Azienda Ospedaliera Di Perugia

Intestinal fibrosis is a severe complication of Crohn's disease for which therapy remains suboptimal. Probiotics are widely used in the treatment of intestinal inflammation, but all major guidelines do not recommend in favor of their use, with the exception of an 8-strains bacterial formula, which is recommended for the treatment of pouch inflammation in ulcerative colitis. Using this 8-strains formulation as a comparator, we characterized a 9-strains probiotic formulation enriched with Lactobacillus rhamnosus and paracasei in a mouse model of intestinal inflammation and fibrosis. Our findings demonstrated that while both formulations exerted similar protective effects in acute colitis, only the 9-strains probiotic attenuates inflammation and fibrosis in chronic colitis. Mechanistically, we found that the 9-strains formulation remodeled the microbiota composition and the structure of microbiota-derived secondary bile acids, leading to the selective enrichment of those bile acids that act as GPBAR1 agonists, including 3-oxo-DCA, which in vitro directly attenuates activation of intestinal fibroblasts. Confirming the role of this pathway, feeding Gpbar1^⁻/⁻ mice with 9-strains probiotic formulation abrogates its beneficial effects on inflammation and fibrosis. These findings highlight the importance of microbial metabolites in shaping probiotic efficacy and support the development of probiotic formulations that target host-microbiota interactions through bile acid signaling.

Aldosterone synthase inhibitors (ASIs) are novel drugs for cardiorenal protection. These compounds block aldosterone production and lower blood levels by targeting its biosynthesis pathway. ASIs induce a complete suppression of both genomic and nongenomic aldosterone effects, while reducing the risks of hyperkalaemia and aldosterone escape. In the present review, we will summarize the clinical potential of current ASIs in hypertension and chronic kidney disease (CKD).

Selective ASIs have been extensively evaluated in patients with both primary and resistant hypertension, and are promising therapeutic agents in CKD. Baxdrostat and lorundrostat effectively lowered blood pressure in patients with resistant or uncontrolled hypertension and showed favourable effects on renal outcomes. In CKD patients, vicadrostat determined a dose-dependent reduction of albuminuria and additive beneficial effects when used on top of empagliflozin.

In randomized controlled trials, patients assigned to second generation ASIs had beneficial effects on blood pressure and albuminuria, with enhanced safety profiles. Although long-term clinical outcomes are still under investigation, ASIs have the potential to narrow critical gaps in cardiorenal care.

Patients undergoing Transcatheter Aortic Valve Replacement (TAVR) are at risk for delirium. In Italy, the perioperative management of TAVR lacks standardization: this survey aims to investigate TAVR management across the country, focusing on delirium.

A multiple-choice survey was conducted anonymously among 40 high-volume cardiac surgery centers in Italy: questions addressed logistics, surgical procedures, anesthetic management and delirium assessment.

The response rate was 68%. Low-volume centers were excluded, resulting in a final sample of 22 hospitals, including 7 of the top 10 highest-volume TAVR centers in Italy. Only 36% of the participating centers routinely assessed delirium onset after TAVR, and just 18% utilized a validated delirium diagnostic scale. Only one-third of the hospitals systematically assessed patient frailty in the preoperative period. Fast-track protocols for TAVR patients were implemented in 68% of the centers. The transfemoral approach was consistently the first choice, with conscious sedation being the preferred anesthetic strategy (82%). Invasive blood pressure monitoring with a dedicated line was routinely performed in 91% of centers, while urinary catheters were used in half of the hospitals, including 47% of those with fast-track protocols. Postoperatively, 55% of patients were admitted to a Subacute or Coronary Care Unit, while 41% were managed in the Cardiology ward. In most cases, the hospital length of stay was three days or more.

This survey reveals substantial heterogeneity in perioperative management, delirium prevention and assessment after TAVR in Italy. This heterogeneity may contribute to differences in hospital stay and clinical outcomes.