Critical Care最新文献

{"title":"Association of healthy sleep patterns with incident sepsis: a large population-based prospective cohort study","authors":"Meina Zou, Di Lu, Zhexin Luo, Ninghao Huang, Wenxiu Wang, Zhenhuang Zhuang, Zimin Song, Wendi Xiao, Tao Huang, Renyu Ding","doi":"10.1186/s13054-025-05287-w","DOIUrl":"https://doi.org/10.1186/s13054-025-05287-w","url":null,"abstract":"The role that sleep patterns play in sepsis risk remains poorly understood. The objective was to evaluate the association between various sleep behaviours and the incidence of sepsis. In this prospective cohort study, we analysed data from the UK Biobank (UKB). A total of 409,570 participants who were free of sepsis at baseline were included. We used a composite sleep score that considered the following five sleep behaviours: sleep chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Cox proportional hazards regression analysis was used to estimate the associations between healthy sleep scores and incident sepsis. During a mean follow-up of 13.54 years, 13,357 (3.26%) incident sepsis cases were recorded. Among the 409,570 participants with a mean age of 56.47 years, 184,124 (44.96%) were male; 9942 (2.43%) reported 0 to 1 of the five healthy sleep behaviours; 46,270 (11.30%) reported 2 behaviours; 115,272 (28.14%) reported 3 behaviours; 150,522 (36.75%) reported 4 behaviours; and 87,564 (21.38%) reported 5 behaviours at baseline. Each one-point increase in the sleep score was associated with a 5% lower risk of developing sepsis (hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.93–0.97). Compared with a healthy sleep score of 0–1, for a sleep score of 5, the multivariate-adjusted HR (95% CI) for sepsis was 0.76 (0.69–0.83). In addition, we found that the negative correlation was stronger in participants who were aged < 60 years than in their older counterparts (p for interaction < 0.001). However, healthy sleep pattern was not associated with sepsis-related death and critical care admission. Findings from this cohort study suggest that a healthy sleep pattern may reduce the risk of developing sepsis, particularly among younger individuals.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"22 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055312","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":"Ulinastatin treatment mitigates glycocalyx degradation and associated with lower postoperative delirium risk in patients undergoing cardiac surgery: a multicentre observational study","authors":"Xiao Ran, Tingting Xu, Jieqiong Liu, Shaobing Yang, Fang Luo, Rongxue Wu, Juan Tan, Hang Ruan, Qin Zhang","doi":"10.1186/s13054-025-05296-9","DOIUrl":"https://doi.org/10.1186/s13054-025-05296-9","url":null,"abstract":"Ulinastatin (UTI), recognized for its anti-inflammatory properties, holds promise for patients undergoing cardiac surgery. This study aimed to investigate the relationship between intraoperative UTI administration and the incidence of delirium following cardiac surgery. A retrospective analysis was performed on a retrospective cohort of 6,522 adult cardiac surgery patients to evaluate the relationship between UTI treatment and the incident of postoperative delirium (POD) in patients ongoing cardiac surgery. This was followed by a prospective observational cohort study of 241 patients and an in vitro study to explore the findings and the potential role of UTI in preventing cardiac ischemia–reperfusion induced glycocalyx degradation. Both univariate and multivariate logistic regression analyses in retrospective cohort indicated that intraoperative administration of UTI was associated with a significant lower risk of POD among cardiac surgery patients, a finding confirmed through employing propensity score matching. The subsequent prospective observational cohort further supported these findings (adjusted Odds Ratio = 0.392, 95% CI: 0.157–0.977, P = 0.044). Furthermore, UTI mitigated glycocalyx degradation, as demonstrated by in vitro study. UTI administration may mitigate glycocalyx degradation, potentially lowering the risk of POD in cardiac surgery patients, offering valuable insights for future interventions to prevent POD and enhance patient outcomes. Trial registration number ClinicalTrials.gov (No. NCT06268249). Retrospectively registered 4 February 2024.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"39 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055310","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":"Effect of early administration of fibrinogen replacement therapy in traumatic haemorrhage: a systematic review and meta-analysis of randomised controlled trials with narrative synthesis of observational studies","authors":"Tom Burt, Ashley Guilliam, Elaine Cole, Ross Davenport","doi":"10.1186/s13054-025-05269-y","DOIUrl":"https://doi.org/10.1186/s13054-025-05269-y","url":null,"abstract":"In severely injured trauma patients, hypofibrinoginaemia is associated with increased mortality. There is no evidence-based consensus for what constitutes optimal fibrinogen therapy, treatment dose or timing of administration. The aim of this systematic review was to evaluate the effects of early fibrinogen replacement, either cryoprecipitate or fibrinogen concentrate (FgC) on mortality, transfusion requirements and deep venous thrombosis (DVT). A systematic search of studies was performed on MEDLINE, EMBASE and clinicaltrials.gov databases using standardised search criteria. All clinical studies which examined the use of either cryoprecipitate or FgC in patients with traumatic haemorrhage within 4 h of admission to hospital were included. Primary outcome was mortality (28-day, 30-day or in-hospital). Secondary outcomes were DVT incidence and blood component transfusions. A narrative synthesis was performed for all observational studies. Meta-analysis was completed for all included RCTs for mortality with pre-defined sub-group analysis of FgC and cryoprecipitate use. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the quality of evidence. Overall, 1906 studies were screened with 12 studies included and five RCTs (all suitable for meta-analysis) totalling 1758 participants. Three RCTs reported FgC therapy, and two used cryoprecipitate. Four out of five RCTs examined empiric fibrinogen replacement for suspected traumatic haemorrhage. There was no difference in the primary outcome of mortality: early fibrinogen replacement (24%) vs control (25%), OR 1.03 (95% CI; 0.68–1.56). Subgroup analysis found no difference in outcome between the FgC and control: 18.1% vs 10.9% respectively, OR 1.99 (95% CI; 0.80–4.94). Similarly for cryoprecipitate, there was no difference in mortality between groups: cryoprecipitate (24.9%) vs control (26.1%), OR 0.71 (95% CI, 0.25–2.01). Reporting of transfusion data precluded meta-analysis. There was no difference in DVT incidence: fibrinogen replacement (3%) vs control (4%), OR 0.73 (0.43, 1.25). Overall, the quality of evidence was graded as low due to indirectness and imprecision. There is no association between early fibrinogen replacement and mortality, DVT or transfusion requirements. We found no superiority between FgC or cryoprecipitate. This systematic review highlights the urgent need for further RCTs to assess the efficacy of early fibrinogen replacement, preferred strategy (goal-directed vs empiric) as well as optimal therapeutic product for both patient outcome and cost effectiveness.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"25 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049744","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":"Early phosphate changes as potential indicator of unreadiness for artificial feeding: a secondary analysis of the EPaNIC RCT","authors":"C. Lauwers, L. Langouche, P. J. Wouters, A. Wilmer, G. Van den Berghe, M. P. Casaer, J. Gunst","doi":"10.1186/s13054-025-05273-2","DOIUrl":"https://doi.org/10.1186/s13054-025-05273-2","url":null,"abstract":"As compared to withholding parenteral nutrition (PN) until one week after intensive care unit (ICU) admission, Early PN prolonged ICU dependency in the EPaNIC randomized controlled trial (RCT). The Refeeding RCT showed improved outcome by temporary macronutrient restriction in ICU patients developing refeeding hypophosphatemia, defined as a phosphate decrease of > 0.16 mmol/L to levels < 0.65 mmol/L. We hypothesized that early phosphate changes may identify critically ill patients who are harmed by Early PN, and that dynamic phosphate changes are more discriminative than an absolute threshold for hypophosphatemia. In this secondary analysis of the EPaNIC RCT, we studied whether absolute hypophosphatemia (AHP; < 0.65 mmol/L on the second ICU-day), relative hypophosphatemia (RHP; > 0.16 mmol/L decrease over the first 2 ICU-days), or a combination of both (CHP) interacted with the randomized nutritional strategy for its impact on outcome, adjusted for risk factors. In case of significant interaction, we studied whether the respective change could be predicted by baseline characteristics. Of 3520 patients with available phosphate measurements, AHP developed in 9.1%, RHP in 23.7%, and CHP in 5.3% of patients. RHP, but not AHP or CHP, interacted with the randomized intervention for its impact on outcome (p = 0.01). In RHP patients, Early PN independently associated with a lower likelihood of an earlier discharge alive from ICU (adjusted HR 0.75 [0.65–0.87]). In patients without RHP, Early PN did not significantly associate with this outcome (adjusted HR 0.93 [0.86–1.00]). Development of RHP was only poorly predicted by admission characteristics (adjusted pseudo R-squared = 1.7%). Development of RHP may identify patients who are particularly harmed by early PN. Future studies should prospectively validate the potential of including RHP in a ready-to-feed indicator.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"25 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049745","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":"Heterogeneity of treatment effect: the case for individualising oxygen therapy in critically ill patients","authors":"Daniel S. Martin, Michael P. W. Grocott","doi":"10.1186/s13054-025-05254-5","DOIUrl":"https://doi.org/10.1186/s13054-025-05254-5","url":null,"abstract":"Oxygen therapy is ubiquitous in critical illness but oxygenation targets to guide therapy remain controversial despite several large randomised controlled trials (RCTs). Findings from RCTs evaluating different approaches to oxygen therapy in critical illness present a confused picture for several reasons. Differences in both oxygen target measures (e.g. oxygen saturation or partial pressure) and the numerical thresholds used to define lower and higher targets complicate comparisons between trials. The duration of and adherence to oxygenation targets is also variable with consequent substantial variation in both the dose and the dose separation. Finally, heterogeneity of treatment effects (HTE) may also be a significant factor. HTE is defined as non-random variation in the benefit or harm of a treatment, in which the variation is associated with or attributable to patient characteristics. This narrative review aims to make the case that such heterogeneity is likely in relation to oxygen therapy for critically ill patients and that this has significant implications for the design and interpretation of trials of oxygen therapy in this context. HTE for oxygen therapy amongst critically ill patients may explain the contrasting results from different clinical trials of oxygen therapy. Individualised oxygen therapy may overcome this challenge, and future studies should incorporate ways to evaluate this approach. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"47 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049742","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":"Sorbents therapies in burn patients with septic shock on continuous kidney replacement therapy: an added value for a selected population","authors":"Filippo Mariano, Alberto Mella, Domenico Greco’, Luigi Biancone","doi":"10.1186/s13054-025-05284-z","DOIUrl":"https://doi.org/10.1186/s13054-025-05284-z","url":null,"abstract":"&lt;p&gt;We read with great interest the review addressing the issue of the use of extracorporeal blood purification therapies in sepsis [1]. We congratulate the authors for their excellent work. There are issues that we want to highlight and comment on.&lt;/p&gt;&lt;p&gt;The authors highlighted the extreme difficulty in demonstrating the effectiveness of these therapies in large randomized studies, with mortality as the primary end-point. Practical experience teaches that in critically ill patients the effectiveness, in terms of survival, of some therapeutic approaches with great clinical impact (volume filling, the use of diuretics, extracorporeal replacement treatment, and so on) can be very different from patient to patient, resulting in the same treatment being beneficial to one patient, and not beneficial, or even deleterious for another patient. Treatment must be directed at targets tailored for the individual patient, not at common target values that may be appropriate for some but certainly not for all [2].&lt;/p&gt;&lt;p&gt;Among these therapies, the potential benefits of coupled-plasma filtration adsorption (CPFA) were first documented in patients with Acute Kidney Injury (AKI) on Continuous Kidney Replacement Therapy (CKRT) [1] and later confirmed in a cohort of burn ICU patients undergoing CKRT [3]. A significant reduction in mortality was observed in the group of 39 burn patients treated with CKRT-CPFA, compared to the group of 87 patients treated with CKRT alone (51.3% and 77.1%, respectively). Then, the next Compact-2 study, which compared patients with septic shock treated with CKRT-CPFA (CPFA-CKRT group) as an adjunctive therapy and patients who did not receive it (control group), could not confirm the benefit. The study was prematurely stopped because of a suspected excess of early mortality in the CPFA-treated group, particularly present in the CPFA-CKRT group among patients without renal failure, who would not have required per se the renal replacement therapy [1]. As an explanation of these surprising results, it has been hypothesized that extracorporeal therapy could eliminate a significant portion of antibiotics, particularly when an absorptive component was associated with it. Concerning a life-saving antibiotic such as colistin, during CPFA-CKRT plasma perfusion was very efficient in removing the drug, as the post-cartridge colistin concentration was not detectable [3, 4]. Therefore, CPFA could be harmful to subject a patient with septic shock but good renal function. Because of CPFA-CKRT doubling the purifying function some substances such as antibiotic therapy at standard dosage could be eliminated at an excessive rate [1, 4].&lt;/p&gt;&lt;p&gt;Nowadays CytoSorb® is one of the most promising sorbent therapy currently available for septic shock. Recently it has been documented that in burn patients on CKRT with septic shock, and poorly responsive to therapy, an additive CytoSorb® treatment was associated with an improvement in clinical outcome and reduced in-ho","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"48 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044139","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":"Solid-state esophageal pressure sensor for the estimation of pleural pressure: a bench and first-in-human validation study","authors":"Julien P. van Oosten, Nico Goedendorp, Amne Mousa, Rutger C. Flink, Rik Schaart, Merel Flinsenberg, Peter Somhorst, Diederik A. M. P. J. Gommers, Leo Heunks, Annemijn H. Jonkman","doi":"10.1186/s13054-025-05279-w","DOIUrl":"https://doi.org/10.1186/s13054-025-05279-w","url":null,"abstract":"Advanced respiratory monitoring through the measurement of esophageal pressure (Pes) as a surrogate of pleural pressure helps guiding mechanical ventilation in ICU patients. Pes measurement with an esophageal balloon catheter, the current clinical reference standard, needs complex calibrations and a multitude of factors influence its reliability. Solid-state pressure sensors might be able to overcome these limitations. To evaluate the accuracy of a new solid-state Pes transducer (Pessolid). We hypothesized that measurements are non-inferior to those obtained with a properly calibrated balloon catheter (Pesbal). Absolute and relative solid-state sensor Pes measurements were compared to a reference pressure in a 5-day bench setup, and to simultaneously placed balloon catheters in 15 spontaneously breathing healthy volunteers and in 16 mechanically ventilated ICU patients. Bland–Altman analysis was performed using mixed effects modelling with bootstrapping to estimate bias and upper and lower limits of agreement (LoA) and their confidence intervals. Bench study: Solid-state pressure transducers had a positive bias (Psolid – Pref) of around 1 cmH2O for the absolute minimal and maximum pressures, and no bias for pressure swings. Healthy volunteers: the solid-state transducer revealed a bias (i.e., Pessolid – Pesbal) [upper LoA; lower LoA] of 1.59 [8.21; − 5.02], − 2.32 [4.27; − 8.92] and 3.91 [11.04; − 3.23] cmH2O for end-expiratory, end-inspiratory and ΔPes values, respectively. ICU patients: the solid-state transducer showed a bias (Pessolid–Pesbal) [upper LoA; lower LoA] during controlled/assisted ventilation of: − 0.15 [1.41; − 1.72]/− 0.19 [5.23; − 5.62], 0.32 [3.45; − 2.82]/− 0.54 [4.81; − 5.90] and 0.47 [3.90; − 2.96]/0.35 [4.01; − 3.31] cmH2O for end-expiratory, end-inspiratory and ΔPes values, respectively. LoA were ≤ 2cmH2O for static measurements on controlled ventilation. The novel solid-state pressure transducer showed good accuracy on the bench, in healthy volunteers and in ventilated ICU-patients. This could contribute to the implementation of Pes as advanced respiratory monitoring technique. Clinicaltrials.gov identifier: NCT05817968 (patient study). Registered on 18 April 2023.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"113 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044138","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":"A few words of caution on blood purification in sepsis","authors":"Klaus Stahl, Pedro David Wendel-Garcia, Christian Bode, Sascha David","doi":"10.1186/s13054-025-05268-z","DOIUrl":"https://doi.org/10.1186/s13054-025-05268-z","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;With great interest we read the recent review by &lt;i&gt;Bottari &lt;/i&gt;et al&lt;i&gt;.&lt;/i&gt; describing various technologies and concepts of extracorporeal blood purification (EBP) in patients with sepsis [1]. We would like to congratulate the authors for their thorough and balanced review of the challenges associated with EBP in sepsis. However, it must be underlined that the clinical use of EBP remains complex and is not yet supported by robust evidence. We believe that the current review, by presenting concrete suggestions for routine clinical application, is partly too optimistic and could potentially lead to overuse and inadvertent harm. We have selected a few examples that may serve as a basis for further discussion:&lt;/p&gt;&lt;p&gt;While we agree with the overall conclusions of this review, we respectfully disagree with the &lt;i&gt;“considerations for current clinical practice”&lt;/i&gt; proposed by our esteemed colleagues. Specifically, given the concerning signals of harm from recent studies [2, 3] and the significant knowledge gaps related to optimal timing, dosing, immune monitoring and compartmentalization, we believe that EBP should not be used in routine clinical practice. Instead, it should remain restricted to clinical trials. How can we justify personalizing treatment when we currently lack the essential understanding needed to determine how this could be effectively achieved?&lt;/p&gt;&lt;p&gt;The authors further suggest rather arbitrarily chosen cut-offs of vasopressor support, SOFA score, lactate, and Interleukin (IL)-6 concentrations for considering cytokine hemoadsorption in patients with sepsis. Their suggested cut-off values are retrieved from uncontrolled retrospective registers and observational studies but not from randomized trials. Realistically, these suggested cut-offs apply to many patients with septic shock and, therefore, do not warrant the term “personalized medicine”. In a larger propensity-score-matched analysis suggesting improved outcomes with cytokine adsorption, the patients exhibited severe refractory shock indicated by significant higher vasopressor doses (mean norepinephrine 0.48 ug/kg/min) and lactate concentrations (mean 6.4 mmol/l) at study inclusion [4]. Comparable high shock severity was also found in two prospective studies demonstrating rapid hemodynamic stabilization following TPE [5, 6]. Interestingly, in these studies, especially lactate concentrations at baseline were strong predictors of subsequent treatment response [7]. Nevertheless, patient selection by means of biomarkers for EBP remains more than elusive [3], and future research on predicting treatment response to extracorporeal blood purification therapies in septic shock should focus on exploring patient-specific approaches, such as biomarker-driven identification of inflammatory or coagulopathic [8, 9] sepsis phenotypes.&lt;/p&gt;&lt;p&gt;Another concerning suggestion by Bottari et al. is the proposed sorbent change interval of 12–24 h, for which we believe there is curr","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"113 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031042","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":"Pulmonary pathology in culture-negative sepsis: a potential confounder for sepsis treatment and research","authors":"Brett Biebelberg","doi":"10.1186/s13054-025-05267-0","DOIUrl":"https://doi.org/10.1186/s13054-025-05267-0","url":null,"abstract":"&lt;p&gt;The recent study by Chang et al. observed differences between sepsis with positive cultures and sepsis with negative cultures [1]. Given the significant frequency and mortality of sepsis associated with pulmonary infection [2], there remains a need to explain why pulmonary infection and respiratory failure were more common in the culture-negative sepsis cohort than the culture-positive cohort. Two hypotheses may help explain these findings.&lt;/p&gt;&lt;p&gt;First, the imperfect sensitivity of culture data can make identifying bacterial pulmonary pathogens challenging. Lack of hematogenous spread from the lungs may limit the utility of blood cultures in diagnosing bacterial pneumonia [3]. Even when sputum cultures are obtained, only a minority of samples may be diagnostic due to limitations of sample yield, contamination, or sensitivity [4].&lt;/p&gt;&lt;p&gt;Second, a number of these culture-negative “pulmonary infections” may have been misdiagnosed. Many non-infectious conditions can mimic pneumonia on chest radiography, including pulmonary edema, malignancy, interstitial lung disease, and pneumonitis from aspiration or medication. These pulmonary pathologies can also cause respiratory compromise and, therefore, the worsened PaO2/FiO2 ratios observed by the authors in their culture-negative cohort. In our own prior analysis of culture-positive sepsis vs. culture negative sepsis, we, too, found diagnosis of pneumonia and initiation of mechanical ventilation were more common in our culture-negative cohort, offering validation of the authors’ findings [5]. However, when we completed a post-hoc review of chest imaging from culture-negative sepsis patients with presumed pulmonary infection, we found their chest imaging was commonly interpreted by radiologists as having equivocal findings. In the absence of true infection, many of these patients may not have had sepsis at all.&lt;/p&gt;&lt;p&gt;Pulmonary pathology in culture-negative sepsis may therefore represent a confounding factor in sepsis treatment and investigation: a subset of patients who either have infectious pathogens that are difficult to identify, or who lack infection altogether and therefore won’t respond to antibiotics.&lt;/p&gt;&lt;p&gt;I thank the authors for their valuable contribution and hope this perspective aids in the interpretation of their findings.&lt;/p&gt;&lt;p&gt;No datasets were generated or analysed during the current study.&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;Chang Y, Oh JH, Oh DK, et al. Culture-negative sepsis may be a different entity from culture-positive sepsis: a prospective nationwide multicenter cohort study. Crit Care. 2024;28:385. https://doi.org/10.1186/s13054-024-05151-3.&lt;/p&gt;&lt;p&gt;Article PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;li data-counter=\"2.\"&gt;&lt;p&gt;Biebelberg B, Rhee C, Chen T, McKenna C, Klompas M. Heterogeneity of sepsis presentations and mortality rates. Ann Intern Med. 2024;177(7):985–7. https://doi.org/10.7326/M24-0400.&lt;/p","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"138 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027229","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 role of programmed cell death in organ dysfunction induced by opportunistic pathogens","authors":"Yangyanqiu Wang, Li Weng, Xunyao Wu, Bin Du","doi":"10.1186/s13054-025-05278-x","DOIUrl":"https://doi.org/10.1186/s13054-025-05278-x","url":null,"abstract":"Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple organ dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, and intestinal systems. It is well-established that pathogen infections lead to immune dysregulation, which subsequently contributes to MODS in sepsis. However, recent evidence suggests that sepsis-related opportunistic pathogens can directly induce organ failure by promoting PCD in parenchymal cells of each affected organ. This study provides an overview of PCD in damaged organ and the induction of PCD in host parenchymal cells by opportunistic pathogens, proposing innovative strategies for preventing organ failure in sepsis.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"63 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027230","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}