The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial

BMJ, Год журнала: 2025, Номер unknown, С. e082583 - e082583

Опубликована: Янв. 15, 2025

Abstract Objective To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis. Design Multicentre, double blinded, placebo controlled phase 3 trial. Setting 22 centres China, September 2016 to December 2020. Participants 1106 aged 18-85 years a diagnosis of sepsis according sepsis-3 criteria and randomly assigned 1:1 ratio receive (n=552) or (n=554). A stratified block method was used for randomisation, participants were by age (<60 ≥60 years) centre. Interventions Subcutaneous injection every 12 hours seven days unless discontinued owing discharge from intensive care unit, death, withdrawal consent. Main outcome measure The primary 28 day all cause after randomisation. All analyses based on modified intention-to-treat set, including who received at least one dose study drug. Results Of enrolled study, 1089 included (thymosin group n=542, n=547). occurred 127 (23.4%) 132 (24.1%) (hazard 0.99, 95% confidence interval 0.77 1.27; P=0.93 log-rank test). No secondary safety differed statistically significantly between two groups. prespecified subgroup analysis showed potential differential effect years: hazard 1.67, 1.04 2.67; 0.81, 0.61 1.09; P interaction=0.01) diabetes (diabetes: 0.58, 0.35 0.99; no diabetes: 1.16, 0.87 1.53; interaction=0.04). Conclusions This trial found clear evidence suggest that decreases Trial registration ClinicalTrials.gov NCT02867267 .

Язык: Английский

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The ‘analysis of gene expression and biomarkers for point-of-care decision support in Sepsis‘ study; temporal clinical parameter analysis and validation of early diagnostic biomarker signatures for severe inflammation andsepsis-SIRS discrimination

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 25, 2024

Introduction Early diagnosis of sepsis and discrimination from SIRS is crucial for clinicians to provide appropriate care, management treatment critically ill patients. We describe identification mRNA biomarkers peripheral blood leukocytes, able identify severe, systemic inflammation (irrespective origin) differentiate Sepsis SIRS, in adult patients within a multi-center clinical study. Methods Participants were recruited Intensive Care Units (ICUs) multiple UK hospitals, including fifty-nine with abdominal sepsis, eighty-four pulmonary forty-two Out-of-Hospital Cardiac Arrest (OOHCA), sampled at four time points, addition thirty healthy control donors. Multiple parameters measured, SOFA score, many differences observed between groups. Differential gene expression analyses performed using microarray hybridization data analyzed combination parametric non-parametric statistical tools. Results Nineteen high-performance, differentially expressed identified combined SIRS/Sepsis groups (FC&gt;20.0, p&lt;0.05), termed ‘indicators inflammation’ (I°I), CD177, FAM20A OLAH. Best-performing minimal signatures e.g. FAM20A/OLAH showed good accuracy determination (AUC&gt;0.99). Twenty entities, ‘SIRS or Sepsis’ (S°S) biomarkers, (FC&gt;2·0, p-value&lt;0.05). Discussion The best performing signature discriminating was CMTM5/CETP/PLA2G7/MIA/MPP3 (AUC=0.9758). I°I S°S variably other independent datasets, this may be due technical variation the study/assay platform.

Язык: Английский

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A Nomogram for Predicting Overall Survival in Primary Central Nervous System Lymphoma: A Retrospective Study

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 2091 - 2103

Опубликована: Фев. 1, 2025

Purpose: Current prognostic scoring systems for newly diagnosed primary central nervous system lymphoma (PCNSL), such as IELSG score and MSKCC score, are widely used but have limitations in clinical practice. This study aimed to develop a novel model based on real data compare it with existing systems. Patients Methods: A total of 288 patients PCNSL were recruited. randomly allocated the development validation cohorts. The least absolute shrinkage selection operator (LASSO) regression multivariate Cox analysis identify risk factors overall survival (OS) construct nomogram. Additionally, Kaplan-Meier curves plotted show stratification ability groups. Results: Eastern Cooperative Oncology Group performance status (ECOG-PS), albumin, two inflammatory biomarkers D-Dimer, neutrophil-to-lymphocyte ratio (NLR)—were independent predictors inferior OS. demonstrated concordance Index (C-index) 0.731 0.679 cohorts, respectively. In terms time dependent area under curve (AUC) values OS, cohort exhibited 0.765, 0.762, 0.812 1-year, 3-year, 5-year corresponding AUC 0.711, 0.731, 0.840, calibration showed excellent concordance. also provided superior compared Conclusion: presents predicting OS PCNSL. accurately effectively stratifies prognosis offers valuable guidance decision making. Keywords: PCNSL, model, stratification, NLR, D-Dimer

Язык: Английский

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Evaluation of Novel Combined CBC‐Derived Systemic Inflammatory Ratios and Their Dynamic Changes as ICU Mortality Predictors, a Retrospective Cohort

Health Science Reports, Год журнала: 2025, Номер 8(3)

Опубликована: Март 1, 2025

Novel biomarkers, such as neutrophil lymphocyte ratio, monocyte to platelet derived systemic immune-inflammation index, inflammation response and aggregate index of inflammation, have shown promising prognostic value, especially in ICU settings. We aimed evaluate the potential mentioned factors mortality predictors a heterogeneous cohort. conducted retrospective cohort study using data obtained from intensive care unit (ICU) records 311 patients. evaluated strength inflammatory parameters upon admission, 48 h later, their dynamic changes within this period predicting mortality. used multivariate logistic regression with backward elimination, which were further validated ROC calibration curves. Interaction terms added assess possible modifications predictive performance ratios across various subgroups NLPR, post admission (p < 0.001, OR: 7.3436, 95% CI: 3.2986-17.2619) NLPR during first = 0.018, 2.3826, 1.2069-6.7112), significant models. The model, including 48-h had highest AUC ROC, slope, lowest AIC (0.8671, 0.8622, 229.12, respectively). Also, decreases significantly among patients background CVA. level, post-ICU its stay, predict critically ill These findings can serve practical accessible mortality, particularly settings, where traditional scoring systems may not be routinely available.

Язык: Английский

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Impact of the hemoglobin-to-red cell distribution width ratio on 30-day readmission in patients with heart failure

BMC Cardiovascular Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Март 25, 2025

Predicting all-cause readmission in patients with heart failure (HF) is crucial. This study investigated the independent risk factors for short-term and assessed potential mediators involved this process. We evaluated data from 2,254 HF admitted to our institution between January 2019 December 2020. Logistic regression analysis was used examine association sarcopenia index (SI), neutrophil-to-lymphocyte ratio (NLR), hemoglobin-to-red cell distribution width (HRR), 30-d readmission. A restricted cubic spline model three knots non-linear relationships confounders risk. mediation performed evaluate direct indirect effects, as well proportion of mediation. The mean age participants 72 ± 12 years, 1,324 males (58.7%). rate 7.1%. HRR independently associated among biomarkers, whereas SI NLR showed no significant correlation. relationship found risk, an inflection point at 0.94. Patients < 0.94 exhibited a significantly higher readmission, ≥ Mediation revealed that N-terminal pro-B-type natriuretic peptide (NT-proBNP) partially mediated relationship, which accounted 13.6% effect. predictor observed. An inverse 0.94, Additionally, NT-proBNP identified partial mediator relationship.

Язык: Английский

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Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Long-Term Survival in Older Adults at a Mental Health Care Center: A Historical Cohort Analysis

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(7), С. 2509 - 2509

Опубликована: Апрель 7, 2025

Background/Objectives: Identifying reliable biomarkers for healthy aging and longevity is a fundamental challenge in research medical sciences. The neutrophil-to-lymphocyte ratio (NLR) readily measurable indicator of immune balance that reflects the interplay between innate activation adaptive suppression. Methods: This study examined NLR values 204 physically residents (98 men 106 women) stratified into four lifespan categories based on death certificates. Page's test ordinal regression (Cumulative Link Model) were used to assess trends with longevity. Results: In men, downward trend was observed. women, significant age-related decline identified, longer-lived individuals showing notably lower compared their shorter-lived counterparts. findings suggest associated longer survival, particularly older reflecting superior regulation reduced systemic inflammation. Conversely, elevated may indicate dysfunction heightened inflammatory burden. Conclusions: results this complement existing findings, reinforcing critical importance supporting These also underscore potential as robust biomarker evaluating function anticipating resilience decline, offering practical tool assessing health population.

Язык: Английский

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Inflammatory indices reflect distinct pathogenic cellular programs driving sepsis progression: The role of mmp9 protein macromolecules

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 143024 - 143024

Опубликована: Апрель 1, 2025

Язык: Английский

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The nonlinear correlation of neutrophil-lymphocyte ratio on 1-year mortality risk in patients with severe acute heart failure

BMC Cardiovascular Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 11, 2025

This retrospective cohort study was designed to examine the relationship between neutrophil-lymphocyte ratio (NLR) and 1-year risk of death in patients with acute heart failure (AHF) intensive care unit (ICU). We retrospectively analyzed 1,176 AHF from MIMIC-IV database. Cox regression used evaluate NLR mortality after adjusting for covariates. Nonlinear associations optimal cutoff values were determined using restricted cubic splines. Propensity score matching eliminate imbalances baseline confounders. Kaplan-Meier survival analysis further confirmed correctness threshold. The ROC diagnostic accuracy long-term outcomes. Subgroup analyses performed assess generality specific populations. rate lowest lower tertile group (< 5.43) highest upper (> 13.53, P trend < 0.001). showed a nonlinear correlation (P Non-linearity = 0.0075), increasing significantly when exceeded 11.11. AUC predicting 0.579 (95%CI 0.542-0.617). not different outcomes most groups, but association stronger who did have sepsis. Elevated NLR, marker heightened systemic inflammation, associated higher ICU AHF. Not applicable.

Язык: Английский

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Comparison of Inflammatory Marker Scoring Systems and Conventional Inflammatory Markers in Patients over 65 Years of Age Admitted to the Intensive Care Unit: A Multicenter, Retrospective, Cohort Study

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(14), С. 4011 - 4011

Опубликована: Июль 9, 2024

: The aim of the current study is to evaluate effects inflammation markers on infection and mortality in patients over 65 years age monitored intensive care unit (ICU). In this study, we attempted determine significance pan-immune-inflammation value (PIV); neutrophil-lymphocyte ratio (NLR); platelet-lymphocyte (PLR); monocyte-lymphocyte (MLR); systemic immune-inflammatory index (SII); immune response (SIRI); multi-inflammatory indices (MIIs) 1, 2, 3; CRP/albumin (a new biomarker) as prognostic being ICU.

Язык: Английский

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Insights into the Neutrophil-to-Lymphocyte Ratio and the Platelet-to-Lymphocyte Ratio as Predictors for the Length of Stay and Readmission in Chronic Heart Failure Patients

Diagnostics, Год журнала: 2024, Номер 14(18), С. 2102 - 2102

Опубликована: Сен. 23, 2024

Background/Objectives: Chronic heart failure (CHF) is characterized by complex pathophysiology, leading to increased hospitalizations and mortality. Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR) platelet-to-lymphocyte (PLR) provide valuable diagnostic insights. Methods: This study evaluates prognostic relationship between NLR, PLR, and, in a specific subcohort, N-terminal pro B-type natriuretic peptide (NT-proBNP), alongside length of stay (LOS) 90-day readmission rates CHF patients, irrespective phenotype. A retrospective analysis 427 admissions (males = 57.84%) was conducted. Results: The mean age entire population 68.48 ± 11.53 years. average LOS 8.33 5.26 days, with rate 73 visits (17.09%) for 56 patients. NLR (3.79 3.32) showed low but positive correlation (r 0.222, p < 0.001). Conversely, PLR (144.84 83.08) did not demonstrate significant association LOS. presented negative days until next admission −0.023, 0.048). In prespecified subanalysis 323 admissions, NT-proBNP exhibited Pearson 0.241, 0.001) 0.151, 0.006). Conclusions: impact across phenotypes may suggest role systemic inflammation understanding managing CHF.

Язык: Английский

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