Background: Inflammation plays a pivotal role in the pathogenesis of both acute and chronic heart failure. Recent studies showed that the neutrophil-to-lymphocyte ratio (NLR) could be related to adverse outcomes in patients with cardiovascular diseases. We sought to evaluate whether NLR could predict mortality in patients with acute heart failure by means of a meta-analysis. Methods: A comprehensive literature search was performed in PubMed, Embase, and Cochrane databases through January 2023 for studies evaluating the association of NLR with mortality in patients with acute heart failure. Primary outcomes were in-hospital mortality and long-term all-cause mortality. Endpoints were pooled using a random-effects DerSimonian-and-Laird model and were expressed as a hazard ratio (HR) or mean difference (MD) with their corresponding 95% confidence intervals. Results: A total of 15 studies with 15,995 patients with acute heart failure were included in the final study. Stratifying patients based on a cut-off NLR, we found that high NLR was associated with a significantly higher in-hospital mortality [HR 1.54, 95% CI (1.18–2.00), p < 0.001] and long-term all-cause mortality [HR 1.61, 95% CI (1.40–1.86), p < 0.001] compared to the low-NLR group. Comparing the highest against the lowest NLR quartile, it was shown that patients in the highest NLR quartile has a significantly heightened risk of long-term all-cause mortality [HR 1.77, 95% CI (1.38–2.26), p < 0.001] compared to that of lowest NLR quartile. However, the risks of in-hospital mortality were compared between both quartiles of patients [HR 1.78, 95% CI (0.91–3.47), p = 0.09]. Lastly, NLR values were significantly elevated among non-survivors compared to survivors during index hospitalization [MD 5.07, 95% CI (3.34–6.80), p < 0.001] and during the follow-up period [MD 1.06, 95% CI (0.54–1.57), p < 0.001]. Conclusions: Elevated NLR was associated with an increased risk of short- and long-term mortality and could be a useful tool or incorporated in the risk stratification in patients with acute heart failure.

Introduction: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. Methods: We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). Results: Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16–1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13–1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. Conclusions: Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.

Congestive heart failure (CHF) is associated with significant morbidity and mortality. There has been renewed interest in using thrombo-inflammatory markers as prognostic tools in patients with CHF. To determine if thrombo-inflammatory markers are independent risk factors for 28-day mortality in hospitalized CHF patients, we retrospectively analyzed admission data extracted from 2008 consecutive patients admitted with a diagnosis of CHF to Zigong Fourth People’s Hospital. Multivariate Cox proportional hazards analysis demonstrated that the thrombo-inflammatory markers thrombin time, platelet/lymphocyte ratio (PLR), and D-dimer level were independent predictors of mortality. In addition, variables reflecting the severity of CHF (New York Heart Association class > 2), impaired renal function (elevated serum creatinine [SCr]), impaired organ perfusion (elevated BUN), and chronic liver disease were also independent predictors of mortality. Thrombo-inflammatory biomarkers were only weakly associated with SCr and the burden of co-morbidity, suggesting that thrombo-inflammation may in large part be attributable to CHF itself and that, moreover, its presence may confer an increased risk of mortality. Further large-scale prospective studies are needed to determine the existence and the consequences of a thrombo-inflammatory phenotype among patients with CHF.

Background: Septic shock is a heterogeneous syndrome with diverse clinical presentations and pathophysiology, yet current management guidelines largely treat it as a homogenous entity. Early risk stratification relies on lactate and different predictive scoring systems, which may not capture the underlying heterogeneity in host responses. Aim: To identify discrete subphenotypes of septic shock using admission demographics and laboratory parameters, and to evaluate their relationship with in-hospital outcomes. Methods: We conducted a retrospective multicenter cohort study of 10,462 adult patients with ICD-10-defined septic shock admitted to intensive care units between 2014 and 2015. We used Two-Step Cluster Analysis using log-likelihood distance and the Bayesian Information Criterion to identify two distinct phenotypes. We compared clusters on baseline characteristics, in-hospital outcomes including mortality, days on mechanical ventilation, vasopressor use, acute kidney injury (AKI), AKI requiring renal replacement therapy (RRT), and ICU and hospital lengths of stay. Results: We identified two clusters (Cluster 1, n = 5355 and Cluster 2, n = 5107) in our study. Cluster 1 showed greater biochemical severity at presentation, including higher median lactate (2.40 vs. 2.20 mmol L⁻¹; p < 0.001), serum creatinine (1.39 vs. 1.20 mg dL⁻¹; p < 0.001), blood urea nitrogen (28 vs. 25 mg dL⁻¹; p < 0.001), and neutrophil-to-lymphocyte ratio (11.12 vs. 10.38; p < 0.001), and a higher mean SOFA score (7.05 ± 3.85 vs. 6.76 ± 3.87; p < 0.001). Despite this, Cluster 1 required mechanical ventilation more frequently (46.1% vs. 42.2%; p < 0.001) and had a higher incidence of AKI (58.1% vs. 55.6%; p = 0.009), including more stage 3 AKI (17.2% vs. 15.2%; p < 0.001) and dialysis (6.6% vs. 5.2%; p = 0.005), yet experienced similar in-hospital mortality (15.4% vs. 15.8%; p = 0.615) and comparable ICU (2.18 vs. 2.26 days; p = 0.254) and hospital lengths of stay (6.63 vs. 6.80 days; p = 0.251). Conclusions: Two septic shock phenotypes were identified, one with marked early organ dysfunction (Cluster 1) and another with milder initial derangements (Cluster 2), yet both showed convergent short-term mortality and lengths of stay despite divergent support needs. These results challenge reliance on single-parameter severity markers and underscore the need for phenotype-guided risk stratification and personalized management strategies in septic shock.

Background: Cardiorenal syndrome (CRS) reflects bidirectional heart–kidney injury whose mechanisms extend far beyond hemodynamics. High-throughput genomics and multi-omics now illuminate the molecular circuits that couple cardiac and renal dysfunction. Methods: We narratively synthesize animal and human studies leveraging transcriptomics, proteomics, peptidomics, metabolomics, and non-coding RNA profiling to map convergent pathways in CRS and to highlight biomarker and therapeutic implications. Results: Across acute and chronic CRS models, omics consistently converge on extracellular matrix (ECM) remodeling and fibrosis (e.g., FN1, POSTN, collagens), immune–inflammatory activation (IL-6 axis, macrophage/complement signatures), renin–angiotensin–aldosterone system hyperactivity, oxidative stress, and metabolic/mitochondrial derangements in both organs. Single-nucleus and bulk transcriptomes reveal tubular dedifferentiation after cardiac arrest-induced AKI and myocardial reprogramming with early CKD, while quantitative renal proteomics in heart failure demonstrates marked upregulation of ACE/Ang II and pro-fibrotic matricellular proteins despite near-normal filtration. Human translational data corroborate these signals: urinary peptidomics detects CRS-specific collagen fragments and protease activity, and circulating FN1/POSTN and selected microRNAs (notably miR-21) show diagnostic potential. Epigenetic and microRNA networks appear to integrate these axes, nominating targets such as anti-miR-21 and anti-fibrotic strategies; pathway-directed repurposing exemplifies dual-organ benefit. Conclusions: Genomics and multi-omics recast CRS as a systems disease driven by intertwined fibrosis, inflammation, neurohormonal and metabolic programs. We propose a translational framework that advances (i) composite biomarker panels combining injury, fibrosis, and regulatory RNAs; (ii) precision, pathway-guided therapies; and (iii) integrated, longitudinal multi-omics of well-phenotyped CRS cohorts to enable prediction and personalized intervention.

Background: Melatonin has antioxidant and anti-inflammatory properties that may attenuate ischemia-reperfusion injury, but randomized cardiovascular trial data remain inconsistent. Objectives: This study sought to evaluate the association of melatonin supplementation with cardiovascular outcomes across randomized trials. Methods: We performed a systematic review and meta-analysis of randomized trials comparing melatonin with placebo, usual care, or no melatonin in patients with cardiovascular disease. PubMed, Embase, and CENTRAL were searched from inception to 1 January 2026. Random-effects models with Hartung–Knapp–Sidik–Jonkman confidence intervals were used. Prespecified outcomes included left ventricular ejection fraction (LVEF), change in LVEF, troponin, infarct size by cardiac magnetic resonance, heart failure outcomes, inflammatory and oxidative stress biomarkers, and adverse events. Results: A total of 14 randomized controlled trials involving 1027 participants were included. Melatonin significantly improved change in LVEF from baseline to follow-up (mean difference: 3.95 percentage points; 95% CI: 1.70–6.20; p < 0.001), with the most consistent signal in coronary artery bypass grafting studies (mean difference: 4.65 percentage points; 95% CI: 2.56–6.74). Final LVEF was numerically higher with melatonin but not statistically significant. Troponin reduction was not significant. Narrative synthesis suggested lower inflammatory and oxidative stress markers after coronary artery bypass grafting and improvement in heart failure symptoms and quality of life, whereas infarct size findings in ST-segment elevation myocardial infarction were mixed and timing-dependent. Conclusions: Melatonin was associated with improved LVEF change, particularly in coronary artery bypass grafting settings, but benefit was not consistently demonstrated across final LVEF, troponin, or infarct size outcomes.