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Relationship between Muscle Mass, Bone Density and Vascular Calcifications in Elderly People with SARS-CoV-2 Pneumonia.
Del Toro, R, Palmese, F, Feletti, F, Zani, G, Minguzzi, MT, Maddaloni, E, Napoli, N, Bedogni, G, Domenicali, M
Journal of clinical medicine. 2023;(6)
Abstract
BACKGROUND Little is known about the changes in organs and tissues that may make elder patients more vulnerable to acute stressors such as SARS-CoV-2 infection. METHODS In 80 consecutive elderly patients with SARS-CoV-2 infection, we evaluated the association between the descending thoracic aorta calcium score, L1 bone density and T12 skeletal muscle density measured on the same scan by high-resolution computed tomography. RESULTS At median regression, the ln-transformed DTA calcium score was inversely associated with L1 bone density (-0.02, 95%CI -0.04 to -0.01 ln-Agatston units for an increase of 1 HU) and with T12 muscle density (-0.03, -0.06 to -0.001 ln-Agatston units for an increase of 1 HU). At penalized logistic regression, an increase of 1 ln-Agatston unit of DTA calcium score was associated with an OR of death of 1.480 (1.022 to 2.145), one of 1 HU of bone density with an OR of 0.981 (0.966 to 0.996) and one of 1 HU of muscle density with an OR of 0.973 (0.948 to 0.999). These relationships disappeared after correction for age and age was the stronger predictor of body composition and death. CONCLUSIONS Age has a big effect on the relationship between vascular calcifications, L1 bone density and T12 muscle density and on their relationship with the odds of dying.
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Association between Mediterranean Diet and Fatty Liver in Women with Overweight and Obesity.
Leone, A, Bertoli, S, Bedogni, G, Vignati, L, Pellizzari, M, Battezzati, A
Nutrients. 2022;14(18)
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Non-alcoholic fatty liver disease (NAFLD) is a condition resulting from excessive lipid accumulation in the liver in individuals with low alcohol consumption. Obesity is an established risk factor for the development of NAFLD, and 50% to 75% of people with obesity also have NAFLD. The aim of this study was to evaluate the association between Mediterranean diet and non-invasive indices of fatty liver in a large sample of women with overweight and obesity. This study is a cross-sectional study of 2967 consecutive women with overweight and obesity. Results show that higher adherence to the Mediterranean diet was associated with lower indices of fatty liver in women with overweight and obesity (particularly obese women than in women who are overweight). Authors conclude that women with obesity, especially during the premenopausal period, may benefit more from following a Mediterranean-style diet.
Abstract
Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = -0.60, 95% CI: -1.04, -0.16, p = 0.008), NAFLD-FLS (β = -0.092, 95% CI: -0.134, -0.049, p < 0.001) and HSI (β = -0.17, 95% CI: -0.30, -0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD.
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Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial.
Coppola, S, Nocerino, R, Paparo, L, Bedogni, G, Calignano, A, Di Scala, C, de Giovanni di Santa Severina, AF, De Filippis, F, Ercolini, D, Berni Canani, R
JAMA network open. 2022;5(12):e2244912
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Gut microbiome (GM) could play a role in obesity. A metabolically healthy GM is maintained by a diet rich in fibre. Plant foods are fermented by the gut microbiome to produce the antiobesogenic short-chain fatty acid butyrate. The aim of this study was to evaluate whether butyrate supplementation can be effective in paediatric obesity treatment. This study was a randomised, quadruple-blind, parallel-group, placebo-controlled trial. Children were randomly assigned to the treatment group or placebo in a 1:1 ratio. Results showed that in children with obesity, oral butyrate supplementation produced a reduction of body mass index and exerted beneficial effects on glucose metabolism and inflammation. In fact, butyrate supplementation decreased homeostatic model assessment of insulin resistance [HOMA-IR] and fasting insulin levels in children with obesity. Additionally, the GM analysis supported the role of butyrate in glucose metabolism, as suggested by a more positive response in children with a higher abundance of butyrate-producing bacteria at baseline. Authors conclude that their findings support the importance of the GM-derived metabolite butyrate as a protective factor against obesity, highlighting the central role of a healthy diet and GM function to achieve an optimal endogenous production of butyrate.
Abstract
IMPORTANCE The pediatric obesity disease burden imposes the necessity of new effective strategies. OBJECTIVE To determine whether oral butyrate supplementation as an adjunct to standard care is effective in the treatment of pediatric obesity. DESIGN, SETTING, AND PARTICIPANTS A randomized, quadruple-blind, placebo-controlled trial was performed from November 1, 2020, to December 31, 2021, at the Tertiary Center for Pediatric Nutrition, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy. Participants included children aged 5 to 17 years with body mass index (BMI) greater than the 95th percentile. INTERVENTIONS Standard care for pediatric obesity supplemented with oral sodium butyrate, 20 mg/kg body weight per day, or placebo for 6 months was administered. MAIN OUTCOMES AND MEASURES The main outcome was the decrease of at least 0.25 BMI SD scores at 6 months. The secondary outcomes were changes in waist circumference; fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, ghrelin, microRNA-221, and interleukin-6 levels; homeostatic model assessment of insulin resistance (HOMA-IR); dietary and lifestyle habits; and gut microbiome structure. Intention-to-treat analysis was conducted. RESULTS Fifty-four children with obesity (31 girls [57%], mean [SD] age, 11 [2.91] years) were randomized into the butyrate and placebo groups; 4 were lost to follow-up after receiving the intervention in the butyrate group and 2 in the placebo group. At intention-to-treat analysis (n = 54), children treated with butyrate had a higher rate of BMI decrease greater than or equal to 0.25 SD scores at 6 months (96% vs 56%, absolute benefit increase, 40%; 95% CI, 21% to 61%; P < .01). At per-protocol analysis (n = 48), the butyrate group showed the following changes as compared with the placebo group: waist circumference, -5.07 cm (95% CI, -7.68 to -2.46 cm; P < .001); insulin level, -5.41 μU/mL (95% CI, -10.49 to -0.34 μU/mL; P = .03); HOMA-IR, -1.14 (95% CI, -2.13 to -0.15; P = .02); ghrelin level, -47.89 μg/mL (95% CI, -91.80 to -3.98 μg/mL; P < .001); microRNA221 relative expression, -2.17 (95% CI, -3.35 to -0.99; P < .001); and IL-6 level, -4.81 pg/mL (95% CI, -7.74 to -1.88 pg/mL; P < .001). Similar patterns of adherence to standard care were observed in the 2 groups. Baseline gut microbiome signatures predictable of the therapeutic response were identified. Adverse effects included transient mild nausea and headache reported by 2 patients during the first month of butyrate intervention. CONCLUSIONS AND RELEVANCE Oral butyrate supplementation may be effective in the treatment of pediatric obesity. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04620057.
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Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial.
Carucci, L, Nocerino, R, Paparo, L, De Filippis, F, Coppola, S, Giglio, V, Cozzolino, T, Valentino, V, Sequino, G, Bedogni, G, et al
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2022;(8):e13836
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Abstract
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.
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Growth patterns in children with spinal muscular atrophy.
De Amicis, R, Baranello, G, Foppiani, A, Leone, A, Battezzati, A, Bedogni, G, Ravella, S, Giaquinto, E, Mastella, C, Agosto, C, et al
Orphanet journal of rare diseases. 2021;(1):375
Abstract
BACKGROUND Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle atrophy and weakness. SMA type 1 (SMA1) is the most severe form: affected infants are unable to sit unaided; SMA type 2 (SMA2) children can sit, but are not able to walk independently. The Standards of Care has improved quality of life and the increasing availability of disease-modifying treatments is progressively changing the natural history; so, the clinical assessment of nutritional status has become even more crucial. Aims of this multicenter study were to present the growth pattern of treatment-naïve SMA1 and SMA2, and to compare it with the general growth standards. RESULTS Body Weight (BW, kg) and Supine Length (SL, cm) were collected using a published standardized procedure. SMA-specific growth percentiles curves were developed and compared to the WHO reference data. We recruited 133 SMA1 and 82 SMA2 (48.8% females). Mean ages were 0.6 (0.4-1.6) and 4.1 (2.1-6.7) years, respectively. We present here a set of disease-specific percentiles curves of BW, SL, and BMI-for-age for girls and boys with SMA1 and SMA2. These curves show that BW is significantly lower in SMA than healthy peers, while SL is more variable. BMI is also typically lower in both sexes and at all ages. CONCLUSIONS These data on treatment-naïve patients point toward a better understanding of growth in SMA and could be useful to improve the clinical management and to assess the efficacy of the available and forthcoming therapies not only on motor function, but also on growth.
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Predictive fat mass equations for spinal muscular atrophy type I children: Development and internal validation.
Foppiani, A, De Amicis, R, Leone, A, Ravella, S, Bedogni, G, Battezzati, A, D'Amico, A, Bertini, E, Pedemonte, M, Bruno, C, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1578-1587
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BACKGROUND Body composition assessment is paramount for spinal muscular atrophy type I (SMA I) patients, as weight and BMI have proven to be misleading for these patients. Despite its importance, no disease-specific field method is currently available, and the assessment of body composition of SMA I patients requires reference methods available only in specialized settings. OBJECTIVE To develop predictive fat mass equations for SMA I children based on simple measurements, and compare existing equations to the new disease-specific equations. DESIGN Demographic, clinical and anthropometric data were examined as potential predictors of the best candidate response variable and non-linear relations were taken into account by transforming continuous predictors with restricted cubic splines. Alternative models were fitted including all the dimensions revealed by cluster analysis of the predictors. The best models were then internally validated, quantifying optimism of the obtained performance measures. The contribution of nusinersen treatment to the unexplained variability of the final models was also tested. RESULTS A total of 153 SMA I patients were included in the study, as part of a longitudinal observational study in SMA children conducted at the International Center for the Assessment of Nutritional Status (ICANS), University of Milan. The sample equally represented both sexes (56% females) and a wide age range (from 3 months to 12 years, median 1.2 years). Four alternative models performed equally in predicting fat mass fraction (fat mass/body weight). The most convenient was selected and further presented. The selected model uses as predictors sex, age, calf circumference and the sum of triceps, suprailiac and calf skinfold thicknesses. The model showed high predictive ability (optimism corrected coefficient of determination, R2 = 0.72) and internal validation indicated little optimism both in performance measures and model calibration. The addition of nusinersen as a predictor variable did not improve the prediction. The disease-specific equation was more accurate than the available fat mass equations. CONCLUSIONS The developed prediction model allows the assessment of body composition in SMA I children with simple and widely available measures and with reasonable accuracy.
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Development and Internal Validation of Fatty Liver Prediction Models in Obese Children and Adolescents.
Bedogni, G, Tamini, S, Caroli, D, Cicolini, S, Domenicali, M, Sartorio, A
Journal of clinical medicine. 2021;(7)
Abstract
To develop predictive models of fatty liver (FL), we performed a cross-sectional retrospective study of 1672 obese children with a median (interquartile range) age of 15 (13-16) years. The outcome variable was FL diagnosed by ultrasonography. The potential predictors were: (1) binary: sex; (2) continuous: age, body mass index (BMI), waist circumference (WC), alanine transaminase (ALT), aspartate transaminase, gamma-glutamyltransferase, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HDL-cholesterol, LDL-cholesterol, triglycerides, mean arterial pressure, uric acid, and c-reactive protein; (3) ordinal: Pubertal status. Bootstrapped multivariable logistic regression with fractional polynomials was used to develop the models. Two models were developed and internally validated, one using BMI and the other using WC as the anthropometric predictor. Both models included ALT, HOMA-IR, triglycerides, and uric acid as predictors, had similar discrimination (c-statistic = 0.81), and were similarly well calibrated as determined by calibration plots. These models should undergo external validation before being employed in clinical or research practice.
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Rice flour fermented with Lactobacillus paracasei CBA L74 in the treatment of atopic dermatitis in infants: A randomized, double- blind, placebo- controlled trial.
D'Auria, E, Panelli, S, Lunardon, L, Pajoro, M, Paradiso, L, Beretta, S, Loretelli, C, Tosi, D, Perini, M, Bedogni, G, et al
Pharmacological research. 2021;:105284
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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.
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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.
Nocerino, R, Bedogni, G, Carucci, L, Cosenza, L, Cozzolino, T, Paparo, L, Palazzo, S, Riva, L, Verduci, E, Berni Canani, R
The Journal of pediatrics. 2021;:183-191.e3
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Abstract
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.
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Changes of Body Weight and Body Composition in Obese Patients with Prader-Willi Syndrome at 3 and 6 Years of Follow-Up: A Retrospective Cohort Study.
Bedogni, G, Grugni, G, Cicolini, S, Caroli, D, Tamini, S, Sartorio, A
Journal of clinical medicine. 2020;(11)
Abstract
Few short-term studies of weight loss have been performed in adult patients with Prader-Willi syndrome (PWS) undergoing metabolic rehabilitation. We performed a retrospective cohort study of 45 adult obese PWS patients undergoing a long-term multidisciplinary metabolic rehabilitation program based on diet and physical activity. Body composition was evaluated by dual-energy X-ray absorptiometry in 36 (80%) patients. The mean (95% CI) weight change was -3.6 (-7.6 to 0.4, p = 0.08) kg at 3 years and -4.6 (-8.5 to -0.8, p = 0.02) kg at 6 years, and that of BMI was -1.7 (-3.4 to 0.1, p = 0.06) kg/m2 at 3 years and -2.1 (-3.8 to -0.4, p = 0.02) kg/m2 at 6 years. A decrease of about 2% in fat mass per unit of body mass was observed, which is in line with the expectations for moderate weight loss. A possibly clinically relevant decrease in total and low-density lipoprotein cholesterol was also observed. These long-term results are important for patients with PWS, which is characterized by severe hyperphagia, behavioral disturbances, and cognitive impairment and is generally considered "resistant" to classical weight loss interventions.