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Purpose: Optimal timing of intubation is controversial. We attempted to investigate the association between timing of intubation and clinical outcomes of critically ill patients., Methods: PubMed was systematically searched for studies reporting on mortality of critically ill patients undergoing early versus late intubation. Studies involving patients with new coronavirus disease (COVID-19) were excluded because a relevant meta-analysis has been published. "Early" intubation was defined according to the authors of the included studies. All-cause mortality was the primary outcome. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42021284850)., Results: In total, 27 studies involving 15,441 intubated patients (11,943 early, 3498 late) were included. All-cause mortality was lower in patients undergoing early versus late intubation (7338 deaths; 45.8% versus 53.5%; RR 0.92, 95% CI 0.87-0.97; p = 0.001). This was also the case in the sensitivity analysis of studies defining "early" as intubation within 24 h from admission in the intensive care unit (6279 deaths; 45.8% versus 53.6%; RR 0.93, 95% CI 0.89-0.98; p = 0.005)., Conclusion: Avoiding late intubation may be associated with lower mortality in critically ill patients without COVID-19., Competing Interests: Declaration of Competing Interest None declared for all authors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Despite numerous publications on mitochondrial DNA (mtDNA) in the last decade it remains to be seen whether mtDNA can be used clinically. We conducted a systematic review to assess circulating cell-free mtDNA as a biomarker of mortality in critically ill patients., Methods: This systematic review was registered with PROSPERO (CRD42016046670). PubMed, CINAHL, the Cochrane Library, Embase, Scopus, and Web of Science, and reference lists of retrieved articles were searched. Studies measuring circulating cell-free mtDNA and reporting on all-cause mortality in critically ill adult and pediatric patients were included. The primary and secondary outcomes were mortality and morbidity, respectively., Results: Of the 1,566 initially retrieved publications, 40 studies were included, accounting for 3,450 critically ill patients. Substantial differences between studies were noted in how mtDNA was isolated and measured. Sixteen of the 40 included studies (40%) explored the association between mtDNA levels and mortality; of those 16 studies, 11 (68.8%) reported a statistically significant association. The area under the receiver operating characteristic (AUROC) curve for mtDNA and mortality was calculated for 10 studies and ranged from 0.61 to 0.95., Conclusions: There is growing interest in mtDNA as a predictor of mortality in critically ill patients. Most studies are small, lack validation cohorts, and utilize different protocols to measure mtDNA. When reported, AUROC analysis usually suggests a statistically significant association between mtDNA and mortality. Standardization of mtDNA protocols and the completion of a large, prospective, multicenter trial may be warranted to firmly establish the clinical usefulness of mtDNA., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Necroptosis is a form of programmed necrotic cell death that is rapidly emerging as an important pathophysiological pathway in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3), a protein shown to play an important role in experimental models of critical illness. However, there is limited clinical evidence regarding the role of extracellular RIPK3 in human critical illness., Methods: Plasma RIPK3 levels were measured in 953 patients prospectively enrolled in 5 ongoing intensive care unit (ICU) cohorts in both the USA and Korea. RIPK3 concentrations among groups were compared using prospectively collected phenotypic and outcomes data., Results: In all 5 cohorts, extracellular RIPK3 levels in the plasma were higher in patients who died in the hospital compared with those who survived to discharge. In a combined analysis, increasing RIPK3 levels were associated with elevated odds of in-hospital mortality (odds ratio [OR] 1.7 for each log10-unit increase in RIPK3 level, P < 0.0001). When adjusted for baseline severity of illness, the OR for in-hospital mortality remained statistically significant (OR 1.33, P = 0.007). Higher RIPK3 levels were also associated with more severe organ failure., Conclusions: Our findings suggest that elevated levels of RIPK3 in the plasma of patients admitted to the ICU are associated with in-hospital mortality and organ failure., Funding: Supported by NIH grants P01 HL108801, R01 HL079904, R01 HL055330, R01 HL060234, K99 HL125899, and KL2TR000458-10. Supported by Samsung Medical Center grant SMX1161431.

Background: Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the benefit of early versus late or no tracheostomy on mortality and pneumonia in critically ill patients who need mechanical ventilation., Methods: We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. Mortality during the stay in the intensive-care unit was a composite endpoint of definite intensive-care-unit mortality, presumed intensive-care-unit mortality, and 28-day mortality. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis., Findings: Analyses of 13 trials (2434 patients, 648 deaths) showed that all-cause mortality in the intensive-care unit was not significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·80, 95% CI 0·59-1·09; p=0·16). This result persisted when we considered only trials with a low risk of bias (511 deaths; OR 0·80, 95% CI 0·59-1·09; p=0·16; eight trials with 1934 patients). Incidence of ventilator-associated pneumonia was lower in mechanically ventilated patients assigned to the early versus the late or no tracheostomy group (691 cases; OR 0·60, 95% CI 0·41-0·90; p=0·01; 13 trials with 1599 patients). There was no evidence of a difference between the compared groups for 1-year mortality (788 deaths; RR 0·93, 95% CI 0·85-1·02; p=0·14; three trials with 1529 patients)., Interpretation: The synthesised evidence suggests that early tracheostomy is not associated with lower mortality in the intensive-care unit than late or no tracheostomy. However, early, compared with late or no, tracheostomy might be associated with a lower incidence of pneumonia; a finding that could question the present practice of delaying tracheostomy beyond the first week after translaryngeal intubation in mechanically ventilated patients. Nevertheless, the scarcity of a beneficial effect on long-term mortality and the potential complications associated with tracheostomy need careful consideration; thus, further studies focusing on long-term outcomes are warranted., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: There is controversy on whether catheter-related bloodstream infections (CR-BSI) affect the mortality of critically ill patients., Design: Meta-analysis of comparative studies that reported on mortality of intensive care unit (ICU) adult patients with and without CR-BSI., Methods: PubMed, Current Contents, and reference lists of retrieved publications were searched with no language or time restrictions. Heterogeneity was assessed by means of I-statistic and chi-square test. Publication bias was detected by the funnel plot method using Egger's test. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated by implementing both the Mantel-Haenszel fixed effect and the DerSimonian-Laird random effects model., Results: Eight studies, involving 2,540 ICU patients, were included. Heterogeneity was detected (I = 0.67, 95% CI 0.32-0.85, p = 0.003). Publication bias was not found (Egger's test, p = 0.28). All-cause in-hospital mortality was higher in ICU patients with CR-BSI than in those without CR-BSI (fixed effect model: OR = 1.81, 95% CI 1.44-2.28; random effects model: OR = 1.96, 95% CI 1.25-3.09). This was also the case for the subgroup analysis of the studies that were matched for severity of illness (fixed effect model: OR = 1.65, 95% CI 1.28-2.13; random effects model: OR = 1.70, 95% CI 1.00-2.90)., Conclusion: Presence, as opposed to absence, of CR-BSI is associated with higher mortality in critically ill adult patients. This finding seems to justify and may enhance efforts to prevent CR-BSI in such patients.

There has been increasing concern regarding the rise of Acinetobacter infections in critically ill patients. We extracted information regarding the relative frequency of Acinetobacter pneumonia and bacteraemia in intensive-care-unit (ICU) patients and the antimicrobial resistance of Acinetobacter isolates from studies identified in electronic databases. Acinetobacter infections most frequently involve the respiratory tract of intubated patients and Acinetobacter pneumonia has been more common in critically ill patients in Asian (range 4-44%) and European (0-35%) hospitals than in United States hospitals (6-11%). There is also a gradient in Europe regarding the proportion of ICU-acquired pneumonias caused by Acinetobacter with low numbers in Scandinavia, and gradually rising in Central and Southern Europe. A higher proportion of Acinetobacter isolates were resistant to aminoglycosides and piperacillin/tazobactam in Asian and European countries than in the United States. The data suggest that Acinetobacter infections are a growing threat affecting a considerable proportion of critically ill patients, especially in Asia and Europe.

Introduction: There has been a continuing controversy about whether infection with Acinetobacter baumannii increases morbidity and mortality independently of the effect of other confounding factors., Methods: We performed a systematic review of matched case-control and cohort studies examining the mortality attributable to infection with or acquisition of A. baumannii (infection or colonization). We included in our review studies that compared mortality and/or morbidity of patients with acquisition of or infection with A. baumannii (cases) with the outcomes of matched patients without A. baumannii isolation from clinical specimens (controls). The relevant studies were identified from searches of the PubMed and the Cochrane Library databases. Two independent reviewers performed the literature search, study selection, and data extraction from nine identified relevant studies., Results: The attributable mortalities, in the hospital and in the intensive care unit, of patients with A. baumannii infection in six matched case-control studies included in our review ranged from 7.8% to 23% and from 10% to 43%, respectively. In addition, a statistically significantly higher mortality was reported for patients with A. baumannii acquisition; that is, colonization or infection (cases) compared with controls without such an acquisition in all four reviewed studies that reported data on this comparison., Conclusion: Although definitive statements about the mortality attributable to the acquisition of A. baumannii cannot be made from the available studies because of their methodological heterogeneity, the reviewed data suggest that infection with or acquisition of A. baumannii seems to be associated with increased mortality.