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Treating obesity in children and adolescents is complex, given the dynamic nature of growth and development during this life stage. The role of pharmacological treatments in the management of pediatric obesity remains uncertain, particularly with respect to outcomes beyond weight reduction, including quality of life and long-term adverse events. To assess the benefits and harms of pharmacological interventions for the treatment of obesity in children and adolescents. We searched CENTRAL, MEDLINE, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov on 3 July 2023 without language restrictions. In June 2025, we checked the status of ongoing studies and updated results accordingly. We included randomized controlled trials (RCTs) evaluating pharmacological interventions in children (0 to 9 years) and adolescents (10 to 19 years) with essential obesity. Eligible studies administered any medication, at any dose, as monotherapy or in combination, for at least three months and reported outcomes after a minimum follow-up of six months. Critical outcomes were change in body mass index (BMI), change in weight, any adverse events, discontinuation due to adverse events, and incidence or severity of obesity-related outcomes. Important outcomes were health-related quality of life, mental and physical well-being, and obesity-related disability. We used the RoB 2 tool to assess bias in the included RCTs. We calculated mean differences (MDs) and standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, with their corresponding 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for critical outcomes and quality of life. We included 37 RCTs with a total of 4218 participants. Two were cross-over trials; 35 were parallel-group trials. We identified seven ongoing studies and six studies as awaiting classification. Of the included studies, 25 involved adolescents only. Eleven studies planned to include both children and adolescents, but only eight actually did. One study intended to include children but did not specify participants' age at inclusion. Trials randomized participants to pharmacological interventions or control alongside common baseline treatments (e.g. behavioral or lifestyle approaches, diet, and physical activity). Of the 37 included studies, 31 used placebo and six used no intervention (baseline treatment alone) as the comparator. The studies were conducted across 17 high-income, six middle-income, and three low-income countries. Length of follow-up ranged from six to 31 months, with a median of 11 months. Pharmacological interventions versus placebo Compared to placebo, pharmacological interventions (glucagon-like peptide-1 [GLP-1] receptor agonists, metformin, orlistat, sibutramine, topiramate, phentermine plus topiramate) may reduce BMI (change from baseline) by 1.80 kg/m2 (95% CI -2.36 to -1.24; I2 = 87%; 25 studies, 3091 participants; low-certainty evidence) and weight (change from baseline) by 5.47 kg (95% CI -7.45 to -3.50; I2 = 89%; 20 studies, 2380 participants; low-certainty evidence). Adverse events were frequent. Pharmacological interventions (GLP-1 agonists, sibutramine, phentermine, topiramate) likely make little to no difference in the risk of any adverse events compared to placebo (RR 1.03, 95% CI 1.00 to 1.07; I2 = 0%; 8 studies, 1877 participants; moderate-certainty evidence). Pharmacological interventions (GLP-1 agonists, metformin, orlistat, sibutramine, phentermine, topiramate) may make little to no difference in the risk of discontinuation due to adverse events, although the risk was slightly higher with the medications (RR 1.50, 95% CI 0.82 to 2.75; I2 = 17%; 13 studies, 2213 participants; low-certainty evidence). One study (46 participants), comparing sibutramine to placebo, found that there may be little to no difference in the incidence of obesity-related outcomes for adolescents with comorbidities (assessed as changes in glycemia, blood pressure, total cholesterol, and triglycerides). We were unable to pool other data on incidence or severity of obesity-related outcomes. Compared to placebo, pharmacological interventions (GLP-1 agonists, phentermine plus topiramate) likely result in little to no difference in quality of life, assessed with the Impact of Weight on Quality of Life-Kids (IWQOL) questionnaire (MD 1.02, 95% CI -1.94 to 3.98; I2 = 48%; 4 studies, 741 participants; moderate-certainty evidence). Pharmacological interventions versus no intervention Compared to no intervention, metformin may reduce BMI (change from baseline) by 1.51 kg/m2 (95% CI -2.29 to -0.73; I2 = 0%; 3 studies, 151 participants) and weight (change from baseline) by 3.20 kg (95% CI -6.12 to -0.28; 1 study, 42 participants), but the evidence for both outcomes is very uncertain. Compared to no intervention, pharmacological interventions (metformin and orlistat) may increase the risk of discontinuations due to adverse events, but the evidence is very uncertain (RR 13.70, 95% CI 0.83 to 225.43; 2 studies, 84 participants). None of the studies comparing pharmacological interventions to no intervention reported data on adverse events, obesity-related outcomes, and quality of life that could be pooled in meta-analysis. Only eight of the 37 included studies enrolled children, and data were seldom disaggregated by age, limiting the ability to draw conclusions about benefits or harms in children. This review includes clinical trials assessing the benefits and harms of pharmacological treatments - including GLP-1 agonists, metformin, orlistat, phentermine, sibutramine, and topiramate - for weight management in adolescents with obesity. Evidence suggests that pharmacological treatments may result in small reductions in BMI and weight, which could be clinically important, although effects vary by medication. Evidence on desirable and undesirable effects in children is scant. Uncertainties remain about the optimal duration of treatment, consequences of treatment discontinuation, and long-term benefits and harms, particularly considering the physiology of children and impact on growth. Studies with longer follow-up are needed to evaluate outcomes beyond BMI and weight change, including the potential effects of treatment discontinuation. The Department of Nutrition and Food Safety at the WHO commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation (NORAD), the Swedish International Development Cooperation Agency (SIDA), the Government of the Grand Duchy of Luxembourg, the Government of Germany (BMG), and the Government of Greece to the WHO Department of Nutrition and Food Safety. Our protocol is registered in PROSPERO: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433123.
This study aims to search, evaluate, and summarize the existing evidence on perioperative nutritional management of transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhotic portal hypertension (CPH) and provide the basis for evidence-based clinical practice. According to the "6S" model of evidence-based sources, the evidence on perioperative nutrition management of TIPS in patients with CPH from relevant databases and websites was systematically searched, including clinical decisions, guidelines, expert consensus, systematic review, and evidence summary. The search range is from the establishment of the databases to August 17, 2024. Two authors independently screened the literature following the inclusion and exclusion criteria. The quality of the literature was evaluated by a total of 4 authors using appropriate tools, including Appraisal of Guidelines for Research and Evaluation II (AGREE II), the evaluation tool of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center, and CASE (Critical Appraisal for Summaries of Evidence). Two authors were responsible for extracting and summarizing the evidence. The level of evidence was classified according to the JBI Evidence Pre-Classification and Evidence Recommendation Level System (2014 version). A total of 18 articles were included, including 3 clinical decisions, 6 guidelines, 6 expert consensuses, 2 evidence summaries, and 1 systematic review. 30 pieces of evidence covering 5 key themes were summarized: nutritional risk screening and status assessment, nutritional goals, nutritional support modalities and measures, nutritional management of complications, and follow-up and education. This study systematically retrieved and evaluated the existing evidence on perioperative nutritional management in patients with CPH undergoing TIPS. On the basis of the current level of evidence, this study proposed a preliminary framework for perioperative nutritional management and suggests that future high-quality prospective studies be conducted to further clarify the relevant recommendations. In clinical practice, healthcare professionals should exercise professional judgment, integrating clinical conditions with patient preferences, habits, and tolerability when applying the evidence.
Heart failure (HF) is a chronic condition associated with frequent hospitalizations and impaired quality of life. Malnutrition is common in HF and is linked to adverse clinical outcomes, while self-care is an important component of HF management. This study aimed to examine the associations between nutritional status, self-care behaviors, and clinical characteristics in patients with chronic HF. A cross-sectional study was conducted among 100 hospitalized HF patients (mean age 75.9 ± 9.8 years; 63% men). Nutritional status was assessed using the Mini Nutritional Assessment (MNA), and self-care using the nine-item European Heart Failure Self-care Behaviour Scale (9-EHFScBS). Clinical variables included NYHA class, LVEF, comorbidities, BMI, and laboratory parameters. Comparative analyses and multivariate linear regression were performed. Patients who were malnourished or at risk of malnutrition had significantly higher NT-proBNP levels (p = 0.004) and higher NYHA class (p = 0.002), whereas well-nourished individuals had significantly higher triglyceride levels (p = 0.032). Nutritional status was negatively associated with NYHA class and NT-proBNP, and positively associated with BMI. Among laboratory parameters, significant positive correlations were observed with hemoglobin, hematocrit, albumin, and triglyceride levels. In multivariate analysis, the following variables were independently associated with MNA score: self-care score (B = 0.083 per point), BMI (B = 0.368 per kg/m2), comorbidity burden (B = -0.401 per comorbidity), and NYHA class (NYHA III: B = -2.425; NYHA IV: B = -5.966, vs. NYHA II). In patients with chronic heart failure, nutritional status is associated with disease severity, metabolic parameters, comorbidity burden, BMI, and self-care behaviors. These findings support the importance of routine nutritional screening as part of comprehensive HF management.
The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Whether meat consumption increases the risk of gastric cancer (GC) and esophageal cancer or not remains unclear. Moreover, the number of prospective studies evaluating the associations by anatomical and histological types of GC is limited. We aimed to assess the associations of red, processed, and white meat with all gastric adenocarcinomas by anatomical site and histological type, and with esophageal adenocarcinoma (EAC), using data from the European Prospective Investigation into Cancer and Nutrition study of 450,112 individuals (131,426 men/318,686 women). Over 14.1 years of follow-up, 876 GC and 215 EAC cases were identified. Among the GC cases, 233 were located in cardia and 329 in non-cardia regions. Histologically, 624 were classified as intestinal type and 208 as diffuse type. The associations between meat intake and risk of GC or EAC were assessed using multivariable Cox models. A 30 g/day increase in processed meat consumption was associated with a 9% (95% CI: 2-17) increase in GC risk and a 13% (95% CI: 0-27) increase in EAC risk. Additionally, a 20 g/day increase in white meat intake was associated with a 12% (95% CI: 2-24) increase in non-cardia GC risk. Processed meat was also associated with intestinal GC (11%, 95% CI: 2-20) and higher consumption with diffuse GC. Only processed meat was associated with GC among men while processed and white meat were both positively associated with GC among women. In conclusion, processed meat may increase the risk of GC and EAC, although further research is needed to clarify the effects of white meat consumption.
The incidence of early-onset cancers (EOCs), defined as cancers diagnosed before 50 years of age, has risen globally over the past three decades. The association between modifiable lifestyle factors and EOC risk has been poorly investigated. Participants enrolled before age 50 in EPIC (39,459 men; 110,991 women) and the UK Biobank (52,188 men; 62,528 women) were analysed. We examined the association between smoking, alcohol consumption, body mass index (BMI), physical activity and diet, and risk of lifestyle-related EOCs - including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others. Each risk factor was scored from 0 (most unfavourable) to 4 (most favourable). Cohort-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated in Cox regression models and pooled via a meta-analytic approach. We observed 361 lifestyle-related EOCs in men and 2618 in women, including 1765 breast cancers. In men, one-point increase in the smoking score, indicating less smoking, was inversely associated with risk of lifestyle-related EOC (HR 0.82, 95% CI: 0.76-0.88). In women, each one-point increase in smoking (less smoking), BMI (lower BMI), and physical activity (more active) scores was inversely associated with risk of lifestyle-related EOC excluding breast cancer (HRs: 0.89 [0.84-0.93], 0.93 [0.89-0.98], 0.95 [0.90-1.00], respectively). For breast cancer, only physical activity showed a statistically significant association (HR 0.95 [0.91-0.995]). Alcohol and diet showed no association. These findings support the importance of adopting a healthy lifestyle early in life to reduce cancer risk before the age of 50.
Mild cognitive impairment (MCI) is characterized by a decline in cognitive functions while the ability to perform daily activities remains intact. This pathological condition is a recognized as risk factor for dementia-related disorders, and the current lack of therapies is the critical issue. Our preclinical studies indicated that a formulation (named GeNeurofil™) exhibited a synergistic neuroprotective effect in an animal model of amyloid beta toxicity. Therefore, the present study aimed to evaluate the efficacy of GeNeurofil™ in patients with mild cognitive impairment. A six-months, randomized, double-blind, placebo-controlled pilot trial (retrospectively registered on ISRCTN registry-number ISRCTN11405046-01/07/2026) was performed enrolling 54 patients with mild to moderate MCI (Clinical Dementia Rating Scale ranging from 0.5 to 2). Patients, concurrently maintained under their usual medications, received either the GeNeurofil™ (0.7 mL × 3/day) or an identical placebo (0.7 mL × 3/day) for six months. The psychometric assessments were performed using the Mini Mental State Examination (MMSE) tests and depressive symptoms were evaluated with the Zung Test. Plasma samples were analyzed for NfL and p-TAU. After six months of treatment, GeNeurofil™ supplementation improved CDR, MMSE, and Zung scores. Furthermore, the treatment reduced plasmatic levels of light neurofilaments (NfL) and phosphorylated Tau protein (p-TAU) compared to placebo. Our findings indicate that six months of supplementation with GeNeurofilTM might represent a helpful adjuvant strategy for cognitive impairment. GeNeurofil™ nutraceutical supplementation demonstrates a favorable safety profile, however given the exploratory nature of this pilot feasibility trial, these preliminary findings will further followed by confirming definitive clinical efficacy in larger clinical trials.
Chronic obstructive pulmonary disease (COPD) often coexists with sarcopenia, contributing to poorer exercise tolerance, quality of life, and prognosis. Although interest in this topic has increased, a comprehensive bibliometric overview is still lacking. English-language articles and reviews on COPD complicated with sarcopenia published between 2005 and 2025 were retrieved from the Web of Science Core Collection and Scopus. After screening and deduplication, bibliometric and visualisation analyses were conducted using bibliometrix/biblioshiny, VOSviewer, and CiteSpace to evaluate publication trends, major contributors, collaboration networks, co-citation patterns, and keyword evolution. A total of 922 publications from 421 journals were included. Output increased markedly over time, especially after 2018, peaking in 2025. The United States and China were the main contributors and major collaboration hubs, while several European countries showed strong international collaboration and high citation impact. Core journals included International Journal of Chronic Obstructive Pulmonary Disease, Journal of Cachexia, Sarcopenia and Muscle, and Clinical Nutrition. Co-citation analysis showed that the knowledge base was mainly supported by studies on COPD systemic effects and body composition, together with consensus documents on sarcopenia definition and grading. Research hotspots evolved from early work on weight loss, malnutrition, and muscle wasting to functional assessment and clinical outcomes, and more recently to interventions such as nutrition support, resistance training, and pulmonary rehabilitation, alongside emerging mechanistic themes including inflammation, oxidative stress, and metabolic abnormalities. Research on COPD complicated with sarcopenia has shifted from descriptive phenotypes to standardised assessment, functional outcomes, and clinical management. Future studies should strengthen multicentre longitudinal designs and multidisciplinary collaboration to better integrate mechanisms with clinical assessment and intervention.
MODY (Maturity-Onset Diabetes of the Young) is characterized by autosomal dominant mode of inheritance, early onset of diabetes in the absence of autoimmunity directed to pancreatic β-cells, impaired insulin secretory capacity, however, maintained over time, and extra-pancreatic manifestations in some patients. Its prevalence has been estimated 0.6% to 6.5% of all diabetes in Europe and the USA. Pathogenic variants in the genes encoding glucokinase or transcription factors HNF1A or HNF4A are responsible for the majority of cases of monogenic forms of diabetes referred to as MODY. The objective of the French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins) dedicated to GCK-MODY (formerly MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1) is to provide to health professionals a guide for optimal management and care of patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Thorough analysis of personal and family history, clinical examination and biochemical testing are key to raise the diagnosis, which has to be confirmed by molecular analysis. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. Overall, the management of patients with MODY requires the collaboration of several health care providers.
Immune checkpoint inhibitors (ICIs) have transformed the management of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), yet most patients eventually develop resistance. Investigational immunotherapy strategies beyond checkpoint blockade are being explored, but their clinical activity and associated biomarkers remain poorly defined. To evaluate the safety, antitumor activity, and biomarkers associated with novel immunotherapy agents in patients with recurrent or metastatic HNSCC treated in early-phase clinical trials. This retrospective cohort study was conducted at The University of Texas MD Anderson Cancer Center Department of Investigational Cancer Therapeutics and included adult patients (aged ≥18 years) with advanced HNSCC treated with novel immunotherapy agents in early-phase clinical trials between January 1, 2015, and May 31, 2025. Patients were followed up from treatment initiation until disease progression, death, or last clinical contact. Treatment with investigational immunotherapy agents administered in early-phase clinical trials. The primary outcomes included treatment-related adverse events, objective response rate (complete or partial response), clinical benefit rate (complete or partial response or stable disease lasting ≥6 months), progression-free survival, and overall survival. Logistic regression was used to evaluate biomarkers associated with the clinical benefit rate, including clinical, genomic, and treatment-related variables, while survival outcomes were estimated using the Kaplan-Meier method. The sample included 158 patients (median [range] age, 60.7 [25.7-84.6] years; 136 male [86.1%]). The oropharynx was the most common primary site (94 patients [59.6%]). Patients had received a median of 3 prior lines (range, 0-8 prior lines) of systemic therapies, and 126 patients (79.7%) had prior ICI exposure. A total of 91 of 153 patients (59.5%) had human papillomavirus-positive tumors, and PD-L1 combined positive score of at least 1 was observed in 67 of 87 patients (77.0%). Most patients received combination immunotherapy (106 [67.1%]), with a median treatment duration of 2.3 months (range, 0.1-19.7 months). Treatment-related adverse effects occurred in 85 patients (53.8%), including grade 3 or higher events in 23 patients (14.6%). The overall response rate was 7.7% (12 patients), and the clinical benefit rate was 16.1% (25 patients). Bispecific antibodies were associated with improved clinical benefit (odds ratio, 1.95; 95% CI, 1.23-4.15), whereas PIK3CA alterations were associated with reduced benefit (odds ratio, 0.03; 95% CI, 0.00-0.51). Median progression-free survival was 2.3 months (95% CI, 2.0-2.9 months) and median overall survival was 8.3 months (95% CI, 7.2-11.0 months). This retrospective cohort study of heavily pretreated patients with HNSCC treated in early-phase clinical trials found that novel immunotherapy agents may have manageable toxic effects but modest antitumor activity. Bispecific antibodies may have encouraging activity while genomic alterations may help inform treatment stratification.
Development of organ dysfunction or death is still common in patients undergoing cardiac surgery. Yet, current risk stratification tools fail to adequately incorporate both preoperative vulnerability and immediate postoperative physiological derangements. This study aims to develop a predictive model integrating these critical timepoints to identify high-risk patients for presence of organ dysfunction or death 48 hours after surgery. This is a post hoc analysis of an international, multicenter, randomized, controlled trial in patients undergoing cardiac surgery (n=1394). Prespecified patient characteristics (age, Clinical Frailty Scale, at nutrition risk, combined procedures, urgent surgery, moderate-severe chronic kidney disease, left ventricular ejection fraction, European System for Cardiac Operative Risk Evaluation II, cardiopulmonary bypass duration, sex, Charlson Comorbidity Index, and Sequential Organ Failure Assessment score) were included in logistic regression models employing bootstrap validation. A total of 434 (31.1%) patients had organ dysfunction or died 48 hours after surgery. The preoperative model identified Clinical Frailty Scale, nutrition risk, urgent surgery and European System for Cardiac Operative Risk Evaluation II as significant predictors of organ dysfunction or death 48 hours after surgery (optimism-corrected area under the receiver operating characteristic curve, 0.644 [95% CI, 0.610-0.678]). Incorporation of postoperative variables (Sequential Organ Failure Assessment score at intensive care unit admission, and cardiopulmonary bypass duration) improved predictive performance (area under the receiver operating characteristic curve, 0.773 [95% CI, 0.745-0.801]). Incorporation of variables collected the day of surgery substantially improved the ability to predict organ dysfunction or death 48 hours after surgery compared with using presurgical variables only. This pragmatic, clinically actionable model may enable targeted resource allocation and personalized interventions and may provide a stratification tool for future research. URL: clinicaltrials.gov; Unique Identifier: NCT02002247.
Osteoporosis increases fracture risk in older adults and is associated with impaired health-related quality of life (HRQoL). Osteoporosis-specific HRQoL instruments are widely used, but their measurement performance in older populations has not been comprehensively synthesised. To systematically identify and synthesise development and validation studies of osteoporosis-specific HRQoL instruments for older adults, and to appraise their measurement properties using COSMIN criteria and a modified GRADE approach to inform instrument selection for clinical trials, routine care, and research. Systematic review. Community-dwelling; Long-term care facility; Primary care facility. Older persons aged 60 years or over. We searched Medline (Ovid), Embase, PsycINFO (Ovid), and AMED (Ovid) from inception to August 2024. We extracted and appraised evidence for COSMIN-defined measurement properties: content validity, structural validity, internal consistency, cross-cultural validity or measurement invariance, reliability, measurement error, criterion validity, hypothesis testing for construct validity, and responsiveness. Methodological quality was assessed using the COSMIN Risk of Bias checklist, measurement properties were rated against COSMIN criteria for good measurement properties, and certainty of evidence was graded using a modified GRADE approach. Forty-three studies reported the development and/or validation of nine osteoporosis-specific HRQoL instruments; language and version adaptations resulted in 15 instrument variants. Content validity was the most prominent limitation: only OPTQoL and the English Mini-OQLQ demonstrated sufficient evidence for multiple content validity components, while most widely used instruments lacked adequate evidence on item relevance, comprehensiveness, or comprehensibility. Evidence for internal structure was limited, with structural validity sufficient for ECOS-16 and QoLOS-NVFX, insufficient for QUALEFFO-41, and indeterminate for most other instruments. Cross-cultural validity and measurement invariance were almost entirely unexamined. By contrast, reliability and hypothesis testing for construct validity were more consistently supported, often with moderate-to-high certainty. Measurement error, interpretability, and responsiveness were poorly reported across instruments. The evidence base supports purpose-driven selection of osteoporosis-specific HRQoL instruments rather than a single preferred instrument. Across included studies, ECOS-16 shows the most consistently supported measurement properties in older adults for longitudinal assessment, although important evidence gaps remain (notably measurement error and cross-cultural validity). When brevity is the primary feasibility constraint in routine care, the Mini-OQLQ may be considered; however, evidence for responsiveness is limited.
Feeding difficulties and swallowing dysfunction are common clinical problems in children with inherited metabolic diseases (IMDs); however, evidence in the literature remains limited. This cross-sectional study aimed to evaluate food refusal and swallowing function in children with IMDs receiving diet therapy and to investigate their relationship with malnutrition risk. This cross-sectional study included 49 children aged 2-6 years diagnosed with carbohydrate (30.6%) and protein (69.4%) metabolism disorders. The STRONGkids tool was used to evaluate malnutrition risk, while nutritional classification was based on WHO-derived anthropometric Z-scores. Swallowing function was assessed using the Pedi-EAT-10, and food refusal behaviors were evaluated with the Food Refusal Scale. Sociodemographic characteristics, dietary habits and anthropometric measurements were recorded. Logistic regression analysis was performed to determine independent predictors of high malnutrition risk. According to STRONGkids results, 85.7% of the participants were at moderate risk and 14.3% were at high risk of malnutrition. Higher Pedi-EAT-10 scores were significantly associated with early complementary feeding, prolonged feeding duration, extended total daily feeding time, and reported feeding difficulties (p < 0.05). Logistic regression analysis demonstrated that Pedi-EAT-10 (OR: 1.125; 95% CI: 1.025-1.236; p = 0.013), selectivity (OR: 1.241; 95% CI: 1.110-1.645; p = 0.044), and neophobia (OR: 1.430; 95% CI: 1.117-1.829; p = 0.005) were independently associated with high malnutrition risk. Food refusal behaviors and swallowing dysfunction are significantly associated with malnutrition risk in children with IMDs. Comprehensive assessment of feeding behavior and swallowing function may facilitate early identification of nutritional vulnerability and support individualized dietary management strategies.
Low diet diversity is the major contributor to micronutrient inadequacy among children, underscoring a need for a rapid assessment tool to assess micronutrient adequacy. This study aimed to (i) develop a context-specific diet diversity score (DDS) tool (ii) evaluate the performance of the DDS scoring system against mean probability of adequacy for 10 micronutrients, 5 biomarkers of micronutrient status and (iii) identify an optimal DDS cut-off by applying minimum portion size threshold to support its potential use as a practical screening tool. A cross-sectional study was conducted among 6-10-year-old children (n = 76) in two villages of Ghatkesar sub-district, Telangana. Portion sizes of commonly consumed fruits and vegetables were standardized. Data on household demographics, anthropometry, and biomarkers of micronutrient status were collected using a pretested questionnaire and standardized protocols. Three non-consecutive 24-hour-dietary-recalls were obtained using the weighment method. DDS was developed based on the nutrient content of consumed foods; minimum intake thresholds of 0.1 g, 5 g and 10 g was applied while scoring. Mean probability of adequacy (MPA) for 10 micronutrients was estimated using ICMR-EAR values. Correlations of DDS with MPA and biomarkers were examined, and sensitivity and specificity were assessed using ROC curves, considering MPA ≥ 70% as adequate. The DDS included 13 food groups. Mean DDS (5 g threshold) was 8.67 ± 1.50 and correlated significantly with MPA (r = 0.58), and hemoglobin (t = 2.07). A DDS-5 g cut-off of ≥10 predicted MPA > 70%, with an AUC of 0.89. The DDS showed good predictive performance for micronutrient adequacy, but requires further field validation before programmatic use.
Oral hydrolyzed collagen (HC) supplementation is widely recommended for improving age-related skin changes. However, clinical evidence remains inconsistent. This systematic literature review (SLR) synthesizes the findings from randomized controlled trials (RCTs) evaluating the efficacy, safety, and quality of life (QoL) outcomes of HC supplementation in adults. We systematically searched Embase, MEDLINE, and MEDLINE In-Process from inception through April 1, 2023, to identify RCTs assessing oral HC versus placebo or active comparators. Outcomes of interest included skin hydration, elasticity, wrinkles, transepidermal water loss (TEWL), safety, and QoL. Risk of bias was assessed using Cochrane Risk of Bias v2.0, and results were synthesized descriptively. Twenty-five RCTs (sample sizes ranging from 13 to 236 participants) were included. While most studies were conducted in healthy volunteers, seven studies enrolled patients with chronic disease conditions. HC supplementation demonstrated significant improvements over placebo in key skin parameters: skin hydration (improved in 10 of 15 trials), skin elasticity (10 of 13 trials), and wrinkle depth or volume (9 of 10 trials). Results regarding TEWL were less consistent. HC supplementation was generally well-tolerated, with a low incidence of adverse events. QoL outcomes, assessed in seven studies primarily among osteoarthritis or rheumatoid arthritis patients, showed variable improvements depending on the assessment tool and study population. The majority of included trials were rated as having a high risk of bias. Preliminary evidence suggests that HC supplementation may offer dermatological benefits, but high-quality, standardized, adequately powered, and longer-term RCTs are needed to confirm its efficacy and safety.
Management of cryptoglandular anal fistula is characterised by wide variation in diagnostic strategies, surgical techniques and outcome reporting, limiting comparison between studies and hindering evidence-based guideline development. This study aims to implement a standardised core outcome measurement set within a large international observational framework and to evaluate the feasibility of a scalable digitally supported model for global collaborative surgical research. Cryptoglandular anal fistula treatment is a prospective, international, multicentre observational study comprising two components: a short-term audit capturing clinician-reported outcomes at 3 months and a long-term cohort capturing clinician- and patient-reported outcomes over twelve months. Adults undergoing surgery for primary or recurrent cryptoglandular anal fistula are eligible, excluding non-cryptoglandular aetiologies. Data are collected using secure electronic case report forms and digitally administered patient-reported outcome measures, with paper alternatives available where required. Outcomes are defined according to the Anal Fistula Core Outcome Measurement Set and include clinical and radiological healing, recurrence, complications, reintervention, development of additional fistulas, symptoms, psychological impact of treatment, continence, quality of life and additionally work productivity. The study was designed around a predefined nine-step framework, including multidisciplinary coordination, central ethical approval to support local submissions, artificial intelligence-assisted translation of study materials with native review and implementation of secure digital data capture systems. Based on previous European Society of Coloproctology studies and expected centre volumes, the audit arm aims to include approximately 1000 patients and the cohort arm 500 to 750 patients. Central ethical approval has been obtained from the Medical Ethics Review Committee of the Maastricht University Medical Centre+ under METC 2024-0374 (audit arm) and METC 2024-0361 (cohort arm) with local approvals or waivers secured in participating countries according to national regulations. Written informed consent is obtained for cohort participation. Results will be disseminated through peer-reviewed publications and international conferences, with the aim of informing future guideline development and supporting patient-centred care in cryptoglandular anal fistula management.
Vitamin D is essential for bone and metabolic health. Deficiency remains a global health issue, particularly among older adults and ethnic minorities with darker skin pigmentation. Data on circannual variation these groups remain sparse. This study reports vitamin D status in older adults ( ≥ 65 years) and ethnic adults ( ≥ 18 years, Fitzpatrick classes IV-VI) in northern Britain, assessed during the screening phase of a supplementation trial. Participants were screened for inclusion between December 2024 and August 2025. Serum 25-hydroxyvitamin D (25(OH)D) was assessed in dried blood spots followed by LC-MS/MS analysis. In total, 299 participants were screened. Vitamin D insufficiency or deficiency ( < 50 nmol/L) was noted in 54.8% of older adults and 72.1% of ethnic individuals. These rates did not decline during summer months. These findings highlight persistently high rates of vitamin D insufficiency across high-risk groups in northern Britain and underscore the inadequacy of sunlight exposure as a corrective measure.
Especially, the coxsackievirus B group of enteroviruses has been linked to the development of islet autoimmunity and type 1 diabetes in genetically susceptible individuals. Our aim was to study the possible associations of 10 different microbial infections with islet autoimmunity in a large international prospective study. In a nested case-control study within the TRIGR study, follow-up serum samples from 240 islet autoantibody-positive case children and 436 age- and country-matched control children were analysed for IgG class antibodies against 10 different respiratory and gastrointestinal microbes using an enzyme immunoassay, and for neutralising antibodies against all six coxsackievirus B types. The samples were obtained at several time points prior to and at the time of seroconversion for multiple islet autoantibodies. All children had a first-degree relative with type 1 diabetes, and they carried risk-associated HLA-DQ alleles. Coxsackievirus B5 was associated with an increased risk of islet autoimmunity (OR 2.22, 95% CI 1.29-3.80, p = 0.004, corrected p = 0.024), which remained after adjustment for HLA, sex, and maternal type 1 diabetes. This association was particularly seen for infections occurring more than 12 months (OR 2.02, 95% CI 1.06-3.84, p = 0.032) and 0-6 months (OR 2.66, 95% CI 1.11-6.35, p = 0.028) before the first detection of multiple islet autoantibodies. After correction for multiple comparisons, none of the other viruses showed an association with islet autoimmunity. This study supports previous evidence of the risk association of coxsackievirus B infections. These results support the role of certain virus infections as possible modulating factors in the pathogenesis of type 1 diabetes.
Gut dysbiosis is a characteristic feature of malnutrition; however, a standardized microbial index for assessing gut health in community settings is lacking. This study aimed to assess the relative abundance of key bacterial communities in underweight, obese, and normal-weight children and adolescents using quantitative polymerase chain reaction (qPCR). We conducted a 12-month case-control study (February 2023-February 2024) in Hyderabad, India, involving 70 children aged 8-18 years. Participants were categorized as thin (Body Mass Index-for-age Z-score (BAZ) < -2 SD; n = 23), normal-weight (n = 24), or obese (BAZ > +2 SD; n = 23). Socio-demographic and anthropometric data were collected. Fecal samples were analyzed for relative abundance of target bacteria species using quantitative PCR (Roche Light Cycler 480). Conditional and unconditional logistic regression models were used to assess associations between bacterial abundance and nutritional status. Obese children had higher odds of Lactobacillus spp. (matched odds ratio [mOR] 12.92, 95% CI 1.48-112.86; p = 0.02) and Faecalibacterium prausnitzii (mOR 5.49, 95% CI 1.06-28.49; p = 0.04) compared with normal-weight children. Bacteroides spp. were more abundant in obese (mOR 11.10, 95% CI 1.15-107.20; p = 0.04) and thin children (mOR 8.10, 95% CI 0.87-75.99; p = 0.07). In contrast, Bifidobacterium spp. showed lower abundance in both obese (mOR 0.006, 95% CI 0.00-0.07) and thin children (mOR 0.54, 95% CI 0.01-0.47) relative to normal-weight peers. This study identified distinct patterns of gut bacterial dysbiosis, characterized by altered relative abundances of Lactobacillus, Faecalibacterium prausnitzii, Bacteroides, and Bifidobacterium, among children and adolescents across different nutritional statuses. These microbial signatures may serve as potential early indicators of malnutrition-related dysbiosis and warrant further investigation.
Metabolic alterations are a fundamental part of critical illness, but changes during prolonged ICU stay are inadequately understood. This study aimed to describe longitudinal trends in energy expenditure and substrate utilisation in persistent critical illness, defined as an ICU stay of ≥ 10 days. This prospective, observational, multicentre study was conducted from 2022 to 2024 at five European and two Australian ICUs. The primary outcome was the change in energy expenditure over time. Adult patients with ≥ 1 indirect calorimetry and length of stay ≥ 10 days were included. Clinical parameters, markers of inflammation and protein catabolism were collected at each measurement. Longitudinal trends were analysed using mixed-effects models with restricted cubic splines. Latent class analysis was performed with identical covariates. 433 patients with 1194 measurements were included. The mean age was 56 years, and 70% were male. An initial increase in energy expenditure, peaking around day 10, and subsequent decline were found (p < 0.001), remaining significant after adjustment for sex, age, CRP, FiO2, presence of fever, BMI, renal replacement therapy, administered protein as fixed effects and patient and site as random effects (p = 0.001, conditional R² = 0.76). The association between the respiratory quotient and time was non-significant (p = 0.067). The urea: creatinine ratio increased over the first 10 days (p < 0.001). Latent class analysis identified three trajectories of energy expenditure: hypo-, normo-, and hypermetabolism (entropy 0.63). Mean energy expenditure follows a biphasic pattern during prolonged ICU stay, with the inflection point coinciding with the empirical onset of persistent critical illness. Further research is required to validate potential metabolic subgroups and explore their biological correlates in this population. The study, including the statistical analysis plan, was prospectively registered at clinicaltrials.gov (NCT05124860, registered 2021-11-15).