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Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

ABSTRACT: Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

SUBMITTER: Huang JJ

PROVIDER: S-EPMC10729002 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Huang Jia-Jia JJ Cai Ji-Zhen JZ Zhou Zhi-Peng ZP Liu Yan Y Yang Zhen-Jia ZJ Li Da-Zheng DZ Chen Yu-Hua YH Luan Ying-Yi YY Yao Yong-Ming YM Wu Ming M

Frontiers in pharmacology 20231204

<b>Background:</b> Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. <b>Methods:</b> A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombos ...[more]

PMID: 38116082

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Project description:Previous research has shown a strong correlation between sepsis and brain structure. However, whether this relationship represents a causality remains elusive. In this study, we employed Mendelian randomization (MR) to probe the associations of genetically predicted sepsis and sepsis-related death with structural changes in specific brain regions. Genome-wide association study (GWAS) data for sepsis phenotypes (sepsis and sepsis-related death) were obtained from the IEU OpenGWAS. Correspondingly, GWAS data for brain structural traits (volume of the subcortical structure, cortical thickness, and surface area) were derived from the ENIGMA consortium. Inverse variance weighted was mainly utilized to assess the causal effects, while weighted median and MR-Egger regression served as complementary methods. Sensitivity analyses were implemented with Cochran Q test, MR-Egger regression, and MR-PRESSO. In addition, a reverse MR analysis was carried out to assess the possibility of reverse causation. We identified that genetic liability to sepsis was normally significantly associated with a reduced surface area of the postcentral gyrus (β = -35.5280, SE = 13.7465, P = .0096). The genetic liability to sepsis-related death showed a suggestive positive correlation with the surface area of fusiform gyrus (β = 11.0920, SE = 3.6412, P = .0023) and posterior cingulate gyrus (β = 3.6530, SE = 1.6684, P = .0286), While it presented a suggestive negative correlation with surface area of the caudal middle frontal gyrus (β = -11.4586, SE = 5.1501, P = .0261) and frontal pole (β = -1.0024, SE = 0.4329, P = .0206). We also indicated a possible bidirectional causal association between genetic liability to sepsis-related death and the thickness of the transverse temporal gyrus. Sensitivity analyses verified the robustness of the above associations. These findings suggested that genetically determined liability to sepsis might influence the specific brain structure in a causal way, offering new perspectives to investigate the mechanism of sepsis-related neuropsychiatric disorders.

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Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Publications

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

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