Search Results (9,780)

Inherited retinal dystrophies (IRDs) are a diverse group of monogenic disorders associated with dysfunction of the retina. High myopia, commonly defined as a spherical equivalent ≤ −6.00 D or axial length ≥ 26.5 mm, is a recurring clinical feature across several IRDs, and could serve as an early diagnostic clue. This review provides a summary of IRDs associated with high myopia to guide the clinician in establishing a molecular diagnosis for patients. We performed a comprehensive literature review of articles in PubMed, ScienceDirect, and JAMA Network to identify associations between monogenic IRDs and high myopia. Genes associated with IRDs and high myopia clustered into functional categories that included collagen/structural integrity (COL2A1, COL9A1, COL11A1, COL18A1, P3H2), phototransduction and visual cycle (PDE6C, PDE6H, GUCY2D, ARR3, RBP3), ciliary trafficking and microtubule-associated genes (RPGR, RP2, IFT140, CFAP418, FAM161A), synaptic ribbon and bipolar cell signaling (NYX, CACNA1F, TRPM1, GRM6, LRIT3, GPR179), opsin-related genes (OPN1LW, OPN1MW), and miscellaneous categories (VPS13B, ADAMTS18, LAMA1). Associations between IRDs and high myopia spanned stationary and progressive retinal disorders and included both cone-dominant and rod-dominant diseases. High myopia accompanied by other visual symptoms and signs such as nyctalopia, photophobia, or reduced best-corrected visual acuity should heighten suspicion for an underlying IRD. Earlier diagnosis of IRDs for patients could facilitate timely genetic counseling, participation in clinical trials, and interventions for patients to preserve vision.: Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases. Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases were recruited through an existing clinical trial. Using an iterative survey and in-person discussions, experts provided input on priority areas, which were thematically grouped and refined across rounds. Structured feedback supported real-time refinement and consensus-building. Results: Twenty experts participated in the process, generating 25 priority items in Round 1 through open-ended responses. These were narrowed to seven key priorities through structured voting and discussion. The final items were clustered into three intersecting themes: Care Settings, Prescriptions, and Strategies. Care Settings focused on high-impact areas such as outpatient clinics and intensive care units, where misuse is common and/or care is complex. The prescriptions theme prioritized shorter durations and narrow-spectrum agents. The strategy theme highlighted the need for outcome-based metrics, improved diagnostic stewardship, and routine tracking of patient outcomes to guide and assess stewardship efforts. Conclusions: This expert consensus identified key priorities for pediatric ASPs, providing a foundation for future interventions. Findings can be used to inform policy and practice, improving the appropriate use of antimicrobials in pediatrics and combating AMR. Full article

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered. Full article

Background/Objectives: The prebiotic effect of resistant potato starch (RPS) has been demonstrated, but the role of this nutrient in choline metabolism and the production of microbially modified choline-derived toxins is unknown. Methods: We performed post hoc analysis comparing changes in choline and related metabolites in serum from baseline to the week 4 time point in a human clinical trial evaluating daily consumption of 3.5 g RPS versus a placebo. Results: Choline levels increased in the RPS consuming group, while levels of trimethylamine decreased and levels of the cardiovascular toxin trimethylamine oxide were unaffected by RPS consumption. Increases in choline were positively correlated with increases in Akkermansia in the gut. Oxidation of choline to betaine was unaffected by RPS, as was acetylcholine metabolism. Levels of various saturated even acyl chain and hydroxylated acyl chain sphingomyelins were increased in RPS consuming participants, and levels of phospholipid degradation products phosphocholine and glycerophosphocholine were decreased. Conclusions: These data suggest that RPS enhances choline absorption without increasing TMAO and stimulates the incorporation of choline into sphingomyelins containing saturated even acyl chains and hydroxylated acyl chains. Future studies assessing the physiological consequences, such as cognitive or neurological benefits, of enhanced choline absorption and sphingomyelin levels in people consuming RPS are warranted. Full article

Background/Objectives: Previous studies show that allocating carbohydrates earlier and vegetables/protein later in late-evening meals improves glycemic control in both healthy individuals and those with type 2 diabetes. However, evidence remains insufficient regarding the effects of distributing carbohydrate intake across the day by dividing three regular meals into five smaller meals. Methods: We conducted a randomized, controlled, crossover trial to compare the effects of two dietary patterns: (1) a conventional three-meal pattern with simultaneous intake of all food components, and (2) a five-meal pattern incorporating divided carbohydrate portions and a fixed food order—vegetables first, followed by protein, and then carbohydrates. Eighteen healthy young women consumed the same test meals under both patterns. Glucose fluctuations were monitored using an intermittently continuous glucose monitoring system. Results: The five-meal pattern with food sequencing significantly improved the mean amplitude of glycemic excursions (MAGE; 2.56 ± 0.13 vs. 3.49 ± 0.32 mmol/L, p < 0.01), glucose peak, and incremental area under the glucose curve for breakfast, lunch, and dinner, and the time above the target glucose range [>7.8 mmol/L; 1.4 ± 0.6 vs. 4.2 ± 1.0%, p < 0.01] compared to the three-meal pattern. Conclusions: These findings suggest that divided carbohydrate intake and food order ameliorates the MAGE in healthy young women. Full article

Background/Objectives:Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies. Full article

Telerehabilitation is an effective, accessible addition or alternative to conventional rehabilitation for fracture management, especially in older adults after hip fractures, leveraging video visits, mHealth apps, virtual reality (VR), and wearable sensors to deliver exercise, education, and monitoring at home with high satisfaction and adherence. Across non-surgical and surgical contexts, telemedicine shows feasibility and cost benefits, with mixed superiority but consistent non-inferiority for functional outcomes versus in-person care. In hip fracture populations, randomized and non-randomized studies indicate improvements in functional independence measure (FIM), Timed Up and Go test (TUG), Activities of Daily Living/Instrumental Activities of Daily Living (ADLs/IADLs), and quality of life, with some evidence for reduced anxiety and depression, while effects on mobility, pain, and adverse events remain uncertain overall. In patients with upper-limb fractures, telerehabilitation appears to improve function and pain, though strength gains may lag compared with in-person therapy in some trials; adjuncts like motor imagery and virtual reality may enhance outcomes and motivation. Application is facilitated by user-friendly platforms, caregiver involvement, and simple modalities such as structured phone follow-up. Limitations include small samples, heterogeneous protocols, scarce long-term data, and a predominance of non-inferiority or complementary designs, warranting larger, definitive trials. This technology can lead to improved patient management at home, effortlessly verifying treatment compliance, efficacy, and safety, while simultaneously reducing the need for hospitalization, promoting a more peaceful recovery. Here, we have undertaken a narrative review of the medical–scientific literature in this field. Full article

Background/Objectives: The 2-minute walk test (2MWT) is a time-based gait assessment commonly employed for populations with limited walking ability for greater tolerability compared to the longer 6-minute test. The recommended distance to perform the tests is a 30 m straight path, a space requirement that is not always available in non-laboratory contexts. Shorter paths are therefore often adopted, but associated changes in gait patterns are not clear. The aim of the study is therefore to investigate how different walking path lengths affect gait patterns during the 2MWT. Methods: Twenty healthy young adults performed three walking trials on a straight hallway of 5 m, 15 m, and 30 m lengths. Spatiotemporal gait parameters were measured using three inertial measurement units on both distal tibiae and at pelvis level. Results: The 5 m path showed the greatest deviations, specifically in walking distance, walking speed, stride duration, stance time, swing time, single support time, and cadence, if compared to longer distances (p < 0.05). The 15 m path showed differences only in walking distance and walking speed (p < 0.05), if compared to the 30 m path. Conclusions: Shorter path lengths, particularly the 5 m, significantly impact gait patterns and should be considered when interpreting 2MWT results in clinical settings. The 30 m path is recommended as the gold standard, with 15 m as a viable alternative for assessing temporal parameters. Nevertheless, the extent to which each feature would be over/underestimated when walking in limited spaces is also addressed. Full article

This randomized controlled clinical trial compared a conventional combined screw- and cement-retained prosthesis (CSCRP) workflow (control group) with a fully digital cementless screw-retained prosthesis (CL-SRP) system (test group) for single posterior implant restorations. A total of 40 implants in 35 patients were allocated to either workflow. Clinical procedure times, prosthetic accuracy, peri-implant soft tissue changes, and marginal bone loss (MBL) were assessed. The test group demonstrated significantly shorter total prosthetic time (p < 0.001) and impression-taking time (p < 0.001) compared with the control group. Prosthetic adjustment time (p = 0.211) and adjustment volume (p = 0.474) did not differ significantly. Gingival shape changes were likewise not statistically significant (p = 0.966). MBL was significantly lower in the test group (p < 0.05). From a prosthetic standpoint, both workflows yielded clinically acceptable outcomes; however, the digital CL-SRP approach improved procedural efficiency and early peri-implant bone preservation without compromising prosthetic quality. This trial had inherent limitations, including a short follow-up duration, a relatively small sample size, combined test conditions, and restriction to single posterior implants. Therefore, further long-term studies are warranted to confirm durability and broader clinical applicability. Full article

Background and Objectives: Frail patients after open-heart surgery often experience worse treatment outcomes in improving physical performance and muscle strength. As the functional recovery of frail patients after open-heart surgery is slower, conventional rehabilitation is frequently insufficient to achieve treatment goals. Therefore, the inclusion of additional exercise interventions in cardiac rehabilitation is becoming more relevant. The aim of this study was to assess and compare the effectiveness of additional exercise interventions—multicomponent and computer-based programs—applied along with conventional cardiac rehabilitation in improving the functional capacity and strength of frail patients after open-heart surgery. Materials and Methods: The population of this single-center, three-arm, parallel-group, randomized controlled trial comprised 153 frail patients aged more than 65 years who underwent open-heart surgery. All patients were randomized into three groups: control (CG, n = 51), intervention 1 (IG-1, n = 51), and intervention 2 (IG-2, n = 51). All groups received conventional rehabilitation program six times/week, while the IG-1 additionally received the multicomponent dynamic training program 3 times/week, and the IG-2, the combined computer-based program 3 times/week. The primary outcome measure was change in the Short Physical Performance Battery (SPPB) score. Secondary outcome measures included the 6 min walk distance (6MWD), peak workload, grip strength, and leg press. Primary and secondary outcome measures were assessed before and after cardiac rehabilitation. Results: A total of 138 patients completed rehabilitation (46 in each group), and their data were included in the main analysis that followed a per-protocol approach. Although significant differences in the primary outcome—the SPPB score—were found in each group while performing within-group comparisons (p < 0.001), no significant pre-to-post rehabilitation differences were observed compared to all three groups (p = 0.939), and the effect sizes were small. Regarding secondary outcome measures, within-group comparison revealed significant differences in all parameters of all groups (p < 0.05), except for the grip strength of both hands in the IG-1. Between-group comparisons showed that the pre-to-post 6MWD difference between the CG and the IG-1 was significant (p = 0.014), but the effect size was small (ES = 0.240). Moreover, significant pre-and-post leg press 1RM differences (p < 0.001) were found between the CG and the IG-1 as well as between the CG and the IG-2 with the effect sizes being moderate (ES = 0.480) and large (ES = 0.613), respectively. Conclusions: Within-group comparison showed that all three rehabilitation programs are effective in improving almost all parameters of physical performance and muscle strength in frail patients after open-heart surgery. However, between-group comparisons indicated that computer-based interventions were more effective in improving leg press 1RM with a large effect size, while multicomponent training resulted in more effective gains in the 6MWD, although with a small effect size. These findings suggest that in clinical practice, computer-based exercise programs may be more suitable for patients with muscle weakness, while multicomponent exercise programs may be for those with reduced endurance. Full article

Chronic wounds, such as diabetic ulcers, remain a significant clinical challenge due to high infection risk and delayed healing. This study presents a comprehensive evaluation of a novel wound dressing incorporating curcumin-functionalized silver–zinc oxide (Ag-ZnO) nanoparticles. The formulation was rationally designed based on molecular docking simulations that identified curcumin as a high-affinity ligand for Staphylococcus aureus Protein A. The synthesized nanoparticles demonstrated potent, broad-spectrum antibacterial activity, achieving complete inhibition of multidrug-resistant pathogens, including MRSA, within 60 s. A critical comparative assessment, incorporating an unloaded Ag-ZnO nanoparticle control group, was conducted in both a rabbit wound model and a randomized clinical trial (n = 75 patients). This design confirmed that the enhanced wound-healing efficacy is specifically attributable to the synergistic effect of curcumin combined with the nanoparticles. The curcumin-loaded Ag-ZnO treatment group showed a statistically significant reduction in healing time compared to both standard care and unloaded nanoparticle controls (e.g., medium wounds: 19.6 days vs. 90.6, p < 0.001). These findings demonstrate that curcumin-functionalized Ag-ZnO nanoparticles offer a safe and highly effective therapeutic strategy, providing robust antibacterial action and significantly accelerated wound healing. Full article

Background: Deep vein thrombosis (DVT) is a serious thromboinflammatory complication of acute ischemic stroke (AIS). The true incidence, mechanistic risk factors, and optimal prophylactic strategies remain uncertain, particularly in the era of reperfusion therapy. Methods: This systematic review and meta-analysis (IRIS-DVT) searched PubMed, Embase, Cochrane, Scopus, and Web of Science for studies reporting DVT incidence, risk factors, or prophylaxis in AIS (2004–2025). Random-effects models were used to generate pooled prevalence and effect estimates, and the certainty of evidence was graded using the GRADE framework. Results: Forty-two studies (n = 6,051,729 patients) were included. The pooled prevalence of DVT was 7% (95% CI, 6–9%), approximately seventy-fold higher than in the general population, with wide heterogeneity influenced by screening timing and diagnostic modality. Pathophysiological risk factors included higher stroke severity (NIHSS; SMD 0.41; 95% CI, 0.38–0.43), older age (SMD 0.32; 95% CI, 0.18–0.46), elevated D-dimer (SMD 0.55; 95% CI, 0.38–0.72), female sex (OR 1.33; 95% CI, 1.19–1.50), and malignancy (OR 2.69; 95% CI, 1.56–5.22), supported by moderate-certainty evidence. Respiratory infection and admission hyperglycemia showed weaker, low-certainty associations. Traditional vascular risk factors (hypertension, diabetes, atrial fibrillation, dyslipidemia) were not significantly related to DVT risk. Evidence for prophylaxis with low-molecular-weight heparin, direct oral anticoagulants, or intermittent pneumatic compression was limited and graded very low certainty. Conclusions: DVT complicates approximately one in fourteen AIS cases, reflecting a distinct thromboinflammatory process driven more by acute neurological severity, systemic hypercoagulability, and malignancy than by conventional vascular risk factors. Early systematic screening (≤72 h) and consistent use of mechanical prophylaxis are warranted. Dedicated AIS-specific mechanistic and interventional trials are urgently needed to refine prevention strategies and improve post-stroke outcomes. Full article

Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities such as surgery and radiotherapy. Methods: Peer-reviewed articles published between January 2000 and August 2025 were searched manually in four databases: Scopus, ScienceDirect, PubMed and MEDLINE, using the keywords “Merkel cell carcinoma” AND “immunotherapy” AND “immune checkpoint inhibitors”. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was employed. Results: ICIs can be given in different settings: (A) Neoadjuvant: The CheckMate 358 trial reported a 54.5% response rate among 33 radiologically evaluable patients treated with nivolumab, each showing over 30% tumor reduction. (B) Adjuvant: (1) The ADMEC-O phase II trial demonstrated improved disease-free survival with adjuvant nivolumab. (2) The ADAM phase III trial evaluates adjuvant avelumab in node-positive patients post-surgery/radiation, with common side effects including nausea, fatigue, and itching. (3) STAMP, a phase III trial, investigates pembrolizumab in stage I–III MCC. Both ADAM and STAMP have completed accrual and results are pending. (C) Primary therapy: KEYNOTE-017 and JAVELIN trials reported a 60% overall response rate and ~40% 3-year progression-free survival with first-line pembrolizumab or avelumab. Both agents also show promise as salvage therapies. Conclusions: ICIs demonstrate encouraging outcomes in MCC across various treatment stages. Continued research is essential to optimize treatment timing and integrate multimodal therapies. Full article

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

Background: Optimal energy and protein delivery during the early phase of severe trauma remains unclear. Observational studies frequently contradict the findings of randomized controlled trials, raising concerns about confounding factors. The aim of this study is to assess nutritional adequacy and daily variability in the energy gaps and its impact on outcomes using innovative statistical methods. Methods: Prospective observational study enrolled severely injured patients in the ICU at the Level 1 trauma center between October 2023 to April 2025. To describe the evolution of calorie and protein deficits during the first 10-day ICU stay, we utilized a linear mixed-effects model to estimate each patient’s individual energy gap trajectory. Results: 286 patients were analyzed. Median APACHE II and ISS score was 16.0 (12.0–20.0) and 22.0 (18.0–27.0), respectively. Mortality rate was 35.3%. Patients received 68.3% of prescribed calories and 76.8% of proteins. Admission energy deficit, rate of caloric intake, and their interaction are associated with ICU mortality. Increased day-to-day energy variability was associated with longer duration of mechanical ventilation (HR = 0.55, 95% CI: 0.31–0.99; p = 0.047). Patients who achieved better caloric (HR = 0.68, 95% CI: 0.48–0.98, p = 0.036) and protein (HR = 0.29, 95% CI: 0.09–0.96, p = 0.043) nutrition had a lower hazard of developing nosocomial infection. Conclusions: This study supports the 2023 ESPEN guidelines, showing that achieving the recommended energy and protein intake during the early phase of severe trauma is linked to lower mortality rates, shorter mechanical ventilation time, and reduced risk of nosocomial infections. Full article