Search Results (10,432)

Type 2 diabetes is increasingly prevalent among children and adolescents with overweight or obesity, and although lifestyle interventions remain first-line preventive strategies, long-term adherence and effectiveness are often limited. Metformin has demonstrated efficacy in delaying type 2 diabetes onset in adults at high risk, but its preventive role in pediatric populations remains unclear. This systematic review and meta-analysis aims to evaluate the effectiveness of metformin, alone or in combination with lifestyle interventions, in preventing or delaying type 2 diabetes among children and adolescents with overweight or obesity. The protocol is registered in PROSPERO (CRD42024615622), MEDLINE (PubMed), Embase, Cochrane Library, Scopus, and Web of Science and will be searched from inception to June 2025. Eligible studies include randomized controlled trials, quasi-experimental studies, and prospective cohort studies involving individuals under 18 years of age. The primary outcome is incidence of type 2 diabetes, with secondary outcomes including fasting plasma glucose, HbA1c, insulin resistance, BMI z-score, adherence, and adverse events. Where appropriate, random-effects meta-analyses will be conducted. This review will synthesize current evidence on metformin for pediatric type 2 diabetes prevention and inform future preventive strategies and clinical decision-making. Full article

Background: The UGT1A1 gene is associated with the toxicity caused by SN38, the cytotoxic component of Sacituzumab govitecan (SG) used in the treatment of metastatic triple-negative breast cancer (mTNBC), among other approved indications. In this study, we aimed to analyze the effect of UGT1A1*28 allele on the safety and, secondarily, the effectiveness of SG in mTNBC. Methods: This was a multicenter, ambispective study that included patients treated with SG for mTNBC. Genotyping for UGT1A1*28 was performed using real-time polymerase chain reaction (PCR). Adverse events (AEs) of grade ≥ 2 during the first three cycles were compared between patients who were homozygous mutant (UGT1A1*28/*28) and those with wild-type (WT) or heterozygous genotypes. Effectiveness between the two groups was also compared using progression-free survival (PFS) and overall survival (OS) assessed with the Kaplan–Meier method. Results: A total of 81 patients were included: 37.0% were WT, 55.6% heterozygous, and 7.4% homozygous mutant. All UGT1A1 *28/*28 patients experienced grade ≥ 2 AEs (100% vs. 69.3%; p = 0.109), with a statistically significant association in the case of febrile neutropenia (33.3% vs. 6.7%; p = 0.025), and a trend towards higher rates of anemia and diarrhea (50.0% vs. 17.3%; p = 0.053). Genotype did not influence PFS or OS; however, dose reductions were associated with better survival outcomes. Conclusions: This real-world study shows a correlation between toxicity and the presence of the UGT1A1*28 mutation in patients treated with SG for mTNBC. Improving treatment tolerability through dose reductions may enhance SG effectiveness. These findings support the implementation of UGT1A1 genotyping in routine clinical practice. Full article

Background/Objectives: Recurrent oral ulcers (ROUs) are a common condition that significantly impacts patients’ quality of life. This pilot study was conducted to evaluate the feasibility and preliminary results of using non-thermal plasma (NTP) compared to low-level laser therapy (LLLT) and placebo to treat these ulcers. Methods: A prospective, controlled, randomised, parallel-group pilot study was conducted using a convenience sample of 50 patients with ROUs. Patients were randomly assigned (2:2:1) to one of three groups: NTP (n = 20), LLLT (n = 20), and placebo (n = 10). Feasibility and preliminary data acquisition were the primary goals. Exploratory outcomes included ulcer size reduction and safety profile. This was a single-blinded trial, where participants and outcome assessors were masked to group assignment. Ulcer size, pain perception, and time to complete healing were measured. For statistical analysis, ANOVA was used, with a p-value ≤ 0.05. Results: The groups were comparable at baseline. Exploratory results suggest that NTP demonstrated a promising trend in accelerating healing, with a mean healing time difference of 5.5 days compared to LLLT (2.5 ± 1.9 days vs. 8.0 ± 4.3 days) and 7.1 days compared to placebo (2.5 ± 1.9 days vs. 9.6 ± 5.3 days) (p < 0.001). Regarding pain, NTP provided significant and sustained relief. Patients in the NTP group were asymptomatic on day 2, unlike the LLLT and placebo groups, where pain persisted significantly (NTP VAS score at 1 h: 1.1 ± 2.1 vs. LLLT/Placebo VAS score at 1 h: 3.4 ± 2.4 and 7.3 ± 1.9, respectively) (p < 0.001). NTP was well tolerated, and no adverse events were reported. Conclusions: This pilot study suggests that NTP is a potentially safe and effective therapy for recurrent oral ulcers. Preliminary results indicate that it may accelerate healing and offer superior pain relief, warranting a large-scale clinical trial to confirm these findings. Full article

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An umbrella review was conducted following PRISMA guidelines and registered in PROSPERO. High-quality systematic reviews with meta-analysis evaluating BoNT-A efficacy were identified through five databases up to August 2024. Primary outcomes included monthly headache frequency and severity. Methodological quality and risk of bias were assessed using the umbrella review checklist. Fourteen articles were included. Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Though the adverse events were frequent, BoNT-A was generally well-tolerated. Comparative data suggested superior tolerability versus topiramate and a safety profile like CGRPmAbs. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments. Full article

While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological “instruction sets,” and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing. Full article

Background: Respiratory Syncytial Virus is a predominant source of morbidity and mortality, particularly among babies, the elderly, and immunocompromised patients. Recent developments in RSV vaccines, approved by the FDA for high-risk groups, have highlighted the necessity for post-marketing surveillance to evaluate their real-world safety and efficacy. Method: This study utilized data from the Vaccine Adverse Event Reporting System (VAERS) covering RSV vaccine administration between 2023 and May 2025. The VAERS database reported data on vaccine types, including Arexvy^®, Abrysvo^®, and mRESVIA^® was analyzed for adverse events and vaccination errors. The demographic information, vaccination trends, and hospitalizations post-vaccination among the vaccinated individuals were accessed. Results: The analysis revealed that the most common adverse events were mild, such as injection site pain, erythema, fatigue, and extremity pain. The data also showed a gradual increase in hospitalization rates from 4.8% in 2023 to 7.5% in 2025. Vaccination errors, including inappropriate administration during pregnancy and excess doses, were also observed. A notable trend was the growing proportion of patients who experienced no adverse events, with the highest rate of symptom-free reports seen in 2025 (25.9%). Conclusions: RSV vaccines demonstrate a generally acceptable safety profile based on post-marketing surveillance data. However, the observed increase in hospitalization rates, vaccination errors, and pregnancy-related outcomes warrants continued active surveillance and cautious interpretation. Full article

Background: Metabolically associated fatty liver disease (MASLD) constitutes a major burden. Glucagon-like peptide-1 agonists (GLP-1) could improve hepatic steatosis as well as weight loss. However, the effect of GLP-1 agonists on patients with and without diabetes and the effect of newer drugs (dual and triple agonists) are unclear. Objective: To investigate the effect of GLP-1 agonists, including dual and triple agonists, in patients with metabolic-associated liver steatosis and steatohepatitis, while exploring their effect on patients with and without type 2 diabetes. Methods: We searched PubMed, Scopus, and Web of Science in October 2025 for randomized parallel controlled trials that investigated the effect of GLP-1 agonists in patients with MASLD or metabolic-associated steatohepatitis (MASH). We assessed the quality of the included studies using Cochrane ROB2. We performed the analysis using RevMan 5.4. We performed subgroup analysis based on the status of diabetes, the control group, and the class of GLP-1 agonist (single, dual, or triple). Results: We included twenty studies. Compared to the control group, GLP-1 agonists were associated with a statistically significant increase in the resolution of MASH without worsening fibrosis (RR 3.03, p < 0.0001) and at least one stage of liver fibrosis without the worsening of MASH compared to the control group (RR: 1.45, p < 0.00001). GLP-1 agonists were associated with a statistically significant weight reduction (SMD −1.11, p < 0.0001), glycosylated hemoglobin (SMD −0.81, p < 0.00001), levels of aspartate aminotransferase (SMD −0.48, p = 0.008), and alanine aminotransferase (SMD −0.54, p = 0.008). However, in patients without type 2 diabetes, GLP-1 agonists had no significant effect on weight loss (SMD −0.97, p = 0.12) or improvement in fibrosis (RR 1.54, p = 0.24). There was a statistically significant increase in the overall adverse events (RR 1.10, p < 0.00001), while there was no significant difference in serious adverse events (p = 0.35). Conclusions: GLP-1 agonists improved liver fibrosis, steatohepatitis, weight loss, HbA1c, and liver enzymes in patients with MASLD or MASH. Overall, GLP-1 agonists were associated with a significantly higher risk of adverse events compared to the control, while serious adverse events were comparable between both groups. There was no significant effect on weight loss or improvement in fibrosis in patients without type 2 diabetes. However, there was a limited number of studies in this population. Thus, further research is needed before recommendations can be made for this subgroup. Full article

Background/Objectives: There is limited data regarding the association of anti-drug antibody (ADA) levels with the efficacy of anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). We aimed to investigate the association between antibody to adalimumab (ATA) and antibody to infliximab (ATI) levels and treatment failure in IBD. Methods: This single-center, retrospective cohort study included consecutive IBD patients with ADA evaluated with a drug-tolerant assay between September 2012 and February 2023. A time-to-event analysis was performed for treatment failure, defined as the need for drug discontinuation due to primary non-response, loss of response, a serious adverse event, or an IBD-related surgery. Patients were followed from first positive ADA until treatment failure or the end of the follow-up (May 2024). Results: The study population consisted of 134 patients with IBD [n = 58 (43%) on adalimumab; n = 86, (64%) with Crohn’s disease]. Multiple COX regression analysis identified higher ADA levels to be associated with treatment failure (HR: 1.034, 95%CI: 1.024–1.045, p < 0.001). A ROC analysis identified an ATA and ATI level threshold of 5.2 U/mL (AUC: 0.705; 95%CI: 0.569–0.841; p = 0.003; sensitivity: 64%; specificity: 82%) and 8.8 U/mL (AUC: 0.809; 95%CI: 0.713–0.906; p < 0.001; sensitivity: 69%; specificity: 93%), respectively, to distinguish patients with or without treatment failure. Conclusions: In this large retrospective cohort study, higher levels of ADA were associated with treatment failure to anti-TNF therapy in IBD. Moreover, we identified ATA and ATI level thresholds of 5.2 U/mL and 8.8 U/mL, respectively, to be associated with treatment failure. Full article

Background: Glioblastoma multiforme (GBM), the most aggressive primary brain malignancy in adults, is associated with poor prognosis and recurrence despite standard of care and newer immunotherapies. This warrants exploration of synergistic approaches such as combination immunotherapy for improved tumor control. Methods: We initiated a systematic review of articles from 2015–2025 in PubMed, Embase, Scopus, Cochrane, and Web of Science if they assessed immunotherapy for GBM. Results: We included 49 studies (n = 3002 patients) with no significant demographic differences across publications. Combination immunotherapy regimens demonstrated higher pooled ORRs in limited comparative analyses, though findings were driven by a small number of studies. Single-arm analysis for overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs), and ORR showed no significant differences among the groups. However, treatment–control arm analysis showed pooled ORs of 9.51 for combination immunotherapies and 0.44 in the control group. Conclusions: Combining immunotherapeutics across mechanisms may potentiate immune response effectiveness against GBM. Full article

Saliva substitutes are the standard treatment for dry mouth. This study aimed to evaluate the clinical effectiveness of a novel artificial saliva gel (RSU gel) compared with a commercial product (GC Dry Mouth Gel^®). A randomized, double-blind, two-phase crossover clinical trial was conducted with 37 participants with xerostomia. In the short-term phase, oral wetness, xerostomia scores, and clinical score of oral dryness (CSOD) were assessed up to 60 min after a single gel application. In the short-term repeated-use phase, each gel was applied 4 times daily for 14 days, separated by a 14-day washout period. The same parameters, including patient satisfaction and adverse events, were re-evaluated. Data were analyzed using generalized linear mixed models and generalized estimating equations. Both the RSU and GC Dry Mouth Gel^® significantly improved oral wetness immediately after a single application. No significant difference was observed for the RSU gel relative to the GC Dry Mouth Gel^® for oral wetness (OR = 1.01, 95% CI 0.98, 1.04, p = 0.248), xerostomia score (OR = 1.10, 95% CI 0.42, 2.88, p = 0.661), or CSOD (OR = 0.95, 95% CI 0.58, 1.55, p = 0.765) at 60 min. After 14 days of use, oral wetness increased significantly in both groups (2.94%, 95% CI 0.30%, 5.76%, p = 0.030) and did not differ significantly between the two products (p = 0.110). The xerostomia scores and CSOD also significantly improved, independent of product type (OR = 7.21, 95% CI 2.56, 20.34, p < 0.001, and OR = 2.82, 95% CI 1.50, 5.32, p = 0.001, respectively). The participants reported high satisfaction and acceptable taste, and no adverse effects were detected in those using the RSU gel throughout the study. Its lower cost and local availability make it a practical option for xerostomia management, particularly in populations with limited access to commercial saliva substitutes. Full article

Intermittent claudication (IC) is the most frequent symptomatic manifestation of lower-extremity peripheral artery disease (PAD). Supervised exercise therapy (SET) and endovascular revascularization (ER) are established treatments, but their relative and combined effects on health-related quality of life (HRQoL) remain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing SET, ER, and ER+SET, with HRQoL as the primary outcome. Methods: Following PRISMA 2020, PubMed, Embase, and CENTRAL were used in December 2024. Eligible RCTs enrolled with IC (excluding critical limb-threatening ischemia) and reported validated HRQoL outcomes at ≥3 months. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2.0 tool. Random-effects meta-analyses pooled standardized mean differences (SMDs) for HRQoL and mean differences (MDs) for walking distance. Results: Five RCTs (n = 728) were included. Compared with optimal medical therapy, both SET and ER improved HRQoL and walking distance. At 12 months, no significant effect was observed between SET and ER (SMD 0.02; 95% CI: −0.18 to 0.22). ER+SET was superior to SET alone (SMD 0.35; 95% CI: 0.12–0.57). Beyond 24 months, improvements were sustained with SET but attenuated with ER, accompanied by higher reintervention rates in ER-containing arms (approximately 20–30% by 2 years). Adverse events were rare (<1%). Conclusions: Given moderate-certainty evidence (GRADE), SET should remain the first-line therapy for intermittent claudication because it provides durable improvements in patient-centered outcomes with minimal harm. Endovascular revascularization (ER) can provide faster symptom relief, but its long-term benefits are constrained by restenosis and repeat procedures, particularly in femoropopliteal disease. Full article

Background/Objectives: Endoscopic biliary stenting is the standard palliative intervention for malignant biliary obstruction, aimed at restoring ductal patency. Radiofrequency ablation (RFA) has been introduced as an adjunct technique to improve stent durability and patient outcomes. However, the literature remains inconclusive regarding which patients are most likely to benefit from the combination of RFA and stenting. Methods: We retrospectively described clinical outcomes of 24 patients undergoing endobiliary RFA combined with biliary stenting for malignant biliary obstruction. Post-procedural and 6-month outcomes were assessed using technical success and changes in serum bilirubin; procedure-related adverse events were extracted from available medical records. Results: Nineteen females and five males were included in the study. The most prevalent diagnoses were metastatic adenocarcinoma (n = 8) and cholangiocarcinoma (n = 6). 25% of patients did not complete the 6-month follow-up due to malignancy progression. 16 out of 18 maintained the patency of biliary stents. Repeat endoscopic intervention for suspected stent dysfunction was documented in one patient. When analyzed in an intention-to-treat manner (counting deaths before 6 months as failures), the corresponding 6-month patency/clinical success rate was 16/24 (66.7%) Conclusions: In this retrospective single-center experience, RFA combined with biliary stenting was feasible and was associated with maintained biliary drainage in a majority of patients who survived to the 6-month assessment. Full article

Background: Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for clavicle fracture pain management carry significant adverse effect and allergic reaction risks. This study assessed ultrasound-guided nerve block (USNB) efficacy for acute clavicle fracture pain in emergency department (ED) patients, providing an alternative to NSAIDs and opioids with fewer adverse effects. Methods: This retrospective, single-center observational study was conducted in accordance with Methods of Medical Record Review Studies in Emergency Medicine Research guidelines. Adult patients (≥20 years) who presented to the ED with traumatic clavicle fractures between 1 January 2015 and 30 November 2023 were included. Of the 343 eligible patients, 12 received ultrasound-guided nerve blocks (USNB) and 331 received standard care. To improve exchangeability, 1:10 matching with replacement was performed according to patients’ characteristics, such as age, sex, initial pain score, and comorbidities. The primary outcome was pain relief, assessed via the pain intensity difference (PID) on the Numerical Rating Scale within 360 min post-intervention. Meaningful pain relief was defined as a PID ≥ 4. Secondary outcomes included rescue opioid use, ED length of stay, hospital length of stay, and USNB-associated complications, such as vascular puncture, nerve injury, or local anesthetic systemic toxicity. Data were analyzed using time-course, time-to-event (time to meaningful pain relief), and linear regression analyses. Results: A total of 12 patients in the USNB group and 85 matched patients in the standard care group were analyzed after baseline characteristics matching with replacement. Compared to standard care, USNB was associated with significantly greater pain relief (p < 0.001). In the time-to-event analysis, USNB led to a 3.41-fold faster achievement of meaningful pain relief compared with that achieved with standard care (HR = 3.41; 95% CI, 1.47–7.90; p = 0.004). No significant differences were observed between groups in rescue opioid use, ED length of stay, or hospital length of stay. No USNB-associated complication developed in the USNB group. Conclusions: In patients with traumatic clavicle fractures, USNB provides more rapid and sustained pain relief than standard analgesic care in the ED, without increasing the ED length of stay. Large prospective studies are needed to confirm these findings. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

Background. The aim of this study was to develop a predictive model of anticancer drug therapy toxicity in patients with gastric cancer. Methods. The retrospective study included 100 patients with stage II–IV gastric cancer who underwent 4 chemotherapy cycles. Initial significant toxicity factors included age, gender, height, body mass, body mass index, disease stage, skeletal muscle index (SMI), as well as plasma levels of trace elements (copper, zinc, selenium, manganese) and thyroid-stimulating hormone, cancer histology type and treatment regimen. The CTCAE v5.0 scale was employed to assess the severity of adverse events. Statistical analysis and building of mathematical neural network models were carried out in SPSS Statistics (v19.0). Results. Lower SMI values were associated with higher rates of toxicity-related complications of anticancer drug therapy (p < 0.05): leukopenia, hypoproteinemia, nausea, vomiting, cardiovascular events. Anemia, thrombocytopenia, hepatic cytolysis syndrome, nausea, diarrhea, constipation and stomatitis showed a weaker correlation with SMI. An increase in TSH was associated with higher rates of thrombocytopenia, nausea and vomiting. A decrease in Cu/Zn in plasma correlated with the severity of leukopenia and diarrhea, whereas Se/Mn showed an inverse correlation with the severity of anemia. Conclusions. Sarcopenia, abnormal thyroid status and imbalances in copper, zinc, selenium and manganese in blood plasma of patients with gastric cancer may be used as predictors of increased toxicity of anticancer drug therapy. Full article