Critical thinking and diagnostic reasoning when assessing problems with the genitourinary system

Urological conditions have become increasingly common and early diagnosis is key to achieving better outcomes. This article discusses the importance of having a comprehensive understanding of urological disorders, having the skills to interpret relevant information, and recognising the relationships among given elements to make an appropriate clinical diagnosis.

A prospective validation of nomograms based on BC-116 and BC-106 urine peptide biomarker panels for bladder cancer diagnostics and monitoring

Purpose: Non-invasive urine-based biomarkers for bladder cancer (BC) diagnosis and surveillance can potentially improve current diagnostic and monitoring protocols by guiding cystoscopy. Here, we aim to access the diagnostic performance of nomograms based on published biomarker panels for BC detection (BC-116) and monitoring of recurrence (BC-106) in combination with cytology, in two prospectively collected patient cohorts. Experimental Design: 602 recruited patients were screened for presence of BC, out of which 551 were found eligible for further analysis. For the primary setting, urine samples from 73 eligible patients were analyzed from those diagnosed with primary BC (n=27) and benign urological disorders (n=46). For the surveillance setting, 478 eligible patients were considered (83 BC recurrences; 395 negative for recurrence). Urine samples were analyzed with capillary electrophoresis coupled to mass spectrometry and the biomarker score was estimated via a support vector machine-based software. Results: Validation of the BC-116 biomarker panel resulted in 89% sensitivity and 67% specificity (AUCBC-116=0.82), similar to the published estimates. The nomogram based on cytology and BC-116 resulted in good (AUCNom116=0.85) but not significantly better performance than the BC-116 alone (P=0.5672). BC-106 biomarker panel showed 89% sensitivity and 32% specificity for surveillance, while improved performance was achieved when a nomogram including BC-106 and cytology was evaluated (AUCNom106=0.82), significantly outperforming both cytology (AUCcyt=0.72;P=0.0022) and BC-106 alone (AUCBC-106=0.67;P=0.0012). Conclusions: BC-116 biomarker panel is a useful test for detecting primary BC. BC-106 classifier integrated with cytology and showing >95% negative predictive value, might be useful for decreasing the number of cystoscopies during surveillance.

Initial Evaluation of Uroplakins UPIIIa and UPII in Selected Benign Urological Diseases

Background: Uroplakins (UPs) are glycoproteins that play a specific role in the structure and function of the urothelium. Disorders which affect the normal expression of UPs are associated with the pathogenesis of infections and neoplasms of the urinary tract, primary vesicoureteral reflux, hydronephrosis and renal dysfunction. The appearance of uroplakins in the urine and/or plasma may be of potential importance in the detection of urinary tract dysfunction. The aim of the present study was to investigate uroplakin IIIa (UPIIIa) and uroplakin II (UPII) expression in patients with selected urological diseases. Methods: Plasma and urine from patients with benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis were compared to healthy people without urological disorders. UPs concentrations were measured by the immunoenzymatic method. Results: In patients with BPH and UTI, concentrations of UPIIIa in urine and plasma, as well as UPII in urine, were statistically significantly higher than in the control groups. In the US group, only the plasma UPIIIa concentration differed significantly from the control. Conclusion: The conducted research shows that benign urological diseases may affect the state of the urothelium, as manifested by increased concentrations of both UPs in patients’ urine and plasma, especially in BPH and UTI.

The Therapeutic Potential of Saw Palmetto Extract in Urological Disorders

Saw palmetto extract (SPE) has been widely used as a therapeutic remedy for urinary dysfunction in western countries. Furthermore, as an herb drug, it can be used as an alternative therapy for benign prostatic hyperplasia (BPH) due to its safety and minimum adverse effects. Reportedly, SPE improves the urinary symptoms, which mainly depend on anti-androgenic effects and effects on autonomic receptors in the lower urinary tract. However, the mechanisms of action responsible for the therapeutic roles of SPE have not been fully elucidated. Relevant studies indicate that SPE has some positive effects on the treatment of urological diseases in animals, and clinical trials are ongoing. In this review, we summarize the pharmacological properties and discuss the possible therapeutic mechanisms of SPE in urological diseases, including anti-androgenic effects, effects on autonomic receptors in the lower urinary tract, anti-inflammatory activity, anti-proliferative and pro-apoptotic effects, and highlight a potential therapeutic approach in the clinical treatment of patients with BPH, prostate cancer, chronic prostatitis (CP) and erectile dysfunction (ED).

Initial Evaluation of Uroplakins UPIIIa and UPII in Selected Benign Urological Diseases

BackgroundUroplakins (UPs) are glycoproteins that play a specific role in the structure and function of the urothelium. Disorders of normal expression of uroplakins are associated with the pathogenesis of infections and neoplasms of the urinary tract, primary vesicoureteral reflux, hydronephrosis and renal dysfunction. The appearance of uroplakins in the urine and/or plasma may be of potential importance in the detection of urinary tract dysfunction. The aim of the study was to investigate uroplakin IIIa (UPIIIa) and uroplakin II (UPII) expression in patients with selected urological diseases. Plasma and urine from patients with benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis, were compared to healthy people without urological disorders. MethodsA total 152 of human urine and plasma samples from normal and patients with selected benign urological diseases were analyzed. UPs concentration was measured by immunoenzymatic method. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.).ResultsIn patients with BPH and UTI, UPIIIa in urine and plasma also UPII in urine concentrations were statistically significantly higher than in the control groups. In the US group, only the plasma UPIIIa concentration differed significantly from the control. There were no significant differences between the concentrations of UPs compared to the controls in both the urine and plasma of patients with urolithiasis. ConclusionThe conducted research shows that benign urological diseases may affect the state of the urothelium, as manifested by an increased concentration of both UPs in patients’ urine and plasma, especially in BPH and UTI.

Genetic Prioritization, Therapeutic Repositioning and Cross-Disease Comparisons Reveal Inflammatory Targets Tractable for Kidney Stone Disease

BackgroundFormation of kidney stones resulting in urological disorders remains a major cause of morbidity in renal diseases and many others. Innate immunity, mainly inflammasome, has demonstrated a key role in the development of kidney stone disease (or “nephrolithiasis”), but a molecular rationale for therapeutic intervention targeting immunity is far from clear. We reason that identifying inflammatory gene networks underlying disease risk would inform immunotherapeutic targets for candidate drug discovery.ResultsWe generated an atlas of genetic target prioritization, with the top targets highly enriched for genes involved in the NF-kB regulation, including interaction neighbors of inflammasome genes. We identified a network of highly ranked and interconnecting genes that are of functional relevance to nephrolithiasis and mediate crosstalk between inflammatory pathways. Crosstalk genes can be utilized for therapeutic repositioning, as highlighted by identification of ulixertinib and losmapimod that are both under clinical investigation as inhibitors of inflammatory mediators. Finally, we performed cross-disease comparisons and druggable pocket predictions, identifying inflammatory targets that are specific to and tractable for nephrolithiasis.ConclusionGenetic targets and candidate drugs, in silico identified in this study, provide the rich information of how to target innate immune pathways, with the potential of advancing immunotherapeutic strategies for nephrolithiasis.

Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01–5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.