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Open research questions in Inflammatory Biomarkers in Disease Prognosis

67 unresolved questions extracted from the limitations and future-work sections of 301 Inflammatory Biomarkers in Disease Prognosis papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The neutrophil percentage-to-albumin ratio (NPAR), integrating inflammatory, and nutritional markers, has shown prognostic value in other conditions but remains underexplored in CKD.

    The prognostic value of the neutrophil percentage-to-albumin ratio for all-cause and cardiovascular mortality in chronic kidney disease: A retrospective cohort study using NHANES 1999 to 2018 · 2026 · DOI

  • The C-reactive protein–albumin–lymphocyte (CALLY) index, reflecting inflammation, nutritional status, and immune function, has shown prognostic value in various diseases, but its role in HFpEF remains unclear.

    The CALLY Index as an integrated inflammation–nutrition biomarker for risk stratification in HFpEF · 2026 · DOI

  • Rather, it may serve as a complementary risk marker to help identify patients who could benefit from closer postoperative surveillance or further investigation of haematological vulnerability. Future prospective and multicentre studies are warranted to validate these results and to further elucidate the biological pathways linking haematological profiles to cSDH recurrence.

    Prognostic Value of Peripheral Blood Inflammatory Markers in Chronic Subdural Haematoma: A Retrospective Cohort Study · 2026 · DOI

  • Its prognostic significance for mortality in patients with hyperuricemia (HUA) or gout remains incompletely understood, and whether this association differs between asymptomatic HUA and gout has not been examined.

    Prognostic value of the neutrophil percentage-to-albumin ratio for mortality in patients with hyperuricemia and gout · 2026 · DOI

  • Background Miscarriage affects 15%–20% of clinically recognized pregnancies, yet reliable biomarkers for risk stratification remain elusive.

    The “Goldilocks Zone” of immune balance: association of neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios with miscarriage · 2026 · DOI

  • Abstract Introduction Although monocyte-to-lymphocyte ratio (MLR), monocyte-to-HDL cholesterol ratio (MHR), and prognostic nutritional index (PNI) – have been associated with renal function in patients with diabetes mellitus, their repeatability and predictive value remain unclear.

    Reliability and predictive value of inflammatory indices for eGFR change in diabetic patients: A 6-month follow-up study · 2026 · DOI

  • The present study has several strengths, including its large sample size and the consideration of clinical and laboratory measures to evaluate hemostatic function. The validity of the results is also increased with the use of various statistical approaches. Nevertheless, some limitations should be noted. The study is cross- sectional, which impedes causal inference. The findings may not be generalized because of convenience sampling and may be subject to reporting bias due to self-reported bleeding symptoms. To determine the correlation between platelet dysfunction and bleeding in CKD, longitudinal studies are needed. Medications, including antiplatelet agents and NSAIDs, could have influenced bleeding, which was not considered in the regression analysis. In addition, the bleeding assessment relied on a study-specific symptom questionnaire rather than a formally validated bleeding assessment tool, potentially affecting the precision and reproducibility of bleeding classification. Furthermore, direct platelet function testing was not performed. Therefore, the proposed explanation of qualitative platelet dysfunction remains speculative and could not be confirmed by the present study. Additionally, MPV may be influenced by pre-analytical and analytical factors, including sample processing conditions and laboratory methodology, which were not evaluated in this study.

    Coexistence of Elevated Mean Platelet Volume and Bleeding Symptoms in Chronic Kidney Disease: A Discordant Hemostatic Profile · 2026 · DOI

  • Data availability statement Strengths include a biologically informed design, rigorous model development with LASSO selection and bootstrap validation, external temporal validation, and mediation analysis providing insight into potential pathways. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

    Systemic immune-inflammation index predicts post-thrombectomy outcomes and reveals a mediating role in the association between neurocardiac stress and prognosis: a multicenter study · 2026 · DOI

  • it cannot fully elucidate This study has several limitations. First, as a retrospective cross-sectional study, the causal relationship between SIRI, TyG, and the severity of coronary artery stenosis. Future prospective cohort studies are needed to confirm our findings and provide a clearer understanding of their causal relationship. Second, this study specifically enrolled patients aged 60 years and above. This age restriction was adopted for two primary reasons. First, the prevalence and severity of coronary atherosclerosis increase substantially after the sixth decade of life, making this age group a clinically relevant, high-burden population for investigating novel risk FIGURE 3 Reciprocal mediation effects of SIRI and TyG on severe stenosis. Adjusted for age, BMI, smoking, hypertension, diabetes, HbA1c, LDL-C, HDL-C, creatinine, leukocytes, uric acid, CRP, and fibrinogen. (A) SIRI affects severe stenosis with TyG as a mediator; (B) TyG affects severe stenosis with SIRI as a mediator. SIRI, systemic inflammation response index; TyG, triglyceride-glucose index; CI, confidence interval; ACME, average causal mediation effect; ADE, average direct effect.

    Association of systemic inflammation response index and triglyceride-glucose index with the severity of coronary artery stenosis in elderly patients: a retrospective cross-sectional study · 2026 · DOI

  • The paper acknowledges that resource constraints precluded comprehensive immunological assessments such as CD8-positive and CD4-positive T-lymphocyte enumeration, viral load quantification, and specific dengue serotype identification. Future studies in resource-limited settings should integrate flow cytometry analysis of T-cell populations and viral serotyping to elucidate the exact mechanisms driving the inverse relationship between Platelet-to-Lymphocyte Ratio and severe dengue manifestations.

    Inverse Association between Platelet-to-Lymphocyte Ratio and Clinical Severity in Pediatric Dengue Infection: A Retrospective Cross-Sectional Analysis at Wangaya Hospital, Indonesia · 2026 · DOI

  • The modest Spearman correlation value of -0.293 indicates the Platelet-to-Lymphocyte Ratio explains only approximately 8.5 percent of observed clinical variance in dengue severity. Future research should prospectively incorporate additional comprehensive laboratory assessments and immunological markers to identify multivariate combinations that improve predictive accuracy beyond the standalone ratio's Area Under the Curve of 0.685.

    Inverse Association between Platelet-to-Lymphocyte Ratio and Clinical Severity in Pediatric Dengue Infection: A Retrospective Cross-Sectional Analysis at Wangaya Hospital, Indonesia · 2026 · DOI

  • The absence of immunoglobulin G avidity testing prevented stratification of patients into primary versus secondary dengue infection status. Future studies must incorporate complete immunoglobulin G avidity testing to distinguish primary and secondary heterotypic infections, as secondary infections drive the massive cytokine storms and Antibody-Dependent Enhancement pathways that severely skew the Platelet-to-Lymphocyte Ratio.

    Inverse Association between Platelet-to-Lymphocyte Ratio and Clinical Severity in Pediatric Dengue Infection: A Retrospective Cross-Sectional Analysis at Wangaya Hospital, Indonesia · 2026 · DOI

  • The retrospective, cross-sectional study design prevents tracking of continuous day-to-day fluctuations of the Platelet-to-Lymphocyte Ratio throughout the entire longitudinal illness trajectory. Longitudinal studies are required to map the daily kinetics of this ratio from initial fever spike through the convalescent phase, capturing viral clearance, cytokine storm resolution, and bone marrow rebound.

    Inverse Association between Platelet-to-Lymphocyte Ratio and Clinical Severity in Pediatric Dengue Infection: A Retrospective Cross-Sectional Analysis at Wangaya Hospital, Indonesia · 2026 · DOI

  • The study population consisted entirely of Chinese patients, and MPV measurement is susceptible to methodological variations (e.g., timing of analysis and anticoagulant choice); inter-laboratory systematic errors may exist, and external validity requires further verification in other ethnic populations.

    Interaction between high-sensitivity C-reactive protein and mean platelet volume for 1-year major adverse cardiovascular events in stable coronary artery disease · 2026 · DOI

  • The one-year follow-up in stable CAD patients resulted in a relatively limited number of clinical events, which may have constrained statistical power and potentially obscured modest associations in isolated exposure groups.

    Interaction between high-sensitivity C-reactive protein and mean platelet volume for 1-year major adverse cardiovascular events in stable coronary artery disease · 2026 · DOI

  • Future research incorporating additional inflammatory, iron status, and erythropoietin parameters could provide more nuanced insight into precise underlying mechanisms driving the relationship between RDW and eGFR in CKD.

    Relationship between Red Cell Distribution Width (RDW) and Severity of Chronic Kidney Disease (CKD) · 2026 · DOI

  • The study did not evaluate other potential confounding factors or mediators, such as specific inflammatory markers (hs-CRP, procalcitonin), detailed iron status parameters (serum ferritin, transferrin saturation), or endogenous erythropoietin levels.

    Relationship between Red Cell Distribution Width (RDW) and Severity of Chronic Kidney Disease (CKD) · 2026 · DOI

  • The cross-sectional design prevents establishment of definitive causal relationship between RDW and eGFR, as it is not possible to ascertain whether elevated RDW directly contributes to CKD progression or merely represents a consequence of advanced kidney disease.

    Relationship between Red Cell Distribution Width (RDW) and Severity of Chronic Kidney Disease (CKD) · 2026 · DOI

  • The correlation of the interleukin (IL)-10 gene and tumor necrosis factor alpha (TNF-α) polymorphisms with ITP susceptibility has been previously investigated, but the association with clinical and prognostic parameters remains unclear.

    Role of tumor necrosis factor-alpha–308 G/A and interleukin-10 promotor–592 C/A polymorphisms in adult immune thrombocytopenic purpura · 2022 · DOI

  • Objective: There is a lack of data in the current literature regarding the spontaneous progression of inflammatory biomarkers early after cardiovascular implantable electronic device (CIED) placement.

    Progression of Inflammatory Biomarkers Early after Cardiovascular Implantable Electronic Device Placement · 2020 · DOI

  • AIM: The role of inflammatory condition assessed using routine laboratory tests in cardiac resynchronisation therapy (CRT) response has not been investigated thoroughly.

    The role of baseline indirect inflammatory markers in prediction of response to cardiac resynchronisation therapy · 2015 · DOI

  • Future research should consider integrating immune microenvironment-related molecular biomarkers to explore  more precise and comprehensive predictive models.

    Prognostic significance of baseline C-reactive protein/albumin ratio for long-term outcomes in advanced gastric cancer under immunochemotherapy · 2026 · DOI

  • However, their comparative utility in predicting PD-associated peritonitis (PDAP) remains unclear.

    Predictive value of complete blood cell count-based inflammatory markers for peritonitis risk in peritoneal dialysis patients: A multicenter cohort study · 2026 · DOI

  • While systemic inflammatory markers derived from routine complete blood count have shown promise in identifying associations with adverse pregnancy outcomes, their association with miscarriage has not been systematically evaluated.

    The “Goldilocks Zone” of immune balance: association of neutrophil-to-lymphocyte and lymphocyte-to-monocyte ratios with miscarriage · 2026 · DOI

  • The limitations of this study are: 1) This study only consists of subjects who underwent surgery with sur- gical complexity levels 2 and 3, these results cannot represent subjects with surgical complexity levels 4, 5 and 6.

    The effect of oral protein and carbohydrate solution administration on NLR, IL-6 and CRP levels in patients undergoing surgery · 2026 · DOI

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67 open questions have been extracted from the limitations and future-work passages of 301 Inflammatory Biomarkers in Disease Prognosis papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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