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The positive association between overweight, obesity, and cardiovascular and all-cause mortality is well established, even though this relation is typically U shaped with an increased risk also in low-weight subjects. However, being overweight or obese has been associated with a better prognosis in subjects suffering from chronic diseases, id est the “obesity paradox”. In both community-dwelling and hospitalized patients with COPD, several studies have reported a significant protective effect of obesity on all-cause mortality, indicating that also in obstructive pulmonary diseases, an obesity paradox may be present. Interestingly, the “paradox” is more evident for subjects with severe bronchial obstruction (i.e., a lower FEV1), while in mild–moderate conditions, the weight-related mortality shows a behavior similar to that observed in the general population. Several factors may confound the relation between COPD, obesity and mortality. The lower FEV1 found in obese people may be linked to a restrictive defect rather than to an obstructive one. Due to the modified chest wall mechanical properties—related to increased fat mass—obese COPD patients may present, respect to their lean counterpart, a lower lung hyperinflation which is associated with higher mortality. The traditional classification of COPD attributes to obese “blue bloaters” a low-grade emphysema in opposition to lean “pink puffers”; the fact that emphysema extent is related to mortality may bias the relationship between weight and survival. It is also to underline that the majority of the studies, consider BMI rather than body composition (a better predictor of mortality) when studying the intriguing relation between weight, COPD, and mortality. Reverse bias has also to be taken into account, hypothesizing that an unintentional weight loss may be the deleterious factor related to mortality, rather than considering obesity a protective one. Further prospective studies are needed to shed light on the complexity of this emerging issue. Level of evidence Level V: Narrative Review.

Intermittent fasting (IF) has gained attention as a potential intervention for cardiometabolic health, though its long-term effects remain unclear. In this randomized clinical trial, we assessed the impact of 6 months of IF on body composition, cardiovascular risk factors, and related molecular pathways in middle-aged (30-65 years) men and women with overweight (BMI 24.8–35 kg/m²). In this trial, 41 participants were randomized to either an intermittent fasting (IF) intervention or to maintain their habitual diet. The primary outcome (circulating CRP concentration) was previously reported; here, we present exploratory analyses focusing on metabolomic and transcriptomic responses. IF led to an 8% reduction in body weight, a 16% decrease in body fat, and significant improvements in lipid profile, including substantial reductions in plasma LDL-cholesterol, non-HDL-cholesterol, and triglycerides ( p  = 0.001). However, no significant changes were observed in other cardiometabolic risk factors. To investigate the underlying molecular mechanisms, we performed untargeted plasma metabolomics and transcriptomic analysis of colon mucosa biopsies. Significant multi-omic changes were identified, particularly in lipid metabolism, bile acid signaling, and enteroendocrine regulation. Notably, there was a downregulation of transcripts related to glucagon-like peptide 1 (GLP-1) and related enteroendocrine hormones. Correlation analysis highlighted key molecular pathways, with PPAR-α and B-cell-mediated immune processes significantly associated with changes in non-HDL cholesterol. Our findings extend the understanding of IF in humans beyond weight loss, providing key mechanistic insights to inform targeted therapies for improving cardiometabolic health. ClinicalTrials.gov NCT01964118 Intermittent fasting is investigated as an alternative to caloric restriction as a treatment modality for weight loss and improvement of cardiometabolic risk factors. Here the authors report the secondary and exploratory outcomes of a randomized controlled cross-over trial showing that six months of intermittent fasting reduced body weight and improved lipid profiles, which associated with altered GLP−1–related enteroendocrine signaling and B-cell pathways based on colon transcriptomics and plasma metabolimics.

Background Insulin-like growth factor (IGF)-1 and its binding proteins are important in cancer growth, especially in prostate cancer. Observational studies suggest that protein restriction can lower IGF-1 levels. However, it is unclear whether an isocaloric protein-restricted diet affects IGF-1 and IGFBPs in men with prostate cancer. Methods In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded end-point trial, 38 consenting overweight (BMI 30.5 ± 5.5 kg/m 2 ) men with localized prostate cancer, aged 43–72 years, were randomized (1:1) with permuted blocks to 4–6 weeks of customized isocaloric PR diets (0.8 g protein/kg lean body mass) or their usual diet. Biomarkers influencing cancer biology, including serum IGF-1 and its binding proteins were measured longitudinally. Results Contrary to our hypothesis, feeding individuals an isocaloric protein-restricted diet did not result in a significant reduction in serum IGF-1. Moreover, there was no observed increase in serum IGFBP-1 or IGFBP-3 concentration. Conclusion These findings demonstrate that protein restriction without calorie restriction does not reduce serum IGF-1 concentration or increase IGFBP-1 and IGFBP-3 in men with localized prostate cancer. Further research is needed to identify dietary interventions for safely and effectively reducing IGF-1 in this patient group.

Background and objective Health-related quality of life (HRQL) in respiratory diseases has been generally investigated in clinical settings, focusing on a single disorder. In this study on a general population sample, we assessed the relationship between HRQL and several respiratory diseases studied simultaneously (COPD, current (CA) and past (PA) asthma, allergic (AR) and non-allergic (NAR) rhinitis and chronic bronchitis (CB). Methods Controls ( n  = 328) and cases of NAR ( n  = 95), AR ( n  = 163), CB ( n  = 48), CA ( n  = 224), PA ( n  = 126) and COPD ( n  = 28) were recruited in the centre of Verona in the frame of the Italian multi-case control GEIRD (Gene Environment Interactions in Respiratory Diseases) study; HRQL was measured through the SF-36 questionnaire. The relationships between HRQL (in terms of Physical (PCS) and Mental Component Scores (MCS)), respiratory diseases, and covariates were evaluated. Results With respect to controls, the adjusted PCS median score was worse in subjects suffering from current asthma (− 1.7; 95%CI:-2.8;-0.6), CB (− 3.8; 95%CI:-5.7;-1.9), and COPD (− 5.6; 95%CI:-8.1;-3.1). MCS was worse in current asthmatics (− 2.2; 95%CI:-4.1;-0.3), CB (− 5.5; 95%CI:-8.7;-2.2), and COPD cases (− 4.6; 95%CI:-8.8;-0.5) as well. Conclusions To our knowledge, this is the first study in the general population that analyzed HRQL performing a simultaneous comparison of HRLQ in several respiratory disorders. We found that subjects suffering from COPD, CA, and CB had the poorest HRQL. Clinicians should carefully consider the possible impact of respiratory disorders as CB and not only that of CA and COPD.

The research was conducted in the frame of a population-based, case control study, called Genes Environment Interaction in Respiratory Disease. To assess the association between protein intake and physical performance in a general population sample. Researchers investigated the association between the participants' dietary information and their physical performance using the 6-min walking test and the distance walked in metres (6MWD) as main outcome measure. Information on dietary intake was collected using the validated European Investigation into Cancer and Nutrition food frequency questionnaires (FFQs). Then, daily intake of energy and macronutrients was estimated by means of the NAF software (nutritional analysis of FFQ). Linear regression models were used to evaluate the associations between vegetable, animal and total protein intakes and the 6MWD. The models were adjusted for socio-demographic features, total fats and available carbohydrate intakes. The participants were 223 subjects (57% females) aged between 23 and 68 years. Their mean vegetable and animal proteins intake for gram/kg of body weight/day were, respectively, 0.4 and 0.7. After adjusting for all the potential confounders, there was a significant increase of 20.0 (95% CI 0.8; 39.2) m in the distance walked for an increase in 10 g/day of vegetable proteins and non-significant variations of -1.8 (95% CI -9.3; 5.7) m for an increase in 10 g/day of animal proteins and of 0.5 (95% CI -6.8; 7.7) for an increase in 10 g/day of total proteins. Our result suggests a positive role of vegetable proteins on physical performance. Whether this result is related to the high protein intake itself or may be a consequence of the other properties of plant-based foods deserves further investigation.

Calorie restriction (CR) and physical exercise (EX) are well‐established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long‐term follow‐up. This study compared BioAge biomarkers in 41 middle‐aged and older adult long‐term CR practitioners, 41 age‐ and sex‐matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood‐biomarkers. Additionally, a subset of participants (12 CR, 11 EX, and 12 WD) underwent multi‐omic profiling, including DNA methylation and RNAseq of colon mucosa, blood metabolomics, and stool metagenomics. A group of six young WD subjects (yWD) served as a reference for BioAge calculation using Mahalanobis distance across six omic layers. The results demonstrated consistently lower BioAge biomarkers in both CR and EX groups compared to WD controls across all layers. CR participants exhibited lower BioAge in gut microbiome and blood‐derived omics, while EX participants had lower BioAge in colon mucosa‐derived epigenetic and transcriptomic markers, suggesting potential tissue‐specific effects. Multi‐omic pathway enrichment analyses suggested both shared and intervention‐specific mechanisms, including oxidative stress and basal transcription as common pathways, with ether lipid metabolism uniquely enriched in CR. Despite limitations due to sample size, these findings contribute to the broader understanding of the potential anti‐aging effects of CR and EX, offering promising directions for further research. We observed lower biomarkers of biological aging in individuals practicing calorie restriction (CR) and endurance exercise runners (EX) compared to sedentary controls following a Western diet (WD), based on multiple omic analyses. These findings support recent epidemiological findings about the beneficial effect of CR and EX, suggest potential tissue‐specific effects, and highlight the reduction of oxidative stress damage as a key mechanism underlying the anti‐aging benefits of both CR and EX.

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence—a state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training.

The spread of SARS-COV-2 has affected many economic and social systems. This paper aims at estimating the impact on regional productive systems in Italy of the interplay between the epidemic and the mobility restriction measures put in place to contain the contagion. We focus then on the economic consequences of alternative lockdown lifting schemes. We leverage a massive dataset of human mobility which describes daily movements of over four million individuals in Italy and we model the epidemic spreading through a metapopulation SIR model, which provides the fraction of infected individuals in each Italian district. To quantify economic backslashes this information is combined with socio-economic data. We then carry out a scenario analysis to model the transition to a post-lockdown phase and analyze the economic outcomes derived from the interplay between (a) the timing and intensity of the release of mobility restrictions and (b) the corresponding scenarios on the severity of virus transmission rates. Using a simple model for the spreading disease and parsimonious assumptions on the relationship between the infection and the associated economic backlashes, we show how different policy schemes tend to induce heterogeneous distributions of losses at the regional level depending on mobility restrictions. Our work shed lights on how recovery policies need to balance the interplay between mobility flows of disposable workers and the diffusion of contagion.

Anastomotic dehiscence is one of the most morbidity related and deadly complication after foregut oncologic surgery. The aim of the study is to evaluate the effectiveness of double layer stents (Niti-S™ Beta™ Esophageal Stent) in the management of dehiscences after upper gastrointestinal oncologic surgery. We retrospectively studied consecutive patients who underwent Niti-S™ Beta™ esophageal stent placement from June 2014 to September 2019 for the treatment of anastomotic leaks/fistula following esophagectomy or gastrectomy for cancer. Univariate two-sided logistic regression analysis was used to evaluate possible predictors of successful anastomotic leak/fistula closure. A total of 37 patients were studied and 75 stents were positioned in these patients during the endoscopic procedures. Effective leak/fistula closure was obtained in 23/37 (62.2%). No technical endoscopic failure or complications ensued during the placing of the devices. Regarding delayed complications, migration was observed in 17/75 (22.7%) procedures and stent leaking in 29/75 (38.6%). Three variables significantly favoured stent treatment failure, namely previous neoadjuvant therapy (OR 9.3, P = 0.01), fistula (instead of leak) (OR 6.5, P = 0.01), and stent leak (OR 17.0, P = 0.01). Placement of Beta Niti-S esophageal stent is a safe and effective method that could be considered for the management of leaks and fistula after upper gastrointestinal cancer. Crucial points in the management of post-surgical leaks with this technique are the prompt recognition of leaks and fistula, the prompt endoscopic/radiologic drain of collection and the choice of adequate size of the stent.

Telemedicine is considered an excellent tool to support the daily and traditional practice of the health profession, especially when referring to the care and management of chronic patients. In a panorama in which chronic pathologies with childhood onset are constantly increasing and the improvement of treatments has allowed survival for them into adulthood, telemedicine and remote assistance are today considered effective and convenient solutions both for the chronic patient, who thus receives personalized and timely assistance, and for the doctors, who reduce the need for direct intervention, hospitalizations and consequent management costs. This Consensus document, written by the main Italian Scientific Societies involved in the use of telemedicine in pediatrics, has the objectives to propose an organizational model based on the relationships between the actors who participate in the provision of a telemedicine service aimed at minors with chronic pathologies, identifying specific project links between the areas of telemedicine in the developmental age from the first 1000 days of life to the age adult. The future scenario will have to be able to integrate digital innovation in order to offer the best care to patients and citizens. It will have to be able to provide the involvement of patients from the very beginning of the design of any care pathway, increasing where possible the proximity of the health service to citizens.