Background and Objectives: Chronic critical illness (CCI) is a growing problem in modern intensive care, though its pathophysiology remains incompletely defined. While the ICS triad is thought to perpetuate organ dysfunction, the temporal interplay between its components has not been studied. The objective was to characterize the temporal dynamics of each component and to assess their synchrony in CCI patients. Materials and Methods: This retrospective cohort study analyzed data from the Russian Intensive Care Dataset (RICD v3.0). Adult ICU patients with at least one documented ICS episode (CRP > 20 mg/L, albumin < 30 g/L, lymphocytes < 0.8 × 109/L within 24 h) were included. Daily binary statuses were generated for each domain using an episode-persistence algorithm. Pairwise concordance was assessed using Cohen’s κ with bootstrap resampling and generalized estimating equation (GEE) models; domain burden, episode frequency, and status combinations were also evaluated. Results: A total of 820 CCI patients contributed 18,525 non-critical patient-days. CRP and albumin domains were persistently positive (median burden 100% both), while lymphocyte positivity was brief (median burden 34.2%) and recurrent (≥2 episodes in 45.1%). CRP and lymphocyte domains were discordant in 81.2% of days (κ = −0.024; OR 0.60; Holm-adjusted p = 0.005); lymphocyte and albumin domains in 77.0% (κ = −0.021; OR 0.49; Holm-adjusted p < 0.001). CRP and albumin were largely concordant (78.5%; κ = 0.299; OR 2.71; Holm-adjusted p < 0.001). Isolated lymphopenia was rare (0.6%), whereas complete compensation was seen in 7.7% of observations. Conclusions: These findings suggest that the ICS triad components follow distinct, temporally discordant trajectories after CCI onset, questioning the view of CCI as a unified state. While periods of complete compensation were observed, their relationship to clinical resolution of CCI requires further investigation.

Background: Chronic critical illness (CCI) affects ~7.6% of ICU patients worldwide and is associated with poor outcomes, including 25% in-hospital and 50% one-year mortality. A proposed key mechanism is the inflammation-immunosuppression-catabolism (ICS) triad, which contributes to multiple organ failure and independently increases mortality. Although early identification of ICS could improve risk stratification, no clinically applicable predictive tool currently exists. This study aimed to develop and validate a prognostic nomogram to predict ICS development in ICU (Intensive Care Unit) patients. Methods: This real-world analysis used electronic health records from the Russian Intensive Care Dataset (RICD). ICS was defined as C-reactive protein > 20 mg/L, albumin < 30 g/L, and lymphocyte count < 0.8 × 109/L. Variables with >30% missing data were excluded, and remaining missing values were handled by multiple imputation. A Cox proportional hazards model was used to construct the nomogram. Internal validation was performed using an 8:2 training-validation split. Results: Among 1963 eligible patients, 540 (27.5%) developed ICS. LASSO (Least Absolute Shrinkage and Selection Operator) regression identified nine significant predictors: age, body mass index, SOFA (Sequential Organ Failure Assessment) and FOUR (Full Outline of UnResponsiveness) scores at admission, pneumonia and anemia at admission, platelet count, total protein, and creatinine. The nomogram showed good discrimination, with C-indices of 0.763 (95% CI: 0.741-0.783) in the training set and 0.735 (95% CI: 0.689-0.784) in the validation set. At the optimal cutoff, sensitivity was 0.75, specificity was 0.63, positive predictive value was 0.43, and negative predictive value was 0.87. Conclusions: This study presents the first nomogram for predicting ICS in ICU patients, using nine admission variables to reliably identify low-risk individuals. Further external validation is required.

Background: Ultrasonographic assessment of the diameters of various veins and their indices are among the most applied diagnostic tools for evaluating fluid responsiveness in clinical practice. Despite their widespread use, there is no definitive answer on which is preferable. Our study aimed to investigate the diagnostic accuracy of different venous diameters and their indices to assess fluid responsiveness. Methods: We conducted a systematic review and network meta-analysis, analyzing prospective studies evaluating the diagnostic accuracy of venous diameters (inferior vena cava [IVC], internal jugular vein [IJV], superior vena cava, and subclavian vena) and their indices for fluid responsiveness. Electronic databases were searched from inception until March 2024; this search was supplemented by snowballing methods. The risk of bias was evaluated with QUADAS-2, and evidence certainty was assessed using the GRADE approach. Nine prospective cohort studies (560 patients) were included. Results: The network meta-analysis revealed that the ΔCaval index exhibited a significant performance advantage over other “venous” test parameters. The caval index significantly outperformed IJV min/max and IVCmax. IJV index and IVCmin significantly outperformed IJVmin/max. The caval index was comparable to the IJV index. The caval index was comparable during mechanical ventilation and spontaneous breathing. Conclusions: In this meta-analysis, the ΔCaval index test showed higher diagnostic accuracy for fluid responsiveness compared with other venous tests. Caval and jugular indices displayed similar accuracy, and caval indices were consistent under mechanical ventilation and spontaneous breathing. Indices generally outperformed absolute values, except for IVCmin, which equaled the caval index in efficacy. This study was registered on the International Platform for Registered Protocols for Systematic Reviews and Meta-Analyses: INPLASY202430104.

BACKGROUND:Pulmonary fibrosis is a major complication of the Acute Respiratory Distress Syndrome (ARDS). Pirfenidone is an approved treatment for idiopathic pulmonary fibrosis. It may attenuate ARDS-related fibrosis and decrease the need for prolonged ventilation. Accordingly, we aimed to evaluate the effect of pirfenidone on ventilator-free days in patients with ARDS. METHODS:In a multi-center, randomized, double-blind, placebo-controlled trial, we plan to randomly assign 130 adults invasively ventilated for ARDS to receive pirfenidone or placebo for up to 28 days. The primary outcome is days alive and ventilator free at 28 days. Secondary outcomes include ICU-free days, hospital free days all at 28 day, ICU mortality and hospital mortality. We will also assess fibroproliferative changes on high-resolution CT scans at ICU discharge and quality of life. Data analysis will be on an intention-to-treat basis. DISCUSSION:The trial is ongoing and currently recruiting. It will be the first randomized controlled study to investigate whether, compared to placebo, pirfenidone increases the number of days alive and ventilator-free in patients with ARDS. Its double-blind multicenter design will provide internal validity, minimal bias, and a degree of external validity. If our hypothesis is confirmed, this treatment would justify larger trials of this intervention. TRIAL REGISTRATION:This trial was registered on ClinicalTrials.gov with the trial identification NCT05075161.

BACKGROUND:Major noncardiac surgery is associated with high rates of postoperative myocardial injury and other complications. Remote ischemic preconditioning (RIPC) was reported to decrease these complication rates. However, such supportive evidence lacks robustness. METHODS:In a multinational, double-blind trial, we randomly assigned adult high-risk patients undergoing noncardiac surgical procedures to receive RIPC or sham RIPC after the induction of general anesthesia and before surgery. RIPC involved three 5-minute ischemic cycles, each followed by 5 minutes of reperfusion, using a blood pressure cuff inflated to 200 mm Hg. The primary end point was the rate of myocardial injury, defined by an increase in postoperative troponin levels above the highest 99th percentile of reference values. Secondary outcomes included myocardial infarction, stroke, acute kidney injury, need for intensive care unit, length of hospital stay, and 30-day all-cause mortality. RESULTS:We recruited 1213 patients in 25 hospitals and 8 countries. We randomly assigned 599 patients to RIPC and 614 to sham RIPC. The most frequent surgical procedures were abdominal or intrathoracic surgeries (406 patients [33.6%]). RIPC was applied to the upper limb in 1014 patients (84.8%) and to the lower limb in 182 patients (15.2%). Postoperative myocardial injury occurred in 215 of 566 patients (38.0%) in the RIPC group and in 223 of 596 patients (37.4%) in the sham RIPC group (relative risk, 1.02 [95% CI, 0.88-1.18; P=0.84). There were no significant differences in the rate of any secondary outcomes. We observed 11 episodes of limb petechiae (10 [1.7%] in the RIPC group versus one [0.2%] in the sham RIPC group) and 34 (6.0%) hospital readmissions in the RIPC group versus 20 (3.5%) in the sham RIPC group. CONCLUSIONS:Among adult patients undergoing noncardiac surgery, RIPC did not reduce myocardial injury or other postoperative complications. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02427867.

Background/Objectives: Surgical procedures in chronic obstructive pulmonary disease (COPD) patients carry a high risk of postoperative respiratory failure, often causing the need for mechanical ventilation and prolonged intensive care unit (ICU) stays. Accompanying COPD with heart failure further increases the risk of complications. This study aimed to identify predictors of mortality, prolonged ICU and hospital stays, the need for mechanical ventilation, and vasoactive drug usage in ICU patients with moderate to severe COPD undergoing elective non-cardiac surgery. Methods: This retrospective cohort study analyzed eICU-CRD data, including adult patients with moderate to severe COPD admitted to the ICU from the operating room following elective non-cardiac surgery. Spearman’s correlation analysis was performed to assess associations between intraoperative ventilation parameters and ICU/hospital length of stay, postoperative laboratory parameters, and their perioperative dynamics. Results: This study included 680 patients (21% with severe COPD). Hospital and ICU mortality were 8.6% and 4.4%, respectively. Median ICU and hospital stays were 1.9 and 6.6 days, respectively. Intraoperative tidal volume, expired minute ventilation, positive end-expiratory pressure, mean airway pressure, peak inspiratory pressure, and compliance had no statistically significant association with mortality, postoperative mechanical ventilation, its duration, or the use of vasopressors/inotropes. Tidal volume correlated positively with changes in monocyte count (R = 0.611; p = 0.016), postoperative lymphocytes (R = 0.327; p = 0.017), and neutrophil count (R = 0.332; p = 0.02). Plateau pressure showed a strong positive association with the neutrophil-to-lymphocyte ratio (R = 0.708; p = 0.001). Conclusions: Intraoperative ventilation modes and parameters in COPD patients appear to have no significant impact on the outcomes or laboratory markers, except possibly for the neutrophil-to-lymphocyte ratio, although its elevation cause remains unclear.

BACKGROUND:Patients undergoing cardiac surgery often receive red-cell transfusions, along with the associated risks and costs. Early intraoperative normovolemic hemodilution (i.e., acute normovolemic hemodilution [ANH]) is a blood-conservation technique that entails autologous blood collection before initiation of cardiopulmonary bypass and reinfusion of the collected blood after bypass weaning. More data are needed on whether ANH reduces the number of patients receiving allogeneic red-cell transfusion. METHODS:In a multinational, single-blind trial, we randomly assigned adults from 32 centers and 11 countries who were undergoing cardiac surgery with cardiopulmonary bypass to receive ANH (withdrawal of ≥650 ml of whole blood with crystalloids replacement if needed) or usual care. The primary outcome was the transfusion of at least one unit of allogeneic red cells during the hospital stay. Secondary outcomes were death from any cause within 30 days after surgery or during the hospitalization for surgery, bleeding complications, ischemic complications, and acute kidney injury. RESULTS:A total of 2010 patients underwent randomization; 1010 were assigned to ANH and 1000 to usual care. Among patients with available data, 274 of 1005 (27.3%) in the ANH group and 291 of 997 (29.2%) in the usual-care group received at least one allogeneic red-cell transfusion (relative risk, 0.93; 95% confidence interval, 0.81 to 1.07; P = 0.34). Surgery for postoperative bleeding was performed in 38 of 1004 patients (3.8%) in the ANH group and 26 of 995 patients (2.6%) in the usual-care group. Death within 30 days or during hospitalization occurred in 14 of 1008 patients (1.4%) in the ANH group and 16 of 997 patients (1.6%) in the usual-care group. Safety outcomes were similar in the two groups. CONCLUSIONS:Among adults undergoing cardiac surgery, ANH did not reduce the number of patients receiving allogeneic red-cell transfusion. (Funded by the Italian Ministry of Health; ANH ClinicalTrials.gov number, NCT03913481.).

Objective To determine the incidence of perioperative covert strokes following elective carotid artery (CA) surgery, to identify associated risk and protective factors, and assess the clinical implications of covert strokes. Design and method This meta-analysis adheres to the PRISMA and Cochrane Collaboration guidelines. The protocol was prospectively registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) under the IDs INPLASY202450124 and INPLASY202530021. A comprehensive literature search drew on PubMed (Medline) and the Cochrane Library (CENTRAL), with additional references identified through snowballing via Litmaps. Eligible studies comprised prospective and retrospective cohort designs as well as randomized controlled trials that reported on the incidence of covert (silent) stroke and associated in-hospital or post-discharge outcomes in adults undergoing CA surgery. Studies were excluded if they (1) did not involve CA surgery, (2) lacked relevant outcome data, or (3) utilized inadequate methods for detecting covert strokes. Data analysis was conducted using STATA 18.0 (StataCorp LLC, TX, USA). To explore associations between covert stroke incidence and clinical covariates, we applied a random-effects meta-regression based on the REML model, along with subgroup analyses. The Trial Sequential Analysis (TSA) approach served to evaluate the robustness and conclusiveness of the cumulative evidence. To assess study quality, we used the CLARITY risk of bias tool, while the GRADE framework was applied to determine the overall certainty of the evidence. Results and conclusions A total of 27 studies, including 5,644 patients (994 following carotid artery [CA] stenting and 4,650 after carotid endarterectomy [CEA]), met the inclusion criteria. The pooled incidence of perioperative covert stroke was estimated at 19% (95% confidence interval, CI: 14-24%). Diabetes mellitus (p<0.001) and hypertension (p=0.036) were identified as significant risk factors, while statin therapy was associated with a protective effect (p=0.012). Notably, MRI detected covert strokes at a significantly higher rate than CT (22% vs. 3%, p<0.001). Covert strokes were markedly more frequent after CA stenting (38%) compared to CEA (10%), with a relative risk of 3.75 (95% CI: 2.89–4.87), translating to a relative risk reduction of 73.3% in favor of CEA. TSA confirmed the sufficiency of the accumulated evidence, with the cumulative Z-curve crossing the O’Brien–Fleming efficacy boundary. Based on the GRADE framework, the certainty of evidence was rated as moderate to high.Contrary to widely held assumptions, no significant increases in postoperative cognitive dysfunction, focal neurological deficits, or mortality were observed among patients with covert strokes.Conclusions: Perioperative covert strokes occur in about 20% of elective carotid artery surgeries, based on high-certainty evidence. The risk is 3.75 times greater following carotid artery stenting compared to carotid endarterectomy, with a moderate level of evidence. Notably, an estimated 75% of covert strokes associated with stenting may be preventable through the selection of an alternative surgical approach. However, covert strokes were not associated with a statistically significant increase in the incidence of postoperative cognitive dysfunction, focal neurological deficit, or mortality.

Background: Advances in intensive care have markedly improved survival from acute critical illness. Nevertheless, the subsequent trajectory of these patients is heterogeneous: while most recover and are eventually discharged, approximately 10% remain dependent on life-support systems, forming a distinct group classified as chronic critical illness (CCI). These patients experience prolonged ICU stays, high mortality, and poor long-term outcomes. Prognostication in CCI remains challenging, as traditional severity scores based on admission data seem to lose prognostic accuracy progressively over longer ICU stays. This is particularly relevant in traumatic brain injury (TBI), where patients constitute a significant proportion of the CCI population and require specialized prognostic approaches. Objective: To develop and validate prognostic models for in-hospital mortality in patients with TBI who progress to chronic critical illness, comparing the performance of a traditional admission-based (left-aligned) model with a novel dynamic (right-aligned) model utilizing data from the week preceding the outcome. Methods: A real-world data analysis was conducted using the Russian Intensive Care Dataset (RICD v2.0). The cohort included 430 ICU admissions of adult TBI patients with a stay of ≥7 days. Multivariable logistic regression was used to develop two nomograms: one using parameters from ICU admission and another using data from 7 days prior to discharge or death. Model performance was assessed via ROC analysis, sensitivity, specificity, and predictive values. Results: The left-aligned model, based on admission data (coronary artery disease, multiorgan failure, CRP), showed moderate discriminative capacity (AUROC 0.720). In contrast, the right-aligned model, incorporating dynamic parameters from the pre-outcome period (lymphocyte count, platelet count, urea, CRP), demonstrated excellent predictive performance (AUROC 0.889), with 90.0% sensitivity and 98.6% negative predictive value. A high score on the right-aligned nomogram was associated with a 19.7-fold increased risk of mortality within the subsequent week. Conclusions: For patients with CCI following TBI, a dynamic prognostic model based on data from the immediate pre-outcome period significantly outperforms traditional admission-based models. The high negative predictive value of the right-aligned model provides a reliable tool for identifying patients with a low short-term risk of mortality, supporting a paradigm shift towards dynamic risk stratification in chronic critically ill patients.

Introduction. The passive leg raising (PLR test) test is a widely used diagnostic test for assessing fluid responsiveness. However, there is no generally accepted methodology describing the details of its implementation.The objective was to establish criteria for conducting the PLR test based on the diagnostic accuracy of various variations.Materials and methods. A systematic review and meta-analysis included prospective cohort studies that evaluated the diagnostic accuracy of different PLR test variations. The primary endpoint was the area under the ROC curve (AUROC). The search was conducted up to March 2024 and included «snowball» method. The covariate influence was assessed via univariate meta-regression. The risk of bias was evaluated using QUADAS-2, and evidence certainty was assessed with GRADE.Results. The meta-analysis included 33 prospective cohort studies, 1,607 critically ill patients The AUROC for the PLR test was 0.882 [0.849; 0.916] (moderate certainty of evidence). Transthoracic and transesophageal echocardiography, transpulmonary thermodilution, and pulse contour analysis showed comparable results for assessing cardiac hemodynamics during PLR test, p = 0.253 (moderate certainty of evidence). Evaluating hemodynamic changes within the first two minutes of the PLR test increased diagnostic accuracy (high certainty of evidence). The starting body position (low Fowler’s position or supine) during the PLR test did not impact diagnostic accuracy (low certainty of evidence). Baseline covariates (age and gender) had no effect on diagnostic accuracy of the PLR test in critically ill patients (high certainty of evidence).Conclusion. For assessing fluid responsiveness in critically ill patients, the PLR test should include intracardiac hemodynamic assessment within two minutes using any common method. Low Fowler’s position is preferable starting position of the body for PLR test.

OBJECTIVES:Proton pump inhibitors have dose-dependent immunomodulatory effects. We tested the hypothesis that mega-dose esomeprazole therapy would reduce organ dysfunction in patients with sepsis or septic shock. DESIGN:A multinational, randomized, double-blind, placebo-controlled clinical trial. SETTING:Seventeen ICUs or emergency departments in three countries. PATIENTS:Adult patients with sepsis or septic shock. INTERVENTIONS:Mega-dose (1024 mg) esomeprazole or placebo over a 72-hour period. MEASUREMENTS AND MAIN RESULTS:The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score to day 10. Secondary outcomes included antibiotics-free days, ICU-free days at day 28, and all-cause mortality. We also conducted a mechanistic study of the in vitro effects of esomeprazole in sepsis. We randomized 307 patients and assigned 148 to esomeprazole and 159 to placebo. Mean age was 71 years; 166 patients (54%) had septic shock and median SOFA score at randomization was 7. The median mean daily SOFA score in the first 10 days post-randomization was 5 (interquartile range [IQR], 3-9) in the esomeprazole group and 5 (IQR, 3-8) in the placebo group (risk difference, 0.1; 95% CI, -0.8 to 1.0; p > 0.99). No differences were observed in secondary outcomes. Monocytes isolated from patients' peripheral blood and activated with a toll-like receptor agonist exhibited a pro-inflammatory phenotype, which was not affected by esomeprazole therapy. CONCLUSIONS:Among patients with sepsis or septic shock, mega-dose esomeprazole did not reduce organ dysfunction or other patient-related or biological secondary outcomes.

BackgroundThe optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain.ObjectivesTo compare alternative empiric antibiotic regimens in HAP using a network meta-analysis (NMA).MethodsData sources: Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023.Study eligibility criteriaRandomized controlled trials (RCT).ParticipantsAdults with clinical suspicion of HAP.InterventionAny empiric antibiotic regimen versus another, placebo, or no treatment.Assessment of risk of biasPaired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials.Methods of data analysisPaired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects NMAs for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Results39 trials proved eligible. 30 RCTs involving 4,807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs antipseudomonal cephalosporins or antipseudomonal carbapenems vs antipseudomonal cephalosporins. 11 RCTs involving 2,531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis.ConclusionsFor empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure in HAP. Empiric MRSA coverage may not exert additional benefit in reducing mortality in HAP.RegistrationPROSPERO (CRD 42022297224)

Objectives:The quality of postoperative analgesia in total knee arthroplasty is crucial for patient recovery, rehabilitation, and hospital stay duration. In line with the above, a single-shot adductor canal block has been considered as an improved method over continuous femoral nerve block. However, continuous adductor canal block and single-shot femoral nerve block have been not adequately addressed in the discussion. This study aimed to compare the effectiveness of various types of adductor and femoral nerve blocks on clinically relevant outcomes in patients following total knee arthroplasty. Methods:A systematic review and network meta-analysis were conducted following "PRISMA-NMA" and Cochrane Handbook guidelines. The eligibility criteria included randomized trials and, where these were lacking for a comparison, nonrandomized studies involving adults undergoing primary total knee arthroplasty, comparing single-shot adductor canal block, continuous adductor canal block, single-shot femoral nerve block, and continuous femoral nerve block. Results:A total of 36 studies involving 3308 patients were included. Single-shot adductor canal block showed higher pain scores and opioid consumption but better functional recovery at 24 h compared with continuous femoral nerve block. However, this trend vanishes by the 48 h assessment postsurgery. Continuous adductor canal block required higher opioid consumption but better functional recovery and shorter hospital stay compared with continuous femoral nerve block. Single-shot adductor canal block showed higher pain scores but comparable opioid consumption and functional recovery to continuous adductor canal block. Discussion:The shift from continuous femoral nerve block to single-shot adductor canal block as the preferred method for pain relief after total knee arthroplasty may be premature. While the latter improves mobility, it falls short in pain control and does not shorten hospital stays. Continuous adductor canal block shows promise but is currently underappreciated, and single-shot femoral nerve block is often overshadowed by other techniques in regional anesthesia. Further high-quality, multicenter randomized controlled trials are needed to validate these findings.

Introduction: The reliability of statistical analysis and its results is becoming a focal point in scientific discourse, overshadowing concerns about statistical significance. Systematic reviews and meta-analyses are characterized by a range of serious statistical and methodological limitations, including insufficient statistical power, clinical and statistical heterogeneity, systematic errors, potential low quality of included examinations, limited data availability, and publication bias. In this context, “Trial Sequential Analysis” (TSA) emerges as a promising methodological tool used in combination with meta-analyses to enhance the precision and robustness of scientific conclusions. Objective: The study is aimed to demonstrating potential scenarios for the using TSA and its role in improving the reliability of scientific conclusions through meta-analyses published in Russian journals on anesthesiology-resuscitation, as well as the authors’ own meta-analyses.Methods: This study is a systematic review without a detailed description of the case studies. The search for meta-analyses was conducted using the keywords “meta-analysis”, “mortality”, “delirium”, “sedation”. Two researchers independently reviewed the titles and abstracts of the selected meta-analyses and extracted data. TSA was conducted for all meta-analyses using “TSA software” (Copenhagen, Denmark). Results: 6 studies were considered, and 7 TSA evaluations were performed. Six out of the seven TSA evaluations confirmed the conclusions of the pertinent meta-analyses. In one TSA, the cumulative Z-line did not reach the required sample size, highlighting the need for additional studies to definitively confirm the result. In two TSAs, the sample size in the meta-analysis was insufficient to draw definitive conclusions. The application of TSA in these cases could provide more substantiated and cautious conclusions.Conclusion: This study explores various scenarios for the application of TSA in meta-analyses published in both Russian and international journals in the fields of anesthesiology and resuscitation. The significance of TSA for enhancing the validity and clinical relevance of research findings was substantiated. Received 3 February 2024. Revised 18 March 2024. Accepted 20 March 2024. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: M.Ya. YadgarovData collection and analysis: M.Ya. Yadgarov, L.B. Berikashvili, P.A. PolyakovStatistical analysis: M.Ya. Yadgarov, P.A. PolyakovDrafting the article: M.Ya. Yadgarov, L.B. Berikashvili, K.K. Kadantseva, A.V. Smirnova, I.V. Kuznetsov, A.A. YakovlevCritical revision of the article: V.V. LikhvantsevFinal approval of the version to be published: M.Ya. Yadgarov, L.B. Berikashvili, P.A. Polyakov, K.K. Kadantseva, A.V. Smirnova, I.V. Kuznetsov, A.A. Yakovlev, V.V. Likhvantsev

Background: Postoperative agitation is common after non-cardiac surgery. It is associated with postoperative delirium and cognitive dysfunction, leading to prolonged hospital stay and delayed social readjustment. Prevention and treatment strategies are lacking. We assessed the efficacy of a novel approach, the Wash In/Wash Out procedure, in reducing post-anesthetic agitation. Methods: This multicenter, parallel-group, double-blind randomized controlled trial is enrolling 200 patients undergoing open abdominal surgery. Participants are randomly assigned to either a control group receiving standard recovery methods or an investigational group undergoing the Wash In/Wash Out procedure. In the Wash In/Wash Out procedure group, sevoflurane is stopped and then promptly restarted when the patient shows the first signs of awakening to achieve an end-tidal concentration of 1 minimum alveolar concentration (MAC) for 5 min. This stop-and-restart cycle is performed three times. The trial's primary outcome is the rate of postoperative agitation. Secondary outcomes include rate of postoperative delirium and cognitive dysfunction, postoperative nausea and vomiting, and length of intensive care and hospital stay. Discussion: The OPERA trial investigates the effect of the Wash In/Wash Out procedure to reduce post-anesthetic agitation in non-cardiac surgery. This study could offer a significant contribution to improving patient outcomes and optimizing recovery protocols in surgical settings.

BackgroundWith machine learning (ML) carving a niche in diverse medical disciplines, its role in sepsis prediction, a condition where the ‘golden hour’ is critical, is of paramount interest. This study assesses the factors influencing the efficacy of ML models in sepsis prediction, aiming to optimize their use in clinical practice.MethodsWe searched Medline, PubMed, Google Scholar, and CENTRAL for studies published from inception to October 2023. We focused on studies predicting sepsis in real-time settings in adult patients in any hospital settings without language limits. The primary outcome was area under the curve (AUC) of the receiver operating characteristic. This meta-analysis was conducted according to PRISMA-NMA guidelines and Cochrane Handbook recommendations. A Network Meta-Analysis using the CINeMA approach compared ML models against traditional scoring systems, with meta-regression identifying factors affecting model quality.ResultsFrom 3,953 studies, 73 articles encompassing 457,932 septic patients and 256 models were analyzed. The pooled AUC for ML models was 0.825 and it significantly outperformed traditional scoring systems. Neural Network and Decision Tree models demonstrated the highest AUC metrics. Significant factors influencing AUC included ML model type, dataset type, and prediction window.ConclusionThis study establishes the superiority of ML models, especially Neural Network and Decision Tree types, in sepsis prediction. It highlights the importance of model type and dataset characteristics for prediction accuracy, emphasizing the necessity for standardized reporting and validation in ML healthcare applications. These findings call for broader clinical implementation to evaluate the effectiveness of these models in diverse patient groups.Systematic review registrationhttps://inplasy.com/inplasy-2023-12-0062/, identifier, INPLASY2023120062.

BackgroundBreast cancer (BC) mortality primarily stems from metastases rather than the primary tumor itself. Perioperative stress, encompassing both surgical and anesthetic factors, profoundly impacts the immune system, leading to alterations in neuroendocrine pathways and immune functions, potentially facilitating tumor progression and metastasis. Understanding the immunomodulatory effects of different anesthesia techniques is crucial for optimizing perioperative care in patients with BC. The neutrophil-to-lymphocyte ratio (NLR) serves as one of the key indicators of perioperative immune response.ObjectiveTo compare the effects of inhalation anesthesia (IA) and total intravenous anesthesia (TIVA) on perioperative immune response in BC surgery patients.MethodsIn this randomized, double-blind clinical trial, BC surgery patients were randomized to receive either TIVA with propofol or IA with sevoflurane. The primary endpoint was NLR assessment. Secondary immune parameters measured included natural killer cells, various T cell subsets, B cells, the immuno-regulatory index [T-helpers (CD3+CD4+)/cytotoxic T-cells (CD3+CD8+)], matrix metallopeptidases (MMP-9), complement components, and immunoglobulins, preoperatively and at 1 and 24 hours postoperatively.ResultsThe study included 98 patients (IA: 48, TIVA: 50). The baseline characteristics exhibited remarkable similarity across the groups. No significant difference in absolute NLR values was found between IA and TIVA groups at any time point (1 hour: p = 0.519, 24 hours: p = 0.333). Decreased IgA and IgM levels post-surgery suggested potential negative impacts of IA on humoral immunity compared to TIVA. CRP levels increased more by 24 hours (p = 0.044) in IA compared to TIVA. No significant differences were observed in natural killer cells, T cell subsets, B cells, MMP-9 levels or complement components between groups. Significant differences in the immuno-regulatory index between the TIVA and IA groups at one hour postoperatively (p = 0.033) were not maintained at 24 hours.ConclusionWhile there were no notable differences in NLR among the types of anesthesia, the observed disparities in immunoglobulin content and C-reactive protein levels between groups suggest that we cannot dismiss the potential immunosuppressive effects of inhalational anesthesia in breast cancer surgeries. Further investigation needed to clarify the impact of various anesthesia methods on immune function and their implications for long-term cancer outcomes.

Remote ischemic preconditioning (RIPC) is a clinical procedure aimed at inducing myocardial protection by causing brief ischemia-reperfusion episodes in an organ remote from the heart. We aim to assess whether RIPC provides myocardial protection in patients undergoing non-cardiac surgery. This study, called remote ischemic PReconditioning In Non-Cardiac surgEry (PRINCE), is a double-blind, multinational randomized clinical trial (1:1 allocation ratio) which plans to enroll 1100 patients. The intervention arm will receive RIPC at the beginning of surgery by inflating a blood pressure cuff around a limb for three cycles of ten minutes (inflated cuff for five minutes followed by deflated cuff for five minutes). In the control group, a blood pressure cuff will be put on a limb, and a sham inflation will be performed. Given a potential interaction of propofol with RIPC, induction and maintenance of anesthesia will be performed without propofol. The primary endpoint of the study is to document a significant reduction in postoperative cardiac troponin values among patients receiving RIPC. Secondary endpoints will be cardiac ischemic events at 30 days and 1 year, mortality at 30 days and 1 year, neurologic events at 30 days and 1 year, acute kidney injury at 7 days, need for intensive care unit admission and length of hospital stay. The trial will provide evidence for the effects of RIPC on cardioprotection and other relevant outcomes in high-cardiac risk patients undergoing non-cardiac surgery. Clinical Trial Registration: NCT02427867.