Search Results (1,232)

Background: The causal role of homocysteine (tHcy) in atrial fibrillation (AF) is unclear. Objectives: To (re)explore the causal effect of tHcy in non-valvular AF (NVAF). Methods: In a case–control study in overweight/obese adults, cases were patients with NVAF and controls were their peers without AF. They were assessed for clinical, laboratory, and echocardiographic particulars and were genotyped for MTHFR 677C>T (rs1801133), PITX2 C>T (rs2200733), and KCNE1 112A>G (rs1805127) polymorphisms. We employed a conventional case–control, mediation analysis, and one-sample Mendelian randomization (MR) analyses to evaluate forward and reverse tHcy-NVAF associations. Results: We enrolled 180 cases and 179 controls. With an extensive confounder control (i) the MTHFR 677C>T variant allele associated with higher tHcy; (ii) PITX2 C>T variant allele associated with NVAF while KCNE1 112A>G did not; (iii) MTHFR variant associated with NVAF indirectly, through tHcy assuming wild type but not variant genotype (exposure–mediator interaction); (iv) considering all subjects, tHcy associated with NVAF through the effect on renal function and NT-proBNP levels (no exposure–mediator interaction); (v) considering MTHFR wild-type subjects (n = 160), tHcy “directly” strongly associated with NVAF, and considering variant carriers (n = 199), it indirectly associated with NVAF and directly tended to associate with a lower probability of NVAF; (vi) in MR analysis (MTHFR SNP instrument), tHcy associated with NVAF; and vii) mediation and MR analyses [PITX2 SNP (exposure/instrument)—NVAF, (mediator/exposure)—tHcy outcome] excluded the reverse tHcy-NVAF association. Conclusions: Data strongly support the causal role of tHcy in NVAF in overweight/obese patients and suggest that the effect might be modified by the MTHFR 677C>T variant allele. Full article

Background/Objectives: Pseudoarthrosis continues to be a public health problem; however, in our country, information is scarce, particularly when talking about the clinical and sociodemographic characterization of the Mexican population with pseudoarthrosis. Methods: In this study, clinical and sociodemographic characteristics such as sex, age, educational level, nutritional status, comorbidities, affected bone, fracture characteristics, degree of exposure, and waiting time for the patient to undergo surgery were analyzed. Results: A total of 267 patients were included in the present study. A higher frequency of men (53.6%) was identified compared to women, and the main age group was 46–75 years (50.1%). The main comorbidities identified in our population were smoking (n = 141; 52.8%) and osteoporosis (n = 84; 31.5%). When evaluating the clinical characteristics of pseudoarthrosis, the tibia (n = 65; 24.3%) and radius (n = 54; 20.2%) were the main bones affected. Fracture exposure could be identified in 17.65% (n = 47) of the population, and the main grade of involvement was II (46.8%). Regarding the prevalence of the affected bone, the tibia was the main one, with 13.5% (9.38–17.58%) female patients, 12.7% (8.73–16.73%) with overweight, 18.0% (13.37–22.59%) with osteoporosis, and 14.2% (10.04–18.42%) with a history of smoking. Conclusions: In our cohort, we identified a high prevalence of the tibia as the affected bone, while overweight, obesity, osteoporosis, and smoking were the clinical and sociodemographic characteristics that characterized our population. The findings of this study lay the groundwork for understanding the clinical and sociodemographic context of a Mexican cohort with nonunion. Full article

Background: Migraine is a common, disabling neurological disorder with substantial genetic and environmental contributions. Dietary exposures are widely discussed by patients and clinicians as potential triggers or modifiers of attack frequency and severity. We synthesized contemporary evidence on dietary patterns, specific nutrients, and elimination strategies relevant to migraine prevention and management. Methods: We performed a narrative review of PubMed and Google Scholar (inception–August 2025) using combinations of “migraine”, “diet”, “nutrition”, “ketogenic”, “Mediterranean”, “omega-3”, and “gluten”. We prioritized randomized/controlled studies, recent systematic reviews/meta-analyses, and representative observational studies; evidence quality and applicability were appraised descriptively. Results: Higher adherence to a Mediterranean-style diet is associated with lower migraine frequency and disability in observational cohorts. Very low-calorie ketogenic diets significantly reduced monthly migraine attack frequency compared with isocaloric non-ketogenic comparators in an adult randomized controlled trial of participants with overweight or obesity (≥50% responder rate: 74% vs. 6%). Additional supportive evidence from uncontrolled studies, including those involving medium-chain triglyceride supplementation, further corroborates these findings. Omega-3 fatty acids (EPA/DHA) show prophylactic benefit in randomized trials and network meta-analyses, with favorable tolerability. Gluten-free diets may improve headaches in celiac disease and may help selected non-celiac patients. Alcohol (especially red wine) and high, irregular caffeine intake are frequently reported triggers, while evidence for specific foods/additives remains inconsistent. Weight loss and regular physical activity may further reduce burden in people with obesity. Conclusions: Current evidence supports recommending Mediterranean-style eating, consideration of omega-3 supplementation, and selective trials of ketogenic or elimination approaches in appropriate patients, alongside weight management and lifestyle optimization. High-quality, longer-duration RCTs using standardized dietary protocols and adherence biomarkers are needed to define dose–response relationships and enable personalized nutrition in migraine. Full article

Background: Oral semaglutide is the first oral GLP-1 receptor agonist approved for treating patients with type 2 diabetes mellitus (T2DM). This real-world retrospective study evaluated its effectiveness and tolerability in patients requiring a third-line antidiabetic agent due to poor glucoregulation. Methods: Adult patients with T2DM who were taking oral semaglutide and were monitored at tertiary diabetes centers in Croatia were identified through electronic medical records between October 2022 and December 2024. Patients’ data were included in the analysis if they had been on oral semaglutide for at least six months. Results: A total of 163 patients (72 females and 91 males) were recruited, with 96.9% classified as overweight or obese. Among them, 145 had a BMI greater than 30 (mean BMI: 34.18 ± 4.60). The addition of oral semaglutide to their treatment regimen resulted in significant reductions in BMI, HbA1c, and both postprandial and fasting blood glucose levels, as well as in AST and ALT levels (all p < 0.05). There was also an increase in HDL levels (p = 0.007). The side effects observed were consistent with those previously recognized. Conclusions: This study demonstrates that oral semaglutide is safe and effective for glycemic and extraglycemic management in a real-world setting when used as a third-line agent. The best outcomes in terms of weight and HbA1c reduction can be expected when it is introduced early, ideally within the first five years of diabetes duration, and particularly in patients who are insulin naive. Full article

Background: During adolescence, the brain is undergoing anatomical and physiological maturation processes with changes to cognitive development. However, in adolescents with phenylketonuria (PKU), executive function and mental health are adversely affected by high blood phenylalanine (Phe) levels. Objectives: We aim to describe clinical outcomes in adolescents with PKU. Methods: Cross-sectional questionnaires were performed on quality of life (EuroQol “EQ-5D-5L” questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale- HADS) and food neophobia in a single PKU centre. Retrospective data on metabolic control (previous 12 months) and medical history, and current data on anthropometry, dietary treatment, and comorbidities were collected. Results: In total, 33 adolescents with PKU participated with a mean age of 13.5 ± 1.3 y (16 boys, 17 girls). All were on a Phe restricted diet, with 3 also prescribed sapropterin. Questionnaires were self-completed by n = 25/33 (76%) adolescents. A mean of 36 ± 26 blood Phe spots were performed over 12 months. There was a mean of 83% of blood Phe < 600 µmol/L and 49% < 360 µmol/L. In total, 39% (n = 13/33) of adolescents were overweight/obese, 18% (n = 6/33) overweight and 21% (n = 7/33) obese. Medical history documented mental health disorders (anxiety/depression) in 7 cases, low mood, suicidal thoughts and self-harming in 5, and neuro diversity in 4 (autism and/or attention-deficit hyperactivity disorder (ADHD). In the HADS questionnaire, 12% (n = 3/25) of adolescents scored borderline abnormal for anxiety and 12% (n = 3/25) abnormal for depression. Mean anxiety scores for females were almost twice as high compared to males. No significant correlation was found between blood Phe and anxiety/depression scores. However, higher Phe levels showed a trend towards reduced enjoyment and emotional responsiveness, including lower scores on measures of pleasure, cheerfulness, and emotional reactivity. Although not statistically significant, these findings suggest a potential subtle association between poorer metabolic control and mood disturbances in adolescents with PKU. No food neophobia was identified in our study. Conclusions: Adolescents with PKU presented with high levels of depression and anxiety. Long term studies focusing on quality of life and neurocognition even when achieving the PKU European guidelines are necessary. Different therapeutic options are needed to improve the outcome of patients with PKU. Full article

Lifestyle-related diseases, such as overweight/obesity, diabetes mellitus type 2 (T2DM), cardiovascular disease, or osteoarthritis, are a major health burden in Western societies. Due to common risk factors, most patients suffer from multimorbidity, i.e., have been diagnosed with more than one of these diseases. Physical activity (PA) is known to have a positive effect on all of these diseases; however, little is known about the effects of PA on patients with multimorbidity. In particular, so far, no reliable biomarkers have been found to predict and monitor the effects of PA-based lifestyle intervention programs on these subjects. Employing a metabolomics approach with dried blood spots, we analyzed the concentrations of different metabolites in subjects with multimorbidity over the course of the lifestyle intervention program MultiPill-Exercise. We found increased concentrations of all tested amino acids (AAs), total carnitine (Cx), and short- (C2-C6) and long- (>C12) chain acylcarnitines (ACs) after 12 weeks (t1) and/or 24 weeks (t2) of intervention. When correlating baseline (t0) metabolite concentrations with changes in physiological and clinical parameters, we observed associations of various metabolite concentrations with changes in metabolic and cardiovascular parameters. When analyzing metabolite acute reactions in response to exhaustive exercise (ergometer test), however, few overall changes were observed. Nevertheless, a significant negative correlation was found between the mobilization of medium-chain acylcarnitines (MC-ACs) at t2 and changes in peak power output (PPO) between t0 and t2. Taken together, these data suggest that specific AAs and ACs might be candidate biomarkers to predict and monitor the effects of PA-based lifestyle intervention programs in subjects with multimorbidity, a hypothesis that should be further tested in larger cohorts. Full article

Objectives: The systematic increase in the number of overweight and obese people in recent years has led to the recognition of this condition as a chronic, non-infectious disease of civilization, declared a global epidemic by WHO in 1997. This phenomenon is particularly dangerous in children, because it negatively affects their later existence in the health, mental and social spheres. This phenomenon is particularly concerning in the pediatric population, as it may have long-term adverse effects on physical health, psychological well-being, and social functioning. Objective: The aim of this study was to assess anthropometric parameters and physical fitness using the EUROFIT test in children and adolescents diagnosed with obesity. Materials and Methods: The study group consisted of 123 pediatric patients attending the Endocrinology and Diabetology Clinic and Pediatric Rehabilitation IP-CZD aged 8–16 (64 boys—52% and 59 girls—48%) with diagnosed simple obesity. Obesity was diagnosed according to the CDC standard using percentile charts from the OLAF study. Physical fitness was assessed using the EUROFIT test using 8 samples, and body mass composition was examined using the bioimpedance method with the BC 418 Tanita analyzer. Results: The results of our own research obtained in this study were compared to population standards. The total results of the EUROFIT test in the study group were statistically significantly lower than the norm. The results of the balance, upper limb movement speed, jumping, trunk strength, functional strength and agility tests were lower than the norm, the flexibility result was within the norm, and only hand strength was higher than the norm. In 4 out of 8 fitness tests, girls achieved significantly better results than boys. Conclusions: Reduced physical fitness is characteristic of children and adolescents with simple obesity. Worse physical fitness shows significant correlations with the results of anthropometric measurements. Full article

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication of SARS-CoV-2, often with cardiac involvement. Myocardial strain imaging may detect dysfunction missed by conventional echocardiography. The objectives of this study are to characterize cardiac manifestations of MIS-C and assess the value of strain imaging in children with preserved and reduced left ventricular ejection fraction (LV-EF). Methods: We retrospectively analyzed 22 MIS-C patients admitted between September 2020 and January 2024, all with cardiac involvement. Clinical, laboratory, and echocardiographic data—including 2D and speckle-tracking strain—were collected at the day of worst dysfunction (DWD) and discharge (DD) and compared with 22 matched controls. Results: Median age was 4.65 years; 59% male; 45% overweight/obese. LV systolic dysfunction (LV-EF < 50%) occurred in 54.5%, coronary abnormalities in 36.4%, and pericardial effusion in 95.5%. LV global longitudinal strain (LVGLS) was significantly lower than controls at the DWD (−15.45 ± 4.76%, p < 0.0001) and DD (−20.63 ± 4.66%, p = 0.014). Strain abnormalities persisted despite LV-EF recovery, and even patients with preserved LV-EF showed significant segmental strain reduction. LVGLS and apical infero-septal strain were strongest predictors of reduced LV-EF. Conclusions: MIS-C often causes systolic dysfunction and coronary changes, but strain imaging reveals persistent subclinical myocardial injury. Long-term cardiac monitoring is warranted. Full article

Background/Objectives: Lipedema is a chronic, progressive disorder of the adipo-fascial tissue characterized by abnormal subcutaneous fat accumulation, inflammation, fibrosis, pain, and edema. Despite its considerable impact on patients’ quality of life, it remains underdiagnosed. Recent studies have suggested a potential overlap between lipedema and hypermobility spectrum disorders (HSDs), both involving connective tissue dysfunction. This work explores the shared pathophysiological features of lipedema and HSD, highlighting clinical correlations, comorbidities, and the need for integrated diagnostic and therapeutic approaches. Methods: A cross-sectional observational study was conducted through an online survey targeting individuals with lipedema and a control group with lymphedema. The questionnaire assessed symptoms typically associated with HSD, including musculoskeletal, gastrointestinal, urogynecological, vascular, and neuropsychological manifestations. Descriptive statistics were used to evaluate clinical patterns in both groups. Results: Among the lipedema patients, 44% reported joint hypermobility and 60% recalled being hypermobile during childhood. High rates of pediatric overweight (50%), low muscle tone (55%), and exercise-induced fatigue (70%) were observed. Adult symptoms included joint pain (notably in the ankles, knees, cervical spine, sacrum, and feet), digestive issues (50%), and thyroid disorders (24.4%). Compared with the control group, patients with lipedema showed significantly more connective tissue-related motor deficits and systemic symptoms. Conclusions: Connective tissue laxity may play a critical role in the pathogenesis of lipedema, contributing to multisystemic manifestations through vascular, lymphatic, gastrointestinal, and musculoskeletal involvement. The high prevalence of HSD-like features calls for a paradigm shift in the understanding of lipedema as a systemic disorder. Early identification of connective tissue alterations, especially in children with familial predisposition, could enable timely interventions, potentially mitigating disease progression. A multidisciplinary, evidence-based approach is essential for accurate diagnosis and effective management. Full article

Background and Objectives: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic procedure that has demonstrated both safety and effectiveness in the treatment of obesity. By reducing the stomach’s volume without the need for surgical incisions, ESG promotes weight loss and can improve obesity-related comorbidities. However, patient responses to ESG can vary significantly. Materials and Methods: A comprehensive search was performed on PubMed, Embase, and Cochrane for studies with endoscopic sleeve gastroplasty; the main outcomes of interest are BMI, weight loss, and postinterventional complications. The search strategy employed a combination of keywords and Medical Subject Heading (MeSH) terms, including “endoscopic sleeve gastroplasty,” “endoscopy,” and “overweight”. To ensure the thoroughness of the review, additional manual searches of key journals and the reference lists of identified studies were performed. Grey literature, such as dissertations and conference abstracts, meta-analysis, and systematic reviews, was excluded to maintain a focus on peer-reviewed evidence. Duplicate records were identified and removed using Rayyan software to streamline the screening process. The I2 test was employed for heterogeneity assessment, while the risk of bias was evaluated utilizing ROBINS-I. Results: Our literature search resulted in the inclusion of 38 studies. Endoscopic sleeve gastroplasty for weight loss is important since it is more effective than pharmacological treatments and lifestyle changes and presents lower adverse event rates compared to bariatric surgery. Long-term weight loss outcomes varied, with total body weight loss ranging from 16% to 20.9% over a period from 2 to 5 years, while excess weight loss ranged from 13% to 79%. Revisional procedures showed higher failure rates, with up to 34.3% of patients experiencing insufficient weight loss. Most interventions led to clinically significant and sustained weight loss, though variability in outcomes highlights the need for further research to optimize long-term weight management strategies. Conclusions: Endoscopic sleeve gastroplasty (ESG) emerges as a promising minimally invasive option for weight loss, offering significant improvements in both weight reduction and obesity-related comorbidities, such as diabetes, hypertension, and dyslipidemia. Full article

Background: Appendiceal adenocarcinoma is a rare malignancy, and data guiding its systemic treatment in metastatic settings are limited. This study aimed to determine the clinical outcomes, treatment efficacy, biomarkers, and prognostic factors in patients with metastatic or unresectable appendiceal adenocarcinoma receiving palliative chemotherapy. Methods: We retrospectively reviewed patients with metastatic appendiceal adenocarcinoma who received first-line palliative systemic chemotherapy at the Peter MacCallum Cancer Centre between January 2015 and December 2024. Results: Of the 40 patients included, fluoropyrimidine-based doublet regimens were most commonly used (82.5%) in first-line setting, achieving an objective response rate of 39.4%. Median overall survival (OS) was 21.6 months, and median first-line progression-free survival (PFS) was 8.9 months. 22 patients (55.0%) received second-line treatment. Median OS and PFS were 21.6 and 8.9 months, respectively, among patients treated with oxaliplatin-based doublet regimens, and 66.4 and 10.8 months, respectively, among those treated with irinotecan-based doublet regimens. Molecular biomarker testing was performed in 35 patients (87.5%). KRAS and NRAS mutations were identified in 68.6% and 2.9% of tested patients, respectively. Factors associated with poorer OS included male sex, elevated carcinoembryonic antigen levels, and overweight status. Bevacizumab use was not clearly associated with survival. Conclusions: Palliative systemic chemotherapy, particularly fluoropyrimidine-based doublet regimens, appears to be a reasonable and effective treatment option for patients with advanced appendiceal adenocarcinoma. Although this study was underpowered for formal comparison, the numerically longer OS and PFS of irinotecan-based regimens are hypothesis-generating and support further prospective evaluation. Molecular profiling emphasizes the need for personalized targeted therapeutic strategies. The identified prognostic factors may help guide risk stratification and patient counseling for treatment planning. Full article

The disease COVID-19, which has befallen mankind in recent years, was a challenge that we had not faced for centuries. The first registered patient case was in China. This review is performed by the inspection of a large body of worldwide investigations conducted in the peak period of the disease’s progress. The disease is spread by airborne droplets and develops mainly with fever, cough, sputum, and shortness of breath. Laboratory tests show leukopenia, lymphopenia, a decrease in the levels of sodium, potassium, and calcium, and an increase in the levels of CRP, LDH, and D-dimer. Radiological changes in most cases are bilateral and of the “ground glass” type in the lower parts of the lungs. The most severe complication of COVID-19 pneumonia is ARDS. The risk groups are people with chronic lung diseases, the elderly, and those who are overweight. This article analyzes and summarizes the main characteristics of SARS-CoV-2 pneumonia in order to better understand and apply better clinical management of this condition. Full article

Objective: The objective of this study was to clarify the connection between BTX-A injections and local changes in skin temperature and to assess the correlation between post-BTX-A injection facial vascular hyperthermia and subcutaneous adipose tissue thickness (SAT) in the frontal area using thermography. Methods: The study involved 30 patients (mean age 42 ± 0.5 years; 18 women, 12 men). Facial skin temperature was measured via thermography (Thermo GEAR G30) before, immediately after, and 20 min after subcutaneous injection of BTX-A with hemagglutinin complex, gelatin (6 mg), and maltose monohydrate (12 mg). SAT development was graded by combined visual-palpation assessment. Statistical analysis included Student’s t-test and the Mann–Whitney U-test. Results: Biphasic thermal response: immediately post-injection: Significant decrease in min (−1.1 °C) and mean (−0.3 °C) facial temperatures (p < 0.05); 20 min post-injection: pronounced increase in mean (+1.5 °C), max (+1.3 °C), and min (+1.6 °C) temperatures (p < 0.001), attributed to BTX-A-induced vasodilation and local inflammation. Subjects with pronounced SAT exhibited significantly higher baseline temperatures (Me = 33.1 °C vs. 29.8 °C; p < 0.001) and more intense hyperthermic responses (+1.6 °C mean increase vs. +1.1 °C in low-SAT group; p < 0.001). Pronounced SAT was predominantly female (10/15; p < 0.05) and linked to higher BMI (33.3% overweight vs. 0% in low-SAT; *p = 0.036*). Conclusions: SAT thickness is a key determinant of post-BTX-A vascular hyperthermia, with pronounced SAT predicting stronger reactions. Practical Recommendation: Targeted local hypothermia (+4 °C to +8 °C for 5–7 min post-injection, adjustable by SAT thickness) mitigates hyperemia, edema, hematoma risk, and potential toxin diffusion, especially in high-SAT individuals. Full article

Introduction: Over the last two decades, obesity has evolved into a global pandemic. Environmental pollutants, as endocrine disruptors, may play a key role in the development of obesity. The study aimed to assess the relationship between the concentration of certain trace elements and heavy metals (Cu, Zn, Mn, Co, Cr and Fe) and ferritin in blood serum, with anthropometric and physiological parameters associated with overweight and obesity in individuals following myocardial infarction and without a previous myocardial infarction. Method: The study was conducted in a group of 146 respondents divided into two groups: a study group (SG) of patients that had a history of myocardial infarction (n = 74) and a control group (CG) of patients that had no history (n = 72). The inductively coupled plasma mass spectrometry was employed to assess the concentration of trace elements and heavy metals. Measurements were taken to determine the anthropometric indices associated with overweight and obesity. Results: In the SG, there was a positive correlation between Cr concentration and body adiposity index (BAI) and a negative correlation between Zn, Zn/Cu, and ferritin level and percentage body fat (FM%). In the CG, there was a positive correlation between Zn concentration and WHtR and between ferritin level and BMI, WC, WHR and WHtR. Additionally, a negative correlation was found between Mn concentration and WHR and ferritin level and BAI and FM%. Conclusions: This study found a link between certain blood concentrations of trace elements and heavy metals and anthropometric and physiological indices associated with overweight and obesity. It, therefore, has substantial implications for public health. Full article

Obesity is a risk factor associated with cardiovascular diseases that may lead to heart failure (HF). However, in HF, overweight and obese patients have longer survival than underweight patients, a phenomenon known as the obesity paradox. MiRNAs play a fundamental role in gene regulation involved in obesity and HF. The main objective of this study was to identify and validate differentially expressed circulating miRNAs in HF–obese and HF–lean patients. This case–control study was carried out in two phases: discovery and validation. In the discovery phase, plasma samples from 20 HF patients and from 10 healthy controls were analyzed using the miRNA 4.0 Affymetrix GeneChip array. Differentially expressed miRNAs were ranked and selected for validation. In this phase, plasma miRNAs -451a, -22-3p, and -548ac from 80 patients and controls were analyzed by qPCR. Target analysis and functional enrichment analysis were performed. When comparing HF–lean and HF–obese groups compared to controls, miRNAs -451a and -22-3p were up-regulated in both discovery and validation phases, while -548ac was down-regulated in the discovery phase and up-regulated in the validation phase, indicating that miRNA changes are independent of obesity. These miRNAs regulate genes and different biological processes associated with metabolic, morphological, and functional outcomes. Full article