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.

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.

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.

Enhanced Physical Capacity and Gastrointestinal Symptom Improvement in Southern Italian IBS Patients following Three Months of Moderate Aerobic Exercise.

Moderate-intensity aerobic exercise improves gastrointestinal (GI) health and alleviates irritable bowel syndrome (IBS) symptoms. This study explored its effects on physical capacity (PC) and IBS symptoms in 40 patients from Southern Italy (11 males, 29 females; 52.10 ± 7.72 years). The exercise program involved moderate-intensity aerobic exercise (60/75% of HRmax) for at least 180 min per week. Before and after the intervention, participants completed the IBS-SSS questionnaire to assess IBS symptoms, reported their physical activity levels, and underwent field tests to evaluate PC. PC was quantified as the Global Physical Capacity Score (GPCS). A total of 38 subjects (21 males, 17 females; 53.71 ± 7.27 years) without lower GI symptoms served as a No IBS group. No significant differences were found between IBS patients and No IBS subjects, except for the symptom score, as expected. After the exercise, all participants experienced significant improvements in both IBS symptoms and PC. Higher PC levels correlated with greater benefits in IBS symptomatology, especially with GPCS reaching above-average values. Engaging in moderate-intensity aerobic exercise for at least 180 min per week positively impacts IBS symptoms and PC. Monitoring GPCS in IBS patients provides insights into the connection between physical activity and symptom severity, aiding healthcare professionals in tailoring effective treatment plans.

The Impact of a Twelve-Week Moderate Aerobic Exercise Program on Gastrointestinal Symptom Profile and Psychological Well-Being of Irritable Bowel Syndrome Patients: Preliminary Data from a Southern Italy Cohort.

Walking is popular moderate-intensity aerobic exercise that improves mental and gastrointestinal (GI) health. It can relieve symptoms associated with irritable bowel syndrome (IBS), e.g., intestinal gas, abdominal distension, and bowel disturbances. This study examined the impact of a moderate-intensity aerobic exercise program on the clinical and psychological parameters of IBS patients. In total, 40 IBS patients (11 males and 29 females; mean age 51.9 ± 7.8 years) participated in a 12-week aerobic exercise program. Participants completed questionnaires assessing GI symptoms, psychological profiles, and quality of life (QoL) before and after the intervention. Field tests, anthropometric measurements, and bioimpedance assessments were also conducted. The present findings confirmed a significant improvement in IBS symptoms after the aerobic exercise program. Bloating was the most common symptom and, together with abdominal pain, was significantly reduced after treatment. Psychological and QoL questionnaires indicated decreased anxiety, depression, somatization, and stress levels. Correlations were found between anxiety/depression and the severity of abdominal pain as well as between stress and the severity of abdominal distension. Moderate-intensity aerobic exercise positively impacted GI symptoms and psychological well-being, complementing dietary and psychological support as a non-pharmacological therapy for the management of IBS. These findings emphasize the importance of alternative approaches for IBS treatment.

Lifestyle Modification: Evaluation of the Effects of Physical Activity and Low-Glycemic-Index Mediterranean Diet on Fibrosis Score.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is one the most prevalent causes of chronic liver disease worldwide. In the absence of an approved drug treatment, lifestyle modification is the first intervention strategy. This study aimed to estimate the main effect of two different physical activity (PA) programs, and a Low-Glycemic-Index Mediterranean Diet (LGIMD), or their combined effect on liver fibrosis parameters in subjects with NAFLD. METHODS: Subjects with moderate or severe NAFLD grade of severity (n = 144) were randomly assigned to six intervention arms for three months: LGIMD, PA programs, and their combination. Data were collected at baseline, 45 days, and 90 days. Transient elastography was performed to assess the outcome. RESULTS: at 90 days, a statistically significant reduction in kPa was found among subjects following LGMID (-2.85, 95% CI -5.24, -0.45) and those following an LGIMD plus PA1 (-2.37, 95% CI -4.39, -0.35) and LGIMD plus Pa2 (-2.21, 95% CI -4.10, -0.32). The contrast between time 2 and time 1 of the LGIMD plus PA2 treatment showed a statistically significant increase, and vice versa: the contrast between time 3 and time 2 of the same treatment showed a statistically significant reduction. The PA1 and PA2 arms also showed reduced kPa, although the results did not reach statistical significance. CONCLUSIONS: The intervention arms, LGIMD, LGIMD+PA1, and LGIMD+PA2, reduced the fibrosis score.

Diet and Exercise Exert a Differential Effect on Glucose Metabolism Markers According to the Degree of NAFLD Severity.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes (T2D) are highly prevalent diseases worldwide. Insulin Resistance (IR) is the common denominator of the two conditions even if the precise timing of onset is unknown. Lifestyle change remains the most effective treatment to manage NAFLD. This study aimed to estimate the effect of the Low Glycemic Index Mediterranean Diet (LGIMD) and exercise (aerobic and resistance) over a one-year period on the longitudinal trajectories of glucose metabolism regulatory pathways. MATERIALS AND METHODS: In this observational study, 58 subjects (aged 18-65) with different degrees of NAFLD severity were enrolled by the National Institute of Gastroenterology-IRCCS "S. de Bellis", to follow a 12-month program of combined exercise and diet. RESULTS: The mean age was 55 ± 7 years old. Gender was equally distributed among NAFLD categories. There was a statistically significant main effect of time for glycosylated hemoglobin (Hb1Ac) over the whole period (-5.41, 95% CI: -7.51; -3.32). There was a steady, statistically significant decrease of HbA1c in participants with moderate and severe NAFLD whereas this effect was observed after the 9th month in those with mild NAFLD. CONCLUSIONS: The proposed program significantly improves glucose metabolism parameters, especially HbA1c.

The Effect of Low Glycemic Index Mediterranean Diet and Combined Exercise Program on Metabolic-Associated Fatty Liver Disease: A Joint Modeling Approach.

BACKGROUND: Excessive caloric intake and reduced energy expenditure are associated with the onset of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to probe the benefits of a low glycemic index Mediterranean diet (LGIMD) and a combined exercise program (CEP) on MAFLD by monitoring the clinical process through anthropometric measurement, body mass index (BMI), and specific biomarkers, such as the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). METHODS: The study was conducted at the National Institute of Gastroenterology, 'S. de Bellis', Italy. Subjects were invited to join the study for 12 months. RESULTS: 54 participants were enrolled. Joint modeling of longitudinal and time-to-event data was applied. Overall, a statistically significant direct effect of LGIMD/CEP adherence on ln (BMI), a statistically significant direct effect of LGIMD/CEP adherence on time-to-event and a strong statistically significant direct effect of log (BMI) on time-to-event were observed. In addition, a statistically significant direct effect of LGIMD/CEP adherence on ln(HOMA-IR), a statistically significant direct effect of LGIMD/CEP adherence on time-to-event and a statistically significant direct effect of ln(HOMA-IR) on time-to-event were observed. CONCLUSIONS: LGIMD/CEP significantly improved MAFLD status; in addition, longitudinal BMI and HOMA-IR were good predictors of the disappearance of diagnostic criteria for MAFLD.

A Low Glycemic Index Mediterranean Diet Combined with Aerobic Physical Activity Rearranges the Gut Microbiota Signature in NAFLD Patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, and its prevalence worldwide is increasing. Several studies support the pathophysiological role of the gut-liver axis, where specific signal pathways are finely tuned by intestinal microbiota both in the onset and progression of NAFLD. In the present study, we investigate the impact of different lifestyle interventions on the gut microbiota composition in 109 NAFLD patients randomly allocated to six lifestyle intervention groups: Low Glycemic Index Mediterranean Diet (LGIMD), aerobic activity program (ATFIS_1), combined activity program (ATFIS_2), LGIMD plus ATFIS_1 or ATFIS2 and Control Diet based on CREA-AN (INRAN). The relative abundances of microbial taxa at all taxonomic levels were explored in all the intervention groups and used to cluster samples based on a statistical approach, relying both on the discriminant analysis of principal components (DAPCs) and on a linear regression model. Our analyses reveal important differences when physical activity and the Mediterranean diet are merged as treatment and allow us to identify the most statistically significant taxa linked with liver protection. These findings agree with the decreased 'controlled attenuation parameter' (CAP) detected in the LGIMD-ATFIS_1 group, measured using FibroScan®. In conclusion, our study demonstrates the synergistic effect of lifestyle interventions (diet and/or physical activity programs) on the gut microbiota composition in NAFLD patients.

Effects of weight change on all causes, digestive system and other causes mortality in Southern Italy: a competing risk approach.

Weight change is associated with all causes of death, cardiovascular, and cancer mortality and a heterogeneous group of other causes of death. We aimed to estimate the effect of weight change on all causes and cause-specific mortality in a cohort with a high prevalence of deaths due to diseases of the digestive system.MethodsIn this prospective cohort study, 2230 subjects aged 30 to 50 years were examined. The study consisted of a 32-year longitudinal study period (January 1985 to December 2017) and mortality follow-up. Outcomes were mortality from all causes and deaths from gastrointestinal disease. Root Mean Squared Error (RMSE) was evaluated to capture individual residual variation in Body Mass Index (BMI) after adjustment for baseline BMI, and the relationship of residual variation with mortality was calculated as cumulative incidence function and cause-specific hazard (CSH) rate.ResultsIn total, 793 participants died during the follow-up, 96 of them due to Digestive system causes. Magnitude of residual variation weight in the last quintile was associated with all-cause mortality (relative risk, 2.00; 95% CI, 1.54-2.59) and Digestive system causes (relative risk, 3.82; 95% CI, 1.86-7.81).ConclusionThe findings suggest an association between weight change and gastrointestinal disease mortality. Epidemiological works studying the correlation between weight change and mortality should consider this aspect.

Modified WCRF/AICR Score and All-Cause, Digestive System, Cardiovascular, Cancer and Other-Cause-Related Mortality: A Competing Risk Analysis of Two Cohort Studies Conducted in Southern Italy.

BACKGROUND: In real life, nutrition goes beyond purely biological domains. Primary prevention is the most efficient approach for reducing the risk of mortality. We aimed to study the association of lifestyle, as measured by a modified World Cancer Research Fund/American Institute for Cancer Research (mWCRF/AICR) scoring system with all-cause, digestive system disease-related (DSD-related), cardiovascular disease-related (CVD-related), cancer-related and other cause-related mortality using data from two population-based cohort studies conducted in Southern Italy. METHODS: A random sample of 5271 subjects aged 18 years or older was enrolled in 2005-2006 and followed up until 2020. Usual food intakes were estimated using a validated dietary questionnaire. Competing risks survival models were applied. RESULTS: High adherence to the mWCRF/AICR score was found to be statistically significant and negatively associated with all-cause mortality (HR 0.56, 95%CI 0.39; 0.82), DSD-related mortality (SHR 0.38, 95%CI 0.15; 0.97) and cancer-related mortality (SHR 0.43, 95%CI 0.19; 0.97) in the male sub-cohort and other-cause mortality (SHR 0.43, 95%CI 0.21; 0.88) only in the female group. CONCLUSIONS: This mWCRF/AICR score can be seen as a simple, easy tool for use in clinical practice to evaluate both qualitative and quantitative aspects of the diet.

Development and validation of a neural network for NAFLD diagnosis.

Non-Alcoholic Fatty Liver Disease (NAFLD) affects about 20-30% of the adult population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Liver ultrasound (US) is widely used as a noninvasive method to diagnose NAFLD. However, the intensive use of US is not cost-effective and increases the burden on the healthcare system. Electronic medical records facilitate large-scale epidemiological studies and, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. Our goal was to develop and validate a simple Neural Network (NN)-based web app that could be used to predict NAFLD particularly its absence. The study included 2970 subjects; training and testing of the neural network using a train-test-split approach was done on 2869 of them. From another population consisting of 2301 subjects, a further 100 subjects were randomly extracted to test the web app. A search was made to find the best parameters for the NN and then this NN was exported for incorporation into a local web app. The percentage of accuracy, area under the ROC curve, confusion matrix, Positive (PPV) and Negative Predicted Value (NPV) values, precision, recall and f1-score were verified. After that, Explainability (XAI) was analyzed to understand the diagnostic reasoning of the NN. Finally, in the local web app, the specificity and sensitivity values were checked. The NN achieved a percentage of accuracy during testing of 77.0%, with an area under the ROC curve value of 0.82. Thus, in the web app the NN evidenced to achieve good results, with a specificity of 1.00 and sensitivity of 0.73. The described approach can be used to support NAFLD diagnosis, reducing healthcare costs. The NN-based web app is easy to apply and the required parameters are easily found in healthcare databases.

Physical Activity Reduction and the Worsening of Gastrointestinal Health Status during the Second COVID-19 Home Confinement in Southern Italy.

Due to the COVID-19 pandemic, in December 2020, the Italian government established a second home confinement during the Christmas holidays. These restrictions offered the opportunity to utilize a well-defined model for observing the consequences of lifestyle changes of healthy individuals. This study aimed at estimating in healthy subjects from Southern Italy the physical activity (PA), the presence and the severity of gastrointestinal (GI) symptoms, and the association between the possible worsening of GI health status and the PA levels. An adapted version of the International PA Questionnaire-short form (IPAQ-SF) and the Gastrointestinal Symptom Rating Scale (GSRS) were proposed through Google's online survey platform in three different periods via WhatsAppTM to 499 healthy subjects (62% females) from Apulia (25%), Calabria (37%), and Campania (38%). Our results showed statistically significant changes during the home confinement: reduced energy expenditure (EE) among overweight subjects (-239.82, 95%CI -405.74; -73.89) or those who had high GSRS total score (-1079.54, 95%CI -2027.43; -131.66). An increase in GSRS total score was observed in overweight subjects, reaching statistical significance in those from Campania. Our study supports the importance of PA to reduce health risks, including those related to the possible onset of GI tract diseases.

Decreased levels of physical activity: results from a cross-sectional study in southern Italy during the COVID-19 lockdown.

BACKGROUND: During the COVID-19 pandemic, the Italian government took security measures to try to limit infections. Restrictive measures included social distancing, home confinement and the closure of all public structures like gyms and swimming pools. The impact of these limitations on health and lifestyle was inevitably negative. The purpose of this study was to establish the level of physical activity (PA), expressed as energy expenditure (MET-minute/week) in a Southern Italian population before and during the COVID-19 lockdown. METHODS: An adapted version of the International Physical Activity Questionnaire-short form (IPAQ-SF) was published on the official website of the National Institute of Gastroenterology IRCCS S. de Bellis, Castellana Grotte, Bari, Italy and on several social media in May 2020. RESULTS: Three hundred ten replies (72% women) from Apulia (60%), Calabria (28%), Campania (11%) and Sicily (1%) were included in the study. The COVID-19 lockdown had a negative effect on the vigorous PA intensity level and on walking, but not on the moderate PA intensity level. Additionally, daily time spent sitting down increased by more than 12% during the COVID-19 lockdown. CONCLUSIONS: Isolation changed PA behaviors. The decreased energy expenditure (MET-minute/week) during the lockdown had a negative impact in both genders, especially on the young adults and adults' groups.

The effect of the Mediterranean Diet on lifespan: a treatment-effect survival analysis of a population-based prospective cohort study in Southern Italy.

BACKGROUND: The Mediterranean diet (MedDiet) is associated with good health. We aimed to estimate the effect of levels of adherence to the MedDiet on lifespan by performing treatment effects survival analysis. METHODS: A sample of 5250 subjects aged ≥18 years were randomly selected from the electoral list of Castellana Grotte and Putignano (Apulian Region, Italy). Cohorts were enrolled in 2005-06 and followed-up until December 2018. The adherence to the MedDiet was measured by the relative Mediterranean score (rMED) and categorized as high, medium and low. Time-to-death (all-causes) as estimated by average treatment effect on the treated (ATET), potential outcome mean (POM) and relative efficiency of exposure were the outcomes. RESULTS: A total of 4896 subjects were included. The median follow-up time was 12.82 (inter quartile range (IQR) 12.22-13.05), 12.91 (IQR 12.21-13.27) and 12.84 (IQR 12.19-13.03) years for high, medium and low rMED subjects respectively. By December 2018, 453 (9.25%) had died. There was a strong effect of medium and low rMED {ATET, -5.10 [95% confidence interval (CI) -9.39, -0.80] and -8.91 (95%CI -13.37, -4.45), respectively}. High rMED has an important effect on mean age at death [POM 90.16 (95% CI 86.06, 94.25)]. The relative effect size for medium and low rMED subjects was a lower lifespan of 5.62% (95% CI 1.01, 10.3) and 9.90% (95% CI 5.30, 5.30), respectively. CONCLUSIONS: We observed an important benefit in additional years of survival from adherence to MedDiet in this southern Italian cohort. Further investigation corroborating our findings in other population groups in other geographic regions will be an important contribution to promoting health and longevity.

Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease worldwide, and lifestyle modification is the current standard treatment. The aim of the study was to estimate the effect of two different physical activity (PA) programs, a Low Glycemic Index Mediterranean Diet (LGIMD), and their combined effect on the NAFLD score as measured by FibroScan®. METHODS: Moderate or severe NAFLD subjects (n = 144) were randomly assigned to six intervention arms during three months. Interventions arms were a control diet, LGIMD, aerobic activity program (PA1), combined activity program (PA2), and LGIMD plus PA1 or LGIMD plus PA2. The data were compared at baseline, at 45 days, and at 90 days. Analysis of variance was performed under the intention-to-treat principle. RESULTS: There was a statistically significant reduction in the NAFLD score after 45 days of treatment in every working arm except for Arm 1 (control diet). After 90 days, the best results were shown by the intervention arms in which LGIMD was associated with PA: LGIMD plus PA1 (-61.56 95% CI -89.61, -33.50) and LGIMD plus PA2 (-38.15 95% CI -64.53, -11.77). CONCLUSION: All treatments were effective to reduce NAFLD scores, but LGIMD plus PA1 was the most efficient.

Selecting the best machine learning algorithm to support the diagnosis of Non-Alcoholic Fatty Liver Disease: A meta learner study.

BACKGROUND & AIMS: Liver ultrasound scan (US) use in diagnosing Non-Alcoholic Fatty Liver Disease (NAFLD) causes costs and waiting lists overloads. We aimed to compare various Machine learning algorithms with a Meta learner approach to find the best of these as a predictor of NAFLD. METHODS: The study included 2970 subjects, 2920 constituting the training set and 50, randomly selected, used in the test phase, performing cross-validation. The best predictors were combined to create three models: 1) FLI plus GLUCOSE plus SEX plus AGE, 2) AVI plus GLUCOSE plus GGT plus SEX plus AGE, 3) BRI plus GLUCOSE plus GGT plus SEX plus AGE. Eight machine learning algorithms were trained with the predictors of each of the three models created. For these algorithms, the percent accuracy, variance and percent weight were compared. RESULTS: The SVM algorithm performed better with all models. Model 1 had 68% accuracy, with 1% variance and an algorithm weight of 27.35; Model 2 had 68% accuracy, with 1% variance and an algorithm weight of 33.62 and Model 3 had 77% accuracy, with 1% variance and an algorithm weight of 34.70. Model 2 was the most performing, composed of AVI plus GLUCOSE plus GGT plus SEX plus AGE, despite a lower percentage of accuracy. CONCLUSION: A Machine Learning approach can support NAFLD diagnosis and reduce health costs. The SVM algorithm is easy to apply and the necessary parameters are easily retrieved in databases.

Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.

BACKGROUND AND AIMS: Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS: Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS: RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.

Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy.

BACKGROUND: The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing. STUDY DESCRIPTION: In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease. CONCLUSIONS: This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.