Background: Frailty is highly prevalent among older adults with cardiovascular disease (CVD) and strongly predicts disability and mortality after cardiac events. Although cardiac rehabilitation (CR) improves prognosis, frail older patients often face barriers to participating in in-person programs. eHealth-based, home-delivered CR programs incorporating tele-rehabilitation and remote monitoring may improve accessibility, yet evidence regarding their effectiveness on frailty status remains limited. Methods: We designed a multicenter, randomized, parallel-group trial enrolling people ≥65 years recently hospitalized for acute heart failure (AHF) and/or acute coronary syndrome (ACS). Participants were randomized 1:1 to an eHealth home-based tele-rehabilitation program or the usual care. The primary endpoint is frailty prevalence at follow-up, defined by an Essential Frailty Toolset (EFT) score ≥3, with co-primary outcomes being between-group differences in the mean levels of EFT and Short Physical Performance Battery (SPPB) scores after 3–6 months. Secondary endpoints include mortality and hospitalization, among others. Results: The full protocol and study procedures are reported. Between May 2024 and December 2025, 589 patients were screened at the two Italian centers involved; 442 met eligibility criteria and 209 were enrolled and randomized. Baseline characteristics were largely comparable between groups. The mean age was 77 ± 9 years, 70% were male, and 55% had ACS. Lower-than-expected enrollment was mainly attributable to refusal related to difficulties in using digital devices. Conclusions: This randomized trial will evaluate whether a multidomain, eHealth-based CR intervention can reduce the prevalence or degree of frailty in older people after AHF or ACS. We report the study protocol and baseline characteristics of the enrolled cohort, highlighting the challenge of digital illiteracy in contemporary older populations.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in PKD1 or PKD2 genes, encoding polycystin-1 (PC1) or polycystin-2 (PC2), respectively, characterized by excessive cell proliferation and fluid secretion, resulting in renal cyst formation and growth. PC1 and PC2 form a complex localized on the plasma membrane, endoplasmic reticulum, and primary cilia. PC2 is a non-selective cation channel which, in renal epithelial cells, contributes to calcium transport and signaling. It has been previously shown in renal cells that high external calcium increases whole-cell currents likely mediated by PC2. In this study, we explored the possibility that the Calcium Sensing Receptor (CaSR) is involved in the functional regulation of PC2. To test this hypothesis, human conditionally immortalized Proximal Tubular Epithelial cells, isolated from urine sediments, wt or with stably downregulated PKD1 (PC1KD) or PKD2 (PC2KD) were used. Interestingly, CaSR and PC2 co-immunoprecipitated and Proximity Ligation Assay demonstrated a direct physical interaction at endogenous protein levels. Membrane potential measurements demonstrated that selective CaSR activation, elicited by the calcimimetic R568, caused plasma membrane depolarization, consistent with the modulation of PC2-mediated cation currents, which was significantly lower in PC2KD with respect to wt and PC1KD cells. To conclude, this study provides evidence for a functional coupling of CaSR and PC2, which might be relevant for therapeutic strategies to correct dysregulations occurring in ADPKD.

Background: Frailty is highly prevalent among older adults with cardiovascular disease (CVD) and strongly predicts disability and mortality after cardiac events. Although cardiac rehabilitation (CR) improves prognosis, frail elderly patients often face barriers to participate to in-person programs. eHealth-based, home-delivered CR programs incorporating tele-rehabilitation and remote monitoring may improve accessibility, yet evidence regarding their effectiveness on frailty status remains limited. Methods: We designed a multicenter, randomized, parallel-group trial enrolling people ≥65 years recently hospitalized for acute heart failure (AHF) and/or acute coronary syndrome (ACS). Participants were randomized 1:1 to an eHealth home-based tele-rehabilitation program or usual care. The primary endpoint is frailty prevalence at follow-up, defined by an Essential Frailty Toolset (EFT) score ≥3, with co-primary outcomes being between-group differences in the mean levels of EFT and Short Physical Performance Battery (SPPB) scores after 3–6 months. Secondary endpoints include mortality and hospitalization, among others. Results: The full protocol and study procedures are reported. Between May 2024 and December 2025, 589 patients were screened at the two Italian centers involved; 442 met eligibility criteria and 209 were enrolled and randomized. Baseline characteristics were largely comparable between groups. Mean age was 77 ± 9 years, 70% were male, and 55% had ACS. At the time of reporting, follow-up had been completed in 172 individuals, with balanced dropout between groups. Lower-than-expected enrollment was mainly attributable to refusal related to difficulties in using digital devices. Conclusions: This randomized trial will evaluate whether a multidomain, eHealth-based CR intervention can reduce the prevalence or degree of frailty in older people after AHF or ACS. We report the study protocol and baseline characteristics of the enrolled cohort, highlighting the challenge of digital illiteracy in contemporary elderly populations.