Medicina

Background: Frailty is highly prevalent in acute heart failure (AHF), yet whether it is more strongly associated with all-cause mortality or with non-fatal heart-failure events, and whether it adds information beyond cardiac severity, is seldom examined. Methods: In a prospective single-center registry of 530 consecutive patients hospitalized for AHF (February 2023–June 2025), frailty was graded at admission by the Clinical Frailty Scale (CFS; strata 1–3, 4–5, 6–9, and CFS ≥ 5) from patient and collateral history. The primary outcome was 12-month all-cause mortality; first AHF rehospitalization was analyzed with death and renal replacement therapy (RRT) as competing events, using Aalen–Johansen cumulative incidence and cause-specific and Fine–Gray models. Incremental value was tested against a cardiorenal model (age, log NT-proBNP, admission estimated glomerular filtration rate and left ventricular ejection fraction [LVEF]). Results: Frailty was highly prevalent (CFS ≥ 5, 66.4%) and was associated with older age, female sex, renal impairment, right heart failure, multivalvular disease and higher, rather than lower, LVEF. Mortality rose steeply across strata (4.5%, 19.3%, 49.7%; hazard ratio 3.29 per stratum, 95% CI 2.43–4.45), whereas the cumulative incidence of first AHF rehospitalization rose less steeply (4.5%, 29.2%, 33.0%; cause-specific hazard ratio 1.86, 95% CI 1.42–2.45; subdistribution hazard ratio 1.51, 95% CI 1.19–1.92). Frail patients with below-median NT-proBNP had mortality comparable to that of patients with CFS < 5 and above-median NT-proBNP (24.3% vs. 22.0%). Adding CFS to the cardiorenal model improved discrimination (C-index 0.701 → 0.734; optimism-corrected 0.694 → 0.726; apparent ΔC-index 0.033, 95% CI 0.007–0.063) and fit (likelihood-ratio χ² = 27.7, p < 0.001). Discharge prescription of disease-modifying therapy declined with increasing frailty. Conclusions: In elderly patients with AHF, frailty was more strongly associated with all-cause mortality than with documented non-fatal AHF rehospitalization, carried prognostic information complementary to natriuretic peptides, and added discrimination beyond cardiorenal variables, supporting structured frailty assessment alongside heart-failure-directed therapy.

Background and Objectives: Gestational diabetes mellitus (GDM) is characterized by insulin resistance and metabolic dysregulation, in which adipokines may be involved. We evaluated serum Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) and C1q/TNF-related protein-1 (CTRP1) in women with GDM and normal glucose tolerance and assessed their relationships with glucose–insulin homeostasis and cross-sectional discriminatory ability. Materials and Methods: This exploratory cross-sectional biomarker study with prospective obstetric follow-up included 100 pregnant women at 24–28 weeks of gestation (50 GDM and 50 controls). WISP-1, CTRP1, HOMA-IR, and GDM status were assessed during the same gestational period; therefore, the principal biomarker analyses were cross-sectional. GDM was diagnosed using the one-step 75-g oral glucose tolerance test criteria recommended by the American Diabetes Association Standards of Care 2026. WISP-1 and CTRP1 were measured by ELISA. Group comparisons, correlation analyses, ROC analyses, nested logistic regression, and bootstrap internal validation were performed. Results: WISP-1 was higher in GDM than in controls (422.80 [387.10–471.85] vs. 315.00 [288.30–351.55] pg/mL; p < 0.001), as was CTRP1 (34.13 ± 6.74 vs. 26.50 ± 5.65 ng/mL; p < 0.001). WISP-1 showed a higher apparent AUC than CTRP1 in the present cohort (0.908 vs. 0.802; DeLong p = 0.034). In the final model adjusted for maternal age and BMI, both WISP-1 (adjusted OR per 1-SD increase 7.53, 95% CI 2.95–19.21; p < 0.001) and CTRP1 (3.61, 95% CI 1.45–8.99; p = 0.006) remained associated with GDM status after adjustment for these covariates. Within GDM, the age- and BMI-adjusted association between WISP-1 and HOMA-IR remained significant (partial ρ = 0.574; p < 0.001), whereas CTRP1 was not associated with HOMA-IR. Conclusions: WISP-1 and CTRP1 were elevated in GDM, with WISP-1 showing a stronger association with HOMA-IR and a higher internally derived AUC in this cohort. These findings support further investigation of WISP-1 and CTRP1 as exploratory metabolic biomarkers associated with GDM but do not establish diagnostic or predictive utility. Independent external validation is required before any potential clinical application.

Background and Objectives: In Turkey, access to adult rheumatology outpatient clinics requires referral from another specialty, mostly internal medicine, and no standardized referral algorithms are in use. We estimated the diagnostic yield of new inflammatory rheumatic disease (IRD) diagnoses among internal medicine referrals who completed rheumatology evaluation and identified referral-stage characteristics associated with a new IRD diagnosis. Materials and Methods: In this retrospective cohort study, 2233 patients referred from internal medicine clinics to rheumatology outpatient clinics between 1 September and 30 November 2022 were screened. Patients with a prior diagnosis of IRD (n = 539) and those who did not attend their scheduled appointment (n = 732) were excluded, leaving 962 patients who completed rheumatology evaluation for analysis. Findings documented at referral were compared between patients with and without a new IRD diagnosis, and associations were examined with a clinically selected multivariable logistic regression model without laboratory variables, because laboratory tests had been ordered selectively. Results: Among the 962 patients who completed rheumatology evaluation, 141 (14.6%) received a new IRD diagnosis, corresponding to 6.3% of all 2233 referrals; the diagnostic status of the 732 patients who did not attend is unknown. In the multivariable model, swollen and tender joints were associated with a new IRD diagnosis (odds ratio [OR] 5.24, 95% confidence interval [CI] 3.17–8.68), whereas sicca symptoms (OR 1.45, 95% CI 0.83–2.55) and constitutional symptoms (OR 1.66, 95% CI 0.76–3.64) were not independently associated. Conclusions: Among patients referred from internal medicine to a tertiary rheumatology clinic who completed evaluation, approximately one in seven received a new IRD diagnosis. Referral appropriateness was not assessed, and the high non-attendance rate limits generalization to all referrals. Swollen and tender joints were the only referral characteristic independently associated with a new diagnosis. Whether structured referral criteria, medical education, or triage strategies improve the yield of referrals is a hypothesis for prospective evaluation.