Journal of Clinical Medicine

Hypospadias, a common congenital anomaly requiring surgical correction, has seen growing research in surgical techniques and outcomes. However, no comprehensive bibliometric or disruption-based analysis exists to map the fields evolution. This study uses bibliometrics and the Disruption Index (DI) to identify key transformational research in hypospadias. A systematic search of five databases (PubMed, Web of Science, ScienceDirect, Scopus, and Dimensions) from January 1990 to December 2023 was conducted, yielding 7,732 articles. After applying inclusion criteria, 200 studies were analyzed. Citation data and DI scores were calculated using OpenCitations. Spearmans rank test assessed correlations between DI and citation metrics. A subgroup analysis identified trends based on the latest hypospadias research priorities. The mean citation count was 72.3 (SD = 43.1) with a mean DI of 0.011 (SD = 0.17). Five studies, focusing on complications, analgesia, and surgical techniques, had the highest DI (1.0). A moderate positive correlation was found between DI and citation rate ({rho} = 0.405, p < 0.001). Subgroup analysis showed most research focused on surgical techniques (30.5%) and etiology (25.8%), while areas like surgical training (2.6%) and innovation (0%) were underrepresented. This study identifies critical gaps in hypospadias research. The DI reveals influential studies that redirect research trajectories. Future work should focus on innovation and translational research to accelerate advancements in hypospadias care.

An increasing number of studies highlight the role of saccadic remodulation in compensatory mechanisms following vestibular injury, and the reappearance of SHIMP saccades correlates with symptom improvement measured by the Dizziness Handicap Inventory (DHI). To investigate the influence of attentional processes and working memory on visuo-vestibular interaction, three independent but interrelated experiments were conducted. In the first two experiments, healthy subjects and patients with unilateral or bilateral vestibular deficits underwent vHIT in SHIMP mode and the Functional Head Impulse Test (fHIT), performed first separately and subsequently simultaneously. Mean latency and clustering of SHIMP saccades, together with Landolt C recognition rates, were analyzed. Differences between separate and combined protocols were assessed, and, in patients, correlated with symptom severity measured by the DHI, to determine whether the near-simultaneous execution of tasks mediated by shared parietal cortical substrates influenced performance. In the third experiment, vHIT in HIMP mode and fHIT were performed using separate and combined protocols to evaluate whether recognition-related cognitive load affected recovery saccade latency and clustering. Results suggest that visual recognition modulates visuo-vestibular interaction, supporting integrated dual-task protocols for ecological balance assessment and helping explain clinical discrepancies.

Background Inflammatory markers play an important role in the pathophysiology of Lumbar disc herniation (LDH). This study presents a comprehensive multi-assessment of the inflammatory landscape by combining serum inflammatory cytokines quantification, their diagnostic performance, associations with radiological features, and integrating the experimental findings into an in-silico protein-protein interaction network. Methods A multifaceted study design was utilized to quantify and compare the distribution of selected inflammatory cytokines in patients with LDH and control subjects. The diagnostic ability of these cytokines was assessed using receiver operating characteristic curve analysis. The cytokines values were correlated with selected radiological findings including disc herniation subtypes (protrusion, extrusion, and sequestration), and further categorized as contained and non-contained in patients using a Spearmans rank correlation test. Additionally, computational analysis was performed to identify the central hubs and functionally enriched pathways. Results In patients with LDH, IL-6 and IL-1{beta} showed statistically significant (IL-6: p < 0.001; IL-1{beta}: p = 0.001) rise, but IL-6 showed high diagnostic and discriminative power (AUC = 0.99; cut-off: 19.99 pg/mL). Further IL-1{beta} exhibited a positive correlation with non-contained disc herniation (extrusion and sequestration), while displaying a significant (p < 0.05) negative correlation with protrusion. In silico analysis identified IL-1{beta}, IL-8, TNF-, IL-6, IL-1, CSF2, CSF3, and IL-10 as central hubs, with IL-1{beta} being the top ranked hub in determining functionally enriched cytokine-cytokine receptor interaction. Conclusions Study confirmed IL-6 as a powerful diagnostic marker for LDH, while IL-1{beta} aids in determining contained and non-contained disc herniation. Further, IL-1{beta} was identified as the central hub, triggering functionally enriched pathways in the pathogenesis of LDH.

Background: Radiographic detection of caries lesions adjacent to restorations is challenging due to limitations of two-dimensional imaging and difficulties distinguishing true lesions from restorative or anatomical radiolucencies. Artificial intelligence (AI)-based clinical decision support systems (CDSSs) have been introduced to assist radiographic interpretation; however, different AI tools may yield variable diagnostic outputs, and their comparative performance remains unclear. Objective: To compare the diagnostic performance of commercial and experimental AI algorithms for detecting secondary caries lesions on bitewings. Methods: This cross-sectional diagnostic accuracy study included 200 anonymized bitewings comprising 885 restored tooth surfaces. A consensus group reference standard identified all surfaces with a caries lesion and classified each lesion by type (primary/secondary) and depth (enamel-only/dentin-involved). Five commercial (Second Opinion, CranioCatch, Diagnocat, DIO Inteligencia, and Align X-ray Insights) and three experimental (Mask R-CNN-based and Mask DINO-based) systems were tested. Diagnostic performance was expressed through sensitivity, specificity, and overall accuracy (95% CI). Comparisons used generalized estimating equations, adjusted for clustered data. Results: Specificity was high across all systems (0.957-0.986), confirming accurate recognition of non-carious surfaces, whereas sensitivity was moderate (0.327-0.487), reflecting frequent missed detections of enamel and dentin lesions. Accuracy ranged from 0.882 to 0.917, with no significant differences among models (p >= 0.05). Confounding factors, such as radiographic overlapping, marginal restoration defects, and cervical artifacts, were the main sources of misclassification. Conclusions: AI algorithms, regardless of architecture or commercial status, showed similar diagnostic capabilities and a conservative detection profile, favoring specificity over sensitivity. Improvements in dataset diversity, labeling precision, and explainability may further enhance reliability for secondary caries detection. Clinical Significance: AI-based CDSSs assist clinicians by providing consistent detection. Their high specificity is particularly valuable in minimizing unnecessary invasive treatments (overtreatment), though they should be used as adjuncts rather than a replacement for expert judgment.

A multiplex diagnostic test is evaluated for self-reported long COVID associated persistent symptoms and a poor recovery from a SARS-CoV-2 infection. A mass-standardised concentration of total antibodies (AC), high-quality (HQ) antibodies and percentage of HQ antibodies (HQ%) is assessed against a spectrum of spike proteins to the SARS-CoV-2 variants: Wuhan, , {delta}, and the Omicron variants BA.1, BA.2, BA.2.12.1, BA.2.75, BA.5, CH.1.1, BQ.1.1 and XBB.1.5 in three cohorts. A cohort of control patients (n = 46) recovered (CC) and a cohort of self-declared long COVID patients (n = 113) (LCC). A nested Receiver Operating Characteristic (ROC) analysis, performed for the variant with lowest HQ concentration in the spectrum, produced an area under the curve and AUC = 0.61 (0.53-0.70) for the CC vs LCC cohorts. For the LCC cohort, the cut-off thresholds for AC = 0.8 mg/L, HQ = 1.5 mg/L and HQ% of 34% were determined, leading to a 71% sensitivity and 66% specificity derived by the Youden metric. The cohorts may be fully classified based on ROC and outlier analysis to give an incidence of persistent virus 62% (95% CI 52% - 71%), hyperimmune 12% (95% CI 7% - 20%) and unclassified, 26% (95% CI 18% - 35%). The overall diagnostic accuracy for both the hyper and hypo immune is 69%. All clinical interventions can now be tailored for the heterogenous long COVID patient cohort.

PurposeObstructive sleep apnea (OSA) is a common comorbidity in heart failure (HF) patients with prevalence increasing as HF severity worsens. While CPAP/BiPAP has been shown to reduce disease burden and mortality in the general HF population, it is unclear whether these benefits extend to patients with left ventricular assist devices (LVADs). We sought to determine whether OSA affects long-term survival in newly implanted LVAD patients and whether CPAP/BiPAP treatment confers mortality benefits. MethodsThis single-center retrospective study included patients who underwent LVAD implantation between January 2007 and February 2022. Recipients were stratified by OSA status (OSA vs No-OSA), and those with OSA were further categorized based on CPAP/BiPAP compliance. Comparative statistics and Kaplan-Meier survival analyses were performed, with log-rank tests used to compare groups and assess survival differences. A Cox proportional hazards model was conducted to evaluate the association between risk factors and survival among patients with OSA and No-OSA. ResultsBefore LVAD implantation, patients with OSA had higher body mass index, hypertension, and a higher rate of implantable cardioverter-defibrillator placement than those without OSA. OSA was not associated with increased postoperative complications. Although survival did not differ significantly between OSA and No-OSA patients (p=0.33), CPAP/BiPAP-compliant OSA patients had significantly better survival than noncompliant patients (p=0.0099). ConclusionsLVAD patients with OSA who consistently use CPAP/BiPAP have better survival than those who do not. CPAP/BiPAP is a simple, low-risk treatment that can reduce mortality in this population. Therefore, increased perioperative screening for OSA should be considered for patients receiving LVADs. Multicenter studies are needed to confirm our findings further.

Backgound: Accurate assessment of diastolic function and left ventricular (LV) filling pressure is central to heart failure diagnosis and risk stratification. Contemporary guideline algorithms rely on complex parameters that are not consistently available in routine clinical practice. Objective: To compare the diagnostic and prognostic performance of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) and 2025 ASE guidelines with a deep learning model based on routinely acquired echocardiographic variables. Methods: This study evaluated the guideline-based algorithms and a deep learning model in participants from the Atherosclerosis Risk in Communities (ARIC) cohort (n=5450) for prognostication and two invasive hemodynamic validation cohorts from the United States (n=83) and Japan (n=130) for detection of elevated left ventricular filling pressure. Results: In the ARIC cohort, the deep learning model demonstrated superior prognostic performance compared with the 2016 and 2025 guidelines (C-index: 0.676 vs. 0.638 and 0.602, respectively; both p<0.001). Similar findings were observed among participants with preserved ejection fraction (C-index: 0.660 vs. 0.628 and 0.590; both p<0.001), with improved performance compared with the H2FPEF score (C-index: 0.660 vs. 0.607; p<0.001). In the US hemodynamic validation cohort, the deep learning model showed higher diagnostic performance than the 2025 guidelines (AUC: 0.879 vs. 0.822; p=0.041) and similar performance compared with the 2016 guidelines (AUC: 0.879 vs. 0.812; p=0.138). In the Japanese hemodynamic validation cohort, the deep learning model outperformed both guidelines (AUC: 0.816 vs. 0.634 and 0.694; both p<0.05). Conclusions: A deep learning model leveraging routinely available echocardiographic parameters demonstrated improved diagnostic and prognostic performance compared with contemporary guideline-based approaches, potentially offering a scalable alternative for assessing diastolic function and left ventricular filling pressures.

ObjectiveOnly preliminary investigations on the use of the 445 nanometer wavelength blue light laser (BLL) for various laryngeal pathologies have been described. Currently, no standard exists for reporting treatment technique and tissue effect with this modality. Here, we aim to establish and validate a classification system to describe laser-induced tissue effects. Study DesignRetrospective video-based study for classification development and reliability validation. MethodsVideo recordings from procedures performed with the BLL by multiple academic laryngologists were retrospectively reviewed. A preliminary 6-point classification (BLL 1-6) was developed based on expert consensus. Thirteen additional procedural clips were independently rated utilizing the classification schema to assess perceived tissue effect, and measure inter- and intra-rate reliability. ResultsThe final 5-point classification system (BLL 1-5) included angiolysis, blanching, tissue vaporization, ablation with mechanical tissue removal, and cutting. The consensus of the combined reviewers in rating all cases was 89% (58 of 65). Complete consensus was not achieved in 11% (7/65) of cases. Of those incorrect, 57% (4/7) were of clips illustrating the BLL-2 classification. Intra-rater reliability amongst the reviewers was 100%. ConclusionTissue effect of the 445 nm blue light laser can reliably be standardized with this proposed classification system. This rating system can be used to facilitate future systematic study of outcomes and effective communication between laryngologists and trainees.

Background. Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a pro-inflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. Methods. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 males, 40 self-identified Black-Americans) with recent hospitalization for HFrEF, and systemic inflammation (C reactive protein [CRP] levels >2 mg/L) who were assigned to anakinra (N=42 [66.7%]) or placebo (N=21 [33.3%]) as part of the REDHART2 clinical trial (NCT0014686). Cardiorespiratory fitness was measured as peak oxygen consumption (peak VO2). Results. Baseline plasma IL-1Ra levels were 380 pg/ml (290 to 1046). On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra vs placebo (3,994 pg/ml [3,372 to 5,000] vs 492 pg/ml [304 to 1370], P<0.001). The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%) and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R=-0.269, P=0.033 and R=-0.355, P=0.004, respectively) and no statistically significant correlations with peak VO2 values (P>0.05). Conclusions. Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, have a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels however show only a modest correlation with CRP levels and not with peak VO2.

Introduction: Accurate stratification of hard atherosclerotic cardiovascular disease (ASCVD) risk remains challenging despite advances in prevention. Liver function biomarkers (LFBs), particularly gamma - glutamyl transferase (GGT), have been linked to cardiovascular outcomes, yet their contribution to hard ASCVD risk prediction is not well defined. Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2005 - 2018) to assess cross - sectional associations between LFBs and 10 - year hard ASCVD risk estimated by the ACC/AHA Pooled Cohort Equations. Multivariable regression, restricted cubic splines, and mediation analyses were applied to examine independent and dose - response relationships. External validation was performed in the China Health and Retirement Longitudinal Study (CHARLS) and NHANES using machine learning models (CoxBoost, Naive Bayes and Random Forest). Results: Among 5,731 NHANES participants, GGT showed an independent linear association with hard ASCVD risk (P - trend = 0.003), partly mediated by systolic blood pressure (44.8%), HbA1c (19.0%), and high density lipoprotein cholesterol (13.4%). Machine learning (ML) models incorporating GGT, alkaline phosphatase (ALP), and globulin alongside traditional risk factors improved predictive accuracy, with Naive Bayes achieving an AUC of 0.751 in NHANES validation. Conclusions: GGT is an independent and biologically plausible biomarker of hard ASCVD risk, acting through cardiometabolic pathways. Incorporating LFBs into risk prediction models, particularly with machine learning, enhances risk stratification and may facilitate early identification of high - risk individuals.

Sickle cell disease (SCD) is associated with substantial cardiovascular morbidity, but echocardiographic data from Latin American populations remain scarce. We aimed to characterise the structural, functional, and haemodynamic echocardiographic profile of adults with SCD attending a tertiary referral centre in Cali, Colombia. We conducted an observational, cross-sectional study based on systematic review of medical records and transthoracic echocardiography reports of consecutive adult patients ([&ge;]18 years) with confirmed SCD evaluated between January 2022 and December 2024. Patients with complex congenital heart disease, severe valvular disease of unrelated aetiology, pregnancy, or echocardiograms of insufficient quality were excluded. Of 669 patients screened, 57 met inclusion criteria. Reporting followed STROBE recommendations. The median age was 24 years (interquartile range [IQR] 21-32) and 59.6% were female; the SS genotype was the most frequent (76.4%) and 71.4% were on hydroxyurea. Median haemoglobin was 10.2 g/dL (IQR 9.3-11.4) and median NT-proBNP 491 pg/mL (IQR 98-1290). Most patients had preserved left ventricular dimensions and systolic function (median ejection fraction 63%, IQR 57-66.5; mean global longitudinal strain -18.9% {+/-} 2.9). Right ventricular function was preserved (mean tricuspid annular plane systolic excursion 25.4 {+/-} 4.6 mm). Left ventricular geometry was normal in 42.1%, with concentric remodelling in 24.6%, concentric hypertrophy in 21.1%, and eccentric hypertrophy in 12.3%. Diastolic function was normal in 71.4%. Valvular disease, when present, was predominantly mild. Tricuspid regurgitation velocity exceeded 2.5 m/s in 29.8% of patients and exceeded 3.0 m/s in 10.5%, identifying a substantial subgroup at intermediate-to-high probability of pulmonary hypertension. In this Colombian cohort of relatively young adults with SCD, cardiac structure and biventricular function were largely preserved, but nearly one-third of patients had echocardiographic findings suggestive of pulmonary hypertension. These findings support the routine use of transthoracic echocardiography as an accessible tool for early cardiovascular risk stratification in adults with SCD in low- and middle-income settings.

While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

Introduction: Spontaneous coronary artery dissection (SCAD) is frequently accompanied by persistent symptoms of unknown pathogenesis after the index event. Autonomic dysfunction is a plausible mechanism for these but has not been systematically characterized. We quantified antecedent and contemporary autonomic symptoms in survivors of SCAD and examined their associations with cardiac and extra-cardiac symptoms and health-related quality of life. Methods: This cross-sectional study recruited 227 volunteers from multiple countries with a self-reported history of SCAD. Participants completed validated patient-reported measures, including the Composite Autonomic Symptom Score-31 (COMPASS-31), Anxiety Sensitivity Index-3 (ASI-3), and EuroQol-5 Dimension-5L (EQ-5D-5L). They also completed an internally derived retrospective autonomic predisposition score assessing symptoms during adolescence and early adulthood. Results: Participants were predominantly female (97.8%), median age 53 (47-58) years, and were surveyed a median of 3 (1-5) years after their index SCAD event. 21.6% reported SCAD recurrence. Moderate autonomic symptom burden (COMPASS-31 20) was present in 56.4% and severe burden (40) in 16.3%. History of antecedent autonomic symptoms was the strongest independent predictor of contemporary autonomic symptom burden after adjustment for demographic and clinical covariates (=0.514; P <0.001). Greater autonomic symptom burden independently predicted lower EQ-5D health utility (=0.150; P=0.029) and was associated with the ASI-3 physical concerns (=0.232; P <0.001), but not social concerns domain. Autonomic symptoms were not associated with SCAD recurrence. Conclusion: Symptoms of autonomic dysregulation are common in survivors of SCAD and are associated with reduced quality of life. Their association with antecedent dysautonomic features during adolescence and early adulthood suggests a longstanding predisposition, the significance of which warrants further evaluation.

Background: Even for experienced operators, endovascular treatment of unruptured intracranial aneurysms involves intraoperative uncertainty that may lead to adjustments in strategy, prolong the procedure, and potentially cause inefficiency and device waste. This study aimed to evaluate whether pre-procedural testing (PPT) of endovascular treatment using patient-specific models was associated with increased operator confidence and perceived clinical utility, including improvements in procedural efficiency and reduced resource waste. Methods: We enrolled a cohort of patients who underwent PPT before endovascular treatment for complex unruptured intracranial aneurysms and compared their outcomes with a control group treated without PPT. The primary outcome was the Training Fidelity Score, a composite of three operator-reported Likert items defined a priori. Secondary outcomes included perceived clinical utility, intraoperative strategy changes, procedural time, radiation exposure, device waste and safety. Results: A total of 85 patients met the inclusion criteria (PPT=40; control=45). The Training Fidelity Score was high across the PPT group (median, 4.33/5). Perceived clinical utility was high and further increased significantly after the procedure. A significant reduction was observed in intraoperative strategy changes, with no changes recorded in the PPT group, compared to 6/45 in the control group (RR 0.09; p=0.027). Reductions in treatment time, radiation exposure and device waste were also noted. Conclusion: PPT using patient-specific models was associated with increased operator confidence, fewer intraoperative strategy changes, improved procedural efficiency, and reduced device waste without compromising safety. These findings support its use in pre-interventional preparation, but require prospective multicenter validation.

STRUCTURED ABSTRACTO_ST_ABSImportanceC_ST_ABSSexual dysfunction can occur after midurethral sling (MUS) and transvaginal prolapse surgery. It remains unclear whether these procedures impact the clitoris, despite its role in sexual function and proximity to the MUS and vagina. ObjectivesTo compare postoperative sexual function and clitoral features by MUS and vaginal surgery approach after transvaginal prolapse repair with/without concomitant MUS. DesignCross-sectional ancillary study of magnetic resonance imaging (MRI) and sexual function data from the Defining Mechanisms of Anterior Vaginal Wall Descent study. SettingEight clinical sites in the US Pelvic Floor Disorders Network. Participants: 88 women with uterovaginal prolapse who underwent vaginal mesh hysteropexy or vaginal hysterectomy with uterosacral ligament suspension with/without MUS between 2013-2015. Data were analyzed between September 2021-June 2023. ExposuresBetween June 2014-May 2018, participants underwent pelvic MRI 30-42 months after surgery, or earlier if reoperation was desired. Sexual activity and function at baseline and 24-48-month follow-up were evaluated using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Clitoral features were obtained from postoperative MRI-based 3-dimensional models. Main Outcomes and MeasuresPISQ-IR scores and clitoral features (size, position). ResultsEighty-two women (median [range] age, 65 [47-79] years) were analyzed: 45 MUS (22 hysteropexy, 23 hysterectomy) and 37 No-MUS (19 hysteropexy, 18 hysterectomy). Postoperatively, 25 MUS, 12 No-MUS, 20 hysteropexy, and 17 hysterectomy patients were sexually active (SA). Overall, within the MUS and vaginal surgery groups, sexual function remained unchanged or improved (most PISQ-IR change from baseline scores were [&ge;]0) among SA and NSA women. Among SA women after surgery, the MUS group (vs No-MUS) had a poorer PISQ-IR arousal/orgasm (SA-AO) score (median, 3.5 vs 4.3; P=.02). The hysteropexy group (vs hysterectomy) had less improvement in PISQ-IR SA-AO score (median, 0.0 vs 0.3; P=.01). Women with MUS (vs without) had a smaller clitoral glans thickness (median, 9.0 mm vs 10.0 mm; P=.008) and clitoral body volume (median, 2783.5 mm3 vs 3587.4 mm3; P=.01). Conclusions and RelevanceSA women with MUS (vs without) or hysteropexy (vs hysterectomy) experienced poorer postoperative sexual function. MUS was linked to a smaller clitoris. Future studies should explore surgery-induced changes in clitoral anatomy and sexual function. KEY POINTSO_ST_ABSQuestionC_ST_ABSHow do sexual function and clitoral anatomy differ by midurethral sling placement and vaginal surgery approach? FindingsThis cross-sectional study compared patient-reported sexual function outcomes and 30-42-month postoperative magnetic resonance imaging-based 3-dimensional clitoral models of 82 women after vaginal prolapse surgery with or without concomitant midurethral sling. Midurethral sling (vs no sling) and vaginal mesh hysteropexy (vs vaginal hysterectomy) were associated with poorer postoperative sexual function outcomes. Additionally, midurethral sling was associated with a smaller clitoral glans and body. MeaningMidurethral sling and vaginal mesh hysteropexy were associated with, and may adversely alter, postoperative sexual function and/or clitoral anatomy. VISUAL ABSTRACT/PROMOTIONAL IMAGE O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/26351291v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@904497org.highwire.dtl.DTLVardef@187514aorg.highwire.dtl.DTLVardef@e9e799org.highwire.dtl.DTLVardef@640f1a_HPS_FORMAT_FIGEXP M_FIG C_FIG

ObjectiveThis study evaluates the impact of systemic GLP-1 receptor agonist (GLP-1RA) use on surgical wound healing in high-risk surgical populations, including patients with diabetes, and implications for perioperative planning and healing outcomes. ApproachThis pilot retrospective cohort study compared adult surgery patients with non-healing postoperative wounds by their GLP-1RA use. Outcomes included healing status, time to wound closure, and number of surgical interventions. ResultsThe cohort included 35 non-GLP-1RA users and 16 GLP-1RA users with comparable baseline characteristics, except for significant higher prevalence of venous insufficiency among users. Though median time to closure was similar for all patients, users required fewer surgical interventions and their wounds reached closure in significant difference from non-users. Among patients with diabetes, all GLP-1RA users healed significantly compared to non-users. InnovationThe impact of GLP-1RA therapy on wound healing in high-risk reconstructive and soft-tissue surgery remains poorly defined. This pilot cohort addresses that gap, offering an early signal that GLP-1RA use is associated with improved wound healing and fewer postoperative interventions. These findings may inform perioperative practice by identifying a systemic pharmacologic factor that optimizes surgical outcomes in high-risk populations. ConclusionGLP-1RA use was associated with higher healing rates and fewer interventions, particularly among patients with diabetes. These findings support a beneficial role in surgical wound healing and warrant larger multi-site studies.

Background: Elevated lipoprotein(a) [Lp(a)] is a known risk factor for several cardiovascular-related diseases established from multiple genetic and observational studies. However, the underlying mechanisms mediating the effects of Lp(a) levels on cardiovascular disease risk and major adverse cardiovascular events (MACE) are unclear. The aim of this study was to identify proteins downstream of Lp(a) using mendelian randomization (MR) - a genetic causal inference approach. Methods: A two-sample MR was performed by initially identifying Lp(a) genetic instruments based on data from genome wide association studies (GWAS) of Lp(a) blood concentrations. These instruments were then tested for association with proteins from proteomic pQTL data (Olink from UK Biobank, 2940 proteins and SomaScan from deCODE, 4907 proteins). Results: A total of 521 proteins associated with Lp(a) were identified. Using pathway enrichment analysis, the following MACE-relevant pathways were identified comprising a total of 91 Lp(a) downstream proteins: oxidized phospholipid-related, chemotaxis of immune cells and endothelial cell activation, pro-inflammatory monocyte activation, neutrophil activity, coagulation, and lipid metabolism. Conclusion: The results suggest that the influence of Lp(a) treatments is primarily through modifying inflammation rather than lipid-lowering, thus providing insight into the mechanistic framework which mediates the effects of elevated Lp(a) on atherosclerotic cardiovascular disease.

Background: Patients with kidney failure undergoing maintenance hemodialysis suffer high rates of major adverse cardiovascular events(MACE) that are not accurately predicted by traditional cardiovascular risk models. There is an urgent need to identify novel, modifiable cardiovascular risk factors for these patients. Methods: We analyzed associations of 6287 circulating proteins with MACE among 1048 participants undergoing hemodialysis in the Chronic Renal Insufficiency Cohort(CRIC) (14-year follow-up) with validation in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study(PACE) (7-year follow-up). In both cohorts, proteins were measured shortly after dialysis initiation and one year later. We compared protein-based risk models derived by elastic net regression to the Pooled Cohort Equations(PCE) optimized for these cohorts(Refit PCE), and to an Expanded Refit PCE that included Troponin T and N-terminal pro-B-type natriuretic peptide. Results: In CRIC, 149 proteins were associated with MACE at false discovery rate<0.05. Among 22 proteins significant at Bonferroni p<8x10-6, proteins that validated in PACE included Sushi von Willebrand factor type A EGF and pentraxin domain-containing protein 1(SVEP1), Complement component C7, R-spondin 4, Tenascin, Fibulin-3 and Fibulin-5. Complement pathways were prominent in network analyses. SVEP1 surpassed other markers by statistical significance, with CRIC HR per log2 1.8 (p=2.1x10-12) and HR per annual doubling 1.6 (p=6.8x10-6). For 2-year MACE, AUC(95%CI) for SVEP1 alone was 0.72(0.59, 0.84) in CRIC, and 0.73(0.63, 0.81) in PACE. SVEP1 surpassed the Expanded Refit PCE in CRIC (0.61 (0.48, 0.73)) (p=0.038). In the pooled CRIC + PACE cohort, SVEP1 AUC(95%CI) (0.79(0.70, 0.88)) surpassed Refit PCE (0.61(0.51, 0.72)) (p=0.004). Conclusions: SVEP1, a 390 kDa protein unlikely to be renally cleared, surpassed over 6000 other proteins and by itself outperformed traditional clinical risk models in predicting MACE in two populations of patients undergoing maintenance hemodialysis. Future studies should provide mechanistic insights behind these findings.

Cardiovascular disease (CVD) remains the leading cause of mortality in the United States, despite being largely preventable through effective management of risk factors. This study evaluates the impact of Phase II cardiac rehabilitation (CR) on functional capacity and quality of life, using data from the Montana Outcomes Project Cardiac Rehabilitation Registry. Functional capacity improvements were assessed via the six-minute walk test (6MWT) and Dartmouth COOP questionnaire, with statistical analyses exploring the influence of CR session attendance, demographic factors, and referring diagnoses. Results demonstrated significant gains in 6MWT, with a mean improvement of 330.73 feet (p < .0001), and quality of life scores across all subgroups. A dose-response relationship was observed, indicating greater improvements with increased CR sessions (p < .0001), though diminishing returns were observed beyond 24-35 visits. Demographic factors and complex conditions influenced outcomes, underscoring the need for tailored strategies to enhance CR access and effectiveness. These findings highlight the critical role of CR in improving patient outcomes and emphasize the importance of addressing barriers to participation in underserved populations.

BackgroundChemokine receptor type 5 (CCR5) is expressed on hepatic stellate cells (HSCs), which, together with fibroblasts, are major producers of extracellular matrix during liver fibrosis. Leronlimab is a humanized IgG4{kappa} monoclonal antibody that binds to CCR5. The objective of the present study was to evaluate the antifibrotic effects of leronlimab in three independent preclinical studies using two mouse models of liver fibrosis. MethodsIn STAM (Stelic Animal Model) model 1, leronlimab was administered at doses of 5 or 10 mg/kg/week for 3 weeks. STAM model 2 was conducted as a confirmatory study to validate the antifibrotic effect observed with the 10 mg/kg/week dose in STAM model 1. In a third study, a carbon tetrachloride (CCl)-induced liver fibrosis mouse model was used to evaluate leronlimab administered at 10 mg/kg/week for 3 weeks. An isotype-matched control antibody was included in all studies for comparison. Evaluations included liver enzymes and histological assessment of liver fibrosis. ResultsIn STAM model 1, leronlimab at 10 mg/kg/week significantly reduced fibrosis area compared with the isotype control (p = 0.0005). These findings were confirmed in STAM model 2 (p < 0.0001). Consistent antifibrotic effects were also observed in the CCl-induced liver fibrosis model (p = 0.0006). ConclusionsCollectively, these preclinical results demonstrate that CCR5 blockade by leronlimab is associated with a significant reduction of established liver fibrosis in multiple mouse models and support further evaluation of leronlimab as a potential therapeutic option, either as monotherapy or in combination regimens, for chronic liver diseases with fibrosis.