Mediterranean-Oriented Dietary Intervention Is Effective to Reduce Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: Results from an Italian Clinical Trial.

Results: One hundred and fifty five subjects aged 20-59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). Three of the healthy controls developed NAFLD. The NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline. Conclusions: Mediterranean dietary advices, without a personalised meal planning, were efficient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identification and lifestyle intervention. This trial is registered with NCT03300661.

Cooking Skills, Eating Habits and Nutrition Knowledge among Italian Adolescents during COVID-19 Pandemic: Sub-Analysis from the Online Survey COALESCENT (Change amOng ItAlian adoLESCENTs).

BACKGROUND: Cooking skills (CS) have the potential to improve self-care behaviours and healthy development among adolescents. The COVID-19 pandemic has affected lifestyles worldwide, and the present study aims to investigate the level of CS after the pandemic, as well as its associations with nutrition knowledge and eating behaviours among a cohort of Italian adolescents. METHODS: We submitted an online survey about lifestyle changes to students aged 13-21 years during the pandemic. Based on overall culinary abilities, we divided respondents into high, medium and low CS. Worsening or improvement in diet quality was detected by assigning an eating habit index (EHI; 0-54). RESULTS: Out of the 1686 questionnaires collected, 21.5%, 63.6% and 14.9% reported high, medium and low CS, respectively. The EHI scores were statistically higher among students who were able to cook more than 20 recipes compared to those reporting no cooking abilities (30.2 ± 5.9 vs. 26.6 ± 5.7; p = 0.0001). High CS significantly correlated with better EHI (OR 1.44; p = 0.009), lower consumption of ultra-processed food (OR 1.80; p < 0.0001) and better nutrition knowledge (OR 1.42; p = 0.007). CONCLUSIONS: Adolescents with good CS showed better nutrition knowledge and healthier eating habits, including lower consumption of ultra-processed foods. Projects aimed to improve CS in adolescents can therefore promote healthier development.

Is weight gain preventable in women with early breast cancer undergoing chemotherapy? A real-world study on dietary pattern, physical activity, and body weight before and after chemotherapy.

PURPOSE: We aimed to investigate the role of a lifestyle intervention and clinical and therapeutic factors for preventing weight gain in early breast cancer (BC) patients from one week before to 12 months after chemotherapy. METHODS: Dietary assessments were conducted by a trained dietician using a food-frequency questionnaire at each clinical assessment. Total energy, macronutrients intakes, and physical activity were estimated and the Mediterranean Diet Score (MDS) for adherence to Mediterranean diet was calculated. At each follow-up visit, patients were provided with dietary advices according to Mediterranean and Italian guidelines by a registered dietician, after evaluation of their food records. The associations of clinical characteristics, dietary pattern, and physical activity with weight gain were evaluated by multiple logistic regression, with weight gain ≥5% from baseline value as a dichotomous dependent variable. RESULTS: 169 early BC patients who met all follow-up visits and provided complete data were included in the analysis. From baseline to last assessment, weight loss (≥5% decrease from baseline value), stable weight, and weight gain were observed in 23.1%, 58%, and 18.9% women, respectively. Overall, a 0.68 kg mean decrease in women's weight (-1.1% from baseline) was observed. The risk of gaining weight increased for having normal weight/underweight at baseline, receiving hormone therapy, MDS worsening, and physical activity decreasing from baseline to last assessment. CONCLUSION: Providing simple suggestions on Mediterranean diet principles was effective for preventing weight gain in normal weight women and favoring weight loss in overweight and obese women.

What does not look like celiac disease and instead it is.

The celiac disease (CD) diagnosis sometimes is challenging and diagnostic process cannot always follow a simple algorithm but it requires a close collaboration between histo-pathologists, clinicians, laboratory and genetic experts. The genetic predisposition for CD is related to HLA-DQ2 and/or DQ8 but other HLA haplotypes and non-HLA genes may be involved in genetic predisposition. In particular DQ7 may represent an additive and independent CD risk associated haplotype. We describe an unusual case of a female 42 year old with a previous diagnosis of Hodgkin lymphoma, who has a clinical presentation suggestive for CD with negativity for anti-transglutaminase and anti-endomysium antibodies and HLA-DQ7 positivity.

Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells as Novel Diagnostic Tools for Non-Alcoholic Fatty Liver Disease: Visualizing Relationships with Known and Potential Disease Biomarkers.

Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.

Taste Alterations Do Not Affect Change in Food Habits and Body Weight in Breast Cancer Patients.

BACKGROUND/AIM: Chemotherapy-induced taste alterations (TAs) affect approximately 53-84% of breast cancer patients with significant consequences on flavor perception, possibly leading to food aversion and changes in daily dietary habits. The aim of this study was to investigate the relationship between TAs and changes in food habits and body weight among early breast cancer (EBC) patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: TAs were prospectively evaluated in 182 EBC patients from April 2014 to June 2018. TAs, dietary habits, and body weight were collected by a trained dietician. TAs were classified into different subtypes according to the following basic taste perception: metallic, sweet, bitter, salty, sour, and umami taste. RESULTS: During adjuvant chemotherapy, a significant reduction in the consumption of bread, breadsticks, red meat, fat salami, snacks, added sugar, milk, and alcoholic beverages was observed, regardless of TAs onset. No correlation between these dietary changes and different TAs subtypes was found. Body weight remained stable in most EBC patients (71.4%) and was not influenced by TAs onset and by different TAs subtypes. CONCLUSION: EBC patients change their dietary habits during adjuvant chemotherapy, mostly following the World Cancer Research Fund recommendations, irrespective of TAs onset and without affecting body weight.

Changes in eating habits and food preferences in breast cancer patients undergoing adjuvant chemotherapy.

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2-3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt "healthier dietary patterns" during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.

The Effects of Cow-Milk Protein Supplementation in Elderly Population: Systematic Review and Narrative Synthesis.

BACKGROUND: To review currently available evidence on the effect of cow-milk proteins supplementation (CPS) on health in the elderly. METHODS: Five electronic databases (Pubmed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov) were searched for studies about CPS among older people. All types of publications were included, with the exception of systematic reviews, meta-analyses, opinion letters, editorials, case reports, conference abstracts and comments. An additional search in Google Scholar and a manual review of the reference lists were performed. RESULTS: Overall, 103 studies were included. Several studies explored the role of CPS in the preservation or improvement of muscle mass among healthy subjects (40 studies) and pre-frail, frail or sarcopenic patients (14), with evidence of beneficial effects. Other studies assessed the effect of CPS on bones (12), cardiovascular disease (8), inflamm-aging (7), chronic pulmonary disease (4), neurocognitive function (4), and vaccines (2), with weak evidence of positive effects. Seven studies in the field of protein metabolism investigated the role of CPS as an important contributor to nutritional needs. Other investigational areas are considered in the last five studies. CONCLUSIONS: The beneficial effects of CPS in achieving aged-related nutritional goals, in preserving muscle mass and in recovering after hospitalization may be particularly relevant in the elderly.

A new self-administered semi-quantitative food frequency questionnaire to estimate nutrient intake among Italian adults: development design and validation process.

Food Frequency Questionnaires (FFQs) are valuable research tools in nutritional epidemiology. This study aimed to develop and validate a new semi-quantitative FFQ, specifically designed for the Italian population and best fitted for self-administration. During the development process, we adapted to Italian needs the validated FFQ proposed by the Fred Hutchinson Cancer Research Center, revising food items, food frequency scale, portion sizes, and time frame. To assess the validity of the proposed FFQ, we compared the estimated daily intake using FFQ with the mean of 3-day food diaries and one 24-hour recall (considered as reference method). The validation process was conducted among a cohort of 51 healthy subjects enrolled in a clinical trial. Four statistical tests were applied on 23 estimated nutrient intakes. Spearman's coefficients ranged from 0.223 (sodium) to 0.748 (alcohol) and were good (≥0.50) and acceptable (0.20-0.49) for 7 and 16 nutrients, respectively. Cross classification showed a good agreement (≥50% in the same tertile or ≤10% in the opposite tertile) for 7 nutrients. The weighted Cohen's kappa values indicated an acceptable outcome (0.20-0.60) for 13 nutrients. Bland Altman plots did not show heteroscedasticity in the error terms, despite the presence of a bias. Our study provided a new Italian semi-quantitative FFQ for self-administration with an acceptable validation level. Its definitive release requires additional refinements and efforts.

Evaluation of systo-diastolic cardiac function and arterial stiffness in subjects with new diagnosis of coeliac disease without cardiovascular risk factors.

In literature, there are conflicting opinions on the development of cardiovascular disease risk in patients with coeliac disease (CD). The aim of the research was to identify in young subjects without cardiovascular risk factor and newly diagnosed CD, alterations in different instrumental parameters that are associated with an augmented cardiovascular risk. Twenty-one consecutive young adults with a new diagnosis of CD and without cardiovascular risk factors were prospectively enrolled and underwent transthoracic echocardiography to analyse ascending aorta elastic properties [including tissue Doppler imaging strain (TDI-ε)] and left ventricular 2D strains (global longitudinal, radial and circumferential), and applanation tonometry by SphygmoCor. Cases were compared with 21 age- and sex-matched healthy controls. Mean age of the cases was 38 ± 9 years and 15 of them (71%) were female. Brachial and central blood pressure was higher in the CD group. Elastic properties of the ascending aorta were all impaired in the CD group: TDI-ε was altered in 57% of cases (0% of controls, p < 0.001). Concentric remodelling and grade I diastolic dysfunction were present in 38% and 24% of cases, respectively (0% of controls, p < 0.001). Global longitudinal strain was normal in all subjects, while radial and circumferential strain were altered in 67% and 35%, respectively (0% of controls, p < 0.001). In young subjects without cardiovascular risk factor, a newly diagnosed CD is associated with altered aortic elastic properties, left ventricular concentric remodelling and diastolic dysfunction and altered radial and circumferential strain.

Phyllanthus niruri versus Placebo for Chronic Hepatitis B Virus Infection: A Randomized Controlled Trial.

BACKGROUND: This study aimed to investigate the efficacy and safety of a 12-month treatment with Phyllanthus niruri in subjects with chronic hepatitis B virus (HBV) infection. PATIENTS AND METHODS: A placebo-controlled, parallel-group double-blind trial was performed. Clinical assessments took place at baseline and at 1, 3, 9, and 12 months after the treatment start and 6 months after treatment end. RESULTS: In the first 2 years, 50 eligible subjects with chronic HBV accepted to participate. Of those, 47 completed all the study-related visits (6% drop-out rate): 24 of the 26 (92%) allocated to the Phyllanthus group and 23 of the 24 (96%) allocated to the placebo group completed the study. No statistically significant differences in viral load were found between the intervention and placebo groups after 12 months and no subjects showed HBsAg clearance. With regards to safety, there were no changes in renal function parameters in both groups after 12 months and no serious adverse events occurred due to the treatment. The study was stopped at the end of the second year because there was no apparent benefit of the treatment. CONCLUSION: This study does not support the use of Phyllanthus niruri for the treatment of chronic hepatitis B.

Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet.

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12-18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696].

Triticum monococcum in patients with celiac disease: a phase II open study on safety of prolonged daily administration.

BACKGROUND AND AIMS: To assess safety of prolonged daily administration of Triticum monococcum (Tm) using clinical, serological and histological criteria. Tm is an ancient wheat suitable for production of palatable baked goods that contains gluten devoid of strongly immunostimulatory epitopes and potentially safe for celiac disease (CD) patients as suggested by in vitro and ex vivo studies. METHODS: Protocol involved 60-day administration of 100 g/day Tm water biscuits to CD patients in remission on gluten-free diet. Symptoms Gastrointestinal Symptom Rating Scale questionnaire (GSRS) and CD-related serology were assessed at time (T) 0, T30 and T60 days, and duodenal biopsy was obtained at T0 and T60. RESULTS: Eight patients (F/M: 6/2, median age 26) were enrolled. One patient was excluded at T0 because of positive serology, and two patients dropped out because of symptoms recurrence. In the five patients completing the study, there was no difference in GSRS score at T0 to T60. All patients had Marsh II lesion at T0, four had Marsh III and one had recurrence of dermatitis herpetiformis at T60. CD-related antibodies converted from negative to positive at T60 in three patients. CONCLUSIONS: Our study shows that Tm is toxic for CD patients as judged on histological and serological criteria, but it was well tolerated by the majority of patients, suggesting that Tm is not a safe cereal for celiacs, but that it may be of value for patients with gluten sensitivity or for prevention of CD.

Clinical expression of lymphocytic duodenosis in "mild enteropathy" celiac disease and in functional gastrointestinal syndromes.

OBJECTIVE: Abnormally high number of duodenal intraepithelial lymphocytes is frequently found in many conditions including mild enteropathy celiac disease (CD) and functional gastrointestinal syndromes, but is unclear whether lymphocytosis affects the clinical phenotype particularly in functional syndromes. MATERIALS AND METHODS: We compared clinical characteristics of celiac patients with lymphocytic duodenosis and normal villous structure with those of patients with functional gastrointestinal syndromes with and without lymphocytic duodenosis. We retrospectively identified 3 cohorts among patients referred for suspected CD: (1) "CoelD", 135 patients (age 36 ± 14 years) with mild enteropathy CD; (2) "LymD", 245 patients (38 ± 12 years) with functional gastrointestinal syndromes and lymphocytic duodenosis; and (3) "NorD", 147 patients (37 ± 15 years) with functional syndromes and normal duodenal histology. RESULTS: Prevalence of gastrointestinal symptoms was similar in the three cohorts, but prevalence of extra-intestinal manifestations (42% vs. 27% vs. 18%, p < 0.003) and of associated diseases (35% vs. 15% vs. 14%, p < 0.0001) was higher in "CoelD" than in "LymD" and "NorD", respectively. Prevalence of Helicobacter pylori infection was similar in the three cohorts. The proportion of patients with final diagnosis of irritable bowel syndrome-diarrhea (38% vs. 37%), dyspepsia (31% vs. 27%), functional pain (14% vs. 19%), and functional diarrhoea (14% vs. 11%) was virtually the same in the cohorts with (LymD) and without (NorD) lymphocytic duodenosis. CONCLUSIONS: Lymphocytic duodenosis has different clinical presentation in patients with mild enteropathy CD than those with functional gastrointestinal syndromes, and is not specific for any particular functional syndrome.

Factors that contribute to hypertransaminasemia in patients with celiac disease or functional gastrointestinal syndromes.

BACKGROUND & AIMS: Transaminasemia develops via different pathways in patients with celiac disease; no information is available on risk factors specifically attributable to celiac disease. METHODS: We analyzed data collected from consecutive patients referred from January 1997 through December 2009 to the celiac disease clinic at the Spedali Civili of Brescia, Italy. We assessed the factors affecting hypertransaminasemia in 683 patients with celiac disease (based on serologic and biopsy analysis, cohort A; 34 ± 14 years of age) and 304 with functional syndromes (cohort B; 37 ± 13 years of age). RESULTS: Hypertransaminasemia was detected in 138 patients in cohort A (20%). It was associated with malabsorption (odds ratio [OR], 2.22; P = .004), diarrhea (OR, 1.72; P = .005), and increasing severity of mucosal lesion (Marsh-Oberhuber class; OR, 1.46; P = .001) but not with body mass index (BMI) or the serum level of tissue-transglutaminase antibodies (tTG). Hypertransaminasemia was detected in 22 patients in cohort B (7%) and was associated with the World Health Organization's BMI categories (OR, 7.9; P < .001). In subsets of patients studied with the same analytical method (313 of cohort A and 188 of cohort B), the level of tTG was significantly higher in cohort A at baseline (25.2 ± 16.9 U/L aspartate aminotransferase [AST]) than in cohort B (20.6 ± 9.9 U/L AST, P < .0001) and was related to BMI in cohort B (P = .0012) but not cohort A. When patients were placed on gluten-free diets, the levels of AST decreased from 25.2 ± 16.9 U/L to 19.9 ± 6.6 U/L (P < .0001), independently of the changes of duodenal histology and tTG and correlated with BMI (P = .0007); the prevalence of hypertransaminasemia decreased from 13% to 4%. CONCLUSIONS: Patients with celiac disease have a higher prevalence of hypertransaminasemia than controls (patients with functional syndromes). Hypertransaminasemia is related to the severity of the duodenal lesion and malabsorption but not BMI. By contrast, there was a positive correlation between the levels of AST and BMI in controls; this relationship was restored when patients with celiac disease were placed on gluten-free diets.

Addicts with chronic hepatitis C: difficult to reach, manage or treat?

AIM: To assess the acceptance, safety and efficacy of care and treatment for chronic hepatitis C (CHC) in drug addicts. METHODS: We designed a multidisciplinary, phase IV prospective cohort study. All illicit drug users (IDUs) visited a Territorial Addiction Service (SerT) in the District of Brescia, and hepatitis C antibody (HCVAb) testing positive were offered as part of a standardised hepatologic visit in our Gastroenterology Unit. Patients with confirmed CHC and without medical contraindications were administered peginterferon alfa-2b 1.5 µg/kg per week plus ribavirin (800-1400 mg/d) for 16-48 wk. All IDUs were unselected because of ongoing addiction and read and signed an informed consent form. Virologic responses at weeks 4 and 12 of therapy, at the end of treatment and 24 wk after the end of treatment were the main measures of efficacy. Adherence was estimated according to the 80/80/80 criteria. RESULTS: From November 2007 to December 2009, 162 HCVAb+ IDUs were identified. Sixty-seven patients (41% of the initial cohort) completed the diagnostic procedure, and CHC was diagnosed in 54 (33% of the total). Forty-nine patients were offered therapy, and 39 agreed (80% of acceptance rate). The prevalent HCV genotype was type 1, and the HCV RNA baseline level was over 5.6 log/mL in 61% of cases. Five patients dropped out, two because of severe adverse events (SAEs) and three without medical need. Twenty-three and 14 patients achieved end of treatment responses (ETRs; 59%) and sustained virologic responses (SVRs; 36%), respectively. Thirty-one patients were fully compliant with the study protocol (80% adherence). The prevalence of host and viral characteristics negatively affecting the treatment response was high: age over 40 years (54%), male gender (85%), overweight body type (36%), previous unsuccessful antiviral therapy (21%), HCV genotype and viral load (60% and 62%, respectively), earlier contact with HBV (40%) and steatosis and fibrosis (44% and 17%, respectively). In a univariate analysis, alcohol intake was associated with a non-response (P = 0.0018, 95%CI: 0.0058-0.4565). CONCLUSION: Drug addicts with CHC can be successfully treated in a multidisciplinary setting using standard antiviral combination therapy, despite several "difficult to reach, manage and treat" characteristics.

Impact of gluten-free diet on cardiovascular risk factors. A retrospective analysis in a large cohort of coeliac patients.

BACKGROUND: Concerns have been raised on whether a gluten-free diet affects the cardiovascular risk profile of coeliac patients. AIMS: To assess changes of multiple cardiovascular risk factors in coeliac patients evaluated before and during a gluten-free diet. METHODS: Retrospective analysis of the effects of 1-5 years of gluten-free diet on indicators of cardiovascular risk and on distribution in cardiovascular risk categories in 715 coeliac patients. RESULTS: Compared to baseline, significant increases were found in body mass index (21.4±3.4 vs. 22.5±3.5; p<0.0001), total cholesterol (171.2±37.4mg/dL vs. 181.4±35.1mg/dL; p<0.0001), and γ-glutamyl transpeptidase (16.5±14.9 vs. 19.5±19.2U/L; p<0.0001). Significant reductions were found in serum triglycerides (87.9±49.5 vs. 80.2±42.8mg/dL; p<0.0001) and homocysteine (16.9±9.6 vs. 13.3±8.0µmol/L; p=0.018) during gluten-free diet. The proportion of patients included in an arbitrarily defined category of "lowest cardiovascular risk profile" decreased from 58% at baseline to 47% during gluten-free diet. CONCLUSIONS: A gluten-free diet significantly affects cardiovascular risk factors in coeliac patients, but changes do not consistently point towards worse or better risk profiles, thus suggesting that the diet is unlikely to be atherogenic.