Psychological conditions of caregivers of adult subjects with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder. Individuals with PWS face a range of cognitive, behavioral, and emotional challenges that require comprehensive and lifelong care, posing significant demands on their caregivers. The study is not only aimed to assess the psychological conditions of caregivers of adult subjects with PWS focusing on psychological distress and coping, but also to shed light on a crucial yet often overlooked aspect of healthcare. This study aims to compare the psychological well-being of individuals with PWS and their caregivers, providing valuable insights that can potentially improve the quality of care for these individuals. The sample recruited at the Division of Auxology, IRCCS Istituto Auxologico Italiano, was composed of 30 adult subjects with PWS (11 men and 19 women; mean age ± SD: 36.4 ± 10.31 years; mean Body Mass Index (BMI): 35.7 ± 8.92: kg/m2) and their caregivers (10 men and 20 women). To assess the psychological condition of caregivers, the Italian-validated versions of the Depression Anxiety and Stress Scale (DASS-21) and the Coping Orientation to the Problems Experiences (COPE) were used, while to assess the psychological well-being of individuals with PWS and their caregivers, the Italian validated version of the Psychological General Well-Being Index (PGWBI) was used. RESULTS: Depression (p < 0.001), Stress (p = 0.050), and Total score (p = 0.009) of DASS 21 were higher in the caregivers of subjects with PWS than in the general population. PGWBI scores of caregivers were significantly lower than in individuals with PWS in Positive Well-being (p < 0.001), General Health (p = 0.006), Vitality (p = 0.004), and the total score (p = 0.006). The depression subscale of PGWBI was higher in caregivers than in subjects with PWS. Correlations between the subscales of COPE and the total score of PGWBI in caregivers revealed that the Avoidance subscale of COPE had a negative significant correlation with the total score of PGWBI (p = 0.003). CONCLUSIONS: Our results highlighted several critical insights into the profound emotional and psychological challenges faced by the caregivers of individuals with PWS.

Characterization of Circulating Protein Profiles in Individuals with Prader-Willi Syndrome and Individuals with Non-Syndromic Obesity.

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by distinctive physical, cognitive, and behavioral manifestations, coupled with profound alterations in appetite regulation, leading to severe obesity and metabolic dysregulation. These clinical features arise from disruptions in neurodevelopment and neuroendocrine regulation, yet the molecular intricacies of PWS remain incompletely understood. Methods: This study aimed to comprehensively profile circulating neuromodulatory factors in the serum of 53 subjects with PWS and 34 patients with non-syndromic obesity, utilizing a proximity extension assay with the Olink Target 96 neuro-exploratory and neurology panels. The ANOVA p-values were adjusted for multiple testing using the Benjamani-Hochberg method. Protein-protein interaction networks were generated in STRING V.12. Corrplots were calculated with R4.2.2 by using the Hmisc, Performance Analytics, and Corrplot packages Results: Our investigation explored the potential genetic underpinnings of the circulating protein signature observed in PWS, revealing intricate connections between genes in the PWS critical region and the identified circulating proteins associated with impaired oxytocin, NAD metabolism, and sex-related neuromuscular impairment involving, CD38, KYNU, NPM1, NMNAT1, WFIKKN1, and GDF-8/MSTN. The downregulation of CD38 in individuals with PWS (p < 0.01) indicates dysregulation of oxytocin release, implicating pathways associated with NAD metabolism in which KYNU and NMNAT1 are involved and significantly downregulated in PWS (p < 0.01 and p < 0.05, respectively). Sex-related differences in the circulatory levels of WFIKKN1 and GDF-8/MSTN (p < 0.05) were also observed. Conclusions: This study highlights potential circulating protein biomarkers associated with impaired oxytocin, NAD metabolism, and sex-related neuromuscular impairment in PWS individuals with potential clinical implications.

Effects of Melatonin on Exercise-Induced Oxidative Stress in Adults with Obesity Undergoing a Multidisciplinary Body Weight Reduction Program.

Background: Obesity is characterized by increased oxidative stress, which, in a vicious circle, promotes chronic low-grade inflammation. Melatonin, a well-documented antioxidant, might be useful as a supplement to enhance the cardiometabolic benefits of any body weight reduction program (BWRP). Objectives/Methods: The present study aimed to evaluate the post-exercise oxidative stress and inflammation in a group of subjects with obesity treated with melatonin (2 mg/die) or placebo, undergoing a 2-week BWRP, with the administration of a single bout of acute exercise at the start and the end of the protocol (G1-G15). Results: Eighteen adults with obesity were enrolled and distributed to the two arms of the study: the melatonin group (F/M: 7/2; age: 27.8 ± 5.6 years; body mass index [BMI]: 43.0 ± 4.9 kg/m2) and the placebo group (F/M: 6/3; age: 28.8 ± 5.0 years; BMI: 42.8 ± 4.0 kg/m2). BWRP induced a decrease in BMI and waist circumference (WC) in both groups; plasma glucose, blood glycated hemoglobin (HbA1c), and neutrophil to lymphocyte ratio (NLR) were reduced only in the placebo group. Importantly, plasma biological antioxidant potential (BAP) increased throughout BWRP. Paradoxically, melatonin enhanced post-exercise production of plasma derivatives of reactive oxygen metabolites (d-ROMs) and erythrocytic glutathionyl-Hb (HbSSG) (at G1 and G15). Finally, differently from the placebo group, melatonin-treated subjects did not exhibit the BWRP-induced decrease in plasma levels of interleukin-6 (IL-6), before and after exercise, at the end of two weeks (G15). Conclusions: Melatonin is presumably an antioxidant with "conditional" prooxidant actions. The use of melatonin as a supplement in subjects with obesity might be deleterious due to the abolishment of BWRP-induced cardiometabolic benefits.

Metabolomic profiling of Prader-Willi syndrome compared with essential obesity.

Introduction: Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study was to determine the metabolomic profile that characterizes PWS compared to EOB. Methods: A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to measure a total of 188 endogenous metabolites in plasma samples of 32 patients with PWS (F/M = 23/9; age: 31.6 ± 9.2 years; body mass index [BMI]: 42.1 ± 7.0 kg/m2), compared to a sex-, age- and BMI-matched group of patients with EOB (F/M = 23/9; age: 31.4 ± 6.9 years; BMI: 43.5 ± 3.5 kg/m2). Results: Body composition in PWS was different when compared to EOB, with increased fat mass and decreased fat-free mass. Glycemia and HDL cholesterol were higher in patients with PWS than in those with EOB, while insulinemia was lower, as well as heart rate. Resting energy expenditure was lower in the group with PWS than in the one with EOB, a difference that was missed after fat-free mass correction. Carrying out a series of Tobit multivariable linear regressions, adjusted for sex, diastolic blood pressure, and C reactive protein, a total of 28 metabolites was found to be associated with PWS (vs. non-PWS, i.e., EOB), including 9 phosphatidylcholines (PCs) ae, 5 PCs aa, all PCs aa, 7 lysoPCs a, all lysoPCs, 4 acetylcarnitines, and 1 sphingomyelin, all of which were higher in PWS than EOB. Conclusions: PWS exhibits a specific metabolomic profile when compared to EOB, suggesting a different regulation of some biochemical pathways, fundamentally related to lipid metabolism.

The Lipid Accumulation Product Index (LAP) and the Cardiometabolic Index (CMI) Are Useful for Predicting the Presence and Severity of Metabolic Syndrome in Adult Patients with Obesity.

Background: The concomitant occurrence of obesity and metabolic syndrome (MetS) causes a significant worsening of a patient's clinical condition. Indexes that employ anthropometric measurements alone or associated with blood parameters have been investigated for their ability to identify MetS. This study aimed to evaluate the diagnostic accuracy of three of these indexes, the body adiposity index (BAI), the lipid accumulation product index (LAP), and the cardiometabolic index (CMI), in a cohort of 1912 adult subjects with obesity. Methods and Results: MetS was found in 62.3% of the enrolled subjects, with a higher prevalence in males (72.5%) than females (60.9%). Receiver operating characteristic (ROC) analysis was used to define which index performed better. The BAI was found to be the lowest-performing index, with an ROC area of 0.50, a sensitivity of 30.31%, a specificity of 74.48%, and a likelihood ratio of 1.19. On the contrary, the LAP and the CMI showed a comparable ROC area of 0.82. The LAP had a sensitivity of 63.06%, a specificity of 86.55%, and a likelihood ratio of 4.69, while the CMI had a sensitivity of 67.59%, specificity of 81.55%, and a likelihood ratio of 3.66. The analysis was also performed in the group divided into males and females, with overlapping results. Conclusions: The LAP and the CMI performed better than the BAI in detecting MetS both in the general population with obesity and in the male/female subgroups. In the future, it will be important to validate these useful diagnostic tools in order to employ them in clinical practices.

Emotional and Behavioral Impairment and Comorbid Eating Disorder Symptoms in Adolescents with Obesity: A Cross-Sectional Study.

Background: The current study aims to assess the psychological conditions of Italian adolescents with obesity seeking an in-hospital multidisciplinary body weight reduction program, by exploring their psychological adjustment, emotional states, and co-occurring eating disorder symptoms. Methods: The study involved ninety-two consecutive Italian adolescents with obesity (31 males, 61 females), with a mean age ± SD: 16.4 ± 1.1 years and body mass index (BMI): 38.3 ± 6.04 kg/m2). The Strengths and Difficulties Questionnaire (SDQ), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Eating Attitude Test-26 (EAT-26) were used for the evaluations. Differences between genders, degrees of obesity (Group 1 = BMI SDS 2-2.99 and Group 2: BMI SDS > 3), and those with or without eating disorder symptoms (Group 1: EAT-26 ≤ 20 and Group 2: EAT-26 > 20) were explored. Results: The results showed that females reported higher scores on the Emotional Symptoms, Prosocial Behaviors, Total Difficulties, and Total Impact subscales of the SDQ, the BDI, both subscales of the STAI, and the Bulimia subscales of the EAT-26 than males, independently from the degrees of obesity. Participants with eating disorder symptoms (Group 2: EAT-26 > 20) showed higher scores on the Emotional Symptoms and Total Difficulties subscales of the SDQ, the BDI, and both subscales of the STAI than those of Group 1 (EAT-26 ≤ 20). Conclusions: The study explores the psychological conditions of adolescents with obesity. The results can inform appropriate treatment approaches for the management of obesity in developmental age groups, which not only take into account the medical and physical aspects of obesity, but also the behavioral, emotional, and social difficulties expressed by adolescents, in addition to specific eating disorder symptoms.

Complete Blood Count-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Background: Childhood obesity is a globally increasing pathological condition leading to long-term health issues such as cardiovascular diseases and metabolic syndrome (MetS). This study aimed to determine the clinical value of the Complete Blood Count-derived inflammation indexes Monocyte/HDL-C ratio (MHR), Lymphocyte/HDL-C ratio (LHR), Neutrophil/HDL-C ratio (NHR), and System Inflammation Response Index (SIRI) to predict the presence of metabolic syndrome and its association with cardiovascular risk markers (HOMA-IR, TG/HDL-C, and non-HDL-C) in children and adolescents with obesity. Methods: The study included a total of 552 children/adolescents with severe obesity (BMI: 36.4 [32.7-40.7] kg/m2; 219 males, 333 females; age: 14.8 [12.9-16.3] years), who were further subdivided based on the presence or absence of metabolic syndrome (MetS+ and MetS respectively). Results: The MHR, LHR, and NHR indexes (p < 0.0001), but not SIRI (p = 0.524), were significantly higher in the MetS+ compared to the MetS- subgroup, showing a positive correlation with the degree of MetS severity (p < 0.0001). Furthermore, MHR, LHR, and NHR were positively associated with cardiometabolic risk biomarkers (HOMA-IR: MHR p = 0.000, LHR p = 0.001, NHR p < 0.0001; TG/HDL-C: MHR, LHR, NHR p < 0.000; non-HDL-C: MHR, LHR p < 0.0001, NHR p = 0.000). Finally, the ROC curve analysis demonstrated that among the analyzed indexes, only MHR, LHR, and NHR had diagnostic value in distinguishing MetS patients among children and adolescents with obesity (MHR: AUC = 0.7045; LHR: AUC = 0.7205; NHR: AUC = 0.6934; p < 0.0001). Conclusions: In conclusion, the MHR, LHR, and NHR indexes, but not the SIRI index, can be considered useful tools for pediatricians to assess the risk of MetS and cardiometabolic diseases in children and adolescents with obesity and to develop multidisciplinary intervention strategies to counteract the widespread disease.

Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity.

Background: Metabolic syndrome (MetS) is a globally increasing pathological condition. Recent research highlighted the utility of complete blood count-derived (CBC) inflammation indexes to predict MetS in adults with obesity. Methods: This study examined CBC-derived inflammation indexes (NHR, LHR, MHR, PHR, SIRI, AISI, and SII) in 231 adults with severe obesity (88 males, 143 females; age: 52.3 [36.4-63.3] years), divided based on the presence (MetS+) or absence (MetS-) of MetS. The relationships between the indexes and the cardiometabolic risk biomarkers HOMA-IR, TG/HDL-C, and non-HDL-C were also evaluated. Results: Individuals with metabolic syndrome (MetS+) had significantly higher values of MHR, LHR, NHR, PHR, and SIRI than those without (MetS-) (MHR and NHR: p < 0.0001; LHR: p = 0.001; PHR: p = 0.011; SIRI: p = 0.021). These values were positively correlated with the degree of MetS severity. Logistic regression (MHR and NHR: p = 0.000; LHR: p = 0.002; PHR: p = 0.022; SIRI: p = 0.040) and ROC analysis (MHR: AUC = 0.6604; LHR: AUC = 0.6343; NHR: AUC = 0.6741; PHR: AUC = 0.6054; SIRI: AUC = 0.5955) confirmed the predictive potential of CBC-derived inflammation indexes for MetS in individuals with severe obesity. CBC-derived inflammation indexes also correlated with HOMA-IR (MHR, LHR, and NHR: p < 0.0001; PHR: p < 0.001; SIRI: p = 0.000) and TG/HDL-C (MHR, LHR, NHR and PHR: p < 0.0001; SIRI: p = 0.006). Conclusions: In conclusion, this study validates CBC-derived inflammation indexes for predicting MetS in individuals with severe obesity. The relationships between these indexes and cardiometabolic risk factors can enable clinicians to better grade MetS associated with obesity.

Behavioral and Emotional Problems in Children and Adolescents with Obesity: A Preliminary Report.

BACKGROUND: Parent-child agreement regarding emotional and behavioral problems in adolescents with obesity was measured. METHODS: One hundred Italian adolescents with obesity (36 males, 64 females, mean age ± SD: 15.3 ± 1.61 years, mean body mass index, BMI: 37.9 ± 5.48 kg/m2), hospitalized for a 3-week multidisciplinary body weight reduction program at Istituto Auxologico Italiano, Piancavallo-Verbania, Italy, and one of their parents (n = 100, 40 fathers, 60 mothers) participated in the study. Achenbach's Child Behavior Checklist (CBCL) for parents and the Youth Self Report (YSR) for teens were administered. RESULTS: Most of the CBCL and YSR scores were normal, with more borderline and clinical scores being found in CBCL (29% of borderline scores in attention problems, 28% in affective problems, and 26% in ADHD; 32% of clinical scores in affective problems, 23% in withdrawn/depressed, and 22% in anxiety problems and somatic complains subscales) than in YSR (19% of borderline scores in affective behaviors and 17% in somatic complains; 15% of clinical scores in anxiety problems and 17% in withdrawn/depressed subscale). Young females reported greater anxiety problems (p = 0.009), oppositional defiant problems (p = 0.029), anxiety/depressed (p = 0.030), and internalizing problems (p = 0.045) than males. Pearson's coefficients ranged between 0.273 to 0.517. CONCLUSIONS: This study provides information on the cross-informant evaluation of psychological profiles with CBCL and YSR in a clinical sample of adolescents with obesity and their parents.

Proteome profiling identifies circulating biomarkers associated with hepatic steatosis in subjects with Prader-Willi syndrome.

Introduction: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by loss of expression of paternal chromosome 15q11.2-q13 genes. Individuals with PWS exhibit unique physical, endocrine, and metabolic traits associated with severe obesity. Identifying liver steatosis in PWS is challenging, despite its lower prevalence compared to non-syndromic obesity. Reliable biomarkers are crucial for the early detection and management of this condition associated with the complex metabolic profile and cardiovascular risks in PWS. Methods: Circulating proteome profiling was conducted in 29 individuals with PWS (15 with steatosis, 14 without) using the Olink Target 96 metabolism and cardiometabolic panels. Correlation analysis was performed to identify the association between protein biomarkes and clinical variables, while the gene enrichment analysis was conducted to identify pathways linked to deregulated proteins. Receiver operating characteristic (ROC) curves assessed the discriminatory power of circulating protein while a logistic regression model evaluated the potential of a combination of protein biomarkers. Results: CDH2, CTSO, QDPR, CANT1, ALDH1A1, TYMP, ADGRE, KYAT1, MCFD, SEMA3F, THOP1, TXND5, SSC4D, FBP1, and CES1 exhibited a significant differential expression in liver steatosis, with a progressive increase from grade 1 to grade 3. FBP1, CES1, and QDPR showed predominant liver expression. The logistic regression model, -34.19 + 0.85 * QDPR*QDPR + 0.75 * CANT1*TYMP - 0.46 * THOP1*ALDH1A, achieved an AUC of 0.93 (95% CI: 0.63-0.99), with a sensitivity of 93% and specificity of 80% for detecting steatosis in individuals with PWS. These biomarkers showed strong correlations among themselves and were involved in an interconnected network of 62 nodes, related to seven metabolic pathways. They were also significantly associated with cholesterol, LDL, triglycerides, transaminases, HbA1c, FLI, APRI, and HOMA, and showed a negative correlation with HDL levels. Conclusion: The biomarkers identified in this study offer the potential for improved patient stratification and personalized therapeutic protocols.

Effects of combined training or moderate intensity continuous training during a 3-week multidisciplinary body weight reduction program on cardiorespiratory fitness, body composition, and substrate oxidation rate in adolescents with obesity.

This study aimed to investigate the effects of combined training (COMB, a combination of moderate-intensity continuous training-MICT and high-intensity interval training-HIIT) vs. continuous MICT administered during a 3-week in-hospital body weight reduction program (BWRP) on body composition, physical capacities, and substrate oxidation in adolescents with obesity. The 3-week in-hospital BWRP entailed moderate energy restriction, nutritional education, psychological counseling, and two different protocols of physical exercise. Twenty-one male adolescents with obesity (mean age: 16.1 ± 1.5 years; mean body mass index [BMI] 37.8 ± 4.5 kg m-2) participated in this randomized control trial study (n:10 for COMB, n:11 MICT), attending ~ 30 training sessions. The COMB group performed 3 repetitions of 2 min at 95% of peak oxygen uptake (V'O2 peak) (e.g., HIIT ≤ 20%), followed by 30 min at 60% of V'O2 peak (e.g., MICT ≥ 80%). Body composition, V'O2 peak, basal metabolic rate (BMR), energy expenditure, and substrate oxidation rate were measured during the first week (W0) and at the end of three weeks of training (W3). The two training programs were equivalent in caloric expenditure. At W3, body mass (BM) and fat mass (FM) decreased significantly in both groups, although the decrease in BM was significantly greater in the MICT group than in the COMB group (BM: - 5.0 ± 1.2 vs. - 8.4 ± 1.5, P < 0.05; FM: - 4.3 ± 3.0 vs. - 4.2 ± 1.9 kg, P < 0.05). V'O2 peak increased only in the COMB by a mean of 0.28 ± 0.22 L min-1 (P < 0.05). The maximal fat oxidation rate (MFO) increased only in the COMB group by 0.04 ± 0.03 g min-1 (P < 0.05). COMB training represents a viable alternative to MICT for improving anthropometric characteristics, physical capacities, and MFO in adolescents with obesity during a 3-week in-hospital BWRP.

Ceramide Risk Score in the Evaluation of Metabolic Syndrome: An Additional or Substitutive Biochemical Marker in the Clinical Practice?

Ceramide risk score (CERT1, ceramide test 1), based on specific ceramides (Cers) and their corresponding ratios in the plasma, has been reported as a promising biochemical marker for primary and secondary prediction of cardiovascular disease (CVD) risk in different populations of patients. Thus far, limited attention has been paid to metabolic syndrome, a condition considered at high CVD risk. The aim of the present study was to evaluate CERT1 in a group of obese subjects without (OB-MetS-) and with (OB-MetS+) metabolic syndrome (according to the International Diabetes Federation (IDF) diagnostic criteria), compared to an age- and sex-matched normal-weight (NW) group. In all participants, plasma levels of Cer 16:0, Cer 18:0, Cer 24:1, and Cer 24:0 were measured, and the corresponding ratios Cer 16:0/24:0, Cer 18:0/24:0, and Cer 24:1/24:0 were calculated together with CERT1. Subjects with obesity showed higher CERT1 values than the NW group (p < 0.05), with no difference between OB-MetS- and OB-MetS+ groups. Waist circumference (WC), homeostatic model assessment of insulin-resistance (HOMA-IR) (surrogates of IDF diagnostic criteria for metabolic syndrome), and C reactive protein (CRP) (a marker of inflammation) were predictors of CERT1 (p < 0.05), with the contribution of the other IDF criteria such as arterial hypertension and dyslipidemia being negligible. Adjustment for WC resulted in a loss of the difference in CERT1 between OB-MetS- and NW subjects, with the combination of WC and HOMA-IR or CRP as covariates being necessary to yield the same effect for the difference in CERT1 between OB-MetS+ and NW subjects. Importantly, an association was found between CERT1 and vascular age (VA) (p < 0.05). Proportions of NW, OB-MetS- and OB-MetS+ subjects appeared to be distributed according to the CERT1-based risk groups (i.e., low, moderate, increased, and high risk; p < 0.05), with some OB-MetS- subjects included in the increased/high-risk group and some OB-MetS+ in the low/moderate-risk one. In conclusion, the clinical diagnosis of metabolic syndrome seems to be inaccurate to assess CVD risk in the obese population; however, further studies are needed before considering CERT1 as an additional or substitutive biochemical marker in clinical practice.

Measured vs estimated resting energy expenditure in children and adolescents with obesity.

Pediatric obesity requires early targeted interventions consisting mainly of a low-calorie diet prescribed based on resting energy expenditure (REE), often estimated through predictive equations. The aim of this study was to define the prevalence of "hypo-", "normo-" and "hypermetabolic" in a large cohort of children and adolescents with obesity by comparing measured and estimated REE and to evaluate the characteristics related to these metabolic statuses in both males and females. The study population was divided into the three subgroups by comparing REE measured using indirect calorimetry and estimated using the Molnar equation, and subsequently analyzed. The majority of the participants (60.6%) were normometabolic, 25.5% hypermetabolic and 13.9% hypometabolic. No significant differences in age, Tanner stage, systolic blood pressure, or the presence of metabolic syndrome were found. However, the hypermetabolic subgroup was significantly lighter, shorter, with lower hip and waist circumferences, had a greater amount of fat-free mass and lower fat mass, significantly lower diastolic blood pressure, and a significantly higher frequency of non-alcoholic liver steatosis. Pediatric obesity is more associated with normal or increased REE than with a hypometabolic condition, suggesting that estimation of energy expenditure with predictive equations is still inadequate for prescribing the appropriate diet plan.

Fatigue Perception in Adolescents with Obesity and Their Caregivers.

Although fatigue is a frequently occurring symptom in young patients with obesity, relatively few studies have assessed their perception of fatigue and its impact on their quality of life so far. Comparisons between the reports of fatigue in children/adolescents with obesity and their parents were assessed using the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL-MFS). One hundred Italian children/adolescents (36 males; 64 females), aged between 11 and 17 (mean age = 15.3; SD = 1.61) with severe obesity [mean Body Mass Index (BMI: kg/m2) = 38; SD = 5.48] and their caregivers were enrolled. Perception of fatigue did not change by sex and rates of obesity in adolescents, while there was a difference (p = 0.040) in parents' reports of cognitive fatigue between parents of children/adolescents of Group 1 (BMI SDS 2-2.99) and Group 2 (BMI SDS > 3), with a higher perception of fatigue in parents of the less heavy obese children. Significant differences in reports of general fatigue subscale were found between children/adolescents and their parents, being higher in their parents than in the young subjects with obesity (p < 0.001). Significant moderate correlations between all the subscales of PedsQL-MFS for children and parents were found with Pearson's coefficients ranging from 0.529 to 0.571 (p < 0.001). The perception of fatigue measured with the PedsQL-MFS was comparable between obese children and their parents, thus indicating that this symptom is not hidden by children and is clearly perceived by their parents.

Cardiometabolic Index (CMI) and Visceral Adiposity Index (VAI) Highlight a Higher Risk of Metabolic Syndrome in Women with Severe Obesity.

Recent evidence shows that simple and inexpensive anthropometric measurements can be used to identify, at an early stage, women with obesity at increased risk of developing metabolic syndrome (MetS). Thus, the aim of this study was to compare the accuracy of five different indexes of adiposity and/or body composition in identifying MetS in a group of 876 women (mean age ± SD: 52.1 ± 13.8 years; body mass index (BMI): 43.6 ± 6.1 kg m-2). The following indexes were determined for each subject: waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), body mass fat index (BMFI), visceral adiposity index (VAI), and cardiometabolic index (CMI). Overall, the presence of MetS was detected in 544 patients (62%). Pearson correlation coefficients were calculated to evaluate the relationships between body composition indexes and metabolic characteristics of the women. Receiver operating characteristic (ROC) analysis was used to determine the best predictor for each adiposity index among metabolic risk factors. The ROC analysis showed VAI (AUC = 0.84) and CMI (AUC = 0.86) showed the best performance in predicting MetS. Differences were found between the ROC area of CMI and VAI with all other indexes (p < 0.05). The optimal cutoff point for early diagnosis of MetS was >0.92 for WHR, >0.76 for WtHR, >30.1 kg m-1 for BMFI, >1.94 for VAI, and >0.84 for CMI. In addition, VAI and CMI were the most sensitive and specific indexes compared with other indexes. In conclusion, VAI and CMI represent the most useful and reliable indexes to be used for detecting MetS in women suffering from obesity in clinical practice.

The neutrophil to lymphocyte ratio (NLR) positively correlates with the presence and severity of metabolic syndrome in obese adults, but not in obese children/adolescents.

Metabolic syndrome (MetS) associated with obesity is a pathological condition increasing worldwide. Recent studies have demonstrated that the neutrophil to lymphocyte ratio (NLR) can be successfully used to stage MetS in obese adults. The aim of the study was to evaluate NLR values in 552 children/adolescents (M 219, F 333; 14.8 [12.9-16.3] years) and 231 adults (M 88, F 143; 52.3 [36.4-63.3] years) with morbid obesity, subdivided into subgroups according with the presence or absence of MetS. Adult patients with obesity showed a higher prevalence of MetS compared to the pediatric population (71% vs 26%), associated with a greater number of subjects with 3 and 4-5 altered components for MetS. NLR was higher (P-value = 0.041) in adults with MetS compared with those without. NLR values also positively correlated with the severity grade of the syndrome (P-value = 0.032). By contrast, in pediatric subjects with obesity with MetS, NLR values were comparable with those recorded in subjects without MetS (P-value = 0.861), no correlation being found with MetS severity (P-value = 0.441). Our study confirms the importance of NLR as an inflammatory indicator associated with MetS in adult subjects with severe obesity, while it excludes a similar role in children/adolescents.

High Tg/HDL-Cholesterol Ratio Highlights a Higher Risk of Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Few data are currently available on the reliability of the different anthropometric, instrumental and biochemical indexes in recognizing the presence of metabolic syndrome (MetS) in children and adolescents with severe obesity. Therefore, the objective of our study was to find out the simplest and most accurate predictive index of MetS in this population at-risk. In 1065 children and adolescents (563 f, 502 m), aged 14.6 ± 2.1 years (range 10-17), with severe obesity [BMI-SDS 3.50 ± 0.36 (range 3.00-5.17)], the following indexes were evaluated: BMI, BMI-SDS, Tri-Ponderal Mass Index, Waist-to-Height ratio, TG/HDL-Cholesterol ratio, Cardiometabolic Index (CMI), and Visceral Adiposity Index (VAI). For each subject, all the components of MetS, defined according to the IDF criteria, were determined. Overall, the presence of MetS was found in 324 patients (30.4%), 167 males (33.3%) and 157 females (27.9%). According to the ROC analysis, three indexes (VAI, CMI and TG/HDL-Cholesterol ratio), performed significantly better than the other ones in identifying MetS, with no difference among them. In conclusion, the TG/HDL ratio, which just needs the evaluation of two simple biochemical parameters, offers the same accuracy as other more sophisticated indexes in recognizing MetS in children and adolescents with severe obesity, thus making it the best predictor to be easily used.

Correction: Rigamonti et al. The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents. Metabolites 2022, 12, 155.

In the original publication [...].

The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents.

The aspartate transaminase to platelet ratio index (APRI) has been proposed as an easy-to-use biochemical marker in obese adults with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH). The objective of the present study was to evaluate the clinical and predictive value of APRI in a paediatric obese population. Seven hundred fifty-seven obese children and adolescents (BMI standard deviation score, SDS: >2.0; age range: 10-18.5 years), not consuming alcohol and without hepatitis B or C, were recruited after having been screened for NAFLD by ultrasonography. A series of demographic, biochemical and clinical parameters was compared between the two subgroups (with or without NAFLD); the same parameters were correlated with APRI; and finally, univariable and multivariable logistic regression was used to evaluate the predictors of NAFLD. NAFLD was diagnosed in about 39% of the entire paediatric population, predominantly in males and in subjects suffering from metabolic syndrome. APRI was correlated with the waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), uric acid, total bilirubin, C reactive protein (CRP) and systolic blood pressure (SBP). Furthermore, APRI was higher in males than females, but independent from steatosis severity and metabolic syndrome. With the univariable analysis, the BMI SDS, triglycerides (TG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), APRI, uric acid and metabolic syndrome were positive predictors of NAFLD, with female sex being negative predictor. At multivariable analysis; however, only BMI SDS, TG, HOMA-IR and APRI were positive predictors of NAFLD, with female sex being a negative predictor. The accuracy of APRI as a biochemical marker of NAFLD was about 60%.In conclusion, in a large (Italian) paediatric obese population, parameters, such as BMI SDS, TG, HOMA-IR and APRI, were positive predictors of NAFLD, with female sex being a negative predictor and most of the prediction explained by APRI. Nevertheless, APRI appears to be a simple biochemical marker of liver injury rather than of NAFLD/NASH and, moreover, is endowed with a limited accuracy for the prediction/diagnosis of NAFLD.

A three-week in-hospital multidisciplinary body weight reduction program exerts beneficial effects on physical and mental health and fatiguability of elderly patients with obesity.

Introduction: Obesity represents one of the most serious problems of public health affecting elderly populations in an increasingly relevant way. The aim of the current study was to assess the effects of a 3-week in-hospital multidisciplinary body weight reduction program (BWRP) in a sample of elderly patients with obesity on reducing body mass index (BMI), improving fatigue, muscle performance, and psychological well-being. Methods: Two hundred and thirty-seven consecutive elderly in-patients with obesity (males = 84; females = 153; age range = 65-86 yrs.; mean BMI = 43.7) undergoing a three-week multidisciplinary BWRP participated in the study. Data on BMI, fatiguability (measured with the Fatigue Severity Scale, FSS), muscle performance (evaluated with the Stair Climbing Test, SCT), and psychological well-being (assessed with the Psychological General Well- Being Index, PGWBI) were collected before and after the intervention. Results: Results showed that BWRP was capable to reduce BMI [F(1.00, 235.00) = 1226.8; p < 0.001; ƞ 2 = 0.024], improve perceived fatigue [F(1,234) = 296.80125; p < 0.001; ƞ 2 = 0.129], physical performance [F(1.00,158.00) = 119.26; p < 0.001; ƞ 2 = 0.026], and enhance psychological well-being [F(1,235) = 169.0; p < 0.001; ƞ 2 = 0.103] in both males and females. Discussion: Although it will be necessary to demonstrate with further longitudinal studies whether the reported beneficial effects will be maintained over time, the effectiveness of a 3-week BWRP on different aspects involved in determining a level of autonomy and good quality of life of elderly obese patients appears to represent a valid attempt to counteract - at least in part - the unavoidable and progressive disability of these patients.