Seroprevalence and incidence of hepatitis E virus infection in the general population of Iwate prefecture, Japan: A retrospective cohort study.

AIM: Hepatitis E virus (HEV) causes subclinical or acute self-limiting hepatitis. We surveyed the current seroprevalence and incidence of HEV infection among the general population in Iwate Prefecture, Japan, where the endemic infection is presumed to be low. METHODS: Between 2014 and 2016, we recruited individuals from Iwate Prefecture, Japan, who visited a general medical work-up program. Serum anti-HEV antibody and HEV RNA were measured twice, with an interval of 2 years. Anti-HEV antibody was measured with enzyme-linked immunosorbent assay and HEV RNA with reverse transcription-polymerase chain reaction. RESULTS: Study participants comprised 1284 Japanese (650 men and 634 women) with age ranging 20-89 years. A total of 90 participants were found to be positive for anti-HEV immunoglobulin G on the first visit, with a prevalence of 7.0% (95% confidence interval [CI] 5.6%-8.4%). Seroprevalence was higher in men than in women (10.1% vs. 3.7%, p < 0.001), and in those aged in their 50s-80s than in those aged in their 20s-40s (p = 0.006). Positive seroconversion indicating new HEV infection was found in seven of 1194 seronegative participants (0.59%; 95% CI 0.15%-1.0%), indicating the incidence of HEV infection to be 272 per 100 000 person-years (95% CI 109-561). CONCLUSIONS: Our observations suggest that the incidence of HEV infection is high and that it is a leading cause of hepatitis virus infection in Iwate Prefecture, Japan.

Invasive Salmonella Enteritidis infection complicated by bacterial meningitis and vertebral osteomyelitis shortly after influenza A infection in an immunocompetent young adult.

Non-typhoidal Salmonella usually manifests as a self-limited acute gastroenteritis but may also cause severe invasive infections almost exclusively among children or immunosuppressed patients. A previously healthy 22-year-old man developed high fever with coma, multiple organ failure and shock. He had visited another hospital complaining of fever 2 days previously and was diagnosed with a common cold. No obvious site of infection was identified by radiology and a rapid test for influenza A virus was positive, indicating possible influenza-associated encephalopathy. However, blood as well as CSF culture yielded Salmonella enterica serotype Enteritidis. Therefore, the patient was considered to be suffering from bacterial meningitis with septic shock concomitant with influenza infection. Antiviral drugs and therapy for septic shock were initiated. He stabilized relatively quickly and his mental status dramatically improved. The patient denied preceding gastrointestinal symptoms, but mentioned that he received positive fecal Salmonella species culture results without medical intervention about 3 months previously. His laboratory values showed marked improvement but his elevated inflammatory markers and fever were sustained. On the 17th day of hospitalization, he complained of back pain and MRI showed lumbar vertebral osteomyelitis. This case indicates that (i) invasive Salmonella infection can be developed even in previously healthy adults; (ii) chronic carriage of Salmonella is a predisposing factor to development of invasive infections, and influenza infection may contribute to such "breakthrough infections"; (iii) attention to manifestation of metastatic extra-intestinal foci even after resolution of sepsis is necessary.

Acquired factor XIII deficiency in two patients with bleeding events during veno-venous extracorporeal membrane oxygenation treatment.

We report two cases of acquired factor XIII deficiency with bleeding events during veno-venous extracorporeal membrane oxygenation (ECMO). Case 1: A 76-year-old man diagnosed with aspiration pneumonia after near-drowning was started on ECMO. Later, the patient presented with hemoptysis and anemia. Blood tests showed a decreased factor XIII activity of 29%. Although the patient recovered after receiving 1200 International Units of factor XIII concentrate, the patient had another episode of decreased factor XIII activity and bloody stool and was treated again with factor XIII concentrate. Case 2: A 48-year-old female diagnosed with pneumonia was started on ECMO. Soon after, she presented with hemoptysis and anemia. Blood tests showed a decreased factor XIII activity of 39%. The patient was treated with 720 IU of factor XIII concentrate with good recovery. Acquired factor XIII deficiency cannot be detected by routine coagulation tests, therefore it may be under-diagnosed in the ICU. Detection of acquired factor XIII deficiency is essential when treating a bleeding ECMO patient.

Anti-adhesive effects of human soluble thrombomodulin and its domains.

We reported previously that leukocyte ß2 integrins (LFA-1 and Mac-1) bind to the serine/threonine-rich domain of thrombomodulin (TM) expressed on vascular endothelial cells (VECs). Recombinant human soluble TM (rhsTM, TMD123) has been approved as a therapeutic drug for septic disseminated intravascular coagulation. However, the roles of TMD123 on the adhesion of leukocyte integrins to VECs remain unclear. In the current study, we have revealed that an integrin-dependent binding between human peripheral blood mononuclear cells (PBMCs) and VECs was inhibited by TMD123. Next, using mutant proteins composed of isolated TM extracellular domains, we examined the structural characteristics responsible for the anti-adhesion properties of TMD123. Namely, we investigated whether the effects of the binding of TM and leukocytes was inhibited by the administration of TMD123. In fact, we confirmed that TMD123, TMD1, and TMD3 inhibited the binding of PBMCs to the immobilized recombinant proteins TMD123 and TMD3. These results indicate that TMD123 inhibited the adhesion of leukocytes to endothelial cells via ß2 integrins and endothelial TM. Moreover, since TMD1 might bind to leukocytes via other adhesion receptors than integrins, TMD1 and TMD3 appear to inhibit leukocyte binding to TM on VECs via different mechanisms. In summary, TMD123 (rhsTM), TMD1 or TMD3 is a promising treatment option for sepsis that attenuates integrin-dependent binding of leukocytes to VECs, and may inhibit the undesirable adhesion and migration of leukocytes to VECs in sepsis.

Immune checkpoint inhibitor-associated colitis in unresectable hepatocellular carcinoma: two cases of early onset after treatment with durvalumab plus tremelimumab.

The HIMALAYA trial is the first chemotherapeutic trial to demonstrate the efficacy of combined immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (u-HCC). The STRIDE regimen used in this trial consists of a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor and programmed cell death ligand 1 (PD-L1) inhibitor. Herein, we report two cases of ICI-colitis that occurred immediately after the initiation of the STRIDE regimen for u-HCC. A 73-year-old man and 75-year-old man with u-HCC were treated with the STRIDE regimen. Both patients developed grade 3 diarrhea (Common Terminology Criteria for Adverse Events, ver. 5.0) within 10 days of treatment initiation. Colonoscopy revealed aphthous erosions and erythema extending from the terminal ileum to the rectum in one case, while the other showed aphthous ulcers in the terminal ileum and shallow ulcers in the colorectum. Histopathological examination of a biopsy specimen revealed epithelial cell apoptosis and neutrophil infiltration bodies, consistent with ICI-colitis. Prednisolone (0.5 mg/kg) was effective in both patients. Our experience suggests the need for both careful monitoring and early endoscopic examination of ICI colitis in patients with unresectable HCC treated with the STRIDE regimen.

Pediatric mumps with laryngeal edema.

Mumps virus infection primarily affects the salivary glands and may incur various complications. Laryngeal edema is such a rare complication that few adult cases have been reported. We report the first known pediatric patient with mumps with laryngeal edema. An 8-year-old boy developed dyspnea after a rapidly progressive swelling of his face and neck. Laryngoscopy revealed edematous changes in the supraglottic and subglottic regions, and computed tomography confirmed significant laryngeal edema in addition to swelling of the cervical soft tissue and the salivary glands. Laboratory findings revealed a high serum amylase level and confirmed the diagnosis of mumps. Intravenous steroid administration alleviated the dyspnea, although the patient required temporary tracheal intubation to maintain airway patency. He did not need tracheotomy and did not experience any other complications. Laryngeal edema must be regarded as a rare, potentially life-threatening complication of mumps. When mumps is diagnosed with significant swelling of the neck, an emergency airway should be established to prevent airway obstruction.

Current status of long-term follow-up system for women with a history of hypertensive disorders of pregnancy: the HDP-PPAP study (HDP-Postpartum in Aomori prefecture study).

OBJECTIVE: Women with a history of hypertensive disorders of pregnancy (HDP), especially those with gestational hypertension and preeclampsia, are more likely to develop hypertension, cerebrovascular disease, ischemic heart disease, diabetes mellitus, dyslipidemia, and chronic kidney disease later in life. However, the risk of lifestyle-related diseases in the immediate postpartum period among Japanese women with preexisting HDP is unclear, and a follow-up system for women with preexisting HDP has not been established in Japan. The purpose of this study was to examine the risk factors for lifestyle-related diseases in Japanese women in the immediate postpartum period and the usefulness of HDP follow-up outpatient clinics based on the situation of the HDP follow-up outpatient clinic at our hospital. METHOD: We included 155 women with a history of HDP who visited our outpatient clinic between April 2014 and February 2020. We examined the reasons for dropout during the follow-up period. We also examined the number of new cases of lifestyle-related diseases and compared Body Mass Index(BMI), blood pressure values, and blood and urine test results at 1 and 3 years postpartum in 92 women who had been continuously followed for more than 3 years postpartum. RESULTS: The average age of our patient cohort was 34.8 ± 4.5 years. A total of 155 women with previous HDP were continuously followed for more than 1 year, of whom 23 had new pregnancies, and eight had recurrent HDP (recurrence rate 34.8%). Of the 132 patients who were not newly pregnant, 28 dropped out during follow-up, the most common reason being that the patient did not show up. The patients in this study developed hypertension, diabetes mellitus, and dyslipidemia within a short period. Both systolic and diastolic blood pressures were at normal high levels at 1-year postpartum, and BMI significantly increased at 3 years postpartum. Blood tests revealed significant deterioration in creatinine (Cre), estimated glomerular filtration rate (eGFR), and γ-glutamyl transpeptidase (γGTP) levels. CONCLUSION: In this study, women with preexisting HDP were found to have developed hypertension, diabetes, and dyslipidemia several years postpartum. We also found a significant increase in BMI and worsening of Cre, eGFR, and γGTP levels at 1 and 3 years postpartum. Although the 3-year follow-up rate at our hospital was relatively good (78.8%), some women discontinued follow-up due to self-interruption or relocation, suggesting the need to establish a nationwide follow-up system.

Continuous High Positive-End Expiratory Pressure May Worsen Renal Function in Patients With Acute Respiratory Distress Syndrome: Retrospective Analyses of a Nationwide, Multicenter Observational Study in Japan.

BACKGROUND: Positive end-expiratory pressure (PEEP), especially continuous high PEEP, is thought to be a risk factor for worsening renal function (WRF) due to impaired venous return and the development of renal interstitial edema. In this study, we investigated whether PEEP is a risk factor for WRF in patients with acute respiratory distress syndrome (ARDS), a representative pathology that requires continuous high PEEP for respiratory management. METHODS: We performed retrospective sub-analyses of the Japanese Association for Acute Medicine, a nationwide prospective observational registry of ARDS (FORECAST ARDS registry) prospective multicenter cohort study. WRF was defined on the basis of a worsening renal Sequential Organ Failure Assessment (SOFA) score. We performed univariate and multivariable analyses to identify possible risk factors for WRF, and propensity score analyses to compare the frequency of WRF according to cutoff values for the difference in PEEP between day 1 and day 4. RESULTS: We analyzed 151 cases. Multivariable analysis showed that the difference in PEEP (odds ratio (OR) 1.123 (95% confidence interval (CI) 1.017-1.240), P = 0.022) and male sex (OR 3.287 (95% CI 1.029-10.502), P = 0.045) were risk factors for WRF. Propensity score analysis showed trends towards an increased risk for WRF in each cutoff value for the difference in PEEP: -5 cmH2O (OR 0.389 (95% CI 0.084-1.799), P = 0.229), 0 cmH2O (OR 2.222 (95% CI 0.755-6.540), P = 0.150), and 5 cmH2O (OR 3.277 (95% CI 0.940-11.425), P = 0.065). CONCLUSIONS: This study revealed that the difference in PEEP between days 1 and 4 was positively associated with WRF. However, a significant cutoff value for the difference in PEEP was not determined.

A Case of Autoimmune Hepatitis Complicated by Undiagnosed Factor VII Deficiency: A Pitfall of Coagulopathy.

Prothrombin time (PT) is a key parameter for assessing the severity of liver disease. We present the case of a 37-year-old woman with severe acute liver injury due to autoimmune hepatitis. Although prednisolone drastically improved her hepatocyte function, her PT did not recover to the reference range. A review of her medical records revealed that the patient had normal transaminase levels and prolonged PT 2 years previously. Further examinations of her coagulopathy revealed that she had low factor VII activity, suggesting a diagnosis of factor VII deficiency. Our experience suggests that altered coagulopathy should be considered in cases of liver injury with an extraordinary PT.

Cardiac Arrest Induced by an Anaphylactic Reaction Associated With the First Dose of Cetuximab.

Cetuximab is a chimeric mouse-human monoclonal antibody biologic used for the treatment of epidermal growth factor receptor-positive colorectal cancer and head and neck cancer. The incidence of severe anaphylaxis after infusion of cetuximab is a rare but fatal complication. Galactose-α-1,3-galactose (α-gal), a side-chain component in cetuximab, can cause the α-gal syndrome, an allergic cross-reaction to the α-gal contained in mammalian muscle. Here, we report a case of cardiac arrest induced by an anaphylactic reaction from cetuximab infusion. After the initial dosing of cetuximab in an outpatient setting, the patient developed sudden cardiac arrest. Flushing of the skin and bronchoconstriction led to the diagnosis of a severe anaphylactic reaction, whereupon he was treated with repeated doses of epinephrine, steroids, and continuous epinephrine infusion. The patient responded well to initial treatment, leading to a full recovery. The patient's history and subsequent blood tests did not show any meat allergies. As an increasing number of patients receive chemotherapy as outpatients, it is important to be aware of the possibility of severe allergic reactions induced by these drugs.

Sequential organ failure assessment score as a predictor of the outcomes of patients hospitalized for classical or exertional heatstroke.

Heatstroke is a life-threatening event that affects people worldwide. Currently, there are no established tools to predict the outcomes of heatstroke. Although the Sequential Organ Failure Assessment (SOFA) score is a promising tool for judging the severity of critically ill patients. Therefore, in this study, we investigated whether the SOFA score could predict the outcome of patients hospitalized with severe heatstroke, including the classical and exertional types, by using data from a Japanese nationwide multicenter observational registry. We performed retrospective subanalyses of the Japanese Association for Acute Medicine heatstroke registry, 2019. Adults with a SOFA score ≥ 1 hospitalized for heatstroke were analyzed. We analyzed data for 225 patients. Univariate and multivariable analyses showed a significant difference in the SOFA score between non-survivors and survivors in classical and exertional heatstroke cases. The area under the receiver operating characteristic curve were 0.863 (classical) and 0.979 (exertional). The sensitivity and specificity of SOFA scores were 50.0% and 97.5% (classical), 66.7% and 97.5% (exertional), respectively, at a cutoff of 12.5, and 35.0% and 98.8% (classical), 33.3% and 100.0% (exertional), respectively, at a cutoff of 13.5. This study revealed that the SOFA score may predict mortality in patients with heatstroke and might be useful for assessing prognosis.

Septic pulmonary embolism and subsequent bilateral pneumothorax in patients undergoing chemoradiotherapy for head angiosarcoma: An autopsy case report and literature review.

RATIONALE: Septic pulmonary embolism (SPE) and subsequent pneumothorax are rare but serious conditions. We report a case of SPE and pneumothorax caused by central venous port (CV port) infection. PATIENT CONCERNS: A 73-year-old woman, who underwent chemoradiotherapy for a head angiosarcoma and a CV port placement, presented with general malaise and myalgia. DIAGNOSIS: A laboratory examination showed high levels of inflammatory markers. Chest computed tomography showed fluid collection around the CV port and multiple ground-glass opacities and nodular shadows in the bilateral lung field. She was admitted with a diagnosis of SPE due to CV port infection. The port was removed, and antibiotic administration was initiated; however, she was intubated because of refractory septic shock. Methicillin-susceptible Staphylococcus aureus was detected in the blood and pus around the port site. INTERVENTIONS: Her respiratory status did not improve despite recovering from septic shock, and radiologic findings showed a left pneumothorax and exacerbation of SPE on day 9. Her condition was judged ineligible for surgery for pneumothorax, and chest tube thoracostomy was continued. OUTCOMES: Air leaks persisted after chest tube thoracostomy, and her respiratory status did not improve despite ventilator management and recruitment maneuvers. Moreover, a right pneumothorax developed on day 19. Her respiratory status gradually worsened, and she died on day 21. Autopsy showed multiple cavitary lesions in the bilateral lungs and emboli containing organization and inflammatory cells that obstructed the pulmonary arterioles. LESSONS: This case indicates that CV port-related infections are infrequent and difficult to diagnose; understanding the clinical features of SPE is important because of its high mortality rate; and pneumothorax secondary to SPE is a rare but serious condition and is difficult to treat during ventilator management.

Conservative medical management combined with follow-up multidetector computed tomography of tracheobronchial injury caused by penetrating injuries: A case report.

Tracheobronchial injury (TBI) associated with penetrating injuries has various clinical symptoms and often requires urgent surgical repair. A tracheal tube and/or placement of a drainage tube combined with multidetector computed tomography (CT) could be used to manage TBI without surgical repair in eligible patients. In this case report, we describe an 86-year-old woman with subcutaneous emphysema and suspected TBI caused by three knife wounds in her neck. After tracheal intubation at a local hospital, she was transferred to our hospital. On admission, she was diagnosed with subcutaneous and mediastinal emphysema due to TBI, as well as bilateral pneumothorax. We adjusted the position of the tracheal tube to a distal location from the TBI, and placed bilateral thoracic drainage tubes by referring to the CT images taken on admission and during the follow-up. The follow-up CT images revealed healing of the TBI. She did not show any worsening of her symptoms and she was successfully extubated on day 10 of her hospital stay. On day 18, she was considered self-reliant and was transferred to her previous hospital. Based on our experience in this case, we believe that ventilation with appropriate sedation, placement of a tracheal tube, and drainage are important conservative therapies for TBI caused by penetrating injuries. CT is also useful for evaluating the status of TBI.

Anticoagulant-free venovenous extracorporeal membrane oxygenation for diffuse alveolar hemorrhage with bowel bleeding caused by antineutrophil cytoplasmic antibody-associated vasculitis: A case report.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is sometimes complicated by diffuse alveolar hemorrhage (DAH), which may cause respiratory failure. Venovenous extracorporeal membrane oxygenation (VV-ECMO) without an anticoagulant because of hemorrhagic status, showed the effectiveness for severe respiratory failure by DAH with AAV. A 44-year-old woman developed DAH with bowel bleeding following the onset of AAV, with positive anti-proteinase-3 (PR3) antibodies. Although ventilator management could not support her respiratory status, VV-ECMO was performed. The patient was given immunosuppressive therapy comprising a steroid pulse, plasma exchange, and cyclophosphamide. After about 10 days of VV-ECMO and immunosuppressive therapy, VV-ECMO was withdrawn, and on day 12, ventilator support was stopped. Although a thrombus developed within the inferior vena cava (IVC), which required IVC filtration, the patient was discharged on day 51. VV-ECMO support was effective for treating DAH in this patient with new-onset AAV, which takes some time to achieve remission with immunosuppressive therapy.

The Lectin-Like Domain of Thrombomodulin Inhibits ß1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.

Thrombomodulin is a molecule with anti-coagulant and anti-inflammatory properties. Recently, thrombomodulin was reported to be able to bind extracellular matrix proteins, such as fibronectin and collagen; however, whether thrombomodulin regulates the binding of human breast cancer-derived cell lines to the extracellular matrix remains unknown. To investigate this, we created an extracellular domain of thrombomodulin, TMD123-Fc, or domain deletion TM-Fc proteins (TM domain 12-Fc, TM domain 23-Fc) and examined their bindings to fibronectin in vitro by ELISA. The lectin-like domain of thrombomodulin was found to be essential for the binding of the extracellular domain of thrombomodulin to fibronectin. Using a V-well cell adhesion assay or flow cytometry analysis with fluorescent beads, we found that both TMD123-Fc and TMD12-Fc inhibited the binding between ß1 integrin of human breast cancer-derived cell lines and fibronectin. Furthermore, TMD123-Fc and TMD12-Fc inhibited the binding of activated integrins to fibronectin under shear stress in the presence of Ca2+ and Mg2+ but not under strong integrin-activation conditions in the presence of Mg2+ without Ca2+. This suggests that thrombomodulin Fc fusion protein administered exogenously at a relatively early stage of inflammation may be applied to the development of new therapies that inhibit the binding of ß1 integrin of breast cancer cell lines to fibronectin.

Cardiopulmonary resuscitation of a cardiac arrest patient with left ventricular assist device in an out-of-hospital setting: A case report.

RATIONALE: Despite increasing number of left ventricular assist device (LVAD) implantation, standardized cardiopulmonary resuscitation (CPR) protocol for patients with LVAD, especially in out-of-hospital settings are not well known. PATIENT CONCERNS: A 41-year-old LVAD implanted man became cardiac arrest in an out-of-hospital setting. Bystander CPR was started and the patient was brought to our hospital without noticing LVAD. Upon arrival, the medical staff noted the LVAD and that the battery of the LVAD was exhausted. DIAGNOSIS: Cardiac arrest on LVAD. INTERVENTIONS: It took 50 minutes to change the battery, then the patient has become ventricular fibrillation; hence, we introduced extracorporeal membranous oxygenation and defibrillated the patient. After the sinus rhythm was restored, the LVAD started working uneventfully. OUTCOMES: The patient became brain dead. LESSONS: There are several difficulties in treating these patients. First, hemodynamic collapse is difficult to diagnose. Second, chest compression for LVAD implanted patients remains controversial. Third, education to first responders who are not familiar with LVAD are not enough. Appropriate education for those issues is needed.

Integrin and PD-1 Ligand Expression on Circulating Extracellular Vesicles in Systemic Inflammatory Response Syndrome and Sepsis.

Extracellular vesicles (EVs) in the plasma mediate important intercellular communications in the pathogenesis of cancer and inflammatory diseases. EVs express integrins that regulate target specificities and programmed cell death ligand 1 and 2 (PD-L1 and 2) that suppress lymphocyte activation. However, the roles of these molecules on EVs in systemic inflammatory response syndrome (SIRS) and sepsis remain little understood. This study aimed to investigate how the EV expression of integrins and PD-1 ligands might differ in SIRS and sepsis, compared with healthy controls, and to correlate their expression with the clinical parameters reflecting pathogenesis. Twenty-seven SIRS patients without sepsis, 27 sepsis patients, and 18 healthy volunteers were included. EVs were isolated from plasma samples. The expression of three major integrins (ß1, ß2, ß3 integrins) and PD-L1 and 2 were measured. The EV expression of ß2 integrin and PD-L2 was significantly increased in sepsis patients compared with healthy controls. EV expression of PD-L1 was not elevated in sepsis and SIRS; however, circulating soluble PD-L1 levels were significantly higher in sepsis. Furthermore, EV expression of ß2 integrin in sepsis patients correlated with hypotension and reduced kidney function. In addition, soluble PD-L1 levels correlated with sepsis severity, impaired kidney function, and impaired central nervous system function. These results suggest the potential involvements of the EV ß2 integrin, as well as EV PD-L2 and soluble PD-L1, in the septic pathogenesis that occurs with the systemic immune activation leading to multiple organ dysfunctions.

Laparoscopically assisted cervical canalization and neovaginoplasty in a woman with cervical atresia and vaginal aplasia.

Cervical atresia is a Müllerian duct system anomaly, and it is often associated with vaginal aplasia. We report the case of a 17-year-old girl who presented with primary amenorrhea and cyclical abdominal pain, and was diagnosed with cervical atresia and vaginal aplasia that were treated laparoscopically. Laparoscopically assisted cervical canalization and neovaginoplasty were performed to relieve dysmenorrhea and allow for sexual intercourse and fertility. We did not use a bowel segment, skin, or peritoneum as a graft for the neovaginoplasty. To prevent adhesions and promote epithelialization, we used an estrogen-containing cream. Moreover, we did not use a vaginal mold. The patient is free of cervical stenosis and able to have intercourse. Long-term follow-up is necessary to ensure a future pregnancy and childbirth.

Two cases of life-threatening arrhythmia induced by risperidone: evaluation of risperidone and 9-hydroxy-risperidone concentrations.

Cases: Case 1: A 20-year-old woman suffering a suspected overdose was transported to the hospital. She presented bradycardia with wide QRS waves and QT prolongation, followed by cardiac arrest. Extracorporeal cardiopulmonary resuscitation was implemented, improving circulation. Risperidone and 9OH-RIS levels were 9.6 ng/mL and 127.6 ng/mL, respectively. Case 2: A 54-year-old woman was hospitalized for femoral fracture and underwent surgery. Her electrocardiogram showed bradycardia and complete AV block. Risperidone and 9OH-RIS levels were 3.2 ng/mL and 61.4 ng/mL, respectively. Outcome: In both cases, only serum concentration of 90H-RIS were elevated. Conclusion: Arrhythmia related to risperidone has proven rare but sometimes fatal. Serum concentrations of risperidone and the metabolite 9-hydroxy-risperidone (9OH-RIS) during these events are seldom documented. As 9OH-RIS shows pharmacological activity equivalent to risperidone, it may induce life-threatening arrhythmia (regardless of the intake dosage). It is critical to evaluate the serum concentration of 9OH-RIS in suspected risperidone toxicity.

A case of bilateral tubal pregnancy.

Bilateral tubal pregnancy is very rare and occurs in only 1 out of every 200,000 spontaneous pregnancies. In this case, a 29-year-old woman with a history of primary infertility underwent treatment with human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG), and became pregnant. A gestational sac (GS) was not detected in the uterus and transvaginal ultrasonography (USG) revealed GS with fetal heartbeat in the left adnexa at 7 weeks and 6 days of gestation. The patient underwent laparoscopic surgery and ultimately, bilateral tubal pregnancy was diagnosed. Consequently, bilateral fallopian tube resection was performed. Afterwards, she conceived by assisted reproductive technology (ART) and delivered vaginally. This case suggests that even if a GS is found in one fallopian tube by USG, it is important to evaluate the other fallopian tube carefully. Abbreviations: TV-USG, transvaginal ultrasound; hCG, human chorionic gonadotropin; DD, dichorionic-diamniotic.