A meta-analysis on the changes of BMI during an inpatient treatment with different follow-up lengths (short and long term) compared with the outpatient phase in obese patients.

BACKGROUND: The management of obesity should be multidimensional based on the choice of the treatment and the intensity of the therapeutic-rehabilitative intervention. This meta-analysis aims to compare the changes on body weight and body mass index (BMI) during an inpatient treatment (hospitalized weight loss programs with different durations in terms of weeks) compared with the outpatient phase. METHODS: The data obtained from the studies on inpatients have been layered into two categories: short term (studies with follow-up of max 6 months) and long term (studies with follow-up up to 24 months). Furthermore, this study evaluates which of the two approaches show the best impact on weight loss and BMI during 2 follow-ups at 6 to 24 months. RESULTS: The analysis, which included seven studies (977 patients), revealed that the subjects underwent a short hospitalization had greater benefit, compared to those who were followed for a long time. The meta-analyzed mean differences for random effect (MD) showed a statistically significant decrease on BMI of -1.42 kg/m2 (95% CI: -2.48 to -0.35; P = 0.009) and on body weight -6.94 (95% CI: -10.71 to -3.17; P = 0.0003) for subjects who carry out a short hospitalization compared to outpatients. No reduction of body weight (p = 0.07) and BMI (p = 0.9) for subjects who undergo a long hospitalization compared to an outpatient. CONCLUSIONS: A short-term inpatients multidisciplinary weight loss program could be the best choice for the management of obesity and its related comorbidities; on the contrary, if the follow-up is of long duration, the significance is not confirmed. The hospitalization at the beginning of any obesity treatment is significantly better than only outpatients treatment.

Associations of urinary and dietary cadmium with urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and blood biochemical parameters.

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy province of Reggio Emilia (mean age 47 years, range 30-60 years) in the 2017-2019 period. We used a semi-quantitative food frequency questionnaire to estimate dietary cadmium intake and urine samples to assess concentrations of urinary cadmium and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Median urinary cadmium and 8-oxodG concentrations were 0.21 µg/L (interquartile range (IQR): 0.11-0.34 µg/L) and 3.21 µg/g creatinine (IQR: 2.21-4.80 µg/g creatinine), respectively, while median dietary cadmium intake was 6.16 µg/day (IQR: 5.22-7.93 µg/day). We used multivariable linear and spline regression models to estimate mean differences exposure concentrations. Dietary and urinary cadmium were positively correlated, and both were positively and linearly correlated with 8-oxodG. We found a positive association of urinary cadmium with blood alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol and thyroid-stimulating hormone (TSH) concentrations. We also observed a positive association with triglycerides, in both linear (beta regression coefficient = 77.03, 95% confidence interval 32.27-121.78) and non-linear spline regression analyses. Despite the positive correlation between dietary and urinary cadmium estimates, dietary cadmium intake showed inconsistent results with the study endpoints and generally weaker associations, suggesting a decreased capacity to reflect actual cadmium exposure. Overall, these findings suggest that even low levels of cadmium exposure may adversely alter hematological and biochemical variables and induce oxidative stress.

Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in TMC1 Gene.

INTRODUCTION: Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in TMC1 gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. METHODS: A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in TMC1 were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. RESULTS: DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in TMC1 was detected [c.962G>A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. DISCUSSION/CONCLUSION: Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.

Forkhead box G1 gene haploinsufficiency: an emerging cause of dyskinetic encephalopathy of infancy.

BACKGROUND: 14q12 deletions, including the Forkhead Box G1 (FOXG1) gene and point mutations of this gene, are associated with a complex encephalopathy described as a congenital variant of Rett syndrome. A mixture of jerks, athetosis, chorea, and dystonia is observed early in life in many patients. The aim of this article is to report on the spectrum of movement disorders associated with FOXG1 haploinsufficiency, as described in the literature. PATIENTS AND METHODS: We provide a review of the cases reported in the literature, adding two new patients. We searched for a comprehensive set of clinical features, including age at onset and semiology of the movement disorder, occurrence and type of stereotypies, and neurological outcome. RESULTS: A total of 51 cases were included in our study. Nonepileptic abnormal movements occurred in 33 cases, often variably combined and presenting during the first year of life. CONCLUSION: The neurological phenotype of FOXG1 haploinsufficiency shows the features of a dyskinetic encephalopathy of infancy.

Homozygous TNNI3 Mutations and Severe Early Onset Dilated Cardiomyopathy: Patient Report and Review of the Literature.

The TNNI3 gene encodes for the cardiac isoform of troponin I, a pivotal component of the sarcomeric structure of the myocardium. While heterozygous TNNI3 missense mutations have long been associated with autosomal dominant hypertrophic and restrictive cardiomyopathies, the role of TNNI3 null mutations has been more debated due to the paucity and weak characterization of reported cases and the low penetrance of heterozygous genotypes. In recent years, however, an increasing amount of evidence has validated the hypothesis that biallelic TNNI3 null mutations cause a severe form of neonatal dilated cardiomyopathy. Here, we expand the case series reporting two unrelated patients afflicted with early onset dilated cardiomyopathy, due to homozygosity for the p.Arg98* TNNI3 variant, which had thus far been documented only in heterozygous patients and apparently healthy carriers, and the recurrent p.Arg69Alafs*8 variant, respectively. A review of previously reported biallelic TNNI3 loss-of-function variants and their associated cardiac phenotypes was also performed.

Truncating variants in the penultimate exon of TGFBR1 escaping nonsense-mediated mRNA decay cause Loeys-Dietz syndrome.

Pathogenic variants in TGFBR1 are a common cause of Loeys-Dietz syndrome (LDS) characterized by life-threatening aortic and arterial disease. Generally, these are missense changes in highly conserved amino acids in the serine-threonine kinase domain. Conversely, nonsense, frameshift, or specific missense changes in the ligand-binding extracellular domain cause multiple self-healing squamous epithelioma (MSSE) lacking the cardiovascular phenotype. Here, we report on two novel variants in the penultimate exon 8 of TGFBR1 were identified in 3 patients from two unrelated LDS families: both were predicted to cause frameshift and premature stop codons (Gln448Profs*15 and Cys446Asnfs*4) resulting in truncated TGFBR1 proteins lacking the last 43 and 56 amino acid residues, respectively. These were classified as variants of uncertain significance based on current criteria. Transcript expression analyses revealed both mutant alleles escaped nonsense-mediated mRNA decay. Functional characterization in patient's dermal fibroblasts showed paradoxically enhanced TGFß signaling, as observed for pathogenic missense TGFBR1 changes causative of LDS. In summary, we expanded the allelic repertoire of LDS-associated TGFBR1 variants to include truncating variants escaping nonsense-mediated mRNA decay. Our data highlight the importance of functional studies in variants interpretation for correct clinical diagnosis.

From clinical to molecular diagnosis: relevance of diagnostic strategy in two cases of branchio-oto-renal syndrome - case report.

BACKGROUND: Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by deafness, branchiogenic malformations and renal abnormalities. Pathogenic variants in EYA1, SIX1 and SIX5 genes cause almost half of cases; copy number variants (CNV) and complex genomic rearrangements have been revealed in about 20% of patients, but they are not routinely and commonly included in the diagnostic work-up. CASE PRESENTATION: We report two unrelated patients with BOR syndrome clinical features, negative sequencing for BOR genes and the identification of a 2.65 Mb 8q13.2-13.3 microdeletion. CONCLUSIONS: We highlight the value of CNV analyses in high level of suspicion for BOR syndrome but negative sequencing for BOR genes and we propose an innovative diagnostic flow-chart to increase current detection rate. Our report confirms a mechanism of non-allelic homologous recombination as causing this recurrent 8q13.2-13.3 microdeletion. Moreover, considering the role of PRDM14 and NCOA2 genes, both involved in regulation of fertility and deleted in our patients, we suggest the necessity of a longer follow-up to monitor fertility issues or additional clinical findings.

The Potential Roles of Very Low Calorie, Very Low Calorie Ketogenic Diets and Very Low Carbohydrate Diets on the Gut Microbiota Composition.

Several studies have described a strong correlation between diet, weight loss, and gut microbiota composition. The aim of this review was to evaluate the potential effects of energy-restricted diets, namely very low calorie diets (VLCDs), very low calorie ketogenic diets (VLCKDs), and very low carbohydrate diets (VLCarbDs), on the composition of the gut microbiota in humans. We performed a literature search using the following terms (with their abbreviations or acronyms): "very low calorie diet", "very low calorie ketogenic diet", "very low carbohydrate diet", and "gut microbiota". Our search strategy retrieved nine eligible studies. Overall, VLCDs and VLCarbDs affected the Bacteroidetes to Firmicutes ratio in obese patients, leading to a reduction in short-chain fatty acid production by fecal microbiota associated with Clostridial cluster XIVa. This reduction particularly affected Roseburia and Eubacterium rectale, the two most abundant butyrate-producing bacteria in human feces. VLCKDs preserved the core fecal microbiome, but altered the composition of fecal microbial populations in relation to the plasma metabolome and fecal bile acid composition. In particular, VLCKD-induced weight loss resulted in a reduction in E. rectale and Roseburia, an increase in Christensenellaceae and Akkermansia while not all studies show a decrease in Faecalibacterium prausnitzii. Although very few studies have analyzed the effects of VLCarbDs and VLCDs on gut microbiota, significant diet-induced changes in fecal microbiota composition have been observed. Further studies are needed.

Corrigendum: The Potential Roles of Very Low Calorie, Very Low Calorie Ketogenic Diets and Very Low Carbohydrate Diets on the Gut Microbiota Composition.

[This corrects the article DOI: 10.3389/fendo.2021.662591.].

DFNA20/26 and Other ACTG1-Associated Phenotypes: A Case Report and Review of the Literature.

Since the early 2000s, an ever-increasing subset of missense pathogenic variants in the ACTG1 gene has been associated with an autosomal-dominant, progressive, typically post-lingual non-syndromic hearing loss (NSHL) condition designed as DFNA20/26. ACTG1 gene encodes gamma actin, the predominant actin protein in the cytoskeleton of auditory hair cells; its normal expression and function are essential for the stereocilia maintenance. Different gain-of-function pathogenic variants of ACTG1 have been associated with two major phenotypes: DFNA20/26 and Baraitser-Winter syndrome, a multiple congenital anomaly disorder. Here, we report a novel ACTG1 variant [c.625G>A (p. Val209Met)] in an adult patient with moderate-severe NSHL characterized by a downsloping audiogram. The patient, who had a clinical history of slowly progressive NSHL and tinnitus, was referred to our laboratory for the analysis of a large panel of NSHL-associated genes by next generation sequencing. An extensive review of previously reported ACTG1 variants and their associated phenotypes was also performed.

Ideal food pyramid for patients with rheumatoid arthritis: A narrative review.

Emerging literature suggests that diet plays an important modulatory role in rheumatoid arthritis (RA) because diet is an environmental factor that affects inflammation, antigen presentation, antioxidant defense mechanisms and gut microbiota. Patients with RA frequently ask their doctors about which diets to follow, and even in the absence of advice from their physicians, many patients are undertaking various dietary interventions. Given this background, the aim of this review is to evaluate the evidence to date regarding the ideal dietary approach for management of RA in order to reduce the counteracting inflammation, and to construct a food pyramid for patients with RA. The pyramid shows that carbohydrates should be consumed every day (3 portions of whole grains, preferably gluten free), together with fruits and vegetables (5 portions; among which fruit, berries and citrus fruit are to be preferred, and among the vegetables, green leafy ones.), light yogurt (125 ml), skim milk (200 ml), 1 glass (125 ml) of wine and extra virgin olive oil; weekly, fish (3 portions), white meat (3 portions), legumes (2 portions) eggs (2 portions), seasoned cheeses (2 portions), and red or processed meats (once a week). At the top of the pyramid, there are two pennants: one green means that subjects with RA need some personalized supplementation (vitamin D and omega 3) and one red means that there are some foods that are banned (salt and sugar). The food pyramid allows patients to easily figure out what to eat.

Is Probiotic Supplementation Useful for the Management of Body Weight and Other Anthropometric Measures in Adults Affected by Overweight and Obesity with Metabolic Related Diseases? A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis is to assess the effectiveness of probiotics in inducing body weight loss in patients with overweight or obesity with related metabolic diseases. The research was carried out on PubMed and Scopus, focusing on studies reporting the effect on anthropometric measures (weight, body mass Index (BMI), waist circumference (WC), and hip circumference (HC) after administration of various probiotic strains compared to placebo. Twenty randomized controlled trials, that included 1411 patients, were considered. The meta-analyzed mean differences (MD) for random effects showed no significant decrease in body weight after probiotic supplementation (-0.26 kg [-075, 0.23], p = 0.30), while a significant BMI decrease was found (-0.73 kg/m2 [-1.31, -0.16], p = 0.01). For WC and HC, the meta-analyzed MD for random effects showed a significant decrease (WC: -0.71 cm [-1.24; -0.19], p = 0.008 and HC: -0.73 cm [-1.16; -0.30], p = 0.0008). The risk of bias was also evaluated considering a high risk and a low risk according to PRISMA criteria. In conclusion, the results of this meta-analysis highlight a positive trend of probiotics supplementation on the amelioration of anthropometric measures of overweight and obese patients with related metabolic diseases. However, further research is needed before recommending the use of probiotics as a therapeutic strategy for these patients. The focus of the future research should be to evaluate the efficacy of different probiotic strains, the quantities to be administered, and the duration of the intervention.

Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption.

Sarcopenia is defined as a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength and it is diagnosed by measurements of muscle mass, muscle strength, and physical performance. Sarcopenia affects quality of life and is associated with several adverse health effects. Muscle decline is aggravated by a sedentary lifestyle and can be prevented through proper nutrition, together with adequate physical activity. Fish contains biologically active compounds, such as omega-3 polyunsaturated fatty acids, proteins, vitamin D, magnesium, and carnitine, which are able to intervene positively on muscle metabolism. This narrative literature review was performed to evaluate evidence regarding the actual benefit of fish consumption in the prevention of sarcopenia and the positive action on the muscle mass of the biological compounds present in fish. The results demonstrated that fish consumption has a protective and anti-inflammatory function on skeletal muscle and that its biologically active compounds help to maintain good muscle performance, preventing sarcopenia. Considering the nutritional and health benefits, elderly with sarcopenia should consume at least three servings per week of fish in order to have a minimum intake of 4-4.59 g daily of omega 3, and reaching the 50% RDA in Vitamin E and D. High biological value of proteins in 150 g of fish and its high available magnesium (20% of RDA in 150 g of fish) are an added value that could suggest fish as a "functional food" in order to prevent and treat sarcopenia.

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate.

BACKGROUND: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. METHODS: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. RESULTS: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.

Use of ultrasound in treatment decisions for patients with rheumatoid arthritis: an observational study in Italy.

In rheumatoid arthritis (RA), treatment response is generally assessed using standard clinical disease activity measures. However, ultrasound has become increasingly popular among rheumatologists to monitor disease activity and response. The purpose of this analysis of ECOgraphic evaluation for STaging ARthritis (ECOSTAR) study data was to determine how ultrasound affects clinicians' decisions about changing treatment in RA. ECOSTAR was an observational, cohort study conducted between March 2010 and December 2012 at nine clinical centers in Italy in RA patients being considered for treatment change. After clinical evaluation of each patient, patients underwent diagnostic ultrasound (US) investigations and each patient was given a total echography score using a combination of scores for joint effusion, synovial hypertrophy, and power Doppler. The US results were provided to the clinicians and the influence of US on the clinicians' treatment choices were recorded. Ninety-five patients screened for study inclusion had confirmed RA (mean age 53.9 years; mean disease duration 8.9 years). Therapy changes were made by clinicians according to the hand and wrist joint US scores: score 0 appeared to have no influence on clinicians' decision to modify treatment, scores >0-3 were associated with a numerically higher estimated probability of not changing therapy than changing therapy, and scores >3 had a greater influence on the clinician to modify therapy and an increased probability of the clinician changing therapy versus not changing therapy. Ultrasonography scores appear to influence treatment decisions in patients with RA, with clinicians appearing less likely to alter treatment regimens in patients with low ultrasound scores and more likely to change treatment regimens when higher scores are obtained. Further research is warranted.

A Hunter Patient with a Severe Phenotype Reveals Two Large Deletions and Two Duplications Extending 1.2 Mb Distally to IDS Locus.

Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an X-linked lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS), an enzyme involved in the glycosaminoglycans (GAGs) degradation. We here report the case of a 9-year-old boy who was diagnosed with an extremely severe form of MPS II at 10 months of age. Sequencing of the IDS gene revealed the deletion of exons 1-7, extending distally and removing the entire pseudogene IDSP1. The difficulty to define the boundaries of the deletion and the particular severity of the patient phenotype suggested to verify the presence of pathological copy number variations (CNVs) in the genome, by the array CGH (aCGH) technology. The examination revealed the presence of two deletions alternate with two duplications, overall affecting a region of about 1.2 Mb distally to IDS gene. This is the first complex rearrangement involving IDS and extending to a large region located distally to it described in a severe Hunter patient, as evidenced by the CNVs databases interrogated. The analysis of the genes involved in the rearrangement and of the disorders correlated with them did not help to clarify the phenotype observed in our patient, except for the deletion of the IDS gene, which explains per se the Hunter phenotype. However, this cannot exclude a potential "contiguous gene syndrome" as well as the future rising of additional pathological symptoms associated with the other extra genes involved in the identified rearrangement.

The impact of the profile of biologics on treatment costs.

In the perspective of the payer, it is important to know the details concerning the management costs of biological drugs in an effort to optimise expenditures. We have therefore examined how the expenditure varies with regard to the purchase of biologics, the mode of administration, and the management of serious adverse events secondary to the use of various drugs. The average expenditure for the purchase of the drug, including VAT, is € 12,005, while expenditures for the administration and management of serious adverse events are minimal, i.e. € 32 and € 124, respectively. An analysis of how the cost of various items affects the overall cost revealed no significant differences that would steer the choice towards one biologic drug rather than another.

De novo trisomy 20p characterized by array comparative genomic hybridization: report of a novel case and review of the literature.

We report on a boy with speech delay, mental retardation, motor clumsiness, hyperactivity, dysmorphic facial features, brachytelephalangy and short stature. Electrocardiogram, echocardiography, renal ultrasound, electroencephalogram, fundoscopic exam and auditory brainstem responses were all normal. Brain magnetic resonance imaging showed a left temporal arachnoid cyst and a small pineal gland cyst. High resolution karyotype and FISH analysis detected a de novo duplication of the short arm of chromosome 20. A molecular characterization of the chromosomal anomaly was performed by array-CGH, confirming a 17.98 Mb duplication of the short arm of chromosome 20 associated with a small duplication on chromosome 3p, that was shown to be maternally inherited. This is one of the few cases of de novo trisomy 20p with extensive workup, characterization at molecular level and close follow-up from the neonatal period to age 30 months. We also compared the phenotype of our patient with that previously reported in literature, therefore contributing to better define the trisomy 20p syndrome and helping pediatricians and geneticists to better counsel families about the developmental prognosis of these children.