Critical Care最新文献

{"title":"Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness","authors":"Anna Kleyman, Walter Pisciotta, Charlotte Gaupp, Waqas Khaliq, Daniel Hofmaenner, David Brealey, Bernardo Bollen Pinto, Davide Tommaso Andreis, Mark Gerard Waugh, Miranda J. Melis, Muska Miller, Klea Mehmetaj, Michael Bauer, Adrian Press, Mervyn Singer","doi":"10.1186/s13054-025-05638-7","DOIUrl":"https://doi.org/10.1186/s13054-025-05638-7","url":null,"abstract":"Sepsis-induced cardiomyopathy (SIM) is characterized by myocardial dysfunction, diminished catecholamine responsiveness and worse outcomes. Hypocholesterolemia is also a well-recognized prognosticator of poor outcomes in sepsis. In vitro physiology/pharmacology studies indicate that low cholesterol levels within the cardiomyocyte membrane regulate ß-adrenergic receptor activity. We therefore hypothesized that cardiomyocyte membrane cholesterol levels are reduced in sepsis and this contributes to SIM. Cardiovascular biomarkers and plasma lipid profiles measured sequentially (6, 24 and 72 h) in a fluid-resuscitated rat model of fecal peritonitis were compared against those measured in 27 septic patients on Days 1–3 of ICU admission. In separate studies, rat hearts were excised at the same time points for measurement of cardiomyocyte membrane cholesterol and downstream adrenergic signaling. In a final study, the impact of a 15-hour infusion of cholesterol, either given as HDL-cholesterol or liposomal cholesterol, commencing at 6 h post-sepsis induction, on dobutamine responsiveness and cardiomyocyte membrane cholesterol levels was assessed. The magnitude of fall in stroke volume, rise in heart rate, plasma troponin and BNP, and fall in plasma HDL-cholesterol on ICU Day 1 in septic patients and at 6 h in the rat model all prognosticated for poor outcomes. In parallel, cardiomyocyte membrane cholesterol fell in the rats, more so in poor prognosis animals, with a blunted inotropic response to dobutamine, indicative of SIM. Cholesterol administration restored cardiomyocyte membrane cholesterol, dobutamine responsiveness and adrenergic signaling. In a long-term rat model of sepsis, that parallels changes seen in septic patients, cardiomyocyte membrane cholesterol fell with associated decreases in catecholamine responsiveness. These features could be restored by cholesterol infusion, suggesting potential utility as a therapeutic.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"2 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133655","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":"Ultrasound-measured brachial artery reactive hyperemia in critically ill patients: an observational study","authors":"Casey R. Storms, Tristan Bice, Jimmy Zhang, Elizabeth Levy, Tetsuro Maeda, Neha Kumar, Lijo C. Illipparambil, Amy M. K. Rovitelli, Heather Clark, Orren Wexler, Michelle Malnoske, Christina Dony, Alex Z. Fe, Rebecca Shultz, Anthony P. Pietropaoli","doi":"10.1186/s13054-025-05646-7","DOIUrl":"https://doi.org/10.1186/s13054-025-05646-7","url":null,"abstract":"Ultrasound-measured brachial artery reactive hyperemia (RH) is independently predictive of hospital mortality in critically ill patients with sepsis. Its association with mortality is uncertain in critically ill patients in general. This was a combined case-control and prospective cohort study. Ultrasound was used to measure brachial artery reactive hyperemia in 150 critically ill patients at a single academic medical center and in 44 control subjects without acute illness. Measurements were compared in cases versus controls, septic vs. non-septic critically ill patients, and hospital survivors vs. non-survivors. Follow-up measurements were obtained 3–5 days later in a sub-sample of patients. RH was calculated as the percent change in pre- vs. post-ischemic brachial artery velocity-time integral measured by Doppler ultrasound. RH was impaired in critically ill compared to control subjects (194 [179–210] vs. 369 [314–433]%, p < 0.001; results expressed as mean [95% confidence interval]) but similar in septic compared to non-septic patients (196 [177–217] vs. 199 [170–233], p = 0.88). RH was significantly lower in hospital non-survivors compared to survivors (144 [120–173] vs. 204 [187–222], p = 0.003). Multivariable analysis showed that the difference between survivors and non-survivors was not confounded by age or comorbidities (odds ratio for hospital death = 0.26 per log unit rise in RH, 95% confidence interval = 0.08–0.83, p = 0.02). The magnitude of RH improved over 3–5 days in hospital survivors (n = 63, 204 [180–232] vs. 239 [208–275], p = 0.02), but did not change in non-survivors (n = 11, 133 [107–165] vs. 128 [75–220]. Reactive hyperemia of the brachial artery is impaired in undifferentiated critically ill patients, lower in non-survivors compared to survivors, and independently associated with hospital mortality. Brachial artery reactive hyperemia improves significantly over time in survivors but not in non-survivors. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"1 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133656","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":"Correction: Cost-effectiveness of rapid, ICU-based, syndromic PCR in hospital-acquired pneumonia: analysis of the INHALE WP3 multi-centre RCT","authors":"Adam P. Wagner, Virve I. Enne, Vanya Gant, Susan Stirling, Julie A. Barber, David M. Livermore, David A. Turner","doi":"10.1186/s13054-025-05645-8","DOIUrl":"https://doi.org/10.1186/s13054-025-05645-8","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Critical Care (2025) 29: 352&lt;/b&gt;&lt;/p&gt;&lt;p&gt; &lt;b&gt;https://doi.org/10.1186/s13054-025-05428-1&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Following publication of the original article [1], the authors identified an error in the author name of Virve I. Enne.&lt;/p&gt;&lt;p&gt;The incorrect author name is: Virvel Enne.&lt;/p&gt;&lt;p&gt;The correct author name is: Virve I. Enne.&lt;/p&gt;&lt;p&gt;The author group has been updated above and the original article [1] has been corrected.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Wagner AP, Enne VI, Gant V, Stirling S, Barber JA, Livermore DM, Turner DA, and the INHALE WP3 study group. Cost-effectiveness of rapid, ICU-based, syndromic PCR in hospital-acquired pneumonia: analysis of the inhale WP3 multi-centre RCT. Crit Care. 2025;29:352. https://doi.org/10.1186/s13054-025-05428-1&lt;/p&gt;&lt;p&gt;Article PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK&lt;/p&gt;&lt;p&gt;Adam P. Wagner, David M. Livermore &amp; David A. Turner&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Applied Research Collaboration East of England (NIHR ARC EoE, National Institute for Health and Care Research (NIHR), Cambridgeshire and Peterborough NHS Foundation Trust, Norwich, UK&lt;/p&gt;&lt;p&gt;Adam P. Wagner&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Centre for Clinical Microbiology, University College London, London, UK&lt;/p&gt;&lt;p&gt;Virve I. Enne&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Norwich Clinical Trials Unit, University of East Anglia, London, UK&lt;/p&gt;&lt;p&gt;Susan Stirling, Antony Colles, Kerry Dresser, Juliet High, Justin O’Grady, Charlotte Russell &amp; Ann Marie Swart&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Statistical Science, University College London, London, UK&lt;/p&gt;&lt;p&gt;Julie A. Barber, Naseem Ahmed, Zaneeta Dhesi, Robert Horne, Nigel Klein, Federico Ricciardi, Laura Shallcross &amp; Sarah-Jane Stewart&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Microbiology, University College London Hospitals, London, UK&lt;/p&gt;&lt;p&gt;Vanya Gant, Georgia Bercades, Ingrid Hass &amp; Deborah Smyth&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Adam P. Wagner&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;Search author on:&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Virve I. Enne&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;Search author on:&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Vanya Gant&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;Search author on:&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Susan Stirling&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;Search author on:&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Julie A. Barber&lt;/span&gt;View author publications&lt;p&gt;&lt;span&gt;Search author on:&lt;/span&gt;&lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"11 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068094","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":"Female first and senior authorship in high-impact critical care journals 2005–2024","authors":"Nora Bruns, Pia Brensing, Sandra Greve, Sandra Horsch, Ursula Felderhoff-Müser, Christian Dohna-Schwake, Simone Schwarz","doi":"10.1186/s13054-025-05649-4","DOIUrl":"https://doi.org/10.1186/s13054-025-05649-4","url":null,"abstract":"Gender disparities persist in medical research. This study assessed gender representation trends in first and senior authorships in the five highest-ranked critical care journals (by impact factor) over a 20-year period. We analyzed author gender distribution from 2005 to 2024. Author gender was determined using NamSor for web-based gender prediction. We assessed trends in female first, senior, and combined first and senior authorships by calculating percentages, and annual changes by linear regression for multiple and single author publications. Among 42,970 articles, 34,743 had multiple authors and 8,227 had a single author. Despite progress over the past two decades, women remain underrepresented in critical care research leadership with 7.8% of publications having both female first and senior authors, compared to 56.7% with both positions held by men. Single authors were female in 23.6%. Linear regression showed increasing female authorships between − 0.1 and + 0.6% points per year depending on the journal, author position, and time period. Sensitivity analyses including only publications with more than 80% probability of correct gender classification yielded congruent results. Despite small but constant growth rates of female representation as first or senior authors in high impact critical care journals over the past 20 years, women remain clearly underrepresented. Given the current rate of change, it will take decades to achieve gender parity. The observed gender disparity in authorships likely reflects underlying gender inequities in critical care career trajectories, highlighting the need for institutional changes.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"112 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017572","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":"Plasma proteomics identifies molecular subtypes in sepsis","authors":"Thilo Bracht, Kerstin Kappler, Malte Bayer, Franziska Grell, Karin Schork, Lars Palmowski, Björn Koos, Tim Rahmel, Dominik Ziehe, Matthias Unterberg, Lars Bergmann, Katharina Rump, Martina Broecker-Preuss, Ulrich Limper, Dietrich Henzler, Stefan Felix Ehrentraut, Thilo von Groote, Alexander Zarbock, Stephanie Pfaender, Nina Babel, Katrin Marcus-Alic, Martin Eisenacher, Michael Adamzik, Barbara Sitek, Hartmuth Nowak","doi":"10.1186/s13054-025-05639-6","DOIUrl":"https://doi.org/10.1186/s13054-025-05639-6","url":null,"abstract":"The heterogeneity of sepsis represents a significant challenge to the development of personalized sepsis therapies. Sepsis subtyping has therefore emerged as an important approach to this problem, but its impact on clinical practice was limited due to insufficient molecular insights. Modern proteomics techniques allow the identification of subtypes and provide molecular and mechanistical insights. In this study, we analyzed a prospective multi-center sepsis cohort using plasma proteomics to describe and characterize sepsis plasma proteome subtypes. Plasma samples were collected from 333 patients at days 1 and 4 of sepsis and analyzed using liquid chromatography coupled to tandem mass spectrometry. Plasma proteome subtypes were identified using K-means clustering and characterized based on clinical routine data, cytokine measurements, and proteomics data. A random forest machine learning classifier was generated to showcase future assignment of patients to subtypes. Four subtypes with different sepsis severity were identified. Cluster 0 represented the most severe form of sepsis, with 100% mortality. Cluster 1, 2 and 3 showed a gradual decrease of the median SOFA score, as reflected by clinical data and cytokine measurements. At the proteome level, the subtypes were characterized by distinct molecular features. We observed an alternating immune response, with cluster 1 showing prominent activation of the adaptive immune system, as indicated by elevated levels immunoglobulin (Ig) levels, which were verified using orthogonal measurements. Cluster 2 was characterized by acute inflammation and the lowest Ig levels. Cluster 3 represented the sepsis proteome baseline of the investigated cohort. We generated an ML classifier and optimized it for the minimum number of proteins that could realistically be implemented into routine diagnostics. The model, which was based on 10 proteins and Ig quantities, allowed the assignment of patients to clusters 1, 2 and 3 with high confidence. The identified plasma proteome subtypes provide insights into the immune response and disease mechanisms and allow conclusions on appropriate therapeutic measures, enabling predictive enrichment in clinical trials. Thus, they represent a step forward in the development of targeted therapies and personalized medicine for sepsis.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"27 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928040","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":"Impact of ECPR initiation time and age on survival in out-of-hospital cardiac arrest patients: a nationwide observational study","authors":"Dongju Kim, Hyeji Lee, Hanna Park, Youn-Jung Kim, Won Young Kim","doi":"10.1186/s13054-025-05635-w","DOIUrl":"https://doi.org/10.1186/s13054-025-05635-w","url":null,"abstract":"&lt;p&gt;Extracorporeal cardiopulmonary resuscitation (ECPR) is a critical rescue strategy for refractory out-of-hospital cardiac arrest (OHCA), but its success is highly dependent on patient selection and timely initiation [1]. Older age and prolonged extracorporeal membrane oxygenation (ECMO) initiation time are known to negatively affect outcomes [2, 3]. Guidelines recommend initiating ECMO within 60 min of cardiac arrest, and experts advocate for early consideration of ECPR [1]. Despite these recommendations, the upper time limit for ECPR effectiveness remains uncertain, particularly in older OHCA patients. This study aims to define the upper limit for ECPR initiation time and investigate how advanced age influences this threshold.&lt;/p&gt;&lt;p&gt;We conducted a retrospective cohort study using data from the nationwide Korean OHCA database from 2016 to 2021. The database systematically records consecutive adult OHCA cases attended by emergency medical services (EMS) following standardized Utstein guidelines. The study included 483 adult (≥ 18 years) patients who received ECPR for non-traumatic OHCA. ECPR initiation time was defined as the time from hospital arrival to ECMO pump-on time. The primary outcome was a survival-to-discharge rate. The Institutional Review Board of Asan Medical Center granted ethical approval with a waiver for informed consent (IRB No. 2023–0438).&lt;/p&gt;&lt;p&gt;Patients were stratified into two groups: elderly (age &gt; 65 years, n = 104) and non-elderly (age ≤ 65 years, n = 379). We used multivariable logistic regression to assess the effects of age, ECPR initiation time, and their interaction on survival. Variables included in the multivariable model were selected based on clinical relevance and variance inflation factor &lt; 10. Dynamic and cumulative survival proportions were used to identify time thresholds [4].&lt;/p&gt;&lt;p&gt;Age distribution for elderly (&gt; 65 years) and non-elderly (≤ 65 years) patients is presented in Supplementary Fig. 1. The median (interquartile range) age was 70.0 (68.0–74.0) years in the elderly group and 52.0 (44.0–60.0) years in the non-elderly group.&lt;/p&gt;&lt;p&gt;The overall survival-to-discharge rate was 18.2% (88 of 483 patients). After adjusting for confounding variables, both increasing age (adjusted OR: 0.97, 95% CI: 0.95–0.99, &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and longer ECPR initiation time (adjusted OR: 0.97, 95% CI: 0.95–0.98, &lt;i&gt;P&lt;/i&gt; = 0.003) were independently associated with decreased survival. A significant interaction was found between age and initiation time (adjusted OR: 0.999, 95% CI: 0.998–1.000, &lt;i&gt;P&lt;/i&gt; = 0.021), indicating that treatment delays have a more pronounced negative effect on older patients (Supplemental eTable1).&lt;/p&gt;&lt;p&gt;Age-stratified analysis revealed significantly different time windows for effective treatment (Fig. 1). In elderly patients, the probability of survival dropped below 10% when ECPR initiation was delayed beyond 21 (0–33 min) minutes, and it fell below 1% after 40 min (33–42 min). In cont","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"66 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930699","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":"Pharmacokinetic/Pharmacodynamic of ceftolozane/tazobactam in critically ill patients receiving extracorporeal membrane oxygenation (ECMO): a retrospective cohort analysis","authors":"Alexandre Coppens, Melchior Gautier, Noël Zahr, Helga Junot, Brigitte Rached, David Levy, Ouriel Saura, Juliette Chommeloux, Guillaume Hekimian, Matthieu Schmidt, Alain Combes, Alexandre Bleibtreu, Charles-Edouard Luyt","doi":"10.1186/s13054-025-05641-y","DOIUrl":"https://doi.org/10.1186/s13054-025-05641-y","url":null,"abstract":"<p>Ceftolozane/tazobactam (C/T), a β-lactam/β-lactamase inhibitor combination, demonstrates potent activity against difficult-to-treat resistance Gram-negative pathogens, including <i>Pseudomonas aeruginosa</i> and ESBL-producing Enterobacterales. Pharmacokinetic (PK) alterations in ECMO patients—due to drug adsorption, increased volume of distribution, and altered clearance—raise concerns about antibiotic underdosing [1]. While an ex vivo study reported minimal C/T adsorption on ECMO circuits (≤ 12.95% concentration loss over 8 h), PK evaluation in a porcine ECMO model found no significant effect on ceftolozane exposure, whereas ECMO was associated with reduced renal clearance of tazobactam by 37%, potentially affecting its plasma concentrations [2]. This study aimed to characterize C/T PK parameters—including trough (Cmin), peak (Cmax), and concentration at 50% of the dosing interval (CT50)—in patients who received C/T as empirical therapy for ≥ 48 h undergoing ECMO, post‑decannulation data were included only as exploratory, secondary observations. PK/PD target attainment was calculated using predefined MIC thresholds for ceftolozane and tazobactam, as detailed in the Online Supplement.</p><p>This was a single-center, observational, retrospective study conducted at Pitié-Salpêtrière University Hospital (Paris, France). The study was approved by the SRLF ethics committee (CE SRLF 19–70). 42 patients were included in the study, including 39 patients on ECMO support and 3 recently weaned ECMO patients. Baseline characteristics and C/T PK parameters are summarized in Table 1. C/T dosing regimens were adjusted to renal function (Supplementary file), with 45% receiving the highest dose (2 g/1 g q8h).</p><figure><figcaption><b data-test=\"table-caption\">Table 1 Demographic, clinical characteristics and pharmacokinetics data of patients</b></figcaption><span>Full size table</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>In ECMO patients, median ceftolozane trough concentration was 21.2 mg/L [11.4–43.5], with 100% of patients achieving concentrations above the MIC (100% fT &gt; MIC) and 61% (23/38) reaching 4×MIC (16 mg/L). Median peak concentration was 68.7 mg/L [29.7–95.9]. Tazobactam trough concentrations had a median of 0.6 mg/L [0–2.9], with 50% (15/30) achieving 100% fT &gt; 1 mg/L and 76% (28/37) reaching CT50 &gt; 1 mg/L.</p><p>Among the three patients recently weaned from ECMO, median ceftolozane trough was 9.9 mg/L [9.6–52.8], with 33% (1/3) reaching 4×MIC. Median tazobactam trough was 0 mg/L [0–3.2], with 67% (2/3) maintaining CT50 &gt; 1 mg/L.</p><p>Ceftolozane trough concentrations varied with renal function (Fig. 1): severe impairment (CrCl ≤ 30 mL/min) 93.6 mg/L [85.1–108.4], intermittent hemodialysis 55.3 mg/L [47.3–98.1], continuous venovenous hemodiafiltration 12.2 mg/L [10.1–15.8], augm","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"52 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923870","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":"Cell-specific expression and signaling of glucocorticoid receptor isoforms over time in critically ill patients with a low inflammatory response","authors":"Georgios Poupouzas, Nikolaos S Lotsios, Charikleia S Vrettou, Vasileios Issaris, Chrysi Keskinidou, Kostas A Papavassiliou, Asimenia Halioti, Efthymia Botoula, Marinella Tzanela, Athanasios G Papavassiliou, Anastasia Kotanidou, Dimitra A Vassiliadi, Alice G Vassiliou, Ioanna Dimopoulou","doi":"10.1186/s13054-025-05628-9","DOIUrl":"https://doi.org/10.1186/s13054-025-05628-9","url":null,"abstract":"Glucocorticoid (GC) signaling plays a crucial role in immune regulation during critical illness, but cell-specific responses remain poorly understood. While previous studies have predominantly examined glucocorticoid receptor (GCR)-α and GCR-β, the roles of alternative isoforms (GCR-γ, GCR-P) and the downstream effectors GC-induced leucine zipper (GILZ) and dual-specific phosphatase 1 (DUSP1) across different immune cell populations in critical illness remain unexplored. In this prospective, observational study, we enrolled 43 critically ill patients and 25 healthy controls. Longitudinal blood samples were collected at ICU admission (24–48 h) and days 4 (4d), 8 (8d), and 14 (14d). We quantified the mRNA expression of four GCR variants (GCR-α, GCR-β, GCR-γ, and GCR-P) and GC downstream targets (GILZ and DUSP1) in isolated polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells (PBMCs) via RT‒PCR. Serum cortisol, adrenocorticotropic hormone (ACTH), and cytokines (interleukin (IL)-6 and IL-10) were measured concurrently. Statistical analyses included mixed-effects modeling to assess temporal and cell-specific patterns. PMNs exhibited sustained downregulation of GCR-α, GCR-β, and GCR-γ, with preserved GILZ expression, while GCR-P remained stable. In PBMCs, GCR-α, GCR-β, GCR-γ, and GILZ levels showed no significant changes compared to controls, yet GCR-P was upregulated. DUSP1 was downregulated in PMNs and elevated in PBMCs. Negative correlations emerged between IL-6 and both GILZ and DUSP1. All expression patterns remained stable across time points in the subset of patients who completed the 2-week study despite dynamic ACTH changes and persistently elevated cortisol. PMNs show reduced GCR-α/β/γ with preserved GILZ, while PBMCs maintain GCR-α/β/γ but upregulate GCR-P and DUSP1. These findings highlight divergent GC responsiveness between innate and adaptive immune cells, with implications for cortisol’s role in immune regulation during critical illness and may reflect cell-specific effects driven by changes in glucocorticoid receptor signaling.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"11 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915495","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":"Left-digit bias in outcomes and invasive treatments among out-of-hospital cardiac arrest patients with shockable rhythm: a nationwide multicenter observational study with regression discontinuity design analysis","authors":"Yuki Miyamoto, Tetsuhisa Kitamura, Ling Zha, Sho Komukai, Sho Oka, Tadaharu Shiozumi, Koki Nakada, Tasuku Matsuyama","doi":"10.1186/s13054-025-05629-8","DOIUrl":"https://doi.org/10.1186/s13054-025-05629-8","url":null,"abstract":"<p>Left-digit bias (LDB) occurs when the leftmost digit of a number disproportionately influences decision-making, creating discontinuities at round-number thresholds. In healthcare setting, patients aged 79 are perceived as “in their 70s” while those aged 80 are seen as “in their 80s,” despite minimal actual differences. Previous studies documented LDB across medical specialties, such as myocardial infarction treatment decisions [1]. However, studies in cardiac arrest populations showed negative results, with no significant LDB found in either in-hospital or witnessed out-of-hospital cardiac arrest (OHCA) [2, 3]. These negative findings might reflect the heterogeneity of cardiac arrest populations and the protocolized nature of pre-hospital care, which can mask biases. Additionally, in-hospital decisions about resource-intensive interventions like extracorporeal cardiopulmonary membrane oxygenation (ECMO) involve greater physician discretion under time pressure—conditions that can reveal LDB effect. This study investigated whether LDB affects clinical outcomes and invasive treatment implementation in OHCA patients with shockable rhythms (ventricular fibrillation or pulseless ventricular tachycardia) using the OHCA registry containing in-hospital data in Japan.</p><p>We conducted a secondary analysis of the JAAM-OHCA Registry, a prospective multicenter observational cohort involving approximately 140 hospitals across Japan [4]. Further details of the registry and the present analysis were described in the Supplemental Materials. We included adult patients (≥ 18 years) enrolled between June 2014 and December 2020 with shockable initial rhythm documented by emergency medical services. Patients with transport time exceeding 121 min were excluded. Primary outcome was favorable neurological outcome at 1 month (Cerebral Performance Category 1–2). Secondary outcomes included 1-month survival and implementation of extracorporeal membrane oxygenation (ECMO), targeted temperature management (TTM), and coronary angiography (CAG).</p><p>Regression discontinuity design (RDD) identified potential discontinuities at ages 60, 70, and 80. RDD exploits quasi-random assignment of patients just below and above thresholds—patients aged 69 and 70 should be similar except for age perception. We implemented local linear regression with triangular kernel weighting, adjusting for sex, witness status, bystander cardiopulmonary resuscitation provision, bystander automated external defibrillator use, physician-staffed pre-hospital care involvement, transport to a tertiary care center, interval from emergency call to hospital arrival, advanced airway management, initial rhythm upon hospital arrival, weekend admission, and nighttime admission.</p><p>Among 72,041 OHCA patients, 5,943 met inclusion criteria (eFigure 1 in the Supplemental Materials). The mean age was 64.4 ± 15.5 years (18–59 years: 35.1%; 60–69 years: 23.7%; 70–79 years: 24.2%; ≥80 years: 16.9%). The majority wer","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"23 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915496","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":"Factors associated with women authorship over 25 years in high-impact critical care randomized controlled trials: the pipeline is still leaking","authors":"Joris Pensier, Clémence De Caumia-Baillenx, Antoine De Caumia-Baillenx, Inès Lakbar, Julie Carr, Karolina Griffiths, David Costa, Mathieu Capdevila, Samir Jaber, Audrey De Jong","doi":"10.1186/s13054-025-05627-w","DOIUrl":"https://doi.org/10.1186/s13054-025-05627-w","url":null,"abstract":"Studies have shown an underrepresentation of women in clinical research, but little is known about trends over time and factors associated with this underrepresentation. This study aimed to investigate the evolution and the independent factors associated with the proportion of women in the authorship of high-impact critical care randomized controlled trials (RCTs) over 25 years. This meta-epidemiological study screened adult critical care RCTs published between 1999 and 2023 in the six highest-impact general and critical care journals. Sex was assessed using a combination of authors’ biographies, available photographs, the gender R package, and a native Chinese speaker’s assistance to ensure cultural accuracy. The primary outcome was the proportion of women among the authors. Unadjusted and adjusted generalized linear mixed models were performed. Of 1,203 RCTs, the sex of all authors was determined in 1,199 (99.7%). Overall, 4,335 out of 16,057 authors (27%) were women. Women were less frequently first (247/1,199 [21%], p < 0.001) or senior authors (174/1,199 [15%], p < 0.001) compared to other positions. The proportion of women among authors increased by a change rate of 0.7% per year ([0.5%—0.9%]) from 18% in 1999 to 32% in 2023. In multivariable analysis, the proportion of women increased significantly per year of publication (odds ratio [OR] = 1.05, 95% confidence interval [1.02–1.09], p < 0.01) and sample size (OR = 1.007 [1.003–1.012] per 100 patients increase, p = 0.01), and decreased significantly in European RCTs (OR = 0.53 [0.33–0.85], p < 0.01), RCTs on ventilation (OR = 0.50 [0.25–0.97], p = 0.04) but not sepsis (OR = 0.74 [0.37–1.46], p = 0.39), mortality as primary outcome (OR = 0.36 [0.14–0.92], p = 0.03), and with endorsement by a study group (OR = 0.36 [0.18–0.69], p < 0.01). Although the proportion of women in authorship has risen over 25 years, women are still widely underrepresented in the authors of high-impact RCTs, especially as first and senior authors. This underrepresentation is exacerbated in Europe, in trials with mortality as primary outcome, on ventilation, or endorsed by a study group. This illustrates the “leaky pipeline” framework: women are still excluded from the highest-level of critical care research.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"27 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911001","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}