Frontiers in Medicine

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

Purpose. To evaluate two smartphone-based methods for measuring the surface area of chronic wounds using : Woundtrack (semi-automated measurement: WT) and Woundsize (automated measurement: WS), and comparing them with the reference technique: digitized planimetry (PL). Population and methods. Pixaire 1 is an open-label, single-center study involving 42 patients, from May to June 2023. Wound surfaces were measured using the three methods by two independent experts. We realized a four steps statistical analysis: multivariate analysis of variance; correlation between the two experts (precision); agreement between the two evaluated methods and the reference (accuracy); analysis of non-conformities (differences of more than 20% in absolute values compared with the PL measurement) in a subset of wound less than 8 cm2. Results. Of the 42 patients, 6 were excluded from the statistical analysis (multiplanar wound: 4; difficult edge delineation: 2). We found no difference in multivariate analysis We showed excellent agreement (ICC > 0, 9) of repeated measures (precision) for all three protocols. We also demonstrated excellent agreement (ICC > 0, 9) between WT and WS measurements versus PL (accuracy). However, accuracy and precision were better for WT than for WS. Analysis of non-conformities in small areas wounds showed no difference in variance and distribution between WT and PL, and showed a significant difference between WS and PL. Conclusion. Woundtrack is close to Digitized Planimetry, in terms of precision (reproductibility of the measure) and accuracy (correlation of measures with digitized planimetry). Despite the existence of non-conformities in small wounds, WT does not significantly differ of PL in this subset. WT should be considered as an effective method to measure the area of the wound, similar to PL, with a real benefit in implementation in current care setting (easy to realize, less time consuming). Woundsize showed less consistent results, despite a reliability and an accuracy that remains good. Its integration in a "Algorithm: propose then Clinician: correct and validate" procedure seems most efficient way to implement such methods.

Introduction: Infectious and wound-healing complications after colorectal surgery often increase the complexity of local care and the need for specialized enterostomal therapy follow-up after hospital discharge. Despite the growing use of predictive models in digestive surgery, a translational gap remains between perioperative prediction and the practical organization of specialized care. Therefore, the aim of this study was to develop and temporally validate a machine-learning-based risk stratification model to estimate the probability of post-discharge outcomes associated with greater demand for enterostomal therapy after colorectal surgery. Methods: This was a retrospective observational study including 7,908 patients who underwent colorectal surgery between 2005 and 2014. The outcome was defined as the occurrence of superficial surgical site infection, delayed wound healing, or abdominal sinus formation. Routinely available preoperative and intraoperative variables were used as predictors. The primary model was based on gradient boosting with isotonic calibration. Temporal validation was performed by separating cohorts according to year of surgery. Performance was assessed using ROC-AUC, PR-AUC, Brier score, calibration, and decision-oriented clinical metrics. Clinical utility was examined through percentile-based risk stratification and Decision Curve Analysis (DCA). Results: The outcome prevalence in the test set was 6.6%. The calibrated model achieved a ROC-AUC of 0.64 and a PR-AUC of 0.11, with a Brier score of 0.061. The Top-10% risk stratum concentrated approximately twice the baseline event rate ({approx}14% vs. 6.6%), with a number needed for intensified follow-up of 7 patients to identify one event. Decision curve analysis showed greater net benefit than strategies of following all or no patients, particularly for threshold probabilities between 3% and 13%. Models based exclusively on preoperative or intraoperative variables performed worse than the combined model. Conclusion: STOMAPY demonstrated the ability to organize patients along a continuous gradient of risk for post-discharge outcomes associated with greater demand for enterostomal therapy. Although discriminatory performance was moderate, the adequate calibration, temporal validation, and net benefit observed across clinically plausible thresholds support its usefulness as a tool for proportional care prioritization rather than as an individual diagnostic test. Prospective studies and external validations are needed to confirm direct clinical impact.

Accurate risk stratification of pigmented skin lesions is critical for early melanoma detection and for reducing unnecessary excisions. Artificial intelligence (AI) is increasingly applied to dermoscopic image analysis, but its diagnostic performance relative to standard dermoscopy in real-world clinical settings remains uncertain. To address this gap, we conducted a systematic review and meta-analysis of prospective clinical studies directly comparing AI alone, dermoscopy, and AI-assisted clinicians for malignancy risk assessment of pigmented skin lesions. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library from inception to January 2026. Ten studies with 17 diagnostic arms (10 dermoscopy arms, 6 AI-alone arms, and 1 AI-assisted clinician arm) were included. Pooled sensitivity and specificity were 0.773 (95% CI, 0.648-0.863) and 0.793 (95% CI, 0.673-0.877) for dermoscopy, and 0.757 (95% CI, 0.428-0.928) and 0.859 (95% CI, 0.619-0.958) for standalone AI. Summary ROC curves showed overlapping performance, indicating that autonomous AI is broadly comparable to dermoscopy but does not demonstrate a consistent advantage. Heterogeneity in AI performance was driven almost entirely by threshold effects rather than by differences in inherent model capacity. AI-assisted clinicians showed promising results (sensitivity 1.000, specificity 0.837) in a single study, but more evidence is needed. Our findings suggest that, at present, AI should be viewed as a complementary decision-support tool rather than a replacement for dermoscopic evaluation. The study provides valuable evidence for clinicians, guideline developers, and researchers working on AI integration into melanoma diagnostic pathways.

Background Urinary catheterization is a routine procedure after ureteroscopy lithotripsy URSL , but it often causes catheter-related bladder discomfort (CRBD) and urethral pain, which aggravates patients' postoperative discomfort. This study finds out the effect of topical anesthesia on CRBD and urethra pain in patients undergoing ureteroscopy lithotripsy and urinary catheterization. Methods In this study, 330 patients undergoing ureteroscopy lithotripsy enrolled, with 160 cases in the control group and 170 cases in the experimental group. The experimental group divided into two subgroups based on the local anesthetic used: Tetracaine Hydrochloride Gel subgroup and Oxybuprocaine Gel subgroup. Postoperative assessments conducted using CRBD scores and urethra pain numerical rating scale (NRS) score. CRBD and urethra pain NRS scores measured at T0, T1, T2, T3, T4, T5, and T6. Results Compared to the control group, the use of local anesthetics significantly reduced both CRBD scores and urethra pain NRS scores in the experimental group, with the differences being statistically significant (P < 0.01). In male patients, patients who used local anesthetics markedly decreased CRBD scores and urethra pain NRS scores compared to those not receiving local anesthetics, showing statistical significance (P < 0.01), whereas no significant difference followed in female patients. No statistically significant differences found between Rigid ureteroscopy lithotripsy R-URSL and Flexible ureteroscopy lithotripsy F-URSL) regardless of the use of local anesthetics. Within the experimental group, the effects of different local anesthetics were similar, with comparable impacts on CRBD scores and urethra pain NRS scores, and no statistical differences noted. These findings suggest that local anesthetics are effective in reducing postoperative CRBD scores and urethra pain NRS scores, especially in male patients. Conclusion Topical anesthesia following ureteroscopy lithotripsy reduces CRBD scores and urethra pain NRS scores in patients undergoing urinary catheterization, especially in male patients.

Vitiligo is an acquired pigmentary disorder of the skin and mucus membranes. Previous study has demonstrated that autologous cultured epithelial grafts (ACEG) is an effective treatment for stable vitiligo. However, extraction of full-thickness skin might result in scar formation at donor site, which have hindered the wider application of this technology, especially for patients requiring large-area transplantation. Hair follicle as a source of keratinocyte and melanocyte, could be potential source of cells for preparation of autologous cultured sheet. Through culture system optimization, we have demonstrated maintenance of undifferentiated hair follicle-derived cells in feeder-independent culture system. After expansion, the hair follicle cells were directed to differentiate into a multi-layered, epidermis-like sheet. Cell identity, viability, purity, genomic stability, and antiseptic testing for hair follicle-derived epithelial sheet (HFES) were evaluated to ensure its safety. Immunofluorescence staining showed that basal keratinocytes were the main cell type of the autologous HFES. Optimization of culture conditions leads to increased melanocyte proliferation and functionality. Transcriptomic analysis confirmed upregulation of melanosome maturation genes. The proportions of cells are also similar to composition of cells under physiological conditions. Transplantation of HFES to depigmented areas in patients with stable vitiligo results in skin repigmentation. This technology provides a novel therapeutic option for vitiligo management.

BackgroundTo investigate the safety and efficacy of CT-guided lung nodule localization needles for the preoperative localization of small pulmonary nodules. MethodsA retrospective study was conducted on 102 patients with a total of 113 small pulmonary nodules who underwent preoperative localization at Jinan Fourth Peoples Hospital from January 2024 to December 2025. Nodule diameter and depth, localization time, the number of pleural punctures, the localization success rate, and postoperative complications (hook dislodgement, hemorrhage, and pneumothorax) were recorded. All patients underwent video-assisted thoracoscopic surgery (VATS) after localization. ResultsThe mean nodule diameter was 0.97{+/-}0.36 cm, the mean depth was 1.26{+/-}0.48 cm, and the mean localization time was 9.8{+/-}3.65 minutes. The hook dislodgement rate was 0.98% (1/102), the intrapulmonary hemorrhage rate was 14.71% (15/102), and the pneumothorax rate was 16.67% (17/102). All pulmonary nodules were successfully resected by VATS at 73.82{+/-}13.83 minutes after localization, and no severe complications occurred. ConclusionsThe use of a CT-guided lung nodule localization needle for the preoperative localization of small pulmonary nodules decreases the time needed for intraoperative nodule detection and operation time. This strategy is a simple, safe, and accurate preoperative localization method that is worthy of increased clinical use.

BackgroundLasers have wide applications in medicine and dermatology, but are associated with pain and anxiety, particularly in younger patients. Pain mitigation is often limited to topical anesthetics in the outpatient setting. Distraction techniques are limited by the need for ocular protection, which can include adhesive eye patches that can completely occlude vision. Virtual reality is effective at managing procedural pain and anxiety under other short medical procedures and is a promising tool for this population. ObjectiveThis trial aims to assess the safety, feasibility, and efficacy of Virtual Reality Pain Alleviation Therapeutic (VR-PAT) for pain management during outpatient laser procedures. Methods40 patients requiring outpatient laser therapy for at least two sessions will be recruited from a pediatric hospital in the midwestern United States for this crossover randomized, two-arm clinical trial with a 1:1 allocation ratio. During the first laser visit, the participant will be randomly assigned to either play the VR-PAT game during their procedure or wear the headset with a dark screen. Participants will answer questions about their pain (Numeric Rating Scale (NRS) 0-10), anxiety (State Trait Anxiety Inventory for Children, NRS 0-10, Modified Yale Preoperative Anxiety Scale (mYPAS)), and pain medication usage. Those playing the VR-PAT will additionally report simulator sickness symptoms and their experience playing the game. At their second laser visit, participants will crossover to the opposite intervention from their first visit. The primary outcomes are the difference in self-reported pain and anxiety between the two interventions. Feasibility outcomes include the proportion of screened patients who are eligible, consent, and complete both visits and adverse events reported. To evaluate the efficacy of pain reduction, composite scores of pain score, pain medication will be calculated for each laser visit. To evaluate the efficacy of anxiety reduction, the change of mYPAS scores will be compared between control and VR groups at each visit using Wilcoxon rank sum tests. All statistical analyses will follow the intention-to-treat principle in regard to intervention assignment at each visit. ResultsThe study was funded in January 2023 and began enrollment at that time. A total of n=44 participants were recruited and data collection was completed in November 2025, with n=40 subjects completing both visits. The sample was balanced with n=40 subjects using the intervention and participating in the control condition. The age range of the complete sample was 6 to 21 years at recruitment and was 55% female sex. Data analysis is in progress with final results planned for June 2026. ConclusionsFindings from this innovative randomized clinical trial will provide early evidence on the efficacy of the VR-PAT for reducing self-reported pain and anxiety during outpatient laser procedures. The results from this trial will inform a large-scale, multisite study. Trial RegistrationClinicalTrials.gov: NCT05645224 [https://clinicaltrials.gov/study/NCT05645224]

COVID-19 has spread rapidly and caused a global pandemic making it one of the deadliest in history. Early identification of patients with coronavirus disease 2019 who may develop critical illness is of immense importance. Therefore, novel biomarkers were needed to identify patients who will suffer rapid disease progression to severe complications and death. Many treatments were adopted including the antiviral Remdesivir, the antiretroviral Lopinavir /Ritonavir and Tocilizumab. Our study aimed not only to specify high-risk factors and biomarkers of fatal outcome in hospitalized subjects with coronavirus but also to compare the efficacy of the three considered treatments to help clinicians better choose a therapeutic strategy and reduce mortality. We divided the population (n=711) into four main groups based according to the WHO ordinal severity scale. The percentage of mortality, in and out the hospital, the length of stay in the hospital, the pulmonary inflammatory lesion and its distribution, the SARS-CoV-2 IgM and IgG variations at admission, the inflammatory markers, the complete blood count, the coagulation factors and enzymes, proteins and electrolytes profile, glucose and lipid profile, and other relevant markers were measured. The significance of the observed variation was assessed by multivariate and ANOVA analyses. We succeeded to establish a novel predictive scoring model of disease progression based on a cohort of Lebanese hospitalized patients relying on the pulmonary inflammatory lesions, inflammation biomarkers such as LDH, D-Dimer, CRP, IL-6 and the lymphocyte count, the number of comorbidities and the age of the patient which all were significantly correlated with the illness severity showing best outcomes with immunomodulatory and anticoagulant treatments by the results. As top tier, Tocilizumab was more efficient than the two other treatments in non-severe cases but none of the used treatments was insanely effective alone to reduce mortality in severe cases.

BackgroundBiologics and Janus kinase (JAK) inhibitors carry specific risks for Ankylosing Spondylitis patients at risk of tuberculosis infection or those with contraindications such as a history of cancer, there is an urgent need to explore safe and effective alternative treatment options. AimsTo evaluate the efficacy and safety of Iguratimod combined with Yunke injection in the treatment of ankylosing spondylitis at risk of tuberculosis infection or those with a history of cancer. Study DesignRetrospective cohort study. MethodsA retrospective study was conducted on 48 patients with ankylosing spondylitis who had received treatment over the past 3 years and had a history of tuberculosis infection or malignancy. Their treatment regimens and therapeutic outcomes were analyzed, with particular attention to the progression of tuberculosis and malignancy. ResultsThere was 30 patients receiving Iguratimod combined with Yunke injection treatment, and non-steroidal anti-inflammatory drugs (NSAIDs) were added when pain was severe,referred to as the observation group; 18 patients took Iguratimod and NSAIDs, referred to as the contral group. After treatment of 24 months, both groups showed significant improvements in Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Erythrocyte Sedimentation Rate (ESR), and C-Reactive Protein (CRP), and overall levels could achieve low disease activity. However, the improvement of observation groupin was better than that in the control group, P<0.05. Moreover, the use of NSAIDs in the observation group was significantly less than that in the control group, P<0.001. ConclusionThis study shows that Iguratimod combined with Yunke injection has good efficacy in patients with ankylosing spondylitis who cannot use biologics or JAK inhibitors, not only alleviating pain and morning stiffness but also slowing radiographic progression and reducing the dose of NSAIDs. The combination has a synergistic effect and does not increase adverse reactions. This therapy provides a novel option for patients with specific ankylosing spondylitis.

This study mapped the age- and region-specific risks of eye diseases in the Brazilian population, evaluating temporal trends and geographical inequalities in access to healthcare. Secondary data from DATASUS, covering the 27 Brazilian federative units from 2010 to 2024, were used, employing hierarchical negative binomial regression. A significant national increase in hospital admission rates was observed during the studied period, with increases of 160.8% for retinopathy, 126.4% for eye and appendage diseases, and 122.8% for glaucoma. State-level heterogeneity was extreme, with variations spanning from -93.1% to +3588% for glaucoma, for example. Even so, regional disparities were observed throughout the period; the South region reported an average 43.2% higher than the national average for retinopathies, and the Southeast 28.5% higher for eye and adnexal diseases, while the North region reported the lowest rates. Projections up to 2036 predict a further national increase of up to +377.0% for retinopathies, with interventions covering more than an order of magnitude. In addition to the temporal projection, rates in state, age, and year components on a logarithmic scale with calibrated uncertainty were verified. Out-of-sample tests show that the chosen modeling outperforms the last observed value maintenance method and naive linear extrapolation in all three diseases considered. Thus, the escalating, age-driven burden of ophthalmological diseases and profound geographic disparities highlight an urgent need to decentralize specialized care and target resource allocation within the public health system.

Background: Multi-drug resistant Bacterial (MDRB) Infections in the intensive care units (ICUs) substantially elevate patient mortality, prolong hospital stays, and impose heavy healthcare cost burdens. Existing predictive models for ICU-acquired MDRB infection predominantly focus on static admission-risk assessment, lacking the capacity to leverage longitudinal treatment data for dynamic risk re-stratification during the ICU stay. Meanwhile, most models suffer from poor clinical interpretability, overreliance on hard-to-collect biomarkers, or absence of deployable clinical tools, limiting real-world translation. Therefore, there is an urgent need to develop a parsimonious, interpretable tool based on routine cumulative data to guide timely intervention. This study aimed to develop a interpretable model with a web calculator to improve clinical applicability. Methods: In this study, we conducted a retrospective analysis of ICU inpatients at the First Affiliated Hospital of Dali University between January 1, 2023, and January 1, 2026. Using the create Data Partition function in R software (random seed = 42), the dataset was stratified and divided into a training group and a validation group in a 7:3 ratio. Feature selection was performed using the Boruta algorithm to validate variable rationality. A multivariable logistic regression model was constructed and visualized as a nomogram, and its performance was compared with six machine learning algorithms (Random Forest, XG Boost, Neural Network, etc.). Model validation was conducted using receiver operating characteristic curves (ROC), Decision Curve Analysis (DCA), and SHAP value interpretation. Finally, an online R Shiny calculator was developed based on the final model. Results: A total of 3,631 patients were enrolled and divided into a training group (n=2,543) and a validation group (n=1,088) using stratified random sampling. Five independent predictors were identified in the training group, which were hypertension combined with diabetes, antibiotic types, ventilator days, urinary catheter days, and PCT abnormality times. The Logistic regression model achieved an AUC of 0.772 (95%CI: 0.733-0.812) in the validation group, outperforming XG Boost (0.763) and Random Forest (0.703). The model demonstrated excellent calibration (Hosmer-Leme show {chi}{superscript 2} = 1.94, P = 0.9829) and positive net clinical benefit across threshold probabilities of 0%-40%. SHAP analysis aligned with regression-derived variable importance rankings, confirming predictor contributions. An open-access online calculator was successfully deployed (https://dongfangshao666.shinyapps.io/MDR_shiny2/), enabling real-time individualized risk stratification at the bedside. Conclusion: This study developed and validated a dynamic, interpretable multi-drug-resistant bacterial infection risk prediction model requiring only five routinely collected clinical indicators. The model balances robust predictive performance with high transparency, overcoming key limitations of prior tools. The accompanying web calculator supports dynamic risk reassessment throughout the ICU stay, facilitating precise antimicrobial stewardship, targeted infection control interventions, and optimized resource allocation, bridging the gap between statistical modeling and frontline clinical decision-making.

Background: The prevalence of lumbar disc herniation (LDH) is increasing, and the associated pain and functional limitations severely impact patients' quality of life. Daoyin, a traditional Chinese exercise, has a history of thousands of years in managing musculoskeletal pain. However, its application in LDH has not been sufficiently investigated, and there is a notable scarcity of rigorous randomized controlled trials (RCTs). This paper outlines the protocol for an RCT based on the theory of goal attainment (TGA), which aims to investigate whether Daoyin is more effective than other exercise therapies in improving symptoms in patients with LDH. Methods: We conducted a 6-week RCT in which participants were randomly assigned to either Daoyin or core stability exercise (CSE). During the first two weeks, the participants performed their assigned exercises five times per week. Outcome data were collected at baseline, week 2, and week 6. The primary outcome was pain intensity at 6 weeks, which was assessed via the visual analogue scale (VAS). The secondary outcomes included the Japanese Orthopaedic Association (JOA) score, the Oswestry Disability Index (ODI), the MOS 36-item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), surface electromyography (sEMG), gait analysis, and electroencephalography (EEG). A generalized estimating equation (GEE) model will be used to analyse longitudinal changes and between-group differences. Discussion: This trial seeks to assess the efficacy of Daoyin for LDH and to elucidate its underlying neuromuscular mechanisms. Should the intervention prove feasible, the findings will inform the design of a subsequent large-scale RCT and are expected to contribute to a solid evidence base for the broader clinical application of Daoyin. Trial registration: https://itmctr.ccebtcm.org.cn/, Registration number (ITMCTR2025001239).

Background: Microbiota dysbiosis of the skin has been implicated in ulcer formation. Individuals with diabetes remain at high risk for diabetic foot ulcers (DFUs) even after ulcer healing. Topical chlorhexidine gluconate (CHG) is a broad-spectrum antiseptic commonly used to reduce microbial burden. In a prior randomized clinical trial comparing daily CHG foot treatment with soap-and-water treatment, no statistically significant reduction in new DFUs was observed, prompting evaluation of whether CHG produced durable changes in the skin microbiota. Objective: To compare changes in foot skin microbiota (including bacterial bioburden, diversity, and community composition) associated with daily CHG versus soap-and-water use over one year in people with diabetes and prior foot complications. Methods: In a single-center, double-blind, placebo-controlled randomized trial, 87 participants were randomized to daily CHG wipes or soap-and-water wipes for 12 months. Foot swabs were collected at baseline, 3 and 12 months, and 4 weeks post-treatment. Bacterial bioburden was quantified. Microbiota composition was assessed using 16S rRNA and ITS amplicon sequencing. Key Results: CHG treatment significantly reduced bacterial bioburden, increased microbial diversity, and altered community composition, including sustained reductions in Staphylococcus abundance. Several microbiota changes persisted more than 4 weeks after treatment cessation. Soap-and-water treatment showed similar but smaller and largely nonsignificant trends. Conclusions: Daily CHG use durably modifies foot skin microbiota in high-risk individuals with diabetes. However, this alone may be insufficient to prevent new foot complications, highlighting the need for additional interventions. These findings have implications for long-term CHG use in populations at risk for staphylococcal infections.

BackgroundThere is a close correlation between neuroendocrine regulation and pulpitis progression. This study aims to identify key neuroendocrine regulation-related genes in pulpitis, providing insights for its treatment. MethodsGSE77459 and GSE92681 datasets were used to validate experimental findings. Key neuroendocrine regulation-related genes were identified via Cytoscape plugin cytoHubba and expression validation. Gene set enrichment analysis, RNA-binding protein regulatory networks, post-translational modifications, molecular regulatory networks, and drug prediction were performed. Key gene expression was experimentally verified in clinical samples. ResultsTop 10 genes were obtained via cytoHubba; 4 (IL6R, OSM, IL1RN, CCL4) with significant differences between pulpitis and control samples and consistent trends in both datasets were identified as key genes. Gene set enrichment analysis showed key genes participate in pathways like cytokine-cytokine receptor interaction. Related RNA-binding proteins were ELAVL1 and HNRNPA1, with phosphorylation as the main post-translational modification. Core regulatory microRNAs included miR-519, miR-765, miR-23, and regulatory factors included FOXC1, PRRX2. Targeted drugs (e.g., sarilumab, haloperidol decanoate, cyclosporine) were predicted, and clinical sample verification confirmed consistent expression trends. Conclusion4 key neuroendocrine regulation-related genes were identified, which may have clinical significance for the diagnosis and treatment of pulpitis.

Background: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease associated with clinical, psychosocial, and economic burden. Accurate severity assessment is essential for guiding treatment escalation and monitoring disease activity, yet clinician-based scoring systems such as the Eczema Area and Severity Index (EASI) are limited by subjectivity and considerable inter- and intra-rater variability. Erythema, a key driver of AD severity grading, is particularly prone to inconsistent evaluation due to differences in ambient lighting, device quality, skin tone, and rater experience, underscoring the need for objective, reproducible assessment tools. Objective: To develop and validate an artificial intelligence (AI) pipeline for grading erythema, excoriation, and lichenification severity in AD from clinical photographs. The study evaluated the level of agreement between AI severity ratings in each category against dermatologists, non-specialists, and a consensus reference standard, with erythema as the primary outcome of interest. Methods: A two-stage AI pipeline was developed using EfficientNet B7 convolutional neural networks (CNNs). The first CNN was trained as a binary AD classifier on 451 AD and 601 non-AD images for lesion detection and segmentation. The second CNN was trained on 173 dermatologist-annotated AD images which were scored on a 0-3 ordinal scale for erythema, excoriation, and lichenification. This CNN had a downstream feature extraction algorithms such red channel contrast for erythema, Law's E5L5 for excoriation, and S5L5 texture maps for lichenification. In a cross-sectional validation study, 41 independent test images were scored by two blinded dermatologists and two blinded physicians. AI predictions were compared to individual rater groups and mode-derived consensus scores using weighted Cohen's kappa, classification accuracy, confusion matrices, and error direction analyses. Results: On internal validation, the severity CNN achieved 84% overall accuracy (averaged across all three attributes), 86% sensitivity, 87% specificity, and a macro-averaged area under the receiver operating characteristic curve (AUC) of 0.90. In the external comparison with blinded human raters, erythema agreement between the AI and dermatologist consensus was substantial (accuracy 80.7%; kappa = 0.68), with no large (>2-point) misclassifications. Physician consensus agreement was lower (accuracy 54.8%; kappa = 0.34), reflecting greater variability among primary care physicians (non-specialists). For excoriation, AI-dermatologist agreement was moderate (accuracy 72.4%; kappa = 0.62); for lichenification, agreement was similar (accuracy 71.4%; kappa = 0.59). Across all features, disagreements were predominantly between adjacent severity categories. The AI was able to generate erythema severity grades for images of darker skin tones that dermatologists typically would not rate and were marked as "unable to assess". Limitations: The validation set was small (41 images), severe cases (score 3) were underrepresented, one rater participated in both training annotation and validation scoring, and sample size was insufficient for robust stratification by skin tone or body site. Conclusion: The AI pipeline demonstrated dermatologist-level accuracy for erythema scoring, consistent moderate agreement for excoriation and lichenification, and a potential advantage in assessing erythema on darker skin tones. These findings support its potential as a standardized, objective tool for AD severity assessment. Prospective validation in larger, more diverse cohorts is warranted.

BACKGROUND & AIMS Conventional reusable endoscopes incur significant expenses in the form of purchase, maintenance, reprocessing, and disinfection. Reprocessing is frequently ineffective even following the use of high-level disinfectants (HLDs). Disposable gastroscopy might be a strategy to decrease infectious outbreaks associated with reusable endoscope. The aim of this study was to analyze and evaluate the performance, efficiency and safety in gastroscopy observation and subsequent potential EMR procedure via the disposable gastroscope in a clinical setting. METHODS Patients who required gastroscopies and met the criteria were recruited to this prospective, open-label, non-inferiority study. After obtaining the written informed content, the enrolled subjects selected themselves independently to the disposable group or reusable group. The primary measure was to evaluate the acceptable image quality and whether the disposable endoscope devices could meet the basic clinical demands with a noninferiority margin of -8%. The second measures were to analyze and evaluate the image conditions, accepted endoscopic maneuverability, efficiency and safety of observation and advanced potential EMR procedure. Appropriate statistical methods were conducted via PASS software and SAS 9.4. A two-tailed P value < 0.05 was considered statistically significant. RESULTS A total of 90 individuals (the number of those in disposable group and reusable group was both 45) were recruited to this study. The success rate of acceptable image quality via photographing iconic anatomical sites between two groups was 100.0% (45/45, 95% confidence interval (CI): 0.9213,1.0000) and the lower limit of the 95%CI (-7.8654%, 7.8654%) was larger than the noninferiority margin of -8% (Newcombe-Wilson score method). Significant differences were showed in the measures of image conditions (image acquisition, image quality, brightness, contrast and sharpness) and accepted endoscopic maneuverability (endoscopy body rigidity). No significant differences were observed in the field of knob operation, sharp angle adaptability, and the auxiliary features including air supply, water supply and suction. In terms of efficiency, the total operating time, insertion time and withdrawal time were longer in the disposable group. The En-bloc resection rate of those observed polyps and required to EMR procedure due to relatively larger diameter (5mm-15mm) was the same 100% in both groups (26/26 vs 23/23, 95%CI: 0.8713,1.0000). Nevertheless, the procedure time of EMR for each polyp was significantly longer in the disposable group. This study showed no intraoperative bleeding, delayed bleeding, perforation or other study-related adverse events among 90 patients. No dramatic fluctuations in vital signs were showed in perioperative period. CONCLUSIONS In consideration of the efficiency, efficacy and safety evaluation, the disposable gastroscopes might represent an alternative to conventional reusable gastroscopes in routine examination and endoscopic mucosal resection.

Aminoglycoside drugs, amikacin, streptomycin, and amikacin liposome inhalation suspension are crucial for treating refractory Mycobacterium avium-intracellulare complex pulmonary disease. In Mycobacterium tuberculosis, cross-resistance occurs between amikacin and kanamycin, but not between amikacin and streptomycin in genetic drug susceptibility testing. However, the occurrence of cross-resistance among aminoglycosides remains unclear in M. avium-intracellulare complex. We aimed to evaluate cross-resistance among aminoglycosides to determine whether streptomycin or kanamycin remains effective after the development of amikacin resistance. This single-center retrospective study included 20 patients with amikacin-resistant M. avium-intracellulare complex harboring rrs mutations. Paired analyses of streptomycin and kanamycin minimum inhibitory concentration values before and after amikacin resistance development were performed. In addition, streptomycin- and kanamycin-resistant strains were generated in vitro and resistance-associated mutations were identified using whole-genome sequencing. No significant increase was observed in streptomycin minimum inhibitory concentration values following amikacin resistance. In contrast, kanamycin values uniformly increased to >256 g/mL after the acquisition of amikacin resistance. Furthermore, amikacin- and kanamycin-resistant isolates shared mutations at position 1408 in the rrs gene, whereas streptomycin-resistant isolates exhibited mutations at position 20 in the rrs gene. These results suggest that amikacin and kanamycin exhibit cross-resistance in M. avium-intracellulare complex, whereas amikacin and streptomycin may not. Two cases in our cohort in which streptomycin treatment was effective after the acquisition of amikacin resistance further support these findings. In conclusion, streptomycin may be a potential therapeutic alternative for amikacin-resistant M. avium-intracellulare complex pulmonary disease. Future studies correlating streptomycin minimum inhibitory concentration values with clinical outcomes are required.

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.

Introduction Aquablation for surgical treatment of benign prostatic enlargement (BPE) causing bladder outflow obstruction (BOO) has demonstrated good functional outcomes, even for large glands, with high rates of ejaculatory preservation reported. This is a protocol for a study that aims to review real-world outcomes of ejaculatory preservation or restoration post-Aquablation in an unselected cohort and compare to published clinical trial outcomes. Methods Retrospective data will be collected from a prospectively maintained consecutive case series of patients who underwent Aquablation, in a single UK centre. The primary outcome is ejaculatory function subjectively reported by men post-operatively, and classified as: antegrade ejaculation, retrograde/low volume ejaculation, anejaculation or not sexually active. Secondary outcomes are International Prostate Symptom Severity (IPSS), Quality of Life (QoL) Score, post-void residual (PVR), and incontinence. Descriptive and comparative statistical tests will be performed. Conclusions This study will review real-world ejaculatory function and clinical outcomes following robotic Aquablation for prostatic bladder outflow obstruction and compare this to published clinical trial outcomes.