Search Results (1,433)

Background: Lateral tibial hemiepiphysiodesis with tension band plates is an established method for correcting genu varum in skeletally immature patients. However, outcomes may vary depending on underlying pathology and patient characteristics. Methods: This retrospective cohort study evaluated 31 patients (53 knees) treated between 2011 and 2024 at a tertiary pediatric orthopedic center. Patients were categorized as idiopathic or non-idioathic genu varum based on diagnosis. Inclusion criteria required open physes, absence of previous or concomitant knee surgeries for alignment correction, and availability of standardized long-standing radiographs. Radiographic parameters, including mechanical axis deviation (MAD), hip–knee–ankle angle (HKA), and medial proximal tibial angle (MPTA), were assessed pre-operatively and at implant removal. Outcomes were classified as complete correction, partial correction, absent correction, overcorrection, or progression of deformity. Results: Overall, 64.2% of knees achieved complete correction. Success was significantly higher in idiopathic cases (82.1%) than in non-idiopathic deformities (44%). Success was also more frequent in males (p = 0.040). In multivariable analysis, non-idiopathic patients (β = 351.9; p = 0.002), HKA improvement (β = 1.4; p = 0.010) and change in BMI z-score (β = 202.4; p = 0.009) independently predicted surgical success. No major complications (Clavien–Dindo–Sink grade > 2) were observed. Conclusions: Lateral tibial hemiepiphysiodesis is effective for idiopathic genu varum, offering minimally invasive correction with low complication rates. However, outcomes in non-idiopathic deformities are less predictable, emphasizing the need for individualized treatment planning and counseling. Early intervention, careful implant positioning, and rigorous follow-up are essential to optimize results and prevent unintended overcorrection. Full article

Solid organ transplant recipients (SOTRs) are at high risk of severe coronavirus disease 2019 (COVID-19), therefore early treatment of mild infections is crucial to prevent increased morbidity and mortality. The effectiveness of early treatment in SOTRs has yet to be fully characterized due to the emergence of new SARS-CoV-2 variants and to COVID-19 vaccination implementation. The aim of this single-center retrospective study is to evaluate the outcomes, safety and impact on SARS-CoV-2 viral load kinetics of COVID-19 early treatment in SOTRs. The study includes 80 SOTRs with a laboratory-confirmed diagnosis of symptomatic SARS-CoV-2 infection enrolled between January and October 2022 and treated with either monoclonal antibodies or antivirals. All patients received COVID-19 vaccination and 68.8% of them showed detectable levels of anti-spike (S) antibodies. The occurrence of clinical events (hospitalization, intensive care unit admission, or death) was assessed within 30 days after treatment initiation. The quantification of SARS-CoV-2 viral load were performed at baseline and at day-7. The rate of hospitalization was 2.5% [0.3–9%] and no deaths occurred. All patients completed treatment with no serious adverse events. Median viral load decrease was 0.48 [0.26–0.69] log₂ cycle threshold (ct) values, with no significant differences between SOTRs treated with monoclonal antibodies and those treated with antivirals. Viral load decrease was significantly associated with positive anti-s serology at baseline ($\beta$ = 0.196, p = 0.01), number of days between symptom onset and treatment ($\beta$ = 0.05, p = 0.03) and the number of comorbidities ($\beta$ = −0.05, p = 0.03). We provide evidence of real-world effectiveness of early therapy in SOTRs infected with SARS-CoV-2 and demonstrate the relevant role of humoral response to vaccination in enhancing early viral load decay during treatment. Full article

Background: The growing challenge of multimorbidity for healthcare systems worldwide demands a dual prevention framework, targeting both primary and secondary prevention. Multimorbidity–multibehaviours can provide such a theoretical and clinical framework to explore new aetiological evidence for multimorbidity risk. While the role of single health risk behaviours, such as smoking, nutrition, alcohol, and physical activity (SNAP), in chronic disease prevention is well-documented, their synergistic effect on multimorbidity has received relatively little attention. Methods: Using retrospective observational data from electronic health records of 21,079 patients from a convenience sample of three general practices in Staffordshire, UK (2015–2018), we examined the association between SNAP-multibehaviours and multimorbidity risk, defined as follows: MM2+ (≥2 morbidities), MM3+ (≥3 morbidities), and complex multimorbidity (accumulated morbidities affecting ≥3 body systems). Multiple logistic regression models, stratified by sex and adjusted for age and area, were applied to analyse the associations between both combined and accumulative SNAP-health risk behaviours (HRBs) and all multimorbidity operational definitions. Results: A dose–response association was observed, indicating increased multimorbidity risk with greater accumulation of SNAP-HRBs. Additionally, sex-specific patterns were identified, which varied according to the operational definitions of multimorbidity. These findings underscored both the clinical significance of the identified outcomes for promoting tailored multimorbidity guidelines and the need for further sex-sensitive research. Conclusion: These findings support the importance of transcending traditional silos in healthcare and public health research by integrating preventive and curative medicines under a multimorbidity–multibehaviour framework. Embracing the complexity of coexisting morbidities and health risk behaviours, healthcare systems can move beyond disease-specific and behaviour-specific paradigms. This approach has the potential to enhance clinical outcomes and to address the complex needs of individuals with multimorbidity in real-world healthcare settings. Full article

In welding applications, line-structured-light vision is widely used for seam tracking, but intense noise from arc glow, spatter, smoke, and reflections makes reliable laser-stripe segmentation difficult. To address these challenges, we propose EUFNet, an uncertainty-driven symmetrical two-stage segmentation network for precise stripe extraction under real-world welding conditions. In the first stage, a lightweight backbone generates a coarse stripe mask and a pixel-wise uncertainty map; in the second stage, a functionally mirrored refinement network uses this uncertainty map to symmetrically guide fine-tuning of the same image regions, thereby preserving stripe continuity. We further employ an uncertainty-weighted loss that treats ambiguous pixels and their corresponding evidence in a one-to-one, symmetric manner. Evaluated on a large-scale dataset of 3100 annotated welding images, EUFNet achieves a mean IoU of 89.3% and a mean accuracy of 95.9% at 236.7 FPS (compared to U-Net’s 82.5% mean IoU and 90.2% mean accuracy), significantly outperforming existing approaches in both accuracy and real-time performance. Moreover, EUFNet generalizes effectively to the public WLSD benchmark, surpassing state-of-the-art baselines in both accuracy and speed. These results confirm that a structurally and functionally symmetric, uncertainty-driven two-stage refinement strategy—combined with targeted loss design and efficient feature integration—yields high-precision, real-time performance for automated welding vision. Full article

Background: ESC recommends ticagrelor over clopidogrel for the treatment of acute coronary syndrome (ACS) but the lack of evidence for elderly patients (≥75) and concerns over bleeding has led to significant variability in its use within the UK. Our aim is, therefore, to compare the safety of ticagrelor compared to clopidogrel in real-world elderly patients admitted with ACS and managed either medically or through percutaneous intervention. Methods: Unselected elderly patients (≥75) admitted to Royal Berkshire Hospital with ACS (2013–2015) were identified and followed for 1 year. The primary outcomes were bleeding events (TIMI criteria), all-cause mortality, cardiovascular mortality, ischemic stroke, angina, NSTEMI and STEMI. Results: A total of 288 patients with ACS were discharged with aspirin and either clopidogrel (137) or ticagrelor (151). In total, 152 of these patients underwent invasive angiography and revascularization. The baseline clinical characteristics and crusade bleeding score were similar between the groups receiving ticagrelor or clopidogrel. There were no significant differences in all-cause mortality (8.8% vs. 10.6%), cardiovascular mortality (2.9% vs. 2.0%), ischemic stroke (0.7% vs. 2.0%), angina (6.6% vs. 5.3%) or STEMI (2.2% vs. 1.3%). Patients on clopidogrel, however, had increased events of NSTEMI compared to ticagrelor (8.0% vs. 2.0%, OR 4.481, 95% CI 1.223–16.42) and overall MI (10.2% vs. 3.3%, p = 0.030). No difference was observed in either major (8.8 vs. 8.6%) or minor TIMI bleeding (18.2% vs. 20.5%) and after propensity score matching (minor bleeding p = 0.39, major bleeding p = 0.76). Conclusions: In this real-world analysis, ticagrelor did not increase major or fatal bleeding compared to clopidogrel in elderly patients. In view of the mortality benefit in the large trials, additional cardiovascular benefit of ticagrelor should not be withheld on the basis of age as a perceived risk factor for bleeding in ACS. Full article

Clinical trials in nephrology have historically been hindered by significant challenges, including slow disease progression, patient heterogeneity, and recruitment difficulties. While recent therapeutic breakthroughs have transformed care, they have also created a ‘paradox of success’ by lowering baseline event rates, further complicating traditional trial designs. We hypothesize that integrating innovative trial methodologies with advanced computational tools is essential for overcoming these hurdles and accelerating therapeutic development in kidney disease. This narrative review synthesizes the literature on persistent challenges in nephrology trials and explores methodological innovations. It investigates the transformative impact of computational tools, specifically Artificial Intelligence (AI), techniques like Augmented Reality (AR) and Conditional Tabular Generative Adversarial Networks (CTGANs), in silico clinical trials (ISCTs) and Digital Health Technologies across the research lifecycle. Key methodological innovations include adaptive designs, pragmatic trials, real-world evidence, and validated surrogate endpoints. AI offers transformative potential in optimizing trial design, accelerating patient stratification, and enabling complex data analysis, while AR can improve procedural accuracy, and CTGANs can augment scarce datasets. ISCTs provide complementary capabilities for simulating drug effects and optimizing designs using virtual patient cohorts. The future of clinical research in nephrology lies in the synergistic convergence of methodological and computational innovation. This integrated approach offers a pathway for conducting more efficient, precise, and patient-centric trials, provided that critical barriers related to data quality, model validation, regulatory acceptance, and ethical implementation are addressed. Full article

Metagenomic next-generation sequencing (mNGS) is transforming infectious disease diagnostics by enabling simultaneous, hypothesis-free detection of a broad array of pathogens—including bacteria, viruses, fungi, and parasites—directly from clinical specimens such as cerebrospinal fluid, blood, and bronchoalveolar lavage fluid. Unlike traditional culture and targeted molecular assays, mNGS serves as a powerful complementary approach, capable of identifying novel, fastidious, and polymicrobial infections while also characterizing antimicrobial resistance (AMR) genes. These advantages are particularly relevant in diagnostically challenging scenarios, such as infections in immunocompromised patients, sepsis, and culture-negative cases. Despite its potential, mNGS remains underutilized in clinical microbiology due to persistent gaps between its technical capabilities and routine diagnostic adoption. This review addresses key translational challenges that limit the broader implementation of mNGS, especially in resource-constrained and critical care settings. We provide a comprehensive overview of the entire workflow—from sample processing and host DNA depletion to sequencing platforms and downstream bioinformatics—and highlight sources of variability, including contamination, human DNA interference, and inconsistencies in resistance gene annotation. Additionally, we explore the ethical, legal, and privacy implications of host genomic data, as well as economic and regulatory obstacles hindering mNGS integration into standard clinical practice. To illustrate clinical relevance, we examine real-world evidence from large-scale trials such as MATESHIP, GRAIDS, DISQVER, and NGS-CAP. Finally, we outline future directions involving artificial intelligence, multi-omics integration, cloud-based analytics, and portable sequencing technologies for point-of-care diagnostics. By addressing both current limitations and emerging innovations, this review offers a translational framework for integrating mNGS into precision diagnostics and infection management across diverse healthcare environments. Full article

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular disorder and a leading genetic cause of infant mortality. The past decade has witnessed a paradigm shift in SMA management with the advent of disease-modifying drugs (DMDs). This narrative review aims to (i) summarize pivotal randomized controlled trials (RCTs) that led to the approval of DMDs for SMA Types 1 and 2; (ii) synthesize real-world evidence on their safety and effectiveness; and (iii) explore emerging therapeutic frontiers, including gene modifiers, predictive biomarkers, prenatal interventions, and combination strategies. Pivotal RCTs and real-world studies demonstrate that onasemnogene abeparvovec (a single-dose gene therapy), nusinersen (an intrathecal antisense oligonucleotide), and risdiplam (an oral SMN2 splicing modifier) each significantly improve survival and motor function milestones compared to natural history in Type 1 and Type 2 SMA, with the majority of treated patients achieving independent sitting and prolonged ventilator-free survival, while safety profiles are generally manageable and distinct for each therapy. Similar outcomes have been demonstrated for presymptomatic patients with SMA. The introduction of DMDs has transformed the prognosis of SMA, particularly for early-onset forms, with robust evidence supporting their efficacy and safety. Continued real-world monitoring and exploration of adjunctive therapies are essential to optimize outcomes across the SMA setting and address unmet needs in non-responders and older patients. Full article

Background: In recent years, multiple transcatheter devices have been developed for tricuspid valve intervention. The aim of this study was to evaluate acute tricuspid annular remodeling following percutaneous leaflet repair using a leaflet approximation device for the reduction of tricuspid regurgitation (TR). Methods: This retrospective cohort study included 26 consecutive patients treated at two centers. Tricuspid annular geometry was assessed using three-dimensional transesophageal echocardiography during the procedure. Results: The mean age of the cohort was 79.3 years, and 88.5% were female. All patients had severe or greater TR pre-procedure, mostly due to annular dilation. The procedure was successful in all cases, with at least a one-grade reduction in TR observed prior to hospital discharge. Significant reductions were observed in the mean septal-lateral diameter (4.09 ± 0.44 cm vs. 3.54 ± 0.53 cm, p < 0.0001), mean major diameter (4.65 ± 0.63 cm vs. 4.28 ± 0.65 cm, p = 0.0002), planimetric area (14.00 ± 2.91 cm² vs. 11.25 ± 2.91 cm², p < 0.0001), and perimeter (13.62 ± 1.43 cm vs. 12.42 ± 1.62 cm, p < 0.0001) of the tricuspid annulus. Conclusions: In this small real-world cohort, transcatheter edge-to-edge repair was found to be both effective and safe. The use of a leaflet approximation device not only reduced TR severity but also led to significant reductions in annular dimensions. To our knowledge, this study provides additional evidence of acute tricuspid annulus remodeling following edge-to-edge repair, which may have significant therapeutic implications. Full article

Background/Objectives: This study compared overall survival (OS) associated with common real-world treatment sequences in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the United States. Methods: Utilizing the nationwide Flatiron Health electronic health record-derived de-identified database, adult CLL/SLL patients who initiated systemic therapy (JAN2016-NOV2023) and received at least two lines of therapy (LoTs) were analyzed. Treatment regimens were categorized based on drug class, and most frequent (n ≥ 50) sequences (first LoT followed by [→] second LoT) were compared. OS from initiation of the first LoT was compared using multivariable Cox proportional hazard models, and adjusted hazard ratios with 95% CIs were reported. Results: Among 2354 eligible patients, n = 1711 (73%) received the 16 most frequent treatment sequences. Sequencing chemoimmunotherapy (CIT) → CIT (HR: 2.29 [1.23–4.28]), anti-CD20 monoclonal antibody (anti-CD20mab) monotherapy → CIT (1.95 [1.03–3.69]), and covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapy → anti-CD20mab monotherapy (2.00 [1.07–3.74]) were associated with worse OS compared to patients treated with cBTKi monotherapy → B-cell lymphoma 2 inhibitors (BCL2i) + anti-CD20mab (reference). Conclusions: OS associated with other sequences were not significantly different from the reference sequence in adjusted analyses, suggesting a lack of evidence for the optimal standard of care for sequencing the first two LoTs in real-world settings. Future research should reassess sequencing outcomes as novel treatments become adopted into clinical practice. Full article

Determining the transmission routes of pathogens in indoor environments is challenging, with most studies limited to specific case analyses and pilot experiments. When pathogens are instantaneously released by a patient in an indoor environment, the peak infection risk may not occur immediately but may instead appear at a specific moment during the pathogen’s spread. We developed a concise model to describe the temporal crest of infection risk. The model incorporates the transmission and degradation characteristics of aerosols and surface particles to predict infection risks via air and surface routes. Only four real-world outbreaks met the criteria for validating this phenomenon. Based on the available data, norovirus is likely to transmit primarily via surface touch (i.e., the fomite route). In contrast, crests of infection risk were not observed in outbreaks of respiratory diseases (e.g., SARS-CoV-2), suggesting a minimal probability of surface transmission in such cases. The new model can serve as a preliminary indicator for identifying different indoor pathogen transmission routes (e.g., food, air, or fomite). Further analyses of pathogens’ transmission routes require additional evidence. Full article

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article

Background: Renal cell carcinoma (RCC) is a common malignancy with a rising global incidence. While cytoreductive nephrectomy (CRN) was historically a cornerstone in the management of metastatic RCC (mRCC), its role has been questioned following pivotal trials such as CARMENA and SURTIME. With the advent of immune checkpoint inhibitors (ICIs) and targeted therapies, the contemporary relevance of CRN coupled with first-line immunotherapy and targeted therapy combination regimens warrants re-evaluation. Methods: This retrospective cohort study utilized the TriNetX research network to identify patients aged 18–90 years diagnosed with mRCC between 2005 and 2024 who received first-line systemic therapies. Patients were stratified into two cohorts based on receipt of CRN status within one year of diagnosis. Propensity score matching (1:1) was done to adjust baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards modeling were used to compare five-year overall survival between the groups. Results: Among 5960 eligible patients, 1776 (888 CRN matched to 888 who did not) formed the cohort of analysis. The CRN group demonstrated significantly higher five-year survival (57.7% vs. 45.0%, p < 0.0001) with a hazard ratio of 1.56 (95% CI: 1.33–1.83). Subgroup analyses showed consistent survival benefits across all four NCCN-recommended first-line regimens—Axitinib + Pembrolizumab: 64.0% (CRN) vs. 53.3% (no CRN), p = 0.01; Cabozantinib + Nivolumab: 50.1% vs. 40.4%, p = 0.004; Lenvatinib + Pembrolizumab: 37.4% vs. 22.8%, p = 0.012; Nivolumab + Ipilimumab: 56.4% vs. 46.1%, p = 0.005. Conclusions: In the era of modern immunotherapy and targeted agents, CRN remains associated with improved survival in patients with mRCC receiving NCCN-recommended first-line regimens. These findings support the continued evaluation of CRN as a component of multimodal therapy, particularly in patients with favorable risk profiles. Full article

Background: RSV remains a leading cause of infant hospitalization worldwide, and the recently approved nirsevimab could represent an effective and safe prophylactic strategy to prevent severe infections in the general neonatal population. Objectives: We conducted a retrospective observational monocentric pilot study in a mixed preterm/term birth cohort to add real-world evidence of the efficacy and safety of nirsevimab in preventing severe RSV infection. Methods: We included a total of 2035 consecutive infants admitted to the Neonatal Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, from November 2024 to April 2025. We evaluated 30-day safety profiles and season-wide RSV infection rates, and the outcomes were also compared to newborns’ birth rate in the two previous seasons (2022–2023 and 2023–2024). Results: After the introduction of nirsevimab, a lower RSV infection rate was reported compared to previous seasons, and no adverse effects were observed. Compared to previous seasons, the clinical outcomes were more favorable, as only one unvaccinated neonate with RSV infection required invasive ventilation. Conclusions: In this real-world analysis, we demonstrated a good short-term safety profile of nirsevimab, as well as a potentially high efficacy in the general neonatal population with lower RSV infection incidence. However, future studies are needed to better assess its long-term safety and season-wide efficacy. Full article

Autologous therapies are currently being studied to determine if they can modulate the course of knee osteoarthritis symptoms and/or disease progression. One potential therapeutic target is the polarization of pro-inflammatory M1 macrophages to pro-healing M2 macrophages. The autologous therapy, Autologous Protein Solution (APS), was incubated with donor-matched human peripheral-derived macrophages for 10 days. M1 pro-inflammatory macrophages were determined by the percentage of CD80+ and M2 pro-healing macrophages were determined by CD68+ and CD163+ by epifluorescent microscopy. To determine clinical effectiveness, an APS-specific minimal clinically important improvement (MCII) using an anchor-based method was calculated in a randomized controlled trial of APS (n = 46) and then applied to a real-world registry study (n = 78) to determine the percentage of pain responders. Compared to control media, APS statistically increased the percentage of M2 macrophages and decreased the percentage of M1 macrophages, while platelet-poor plasma had no effect on polarization. In the randomized controlled trial (RCT), the MCII at the 12-month follow-up visit was calculated as 2.0 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and 7.5 points on the WOMAC function scale. Applying this MCII to the real-world registry data, 62.5% of patients met the MCII with an average of 4.7 ± 2.5 points of improvement in pain. Autologous therapies can influence macrophage polarization and have demonstrated clinical effectiveness in a real-world patient setting. Full article