Fibroblast growth factor 23: translating analytical improvement into clinical effectiveness for tertiary prevention in chronic kidney disease

Fibroblast growth factor 23 (FGF23) plays a key role in the pathophysiology of chronic kidney disease (CKD) and of the associated cardiovascular diseases, ranking on the crossroads of several evolving areas with a relevant impact on the health-care system (ageing, treatment of CKD and prevention from cardiovascular and renal events). In this review, we will critically appraise the overall issues concerning the clinical usefulness of FGF23 determination in CKD, focusing on the analytical performances of the methods, aiming to assess whether and how the clinical introduction of FGF23 may promote cost-effective health care policies in these patients

Resting energy expenditure in children and adolescents with cerebral palsy: accuracy of available prediction formulas and development of population-specific methods

IntroductionEnergy requirements are difficult to estimate in children with cerebral palsy (CP). Resting energy expenditure (REE), necessary to implement personalized nutritional interventions, is most commonly estimated using prediction formulae since indirect calorimetry, the reference method, is not available in all nutrition units. The aims of the present study were: (1) to evaluate the accuracy of the most commonly used REE prediction formulae developed for healthy children, in children with CP; (2) to assess the accuracy of the REE population-specific formula for CP children proposed in our preliminary report; (3) to develop new population-specific methods.MethodsREE was measured by indirect calorimetry in 100 children and adolescents with spastic quadriplegic cerebral palsy (SQCP) and estimated on the basis of predictive formulas selected by the clinicians [World Health Organization (WHO), Harris-Benedict, Schofield weight, Schofield weight & height, Oxford, Mifflin formulae and a population-specific formula for CP children developed in our preliminary report].Results100 children with SQCP (35 girls, 35%) classified as level V according to gross motor function classification system (GMFCS-V); 64% with oral nutrition, 29% total enteral nutrition (nasogastric tube feeding, percutaneous endoscopic gastrostomy, percutaneous endoscopic transgastric jejunostomy) and 7% mixed nutrition. The median (IQR) REE was 41.96 (17.5) kcal/kg/day.Statistical analysis highlighted a proportional bias between the indirect calorimetry and all considered predictive formulae for REE determination. By studying the relationship between the bias and the mean values of REE, specific conversion equations were obtained. With a pre-specified model having as predictors the variable weight and the variable Triceps Skinfold (TSF) and, as response the variable REE measured by indirect calorimetry, a predictive nomogram was developed to estimate the REE in this population of children.ConclusionsWe suggest using predictive formulae for healthy children with caution, and where possible carrying out indirect calorimetry to assess REE in children with CP. However, we propose a new tool which could be developed to become an additional help for assessment of REE in the clinical practice.Future objectives will be to obtain a larger sample size, in a multicenter perspective study, to build a specific predictive model for the REE of the studied population

A Multivariate Analysis of "Metabolic Phenotype" Patterns in Children and Adolescents with Obesity for the Early Stratification of Patients at Risk of Metabolic Syndrome

Background: Metabolic syndrome (MS) is closely linked to obesity; however, not all individuals with obesity will develop obesity-related complications and a metabolically healthy obesity (MHO) group is also described. Objective: To perform a multivariate analysis (MVA) of the anthropometric and biochemical data in pediatric patients with obesity to reveal a "phenotype" predictive for MS. Methods: We analyzed 528 children with obesity (OB) and 119 normal-weight pediatric patients (NW). Adiposity indices were recorded, and MS was detected. MVA was performed. Results: Analysis of the structure of correlation of the variables showed that the variables of waist circumference (WC), body mass index (BMI), and estimated fat mass (eFM) were positively correlated with each other as a whole. In addition, the variables of the triglycerides (TG), triglyceride-glucose (TyG) index, and visceral adiposity index were positively correlated with each other as a whole, although none were correlated with the variables of BMI z-score, waist-to-height ratio, WC, eFM, or weight. The variables that related to insulin resistance (IR) and dyslipidemia were crucial for the early stratification of patients at risk of MS. Conclusions: Independently of body weight, IR, dyslipidemia, hypertriglyceridemia, and fat distribution seem to be the strongest MS risk factors. The early detection of and intervention in these modifiable risk factors are useful to protect children's health

Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study

Purpose: Circulating insulin-like growth factor-1 (IGF-1) is positively associated with the risk of BC recurrence, and is more frequently dysregulated in older people, especially in those with metabolic syndrome (MetS) and obesity. This study aimed to analyze the association between IGF-1 levels and indices of MetS and insulin resistance in BC survivors. Methods: Baseline data of 563 BC survivors enrolled in the DIet and ANdrogen-5 (DIANA-5; NCT05019989) study were analyzed. Results: Lower circulating IGF-1 levels in subjects with MetS than in those without MetS were found. After stratification of the patients according to the diagnosis of MetS, we highlighted that the insulin was the main predictor of elevated IGF-1 levels only in subjects without MetS. Moreover, we found an interaction between high-density lipoprotein cholesterol (HDL-C), glycemia, and IGF-1 levels, showing a positive correlation between HDL-C and IGF-1, especially in subjects with higher values of glycemia and without a diagnosis of MetS. Conclusions: While IGF-1 levels appear to be much more impaired in subjects diagnosed with MetS, in non-MetS subjects, IGF-1 levels may respond better to metabolic parameters and lifestyle changes. Further studies are needed to analyze the role of physical activity and/or dietary intervention in modulating IGF-1 concentrations in BC survivors. Implications for cancer survivors: These results could have important clinical implications for planning customized strategies aimed at modulating IGF-1 levels in BC survivors. In fact, while the IGF-1 system seems to be much more compromised in subjects with a diagnosis of MetS, in noMetS subjects, IGF-1 levels could better respond to lifestyle changes

Thyroid Function and Metabolic Syndrome in Children and Adolescents with Neuromotor Disability

Thyroid function plays a crucial role in nervous system integrity and metabolic homeostasis. We evaluated the pattern of TSH, FT4 and FT3 release in children with neuromotor impairment (NI) in relationship with metabolic syndrome (MS). We enrolled 55 patients with NI and 30 controls. Clinical parameters, thyroid function and MS presence were recorded. Principal component analysis (PCA), cluster analysis, and logistic regression models were performed. MS was detected in 54.5% of patients. Four clusters were identified: the first one included only controls and, contrasting with cluster 4, was exclusively characterized by children with disability and MS. This latter showed increased FT4 and FT3 and decreased TSH levels. Cluster 2, characterized by disability without MS showed high FT4 and FT3, whereas cluster 3 with low FT4 and FT3 mainly included disability (90%) and showed prevalent MS (57%). The association between TSH and NI is represented by a U-shape structure. The TSH, FT3 and FT4 release patterns may reflect thyrotropic adaptation, allostatic response and compensatory mechanisms. These mechanisms, found in both MS and disability, show that the odds of having a condition of NI with or without MS increase as the TSH values deviate, in both directions, from a value of 2.5 mLU/mL

An Italian Delphi study to evaluate consensus on adjuvant endocrine therapy in premenopausal patients with breast cancer: the ERA project

Abstract Background Several trials evaluated the role of ovarian function suppression for the adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer. Based on the results of the SOFT and TEXT trials, international guidelines recommend the addition of ovarian function suppression to standard adjuvant endocrine therapy for patients at higher risk of relapse. Methods The ERA project (Evaluation of Risk factors in the Adjuvant treatment of breast cancer in premenopausal patients) was devised with the objective of obtaining a consensus on the identification of risk factors and the use of ovarian function suppression in the adjuvant treatment of these women. To this aim, a panel of 31 Italian oncologists with expertise in breast cancer participated in a Delphi consensus study in June 2017. Results A total of 29 statements related to prognostic factors, therapeutic strategies and ovarian function suppression were defined and voted to gain final consensus. For each topic we report data supporting the acquired consensus and the relevant issues discussed. Conclusions The SOFT and TEXT trials have changed the standard adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer, but the available treatment options require a careful risk assessment and toxicities evaluation to ensure the greatest clinical benefit for each patient

Influenza Vaccination Campaign during the COVID-19 Pandemic: The Experience of a Research and Teaching Hospital in Milan

Background: During the COVID-19 pandemic, more than ever, optimal influenza vaccination coverage among healthcare workers (HCWs) is crucial to avoid absenteeism and disruption of health services, as well as in-hospital influenza outbreaks. The aim of this study is to analyze the 2020 influenza vaccination campaign, comparing it with the previous year’s in a research and teaching hospital in Northern Italy. Methods: adopting an approach based on combined strategies, three interventions were deployed: a promotional and educational campaign, vaccination delivery through both ad hoc and on-site ambulatories, and a gaming strategy. Personal data and professional categories were collected and analyzed using univariate logistic regression. Vaccinated HCWs were asked to fill in a questionnaire to describe their reasons for vaccination adherence. Results: the vaccination coverage rate (VCR) was 43.1%, compared to 21.5% in 2019. The highest increase was registered among administrative staff (308.3%), while physicians represent the most vaccinated category (n = 600). Moreover, residents (prevalence ratio (PR): 1.12; 95% CI 1.04–1.20), as well as intensive care (PR: 1.44; 95% CI: 1.24–1.69) and newborn workers (PR: 1.41; 95% CI: 1.20–1.65) were, respectively, the categories most frequently vaccinated for the first time. Conclusion: the significant increase in vaccination coverage rate confirms the suitability of the combined strategy of delivering the flu vaccination campaign and represents a first step towards reaching WHO recommended vaccination rates

Prevalence of SARS-CoV-2 in an area of unrestricted viral circulation: Mass seroepidemiological screening in Castiglione d'Adda, Italy.

Castiglione D'Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass serological screening. We searched for SARS-CoV-2 IgGs in the entire population on a voluntary basis using lateral flow immunochromatographic tests (RICT) on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs (NPS) in a randomized representative sample and in each subject with a positive rapid test. Factors associated with RICT IgG positivity were assessed by uni- and multivariate logistic regression models. Out of the 4143 participants, 918 (22·2%) showed RICT IgG positivity. In multivariable analysis, IgG positivity increases with age, with a significant non-linear effect (p = 0·0404). We found 22 positive NPSs out of the 1330 performed. Albeit relevant, the IgG prevalence is lower than expected and suggests that a large part of the population remains susceptible to the infection. The observed differences in prevalence might reflect a different infection susceptibility by age group. A limited persistence of active infections could be found after several weeks after the epidemic peak in the area