71st day from discharge, combined with 0.5 mg/kg/day of prednisolone.


A 65-year-old-female with a medical history of hypertension and diabetes mellitus presented to the emergency department with left-sided chest pain for 3 days. The pain was located in the midline and characterized as pressure-like, nonradiating, sometimes worse with ambulation, and occasionally relieved by rest. During the first encounter, the patient was afebrile and had blood pressure (BP) of 172/92 mmHg with an HR of 49/min, respiratory rate (RR) of 16/min, and oxygen saturation of 98% on room air. ECG revealed sinus bradycardia with HR of 54/min and nonspecific T wave changes in the inferior leads (). Blood tests revealed brain natriuretic peptide of 85 pg/mL (reference, <100 pg/mL) and thyroid-stimulating hormone of 0.69 mU/L (reference range, 0.5-5.0 mU/L), excluding heart failure and hypothyroid induced bradycardia. Myocardial infarction was ruled out by serial negative troponin tests. Because the patient had uncontrolled hypertension upon admission, medical optimization with losartan 50 mg daily and nifedipine ER 30 mg daily for better BP control was performed. Transthoracic echocardiogram showed left ventricular ejection fraction of 60%-65% with no significant valvular heart disease.
The following day, the patient reported some improvement in her chest pain. Given the presence of CAD risk factors with angina-like chest pain, further testing for ischemic heart disease evaluation was pursued. She performed an exercise Bruce protocol up to stage 2 with an exercise duration of 5 minutes, maximum metabolic equivalents of 7, and a maximum HR of 141/min (90% of maximal, age-predicted HR). Prior to starting the exercise stress test, her vital signs were BP of 145/75 mmHg and HR of 65/min. During the recovery phase, the patient developed an atrioventricular (AV) dissociation episode with a junctional rhythm at 1 minute and 19 seconds (). Her HR was 60/min, BP was 90/60 mmHg, and RR was 18/min with oxygen saturation of 98% on room air. The patient reported dizziness and sweating. We immediately laid her down on the table and started intravenous (IV) fluid with normal saline while closely monitoring her HR. Telemetry monitoring showed the lowest HR was 54/min with competing junctional rhythm at recovery stage three, 2 minutes 50 seconds after exercise (). The patient then experienced a transient syncopal episode for a few seconds. She began feeling better with the IV saline infusion, and ECG revealed that sinus rhythm with occasional premature ventricular contraction took over the junctional rhythm at recovery stage six, 5 minutes 50 seconds ().
She was feeling better on the following day without any focal weakness but still experienced intermittent chest pain. Given the presence of residual chest pain with transient syncope, she underwent coronary angiography that showed nonobstructive CAD with a 30% ostial lesion in the left anterior descending second diagonal artery. The next day, ECG and continuous telemonitoring showed no heart block, pauses, or junctional rhythm (). Because of the isolated bradycardic event after exercise, we decided to perform additional continuous cardiac monitoring with a loop recorder rather than placing a permanent pacemaker. The patient was discharged home without any further events on day 4 of hospitalization, along with guideline-directed medical therapy of losartan 50 mg daily, nifedipine ER 30 mg daily, atorvastatin 40 mg daily, and metformin 500 mg twice a day. She was seen in the outpatient cardiology clinic without any symptoms 1 week later and 2 to 3 months thereafter.


A 46-year-old female with a four-year history of PV presented to the dermatology clinic with new oral erosions and a tongue fissure consistent with active disease. Her diagnosis of PV was supported by direct immunofluorescence (DIF) of a skin biopsy, indirect immunofluorescence (IIF) of serum, and ELISA for anti-Dsg1 and anti-Dsg3 antibodies. The multidrug protocol was initiated with a prednisone taper, IVIg (Octagam® 2 g/kg per month divided into 5 consecutive daily infusions), mycophenolate mofetil 1000 mg BID, doxycycline 100 mg BID, niacinamide 500 mg TID, calcium supplementation, and a multivitamin. During her course, the patient was transitioned off from mycophenolate mofetil to rituximab 700 mg IV weekly as she was refractory to treatment.
During the fourth day of her IVIg infusion, the patient was noted to have a triangular-shaped, nontender nodule behind her right ear after receiving 12 grams of IVIg at an infusion rate of 75 ml/h. Vital signs remained stable and the patient denied any preceding illness. Examination demonstrated a 3 × 4 cm soft nodule within the right posterior triangle of the neck, consistent with postauricular lymphadenopathy (Figure ). The IVIg infusion was stopped, diphenhydramine IM 25 mg was administered, and the nodule resolved within 30 min. When the infusion was restarted at a slower rate of 50 ml/h, the lymphadenopathy reappeared within two minutes, and once again resolved within minutes of stopping the infusion and administering the antihistamine. IVIg infusion was once again restarted at a rate of 75 ml/h, and the patient completed the treatment uneventfully. The lymphadenopathy did not recur with subsequent IVIg treatments. The Naranjo algorithm or Adverse Drug Reaction Probability Scale indicates a “probable” causal relationship between the patient's lymphadenopathy and the IVIg administration.


This case report involved a 71-year-old male with advanced NSCLC (cT2N2M0 IIIa), without tumor driver genes mutations. The patient was diagnosed by percutaneous needle lung biopsy (PNLB) in October 2019. The main past history including the anticoagulant therapy for thrombus in the lower extremity veins from December 2019, a smoking history of 50 years, and the death of his sister from ovarian cancer. The Tumor Mutational Burden (TMB) of the patient was 9.68 mut/Mb. The expression rate of PD-L1 was 80% to 90% in tumor cells, and approximately 1% in immune cells. The patient was treated with first-line chemotherapy alone (pemetrexed plus carboplatin), rather than a combination therapy with ICIs or bevacizumab, due to medical expense and anticoagulant therapy (for thrombus in the lower extremity veins). When the tumor did not respond to this treatment, the patient agreed to a treatment of a single cycle of the ICI Tislelizumab (200 mg d1, 21 days a cycle; BeiGene, China) on March 12, 2020. Fever, weakness, and cough appeared in the afternoon and evening of the first day of treatment.
A computerized tomography (CT) of chest scan showed the presence of the tumor before ICI treatment (), and two weeks after the treatment, interstitial pneumonia appeared around the tumor (). An increase in serum interleukin-6 (IL-6) and tumor necrosis factor (TNF) was detected (). Myalgia occurred 10 days after the termination of ICI treatment. Anti-inflammatory treatment (Prednisone, 20 mg, qd; meloxicam,7.5 mg, qd) was administrated. Five days later, the patient felt weakness in the lower extremities (muscle force, grade 3) and could not stand or walk. The patient would gasp for breath after activity. It is not uncommon that ICI treatment of patients can result in the late-onset of immunological complications, including those involving the musculature, nervous, pulmonary, and endocrine systems.
The ability of the patient to perform daily physical activities was limited, especially in the lower limbs. Serum levels of creatine kinase (CK), lactic dehydrogenase (LDH), and α-hydroxybutyric dehydrogenase (α-HBDH) had increased (). Electromyography showed neural normal conduction, myotonic discharges in the bilateral anterior tibial, right quadriceps, iliopsoas, and biceps brachii were detected. Magnetic resonance imaging (MRI) found a diffuse exudation in the muscles of the backside and lower limbs (). Although the antinuclear antibody spectrum, myositis auto-antibody spectrum, immunoglobulin, and alexin were all negative, severe myositis was still considered a possible irAE based on the clinical manifestation above.
Myocarditis was believed to be another irAE concurrent with myositis. The level of cardiac troponin T (TNT) was remarkably high (). An electrocardiogram (ECG) indicated complete right bundle branch block (CRBBB), and potential inferior myocardial infarction, rather than the normal manifestation prior to ICI therapy (). Cardiac ultrasonography (UCG) and cardiac magnetic resonance (CMR) did not indicate abnormalities in the structure and function of the heart. The possibility of acute myocardial infarction (AMI) and pulmonary embolism (PE) were excluded by coronary and pulmonary angiography. Myocardial damage was considered to be an irAE induced by ICI therapy based on the clinical manifestations above.
Both serum glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) also increased (). The patient denied a history of hepatic diseases. Hepatic damage was considered an irAE based on a comparison of AST and ALT pre- and post-ICI treatment.
The level of cortisol (COR) and adrenocorticotrophic hormone (ACTH) was lower than normal values from April 17, which fluctuated following glucocorticoid therapy (). The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (TESTO) were normal, yet transitorily lower than the base value on April 17, while thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were normal. (). Secondary adrenal insufficiency was clinically diagnosed as an irAE (hypophysitis) with isolated ACTH deficiency (IAD) despite the lack of a pituitary MRI.
This patient initially accepted 80 mg of methylprednisolone intravenously to suppress the autoimmune reaction with the dose reduced gradually, until adjusted to oral prednisone with reduction sequentially. In addition, meloxicam (7.5 mg, qd) and total glucosides of paeonia (TGP) (0.6 g, tid) were administered to suppress inflammation and to regulate immune function. Coenzyme Q (Co-Q), fructose1, 6-diphosphate (FDP), and vitamin C were administered to protect the myocardium. Metroprolol succinate was administered to alleviate the workload of heart. To reverse the ICI-induced hepatic damage, reduced glutathione was administered. After the comprehensive treatment, the abnormal indications induced by ICI gradually recovered to normal. And the diffuse exudation reduced in the muscles of the right lower limbs (). The therapeutic process of irAEs is shown in .
Although the multiple-organs irAEs appeared, the efficacy of ICI therapy was encouraging. Following the treatment, the tumor lesion and inflammation around the tumor both diminished gradually until the final disappearance (). Meanwhile, the serum tumor markers (CA125, CYFRA211, and CEA) showed a downward trend (). Despite this initial success, cancer reoccurred in the right lung 4 months after the termination of ICI treatment ().
Positron emission tomography-computed tomography (PET-CT) examination confirmed the relapse of the tumor (). As a result of the seriousness of the irAEs of the patient, an ICI re-challenge therapy was not administered, and chemotherapy (vinorelbine plus carboplatin) plus bevacizumab was initiated as the subsequent treatment. After two cycles of the treatment, the area of the right lung lesion was reduced ().
After six cycles of the chemotherapy (vinorelbine plus carboplatin) plus bevacizumab, the right lung lesion increased again and directly invaded the pleura, then the patient chose the argon-helium knife cryotherapy as local therapy, and the chemotherapy (Abraxane plus carboplatin) plus bevacizumab as systemic therapy. However, after two cycles of the chemotherapy, serious myelosuppression appeared, and, meanwhile, the physical condition was poor, the patient began to accept the optimal supportive care until August 8, 2021.
The overall survival of this patient is 22 months up to now. Although multiple-organs irAEs occurred after only one cycle of immunotherapy, the patient may still obtain a benefit from the remarkable efficacy of immunotherapy to prolong survival.


A 47-year-old male with a past medical history of hypertension and pre-diabetes presented to the emergency department with three days of shortness of breath and two days of progressive left lower extremity pain and swelling. The patient reported testing positive for COVID-19 six days prior to presentation. The patient endorsed changes in taste and smell, fatigue, chills, and nausea. There was no prior history of DVT or pulmonary embolism. Physical exam was significant for tachypnea, oxygen saturation of 91% on room air, improved with supplemental oxygen to 100%. The entire left lower extremity was edematous and painful to palpation, with cold digits and non-palpable dorsalis pedis and posterior tibialis pulses, but present with Doppler. A venous duplex ultrasound of the left lower extremity revealed extensive DVT involving the common femoral vein, great saphenous vein, superficial and deep femoral veins, and popliteal vein (Figures -). Given his hypoxia, there were concerns for pulmonary embolism but because the patient had new renal dysfunction, it was decided to proceed with a monitored ventilation/perfusion (V/Q) scan. The V/Q scan revealed multiple, large, segmental perfusion defects in the bilateral lungs representing a high probability for pulmonary embolism (Figure ). Bedside echocardiogram revealed evidence of acute right heart strain with a dilated right ventricle and paradoxical septal wall motion (Video ).
Interventional radiology was consulted in the emergency department for concerns of phlegmasia cerulea dolens and sub-massive pulmonary embolism. The patient was emergently started on heparin and taken for left lower extremity venography which revealed extensive thrombosis of the femoral system, and thrombosis of the left iliac vein extending into the inferior vena cava (IVC). Interventional radiology took the patient for catheter-directed alteplase administration to the left femoral vein, left pulmonary artery, and main pulmonary artery. They also placed an IVC filter just below the renal veins. The patient stayed in the intensive care unit (ICU) for three days where he received continued alteplase administration, heparin, and supportive care. subsequent echocardiogram showed improvement of right ventricular distention, renal function, and vital signs. The patient was subsequently discharged on a rivaroxaban and appropriate follow up.


A 10-year-old boy who was otherwise healthy visited a private practice due to high fever, which had persisted for about 1 month. A blood test showed a high level of C-reactive protein (13.1 mg/dl; normal value: < 0.01 mg/dl), so he was referred to a nearby hospital for a further investigation.
Abdominal ultrasonography at that hospital revealed a solid large tumor in the liver (approximately 6.3 × 5.3 cm at the time). Enhanced computed tomography (CT) showed that the tumor was mainly located at S4 and S5 in the liver (Fig. ). The tumor was well-circumscribed and showed gradual weak enhancement from the arterial phase to the portal phase. On magnetic resonance imaging (MRI), the tumor showed low intensity on T1-weighted imaging and a high intensity on T2-weighted imaging, with partial diffusion restriction (Fig. ). 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed the marked uptake of FDG by the tumor, with an early maximum standardized uptake value (SUVmax) of 8.8 (Fig. ). There was no evidence of distant metastasis on any of the imaging modalities.
The levels of tumor markers, including α-fetoprotein (AFP), protein induced by vitamin-K antagonist-II (PIVKA-II), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), were all within the normal limits. Based on these findings, the most likely differential diagnosis was suspected to be undifferentiated sarcoma; thus, he was referred to our hospital for surgical treatment.
First, to confirm the diagnosis and develop an operation plan, a core needle biopsy was performed at our hospital. Based on the findings of the preoperative examination, including the biopsy results, the preoperative diagnosis was suspected hepatocellular carcinoma. The Child–Pugh score was 8 (albumin, 3; prothrombin time, 2; bilirubin, 1; ascites, 1; and encephalopathy, 1), and the indocyanine green retention rate (ICG-R15) was 2.9%. On enhanced CT just before the operation, the tumor was 8.7 × 10.4 × 13.1 cm in size, showing marked growth within a one-month period. We planned to perform elective surgical resection by laparotomy. At the operation, a large mass was located in the central portion of liver with no findings of peritoneal dissemination or intra-abdominal metastasis. The tumor involved liver segments 4, 5 and 8; however, the dorsal portion of segment 8 had been spared. The tumor did not actually invade Glisson’s sheath at the liver hilum, and the distance between the tumor and the umbilical portion of portal vein was 1 cm. After removing the gallbladder, hepatic parenchymal transection was performed with a water-jet hybrid knife (erbe JET2®; Erbe Elektromedizin GmbH, Tubingen, Germany) using the Pringle maneuver while confirming the tumor location using intraoperative ultrasonography. The dorsal portion of Segment 8 was successfully preserved. The blood supply of the area was confirmed by intraoperative ultrasonography after resection. Finally, the tumor was resected en bloc with a margin. The operative time was 521 min, and the blood loss was 490 ml. He was transferred to the previous hospital on postoperative day 12. Macroscopic findings showed a yellowish white, solid tumor of 10 × 9 cm in size with hemorrhage and necrosis (Fig. ). Although the tumor was well-circumscribed macroscopically, in a histopathological examination, the tumor cells showed an infiltrative growth pattern (Fig. a) and vascular invasion was observed (Fig. b). The tumor was composed of polygonal or oval-shaped cells arranged around blood vessels (Fig. c), spindle cells arranged in fascicles (Fig. d), and round epithelioid cells with clear cytoplasm (Fig. e). Tumor cells showed a high nuclear grade and multinucleated giant cells were also noted (Fig. f, indicated with yellow arrows). Mitotic figures were easily recognized; the mitotic activity was 30/50 hpf, including abnormal mitosis (Fig. f, highlighted with a red arrow). Immunohistochemistry revealed that some cells were positive for α-SMA and melan A, while approximately 50% of cells were positive for HMB-45 (Fig. ). These histopathological findings, along with immunoreactivity with melanocytic markers, were consistent with a diagnosis of perivascular epithelioid cell tumor. The diagnosis was also confirmed by a central review committee in the Japan Children’s Cancer Group (JCCG). After discharge from our hospital, he was followed up at another hospital. In the 6th month after the initial surgery, he complained of shoulder pain. MRI showed dumbbell-like shaped tumor at the 2nd thoracic vertebrae, which was confirmed to be bone metastasis of PEComa by biopsy. After reducing the tumor size by chemotherapy (including ifosfamide and doxorubicin), vertebrectomy was performed. Postoperatively he suffered from cerebrospinal fluid leakage and meningitis, which were treated by vancomycin. Additional therapy was judged to be unnecessary because no viable cells were found in the specimen. At two years from the relapse, in a regular follow-up visit, thoracoabdominal CT showed a 10-cm solid mass occupying the pelvis and a 15-mm nodule in the middle lobe of the right lung. The pelvic tumor was extirpated by laparotomy, while a nodule in right lung was removed in a thoracoscopic procedure. A pathological examination revealed that both lesions were PEComa, and genetic alteration of the TSC2 gene was identified in tumor cells. At four months after second relapse, pelvic metastasis appeared again. Since the third relapse, he has been carefully treated with a mammalian target of rapamycin (mTOR) inhibitor.


A 57-year-old Chinese man presented to our hospital with acute left lower quadrant abdominal pain in April 2019. He denied dyspnea, fever, night sweats, and weight loss. He is a non-smoker and a teetotaller. He denied any personal or family history of cancer. Physical examination was unremarkable, and his Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 1. An abdominal computed tomography (CT) scan showed an 8.9 ×5.7 cm solid mass in the left abdominal cavity (), and many soft tissue density shadows were observed in the abdominal cavity, especially in the rectovesical pouch (). Partial intestinal resection was performed with a mechanical side-to-side anastomosis and negative margins were confirmed intraoperatively in April 2019.The pathological result after the operation was as follows: small intestinal spindle cell tumor (
). Combined with morphological and immunohistochemical results, follicular dendritic cell sarcoma was diagnosed pathologically. Multiple tumor nodules were found in mesentery. Immunohistochemistry (): tumor cells CD21 (+, partial), CD23 (+ partial), CD35 (weak positive), sstr-2 (+, partial), CD163 (+ partial), cd68/pgm-1 (+, focal area), HMB45 (–), PCK (–), ALK (–), LCA (–), EMA (–), STAT-6 (–), syn (–), TLE (–), DOG-1 (–), SDHB (without delated), CD117 (–), DES (–), CD34(-), SMA (–), S100 (–), Ki-67 (+, 10% - 20%), in situ hybridization EBER1/2 (–), PD-1 (–), and PD-L1 (+90%) (). Next-generation sequencing (NGS) was applied in the specimen of the patient, but result of targeted genetic testing was negative. The CT after surgery showed multiple nodules in the mesentery, pelvic cavity and rectovesical pouch, and the largest nodule was 2.5*2.2 cm located in the rectovesical pouch (). However, PET/CT did not show focal hypermetabolism of those lesions corresponding to the nodules in CT (). The laboratory tests, including complete blood count, liver function, renal function, serum lactate dehydrogenase level and cardiac function, were in normal limits.
The patient received eight cycles of CHOP chemotherapy (Cyclophosphamide 750 mg/m2 d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1 and Prednisone 100mg d1-5 every 3 weeks) from May 2019 to January 2020. Following two cycles of CHOP chemotherapy, partial response (PR) was achieved based on the CT evaluation, and the largest lesion in the rectovesical pouch was 1.7*1.4 cm. (). Then, he accepted four additional cycles of CHOP. Due to the influence of coronavirus disease 2019 (COVID-19), he did not undergo imaging evaluation at the end of CHOP treatment. No serious nonhematological or late toxicities occurred during therapy. Unfortunately, only 2 months after receiving first-line chemotherapy, he had enlarged target nodal masses and newly occurring metastases in the mesentery by contrast-enhanced CT examinations in March 2020. The mass in the left midabdomen was 2.7 cm*2.8 cm (), and the largest lesion in the rectovesical pouch was 2.0 cm*1.6 cm (). Then, he achieved 2 cycles of ABVD chemotherapy (Adriamycin 25mg/m2 d1,15, Bleomycin 10mg/m2 d1,15, Vinblastine 6mg/m2 d1,15 and Dacarbazine 375mg/m2 d1,15 every 4 weeks) as a second-line treatment. Except for the mild nausea during the treatment, there was no other discomfort or obvious toxicity. However, the mass in the left midabdomen enlarged to 3.2 cm*3.0 cm, and the lesion in the rectovesical pouch increased to 2.0 cm*1.9 cm in June 2020 (). In June 2020, we administered to the patient a PD-1 inhibitor combined with an antiangiogenic agent: sintilimab 200 mg i.v. every three weeks and lenvatinib 14 mg orally once a day. After three cycles of treatment, the lesions size decreased (). After another three cycles of treatment, the mass lesion size continued to decrease, the mass in the left mid-abdomen shrank to 1.7 cm*2.2 cm (), and the lesion in the rectovesical pouch also decreased in December 2020 (). During the course of sintilimab combined with lenvatinib, the patients presented good tolerance to the combined approach. Myelosuppression, hypertension, diarrhea, or other adverse events, apart from fatigue, were not apparent. Disease developed again, as shown by a CT scan, in January 2021. PFS was 7 months following sintilimab and lenvatinib ().


A 71-year-old Irish Caucasian female presented with sub-acute bilateral lower limb pitting edema and dyspnea. Her background history included obesity (BMI 45.5), atrial fibrillation, obstructive sleep apnea, subclinical hyperthyroidism, eosinophilic colitis, and diverticular disease. She was an ex-smoker with a 20 pack-year history. Furthermore, she was under surveillance for a 3 cm ovarian cyst with the local gynecology services.
The patient had normal cardiac and respiratory examinations. Her transthoracic echocardiogram showed an ejection fraction of more than 50% with normal left and right ventricles and valves. Her chest radiograph was also unremarkable. An abdominal ultrasound was performed to assess for a pelvic mass that could impede pelvic venous return leading to peripheral edema. Ultrasound revealed an 8 cm hyperechoic mass lesion at the superior pole of the right kidney as well as a 2 cm hypoechoic liver lesion (Figure ). Subsequent computed tomography (CT) the of abdomen and pelvis with contrast confirmed an 8 cm smoothly defined heterogeneous right adrenal mass (Hounsfield Unit 57.75) and a number of low attenuation lesions throughout the liver (Figure ).
The patient exhibited potential features of cortisol excess including weight gain of 11 kg over two months and depression. She also had a newly diagnosed type 2 diabetes mellitus prior to admission with glycated hemoglobin (HbA1c) of 50 mmol/mol. The hormonal evaluation was consistent with hypercortisolism with failure to suppress on overnight dexamethasone suppression test and elevated 24-hour urinary free cortisol (Table ). There was no clinical or laboratory evidence of pheochromocytoma, hyperaldosteronism, or increased sex hormone production.
The patient was transferred to a tertiary referral center for surgical evaluation. Magnetic resonance imaging (MRI) and repeat CT thorax, abdomen, and pelvis demonstrated a large necrotic adrenal mass consistent with a primary adrenocortical carcinoma with direct invasion into the intrahepatic inferior vena cava. Multiple lung nodules concerning pulmonary metastasis were also observed. A diagnosis of adrenocortical carcinoma with pulmonary and hepatic metastasis was made. Due to metastatic disease, she was deemed unsuitable for surgery and treated pharmacologically with mitotane and metyrapone to manage symptoms caused by excess cortisol production by the tumor. She subsequently progressed to palliative care and died three months after diagnosis.


A 64-year-old male with a past medical history of hypertension presents to our facility with complaints of worsening abdominal pain for the last week. The patient reported that he had been experiencing abdominal discomfort that he initially attributed to gastric reflux, for which he was prescribed anti-reflux medications by his primary care physician, without improvement of symptoms. He stated that the abdominal pain was initially intermittent but subsequently progressed to persistent and constant abdominal pain. He also reported associated abdominal distension during the past week, with nausea and vomiting that began one day prior to presentation. The patient additionally reported not having a bowel movement for the past three weeks. The patient denies previous abdominal operations as well as ever undergoing a colonoscopy or upper endoscopy. He denies any family history of cancer. He reported denied a history of tobacco, alcohol or illicit substance use. He reported his occupation as a mechanic.
The patient’s vitals were stable on first encounter, apart from mild tachycardia of 103 beats per minute that normalized with intravenous crystalloid resuscitation. A complete blood count as well as chemistry panel were within normal limits. Lactic acid level was 1.2 mmol/Liter.
The patient’s physical exam was significant for abdominal distension that was tympanic to percussion in all four quadrants. The patient’s abdomen was diffusely tender to palpation, with increased tenderness in the epigastrium, but without peritonitis. No hernia was palpated in the bilateral inguinal regions. There were no prior surgical scars on the abdomen or pelvis.
Computed tomography (CT) of the abdomen and pelvis with intravenous contrast only demonstrated a high-grade obstruction with dilated, fluid-filled loops of small bowel and a transition point in the right lower quadrant (Figure ). The transition point demonstrated a segment of circumferential wall thickening without fat stranding (Figure ). There was no free air or fluid noted.
The patient underwent an exploratory laparotomy where an 8 cm stenotic segment of proximal ileum was noted with decompressed small intestine distally (Figure ). The stenotic segment was palpated and noted to be hard and fibrotic. No intestinal contents were able to be milked through this stricture distally. We decided to resect the stenotic segment and perform a primary anastomosis, which was performed without issue using staples. The remaining small bowel as well as the large bowel were inspected, and no further lesions were noted. The abdomen was closed in a standard fashion. On the backtable, the resected segment of small bowel was inspected and a thick fibrotic submucosal layer was noted with mucosal ulceration (Figures , ).
The patient’s post-operative course was rather unremarkable. The patient was ambulating on post-operative day #1, with bowel function returning on post-operative day #3. The patient was started on a liquid diet, which he tolerated well and was advanced accordingly. The was subsequently discharged on post-operative day #5. Histopathology of the resected segment of bowel demonstrated circumferential tubulo-villous adenoma with ulceration and fibrosis. No foci of carcinoma were noted.


A 19 year old male farmer from rural area in Sudan presented to our clinic at Omdurman Hospital –Sudan, complaining of chronic ankle pain, swelling and abscess formation for one year, it started with small painless swelling that gradually increasing in size, over period of time his life style had been affected by increasing pain intensity, walking difficulties and inactivity, symptoms became more severe when limited restriction of movement involved the subtalar joint. Sinus formation with purulent pale discharge and black grains were noted. Initially and without proper assessment, he was diagnosed with cellulitis and abscess formation, thus he was treated accordingly by incision and drainage. No biopsies or swabs had been taken for culture and sensitivity. Post-operative course oral antibiotic has been prescribed for 7 days. Since then the deterioration in his general condition had been growing steadily. Painful limping, swelling and limitation of movement on the affected side had been worsening dramatically. Furthermore he ended by using crutches. On clinical examination there was obvious ankle swelling and tenderness mainly at the lateral side of the hind foot, single sinus with active greenish discharge was identified [Fig. ]. Hematological investigations were unremarkable, X-ray revealed calcaneus scalloping lesion forming 2 cavities posterior to the posterior facet of the calcaneus consistent with chronic osteomyelitis [Figs. , ]. Surgical debridement under spinal anesthesia and tourniquet was employed in lateral decubitus position with lateral extensile calcaneus approach. Debridement was done and the 2 cavities were cleaned with aggressive curettage, the black grains consist of eumycetoma were confirmed by histopathology [Fig. ]. Hence, Itraconazole 400 mg daily for at least 1 year was prescribed. Six months follow up as it shown in the Table below:


Our patient is a 25-year-old, relatively short stature Hispanic male with a past medical history of polydactyly, severe anemia, thrombocytopenia, recurrent oral infections from Guatemala who presented to the emergency department (ED) with a chief complaint of a one-month duration of progressively worsening weakness and fatigue. He had poor exercise tolerance, dizziness, multiple recurrent near syncopal episodes, and one unwitnessed syncopal episode. The patient also endorsed weight loss for the past few months; however, he could not quantify it. On review of systems, the patient denied tongue biting, urine incontinence, fever, nausea, vomiting or diarrhea, black stools, blood in urine, or epistaxis. Social history was significant for chronic alcohol consumption. He denied any family history of cancer or bleeding disorders.
The patient was awake, alert, oriented, and hemodynamically stable upon ED admission. He was afebrile, borderline tachycardia at 101 beats per minute, respiration rate 20 breaths/min, O2 saturation was 100% on room air, and blood pressure was 107/68 mmHg. The physical exam showed short stature with normocephalic/atraumatic, possible microcephaly with pupil equal, round, reactive to light and accommodation, extraocular movement intact, slight icteric sclera, widely spaced teeth, irregular ridged ovoid tongue. The neck was supple, no lymphadenopathy, and jugular venous pulsations (JVP) of 6-8 cm. Lungs clear to auscultation bilaterally. The cardiac exam showed regular rate rhythm with S1, S2 heard, no murmur, rub, and gallops. The abdomen was soft, non-tender, non-distended, normal active bowel sounds; no organomegaly or masses were noted. The extremities exam was significant for black streak and vertical nail ridges on all four extremities. Skin exam showed petechiae of palms and soles. Whitish spots throughout the body and blackish purple papules in groups were observed on bilateral arms.
Laboratory test results were as follows: normal white blood cell count: 8.0 K/uL, differential count (polymorphous leukocyte 72%, slightly low lymphocytes at 16%, monocytes 7%, basophils 2%, minimally increased metamyelocytes at 1%), severe anemia with RBC 1.09 M/uL, hemoglobin at 3.8 GM/dL, reticulocyte 6.8%, hematocrit 12.2%, mean corpuscular volume (MCV) 111.9 FL, mean corpuscular hemoglobin (MCH) 34.4 PG, mean corpuscular hemoglobin concentration (MCHC) 30.7 G/dL, red cell distribution width (RDW) 20.3%, platelet 54K/uL, mean platelet volume (MPV) 11.3 FL, glucose level 134 mg/dL, slightly low calcium 8.5 mg/dL, elevated urobilinogen 4.0 E.U/dL, slightly elevated prothrombin time (PT) and activated partial thromboplastin time (APTT) at 15.0 sec and 22.8 sec respectively, elevated alanine aminotransferase (ALT) at 75 U/L, lactate dehydrogenase 478. Blood work did not show any vitamin deficiencies nor malnutrition.
The patient had a low absolute reticulocyte count at 2.0 and reticulocyte index at 0.79, which indicated hypo-proliferation. Hematology-oncology was consulted, who reviewed the peripheral smear that showed nucleated RBC and teardrop cells. Bone marrow biopsy was recommended, and specimens were drawn from the right posterior iliac bone. The biopsy showed myeloid neoplasm with complex genetic abnormalities, nearly 100% hyperplastic marrow with marked trilineage dysplasia, relative myeloid hyperplasia with increased abnormal eosinophilic precursors, erythroid left shift, atypical megakaryocytes, no increase in blasts or mast cell proliferation, mild reticulin fibrosis. Given the biopsy findings, a defined diagnosis could not be obtained, and cytogenic analysis, flow cytometry, and karyotype were recommended. The laboratory results are discussed in (Tables -).
The bone marrow biopsy does not suggest any form of AML. It showed hypercellularity with some erythroid dysplasia on the smear. As a result, DiGuglielmo’s syndrome was suspected. While the patient is young for MDS, based on the FISH panel, flow cytometry, and karyotype, MDS was suspected. The patient had been managed with necessary blood transfusion, fresh frozen plasma, and continuous monitoring for hemoglobin and platelet status. In light of short stature, microcephaly, suspected cognitive deficiency, and another congenital disorder was suspected. As a result, the patient was transferred to another hematology facility for further evaluation.


We describe the case of a 63-years-old man who was transferred to the Department of Burns and Plastic Surgery of the University Hospital Brno, Czech Republic, with deep burns in the region of thorax and abdomen, covering 5% of the total body surface area (TBSA). His vitals on admission showed a body temperature of 37.2 °C, blood pressure of 163/87 mmHg, and a heart rate of 98/min. On admission, the patient suffered from massive cutaneous myiasis, pediculosis of the head, and phlegmon of the thorax. The patient lived in poor and unhygienic conditions (homeless/staying in shelters for homeless people overnight). He admitted to tobacco and alcohol abuse; he also had hepatitis A in the past. He reported that his burns were the result of an injury that happened two weeks prior, when his shirt caught fire while smoking a cigarette. Right after the injury, first aid was provided by the shelter employee. For the next two weeks, however, the wound was left unattended. The wound showed signs of accidental myiasis, redness, and edema ().
The maggot infestation was immediately mechanically removed, and swabs were taken for microbiological analysis. Local therapy included Octenisept® (Schülke & Mayr GmbH, Norderstedt, Germany) for antisepsis and Flamazine® cream 1% w/w (Smith & Nephew Pharmaceuticals Ltd., Hessle Road, Hull, UK) for wound-bed preparation; at the same time, systemic oral therapy with amoxicillin, clavulanic acid (1 g every 8 h) and metronidazole (500 mg every 8 h) was initiated. Dressings were changed every 2 days; no maggots were observed after the first infestation removal and the wound bed was prepared for closure. Staphylococcus aureus, Streptococcus pyogenes, and W. chitiniclastica were isolated from the initial swab, all susceptible to amoxicillin and clavulanic acid. On day 7, debridement under general anesthesia was performed and defects were finally covered with split-thickness skin grafts on 3% TBSA ().
The next series of swabs revealed only coagulase-negative Staphylococcus in a single spot; hence, the systemic therapy with amoxicillin and clavulanic acid continued for 8 days. All skin defects were completely healed, and the patient was discharged to our outpatient care and long-term care ward for intensive rehabilitation ().
As a part of the microbiological examinations, swabs from the patient’s burn areas were transferred to culture media suitable for both aerobic and anaerobic growth; blood agar (Merck KGaA, Darmstadt, Germany), McConkey agar (selective medium for growth of gram-negative bacteria; Pronadisa, Conda Laboratories, Madrid, Spain) and blood agar with NaCl addition (selective agar for staphylococci; Merck KGaA, Germany) were used for aerobic culture and VL agar (Bio-Rad Laboratories Chemical Division, Richmond, CA, USA) was used for anaerobic culture. The inoculated culture media were then incubated for 18–24 h at 35–37 °C; blood agar and chocolate agar (OXOID CZ, Brno, Czech Republic) in the atmosphere with elevated CO2 concentration, VL agar in the anaerobic atmosphere, and the remaining media in a normal atmosphere. The growth of the W. chitiniclastica strain on the culture media and the morphology of the individual colonies are shown in .
The colonies were then identified using the MALDI-TOF Biotyper (Bruker Daltonics, GmbH, Leipzig, Germany) and software MALDI TOF MS, version 3.1.
In addition, bacterial DNA obtained from the culture of W. chitiniclastica was isolated by the QIAamp BiOstic Bacteremia DNA Kit (QIAGEN Redwood City, CA, USA). DNA was analyzed by the 16S rRNA Sanger sequencing method (SEQme s.r.o., Dlouha 176 26,301 Dobris, Czech Republic), forward primer 5′-AYTGGGYDTAAAGNG-3′ and reverse primer 500B4-CCGTCAATTYYTTTRAGTTT-3′ were used. A 98% match of the specified sequence with the sequence of W. chitiniclastica DSM 18,708 strain S5 16S rRNA was found using the basic local alignment search tool (BLAST) provided by the National Center for Biotechnology Information (NCBI) [] ().
The susceptibility of W. chitiniclastica to antibiotics was established by determining the minimum inhibitory concentration using the MicroScan WalkAway MIC instrument (Beckman Coulter, Brea, CA, USA). Susceptibilities were evaluated using a disc diffusion method according to the EUCAST standard–PK/PD (non-species related) breakpoints (EUCAST Clinical Breakpoints Tables, v.10.0, January 2020). The W. chitiniclastica strain was sensitive to the tested antibiotics, including the amoxicillin/clavulanate used in the therapy ().


A 63-year-old Taiwanese woman presented to our emergency department with sudden onset of weakness in both lower limbs. Her medical history included hypertension, anemia, and a cardiovascular accident without neurological sequelae. Two hours before admission, she experienced acute onset of bilateral lower back pain while bathing. She rated the pain as 5 out of 10 on the numeric rating scale (NRS). Approximately 30 min after her bath, while she was resting and watching television, she experienced sudden bilateral lower limb pain, weakness, and numbness. The numbness was described as the same feeling that follows electric shock. The back and lower limb pain worsened, and the NRS score rose from 5/10 to 10/10. She was unable to walk or even stand up because of the weakness and pain in both limbs. After calling the emergency number, she was sent to the regional hospital where magnetic resonance imaging of the thoracic spine to lumbar spine revealed an epidural hematoma extending from the levels of T12 to L1 (Figs. and ). Some analgesic medication was injected twice, but the pain persisted. She was then transferred to our medical center for further treatment.
During history taking, the patient denied any other discomfort such as nausea, vomiting, dizziness, headache, choking, seizure, focal neurological deficits (such as visual change or aphasia), urinary incontinence, fecal incontinence, fever, neck pain, abdominal pain, or any history of back trauma. Although this patient had a stroke ~ 12 years ago, she had recovered almost entirely after undergoing rehabilitation for 2 years, and she had consumed neither aspirin nor anticoagulant since then. She had undergone acupuncture 2 years earlier for her chronic sciatica. The patient did drink alcoholic beverages and chewed betel nuts over the previous 30 years, but she had never smoked.
During admission to our emergency department, her body temperature was 36.4 °C, respiratory rate was 18 per min, pulse rate was 67 bpm, blood pressure was 185/106 mm Hg, and oxygen saturation was 90% on room air. The physical examinations over the head, neck, chest, heart, and abdomen yielded normal findings. In both lower limbs, however, her muscle power was only approximately 3 (measured by Medical Research 58 Council Manual Muscle Testing scale). No edema or wound was present over the extremities. The deep tendon reflex was normal (2+) in both upper arms but decreased (1+) in both lower limbs. Tenderness over the back and both lower limbs was identified. Blood examinations did not show any significant findings and they were shown in Table .
For analgesic control, we initially prescribed celecoxib (Celebrex), 200 mg/cap BID; tramadol (Tramacet), 37.5 mg QHS; and acetaminophen, 325 mg QHS. However, her pain persisted; on the NRS, it remained as 9/10 or 10/10.
A neurosurgeon was consulted for the diagnosis of spinal epidural hematoma. The patient underwent emergency surgery to remove the epidural hematoma and laminectomy for decompression of T11–L3. After the operation, she was able to move her lower limbs with a greater range of motion, and the muscle power was ~ 4. The pain over the lower limbs was relieved, and the only pain she experienced was in the area of the surgical wound over the back. Acetaminophen for analgesic control was given for the wound pain. Tramadol was given occasionally for further pain control. Because the patient’s general condition was stable and she recovered well from the surgery without any neurological deficit, she was discharged from our hospital after 2 weeks. Physiotherapy for rehabilitation was recommended and the patient was well followed up indeed.


A thirty-six year-old woman became pregnant after infertility treatment consisting of ovulation stimulation and intrauterine insemination. Pregnancy was complicated by a history of cervical insufficiency (cervical cerclage in 30th week of pregnancy) and cervical infections (Klebsiella pneumoniae, Enterococcus foecium—both widely susceptible) successfully treated with antibiotics.
At 34 weeks and 3 days, a gestational age premature baby girl was born by caesarean section as a first of the triplets, with birth weight 1720 g and Apgar score of 9, 8, and 9 at 1, 5, and 10 min, respectively. After delivery room stabilization, she was placed into an incubator with passive oxygen therapy. The newborn received total parenteral nutrition and trophic feeding of expressed mother’s colostrum in the first day of life, then was supported with donor human milk from the Human Milk Bank through orogastric feeding tube. On the second day of life, patient received phototherapy due to abnormal total serum bilirubin concentration (10.2 mg/dL). At the end of the third day, the infant’s health suddenly deteriorated, requiring intubation and ventilation. From the first symptoms and abnormal infections markers (high CRP—247.5 mg/L, PCT—17.14 ng/mL, low leukocyte—3.4 G/L, and platelet count—29 g/L) she was treated with meropenem (40 mg/kg/dose twice a day) and vancomycin (15 mg/kg/dose twice a day). Blood culture was positive and C. sakazakii NMI5563_17 isolate had been identified on the sixth day of life. Phenotypic detection of ESBL was carried out by the ESBL double-disc synergy test (DDST) as described previously []. The antibiotic susceptibility testing was evaluated using gradients tests and broth microdilution method for colistin (; accessed on 1 June 2021). Isolate showed resistance to ampicillin, piperacillin, ceftazidime, cefotaxime, and aztreonam ().
On the fifth day of life, the platelet transfusion was performed. The culture of cerebrospinal fluid was negative. Despite appropriate antimicrobial treatment with meropenem (according to the susceptibility profile of the bacteria), the infant had developed sepsis with multiorgan failure and meningitis with multiple brain abscesses. Cerebral ultrasound showed multiple brain abscesses with disintegration tendency and complete obliteration of brain structures. The electroencephalography examination showed low voltage signal. After discussion with her parents, care was redirected to palliation, and the infant died at 12 days of age.
The other triplets (II-female 1500 g and III-male 1430 g) have been fed in the same way (orogastric tube and own mother’s breastmilk supplemented by donor milk) and were in good condition with no symptoms of infection. They were discharged after 27 days of hospitalization.
In the course of epidemiological investigation, mother’s skin (axillary and inguinal regions), hospital surfaces, and equipment were swabbed, milk samples (from mother’s breastmilk and Human Bank Milk) together with milk expressing devices including breast pump kits, underwent microbiological examination. The analysed surfaces, devices, and milk did not show Cronobacter contamination.


A previously healthy 44-year-old woman presented to the infectious diseases outpatient department of the University Hospital (IHU Méditerranée Infection) of Marseille, France, in May 2019 for a non-healing ulcer located under her right ear slightly extending to the lower part of the ear lobe, which evolved since the end of January ().
Regarding her travel history, she reported a stay of ten days in Mexico during the Christmas vacation in the Yucatan region with only half a day walking in the tropical forest. She reported paresthesia in the area surrounding the lesion. With a the cervical and thoracic CT-scan, there was no lymphadenitis observed but a slight increase of size of the left parotid gland under the skin lesion. Routine laboratory tests were normal, including C-reactive protein level and blood cell counts. Swab samples of the ulcer were collected for microbiological investigations. Polymerase chain reaction (PCR) and culture aimed at detecting Mycobacterium spp, dermatophytes and pyogenic bacteria were negative. Real-time PCR tests targeting the kinetoplastic minicircle gene successfully detected Leishmania spp. []. Subsequent sequencing targeting both the ITS1 and ITS2 region of the rRNA gene performed by the laboratory of the National Reference Center—Laboratory Expert (CNRL) for Leishmania (Montpellier, France) found 100% identity with L. mexicana (Genbank FJ948435.1). Serological investigation showed a positive serology for Leishmania spp. only on immunoblotting assay (LD-Bio Diagnostic, Lyons, France). The diagnosis of cutaneous leishmaniasis due to L. mexicana was retained. At a one month of follow-up, the patient had recovered and skin ulceration and inflammation had disappeared ().
We performed a review of the literature in Medline in the English language using the following keywords “Cutaneous leishmaniasis”, “Leishmania mexicana” AND “travel” OR “traveler”. We found 12 references reporting a total of twenty-eight humans cases of CL caused by L. mexicana in travelers () [,,,,,,,,,,]. Most cases were reported in male travelers returning from Belize, followed by Mexico. Two references reported cases in soldiers who underwent jungle military training in Belize [,]. The others reported travels were mainly for touristic reasons. Except for the present case, none involved a French traveler. Regarding clinical features, only three patients presented with the typical localization involving the ear, and three patients had lesions on the face (nose and eyelid). For all patients except our case, the diagnosis was performed on a skin biopsy. The reported treatment strategies were highly heterogeneous. Only two cases, (including ours) received no treatment and healed spontaneously. The other treatments reported in the literature included liposomal amphotericin B, intravenous and intralesional sodium stibogluconate, IV or oral fluconazole, cryotherapy, thermotherapy and topical imiquimod. Two patients had recurrence of their lesions after a first line of treatment and required a second-line treatment for healing.


Patient 1 is a 45-year-old man with no significant past medical history. He presented to the hospital with abdominal pain and malaise of 2 weeks. Laboratory studies were notable for macrocytic anemia (10.6 g/dl, reference range 12.0–18.0 g/dl; 102.0 fl, reference range 78.0–94.0 fl) and profound thrombocytopenia (19,000/μl, reference range 140,000–440,000/μl). Initial bloodwork also identified 33% blasts in the peripheral blood. Physical exam was notable for a palpable spleen to the left umbilicus with mild tenderness to palpation. An ultrasound examination demonstrated an enlarged spleen measuring 22.2 × 21.0 cm without focal lesions or perisplenic collections. The patient was subsequently admitted to the hematology service for further workup.
Bone marrow biopsy () demonstrated markedly hypercellular marrow (90% cellular), with approximately 50% of the cellularity composed of pale, round, degranulated mast cells scattered and in clusters, aberrantly expressing CD25. Aspirate smears revealed approximately 48% abnormal degranulated mast cells and 23% myeloblasts. The patient was diagnosed with mast cell leukemia, aleukemic variant, with concurrent acute myeloid leukemia (MCL-AML). His serum tryptase level was 614 μg/l (reference range <11.0 μg/l) at the time of diagnosis.
The patient received chemotherapy with 7 + 3 regimen (cytarabine 100 mg/m2/day and idarubicin 12 mg/m2) with midostaurin (50 mg daily). After salvage cladribine (0.13 mg/kg daily for 5 days) with high-dose midostaurin, his recovery marrow showed persistent mast cell leukemia with no increase in blasts. The patient was subsequently switched to avapritinib, and his tryptase levels decreased from 391 to 22 UI/l after 6 months. The patient’s bone marrow at 8 months following initial diagnosis showed 15% mast cells without evidence of AML, compared to 50% mast cells at initiation of avapritinib. He received a matched unrelated donor peripheral blood stem cell transplant 10 months after initial diagnosis, which was complicated by severe gastrointestinal graft-versus-host-disease. Currently, the patient is 17 months from his initial diagnosis; he remains on avapritinib with regular follow-up.
Four additional patients with MCL-AHN were identified within our institution, and all available records were reviewed (). Patient 2 was a 71-year-old man who presented for evaluation of extreme fatigue. Workup revealed early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), and the patient was started on combination chemotherapy consisting of 6-mercaptopurine, vincristine, methotrexate, and prednisone (POMP) with low-intensity intrathecal methotrexate. A posttreatment bone marrow biopsy/aspirate 3 months later demonstrated no evidence of residual leukemia but marked mastocytosis (63%) with aberrant positive expression of CD25 and CD2, consistent with MCL. Flow cytometry revealed recurrent ETP-ALL 19 months after the first diagnosis of malignancy despite maintenance chemotherapy. He died of disease 2 months later.


Patient 3 was a 74-year-old man who was evaluated 14 years prior for chronic anemia. His bone marrow biopsy at that time revealed myelodysplastic syndrome with ringed sideroblasts, and he was managed on observation. Eight years later, a repeat marrow biopsy was performed for worsening anemia, demonstrating persistent myelodysplastic syndrome and 3% mast cells. He was started on Aranesep and red blood cell transfusions. Repeat bone marrow 2 years later revealed persistent myeloid neoplasm with mast cell aspirate count of 20%, consistent with MCL-AHN. He began midostaurin and received darbepoetin every other week. The patient died 4 years after the diagnosis of MCL-AHN from pneumonia with persistent mastocytosis at time of death.


Patient 4 was a 60-year-old man who presented to the hospital with a suspected cardiovascular accident. His initial bone marrow biopsy demonstrated AML with abnormal mast cells (positive for CD25 and CD2) involving <5% marrow cellularity. He was treated with standard induction chemotherapy followed by consolidation. A repeat marrow biopsy 10 months later demonstrated no evidence of AML but 37% mast cells consistent with MCL. He received cladribine, then switched to midostaurin for persistent disease. The patient failed to respond significantly to any MCL therapy, and subsequent bone marrow biopsies continued to show persistent MCL without evidence of AML. He died of disease less than 2 years after his initial diagnosis.


Patient 5 was a 68-year-old female who was diagnosed with AML after presenting with fatigue and increased peripheral blood myeloblasts. The patient was started on standard induction chemotherapy and achieved morphologic remission on day 14. One month later, a bone marrow aspirate revealed 11% myeloblasts with 34% mast cells, which aberrantly expressed CD25. The patient underwent consolidation therapy with a matched unrelated donor stem cell transplant. Unfortunately, the patient demonstrated AML relapse and persistent low-level mastocytosis. She died of disease 47 months after her initial diagnosis of AML.


In 2005, a 66-year-old female consulted for nasal obstruction and rhinorrhea evolving since 8 months. Clinical examination documented a left polypoid nasal lesion; tumor biopsy revealed an ACC. The patient underwent surgery followed by radiation therapy (64Gy). During follow-up, after 8 years, the patient presented a distant recurrence of the disease with solitaire lung metastases. No local relapse was observed. Metastasectomy of the lesion was practiced with economic margins, followed by radiotherapy (60Gy). In April 2019, the patient presented at the hospital for a pain in the right flank. No other symptoms were reported. Computed tomography (CT) of the abdomen showed multiple hypodense nodular lesions of the two kidneys, the larger one measuring 30 × 25 × 40 mm in the right kidney ().
The patient was referred fora CT-guided renal biopsy. Histology showed a cribriform growth pattern with two types of cells, monomorphic epithelial cells with a basophilic cytoplasm and myoepithelial cells, which was consistent with kidney metastases from ACC ().
The patient was treated with chemotherapy: CAP (Cyclophosphamide-Adriamycin-Cisplatinum) regimen (cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2, and cis-platinum 50 mg/m2). The radiological evaluation by a CT scan after six cycles of chemotherapy showed a stable disease. Within 7 months, a progression of the disease was observed with the occurrence of lung and bone metastases. Therefore, second-line chemotherapy was indicated: capecitabine with bisphosphonates. Actually, the patient is still alive. After four cycles of capecitabine, a further line of chemotherapy has been started because of a progression of bone metastases. She is still receiving chemotherapy based on paclitaxel with disease stability.


A 57-year-old multiparous woman with a history of cystocele which was corrected with colporrhaphy three years prior presented to the hospital with four weeks of sharp, unrelenting right-sided gluteal pain that radiated down her right leg; the pain was worse with urination and defecation and associated with red-brown and purulent vaginal discharge. Medical history was notable for oral hormone replacement with estradiol, otherwise not relevant to her presenting condition. Surgical history was notable for colporrhaphy three years prior, as well as abdominal hysterectomy eighteen years prior for ovarian cysts. She smoked a half-pack of cigarettes per day and was monogamous with her husband, and neither of them had ever had a sexually transmitted infection.
Upon initial evaluation, vital signs were notable for temperature of 37.9 degrees Celsius and a blood pressure of 96/55 mmHg. Serologies demonstrated hypokalemia of 2.8 mmol/L, white blood cell count of 14,980/uL, and were otherwise unremarkable. Urinalysis was cloudy with trace protein, red blood cells 26–50/hpf, white blood cells >50/hpf, bacteria >50/hpf, and epithelial cells >10/hpf; culture grew mixed urogenital flora all at <10,000 cfu/mL. Vaginitis screen was negative for trichomonas, Gardnerella vaginalis, and Candida species. Computerized tomography (CT) of the abdomen and pelvis with contrast showed a 6.0 × 5.0 × 5.9 cm multiloculated abscess along the right lateral pelvic wall and within the gluteus maximus ().
She was admitted to the hospital, started on ceftriaxone and metronidazole, and gynecology and interventional radiology were consulted. A drain was placed into the abscess by the interventional radiologist on hospital day 1. The gynecology consultant considered the patient's nidus for infection to be the non-absorbable sutures from her colporrhaphy. Cultures from the wound demonstrated heavy growth of A. turicensis and moderate growth of Streptococcus constellatus on hospital day 4. Antibiotics were then transitioned to oral amoxicillin/clavulanate 875/125 mg twice daily. She was discharged home on hospital day 4 in good condition, on antibiotics and with her drain in place.
Six days post-discharge, the interventional radiologist replaced the patient's drain to access a deeper area of the abscess. Eleven days post-discharge, she had one stitch removed at the bedside during follow-up with gynecology, who also confirmed both by chart review and discussion with the surgeon who performed the colporrhaphy that there was a second suture placed in the right apex of the vagina and tied down to the right uterosacral ligament. On follow-up with infectious disease, she was continued on her antibiotic course for a total of 6 weeks, after which they determined her abscess had resolved. Her drain was removed by the interventional radiologist 50 days post-hospitalization after fluoroscopic evaluation demonstrated complete drainage of the cavity (). She then underwent surgical exploration 53 days post-discharge, and no additional sutures or foreign bodies were identified. During post-surgical follow-up with gynecology, they determined that her abscess had completely resolved.


The proband is an 8-year-old male born as the sole child of healthy and non-consanguineous Chinese parents. The mother did not report any history of exposure to teratogenic pathogens or drugs during gestation. Birth weight of the child was 3,150 g (25th percentile), birth length was 51 cm (75th percentile), and occipitofrontal circumference (OFC) was 36 cm (>95th percentile) on week 39 of gestation. He has been suffering from severe hypotonia and feeding difficulty since birth. The proband was able to grasp at 6 months and could sit at 9 months. At 13 months of age, the patient was admitted to Beijing Children’s Hospital affiliated to Capital Medical University for astasia, development delay and failure to thrive with feeding difficulty. He manifested dystonia in the extremities, with complete inability to stand up and walk. He could not speak, even simple words such as “baba” and “mama”. Electroencephalograph (EEG) analysis did not reveal any abnormalities, whereas brain magnetic resonance imaging (MRI) showed bilateral dilation of lateral ventricles, periventricular leukomalacia and delayed myelination. No definite diagnosis existed to that time, and he did not undergo any adjuvant therapy. At the age of five, he presented to our hospital for severe psychomotor development. On examination, he had severe intellectual disability, hypotonia, strabismus and esotropia. He was unable to speak or communicate. He was able to walk with some aid but exhibited poor balance and he could not jump on one foot. In addition, the subject suffered from constipation. Facial dysmorphisms included a triangular face, microcephaly, low-set posterior rotated ears, and a thin and tented upper lip. He had long and slender fingers. His height, weight and head circumference were 107 cm (14th percentile), 15.5 kg (4th percentile) and 47.1 cm (<1st percentile), respectively.
In this family, we identified only one patient (proband) and proband’s father and mother is normal. We therefore used SNP array analysis and whole genome sequencing to search for any evidence of the disease.


A 71-year-old Japanese man presented with nausea, upper abdomen discomfort, and weight loss of 10% during the past year (62.9 kg at presentation; the former body weight was 70 kg). He had a surgical history of distal gastrectomy with Billroth II reconstruction for a benign gastric ulcer when he was 27 years old.
The physical examination was unremarkable. Laboratory tests revealed slightly elevated C-reactive protein (1.28 mg/dL) with no signs of pancreatitis, cholangitis (total amylase: 119 U/L, total bilirubin: 1.0 mg/dL, alkaline phosphatase: 283 U/L, aspartate aminotransferase: 21 UL, alanine aminotransferase: 14 U/L; all were at normal level). γ-Glutamyl transpeptidase was slightly elevated (69 U/L). The tumor markers, carbohydrate antigen 19-9 and carbohydrate antigen 125 were also elevated (310 U/ml and 37.0 U/mL, respectively). Abdominal contrast-enhanced computed tomography revealed thickening of the anastomosis site of the gastrojejunostomy as well as significant dilation of the afferent loop, common bile duct, bilateral intrahepatic bile ducts, and gallbladder (Fig. ). Gastrointestinal fiberscopy revealed a 2-cm nodular lesion at the anterior wall of the stomach just near the anastomosis site (Fig. a). Irregular and hemorrhagic mucosa spread circularly from the nodular lesion to the anastomosed jejunum, which was suspected to be the spread of the tumor (Fig. b). The stoma of the afferent loop was not visible, indicating complete obstruction of the afferent loop. Thus, endoscopic decompression was not feasible. Meanwhile, the orifice of the efferent loop was patent (Fig. c). Based on these findings, the patient was clinically diagnosed with remnant gastric cancer with afferent loop syndrome. In order to prevent obstructive pancreatitis and cholangitis while providing time for preoperative scrutiny, a sonography-guided PTCD procedure was performed 3 days following the presentation. To decompress the afferent loop, an 8.5-French pigtail catheter was inserted via the lateral inferior branch of the intrahepatic bile duct, with the catheter tip placed in the duodenum (Fig. a).
Biopsy of the nodular lesion revealed a well-differentiated tubular adenocarcinoma. There were no sign of distant metastasis or peritoneal dissemination. Therefore, radical surgery was considered.
However, 18 days following the first PTCD, the patient developed a fever, and laboratory values revealed elevated total bilirubin (3.6 mg/dL), alkaline phosphatase (467 U/L), γ-glutamyl transpeptidase (230 U/L), total amylase (503 U/L), and transaminase (aspartate aminotransferase: 37 UL, alanine aminotransferase: 46 U/L). White blood cell count (9200/μL) and C-reactive protein level (14.87 mg/dL) were also elevated. On computed tomography, the afferent loop was still dilated, but to a lesser extent than the first PTCD. The patient was thought to have developed obstructive cholangitis and pancreatitis owing to insufficient decompression of the afferent loop. Since emergency surgery was considered risky in a situation where the patients had developed acute cholangitis and pancreatitis, sonography-guided PTCD was performed again. The former catheter placed in the duodenum was replaced by an 8.5-Fr multiside hole pigtail catheter, and a 7-French multiside hole straight catheter was added to the common bile duct via the same insertion point and intrahepatic bile duct (Fig. b). Defervescence was promptly achieved, and the serum total bilirubin, amylase, transaminase, C-reactive protein levels, and white blood cell count were normalized within a week from the second PTCD.
Although no signs of malnutrition were detected in the laboratory test results at presentation (serum albumin: 3.8 g/dL, total protein 7.3 g/dL, lymphocyte counts: 1500/μL; all were at normal level), the patient showed weight loss of 10% during the past one year; since it was considered to indicate malnutrition, we performed active nutrition therapy from the time of admission. Enteral nutrition was performed through a nasal feeding tube inserted into the efferent loop. The drainage of the PTCD tube was also administered via the feeding tube. Weight loss was not observed until the operation. Serum albumin level, total protein level, and lymphocyte counts had dropped at the operation (serum albumin: 2.8 g/dL, total protein: 5.8 g/dL, lymphocyte counts: 1100/μL), and it was thought to be owing to cholangitis and pancreatitis.
After subsiding cholangitis and pancreatitis by second PTCD, an elective surgery was performed 10 days following the second PTCD. No signs of distant metastasis or peritoneal dissemination were observed during the operation, and the peritoneal lavage cytology was negative. The gastrojejunostomy of the former operation was performed via antecolic Billroth II without Braun’s anastomosis (Fig. ). Total remnant gastrectomy, Roux-en-Y reconstruction, and jejunostomy were performed curatively. The patient developed intestinal obstruction due to bending of the jejunum at the jejunostomy site, but it was successfully managed with supportive therapy. The patient was discharged from the hospital on postoperative day 56th. Histopathological examination of the specimen revealed moderately differentiated tubular adenocarcinoma with invasion to the subserosal layer and no metastasis in the lymph nodes. All the surgical margins were intact. Postoperative adjuvant chemotherapy was not administered. The patient died 8 months following the operation owing to peritoneal dissemination.


A 17-year-old boy came with a chief complaint of lump and pain on his left elbow. He previously fell from the stairs about 1 m in height with the elbow hitting the ground, but the pain is subsided in two days. One month later, the patient felt there was a lump with a size of a marbleon the left elbow, which getting bigger to a size of a tenis ball, and was accompanied by pain. General examination showed there was no abnormality but the patient complained of decrease 5 kg of total bodyweight. The local state of the left elbow shows fixed, solid mass on the posterior aspect of the elbow, with the size 14x12cm, 30 cm circumferentially (contralateral 27 cm) (). The range of motion of the left elbow joint could not be measured because of pain. On radiographs obtained at the first examination, an osteolytic lesion and periosteal reaction of the distal humerus was observed (). On magnetic resonance imaging (MRI), a low intensity was observed on T2-weighted imaging (). Computed tomography of the chest showed that there was no abnormality. The patient underwent histopathological and immunohistochemistry examination, with the result of conventional osteosarcoma (). The diagnosis of osteosarcoma was made.
The patient underwent neoadjuvant chemotherapy with cisplatin, ifosfamide, and adriamycin for 3 cycles. Limb salvage surgery by wide excision, cryosurgery followed by total elbow arthroplasty and ORIF with plate and screw. The patient was positioned right lateral decubitus position under general anaesthesia. The tumor was exposed and shaft humerus osteotomy within 5 cm above the tumor was performed. The radial artery, radial nerve, and ulnar nerve was identified and preserved. The bony segment was resected and prepared for autoclave processing. A thorough debridement of all the tumor and soft tissues from the resected bony segment was performed and the excised bony segment was frozen in pot containing liquid nitrogen for 20 min, thawed at room temperature for 15 min, thawed at room temperature for 15 min. The excised segment then thawed in distilled water for 10 min and reimplanted and fixed in place. Total elbow arthroplasty and ORIF with plate and screw was performed, the bone cement was also added. The implant was secured using advancement of extensor carpi ulnaris muscle and the wound was closed using primary suture.().
Postoperatively we performed an X-Ray to evaluate the reconstruction. From the X-ray, the plate and screws are well-fixated (). One month postoperatively, the implant was well-fixated and the patient can slowly move his elbow without limitation.


A 6-year-old female spayed Miniature Schnauzer was referred for evaluation of lower urinary tract signs secondary to a persistent urinary tract infection. An initial urinalysis performed by the referring veterinarian revealed a pH of 8.0, > 50 white blood cells (WBC)/high powered field (hpf), 2 + magnesium ammonium phosphate (struvite) crystalluria, and rod bacteriuria. Failure to improve following a 10-day course of empiric cephalexin led to the identification of 4–5 urocystoliths on abdominal radiographs. A cystotomy with stone analysis diagnosed struvite urolithiasis, after which a stone prevention diet (Royal Canin® Urinary SO) was initiated. Despite these therapies, there was no improvement in clinical signs and the aforementioned urinalysis abnormalities persisted. A 10-day course of empiric enrofloxacin was subsequently initiated; however, due to the persistence of clinical signs, a urine culture was performed that lead to the identification of Corynebacterium urealyticum. Referral for treatment of the multidrug resistant urinary tract infection was pursued.
At the time of referral, no physical examination abnormalities were detected; however, when walked outside, the dog postured frequently producing a small volume of bloody urine each time. Urinalysis revealed a pH of 8.5, 40–61 WBC/hpf, rare struvite crystals, and large numbers of rod bacteria. Ultrasonography of the urinary bladder demonstrated multifocal hyperechoic foci adhered to a diffusely thickened wall, consistent with encrusting cystitis [] (Fig. ).
Urine culture grew > 100,000 colony forming units (CFU)/mL of Corynebacterium urealyticum. C. urealyticum was identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and susceptibility testing was performed by determining the minimum inhibitory concentrations (MICs) of antimicrobial drugs by broth microdilution in Mueller–Hinton broth with lysed horse blood using a commercial plate. Following a 24-h incubation at 35ºC in ambient air, the MICs were read and interpreted on a commercial reader using Clinical Laboratory Standards Institute (CLSI) breakpoints programmed into the instrument’s software. Programmed breakpoints were based on breakpoints published in CLSI documents VET06 and VET08 [, ]. The organism was susceptible to rifampin, gentamicin, tetracyclines, and vancomycin (Culture #1 in Table ). Despite low levels of urinary excretion, treatment with doxycycline 5 mg/kg PO q12h for 4 weeks was initiated based on in vitro susceptibility and in vivo efficacy []. Methionine 53 mg/kg PO q12h was additionally initiated for urinary acidification and the previously prescribed stone prevention diet was continued.
At a recheck 4 weeks later, the lower urinary tract signs were improved (less frequent stranguria, pollakiuria, hematuria) but unresolved. Alkalinuria, pyuria, and bacteriuria persisted on urinalysis and Corynebacterium urealyticum was cultured from the urine (Culture #2 in Table ). Treatment with chloramphenicol 27 mg/kg PO q8h for 4 weeks was initiated based on previously documented Corynebacterium urealyticum in vitro susceptibility to this antibiotic []. Although this treatment initially resulted in some abatement of clinical signs, the lower urinary tract symptoms ultimately worsened on treatment. C. urealyticum was again cultured from the urine (Culture #3 in Table ).
The failure of outpatient treatment to clear the infection and owner decision to pursue euthanasia if unresolved prompted hospitalization. Vancomycin 15 mg/kg IV q8h and gentamicin 6 mg/kg intravesical as a single dose were administered []. An indwelling Foley urinary catheter was placed to facilitate gentamicin infusion into the bladder, with instillation immediately causing appreciable discomfort. Following infusion, the catheter was occluded to prevent the dog from voiding. The intended dwell time was 6 h; however, urine leaked around the catheter, thus the volume of gentamicin that remained within the bladder during the dwell time was unknown. A second dose of intravesical gentamicin originally intended for administration 24 h following the initial dose was aborted because the urinary catheter became obstructed with debris and was subsequently removed. Despite 6 days of intravenous vancomycin and a single dose of intravesical gentamicin, the lower urinary tract signs persisted. Therefore, surgical debridement of the urinary bladder was pursued. A urinalysis performed on the day of surgery revealed a pH of 7.0, 8–15 white blood cells/hpf, and no struvite crystalluria or bacteriuria, all improvements compared to prior urinalyses. The markedly improved pyuria and lack of bacteria indicated in vivo vancomycin efficacy.
A caudal midline celiotomy and ventral cystotomy were performed. The urinary bladder was hyperemic and thickened on palpation. Following exposure of the urinary bladder lumen, multiple grey-green calcified plaques were visible on the mucosal surface, with most concentrated along the ventral surface and around each ureteral papilla. A full thickness bladder wall biopsy was submitted for histologic analysis and a sample of mucosa with calcified plaques was submitted for bacterial culture. The mucosal plaques were debrided using a #15 blade. Copious flushing and subsequent maximal distension of the urinary bladder with a 10-Fr red rubber catheter and sterile saline was then performed, during which the dog experienced acute bradycardia and hypotension progressing to asystole. The celiotomy incision was extended cranially to the xyphoid, whereby a diaphragmatic incision allowing access to the thoracic cavity was performed. Cardiac massage and resuscitative drug therapy (atropine) was administered, resulting rapidly in patient revival. Once stabilized, the diaphragm, urinary bladder, and abdominal incisions were closed. Prior to anesthetic recovery, an indwelling urinary catheter was placed to monitor urine appearance and output post-operatively. Anesthetic recovery was uneventful, with all normal vital parameters.
Histologic examination of the urinary bladder wall revealed severe suppurative and necrotizing cystitis of the mucosal and submucosal layers. Mineralization of these same layers was also present (Fig. ). These histopathologic findings are identical to those described in previous reports of encrusting cystitis [, ]. Culture of the bladder mucosa containing calcified plaques was negative for bacterial growth (Culture #4 in Table ), indicating adequate penetration of vancomycin into the diseased urinary bladder wall.
Postsurgical care included the administration of intravenous fluids, vancomycin 15 mg/kg IV q8h, methionine 53 mg/kg PO q12h, and meloxicam 0.1 mg/kg PO q24h. Urine draining from the indwelling urinary catheter immediately following surgery was serosanguinous; however, it was grossly normal the following morning and the catheter was removed. The other lower urinary tract signs (stranguria and pollakiuria) were dramatically improved at the time of discharge 8 days after surgery. The dog received a total of 14 days of vancomycin therapy (6 days prior to and 8 days after surgery) and one dose of intravesical gentamicin during hospitalization. A urine culture performed 5 weeks following treatment was negative for bacterial growth and the dog was lower urinary tract symptom free. A phone update with the owner 3 and 9 months after treatment revealed the dog to still be clinically normal.


A six-month-old Caucasian male with no significant past medical history presented to the pediatric emergency department for a chief complaint of frequent unusual eye movements as reported by the parents. The patient began having intermittent rotary nystagmus approximately three weeks ago, and since then it progressed and became more continuous, worsened by changes in position or flashing lights from toys brought in his visual field. The parents also noticed the patient sleeping more than usual, only staying awake for an hour at a time, and had a subsequent severe regression in milestones, with an inability to roll over or sit unsupported.
Initial workup in the emergency department included a CT brain without contrast, which showed evidence of thickening of the bilateral optic nerves with associated masses and diffuse bilateral ventriculomegaly (Figure ). This finding was concerning for possible bilateral optic pathway gliomas, at which point a dedicated MRI of the brain and orbits was recommended, along with further genetic workup for possible neurofibromatosis I.
MRI of the brain and orbits confirmed these findings, showing diffuse enlargement of the optic tracts extending from the lateral geniculate nuclei to the optic chiasm and into the bilateral optic nerves, with a mass demonstrating 270º encasement of the bilateral supraclinoid internal carotid arteries and near circumferential encasement of the bilateral A1 segments of the anterior cerebral arteries (Figures , ).
These imaging findings confirmed the suspicion of bilateral optic pathway glioma, and as a result, the patient was admitted to the hospital and evaluated by both neurosurgery and pediatric hematology-oncology. Neurosurgery did not recommend any surgical intervention at the time, and the hematology-oncology team recommended proceeding with chemotherapy. His genetic testing results showed no evidence of clinically significant variants of neurofibromatosis I or II, suggesting a sporadic bilateral optic pathway glioma. The patient was then discharged and was followed up on an outpatient basis by both ophthalmology and pediatric hematology-oncology for maintenance chemotherapy with carboplatin and vincristine.


A 45-year-old woman with a previous history of two cysts in the right axillary region (never excised), admitted to surgically remove one of the two, which measured 0.95 cm. To our knowledge, she does not have any prior disease. The cyst was removed without any complication and sent for analysis with the diagnosis of epidermoid cyst. The healing was uneventful. The histopathological analysis reveal a cystic lesion in the dermis (). The cyst is lined in part by a squamous epithelium with an intact granular layer, sometimes atrophic, and in part by a distended apocrine epithelium. The passage between the two different epithelia is abrupt. We estimate that the apocrine component represents 30% of the epithelium. The cyst is filled with keratin lamellae. In proximity of the cyst’s wall, there are some apocrine and some sebaceous glands. No further exam was performed.


A 45-year-old lady presented with recurrent narrow QRS short-RP tachycardia. Baseline ECG was normal with no evidence of pre-excitation. Echocardiography was unremarkable. During her electrophysiology study, Para-Hisian pacing (PHP) maneuver was performed before induction of tachycardia. Both the RV catheter and His catheter were placed at His bundle (HB) region (Appendix ). Pacing at variable output at fixed cycle length was performed from RV distal (RVD) bipole. It was started at an output of 10 mA at a pulse width of 2 ms and the output was gradually reduced till there was widening of paced QRS complex suggestive of loss of HB capture. The measurement of Stim-to-A time interval (SAT) recorded in the proximal coronary sinus (PCS was positioned at CS ostium) bipole was only 42 ms (Figure ).
What is the mechanism behind such a short SAT? Is it due to inadvertent simultaneous atrial capture at the high output (hence making the maneuver uninterpretable) or could this be a genuine VA conduction suggestive of nodal VA conduction?


A 33-year-old Native American man, a welder by profession, with a past medical history significant for alcohol use, hypertension, and asthma presented to the hospital with complaints of cough with occasional bloody sputum production. His cough started four days before presentation, was initially dry but progressively worsened, and became productive. It was also associated with dyspnea and orthopnea along with new-onset lower extremity edema. He further endorsed preceding nausea, vomiting, and diarrhea without abdominal pain, melena, or hematemesis. He reported an extensive history of alcohol consumption and had quit smoking 6 years ago.
On physical examination, he appeared restless and his vitals comprised a temperature of 98.5°F, blood pressure 158/91 mm of Hg, respiratory rate 30 breaths/minute, pulse 116 beats/minute, oxygen saturation 96% on 2 liters of supplemental oxygen via a nasal cannula, weight 290 pounds, and a body mass index of 39.32. His pertinent laboratory findings included a white blood cell count of 16.3 K/uL, hemoglobin 8.6 g/dL, platelets 124,000 K/uL, potassium 3.0 mEq/L, sodium 125 mEq/L, magnesium 1.6 mg/dL, folate level 5.7 ng/mL, creatinine kinase 455 U/L, lactate dehydrogenase 310 U/L, albumin 2.9 g/dL, CRP 16.9 mg/L, lactic acid 3.1 mmol/L, procalcitonin 0.14 ng/mL, and D-dimer 10.56 ug/mL FEU. His ethanol level was 96.7 mg/dL, while liver function tests showed aspartate transaminase 132 U/L, alanine transaminase 33 U/L, and alkaline phosphatase 219 U/L. Testing for SARS-CoV-2, Human Immunodeficiency Virus (HIV), influenza, and methicillin-resistant Staphylococcus aureus (MRSA) nasal screen was negative.
His computed tomographic angiogram of the chest () revealed bilateral infiltrates more extensive on the left as compared to the right and excluded pulmonary embolism. Ultrasound abdomen revealed hepatomegaly. An echocardiogram showed an ejection fraction of 65–70% with moderate left ventricular hypertrophy, left atrial enlargement, and right atrial dilation. He was started on empiric treatment with ceftriaxone 2 gm daily and doxycycline 100 mg twice a day for suspected bacterial pneumonia along with management of possible alcoholic hepatitis with thiamine and folic acid and Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol.
On day 2 of hospitalization, his hemoptysis and breathing deteriorated, and his white cell count rose further to 18.1 K/uL. His supplemental oxygen requirements increased, and chest X-ray (CXR) () showed worsening left-sided infiltrates. Following this, the antibiotic regimen was broadened to cefepime 2 gm three times a day for 8 days and vancomycin dosed by the pharmacy for 5 days. Urine Legionella antigen, Streptococcus pneumoniae direct antigen, Aspergillus, Blastomyces, Coccidiodes, histoplasma antibodies, and repeat SARS-CoV-2 testing were all negative. Blood cultures and sputum cultures were obtained and were found to have no growth. Bronchoscopy was performed revealing DAH thought secondary to pulmonary edema. Intravenous (IV) steroids were started, and further infectious and autoimmune workup was undertaken. Bronchoalveolar lavage sampling was negative for acid-fast bacilli, Nocardia cultures, and CMV DNA. With the continued decline in respiratory function, he underwent endotracheal intubation.
While on mechanical ventilation, aggressive diuresis was initiated for pulmonary edema. Thereafter, he was weaned off the ventilator and extubated within a week. His hemoptysis resolved, but he continued to cough with infrequent mucoid phlegm. Antibiotics were discontinued after ten days when he was clinically better, and repeat CXR exhibited slight improvement in left-sided infiltrates along with the resolution of his right lung consolidation.
Steroids were transitioned from IV to oral prednisolone 40 mg daily for 26 days followed by a taper to cover for suspected alcoholic hepatitis. His mental function improved with alcohol withdrawal treatment and he became more alert and oriented. On further questioning, he recalled having exposure to sick kittens and mice few days before admission. He was tested for Hantavirus, Q fever, leptospirosis, and toxoplasmosis, and empiric treatment with doxycycline 100 mg twice a day was initiated for 3 weeks. TB testing (QuantiFERON, sputum acid-fast bacilli, and PPD) and antibodies for leptospirosis and Q fever were all negative.
On day 18, the patient was hemodynamically stable with complete resolution of respiratory failure and was deemed stable for discharge. Four days after discharge, Hantavirus IgM returned positive with equivocal IgG. Retrospectively, his presentation correlated with HCPS. Upon follow-up in the clinic 10 days after discharge from the hospital, he reported improvement in cough and dyspnea. Outpatient CXR () revealed mild improvement of left upper lobe consolidation.


A 63-year-old woman without a smoking history presented with cough lasting for one month. Computed tomography (CT) of the thorax showed a nodule in the right upper lobe of the lung, measuring 1.5 × 2 cm (Figure ). Isotope bone scan was performed which indicated the presence of a metastatic bone lesion (Figure (a)). A biopsy sample of the right supraclavicular node mass was suggestive of a poorly differentiated adenocarcinoma (Figure ). Immunohistochemical (IHC) positive staining of thyroid transcription factor-1 (TTF-1, Figure ) and cytokeratin 7 (CK7, Figure ) supported the diagnosis of supraclavicular node metastasis from lung cancer.
Finally, a diagnosis of IVa stage (T1N3M1b) adenocarcinoma lung cancer with bone metastasis was made. Amplification refractory mutation system (ARMS) testing showed an epidermal growth factor receptor (EGFR) exon 21 p.L858R mutation. The patient commenced gefitinib treatment in March 2016. One month later, a partial response had been achieved according to the CT scan (Figure ). The patient continued gefitinib treatment for a further 2 years until several new bone metastasis were detected on isotope bone scan in March 2018 (Figure (b)). The patient had accompanying lumbar vertebra pain. CT of the thorax showed the nodule remained stable in the right lung (Figure ). Quantified paired plasma and leukocyte samples from the patient were sequenced by targeted NGS with a specific 122-gene panel. The captured samples were then subjected to Illumina HiSeq X-Ten for paired-end sequencing and information of gene features were obtained from Genecast Biotechnology. NGS revealed the appearance of EGFR exon 20 p.T790M mutation (p.T790 M) from cell free DNA in plasma. Osimertinib treatment was commenced and her pain quickly subsided. Three months later, a partial response had been achieved according to the CT scan (Figure ). Osimertinib treatment was continued for another 2 years and then in April 2020, the patient again experienced lumbar vertebra pain. Abnormal vaginal bleeding and discharge were also observed at this time. CT scan of the thorax showed a larger nodule in the upper lobe (Figure ), and magnetic resonance imaging (MRI) of the pelvis showed a mass in the uterine cervix (Figure ).
A biopsy sample was obtained from the uterine cervical mass. Hematoxylin-eosin (HE) staining of the uterine cervical biopsy sample identified an invasive poorly differentiated adenocarcinoma (Figure ). IHC staining was strongly positive for TTF-1 and CK7 (Figure ), while p63, CK20 were negative. The results suggested that the uterine cervical mass was metastatic adenocarcinoma of the lung. In addition, using formalin-fixed paraffin-embedded tissues, 15 slides with 5 μm sliced tissues were prepared for NGS analysis. Meanwhile, quantified paired plasma and leukocyte samples from the patient were sequenced by NGS with the same panel again. EGFR exon 21 p.L858R mutation was again detected which further verified that the uterine cervical tumor was a metastasis from primary lung adenocarcinoma. The detailed mutation results detected by NGS are described in Table .


Case 1 was a 77-year-old woman. A right VA asymmetrically dilated fusiform aneurysm (14 × 32 mm) was incidentally found on brain magnetic resonance imaging (MRI) at checkup during treatment for otorhinolaryngologic disease. Preoperative MRI revealed that the proximal and distal necks were located at the height of the cerebellomedullary fissure and compressed the medulla oblongata from the anterior side (). On preoperative digital subtraction angiography (DSA), PICA originated from the VA just distal to the penetration part of the posterior dura, while no apparent branches from the aneurysm were identified (). The right VA was the non-dominant side, with atherosclerotic changes obvious in the affected VA and in all intracranial arteries. On the basis of the aneurysmal size and the patient's request, we decided to treat the lesion.
The dilated part mainly protruded outward and the entire aneurysm was localized around the cerebellomedullary fissure beneath the lower cranial nerves (LCNs). Thus, reconstructive clipping was considered anatomically and technically possible. During surgery, after confirming both the proximal and distal aneurysmal necks, we performed aneurysmal trapping with direct visualization and preservation of the peripheral perforators, and then incised the lateral wall of the aneurysm, decompressed the aneurysmal body, and obliterated the aneurysm by confrontation clipping with four clips (). The actual surgical procedures of case 1 is shown in .