Search Results (16,851)

Background/Objectives: Lifestyle modification is central to non-alcoholic fatty liver disease, now termed metabolic dysfunction-associated steatotic liver disease (NAFLD/MASLD), yet comparable health-promoting lifestyle (HPL) data for patients and family members are limited. This study compared two independent samples and examined psychosocial correlates. Methods: Two convenience samples recruited at one tertiary hospital were analyzed: 305 adults with NAFLD/MASLD and 299 adult family members of affected patients. A self-administered electronic questionnaire comprised the Health-Promoting Lifestyle Profile II (HPLP-II), the Self-Rated Abilities for Health Practices scale, autonomous-motivation items from the Treatment Self-Regulation Questionnaire, the Medical Outcomes Study Social Support Survey, and sociodemographic items. Group comparisons used parametric and non-parametric tests. HPL correlates were examined using complete-case regression, HC3 inference, and rank-based sensitivity analysis. Cross-sectional indirect-association decompositions used 5000 bootstrap resamples. Results: HPLP-II scores were 102.2 ± 17.5 in patients and 104.2 ± 17.4 in family members (p = 0.171; Mann–Whitney p = 0.166); the adjusted patient-minus-family difference was −1.14 (HC3 95% CI −3.89 to 1.60; p = 0.413). Physical activity was the lowest-scoring dimension. Self-efficacy was the most robust correlate in both samples; social support was associated in the primary models but weakened under rank transformation in family members. Group-by-correlate interactions were not significant. Exploratory indirect associations through self-efficacy were 0.355 (95% bootstrap CI 0.234–0.512) in patients and 0.163 (0.071–0.287) in family members; reverse-order models were also non-zero. Conclusions: The independent unmatched samples reported similar moderate, physically inactive lifestyles. The results identify associations, not shared-household effects or causal mechanisms; objectively characterized, dyad-matched longitudinal studies are needed. Full article

Patients with chronic liver disease are systematically excluded from acute myocardial infarction (AMI) trials, and prior real-world data rely on administrative coding alone. Whether ICD-coded liver disease and laboratory-defined liver fibrosis identify the same patients, and whether they predict the same outcomes, is unknown. We conducted a single-center retrospective cohort study of 1037 consecutive adults admitted with AMI (ICD-10 I21.x) to a tertiary New York center between November 2022 and December 2024. The primary exposure was ICD-defined advanced liver disease (cirrhosis, hepatic failure, or portal hypertension/decompensation; n = 102). The secondary, lab-based exposure was the Fibrosis-4 (FIB-4) index calculated from earliest admission AST, ALT, and platelet count (computable in 1031 patients, 99.4%), stratified as low (<1.45), indeterminate (1.45–3.25), or advanced (>3.25). Co-primary outcomes were invasive management (diagnostic angiography, percutaneous coronary intervention, or coronary artery bypass grafting) and in-hospital mortality. Multivariable logistic regression adjusted for age, sex, diabetes, chronic kidney disease, heart failure, and ST-elevation; the trend across FIB-4 tiers was assessed with the Cochran–Armitage test. Denominators throughout (including the 168/909 occult-fibrosis estimate) use the full exposure group as denominator under a missing-as-not-exposed convention; the four no-LD and two advanced-LD patients with missing FIB-4 are counted as non-advanced fibrosis for this calculation. Patients with ICD-defined advanced liver disease received invasive management less often (12.7% vs. 50.4%; adjusted odds ratio [aOR] 0.17, 95% CI 0.09–0.32) and died in hospital more often (43.1% vs. 7.9%; aOR 8.22, 95% CI 5.02–13.46) than patients without coded liver disease. Outcomes worsened monotonically across FIB-4 tiers (mortality 4.4% → 9.2% → 27.5%; invasive management 55.2% → 45.6% → 33.5%; both p < 0.001 by Cochran–Armitage trend test). Critically, 168 of 909 patients with no coded liver disease (18.5%) had FIB-4 > 3.25, representing a substantial population of unrecognized advanced fibrosis missed by clinical coding. Coded liver disease identifies a small, severely affected subgroup with markedly lower rates of invasive management and 6- to 8-fold higher mortality after AMI. Routine FIB-4 calculation, a free, three-variable lab score, identifies a much larger population with occult advanced fibrosis and graded excess risk that ICD codes miss entirely. Pending prospective validation, FIB-4 may serve as a low-cost adjunct to bedside risk stratification in AMI care. Full article

Background: Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy in which neurodegeneration may be accompanied by neuroinflammatory and peripheral immune alterations. Whether peripheral inflammatory activity reflects structural degeneration within vulnerable brain networks remains unclear. Methods: This retrospective case–control study included 12 patients with PSP and 12 patients with Parkinson’s disease (PD). Automated volumetric analysis of 3-Tesla MRI was performed using volBrain 2.0. Blood-derived inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and red blood cell distribution with coefficient of variation (RDW-CV). Results: Patients with PSP showed significantly lower normalized superior frontal gyrus and pallidal volumes than patients with PD. Within the PSP group, higher values of selected blood-derived inflammatory indices were associated with lower frontal network volumes. After adjustment for age, MLR was inversely associated with the composite Frontal Network Score (partial r = −0.7333, p = 0.0067, FDR q = 0.020). The strongest regional association was observed between SIRI and medial frontal cortex volume (rho = −0.748, p = 0.0051); however, regional associations did not remain significant after FDR correction. Conclusions: Peripheral inflammatory markers were associated with MRI-derived measures of frontal network degeneration in PSP. The association between MLR and the composite Frontal Network Score supports a link between systemic immune alterations and network-level neurodegeneration in PSP. Full article

Background/Objectives: Antibiotics are the recommended first-line therapy for acute uncomplicated lower urinary tract infections (cystitis), but antibiotic resistance and tolerability concerns require antibiotic-sparing strategies. This study evaluated D-mannose as a stand-alone alternative. Methods: This multicenter, randomized, controlled, double-blind study compared D-mannose to fosfomycin in women aged 18–70 with cystitis. Clinical cure (CC) was assessed using the Acute Cystitis Symptom Score (ACSS) up to day 8, with non-inferiority tested at the 15% margin. Post hoc analytical approaches accounted for potential bias due to low sample sizes and missing values. Results: The study randomized 118 patients. At baseline, severe symptoms (ACSS ≥ 12) were more frequent in the D-mannose group compared to fosfomycin (32.8% vs. 22.8%). Efficacy analyses were performed on the per-protocol set (D-mannose: N = 57; fosfomycin: N = 54). Median time to CC was 5.0 days (D-mannose) and 3.0 days (fosfomycin) overall, and 4.0 days vs. 3.0 days in the subgroup of moderate disease severity. The point estimate for the CC rate difference on day 8 (−10.1%) favored fosfomycin but was within the non-inferiority margin. Due to wide confidence intervals, non-inferiority was not statistically confirmed. The post hoc analysis yielded smaller confidence intervals with estimated CC rates of 84.2% (D-mannose) vs. 83.5% (fosfomycin) on day 8 and statistically demonstrated the comparability of both treatments. Recurrence rates were similar (13.2% vs. 13.3%), and there was no statistically significant difference for additional antibiotic use (19.3% vs. 11.1%). Investigators and patients favored D-mannose over fosfomycin for tolerability, and gastrointestinal adverse events were less frequent (9.8% vs. 24.6%). Conclusions: Post hoc analysis indicated that D-mannose treatment is comparable to fosfomycin in uncomplicated cystitis in line with the prespecified non-inferiority criteria. These findings warrant confirmation in an adequately powered trial but suggest that D-mannose is a promising alternative to antibiotics given its favorable risk–benefit ratio. Full article

Background/Objectives: Carotid intima–media thickness (CIMT) is widely recognized as an established biomarker of systemic atherosclerosis and coronary artery disease (CAD). Nevertheless, the connection between circulating miR-29 family members, CIMT and CAD severity has not yet been determined. The aim of this study was to investigate the association of plasma miR-29a and miR-29c with CIMT and CAD severity. Methods: A total of 628 patients scheduled for elective coronary angiography were included in the study. CAD severity was estimated using the Gensini scoring system and was classified into mild, moderate, and severe categories. Additionally, CIMT was evaluated using high-resolution B-mode ultrasonography, while plasma miR-29a and miR-29c levels were detected using qRT-PCR. Results: CIMT increased significantly with CAD severity (0.76 ± 0.15, 0.94 ± 0.18, and 1.12 ± 0.22 mm for mild, moderate, and severe CAD, respectively; p < 0.001). MiR-29a expression progressively increased, whereas miR-29c expression decreased with advancing CAD (both p < 0.001). MiR-29a correlated positively with CIMT (r = 0.612) and Gensini score (r = 0.658), while miR-29c showed negative correlations (r = −0.527 and −0.584, respectively; all p < 0.001). CIMT, miR-29a, and miR-29c were found to be independently associated with CAD severity. Their combined model demonstrated a powerful association with severe CAD (AUC = 0.927; sensitivity 88.6%; specificity 84.1%). Conclusions: Plasma miR-29a and miR-29c are independent biomarkers of CIMT and CAD severity. Their combination with CIMT can improve diagnosis of severe CAD and may enhance cardiovascular risk stratification. Full article

Background/Objectives: Interleukin-6 is a key proinflammatory cytokine involved in the pathophysiology of Familial Mediterranean Fever (FMF). This study aimed to evaluate interleukin-6 levels and the interleukin-6 rs1800795 variant in pediatric FMF participants and to investigate their associations with clinical manifestations, laboratory findings, and Mediterranean fever (MEFV) mutation status. Methods: The research involved 69 pediatric FMF participants and 50 healthy children. Interleukin-6 levels, laboratory findings, and genotype distributions of the interleukin-6 rs1800795 variant were compared between FMF and control groups. Moreover, the relationship between interleukin-6 levels and clinical findings, MEFV mutation status, and laboratory parameters were evaluated in the FMF group. Results: In the FMF group, interleukin-6, serum amyloid-A (SAA), white blood cell count (WBC), neutrophil, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels were higher compared to the control group. In the FMF group, interleukin-6 levels showed a positive correlation with ISSF score, annual attack frequency, the number of concomitant symptoms, disease duration, SAA, CRP, and ESR. The allele and genotype distribution of the interleukin-6 rs1800795 variant was similar to those in the control and FMF groups. In the FMF group, interleukin-6 values were higher in patients with abdominal pain, fever, chest pain, or arthralgia compared to those without these symptoms. Interleukin-6 levels were higher in both homozygous and compound heterozygous subgroups compared to the heterozygous subgroup. Conclusions: Elevated interleukin-6 levels in symptomatic pediatric FMF patients and those with homozygous or compound heterozygous MEFV mutations suggest that interleukin-6 may reflect both clinical disease severity and MEFV mutation status. Full article

Heart failure (HF) is a systemic syndrome in which prognosis depends on cardiac dysfunction, congestion, cardiorenal and cardiohepatic interactions, inflammation, and metabolic dysregulation. The liver is exposed to elevated systemic venous pressure and reduced forward flow, and contributes to albumin and coagulation factor synthesis, bile acid metabolism, iron homeostasis, and the acute-phase response. Cardiohepatic injury involves hemodynamic stress, sinusoidal endothelial dysfunction, oxidative stress, inflammatory signaling, fibrogenesis, and altered metabolic regulation. Congestive hepatopathy is associated with right-sided HF, tricuspid regurgitation (TR), pulmonary hypertension, and elevated central venous pressure, whereas hypoxic hepatitis develops during low-output states, shock, or acute circulatory deterioration. These mechanisms may coexist, producing congestive/cholestatic, hypoperfusive/ischemic and mixed/systemic reserve profiles. Composite liver-related scores, including Model for End-Stage Liver Disease (MELD), MELD excluding International Normalized Ratio (MELD-XI), MELD with sodium (MELD-Na), MELD-Albumin and albumin–bilirubin (ALBI) score, may reflect congestion, hepatorenal dysfunction, nutritional status and reduced systemic reserve. This review summarizes hemodynamic and molecular mechanisms of cardiohepatic injury, liver-related biomarkers and composite scores, with emphases on advanced HF, left ventricular assist device (LVAD) therapy and heart transplantation. Liver-related abnormalities remain underrecognized in HF. Their serial interpretation may support risk stratification, but composite scores should complement rather than replace comprehensive clinical assessment. Full article

Hematopoietic stem-cell transplantation (HSCT) has evolved from a salvage procedure for otherwise-fatal leukemia into a curative modality spanning nearly every hematological malignancy and several non-malignant disorders. The contemporary landscape has been reshaped by three converging forces: the refinement of disease-specific risk stratification (European LeukemiaNet [ELN] 2022 for acute myeloid leukemia, Molecular International Prognostic Scoring System [IPSS-M] for myelodysplastic syndromes, Mutation-Enhanced International Prognostic Scoring System [MIPSS70+ v2.0], and Myelofibrosis Transplant Scoring System [MTSS] for myelofibrosis); the integration of measurable residual disease (MRD) into dynamic, response-adapted transplant decisions; and the approval of immune effector cell therapies that have displaced transplantation from several long-standing indications while creating new ones (bridge-to-transplant, post-CAR-T consolidation). In parallel, post-transplant cyclophosphamide (PTCy) has largely equalized outcomes across matched sibling, matched unrelated, and mismatched alternative donors, and novel agents (ruxolitinib, belumosudil, axatilimab) have materially reduced graft-versus-host disease (GVHD) morbidity. This narrative review synthesizes current indications for autologous (auto-HSCT) and allogeneic (allo-HSCT) transplantations in adults, and flags areas of persistent controversy where randomized data are still maturing. Across all indications, the clinician’s question is shifting from “transplant or not?” towards “which donor, which conditioning, which bridge, and which post-transplant maintenance?”, each tailored to disease biology, MRD trajectory, and patient fitness. Full article

Background: Raynaud’s phenomenon (RP) may occur in the pediatric age span, sometimes representing the forerunner of devious underlying conditions. Objective: To investigate the prevalence of vitamin D deficiency in a single-center cohort of children and adolescents with idiopathic RP and evaluate changes in RP severity following cholecalciferol supplementation. Patients and Methods: Sixty-one children and adolescents with RP regularly followed at the pediatric rheumatology unit of our University between 2010 and 2025 were retrospectively evaluated. Clinical, laboratory, and nailfold videocapillaroscopy (NVC) findings were collected at baseline; patients were periodically examined for a mean investigation period of 3 ± 1.6 years. RP severity was assessed using the 2-week Raynaud’s Condition Score (RCS). Patients found to have serum 25-hydroxyvitamin D levels < 20 ng/mL received cholecalciferol supplementation for at least 12 weeks. Results: Nineteen out of 61 patients with RP (31.1% of the cohort) had vitamin D deficiency, while other laboratory parameters including inflammatory markers, complement fractions, liver and renal function tests, lipid profile, and autoimmune panel were non-informative. Univariate analysis demonstrated significant differences between vitamin D-deficient and non-deficient patients in terms of mean RP duration (p = 0.0002), baseline 2-week RCS (p = 0.0001), lupus-like anticoagulant positivity (p < 0.001), NVC pattern (p < 0.001), pain visual analogue scale (VAS) (p = 0.0001), and global quality of life VAS (p = 0.0001). After adjustment for age and sex, baseline 2-week RCS remained significantly associated with vitamin D deficiency. In addition, RCS significantly decreased during follow-up among vitamin D-deficient patients who received supplementation of cholecalciferol. Conclusions: Vitamin D deficiency may be common in pediatric idiopathic RP and pinpoint its severity: our exploratory study supports the routine assessment of vitamin D in children and adolescents with severe forms of RP, warranting prospective randomized controlled trials to determine whether correction of vitamin D deficiency may potentially improve disease severity. Full article

Objectives: A percutaneous native kidney biopsy remains the gold standard for diagnosing glomerular, tubulointerstitial and vascular kidney diseases. Although generally safe, it may cause major haemorrhagic complications. Using the French national registry, Kaczmarek et al. developed a simplified bleeding risk score (anaemia, female sex, heart failure, acute kidney injury; range: 0–5), achieving an AUC of 0.755 in native biopsies. We aimed to externally validate this score in a Romanian cohort and to assess whether additional clinically relevant predictors could improve discrimination for major bleeding. Methods: We conducted a retrospective cohort study of all consecutive adults undergoing an ultrasound-guided percutaneous native kidney biopsy at a tertiary nephrology centre in Romania between January 2008 and December 2024. The primary outcome was a composite major bleeding event: clinically significant haematoma or haemorrhage, blood transfusion, angiographic intervention or nephrectomy. The Kaczmarek score was validated using a receiver operating characteristic (ROC) analysis. Candidate predictors were assessed by multivariable logistic regression, and a simplified score was derived from the regression coefficients. Results: Among 3081 patients, 162 (5.3%) experienced major bleeding. The Kaczmarek score showed modest discrimination (AUC: 0.624, 95% CI: 0.585–0.663). In the multivariable analysis (n = 2506 complete cases), anaemia, heart failure, solid neoplasm and fibrinogen were independently associated with major bleeding. An eight-component score (anaemia, heart failure, solid neoplasm, and fibrinogen < 511 mg/dL; female sex, hypertension, liver disease, and eGFR < 30 mL/min/1.73 m²) achieved an AUC of 0.676 (95% CI: 0.631–0.717), outperforming the Kaczmarek score. Conclusions: The French score performed only modestly in our cohort. Adding comorbidities, kidney function and haemostatic parameters, particularly fibrinogen, improved the risk discrimination. Full article

(1) Introduction: Early identification of patients at high risk of recurrent events after hospitalization for acute decompensated heart failure (ADHF) remains challenging. The Larissa Heart Failure Risk Score (LHFRS) is a simple prognostic tool based on hypertension, coronary artery disease, and red blood cell distribution width. Urinary sodium has recently emerged as an objective marker of natriuretic response and decongestion. We prospectively evaluated whether incorporation of urinary sodium improves the prognostic performance of the LHFRS. (2) Methods: This prospective single-center observational study enrolled 130 consecutive adults hospitalized with ADHF. Clinical, laboratory, electrocardiographic, and echocardiographic data were collected at admission. Spot urinary sodium and chloride were measured at admission and 2 h after intravenous loop diuretic administration according to a standardized decongestion protocol. The primary endpoint was heart failure rehospitalization within 3 months. Secondary endpoints included all-cause mortality and the composite of death or heart failure rehospitalization. Multivariable logistic regression with bootstrap internal validation (1000 resamples) was used to identify independent predictors of outcomes. (3) Results: The study population included patients across the spectrum of heart failure phenotypes (HFrEF 58%, HFmrEF 7%, HFpEF 35%). During follow-up, 48 patients (36.9%) experienced heart failure rehospitalization and 23 (17.7%) died. The LHFRS independently predicted 3-month rehospitalization (B = 0.490, p = 0.041). Admission urinary sodium and 2-h urinary sodium provided incremental prognostic information beyond the LHFRS and remained independently associated with rehospitalization after multivariable adjustment (p = 0.008 and p = 0.001, respectively). Urinary chloride demonstrated similar prognostic associations, whereas conventional renal biomarkers, including serum creatinine, urea, estimated glomerular filtration rate, serum sodium, and NT-proBNP, did not consistently retain independent prognostic significance. The LHFRS was also significantly associated with the composite endpoint of death or rehospitalization (B = 1.173, p = 0.002), while its association with mortality alone was not statistically significant (B = −5.551, p = 0.256). (4) Conclusions: Lower admission and 2-h urinary sodium concentrations were associated with 3-month HF rehospitalization after adjustment for the LHFRS. These findings are hypothesis-generating and require confirmation in larger, externally validated multicenter cohorts. Full article

Background: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the tooth-supporting tissues and may substantially impair oral health-related quality of life (OHRQoL). Although the clinical consequences of periodontitis are well documented, the extent to which disease severity is associated with patient-reported outcomes remains insufficiently understood. This study aimed to evaluate the association between periodontitis severity and OHRQoL and to examine sociodemographic, behavioral, and systemic factors associated with poorer OHRQoL. Methods: A cross-sectional analytical study was conducted among 136 adult patients diagnosed with stage II or stage IV periodontitis at the Periodontology Clinic of Universidad Tecnológica de México (UNITEC). OHRQoL was assessed using the Oral Health Impact Profile for Periodontal Disease (OHIP-14-PD). Sociodemographic characteristics, smoking status, and diabetes mellitus were recorded using a structured questionnaire. Periodontal status was determined through standardized clinical and radiographic examinations. The internal consistency of the OHIP-14-PD was evaluated using Cronbach’s alpha coefficient. Bivariate analyses were performed using non-parametric tests. An exploratory, partially adjusted multivariable linear regression model including sex, marital status, diabetes mellitus, and periodontitis stage was also performed. Results: Stage IV periodontitis was more prevalent than stage II periodontitis (55% vs. 45%). The mean OHIP-14-PD score was 24.9 ± 13.7, and the instrument demonstrated excellent internal consistency (Cronbach’s α = 0.89). Patients with stage IV periodontitis had significantly higher OHIP-14-PD scores than those with stage II disease (30.1 ± 12.4 vs. 18.6 ± 12.6; p < 0.001), indicating poorer OHRQoL. In the bivariate analyses, poorer OHRQoL was also observed among current smokers, participants with diabetes mellitus, those with lower educational attainment, and those with lower socioeconomic status (p < 0.05). In the exploratory partially adjusted model, male sex (β = 4.2; 95% CI: 0.1–8.2; p = 0.042), diabetes mellitus (β = 6.5; 95% CI: 2.1–10.9; p = 0.004), and stage IV periodontitis (β = 4.6; 95% CI: 0.4–8.7; p = 0.031) were associated with higher OHIP-14-PD scores. Conclusions: In this single-center cross-sectional sample, patients with stage IV periodontitis reported higher OHIP-14-PD scores than those with stage II periodontitis. These findings indicate an association within the studied clinical population and should not be interpreted as evidence of a causal effect or as directly generalizable to broader populations. Larger multicenter longitudinal studies including patients across all periodontitis stages are required to confirm the magnitude and external validity of this association. Full article

Parkinson’s disease (PD) is associated with motor impairment and altered cortical dynamics. Although resting-state electroencephalography (EEG) has been widely studied for PD classification, walking EEG remains comparatively underexplored despite its relevance to gait dysfunction. This study developed an EEG-only, leakage-free framework for participant-level classification of PD and healthy controls (HCs) using resting- and walking-state EEG data from the OpenNeuro ds007526 dataset. Following selection, preprocessing, and quality control, 132 participants were retained, including 109 individuals with PD and 23 HCs. EEG recordings were resampled to 128 Hz, filtered between 0.5 and 40 Hz, screened for artifacts, harmonized across conditions, and segmented into overlapping 6 s windows. Classical machine-learning (ML) models used participant-level engineered features, whereas deep-learning (DL) models classified pooled resting-state and walking windows. Extra Trees achieved the highest balanced accuracy (0.71) among the ML, while ShallowConvNet-Lite was the strongest standard DL baseline (0.82). The proposed NeuroAtten-PD model achieved an accuracy of 0.86, a balanced accuracy of 0.84, an F1-score of 0.91, an ROC-AUC of 0.90, and a sensitivity of 0.88. After Holm correction, participant-level paired comparisons indicated significant differences from DeepConvNet-Lite and EEGNet-Lite. These findings demonstrate the feasibility of participant-level PD classification using a pooled collection of resting-state and walking EEG windows. With validation in larger, independent, and more balanced clinical cohorts, the proposed framework could support objective EEG-based decision support and provide a foundation for portable or wearable systems for longitudinal monitoring of PD-related cortical changes in clinical and home-based settings. Full article

Background: The Heart Rate Recovery Index (HRRI), derived from post-exercise heart rate recovery (HRR), reflects autonomic function and cardiovascular performance. Whether HRRI reflects early myocardial dysfunction and left atrial remodelling in heart failure with preserved ejection fraction (HFpEF) has not been previously examined. The H₂FPEF score, which integrates clinical and echocardiographic parameters, is used to assess the likelihood of HFpEF. This study investigates the relationship between HRRI, H₂FPEF score, and echocardiographic markers of longitudinal systolic function, including mitral annular plane systolic excursion (MAPSE), as well as left atrial volume index (LAVI), in patients with preserved left ventricular ejection fraction. Methods: A prospective observational study included 241 patients referred for cardiac exercise testing at the Institute of Cardiovascular Diseases Timisoara and the Clinical County Hospital of Sibiu. HRRI was calculated as the ratio of heart rate acceleration time (AT) to deceleration time (DT) during exercise testing. A comprehensive echocardiographic assessment was performed on all patients. Statistical analysis involved univariate testing and multivariable logistic regression with stepwise selection. Results: HRRI was significantly lower in HFpEF patients compared with those without heart failure (1.97 ± 0.66 vs. 2.73 ± 1.08, p < 0.01). HRRI correlated significantly with exercise performance, age, H₂FPEF score, and echocardiographic markers of diastolic and longitudinal systolic dysfunction. ROC analysis identified an HRRI cut-off value of 2.25 for HFpEF detection (AUC = 0.748), while HRRI remained significantly associated with HFpEF after adjustment for the covariates included in the model. The combined HRRI–H₂FPEF score improved diagnostic discrimination compared with the H₂FPEF score alone (AUC 0.897 vs. 0.858), achieving an overall classification accuracy of 82.2%. Conclusions: In our study, HRRI is significantly reduced in HFpEF and distinguishes patients with and without heart failure. It shows associations with echocardiographic markers of diastolic and longitudinal systolic dysfunction, exercise capacity, and H₂FPEF score. Full article

Objectives: Individuals with type 2 diabetes (T2D) remain at high cardiovascular disease (CVD) risk. The pan-immune-inflammation value (PIV) integrates circulating neutrophils, monocytes, platelets, and lymphocytes but does not capture albumin-related nutritional and inflammatory reserve. We investigated associations between the PIV-to-albumin ratio (PIVA) and incident CVD, cardiovascular mortality, and disease progression in individuals with T2D. Methods: This prospective study included 15,355 UK Biobank participants with T2D and no baseline CVD. PIVA was calculated from peripheral blood cell counts and serum albumin and was natural log-transformed. Fine–Gray competing-risk and cause-specific Cox models were used to evaluate incident CVD and cardiovascular mortality. Multi-state models characterized transitions from T2D to CVD and death. We also examined nonlinear associations, renal biomarker mediation, joint associations with the CVD polygenic risk score and triglyceride–glucose index, sensitivity analyses, and external validation of cardiovascular mortality in the National Health and Nutrition Examination Survey. Results: During median follow-ups of 12.94 years for incident CVD and 14.49 years for cardiovascular mortality, 4829 incident CVD events and 514 cardiovascular deaths occurred. Each 1-unit increase in lnPIVA was associated with higher risks of incident CVD (subdistribution hazard ratio [sHR], 1.140; 95% confidence interval [CI], 1.088–1.194) and cardiovascular mortality (sHR, 1.449; 95% CI, 1.247–1.684). Associations were nonlinear. Higher lnPIVA was also associated with transitions from T2D to CVD, from T2D directly to cardiovascular death, and from incident CVD to cardiovascular death. Cystatin C explained a larger proportion of these associations than creatinine. Elevated lnPIVA identified excess cardiovascular risk across strata of genetic susceptibility and insulin resistance, and the findings were generally supported by sensitivity and external validation analyses. Conclusions: lnPIVA was associated with incident CVD, cardiovascular mortality, and adverse cardiovascular transitions in individuals with T2D. As an immune-inflammatory and albumin-based index, PIVA may help identify high-risk individuals beyond conventional cardiometabolic and genetic risk profiles. Full article