Critical Care最新文献

{"title":"Rethinking PbtO₂ responses to hyperoxemia: laying the groundwork for a new approach to multimodal neuromonitoring","authors":"Gurgen Harutyunyan Hovhanisyan, Garnik Harutyunyan Jaghatspanyan, Suren Soghomonyan","doi":"10.1186/s13054-025-05502-8","DOIUrl":"https://doi.org/10.1186/s13054-025-05502-8","url":null,"abstract":"The interpretation of brain tissue oxygen tension (PbtO₂) in neurocritical care remains controversial, particularly during hyperoxemic conditions. In this comment on the article by Bögli et al., we propose that the observed rise in PbtO₂ following increased FiO₂ may be better explained by the conformational transition of hemoglobin from the relaxed (R) to the tense (T) state at the end of cerebral capillaries. This shift, which enhances oxygen release and buffering capacity, helps maintain arterial-like oxygen tension despite low venous oxygen saturation. We discuss the implications of this mechanism for understanding multimodal neuromonitoring (MMM) data, the effects of cerebral autoregulation, and the role of blood storage lesions. Recognizing hemoglobin conformation as a physiological determinant may help refine MMM thresholds and neuroprotective strategies in traumatic brain injury.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"25 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246567","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":"Discovery of a resistant cohort to acute kidney injury: insights from patients with septic shock","authors":"Dana Y. Fuhrman, Towia A. Libermann, Neil A. Hukriede, Luca Molinari, Samir M. Parikh, John A. Kellum","doi":"10.1186/s13054-025-05647-6","DOIUrl":"https://doi.org/10.1186/s13054-025-05647-6","url":null,"abstract":"Acute kidney injury (AKI) is a significant complication among critically ill patients, particularly those with sepsis, yet no specific therapies exist. Progress in some diseases has been achieved by analyzing individuals who appear resistant. This study sought to develop a framework to investigate AKI resistance using clinical phenotyping and biomarkers and applied this framework to a large cohort of patients with septic shock. We performed a retrospective analysis of patients enrolled in the Protocolized Care for Early Septic Shock (ProCESS) trial. We measured urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein 7 (IGFBP7), and kidney injury molecule 1 (KIM-1) 6 h after the start of resuscitation. AKI was defined first as high risk by [TIMP-2]•[IGFBP7] > 1.0 (ng/mL)²/1000 and either meeting Kidney Disease Improving Global Outcomes Criteria (KDIGO) criteria within 7 days after the start of resuscitation or having [KIM-1] > 2.0 ng/ml. AKI resistance was defined as the combination of (a) high-risk by [TIMP-2]•[IGFBP7] > 1.0 (ng/mL)²/1000 but without meeting (b) KDIGO AKI criteria nor (c) [KIM-1] > 2.0 ng/ml. We compared clinical characteristics and outcomes across three groups: AKI-resistant, AKI, and reduced risk, which was defined as [TIMP-2]•[IGFBP7] < 1.0 (ng/mL)²/1000. Among 573 patients, 339 (59.2%) had reduced risk, 194 (33.9%) developed AKI, and 40 (7%) were AKI-resistant. Median (IQR) non-renal SOFA scores were lower for patients at reduced risk for AKI (5 [2–7]) than for those with AKI resistance (6 [4.5-8], P < 0.01) or AKI (6 [5–9], P < 0.01). Baseline characteristics did not differ between AKI-resistant and AKI-affected individuals. However, AKI-resistant patients experienced significantly lower 30-day mortality (10% vs. 32%; adjusted OR 0.26, 95% CI: 0.09–0.80, P = 0.02) and shorter ICU stays when compared to those with AKI. Despite greater illness severity, AKI-resistant patients had similar mortality and length of stay as lower-risk patients but better outcomes than those with AKI. Studying these patients may reveal novel therapeutic targets for AKI prevention and treatment.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"1 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241870","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":"ApoA1/HDL and sepsis-associated vascular endothelial injury: a narrative review","authors":"Kailin Guo, Chang Hu, Le Li, Xiao Liu, Yaohui Liu, Dongsu Zhang, Yujie Fang, Yiming Li, Bo Hu","doi":"10.1186/s13054-025-05668-1","DOIUrl":"https://doi.org/10.1186/s13054-025-05668-1","url":null,"abstract":"Sepsis remains a leading cause of global mortality, primarily driven by microvascular collapse stemming from severe vascular endothelial injury. Within this pathology, the dramatic depletion of Apolipoprotein A1 (ApoA1) and its carrier, high-density lipoprotein (HDL), is a hallmark feature. Despite being recognized as a prognostic biomarker, a comprehensive understanding of the ApoA1/HDL axis as an active participant and therapeutic target in endothelial protection remains fragmented. This review systematically synthesizes current evidence to reframe the ApoA1/HDL axis from a passive indicator to a master regulator of endothelial homeostasis in sepsis. We first delineate the strong correlation between reduced ApoA1/HDL levels and endothelial damage across various infections. Subsequently, we dissect its protective triad of mechanisms: potent anti-inflammatory actions, preservation of endothelial barrier integrity, and restoration of microvascular flow. Furthermore, we explore the emerging interplay between ApoA1 and exosomes, a novel aspect of its regulatory function. Finally, the translational potential of ApoA1-based therapies, including mimetic peptides and recombinant HDL, is evaluated. By providing an integrated mechanistic framework, this review highlights the ApoA1 as a critical therapeutic target and offers a roadmap for developing novel, endothelium-centric treatments for sepsis.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"34 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241872","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":"Reconsidering the urea-to-creatinine ratio as a signal of muscle catabolism in patients with cirrhosis","authors":"Abderrahim Oussalah, Vincent Haghnejad, Alexia Audouy, Maël Silva Rodriguez, Jean-Louis Guéant, Farès Namour, Jean-Pierre Bronowicki","doi":"10.1186/s13054-025-05703-1","DOIUrl":"https://doi.org/10.1186/s13054-025-05703-1","url":null,"abstract":"&lt;p&gt;Dear editor&lt;/p&gt;&lt;p&gt;We read with great interest the recent systematic review and meta-analysis by Paulus MC et al. evaluating the role of the urea-to-creatinine ratio (UCR) as a biomarker of protein catabolism in critically ill patients [1]. The authors should be commended for this comprehensive and methodologically rigorous synthesis, and for underscoring the potential value of an inexpensive, widely available index to inform metabolic assessment and nutrition in the intensive care setting. This is an essential contribution to an area with limited validated bedside biomarkers of catabolic state.&lt;/p&gt;&lt;p&gt;Nonetheless, the interpretation of UCR in patients with cirrhosis and portal hypertension warrants caution [2,3,4,5]. This issue is clinically relevant, as individuals with chronic or advanced liver disease account for a significant proportion of admissions to intensive care and extended care units, with large national cohorts and systematic reviews consistently reporting proportions between 2% and 4.5% of all intensive care admissions [2]. Multicenter data indicate marked variability in ICU burden, with cirrhosis accounting for more than 20% of cases in some centers and up to one-third of patients with chronic liver disease requiring high-dependency or ICU support [3, 4].&lt;/p&gt;&lt;p&gt;Common reasons for ICU admission in patients with cirrhosis include decompensation, acute-on-chronic liver failure, variceal hemorrhage, and hepatorenal syndrome. In this subgroup, both components of the ratio, urea and creatinine, are systematically influenced by processes unrelated to acute protein catabolism, including impaired ureagenesis and sarcopenia [5]. As a result, UCR values in cirrhosis are vulnerable to misclassification if interpreted as direct surrogates of protein catabolism. Failure to account for this subgroup in pooled analyses of critically ill patients may therefore introduce bias, either inflating or attenuating the apparent association between UCR and catabolic state.&lt;/p&gt;&lt;p&gt;On the creatinine side, alterations in cirrhosis primarily reflect impaired muscle homeostasis rather than increased muscle catabolism. Sarcopenia, observed in 14% to 55% of patients with cirrhosis [6, 7], is associated with reduced skeletal muscle mass, which depletes creatine reserves and lowers creatinine generation [8, 9]. In addition, liver disease–related mechanisms further decrease measured creatinine without reflecting improved glomerular filtration, including impaired hepatic creatine synthesis, increased fractional tubular secretion (spontaneous or drug-induced), and analytical underestimation in the setting of hyperbilirubinemia [5, 10]. The combined effect of these processes is a downward shift in serum creatinine for any given actual glomerular filtration rate, so that an elevated UCR in cirrhosis may primarily reflect reduced creatinine production rather than increased protein catabolism.&lt;/p&gt;&lt;p&gt;On the urea side, portal hypertension and hepatocellular dysfunction alte","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"24 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241871","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":"Distinct pathogen spectrum in immunocompromised patients with severe pneumonia","authors":"Wenxiao Zhang, Lingtong Huang, Huanzhang Shao","doi":"10.1186/s13054-025-05704-0","DOIUrl":"https://doi.org/10.1186/s13054-025-05704-0","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Dear editor,&lt;/b&gt;&lt;/p&gt;&lt;p&gt;We read with great interest the manuscript by Contier et al. published in Critical Care [1]. This is a valuable study that highlights the use of rapid molecular pathogen detection in immunocompromised patients—a population in urgent need of early and accurate diagnostic strategies. However, we would like to raise several concerns for consideration by the authors and the readership of Critical Care.&lt;/p&gt;&lt;p&gt;First, the Pneumonia multiplex PCR assay employed in the study detects only 18 bacterial species. Although multiplex PCR offers advantages in terms of speed and sensitivity, its limited pathogen coverage is a significant drawback, particularly in immunocompromised individuals, whose infectious profiles often differ markedly from those of the general population.&lt;/p&gt;&lt;p&gt;In this context, we would like to share insights from our own multicenter retrospective study using metagenomic sequencing. This cohort, previously described in a series of publications, included bronchoalveolar lavage fluid samples from both immunocompromised and immunocompetent patients [2,3,4,5,6,7,8,9]. Our findings revealed substantial differences in pathogen distribution: immunocompromised patients exhibited significantly higher rates of CMV, EBV, Pneumocystis jirovecii, and Aspergillus spp., while typical bacterial pathogens such as Acinetobacter baumannii, Burkholderia cenocepacia, and Klebsiella pneumoniae were less frequently detected (Fig. 1). This suggests that the diagnostic yield of Pneumonia multiplex PCR is likely to be significantly lower in immunocompromised patients compared to immunocompetent individuals.&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 1&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-025-05704-0/MediaObjects/13054_2025_5704_Fig1_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"202\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-025-05704-0/MediaObjects/13054_2025_5704_Fig1_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;Differences in pathogen isolation by clinical metagenomics between immunocompromised and immunocompetent patients. As this is an exploratory analysis, no multiple testing correction was applied. *, p &lt; 0.05; **, p &lt; 0.01; ***, p &lt; 0.001&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;p&gt;Second, co-detection of multiple pathogens is more common in immunocompromised patients, with clinically relevant co-infections frequently involving viruses and fungi rather than bacteria. This further limit the diagnostic utility of a bacteria-restricted panel in this vulnerable population.&lt;/p&gt;&lt;p&gt;In summary, while the study by Jérémy et al. offers meaningful insights for clinica","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"8 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241873","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":"Potential therapeutic benefit of exogenous ketone ester administration in delirium: a narrative review","authors":"Ryan Smith, Fiona Harrison, Julie Bastarache, Shawniqua Williams Roberson, Elma Zaganjor, Pratik Pandharipande, Todd Rice, Wes Ely","doi":"10.1186/s13054-025-05680-5","DOIUrl":"https://doi.org/10.1186/s13054-025-05680-5","url":null,"abstract":"Delirium is a prevalent neuropsychiatric syndrome during critical illness and is associated with prolonged hospitalization, increased mortality, and post-ICU cognitive decline. It is hypothesized to result from systemic inflammation, disrupted neurotransmission, and failure of cerebral energy metabolism. This narrative review highlights the key role of altered neurometabolism and neuroinflammation, which occurs due to peripheral inflammation, compromised blood-brain barrier integrity, and increased microglial glycolysis. These changes limit neuronal glucose uptake, leading to a brain energy crisis and consequently amplifying oxidative and inflammatory stress. We focus on studies of ICU delirium in the setting of acute critical illness with an emphasis on sepsis-associated encephalopathy, where mechanistic data derived from murine models are most robust. Ketones bypass the glycolytic bottleneck and enter the tricarboxylic acid cycle directly, activating signaling pathways that enhance mitochondrial biogenesis, bolster antioxidant defenses, modulate neurotransmission, and reduce inflammation. In models of neurodegenerative diseases and traumatic brain injury, ketosis restores cerebral metabolism, reduces neuroinflammation, and enhances cognitive function. Additionally, preliminary human studies have demonstrated cognitive benefits and patient tolerance of ketone supplementation. Although data in the critically ill are limited, pilot studies suggest that enteral ketone supplementation can safely achieve therapeutic serum concentrations without worsening acidosis or hemodynamic instability. We hypothesize that exogenous ketone ester supplementation may support brain energy production by providing an alternative substrate for energy production, reducing microglial substrate competition, and mitigating the neuronal stress that precipitates delirium. In conclusion, exogenous ketone esters are a biologically plausible, rapidly acting metabolic intervention that warrants rigorous clinical evaluation as a novel strategy to prevent or treat delirium in those who are critically ill. However, randomized controlled trials are essential for verifying safety, determining optimal dosing, and assessing clinical effectiveness in the intensive care setting. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"8 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235940","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":"Beyond diabetes: harnessing the power of metformin in burn care","authors":"Fadi Khalaf, Daniella Touma, Sean Saldanha, Georges Khalaf, Dalia Barayan, Marc G. Jeschke","doi":"10.1186/s13054-025-05662-7","DOIUrl":"https://doi.org/10.1186/s13054-025-05662-7","url":null,"abstract":"Burn injuries are complex and devastating traumas that trigger a profound systemic metabolic response, characterized by hyperglycemia, insulin resistance, and a hypermetabolic state. Notably, hyperglycemia is a critical determinant of worse prognoses in burn patients. While insulin has long been the gold standard for managing post-burn hyperglycemia, its therapy is associated with a risk of hypoglycemic events, which can exacerbate morbidity and compromise patient outcomes. As such, investigation of alternative therapeutics is warranted to improve glycemic control while mitigating associated risks. Recently, metformin, a first-line therapy for the treatment of type II diabetes, has emerged as a potential therapeutic agent for the management of post-burn hyperglycemia as well as other burn injury sequelae. This review examines the mechanistic underpinnings of metformin, its potential application in managing post-burn hyperglycemia, and its comparative advantages over other hypoglycemic agents. Additionally, we examine the broad spectrum of metformin’s pleiotropic effects in the context of burn injury–extending beyond glycemic control to include attenuation of muscle catabolism, suppression of lipolysis, regulation of non-shivering thermogenesis, support of mitochondrial and immune function, enhanced wound healing, and its potential role in addressing burn-induced acceleration of biological aging. Taken together, we discuss how metformin represents a paradigm shift in burn care, with the potential to substantially improve patient outcomes.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"30 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235950","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":"Letter to the authors of “Mind the drain: expanding TIMING-ICP discussion” and to the author of “Rethinking the clinical impact of timing in ICP monitoring initiation”","authors":"Lara Mariani, Frank Rasulo","doi":"10.1186/s13054-025-05699-8","DOIUrl":"https://doi.org/10.1186/s13054-025-05699-8","url":null,"abstract":"&lt;p&gt;We read with great interest the response letter by Brasil et al. [1] to our recent study [2], as it raised several important points regarding the management of invasive intracranial pressure (ICP) monitoring.&lt;/p&gt;&lt;p&gt;We fully agree that the choice of monitoring technique should be guided by clinical needs, since conditions such as hydrocephalus and subarachnoid or intraventricular hemorrhage usually require cerebrospinal fluid drainage through an external ventricular drain (EVD). As the authors rightly noted, this procedure is technically more complex, falls within the neurosurgical domain, and therefore understandably requires longer procedural times. This trend was also observed in our analysis, although the difference did not reach statistical significance due to the limited sample size.&lt;/p&gt;&lt;p&gt;It is important to emphasize that the primary objective of our study was to directly compare intraparenchymal catheter placement performed by intensivists and neurosurgeons within the ICU. In this context, the differences in intervention times proved to be statistically significant. The timing of device placement in other settings (e.g., EVDs used exclusively for intracranial pressure monitoring or intraparenchymal catheters placed in the operating room) were included only as a secondary analysis. Since these procedures were rarely observed during the data collection period of the study, we subsequently continued the investigation by including only intraparenchymal catheters placed in the ICU, in order to obtain comparable groups based on the operator (intensivist vs. neurosurgeon) rather than on the type of procedure.&lt;/p&gt;&lt;p&gt;Complication rates were also compared between groups as a secondary outcome. Since the study was not powered to detect statistically significant differences in this regard, their occurrence was instead analyzed according to device type and found to be consistent with complication rates reported in the literature.&lt;/p&gt;&lt;p&gt;Looking ahead, future research should focus on whether earlier initiation of ICP monitoring translates into better patient outcomes. In fact, as mentioned by Citerio in another accompanying editorial regarding our work and published in this journal, we must bear in mind that although reducing time to insertion is certainly attractive, the real issue is whether earlier ICP values translate into meaningful therapeutic decisions and improved outcomes. A recent systematic review and meta-analysis by Abdollahifard et al. [3] addressed this question but found no significant differences in outcomes between early and late monitoring. These findings, however, require cautious interpretation given certain methodological limitations, some of which were already highlighted in Citerio’s commentary [4]. Most importantly, as emphasized in prior literature by Chesnut [5], ICP monitoring is not a treatment in itself: its true value lies in how clinicians interpret and act upon the information it provides, ideally within a multimodal m","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"106 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235941","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":"Xuebijing injection reduces 28-day mortality in patients with septic shock","authors":"Jing Kang, Dingji Hu, Yixuan Li, Lufeng Ma, Hui Chen, Jianfeng Xie, Yi Yang, Tianyi Yang, Zhiqiao Feng, Yan Liu, Haibo Qiu, Songqiao Liu, Chi Zhang","doi":"10.1186/s13054-025-05666-3","DOIUrl":"https://doi.org/10.1186/s13054-025-05666-3","url":null,"abstract":"&lt;p&gt;Over the past decade, more than 80% of randomized controlled trials (RCTs) in septic shock have failed to identify effective pharmacologic therapies (Supplemental Content 1) [1], underscoring the urgent need for effective treatments. Xuebijing (XBJ) has demonstrated promising efficacy in two recent large-scale RCTs, the EXIT-SEP (&lt;i&gt;n&lt;/i&gt; = 1817) [2] and XBJ-SCAP (&lt;i&gt;n&lt;/i&gt; = 710) [3] trials, by significantly reducing 28-day mortality among patients with sepsis or severe community-acquired pneumonia. However, neither trial specifically targeted patients with septic shock, leaving it uncertain whether XBJ provides a survival benefit in this high-risk subgroup. To address this gap, we conducted a harmonized individual patient-level analysis of both trials (Table S1) to evaluate the association between XBJ treatment and mortality in septic shock.&lt;/p&gt;&lt;p&gt;We reanalyzed patient-level data from EXIT-SEP (NCT03238742) and XBJ-SCAP (ChiCTR-TRC-13003534) to construct a harmonized cohort of patients meeting Sepsis-3 criteria for septic shock. Trial elements, including eligibility criteria, treatment strategies, and follow-up periods, were aligned to ensure consistency across studies (Table S1). Septic shock was defined as infection with a vasopressor requirement to maintain mean arterial pressure ≥ 65 mmHg and a lactate concentration &gt;2 mmol/L at baseline [4]. Patients were randomized to receive either intravenous XBJ (100 mL with saline every 12 h for 5 days) or matching placebo, in addition to standard care. The primary outcome was 28-day all-cause mortality; secondary outcomes included ventilator-free and ICU-free days.&lt;/p&gt;&lt;p&gt;A total of 869 patients fulfilled eligibility criteria (432 randomized to XBJ and 437 to placebo). Eight patients (5 XBJ, 3 placebo) were lost to follow-up at day 28, leaving 861 for complete outcome analysis (Figure S1). Baseline characteristics showed no significant imbalances between groups. Selected variables are shown in Fig. 1A, with the full set of baseline data available in the Supplementary Material (Table S2, S3).&lt;/p&gt;&lt;p&gt;At 28 days, 99 of 427 patients in the XBJ group (23.2%) and 132 of 434 in the placebo group (30.4%) had died, corresponding to an absolute risk reduction of 7.2% (95% CI, 1.3–13.1; &lt;i&gt;p&lt;/i&gt; = 0.02) (Fig. 1B, Table S4). Patients treated with XBJ had more ventilator-free days (mean difference, 2.0; 95% CI, 0.5–3.5; &lt;i&gt;p&lt;/i&gt; = 0.01) and ICU-free days (mean difference, 1.7; 95% CI, 0.4–3.0; &lt;i&gt;p&lt;/i&gt; = 0.02). Additionally, improvement in organ dysfunction, as measured by the SOFA score, was more pronounced by day 6 in the XBJ group (mean difference, − 1.0; 95% CI, − 1.5 to − 0.5; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), indicating enhanced recovery from critical illness (Table S4). Other secondary outcomes, including ICU mortality, hospital length of stay, and APACHE II score changes, did not differ significantly between groups (Table S4). Serious adverse event rates were similar between groups, suggesting no excess safety ris","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"37 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228747","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":"Post-intensive care unit clinics: models and implementation - a systematic review","authors":"Sourav Chatterjee, Swagata Tripathy, Subhasish Nayak, Reena Chakravarty, Parnandi Bhaskar Rao","doi":"10.1186/s13054-025-05634-x","DOIUrl":"https://doi.org/10.1186/s13054-025-05634-x","url":null,"abstract":"Advances in critical care have shifted the focus from survival alone to addressing Post-Intensive Care Syndrome (PICS), which includes persistent physical, cognitive, and psychological challenges after discharge from the intensive care unit (ICU). While post-ICU clinics have been established in high-income countries (HICs), their adoption in low- and middle-income countries (LMICs) remains limited, with structured follow-up care still under development. To systematically review models of post-ICU clinics, examine barriers and facilitators to their implementation, and explore their potential applicability in LMICs. This review was prospectively registered with PROSPERO (CRD42024536147) and conducted according to PRISMA guidelines. A comprehensive search of Medline, Embase, and CINAHL was completed on April 24, 2024. Studies published after 2000 describing adult post-ICU clinic models addressing PICS were included. Nineteen studies—comprising randomized controlled trials, observational studies, and quasi-experimental designs—met inclusion criteria. Risk of bias was assessed using the Joanna Briggs Institute checklists. Thematic synthesis was guided by the Consolidated Framework for Implementation Research (CFIR). Three primary models emerged: (1) hospital-based physical interviews (2), hybrid models incorporating both in-person and telehealth consultations, and (3) fully remote models using telehealth or home visits. Telehealth/home-visit models reported the highest mean attendance (88.7%), followed by hybrid (59%) and physical interview models (51.9%). Common barriers included resource constraints, transportation difficulties, limited awareness, inadequate insurance coverage, and poor interdisciplinary coordination. Facilitators included flexible scheduling, early stakeholder engagement, multidisciplinary team involvement, and use of telehealth technologies. While hybrid models appeared promising for LMICs due to their balance of accessibility and comprehensiveness, the evidence for clinical outcome benefit remains inconclusive, and questions about cost-effectiveness and sustainability persist. Hybrid post-ICU clinic models may offer a feasible pathway for improving follow-up care in LMICs, especially when tailored to local constraints. However, their implementation must consider significant barriers, particularly related to funding and infrastructure, and be guided by emerging but still limited evidence on long-term patient outcomes. These findings aim to inform cautious, context-specific development of post-ICU care strategies in resource-limited settings.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"32 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228751","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}