ReviewCritical care explorations2021
The Effects of Biological Sex on Sepsis Treatments in Animal Models: A Systematic Review and a Narrative Elaboration on Sex- and Gender-Dependent Differences in Sepsis.
Review in Critical care explorations, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Optimization of Preclinical Rodent Research Models of Human Shock: Part One Intra-Abdominal Sepsis.Shock (Augusta, Ga.) · 2026Review
- Differential disease tolerance mediates sex-biased illness severity in sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sex differences in sepsis outcomes across the lifespan: a population-based cohort study in Germany.Critical care (London, England) · 2025Article
- Sex- and Gender-Based Analysis on Norepinephrine Use in Septic Shock: Why Is It Still a Male World?Microorganisms · 2024Article
- Impact of age on the host response to sepsis in a murine model of fecal-induced peritonitis.Intensive care medicine experimental · 2024Article
- Sepsis and obesity: a scoping review of diet-induced obesity murine models.Intensive care medicine experimental · 2024Article
- A Novel Scoring System for Humane Endpoints in Mice with Cecal Ligation and Puncture-Induced Sepsis.Comparative medicine · 2023Article
- BAM15 treats mouse sepsis and kidney injury, linking mortality, mitochondrial DNA, tubule damage, and neutrophils.The Journal of clinical investigation · 2023Article
- Sex-based analysis of treatment responses in animal models of sepsis: a preclinical systematic review protocol.Systematic reviews · 2023Article
- Interactions between Gender and Sepsis-Implications for the Future.Microorganisms · 2023Review
- Sex differences in cardiovascular response to sepsis.American journal of physiology. Cell physiology · 2023Review
- Common Variables That Influence Sepsis Mortality in Mice.Journal of inflammation research · 2023Article
- Let's get loud: Amplifying female voices in sepsis research.EBioMedicine · 2022Article
- Septic cardiomyopathy: Diagnosis and management.Journal of intensive medicine · 2022Review
- On the same page? A qualitative study protocol on collaboration in a multi-laboratory preclinical study.PloS one · 2022Article
- Aged IRF3-KO Mice are Protected from Sepsis.Journal of inflammation research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical studies provide an opportunity to evaluate the relationship between sex and sepsis, and investigate underlying mechanisms in a controlled experimental environment. The objective of our systematic review was to assess the impact of biological sex on treatment response to fluid and antibiotic therapy in animal models of sepsis. Furthermore, we provide a narrative elaboration of sex-dependent differences in preclinical models of sepsis. DATA SOURCES: MEDLINE and Embase were searched from inception to March 16, 2020. STUDY SELECTION: All studies reporting sex-stratified data comparing antibiotics and/or fluid resuscitation with a placebo or no treatment arm in an in vivo model of sepsis were included. DATA EXTRACTION: Outcomes of interest were mortality (primary) and organ dysfunction (secondary). Risk of bias was assessed. Study selection and data extraction were conducted independently and in duplicate. DATA SYNTHESIS: The systematic search returned 2,649 unique studies, and two met inclusion criteria. Both studies used cecal ligation and puncture models with imipenem/cilastatin antibiotics. No eligible studies investigated fluids. In one study, antibiotic therapy significantly reduced mortality in male, but not female, animals. The other study reported no sex differences in organ dysfunction. Both studies were deemed to be at a high overall risk of bias.
conclusionsThere is a remarkable and concerning paucity of data investigating sex-dependent differences in fluid and antibiotic therapy for the treatment of sepsis in animal models. This may reflect poor awareness of the importance of investigating sex-dependent differences. Our discussion therefore expands on general concepts of sex and gender in biomedical research and sex-dependent differences in key areas of sepsis research such as the cardiovascular system, immunometabolism, the microbiome, and epigenetics. Finally, we discuss current clinical knowledge, the potential for reverse translation, and directions for future studies. REGISTRATION: PROSPERO CRD42020192738.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.