Effects of Mediterranean diet during pregnancy on the onset of overweight or obesity in the offspring: a randomized trial.

BACKGROUND/OBJECTIVES: The PREMEDI study was designed to assess the efficacy of nutritional counseling aimed at promoting Mediterranean Diet (MD) during pregnancy on the incidence of overweight or obesity at 24 months in the offspring. METHODS: PREMEDI was a parallel-arm randomized-controlled trial. 104 women in their first trimester of pregnancy were randomly assigned in a 1:1 ratio to standard obstetrical and gynecological care alone (CT) or with nutritional counseling promoting MD. Women enrolled in the MD arm were provided with 3 sessions of nutritional counseling (one session per trimester). The main outcome was the proportion of overweight or obesity among the offspring at the age of 24 months. Maternal MD-adherence and weight gain during pregnancy were also evaluated. Lastly, the evaluation of epigenetic modulation of metabolic pathways in the offspring was analyzed in cord blood. RESULTS: Five women in the MD arm and 2 in the CT arm were lost to follow-up, so a total of 97 completed the study. At 24 months, children of MD mothers were less likely to have overweight or obesity than those of the CT mothers (6% vs. 33%, absolute risk difference = -27%, 95% CI -41% to -12%, p < 0.001; number needed to treat 3, 95% CI 2 to 8, intention to treat analysis). A significantly higher increase of MD-adherence during the trial was observed in the MD arm compared to the CT arm. A similar body weight gain at the end of pregnancy was observed in the two arms. The mean (SD) methylation rate of the leptin gene in cord blood was 30.4 (1.02) % and 16.9 (2.99) % in the CT and MD mothers, respectively (p < 0.0001). CONCLUSIONS: MD during pregnancy could be an effective strategy for preventing pediatric overweight or obesity at 24 months. This effect involves, at least in part, an epigenetic modification of leptin expression.

Predictors of clinical trajectories of patients with acutely decompensated cirrhosis. An external validation of the PREDICT study.

BACKGROUND AND AIMS: The PREDICT study recently showed that acutely decompensated (AD) patients with cirrhosis can present three different clinical phenotypes in the 90 days after admission: (1) pre-ACLF, developing acute-on-chronic liver failure (ACLF); (2) unstable decompensated cirrhosis (UDC), being re-admitted for AD without ACLF and (3) stable decompensated cirrhosis (SDC), not presenting readmission or ACLF. This study aimed to externally validate the existence of these three distinct trajectories and to identify predictors for the occurrence of each trajectory. METHODS: Baseline data, 3-month ACLF and readmission incidence and 1-year survival were analysed in a prospective cohort of patients admitted for AD. A multinomial multivariable model was used to evaluate the association between baseline features and clinical trajectories. RESULTS: Of the 311 patients enrolled, 55% met the criteria for SDC, 18% for UDC and 27% for pre-ACLF, presenting a significantly different 1-year mortality: pre-ACLF 65%, UDC 46%, SDC 21% (p < .001). The presence of hepatic encephalopathy (HE) was associated with UDC (p = .043), while the absence of ascites to SDC (p = .017). Among laboratory parameters, an increase in MELD-Na (p = .001) and C-reactive protein (p = .009) and a decrease in haemoglobin (p = .004) and albumin (p = .008) levels were associated with pre-ACLF. CONCLUSION: The present study confirms that AD patients have three different clinical trajectories with different mortality rates. Besides the severity of cirrhosis, the association with C-reactive protein supports the predominant role of systemic inflammation in ACLF pathophysiology. Finally, HE is associated with the UDC phenotype highlighting the need for better management of this complication after discharge.

Nonalcoholic fatty liver disease: an update.

PURPOSE OF REVIEW: We discuss two recent controversial issues in the research field of fatty liver: the proposal to replace nonalcoholic fatty liver disease (NAFLD) with metabolically associated fatty liver disease (MAFLD) and the suggestion to extend to primary care the noninvasive testing for liver fibrosis that was developed for secondary care. RECENT FINDINGS: There is preliminary evidence that MAFLD-only patients are at greater risk of fibrosis than NAFLD-only patients. There are a large number of false positives associated with the downshift of noninvasive testing for liver fibrosis from secondary to primary care. SUMMARY: More studies are needed to compare the MAFLD and NAFLD operational definitions. Noninvasive testing of liver fibrosis also needs further evaluation before it can be used in primary care or in the general population.

Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database.

INTRODUCTION: We assessed the impact of long-term albumin administration to hyponatremic patients with ascites enrolled in the ANSWER trial. METHODS: The normalization rate of baseline hyponatremia and the 18-month incidence rate of at least moderate hyponatremia were evaluated. RESULTS: The hyponatremia normalization rate was higher with albumin than with standard medical treatment (45% vs 28%, P = 0.042 at 1 month). Long-term albumin ensured a lower incidence of at least moderate hyponatremia than standard medical treatment (incidence rate ratio: 0.245 [CI 0.167-0.359], P < 0.001). DISCUSSION: Long-term albumin administration improves hyponatremia and reduces episodes of at least moderate hyponatremia in outpatients with cirrhosis and ascites.

The step-down approach in children with cow's milk allergy: Results of a randomized controlled trial.

BACKGROUND: The Step-Down Approach for Cow's Milk Allergy (SDACMA) trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary treatment with amino acid-based formula (AAF) and then switching to EHCF containing the probiotic Lacticaseibacillus rhamnosus GG (EHCF + LGG). METHODS: Randomized controlled trial involving IgE-mediated CMA children receiving AAF from at least 4 weeks. EHCF + LGG tolerance was evaluated by the results of double-blind placebo-controlled food challenge (DBPCFC). Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. Immune tolerance acquisition to cow's milk proteins was evaluated with DBPCFC after 12 months of treatment. Allergy screening tests and body growth were also monitored. RESULTS: Sixty IgE-mediated CMA children were enrolled. The proportion of children treated with AAF who resulted tolerant to the first exposure of EHCF + LGG was 0.98 (exact 95% CI 0.91-0.99). The rate of the immune tolerance acquisition to cow milk proteins after 12 months treatment was higher in the EHCF + LGG (0.48, 95% exact CI 0.29-0.67, n/N = 14/29) than in the AAF group (0.03, 95% exact CI 0.001-0.17, n/N = 1/30). There was an absolute benefit increase (ABI) of tolerance rate equal to 0.45 (95% CI 0.23-0.63, Newcombe method 10) for EHCF + LGG versus AAF, corresponding to a NNT of 2 (2-4, Bender's method). A normal body growth pattern was observed in the two study groups. CONCLUSION: In IgE-mediated CMA children the step-down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition.

Fatty Liver Index (FLI) Identifies Not Only Individuals with Liver Steatosis but Also at High Cardiometabolic Risk.

A fatty liver index (FLI) greater than sixty (FLI ≥ 60) is an established score for metabolic dysfunction-associated steatotic liver disease (MASLD), which carries a high risk for diabetes and cardiovascular disease, while a FLI ≤ 20 rules out the presence of steatosis. Thus, we investigated whether FLI was associated with cardiometabolic risk factors, i.e., visceral (VAT), subcutaneous (SC), epicardial (EPI), extrapericardial (PERI), and total cardiac (CARD-AT) adipose tissue, hepatic fat ((by magnetic resonance imaging, MRI, and spectroscopy, MRS), and insulin resistance (IR, HOMA-IR and OGIS-index), and components of metabolic syndrome. All individuals with FLI ≥ 60 had MASLD, while none with FLI ≤ 20 had steatosis (by MRS). Subjects with FLI ≥ 60 had a higher BMI and visceral and cardiac fat (VAT > 1.7 kg, CARD-AT > 0.2 kg). FLI was positively associated with increased cardiac and visceral fat and components of metabolic syndrome. FLI, VAT, and CARD-AT were all associated with IR, increased blood pressure, cholesterol, and reduced HDL. For FLI ≥ 60, the cut-off values for fat depots and laboratory measures were estimated. In conclusion, FLI ≥ 60 identified not only subjects with steatosis but also those with IR, abdominal and cardiac fat accumulation, increased blood pressure, and hyperlipidemia, i.e., those at higher risk of cardiometabolic diseases. Targeted reduction of FLI components would help reduce cardiometabolic risk.

Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of the pediatric population associated with alteration of skin and gut microbiome. Probiotics have been proposed for AD treatment. The ProPAD study aimed to investigate the therapeutic effects of the probiotic Lacticaseibacillus rhamnosus GG (LGG) in children with AD. METHODS: In total, 100 AD patients aged 6-36 months were enrolled in a randomized, double-blind, controlled trial to receive placebo (Group A) or LGG (1 x 1010 CFU/daily) (Group B) for 12 weeks. The primary outcome was the evaluation of the efficacy of LGG supplementation on AD severity comparing the Scoring Atopic Dermatitis (SCORAD) index at baseline (T0) and at 12-week (T12). A reduction of ≥8.7 points on the SCORAD index was considered as minimum clinically important difference (MCID). The secondary outcomes were the SCORAD index evaluation at 4-week (T16) after the end of LGG treatment, number of days without rescue medications, changes in Infant Dermatitis Quality Of Life questionnaire (IDQOL), gut microbiome structure and function, and skin microbiome structure. RESULTS: The rate of subjects achieving MCID at T12 and at T16 was higher in Group B (p < .05), and remained higher at T16 (p < .05)The number of days without rescue medications was higher in Group B. IDQOL improved at T12 in the Group B (p < .05). A beneficial modulation of gut and skin microbiome was observed only in Group B patients. CONCLUSIONS: The probiotic LGG could be useful as adjunctive therapy in pediatric AD. The beneficial effects on disease severity and quality of life paralleled with a beneficial modulation of gut and skin microbiome.

The Impact of Formula Choice for the Management of Pediatric Cow's Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study.

OBJECTIVES: To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. STUDY DESIGN: In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. RESULTS: In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF + LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF + LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG; 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG; 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG; and 3.50 (2.23-5.49, P < .001) for amino acid-based formula vs EHCF + LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF + LGG cohort. CONCLUSIONS: The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Rice flour fermented with Lactobacillus paracasei CBA L74 in the treatment of atopic dermatitis in infants: A randomized, double- blind, placebo- controlled trial.

To assess the effect of a fermented rice-flour obtained from Lactobacillus paracasei CBA L74 in managing infants with moderate to severe atopic dermatitis. Infants with moderate to severe atopic dermatitis, aged 6-36 months, were randomly assigned to receive once-daily consumption of rice flour containing heat-killed probiotic Lactobacillus paracasei CBA L74 or placebo for 12 weeks as supplementary approach to topical treatment. Primary outcome was SCORAD index change from baseline to 12 weeks; secondary outcomes were gut microbiota composition, as evaluated by the analysis of fecal samples, and serum cytokines at baseline and at the end of the intervention period in both groups, and steroid usage over the treatment period and one month after stopping it. V3-V4 region of the 16S ribosomal RNA gene was sequenced to evaluate changes in the gut microbiota. SCORAD index decreased over the treatment period in both groups. The difference in the SCORAD change was -2.1 (-5.5 to 1.3; p = 0.223) for the experimental vs. the placebo group, not reaching the minimal clinical difference of 8.7 units. The use of topical steroids, measured as finger tips units, decreased from 4 to 16 weeks, in both groups; the reduction was significantly higher in experimental than in placebo group (p value from Wilcoxon rank sum test = 0.031). No significant differences were observed for cytokines levels between groups. The composition of gut microbiota at the phylum and class taxonomic levels resulted very similar, at baseline and after intervention, in both groups. Similarly, no significant differences were observed in the relative abundance of bacterial genera between groups. In conclusion, though the heat-killed Lactobacillus paracaseiwas not proved to be effective in reducing the severity of atopic dermatitis, it showed a steroid sparing effect the value of which needs to be further investigated.

Predictive Fat Mass Equations for Children With Inflammatory Bowel Disease.

OBJECTIVE: Evaluate accuracy of skinfold thicknesses and body mass index (BMI) for the prediction of fat mass percentage (FM%) in paediatric inflammatory bowel disease (IBD) and to develop population-specific formulae based on anthropometry for estimation of FM%. METHODS: IBD children (n = 30) and healthy controls (HCs, n = 144) underwent anthropometric evaluation and dual-energy X-ray absorptiometry (DEXA) scan, as the clinical reference for measurement of body composition. Body FM% estimated with skinfolds thickness was compared with FM% measured with DEXA. By means of 4 prediction models, population specific formulae for estimation of FM% were developed. RESULTS: No significant difference in terms of FM% measured by DEXA was found between IBD population and HCs (FM% 29.6% vs 32.2%, P = 0.108). Triceps skinfold thickness (TSF, Model 2) was better than BMI (Model 1) at predicting FM% (82% vs 68% of variance). The sum of 2 skinfolds (biceps + triceps; SF2, Model 3) showed an improvement in the prediction of FM% as compared with TSF, Model 2 (86% vs 82% of variance). The sum of 4 skinfolds (biceps + triceps + suprailiac + subscapular; Model 4) showed further improvement in the prediction of FM% as compared with SF2 (88% vs 86% of variance). CONCLUSIONS: The sum of 4 skinfolds is the most accurate in predicting FM% in paediatric IBD. The sum of 2 skinfolds is less accurate but more feasible and less prone to error. The newly developed population-specific formulae could be a valid tool for estimation of body composition in IBD population and an alternative to DEXA measurement.