OBJECTIVES:Conventional semen analysis often fails to detect hidden functional defects contributing to male infertility. Factors such as sperm DNA-integrity, oxidative stress, MMP, and acrosome integrity are critical for fertilization and early embryonic development. This study aimed to evaluate sperm function defects in normozoospermic infertile men and highlight limitations of routine semen parameters in infertility assessment. METHODS:Semen samples underwent standard semen analysis. Sperm DNA damage was assessed using Acridine Orange staining, acrosome integrity by FITC-PSA staining, and ROS levels along with MMP were measured using flow cytometry. Appropriate statistical analyses were performed to compare infertile men and fertile controls and determine correlations among functional parameters. RESULTS:Among clinically screened infertile patients, 23 % were normozoospermic according to WHO 2010 criteria. Sperm function parameters were evaluated in normozoospermic infertile men (n=45) and fertile controls (n=17). Infertile men exhibited significantly higher ROS levels and DNA damage (p<0.001), alongside reduced acrosome integrity and MMP (p<0.001) compared to controls. ROS showed a positive correlation with DNA damage and acrosome-reacted sperm, and a negative correlation with MMP. CONCLUSIONS:Functional sperm defects may underlie infertility in a substantial proportion of normozoospermic men. Incorporating sperm function tests as second-line investigations may improve diagnosis and management of unexplained male infertility.
Male infertility is a significant reproductive health concern, with genetic abnormalities such as chromosomal aberrations and Y-chromosome microdeletions contributing substantially to severe spermatogenic failure. This cross-sectional study evaluated the prevalence and spectrum of chromosomal abnormalities and Y-chromosome microdeletions in infertile males from Eastern Uttar Pradesh using conventional karyotyping and quantitative fluorescence polymerase chain reaction (QF-PCR). A total of 134 infertile males were enrolled. Semen analysis was performed according to the World Health Organization (WHO) 6th edition guidelines. Peripheral blood samples were subjected to karyotyping, followed by Y-chromosome microdeletion analysis using QF-PCR in individuals with normal karyotypes. Chromosomal abnormalities were identified in 23.1
Intravesical Bacillus Calmette-Guérin (BCG) is the standard adjuvant therapy for intermediate/high-risk non-muscle-invasive bladder cancer (NMIBC) but is limited by failure, toxicity, and global supply constraints. Sequential Intravesical gemcitabine–docetaxel (Gem/Doce) can offer a rational chemotherapy alternative. In this prospective randomized, parallel-arm interventional study comparing efficacy and safety of Gem/Doce versus BCG in BCG-naïve intermediate/high-risk NMIBC, patients aged 18–80 years with complete TURBT of primary localised bladder lesion(s) were included. Gem/Doce induction comprised weekly gemcitabine (1000 mg) and docetaxel (40 mg) Intravesical instillations for 6 weeks, with monthly maintenance per risk group. BCG induction (weekly 80 mg OncoBCG for 6 weeks) was followed by risk-based maintenance as per SWOG protocol. Outcomes (RFS, high-grade RFS, PFS, CSS, OS) were evaluated post-induction, and at 6 and 12 months. Adverse events were graded by CTCAE v5.0. 91 patients (Gem/Doce n = 43; BCG n = 48) were evaluated. At 6 and 12 months, RFS was 95.35
Urinary bladder cancer (UBC) is a leading cause of cancer-related morbidity and mortality worldwide, but current diagnostic methods are invasive and prone to false-negatives. This study aimed to evaluate the diagnostic and prognostic value of HMGB1 protein expression in urothelial carcinoma of the bladder using three distinct methods (serum ELISA, tissue IHC, and mRNA expression) via reverse transcription polymerase chain reaction (RT-PCR) and establishing their correlation. This single-center prospective observational study enrolled adults planned for transurethral resection of bladder tumor (TURBT) from March 2023 to April 2025 at Banaras Hindu University, India. The study enrolled 64 UBC patients and 21 control subject. For analysis, 5 ml of blood and cystoscopic guided tumor tissue were retrieved from UBC patients undergoing TURBT and normal bladder urothelium, and 5 mL blood was retrieved from noncancerous subjects (controls) undergoing cystoscopy for various reasons. Clinicopathologic features including tumor stage (T), grade, risk group, and imaging data also were analyzed with respect to their correlation with HMGB1 expression. Levels of HMGB1 were significantly elevated in the UBC patients compared with the control patients (serum ELISA [p < 0.001], mRNA [p = 0.002], IHC [p = 0.013]). Expression of HMGB1 correlated significantly with tumor stage (T) and grade, with higher levels observed in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Notably, HMGB1 expression was highest in very-high-risk NMIBC patients. However, correlations with age, sex, MRI-VIRADS score, tumor size, and number of growths were statistically insignificant. Elevated levels of HMGB1 correlated with advanced tumor stage, high grade, and MIBC, suggesting its utility in early detection and risk stratification, making it a non-invasive diagnostic and prognostic biomarker for UBC.
Background Urinary microRNAs (miRNAs) hold substantial promise as non-invasive biomarker candidates due to their molecular stability and tumor-selective expression signatures. This study integrates the high-throughput urinary miRNA landscape with clinical data to systematically identify robust, non-invasive biomarkers that facilitate the early diagnosis and better clinical management of urinary bladder cancer (UBC). Methods Urine-derived miRNA sequencing was performed on UBC patients and healthy controls to delineate the miRNA expression profile. Computational filtering further excluded precursor form of miRNA, prioritizing the mature miRNA. Quantitative RT-PCR targeting an independent, age-matched cohort (n = 48) corroborated with the diagnostic potential of candidate miRNAs, evaluated through receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses. Results and limitations Next-generation sequencing unveiled 865 annotated and 11 novel miRNAs, with UBC samples displaying greater miRNA diversity (708 known miRNAs) compared to relative controls (540). Among them, seven mature miRNAs were significantly dysregulated in UBC (p < 0.05), of which quantitative RT-PCR corroborated significant upregulation of miR-6724-5p, miR-1273 h-5p, miR-7704, miR-200-5p, and miR-10400-5p, with fold elevations of 1542.3, 1085.8, 1160.6, 2776.5, and 45.8, respectively (p < 0.01). Stage-stratified profiling underscored dynamic shifts in miRNA expression that correlated with tumor advancement. A three-miRNA panel (miR-6724-5p, miR-10400-5p, and miR-7704) exhibited superior diagnostic performance (AUC > 70%, sensitivity > 90%). However, this study was constrained to a single institute with a small sample size and a short follow-up period, which precluded the correlation between the identified biomarker miRNAs with cancer recurrence and patient survival. Conclusion In this preliminary, single-centre study, mature urinary miRNAs demonstrated reproducible, stage-specific dysregulation in UBC. A combinatorial panel offered potential for a highly sensitive, specific, and non-invasive detection method. These findings propel further multicentre studies to validate the observed signatures, supporting their potential towards future clinical application.
1 Abstract Background Prostate cancer (PCa) diagnosis remains challenged by the limited specificity of prostate-specific antigen (PSA) testing, which cannot reliably distinguish malignancy from benign prostatic hyperplasia (BPH). MicroRNAs (miRNAs) are emerging candidates for liquid biopsy-based diagnostics, but most studies assess expression in isolation within a single compartment (biological source - Tissue, blood, serum, urine etc.), overlooking both compartment-specific behavior and the coordinated relationships among miRNAs. Methods We profiled four candidate miRNAs — miR-19b-3p, miR-21-5p, miR-101-3p and miR-375-3p, across four biological compartments (prostate tumor tissue, urine, serum, and blood) in 179 patients undergoing prostate biopsy for clinical suspicion of PCa (104 PCa, 75 BPH) using qRT-PCR. Urinary exosomal RNA was isolated with a commercial exosome isolation kit so from here onwards this compartment will be referred to as urine. Differential expression was quantified using Cohen’s d ; inter-miRNA coordination was assessed via Spearman correlation and differential correlation (Δ r ) analysis; and a compartment-level network rewiring score was derived as the sum of |Δ r | across miRNA pairs. Cross-compartment structural alignment was evaluated by comparing correlation patterns at the population level. Diagnostic models combining PSA, age, and urinary exosomal-miRNA features were evaluated using Logistic Regression, Elastic Net Logistic Regression and Naive Bayes classifiers under leave-one-out cross-validation (LOOCV). Results Effect sizes were largest and most consistent in urine, with miR-101-3p showing the strongest separation between PCa and BPH ( d = −1.01), followed by miR-21-5p ( d ≈ −0.72) and miR-19b-3p ( d ≈ −0.64). Two markers (miR-19b-3p, miR-375-3p) showed directional reversals across compartments, indicating that disease-associated signals are compartment-specific rather than uniformly conserved. In tumor tissue, PCa was associated with substantial reorganization of inter-miRNA coordination (network rewiring score = 2.46), including the emergence of a strong miR-21-5p–miR-375-3p co-regulatory axis (Δ r = +0.87) and decoupling of the miR-21-5p–miR-19b-3p relationship (Δ r = −0.64). Urine showed a structurally distinct coordination pattern (rewiring score = 1.77), dominated by a miR-101-3p–miR-19b-3p axis (Δ r = +0.56) absent from tissue; cross-compartment comparison showed concordance in only 1 of 6 miRNA pairs, indicating that urine’s architecture is largely independent of tissue’s. For diagnostic translation, the conventional PSA cutoff (4 ng/mL) achieved 100% sensitivity but only 23.5% specificity. In urine, miR-101-3p performs better than other miRNAs, with AUC of 0.71 (95% CI: 0.56–0.85). Adding PSA and age to the urinary miR-101-3p further improved discrimination to an AUC of 0.91 (95% CI: 0.82–0.99), with 70.5% specificity at 92.8% sensitivity; this pattern was consistent across Elastic Net and Logistic Regression classifiers. Expanding the model to include all urinary miRNAs, age, and pair-derived coordination features did not improve on this result (AUC = 0.88), indicating that population-level coordination changes did not translate into additional individual-level diagnostic value in this cohort. Conclusions miRNA signals in extracellular compartments do not represent direct surrogates of tumor-level molecular architecture; each compartment harbors a distinct, transformed coordination structure reflecting its biological context. While these coordination-level changes are mechanistically informative, the most direct translational gain in this study came from a parsimonious model combining PSA, age with a single urinary marker, miR-101-3p, which improved AUC from 0.71 to 0.91, with specificity 70.5% at 90% sensitivity criteria. This combination represents a promising, interpretable candidate for reducing unnecessary prostate biopsies, pending validation in larger, independent cohorts.
AIMS AND OBJECTIVES:To evaluate storage safety parameters and patient-reported bladder/bowel outcomes in adults with incomplete SCI using urodynamics and validated PROMs. MATERIALS AND METHODS:Consecutive adults with incomplete SCI (AIS B-E) underwent NBSS, SF-Qualiveen, NBD, SCIM-III, and urodynamics (capacity, compliance in mL/cmH2O, Qmax, pdet@Qmax, PVR; DSD when available). Poor compliance was prespecified as <20 mL/cmH2O. Analyses were stratified by level and management; safety proportions used measured denominators. Categorical outcomes were compared with χ2; continuous outcomes across ⩾3 groups with Kruskal-Wallis; secondary pairwise tests used Mann-Whitney with Benjamini-Hochberg FDR correction. RESULTS:N = 84; median age 35.5 years. PVR ⩾ 100 mL occurred in 71.4% and differed by neurological level (χ2(3) = 20.77, p = 0.00012). Poor compliance < 20 mL/cmH2O occurred in 26.2% overall and clustered in sacral injuries (72.7%) versus cervical 7.1%, thoracic 10.7%, lumbar 10.0% (χ2(3) = 33.46, p = 2.6 × 10⁻7). Severe NBD (⩾14) differed by management (χ2(3) = 14.92, p = 0.0019). NBSS totals differed by management (H = 52.86, p = 1.96 × 10⁻11), while SF-Qualiveen showed a borderline trend (H = 7.45, p ≈ 0.059). In a complete-case logistic model (outcome low compliance; predictors level, age, sex; reference thoracic), sacral level remained independently associated with poor compliance. CONCLUSIONS:Elevated residual urine and impaired bladder compliance remained common despite neurological sparing. Patient-reported burden varied across bladder-management categories, while sacral lesions demonstrated a disproportionate burden of poor compliance. Combined urodynamic assessment and validated PROMs may help identify patients at risk for unsafe storage and significant symptom burden.
Bladder cancer (BCa) diagnosis typically relies on invasive cystoscopy, which is effective but costly and uncomfortable. Urinary microRNAs (miRNAs), especially exosomal ones, are promising non-invasive biomarkers due to their stability in biological fluids and disease specificity. The let-7c cluster, owing to its tumor-suppressive function and frequent dysregulation in BCa, has emerged as a promising candidate for diagnostic evaluation. This study assessed the diagnostic potential of the urinary exosomal let-7c cluster through Machine Learning (ML)-integrated miRNA profiling, offering early proof-of-concept for its role in BCa classification. Urine samples were collected from 66 participants, including 50 BCa patients and 16 healthy controls (HC). Exosomal miRNAs were isolated and quantified using Quantitative Real-Time-Polymerase-Chain-Reaction (qRT-PCR). Statistical analysis and hypothesis tests were conducted to explore the nature and diagnostic relevance of individual biomarkers. A logistic regression classifier was applied to evaluate both the combined and differential diagnostic capabilities of the selected biomarkers. Accuracy, precision, recall and AU-ROC scores were used to assess model performance. Bioinformatics analysis was performed to identify pathways associated with the features prioritized by the ML models, ensuring their relevance to BCa. Statistically significant differentiation was observed between BCa patients and HC, with miR-99a-5p (p = 0.013, AU-ROC = 0.71) demonstrating preliminary diagnostic performance. In contrast, let-7c-5p (AU-ROC = 0.65, p > 0.1) and miR-125b-5p (p = 0.087, AU-ROC = 0.64) exhibited non-significant trends, showing weaker discrimination. The logistic regression ML model achieved 80.0
Renal cell carcinoma (RCC) is the most common type of kidney cancer and significant patient population experiences relapse and metastasis, resulting in poor survival outcomes. Therefore, there is a need to identify novel biomarkers and therapeutic targets to monitor RCC progression and improve patient outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression and have been implicated in tumor progression. We analysed publicly available datasets to identify differentially expressed miRNAs and their putative targets were identified using miRDB and Starbase ENCORI database. Further, We analysed the expression levels of identified miRNAs and their selected target mRNAs by qRT-PCR. Diagnostic potential of miRNAs were analysed by ROC analysis. Cox regression analysis were performed with target mRNAs to evaluate the potential prognostic utility and their association with clinical outcomes in ccRCC patients. hsa-miR-200b-3p, hsa-miR-320a-3p were downregulated and hsa-miR-34c-5p was upregulated in ccRCC patients. The target genes of identified miRNAs are critical regulators of the OXPHOS, cell death, and inflammatory pathways, involved in the progression of ccRCC. hsa-miR-200b-3p has an AUC of 0.7273 (p < 0.05; cutoff 3.870, LR+ 4.77). Univariable and multivariable cox regression analysis showed low expression of NDUFS1 independently associated with poor survival outcome (p < 0.001) in ccRCC patients. Our study demonstrated, downregulation of hsa-miR-200b-3p in ccRCC holds promise as a potential diagnostic biomarker and its identified target NDUFS1 as an independent prognostic biomarker for patients with ccRCC. These findings need to be validated in a large cohort of patients with RCC.
INTRODUCTION:Pediatric urolithiasis is increasing globally, with metabolic and environmental factors contributing to recurrence despite advances in minimally invasive surgery. Percutaneous nephrolithotomy (PCNL) is now the preferred treatment for large or complex stones in children, yet long-term data on metabolic predictors of recurrence remain limited. OBJECTIVE:This study aims to evaluate the safety, efficacy, and recurrence predictors following PCNL in pediatric patients at a tertiary center in northern India. STUDY DESIGN:A retrospective analysis was conducted on 27 children (≤14 years) who underwent PCNL between January 2021 and May 2023. Preoperative demographic, biochemical, and radiological parameters were recorded. Stone burden was assessed using CT urography or NCCT (non-contrast computed tomography) and graded by Guy's Stone Score (GSS). Standard or mini-PCNL techniques were selected based on stone characteristics. Postoperative biochemical changes, stone composition, outcomes, and recurrence over two years were evaluated. RESULTS:The mean age was 8.8 ± 3.4 years (range 1-14), with a male-to-female ratio of 1.7:1. GSS Grade 2 stones predominated (59.3%), with a mean size of 1.9 ± 0.6 cm. Complete clearance was achieved in all patients, with a mean hospital stay of 3 ± 1 days. Hemoglobin decreased by 0.81 g/dL (p = 0.016), while creatinine remained unchanged. No major complications occurred; minor Clavien-Dindo I-II events were seen in 44.4%. Calcium oxalate stones accounted for 66.7%. At a mean follow-up of 37.5 months, recurrence occurred in 22.2%, mainly in children with acidic urine and low specific gravity. Multivariate analysis revealed no independent predictors, although urine pH and specific gravity showed predictive trends. CONCLUSION:PCNL demonstrated favorable stone clearance with acceptable morbidity in this cohort. Recurrence appeared to be influenced by hydration and metabolic factors, although conclusions are exploratory due to the small sample size.
Urethral stricture remains a frequently encountered urological condition, with urethroplasty often regarded as the standard approach for complex or recurrent cases. However, in specific scenarios, intraoperative assessment may reveal less severe pathology, allowing for a more conservative and less invasive management strategy. This case series describes male patients who were scheduled for urethroplasty but were ultimately treated successfully with periurethral mobilization, adhesiolysis, and catheterization alone. Four male patients, aged between 19 and 51 years (mean age 31 years), presented with lower urinary tract symptoms, including weak urinary stream, straining, incomplete emptying, and acute urinary retention. Preoperative imaging with retrograde urethrogram and micturating cystourethrogram suggested bulbar urethral strictures with stricture length ranging from 0.5 to 2cm (mean 1.5 cm), and all patients were planned for urethroplasty. Initial maximum urinary flow rates (Qmax) ranged from 2 to 6 mL/second, with a mean of 3.75 mL/second, while post-void residual (PVR) urine volumes ranged from 200 to 320 mL, with a mean of 237.5 mL. Intraoperatively, after mobilizing the urethra, dense periurethral adhesions were observed without significant intraluminal narrowing. Gentle insertion of a 16 Fr Foley catheter was successful in each case, leading to the decision to avoid urethroplasty. All patients were managed with adhesiolysis and catheter drainage. Postoperative follow-up demonstrated marked improvement in symptoms, with Qmax ranging from 24 to 27 mL/second, with a mean of 25.25 mL/second, and PVR volumes decreasing to 10 to 15 mL, with a mean of 12.75 mL. This series highlights the importance of intraoperative re-evaluation in patients with suspected urethral stricture. Careful mobilization and catheter testing can help identify those who can be effectively managed without urethroplasty, thereby minimizing surgical morbidity. Incorporating and reinforcing this step into operative planning can support more individualized and less invasive treatment strategies.
Introduction:Constipation has long been recognized to be associated with lower urinary tract symptoms (LUTS). However, there is little clinical data on bowel symptoms in young men who present with LUTS. This study analyses the association of stool consistency with severe LUTS in young men. Methods:This study is a secondary analysis of SciCOM 3 study examining young men presenting with LUTS. Stool consistency was recorded by the Bristol Stool Chart and classified into hard stools (Class 1, 2), normal stools (Class 3, 4), and loose stools (Class 5-7). LUTS, sexual dysfunction, bladder pain, non-bladder myofascial pain, perception of problems related to the bladder, and general well-being were captured by questionnaires along with basic clinical data. The poorest score on every question of each questionnaire was categorized as "severe". Results:Four hundred and forty-eight young men (18-40 years; median 30 years, interquartile range 25-35 years) were studied across 16 centers. Stool consistency was hard, normal, and loose in 105 (23.4%), 284 (63.4%), and 59 (13.2%), respectively. Constipation was not associated with severe LUTS. Loose stools showed an association with six of the 13 questions on the International Consultation on Incontinence Questionnaire for male LUTS. Erectile dysfunction, bladder and nonbladder pain, and general well-being were found to be associated with loose stools but not with constipation. On multinomial logistic regression analysis, recurrent urinary tract infection and low body mass index were associated with hard stools, while low maximum flow rate, severe erectile dysfunction, and severe myofascial pain were associated with loose stools. Conclusions:Loose stools are an important association in young men presenting with severe LUTS.
INTRODUCTION:The laparoscopic (lap) technique is well-established for the repair of vesicovaginal fistula (VVF). However, its main limitation is a lack of expertise in intracorporeal suturing. This retrospective study presents a lap VVF repair using Kumar's knotless technique with V-Loc™ (Medtronic, MN, USA) barbed suture and compares its results with the open VVF repair technique. METHODS:In this retrospective study, we included 14 consecutive patients receiving VVF repair operated on by open conventional repair (open group) or lap knotless techniques (lap group) between March 2020 and March 2024. The data were recorded retrospectively. RESULTS:Comparative analysis between the lap (n = 8) and open (n = 6) groups demonstrated that lap repair significantly reduced intraoperative blood loss (48.75 ± 15.00 mL vs. 108.33 ± 28.71 mL, respectively, p< 0.001), drain duration (3.13 ± 0.35 days vs. 7.17 ± 0.41 days, respectively, p< 0.001), postoperative pain (3.13 ± 1.55 vs. 6.17 ± 1.47, respectively, p < 0.01), and hospital stay (3.38 ± 0.74 days vs. 7.83 ± 0.98 days, respectively, p< 0.001). No significant differences were found between the lap and open groups in terms of mean age (33.25 ± 5.76 vs. 37.33 ± 5.77, respectively, p = 0.103), fistula size (1.56 ± 0.80 cm vs. 1.58 ± 0.37 cm, respectively, p = 0.938), or timing of bowel function return (15.25 ± 2.33 vs. 16.83 ± 3.71, respectively, p = 0.193). These results suggest that lap repair improves recovery outcomes without compromising clinical efficacy. CONCLUSION:Lap VVF repair using Kumar's knotless technique with V-Loc™ barbed suture represents a feasible and safe approach to managing VVF. The technique offers a viable alternative to traditional methods, particularly in settings with limited experience with lap intracorporeal suturing and access to robotic surgery.
Introduction:This study analyzes clinical associations of pain in young men presenting with a primary complaint of a lower urinary tract symptom (LUTS). Methods:A secondary analysis of the SciCOM 3 study examining young men presenting with LUTS was performed. Bladder pain was recorded by Q4 of the Interstitial Cystitis Symptom Score, while nonbladder pain was captured by the Visual Analog Scale. LUTS, sexual dysfunction, stool consistency, perception of problems related to the bladder, and general well-being were captured by questionnaires. Results:A total of 448 young men (18-40 years; median 30 years, interquartile range: 25-35 years) were studied across 16 centers. Eighty-seven (19.8%) reported no pain (Group 1), 143 (32.6%) bladder pain alone (Group 2), 39 (8.9%) only nonbladder pain (Group 3), and 170 (38.7%) both bladder and nonbladder pain (Group 4). Men in Group 4 were more likely to report reduced strength of stream (odds ratio [OR] 1.95; 95% confidence interval [CI]: 1.27 and 3.01), need to stop and start (OR 1.81; 95% CI: 1.19 and 2.74), sense of incomplete evacuation (OR: 2.64; 95% CI: 1.58 and 4.40), and urgency (OR: 1.73; 95% CI: 1.16 and 2.59), while men in Group 2 were more likely to report urine leak for no apparent reason (OR: 1.85; 95% CI: 1.17 and 2.90). Group 1 was the least likely to report an abnormal sense of well-being. Conclusions:Pain is commonly reported by young men presenting with LUTS. The pattern of pain in LUTS is associated with a distinct clinical epidemiology, including both storage and voiding LUTS, with an impact on bother and quality of life. It is important to assess pain in young men presenting with LUTS.
MicroRNAs, small noncoding RNA molecules, are critical in modulating gene expression and contribute substantially to the initiation and progression of urinary bladder cancer (UBCa), a major malignancy affecting people globally. UBCa is known for its high recurrence rates and significant heterogeneity. The stability of miRNAs in body fluids such as urine and blood are excellent potential noninvasive markers for early detection, monitoring treatment progress, and predicting outcomes of patients with UBCa. In addition, miRNAs could also improve the effectiveness of immunotherapy and support the development of personalized treatment strategies. Despite their significant potential, challenges such as variability in the expression of miRNAs and shortcomings in their delivery systems must be carefully addressed. This strength, weakness, opportunity, and threat (SWOT) analysis highlights the crucial role of miRNAs in UBCa and explores their potential in advancing precision oncology.
Unstructured miRNAs represent a transformative advancement in both research and clinical management of urinary bladder cancer (UBC), emerging as clinically significant molecular targets with the potential to revolutionize existing diagnostic standards. This study exploited the robust stability of miRNAs and profiled urinary miRNAs in UBC patients and controls through miRNA sequencing, revealing an expanded and altered miRNA repertoire in cancer samples. Validation in an independent cohort revealed fold changes for miR-6724-5p, miR-1273h-5p, miR-7704, miR-200-5p, and miR-10400-5p ranged from ∼46 to ∼2,777 (p < 0.01). Stage-specific analyses highlighted dynamic miRNA expression linked to tumor progression. Diagnostic evaluation identified an optimal three-miRNA panel comprising miR-6724-5p, miR-10400-5p, and miR-7704, achieving diagnostic accuracies (AUC > 70%) and high sensitivity (>90%). These data demonstrate the potential of urinary mature miRNAs as robust biomarkers for non-invasive detection and monitoring of UBC in early stages, supporting their translation into clinical diagnostic assays pending larger prospective studies. Background Urinary microRNAs (miRNAs) are promising candidates due to their molecular stability and disease-specific expression. miRNAs represent a transformative advancement in both research and clinical management of urinary bladder cancer (UBC), emerging as actionable molecular targets with the potential to revolutionize existing diagnostic standards. Methods Small RNA sequencing was performed on urine samples from UBC patients and healthy controls to profile miRNA expression. Mature miRNAs were prioritized by exclusion of precursor forms using computational filtering. Validation by quantitative RT-PCR was conducted on an independent, age-matched cohort (n = 45). Diagnostic potential of candidate miRNAs was assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses. Results Sequencing identified 865 known and 11 novel miRNAs, with UBC samples showing greater miRNA diversity (708 known miRNAs) compared to controls (540). Ten miRNAs were significantly dysregulated in UBC (p < 0.05). Validation revealed fold changes for miR-6724-5p, miR-1273h-5p, miR-7704, miR-200-5p, and miR-10400-5p ranged from ∼46 to ∼2,777 (p < 0.01). Stage-specific analyses highlighted dynamic miRNA expression linked to tumor progression. A three-miRNA panel (miR-6724-5p, miR-10400-5p, miR-7704) demonstrated superior diagnostic performance (AUC > 70%, sensitivity > 90%). Conclusion Mature urinary miRNAs exhibit reproducible, stage-specific dysregulation in UBC and a combinatorial panel offers sensitive, specific non-invasive detection. These findings warrant further multicenter validation for clinical application. ### Competing Interest Statement The authors have declared no competing interest. Department of Biotechnology, https://ror.org/03tjsyq23 University Grants Commission, https://ror.org/04p800546
Aims: The plaque excision and grating technique is indicated for correcting penile curvature in Peyronie’s disease. We assessed our experience of the modified split graft technique using bovine pericardium after plaque excision. Materials and Methods: Between March 2020 and September 2024, we operated on 12 patients by the excision of plaque and split grafting technique. Here, we discuss our experience customizing a bovine pericardium graft on a table according to the size of the defect and joining pieces of graft and tunica albuginea with a Polydioxanone (PDS) suture to cover the cavernosal defect. Results: Patients’ mean age and follow-up were 48 years and 30 months, respectively. The average size of the plaque and penile curvature was 4.6 cm (range 1.5–8 cm) and 45°, respectively. No residual penile curvature was observed in 83.5% of patients while (16.5%) had curvature of <20°. All patients experienced an improvement in stretched penile length with an average increase of 1.6 cm. Seventy-five percent of patients were able to perform sexual activity without assistance after 3 months. One patient, who had a sizeable cavernosal defect of 8 cm × 2 cm, experienced severe postoperative erectile dysfunction (ED) along with residual penile curvature of 15° and required semi-rigid penile prosthesis. Two patients having mild ED was managed by Tadalafil 10 mg. Another patient with residual chordee of <20° was managed on conservative therapy. Conclusions: In our limited experience, this modified split graft technique using bovine pericardium after plaque excision seems feasible, cost-effective, and safe. It has comparable outcomes to the standard methods reported in the literature and reduces graft material wastage. Further, long-term randomized trials are needed to validate its long-term efficacy and safety compared to conventional grafting approaches.
Introduction:Secondary hydronephrosis is an uncommon but potentially serious complication of lower urinary tract dysfunction. This study examines clinical associations of young men with lower urinary tract symptoms (LUTS) presenting with hydronephrosis. Methods:Secondary analysis of multicentric study examining young men presenting with LUTS. LUTS, stool consistency, sexual dysfunction, bladder pain, nonbladder myofascial pain, perception of problems related to the bladder, and general well-being were captured by questionnaires along with basic clinical data. Hydronephrosis was presumed to be secondary to lower urinary tract dysfunction if there was ureteric dilatation, it was asymptomatic, and there was no other reason based on clinical judgment. Results:Hydronephrosis was noted in 26/442 men (5.9%). Men with hydronephrosis had lower body mass index (BMI), longer duration of symptoms, larger postvoid residual (PVR), and were more likely to be diabetic and/or have a history of urinary infection (all P < 0.05). Association was noted with need to strain, reduced strength of stream, sense of incomplete evacuation, urgency, and urgency incontinence (all P < 0.05). On multivariate logistic regression analysis, BMI (P = 0.007) and PVR (P = 0.010) were independently associated. One-unit reduction in BMI was associated with 30% increase in odds of hydronephrosis, while 100 ml increase in PVR was associated with 82% increase. Receiver operator curve analysis yielded BMI ≤23 and PVR ≥80 ml as predictive of hydronephrosis. Conclusions:Secondary hydronephrosis is seen in a small number of young men with LUTS. Such men show a distinct clinical profile that can offer clinical clues useful in the algorithm for evaluation.