Medicine and Pharmacology

Abstract: Hard flaccid syndrome (HFS) is an emerging condition of male sexual dysfunction characterized by a persistent semi-rigid penis in the flaccid state, altered penile sensation, erectile dysfunction, and pelvic or perineal pain. Single-modality treatments have shown limited success, and multimodal protocols have been reported only in single-patient case studies. Our objective was to conduct a retrospective analysis of clinical outcomes from an integrative multimodal rehabilitation protocol in men with HFS. Thirty-two men with HFS completed a comprehensive protocol combining class IV laser therapy, dry needling, radial pressure wave shockwave therapy, therapeutic ultrasound, biofeedback training, manual therapy, therapeutic exercise, behavioral coaching, and oral tadalafil. Patient-reported outcomes were collected at treatment initiation and completion. The main outcome measures were Erection Hardness Scale (EHS), penile satisfaction, PROMIS Sexual Interest, and PROMIS Global Health Physical and Mental Component scores. In this case series, median EHS increased from 2 to 4 and median penile satisfaction increased from 2 to 5 (both P<0.01). All 32 patients achieved EHS ≥3 by treatment end, compared with 8 of 32 (25%) at baseline. PROMIS Sexual Interest, Physical Component, and Mental Component scores all improved significantly (P<0.01). Common comorbid features included low back pain (53%), hip or groin pain (38%), pelvic floor pain (31%), and urinary symptoms (28%). In this retrospective case series, multimodal treatment produced substantial improvements in erectile function and sexual quality of life in men with HFS, supporting an integrative model in which musculoskeletal and end organ pathologies initiate the syndrome and are amplified by central and peripheral nervous system contributions.

Abstract: Dengue remains a major public health problem in tropical and subtropical regions, particularly in Latin America. Acute kidney injury (AKI) is one of the severe complications associated with dengue and has been linked to worse clinical outcomes, including prolonged hospitalization, need for renal replacement therapy, and increased mortality. This review aimed to summarize the available evidence on the epidemiology, pathophysiology, clinical manifestations, diagnosis, management, and prognosis of dengue-associated AKI, while also providing an overview of the literature from Latin America. This manuscript was developed as a narrative review. For the Latin America-specific overview, a focused structured search was conducted in PubMed, ScienceDirect, Cochrane Library, LILACS, and Web of Science, including studies published up to December 2025. The available data suggest that AKI in dengue is multifactorial, involving plasma leakage, renal hypoperfusion, endothelial dysfunction, tubular injury, rhabdomyolysis, thrombotic microangiopathy, and inflammatory renal damage. Clinically, AKI has been associated with oliguria, proteinuria, elevated serum creatinine, renal replacement therapy, and higher mortality. Only four eligible indexed studies from Latin America were identified in our search, all from Brazil, with small sample sizes and incomplete reporting of renal outcomes; however, additional unpublished or non-indexed local data may exist. In summary, dengue-associated AKI is a relevant complication of severe dengue, but the evidence available from Latin America remains limited. These findings highlight the need for improved renal surveillance and standardized reporting in dengue-endemic settings across Latin America.

Abstract: Background/Objectives: Penile rehabilitation (PR) techniques are claimed to counteract chronic degenerative processes of cavernous tissue such as penile hypoxia, neurovascular damage, and cavernous fibrosis. The objective of this umbrella review is to synthesize findings from existing meta-analyses to evaluate the efficacy of traditional and emerging PR strategies, providing an evidence-based roadmap for clinical management after surgery for prostate cancer. Methods: Conducted in accordance with PRIOR guidelines, a comprehensive literature search of PubMed, The Cochrane Library, and Scopus was performed through April 2026. The review included primarily systematic reviews and meta-analyses investigating pharmacological, physical, surgical, and regenerative interventions for post-prostatectomy erectile dysfunction (ED). Methodological quality was independently assessed using standardized tools. Results: PDE5 inhibitors (PDE5-is) significantly improve erectile function during active treatment, yet evidence supporting their role in promoting spontaneous, "unassisted" recovery remains limited. Vacuum erectile devices demonstrate high efficacy for assisted intercourse but show minimal impact on returning to baseline function compared to placebo. Penile prosthesis (PP) implantation maintains robust efficacy with exceptionally high satisfaction rates (83–85%), proving independent of prior pelvic surgery. Although early-phase trials suggest clinical potential for regenerative therapies like low-intensity extracorporeal shockwave therapy, platelet-rich plasma, and stem cell interventions, the evidence is currently undermined by substantial heterogeneity in study protocols and concerns regarding methodological quality. Conclusions: PR following radical prostatectomy remains a complex challenge characterized by poor evidence. While PDE5-Is are established first-line therapy for assisted function, PP remains the most reliable definitive treatment for refractory ED cases. Regenerative approaches show promise but remain investigational until standardized protocols and large-scale trials are established.

Abstract: Background and hypothesis. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) provide consistent cardiorenal benefits; however, tissue-level mechanisms remain insufficiently characterized. We investigated whether SGLT2i were associated with longitudinal remodeling of organ-specific adipose depots in patients with chronic kidney disease (CKD). Methods. In this observational study cohort (ADIPO-CKD; NCT07309094), adults with CKD stages 1–4 underwent clinical, biochemical and ultrasound imaging assessment at baseline (T0) and 8-month follow-up (T8). Thus, epicardial (EAT) and perirenal adipose tissue (PRAT) thickness were measured. Changes over time between patients under SGLT2i treatment and those without (Non-SGLT2i) were assessed using repeated-measures ANOVA and multivariable linear regression models adjusted for age, sex, baseline estimated glomerular filtration rate (eGFR), diabetes status, concomitant glucagon-like peptide 1 (GLP-1) receptor agonist therapy, body mass index (BMI) and visceral fat area (VFA) changes. Results. Among 189 CKD patients (50 SGLT2i and 139 non-SGLT2i), SGLT2i therapy was associated with significant reductions in PRAT (1.28±0.70 to 0.91±0.61 cm; ΔPRAT −0.37 cm; p<0.002) and EAT (0.57±0.27 to 0.36±0.14 cm; ΔEAT −0.21 cm; p<0.012), whereas no significant changes were observed in the Non-SGLT2i group. In multivariable models, SGLT2i exposure remained independently associated with ΔPRAT (β=0.447; 95% CI 0.211–0.682; p<0.001; R²=0.371) and ΔEAT (β=0.061; 95% CI 0.009–0.113; p<0.021; R²=0.053), including adjustment for changes in BMI and VFA. These findings were accompanied by trends toward improvement in renal function and systemic inflammation biomarkers in the SGLT2i group, although these changes did not reach statistical significance. In a secondary analysis, dapagliflozin was significantly associated with PRAT reduction, whereas a significant association was found between empagliflozin and EAT decrease. Conclusions. In CKD stages 1–4, SGLT2i use was independently associated with reductions in EAT and PRAT. These findings support a potential link between organ-specific adipose tissue and cardiorenal disease; however, given the observational design, these results should be interpreted as associative and hypothesis-generating. Dedicated mechanistic and adequately powered studies are warranted to determine their clinical relevance.

Abstract: Background: Neurogenic bladder in children is a major cause of progressive upper urinary tract deterioration and chronic kidney disease if not diagnosed and managed early. High intravesical pressure, recurrent urinary tract infections, and vesicoureteral reflux are key contributors to renal damage, particularly in resource-limited settings. This study aims to evaluate the clinical course of pediatric patients with neurogenic bladder in Sana’a city, Yemen. Patients and Methods: This multicentric cross-sectional descriptive study was conducted between January and December 2024 across multiple hospitals and specialized clinics in Sana’a city. Children aged 2–15 years with confirmed neurogenic bladder were included. Data collected comprised demographic characteristics, etiology, neurological and lower urinary tract manifestations, management strategies, history of urinary tract infections, renal function parameters, and imaging findings. Renal function was assessed using serum creatinine and estimated glomerular filtration rate, while radiological evaluation was based on ultrasound. Results: A total of 54 children were included, with a mean age of 8.60 ± 3.18 years; 53.7% were females. Myelomeningocele was the most common etiology (57.4%). All patients presented with lower urinary tract symptoms and recurrent urinary tract infections. Hydronephrosis was present in all patients, and vesicoureteral reflux was detected in 92.6%, predominantly bilateral. Renal impairment was universal, with 90% of patients diagnosed with chronic kidney disease and 5.6% requiring regular dialysis. Clean intermittent catheterization was underutilized, while indwelling catheterization and vesicostomy were frequently employed. Conclusion: Pediatric neurogenic bladder in Yemen is associated with a high burden of renal morbidity, largely due to delayed diagnosis and suboptimal early bladder management. Early detection, timely initiation of clean intermittent catheterization, and structured multidisciplinary follow-up are essential to preserve renal function and prevent progression to chronic kidney disease.

Abstract: Background/Objectives: Immunoglobin A nephropathy (IgAN) is a type of chronic kidney disease (CKD) and the most common cause of kidney failure in patients <40 years of age. Previous economic models in CKD have generally defined health states solely by the progression of CKD. This manuscript presents an alternative method which also considers the level of proteinuria in a CKD patient. Methods: A cohort-level state transition model was developed comparing the health benefits of sparsentan, a dual endothelin angiotensin receptor antagonist, to irbesartan, an angiotensin receptor blocker, in IgAN. Within four UP/C (proteinuria) states, patients are assigned to three sub-health states according to CKD stage. Patients with end-stage renal disease are grouped together irrespective of UP/C, and are stratified instead by renal replacement therapy modality. Transition matrices are derived from a combination of data from PROTECT, a clinical trial comparing sparsentan to irbesartan, and the UK RaDaR registry. Health-related quality of life data from a general CKD population is used as a proxy. Results: Patients with IgAN who were modelled to receive treatment with sparsentan had estimated total undiscounted life years of 25.5 years, a gain of 0.9 years in comparison with irbesartan. Patients were also more likely to spend more time in earlier CKD stages while pre-ESRD. This translated to significant quality adjusted life year gains for patients treated with sparsentan in comparison with irbesartan. Conclusions: This study presents a new structure for health economic models in IgAN that more comprehensively captures the effect of proteinuria in combination with CKD progression. This new approach ultimately allows for the more robust implementation of clinical trial data in IgAN and estimates of the cost-effectiveness of new treatments.

Abstract: Background and Aim: Liver disease in patients receiving chronic hemodialysis (HD) is frequently underrecognized and may contribute to adverse outcomes. Its evaluation is complicated by dialysis-related changes in volume status that can influence noninvasive measurements. We aimed to assess the prevalence and determinants of Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) and liver fibrosis using transient elastography (TE), with particular attention to metabolic, volume-related, and dialysis-specific factors, and to examine the effect of a single HD session on Controlled Attenuation Parameter (CAP) and liver stiffness measurement (LSM). Methods: In this prospective cross-sectional study, adult patients receiving maintenance HD for ≥3 months were enrolled. TE (FibroScan®) was performed immediately before (pre-HD) and after (post-HD) a midweek HD session. Steatosis was defined as CAP >257 dB/m and significant fibrosis as LSM ≥8 kPa. Volume status was assessed using interdialytic weight gain (IDWG) and ultrafiltration (UF) volume. Associations with clinical, biochemical, and dialysis-related variables were analyzed. Results: Forty patients were included (mean age, 63.5 ± 17.3 years; 70% male; 30% diabetic). MASLD prevalence was 25% pre-HD and 22.5% post-HD. The prevalence of significant fibrosis decreased from 17.5% pre-HD to 10% post-HD, while mean LSM did not change significantly, suggesting that volume removal may influence fibrosis classification in a subset of patients. CAP correlated positively with body mass index, IDWG, UF volume, and triglyceride levels, and inversely with serum albumin. Post-HD LSM showed a significant inverse association with serum albumin and positive associations with alanine aminotransferase, total cholesterol, and low-density lipoprotein cholesterol, whereas pre-HD LSM was mainly associated with age and bilirubin. The FIB-4 index did not correlate with LSM. Conclusions: In maintenance HD patients, hepatic steatosis is closely associated with metabolic burden and fluid overload, whereas fibrosis assessment is substantially influenced by nutritional status. Dialysis-related volume changes may modify LSM-based fibrosis estimates, supporting post-dialysis TE for more reliable assessment. TE provides clinically informative evaluation and appears superior to surrogate indices such as FIB-4 in this population.

Abstract: Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular ac-cumulation of glycosphingolipids in many tissues and fluids, including the kidney. We report a single family with Fabry disease that includes 7 patients carrying the path-ogenic variant c.797A>C in the GLA gene, with remarkable variability of kidney in-volvement, assessed based on the clinical, biological and histological data. The patients were monitored for a period of 2–9 years, and all of them received enzyme replacement therapy. This study provides valuable insights into kidney involvement evaluated through kidney biopsy, personalized management strategies for family members ac-cording with their phenotype, and long-term follow-up of the kidney function. We un-derscore the importance of molecular screening of the GLA gene in all family members for early identification of the disease and early initiation of specific treatment that can potentially prevent or delay the progression of the disease.

Abstract: Introduction: In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the ‘obesity paradox’ and the impact of body composition on inflammation. The aim of the study was to assess the relationship between body composition, traditional inflammatory markers, and the new NETosis indicators (neutrophil extracellular traps), as well as to determine their impact on 12-month mortality. Methods: The study included 99 patients with end-stage renal disease. Their body composition was assessed using bioelectrical impedance analysis (Seca mBCA 525). Blood serum was tested for inflammatory markers (hs-CRP, IL-6, TNF-α, IL-1B), NETosis markers (citrullinated histone H3, MPO, elastase), and nutritional status parameters (albumin, transferrin). Results: No correlation between BMI and inflammation was demonstrated. Higher contents of the adipose tissue, particularly visceral, were significantly associated with increased levels of IL-6 and hs-CRP, while muscle mass was negatively correlated with inflammation. The use of dialysis catheters stimulated NETosis (higher CH3 levels), which had a negative effect on albumin concentrations. Low albumin levels and high TNF-α levels were independent predictors of death. Conclusions: It is body composition, and not BMI, that determines the severity of inflammation. Visceral obesity promotes inflammation, while muscle mass has a protective effect. Dialysis catheters, by stimulating NETosis, contribute to a decrease in albumin levels and a poorer prognosis.

Abstract: Background: Urolithin A (UA) has therapeutic potential in diabetic kidney disease (DKD), but its molecular targets and mechanisms remain unclear. Methods: Transcriptomic and single-cell datasets were integrated with UA target prediction. Machine learning, ROC analysis, GSEA, immune infiltration, and pseudotime trajectory inference were applied to identify biomarkers and proximal convoluted tubule (PCT) subtypes. Findings were validated in db/db mice and high-glucose-exposed HK-2 cells. Results: Four UA-responsive biomarkers—HSPA1A, ESR2, NUAK1, and PLK1—demonstrated strong diagnostic performance (AUC > 0.7). GSEA implicated these biomarkers in ascorbate/aldarate and butanoate metabolism pathways, while immune profiling revealed elevated CD8+ T cells and reduced naive B cells in DKD. Single-cell analysis identified PCT as a key disease-relevant population comprising three functional subtypes. Pseudotime trajectory revealed PLK1 enrichment at early differentiation stages, whereas NUAK1 was enriched at late stages. In vivo and in vitro experiments confirmed that UA treatment significantly attenuated the aberrant upregulation of NUAK1 and PLK1 in db/db mouse kidneys and HG-exposed HK-2 cells, accompanied by restoration of renal architecture and improved metabolic parameters. Conclusions: UA exerts renoprotective effects in DKD by modulating stage-specific expression of NUAK1 and PLK1 along PCT differentiation, offering insights into its mechanism of action.

Abstract: Chronic kidney disease (CKD) is a common medical condition seen in North America, ranging between 10-12% of the general population, which has significant impact on health care costs and patient survival [1]. Sarcopenia is often seen in between 2.8% to 75% in the CKD population based on the method of measurement and definition chosen to report [2–8]. This qualitative review of the literature for sarcopenia in CKD will focus on the utility of the Psoas muscle measurement. Psoas muscle measurement is a surrogate method to quantify muscle mass and its advantages and disadvantages as a choice for utilization in the sarcopenia definition is explored with the different diagnostic frailty scores published. The role of different comorbidities within the CKD population is further explained in the context of muscle mass measurement and the associated clinical outcomes. The ability and relevance of longitudinal use of muscle mass assessments in the clinical context will be emphasized on clinical evaluation of the CKD patient and follow up nutritional and physical training requirement to rebuild and maintain muscle mass.

Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are traditionally considered acute and self-limited conditions. However, emerging evidence suggests that recurrent and persistent UTIs may contribute to chronic kidney disease (CKD) progression through complex interactions between uropathogens and host responses. This review examines the pathophysiological mechanisms linking UTIs caused by uropathogenic Escherichia coli, Klebsiella spp., and Enterococcus spp. to CKD development. Distinct pathogen-specific strategies, including intracellular persistence, biofilm formation, and chronic colonization, enable sustained infection and recurrent inflammatory insults. These processes activate key molecular pathways, including innate immune signalling, inflammasome activation, oxidative stress, and fibrotic remodelling. The convergence of these mechanisms leads to tubular injury, nephron loss, and a progressive decline in renal function. A comprehensive mechanistic model integrating pathogen-specific persistence strategies and host-mediated responses, including inflammation, inflammasome activation, oxidative stress, and fibrosis, is illustrated in Figure X, highlighting how recurrent and persistent UTIs may drive CKD progression. In addition, biomarkers reflecting inflammation (IL-6, CRP), tubular injury (NGAL, KIM-1), and fibrosis (TGF-β, fibronectin) provide a translational bridge between molecular mechanisms and clinical practice. Host factors such as diabetes, immune dysfunction, and microbiome alterations further modulate disease trajectory, while antibiotic resistance contributes to persistent infection and increased renal risk. These findings underscore the importance of early detection, pathogen-specific management, and biomarker-guided monitoring. Collectively, this review supports a paradigm shift recognizing UTIs not merely as acute infections but also as potential contributors to CKD progression, with important implications for prevention and therapeutic strategies.

Abstract: Background and Clinical Significance: Autosomal dominant tubulointerstitial kidney disease caused by mutation in uromodulin gene (ADTKD-UMOD) is a rare kidney disorder characterized by progressive tubulointerstitial damage and slowly progressive loss of renal function. ADTKD is often under-recognized in the clinical setting. In fact, diagnosis of ADTKD-UMOD can be challenging due to its nonspecific symptoms, being confirmed by genetic testing only. Case presentation: We report the case of a 42-years-old male patient referred for evaluation of renal dysfunction, incidentally discovered in routine laboratory checks. He had no significant medical history and no known familiarity for kidney disease or gout. Physical examination was unremarkable. Renal dysfunction was confirmed, with serum creatinine 1.44 mg/dl and eGFR 59.5 ml/min/1.73 m2. Urinalysis was within physiological limits, with proteinuria of 75 mg/day. Uric acid was mildly elevated (7.5 mg/dl) without gout history. Other laboratory findings including autoantibodies were in normal range. Patient underwent kidney biopsy, which however was not diagnostic showing mild focal tubular atrophy and interstitial fibrosis without glomeruli involvement. Immunofluorescence staining was negative for complement and immunoglobulins. Based on above nonspecific findings, the patient was suspected of a possible diagnosis of ADTKD. Genetic investigation using a clinical exome next-generation sequencing approach identified a novel heterozygous missense variant in the UMOD gene (c.409T>C; p.Cys137Arg). Patient is in regular clinical-laboratory monitoring. After one year, his overall health is good, renal function stable with no proteinuria, uric acid mildly increased without gout attacks. Conclusions: Increased clinical awareness is crucial for detecting ADTKD-UMOD. Genetic testing can help to solve clinical diagnostic challenges in patients with unexplained decreased kidney function.

Abstract: Oxidative stress (OS) is elevated in patients with end-stage kidney disease undergoing maintenance dialysis and contributes to increased cardiovascular risk. While kidney dysfunction and dialysis can generate OS, the acute effects of a single dialysis session remain unclear due to variability in study design and biomarkers used. In this observational study, blood samples from 68 hemodialysis patients were collected before and after a single session. Plasma levels of the reactive oxygen species marker superoxide (O2•⁻) and OS-damage markers lipid hydroperoxides (LOOH), protein-bound malondialdehyde (PrMDA), protein-bound thiobarbituric acid reactive substances (PrTBARS), and protein carbonyls (PrCO) were measured. LOOH increased significantly by 50% post-dialysis, whereas PrMDA and PrTBARS decreased modestly by ~10%. No significant changes were observed in O2•⁻ or PrCO. Dialysis vintage correlated positively with LOOH, PrMDA, and PrTBARS, but not with O2•⁻ or PrCO. Patients undergoing low-flux hemodialysis exhibited a greater post-dialysis increase in LOOH than those treated with high-flux hemodialysis. No significant associations were found between OS markers and comorbidities or medication. The post-dialysis rise in LOOH, an early-formed and least accumulating lipid peroxidation marker, highlights its sensitivity to acute dialysis-related oxidative changes. The rising tendency of PrMDA and PrTBARS with dialysis vintage suggests cumulative OS over time.

Abstract: Background/Objectives: To test the accuracy of two sound-based voided volume measurement applications compared to voided volume based on the measurement of pre- and post-void weight using a high-resolution scale. Methods: Seven male and four female volunteers participated. Male and female volunteers used the ProudP and Healthy Bladder-Voiding Diary mobile apps, respectively, to measure sound-based voided volume (SVV). The difference between pre- and post-void weight was calculated and converted to mL to be the true-voided volume (TVV) using a high-resolution scale. A Pearson correlation coefficient and paired t-test were completed. Results: Eighty-two voids were recorded (42M/40F). Median male participant age was 25.9 years. Male SVV ranged from 42-790 mL and TVV ranged from 61-880 mL. Mean difference was 39 mL (95% CI, 18-59 mL). SVV and TVV comparison revealed a strong correlation (r = 0.977, p < 0.0001). Equivalence testing indicated a p-value of 0.022. Median female participant age was 25.0 years. Female SVV ranged from 28-440 mL and TVV ranged from 10-682 mL. Mean difference was 53 mL (95% CI, 22-84 mL). Equivalence testing indicated a p-value of 0.330. SVV and TVV comparison revealed a correlation (r = 0.888, p < 0.0001). Conclusions: The male and female app have a strong correlation to true void volume (male > female app) and can be used by patients to track voided volume at home. The male app accurately measures voided volume within 60 mL from the TVV; however, the female app is less accurate.

Abstract: Because human prostate cancer (PCa) grows slowly, establishing PCa tumor models is often time-consuming and unpredictable, limiting the efficiency of preclinical theranostic development. To address this, we used a non-viral PiggyBac transposon system to introduce triple reporter genes into PSMA-expressing C4-2 cells, generating orthotopic and subcutaneous xenograft models that allow noninvasive, real-time monitoring of PCa progression and treatment response. Reporter-engineered C4-2 3R cells were produced by co-transfecting constructs encoding the reporter cassette and PB transposase, followed by enrichment using fluorescence microscopy and FACS, and implanted orthotopically or subcutaneously into mice. Tumor growth and response to a single 2 Gy X-ray dose followed by 14.8 MBq ¹⁷⁷Lu-PSMA-617, or to each monotherapy, were monitored weekly using IVIS imaging and confirmed by tumor dissection and H&E staining; PSMA expression was assessed by western blot and ¹⁸F-PSMA-1007 PET/CT. C4-2 3R cells successfully expressed mRFP, luc2, and HSV1-tk, generating detectable orthotopic bioluminescence within one week and persisting for at least five weeks, whereas subcutaneous implantation produced only transient luc2 signals with no tumor formation. X-ray exposure did not increase total PSMA levels but induced PSMA relocation to the cell membrane. Combined external beam radiotherapy (EBRT) and ¹⁷⁷Lu-PSMA-617 treatment produced the highest ¹⁸F-PSMA-1007 uptake and strongest tumor suppression, with minimal residual tumor mass compared to single-treatment or control groups. Overall, the C4-2 3R reporter model enables faster, reliable monitoring of slow-growing PCa tumors and provides an effective platform for evaluating PSMA-targeted therapies with or without the combination of EBRT.

Abstract: Background. Benign prostatic hyperplasia (BPH) is a common condition in aging men that causes urinary symptoms. Current treatments have limitations, necessitating new approaches. Single-cell RNA sequencing (scRNA-seq) provides detailed insights into cellular activity, while Artificial Intelligence (AI) techniques such as large language models (LLMs) can analyze complex queries to identify natural substances that may downregulate overexpressed genes, providing a novel approach for the treatment of BPH. Method. Single-cell RNA sequencing (scRNA-seq) data (GSE226237) were obtained from the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) repository. Gene expression profiles from three large prostates were compared with those from three small prostates to identify differentially expressed genes associated with larger prostate tissue. These genes were evaluated as potential therapeutic targets. Candidate natural compounds that may modulate the activity of overexpressed genes were generated using a structured prompt submitted to the large language model ChatGPT. Results. Single-cell RNA sequencing analysis comparing three large prostates with three small prostates identified distinct gene expression differences associated with prostate enlargement. Several genes involved in immune regulation and cellular structure were downregulated in large BPH, while genes related to epithelial integrity, protein synthesis, and proliferation such as SLC14A1, KRT5, KRT14, KRT15, PRAC1, CSTA, RPL36A, GABARAP, RPS17, and FXYD3 were upregulated. To explore potential therapeutic interventions, these overexpressed genes were analyzed using ChatGPT 5.4 to identify candidate natural compounds capable of modulating their activity. The resulting gene/compound associations include natural products such as resveratrol, curcumin, epigallocatechin gallate (EGCG), genistein, quercetin, sulforaphane, berberine, ashwagandha, and lycopene, highlighting promising directions for natural product based modulation of BPH-associated gene expression. Conclusions. These findings highlight molecular changes in BPH progression and show how single-cell transcriptomics reveals gene expression linked to epithelial proliferation, immune modulation, and metabolism. Integrating AI with omics data offers a framework for identifying potential natural therapeutics, though these AI-generated recommendations remain hypothesis-generating rather than definitive.

Abstract: Background and Objectives: Renal transplantation is the optimal treatment for end-stage renal disease, yet long-term allograft survival remains threatened by immune-mediated injury and chronic nephropathy. Conventional monitoring using serum creatinine and protocol biopsy suffers from limited sensitivity for early, subclinical injury. Liquid biopsy-based biomarkers offer a non-invasive alternative. Materials and Methods: We conducted a systematic narrative review of studies published between January 2010 and December 2024, identified through PubMed, Scopus, and Web of Science. Results: Extracellular vesicles carry injury-specific molecular cargo reflecting the biological state of tubular, glomerular, and endothelial cells; urinary EV CXCL9 protein and exosomal CD3ε mRNA have demonstrated AUC values of 0.81–0.88 for detection of T-cell-mediated rejection. Donor-derived cell-free DNA quantifies global graft cell death; the FDA-cleared AlloSure assay achieves AUC 0.74 and NPV 84% at the validated ≥1.0% threshold established in the DART trial. Donor-specific antibodies—particularly complement-fixing C1q-positive DSA—confer markedly inferior 5-year graft survival compared with DSA-negative recipients (54% versus 93%). Multi-biomarker panels integrating all three modalities yield AUC 0.88–0.94 and NPV 91–95%. Conclusions: The integration of EV, ddcfDNA, and DSA monitoring into a unified surveillance framework offers a clinically meaningful advance over creatinine-based monitoring. Prospective randomized trials confirming improvement in long-term allograft survival will be the critical next step.

Abstract: Background: An accurate D’Amico risk stratification is mandatory for prostate cancer (PCa) management. The purpose of this proof-of-concept study was to establish a methodological framework of integrating validated clinical nomograms with strict data-quality governance in order to generate reliable artificial neural networks (ANN), even when the sample is small. Methods: We performed a retrospective analysis of a curated cohort of 49 patients from one center. A multilayer perceptron (MLP) was trained using 11 variables, including the ISUP biopsy grade and Briganti nomogram. Model development was guided by a proactive data-quality protocol based on FAIR principles, with stringent checks for accuracy, consistency and validity to ensure data were “AI-ready”. A sensitivity analysis was conducted on three data partitioning scenarios (20/80, 34/66 and 39/61). Results: From a starting pool of 76 patients, the FAIR-based data governance architecture was applied to create a highly selected cohort of 49 patients. A multilayer perceptron (MLP) trained on this “AI-ready” dataset achieved a mathematically perfect but clinically uninterpretable discrimination (AUC 1.000) for High vs. Intermediate risk groups on a small internal test set (N=9 for the 20/80 split). However, this complete accuracy is a best-case scenario reflecting the high data quality, not proof of generalizable clinical utility, as the large confidence interval (66.4-100%) and the requirement to exclude instances with unusual attributes for model validation (as described in the methods) highlight. Conclusions: The main contribution of this proof-of-concept study is the effective illustration of a strict, repeatable data governance approach for producing “AI-ready” urological datasets. Although the MLP demonstrated a robust internal signal for risk discrimination, its flawless accuracy is an ideal, non-generalizable situation. The most important deliverable that needs external validation is the framework, not the model’s performance metrics.

Abstract: Multilocular intratesticular cysts are uncommon benign lesions. We report a case associated with testicular microlithiasis in an 85-year-old man presenting with painless enlargement of the left scrotum. Ultrasonography revealed a multilocular cystic lesion with a 3.0-cm main cyst and several adjacent smaller cysts showing posterior acoustic enhancement without mural irregularity or solid components. Bilateral microlithiasis and small epididymal cysts were also detected, and serum tumor markers were normal. The lesions remained stable during 36 months of follow-up. Recognition of the characteristic ultrasonographic features of benign intratesticular cysts is important to avoid unnecessary surgical intervention.