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.

ObjectiveTo clinically evaluate a digital biomarker, the Finger Fold Index (FFI), derived from the ratio of joint diameter to finger fold surface area in hand photographs, for assessing joint swelling in inflammatory arthritis. MethodsSmartphone hand photographs from two routine care cohorts of patients with rheumatoid (RA) and psoriatic arthritis (PsA) were analyzed using a machine learning pipeline for automated detection and processing of proximal interphalangeal (PIP) joints. The FFI was clinically evaluated by correlation with joint swelling scores (0-3) and DAS28-CRP. A healthy cohort was used to establish FFI reference ranges, which were then compared to the arthritis cohorts. ResultsA total of 1275 PIP joint images of 124 arthritis patients and 53 healthy individuals were included. FFI values correlated with swelling scores in the arthritis population with r = 0.443 (95% CI 0.384-0.498). A correlation was observed between the mean FFI and DAS28-CRP dichotomized at 3.2 (r = 0.310, 95% CI 0.123-0.475). FFI values exceeding the healthy reference ranges were associated with swelling (Cramers V = 0.400-0.631; p < 0.001). ConclusionFFI values derived from hand photographs showed a significant association with clinical joint swelling and disease activity in RA and PsA patients. Longitudinal studies are needed to assess sensitivity to change and to establish whether this biomarker can be reliably used for remote patient monitoring.

BackgroundPreventing Stage 1 pressure injuries (PIs) from worsening in the ICU is a key clinical challenge. Early prediction of high-risk patients enables targeted prevention. We aimed to develop a model for this progression using admission data. MethodsIn this retrospective cohort study, eligible ICU patients with Stage 1 pressure injuries were randomly allocated into training (70%) and validation (30%) sets. Predictors were selected using LASSO regression. A multivariable logistic regression model was constructed and visualized as a nomogram. Model performance was evaluated by discrimination (AUC), calibration, and clinical utility (decision curve analysis). ResultsA total of 278 patients were randomly divided into training (n=195) and validation (n=83) sets. LASSO regression identified four independent predictors: diabetes (OR: 3.266; 95% CI: 1.451-7.352), maximum norepinephrine dose (OR: 13.032; 95% CI: 1.212-140.137), use of pneumatic compression pumps (OR: 3.308; 95% CI: 1.444-7.579), and albumin level at ICU admission (OR: 0.836 per unit increase; 95% CI: 0.777-0.900). The nomogram demonstrated excellent discrimination, with an AUC of 0.810 (95% CI: 0.748-0.872) in the training set and 0.805 (95% CI: 0.696-0.914) in the validation set. Good calibration and clinical utility were confirmed. ConclusionsA nomogram incorporating four readily available factors at ICU admission effectively predicts the risk of Stage 1 PI progression. This tool may aid early risk stratification and guide precise preventive measures.

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.

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.

Background: To investigate the safety and efficacy of CTguided lung nodule localization needles for the preoperative localization of small pulmonary nodules. Methods: A retrospective study was conducted on 102 patients with a total of 113 small pulmonary nodules who underwent preoperative localization at Jinan Fourth People's 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. Results: The 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. Conclusions: The use of a CTguided 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.

Our previous studies identified three microRNAs (miR-92a-1-5p, miR-375 and miR-148a-3p) potentially associated with prostate cancer (PCa), particularly in advanced stages such as bone-metastatic PCa. To evaluate their clinical diagnostic utility, we isolated extracellular vesicles (EVs) from the plasma of patients with benign prostatic hyperplasia (BPH) and PCa (including localized and bone-metastatic disease). The absolute quantification of these three miRNAs within plasma EVs was performed using digital PCR. Results indicated that miR-148a-3p alone possessed a good ability to discriminate between PCa and BPH. Notably, a combined panel of all three miRNAs demonstrated improved diagnostic performance, achieving an area under the curve (AUC) of 0.736 for distinguishing PCa from BPH. These findings suggest that the plasma EV-derived miRNA panel (miR-92a-3p, miR-148a-3p, and miR-375-3p) holds promise as an auxiliary diagnostic biomarker for PCa and may aid in identifying bone metastasis.

Anemia, particularly iron-deficiency anemia, is a critical global health concern, with a high prevalence among children under six years of age. Early and non-invasive detection can significantly improve health outcomes. This study proposes a computer vision and machine learning framework for anemia screening and hemoglobin (Hb) level prediction using palmar images from pediatric subjects. The region of interest (palm) was segmented using a U-Net model, achieving a Dice coefficient of 0.96. Images were processed across RGB, CIELab, and HSV color spaces to extract key color features, including red fraction, erythema index, and normalized a-component. For anemia classification, multiple machine learning models were evaluated, with Logistic Regression, Gradient Boosting, and a custom Convolutional Neural Network (CNN) achieving the highest test accuracies of approximately 94.5% and 95.53%, respectively. For hemoglobin regression, a Random Forest model in the CIELab color space achieved a coefficient of determination (R2) of 0.95. The Pearson correlation coefficient in the Lab color space was 0.98 for the Random Forest algorithm and 0.94 for the Linear Regression algorithm. The analysis, supported by SHAP values, identified red-related color features as the most significant predictors. The model demonstrated robust performance across different skin tones, with particularly high accuracy (R2 = 0.9926) in darker-skinned individuals, who constituted the majority of the studied Iranian population. The results confirm that pallor analysis of palmar images using artificial intelligence techniques offers a reliable, non-invasive, and effective tool for pediatric anemia screening and hemoglobin estimation, with strong potential for point-of-care applications.

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).

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.

PurposeUnderstanding patient perspectives is essential to improving quality and satisfaction of care in dermatology clinics. In Saudi Arabia, limited national data exist on patients educational needs and communication barriers. This study aimed to assess patient satisfaction, identify educational gaps, and explore communication challenges in dermatology clinics across Saudi Arabia. Patients and methodsA national cross-sectional survey was conducted among 976 dermatology patients. A structured questionnaire evaluated demographics, perceived knowledge, satisfaction with information provided, communication barriers, and preferred educational methods. Descriptive statistics and chi-square tests were used for analysis. ResultsAmong participants who had attended dermatology clinics (n = 795), 61.6% reported frequent or occasional confusion about their condition, and only 45.4% demonstrated high self-reported knowledge. Overall satisfaction was moderate, with 58.3% satisfied or very satisfied, while 9.9% reported dissatisfaction. The most reported communication barriers were limited consultation time (25.2%) and patient anxiety about asking questions (15.3%). Patients felt least informed about treatment options (22.6%), diagnosis (20.3%), and potential side effects (19.3%). Most participants (70.6%) preferred language communication to be in Arabic, and 78% favored the physical method of face-to-face education consultation. Patient knowledge, barriers and preferences significantly differed with age, gender, and condition complexity (p < 0.05). ConclusionDermatology patients in Saudi Arabia report moderate satisfaction with substantial educational needs and communication barriers. Addressing consultation time constraints, fostering supportive communication environments, and providing patient-centered, language-appropriate education; particularly through direct face-to-face interactions will aid to enhance understanding, satisfaction, and engagement in for an overall better provider-patient dermatologic care.

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.

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.

We genotyped 1189 multidrug-resistant Mycobacterium tuberculosis isolates identified during 2013-2022 in Argentina, through a mixed strategy using PCR-based methods and whole-genome sequencing. Epidemiological, geographic distribution and microbiological data were integrated. Most cases belonged to a cluster (75.7%). The proportion of orphan and clustered cases varied across regions. The Euro-American lineage4 was virtually predominant. The most important clusters, M, Ra, Rb and Callao2 strains, comprised 45.9% of the newly diagnosed cases, and their relative importance varied over time. A preliminary genomic analysis showed that several local transmission chains due to the Callao2 strain, imported from Peru, were active, including a superspreading event that occurred circa 2020. A good performance of the current second-line regimes can be expected for most of the cases. Heightening suspicion of drug-resistance and enhancing timely and active surveillance in specific risk groups could contribute to the tuberculosis management in Argentina, tackling transmission and resistance amplification. BiosketchBiochemist Federico Lorenzo is a professional of the Servicio de Micobacterias, Departamento de Bacteriologia, INEI, ANLIS "C. G. Malbran" and is specialized in the microbiological diagnosis of mycobacterial diseases using next-generation sequencing technologies. His research interests are drug-resistant tuberculosis, non-tuberculous mycobacteria and bioinformatic analysis applied to diagnostics. One-sentence summaryWe evaluated the genotypes associated with multidrug-resistant tuberculosis in Argentina, 2013-2022.

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.

Pentosan polysulfate (PPS) is a semisynthetic sulfated polysaccharide that was approved by the United States Food and Drug Administration (FDA) for treatment of interstitial cystitis (IC). A 2018 study by our group described a vision-threatening macular toxicity associated with long-term use of PPS. However, given the relatively recent characterization of PPS maculopathy, we have limited knowledge of its pathophysiology. The present study therefore investigated the pathophysiology of PPS maculopathy in a cell culture model, assessing impacts of PPS exposure on morphology and mitochondrial function. We treated ARPE-19 cells with increasing doses of PPS and investigated both mitoprotective and cytoprotective mechanisms, mitochondrial reactive oxygen species production (ROS) and respiration, cellular structure, and retinal pigment epithelium (RPE) dysfunction through phagocytosis assays. We found that PPS increased mitochondrial superoxide accumulation and that increased doses of PPS impaired basal and maximal respiration in a Seahorse assay without the expected response of increases in the cellular energy sensor pAMPK. PPS exposure disrupted mitochondrial and cell protective mechanisms against ROS accumulation as assessed through examination of mitochondrial biogenesis markers PGC-1 and SIRT1 and autophagy markers LC3 and p62. PINK1 expression increased with increasing duration of exposure to PPS. Further, we found that PPS led to functional and structural changes to RPE cells, which exhibited an increase in cell aspect ratio and impaired phagocytosis with higher doses of PPS. Lastly, we found an increase in cell death in response to higher doses of PPS, evident through ethidium homodimer cell viability assays. Taken together, our study shows PPS exposure has profound effects on RPE viability and function through impairment of mitochondrial respiration and mito- and cyto-protective mechanisms and highlights mitochondrial insult as a potential focus of future PPS research.