Prediction of gastrointestinal cancers in the ONCONUT cohort study: comparison between logistic regression and artificial neural network.

Background: Artificial neural networks (ANNs) and logistic regression (LR) are the models of chosen in many medical data classification tasks. Several published articles were based on summarizing the differences and similarities of these models from a technical point of view and critically assessing the quality of the models. The aim of this study was to compare ANN and LR the statistical techniques to predict gastrointestinal cancer in an elderly cohort in Southern Italy (ONCONUT study). Method: In 1992, ONCONUT was started with the aim of evaluating the relationship between diet and cancer development in a Southern Italian elderly population. Patients with gastrointestinal cancer (ICD-10 from 150.0 to 159.9) were included in the study (n = 3,545). Results: This cohort was used to train and test the ANN and LR. LR was evaluated separately for macro- and micronutrients, and the accuracy was evaluated based on true positives and true negatives versus the total (97.15%). Then, ANN was trained and the accuracy was evaluated (96.61% for macronutrients and 97.06% for micronutrients). To further investigate the classification capabilities of ANN, k-fold cross-validation and genetic algorithm (GA) were used after balancing the dataset among classes. Conclusions: Both LR and ANN had high accuracy and similar performance. Both models had the potential to be used as decision clinical support integrated into clinical practice, because in many circumstances, the use of a simple LR model was likely to be adequate for real-world needs, but in others in which there were large amounts of data, the application of advanced analytic tools such as ANNs could be indicated, and the GA optimizer needed to optimize the accuracy of ANN.

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.

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.

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.

The Effect of Three Mediterranean Diets on Remnant Cholesterol and Non-Alcoholic Fatty Liver Disease: A Secondary Analysis.

BACKGROUND: Elevated fasting remnant cholesterol (REM-C) levels have been associated with an increased cardiovascular risk in patients with metabolic syndrome (Mets) and Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to estimate the effect of different diets on REM-C levels in patients with MetS, as well as the association between NAFLD and REM-C. METHODS: This is a secondary analysis of the MEDIDIET study, a parallel-arm Randomized Clinical Trial (RCT). We examined 237 people with MetS who underwent Liver Ultrasound (LUS) to assess the NAFLD score at baseline, 3-, and 6-months follow-up. Subjects were randomly assigned to the Mediterranean diet (MD), Low Glycemic Index diet (LGID), or Low Glycemic Index Mediterranean diet (LGIMD). REM-C was calculated as [total cholesterol-low density lipoprotein cholesterol (LDL-C)-high density lipoprotein cholesterol (HDL-C)]. RESULTS: REM-C levels were higher in subjects with moderate or severe NAFLD than in mild or absent ones. All diets had a direct effect in lowering the levels of REM-C after 3 and 6 months of intervention. In adherents subjects, this effect was stronger among LGIMD as compared to the control group. There was also a significant increase in REM-C levels among Severe NAFLD subjects at 3 months and a decrease at 6 months. CONCLUSIONS: fasting REM-C level is independently associated with the grade of severity of NAFLD. LGIMD adherence directly reduced the fasting REM-C in patients with MetS.

Traditional Dietary Patterns and Risk of Mortality in a Longitudinal Cohort of the Salus in Apulia Study.

There is still room for further studies analyzing the long-term health impact of specific dietary patterns observable in regions belonging to the Mediterranean area. The aim of the study is to evaluate how much a diet practiced in southern Italy is associated to a risk of mortality. The study population included 2472 participants first investigated in 1985, inquiring about their frequencies of intake of 29 foods using a self-administered questionnaire covering the previous year. The population was followed up for mortality until 31 December 2017. Cox-based risk modeling referred to single foods, food groups, the results of principal component analysis (PCA), and a priori indexes. Single food analysis revealed eggs, fatty meat, and fatty/baked ham to be inversely associated with mortality. Furthermore, one of the 5 PCA derived dietary patterns, the "Farmhouse" pattern, showed a higher hazard ratio (HR), mostly driven by dairy products. In subsequent analyses, the increased risk of mortality for fresh cheese and decreased risk for fatty ham and eggs were confirmed. The a priori diet indexes (Italian Meddiet, Meddietscore, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay diet (MIND) indexes) showed borderline inverse relationships. In a Mediterranean population with an overall healthy diet, foods such as eggs and fatty meat, reflecting dietary energy and wealth, played a role in prolonging the life of individuals. Our study confirms that some dairy products might have a detrimental role in mortality in the Mediterranean setting.

Trends in adherence to the Mediterranean diet in South Italy: A cross sectional study.

BACKGROUND AND AIMS: Increasing literature data show that adherence to the Mediterranean diet is undergoing profound changes in recent years, albeit with marked differences across nations. In Italy, one of the cradles of the Mediterranean diet, the literature regarding the trend for Mediterranean diet adherence is conflicting. Thus, we aimed to explore the trends of adherence to the Mediterranean diet in a large cohort of participants living in South Italy, over 20 years from 1985-86 to 2005-06. METHODS AND RESULTS: Cross-sectional study with two evaluations, one made in 1985-86 and another in 2005-06; all participants were adults aged 30-70 years of age. The adherence to the Mediterranean diet was evaluated using the score proposed by Panagiotakos et al. This score features values ranging from 0 to 55, higher scores reflecting a greater adherence. The data are reported by age (30-49 vs. 50-69 years). Overall, 2451 subjects were included in 1985-86 and 2375 in 2005-06. A significant reduction was observed in the adherence to the Mediterranean diet (age 30-49 years: 31.82 ± 4.18 in 1985-86 vs. 29.20 ± 4.48 in 2005-06, reduction by 8.2%, p < 0.0001; age 50-69: 32.20 ± 4.09 in 1985-86 vs.30.15 ± 4.27 in 2005-06, reduction by 6.3%, p < 0.0001). Among all these items, the most dramatic change was observed for olive oil consumption, that decreased by 2.35 points in younger and 0.89 in older people. CONCLUSION: The adherence to the Mediterranean diet decreased from 1985-86 to 2005-06 in South Italy, particularly in younger people, above all due to a decreased olive oil consumption.

Reducing NAFLD-screening time: A comparative study of eight diagnostic methods offering an alternative to ultrasound scans.

BACKGROUND & AIMS: The use of ultrasound scan (US) in non-alcoholic fatty liver disease (NAFLD) screening overloads US waiting lists. We hypothesized and tested a hybrid two-step method, consisting of applying a formula, to exclude subjects at low risk, before US. METHODS: The sample included 2970 males and females (937 with NAFLD) diagnosed by US. We selected eight formulas: Fatty Liver Index (FLI), Hepatic Steatosis Index (HIS), body mass index (BMI), waist circumference (WC), Abdominal Volume Index (AVI), waist-to-height ratio (WHtR), waist/height0.5 (WHT.5R) and Body Roundness Index (BRI), and calculated their performance in the two-step method evaluating percentage reduction of the number of liver US (US reduction percentage), percentage of false negative and percentage of NAFLD identified. RESULTS: The US reductions percentage were 52.2% (WHtR), 52.1% (HIS), 51.8% (FLI), 50.8% (BRI), 50.7% (BMI and WHt_5R), 46.5% (WC) and 45.2% (AVI). The false negative percentage were 8.5% (WHtR), 7.9% (BRI), 7.3% (WHt_5R), 7.2% (BMI), 6.7% (HIS), 6.6% (FLI), 5.6% (WC) and 5.2% (AVI). The best percentage of NALFD identified was obtained using AVI (83.6%) before US, then WC (82.2%), FLI (79%), HIS (78.9%), BMI (77.3%), WHt_5R (76.9%), BRI (74.8%) and WHtR (73%). CONCLUSION: The best formula to use in two-step diagnostic NAFLD screening was AVI, which showed a low false negative rate and a higher percentage of identified NAFLD. Other studies evaluating the economic advantages of this screening method are warranted.

Moving the systemic evolutionary approach to cancer forward: Therapeutic implications.

We have previously presented a new Systemic Evolutionary Theory of Cancer (SETOC) based on the failure of proper endosymbiosis in eukaryotic cells. Here, we propose that the progressive uncoupling of two endosymbiotic subsystems (information and energy) inside the cell, as a consequence of long-term injuries, gives rise to alterations (i) in tissue interactions and (ii) in cell organization. In the first case, we argue that the impairment of both the coherent state and the synergy between intercellular communications underpins the onset of tissue dysplasia, that usually evolves towards cancer development. In the second case, we suggest that the rupture of endosymbiosis drives a sort of cell regression towards a protist-like entity represented by the concept of "de-emergence" postulated in our systemic evolutionary approach to carcinogenesis. This conceptual association of the cancer cell with a protist-like organism could support the development of novel cancer therapeutic approaches. To this end, we propose a paradigm shift in cancer pharmacology since: i) our knowledge of cancer pathophysiology as a complex system is insufficient, despite a vast knowledge of molecular mechanisms underlying cancer; ii) current cancer pharmacology deals only with microvariables (e.g. gene or protein targets), which do not account for the integrated pathophysiology of cancer, rather than with macrovariables (e.g. pH, membrane potential, electromagnetic fields, cell communications and so on) and mesovariables (between micro and macro), such as the interaction between various cellular components including cellular organelles. This paradigm shift should allow cancer pharmacology to move forward from molecular treatments (focusing on single targets) to modular treatments that consider cancer-related processes (i.e. inflammation, coagulation, etc.) or even to a sort of ecosystemic treatment addressing the whole functioning of the "cancer ecosystem". Examples of ecosystems treatment may be natural plant derivatives that act synergistically or pulsed electromagnetic fields which can act on particular biological processes in cancer cells. In addition, we need different working theoretical models on which to base new anticancer pharmacological approaches. Finally, we examine what value our systemic evolutionary approach could add to cancer treatments, in particular in liver cancer as a paradigm for developing potential applications.

Menopause Does Not Affect Fatty Liver Severity In Women: A Population Study in a Mediterranean Area.

BACKGROUND AND OBJECTIVE: Estrogens could protect the liver from fatty degeneration, but there is little information about whether menopause is associated with the severity of alcoholic (AFL) and non-alcoholic fatty liver (NAFL). Our aim was to evaluate the distribution of fatty liver detected by ultrasound in pre- and post-menopausal women and the factors associated with these conditions. METHODS: In this cross-sectional study, the years from menopause were investigated through selfreported information. The degree of fatty liver was assessed through a standardized ultrasound examination (scores 0 to 6, higher values reflecting a greater severity). Liver steatosis was classified as NAFL or AFL based on a daily alcohol intake > 20g/d. RESULTS: The study included 752 women in menopause and 535 in pre-menopause. The years from menopause were not associated with the severity of liver steatosis in NAFL (p for trend=0.74; Spearman correlation=0.04; 95%CI: -0.09 to 0.17), whereas all the indexes of adiposity and the number of metabolic syndrome factors were associated with a higher liver steatosis score. Taking AFL liver steatosis as the outcome, the years since menopause were not significantly associated with liver steatosis in AFL (p for trend=0.50; Spearman correlation=0.09; 95%CI: -0.17 to 0.34), whilst the association between anthropometric parameters and liver steatosis severity resulted stronger in postmenopausal compared to pre- menopausal women. CONCLUSION: the higher prevalence of fatty liver observed in post-menopausal women is probably not due to menopause per se, but to the adiposity (particularly abdominal) typical of this age and its consequences (such as metabolic syndrome).

Coffee Intake and Liver Steatosis: A Population Study in a Mediterranean Area.

Coffee drinking seems to have several beneficial effects on health outcomes. However, the effect on hepatic steatosis, depending on a high alcohol consumption (AFLD, alcoholic fatty liver disease) or on metabolic factors (non-alcoholic fatty liver disease, NAFLD), is still equivocal. Thus, we aimed to explore the potential association between coffee consumption and the presence and severity of hepatic steatosis in people with NAFLD or AFLD. In this cross-sectional study, coffee drinking was recorded using a semi-quantitative food frequency questionnaire, and categorized as yes vs. no and as 0, 1, 2, ≥3. The degree of fatty liver was assessed through a standardized ultrasound examination (score 0 to 6, with higher values reflecting higher severity). Liver steatosis was classified as NAFLD or AFLD on daily alcohol intake >30 g/day for men and >20 g/day for women. This study included 2819 middle-aged participants; the great majority were coffee drinkers (86.1%). After adjusting for 12 potential confounders, drinking coffee was not associated with decreased odds for NAFLD (n = 916) (odds ratio, OR = 0.93; 95% confidence intervals, CI: 0.72-1.20) or AFLD (n = 276) (OR = 1.20; 95% CI: 0.66-2.0). The consumption of coffee (categorized as yes vs. no), or an increased consumption of coffee were not associated with the presence of mild, moderate or severe liver steatosis in either NAFLD or AFLD. In conclusion, coffee intake was not associated with any lower odds of hepatic steatosis in either non-alcoholic or alcoholic forms in this large cohort of South Italian individuals.

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline.

Among metabolic syndrome components, the effects of higher plasma glucose levels on cognitive decline (CD) have been considered in few studies. We evaluated the associations among midlife glycemia, total cholesterol, high-density lipoprotein cholesterol, triglycerides, midlife insulin resistance [homeostasis model assessment for insulin resistance (HOMA-index)], and CD in the older subjects of the population-based MICOL Study (Castellana Grotte, Italy) at baseline (M1) and at follow-ups seven (M2) and twenty years later (M3). At M1, a dementia risk score and a composite cardiovascular risk score for dementia were calculated. For 797 subjects out of 833, we obtained a Mini-Mental State Examination (MMSE) score at M3, subdividing these subjects in three cognitive functioning subgroups: normal cognition, mild CD, and moderate-severe CD. Mean fasting glycemia at baseline was significantly higher in moderate-severe CD subgroup (114.6±71.4 mg/dl) than in the normal cognition subgroup (101.2±20.6). Adjusting for gender, age, and other metabolic components, higher fasting glycemia values both at M1 [odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.08-1.59] and M2 (OR = 1.26; 95% CI: 1.01-1.57) were associated with an increased risk of moderate-severe CD. Mean HOMA index value was significantly higher in the moderate-severe CD subgroup (5.7±9.4) compared to the normal cognition subgroup (2.9±1.4) at M1. The dementia risk probability (MMSE < 24) increased moving through higher categories of the dementia risk score and decreased as long as the cardiovascular score increased. The present findings highlighted the indication to control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife for prevention of late-life dementia.

A systemic evolutionary approach to cancer: Hepatocarcinogenesis as a paradigm.

The systemic evolutionary theory of cancer pathogenesis posits that cancer is generated by the de-emergence of the eukaryotic cell system and by the re-emergence of its archaea (genetic material and cytoplasm) and prokaryotic (mitochondria) subsystems with an uncoordinated behavior. This decreased coordination can be caused by a change in the organization of the eukaryote environment (mainly chronic inflammation), damage to mitochondrial DNA and/or to its membrane composition by many agents (e.g. viruses, chemicals, hydrogenated fatty acids in foods) or damage to nuclear DNA that controls mitochondrial energy production or metabolic pathways, including glycolysis. Here, we postulate that the two subsystems (the evolutionarily inherited archaea and the prokaryote) in a eukaryotic differentiated cell are well integrated, and produce the amount of clean energy that is constantly required to maintain the differentiated status. Conversely, when protracted injuries impair cell or tissue organization, the amount of energy necessary to maintain cell differentiation can be restricted, and this may cause gradual de-differentiation of the eukaryotic cell over time. In cirrhotic liver, for example, this process can be favored by reduced oxygen availability to the organ due to an altered vasculature and the fibrotic barrier caused by the disease. Thus, hepatocarcinogenesis is an ideal example to support our hypothesis. When cancer arises, the pre-eukaryote subsystems become predominant, as shown by the metabolic alterations of cancer cells (anaerobic glycolysis and glutamine utilization), and by their capacity for proliferation and invasion, resembling the primitive symbiotic components of the eukaryotic cell.

Coffee Consumption Habits and the Risk of Mild Cognitive Impairment: The Italian Longitudinal Study on Aging.

Coffee, tea, or caffeine consumption may be protective against cognitive impairment and dementia. We estimated the association between change or constant habits in coffee consumption and the incidence of mild cognitive impairment (MCI). We evaluated 1,445 individuals recruited from 5,632 subjects, aged 65-84 year old, from the Italian Longitudinal Study on Aging, a population-based sample from eight Italian municipalities with a 3.5-year median follow-up. Cognitively normal older individuals who habitually consumed moderate amount of coffee (from 1 to 2 cups of coffee/day) had a lower rate of the incidence of MCI than those who never or rarely consumed coffee [1 cup/day: hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.211 to 1.02 or 1-2 cups/day: HR: 0.31 95% CI: 0.13 to 0.75]. For cognitively normal older subjects who changed their coffee consumption habits, those increasing coffee consumption (>1 cup of coffee/day) had higher rate of the incidence of MCI compared to those with constant habits (up to ±1 cup of coffee/day) (HR: 1.80, 95% CI: 1.11 to 2.92) or those with reduced consumption (<1 cup of coffee/day) (HR: 2.17, 95% CI: 1.16 to 4.08). Finally, there was no significant association between subjects with higher levels of coffee consumption (>2 cups of coffee/day) and the incidence of MCI in comparison with those who never or rarely consumed coffee (HR: 0.26, 95% CI: 0.03 to 2.11). In conclusion, cognitively normal older individuals who increased their coffee consumption had a higher rate of developing MCI, while a constant in time moderate coffee consumption was associated to a reduced rate of the incidence of MCI.

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI). RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT. CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening.

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) / Acurácia diagnóstica de um escore de ultrassonografia hepática não invasivo para doença hepática gordurosa não alcoólica (DHGNA) no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI). RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT. CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening. .

CONTEXTO E OBJETIVO: Estratégias não invasivas para avaliar doença hepática gordurosa não alcoólica (DHGNA) têm sido investigadas nas últimas décadas. Nosso objetivo foi avaliar a acurácia diagnóstica de um novo escore de ultrassonografia hepática para DHGNA no estudo ELSA-Brasil. TIPO DE ESTUDO E LOCAL: Estudo de acurácia diagnóstica realizado no centro ELSA, no hospital de uma universidade pública. MÉTODOS: Dos 15.105 participantes do estudo ELSA avaliados para DHGNA, 195 indivíduos foram incluídos neste estudo. Foi realizada ultrassonografia hepática (atenuação do feixe de profundidade, índice hepatorrenal e diâmetro anteroposterior do lobo direito do fígado) que foi comparada aos achados de esteatose hepática da tomografia computadorizada (TC) de alta resolução de 64 canais. Avaliamos também dois índices clínicos relacionados à DHGNA: o índice de gordura hepática (FLI) e o índice de esteatose hepática (HSI). RESULTADOS: Entre os 195 participantes, a frequência de DHGNA foi de 34,4%. Altos índices de massa corpórea, circunferência de cintura, diabetes e hipertrigliceridemia foram associados a aumento da atenuação hepática e do diâmetro anteroposterior do lobo hepático direito, mas não ao índice hepato-renal. A pontuação da ultrassonografia hepática, que incluiu atenuação hepática e diâmetro anteroposterior do lobo direito do fígado, apresentou o melhor desempenho para o rastreio DHGNA sob o ponto de corte ≥ 1 ponto (sensibilidade: 85.1%; especificidade: 73.4%; acurácia: 79.3%), e área sob a curva (AUC, 0,85, IC 95%: 0,78-0,91). FLI e HSI apresentaram menor desempenho (AUC 0,76; IC 95%: 0,69-0,83) comparados à TC. CONCLUSÃO: O escore de ultrassonografia hepática, que incluiu atenuação hepática e o diâmetro anteroposterior do lobo direito do fígado, possui boa reprodutibilidade e acurácia para o rastreio de DHGNA. .

Ultrasound evaluation and correlates of fatty liver disease: a population study in a Mediterranean area.

BACKGROUND: The aim of this study was to evaluate the distribution of fatty liver-nonalcoholic (NAFL) and alcoholic (AFL)-and its association with metabolic syndrome and its components in a population sample from a Mediterranean area. METHODS: A sample of 2974 subjects (1679 males, 1295 females, age range 30-89 years) was randomly drawn from the population of a town in southern Italy. The survey visit included a validated semiquantitative food frequency questionnaire, anthropometric measurements, a blood sample taken in the morning after overnight fasting, as well as abdominal ultrasound examination to evaluate liver fat with a standardized scoring system. The 2001 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition of the metabolic syndrome was adopted. RESULTS: In this Mediterranean population, where alcohol intake is mostly as wine with meals, NAFL is present in 36.8% of men and 25.7% of women and AFL in 13.8% of men and 5.5% of women. NAFL and AFL are associated with metabolic syndrome and its characteristics, body mass index (BMI), and visceral and subcutaneous fat (in AFL subjects, only in women) measured by ultrasound. Stratifying by BMI and controlling for confounders (age, height, smoking habit, and alcohol consumption), in overweight and obese subjects, liver and visceral fat are associated with the metabolic syndrome both in men and women and subcutaneous fat only in women. In normal weight subjects, only liver fat in men is associated with the metabolic syndrome. CONCLUSIONS: Fatty liver is highly prevalent in this Mediterranean population and is associated with metabolic syndrome in overweight and obese men and women as well as in men with normal BMI.