Novel approach to HER2 quantification using phosphor-integrated dots in human breast invasive cancer microarray.

HER2 expression in breast cancer is evaluated to select patients for anti-HER2 therapy. With the advent of newly approved HER2-targeted drugs for low HER2 expression breast cancer, more solid evidence on the whole spectrum of HER2 expression is needed. In this study, we quantitatively assessed HER2 expression from the whole core by combining high-intensity phosphor-integrated dot (PID) immunostaining and whole slide imaging (WSI) analysis. Two types of staining were performed using a 170-core tissue microarray of invasive breast cancer. First, HER2 was stained by immunohistochemistry (IHC), and IHC scores were determined by two practicing pathologists according to the ASCO/CAP HER2 guideline. Second, HER2 was stained with PID, and tentative PID scores were determined by quantitative analysis. The results show that PID can numerically classify HER2 expression status into scores 3+, 2+, 1+, and 0. The HER2 value quantified by PID strongly correlated with the 3, 3'-diaminobenzidine (DAB) IHC score determined by pathologists (R2 = 0.93). PID IHC score 1+ cases included both DAB IHC score 1+ and 0 cases, and low HER2 expression cases appeared to be often evaluated as DAB IHC score 0. Therefore, digital image analysis by PID and WSI can help stratify HER2 IHC. It may also help classify low HER2 expression.

Idarucizumab for Emergency Reversal of the Anticoagulant Effects of Dabigatran: Final Results of a Japanese Postmarketing Surveillance Study.

INTRODUCTION: Idarucizumab, a monoclonal antibody fragment that rapidly reverses the anticoagulant effects of dabigatran, was approved in Japan in September 2016, at which time an all-case, postmarketing surveillance (PMS) study was initiated to collect data on idarucizumab in Japanese patients. Interim results were published previously, and the final results are reported herein. METHODS: This multicenter, open-label, uncontrolled, non-interventional PMS study was conducted in Japanese patients who received idarucizumab at the approved dose (2 × 2.5 g/50 ml) and had uncontrolled bleeding (group A) or required an emergency procedure (group B). The primary endpoint was the frequency of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effects of dabigatran, within 4 h of idarucizumab administration, based on activated partial thromboplastin time (aPTT). RESULTS: The final analysis included 804 patients. ADRs during the idarucizumab treatment and post-treatment periods were reported in 17 of 542 patients (3.1%) in group A and 12 of 240 patients (5.0%) in group B. Thrombotic events were reported in 22 patients (4.1%) in group A and 15 patients (6.3%) in group B, and hypersensitivity occurred in four (0.7%) and five patients (2.1%), respectively. Among 793 patients evaluated for effectiveness, 78 in group A and 26 in group B had aPTT data at baseline (immediately before idarucizumab administration) and within 4 h of idarucizumab administration; in these patients, median maximum percentage reversal within 4 h of idarucizumab administration was 100%. CONCLUSIONS: The final analysis from the PMS study confirms previous findings suggesting that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients in clinical practice. The results support the continued use of idarucizumab in Japan. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT02946931).

Atrial fibrillation is an irregular heart rhythm (arrhythmia), and the type of atrial fibrillation not caused by a heart valve problem is known as "non-valvular atrial fibrillation" or NVAF. People with NVAF have an increased risk of ischemic stroke, in which a blood clot (thrombus) blocks an artery in the brain. Drugs that inhibit blood clots, known as anticoagulants, are prescribed to people with NVAF to prevent ischemic stroke. Historically, warfarin has been one of the most prescribed anticoagulant drugs. However, a novel anticoagulant drug, known as dabigatran, has clinical advantages over warfarin and is approved in many countries for people with NVAF. People who take anticoagulants may experience life-threatening bleeding or need urgent surgery, and thus rapid and effective reversal of the anticoagulant effects is critical. The drug idarucizumab specifically binds to dabigatran to reverse its anticoagulant effects in people with uncontrolled bleeding or who require an urgent procedure. Idarucizumab was approved for use in Japan in September 2016. In Japan, drug companies are obligated to collect data after a new drug is launched as an approval condition, which is done through a postmarketing surveillance study. Here, we report the final results of a postmarketing surveillance study conducted between September 2016 and November 2020 to evaluate the safety and effectiveness of idarucizumab in Japanese patients receiving dabigatran. The results of our study show that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients, and support the continued use of idarucizumab in Japan in clinical practice.

Current status of active cooling, deep body temperature measurement, and face mask wearing in heat stroke and heat exhaustion patients in Japan: a nationwide observational study based on the Heatstroke STUDY 2020 and 2021.

Aim: The study aimed to determine the current status of face mask use, deep body temperature measurement, and active cooling in patients suffering from heat stroke and heat exhaustion in Japan. Methods: This was a prospective, observational, multicenter study using data from the Heatstroke STUDY 2020-2021, a nationwide periodical registry of heat stroke and heat exhaustion patients. Based on the Bouchama heatstroke criteria, we classified the patients into two groups: severe and mild-to-moderate. We compared the outcomes between the two groups and reclassified them into two subgroups according to the severity of the illness, deep body temperature measurements, and face mask use. Cramer's V was used to determine the effect sizes for a comparison between groups. Results: Almost all patients in this study were categorized as having degree III based on the Japanese Association for Acute Medicine heatstroke criteria (JAAM-HS). However, the severe group was significantly worse than the mild-to-moderate group in outcomes like in-hospital death and modified Rankin Scale scores, when discharged. Heat strokes had significantly higher rates of active cooling and lower mortality rates than heat stroke-like illnesses. Patients using face masks often use them during labor, sports, and other exertions, had less severe conditions, and were less likely to be young male individuals. Conclusions: It is suggested that severe cases require a more detailed classification of degree III in the JAAM-HS criteria, and not measuring deep body temperature could have been a factor in the nonperformance of active cooling and worse outcomes.

Water-Dispersible Carboxymethyl Dextran-Coated Melamine Nanoparticles for Biosensing Applications.

In this study, we developed a simple method for preparing highly dispersed, stable, and streptavidin (SA)-functionalized carboxymethyl dextran (CMD)-coated melamine nanoparticles (MNPs) in an aqueous buffer at neutral pH. Dynamic light scattering (DLS) revealed the agglomeration of MNPs in an aqueous buffer at neutral pH. When CMD, N-hydroxysuccinimide (NHS), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were simultaneously mixed with the MNPs, CMD was bound to the MNPs, promoting their dispersibility. Preparation of SA-CMD-MNPs was accomplished simply by adding SA solution to the CMD-MNPs. The amount of SA bound to the CMD-MNPs was quantified by the bicinchoninic assay, and the amount of SA molecules bound to each CMD-MNP was 417 ± 4. SA-CMD-MNPs exhibited high dispersity (polydispersity index = 0.058) in a neutral phosphate buffer and maintained it for 182 days with dispersion using a probe sonicator (5 s) before DLS characterization. The performance of the SA-CMD-MNPs in biosensing was evaluated by immunohistochemistry, which revealed that the nanoparticles could specifically stain MCF-7 cells derived from breast cancer cells with low HER2 expression. This study provides an effective method for synthesizing highly dispersible nanoparticles for biosensing.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Influence of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of heat stroke and heat exhaustion in Japan: a nationwide observational study based on the Heatstroke STUDY 2019 (without COVID-19) and 2020 (with COVID-19).

AIM: To assess heat stroke and heat exhaustion occurrence and response during the coronavirus disease 2019 pandemic in Japan. METHODS: This retrospective, multicenter, registry-based study describes and compares the characteristics of patients between the months of July and September in 2019 and 2020. Factors affecting heat stroke and heat exhaustion were statistically analyzed. Cramér's V was calculated to determine the effect size for group comparisons. We also investigated the prevalence of mask wearing and details of different cooling methods. RESULTS: No significant differences were observed between 2019 and 2020. In both years, in-hospital mortality rates just exceeded 8%. Individuals >65 years old comprised 50% of cases and non-exertional onset (office work and everyday life) comprised 60%-70%, respectively. The recommendations from the Working Group on Heat Stroke Medicine given during the coronavirus disease pandemic in 2019 had a significant impact on the choice of cooling methods. The percentage of cases, for which intravascular temperature management was performed and cooling blankets were used increased, whereas the percentage of cases in which evaporative plus convective cooling was performed decreased. A total of 49 cases of heat stroke in mask wearing were reported. CONCLUSION: Epidemiological assessments of heat stroke and heat exhaustion did not reveal significant changes between 2019 and 2020. The findings suggest that awareness campaigns regarding heat stroke prevention among the elderly in daily life should be continued in the coronavirus disease 2019 pandemic. In the future, it is also necessary to validate the recommendations of the Working Group on Heatstroke Medicine.

Wearing a face mask during controlled-intensity exercise is not a risk factor for exertional heatstroke: A pilot study.

AIM: This study aimed to measure the influence of wearing face masks on individuals' physical status in a hot and humid environment. METHODS: Each participant experienced different physical situations: (i) not wearing a mask (control), (ii) wearing a surgical mask, (iii) wearing a sport mask. An ingestible capsule thermometer was used to measure internal core body temperature during different exercises (standing, walking, and running, each for 20 min) in an artificial weather room with the internal wet-bulb globe temperature set at 28°C. The change in the participants' physical status and urinary liver fatty acid-binding protein (L-FABP) were measured. RESULTS: Six healthy male volunteers were enrolled in the study. In each participant, significant changes were observed in the heart rate and internal core temperatures after increased exercise intensity; however, no significant differences were observed between these parameters and urinary L-FABP among the three intervention groups. CONCLUSION: Mask wearing is not a risk factor for heatstroke during increased exercise intensity.

Quantitative analysis of the impact of COVID-19 on the emergency medical services system in Tokyo.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has imposed a heavy burden on emergency medical services (EMS) systems. Therefore, we quantitatively analyzed impacts of COVID-19 on the EMS system in Tokyo. METHODS: In this retrospective observational study, we used publicly available data, including the daily number of newly diagnosed patients with COVID-19, the weekly number of transport difficulties, and the field activity time, from March 2, 2020, to January 25, 2021. Data for the same period in the previous year were used as controls. RESULTS: The total number of EMS calls decreased by 12.7% in 2020 compared with that in 2019. The number of daily transport difficulties significantly increased in 2020 compared with that in 2019 (89 [72-120] vs 57 [49-63]; P < 0.001). Additionally, the field activity time significantly increased in 2020 compared with that in 2019 (22.7 [22.3-23.8] min vs 20.7 [20.6-21.2] min; P < 0.001). Furthermore, the daily number of new patients with COVID-19 was positively correlated with the number of transport difficulties (R = 0.76) and the field activity time on the scene (R = 0.74). With an increase in the number of people infected with COVID-19 by 1,000, the number of daily transport difficulties increased by 86.4. Per 1,000 infected patients per day, the field activity time increased by 3.48 min. CONCLUSION: This study revealed that the increase in the number of patients with COVID-19 indirectly affected the EMS system in Tokyo.

Accidental hypothermia: characteristics, outcomes, and prognostic factors-A nationwide observational study in Japan (Hypothermia study 2018 and 2019).

AIM: This study describes the clinical characteristics and outcomes as well as the prognostic factors of patients with accidental hypothermia (AH) using Japan's nationwide registry data. METHODS: The Hypothermia study 2018 and 2019, which included patients aged 18 years or older with a body temperature of 35°C or less, was a multicenter registry conducted at 87 and 89 institutions throughout Japan, with data collected from December 2018 to February 2019 and December 2019 to February 2020, respectively. RESULTS: In total, 1363 patients were enrolled in the registry, of which 1194 were analyzed in this study. The median (interquartile range) age was 79 (68-87) years, and the median (interquartile range) body temperature at the emergency department was 30.8°C (28.4-33.6°C). Forty-three percent of patients with AH had a mild condition, 35.2% moderate, and 21.9% severe. AH occurred in an indoor setting in 73.4% and was caused by acute medical illness in 49.3% of patients. A total of 101 (8.5%) patients suffered from cardiopulmonary arrest on arrival at the hospital. The overall 30-day mortality rate was 24.5%, the median (interquartile range) intensive care unit stay was 4 (2-7) days, and the median (interquartile range) hospital stay was 13 (4-27) days. In the multivariable logistic analysis, the prognostic factors were age (≥75 years old), male, activities of daily living (needing total assistance), cause of AH (trauma, alcohol), Glasgow Coma Scale score, and potassium level (>5.5 mEq/L). CONCLUSION: The mortality rate of AH was 24.5% in Japan. The prognostic factors developed in this study may be useful for the early prediction, prevention, and awareness of severe AH.

Portal Venous Gas in Adults: Clinical Significance, Management, and Outcomes of 25 Consecutive Patients.

BACKGROUND: Portal venous gas (PVG) is a rare finding and has a grave prognosis. The most common and critical underlying pathology of PVG is bowel necrosis. However, bowel necrosis is sometimes difficult to accurately diagnose. We retrospectively analyzed data from patients that contributed to the decision to perform emergency surgery and bowel resection. METHODS: Between 2009 and 2019, 25 consecutive adult patients with PVG were identified retrospectively and divided into the Operation and Non-operation groups. The Operation group was further subdivided into the Bowel resection and Non-resection groups. Clinical, laboratory, and radiographic variables were analyzed. RESULTS: Conservative management was successful for 32% (8/25) of patients (Non-operation group: mortality 0%); 68% (17/25) were treated surgically (Operation group: mortality 35.3%). In the Operation group, 52.9% (9/17) underwent bowel resection (Bowel resection group: mortality 55.6%); however, bowel resection was unnecessary in 47.1% (8/17) of cases (Non-resection group: mortality 12.5%). Univariate analysis revealed significant differences between the Operation and Non-operation groups in GCS, APACHE II, abdominal distention, CRP, lactate, and CT findings of bowel dilatation, pneumatosis intestinalis, and attenuation of contrast effects of the bowel wall. However, with the exception of GCS, there was no significant difference between the Bowel resection and Non-resection groups. CONCLUSIONS: Analysis of clinical, laboratory, and radiographic variables can inform decisions on conservative management. However, 47.1% of the present patients who underwent surgery for suspected bowel necrosis did not require bowel resection, suggesting that this approach alone may not be sufficient to avoid non-therapeutic laparotomy. A new approach should be developed to improve this situation.

Cost-effectiveness of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A multi-centre prospective cohort study.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) is an evolving resuscitative method for refractory cardiopulmonary arrests. However, considering the substantial healthcare costs and resources involved, there is an urgent need for a full economic evaluation. We therefore assessed the cost-effectiveness of ECPR for refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). METHODS: We developed a decision model to estimate lifetime costs and outcomes for out-of-hospital cardiac arrest patients with VF/pVT who received either ECPR or conventional cardiopulmonary resuscitation. Quality-adjusted life-years (QALY) was used as the main outcome measure. This model was a combination of a decision tree model for the acute phase based on a prospective observational study (SAVE-J study), together with a Markov model for long-term follow-up periods extrapolated from published data. To evaluate the robustness of this model, we conducted a comprehensive deterministic sensitivity analysis (DSA) and a probabilistic sensitivity analysis (PSA). RESULTS: ECPR was cost-effective, with an incremental cost of ¥3,521,189 (Є30,227), an incremental effectiveness of 1.34 QALY, and an incremental cost-effectiveness ratio of ¥2,619,692 (Є22,489) per QALY gained. DSA revealed that the present model was most sensitive to probability of Cerebral Performance Category 1 after ECPR (¥2,153,977/QALY to ¥3,186,475/QALY), patient age (¥2,170,112/QALY to ¥3,334,252/QALY), and long-term medical cost for modified Rankin Scale 0 (¥2,280,352/QALY to ¥2,855,330/QALY). PSA indicated ECPR to be cost-effective and below the willingness-to-pay threshold of ¥5,000,000 with an 86.7 % possibility. CONCLUSIONS: ECPR was an economically acceptable resuscitative strategy, and the results of the present study were robust even when considering the uncertainty of all parameters.

Diagnosis and prediction of prognosis for Bickerstaff's brainstem encephalitis using auditory brainstem response: a case report.

BACKGROUND: It is difficult to diagnose Bickerstaff's brainstem encephalitis (BBE) in the acute phase, and emergency physicians could diagnose BBE as an unknown cause of consciousness disturbance. CASE PRESENTATION: A 75-year-old woman presented with dizziness and weakness in both arms 1 week after an upper respiratory infection. She experienced gradual worsening of consciousness, had dilated pupils and no light reflex. She was suspected of brainstem dysfunction at the upper part of the brainstem; however, there were not significant findings on magnetic resonance imaging, cerebrospinal fluid, or electroencephalography. The auditory brainstem response demonstrated a low voltage, but there was no prolonged latency. At a later date, she was diagnosed with BBE based on serum immunoglobulin G anti-GQ1b antibody. She was discharged home without any neurological sequelae. CONCLUSION: It is necessary to analyze serum immunoglobulin G anti-GQ1b antibodies to diagnose BBE. Auditory brainstem response would be helpful in detecting lesions and predicting functional recovery.

Clinical characteristics, prognostic factors, and outcomes of heat-related illness (Heatstroke Study 2017-2018).

AIM: Heat-related illness is common, but its epidemiology and pathological mechanism remain unclear. The aim of this study was to report current clinical characteristics, prognostic factors, and outcomes of heat-related illness in Japan. METHODS: We undertook a prospective multicenter observational study in Japan. Only hospitalized patients with heat-related illness were enrolled from 1 July to 30 September 2017 and 1 July to 30 September 2018. RESULTS: A total of 763 patients were enrolled in the study. Median age was 68 years (interquartile range, 49-82 years) and median body temperature on admission was 38.2°C (interquartile range, 36.8-39.8°C). Non-exertional cause was 56.9% and exertional cause was 40.0%. The hospital mortality was 4.6%. The median Japanese Association for Acute Medicine disseminated intravascular coagulation (JAAM DIC), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were 1 (0-2), 4 (2-6), and 13 (8-22), respectively. To predict hospital mortality, areas under the receiver operating characteristic curves were 0.776 (JAAM DIC score), 0.825 (SOFA), and 0.878 (APACHE II). There were 632 cases defined as heatstroke by JAAM heat-related illness criteria, 73 cases diagnosed as having DIC. A total of 16.6% patients had poor neurological outcome (modified Rankin Scale ≥ 4) at hospital discharge. In the multivariate analysis, Glasgow Coma Scale and platelets were independent predictors of mortality. Type of heatstroke, Glasgow Coma Scale, and platelets were independent predictors of poor neurological outcome. Body temperature was not associated with mortality or poor neurological outcome. CONCLUSIONS: In this study, hospital mortality of heat-related illness was <5%, one-sixth of the patients had poor neurological outcome. The APACHE II, SOFA, and JAAM DIC scores predicted hospital mortality. Body temperature was not associated with mortality or poor neurological outcome.

Incidence Rates of Bleeding and Emergency Surgery Due to Trauma or Fracture Among Japanese Patients with Non-valvular Atrial Fibrillation Receiving Oral Anticoagulation Therapy.

INTRODUCTION: In patients with nonvalvular atrial fibrillation (NVAF) receiving oral anticoagulants (OACs), reversal of coagulopathy can be achieved with specific reversal drugs such as idarucizumab, which is indicated for use in patients treated with dabigatran for cases of life-threatening or uncontrolled bleeding or during emergency procedures that may cause serious bleeding. This study examined the incidence rate (IR) of emergency surgeries and major bleeding episodes associated with fractures and trauma in Japanese patients with NVAF receiving OACs. METHODS: This retrospective, non-interventional analysis of health insurance claims was conducted using data from 62,888 OAC-naive adult patients with NVAF who initiated dabigatran, warfarin, apixaban, rivaroxaban, or edoxaban between March 2011 and June 2016. The primary endpoint was overall IR of emergency surgery or major bleeding due to fracture or trauma. RESULTS: Overall IR of emergency surgery or major bleeding due to fracture or trauma considering outcomes until OAC discontinuation was 0.489 per 100 patient-years (PY) (95% confidence interval [CI] 0.406-0.572). Considering first OAC exposure only, the IR was 0.483 per 100 PY (95% CI 0.394-0.573). Emergency surgery/major bleeding events due to fracture or trauma was highest in those aged ≥ 75 years (0.611 per 100 PY [95% CI 0.481-0.741]). CONCLUSIONS: Fewer than one in 200 patients per year with NVAF receiving OACs experience emergency surgeries and major bleeding episodes associated with fractures and trauma; however, the IR of these events is markedly higher in patients of advanced age. TRIAL REGISTRATION: ClinicalTrials.gov 207, NCT03254147.

Patients with an abnormal heart rhythm (nonvalvular atrial fibrillation [NVAF]) have a higher risk of blood clots and stroke (which is when the blood supply to part of the brain is blocked). To reduce these risks, patients can take anticoagulants that slow or prevent the formation of blood clots. However, if the patient needs major emergency surgery or has a severe injury, the anticoagulants can increase their risk of bleeding, which can sometimes be life-threatening. There are drugs (e.g., idarucizumab) that can be used to reverse the effects of anticoagulants in this type of emergency. What we don't know is how many NVAF patients in Japan who are on anticoagulants have emergency surgeries or major bleeding after an injury, and therefore may require a reversal drug. The authors looked at Japanese health insurance claim data from 62,888 adult patients with NVAF who started taking an anticoagulant. They found that, annually, approximately 0.5% of the patients had emergency surgery or a major bleed associated with a fracture or injury. In very elderly patients (aged at least 75 years), the annual percentage was approximately 0.6%, which was almost double the annual percentage in patients aged less than 65 years. The authors concluded that, even though the number of people requiring a reversal agent are quite small, it is important to have an effective reversal agent for patients on anticoagulants, particularly older patients.

Idarucizumab for Emergency Reversal of Anticoagulant Effects of Dabigatran: Interim Results of a Japanese Post-Marketing Surveillance Study.

INTRODUCTION: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran, and it was approved in Japan in September 2016. An all-case post-marketing surveillance is ongoing to collect data in Japanese patients treated with idarucizumab who had serious bleeding (Group A) or required an urgent procedure (Group B). METHODS: The primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effect of dabigatran based on activated partial thromboplastin time (aPTT) within 4 h after idarucizumab administration. RESULTS: This interim analysis included 262 patients who received idarucizumab. Eighteen patients (6.9%) experienced ADRs within 4 weeks. The reversal effect of idarucizumab based on aPTT within 4 h after idarucizumab administration was assessed in 30 patients and the median maximum percentage reversal was 100%. In Group A, the median time to bleeding cessation in patients without intracranial bleeding was 3.3 h. In Group B, normal intraoperative hemostasis was reported in 63 patients (72.4%). CONCLUSIONS: The results of this interim analysis suggest that idarucizumab is safe and effective for the reversal of dabigatran in Japanese patients in a real-world setting, and support the continued use of idarucizumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02946931.

Vasodilator Therapy and Mortality in Nonocclusive Mesenteric Ischemia: A Nationwide Observational Study.

OBJECTIVES: Previous studies have suggested that vasodilator therapy may be beneficial for patients with nonocclusive mesenteric ischemia. However, robust evidence supporting this contention is lacking. We examined the hypothesis that vasodilator therapy may be effective in patients diagnosed with nonocclusive mesenteric ischemia. DESIGN: Retrospective cohort study. SETTING: The Japanese Diagnosis Procedure Combination inpatient database. PATIENTS: A total of 1,837 patients with nonocclusive mesenteric ischemia from July 2010 to March 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared patients who received vasodilator therapy (vasodilator group; n = 161) and those who did not (control group; n = 1,676) using one-to-four propensity score matching. Vasodilator therapy was defined as papaverine and/or prostaglandin E1 administered via venous and/or arterial routes within 2 days of admission. Only patients who did not receive abdominal surgery within 2 days of admission were analyzed. The main outcomes were in-hospital mortality and abdominal surgery performed greater than or equal to 3 days after admission. After propensity score matching, in-hospital mortality was significantly lower in the vasodilator group (risk difference, -11.6%; p = 0.005). The proportion of patients who received abdominal surgery at greater than or equal to 3 days after admission was also significantly lower in the vasodilator group (risk difference, -10.2%; p = 0.002). CONCLUSIONS: Vasodilator therapy with papaverine and/or prostaglandin E1 is associated with lower in-hospital mortality and prevalence of abdominal surgery in patients with nonocclusive mesenteric ischemia.

Intravenous Immunoglobulin Attenuates Cecum Ligation and Puncture-Induced Acute Lung Injury by Inhibiting Apoptosis of Alveolar Epithelial Cells.

PURPOSE: Intravenous immunoglobulin (IVIG) therapy has been used to treat sepsis, but its mechanisms of action remain unclear. Sepsis causes multiple organ failure, such as acute lung injury (ALI), which involves apoptosis of alveolar epithelial cells. In this study, we hypothesized that IVIG suppresses apoptosis in alveolar epithelial cells and evaluated mortality, cytokine levels, histological changes in the lung, and alveolar epithelial cell apoptosis after IVIG administration, in mice with experimentally induced sepsis. METHODS: Mice received an injection of vehicle (saline) or immunoglobulin (100 mg/kg or 400 mg/kg) into the tail vein, after which they underwent cecal ligation and puncture. A sham-operated group was used as the normal control. Survival was assessed in all groups after 72 hours. Plasma levels of TNF-α and IL-6, histopathological changes and wet-to-dry ratio in lung, and alveolar epithelial cell apoptosis were evaluated in all groups at 4 hours after surgery. RESULTS: In the vehicle group, histopathological injury of the lung was severe, and apoptosis of alveolar epithelial cells was significant. Survival and plasma cytokine levels were better in the IVIG treatment groups than in the vehicle group. IVIG 400 mg/kg suppressed apoptosis of alveolar epithelial cells and reduced ALI. CONCLUSION: IVIG suppressed inflammatory cytokine levels and improved survival. Lung histopathology and alveolar epithelial cell apoptosis were improved by IVIG treatment, in a dose-dependent manner. Suppressing apoptosis in alveolar epithelial cells appears to be a mechanism by which IVIG improves survival.

Fatal fulminant Clostridioides difficile colitis caused by Helicobacter pylori eradication therapy; a case report.

A 74-year-old male was referred to our critical care department for refractory severe watery diarrhea with advanced leukocytosis (over 70,000/µl) after multiple administrations of eradication therapy against Helicobacter pylori (HP). He was diagnosed as having fulminant colitis due to Clostridioides difficile after antimicrobial eradication therapy. He was given intravenous metronidazole and oral vancomycin. He also received supportive therapy including continuous hemodiafiltration for severe metabolic acidosis. However, despite emergency open sigmoidectomy, he died. The C. difficile isolate recovered was PCR-ribotype 002, which was positive for toxins A and B but negative for binary toxin. HP eradication therapy for prevention of chronic gastritis and stomach cancer is now in widespread use. Although such secondary severe complications are rare, we consider it to be necessary to pay sufficient attention when administering HP eradication therapy.

Delayed development of portal vein thrombosis in a patient initially detected with portal venous gas and pneumatosis intestinalis: a case report.

BACKGROUND: Portal venous gas (PVG) and pneumatosis intestinalis (PI) are rare pathologic findings, and a delayed appearance of portal vein thrombosis (PVT) in such patients is extremely rare. CASE PRESENTATION: A 51-year-old man complaining of epigastric pain was referred to our hospital. Computed tomography (CT) at admission revealed massive PVG and extensive PI, but no PVT. Emergency laparotomy was carried out, but bowel resection was unnecessary. On follow-up CT on postoperative day 5, thrombosis was noted in the portal venous system, and anticoagulant was started immediately. This patient was discharged and continued to take the anticoagulant. Seven months after discharge, PVT had disappeared on CT without any thromboembolic complications. CONCLUSION: If acute PVT is detected, anticoagulant is needed to prevent bowel ischemia and/or portal hypertension due to the growth of the thrombus. Clinicians should be aware of the potential for such a complication, and make their best efforts to exclude this entity using CT or sonography.

Functional Outcome Following Ultra-Early Treatment for Ruptured Aneurysms in Patients with Poor-Grade Subarachnoid Hemorrhage.

BACKGROUND: Little is known regarding functional outcome following poor-grade (World Federation of Neurosurgical Societies grades IV and V) aneurysmal subarachnoid hemorrhage (aSAH), especially in individuals treated aggressively in the early phase after ictus. METHODS: We provided patients with aSAH with ultra-early definitive treatment, coiling or clipping, within 6 hours from arrival as per protocol. We classified the patients into 3 groups according to their computed tomography findings: Group 1, intraventricular hemorrhage with obstructive hydrocephalus; Group 2, massive intracerebral hemorrhage with brain herniation; and Group 3, neither Group 1 nor Group 2. We retrospectively evaluated patients with poor-grade aSAH who were admitted to our department between January 2013 and December 2016. We evaluated functional outcome at 6 months, defining modified Rankin Scale (mRS) scores of 0-2 as good and those of 3-6 as poor outcomes. RESULTS: A good functional outcome was observed in 39.4% (28/71) of all cases. All-cause mortality at 6 months was 15.5% (11/71). A good outcome in Group 3 was significantly higher than that in the other two groups (Group 1 and 2 vs. Group 3, 20.8% vs. 48.9%, p = 0.02), even after adjustment with a multiple logistic regression analysis (odds ratio 6.1, 95% confidence interval 1.1 to 34.8). CONCLUSIONS: Approximately 40% of patients with poor-grade aSAH became functionally independent, and approximately half of the patients with poor-grade aSAH who had neither intraventricular hemorrhage with obstructive hydrocephalus nor with brain herniation had good functional outcomes. Although further trials are required to confirm our results, ultra-early surgery may be considered for patients with poor-grade aSAH.