Association between initial body temperature on hospital arrival and neurological outcome among patients with out-of-hospital cardiac arrest: a multicenter cohort study (the CRITICAL study in Osaka, Japan)

[Background] The association between spontaneous initial body temperature on hospital arrival and neurological outcomes has not been sufficiently studied in patients after out-of-hospital cardiac arrest (OHCA). [Methods] From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all patients with OHCA of medical origin aged > 18 years for whom resuscitation was attempted and who were transported to participating hospitals between 2012 and 2019. We excluded patients who were not witnessed by bystanders and treated by a doctor car or helicopter, which is a car/helicopter with a physician. The patients were categorized into three groups according to their temperature on hospital arrival: ≤35.9 °C, 36.0–36.9 °C (normothermia), and ≥ 37.0 °C. The primary outcome was 1-month survival, with a cerebral performance category of 1 or 2. Multivariable logistic regression analyses were performed to evaluate the association between temperature and outcomes (normothermia was used as the reference). We also assessed this association using cubic spline regression analysis. [Results] Of the 18, 379 patients in our database, 5014 witnessed adult OHCA patients of medical origin from 16 hospitals were included. When analyzing 3318 patients, OHCA patients with an initial body temperature of ≥37.0 °C upon hospital arrival were associated with decreased favorable neurological outcomes (6.6% [19/286] odds ratio, 0.51; 95% confidence interval, 0.27–0.95) compared to patients with normothermia (16.4% [180/1100]), whereas those with an initial body temperature of ≤35.9 °C were not associated with decreased favorable neurological outcomes (11.1% [214/1932]; odds ratio, 0.78; 95% confidence interval, 0.56–1.07). The cubic regression splines demonstrated that a higher body temperature on arrival was associated with decreased favorable neurological outcomes, and a lower body temperature was not associated with decreased favorable neurological outcomes. [Conclusions] In adult patients with OHCA of medical origin, a higher body temperature on arrival was associated with decreased favorable neurologic outcomes

Clustering out-of-hospital cardiac arrest patients with non-shockable rhythm by machine learning latent class analysis

[Aim] We aimed to identify subphenotypes among patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm by applying machine learning latent class analysis and examining the associations between subphenotypes and neurological outcomes. [Methods] This study was a retrospective analysis within a multi-institutional prospective observational cohort study of OHCA patients in Osaka, Japan (the CRITICAL study). The data of adult OHCA patients with medical causes and initial non-shockable rhythm presenting with OHCA between 2012 and 2016 were included in machine learning latent class analysis models, which identified subphenotypes, and patients who presented in 2017 were included in a dataset validating the subphenotypes. We investigated associations between subphenotypes and 30-day neurological outcomes. [Results] Among the 12, 594 patients in the CRITICAL study database, 4, 849 were included in the dataset used to classify subphenotypes (median age: 75 years, 60.2% male), and 1, 465 were included in the validation dataset (median age: 76 years, 59.0% male). Latent class analysis identified four subphenotypes. Odds ratios and 95% confidence intervals for a favorable 30-day neurological outcome among patients with these subphenotypes, using group 4 for comparison, were as follows; group 1, 0.01 (0.001–0.046); group 2, 0.097 (0.051–0.171); and group 3, 0.175 (0.073–0.358). Associations between subphenotypes and 30-day neurological outcomes were validated using the validation dataset. [Conclusion] We identified four subphenotypes of OHCA patients with initial non-shockable rhythm. These patient subgroups presented with different characteristics associated with 30-day survival and neurological outcomes

Association between serum lactate level during cardiopulmonary resuscitation and survival in adult out-of-hospital cardiac arrest: a multicenter cohort study

We aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). From the database of a multicenter registry on OHCA patients, we included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (≤ 10.6 mEq/L), Q2 (10.6–14.1 mEq/L), Q3 (14.1–18.0 mEq/L), and Q4 (> 18.0 mEq/L). The primary outcome was 1-month survival. Among 5226 eligible patients, the Q1 group had the highest 1-month survival (5.6% [74/1311]), followed by Q2 (3.6% [47/1316]), Q3 (1.7% [22/1292]), and Q4 (1.0% [13/1307]) groups. In the multivariable logistic regression analysis, the adjusted odds ratio of Q4 compared with Q1 for 1-month survival was 0.24 (95% CI 0.13–0.46). 1-month survival decreased in a stepwise manner as the quartiles increased (p for trend < 0.001). In subgroup analysis, there was an interaction between initial rhythm and survival (p for interaction < 0.001); 1-month survival of patients with a non-shockable rhythm decreased when the lactate levels increased (p for trend < 0.001), but not in patients with a shockable rhythm (p for trend = 0.72). In conclusion, high serum lactate level during CPR was associated with poor 1-month survival in OHCA patients, especially in patients with non-shockable rhythm

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan

院外心停止患者における膜型人工肺を活用した蘇生 --膜型人工肺を活用した蘇生と生存率向上との関連--. 京都大学プレスリリース. 2023-11-21.BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57, 754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR

GWAS of bipolar disorder

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10−9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best=5.8 × 10−10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best=1.9 × 10−9), TRANK1 (P best=2.1 × 10−9) and ODZ4 (P best=3.3 × 10−9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for ‘within Japanese comparisons’, Pbest~10−29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for ‘trans-European-Japanese comparison,’ Pbest~10−13, R2~0.27%). This ‘trans population’ effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD ‘risk’ effect are shared between Japanese and European populations

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Interaction of clathrin with liposomes: pH-dependent fusion of phospholipid membranes induced by clathrin

AbstractClathrin, dissociated from coated vesicles of bovine brain and purified by gel chromatography, was found to interact with the lipid bilayer as shown by the spontaneous release of encapsulated fluorescent dye in liposome. Clathrin-induced dye release was enhanced at acidic pH in phosphatidylserine-containing vesicles. A strong correlation between dye release and fusion of liposomes was observed. In general, when there was a fast release of encapsulated dye induced by clathrin, a pH-dependent, clathrin-induced fusion was observed. Clathrin did not induce either dye release or fusion of egg phosphatidylcholine liposomes. The self-association of clathrin at low pH diminished the fusogenic activity. Fusion induced by clathrin at low pH c̀ould be stopped at pH above 5.0 and resumed by lowering the pH below 5.0. This suggests that the interaction of clathrin with phospholipid membranes can be regulated by pH