Leisure-Time Physical Activity, Time Spent Sitting and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in Puglia.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity. OBJECTIVE: The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy. DESIGN: The study is based on two cohort studies, a randomized clinical trial and an observational cost-benefit study. PARTICIPANTS: A total of 1269 participants (51.5% women) drawn from 3992 eligible subjects were enrolled in this study. EXPOSURES: Leisure-time physical activity (LTPA) and time spent sitting (TSS) were assessed using the Italian long form of the International Physical Activity Questionnaire (IPAQ-LF), designed for administration to adults aged 18 to 65 years. MAIN MEASURES: The association of exposures with the probability of belonging to a certain NAFLD degree of severity. KEY RESULTS: The probability of having mild, moderate, and severe NAFLD tends to decrease with increasing LTPA and decreasing TSS levels. We selected a combination of participants aged 50 years and older stratified by gender. Men had a statistically significant difference in the probability of developing moderate NAFLD if they spent 70 h per week sitting and had low LTPA, while among women there was a statistically significant difference in the probability of developing mild or moderate NAFLD if they had moderate LPTA and spent 35-70 h/week sitting. CONCLUSIONS: The study thus showed that the amount of LTPA and the amount of TSS are associated with development and progression of NAFLD, but this relationship is not a linear one-especially in women aged ≥ 50 years old.

Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Siponimod from fingolimod direct switch in patients transitioning in secondary progressive multiple sclerosis: A single center case series.

INTRODUCTION: The transition from fingolimod (FIN) to siponimod (SIP) for Multiple Sclerosis (MS) treatment in the occurrence of Secondary Progressive Multiple Sclerosis (SPMS) diagnosis has increasingly attracted considerable interest in the recent literature. METHODS: We evaluated the efficacy and safety of a direct switch from FIN to SIP in nine MS patients who had switched directly from FIN to SIP due to SPMS diagnosis at the Multiple Sclerosis Center of the University Hospital Policlinico of Bari. RESULTS AND CONCLUSION: Real-world results from our cohort demonstrated that the direct switch from FIN to SIP in patients transitioning in SP course is associated with clinical and disability progression stability, with a favorable safety profile.

Leisure-Time Physical Activity in Subjects with Metabolic-Dysfunction-Associated Steatotic Liver Disease: An All-Cause Mortality Study.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) affects 30% of adults worldwide and is associated with obesity and cardiovascular risk factors. If left untreated, it can progress to severe liver disease. Lifestyle changes such as physical activity and weight loss help to reduce the severity and risk of mortality. This study estimated the impact of MASLD and leisure-time physical activity (LTPA) on mortality and examined how gender mediates this effect in a Southern Italian population. Methods: This work is a population-based prospective cohort study of inhabitants of Castellana Grotte (>30 years old) in Southern Italy, which began in 1985. Participants provided general health information, underwent anthropometric measurements and ultrasonography, and completed a validated questionnaire on their food intake and LTPA. The vital status was tracked through local municipalities Results: In total, 1826 participants (39% with MASLD) were enrolled in this study, drawn from 2970 eligible subjects; the mean age was 51.91 (±14.76) years and 56.2% were men. Subjects with MASLD who practiced low LTPA had a significantly higher risk of death than those who did not have MASLD and practiced high LTPA. In addition, subjects with MASLD who practiced low LTPA were about 19% less likely to survive to the age of 82 years. As regards gender, both men and women with MASLD and low LTPA showed a significant risk of death, but this was higher in women. Conclusions: The presence of MASLD, especially in women, increases the risk of death from all causes. LTPA plays a key role in the disease and reduces mortality in these individuals.

Development and Internal Validation of a Model for Predicting Overall Survival in Subjects with MAFLD: A Cohort Study.

Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort of subjects with MAFLD. Methods: Our work involved two steps: the first was the construction of a bootstrapped multivariable Cox model for mortality risk prognosis and the second was its validation. Results: The study cohort included 1506 subjects, of which 907 were used for internal validation. Discriminant measures for the final model were R2D 0.6845 and Harrell's C 0.8422 in the development and R2D 0.6930 and Harrell's C 0.8465 in the validation. We used the nine independent prognostic factors selected by the LASSO Cox procedure and fitted by the bootstrap Cox survival model, and observed ß were: Gender 0.356 1.42 (p < 0.008), Age 0.146 (p < 0.001), Glycemia 0.004 (p < 0.002), Total Cholesterol -0.0040 (p < 0.009), Gamma Glutamyl Transpeptidase 0.009 (p < 0.001), SBP 0.009 (p < 0.036), DBP -0.016 (p < 0.041), ALP 0.008 (p < 0.071) and Widowhood 0.550 (p < 0.001). Conclusions: We produced and validated a model to estimate the probability of death in subjects with MAFLD. The instruments we used showed satisfactory predictive capabilities.

Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real-world study.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.

Overweight and Obesity in Southern Italy: their association with social and life-style characteristics and their effect on levels of biologic markers / Overweight and Obesity in Southern Italy: their association with social and life-style characteristics and their effect on levels of biologic markers.

BACKGROUND: In the last decades, overweight and obesity have been transformed from minor public health issues to a major threat to public health affecting the most affluent societies and also the less developed ones. OBJECTIVES: To estimate overweight-obesity prevalence in adults, their association with some social determinants and to assess the effect of these two conditions on levels of biologic and biochemical characteristics, by means of a population-based study. METHODS: A random sample of the general population of Putignano was drawn. All participants completed a general pre-coded and a Food Frequency questionnaire; anthropometric measures were taken and a venous blood sample was drawn. All subjects underwent liver ultra-sonography. Data description was done by means of tables and then Quantile Regression was performed. RESULTS: Overall prevalence of overweight and obesity were 34.5

respectively. Both overweight and obesity were more frequent among male, married and low socio-economic position subjects. There were increasing frequencies of normal weight with higher levels of education. Overweight and obese subjects had more frequently Nonalcoholic Fatty Liver Disease, Hypertension and altered biochemical markers. Quantile regression showed a statistically significant association of age with overweight and obesity (maximum about 64.8 yo), gender (female) and low levels of education in both overweight and obesity. More than 10 gr/day of wine intake was associated with overweight. CONCLUSIONS: The prevention and treatment of overweight/obesity on a population wide basis are needed. Population-based strategies should also improve social and physical environmental contexts for healthful lifestyles.