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Journal of Clinical Medicine

MDPI AG

Preprints posted in the last 90 days, ranked by how well they match Journal of Clinical Medicine's content profile, based on 91 papers previously published here. The average preprint has a 0.21% match score for this journal, so anything above that is already an above-average fit.

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Beyond Citations: Identifying Transformational Research in Hypospadias Through Bibliometrics and the Disruption Index

Abbas, T.; Naznine, M.; Mykha, M.; Mancha, M.; Hardas, A.; Raharja, P. A. R.; Chowdhury, M. E. H.

2026-04-20 urology 10.64898/2026.04.18.26351160 medRxiv
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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.

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OGSCalc: Mathematical formulae and web-based application to incorporate rotational discrepancies into translational discrepancies for assessment of accuracy in orthognathic surgery

Hue, J.; Yeo, J.; Saigo, L.

2026-04-04 dentistry and oral medicine 10.64898/2026.04.03.26350094 medRxiv
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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.

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Junctional Hounsfield unit ratio: understanding patient-specific vertebral bone strength for proximal junctional kyphosis risk assessment in adult spinal deformity surgery

Nagatani, Y.; Segi, N.; Ito, S.; Ouchida, J.; Yamauchi, I.; Ode, Y.; Okada, Y.; Takeichi, Y.; Tachi, H.; Kagami, Y.; Morishita, K.; Oishi, R.; Miyairi, Y.; Morita, Y.; Ohshima, K.; Oyama, H.; Ogura, K.; Shinjo, R.; Ohara, T.; Tsuji, T.; Kanemura, T.; Imagama, S.; Nakashima, H.

2026-04-06 orthopedics 10.64898/2026.04.05.26349586 medRxiv
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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.

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Success And Predictors Of Orthodontic Traction For Impacted Maxillary Incisors: A Systematic Review And Meta-Analysis

Mahfouz, M.; Alzaben, E.

2026-04-01 dentistry and oral medicine 10.64898/2026.03.31.26349803 medRxiv
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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

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The UroLume Endoprosthesis and UroLume Cripple Syndrome: A Systematic Review and Meta-Analysis of Pathophysiology, Complications, Surgical Management, Psychological Burden, and Epidemiology of Surviving Patients Worldwide

Kapos, I. P.

2026-03-30 urology 10.64898/2026.03.28.26349606 medRxiv
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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.

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Prognostic Significance of Admission CK-MB and Total CPK Levels in Predicting Adverse Outcomes Among STEMI Patients

Rehman, M. U.

2026-04-15 cardiovascular medicine 10.64898/2026.04.14.26350841 medRxiv
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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.

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Incisor Extraction in Orthodontics: A Systematic Review and Meta-Analysis of Clinical Outcomes and Biomechanics

Mahfouz, M.; Alzaben, E.

2026-03-25 dentistry and oral medicine 10.64898/2026.03.23.26349102 medRxiv
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Background: Incisor extraction represents a strategic yet underutilized orthodontic treatment modality for managing anterior discrepancies. Despite its clinical relevance, the evidence base has not been systematically synthesized with meta-analytic techniques. Objective: To systematically review and meta-analyze the evidence on incisor extraction in orthodontic treatment, evaluating clinical outcomes and biomechanical efficacy in both maxillary and mandibular arches. Methods: A comprehensive search of open-access electronic databases (PubMed, LILACS, SciELO, Google Scholar, DOAJ, OpenGrey) and orthodontic journal archives was conducted from inception to January 11, 2026 following PRISMA guidelines. Eligible studies included randomized controlled trials, prospective cohort studies, and retrospective cohort studies with greater than or equal to 10 patients reporting quantitative outcomes following incisor extraction or incisor movement with premolar extraction. Primary outcomes included space closure efficiency, incisor position changes, root resorption, and stability. Risk of bias was assessed using ROBINS-I for observational studies and Cochrane RoB 2.0 for RCTs. Certainty of evidence was evaluated using GRADE. Results: From 1,842 identified records, 20 primary studies met inclusion criteria (4 RCTs, 16 observational studies), comprising 1,347 patients. Sixteen studies provided data for meta-analysis. With moderate-certainty evidence, mandibular incisor extraction (8 studies, n=412) demonstrated mean space closure of 5.2 mm (95% CI 4.8 to 5.6 mm, I-squared=34%) with favorable long-term stability (mean irregularity increase 0.3 mm, 95% CI 0.1 to 0.5 mm, I-squared=28%). Low-certainty evidence indicates clear aligner accuracy is limited to 78.9% of predicted incisor tip movement (3 studies, n=187, 95% CI 72.3 to 85.5%, I-squared=41%); these findings may not reflect newer generation aligner systems. Low-certainty evidence suggests maxillary incisor movement following premolar extraction (6 studies using tomographic imaging, n=387) results in palatal bone resorption (mean -0.43 mm, 95% CI -0.62 to -0.24 mm, I-squared=52%), with greater effects in adults versus adolescents (mean difference 0.31 mm, p = 0.02); although statistically significant, the magnitude may be clinically negligible in patients with adequate baseline alveolar thickness. Moderate-certainty evidence indicates en-masse retraction results in faster space closure than two-step retraction (4 RCTs, n=214, mean -4.2 months, 95% CI -5.8 to -2.6 months). Moderate-certainty evidence shows root resorption incidence is 12.4% (95% CI 8.7 to 16.1%), with subgroup analysis: greater than 2 mm threshold 13.2% (7 studies), at least one-quarter root length threshold 11.4% (5 studies). Low-certainty evidence suggests extraction versus non-extraction comparisons (4 studies, n=326) show no significant differences in relapse. Conclusions: Mandibular incisor extraction demonstrates favorable long-term stability with minimal profile changes but requires recognition of clear aligner accuracy limitations. Maxillary incisor movement carries risks including palatal bone resorption, particularly in adults, though the clinical significance may vary with baseline alveolar thickness. En-masse retraction results in faster space closure with comparable root resorption risk. Treatment decisions should consider patient-specific factors including age, alveolar bone morphology, malocclusion pattern, and appliance selection.

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Surgical complications during pregnancy following bariatric surgery: a Belgian nationwide population-based study

De Mulder, P.; Benoit, K.; Daelemans, C.; Debieve, F.; Devlieger, R.; Roelens, K.; Van Nieuwenhove, Y.; Vandenberghe, G.

2026-03-31 obstetrics and gynecology 10.64898/2026.03.30.26349694 medRxiv
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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.

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Quantitative Ultrasound Biomarkers of Testicular Spermatogenic Function

Kohn, T. P.; Coady, P. J.; Oppenheimer, A. G.; Walia, A.; Hernadez, B. S.; Kohn, J. R.; Parikh, N.; Bazzi, M.; Stocks, B.; Khera, M.; Lipshultz, L. I.

2026-02-17 urology 10.64898/2026.02.16.26346440 medRxiv
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IntroductionNon-obstructive azoospermia (NOA) represents the most severe form of male infertility. Current clinical tools have limited ability to predict sperm production or guide surgical sperm retrieval. Conventional B-mode ultrasound provides qualitative grayscale images and cannot characterize testicular microstructure relevant to spermatogenesis. Quantitative ultrasound (QUS) provides objective parameters from raw radiofrequency data, which quantitatively measure tissue heterogeneity. We hypothesize that men with spermatogenesis will have different QUS features compared to men without spermatogenesis (measured by total motile count, TMC, on semen analysis), with the goal of identifying imaging biomarkers for prognosis and intraoperative guidance. MethodsWe prospectively analyzed men presenting for infertility evaluation who underwent high-frequency ultrasound imaging and semen analysis. Imaging was performed using a 36-MHz transducer with fixed acquisition parameters. Ninety-two QUS features were extracted from manually annotated testicular regions of interest, including Nakagami distribution parameters (m, {omega}, k), envelope statistics, and texture features. Univariate associations between each QUS feature and TMC were assessed using Spearman correlation with Bonferroni correction. Top-performing features were evaluated using logistic regression and receiver operating characteristic (ROC) analysis to discriminate sperm presence or absence (TMC>0 vs TMC=0). ResultsThirty-seven men (18 azoospermic, 19 with sperm present in the ejaculate) contributed 135 regions of interest. Seventeen of 92 QUS features significantly correlated with TMC after correction. The coefficient of variation of the Nakagami k-factor within the superficial testicular parenchyma (K_Zone1_Cv) demonstrated the strongest correlation ({rho}=0.51, corrected p<0.001), suggesting that greater spatial heterogeneity in the superficial parenchyma was associated with higher sperm counts. K_Zone1_Cv discriminated sperm presence with an AUC of 0.77 (95% CI 0.60-0.92), sensitivity 73.7%, and specificity 83.3%. QUS features with the highest univariate association were highly intercorrelated, suggesting a shared biological signal. ConclusionQuantitative ultrasound-derived measures of testicular microstructure heterogeneity correlate with sperm production and demonstrate moderate discrimination of sperm presence. These findings suggest QUS may provide a non-invasive imaging biomarker of spermatogenesis. Study findings warrant further assessment and validation in male infertility for sperm retrieval prognosis and the potential for intra-operative surgical guidance.

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Real-World Matched Analysis (N=40 per group) Shows Significantly Improved Healing with Intact Fish Skin Graft vs Standard of Care in Stage 3-4 Pressure Ulcers

Miao, H.; LeBoutillier, B.; Lantis, J. C.; Fife, C.

2026-04-11 primary care research 10.64898/2026.04.08.26350429 medRxiv
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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.

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The impact of cognitive processes associated with image recognition on visuo-vestibular interaction

Malara, P.; Tosin, A. G.; Castellucci, A.; Martellucci, S.; Musumano, L. B.; Mandala, M.

2026-04-23 otolaryngology 10.64898/2026.04.22.26351361 medRxiv
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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.

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Age-dependent Dynamics of the Electrocardiographic Parameters in Cardiovascular Disease-Free Children

Haq, K.; McLean, K.; Berul, C.; Posnack, N.

2026-02-09 cardiovascular medicine 10.64898/2026.02.07.26345587 medRxiv
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BackgroundNormative pediatric electrocardiographic (ECG) parameters are standardized, but lack temporal resolution for neonates and infants. These values are clinically important, as they support the diagnosis, risk stratification, and management of cardiovascular diseases (CVD). MethodsFive ECG parameters (heart rate (HR), QRS, PR, QT, QTc intervals) were retrospectively analyzed from 7,346 recordings from 6,967 patients at a large pediatric hospital. Patients were only included if their ECG was adjudicated as normal by a pediatric cardiologist. Patients were assigned to 45 age groups: neonates (1-35 days, 35 groups), infants (2-6 months, 5 groups), and young children (1-5 years, 5 groups). Sensitivity analysis ranked ECG parameters to determine those most affected by age. Z-scores were used to quantify deviations in developmental ECG parameter trajectories in CVD-free patients compared with unrepaired tetralogy of Fallot (TOF, n=305). ResultsDevelopmental shifts in ECGs were observed for all patients, irrespective of whether intensive care unit or CVD patients were included in the analysis. All five ECG parameters differed significantly between early (1-8 days) and late neonates (9-35 days). Sensitivity analysis revealed rapid ECG parameter adaptations during the neonatal stage, with slower changes during infancy and early childhood. Unrepaired TOF patients had significantly different HR, PR, and QRS values in the late neonatal group compared with CVD-free children. Z-scores revealed disease-specific deviations ([&ge;] 2 SD of baseline), including outlier QTc values in 32.7% and 24.3% of early and late neonatal TOF patients, respectively. ConclusionThis study defined the values of five key ECG parameters, with enhanced age-specific resolution in neonates, infants, and children. Neonatal age emerged as the most dynamic stage for ECG parameter changes. This study demonstrated that high temporal resolution of age-specific ECG parameters can identify abnormal deviations, which can provide valuable insight for the diagnosis and management of CVD in early life. CLINICAL PERSPECTIVEO_ST_ABSWhat is knownC_ST_ABSO_LINormative pediatric ECG values derived from healthy children have been reported; however, available reference datasets are often limited by broad age stratification, particularly during the neonatal and infant periods. C_LI What the study addsO_LIHigh-temporal-resolution reference values are reported for five clinically relevant ECG parameters, with day-level resolution in neonates and month-level resolution in infants. C_LIO_LIRetrospective ECG data from a CVD-free pediatric cohort closely align with values reported in healthy pediatric populations, supporting their use as surrogate baseline reference data. C_LIO_LIPostnatal ECG developmental trajectories are preserved in CVD-free pediatric patients but deviate in disease states such as unrepaired tetralogy of Fallot, highlighting the potential clinical utility of these reference trajectories for identifying disease-related alterations. C_LI

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Development and validation of the Food Expectation Questionnaire (FEX-Q) to assess food-related perceptions and symptom expectations

Katsumata, R.; Trindade, I.; Storsrud, S.; Simren, M.; Nybacka, S.

2026-03-11 gastroenterology 10.64898/2026.03.10.26348014 medRxiv
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BackgroundFood-related gastrointestinal (GI) symptoms are highly prevalent in patients with IBS. Although dietary components may trigger symptoms through luminal mechanisms, cognitive expectations may also shape symptom perception within the gut-brain axis. No validated instrument currently exists to measure food-related symptom expectations. Hence, we developed and validated the Food Expectation Questionnaire (FEX-Q). MethodsThe FEX-Q was developed using a stepwise process including focus group interviews and face-to-face validation to ensure content validity. The finalized digital questionnaire presents 44 food images with six items rated on a visual analogue scale (VAS; 0-100), including the core item assessing food-related symptom expectation ("How severe GI symptoms do you expect after eating this food?"). Additional domains assess taste preference, willingness to eat, perceived healthiness, and perceived fat and carbohydrate content. The finalized FEX-Q was administered in a nationwide online validation survey of adults with IBS and non-IBS controls in Sweden. Participants also completed validated questionnaires including GI symptom severity (combined GSRS), psychological distress (HADS), food-related quality of life (FR-QOL), and a screening tool for food avoidance (NIAS). ResultsTwenty adults with IBS and non-IBS controls participated in the face-to-face validation, resulting in a final version of the FEX-Q comprising 44 food images, which were properly identified and provided a range of macronutrient distributions and trigger foods. In the nationwide online study including 134 patients with IBS and 126 non-IBS controls, the FEX-Q demonstrated strong known-groups validity (mean symptom expectation 18.4 in controls vs 50.1 in IBS), strong construct validity (perceived vs actual fat content r=0.78, p<0.001 and carbohydrate content r=0.59, p<0.001), significant convergent validity with GI symptom severity and food-related quality of life, and high internal consistency (split-half reliability Spearman-Brown corrected r=0.88). ConclusionThe FEX-Q can capture individual food-related symptom expectations to distinct food images. This reliable measurement can be useful to reveal the mechanism of food-related symptom expectations and provide clinically relevant insights for personalized dietary management

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Serum ferritin and clinical outcomes in children undergoing pediatric cardiac surgery

Batista, N. O. W.; Fiori, H. H.; Knop, N. C. F.

2026-01-28 intensive care and critical care medicine 10.64898/2026.01.26.26344857 medRxiv
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IntroductionHyperferritinemia is a prognostic marker in critical illness, but its role in postoperative outcomes of pediatric congenital heart defects remains poorly defined, especially in resource-limited settings. This study evaluated early serum ferritin as a predictor of outcomes after congenital heart surgery and its association with the PIM 3 score. MethodsA single-center, prospective cohort study was conducted from April 2023 to October 2024 at a tertiary referral center in southeastern Brazil. Patients aged 29 days to 18 years, of both sexes, admitted to the PICU after congenital heart surgery were included and categorized as cyanotic or acyanotic. Statistical significance was defined as two-sided p < 0.05. ResultsA total of 105 patients were included. Median ferritin was higher in patients with PICU stays < 7 days (183 ng/mL; p = 0.004) and was significantly associated with a PIM 3 score [&ge;] 5% (642 ng/mL; p < 0.006). Cyanotic patients had longer PICU stays (11.0 vs. 7.2 days; p = 0.02), longer use of vasoactive drugs (3.8 vs. 2.6 days; p = 0.01), and accounted for all deaths (p < 0.001). Hemoglobin and hematocrit were also significantly higher in cyanotic patients (14 vs. 13 g/dL and 40% vs. 37%; p < 0.001). ConclusionsSerum ferritin may serve as a marker of secondary outcomes and aid early risk stratification in congenital heart defects patients in the PICU.

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Optimization Of Perioperative Antibiotic Prophylaxis In Oncourology: The Role Of A Clinical Pharmacologist And Assessment Of Clinical And Economic Outcomes

Dovlatbekyan, N. M.; Ochakovskaya, I. N.; Penjoyan, A. G.; Durleshter, V. M.; Onopriev, V. V.; Avagimov, A. D.

2026-04-08 urology 10.64898/2026.04.07.26350335 medRxiv
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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

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Mathematical diabetes disease progression modeling in the integrated glucose-insulin model among individuals with impaired glucose tolerance from the Finnish Diabetes Prevention Study

Ghadzi, S. M. S.; Karlsson, M. O.; de Mello, V.; Uusitupa, M.; Kjellsson, M. C.

2026-03-03 pharmacology and toxicology 10.64898/2026.02.28.708712 medRxiv
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The integrated glucose-insulin (IGI) model describes glucose and insulin after glucose administration in healthy individuals and patients with type 2 diabetes. The model, however, does not include disease progression (DP) from prediabetes to overt diabetes, which is driven by decreased insulin sensitivity and relative beta-cell failure. The objective of this study was to develop the IGI model to include the DP model for glucose and insulin in individuals with impaired glucose tolerance (IGT), with and without lifestyle intervention. Data of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test (OGTT) were obtained from a sub study of the Finnish Diabetes Prevention Study (FDPS) in 101 individuals with IGT, randomly assigned to control and lifestyle intervention groups. A combination of intravenous and oral IGI model was used to fit the baseline until the fourth-year data using NONMEM, with prior information. The first-phase insulin secretion (FPS) and insulin-dependent glucose clearance (CLGI) decreased by 3.0% year and 8.1%/year, due to DP. Baseline insulin concentration (ISS) was increased by 68% from baseline to Year 1, and remained unchanged thereafter. With intervention, a net reduction of 0.1%/year for FPS and reduction of 2.1%/year for CLGI was quantified, translated to a much slower deterioration of the first-phase insulin secretion and insulin sensitivity. The ISS was affected by a net increase of 153% from baseline to Year 1 and remained constant after that, possibly reflecting beta-cell function improvement. The DP was successfully included in the IGI model to describe differences in IGT population, with and without lifestyle intervention.

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CTA versus TOF-MRA for circle of Willis segmentation: Implications for hemodynamic modelling

Vikström, A.; Zarrinkoob, L.; Johannesdottir, M.; Wahlin, A.; Hellström, J.; Appelblad, M.; Holmlund, P.

2026-04-11 cardiovascular medicine 10.64898/2026.04.10.26350583 medRxiv
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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.

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Comparison of anxiety and satisfaction levels in patients undergoing digital versus conventional dental impressions

Farfan, M. E.; Pinzon, A. P.; Armijos Briones, M.

2026-02-06 dentistry and oral medicine 10.64898/2026.02.05.26345703 medRxiv
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Dental impressions are a routine component of prosthodontic care, yet the patient experience may vary depending on the technique used. This study compared dental anxiety and satisfaction among patients undergoing digital versus conventional impressions in a postgraduate clinical setting at the Universidad de Especialidades Espiritu Santo. A total of 85 adult patients were included: 44 received conventional impressions and 41 received digital impressions. Dental anxiety was assessed using the Modified Dental Anxiety Scale (MDAS) before the procedure, and satisfaction was evaluated using a Visual Analog Scale (VAS) immediately after the procedure. Anxiety scores did not differ significantly between groups (p = 0.232). However, patients in the digital group reported significantly greater satisfaction than those in the conventional group (p < 0.001). These findings suggest an association between the use of digital impression techniques and higher levels of patient satisfaction, while no significant association was observed between impression technique and dental anxiety.

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Canine Traction in Orthodontics: A Comprehensive Systematic Review and Meta-Analysis of Biomechanical Principles, Clinical Outcomes, and Emerging Innovations

Mahfouz, M.; Alzaben, E.

2026-03-04 dentistry and oral medicine 10.64898/2026.03.03.26347399 medRxiv
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BackgroundCanine impaction represents one of the most challenging clinical scenarios in orthodontic practice, with maxillary canines being the second most commonly impacted teeth after third molars. The management of impacted canines through orthodontic traction requires an advanced understanding of biomechanical principles, surgical techniques, and patient-specific factors. The decision to attempt traction must be informed by accurate differentiation between mechanical impaction and primary failure of eruption (PFE), as applying orthodontic force to PFE teeth results in failure and iatrogenic ankylosis. Recent systematic synthesis of eruption disorders further underscores the need to differentiate mechanical impaction from genetically mediated eruption failure prior to orthodontic traction [59]. In a companion systematic review, we have synthesized the evidence on genetic etiology and diagnostic accuracy for PFE. The present review focuses specifically on the management of confirmed mechanical impaction requiring orthodontic traction, providing a complete evidence-based framework for clinicians. ObjectiveTo provide the most comprehensive quantitative synthesis to date of orthodontic traction for impacted canines, encompassing biomechanical principles, comparative outcomes of open versus closed surgical exposure techniques, radiographic predictors of traction duration, complications, innovations, and evidence-based clinical recommendations with a practical decision algorithm. MethodsA systematic search of PubMed/MEDLINE and the Cochrane Library was conducted for studies published between January 2000 and February 2026, supplemented by citation tracking in Google Scholar. The PRISMA 2020 guidelines were followed. The protocol was prospectively registered on the Open Science Framework (DOI: 10.17605/OSF.IO/3UDH6). Eligible studies included randomized controlled trials, prospective cohort studies, retrospective cohort studies with at least 20 patients, case-control studies, systematic reviews, and meta-analyses. Risk of bias was assessed using ROBINS-I, RoB 2.0, and ROBIS tools. Meta-analyses employed random-effects models with Hartung-Knapp adjustment. Heterogeneity was assessed using I-squared and tau-squared statistics. Prediction intervals were calculated for meta-analyses with substantial heterogeneity. The GRADE framework evaluated evidence quality. Given the predominance of observational studies, pooled estimates should be interpreted as associations rather than causal effects. ResultsFrom 3,587 records, 94 studies (9,156 patients) met inclusion criteria. Optimal force magnitudes range from 50-150g, with force direction determined by the center of resistance located halfway along the root length. Meta-analyses demonstrated comparable success rates between open (91%, 95% CI: 88-94%) and closed (93%, 95% CI: 89-95%) surgical exposure techniques (9 studies; 3 RCTs, 6 observational; tau-squared = 0.00). Open exposure was associated with reduced traction duration (mean difference -4.7 months, 95% CI: -7.3 to -2.1; I-squared = 87%, tau-squared = 5.82; prediction interval -9.8 to 0.4 months) and lower ankylosis risk (OR 0.15, 95% CI: 0.03-0.83; I-squared = 0%, tau-squared = 0.00). Closed exposure was associated with reduced postoperative pain (mean difference -1.9 VAS, 95% CI: -2.6 to -1.2; I-squared = 0%, tau-squared = 0.00). Radiographic predictors include alpha-angle (beta = 0.16 months/degree), d-distance (beta = 1.20 months/mm), and sector location. Three-dimensional analysis demonstrates that cusp tip displacement explains approximately 55.4% of variance in traction duration. Complications include root resorption (23-48% of adjacent incisors; pooled MD 0.69 mm, 95% CI: 0.58-0.80 mm), alveolar bone loss (pooled MD 0.51 mm, 95% CI: 0.31-0.72 mm), and ankylosis (3.5-14.5%). GRADE evidence quality ranged from high (postoperative pain) to very low (acceleration modalities). Innovations: temporary anchorage devices (moderate-high, established); digital workflows (moderate, emerging); clear aligner-based traction (low, experimental); low-level laser therapy (low-moderate, adjunct only); vibration devices (high-quality negative evidence, not recommended). ConclusionsThis most comprehensive quantitative synthesis demonstrates that both open and closed surgical exposure techniques yield excellent success rates. Open exposure offers advantages in reduced traction duration and lower ankylosis risk, while closed exposure provides superior patient comfort. Radiographic predictors enable accurate pretreatment estimation of treatment duration. The findings of this review, combined with our companion analysis of the genetic and diagnostic basis of PFE [59], support a paradigm shift toward a genetically informed and mechanistically driven approach to all forms of failed tooth eruption. A practical clinical decision algorithm is provided to guide evidence-based management.

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The optimal second arterial graft and sex differences in coronary bypass surgery: 10-year national registry results

Beukers, S.; Daeter, E.; Kelder, H.; Houterman, S.; Kloppenburg, G.

2026-04-06 cardiovascular medicine 10.64898/2026.04.04.26350161 medRxiv
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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.