Minmin Zhu

Background: In critically ill patients with sepsis complicated by type 2 diabetes mellitus (T2DM), renal dysfunction is prevalent; however, the association between dynamic serum creatinine trajectory patterns and short-term mortality risk remains inadequately characterized. Methods: This study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The target population comprised adult intensive care unit (ICU) patients with sepsis complicated by T2DM. Group-Based Trajectory Modeling (GBTM) was employed to categorize the patterns of serum creatinine changes within 72 hours following ICU admission. Multivariable Cox proportional hazards models and Kaplan-Meier (K-M) survival curves were constructed to assess the association between trajectory groups and 28-day all-cause mortality, while restricted cubic spline (RCS) curves were utilized to examine the trend of short-term mortality risk in relation to serum creatinine levels. Furthermore, subgroup analyses and mediation effect analysis of continuous renal replacement therapy (CRRT) were performed. Results: A total of 1909 patients were included in the study, with 439 deaths occurring within 28 days, corresponding to a 28-day all-cause mortality rate of approximately 23.0%. Three distinct serum creatinine trajectory patterns were identified: low-stable, moderate-increasing, and persistently high. Compared with the low-stable trajectory group, patients in the moderate-increasing and persistently high groups exhibited significantly elevated 28-day mortality risk, which remained statistically significant following multivariable adjustment, with adjustments for age, gender, temperature, platelet count, albumin, blood urea nitrogen, pH, renal disease, severe liver disease, mechanical ventilation, 24-hour urine output, and the Charlson Comorbidity Index (model 2: HR = 1.50, 95% CI: 1.16-1.93, p = 0.02; model 3: HR = 1.46, 95% CI: 1.04-2.05, p = 0.03). RCS analysis revealed a significant nonlinear association between serum creatinine levels and mortality risk. The subgroup analysis results revealed significant interaction effects across gender and CRRT subgroups. Mediation analysis demonstrated that CRRT may exert a partial mediating effect on the association between creatinine elevation and mortality risk. Conclusion: The early trajectory of serum creatinine changes following ICU admission is independently associated with 28-day mortality in critically ill patients with sepsis complicated by T2DM. Sustained higher serum creatinine levels are significantly associated with an increased risk of mortality.

Background: Postoperative sleep disturbance (PSD) is a common complication after general anesthesia and is associated with delayed recovery and other adverse postoperative outcomes. Perioperative esketamine may improve postoperative sleep, but current evidence remains inconclusive. This systematic review and meta-analysis assessed the efficacy and safety of perioperative esketamine for preventing PSD in adults undergoing surgery under general anesthesia. Methods: PubMed, Embase, the Cochrane Library, and CNKI were searched from inception to 10 March 2026, for randomized controlled trials comparing perioperative esketamine with placebo or non-esketamine controls. The primary outcomes were the incidence of Postoperative sleep disturbance on postoperative day 1, 2, 3, and 7. Secondary outcomes included common perioperative adverse events. Risk ratios (RRs) with 95% confidence intervals were pooled using a random-effects model. Risk of bias, certainty of evidence, and robustness of key findings were assessed using the Cochrane Risk of Bias tool, GRADE, trial sequential analysis, and leave-one-out sensitivity analyses. Results: Twenty-two randomized controlled trials were included. Esketamine significantly reduced PSD incidence on POD1 (RR = 0.58, 95% CI: 0.51–0.66; I ² = 0%), POD2 (RR = 0.40, 95% CI: 0.28–0.58; I ² = 0%), and POD3 (RR = 0.55, 95% CI: 0.45–0.68; I ² = 9%), but not on POD7 (RR = 0.77, 95% CI: 0.55–1.08). Although statistical heterogeneity was low, clinical heterogeneity should be considered because of differences in surgical populations, patient characteristics, esketamine regimens, and sleep assessment methods. Subgroup analyses generally supported the early postoperative benefit, whereas POD3 findings stratified by preoperative sleep status should be interpreted cautiously. No statistically significant differences were observed in the analyzed adverse events, but safety evidence remains limited. Sensitivity analyses and trial sequential analysis supported the robustness of POD1 and POD3 findings. The certainty of evidence for early PSD outcomes was moderate. Conclusion: Perioperative esketamine may reduce early PSD incidence, particularly from POD1 to POD3. However, evidence mainly reflects subjective binary PSD outcomes, while effects on objective sleep parameters and longer-term sleep recovery remain uncertain. Further high-quality, multicenter trials using standardized and objective sleep assessments are needed. Clinical Trial Registration: PROSPERO (CRD420261364623).

Sleep apnea syndrome (SAS) is closely related to an increased risk of non-alcoholic fatty liver disease (NAFLD), but current clinical tools lack the integr

Objectives: Helicobacter pylori (Hp) seropositivity, linked to inflammatory morbidity, may reflect host inflammation-nutrition imbalance. The red blood cell distribution width-to-albumin ratio (RAR) has been proposed as a composite marker reflecting this axis. Using NHANES data and an external validation cohort of 250 hospital patients, we aimed to examine the association between RAR and H. pylori seropositivity. Methods: This study included U.S. adults from NHANES 1999–2000 and an external validation cohort of 250 hospital patients. Survey-weighted logistic regression assessed the association between RAR and H. pylori seropositivity. Restricted cubic splines (RCS) evaluated non-linearity. In addition, we performed a series of analyses, including restricting the range of RAR to limit inter-queue overlap, excluding subjects with clinical anemia, conducting sensitivity analyses by adjusting spline function parameters and handling extreme values, as well as subgroup analyses. Results: In the main adult dataset of NHANES 1999–2000, RCS regression analysis revealed a significant nonlinear association between RAR and Hp seropositivity rate (overall test p < 0.001; nonlinear test p < 0.001), with the inflection point at RAR = 2.85. Below this point, higher RAR was associated with greater odds of seropositivity (OR = 3.59; 95% CI: 1.76–7.31); above it, higher RAR related to lower odds (OR = 0.73; 95% CI: 0.55–0.97). RCS analysis of the external validation cohort showed a linear RAR-Hp seropositivity association (overall p = 0.457; nonlinear p = 0.937). Most RAR values clustered above the inflection point (2.85), potentially reducing statistical power. Restricting both cohorts to RAR ≥ 2.85 yielded consistent linear downward trends, with no significant nonlinearity in either cohort, indicating the validation cohort reflects post-inflection local relationships. In categorical analyses, the third RAR quartile remained positively associated after full adjustment, whereas the highest quartile did not, consistent with nonlinearity. Subgroup analyses showed no significant associations overall, though potential heterogeneity was observed by hypertension ( p for interaction = 0.040) and age ( p for interaction = 0.046). Conclusion: A statistically significant non-linear association pattern was observed between RAR and the seropositivity rate of Helicobacter pylori in NHANES; however, this association was sensitive to exposure distribution and could be partially explained by hematological factors. The findings were not replicated in the external cohort, and the overall evidence does not support a robust or clinically applicable association. RAR may reflect the inflammation-nutrition microenvironment associated with Helicobacter pylori exposure, rather than functioning as an independent predictive biomarker. Prospective studies are warranted to elucidate the causal relationship and clinical implications.

Background: Inflammatory response and nutritional status are closely related to the prognosis of critically ill patients, especially in elderly patients with delirium, where the situation is more complex. This study aims to explore the relationship between the Lymphocyte-Albumin-Neutrophil Ratio (LANR) and short- and long-term mortality risks in elderly delirium patients, providing valuable insights for clinical management. Methods: This study utilized the MIMIC-IV ICU public database to identify elderly delirium patients based on ICD-9 and ICD-10 codes. First, a qualitative approach was employed using Restricted Cubic Spline (RCS) analysis to visually illustrate the potential relationship between LANR and 30-day and 365-day mortality rates. Second, from a quantitative perspective, a Cox proportional hazards model was used for multivariable regression analysis to assess the independent effect of LANR on short- and long-term mortality risks after adjusting for other confounding factors. Additionally, to further explore heterogeneity, subgroup analyses were conducted, and forest plots were generated to examine potential significant interactions. Results: A total of 1,804 elderly delirium patients were extracted from the MIMIC-IV database, with a mean age of 77.6 ± 7.9 years and an ICU length of stay of 3.3 days [IQR 1.8–6.7 days]. Restricted cubic spline analysis revealed a linear relationship between LANR and 30-day mortality risk reduction in elderly delirium patients ( P for non-linearity>0.05). Although LANR showed a non-linear relationship with 365-day mortality risk, the risk decreased progressively as LANR levels increased. Cox multivariable regression analysis, after adjusting for covariates, indicated that higher LANR levels (T2, 0.21 < LANR≤0.47) were associated with an 26% reduction in short-term mortality risk and an 18% reduction in long-term mortality risk [HR _30-day = 0.74, 95% CI: 0.60–0.91, p = 0.004; HR _365-day = 0.82, 95% CI: 0.70–0.96, p = 0.013]. Extremely high LANR levels (T3, LANR>0.47) were associated with a 45% reduction in short-term mortality risk and a 40% reduction in long-term mortality risk [HR _30-day = 0.55, 95% CI: 0.44–0.69, p < 0.001; HR _365-day = 0.60, 95% CI: 0.51–0.71, p < 0.001]. Subgroup analysis further identified a significant interaction between LANR and vasopressor use in relation to 365-day mortality ( p = 0.018 < 0.05). Conclusion: The inflammatory marker LANR is closely associated with increased short- and long-term ICU mortality risk in elderly delirium patients, highlighting its potential as a prognostic tool in clinical practice.

Background: Postoperative nausea and vomiting (PONV) continue to be some of the most common and troublesome complications following anesthesia. Oliceridine, a G protein-biased µ-opioid receptor agonist, has the potential to provide effective pain relief while reducing the incidence of opioid-associated side effects. Objectives: The aim of this study is to evaluate the effectiveness and safety of oliceridine for preventing PONV compared with morphine and a placebo. Methods: A comprehensive search was performed across PubMed/MEDLINE, Embase (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL) from their inception up to 30 September 2025, without any language limitations. Randomized controlled trials (RCTs) comparing oliceridine with morphine or placebo were included. Outcomes included incidence of nausea, vomiting, and other opioid-related adverse events (ORAEs). Pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Results: This meta-analysis included five studies, with a total of 1,767 patients. The pooled analysis showed that oliceridine significantly reduced the incidence of postoperative nausea compared with morphine (risk ratio [RR] = 0.80; 95% confidence interval [CI] = 0.70–0.90). In dose-specific analyses, the RRs were 0.58 (95% CI = 0.50–0.67) for the 0.1 mg group, 0.82 (95% CI = 0.74–0.92) for the 0.35 mg group, and 1.00 (95% CI = 0.91–1.11) for the 0.5 mg group. Oliceridine also decreased the risk of postoperative vomiting (RR = 0.55; 95% CI = 0.45–0.67) relative to morphine. Subgroup analyses yielded RRs of 0.39 (95% CI = 0.31–0.50), 0.54 (95% CI = 0.38–0.78), and 0.80 (95% CI = 0.68–0.95) for the 0.1 mg, 0.35 mg, and 0.5 mg groups, respectively. Moreover, oliceridine appeared to lower the incidence of opioid-related adverse events, including dizziness (RR = 0.89; 95% CI = 0.76–1.04), dry mouth (RR = 0.50; 95% CI = 0.37–0.69), pruritus (RR = 0.50; 95% CI = 0.35–0.70), and somnolence (RR = 0.61; 95% CI = 0.45–0.82). Based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, the certainty of evidence ranged from moderate to low. Conclusion: Oliceridine, particularly at 0.1–0.35 mg demand doses, reduces PONV and several opioid-related adverse events compared with morphine while maintaining effective analgesia. However, compared with placebo, typical opioid adverse effects remain. Further large-scale RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024604703 , identifier PROSPERO (CRD42024604703).

Background: Coronary artery disease (CAD) ranks among the most prevalent and clinically challenging cardiovascular disorders encountered in the intensive care unit (ICU). Patients with CAD admitted to the ICU typically exhibit elevated mortality rates, intricate pathophysiological alterations, and a high likelihood of adverse outcomes. This study aims to develop and validate a prognostic prediction model for ICU-admitted CAD patients using machine learning (ML) methodologies. Methods: The data were retrieved from two independent cohorts within the Medical Information Mart for Intensive Care (MIMIC) database: MIMIC-IV was utilized for model training, while MIMIC-III served as an external validation dataset. The primary endpoints of the prediction were the 28- and 365-day mortality risks in this patient population. Feature selection was performed using LASSO regression integrated with commonality analysis, and feature importance was quantified via the SHapley Additive exPlanations (SHAP) approach to identify critical risk factors. Subsequently, short-term and long-term mortality risk prediction models for patients with coronary artery disease were developed based on seven interpretable machine learning algorithms. Results: A total of 15,930 patients with coronary artery disease were enrolled in this study (mean age, 70.3 ± 12.1 years; 5,055 females, accounting for 31.7%). To evaluate the mortality risk of patients across different time horizons, we developed predictive models incorporating 40 and 41 feature variables, respectively. Comparative analyses with six other machine learning algorithms revealed that the RandomForest algorithm exhibited the optimal performance in predicting both short-term and long-term mortality risks among patients with coronary artery disease [28-day mortality risk: Internal validation: AUC = 0.858, 95% CI: 0.843–0.872; Accuracy = 88.2%; External validation: AUC = 0.914, 95% CI: 0.904–0.923; Accuracy = 91.4%] [365-day mortality risk: Internal validation: AUC = 0.851, 95% CI: 0.840–0.863; Accuracy = 79.6%; External validation: AUC = 90.1, 95% CI: 0.893–0.909; Accuracy = 85.3%]. Conclusion: The random forest model developed in this study exhibited robust predictive performance and generalization capability in evaluating short-term and long-term mortality risks among critically ill patients with CAD. As a promising predictive tool, it offers data-driven decision support for clinicians to conduct early identification of high-risk patients and perform risk stratification, while its ultimate clinical utility remains to be further validated by prospective studies.

Introduction: Sepsis is a severe systemic inflammatory response to infection, potentially resulting in serious neurological complications. Adenosine-to-inosine (A-to-I) RNA editing is a critical epitranscriptomic process, yet its clinical involvement in different brain regions during sepsis remains to be elucidated. Methods: We conducted a comprehensive editome analysis and experimental validation to characterize A-to-I RNA editing in hippocampal and prefrontal cortical tissues from a sepsis cohort, as well as in brain tissues from a validation cohort. Results: Our findings revealed diverse dysregulation of RNA editing in these brain regions, with a substantial reduction in average RNA editing levels in the hippocampus but not in the prefrontal cortex. Moreover, cross-cohort and cross-tissue analysis identified eight key genes with dysregulated RNA editing during sepsis, particularly mitochondrial antiviral-signaling protein ( MAVS ), whose RNA editing was significantly downregulated. ADAR knockout or knockdown in multiple cell lines reduced both MAVS RNA editing and expression, confirming MAVS as a target of ADAR-mediated A-to-I RNA editing. Moreover, human vascular endothelial cells stimulated with LPS for 2 hours exhibited downregulated MAVS RNA editing, consistent with findings in sepsis patients, as well as reduced ADAR and MAVS expression, suggesting a potential role for ADAR-mediated RNA editing in regulating MAVS expression during inflammation. Consistently, ADAR and MAVS expression showed a positive correlation in both brain regions (Spearman’s ρ > 0.49, P < 1 × 10 ^-7 ). Discussion: Our results thus provide new insight into the importance of the clinical epitranscriptomic landscape in different brain regions during sepsis and warrant further investigation into therapeutic strategies to mitigate cognitive impairment in sepsis.

Objective: This study was designed to investigate the associations among platelet (PLT) count upon admission to the intensive care unit (ICU), postoperative acute kidney injury (AKI), and long-term prognosis (one-year mortality risk) in patients undergoing neurosurgical operations. Methods: This study conducted a retrospective analysis based on the MIMIC-IV database, including patients who underwent neurosurgery and were admitted to the ICU. Platelet count information at admission was collected. The primary endpoint were AKI within 7 days of ICU admission and mortality within one year after surgery. For the primary endpoint, a multivariate logistic regression model combined with restricted cubic spline was used for statistical analysis to explore the potential association between platelet count and AKI, and subgroup analysis was conducted to assess the stability of the results. For the other endpoint, a restricted cubic spline was used to construct a visualization relationship graph, and a Cox multivariate regression model was further established and a cumulative mortality curve was drawn. Sensitivity analyses were performed using both the first recorded platelet count following ICU admission and the 24-hour mean platelet count to assess the robustness of our findings. Additionally, an independent validation cohort was constructed using the MIMIC-III database to conduct external validation. Results: A total of 1605 patients were included in this study, with a median age of 60 years, among whom 875 were male (54.5%). Among the 1605 patients, 607 (37.82%) developed acute kidney injury within 7 days of hospitalization. Logistic regression analysis showed that compared with patients in the first quartile of platelet count (Q1 ≤ 179), those in the third quartile (Q3 > 234) had a significantly lower risk of developing acute kidney injury within 7 days of hospitalization (Model 1:HR = 0.42, 95% CI: 0.33–0.54; Model 2: HR = 0.67, 95% CI: 0.59–0.76; Model 3: HR = 0.57, 95% CI: 0.43–0.74; Model 4: HR = 0.62, 95%CI: 0.47–082; all P-values < 0.050). Furthermore, when the platelet count is below 204 × 10⁹/L, the risk of AKI occurrence in patients increases significantly. Cox multivariate regression analysis of the secondary endpoint showed that both relatively low platelet count (≤ 179) and relatively high platelet count (> 234) were associated with an increased risk of death within 1 year, with the former association being particularly significant (HR = 1.53, 95% CI: 1.17–2, P = 0.002). Sensitivity analyses yielded directionally consistent results. In the MIMIC-III external validation cohort, the associations between platelet levels and risks of AKI as well as long-term mortality remained generally consistent. Conclusion: In neurosurgical patients admitted to the ICU, early platelet levels within the first 24 hours were associated with the incidence of AKI within 7 days and long-term outcomes. A lower platelet count during the early ICU period was associated with an increased risk of AKI and poorer prognosis. This association appeared to be non-linear, the range of 179–234 × 10⁹/L corresponded to a lower risk or better prognosis. Platelet count can be a potential tool for risk stratification, but it is not sufficient to support clinical intervention decisions based on causal relationships.

Background: Propofol and ciprofol are commonly used agents for inducing general anesthesia. Although propofol is preferred for its potent sedative effects and quick recovery, it is associated with a higher incidence of injection-related pain. In contrast, ciprofol may help alleviate this pain. However, evidence regarding its advantage in reducing injection pain remains insufficient. This systematic review aimed to assess the frequency of pain during administration tied to the use of ciprofol as well as propofol. Methods: A systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted to identify randomized controlled trials comparing ciprofol with propofol for the induction of general anesthesia. Two reviewers independently screened studies and extracted data. Meta-analyses were performed using Review Manager software. Results: Ten trials with a total of 1,402 patients were studied in this meta-analysis. Research results showed that ciprofol markedly reduced the occurrence of pain from injections when contrasted with propofol, exhibiting a risk ratio (RR) of 0.15 (95% confidence interval [CI]: 0.11 to 0.20). Ciprofol significantly reduced the incidence of injection pain when the patient was elderly (RR = 0.14, 95% CI: 0.06 to 0.35), and also non-elderly (RR = 0.15, 95% CI: 0.11 to 0.21). In addition, ciprofol significantly reduced the incidence hypotension (RR = 0.63, 95% CI: 0.46 to 0.87). A trend toward lower tachycardia was observed with ciprofol, but this did not reach statistical significance (RR = 0.63, 95% CI 0.39–1.01). The GRADE assessment revealed moderate certainty regarding the outcomes associated with injection pain. Trial sequential analysis (TSA) suggested that the cumulative evidence for injection pain and hypotension was sufficient and that further trials are unlikely to change these conclusions. Conclusion: The study revealed that ciprofol significantly decreases the occurrence of injection-related discomfort and was associated with a reduced incidence of hypotension, while a trend toward lower tachycardia was observed. Trial sequential analysis further supported the robustness of these findings. Systematic review registration: CRD420251003081.