Łukasz Zapała

Background: Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults and is frequently associated with lower urinary tract symptoms (LUTS). Sacral neuromodulation (SNM) has recently emerged as a promising treatment for neurogenic urinary and bowel disorders; however, its application in patients with MS remains underexplored. Case presentation: We report the case of a 46-year-old male with primary progressive MS who presented with severe LUTS, including urgency, urgency urinary incontinence, hesitancy, and urinary retention. These symptoms were attributed to neurogenic lower urinary tract dysfunction with detrusor underactivity during the voiding phase and low-pressure detrusor overactivity during the filling phase. After conventional treatments proved insufficient, the patient underwent a two-stage implantation of an InterStim II SNM device. Although initial complications occurred, including device erosion, subsequent reimplantation with an InterStim X device resulted in substantial symptom improvement, safe removal of the suprapubic catheter, and restoration of spontaneous voiding. Conclusions: This case highlights the potential role of SNM in alleviating LUTS associated with detrusor underactivity in patients with MS. The findings underscore the importance of careful patient selection, multidisciplinary management, and further research into long-term outcomes and strategies for mitigating complications. These observations add to the growing body of evidence suggesting that SNM may represent a therapeutic option for selected patients with neurogenic lower urinary tract dysfunction due to MS when conventional therapies fail.

The purpose of our study was to assess if spinacetin (SPC), a flavonoid found in spinach, can alleviate the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters indicative of the development of hemorrhagic cystitis. The animal experiments were conducted in female Wistar rats. The cohort of 60 animals was grouped as follows: I—control, II—CYP group, III—SPC group, and IV—CYP + SPC group. The cystometry and biochemical analyses were performed after a fortnight of SPC administration. SPC was found to restore normal cystometric parameters in CYP-induced cystitis and, similarly, it normalized c-Fos expression changes in the central micturition regions. SPC further prevented a massive increase in the bladder wall thickness/permeability due to exposition to CYP administration. CYP instillation resulted in the elevation of biomarkers found in urine (brain-derived neurotrophic factor, BDNF, and nerve growth factor, NGF), and in the bladder detrusor muscle (Rho kinase and vesicular acetylcholine transporter, VAChT), which were successfully restored after administration of SPC. As for the biomarkers in the bladder urothelium, the CYP-induced increases in TNF-α, IL-1β, IL-6, calcitonin gene-related peptide (CGRP), malondialdehyde, 3-nitrotyrosine, insulin-like growth factor-binding protein 3 (IGFBP-3), occludin, organic cation transporter 3 (OCT-3), orosomucoid-1 (ORM1), pituitary adenylate cyclase receptor 1 (PAC1), synaptosomal-associated protein 23 (SNAP23), SNAP25, and synaptic vesicle glycoprotein (SV2A) levels were attenuated by SPC. Finally, CYP administration resulted in a decrease in the heparin-binding EGF-like growth factor (HB-EGF), hemopexin (HPX), T-H protein, and tight junction protein (Z01), and we noted the successful restoration of all these changes in concentrations after application of SPC. In summary, SPC robustly mitigated cyclophosphamide (CYP)-induced cystometric dysfunction and biochemical alterations characteristic of iatrogenic hemorrhagic cystitis. These findings position SPC as a compelling therapeutic candidate and warrant further translational investigation for the management of CYP-induced bladder injury.

Background/Objectives: We focused on the expression of a novel immune marker, cytoplasmic stimulator of interferon genes (STING), in the cohort of primary renal cell cancer (RCC) with venous tumor thrombus (VTT), in conjunction with the assessment of tumor-infiltrating leucocytes (TILs). Methods: The study group comprised 82 patients with clear cell RCC and VTT, operated on in the years 2012–2019 in two university urological centers. Tissue microarrays were constructed, and respective antibodies were used for staining purposes. The biomarkers were analyzed in primary RCC and VTT. Results: The frequency of STING expression in both analyzed compartments was similar (p = 0.18). Its presence correlated with no clinicopathological features but for necrosis in VTT only (p = 0.0023). PD-L1 expression in the primary tumor was associated with STING in tumor cells in the same compartment (p = 0.02). On the contrary, VISTA expression was correlated with the presence of STING in VTT. TIL presence was associated with positive PD-L1 (p = 0.008) and STING (p < 0.05) expression in the primary tumor. Strong STING expression in VTT was associated with inferior overall survival (OS) (p = 0.0061). TIL presence emerged as a robust prognostic factor for OS in both primary tumor (p = 0.021) and VTT (p = 0.034). Conclusions: We presented for the first time the prognostic values of STING in a contemporary cohort of RCC patients with VTT. STING expression in VTT showed prognostic potential, while TIL assessment proved to be a particularly valuable prognostic tool that can be readily implemented in routine pathological evaluation.

In the published manuscript [...].

In the published manuscript [...].

Background: Detrusor underactivity (DU) and bladder outlet obstruction (BOO) are common causes of voiding dysfunction in women with lower urinary tract symptoms (LUTS). However, differentiating between them remains challenging due to overlapping clinical presentations and a reliance on invasive urodynamic studies (UDS). This study aimed to develop a non-invasive, office-based clinical prediction model to distinguish DU from BOO in women with non-neurogenic LUTS. Methods: We conducted a retrospective analysis of 88 women who underwent pressure-flow studies at two outpatient clinics between 2012 and 2022. DU was defined using a projected isovolumetric pressure 1 (PIP1) < 30 cm H₂O, and BOO was defined by a Female-Specific Bladder Outlet Obstruction Index (BOOIf) > 18. Clinical symptoms, uroflowmetry (UFL) parameters, and pelvic organ prolapse staging (POP-Q) were evaluated. A multivariate logistic regression model was constructed using a stepwise selection procedure. Results: Of the 88 patients, 38 (43.2%) were diagnosed with DU and 50 (56.8%) with BOO. Four predictors were retained in the final model: hesitancy (OR = 2.06, p = 0.18), incomplete emptying (OR = 3.52, p = 0.02), POP-Q < 3 (OR = 0.15, p = 0.02), and longer time to Qmax on UFL (OR = 1.05, p = 0.004). The model achieved a Harrell’s Concordance Index (C-index) of 0.779. Using a probability cutoff of 0.3, the model demonstrated a sensitivity of 86.8%, specificity of 46.0%, positive predictive value of 55.0%, and negative predictive value of 82.1%. Conclusions: We present a novel non-invasive prediction model incorporating clinical symptoms, UFL metrics, and pelvic exam findings that may aid in differentiating DU from BOO in women with LUTS.

Background and Objectives: Partial nephrectomy (PN) is the preferred option for treating localized cT1 renal cell carcinoma (RCC), as it preserves renal function in most patients and offers non-inferior oncological outcomes compared to radical nephrectomy. In this study, we aimed to construct a predictive model for estimating the glomerular filtration rate (GFR) at one year after PN in patients with RCC, using various machine learning techniques. Methods: Retrospective data were collected from two academic centers, covering surgeries performed between 2010 and 2022. GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration 2021 (CKD-EPI) formula. Univariable linear regression (LR) was used to identify significant clinical predictors of 1-year postoperative GFR, followed by multivariable LR. The dataset was split into training and testing cohorts in a 70:30 ratio. Internal validation was performed on the test cohort, and various machine learning methods, including artificial neural networks (ANNs), support vector machines (SVMs), random forests (RFs), and XGBoost, were compared. Results: Among 615 patients treated with PN, 415 had complete follow-up GFR data and were included in the analysis. Only 8.7% of patients experienced significant GFR loss (>30% decrease) at 1 year. Multivariable LR identified baseline GFR (Estimate: 0.76, p < 0.001), tumor diameter on imaging (Estimate: −1.65, p = 0.005), and Charlson Comorbidity Index (Estimate: −1.95, p < 0.001) as independent predictors of 1-year GFR (R² = 0.67). A 10-fold cross-validation of the multivariable model yielded an R² of 0.68. In the testing cohort, ANN, SVM, RF, and XGBoost did not outperform the LR model, with R² values of 0.68, 0.66, 0.64, and 0.55, respectively. Conclusions: Preoperative factors, including baseline GFR, tumor size on imaging, and Charlson Comorbidity Index, are effective predictors of GFR at 1 year following PN. Our study demonstrates that a conventional LR model based on preoperative variables provides acceptable accuracy for predicting GFR after PN and is not inferior to more complex machine learning techniques.

We aimed to determine whether berbamine (BBM) would have an effect on retinyl acetate (RA)-induced cystometric and biochemical parameters, characteristic of bladder overactivity. BBM exhibits anti-inflammatory, anti-oxidant, and muscle-relaxant effects which could counteract pathophysiological mechanisms observed in overactive bladder (OAB) syndrome. The cohort of 60 rats was divided into 4 groups: I—control, II—RA group, III—BBM, and IV—group with the combination of RA + BBM. The cystometry, BBF, cardiovascular parameters and diuresis, the analysis of the cFos, and biochemical biomarker levels were analyzed 48 h after completion of BRB administration. The examined substance turned out to reverse the cystometric changes and c-Fos expression changes induced by RA when compared to the control group. There were no significant changes observed in the analyzed groups of animals MAP, HR, BBF, or UP. Importantly, BBM also turned out to reduce the level of OAB biomarkers present in urine (NGF, BDNF), urothelium (TRPV1, SNAP29, ATP, CGRP, or OCT-3), bladder detrusor muscle (VAChT, Rho kinase) as well as to reduce the exponents of oxidative stress (3-nitrotyrosine, malondialdehyde). The multifactorial explanation of the successful alleviation of the RA-induced detrusor overactivity makes the concept of incorporation of BBM in the OAB treatment promising for the future research.

Despite the close and clinically confirmed association between depression and overactive bladder, it remains unclear whether this affective disorder is a factor causing overactive bladder or whether overactive bladder is a specific symptom of psychosomatic disorders. This study examined the effects of repeated corticosterone administration on the occurrence of symptoms associated with depression and overactive bladder. Additionally, we examined whether administering TC-G 1008, an antidepressant that selectively activates the GPR39 receptor, could alleviate corticosterone-induced depression-like behavior and detrusor overactivity-related changes in cystometric measurements. We also explored its potential to reverse alterations in various biomarkers associated with both conditions in the serum, urinary bladder, and brain of female rats. The administration of corticosterone (20 mg/kg/day for 14 days) yielded anticipated results, including an increase in the duration of immobility during the forced swim test, alterations in parameters specific to bladder overactivity, a decrease in neurotrophins, and an elevation in pro-inflammatory cytokine levels. Treatment with TC-G 1008 (15 mg/kg/day) alleviated symptoms of both detrusor overactivity and depression, while also restoring the levels of biochemical and cystometric markers to normal ranges. Additionally, antidepressants based on GPR39 agonists could enhance the levels of kynurenic acid in the neuroprotective pathway. These results indicate that the GPR39 agonist receptor might be a promising future therapeutic approach for treating overactive bladder that occurs alongside depression.