Multicenter Observational Study In Japan Research Articles

Prognosis, risk factors, and scoring model of patients resuscitated from traumatic cardiac arrest: A multicenter observational study in Japan.

A subset of patients with traumatic cardiac arrest is salvageable when the reversible causes of cardiac arrest are promptly treated. However, prognosis and risk factors of survivors upon hospital admission after traumatic cardiac arrest remain unclear. We aimed to describe the outcomes, identify risk factors, and develop a simple risk-scoring model for patients resuscitated from traumatic cardiac arrest. This observational multicenter study analyzed data from the Japan Trauma Data Bank from January 1, 2019, to December 31, 2021. Patients who underwent cardiopulmonary resuscitation in the emergency department and survived to the day after hospital admission for traumatic cardiac arrest were included. Factors associated with survival to hospital discharge were determined using mixed-effects multivariable logistic regression analysis. A simple scoring model was developed to stratify the probability of survival to hospital discharge. In total, 452 patients from 119 hospitals (median age, 64 years; 334 [74.4%] men) were included in the analysis. Of these, 130 (28.8%) survived until discharge. Penetrating injury, signs of life upon hospital arrival, and Injury Severity Score were significantly associated with survival at hospital discharge. A scoring model that assigned 1 point each for penetrating injury and signs of life upon hospital arrival effectively stratified the probability of survival to hospital discharge, with scores of 0, 1, and 2 corresponding to survival probabilities of 12.2%, 35.2%, and 83.3%, respectively. This study described the outcomes and risk factors of patients resuscitated from traumatic cardiac arrest. Our simple scoring model effectively stratified the likelihood of survival to hospital discharge. Therapeutic/Care Management; Level III.

Early do-not-attempt resuscitation orders and neurological outcomes in older out-of-hospital cardiac arrest patient: A multicenter observational study.

To explore the association between Do-Not-Attempt Resuscitation (DNAR) orders issued within 6 h of admission and neurological outcomes in older patients with out-of-hospital cardiac arrest (OHCA). Patients aged ≥65 years who experienced OHCA between September 2019 and March 2021 enrolled in the multicenter observational study in Japan (SOS-KANTO 2017) were included. Data regarding DNAR decisions were prospectively collected and the time required to obtain DNAR orders. Patients who received DNAR orders within 6 h of admission (DNAR group) were compared with those who did not (non-DNAR group) using propensity score analysis with inverse probability treatment weighting (IPTW) to adjust for potential confounders. Of the 9909 registered individuals in the SOS-KANTO 2017 study across 42 facilities, 685 were selected for analysis, with 361 (52.7%) in the DNAR group. Even after adjusting for the confounding factors, the frequency of post-admission therapeutic interventions was lower, and the proportion of patients with favorable neurological outcomes was significantly lower (2.6% vs. 19.3%, p < 0.001) in the DNAR group. Twenty-six (7.3%) patients in the DNAR group survived for 1 month, of whom six (1.7%) had favorable neurological outcomes. Older patients with OHCA who had early DNAR had significantly fewer therapeutic interventions after admission and had worse neurological outcomes at 30 days than those without a DNAR order, even after adjusting for demographic and prehospital variables.

Effect of Inhaled Ciclesonide in Non-Critically Ill Hospitalized Patients With Coronavirus Disease 2019: A Multicenter Observational Study in Japan.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. Although systemic steroids play an important role in treating patients with severe COVID-19, the role of inhaled corticosteroids in non-critically ill, hospitalized patients with COVID-19 remains unclear. We analyzed findings in non-critically ill, hospitalized patients with COVID-19 who were >18 years old and were admitted to 64 Japanese hospitals between January and September 2020. We performed propensity score matching analysis to evaluate 28-day and in-hospital mortality rates with or without inhaled ciclesonide within 2 days of admission. Sensitivity analyses using inverse probability weighting analysis, and generalized estimating equation method were also performed. Eligible patients (n = 3638) were divided into ciclesonide (n = 290) and control (n = 3, 393) groups. The 1-to-4 propensity score matching analysis included 271 ciclesonide users and 1084 nonusers. There were no significant differences between the 2 groups for 28-day (3.3% vs 2.3%; risk difference, 1.0% [95% confidence interval, -1.2 to 3.3]) or in-hospital (4.8% vs 2.6%; risk difference, 2.2 [-.5 to 4.9]) mortality rates. The sensitivity analysis showed similar outcomes. From this multicenter observational study in Japan, inhaled ciclesonide did not decrease 28-day or in-hospital mortality rates in non-critically ill, hospitalized patients with COVID-19. Future large, multinational, randomized trials are required to confirm our results.

Clinical features and long-term outcomes of cancer-associated venous thromboembolism: transition from the warfarin era to the direct oral anticoagulant era

Abstract Background/Introduction After the introduction of direct oral anticoagulant (DOAC) for venous thromboembolism (VTE), DOAC for VTE have prevailed all over the world. The usefulness of DOAC for cancer-associated VTE has also been recently reported and may change the daily clinical practice and clinical outcomes. However, there have been still limited data on the issue in the real world. Purpose We aimed to investigate the clinical characteristics, anticoagulation strategies, and long-term clinical outcomes of patients with cancer-associated VTE comparing a large observational study in the warfarin era and that in the DOAC era. Methods The COMMAND VTE Registry-1 (enrolled 3,027 VTE patients among 29 center between January 2010 and August 2014 in the warfarin era) and Registry-2 (enrolled 5,197 VTE patients among 31 centers between January 2015 and August 2020 in the DOAC era) are the series of a multicenter observational study in Japan enrolling consecutive patients with acute symptomatic VTE. In the present study, we evaluated patients with cancer-associated VTE of 695 cases from Registry-1 and 1507 cases from Registry-2. Results As for oral anticoagulation therapy, 83% (2,576/695) of patients were treated with warfarin in the Registry-1 and 80% (1,199/5,197) of patients were treated with DOAC in the Registry-2. Patients in the Registry-2 were slightly older (67±12 vs. 68±13 years, P=0.005), had a slightly higher body weight (55±12 vs. 57±13 kg, P=0.03), and more frequently had pulmonary embolism (44% vs. 49%, P=0.004). Patients in the Registry-2 were less frequently admitted to the hospital among those with out-of-hospital-onset VTE (83% vs. 66%, P&amp;lt;0.001), and median length of hospitalization was shorter in patients in the Registry-2 (16 [IQR: 11-26] vs. 14.5 [IQR: 9-24] days, P=0.01). AS for cancer types, lung cancer, colorectal cancer and stomach cancer were significantly higher in patients in the Registry-1 (18% vs. 15%, P=0.04; 14% vs. 10%, P=0.008; 9% vs. 6%, P=0.007). There was no significant difference in the discontinuation rate of anticoagulation therapy between the 2 groups (56.7% vs. 62.7% at 3-year, Log rank P=0.10). The cumulative 5-year incidence of recurrent VTE, major bleeding and all cause-death were significantly lower in patients in the Registry-2 (17.7% vs. 10.1%, P&amp;lt;0.001; 26.6% vs. 20.4%, P=0.045; 73.1% vs. 64.8%, P=0.003), while there were no significant differences in the cumulative 5-year incidences of intracranial bleeding (5.7% vs. 3.2%, P=0.056) nor major gastrointestinal bleeding between the 2 groups (13.9% vs. 10.1%, P=0.30) (Figure). Conclusion The introduction of DOAC for cancer-associated VTE could have a potential benefit of reducing the risk of recurrent VTE and major bleeding, although gastrointestinal bleeding might be still a major concerns even in the DOAC era.FigureFigure

Clinical features and long-term outcomes of venous thromboembolism in the warfarin era versus in the direct oral anticoagulant era

Abstract Background/Introduction After the introduction of direct oral anticoagulant (DOAC) for venous thromboembolism (VTE), DOAC for VTE have prevailed all over the world, which could change the daily clinical practice and clinical outcomes. However, there have been still limited data on the issue in the real world. Purpose We aimed to investigate demographics, practice patterns and long-term clinical outcomes in patients with VTE comparing a large observational study in the warfarin era and that in the DOAC era. Methods The COMMAND VTE Registry-1 (enrolled 3,027 VTE patients among 29 center between January 2010 and August 2014 in the warfarin era) and Registry-2 (enrolled 5,197 VTE patients among 31 centers between January 2015 and August 2020 in the DOAC era) are the series of a multicenter observational study in Japan enrolling consecutive patients with acute symptomatic VTE. Results Patients characteristics were comparable in most of aspects between the groups, whereas prevalence of active cancer was higher in the Registry-2 (Registry-1: 23% vs. Registry-2: 29%, P&amp;lt;0.001). As for oral anticoagulation therapy, 88% (2,676/3,027) of patients were treated with warfarin in the Registry-1 and 79% (4,128/5,197) of patients were treated with DOAC in the Registry-2. The proportion of patients admitted to the hospital was lower in the Registry-2 (80% vs. 69%, P&amp;lt;0.001). The discontinuation rate of anticoagulation therapy was significantly higher in the Registry-2 (42.8% vs. 52.5% at 3-year, Log rank P&amp;lt;0.001). The cumulative 5-year incidence of recurrent VTE was lower in the Registry-2 (10.5% vs. 9.5%, Log rank P=0.02), which remained significant even after adjusting the confounders (adjusted hazard ratio [HR]: 0.78 (0.65-0.93), P=0.006). There was no significant difference in the cumulative incidence of major bleeding between the groups (12.1% vs. 13.7%, Log-rank P=0.26), which remained insignificant even after adjusting the confounders (adjusted HR: 1.03 (0.89-1.20), P=0.67). After stratifying a total cohort into sub-groups according to the risk classification of recurrent VTE in the current guidelines (major transient risk factors, minor transient risk factors, unprovoked, non-malignant persistent risk factors, and active cancer), the risks of recurrent VTE and major bleeding were significantly lower in the Registry-2 among active cancer group (recurrent VTE: 17.7% vs 10.1% at 5-year, Log rank P&amp;lt;0.001, major bleeding: 26.6% vs 20.4% at 5-year, Log rank P=0.04), while those were not significantly different between the groups among other sub-groups. Conclusion In the current series of large real-world VTE registries, there seemed to be a significant risk reduction of recurrent VTE in the DOAC era compared with in the warfarin era, while there was no sign of increased risk of major bleeding in the DOAC era.

198P Effectiveness of lenvatinib in patients with unresectable hepatocellular carcinoma: A multicenter observational study in Japan

198P Effectiveness of lenvatinib in patients with unresectable hepatocellular carcinoma: A multicenter observational study in Japan

Minimal Residual Disease Detected by the 7NB-mRNAs ddPCR Assay Is Associated with Disease Progression in High-Risk Neuroblastoma Patients: A Prospective Multicenter Observational Study in Japan.

High-risk neuroblastoma (HR-NB) patients remain far from obtaining optimal outcomes, with more than 50% relapse/regrowth rate despite current intensive multimodal therapy. This originated from the activation/proliferation of chemoresistant minimal residual disease (MRD). MRD with a significant prognostic was reported by several quantitative PCR (qPCR) or droplet digital PCR (ddPCR) assays quantitating different sets of NB-associated mRNAs (NB-mRNAs). The 7NB-mRNAs ddPCR assay quantitating CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs was reported to outperform other qPCR assays by a retrospective in-house observational study. In the present study, the Japan Children's Cancer Group (JCCG) Neuroblastoma Committee conducted a prospective multicenter observational study aimed at evaluating a prognostic value of MRD in bone marrow (BM-MRD) and peripheral blood (PB-MRD) detected by 7NB-mRNAs ddPCR assay. Between August 2018 and August 2022, 7 HR-NB patients who registered for JCCG clinical trials (JN-H-11 and JN-H-15) were enrolled. A total of 19 BM and 19 PB samples were collected, and 4/15 BM and 4/15 PB samples were classified as progressive disease (PD)/non-PD samples. BM-MRD and PB-MRD estimated area under curve (AUC) of 0.767 and 0.800 with a significant accuracy (AUC > 0.7). The present study validated a prognostic value of BM-MRD obtained by a previous study (AUC 0.723) and revealed the significant accuracy of PB-MRD as well as BM-MRD.

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm –Multicenter observational study in Japan

Background/objectivesThe detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. MethodsThis multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. ResultsTwo-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). ConclusionsEUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.

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.

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. 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. 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). 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.

Intra-arrest partial carbon dioxide level and favorable neurological outcome after out-of-hospital cardiac arrest: a nationwide multicenter observational study in Japan (the JAAM-OHCA registry).

Little is known about whether guideline-recommended ventilation during cardiopulmonary resuscitation results in optimal partial carbon dioxide (pCO2) levels or favorable outcomes. This study aimed to evaluate the association between intra-arrest pCO2 level and the outcome after out-of-hospital cardiac arrest (OHCA). We performed a secondary analysis of a multicenter observational study, including adult patients with OHCA who did not achieve a return of spontaneous circulation (ROSC) upon hospital arrival and whose blood gas analysis was performed before the ROSC between June 2014 and December 2017. The patients were categorized into four quartiles based on their intra-arrest carbon dioxide levels: Quartile 1 (<66.0 mmHg), Quartile 2 (66.1-87.2 mmHg), Quartile 3 (87.3-113.5 mmHg), and Quartile 4 (≥113.6 mmHg). The primary outcome was 1-month survival with favorable neurological outcomes defined as cerebral performance Category 1 or 2. Multivariate logistic regression analysis was used to evaluate the association between pCO2 and favorable neurological outcomes. During the study period, 20 913 patients were eligible for the analysis. The proportion of favorable neurological outcomes was 1.8% (90/5133), 0.7% (35/5232), 0.4% (19/5263), and 0.2% (9/5285) in Quartiles 1-4, respectively. Multivariable logistic regression analysis demonstrated that the probability of favorable neurological outcome decreased with increased intra-arrest carbon dioxide levels (i.e. Q1 vs. Q4, adjusted odds ratio 0.25, 95% confidence interval 0.16-0.55, P for trend <0.001). Lower intra-arrest pCO2 levels were associated with a favorable neurological outcome.

Safety and Immunogenicity of mRNA Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Lung Cancer Receiving Immune Checkpoint Inhibitors: A Multicenter Observational Study in Japan

IntroductionPatients with cancer have been prioritized for vaccination against severe acute respiratory syndrome coronavirus 2. Nevertheless, there are limited data regarding the safety, efficacy, and risk of developing immune-related adverse events (irAEs) associated with mRNA vaccines in patients with lung cancer, especially those being actively treated with immune checkpoint inhibitors. MethodsThis multicenter observational study was conducted at nine hospitals in Japan. Patients with lung cancer (≥20 y) actively treated with immune checkpoint inhibitors between 4 weeks prefirst vaccination and 4 weeks postsecond vaccination were enrolled. The primary end point was the incidence of irAEs of any grade on the basis of an assumed incidence without vaccination rate of 35%. Immunogenicity was assessed by measuring anti–spike (S)-IgG antibody levels against severe acute respiratory syndrome coronavirus 2. ResultsA total of 126 patients with lung cancer (median age, 71 y; interquartile range, 65–74) were enrolled from May to November 2021 and followed up until December 2021. There were 26 patients (20.6%, 95% confidence interval: 13.9%–28.8%) and seven patients (5.6%, 95% confidence interval: 2.3%–11.1%) who developed irAEs of any grade pre- and postvaccination, respectively, which was lower than the predicted incidence without vaccination. None of the patients experienced exacerbation of preexisting irAE postvaccination. S-IgG antibodies were seroconverted in 96.7% and 100% of the patients with lung cancer and controls, respectively, but antibody levels were significantly lower in patients with lung cancer (p < 0.001). ConclusionsPatients with lung cancer who were actively treated with ICIs were safely vaccinated without an increased incidence of irAEs; however, their vaccine immunogenicity was lower. This requires further evaluation.

Extracorporeal cardiopulmonary resuscitation with temperature management could improve the neurological outcomes of out-of-hospital cardiac arrest: a retrospective analysis of a nationwide multicenter observational study in Japan

BackgroundTarget temperature management (TTM) is an effective component of treating out-of-hospital cardiac arrest (OHCA) after return of spontaneous circulation in conventional cardiopulmonary resuscitation. However, therapeutic hypothermia (32–34 °C TTM) is not recommended based on the results of recent studies. Extracorporeal cardiopulmonary resuscitation (ECPR) with veno-arterial extracorporeal membrane oxygenation is another promising therapy for OHCA, but few studies have examined the effectiveness of ECPR with TTM. Therefore, we hypothesized that ECPR with TTM could have the effectiveness to improve the neurological outcomes for adults following witnessed OHCA, in comparison to ECPR without TTM.MethodsWe performed retrospective subanalyses of the Japanese Association for Acute Medicine OHCA registry. We focused on adults who underwent ECPR for witnessed OHCA. We performed univariate (the Mann–Whitney U test and Fisher’s exact test), multivariable (logistic regression analyses), and propensity score analyses (the inverse probability of the treatment-weighting method) with to compare the neurological outcomes between patients with or without TTM, among all eligible patients, patients with a cardiogenic cause, and patients divided into subgroups according to the interval from collapse to pump start (ICPS) (> 30, > 45, or > 60 min).ResultsWe analyzed data for 977 patients. Among 471 patients treated with TTM, the target temperature was therapeutic hypothermia in 70%, and the median interval from collapse to target temperature was 249 min. Propensity score analysis showed a positive association between TTM and favorable neurological outcomes in all patients (odds ratio 1.546 [95% confidence interval 1.046–2.286], P = 0.029), and in patients with ICPS of > 30 or > 45 min, but not in those with ICPS of > 60 min. The propensity score analysis also showed a positive association between TTM and favorable neurological outcomes in patients with a cardiogenic cause (odds ratio 1.655 [95% confidence interval 1.096–2.500], P = 0.017), including in all ICPS subgroups (> 30, > 45, and > 60 min).ConclusionWithin patients who underwent ECPR following OHCA, ECPR with TTM could show the potential of improvement in the neurological outcomes, compared to ECPR without TTM.

Cardiopulmonary resuscitation duration and favorable neurological outcome after out-of-hospital cardiac arrest: a nationwide multicenter observational study in Japan (the JAAM-OHCA registry)

ObjectiveWe aimed to assess the association between cardiopulmonary resuscitation (CPR duration) and outcomes after OHCA.MethodsThis secondary analysis of a prospective, multicenter, observational study included adult non-traumatic OHCA patients aged ≥ 18 years between June 2014 and December 2017. CPR duration was defined as the time from professional CPR initiation to the time of return of spontaneous circulation or termination of resuscitation. The primary outcome was 1-month survival, with favorable neurological outcomes defined by cerebral performance category 1 or 2. We performed multivariable logistic regression analysis to investigate the association between CPR duration and favorable neurological outcomes. We also investigated the association between CPR duration and favorable neurological outcomes stratified by case features, including the first documented cardiac rhythm, witnessed status, and presence of bystander CPR.ResultsA total of 23,803 patients were included in this analysis. Multivariable logistic regression analysis demonstrated that the probability of favorable neurological outcomes decreased with CPR duration (i.e., 20.8% [226/1084] in the ≤ 20 min group versus 0.0% [0/708] in the 91–120 min group, P for trend < 0.001). Furthermore, the impact of CPR duration differed depending on the presence of case features; those with shockable, witnessed arrest, and bystander CPR were more likely to achieve favorable neurological outcomes after prolonged CPR duration > 30 min.ConclusionThe probability of favorable neurological outcome rapidly decreased within a few minutes of CPR duration. But, the impact of CPR duration may be influenced by each patient’s clinical feature.

Abstract 8883: Pre-hospital Physician’s Presence and Neurological Outcome Among Patients Performed Pre-hospital Advanced Airway Management: A Nationwide Multicenter Observational Study in Japan (the Japanese Association for Acute Medicine-out-of-Hospital Cardiac Arrest Registry)

Purpose: Using the out-of-hospital cardiac arrest (OHCA) registry in Japan, we evaluated the effectiveness of pre-hospital advanced airway management under physicians’ presence after adjusting in-hospital treatments. Methods: This was a multicenter cohort study. We registered all consecutive OHCA patients in Japan who, from 1 June 2014 through 31 December 2017, were transported to institutions participating in the Japanese Association for Acute Medicine OHCA Registry. We included OHCA patients performed pre-hospital advanced airway management, who were ≥18 years of age with medical etiology and who received resuscitation from emergency medical services (EMS) personnel and medical professionals in hospitals. The primary outcome was one-month favorable neurological survival.We estimated the propensity score by fitting a logistic regression model that was adjusted for several variables before the arrival of EMS personnel and/ or pre-hospital physician. A multivariable logistic regression analysis in propensity score-matched patients was used to adjust confounders including extracorporeal membrane oxygenation, percutaneous coronary intervention, intra-aortic balloon pumping, and targeted temperature management. Results: We analyzed 9,672 patients. Among them, 2.3% (N = 218) had a neurologically favorable outcome. The adjusted odds ratio (AOR) of pre-hospital advanced airway management under physicians’ presence compared with their absence for primary outcome was 0.96 (95% confidence interval (CI): 0.61-1.51). Among first documented non-shockable cardiac rhythm, the AOR was 3.10 (95% CI: 1.05-10.77). Among first documented shockable cardiac rhythm, the AOR was 0.90 (95% CI: 0.53-1.53). Conclusion: In Japan, pre-hospital advanced airway management under physicians’ presence was not associated with one-month favorable neurological survival among patients with first documented shockable cardiac rhythm, whereas it was associated with a neurologically favorable outcome among patients with first documented non-shockable cardiac rhythm.

Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: post hoc analysis of a nationwide multicenter observational study in Japan.

Coagulation disorder is a major cause of death in sepsis patients. Recently, sepsis-induced coagulopathy (SIC) scoring was developed as a new criterion for coagulopathy-associated sepsis. We aimed to evaluate the accuracy of the SIC score for predicting the prognosis of septic shock. We analyzed data from a multicenter observational study conducted from 2011 to 2013. We grouped the participants into those who did and did not use vasopressors, and compared the in-hospital mortality rates of SIC and non-SIC patients. Patients who needed vasopressors were considered to have septic shock. We performed survival analysis adjusted by factors independently associated with mortality. SIC developed in 66.4% of patients who used vasopressors and 42.2% of patients who did not. The in-hospital mortality difference between the SIC and non-SIC groups was statistically significant in those who needed vasopressors (35.8% vs 27.9%, p < 0.01). Cox regression analysis indicated that SIC was significantly correlated with mortality risk in patients who used vasopressors (hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.13–1.70; p < 0.01), but not in those who did not (HR 1.38; 95% CI 0.81–2.34; p = 0.23). In conclusion, the SIC score might be a good diagnostic indicator of fatal coagulopathy among sepsis patients who need vasopressors.

Daytime admission is associated with higher 1-month survival for pediatric out-of-hospital cardiac arrest: Analysis of a nationwide multicenter observational study in Japan.

Hospital characteristics, such as hospital type and admission time, have been reported to be associated with survival in adult out-of-hospital cardiac arrest (OHCA) patients. However, findings regarding the effects of hospital types on pediatric OHCA patients have been limited. The aim of this study was to analyze the relationship between the hospital characteristics and the outcomes of pediatric OHCA patients. This study was a retrospective secondary analysis of the Japanese Association for Acute Medicine-out-of-hospital cardiac arrest registry. The period of this study was from 1 June 2014 to 31 December 2015. We enrolled all pediatric patients (those 0-17 years of age) experiencing OHCA in this study. We enrolled all types of OHCA. The primary outcome of this study was 1-month survival after the onset of cardiac arrest. We analyzed 310 pediatric patients (those 0-17 years of age) with OHCA. In survivors, the rate of witnessed arrest and daytime admission was significantly higher than nonsurvivors (56% vs. 28%, p < 0.001: 49% vs. 31%; p = 0.03, respectively). The multiple logistic regression model showed that daytime admission was related to 1-month survival (odds ratio, OR: 95% confidence interval, CI, 3.64: 1.23-10.80) (p = 0.02). OHCA of presumed cardiac etiology and witnessed OHCA were associated with higher 1-month survival. (OR: 95% CI, 3.92: 1.23-12.47, and 6.25: 1.98-19.74, respectively). Further analyses based on the time of admission showed that there were no significant differences in the proportions of patients with witnessed arrest and who received bystander cardiopulmonary resuscitation and emergency medical service response time by admission time. Pediatric OHCA patients who were admitted during the day had a higher 1-month survival rate after cardiac arrest than patients who were admitted at night.

Transcatheter cryo-ablation of septal accessory pathways, multicenter observational study in Japan

BackgroundAblation using radiofrequency energy has to be carefully performed when the arrhythmia substrate is located in close proximity to the atrioventricular (AV) node due to the risk of inadvertent permanent AV block. The aim of this study was to evaluate the efficacy and safety of catheter-based cryo-therapy for septal accessory pathways (APs). MethodsA total of eleven patients (median = 56.3 years, range 13–74 years) with septal APs underwent cryoablation. Ice-mapping was performed during sinus rhythm and an AV reciprocating tachycardia utilizing the APs as a requisite limb with cooling of the catheter tip temperature to a maximum of -30℃ for less than 45 s. Cryo-ablation was performed for 4 min at a temperature of -80℃ only if ice-mapping abolished the pre-excitation or retrograde conduction over the AP without injury to the AV nodal conduction. ResultsCryo-ablation was acutely successful in all eleven patients. No permanent cryo-related complications or adverse outcomes were reported. During the follow-up (range 14–26 months), no patients experienced any arrhythmia recurrences. ConclusionIce-mapping was a feasible and reliable method to determine the exact location of the APs owing to the possibility of validating the ablation site. Cryo-ablation of APs located near the AV junction is a safe and efficacious technique with a high success rate over the long term. IRB informationEthical Committee of Japan Red Cross Yokohama City Bay Hospital #2018−19.

FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan

BackgroundData on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study—a nationwide, multicenter, observational study—FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice. MethodsWe performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings. ResultsOf the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients’ characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2–19.1) months and 6 cycles (range, 1–13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2–13.3), 4.1 (95% CI, 2.6–5.5) months, and 30%, respectively. ConclusionOur findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.

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

AimHeat‐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.MethodsWe 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.ResultsA 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.ConclusionsIn 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.

Maximal sterile barrier precautions independently contribute to decreased central line–associated bloodstream infection in very low birth weight infants: A prospective multicenter observational study

The use of peripherally inserted central catheters (PICCs) in neonates differs among various institutions and countries because there are no random controlled trials or large observational studies regarding maximal sterile barrier (MSB) precautions in neonatal intensive care units. Our objective was to investigate the association of MSB implementation with central line-associated bloodstream infection (CLABSI) in very low birth weight infants. This was a prospective multicenter observational study in Japan of infants with birth weight less than 1501 grams and in whom a PICC was placed for the first time between October 2014 and March 2017. Risk factors for CLABSI, both related and unrelated to MSB, were assessed by the mixed-effects Cox proportional hazards model, with the neonatal center variable as the random effect. In total, 33,713 catheter-days among 2383 infants were included. We observed 70 cases of CLABSI. MSB precautions were implemented in 13.9% of insertions and were associated with a lower CLABSI risk (adjusted hazard ratio, 0.20; 95% confidence interval, 0.05-0.84). We found that MSB implementation during PICC insertion in infants with birth weight less than 1501 grams independently contributed to a decrease in CLABSI risk.