Critical Care最新文献

{"title":"Adjuvant therapies for management of hemorrhagic shock: a narrative review","authors":"Yann Daniel, Frédérique Dufour-Gaume, Amandine Vergnaud, Manon Denis, Louise Giaume, Bertrand Rozec, Nicolas Prat, Benjamin Lauzier","doi":"10.1186/s13054-025-05368-w","DOIUrl":"https://doi.org/10.1186/s13054-025-05368-w","url":null,"abstract":"Severe bleeding remains a leading cause of death in patients with major trauma, despite improvements in care during the acute phase, especially the application of damage control concepts. Death from hemorrhage occurs rapidly after the initial trauma, in most cases before the patient has had a chance to reach a hospital. Thus, the development of adjuvant drugs that would increase the survival of injured patients is necessary. Among the many avenues of research in this area, one is to improve cell survival during tissue hypoxia. During hemorrhagic shock, oxygen delivery to cells decreases and, despite increased oxygen extraction, anaerobic metabolism occurs, leading to acidosis, coagulopathy, apoptosis, and organ dysfunction. We selected six treatments that may help cells cope with this situation and could be used as adjuvant therapies during the initial resuscitation of severe trauma patients, including out-of-hospital settings: niacin, thiazolidinediones, prolyl hydroxylase domain inhibitors, O-GlcNAcylation stimulation, histone deacetylase inhibitors, and adenosine–lidocaine–magnesium solution. For each treatment, the biological mechanism involved and a systematic review of its interest in hemorrhagic shock (preclinical data and human clinical trials) are presented. Promising molecules, some of which are already used in humans for other indications, give us hope for human clinical trials in the field of hemorrhagic shock in the near future.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"11 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734011","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":"Association between mean hemodynamic variables during the first 24 h and outcomes in cardiogenic shock: identification of clinically relevant thresholds","authors":"Bruno Levy, Anais Curtiaud, Kevin Duarte, Clément Delmas, Julien Demiselle, Nicolas Girerd, Caroline Eva Gebhard, Julie Helms, Ferhat Meziani, Antoine Kimmoun, Hamid Merdji","doi":"10.1186/s13054-025-05356-0","DOIUrl":"https://doi.org/10.1186/s13054-025-05356-0","url":null,"abstract":"Cardiogenic shock (CS) remains a critical condition with high mortality rates despite advances in treatment. This study aims to comprehensively evaluate both macrocirculatory and tissue perfusion variables over the initial 24 h post-admission to determine their impact on patient prognosis and identify potential hemodynamic thresholds for optimal outcomes. Secondary aims were to explore the correlation between macrocirculatory and tissue perfusion variables. This is a post hoc analysis of data from two prospective studies, OptimaCC (NCT01367743) and MicroShock (NCT03436641), involving only patients with CS. Both studies applied regular assessment of hemodynamic variables at specific time points (admission, 6, 12, and 24 h) to ensure consistency in data collection, enrolling 118 patients between September 2011 and July 2021, with similar inclusion criteria and care processes. The median age of the cohort was 69 years, 59% being male. The primary outcome, 30-day mortality, occurred in 37% of patients. Average macrocirculation variables over the first 24 h of CS such as mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), and cardiac power index (CPI) were significantly lower in patients meeting the primary outcome. Accordingly, average tissue perfusion variables (ΔPCO2 and ΔPCO2/C(a-v)O2) over the first 24 h of CS were also consistently impaired in patients meeting the primary outcome. The optimal clinically relevant thresholds of the first 24 h time course for poor outcomes, closely approximating the optimal values identified in the analysis, were: mean SAP < 95 mmHg, MAP < 70 mmHg, CO < 3.5 L/min, CI ≤ 1.8 L/min/m2, CPI < 0.27 W/m2, ScvO2 < 70%, ΔPCO2 ≥ 9 mmHg, and ΔPCO2/C(a-v)O2 ≥ 1.5 mmHg/mL. This study is the first to identify critical hemodynamic thresholds, encompassing both macrocirculatory and tissue perfusion variables, within the initial 24 h of CS that are associated with adverse outcomes. The identified thresholds suggest specific hemodynamic targets that may guide resuscitation strategies.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"18 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712784","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":"Complementary role of transcriptomic endotyping and protein-based biomarkers for risk stratification in sepsis-associated acute kidney injury","authors":"Bengi S. Tavris, Christian Morath, Christoph Rupp, Roman Szudarek, Florian Uhle, Timothy E. Sweeney, Oliver Liesenfeld, Mascha O. Fiedler-Kalenka, Simon Dubler, Martin Zeier, Felix C. F. Schmitt, Markus A. Weigand, Thorsten Brenner, Christian Nusshag","doi":"10.1186/s13054-025-05361-3","DOIUrl":"https://doi.org/10.1186/s13054-025-05361-3","url":null,"abstract":"Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and severe complication in critically ill patients. However, diagnostic and therapeutic advancements have been hindered by the biological heterogeneity underlying the disease. Both transcriptomic endotyping and biomarker profiling have been proposed individually to identify molecular subtypes of sepsis and may enhance risk stratification. This study aimed to evaluate the utility of combining transcriptomic endotyping with protein-based biomarkers for improving risk stratification in SA-AKI. This secondary analysis of the PredARRT-Sep-Trial included 167 critically ill patients who met Sepsis-3 criteria. Patients were stratified into three transcriptomic endotypes—inflammopathic (IE), adaptive (AE), and coagulopathic (CE)—using a validated whole-blood gene expression classifier. Eight protein-based biomarkers encompassing kidney function, vascular integrity, and immune response were measured. Predictive performance for the primary endpoint kidney replacement therapy or death was assessed using receiver operating characteristic curve analysis and logistic regression models. Stratification into transcriptomic endotypes assigned 33% of patients to IE, 42% to AE, and 24% to CE. Patients classified as IE exhibited the highest disease severity and were most likely to meet the primary endpoint (30%), compared to AE and CE (17% and 10%, respectively). Kidney function biomarkers showed stepwise increases with AKI severity across all endotypes, whereas non-functional biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], soluble urokinase plasminogen activator receptor [suPAR], and bioactive adrenomedullin [bio-ADM]) exhibited endotype-specific differences independent of AKI severity. NGAL and suPAR levels were disproportionately elevated in the IE group, suggesting a dominant role of innate immune dysregulation in this endotype. In contrast, bio-ADM, a marker of endothelial dysfunction, was the strongest risk-predictor of outcomes in CE. The combination of transcriptomic endotyping with protein-based biomarkers enhanced predictive accuracy for the primary endpoint and 7-day mortality, with the highest area under the receiver operating characteristic curve of 0.80 (95% CI 0.72–0.88) for endotyping + bio-ADM and 0.85 (95% CI 0.78–0.93) for endotyping and suPAR, respectively. Combinations of endotyping with functional and non-functional biomarkers particularly improved mortality-related risk stratification. Combining transcriptomic endotyping with protein-based biomarker profiling enhances risk-stratification in SA-AKI, offering a promising strategy for personalized treatment and trial enrichment in the future. Further research should validate these findings and explore therapeutic applications.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"94 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712785","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":"Bayesian methods as a complementary tool: balancing innovation and rigor in critical care research","authors":"Sen Lu, Kai Liu, Xin-yun Chen, Jing-chao Luo","doi":"10.1186/s13054-025-05380-0","DOIUrl":"https://doi.org/10.1186/s13054-025-05380-0","url":null,"abstract":"&lt;p&gt;The perspective by Patel and Green, “Death by P-value: The Overreliance on P-values in Critical Care Research” [1], offers a timely critique of rigid statistical thresholds in critical care trials. By advocating for hybrid approaches that integrate Bayesian methods with traditional frequentist analysis, the authors highlight the potential of probabilistic reasoning to uncover clinically meaningful effects obscured by borderline p-values. While their argument is thought-provoking, several considerations warrant further discussion to ensure a balanced application of Bayesian methods in this field.&lt;/p&gt;&lt;p&gt;The authors rightly emphasize that Bayesian analysis should complement—not replace—frequentist frameworks. Their examples (e.g., hydrocortisone in traumatic brain injury, β-blockers in septic shock) demonstrate how posterior distributions can contextualize findings when p-values are near 0.05. However, while compelling, such re-analyses must not be conflated with definitive evidence. For instance, the reported 87% posterior probability of hydrocortisone reducing ventilator-associated pneumonia (VAP) risk by ≥ 10% remains hypothesis-generating. Bayesian results should be interpreted as one component of a broader evidentiary hierarchy, alongside biological plausibility, trial design, and external validation.&lt;/p&gt;&lt;p&gt;A key concern in Bayesian analysis is the influence of prior distributions. While the authors employed neutral priors (e.g., mean effect = 0, standard deviation = 10%), even these choices introduce assumptions. Using a standard deviation of 10% in the β-blocker mortality analysis presumes that true effects beyond ± 20% are implausible—a debatable premise in sepsis research. To enhance objectivity, future studies should:&lt;/p&gt;&lt;ul&gt;\u0000&lt;li&gt;\u0000&lt;p&gt;Pre-specify prior distributions in trial protocols, informed by systematic reviews or expert consensus&lt;/p&gt;\u0000&lt;/li&gt;\u0000&lt;li&gt;\u0000&lt;p&gt;Conduct sensitivity analyses using skeptical priors (e.g., centered on harm) or enthusiastic priors (e.g., larger expected benefits)&lt;/p&gt;\u0000&lt;/li&gt;\u0000&lt;li&gt;\u0000&lt;p&gt;Adhere to guidelines such as the ISBA bulletin [2] on Bayesian Hypothesis Testing with transparent reporting of prior justification and Bayes factors&lt;/p&gt;\u0000&lt;/li&gt;\u0000&lt;/ul&gt;&lt;p&gt;The critique of p-values should not overshadow their utility in controlling Type I error rates. More specifically, the continuous versus interrupted chest compressions trial reported a posterior probability of 75% for survival benefit with interrupted compressions. Yet, the frequentist 95% confidence interval (− 1.5 to 0.1%) and corresponding credible interval remind us that the effect could plausibly be null or harmful. Rather than abandoning p-values, a hybrid approach could:&lt;/p&gt;&lt;ul&gt;\u0000&lt;li&gt;\u0000&lt;p&gt;Use Bayesian posterior probabilities to prioritize interventions for further study&lt;/p&gt;\u0000&lt;/li&gt;\u0000&lt;li&gt;\u0000&lt;p&gt;Reserve frequentist analyses for confirmatory endpoints in pre-registered trials&lt;/p&gt;\u0000&lt;/li&gt;\u0000&lt;li&gt;\u0000&lt;p&gt;Report both Bayesian and frequentist results in interim and final analyses&lt;/p&gt;\u0000&lt;/li&gt;\u0000&lt;/","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"41 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695090","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":"Elevated serum pre-arrest cathepsin D concentrations are associated with higher mortality in in-hospital cardiac arrest","authors":"Taline Lazzarin, Paula Schmidt Azevedo, Leonardo Antonio Mamede Zornoff, Sergio Alberto Rupp de Paiva, Filipe Welson Leal Pereira, Raquel Simões Ballarin, Marcos Ferreira Minicucci","doi":"10.1186/s13054-025-05382-y","DOIUrl":"https://doi.org/10.1186/s13054-025-05382-y","url":null,"abstract":"&lt;p&gt;Cathepsin D (CatD) is a lysosomal enzyme implicated in ischemia–reperfusion injury, influencing apoptosis and inflammatory cytokine production [1]. It has been associated with cardiovascular diseases, atherosclerosis, heart failure, and acute conditions such as acute kidney injury (AKI) and pancreatitis [2]. However, its role in cardiac arrest (CA) remains unexplored. Therefore, this study aimed to evaluate the association between pre-arrest CatD levels, return of spontaneous circulation (ROSC), and mortality in in-hospital cardiac arrest (IHCA) patients.&lt;/p&gt;&lt;p&gt;An ambispective cohort study was conducted between August 2021 and April 2023 involving IHCA patients. Ethics approval was obtained (46,717,721.0.0000.5411), and the sample size was calculated using the CatD mean in patients with and without coronary artery disease [3], with a significance level of 5% and a power of 80%, resulting in a required sample size of 170 patients.&lt;/p&gt;&lt;p&gt;Eligible patients were those aged &gt; 18 years who suffered IHCA, underwent cardiopulmonary resuscitation (CPR), and had blood samples available within 48 h before CA. Only index CA events were considered. Data were extracted from electronic medical records, including demographic, laboratory, and clinical variables. Serum pre-arrest CatD levels were measured using ELISA (Elabscience®) from blood samples available in the laboratory that were collected in the last 48 h before CA. The primary outcomes were sustained ROSC (≥ 20 min) and in-hospital mortality.&lt;/p&gt;&lt;p&gt;Statistical analyses were performed using SigmaPlot v12.0 and Stata v15.1. Continuous variables were analyzed using Student’s t-test or Mann–Whitney test, while categorical variables were assessed using the χ&lt;sup&gt;2&lt;/sup&gt; or Fisher's exact test. A receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of pre-arrest CatD for in-hospital mortality. Due to the high mortality rate, penalized likelihood estimation with Firth logistic regression was applied, adjusting for clinically relevant and statistically significant variables. A significance level of 5% was adopted.&lt;/p&gt;&lt;p&gt;We included 199 patients (mean age 66.4 ± 15.5 years; 56.2% male). ROSC occurred in 43.7% of cases, while in-hospital mortality reached 95.0%, with only ten patients surviving. The cerebral performance category (CPC) scale classified 40% of survivors as CPC 1, 30% as CPC 2, and 30% as CPC 3, indicating that 70% had a good neurological outcome. Initial non-shockable rhythm, prolonged CPR, epinephrine use, elevated urea, and high pre-arrest CatD levels were associated with mortality (Table 1). Median pre-arrest CatD levels were significantly higher in non-survivors (39.9 pg/L) than in survivors (7.2 pg/L). ROC analysis demonstrated a strong association between pre-arrest CatD and mortality (AUC 0.822; CI 0.7142–0.9302; p &lt; 0.001—supplementary Fig. 1) at a cutoff of 33.2 pg/L (sensitivity 56.6%, specificity 90%). Firth's penalized logistic regression","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"9 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695100","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":"Influence of alcohol on in-hospital survival rate among patients with traumatic brain injury: a nationwide cohort study","authors":"Kazuma Sasaki, Takashi Tagami, Hirofumi Obinata, Chie Tanaka, Kosuke Otake, Yudai Yoshino, Akihiro Watanabe, Ami Shibata, Kentaro Kuwamoto, Junichi Inoue, Shoji Yokobori","doi":"10.1186/s13054-025-05364-0","DOIUrl":"https://doi.org/10.1186/s13054-025-05364-0","url":null,"abstract":"The impact of alcohol on the prognosis of patients with traumatic brain injury (TBI) remains unclear. While some reports suggest that alcohol may exert neuroprotective effects, others indicate that it can worsen neurological outcomes. This study aimed to evaluate the influence of alcohol consumption on TBI outcomes using a nationwide database in Japan. We analyzed data from approximately 290 hospitals contributing to the Japan Trauma Data Bank between 2004 and 2018. Patients with head injuries and documented pre-injury alcohol consumption were included. To adjust for potential confounders and institutional clustering, we employed propensity score methods—specifically inverse probability weighting (IPTW) and overlap weighting—and conducted multiple logistic regression with a generalized estimating equation. Covariates in the propensity score model included age, sex, day of the week, time of injury, period of injury, and past medical history. The primary outcome was in-hospital survival. Additionally, we fitted a multivariate logistic regression model (with survival as the outcome) to identify potential interactions and confounders. This model included type of trauma (blunt or penetrating), cause and setting of trauma, head Abbreviated Injury Scale score, multiple trauma status, the Injury Severity Score, and the propensity score. Of the 83,789 patients who met the inclusion criteria, 15,752 had reported alcohol consumption prior to injury (alcohol group) and 68,037 did not (non-alcohol group). In-hospital survival was 91.5% in the alcohol group and 86.4% in the non-alcohol group (risk difference: 5.2%; 95% CI: 4.7–5.7). After adjustment, the alcohol group maintained a higher in-hospital survival rate (IPTW: 92.0% vs. 86.1%, risk difference: 6.2%; 95% CI: 5.9–6.2; overlap weighting: 91.7% vs. 85.4%, risk difference: 7.0%; 95% CI: 6.1–7.8). In the multivariate logistic regression, preinjury alcohol consumption was associated with higher survival (odds ratio: 1.58, 95% CI: 1.47–1.70, p < 0.001). In this nationwide study, preinjury alcohol consumption was associated with higher in-hospital survival among patients with TBI. Further research is warranted to elucidate the underlying mechanisms and confirm these findings in more diverse populations.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"34 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695097","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":"Detection of hypovolemia by non-invasive hemodynamic monitoring during major surgery using Ringer´s solution, 5% albumin, or 20% albumin as infusion fluid: a post-hoc analysis of a randomized clinical trial","authors":"François Jardot, Robert G. Hahn, Markus Huber, Patrick Y. Wuethrich","doi":"10.1186/s13054-025-05357-z","DOIUrl":"https://doi.org/10.1186/s13054-025-05357-z","url":null,"abstract":"Fluid loading with crystalloids is the conventional treatment of major hemorrhage but might tend to create fluid overload. We studied hemodynamic profiles of fluid replacement therapies during major surgical hemorrhage and compared the ability of pulse pressure variation (PPV), plethysmographic variation index (PVI), cardiac output (CO) and Guyton´s approach to detect hypovolemia. In this single center randomized controlled trial, fluid replacement therapy to treat hemorrhage in 42 patients was randomized to consist of either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min, both completed by Ringer lactate replacing blood loss in a 1:1 ratio, or Ringer solution alone in a 3:1 ratio. Measurements included CO, PPV, PVI, arterial and central venous pressures, heart rate (HR) and subsequent calculation of Guyton´s physiological parameters. CO was measured by an esophageal Doppler probe. The Ringer-only fluid program resulted in slight hypovolemia (mean, 313 mL), decreased mean arterial pressure (MAP), increased HR, PPV values and vasopressor requirement. The 5% and 20% albumin programs were more effective in filling the vascular system, as evidenced by higher mean circulatory filling pressure and unchanged or decreased PPV over the 5 h observation period. The 20% albumin increased the systemic vascular resistance and the resistance to venous return. Receiver operating characteristics curves indicated that hypovolemia > 500 mL could only be accurately detected by PPV when 5% albumin was used, that PVI was reliable when Ringer was infused, and that CO indicated the hypovolemia when 20% albumin was administered. The trends in PPV, PVI, and CO reflected the changes in intravascular volume, but how well they indicated hypovolemia > 500 mL may differ depending on the choice of infusion fluid. Identifying hypovolemia using non-invasive hemodynamic monitors remains challenging and associated with low predictive values. Trial registration number: NCT05391607, May 26, 2022.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"59 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675220","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":"Influence of SARS-CoV-2 variants and corticosteroid use on the effectiveness of baricitinib therapy in critical COVID-19","authors":"Seung-Hun You, Moon Seong Baek, Tae Wan Kim, Sun-Young Jung, Won-Young Kim","doi":"10.1186/s13054-025-05367-x","DOIUrl":"https://doi.org/10.1186/s13054-025-05367-x","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;We sincerely appreciate the insightful comments provided by Li et al. [1] regarding our correspondence, “Baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study” [2], recently published in &lt;i&gt;Critical Care&lt;/i&gt;. We recognize the need for further clarification on certain aspects to ensure a more precise interpretation of our study findings.&lt;/p&gt;&lt;p&gt;We acknowledge that the emergence of multiple SARS-CoV-2 variants over time could have influenced the therapeutic efficacy of baricitinib and tocilizumab in critically ill patients with COVID-19. Our cohort analysis accounted for temporal variations by stratifying patients based on their inclusion earlier or later in the pandemic. To provide a more granular assessment, we reanalyzed the outcomes by stratifying them according to the predominant SARS-CoV-2 strains circulating in Korea during the study period: Delta (July 2021–December 2021) and Omicron (January 2022–October 2022). The wild-type and Alpha periods were excluded from the analysis, as baricitinib and tocilizumab had not yet been authorized for use in Korea during these phases. Our findings revealed no significant differences in outcomes between patients receiving baricitinib or tocilizumab during the Delta-dominant period. However, during the Omicron-dominant period, patients treated with baricitinib exhibited significantly lower 30-day mortality rates compared to those receiving tocilizumab (53.8% vs 61.5%; odds ratio 0.73; 95% confidence interval 0.56–0.95). This finding aligns with a previous cohort study demonstrating that baricitinib was more effective in mitigating the inflammatory response triggered by the Omicron variant [3]. Among the 98 of 1630 (6.0%) patients hospitalized due to reinfection, only 14 required mechanical ventilation (MV). Consequently, it was not feasible to determine whether the clinical outcomes associated with baricitinib differed in this subgroup of patients.&lt;/p&gt;&lt;p&gt;As noted by Li et al., the concurrent use of corticosteroids could potentially influence the immunomodulatory effects of baricitinib and tocilizumab. The authors suggested conducting a subgroup analysis based on corticosteroid use. However, nearly all patients (98.4% of the initial cohort) received corticosteroids. Therefore, instead of a binary analysis based on corticosteroid administration, we performed subgroup analyses of 30-day mortality based on corticosteroid dosage and treatment duration. Corticosteroid use was defined as the administration of at least one dose of intravenous dexamethasone, hydrocortisone, or methylprednisolone during hospitalization. To standardize comparisons, all doses were converted to prednisolone equivalents [4]. The cut-off values for daily steroid dose and total treatment duration were determined based on the mean values observed in the study population. Among patients who received corticosteroids for fewer than 12 days or at a daily dose below 60 m","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"34 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672401","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":"Ventilation-induced acute kidney injury in acute respiratory failure: Do PEEP levels matter?","authors":"Martín H. Benites, Fernando Suarez-Sipmann, Eduardo Kattan, Pablo Cruces, Jaime Retamal","doi":"10.1186/s13054-025-05343-5","DOIUrl":"https://doi.org/10.1186/s13054-025-05343-5","url":null,"abstract":"Acute Respiratory Distress Syndrome (ARDS) is a leading cause of morbidity and mortality among critically ill patients, and mechanical ventilation (MV) plays a critical role in its management. One of the key parameters of MV is the level of positive end-expiratory pressure (PEEP), which helps to maintain an adequate lung functional volume. However, the optimal level of PEEP remains controversial. The classical approach in clinical trials for identifying the optimal PEEP has been to compare “high” and “low” levels in a dichotomous manner. High PEEP can improve lung compliance and significantly enhance oxygenation but has been inconclusive in hard clinical outcomes such as mortality and duration of MV. This discrepancy could be related to the fact that inappropriately high or low PEEP levels may adversely affect other organs, such as the heart, brain, and kidneys, which could counteract its potential beneficial effects on the lung. Patients with ARDS often develop acute kidney injury, which is an independent marker of mortality. Three primary mechanisms have been proposed to explain lung-kidney crosstalk during MV: gas exchange abnormalities, such as hypoxemia and hypercapnia; remote biotrauma; and hemodynamic changes, including reduced venous return and cardiac output. As PEEP levels increase, lung volume expands to a variable extent depending on mechanical response. This dynamic underlies two potential mechanisms that could impair venous return, potentially leading to splanchnic and renal congestion. First, increasing PEEP may enhance lung aeration, particularly in highly recruitable lungs, where previously collapsed alveoli reopen, increasing lung volume and pleural pressure, leading to vena cava compression, which can contribute to systemic venous congestion and abdominal organ impairment function. Second, in lungs with low recruitability, PEEP elevation may induce minimal changes in lung volume while increasing airway pressure, resulting in alveolar overdistension, vascular compression, and increased pulmonary vascular resistance. Therefore, we propose that high PEEP settings can contribute to renal congestion, potentially impairing renal function. This review underscores the need for further rigorous research to validate these perspectives and explore strategies for optimizing PEEP settings while minimizing adverse renal effects.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"27 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666068","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 novel biomarker t6A accurately identified septic patients at admission but failed to predict outcome","authors":"Marcin F. Osuchowski, Barbara Adamik, Waldemar Gozdzik, Tomasz Skalec, Daniel Mascher, Heinz Redl, Johannes Zipperle, Gerhard Fritsch, Wolfgang Voelckel, Martin S. Winkler, Onnen Moerer, Helmut Schütz, Hermann Mascher","doi":"10.1186/s13054-025-05354-2","DOIUrl":"https://doi.org/10.1186/s13054-025-05354-2","url":null,"abstract":"&lt;p&gt;Sepsis is a life-threatening condition caused by the body’s extreme response to infection [1]. Early diagnosis of sepsis is crucial for improving patient outcomes, yet current diagnostic methods including microbiological cultures are delayed and frequently inconclusive. This has driven the search for novel biomarkers and detection systems capable of recognizing sepsis more rapidly and accurately [2]. Procalcitonin (PCT) is the most widely used biomarker for sepsis detection but its use is limited as circulating PCT concentration is influenced by noninfectious inflammation (e.g. trauma, surgery).&lt;/p&gt;&lt;p&gt;Nucleoside modifications are a hallmark of the post-transcriptional processing of transfer ribonucleic acid (tRNA) that generate multiple structurally modified nucleosides [3]. One of such tRNA-modified nucleosides, N6-threonylcarbamoyladenosine (t&lt;sup&gt;6&lt;/sup&gt;A), is critical for ensuring efficient protein synthesis in health and disease [4]. We discovered that circulating t&lt;sup&gt;6&lt;/sup&gt;A possesses a diagnostic potential in sepsis. Consequently, we evaluated the diagnostic accuracy of t&lt;sup&gt;6&lt;/sup&gt;A in differentiating bacterial sepsis and COVID-19 from two different non-septic patient cohorts: i) patients undergoing elective coronary artery bypass graft (CABG) surgery and ii) severe polytrauma patients. In all cohorts, t&lt;sup&gt;6&lt;/sup&gt;A diagnostic accuracy was compared to PCT. Additionally, we tested t&lt;sup&gt;6&lt;/sup&gt;A potential to predict death/survival in patients with sepsis.&lt;/p&gt;&lt;p&gt;This multicenter retrospective observational study analyzed plasma samples from four cohorts (Supplementary Table 1). The study included 81 patients with bacterial sepsis (cohort 1) and 49 patients with severe COVID-19 infection (cohort 2) diagnosed upon ICU/Emergency admission , 87 patients undergoing elective CABG surgery (cohort 3) and 64 severe (Injury Severity Score &gt; 15) polytrauma patients (cohort 4). Sepsis in cohort 1 was defined according to the Sepsis-3 criteria, and all patients received treatment aligned with the Surviving Sepsis Campaign guidelines. In COVID-19 patients, SARS-CoV-2 infection was confirmed by molecular test. The CABG and polytrauma groups were used as non-septic comparators to assess t&lt;sup&gt;6&lt;/sup&gt;A’s diagnostic specificity and accuracy against patients with sepsis and those with COVID-19. We compared blood samples collected at admission for the sepsis and COVID-19 cohorts, to samples collected 24 h post-surgery (cohort 3) and trauma (cohort 4). Plasma t&lt;sup&gt;6&lt;/sup&gt;A concentrations were measured using tandem mass spectrometry with stable isotope internal standardization. PCT was measured using standard Brahms PCT luminescence immunoassay. Statistical analyses of the receiver operating characteristic (ROC) curves were carried out with a total of 50,000 stratified bootstrap samples to estimate the 95% confidence interval (CI) of the area under the curve (AUC) of the ROC curve and its optimal threshold. The AUCs were compared via De Long’s two-si","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"214 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661396","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}