Open research questions in Sepsis Diagnosis and Treatment
1,227 gap statements mined from Sepsis Diagnosis and Treatment papers in our 7.9M-paper local library, which holds 4,602 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
Existing monitoring systems, such as NEWS2, have limitations in incorporating broader EHR information and longitudinal trajectory. There is a need for a multi-domain EHR approach to improve prediction of clinical deterioration in ICU patients.
Development and internal validation of an EHR machine learning model for clinical deterioration in ICU linked inpatients · 2026 · DOIThe current mortality rate for sepsis-induced DIC remains high, despite advances in critical care. There is a need to evaluate the effectiveness of combination therapy with recombinant thrombomodulin and antithrombin. The study aims to address the gap in knowledge regarding the association between combination therapy and outcomes in adults with sepsis-induced DIC.
Effect of combination therapy with recombinant thrombomodulin and antithrombin on outcomes in patients with sepsis-induced disseminated intravascular coagulation in a surgical intensive care unit: a retrospective observational study · 2026 · DOIThe lack of comparative effectiveness of enoxaparin versus unfractionated heparin on mortality in sepsis patients. The need to minimize confounding due to differential drug clearance in patients with severe renal dysfunction. The importance of evaluating the effect of anticoagulant type on mortality in sepsis patients without severe renal dysfunction.
Comparative effectiveness of enoxaparin versus unfractionated heparin for 30- and 90-day mortality in sepsis patients without severe renal dysfunction: a retrospective cohort study · 2026 · DOIThe paper acknowledges the complexity of sepsis and the need for further research to understand the role of Lcn2 in mitochondrial dysfunction.
Lipocalin‐2 Restores Mitochondrial and Antioxidant Adaptation in a Strain‐Specific Manner During LPS Induced Sepsis · 2026 · DOIThere is limited direct comparative evidence between fluid-based resuscitation strategies, vasopressors, or a combination of both on hemodynamic changes. The timing and sequence of vasopressor therapy is debated.
Hemodynamic Responses to Fluid and Vasopressor Resuscitation Strategies in Experimental Septic Shock: A Randomized Porcine Model Research Protocol · 2026 · DOIHemodynamic incoherence is a core clinical dilemma in septic shock. There is a need to explore the role of SMA Doppler parameters in characterizing the sepsis-severity spectrum.
Superior mesenteric artery Doppler parameters across sepsis severity spectrum and their discriminative performance for refractory septic shock · 2026 · DOIThe study notes the need to correct technical batch effects between the two cohorts. The study references the challenge of identifying optimal predictive models for HCEM features at the single-cell level.
Hypoxia-driven macrophage heterogeneity in sepsis: single-cell transcriptomic insights into immune reprogramming and therapeutic targeting · 2026 · DOIThe gap identified is the need for evaluation of the combined prognostic associations of Annexin V, sFas, and sFasL in sepsis. There is a lack of understanding of how these biomarkers relate to immune dysfunction and adverse outcomes in sepsis.
Prognostic significance of lymphocyte apoptosis markers (Annexin V, sFas, and sFasL) in sepsis: a retrospective clinical study · 2026 · DOIOne challenge is the heterogeneity of the sepsis syndrome, which makes it difficult to identify a single biomarker that captures the full complexity of the disease. Another challenge is the need for a more comprehensive characterization of clinical severity in sepsis patients.
A Multiparametric Approach to the Assessment of Sepsis Severity: The Role of Immature Platelet Fraction and Infection Biomarkers · 2026 · DOIThe current biomarkers used for sepsis diagnosis and prognosis have limitations. There is a need for a more comprehensive characterization of clinical severity in sepsis patients. A multiparametric approach may address this gap by integrating parameters reflecting different biological pathways.
A Multiparametric Approach to the Assessment of Sepsis Severity: The Role of Immature Platelet Fraction and Infection Biomarkers · 2026 · DOIThe lack of specific treatment for sepsis. The limitations of traditional diagnostic methods for identifying sepsis. The need for biomarkers to guide therapy and monitor effectiveness.
Despite growing recognition of the glycocalyx as a therapeutic target, its temporal dynamics and potential pharmacological modulation remain poorly understood.
Persistent Endothelial Glycocalyx Disruption in Sepsis: Translational Evidence for Melatonin‐Mediated Vascular Protection · 2026 · DOIHowever, large-scale randomized controlled trials (RCTs) evaluating MB treatment for mortality benefit in high-dose vasopressor-dependent septic shock patients are currently lacking.
Early Methylene Blue for Mortality Reduction in High-Dose VasoPREssor-Dependent Septic Shock (EMPRESS): protocol for a multicenter randomized controlled trial · 2026 · DOIHowever, their role in regulating mitochondria-mediated apoptosis in sepsis remains underexplored.
Targeting mitochondrial apoptosis in septic lung injury: protective potential of omega-3 fatty acids · 2026 · DOIValidated tools to guide culture ordering at initial patient assessment are lacking.
The SCANNED rule: derivation and validation of a two-step rule for blood culture stewardship in patients presenting with suspected infection · 2026 · DOIHospital capacity, bed constraints, and limited resources are constant issues faced within publicly funded health care systems.
External validation of the model is required, - Prospective operational evaluation of the model is needed, - Further research on the use of EHR data for clinical deterioration…
Development and internal validation of an EHR machine learning model for clinical deterioration in ICU linked inpatients · 2026 · DOILack of a diagnostic gold standard for sepsis - Limited accuracy of clinical signs and biomarkers for sepsis diagnosis - Need for a reliable and accurate diagnostic test…
Diagnostic accuracy of SeptiCyte® RAPID to discriminate sepsis from non-infectious critical illness in patients meeting sepsis criteria according to sepsis-3 definition at ICU admission · 2026 · DOIFurther studies are needed to determine whether combination therapy translates into clinically meaningful benefits, - Research on the optimal dosage and duration of rTM and AT therapy is needed, - Studies on the cost-effectiveness of combination therapy compared to monotherapy are required, - Investigation of the potential benefits of combination therapy in other patient populations…
Effect of combination therapy with recombinant thrombomodulin and antithrombin on outcomes in patients with sepsis-induced disseminated intravascular coagulation in a surgical intensive care unit: a retrospective observational study · 2026 · DOIWide confidence intervals indicate that both clinically meaningful benefit and negligible effect remain compatible with the data, - The study was retrospective, - No severe renal impairment…
Comparative effectiveness of enoxaparin versus unfractionated heparin for 30- and 90-day mortality in sepsis patients without severe renal dysfunction: a retrospective cohort study · 2026 · DOIThe global development trajectory of NET-related sepsis studies is unclear, - The research frontiers of NET-related sepsis studies are not well…
Global trends and emerging frontiers in neutrophil extracellular trap-related sepsis research: a bibliometric analysis · 2026 · DOIDetermine whether rec-Lcn2 exerts similar protective effects in models of microbial sepsis - Delineate the mechanistic interplay between ACOD1 and Lcn2 in regulating iron homeostasis, mitochondrial function, and cell survival pathways during…
Lipocalin‐2 Restores Mitochondrial and Antioxidant Adaptation in a Strain‐Specific Manner During LPS Induced Sepsis · 2026 · DOIInvestigate the relationship between SMA Doppler parameters and intestinal microcirculatory perfusion, - Explore the potential of SMA Doppler as a diagnostic tool for refractory septic shock, - Conduct a multicenter prospective study to validate…
Superior mesenteric artery Doppler parameters across sepsis severity spectrum and their discriminative performance for refractory septic shock · 2026 · DOIFurther studies are needed to establish incremental predictive performance beyond conventional severity scores, - Research on the nonlinear exposure-response patterns for PLR and CLR is needed, - Studies on the association between inflammatory-immune indices and mortality in different populations…
Exploratory associations of composite inflammatory-immune markers with 28-day and 1-year all-cause mortality in patients with sepsis: a retrospective cohort study · 2026 · DOIFurther studies are needed to validate the findings, - The prognostic associations of Annexin V, sFas, and sFasL in sepsis should be evaluated in larger cohorts, - The mechanisms underlying the association between lymphocyte apoptosis and mortality in sepsis should be…
Prognostic significance of lymphocyte apoptosis markers (Annexin V, sFas, and sFasL) in sepsis: a retrospective clinical study · 2026 · DOI
Most-cited papers in Sepsis Diagnosis and Treatment
- The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) · JAMA · 2016 · 24,089 citations
- Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock · New England Journal of Medicine · 2001 · 7,908 citations
- Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study · The Lancet · 2020 · 6,763 citations
- A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study · JAMA · 1993 · 6,335 citations
- The Epidemiology of Sepsis in the United States from 1979 through 2000 · New England Journal of Medicine · 2003 · 4,719 citations
- Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis · New England Journal of Medicine · 2001 · 4,557 citations
- Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 · Intensive Care Medicine · 2021 · 4,458 citations
- Assessment of Clinical Criteria for Sepsis · JAMA · 2016 · 3,368 citations
- Severe Sepsis and Septic Shock · New England Journal of Medicine · 2013 · 3,191 citations
- The Pathophysiology and Treatment of Sepsis · New England Journal of Medicine · 2003 · 3,124 citations
Most recent work
- Executive Summary: Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026 · Critical Care Medicine · 2026
- Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2026 · Intensive Care Medicine · 2026
- Sepsis · The Lancet · 2026
- Artificial Intelligence Drives Advances in Multi-Omics Analysis and Precision Medicine for Sepsis · Biomedicines · 2026
- Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 2026 · Intensive Care Medicine · 2026
- Quantifying immune dysregulation in pneumonia and sepsis with a parsimonious machine-learning model: a multicohort analysis across care settings and reanalysis of a hydrocortisone randomised controlled trial · The Lancet Respiratory Medicine · 2026
- Multicenter Prospective Validation of an Updated Proprietary Sepsis Prediction Model · JAMA Network Open · 2026
- An artificial intelligence-powered learning health system to improve sepsis detection and quality of care: a before-and-after study · npj Digital Medicine · 2026
- Challenges in early detection and prognostication of sepsis: new approaches from the emergency department and intensive care unit · EClinicalMedicine · 2026
- Sepsis Endotypes Defined by Lymphocyte Thresholds and Inflammation Inform Precision Immunomodulation · MedComm · 2026
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