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.

Objectives: Accurate assessment of orthognathic surgical accuracy is essential in the evaluation of operative techniques. Surgical accuracy is often reported as rotational and translational deviations from planned positions. This results in 6 separate values, translation in three planes, anterior-posterior (AP), superior-inferior (SI) and medial-lateral (ML) and rotations about three axes, pitch, roll and yaw. However, rotations will influence 3-dimensional positions and translational discrepancies. Methods: We have derived a mathematical formula using Euclidean geometry and quadratic functions that quantifies the impact of rotations on translational discrepancies. This allows for the calculation of a total discrepancy value that incorporates the three translations and rotations. Furthermore, we developed an interactive web-based application using the open-source shiny R package. Results: We have successfully reduced equations from Euclidean geometry into a quadratic form. The equation is as follows, [4(sin{theta}/2)2-2]x2 + [8d(sin{theta}/2)2-2d]x + 4d2(sin{theta}/2)2 = 0, where {theta} represents the rotational discrepancy in radians and d represents the translation discrepancy. This allows us to solve for the correction needed to be made to translational discrepancies to account for the influence of rotational discrepancies. We successfully developed a web application with a user-friendly graphical user interface. Clinicians upload their own data in the excel (.xlsx) file format and the application automatically performs the necessary calculations over many patients, returning a downloadable table of results. Conclusion: We present a mathematical formula incorporated into a web-application to combine translational and rotational discrepancies for deeper insight when evaluating orthognathic surgical accuracy. Clinical Relevance: This allows surgeons to account for rotational influence on 3-dimensional translational discrepancies.

Study design A retrospective case control study Objective To predict proximal junctional kyphosis (PJK) risk by normalizing individual vertebral bone strength using the ratio of vertebral Hounsfield unit (HU) values around the upper instrumented vertebrae (UIV). Summary of background data PJK poses a significant challenge in treating patients after adult spinal deformity (ASD) surgery. While the vertebral body HU value is associated with PJK risk, the optimal threshold remains unclear, and a relative assessment of HU values within individuals has not been conducted. Methods Data on patients who underwent corrective fusion of the middle to lower thoracic region of the pelvis for ASD were assessed. The 126 patients were categorized into PJK and non-PJK groups. We compared the patients' backgrounds, vertebral body HU, and junctional HU ratio, defined as the HU value of UIV+1 divided by the HU value of UIV (HUUIV+1/HUUIV). The UIV+2/UIV+1 HU ratio was calculated similarly. Results The PJK and non-PJK groups included 30 and 96 patients, respectively. After propensity score matching, 28 patients from each group were analyzed. HU values at UIV+2 and UIV+1 (117.0 {+/-} 46.6 vs 145.1 {+/-} 45.9, p=0.018, and 105.5 {+/-} 36.2 vs 147.3 {+/-} 44.9, p<0.001, respectively) were lower in the PJK group. Junctional HU ratio was significantly lower in the PJK group (0.88 {+/-} 0.18 vs 1.13 {+/-} 0.25, p<0.001), and receiver operating characteristic analysis showed that the junctional HU ratio had the highest discriminative ability (area under the curve 0.812). At the optimal cutoff value (HU ratio of 0.905), the sensitivity and specificity for PJK were 64.3% and 89.3%, respectively. Conclusions A low junctional HU ratio was strongly associated with PJK after ASD surgery. This parameter reflects the bone strength mismatch at the proximal junction and may help improve preoperative risk assessment and UIV selection.

Background: Impacted maxillary incisors present significant clinical challenges requiring interdisciplinary management. To date, no meta-analysis has quantitatively synthesized success rates specifically for impacted maxillary incisors. This systematic review and meta-analysis aimed to determine the pooled success rate of orthodontic traction for impacted maxillary incisors and identify factors influencing outcomes. Methods: A systematic review and meta-analysis of observational studies was conducted following PRISMA 2020 guidelines. A systematic search was performed in PubMed, Epistemonikos, Cochrane Library, and Google Scholar (January 2011 - March 5, 2026). Primary studies reporting success rates of orthodontic traction for impacted maxillary incisors were included. The primary outcome was successful eruption and alignment into the dental arch. Although the protocol was not registered in PROSPERO, the methodology was predefined, documented, and strictly followed to minimize risk of bias. Pooled success rates were calculated using a random-effects model (DerSimonian-Laird method) with R software (meta package). Heterogeneity was assessed using I2 statistics. Publication bias was evaluated using funnel plots and Egger's test. Quality assessment employed ROBINS-I. Results: Eleven studies with 2,847 patients were included in the systematic review; 2,149 patients from 11 studies provided sufficient data for quantitative synthesis. The pooled success rate was 82.3% (95% CI: 78.6-86.0%), with a prediction interval ranging from 70% to 91%. Considerable heterogeneity was observed (I2 = 78%, p < 0.001). Subgroup analysis showed that younger age (<14 years) was associated with significantly higher success rates (88.4% vs. 78.2%, p = 0.01). Mild impaction depth (<5mm) was associated with higher success rates (89.2% vs. 76.5%, p = 0.02). No significant publication bias was detected (Egger's test, p = 0.18); however, the power to detect publication bias is limited with fewer than 15 studies. Certainty of evidence was moderate due to heterogeneity and observational study designs. Conclusions: Orthodontic traction is an effective, though not universally successful, treatment modality, with a pooled success rate of 82.3% for impacted maxillary incisors, and success significantly associated with patient age and impaction severity. Early intervention and favorable impaction characteristics are associated with better outcomes

ABSTRACT Background: The UroLume endoprosthesis (AMS/Endo-care), commercially available 1988-2007 and FDA-approved in 1996, was positioned as a permanent minimally invasive solution for recurrent bulbar urethral stricture and benign prostatic hyperplasia (BPH). Despite early procedural success, long-term data revealed a catastrophic complication profile - including irreversible urethral destruction, spongiofibrosis, MDR infections, chronic kidney disease, and severe psychological morbidity - culminating in the clinical entity termed UroLume Cripple Syndrome. No systematic epidemiological analysis of surviving patients in 2026 currently exists. Objectives: To synthesise four decades of evidence on UroLume pathophysiology, complications, surgical management hierarchy, psychological burden, and cumulative multimorbidity; to perform a pooled meta-analysis of primary complication endpoints; and to present an original epidemiological model estimating surviving patients globally and in Greece in 2026. Methods: PRISMA 2020-compliant systematic review and meta-analysis of PubMed, Embase, and Cochrane Library (all dates to March 2026). Inclusion: peer-reviewed studies of UroLume implantation, explantation, or post-UroLume reconstruction; minimum 12-month follow-up; series n >= 10. Random-effects meta-analysis (DerSimonian-Laird estimator) was performed for three primary complication endpoints across all 43 included studies. An original bottom-up sequential filter epidemiological model was constructed integrating WHO 2021 actuarial tables, published explantation rates, multimorbidity excess mortality, age distributions, complete epithelialisation prevalence, and reconstruction failure rates. Results: Forty-three studies met inclusion criteria (n=3,847 patients). Pooled meta-analysis yielded: restenosis/tissue ingrowth 37.9% (95% CI 36.1%-39.8%, I2=0%); stent explantation 8.7% (95% CI 7.7%-9.8%, I2=0%); urinary incontinence 9.7% (95% CI 8.7%-10.9%, I2=0%). Complete epithelialisation, irreversible after 12 months, affects approximately 8-13% of long-term survivors and defines the UroLume Cripple endpoint. Post-UroLume buccal mucosa graft urethroplasty achieves 76.7% success at 5 years when explantation is feasible. Our epidemiological model estimates 2,500-5,000 surviving patients globally with UroLume in situ in 2026, reducing to fewer than 100 clinically active patients aged <60 years following full multimorbidity adjustment. A six-filter sequential model for Greece converges to a final estimate of 1 surviving patient aged <60 years with complete epithelialisation following failed reconstruction. Conclusions: UroLume Cripple Syndrome is a chronic iatrogenic disease with distinct pathophysiological, reconstructive, psychological, and social dimensions that has received insufficient recognition as a defined clinical entity. The surviving patient population is small but institutionally invisible: no registry exists, no dedicated follow-up protocol has been established, and specialist reconstructive capacity is confined to approximately eight centres worldwide. Registry creation, EAU guideline extension, and specialist referral pathways are the minimum adequate institutional responses. This preprint has been deposited on medRxiv simultaneously with journal submission.

Abstract Background: ST-elevation myocardial infarction (STEMI) is reported to be a leading cause of mortality worldwide. While cardiac troponins are the gold standard for myocardial injury detection but creatine kinase-MB (CK-MB) and total creatine phosphokinase (CPK) retain prognostic use in resource-limited settings. Objective: To evaluate the prognostic significance of admission CK-MB and CPK levels in STEMI patients and to assess their association with hematological parameters for integrated risk stratification. Methods: This cross-sectional study enrolled 15 consecutive STEMI patients from the Punjab Institute of Cardiology, Lahore, during January 2024. Comprehensive laboratory analysis including cardiac biomarkers (CK-MB, CPK, troponin-I, LDH), complete blood count, renal function, serum electrolytes, and metabolic parameters, was performed on admission. Pearson correlation and comparative statistical analyses were also conducted to assess the relationships between cardiac biomarkers and hematological indices. Results: The cohort includes 15 patients (mean age 50.1 +/- 12.2 years; 73.3% male). Cardiac biomarker elevation was prevalent: CK-MB was elevated in 12/15 (80%), CPK was elevated in 12/15 (80%), with concordant elevation in 11/15 (73.3%), which indicates extensive myocardial necrosis. Troponin-I showed the highest elevation rate at 13/15 (86.7%). Hematological abnormalities included anemia (60%), WBC elevation (53.3%), and RBC reduction (40%). Random glucose averaged 150.80 +/- 63.55 mg/dL, with 66.7% highlighted the hyperglycemia. Remarkably, electrolyte balance was preserved in all of the patients (0% sodium, potassium, and bicarbonate abnormalities), indicating maintained homeostasis. Pearson correlation analysis revealed a significant correlation between CK-MB and CPK (r = 0.615, p = 0.0126), while correlations between cardiac biomarkers and hematological parameters were weak (p > 0.05). Risk stratification identified 53.3% of patients as high-risk who required intensive management. Conclusions: CK-MB and CPK demonstrate significant concordance and retain prognostic value in STEMI patients, particularly in resource-limited settings where troponin access may be constrained. While troponin-I remains the most sensitive biomarker, combined assessment of conventional cardiac enzymes supports reliable evaluation of myocardial injury. Hematological parameters reflect systemic response but show limited correlation with cardiac biomarkers.

Objective: To determine the incidence and clinical characteristics of surgical complications during pregnancy in women with a history of bariatric surgery. Design: A nationwide, prospective, population-based cohort study. Setting: High-risk obstetric care in Belgium: 67.6% of maternity units participated, covering 65% of all births in the study period. Participants: Pregnant women with a history of bariatric surgery presenting with a surgical complication (internal hernia, intussusception, volvulus or adhesions; anastomotic ulcer or abscess; gastric band slippage; or incisional hernia) between January 2021 and December 2022. Results: Thirty-three women experienced 35 surgical complications. Internal herniation was most common (n=25), predominantly following Roux-en-Y gastric bypass. Mean gestational age at diagnosis was 27+6 weeks. All women underwent surgical exploration within 24 hours; bowel resection was required in two cases. Caesarean section occurred in 48.5%, with 13 preterm births and one neonatal death. One woman required intensive care. No maternal death occurred. Conclusion: Surgical complications following bariatric surgery in pregnancy are uncommon but carry significant obstetric risks. All observed complications occurred after procedures involving intestinal rerouting, predominantly Roux-en-Y gastric bypass. Prompt surgical management was associated with low maternal morbidity and no mortality, but frequently resulted in preterm birth and emergency caesarean section. These findings highlight the need for a low threshold for surgical evaluation of abdominal pain in pregnant women with previous bariatric surgery and suggest that procedure type is relevant when counselling women of reproductive age.

ObjectiveTo evaluate the real-world effectiveness of Intact Fish Skin Graft (IFSG) compared with standard of care (SOC) in the treatment of Stage 3-4 pressure ulcers, using clinically meaningful outcomes including wound healing rate and percent area reduction (PAR). Materials and MethodsA retrospective matched cohort study was conducted using deidentified electronic health record (EHR) data from the U.S. Wound Registry. Patients with Stage 3-4 pressure ulcers treated with IFSG (n=40) were compared to a matched SOC control group (n=40). 1:1 covariate matching was performed to reduce confounding across key patient and wound characteristics, including age, mobility status, comorbidities (e.g., diabetes, peripheral artery disease), and wound features (age, size, location, and depth). Outcomes included healed status, healed or improved rate, and percent area reduction (PAR). ResultsThe study population represented a high-risk, real-world cohort (n=40 per group), with only 37.5% ambulatory patients and a high prevalence of multiple concurrent wounds. IFSG treatment demonstrated superior clinical outcomes compared to SOC: O_LIHealed or improved: 67.5% (IFSG) vs 55.0% (SOC) (p=0.0379) C_LIO_LIHealed: 45.5% (IFSG) vs 33.3% (SOC) C_LIO_LIPercent area reduction (PAR): 49% (IFSG) vs 34% (SOC) (p=0.0028) C_LI These findings indicate statistically significant improvements in percent area reduction and in the proportion of wounds that were healed or improved with IFSG. The proportion achieving complete healing was numerically higher with IFSG than with SOC, but this difference did not reach statistical significance. ConclusionIn this real-world matched cohort analysis, Intact Fish Skin Graft demonstrated superior effectiveness compared to standard of care in the management of Stage 3-4 pressure ulcers, with improvements in healing-related outcomes and percent area reduction. These results support the use of IFSG as an effective advanced therapy for hard-to-heal pressure ulcers.

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.

Objective. To evaluate the effectiveness of a bundle of interventions involving a clinical pharmacologist aimed at changing surgeons approach to perioperative antibiotic prophylaxis (PAP) in an oncourology department. Materials and Methods. A single-center retrospective observational study was conducted. Data from 226 patients who underwent prostatectomy or nephrectomy in the oncourology department of Regional Clinical Hospital No. 2 (Krasnodar, Russia) between 2023 and 2025 were analyzed. Periods before (n=125) and after (n=101) the implementation of an Antimicrobial Stewardship (AMS) strategy bundle with active participation of a clinical pharmacologist (pre-authorization, audit with feedback, education, handshake stewardship) were compared. The primary endpoint was the proportion of surgeries performed in compliance with the PAP protocol. Secondary endpoints included the incidence of infectious complications, antibiotic consumption (DDD/100 bed-days), direct costs of antibacterial drugs, dynamics of the microbial landscape, and the Drug Resistance Index (DRI). Results. After AMS implementation, the proportion of surgeries performed in accordance with the PAP protocol increased from 0% to 47.7% for prostatectomies and to 55.6% for nephrectomies. The mean duration of antibiotic use decreased from 7 to 2 days (p<0.001). Antibiotic consumption decreased by 31.2%, and costs were reduced by a factor of 4.3. The proportion of ESKAPE organisms in the microbial profile decreased from 26.3% to 16.4%. There was no statistically significant increase in the frequency of infectious complications (2.4% vs. 3.0%; p=1.000) or mortality (0% in both groups). Conclusions. AMS implementation integrating a clinical pharmacologist into the oncourology department workflow significantly improved adherence to clinical guidelines, reduced irrational antibiotic use and financial costs without compromising patient safety. This approach can serve as a model for optimizing PAP in other surgical departments. Keywords: antibiotic prophylaxis, antimicrobial stewardship, drug resistance, clinical pharmacologist, cost-benefit analysis, oncourology

Modelling of hemodynamics in the circle of Willis (CoW) depends on vascular segmentation, which may vary based on imaging modality. Computed tomography angiography (CTA) is commonly used in clinic but involves radiation and injection of contrast agents, whereas magnetic resonance angiography (MRA) offers a non-invasive alternative. This study aims to compare CoW morphology and modelled cerebral perfusion pressure of CTA and MRA segmentations, validating if MRA can replace CTA in modelling workflows. CTA and time-of-flight MRA (TOF-MRA) of the CoW was performed in 19 patients undergoing elective aortic arch surgery (67{+/-}7 years, 8 women). The CoW was semi-automatically segmented based on signal intensity thresholding. A TOF-MRA threshold was optimized against the CTA segmentation, using the CTA as reference standard. Computational fluid dynamics (CFD) modelling with boundary conditions based on subject-specific flow rates from 4D flow MRI simulated cerebral perfusion pressure in the segmented geometries. A baseline simulation and a unilateral brain inflow simulation, i.e., occlusion of a carotid, were carried out. Linear mixed models indicated there was no effect of choice of modality on either average arterial lumen area (CTA - TOF-MRA: -0.2{+/-}1.3 mm2; p=0.762) or baseline pressure drops (0.2{+/-}1.9 mmHg; p=0.257). In the unilateral inflow simulation, we found no difference in pressure laterality (-6.6{+/-}18.4 mmHg; p=0.185) or collateral flow rate (10{+/-}46 ml/min; p=0.421). TOF-MRA geometries can with signal intensity thresholding be matched to produce similar morphology and modelled cerebral perfusion pressure to CTA geometries. The modelled pressure drops over the collateral arteries were sensitive to the segmentation regardless of modality.

Background Disparities between sexes in mortality and morbidity after coronary artery bypass grafting remain incompletely understood. Multi-arterial grafting demonstrates superior outcome compared to single arterial grafting, although the optimal type of a second arterial graft and possible sex-dependent differences in grafting strategy have not been elucidated. We aim to determine whether the right internal thoracic artery or the radial artery is the optimal second arterial graft. Methods We analyzed data from 14,196 patients undergoing primary isolated coronary artery bypass grafting with the left internal thoracic artery and either right internal thoracic artery or radial artery between 2013 and 2022 from the Netherlands Heart Registration. Patients were stratified by sex and type of second arterial graft. Inverse probability treatment weighting was used to balance baseline characteristics. The primary outcome was long-term mortality. Secondary outcomes included short-term complications and repeat revascularization. Results In both sexes, the choice of second arterial graft did not significantly impact long-term survival. Postoperative arrhythmias were more prevalent in both sexes following right internal thoracic artery use (p<0.001). The radial artery was associated with higher rate of repeat revascularization in men (p=0.044 at 5 years follow-up) and more cerebrovascular accidents in women (0.9% vs 0.2%, p=0.028). Conclusion The choice of second arterial graft did not affect long-term survival in either sex. The radial artery was associated with an increased risk of repeat revascularization in men and more cerebrovascular accidents in women. These results underscore the need for further research in the field of sex-specific considerations in operative strategy.

Background: Peak height velocity (PHV) is a critical indicator of pubertal growth timing and is widely used in orthodontics to determine optimal timing for growth modification interventions. Secular trends toward earlier maturation have been reported, but a quantitative synthesis of PHV age reduction across generations is lacking. Objective: To systematically review and quantitatively synthesize evidence for secular trends in age at PHV and to estimate the pooled mean difference in PHV age between historical and contemporary cohorts. Methods: A systematic search was conducted in PubMed and Google Scholar from January 1990 to December 2021. The Directory of Open Access Journals (DOAJ) was also searched but yielded no eligible studies due to the specificity of the search string. Studies were included if they reported age at PHV in two or more birth cohorts separated by at least 20 years, used objective methods to determine PHV (longitudinal growth data with curve fitting), and reported means with standard deviations or standard errors. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects quantitative synthesis (meta-analytic approach) was performed to calculate the pooled mean difference in PHV age between historical and contemporary cohorts. Between-study variance (tau-squared) was estimated using the restricted maximum likelihood (REML) method. Heterogeneity was assessed using I-squared statistics. Given the limited number of eligible studies, findings should be interpreted as preliminary. Results: Two high-quality longitudinal studies met inclusion criteria, comprising 171 participants from historical cohorts (1969-1973) and 71 participants from contemporary cohorts (1996-2000). The pooled mean difference in PHV age was -0.48 years (95% CI: -0.72 to -0.24, P < 0.001), indicating that contemporary children reach PHV approximately 0.5 years earlier than their historical counterparts. PHV velocity showed a pooled increase of 0.71 cm/year (95% CI: 0.48 to 0.94, P < 0.001). Heterogeneity was low (I-squared = 0% for both analyses). Both studies were rated as low risk of bias. These findings are based on a limited number of studies and should be interpreted as preliminary. Conclusions: This preliminary quantitative synthesis provides evidence of a secular decline in age at peak height velocity of approximately 0.5 years in contemporary children compared to historical cohorts, accompanied by an increase in growth velocity. These findings suggest that orthodontic growth modification strategies may need to be initiated earlier than traditionally recommended. However, given the limited evidence base, results should be interpreted with caution and require confirmation in large-scale longitudinal studies.

Objective: Neuroendoscopy has emerged as a crucial minimally invasive strategy for the treatment of intracranial hemorrhage (ICH). This bibliometric analysis aims to systematically delineate the global research architecture and evolution of neuroendoscopic ICH research over the past two decades. Methods: Relevant publications were retrieved from the Web of Science Core Collection using a reproducible search strategy. Bibliometric tools were applied to analyze contributions from countries, institutions, authors, publications, keywords and journals, enabling the construction of a comprehensive knowledge map and evolutionary framework of this field. Results: A total of 403 articles were identified, involving 2128 authors from 555 institutions across 43 countries. The publication trajectory exhibited fluctuating growth, reflecting the dynamic interplay between clinical demand and technological maturation. China contributed the highest publications and citation impact, followed by the US, jointly anchoring the global influence of the field. The research keywords have evolved from ?intracerebral hemorrhage? and ?initial conservative treatment? to ?augmented reality.? Thematic evolution analysis revealed a clear progression from early emphasis on operative feasibility, safety, and perioperative outcomes toward more rigorous evidence appraisal and the refinement of context-specific clinical indications, accompanied by continuous technological innovation. Conclusion: These findings collectively position neuroendoscopy as a cornerstone of modern ICH management, reshaping clinical strategies toward precision, minimal invasiveness, and multimodal intervention. Future progress will depend on strengthened international collaboration to generate high-quality evidence that supports patient stratification. The integration of emerging technologies, including advanced endoscopic robotics, is expected to further accelerate the translational and clinical landscape of neuroendoscopic ICH therapy.

Background: Primary graft dysfunction (PGD) remains one of the leading causes of early mortality after pediatric heart transplant (HT). While neurodevelopmental impacts of congenital heart disease (CHD) are well-characterized, the effect of PGD on long-term neurodevelopmental outcomes in pediatric HT recipients remains unknown. We sought to determine the association between PGD and neurodevelopmental outcomes in this population. Methods: We performed a retrospective cohort study using the United Network for Organ Sharing (UNOS) database. All pediatric (age <18 years) isolated heart transplant recipients from 2010-2025 were included. The most recent pre- and post-transplant neurodevelopmental outcomes including cognitive delay, motor development, academic progress, and function status (stratified by age) were compared between PGD (n=434) and non- PGD groups (n=6956). Results: PGD patients had significantly worse pre-transplant functional status and motor development. Post-transplant, PGD was associated with worse motor development (18.8% vs. 13.0% definite motor delay; p=0.01) and functional status in younger children (39.5% vs. 57.8% able to keep up with peers; p<0.001). Post-transplant stroke occurred 3.5 times more frequently in PGD patients (11.5% vs. 3.3%; p<0.001). Cognitive development (p=0.94) and academic progress (p=0.096) did not differ significantly. Thirty-day (7.8% vs. 1.9%) and 1-year mortality (20.3% vs. 6.4%) were significantly higher in PGD patients (both p<0.001). Conclusions: This is the first study to characterize neurodevelopmental outcomes in pediatric patients undergoing HT with PGD. PGD is associated with significantly worse motor development and functional status independent of pre-transplant baseline. There is a 3.5-fold higher stroke rate providing a plausible neurological mechanism. The findings support targeted developmental surveillance recommendations and early intervention for this high-risk population.

Objective: To investigate the association of the modified cardiometabolic index (MCMI) with cardiovascular-kidney-metabolic (CKM) syndrome staging, all-cause and cardiovascular mortality, and compare its predictive performance with traditional indices. Methods: This prospective cohort study included 5,189 adults with CKM syndrome (stages 0-4) from NHANES 1999-2018 (median follow-up 10.4 years). Associations were assessed using polynomial/ordinal logistic regression, Cox models, and restricted cubic splines. Mediation analysis explored diabetes' role. Competing risks (Fine-Gray), E-values, and sensitivity analyses ensured robustness. Predictive performance was compared using C-index and AUC. Results: MCMI showed a "decelerating increase" nonlinear association with CKM staging (adjusted OR=3.90, 95%CI: 3.38-4.50). For all-cause mortality, MCMI>3.5 exhibited a threshold effect (Q4 vs Q1: HR=1.412, 1.046-1.907); RCS curves identified MCMI<3.5 as a safety interval. For cardiovascular mortality, MCMI showed a fluctuating nonlinear pattern with low-risk (3.0-3.5) and high-risk (<2.5 or >4.0) intervals. Diabetes mediated 45.5% of MCMI-cardiovascular mortality risk (total HR=1.374, indirect HR=1.141). Competing risks revealed substantial underestimation of true effects (Q4 vs Q1 sHR=3.25, trend P<0.001). MCMI remained independently associated with all-cause mortality after extensive adjustments (HR=1.22, 1.05-1.40); E-values (1.73/1.29) indicated robustness. MCMI demonstrated superior predictive performance over CMI and TyG (mean AUC difference 0.0243). Conclusions: MCMI is an independent predictor of CKM progression and mortality. Its cardiovascular mortality risk is predominantly mediated by diabetes. MCMI>3.5 may serve as a clinical cut-off, outperforming traditional metabolic indices for CKM risk stratification. Keywords: modified cardiometabolic index, cardiovascular-kidney-metabolic syndrome, all-cause mortality, cardiovascular mortality, diabetes mellitus, competing risks model, cohort study, risk prediction

Skeletal muscle regeneration is often impaired after acute muscle damage induced by viperid snake venoms, such as that of Bothrops asper, a medically-relevant species in Latin America. It has been shown that traces of venom that remain in the damaged muscle affect myogenic cells in culture, raising the possibility of inhibition of these toxins during the regenerative process as a way to improve regeneration. Using a mouse model of myonecrosis and regeneration, we evaluated the effects of Varespladib (a phospholipase A2 inhibitor) or Marimastat (a metalloproteinase inhibitor) on muscle regeneration when administered intravenously 24 h after the onset of myonecrosis, i.e., after muscle damage has occurred. The regenerative process was evaluated 14 and 28 days after venom injection. Results show that Marimastat, or a combination of both inhibitors, improved the extent of skeletal muscle regeneration and reduced the extent of tissue fibrosis when compared to tissue from mice receiving venom and no inhibitors, as judged by qualitative and quantitative histological assessment. Results underscore the deleterious role of traces of venom components in the damaged muscle during muscle regeneration and suggest that the administration of metalloproteinase inhibitors, or a combination of metalloproteinase and phospholipase A2 inhibitors, even when muscle damage has developed, may be a therapeutic alternative for improving the extent of muscle regeneration.

Background: Smell testing is increasingly recognized as essential in rhinology practice but remains underutilized because of time constraints and limited clinical resources. This study aimed to evaluate the performance (test-retest reliability, accuracy and test completion time) of a self-administered, digital version of SMELL-RS, a non-semantic test of olfactory resolution (SMELL-R) and sensitivity (SMELL-S). Methodology: We performed a test-retest reliability study in a tertiary care facility. We enrolled 100 subjects with and without smell dysfunction. The primary outcome measures were two replicates of olfactory test scores (SMELL-RS composite score, SMELL-R score, SMELL-S score). The secondary outcome measures were Sniffin Sticks score, test completion time, patient demographics, and other clinical characteristics (clinical symptoms, etiologies). Results: The SMELL-RS composite score was reliable (ICC=0.71; p<0.0001) and correlated with the Sniffin Sticks composite score (r=0.68; p<0.0001). Different etiologies have different magnitudes of smell loss as revealed by the SMELL-RS score. SMELL-S reduces misdiagnosis associated with Sniffin Sticks threshold tests. The average completion time of the olfactory resolution test (SMELL-R) was on average 5.9 minutes (SD=1.9), while the average completion time of the olfactory sensitivity test (SMELL-S) was 5.5 minutes (SD=2.7). This is two to three times faster than the corresponding Sniffin Sticks tests. Conclusions: SMELL-RS is a rapid, fully automated, reliable, and accurate olfactory test suitable for self-administration in a clinical setting.

Patient-reported outcomes have become standard in facial skin cancer surgery, yet clinicians currently lack validated tools to predict postoperative appearance satisfaction from preoperative patient characteristics. We developed and internally validated a prediction model for appearance satisfaction three months after facial skin cancer reconstruction. A prospective cohort study enrolled 287 patients at a tertiary referral center (2017-2018); 111 patients with complete data were included in the primary analysis. Patients completed the FACE-Q Skin Cancer Module preoperatively and at three months postoperatively. Our multivariable linear regression model incorporated age, sex, comorbidities, smoking status, and baseline appearance satisfaction. The model explained 23.0% of variance in postoperative appearance satisfaction (R2 = 0.23; adjusted R2 = 0.19; p < 0.001). Baseline appearance satisfaction (B = 0.48; 95% CI 0.28-0.68; p < 0.001) and female sex (B = -7.16; 95% CI -12.52 to -1.81; p = 0.009) emerged as independent predictors. Bootstrap resampling (500 iterations) yielded an optimism-corrected R2 of 0.17, supporting acceptable internal validity. Mean appearance satisfaction remained stable from baseline (54.8 +/- 13.8) to three months (57.0 +/- 16.4; p = 0.27). Baseline appearance satisfaction and female sex independently predict postoperative appearance satisfaction following facial skin cancer reconstruction. External validation in independent cohorts is warranted before clinical implementation.

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.