Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-10-07DOI: 10.1097/CCM.0000000000006780
Jehan Alladina, Amy S Labar, Georgios D Kitsios
{"title":"The authors reply.","authors":"Jehan Alladina, Amy S Labar, Georgios D Kitsios","doi":"10.1097/CCM.0000000000006780","DOIUrl":"https://doi.org/10.1097/CCM.0000000000006780","url":null,"abstract":"","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":"53 10","pages":"e2118-e2119"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-10-07DOI: 10.1097/CCM.0000000000006758
Alexander D Miller, Pooja A Kumar, Amira M Mohammed
{"title":"Confounders and Risks of Bias Should Block Strong Conclusions on Propranolol As a Sedative.","authors":"Alexander D Miller, Pooja A Kumar, Amira M Mohammed","doi":"10.1097/CCM.0000000000006758","DOIUrl":"https://doi.org/10.1097/CCM.0000000000006758","url":null,"abstract":"","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":"53 10","pages":"e2108-e2109"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-10-07DOI: 10.1097/CCM.0000000000006765
Tsai Ling Ting, Shiuan-Chih Chen
{"title":"Reframing Soluble Suppression of Tumorigenicity 2 As a Vascular Signal in Acute Respiratory Failure.","authors":"Tsai Ling Ting, Shiuan-Chih Chen","doi":"10.1097/CCM.0000000000006765","DOIUrl":"https://doi.org/10.1097/CCM.0000000000006765","url":null,"abstract":"","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":"53 10","pages":"e2116-e2117"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-08-05DOI: 10.1097/CCM.0000000000006809
Nozomi Takahashi, Kyle R Campbell, Taka-Aki Nakada, Keith R Walley
{"title":"Decreased Clearance of Low-Density Lipoprotein Cholesterol is Causally Associated With Increased Mortality of Septic Shock.","authors":"Nozomi Takahashi, Kyle R Campbell, Taka-Aki Nakada, Keith R Walley","doi":"10.1097/CCM.0000000000006809","DOIUrl":"10.1097/CCM.0000000000006809","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether low-density lipoprotein cholesterol (LDL-C) levels, set by the balance of clearance and production, causally contribute to septic shock 28-day mortality.</p><p><strong>Design: </strong>We measured LDL-C levels and genotypes in patients with septic shock. Using Genotyping and Genome-Wide Association Study summary statistics from over 150,000 Japanese participants, we genetically predicted pre-infection LDL-C levels. Two-sample Mendelian randomization was used to assess the causal relationship between predicted pre-infection LDL-C levels and 28-day mortality. We analyzed PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) genotypes to determine if LDL-C clearance or production was the underlying mechanism.</p><p><strong>Setting: </strong>Multicenter ICUs in Japan.</p><p><strong>Patients: </strong>Genotyped septic shock patients ( n = 614).</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>Predicted pre-infection LDL-C levels were much higher than directly measured LDL-C levels at the onset of septic shock (141 mg/dL vs. 40 mg/dL, p < 0.001). Two-sample Mendelian randomization revealed that high predicted pre-infection LDL-C levels were causally associated with increased septic shock 28-day mortality (hazard ratio, 2.78; p = 0.039). PCSK9 genetic variants that increase LDL-C clearance via the LDL receptor (genetically proxied PCSK9 inhibitor treatment) were associated with decreased mortality ( p = 0.003) while HMGCR genetic variants that decrease LDL-C production (genetically proxied statin treatment) were not associated with decreased septic shock mortality (indeed the opposite effect was observed, p = 0.039). The two main genetic variants driving the association between high predicted pre-infection LDL-C levels and increased mortality were in apolipoprotein genes ( ApoB100 -rs13306206 and ApoE -rs7412), apolipoproteins involved in LDL-C binding to the LDL receptor.</p><p><strong>Conclusions: </strong>Low LDL-C clearance explains the causal association between high genetically predicted pre-infection LDL-C levels and increased septic shock mortality. PCSK9 , ApoB , and ApoE variants were identified as causal, all related to the LDL receptor or its interaction with LDL-C. Enhancing LDL receptor-mediated clearance of pathogen lipid toxins may improve septic shock outcomes.</p>","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":" ","pages":"e2033-e2042"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Impact of Hospital-Level Median Door-to-Extracorporeal Cardiopulmonary Resuscitation Time on the Prognosis of Patients With Refractory Out-of-Hospital Cardiac Arrest.","authors":"Daisuke Kasugai, Yohei Okada, Yuka Mizutani, Junta Honda, Toru Kondo, Shingo Kazama, Takanori Yamamoto","doi":"10.1097/CCM.0000000000006808","DOIUrl":"10.1097/CCM.0000000000006808","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the impact of hospital-level median door-to-extracorporeal cardiopulmonary resuscitation (ECPR) time on survival and neurologic outcomes in patients with out-of-hospital cardiac arrest (OHCA) requiring ECPR.</p><p><strong>Design: </strong>Secondary analysis of the Japanese Association for Acute Medicine OHCA registry, a nationwide Japanese database of OHCA patients.</p><p><strong>Setting: </strong>Fifty-three hospitals across Japan.</p><p><strong>Patients: </strong>Adult patients who underwent ECPR between 2014 and 2021 were included. Hospitals were categorized into \"rapid\" or \"delayed\" groups based on their median door-to-ECPR times.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>The primary outcome was 30-day survival. Secondary outcomes included 30-day and 90-day survival with favorable neurologic outcomes. Propensity score weighting was applied to adjust for confounders. In total, 2136 patients treated at 53 hospitals were included. Hospitals with shorter median door-to-ECPR times had higher 30-day survival rates (odds ratio [OR], 1.36; 95% CI, 1.21-1.53). Neurologic outcomes were better in the rapid hospital group at both 30 days (OR, 1.47; 95% CI, 1.24-1.73) and 90 days (OR, 1.47; 95% CI, 1.25-1.73) follow-ups.</p><p><strong>Conclusions: </strong>Hospital-level median door-to-ECPR time is a crucial predictor of survival and neurologic outcomes in OHCA patients requiring ECPR. Shorter door-to-ECPR times should be considered a key quality metric for ECPR processes.</p>","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":" ","pages":"e2025-e2032"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-10-07DOI: 10.1097/CCM.0000000000006759
Shiuan-Chih Chen, Chun-Chieh Chen
{"title":"Enhancing Sepsis Outcomes: Prioritizing Local Over Regional Solutions.","authors":"Shiuan-Chih Chen, Chun-Chieh Chen","doi":"10.1097/CCM.0000000000006759","DOIUrl":"https://doi.org/10.1097/CCM.0000000000006759","url":null,"abstract":"","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":"53 10","pages":"e2112-e2113"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-07-10DOI: 10.1097/CCM.0000000000006773
Ashwin Subramaniam, Ryan Ruiyang Ling, Ryo Ueno, Emma J Ridley, Sandra Peake, David Pilcher
{"title":"The Varying Impact of Frailty With Increasing Body Mass Index on Survival Up To 3 Years After ICU Admission: A Retrospective Registry-Based Study.","authors":"Ashwin Subramaniam, Ryan Ruiyang Ling, Ryo Ueno, Emma J Ridley, Sandra Peake, David Pilcher","doi":"10.1097/CCM.0000000000006773","DOIUrl":"10.1097/CCM.0000000000006773","url":null,"abstract":"<p><strong>Objectives: </strong>Frailty is associated with poorer outcomes in critical illness, but it is unclear if this relationship is consistent across different body mass index (BMI) levels.</p><p><strong>Design: </strong>A retrospective multicentric registry-based observational study using the Australia New Zealand Intensive Care Society Adult Patient Database.</p><p><strong>Setting: </strong>Criticallly ill patients admitted to 1170 ICUs between January 1, 2018, and March 31, 2022.</p><p><strong>Patients: </strong>All adults aged 16 years and older with a documented Clinical Frailty Scale (CFS) and BMI.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>The primary outcome was survival up to 3 years following ICU admission. We used Cox proportional hazards models, linear and nonlinear regression models to investigate the association between frailty (defined as CFS, 5-8), in reference to those without frailty, and the mortality risk up to 3 years, and whether this association varied with BMI, after adjusting for key confounders. We included 282,586 patients, of whom 49,070 (17.4%) were frail. Frailty was most prevalent in patients with BMI less than 18.5 kg/m 2 (34.8%), became less frequent as BMI increased, and more prevalent again in BMI greater than or equal to 40 kg/m² (18.8%). Overall, frailty was associated with lower 3-year survival (47.5% vs. 82.2%) and increased mortality (hazard ratio, 1.67; 95% CI, 1.62-1.73). However, the association between frailty and survival was not uniform. The concomitant presence of frailty was associated with progressively larger increases in mortality as BMI categories increased beyond the reference group of 18.5-24.9 kg/m 2 . There was no effect of BMI on the relationship between frailty and mortality for BMI less than 18.5 kg/m 2 . This relationship was consistent in multiple sensitivity analyses.</p><p><strong>Conclusions: </strong>The association between frailty and outcomes after critical illness differed across BMI categories with a larger increase in the risk of mortality noted at higher BMI levels. Our findings may have implications for managing concurrent obesity, frailty, and critical illness.</p>","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":" ","pages":"e1893-e1905"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Critical Care MedicinePub Date : 2025-10-01Epub Date: 2025-08-11DOI: 10.1097/CCM.0000000000006832
Luciano Cesar Pontes Azevedo
{"title":"Surviving Sepsis: Don't Break the Chain.","authors":"Luciano Cesar Pontes Azevedo","doi":"10.1097/CCM.0000000000006832","DOIUrl":"10.1097/CCM.0000000000006832","url":null,"abstract":"","PeriodicalId":10765,"journal":{"name":"Critical Care Medicine","volume":" ","pages":"e2086-e2088"},"PeriodicalIF":6.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}