12 research outputs found
Pretreatment glasgow prognostic score predicts survival among patients administered first-line atezolizumab plus carboplatin and etoposide for small cell lung cancer
BackgroundThere are no established predictive biomarkers for the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with small-cell lung cancer (SCLC). Therefore, the current study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC.MethodsWe reviewed data from 84 patients who received first-line atezolizumab plus carboplatin and etoposide therapy for SCLC at nine Japanese institutions between August 2019 and May 2021. Further, we evaluated the prognostic value of the GPS, NLR, and BMI. The KaplanâMeier and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). Moreover, the GPS, NLR, and BMI consisted of C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively.ResultsThe response rate was 72.6% (95% confidence interval: 63.0â82.1%). The median PFS and OS from the initiation of treatment were 5.4 (95% CI: 4.9â5.9) months and 15.4 (95% CI: 11.4â16.8) months, respectively. The GPS independently predicted the effectiveness of first-line atezolizumab plus carboplatin and etoposide treatment, as a favorable GPS (GPS 0â1) was correlated with significantly better PFS and OS rates compared to a poor GPS (GPS 2) (PFS: 5.8 vs. 3.8 months, p = 0.0005; OS: 16.5 vs. 8.4 months, p<0.0001).ConclusionsThis is the first analysis to evaluate the association between the GPS, NLR, and BMI and the treatment effectiveness of survival among patients receiving first-line atezolizumab plus carboplatin and etoposide therapy for SCLC. Among patients receiving this treatment for SCLC, GPS was significantly associated with the PFS and OS rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
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ćăźćäșșć·źăćœ±éżăă--. äșŹéœć€§ćŠăăŹăčăȘăȘăŒăč. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection
DOCK2 is involved in the host genetics and biology of severe COVID-19
ăăłăăć¶ć§ăżăčăŻăă©ăŒăčăCOVID-19çŸæŁæćæ§éșäŒćDOCK2ăźéçćæ©ćșăè§Łæ --ăąăžăąæ性ăźăă€ăȘăŹăăžăăȘăŒă§COVID-19ăźæČ»çæšçăçșèŠ--. äșŹéœć€§ćŠăăŹăčăȘăȘăŒăč. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (nâ=â61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target
Using the neutrophilâtoâlymphocyte ratio to predict the outcome of individuals with nonsquamous nonâsmall cell lung cancer receiving pembrolizumab plus platinum and pemetrexed
Abstract Background Factors predicting the response to pembrolizumab plus platinum and pemetrexed combination therapy (PembâPltâPEM) in nonsquamous nonâsmall cell lung cancer (nonâsq NSCLC) are unclear. We investigated the Glasgow Prognostic (GP) score, neutrophilâtoâlymphocyte ratio (NLR), and body mass index (BMI) as predictors of response to initial treatment with combination therapy in individuals with advanced nonâsq NSCLC. Methods We retrospectively reviewed 236 patients who received initial treatment with combination therapy for nonâsq NSCLC at 13 institutions between December 2018 and December 2020. The usefulness of the GP score, NLR, and BMI as prognostic indicators was assessed. Cox proportional hazard models and the KaplanâMeier method were used to compare progressionâfree survival (PFS) and overall survival (OS). Results The response rate was 51.2% (95% CI: 44.9â57.5%). The median PFS and OS after beginning PembâPltâPEM were 8.8 (95% CI: 7.0â11.9) months and 23.6 (95% CI: 18.7â28.6) months, respectively. The NLR independently predicted the efficacy of PembâPltâPEMâthe PFS and OS were more prolonged in individuals with NLRâ<5 than in those with NLR â„5 (PFS: 12.8 vs. 5.3âmonths, pâ=â0.0002; OS: 29.4 vs. 12.0âmonths, pâ<â0.0001). BMI predicted the treatment responseâindividuals with BMI â„22.0âkg/m2 had longer OS than did those with BMIâ<â22.0âkg/m2 (OS: 28.4 vs. 18.4âmonths, pâ=â0.0086). Conclusions The NLR significantly predicted PFS and OS, whereas BMI predicted OS, in individuals who initially received PembâPltâPEM for nonâsq NSCLC. These factors might be prognosis predictors in nonâsq NSCLC
Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 (J-ReCIP 2023)
application/pdfProviding standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the âEvidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unitâ to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions.Other authors: Ryo Abe, Takahito Iitsuka, Hiroyasu Inoue, Yuki Uchiyama, Satoshi Endo, Kazuki Okura, Kohei Ota, Takahisa Otsuka, Daisuke Okada, Kengo Obata, Yukiko Katayama, Naoki Kaneda, Mio Kitayama, Shunsuke Kina, Ryuichi Kusaba, Masanari Kuwabara, Naoki Sasanuma, Masahiro Takahashi, Chihiro Takayama, Naonori Tashiro, Junko Tatsuno, Takahiko Tamura, Mitsuhiro Tamoto, Asuka Tsuchiya, Yusuke Tsutsumi, Tadashi Nagato, Chihiro Narita, Tomohiro Nawa, Tadayoshi Nonoyama, Masatoshi Hanada, Kotaro Hirakawa, Akiko Makino, Hirotaka Masaki, Ryosuke Matsuki, Shinya Matsushima, Wataru Matsuda, Saori Miyagishima, Masaru Moromizato, Naoya Yanagi, Kota Yamauchi, Yuhei Yamashita, Natsuhiro Yamamoto, Keibun Liu, Yuki Wakabayashi, Shinichi Watanabe, Hiroshi Yonekura, Nobuto Nakanishi, Tetsuya Takahashi, Osamu Nishid
Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo
International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100â105âMâ, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass âŒ150âMâ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200âMâ and effective aligned spin 0.8 at 0.056 Gpcâ3 yrâ1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpcâ3 yrâ1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]â Deceased, August 2020
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