Laura Franza

Background/objective: Down syndrome (DS) is characterized by premature aging, with comorbidities observed in the older population without DS, a high prevalence of multimorbidity and cognitive decline. The use of multiple medications further increases clinical complexity. The objective of this paper is to evaluate anticholinergic use and the anticholinergic burden (ACB) in a sample of persons with DS. Methods: cross-sectional retrospective study involving community-dwelling persons with DS, afferent to the DS clinics of the Fondazione Policlinico Universitario “A. Gemelli” (Rome, Italy). Individuals were assessed through a standardized clinical protocol. ACB was evaluated according to the anticholinergic cognitive burden scale, with a score ≥ 3 indicating high risk of anticholinergic side effects. Results: 337 individuals were taking ≥ 1 chronic medication, mean age was 37.7 (±14.6), 158 (43.8%) were females. 143 (39.6%) individuals took ≥ 1 medication with known anticholinergic burden, 51 (14.1%) individuals showed high risk ACB score. High risk ACB score prevalence increased with age (n = 0, 0%; 18–39 years n = 14, 8.2%; 40+ years n = 37, 22.3% p < 0.001). Polypharmacy was more prevalent among individuals with high ACB score (n = 20, 39.2% vs. n = 23, 7.4%, p < 0.001). The most prevalent drugs in individuals with high risk ACB score were antipsychotics (n = 34, 66.6% vs. n = 17, 33.3%, p < 0.001). The most prevalent comorbid condition was psychosis (n = 34, 66.6% vs. n = 16, 33.3%, p < 0.001). Discussion: individuals with DS show a high prevalence of anticholinergic drug use, increasing with age and associated with polypharmacy and psychiatric conditions. These medications are directly addressing the underlying psychiatric or neurological conditions in DS, rather than causing them. Nevertheless, these medications are often essential for managing psychiatric disorders, simultaneously increasing ACB, posing a risk of exacerbating pre-existing vulnerabilities (e.g., cognitive decline), which warrants the need for a more personalized strategy. Conclusions: A thorough assessment of drug history is mandatory in the DS population, to apply deprescribing, pharmacological switches, non-pharmacological approaches, to lower or even prevent high ACB, promoting overall a personalized and tailored approach to this population.

Non-communicable diseases (NCDs), including cancer and autoimmune, metabolic, cardiovascular, and neurodegenerative diseases, represent the leading cause of death globally and a growing healthcare burden. The gut microbiota (GM) has been recognized as a key biological component of host health that contributes to the maintenance of immune regulation, metabolic homeostasis, and epithelial barrier function. Several studies are now demonstrating that biological sex has an influence on both GM composition and function, which might explain sex differences in disease predisposition, course, and treatment response. Evidence from both clinical and experimental studies indicates that sex hormones, genetics, and lifestyle-related exposures interact with GM to influence the development and progression of most common NCDs. Some research suggests that estrogens promote diversity in GM with anti-inflammatory immune responses, while androgens and male-abundant taxa are associated with pro-inflammatory conditions. However, the evidence in humans is largely confounded by other variables (such as age, genetics, and lifestyle) and should be interpreted with caution. Unique GM metabolites, such as short-chain fatty acids and secondary bile acids, can have distinct, sex-specific effects on inflammation, metabolic regulation, and even antitumor immunity. While the existence of a sex–gut microbiota axis is gaining increased support, most studies in humans are cross-sectional epidemiological studies with limited mechanistic evidence and little consideration for sex as a biological variable. Future works should prioritize longitudinal, sex-stratified studies and utilize multi-omics integrated approaches to identify causal pathways. Ultimately, integrating sex differences into GM-based approaches could provide new avenues for personalized strategies for the prevention and treatment of NCDs.

Chronic inflammation is an important contributor to the development of cardiovascular disorders, and inflammasomes, especially the NOD-like receptor protein 3 (NLRP3), are emerging as crucial mediators in this context. Inflammasomes are activated through receptor-mediated danger signals, such as cholesterol crystals and cellular damage products, thereby stimulating the secretion of pro-inflammatory cytokines, which sustains inflammation. This mechanism drives atherosclerosis (via plaque formation and destabilization), heart failure (via fibrotic remodeling), and pericarditis (via exacerbation of pericardial inflammation). Therapeutic approaches seek to block inflammasome activation or their pro-inflammatory pathways. Colchicine, interleukin-1 inhibitors (anakinra, canakinumab), and Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors have a positive impact on cardiovascular inflammation. Various new compounds, such as MCC950, have been described as novel specific inhibitors of NLRP3. Further studies are needed to validate the effectiveness and safety of these treatments. Further elucidating the role of inflammasomes in cardiovascular disease could open the way to achieving more effective therapies, allowing for better management of high-risk cardiovascular patients.

Background: Sarcopenia is a syndrome characterized by the loss of skeletal muscle associated with reduced physical strength/performance and could be correlated with depression, that is the most frequent cause of emotional distress in old age and can reduce the quality of life of the older adults. Aim: The aim of the present study is to evaluate the association between probable sarcopenia and depressive symptoms in older adults, and the impact of comorbidity and frailty on this association. Methods: This cross-sectional study included community-dwelling older adults at their first geriatric evaluation. Probable sarcopenia was screened according to SARC-F. Clinically significant depressive symptoms (CSDS) were assessed according to the 5-items geriatric depression scale (GDS.) Frailty was determined through the CHSA-clinical frailty scale (CFS). Comorbidity burden was scored through the Cumulative Illness Rating Scale-Geriatric (CIRS-CI). Results: We included 238 participants with a mean age of 82.4 (± 6.9) years of age, 152 (63.6%) participants were females. Probable sarcopenia was diagnosed in 131 (55.0%) participants, while CSDS were present in 186 (78.2%) participants. In the multiadjusted model, probable sarcopenia was associated with a higher likelihood of CSDS (OR 2.70, 95% CI 1.03–6.12). No significant interaction of frailty and CIRS were found on the association between probable sarcopenia and CSDS. Conclusions: Sarcopenia and depressive symptomatology are highly co-occurring in geriatric patients, and this association may be independent of frailty and comordibity burden.

Cardiovascular diseases (CVDs) are the most common cause of mortality and morbidity in Western countries, thus representing a global health concern. CVDs show different patterns in terms of the prevalence and presentation in men and women. The role of sex hormones has been extensively implicated in these sex-specific differences, due to the presence of the menstrual cycle and menopause in women. Moreover, the gut microbiota (GM) has been implicated in cardiovascular health, considering the growing evidence that it is involved in determining the development of specific diseases. In particular, gut-derived metabolites have been linked to CVDs and kidney disorders, which can in turn promote the progression of CVDs. Considering the differences in the composition of GM between men and women, it is possible that gut microbiota act as a mediator in regard to the sex disparities in CVDs. This narrative review aims to comprehensively review the interplay between sex, GM, and CVDs, discussing potential mechanisms and therapeutic options.

The global health crisis caused by COVID-19 has radically changed the management of several diseases

The microbiota represents a key factor in determining health and disease. Its role in inflammation and immunological disorders is well known, but it is also involved in several complex conditions, ranging from neurological to psychiatric, from gastrointestinal to cardiovascular diseases. It has recently been hypothesized that the gut microbiota may act as an intermediary in the close interaction between kidneys and the cardiovascular system, leading to the conceptualization of the “gut–kidney–heart” axis. In this narrative review, we will discuss the impact of the gut microbiota on each system while also reviewing the available data regarding the axis itself. We will also describe the role of gut metabolites in this complex interplay, as well as potential therapeutical perspectives.

All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 ± 18 years [range 18–100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over ¾ with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2–3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3–3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3–2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in ‘real-world’ epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either anakinra or canakinumab. PFAPA patients seem to be less responsive to measles, mumps, and rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against hepatitis A. In consideration of the clinical frailty of both children and adults with SAIDs, all vaccinations remain ‘highly’ recommended in this category of patients despite the paucity of data available.