Background:Although inflammatory cytokines are pivotal to the pathogenesis of sepsis, determining their causal roles remains challenging due to confounding biases. We employed Mendelian randomization (MR) to investigate genetically determined cytokine levels in sepsis risk, with translational validation in clinical cohorts and experimental models. Methods:A multi-omics framework integrated cis-protein quantitative trait loci (cis-pQTL) of plasma cytokines with the UK Biobank sepsis GWAS using inverse-variance weighted MR and Wald ratio methods. Sensitivity analyses, Bayesian co-localization analysis, phenotype scanning, and bidirectional MR ensured robustness. Clinical validation compared peripheral levels of the result found by MR analysis in severe sepsis patients (n = 15) and non-septic ICU controls (n = 11) within 24 hours of diagnosis. The temporal dynamics were further characterized in the cecal ligation and puncture (CLP) rat model, assessing blood and lung protein and mRNA levels of the result found in MR analysis at 24 hours to 120 hours, along with T-cell exhaustion markers. Results:Genetically elevated levels of CCL4 (Chemokine CC motif ligand 4) were associated with critical sepsis risk (OR = 0.70, 95% CI: 0.58-0.84, P = 1.45×10-4, FDR = 0.017), consistent across sensitivity analyses. Clinically, septic patients exhibited higher peripheral blood levels of CCL4 within 24 hours than controls. In the CLP rat model, peripheral and pulmonary CCL4 protein levels peaked at 24 hours but declined significantly by 120 hours. This decline was accompanied by transcriptomic evidence of T-cell exhaustion, with increased CTLA-4 and decreased IL-2 and IFN-γ. Conclusion:The trajectory of CCL4 follows distinct phases in sepsis-its early elevation is associated with hyperinflammation, while its later decline correlates with T-cell exhaustion. Although causal mechanisms require further validation, our findings propose that monitoring CCL4 dynamics may serve as a potential biomarker for immunophenotype stratification, highlighting its relevance for developing time-sensitive therapeutic strategies.

OBJECTIVE:To explore the survival benefits of beta-blockers in patients with sepsis-induced TnT-positive myocardial injury across different clinical subtypes and to analyze their potential mechanisms of action. METHODS:Based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, 1102 patients meeting sepsis-induced TnT-positive myocardial injury criteria were included. Unsupervised machine learning methods were used for clinical subtype clustering analysis, and multivariate Cox regression was employed to evaluate the impact of beta-blockers on 28-day and 90-day mortality. The mediating role of inflammatory cytokine interleukin-6 (IL-6) and procalcitonin (PCT) was also analyzed. RESULTS:Patients were classified into three subtypes: moderate organ dysfunction sepsis-induced TnT-positive myocardial injury, severe inflammatory high-injury sepsis-induced TnT-positive myocardial injury, mild compensatory stable sepsis-induced TnT-positive myocardial injury. Beta-blocker use was significantly associated with reduced all-cause mortality: in all subtypes, 28-day mortality risk was reduced by 81.3% [hazard ratio (HR) = 0.187], 76.6% (HR = 0.234), and 65.9% (HR = 0.341), respectively, and 90-day mortality risk was reduced by 74.2% (HR = 0.258), 65.1% (HR = 0.349), and 63.6% (HR = 0.364), respectively. Selective beta-1 receptor blockers demonstrated the most optimal effects. The mediating role of IL-6 and PCT was not significant on the 28-day mortality rate in patients receiving beta-blocker. CONCLUSION:Beta-blockers can significantly improve short-term and medium-term survival rates in patients with sepsis-induced TnT-positive myocardial injury across all subtypes, particularly selective beta-1 blockers.

This study aimed to investigate the effects of MCC950 in a rat model of sepsis-associated encephalopathy (SAE). Adult male rats were randomly assigned to 12 groups according to the surgery or treatment received and evaluation times. The SAE model was established using the cecal ligation and puncture (CLP) method. Intraperitoneal injections of normal saline (10 mL/kg) or MCC950 (10 mg/kg) were administered 30 min pre-surgery and daily post-surgery. Changes in survival rates, weight loss, and heart rate were assessed at four time points, and neurobehavioral changes were evaluated using the composite neural reflex function scores, light/dark box test, and open-field test (OFT). Compared with the SAE group, the SAE + MCC950 group had significantly higher survival rates (P < 0.05), lower postoperative weight loss rates (P < 0.05), and higher neurological function scores (P < 0.05); the SAE + MCC950 group also traveled further and crossed the central area more frequently in the OFT (P < 0.05), spent more time in the light compartment at different time points (P < 0.05), and exhibited a lower heart rate at different time points (P < 0.05). MCC950 treatment significantly improved cognitive function and related indices in the SAE rats.

At present, there is insufficient evidence to evaluate the prognosis of patients with sepsis. This study anazed the clinical data of 822 sepsis patients in the ICU of a tertiary Grade A hospital to construct and validate a nomogram model for predicting the 28-day mortality risk in sepsis patients. The model was constructed using multivariate logistic regression analysis to screen for independent risk factors affecting prognosis, and a mortality risk prediction model was built based on these independent risk factors. The performance of the model was evaluated using the Hosmer–Lemeshow test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA). Multivariate logistic regression identified five independent risk factors for 28-day mortality in sepsis patients: Age, SOFA score, CRP, Mechanical ventilation, and the use of Vasoactive drugs. The odds ratios (OR) and 95% confidence intervals (95% CI) for these factors were 1.037 (1.024–1.050), 1.093 (1.044–1.145), 1.034 (1.026–1.042), 1.967 (1.176–3.328), and 2.515 (1.611–3.941), respectively, with all P-values < 0.05. Based on these five independent risk factors, a nomogram model was constructed, with the area under the ROC curve (AUC) in the training set and external validation set being 0.849 (95% CI 0.818–0.880) and 0.837 (95% CI 0.887–0.886), respectively. Both the DCA curve and calibration plot confirmed that the model has good clinical efficacy. The nomogram prediction model established in this study has excellent predictive ability, which can help clinicians identify high-risk patients early and provide guidance for clinical decision-making.

Purpose: This study aimed to identify the risk predictors of non-adherence to inhaler therapy and construct a nomogram prediction model for use in Chinese elderly patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: A cross-sectional study was conducted with 305 participants recruited from a tertiary care hospital in Anhui, China. Adherence was analyzed using the Test of Adherence to Inhalers. Potential predictive factors were incorporated based on the social ecological model, and data were collected through a questionnaire method. R version 4.3.3 was utilized to perform the least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis to identify risk factors and establish a nomogram prediction model. Results: The results of the multivariable analysis revealed that medication beliefs, illness perception, the COPD Assessment Test score, smoking status, and education level were significant risk factors for non-adherence to inhaler therapy in elderly COPD patients (all P < 0.05). The nomogram prediction model for non-adherence to inhaler therapy in elderly COPD patients demonstrated a good discriminative ability, with an area under the receiver operating characteristic curve of 0.912. The C-index was 0.922 (95% CI: 0.879 to 0.965), and the Brier value was 0.070, indicating good consistency and calibration. Decision curve analysis indicated that the use of the nomogram would be more beneficial in clinical practice when the threshold probability of non-adherence exceeds 17%. Conclusion: This study identified predictive factors regarding non-adherence among elderly patients with COPD and constructed a predictive nomogram. By utilizing the nomogram model healthcare professionals could swiftly calculate and comprehend the non-compliance level of COPD patients, thus guiding the development of personalized interventions in clinical practice.

Sepsis is a leading cause of hospital mortality, closely linked to gut dysfunction and dysbiosis. The gut microbiome’s role in sepsis pathogenesis and progression necessitates a comprehensive bibliometric analysis to elucidate current research trends. Utilizing the Science Citation Index Expanded (SCI-E) database, literature was systematically retrieved using the terms: sepsis AND (“gut” OR “gastrointestinal”) AND (“microbiome” OR “microbiota” OR “microflora” OR “bacillus”). After data refinement and duplicate removal, 2485 articles were included for statistical analysis using R software’s bibliometric package, with Excel used to visualize publication trends. Findings demonstrate a progressive annual increase in published studies and citations. The United States and France emerged as primary contributors, exhibiting extensive international collaboration. Among leading institutions, the University of California ranked highest in research output, while Wiersinga WJ from the University of Amsterdam led in publication volume and collaborative networks. Research predominantly focuses on critical care medicine, immunology, and microbiology, with keywords such as sepsis, microbiome, microbiota, and microflora recurring. Current trends indicate a growing focus on the relationship between sepsis and gut microbiome dynamics, with a notable gap in evidence-based clinical applications. The prominence of the United States in the field underscores the need for welldesigned clinical trials and prospective cohort studies to advance therapeutic strategies. Strengthening global collaboration, particularly through increased involvement of Chinese researchers, is crucial for a comprehensive understanding and future advancements in this complex and evolving field.

Abstract In the ICU, patients with sepsis often develop sepsis-associated encephalopathy (SAE), which affects their prognosis. This study aims to construct a predictive model for the 28-day mortality risk of SAE patients using machine learning (ML) methods. We retrospectively collected clinical data of SAE patients admitted to our hospital's intensive care unit (ICU) from January 2018 to June 2023. The primary outcome was whether the patient died within 28 days. We employed six popular machine learning methods to build the predictive model for the 28-day mortality risk of SAE patients, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), support vector machine (SVM), k-nearest neighbor (kNN), random forest (RF), and extreme gradient boosting (XGBoost). Various evaluation metrics were used to analyze the predictive performance of the models. The SHAP analysis method ranked the importance of features influencing the model's output and provided visual output and explanations for individual samples, meeting the need of clinicians to understand model outputs and personalized predictions. In total, this cohort study enrolled 506 SAE patients, with 243 cases (48.02%) resulting in death within 28 days. Overall, the XGBoost model demonstrated superior and stable performance, with the area under the receiver operating characteristic curve (AUC) for both the training and validation sets being higher than the other models, at 0.986 and 0.848, respectively. The SHAP summary plot revealed important clinical features associated with the risk of mortality within 28 days for SAE patients, with a strong dependence on age, SOFA score, and NEUT. Our study indicates that the XGBoost model has good predictive capability for the short-term prognostic outcomes of SAE patients in the ICU and can assist clinicians in the early identification of high-risk patients and the timely implementation of effective treatment strategies to improve the clinical outcomes of SAE patients.

This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

To construct a bundled therapy management and practice program for sepsis and explore its clinical application effect.

To investigate the epidemiological characteristics of sepsis-associated encephalopathy (SAE) in patients with sepsis, analyze its risk factors and build a prediction model, which provides evidence for early clinical identification of SAE patients and improvement of clinical outcomes.

Objectives To define the core competencies essential for specialist training in neurocritical care in China. Design Modified Delphi method and nominal group (NG) technique. Setting National. Participants A total of 1094 respondents from 33 provinces in China participated in the online survey. A NG of 11 members was organised by the Neuro-Critical Care Committee affiliated with the Chinese Association of Critical Care Physicians and the National Center for Healthcare Quality Management in Neurological Diseases. Results 1094 respondents from 33 provinces in China participated in the online survey. A formal list containing 329 statements was generated for the rating by a NG. After five rounds of NG meetings and one round of comments and iterative review, 198 core competencies (54 on neurological diseases, 64 on general medical diseases, 42 on monitoring of practical procedures, 20 on professionalism and system management, five on ethical and legal aspects, three on the principles of research and certification and 10 on scoring systems) formed the final list. Conclusion By using consensus techniques, we have developed a list of core competencies for neurocritical care training, which may serve as a reference for future specialist training programmes in China.

Objective To explore the incidence,clinical characteristic and outcome of malignancy surgical patients with venous thromboembolism (VTE).Methods The clinical data of sixty-eight malignancy surgical cases who suffered from VTE during the postoperative 90 days and hospitalized from January 2003 to April 2013 at Beijing Hospital were reviewed.Results There were 10 967 cases of malignancy surgeries during the observed ten years and 68 cases suffered from VTE during the postoperative 90 days (incidence was 0.62 ％),including gynecological malignancy,lung cancer,urinary system malignancy,digestive tract malignancy,breast cancer and hematological malignancy.Gynecological malignancy and lung cancer had the highest VTE incidence (1.03％ and 0.95％ respectively),there was significant difference with the other types (all P ＜0.05).Among 68 patients,31 cases of male and 37 cases of female were involved,with an average age of (63.94±10.50) years old,average postoperative time of (33 ± 30) days,average anesthesia duration of (172.75± 104.71) minutes,including 29 cases (42.65％) with cardiovascular diseases,34 cases (50.00％) immobilized more than three days after operation,40 cases (58.82 ％) with middle and low differentiation carcinoma in pathology,and 51 cases (75.00％) with Caprini score equal or greater than five.There were 36 cases in elderly group (≥65 years old)and 32 cases in non-elderly group (＜65 years old).Compared with non-elderly group,the body mass index was lower (t =-2.052,P =0.044),Caprini score (t =2.613,P =0.011),D-dimer (Z =-1.976,P =0.048),and incidence of late-onset VTE (occurring in postoperative 5-12 weeks)(x2=8.438,P =0.004) were higher in elderly group.All the three cases of fetal pulmonary thromboembolism were late-onset VTE patients in elderly group without any prophylactic measures.Conclusions The incidence of VTE in malignancy surgery patients during the postoperative 90 days is 0.62％.Gynecological malignancy and lung cancer are the most common types.The observation time for the VTE events should be extended to 12 weeks after surgery in elderly patients,as fetal pulmonary thromboembolism may occur during postoperative 5-12 weeks.

Abstract Background Rapid stratification and appropriate treatment on admission are critical to saving lives of patients with acute pulmonary embolism (PE). None of the clinical prediction tools perform well when applied to all patients with acute PE. It may be important to integrate respiratory features into the 2014 European Society of Cardiology model. First, we aimed to assess the relationship between the arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio and in-hospital mortality, determine the optimal cutoff value of PaO2/FIO2, and determine if this value, which is quick and easy to obtain on admission, is a predictor of in-hospital mortality in this population. Second, we aimed to evaluate the potential additional determinants including laboratory parameters that may affect the in-hospital mortality. We hypothesized that the PaO2/FiO2 ratio would be a clinical prediction tool for in-hospital mortality in patients with acute PE. Methods A prospective single-center observational cohort study was conducted in Beijing Hospital from January 2010 to November 2017. Arterial blood gas analysis data captured on admission, clinical characteristics, risk factors, laboratory data, imaging findings, and in-hospital mortality were compared between survivors and non-survivors. The area under the receiver operating characteristic curve (AUC) for in-hospital mortality based on the PaO2/FiO2 value was determined, and the association between the parameters and in-hospital mortality was analyzed by using logistic regression analysis. Results Body mass index, history of cancer, PaO2/FiO2 value, pulse rate, cardiac troponin I level, lactate dehydrogenase level, white blood cell count, D-dimer level, and risk stratification measurements differed between survivors and non-survivors. The optimal cutoff value of PaO2/FiO2 for predicting mortality was 265 (AUC = 0.765, P < 0.001). Only a PaO2/FiO2 ratio < 265 (95% confidence interval [CI] 1.823–21.483, P = 0.004), history of cancer (95% CI 1.161–15.927, P = 0.029), and risk stratification (95% CI 1.047–16.957, P = 0.043) continued to be associated with an increased risk of in-hospital mortality of acute PE. Conclusion A simple determination of the PaO2/FiO2 ratio at <265 may provide important information on admission about patients’ in-hospital prognosis, and PaO2/FiO2 ratio < 265, history of cancer, and risk stratification are predictors of in-hospital mortality of acute PE.

Objective To find the factors lowering the rate of effective thrombus aspiration in patients with STsegment elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention(PCI). Method From January to December 2008 , a total of 226 AMI patients from Beijing Anzhen Hospital,treated with primary PCI to aspirate the thrombus from the infracted coronary artery via a cannula, were enrolled in a single center retrospective study. The criterion of successful thrombectomy (device success) was defined as the coronary blood flow of involved vessel after PCI resumed to greater than TIMI grade 1. One hundred seventy-eight patients were assigned to effective thrombus aspiration group, and 48 patients without improvement in coronary blood flow of involved vessel after PCI to control group. Data collected after PCI including the normalization of the elevated ST segment,the use of direct stent, ratio of no-flow/slow flow, intra-coronary administration of Tirofiban and the rate of thrombolysis in myocardial infarction (TIMI) flow grade 3 were analyzed with logistic analysis soas to find out the factors affecting the efficacy of thrombus aspiration. Results There were no significant differences in data before PCI between two groups ( P ＞0.05). Compared with the control group, the factors studied such as smoke, diabetes, the rate of pre-PCI TIMI flow grade 0,the post-PCI ratio of no-reflow/slow flow,and the intra-coronary administration of Tirofiban were fewer significantly in the effective thrombus aspiration group. And the rate of post-PCI TIMI flow grade 3, and the rate of direct stent were higher in the effective thrombus aspiration group. Logistic analysis showed that smoke ( OR = 1.551,95%CI: 1.018 ～ 2. 154, P = 0.012), diabetes ( OR = 1. 132,95%CI:0.276 ～ 3.562, P =0.044), and pre-PCI TIMI flow grade 0 OR = 0.544,95%CI:0.368 ～ 1.911,P = 0.035) were independent factors of effective thrombus aspiration. Conclusions Effective thrombus aspiration may improved the coronary blood flow to TIMI flow grade 3 after PCI and reduce the impaiment of myocardial perfusion, and the factors affecting the efficacy of thrombus aspiration should be paid more attention to and should be minimized to achieve the better clinical outcomes.