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Background: Abiraterone (Abi) is an androgen receptor signaling inhibitor that significantly improves patients’ life expectancy in metastatic prostate cancer (PCa). Despite its beneficial effects, many patients have baseline or acquired resistance against Abi. The aim of this study was to identify predictive serum biomarkers for Abi treatment. Methods: We performed a comparative proteome analysis on three Abi sensitive (LNCaPabl, LAPC4, DuCaP) and resistant (LNCaPabl-Abi, LAPC4-Abi, DuCaP-Abi) PCa cell lines using liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Two bioinformatic selection workflows were applied to select the most promising candidate serum markers. Serum levels of selected proteins were assessed in samples of 100 Abi-treated patients with metastatic castration-resistant disease (mCRPC) using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients. Results: Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering workflows four proteins (AMACR, KLK2, FSCN1 and CTAG1A) were selected for ELISA analyses. We found high baseline FSCN1 serum levels to be significantly associated with poor survival in Abi-treated mCRPC patients. Moreover, the multivariable analysis revealed that higher ECOG status (>1) and high baseline FSCN1 serum levels (>10.22 ng/ml by ROC cut-off) were independently associated with worse survival in Abi-treated patients (p< 0.001 and p= 0.021, respectively). In contrast, no association was found between serum FSCN1 concentrations and overall survival in Doc-treated patients. Conclusions: Our analysis identified baseline FSCN1 serum levels to be independently associated with poor survival of Abi-treated, but not Doc-treated mCRPC patients, suggesting a therapy specific prognostic value for FSCN1.

IMPORTANCE: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. OBJECTIVE: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)–based screening with systematic biopsy strategies. DATA SOURCES: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). STUDY SELECTION: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. DATA EXTRACTION: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. MAIN OUTCOMES AND MEASURES: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. DATA SYNTHESIS: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. RESULTS: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). CONCLUSION AND RELEVANCE: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

Introduction: Interstitial fibrosis and tubular atrophy are leading causes of renal allograft failure. Shear wave elastography could be a promising noninvasive method for providing information on the state of the kidney, with specific regard to fibrosis but currently available data in the literature are controversial. Our study aimed to analyze the correlation between shear wave elastography and various kidney dysfunction measures. Methods: This review was registered on PROSPERO (CRD42021283152). We systematically searched three major databases (MEDLINE, Embase, and CENTRAL) for articles concerning renal transplant recipients, shear wave elastography, fibrosis, and kidney dysfunction. Meta-analytical calculations for pooled Pearson and Spearman correlation coefficients (r) were interpreted with 95% confidence intervals (CIs). Heterogeneity was tested with Cochran’s Qtest. I2statistic and 95% CI were reported as a measurement of between-study heterogeneity. Study quality was assessed with the QUADAS2 tool. Results: In total, 16 studies were included in our meta-analysis. Results showed a moderate correlation between kidney stiffness and interstitial fibrosis and tubular atrophy, graded according to BANFF classification, on biopsy findings for pooled Pearson (r= 0.48; CI: 0.20, 0.69; I2= 84%) and Spearman correlations (r= 0.57; CI: 0.35, 0.72; I2= 74%). When compared to kidney dysfunction parameters, we found a moderate correlation between shear wave elastography and resistive index (r= 0.34 CI: 0.13, 0.51; I2= 67%) and between shear wave elastography and estimated Glomerular Filtration Rate (eGFR) (r= -0.65; CI: − 0.81, − 0.40; I2= 73%). All our outcomes had marked heterogeneity. Conclusion: Our results showed a moderate correlation between kidney stiffness measured by shear wave elastography and biopsy results. While noninvasive assessment of kidney fibrosis after transplantation is an important clinical goal, there is insufficient evidence to support the use of elastography over the performance of a kidney biopsy. Graphical abstract:

Soluble dietary fibers are known to reduce the levels of blood glucose and lipids in patients with type 2 diabetes mellitus (type 2 diabetes). Although several different dietary fiber supplements are utilized, to our knowledge, no previous study has ranked their efficacy yet.

Background: Endometriosis is a chronic condition affecting 6–10% of women of reproductive age, with endometriosis-related pain and infertility being the leading symptoms. Currently, the gold standard treatment approach to surgery is conventional laparoscopy (CL); however, the increasing availability of robot-assisted surgery is projected as a competitor of CL. This study aimed to compare the perioperative outcomes of robot-assisted laparoscopy (RAL) and CL in endometriosis surgery. Objectives: We aimed to compare the effectiveness and safety of these two procedures. Methods: A systematic search was conducted in three medical databases. Studies investigating different perioperative outcomes of endometriosis-related surgeries were included. Results are presented as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). Results: Our search yielded 2,014 records, of which 13 were eligible for data extraction. No significant differences were detected between the CL and RAL groups in terms of intraoperative complications (OR = 1.07, CI 0.43–2.63), postoperative complications (OR = 1.3, CI 0.73–2.32), number of conversions to open surgery (OR = 1.34, CI 0.76–2.37), length of hospital stays (MD = 0.12, CI 0.33–0.57), blood loss (MD = 16.73, CI 4.18–37.63) or number of rehospitalizations (OR = 0.95, CI 0.13–6.75). In terms of operative times (MD = 28.09 min, CI 11.59–44.59) and operating room times (MD = 51.39 min, CI 15.07–87.72;), the RAL technique remained inferior. Conclusion: RAL does not have statistically demonstrable advantages over CL in terms of perioperative outcomes for endometriosis-related surgery. Graphical abstract:

Background: Recent oncology guidelines recommend BRCA1/2testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS). Methods: As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations. Results: Our meta-analysis included 16 eligible studies with 348 BRCA1/2positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25–79%), 64% (CI: 43–80%) and 55% (CI: 36–73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26–0.83, p= 0.010) but no OS (HR: 1.41, CI: 0.82–2.42, p= 0.210) benefit for enzalutamide compared to abiraterone-treated patients. Conclusions: Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCApositive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.

Tachykinins (TKs) are involved in both the physiological regulation of urinary bladder functions and development of overactive bladder syndrome. The aim of the present study was to investigate the signal transduction pathways of TKs in the detrusor muscle to provide potential pharmacological targets for the treatment of bladder dysfunctions related to enhanced TK production. Contraction force, intracellular Ca2+concentration, and RhoA activity were measured in the mouse urinary bladder smooth muscle (UBSM). TKs and the NK2 receptor (NK2R)-specific agonist [β-Ala8]-NKA(4–10) evoked contraction, which was inhibited by the NKR2 antagonist MEN10376. In Gαq/11-deficient mice, [β-Ala8]-NKA(4–10)-induced contraction and the intracellular Ca2+concentration increase were abolished. Although Gq/11proteins are linked principally to phospholipase Cβ and inositol trisphosphate-mediated Ca2+release from intracellular stores, we found that phospholipase Cβ inhibition and sarcoplasmic reticulum Ca2+depletion failed to have any effect on contraction induced by [β-Ala8]-NKA(4–10). In contrast, lack of extracellular Ca2+or blockade of voltage-dependent Ca2+channels (VDCCs) suppressed contraction. Furthermore, [β-Ala8]-NKA(4–10) increased RhoA activity in the UBSM in a Gq/11-dependent manner and inhibition of Rho kinase with Y-27632 decreased contraction force, whereas the combination of Y-27632 with either VDCC blockade or depletion of extracellular Ca2+resulted in complete inhibition of [β-Ala8]-NKA(4–10)-induced contractions. In summary, our results indicate that NK2Rs are linked exclusively to Gq/11proteins in the UBSM and that the intracellular signaling involves the simultaneous activation of VDCC and the RhoA-Rho kinase pathway. These findings may help to identify potential therapeutic targets of bladder dysfunctions related to upregulation of TKs.

Platinum is a valid treatment option for BRCA-positive metastatic castration-resistant prostate cancer patients. Different poly (ADP-ribose) polymerase inhibitors are equally effective for progression-free and overall survival.

Acetylcholine plays an essential role in the regulation of detrusor muscle contractions and antimuscarinics are widely used in the management of overactive bladder syndrome. However, several adverse effects limit their application and patients' compliance. Thus, this study aims to further analyze the signal transduction of M2and M3receptors in murine urinary bladder to eventually find more specific therapeutic targets. Experiments were performed on adult, male, wild-type, M2-, M3-, M2/M3- or Gαq/11-knockout (KO) and pertussis toxin (PTX)-treated mice. Contraction force and RhoA activity were measured in the urinary bladder smooth muscle (UBSM). Our results indicate that carbamoylcholine (CCh)-induced contractions are associated with increased activity of RhoA and are reduced in the presence of the Rho-associated kinase (ROCK) inhibitor Y-27632 in UBSM. The CCh-evoked contractile responses and RhoA activation were markedly reduced in detrusor strips lacking either M2or M3 receptors and abolished in M2/M3-KO mice. Inhibiting Gαi-coupled signaling by PTX-treatment shifted the concentration-response curve of CCh to the right and diminished RhoA activation. CCh-induced contractile responses were markedly decreased in Gαq/11-KO mice, however, RhoA activation was unaffected. In conclusion, cholinergic detrusor contraction and RhoA activation are mediated by both M2and M3receptors. Furthermore, whereas both Gαiand Gαq/11proteins mediate UBSM contraction, the activation at the RhoA-ROCK pathway appears to be linked specifically to Gαi. These findings may aid the identification of more specific therapeutic targets for bladder dysfunctions.

Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.

The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.

Abstract: The aim of our study was to find the cause of urinary incontinence and voiding dysfunction in patients undergoing radical cystectomy and orthotopic bladder replacement with modified ileal neobladder (Reddy). Twenty-eight incontinent patients (operated on between 1988 and 2004) were involved in our examination. Based on the complaints of the patients, continence status was evaluated and divided into two groups: group I: partially incontinent (only night-time incontinence) n = 11 (39.3%) and group II: totally incontinent (night-time and daytime incontinence) n = 17 (60.7%). Detailed urodynamic examination (enterocystometry and urethral pressure profile) in addition to involuntary neobladder contractions and capacity detection were carried out on all patients. Furthermore resting pressure and maximal voluntary contraction ability of the sphincter were determined and statistically analyzed in both groups. Significant difference was noticed in resting pressure and maximal voluntary contraction ability of the sphincter among the partially incontinent and totally incontinent patients. Frequency, intensity and duration of involuntary neobladder contractions also showed significant differences between the two groups. Incontinence of neobladder depends not only on the destruction of resting and contraction capability of the urethral sphincter, but also on the presence or absence of involuntary contractions in the wall of the neobladder and decreased capacity of the neobladder.

Methods:Haemodynamic changes were measured noninvasively using impedance cardiography (ICG) in 30 ASA I children during laparoscopic varicocelectomy under general anaesthesia. After induction and intubation, mechanical ventilation was started, then pneumoperitoneum (PP) was created. During the course of anaesthesia, values of endtidal CO2pressue (PECO2), peak inspiratory airway pressure (PIP), heart rate (HR), mean arterial blood pressure (MABP), stroke volume index (SVI), cardiac index (CI) and systemic vascular resistance index (SVRI) were recorded at 1 min intervals. We analysed four periods: T1, before induction; T2, after induction; T3, during PP; T4, after desufflation of PP until awake.

We report a case of bilateral renal cell carcinoma in a horseshoe kidney. To the best of our knowledge this is the second reported case in the international literature. We performed different radiological examinations preoperatively to identify of blood supply, because correct preoperative location of vessels is mandatory.

We evaluated the clinical effectiveness of topical steroid application for balanitis xerotica obliterans in children and analyzed the association of any clinical response with histological findings.