Nutrition and dementia: Evidence for preventive approaches?

In recent years, the possibility of favorably influencing the cognitive trajectory through promotion of lifestyle modifications has been increasingly investigated. In particular, the relationship between nutritional habits and cognitive health has attracted special attention. The present review is designed to retrieve and discuss recent evidence (published over the last 3 years) coming from randomized controlled trials (RCTs) investigating the efficacy of nutritional interventions aimed at improving cognitive functioning and/or preventing cognitive decline in non-demented older individuals. A systematic review of literature was conducted, leading to the identification of 11 studies of interest. Overall, most of the nutritional interventions tested by the selected RCTs were found to produce statistically significant cognitive benefits (defined as improved neuropsychological test scores). Nevertheless, the clinical meaningfulness of such findings was not adequately discussed and appears controversial. In parallel, only 2 studies investigated between-group differences concerning incident dementia and mild cognitive impairment cases, reporting conflicting results. Results of the present review suggest that several dietary patterns and nutritional components may constitute promising strategies in postponing, slowing, and preventing cognitive decline. However, supporting evidence is overall weak and further studies are needed

External validity of randomized controlled trials on Alzheimer's disease: the biases of frailty and biological aging

To date, the external validity of randomized controlled trials (RCTs) on Alzheimer's disease (AD) has been assessed only considering monodimensional variables. Nevertheless, looking at isolated and single characteristics cannot guarantee a sufficient level of appreciation of the AD patients' complexity. The only way to understand whether the two worlds (i.e., research and clinics) deal with the same type of patients is to adopt multidimensional approaches more holistically reflecting the biological age of the individual. In the present study, we compared measures of frailty/biological aging [assessed by a Frailty Index (FI)] of a sample of patients with AD resulted eligible and subsequently included in phase III RCTs compared to patients referring to the same clinical service, but not considered for inclusion. The "RCT sample" and the "real world sample" were found to be statistically similar for all the considered sociodemographic and clinical variables. Nevertheless, the "real world sample" was found to be significantly frailer compared to the "RCT sample," as indicated by higher FI scores [0.28 (SD 0.1) vs. 0.17 (SD 0.1);p < 0.001, respectively]. Moreover, when assessing the relationship between FI and age, we found that the correlation was almost null in the "RCT sample" (Spearman'sr = 0.01;p = 0.98), while it was statistically significant in the "real world sample" (r = 0.49;p = 0.02). The application of too rigid designs may result in the poor representativeness of RCT samples. It may even imply the study of a condition biologically different from that observed in the "real world." The adoption of multidimensional measures capable to capture the individual's biological age may facilitate evaluating the external validity of clinical studies, implicitly improving the interpretation of the results and their translation in the clinical arena

The Role of Immunotherapy in a Tolerogenic Environment: Current and Future Perspectives for Hepatocellular Carcinoma

In contrast to several tumors whose prognoses are radically affected by novel immunotherapeutic approaches and/or targeted therapies, the outcomes of advanced hepatocellular carcinoma (HCC) remain poor. The underlying cirrhosis that is frequently associated with it complicates medical treatment and often determines survival. The landscape of HCC treatment had included sorafenib as the only drug available for ten years, until 2018, when lenvatinib was approved for treatment. The second-line systemic treatments available for hepatocellular carcinoma include regorafenib, cabozantinib, ramucirumab, and, more recently, immune checkpoint inhibitors. However, the median survival remains below 15 months. The results obtained in clinics should be interpreted whilst considering the peculiar role of the liver as an immune organ. A healthy liver microenvironment ordinarily experiences stimulation by gut-derived antigens. This setup elucidates the response to chronic inflammation and the altered balance between tolerance and immune response in HCC development. This paper provides an overview of the mechanisms involved in HCC pathogenesis, with a special focus on the immune implications, along with current and future clinical perspectives

Sex and gender differences in the treatment of Alzheimer's disease: A systematic review of randomized controlled trials

tIn recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influenceof sex and gender on Alzheimer’s disease (AD). Nevertheless, not enough attention has been paid totheir impact on treatment outcomes. The present study is aimed at systematically retrieve, review anddiscuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketedtreatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possiblesex and gender differences in their efficacy, safety and tolerability.A systematic review of literature was performed. None of the retrieved studies reported data on theefficacy, safety and tolerability of considered medications separately in male and female patients withAD. We thus analyzed 48 excluded studies of potential interest, that is, almost all of the currently availabletrials on the four considered drugs. Nearly all the considered RCTs recruited a larger number of femaleparticipants to mirror the sexually unbalanced prevalence of AD. Only two studies took into account thepotential influence of sex and gender on treatment efficacy, reporting no significant differences betweenmen and women. None of the studies investigated potential sex and gender differences in the safety andtolerability of the four considered treatments.The existence of sex and gender differences in the efficacy and tolerability of ChEIs and memantine inAD has, to date, drawn limited to no attention. However, a considerable amount of data, with an adequaterepresentativeness in terms of sex/gender distribution, seem to be already available for dedicated anal-yses on this topic. A greater effort should be made to collect and report data on those factors interactingwith sex and gender that may significantly influence clinical manifestations, outcomes, and trajectoriesover time of AD patients

Promoting the assessment of frailty in the clinical approach to cognitive disorders

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Microbiologically confirmed infections and antibiotic-resistance in a national surveillance study of hospitalised patients who died with COVID-19, Italy 2020-2021

Background: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19. Methods: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility. Results: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively. Conclusions: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance