Search Results (17,521)

Objectives: Glioblastoma multiforme (GBM) is considered the most aggressive primary brain tumor, which often exhibits tumor heterogeneity. Hypoxia is a key aspect of intratumoral heterogeneity that contributes to poor prognosis in GBM. In this study, we aimed to develop machine learning (ML) models using radiomics and clinical features for the prediction of one-year survival for GBM. Methods: Data from 35 patients in the ACRIN 6684 trial, including fluoromisonidazole (FMISO)-positron emission tomography (PET), magnetic resonance (MR) (T1, T2, and fluid-attenuated inversion recovery (FLAIR)) images, and clinical information, were retrieved from The Cancer Imaging Archive (TCIA). Three ML algorithms, namely, support vector machine (SVM), random forest (RF), and linear regression (LR), were utilized to analyze selected features. Receiver-operating characteristic (ROC) curves were utilized to evaluate the predictive performance of the models. Several statistical analyses, namely, the permutation test, the permutation importance of selected features, Fisher's exact test, and the unpaired t-test, were performed to analyze the models and features. Results: FMISO achieved the best performance in radiomics models, with an area under the curve (AUC) of 0.870. The clinical data model achieved the best performance of all models, with an AUC of 0.921, outperforming the combined all sequential forward selection (SFS) model (AUC: 0.862). Female sex (p = 0.030) and younger age (p = 0.0043) were significantly associated with better prognosis. Conclusions: Our proposed models have the potential to predict the one-year survival of GBM and facilitate personalized therapy. Future studies with a larger sample size are needed to confirm the generalizability of the models. Full article

Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation–perfusion matching and unloads the RV without systemic hypotension; nonetheless, its application beyond established neonatal indications remains contentious. Our review synthesizes current mechanistic, translational, and clinical evidence regarding iNO use in three major settings characterized by excessive RV load: (1) neonatal pulmonary hypertension, particularly PPHN; (2) acute and chronic RV overload in older children and adults, including secondary pulmonary hypertension, acute respiratory distress syndrome (ARDS), and acute pulmonary embolism; and (3) perioperative and post-cardiopulmonary bypass (CPB) management in congenital and adult cardiac surgery. In term and near-term infants with hypoxic respiratory failure, pivotal randomized trials show that iNO consistently improves oxygenation and reduces extracorporeal membrane oxygenation (ECMO) use, but this has little effect on survival and long-term neurodevelopment. In ARDS and other adult critical-care indications, iNO provides transient improvements in gas exchange and RV performance without reducing mortality or ventilator duration, and meta-analyses signal an increased risk of acute kidney injury, particularly with prolonged use. In contrast, perioperative studies around CPB demonstrate that prophylactic postoperative iNO and intra-CPB nitric oxide administration can attenuate pulmonary hypertensive crises, facilitate separation from CPB, shorten ventilation and intensive care stay, and, in selected high-risk cohorts, may reduce cardiac surgery-associated acute kidney injury, although survival benefits remain unproven. Across these scenarios, iNO should be used judiciously and in a pathophysiology-driven manner as a time-limited, targeted adjunct to stabilize patients with documented or anticipated RV strain rather than a disease-modifying therapy. Future work should refine patient selection, timing, dosing, and weaning strategies, and define the long-term safety and cost-effectiveness of iNO within contemporary multimodal RV support pathways. Full article

Background: Autoimmune diseases (ADs) are a growing global health burden, driven by chronic inflammation and immune dysregulation. The gut-immune axis plays a central role in their pathogenesis, with dysbiosis linked to several conditions. This has prompted investigation into nutraceuticals such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as adjunctive therapies. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Embase, and Web of Science for randomized controlled trials evaluating these interventions in autoimmune diseases. Results: Twenty-eight randomized control trials (RCTs) involving 2002 patients across 11 countries met inclusion criteria. Across the included RCTs, pooled analyses demonstrated significant reductions in c-reactive protein (CRP) (SMD −0.67, 95% CI −1.00 to −0.33; I² = 80.8%) and Tumor necrosis factor-alpha (TNF-α) (SMD −1.81, 95% CI −2.67 to −0.94; I² = 96%), a significant increase in Interleukin-10 (IL-10) (SMD 2.65, 95% CI 0.64 to 4.66; I² = 98%), and no overall significant effect on Interleukin-6 (IL-6) (SMD −0.89, 95% CI −1.99 to 0.22; p = 0.12). The strongest evidence of benefit was observed in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Pooled effects are limited by extreme between-study heterogeneity (I² 80–98%), leaving interpretation as exploratory rather than definitive. More limited or inconsistent findings were reported for systemic lupus erythematosus, hypothyroidism, axial spondylarthritis, and juvenile idiopathic arthritis. Heterogeneity in study design, probiotic strain selection, dosage, and treatment duration limited comparability across trials. Conclusions: Overall, microbiome-targeted nutraceuticals appear promising for attenuating systemic inflammation in select autoimmune conditions, but results remain mixed. Larger, rigorously designed RCTs with standardized endpoints are needed to clarify efficacy, identify optimal formulations, and define patient populations most likely to benefit. Full article

Background: Older adults, including those with Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD), face barriers in maintaining regular physical activity, which increases their fall risk and reduces their quality of life. The Activity Tracking, Care Partner Co-Participation, Text Reminders, Instructional Education, Video-Guided Physical Rehabilitation, and Exercise trial aims to improve physical activity among older adults. This pilot study aims to assess the feasibility and preliminary efficacy of the ACTIVE intervention. Methods: ACTIVE is a multi-method, two-arm randomized, analyst-blinded crossover pilot trial with an embedded qualitative component. We will recruit 50 community-dwelling dyads (older adult–care partner, n = 100), with and without mild AD/ADRD, in a 1:1 ratio. Each dyad will be randomized to the intervention or control arm, stratified by AD/ADRD diagnosis. The intervention arm will receive activity tracking, motivational texts, walking exercises, educational videos, and video-guided physical rehabilitation sessions, while the control arm will receive only activity tracking. The intervention will run in two halves: a three-week intervention/control, a one-week crossover phase, and a three-week control/intervention phase. The quantitative outcome measures will include feasibility measures (recruitment, adoption, adherence, acceptability, fidelity, and retention), and measures of preliminary efficacy (activity metrics, fall risk and fear of falling, functional limitations, and quality of life). Qualitatively, we will assess participants’ experiences, and facilitators and barriers to engagement in physical activity through semi-structured dyadic interviews and thematic analysis. Conclusions: This pilot study will generate data on the feasibility and preliminary efficacy of the ACTIVE trial. Findings will inform a full-scale implementation trial. Full article

Background and Objectives: Fibromyalgia is a chronic condition characterized by widespread pain, reduced quality of life, and impaired physical function. Given that physical activity is a primary treatment for musculoskeletal health and overall well-being, VR-based active exercise may offer an innovative way to engage individuals with fibromyalgia in therapeutic movement. Methods: A Systematic Review and meta-analysis were conducted following PRISMA guidelines. Randomized controlled trials including adult patients with fibromyalgia undergoing active VR-based exercise interventions were included. Databases searched were PubMed, Scopus, Web of Science, CENTRAL, and PEDro from inception up to 18 July 2025. Primary outcomes were pain intensity, fatigue, and symptom severity. Secondary outcomes included depression, anxiety, kinesiophobia, aerobic capacity, muscle strength, and balance. Risk of bias was assessed using Cochrane’s Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results: Ten randomized controlled trials (203 participants) were included. Active VR interventions significantly reduced pain (SMD = −0.51), fatigue (SMD = −0.53), and symptom severity (MD = −8.41). Moderate effects were found for depression (SMD = −0.51) and anxiety (SMD = −0.41). Non-significant improvements were also observed in aerobic capacity (SMD = 0.28), and muscle strength (SMD = 0.33), while balance slightly favored control group (SMD = −0.19). The overall certainty of evidence for main outcomes was rated low. Subgroup analyses showed VR was superior to both no intervention and other isolated therapies. Conclusions: Active virtual reality-based exercise interventions appear effective for improving physical and psychological outcomes in fibromyalgia, although findings should be interpreted cautiously due to low certainty of evidence. Full article

Background and Objectives: Totally endoscopic aortic valve replacement (TE-AVR) is a minimally invasive technique offering potential benefits of reduced surgical trauma and faster recovery compared with median sternotomy or other minimally invasive access. While isolated aortic valve replacement (AVR) is well established through conventional and minimally invasive access, large-scale evidence for the totally endoscopic approach remains limited. This meta-analysis aimed to systematically assess the safety and feasibility of TE-AVR by aggregating perioperative outcomes, including mortality, stroke, conversion, bleeding, paravalvular leak (PVL), and atrial fibrillation (AF). Materials and Methods: A systematic search of PubMed, Embase, and the Cochrane Library was performed, following PRISMA 2020 guidelines. Observational studies and randomized controlled trials reporting outcomes of totally endoscopic or thoracoscopic AVR were eligible. After independent screening and selection, data were analyzed using a single-arm proportion model. Leave-one-out sensitivity analyses were performed to evaluate the influence of individual studies. The protocol was registered in PROSPERO (CRD42024610128). Results: A total of 11 studies comprising 1135 patients were included. The pooled perioperative mortality was 0.00% (95% CI 0.00–0.23; I² = 0.0%), indicating highly consistent results across cohorts. The stroke incidence was 0.69% (95% CI 0.00–2.07; I² = 42.7%), confirming the low cerebrovascular risk of this approach. Conversion to sternotomy occurred in 0.00% of cases (95% CI 0.00–0.17; I² = 0.0%), with no statistical heterogeneity observed. Reintervention for bleeding occurred in 1.75% (95% CI 0.34–3.85; I² = 43.4%), while PVL was reported in 1.24% (95% CI 0.00–4.22; I² = 64.0%). AF incidence was 10.54% (95% CI 3.79–19.70; I² = 90.5%), with substantial between-study heterogeneity, likely related to non-standardized definitions of new-onset AF and variability in postoperative rhythm monitoring and reporting across studies. Conclusions: TE-AVR is a safe and feasible technique associated with very low perioperative mortality, bleeding, and stroke rates, as well as low PVL incidence. The absent conversion rate in our pooled analysis highlights the technical reliability of the procedure. Variability in AF reporting underscores the need for future randomized studies with harmonized definitions. Overall, TE-AVR offers a promising minimally invasive alternative for aortic valve replacement, with potential advantages in recovery (pooled ICU stay 1.86 days), hospital stay (pooled 7.98 days), and aesthetic outcomes. Full article

Background/Objectives: Zinc is an essential trace element involved in multiple aspects of immune function, including epithelial barrier integrity, innate and adaptive immune responses, regulation of inflammation and oxidative stress. Zinc deficiency has been associated with increased susceptibility to infections, particularly in the pediatric population. This narrative review aims to summarize and discuss current evidence on the role of zinc in the prevention and management of pediatric respiratory infections. Methods: A comprehensive literature review was conducted including randomized controlled trials, real-world studies, and international guidelines published in recent years. Both zinc monotherapy and multicomponent dietary supplements containing zinc were considered. Results: Evidence consistently supports a preventive role of zinc supplementation in reducing the incidence and burden of respiratory infections, particularly in children with recurrent disease and in zinc-deficient populations. Zinc-containing multicomponent supplements demonstrated significant reductions in infection frequency and duration, alongside improved patient and parent-reported outcomes, with a favorable safety profile. In contrast, data on zinc as an adjunctive treatment during acute infections, especially severe pneumonia, are less consistent, with limited impact on major clinical outcomes. The effectiveness of zinc appears to be influenced by treatment duration, baseline nutritional status, and formulation. Conclusions: In conclusion, zinc may represent a valuable component of preventive immune-nutritional strategies for pediatric respiratory infections, especially when administered as part of multicomponent formulations and over prolonged periods. While its role in acute disease management remains uncertain, optimizing zinc status may contribute to reducing infection recurrence and overall disease burden. Further well-designed trials are warranted to clarify optimal dosing, timing, and target populations. Full article

Long COVID is defined as “the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanations”, as reported by the World Health Organization. A growing number of people are dealing with a variety of lingering symptoms even after recovering from an acute infection. These can include fatigue, muscle pain, shortness of breath, headaches, cognitive issues, neurodegenerative symptoms, anxiety, depression, and a feeling of hopelessness, and therapeutic options for long COVID are investigated. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. The aim of this literature search is to analyze the state of the art of a potential role of HBOT to improve chronic fatigue, cognitive impairments and neurological disorders. A literature analysis was performed, focusing on the clinical efficacy of HBOT for treating long COVID symptoms. The results from January 2021 to October 2025, using a standard registry database, showed 21 studies, including one case report, ten randomized controlled trial, eight systematic reviews and three studies regarding the molecular mechanism and markers changing after HBOT. They suggested that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms and cardiopulmonary functions. HBOT is a safe treatment and has shown some benefits for long COVID symptoms. To precisely define indications, protocols, and post-treatment evaluations, we need to conduct more in-depth, large-scale studies. Full article

Hemodiafiltration (HDF) is increasingly used because of its enhanced theoretical clearance of diverse uremic toxins, particularly middle molecules and inflammatory cytokines, relative to conventional hemodialysis (HD), yet evidence on its biochemical benefits remains conflicting. Therefore, this meta-analysis was performed to evaluate the effects of HDF versus HD on uremic toxins, inflammation, anemia, and nutritional parameters. A systematic literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials to identify relevant studies. Only randomized controlled trials (RCTs) were included. Random-effects meta-analyses were performed to evaluate changes in the prespecified outcomes. Twenty-four RCTs involving 6072 dialysis patients were included. Compared with conventional HD, HDF was associated with significant reductions in serum phosphorus (weighted mean difference [WMD] −0.28 mg/dL; 95% CI −0.44 to −0.12) and β2-microglobulin (WMD −4.84 mg/dL; 95% CI −6.13 to −3.54). HDF also significantly reduced serum urea and C-reactive protein (CRP) levels, along with weekly erythropoietin requirements. Serum albumin levels were slightly but significantly lower in the HDF group than in the conventional HD group (WMD –0.06 g/dL; 95% CI −0.10 to −0.01); however, the clinical significance of such a difference remains uncertain. Higher convective volumes were identified as a key determinant of greater reductions in β2-microglobulin and CRP. Compared with conventional HD, HDF demonstrated superior reductions in several surrogate endpoints, including serum phosphorus, urea, β2-microglobulin, CRP, and weekly erythropoietin requirements. Reduced need for phosphate binders and anemia management may lower treatment-related costs. Full article

Objectives: To evaluate the efficacy of resin infiltrants (RIs) in controlling non-cavitated occlusal carious lesions (NCOCLs) in primary and permanent teeth. Methods: This systematic review followed PRISMA guidelines. Randomized clinical trials (RCTs) and in vitro/ex vivo studies comparing RI with placebo or other materials were included. Searches were conducted in five databases and gray literature up to December 2025. Risk of bias was assessed using the RoB 2.0 tool for RCT and an adapted instrument for in vitro/ex vivo studies. Certainty of evidence was evaluated using the GRADE tool, and data were synthesized qualitatively. Results: Eight studies were included, of which only two were RCTs, and six were in vitro and ex vivo studies. RCTs showed reduced caries progression in infiltrant-treated groups compared with controls, with efficacy comparable to conventional sealants. In vitro studies demonstrated improved resin penetration and sealing ability with optimized protocols. Risk of bias ranged from low to moderate. Certainty of clinical evidence was low, primarily due to the limited number of RCTs and methodological limitations. Conclusions: RIs may be effective in managing NCOCLs, with performance comparable to conventional preventive approaches. However, the limited number of clinical trials and short follow-up periods reduce the strength of the evidence. Long-term clinical studies are needed to confirm the sustained effectiveness and durability of RIs. Full article

Obesity is a major global health challenge that substantially affects vitamin D metabolism and status. Numerous studies have consistently demonstrated an inverse relationship between body fat and serum 25-hydroxyvitamin D [25(OH)D] concentrations. Emerging evidence suggests that lower serum 25(OH)D in obesity largely reflects altered distribution and metabolism rather than a uniform state of true functional deficiency. Adipose tissue functions both as a storage compartment and as a metabolically active organ capable of modulating vitamin D handling. Mechanisms include the sequestration of vitamin D in fat, volumetric dilution across a larger body mass, and the local expression of enzymes involved in vitamin D metabolism. As a result, obese individuals typically exhibit a blunted increase in serum 25(OH)D in response to supplementation, consistent with altered pharmacokinetics and increased distribution volume. Weight loss, particularly the reduction in visceral fat, is associated with modest increases in circulating 25(OH)D, further supporting a distribution-based mechanism. Although low 25(OH)D levels in obesity have been linked to insulin resistance, inflammation, and metabolic syndrome, randomized controlled trials have not consistently demonstrated that supplementation improves clinically relevant outcomes in this population. Meta-analyses confirm that the increase in serum 25(OH)D after supplementation is smaller in obese individuals, indicating that higher doses are often required to achieve comparable levels to those in normal-weight subjects. Obesity thus represents a major determinant of vitamin D deficiency, highlighting the need for individualized supplementation strategies alongside weight management. Understanding the mechanistic basis for low 25(OH)D in obesity is essential for distinguishing true deficiency from altered distribution, informing clinical decisions, and optimizing interventions to maintain adequate vitamin D status and support metabolic health. Full article

Background/Objectives: Herbal retention enema is widely used in Traditional Chinese Medicine for the management of endometriosis; however, its clinical efficacy and safety have not been systematically evaluated. Methods: Ten electronic databases were searched up to May 2025 to identify randomized controlled trials evaluating herbal retention enema as a standalone treatment for endometriosis. Primary outcomes included total effective rate and pain-related measures. Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Nine randomized controlled trials involving 614 participants were included. Compared with Western medical therapies, herbal retention enema was associated with greater overall clinical effectiveness (OR = 2.87) and significant improvement in dysmenorrhea. When compared with oral herbal medicine, herbal retention enema demonstrated a higher total effective rate (OR = 7.13). A trend toward improved pregnancy outcomes was observed (p = 0.05). No serious adverse events related to herbal retention enema were reported, and systemic adverse effects were less frequent than with hormonal therapies. Conclusions: Herbal retention enema may represent a potential complementary option for symptom management in endometriosis; however, the certainty of evidence remains low due to important methodological limitations in the included trials. However, given methodological limitations and heterogeneity among studies, further high-quality randomized controlled trials with standardized outcomes and long-term follow-up are required. Full article

Background/Objectives: Plantar fasciitis (PF) is a leading cause of heel pain and functional impairment in adults. Laser therapy, in its low-intensity laser therapy (LLLT), high-intensity laser therapy (HILT), and photobiomodulation (PBMT) modalities, has been proposed as a non-invasive alternative, although its clinical effectiveness remains a subject of debate. The aim of this systematic review and meta-analysis was to evaluate the efficacy of laser therapy in reducing pain, improving function, and modifying fascial thickness in patients with PF. Methods: A comprehensive search was conducted in PubMed, Embase, and PEDro (last search: August 2025). Randomized controlled trials comparing laser therapies versus placebo or alternative physical interventions were included. Two reviewers performed study selection, data extraction, and risk of bias assessment using the PEDro scale. Random-effects meta-analyses were performed for pain (VAS), heel tenderness (HTI), function (FFI, AOFAS, ASQoL, SF-36), and fascial thickness, expressing effects as standardized mean differences (SMDs) or mean differences (MDs). Results: Thirteen trials with 784 participants were included. Laser therapy showed a significant improvement in heel tenderness (SMD = −0.40; 95% CI −0.71 to −0.09; I² = 0%). No significant differences were observed in overall pain (SMD = −0.18), function (SMD = 0.20), or fascial thickness (MD = −0.18 mm). Pain and function analyses showed high heterogeneity. Conclusions: Laser therapy may reduce heel tenderness in plantar fasciitis, but it does not consistently improve overall pain, function, or fascial thickness. Its use should be considered as a therapeutic adjunct and not as a primary intervention. Larger trials with standardized protocols are needed. Full article

Objective: This systematic review aimed to evaluate the efficacy and safety of preoperative nutrition-based interventions on pre-, intra-, and postoperative outcomes in children undergoing cardiac surgical procedures. Methods: CENTRAL, MEDLINE, and EMBASE were systematically searched for interventional and observational studies comparing any nutritional preoperative intervention with a control or alternative strategy in pediatric patients undergoing cardiac surgery, up to July 2025. The main outcome was the postoperative length of stay in the intensive care unit (ICU). The certainty of evidence was assessed using the GRADE approach. Results: Nineteen studies were included (8 randomized controlled trials [RCTs], 1 non-randomized trial, and 10 observational studies), evaluating heterogeneous interventions or exposures, including fatty acids, vitamin D supplementation, and structured preoperative nutritional protocols. Two RCTs demonstrated shorter ICU and hospital stays with extended preoperative nutritional support (2 weeks vs. 1 week; n = 40; and 1 month vs. no support; n = 80). Observational data indicated an association between preoperative nutritional support and reduced hospital length of stay (meta-analysis of four studies; n = 278), as well as fewer days to achieve full enteral feeding postoperatively (meta-analysis of three studies; n = 138). No significant difference in postoperative ICU stay was observed between groups (meta-analysis of two studies; n = 175). No intervention-related serious adverse events were reported. The overall certainty of evidence was very low. Conclusions: This systematic review provides very low-certainty evidence suggesting that preoperative nutrition-based interventions in children undergoing cardiac surgery are safe and may offer clinical benefits. Substantial heterogeneity across studies underscores the need for well-designed trials and standardized preoperative nutritional protocols. PROSPERO number: CRD420251085196. Full article

Introduction: Sarcopenia and frailty are prevalent yet under-recognized contributors to disability, impaired quality of life, and adverse outcomes in chronic obstructive pulmonary disease (COPD). Shared mechanisms, including systemic inflammation, hormonal dysregulation, malnutrition, and physical inactivity, render these syndromes important targets for multimodal intervention. This review summarizes current evidence on exercise-based, nutritional, pharmacological, and adjunctive strategies for their management in COPD. Materials and Methods: This narrative review is based on a structured literature search of PubMed, Scopus, and Embase to identify relevant studies published between January 2000 and May 2025. Eligible publications included randomized controlled trials, meta-analyses, systematic reviews, and observational studies involving adults with COPD and documented sarcopenia and/or frailty. Interventions were categorized by modality, and outcomes included muscle mass, strength, physical performance, quality of life, and hospitalizations. Data were synthesized thematically. Results: Resistance and combined exercise training consistently improved muscle strength and physical function, while endurance training enhanced cardiorespiratory capacity, particularly within pulmonary rehabilitation programs. Nutritional interventions, especially protein, leucine, or β-hydroxy-β-methylbutyrate supplementation, supported gains in lean mass and exercise tolerance. Pharmacological strategies, including anabolic hormones and myostatin inhibitors, showed early promise but require further evaluation regarding safety and long-term efficacy. Adjunctive therapies, such as neuromuscular electrical stimulation and oxygen supplementation, benefited patients unable to participate in conventional exercise training. Conclusions: An integrated, multimodal approach combining structured exercise training and targeted nutritional support should be considered a cornerstone of COPD management to prevent and treat sarcopenia and frailty. Personalized rehabilitation strategies can substantially improve functional outcomes and quality of life, while future research should prioritize biomarker-guided personalization and long-term intervention studies. Full article