The Effectiveness of the Third Dose of COVID-19 Vaccine: When Should It Be Performed?

BACKGROUND: COVID-19 vaccination is the most significant step toward the long-term mitigation of SARS-CoV-2-related complication, avoiding disease and death and decreasing virus spread. This study aimed to evaluate, in a real-world setting, booster dose effectiveness to reduce COVID-19 risk considering the amount of time after the end of the two-dose vaccination cycle. A sub-analysis was conducted to adjust the booster dose effect for occupational and demographic factors. METHODS: About 16,000 COVID-19-vaccinated HCWs of three University Hospital Networks in Milan (HN1/HN2/HN3) were included in the study. Data were collected by Occupational Health Physicians of the HNs within specific computerized databases. RESULTS: In univariable analysis, booster dose administration displayed a slightly higher risk of infection with respect to not receiving it, OR = 1.18, with 95% confidence interval (C.I) [0.99, 1.41]. When the model was adjusted with the modulating effect of time from the completion of the vaccination cycle on booster dose administration, the latter resulted in strong protective effect against infection, OR = 0.43, 95% CI [0.26, 0.74]. However, considering the modifying influence of time from the vaccination cycle's completion, the administration of booster doses appeared to have a protective effect against infection. In HN1, students and resident physicians displayed lower odds of infection with respect to physicians. Lastly, a non-linear effect of age was reported. CONCLUSIONS: Our findings suggest that the correct timing in vaccine scheduling and administration is critical to vaccine effectiveness. These findings, applicable to all vaccinations, should help in setting up more effective vaccination strategies.

Body composition assessment in a large cohort of Olympic athletes with different training loads: possible reference values for fat mass and fat-free mass domains.

AIMS: To assess body composition by means of BOD POD in the large cohort of Italian Olympic athletes of many sport disciplines (studied at the same time), and to provide possible reference values for body composition in elite athletes. METHODS: 1556 elite athletes, who took part in the selection procedure for the 2016 Rio Olympic Games for the National Italian Olympic Committee (CONI), were retrospectively studied. Body composition was determined using air plethysmography-based BOD POD. RESULTS: We observed that Fat Mass (FM) and Fat-free Mass (FFM) should be considered as two mutually independent domains in elite athletes. By performing Principal Component Analysis, we defined two independent main domains (respectively, representing FM and FFM), which presented different trends according to gender and static or dynamic exercise load. Lastly, we reported possible reference values for FM index and FFM index, respectively, representing the largest contributors to FM domain and FFM domain, and calculated as FM or FFM (kg)/height (m2). CONCLUSIONS: Our findings might provide a basis to optimize the practical approach to body composition in athletes, highlighting the importance of considering indicators of fat mass and lean mass "simultaneously" and not specularly, according to different sport disciplines as well. Moreover, these data might contribute to standardize reference values for body composition in elite athletes, with a view to potentially helping to monitor and guide training regimens, prevent related detrimental practices and plan cardiometabolic prevention and rehabilitation programs.

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

Introduction: Energy 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. Methods: REE 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]. Results: 100 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. Conclusions: We 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.

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.

Managing the impact of inter-method bias of prostate specific antigen assays on biopsy referral: the key to move towards precision health in prostate cancer management.

OBJECTIVES: We assessed the inter-method bias of total (tPSA) and free (fPSA) prostate-specific antigen (PSA) immunoassays to establish if tPSA-based risk thresholds for advanced prostate cancer (PCa), obtained from one method (Roche) can be converted into the corresponding concentrations assayed by other methods. Then we evaluated the impact of the bias of tPSA and fPSA on the estimation of the %f/tPSA ratio and performed a re-calibration of the proposed thresholds for the %f/tPSA ratio according to the assay used. METHODS: tPSA and fPSA were measured in 135 and 137 serum samples, respectively by Abbott Alinity i, Beckman Access Dxl, Roche Cobas e801, and Siemens Atellica IM analytical platforms. Scatterplots, Bland-Altman diagrams, Passing-Bablok (PB) were used to inspect and estimate the systematic and proportional bias between the methods. The linear equations with confidence intervals of the parameter estimates were used to transform the tPSA risk thresholds for advanced PCa into the corresponding concentrations measurable by the other analytical methods. To construct a correction coefficient for converting the %f/tPSA ratio from one method to the other, PB and non-parametric boostrapping were used. RESULTS: The inter-method bias is not constant but strictly linear allowing the conversion of PSA results obtained from Roche into the other assays, which underestimate tPSA vs. Roche. Siemens and Abbott vs. Roche and Beckman assays, being characterized by a positive and a negative proportional bias for tPSA and fPSA measurements, tend to overestimate the %f/tPSA ratio. CONCLUSIONS: There is a consistent risk to miss advanced PCa, if appropriate conversion factors are not applied.

Lung involvement in children with COVID-19 multisystem inflammatory syndrome.

Since the beginning of the COVID-19 pandemic, multisystem inflammatory syndrome in children (MIS-C) has been reported in increasing numbers, mostly focusing on cardiac dysfunction. Very few studies have evaluated lung involvement in terms of imaging findings, while data regarding pulmonary function in children with MIS-C are not available. The purpose of our study was to evaluate lung involvement in MIS-C by imaging and lung function by structured light plethysmography (SLP) at hospital admission and 6 months afterwards. Spirometry is the gold standard technique to evaluate lung function in children. However, SLP has the advantage of not requiring contact with the patient, offering an effective solution for the evaluation of lung function during the pandemic. To our knowledge this is the first study that aims to investigate pulmonary function by SLP in children with MIS-C.

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.

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

OBJECTIVES: 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. CONTENT: Our comprehensive critical appraisal of the literature revealed that we are currently unable to establish the clinical usefulness of FGF23 measured by ELISA in CKD, as stability issues and suboptimal analytical performances are the major responsible for the release of misleading results. The meta-analytical approach has failed to report unambiguous evidence in face of the wide heterogeneity of the results from single studies. SUMMARY AND OUTLOOK: Our review has largely demonstrated that the clinical usefulness depends on a thorough analytical validation of the assay. The recent introduction of chemiluminescent intact-FGF23 (iFGF23) assays licensed for clinical use, after passing a robust analytical validation, has allowed the actual assessment of preliminary risk thresholds for cardiovascular and renal events and is promising to capture the iFGF23 clinically relevant changes as a result of a therapeutic modulation. In this perspective, the analytical optimization of FGF23 determination may allow a marriage between physiology and epidemiology and a merging towards clinical outcomes.

Caregivers' Intention to Vaccinate Their Children Under 12 Years of Age Against COVID-19: A Cross-Sectional Multi-Center Study in Milan, Italy.

The impact of Coronavirus disease 2019 (COVID-19) on the pediatric population is increasingly recognized. A widespread vaccination in childhood would provide benefits for children and might help ending the pandemic by enhancing community protection. Following recent approval by the European Medicines Agency (EMA) of Comirnaty (Pfizer-BioNTech) for children aged 5-11 years, we aimed to investigate caregivers' intention to vaccinate their children <12 years of age against COVID-19. A structured questionnaire was administered to caregivers of children aged <12 years visiting the Emergency Department or the outpatient clinics in three major hospitals of Milan, Italy, from 20 September to 17 October 2021. A total of 612 caregivers were invited to participate and 604 accepted (response rate >98%). Three questionnaires were excluded due to compiling errors and 601 were included in the analysis. A total of 311 (51.7%) caregivers stated they would have their child vaccinated, 138 (23%) would refuse to vaccinate their child and 152 (25.3%) were unsure. The intention to vaccinate the child was higher in caregivers vaccinated against COVID-19, in those with a bachelor's degree or higher level of education, and in those with friends/acquaintances who became ill or died due to COVID-19. This study shows that increasing efforts are necessary to provide evidence-based tailored information to caregivers and to promote vaccination in this pediatric age group.

COVID-19 and Influenza Vaccination Campaign in a Research and University Hospital in Milan, Italy.

BACKGROUND: Healthcare workers (HCWs) are a historical key target of influenza vaccination programs. For the 2021-2022 season, WHO considered the coadministration of a flu and a COVID-19 vaccine as acceptable and recommended it to allow for higher uptake of both vaccines. The aim of this study was to investigate demographic and occupational features of vaccinated HCWs, reasons behind flu vaccine acceptance and a possible effect of the coadministration of a COVID-19 vaccine, in order to potentially draw general conclusions on HCWs' attitude towards flu vaccination and inform further strategies for consistent improvement of vaccine acceptance. METHODS: a promotional and educational campaign, a gaming strategy, and vaccination delivery through both a large central hub and on-site ambulatories, were the implemented strategies. In the central hub, the flu/COVID-19 vaccine coadministration was offered. Statistical descriptive analysis, multiple correspondence analysis (MCA) and logistic regression models were performed. RESULTS: 2381 HCWs received the flu vaccine, prompting a vaccination coverage rate (VCR) of 52.0% versus 43.1% in the 2020-2021 campaign. Furthermore, 50.6% vaccinated HCWs belonged to the 18-39 years-old age group. The most expressed reasons for vaccine uptake were "Vaccination is the most effective strategy of prevention" (n = 1928, 81.0%), "As HCW it's my duty to get vaccinated to protect my patients" (n = 766, 32.2%), and the group of COVID-19-related reasons (n = 586, 24.6%). In addition, 23.3% HCWs received the flu vaccine in the current campaign but not in the previous one (newly vaccinated) and the flu/COVID-19 vaccine coadministration was more frequent in this group. A total of 51.0% HCWs were hesitant towards the coadministration, while residents and nurses showed the highest propensity to receive it. CONCLUSIONS: in the second year of the COVID-19 pandemic, the Fondazione's influenza VCR continued to increase, with the greatest participation among HCWs aged 18-39 years. A potential propelling role of the COVID-19 vaccine coadministration was highlighted.

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.

Managing folate deficiency implies filling the gap between laboratory and clinical assessment.

The characterization of folate status in subjects at risk of deficiency and with altered vitamin homeostasis is crucial to endorse preventive intervention health policies, especially in developed countries. Several physiological changes (i.e. pregnancy), clinical situations and diseases have been associated to increased requirement, impaired intake and absorption of folate. However clinical practice guidelines (CPG) endorse folic acid supplementation generally discarding the use of its determination in serum to assess the risk of deficiency and/or its concentration at baseline. Poor confidence on the diagnostic accuracy of serum folate assays still persists in the current CPGs although recent standardization efforts have greatly improved inter-method variability and precision. In this review we critically appraise the methodological issues concerning laboratory folate determination and the evidence on the potential adverse effects of folic acid exposure. The final aim is to build a sound background to promote serum folate-based cost-effective health care policies by optimizing folic acid supplementation in subjects at risk of deficiency and with altered folate homeostasis. Our first result was to adjust in relation to current serum folate assays the thresholds reported by CPGs as index of folate status, defined on the association with metabolic and hematologic indicators. We identify a statistically significant difference between the estimated thresholds and accordingly show that the assessment of folate status actually changes in relation to the assay employed. The use of the method-dependent thresholds here reported may pragmatically endorse the stewardship of folic acid supplementation in clinical practice and increase the cost-effectiveness of health care policies.

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.

A Multivariate Pattern Analysis of Metabolic Profile in Neurologically Impaired Children and Adolescents.

BACKGROUND: The prevalence of pediatric metabolic syndrome is usually closely linked to overweight and obesity; however, this condition has also been described in children with disabilities. We performed a multivariate pattern analysis of metabolic profiles in neurologically impaired children and adolescents in order to reveal patterns and crucial biomarkers among highly interrelated variables. PATIENTS AND METHODS: We retrospectively reviewed 44 cases of patients (25M/19F, mean age 12.9 ± 8.0) with severe disabilities. Clinical and anthropometric parameters, body composition, blood pressure, and metabolic and endocrinological assessment (fasting blood glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, gamma-glutamyl transpeptidase) were recorded in all patients. As a control group, we evaluated 120 healthy children and adolescents (61M/59F, mean age 12.9 ± 2.7). RESULTS: In the univariate analysis, the children-with-disabilities group showed a more dispersed distribution, thus with higher variability of the features related to glucose metabolism and insulin resistance (IR) compared to the healthy controls. The principal component (PC1), which emerged from the PC analysis conducted on the merged dataset and characterized by these variables, was crucial in describing the differences between the children-with-disabilities group and controls. CONCLUSION: Children and adolescents with disabilities displayed a different metabolic profile compared to controls. Metabolic syndrome (MetS), particularly glucose metabolism and IR, is a crucial point to consider in the treatment and care of this fragile pediatric population. Early detection of the interrelated variables and intervention on these modifiable risk factors for metabolic disturbances play a central role in pediatric health and life expectancy in patients with a severe disability.