Feasibility and accuracy of prostate cancer risk calculators in prediction of prostate cancer, extraprostatic extension as well as the risk of lymph nodes metastasis.

Introduction: The aim of this article was to evaluate the accuracy of European Randomized study of Screening for Prostate Cancer (ERSPC 4) and Prostate Cancer Prevention Trial (PCPT 2.0) risk calculator on predicting high-grade prostate cancer (HGPCa) and accuracy of Partin and Briganti nomograms on organ confined (OC) or extraprostatic cancer (EXP), seminal vesicles invasion (SVI) and risk of lymph nodes metastasis. Material and methods: A cohort of 269 men aged between 44-84 years, who underwent radical prostatectomy was retrospectively analysed. Based on estimated calculator risk, patients were divided into risk groups: low (LR), medium (MR) and high (HR). Results obtained with calculators were compared to post-surgical final pathology outcome. Results: In ERPSC4, the average risk for HGPC was LR = 5%, MR = 21%, and HR = 64%. In PCPT 2.0, the average risk for HG was: LR - 8%, MR - 14%, and HR - 30%. In the final results, HGPC was observed in: LR = 29%, MR = 67%, and HR = 81%. In Partin, LNI was estimated to occur in: LR = 1%, MR = 2%, and HR = 7.5% and in Briganti: LR = 1.8%, MR = 11.4%, and HR = 44.2% while finally it was found in: LR = 1.3%, MR = 0%, and HR = 11.6%. Conclusions: ERPSC 4 and PCPT 2.0 corresponded well with each other as well as Partin and Briganti. ERPSC 4 was more accurate in predicting HGPC than PCPT 2.0. Partin was more accurate as for LNI than Briganti. In this study group a large underestimation was observed in reference to Gleason grade.

The New Markers of Early Obesity-Related Organ and Metabolic Abnormalities.

The objective of our study was to identify new markers related to excessive body adiposity and its early consequences. For this purpose we determined serum FGF-19 and FGF-21 concentrations in obese rats, whose role in the pathogenesis of obesity is not yet established. In addition, a total reflection X-ray fluorescence technique was applied to determine the elemental chemistry of certain tissues affected by obesity. Next, the new biochemical and molecular parameters were correlated with well-known obesity-related markers of metabolic abnormalities. Our obese rats were characterized by increased calorie consumption and body adiposity, hypercholesterolemia, elevated levels of liver enzymes and FGF-21, while the level of FGF-19 was reduced. Strong relationships between new hormones and established metabolic parameters were observed. Furthermore, we demonstrated that obesity had the greatest effect on elemental composition in the adipose tissue and liver and that rubidium (Rb) had the highest importance in distinguishing the studied groups of animals. Tissue Rb strongly correlated with both well-known and new markers of obesity. In conclusion, we confirmed serum FGF-19 and FGF-21 as useful new markers of obesity-related metabolic alternations and we robustly propose Rb as a novel indicator of excessive body adiposity and its early consequences. However, further investigations are encouraged to address this clinical issue.

Influence of Antibiotic Administration on the Urinary Bladder Cancer Early Recurrence Rate.

Bladder cancer tends to recur, making treatment one of the most expensive in oncology. The limited efficacy and high cost of adjuvant therapies in the treatment of bladder cancer prompt research on new drugs which could replace them. In vitro studies have established that antibiotics can have a cytostatic and cytotoxic effect on urinary bladder cancer cells. The objective of the study was to investigate the influence of antibiotics on the recurrence rate of bladder cancer. In a retrospective study, we analyzed a group of 199 patients with urinary bladder cancer from four urological centers. The study groups consisted of 40 patients who received ciprofloxacin and 83 patients who received beta-lactams as perioperative antimicrobial prophylaxis. The control group included 76 patients who did not get perioperative antimicrobial prophylaxis. The groups were analyzed for risk stratification, degree of malignancy, and size of the primary tumor. The average follow-up time was 24 months. The main focus of the study was to investigate the early recurrence rate of bladder cancer among studied groups, which could correlate with the effectiveness of currently used intravesical instillations. Additionally, cancer's early progression was examined. Regardless of the division used, the highest recurrence rate was found in the ciprofloxacin group. There were no statistical differences in the recurrence rate between patients who received beta-lactams and patients who did not receive any antibiotics. In addition, there were no differences due to the progression rate between the groups. Perioperative antibiotic administration does not influence the early recurrence rate in patients with nonmuscle invasive urothelial bladder cancer.

Current thromboprophylaxis in urological cancer patients during COVID-19 pandemic.

Introduction: Venous thrombosis is a well-known complication of cancer disease, especially in Urology. However, even though proper antithrombotic prophylaxis is crucial in most urological procedures, we have insufficient high-quality studies on this topic. The European Association of Urology (EAU) Guidelines are outdated and lack data on COVID-19 increased risk of thrombosis. This review aimed to summarize data on thromboprophylaxis after radical prostatectomy, cystectomy, and nephrectomy during COVID-19 pandemic. Material and methods: A thorough analysis of the EAU Guidelines of Thromboprophylaxis was performed and compared to PubMed search, considering updated literature on thromboprophylaxis of radical prostatectomy, cystectomy, nephrectomy, as well as COVID-19 influence on venous thrombosis and urological practice. Results: Each patient should be evaluated individually to balance bleeding and venous thromboembolism (VTE) risk. There is still much uncertainty in low and medium-risk patients and all endoscopic procedures, where thromboprophylaxis could be omitted. Patients with COVID infection bear a significantly higher risk of VTE. All patients should be tested for COVID infection prior to a planned surgery during bursts of infections, undependably of vaccination status. Efforts to maintain early cancer diagnosis and treatment during the pandemic should be maintained. Conclusions: The quality of evidence is inadequate, and when deciding on thromboprophylaxis, we need to base it on individual risk, cancer advancement, procedure type, and our own experience.

Repetitive transcranial direct current stimulation modulates the brain-gut-microbiome axis in obese rodents.

BACKGROUND: Complex interactions between the brain, gut and adipose tissue allow to recognize obesity as a neurometabolic disorder. The recent data have shown that gut microbiota can play a potential role in obesity development. Transcranial direct current stimulation (tDCS) is a safe and non-invasive technique to modulate the activity of cerebral cortex and other connected brain areas also in context of appetite control. The objective of this study was to evaluate the effects of repetitive anodal tDCS (AtDCS) of prefrontal cortex on feeding behavior, metabolic status and selected phyla of gut microbiota in rats with obesity induced by high-calorie diet (HCD). METHODS: 32 female Wistar rats were equally divided into 4 subgroups depending on diet effect (lean versus obese) and type of stimulation (active versus sham tDCS versus no stimulation). Feed intake, body weight, blood lipoproteins and leptin levels as well as Firmicutes and Bacteroidetes in intestines and stool were examined. RESULTS: HCD changed feeding behavior and metabolic parameters typically for obesity-related ranges and resulted in an abundance of Firmicutes at the expanse of Bacteroidetes in the large intestine and stool. AtDCS decreased appetite, body weight, and cholesterol levels. In addition, AtDCS reduced ratio of the average number of Firmicutes to average number of Bacteroidetes in all examined tissues. CONCLUSIONS: Repetitive AtDCS is not only effective for appetite restriction but can also modulate gut microbiome composition which demonstrates the existence of the brain-gut-microbiome axis and points at this technique as a promising complementary treatment for obesity. However, the effects should be further replicated in human studies.

New Kid on the Block: The Efficacy of Phytomedicine Extracts Urox® in Reducing Overactive Bladder Symptoms in Rats.

The aim of the current study was to determine if phytomedicine (Urox®) would reverse retinyl acetate (RA)-induced changes characteristic of bladder overactivity. There were 60 rats divided into the following 4 groups: I-control, II-received RA to induce detrusor overactivity (DO), III-received Urox (840 mg daily for 14 days), and IV-received combination of RA and Urox®. The cystometry was performed 2 days after the last dose of Urox®. Next, urothelium thickness and biochemical parameter measurements were performed. In group IV, a decrease in basal pressure and detrusor overactivity index was noted when compared to group II. Furthermore, in group IV the following parameters were increased: threshold pressure, voided volume, intercontraction interval, and bladder compliance in comparison with group II. There were significant elevations in c-Fos expression in the neuronal voiding centers in group II, while the expression of c-Fos in group IV was normalized. No significant changes in the values of the analyzed biomarkers in group III were found, while in group II, an elevation in BDNF, NGF, CGRP, ATP, Rho kinase, malondialdehyde, 3-nitrotyrosine, TRPV1, OCT-3, and VAChT and then a decrease in E-cadherin and Z01 were found. A successful restoration of all the abovementioned biomarkers' levels was observed in group IV. Phytomedicine extracts (Urox®) were found to be potent in reversing RA-induced changes in several cystometric and biochemical parameters that are determinants of overactive bladder (OAB). The actions of Urox® were proved to be dependent on several factors, such as growth factors and several OAB biomarkers but not pro-inflammatory cytokines.

Potentilla chinensis aqueous extract attenuates cyclophosphamide-induced hemorrhagic cystitis in rat model.

Cyclophosphamide (CYP) damages all mucosal defence lines and induces hemorrhagic cystitis (HC) leading to detrusor overactivity. Patients who undergo combined chemio-radiotherapy are at higher risk of HC. Potentilla chinensis extract (PCE) prevent oxidative stress-dependent diseases. Thus, the aim of the study was to investigate the effect of PCE on urinary bladder function in CYP-induced HC in preclinical study. 60 rats were divided into 4 groups, as follows: I-control, II-rats with CYP-induced HC, III-rats received PCE in dose of 500 mg/kg, and IV-rats with CYP-induced HC which received PCE in dose of 500 mg/kg. PCE or vehicle were administered orally for 14 days. The cystometry was performed 3 days after the last dose of the PCE. Next, urothelium thickness and oedema measurement and biochemical analyses were performed. Cyclophosphamide induced hemorrhagic cystitis. PCE had no influence on the urinary bladder function and micturition cycles in normal rats. PCE diminished the severity of CYP-induced hemorrhagic cystitis. In the urothelium the cyclophosphamide induced the elevation of CGRP, TNF-α, IL-6, IL-1ß, OTC3, NIT, and MAL. Also, the level of T-H protein, HB-EGF, and ZO1 was decreased. Moreover, the level of ROCK1 and VAChT in detrusor muscle increased. cyclophosphamide caused an increased concentration of BDNF and NGF in the urine. In turn, PCE in cyclophosphamide-induced hemorrhagic cystitis caused a reversal of the described biochemical changes within urothelium, detrusor muscle and urine. PCE attenuates detrusor overactivity. In conclusion, our results revealed that PCE attenuates detrusor overactivity in case of cyclophosphamide-induced hemorrhagic cystitis. The potential properties of PCE appear to be important in terms of preventing of oxidative stress-dependent dysfunction of urinary bladder. PCE may become a potential supportive treatment in patient to whom cyclophosphamide-based chemotherapy is used.

Sarcoidosis of the spermatic cord - case report and literature review.

BACKGROUND: Sarcoidosis is a multi-system disease characterized by the formation of non-caseating granulomas in various organs. The lungs remain the most frequently affected organ, whereas lesions in the genitourinary system affect around 0.2% of patients. The primary site found in the spermatic cord is extremely rare. CASE PRESENTATION: We present a patient's case where the spermatic cord involvement was the first manifestation of sarcoidosis. For several months, a number of tests had been performed, which showed, among others, non-caseating granulomas in pathomorphological material, bilateral hilar lymphadenopathy, and leukopenia with lymphopenia. Tumor markers were normal. Infection with urogenital pathogens (including Chlamydia Trachomatis, Neisseria gonorrhea, Mycoplasma hominis) was excluded. The patient did not report any general symptoms such as fever, excessive fatigue, weight loss. He denied swelling, shortness of breath. At the same time, a complete differential diagnosis was carried out, and the extent of the disease was assessed. Due to interdisciplinary management, the patient's quality of life and fertility is preserved. In the discussion, we present the diagnosis, treatment, and prognosis of such patients. CONCLUSION: Sarcoidosis is a multi-system disease, which should not be omitted in the differential diagnosis. Selective excision of the lesion with intraoperative examination plays a significant role while establishing a diagnosis. However, in the primary site in the genitourinary system, the diagnosis is challenging.

RéSUMé: CONTEXTE: La sarcoïdose est une maladie multisystémique caractérisée par la formation de granulomes non caséeux dans divers organes. Les poumons restent l'organe le plus fréquemment touché, alors que les lésions du système génito-urinaire affectent environ 0,2% des patients. La découverte d'un site principal dans le cordon spermatique est extrêmement rare. PRéSENTATION DU CAS: Nous présentons le cas d'un patient où l'atteinte du cordon spermatique a été la première manifestation d'une sarcoïdose. Pendant plusieurs mois, un certain nombre de tests ont été effectués, qui montraient, entre autres, des granulomes non caséeux dans le matériel pathomorphologique, une lymphadénopathie hilaire bilatérale, et une leucopénie avec lymphopénie. Les marqueurs tumoraux étaient normaux. Une infection par des agents pathogènes urogénitaux (y compris Chlamydia Trachomatis, Neisseria gonorrhea, Mycoplasma hominis) a été exclue. Le patient n'a signalé aucun symptôme général tel que fièvre, fatigue excessive, ou perte de poids. Il a nié toute œdème ou essoufflement. Dans le même temps, un diagnostic différentiel complet a été effectué et l'étendue de la maladie a été évaluée. Grâce à la prise en charge interdisciplinaire, la qualité de vie et la fertilité du patient ont été préservées. Dans la discussion, nous présentons le diagnostic, le traitement et le pronostic de ces patients. CONCLUSION: La sarcoïdose est une maladie multisystémique, qui ne doit pas être omise dans le diagnostic différentiel. L'excision sélective de la lésion, avec examen peropératoire, joue un rôle important lors de l'établissement d'un diagnostic. Cependant, en cas de localisation du site primaire dans le système génito-urinaire, le diagnostic est difficile.

Prevalence of frailty syndrome in urological patients undergoing major elective surgical procedure due to malignancy.

Introduction: The group of elderly urological patients is growing. A majority of urological operations is performed in this group. The current model of preoperative assessment is developed to be effective in younger groups of patients but not in the elderly. Frailty syndrome has been confirmed to be an effective risk stratification tool in many surgical settings. It can be diagnosed using a variety of screening tools, but the only objective tool is comprehensive geriatric assessment (CGA). However it is time consuming, difficult and to our best knowledge, has not been attempted in Polish urological patients. Material and methods: We assessed the prevalence of frailty in elderly urological patients undergoing surgery due to malignancy using CGA and screening tests. A total of 68 patients over 65 years of age qualified to elective major urological surgery underwent the preoperative assessment including use of traditional tools (medical history, physical examination, ASA score), CGA and frailty-screening tests. The 30-day postoperative complications rate using the Clavien-Dindo scale was also evaluated. Results: The mean age of patients was 71 years. The most common procedures were radical prostatectomy (47.1%), radical nephrectomy (36.6%) and radical cystectomy (11.8%). The prevalence of frailty was 39.7% using CGA and 4.4-10.3% using screening tests. The complication rate was significantly higher in frail individuals when using CGA. Conclusions: Frailty is common in urological elderly patients. The CGA is a time-consuming but reliable tool to diagnose frailty syndrome and predict complications. Screening tests can be useful for selecting patients who should undergo CGA but their predictive value is low.

A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates.

The aim of this study was to assess the influence of a patient's general status on perioperative morbidity and mortality after radical cystectomy, and to assess which of the used scales is best for the prediction of major complications. The data of 331 patients with muscle-invasive bladder cancer, who underwent radical cystectomy, were analyzed. The general status was assessed according to the American Society of Anesthesiologists (ASA), Charlson Comorbidity Index (CCI), Eastern Cooperative Oncology Group (ECOG), and Geriatric-8 (G-8) scales. Complications were classified according to the Clavien-Dindo classification system. In a group of patients with the highest complication rate according to the Clavien-Dindo scale, (i) statistically more patients rated high according to the ASA and ECOG scales, (ii) patients had significantly higher CCI scores (minor complications (I-II), and (iii) there were significantly more patients rated as frail with G8-predominantly those with 11 points or fewer in the scale. A patient's general status should be assessed before the start of therapy because patients with a high risk of death or serious complications (evaluated with any rating scale) should be offered conservative treatment. None of the scales can describe the risk of cystectomy, because the percentage of patients with major complications among those who achieved worse score results on any scale was not significantly different from the percentage of patients with major complications in the general group.

Calculation of basal metabolic rate in patients with morbid obesity treated in spa conditions.

BACKGROUND: The present study aimed to calculate the basal metabolic rate (BMR) with the Mifflin equation based on the expected body mass for normal body mass index (BMI) values in obese patients treated in spa conditions. METHODS: Patients with morbid obesity (BMI > 40 kg m-2 ) and non-obese controls (BMI < 30 kg m-2 ) were recruited. In total, 104 patients with morbid obesity (mean BMI ± standard deviation, 46.9 ± 2.1 kg m-2 ) treated in spa conditions and 90 non-obese controls (mean BMI, 28 ± 1.3 kg m-2 ) were included in the present study. RESULTS: The mean BMR calculated based on actual body mass was 2088 ± 303 kcal in patients with morbid obesity and 1424 ± 268 kcal in non-obese controls. The BMR calculated based on expected body mass for normal BMI decreased significantly in patients with morbid obesity (p < 0.01), but not in non-obese controls. Accordingly, energy expenditure and planned caloric intake was significantly lower when BMR was calculated based on expected body mass rather than actual body mass in patients with morbid obesity, but not in non-obese controls (p < 0.01). CONCLUSIONS: Expected body mass for normal BMI should be used to calculate the BMR in patients with morbid obesity.

A Comprehensive Approach to Clinical Staging of Bladder Cancer.

BACKGROUND: A significant number of patients with advanced urothelial cell carcinoma are under- or over-staged. Implementation of clinical variables could be useful for improving the accuracy of clinical staging. AIM: To explore the differences between clinical and pathological diagnosis in patients with UCC, and to identify clinical variables that might play a role in under- or overstating. MATERIALS: A total of 553 patients after radical cystectomy were included in the analysis. Clinical stage of the disease was diagnosed according to CT or MRI in relation to clinical data. RESULTS: Higher clinical stage correlated with a higher pathological stage (p < 0.00005), but in 306 patients did not correspond (142 patients were under-staged and 164 over-staged). Over half (54.2%) of the patients staged as cT1-cT2 were misdiagnosed: 137 patients were under-staged and 133 over-staged. Hydronephrosis was associated with a higher pathological stage (p < 0.000005), mostly pT3-4 (45.13% had pT4 disease) and higher risk of nodal metastasis (p = 0.0028). The highest percentage of PSM was found in patients with pT4 (33.12%). CONCLUSIONS: Clinical staging of bladder cancer is poorly executed, with one third of patients under-staged and one third over-staged. To improve accuracy, we recommend a multimodal approach, combining histopathological evaluation with results of imaging studies.

Complication Rate after Radical Cystectomy Depends on the Surgical Technique and Patient's Clinical Status.

PURPOSE: This study aimed to explore the complication rates of radical cystectomy in patients with muscle-invasive bladder cancer and identify potential risk factors. METHODS: A total of 553 patients were included: 131 were operated on via an open approach (ORC), 242 patients via a laparoscopic method (LRC), and 180 by a robot-assisted procedure (RARC). Patient age, gender, American Society of Anesthesiologists (ASA) score, urinary diversion type, preoperative albumin level, body mass index (BMI), pathological (TNM) stage, and surgical times were collected. The severity of complications was classified according to the Clavien-Dindo scale (Grades 1-5). RESULTS: The surgical technique was significantly related to the number of complications (p < 0.00005). Grade 1 complications were observed most frequently following LRC (52.5%) and RARC (51.1%), whereas mostly Grade 2 complications were detected after ORC (78.6%). Those with less severe complications had significantly higher albumin levels than those with more severe complications (p < 0.05). Patients with an elevated BMI had fewer complications if a minimally invasive approach was used rather than ORC. The patient's general condition (ASA score) did not impact the number of complications, and urinary diversion type did not affect the severity of the complications. Mean surgical time differed according to the urinary diversion type in patients with a similar TNM stage (p < 0.005); however, no difference was found in those with more locally advanced disease. Longer operation time and lower protein concentration were associated with higher probability of complication rate, that is, Clavien-Dindo score 3-5. CONCLUSIONS: The risk of complications after RC is not related to the type of urinary diversion, and can be reduced by using a minimally invasive surgical technique, especially in patients with high BMI.

Age and risk of major complications in patients undergoing radical cystectomy for muscle invasive bladder cancer.

INTRODUCTION: Radical cystectomy is the treatment of choice for patients with muscle invasive bladder cancer (MIBC), but it may be unsafe in older patients. AIM: In this study, we investigated whether age and selected clinical characteristics were associated with outcomes of radical cystectomy. MATERIAL AND METHODS: We enrolled 434 patients with MIBC who underwent radical cystectomy between 2012 and 2016, and we classified them into three age groups: < 65, 66-74, and ≥ 75 years. Postoperative complications were classified on the Clavien-Dindo scale. Regression models were used to find predictors of major postoperative complications (Clavien-Dindo score of 3 or more), long hospital stay (> 7 days), blood loss, and operating time. The models included American Society of Anesthesiologists scores, age group, sex, body mass index, Tumor Nodes Metastasis scores, type of urine derivation (ileal conduit or orthotopic bladder vs. ureterocutaneostomy), and operation type (open vs. laparoscopic). RESULTS: In the regression models, age was not a significant predictor of major complications, long hospital stay, or blood loss (p ≥ 0.206). Older age was associated with shorter surgery times (p = 0.002). Higher preoperative American Society of Anesthesiologists scores tended to be associated with a greater risk of major complications (odds ratio, 1.47; p = 0.092). CONCLUSIONS: Older age was not associated with an increased risk of major complications in patients who undergo radical cystectomy because of MIBC. Therefore, older age alone should not be a contraindication to this operation.

Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning.

Clear cell renal cell carcinoma (ccRCC) is the most common histological type of kidney cancer and has high heterogeneity. Stratification of ccRCC is important since distinct subtypes differ in prognosis and treatment. Here, we applied a systems biology approach to stratify ccRCC into three molecular subtypes with different mRNA expression patterns and prognosis of patients. Further, we developed a set of biomarkers that could robustly classify the patients into each of the three subtypes and predict the prognosis of patients. Then, we reconstructed subtype-specific metabolic models and performed essential gene analysis to identify the potential drug targets. We identified four drug targets, including SOAT1, CRLS1, and ACACB, essential in all the three subtypes and GPD2, exclusively essential to subtype 1. Finally, we repositioned mitotane, an FDA-approved SOAT1 inhibitor, to treat ccRCC and showed that it decreased tumor cell viability and inhibited tumor cell growth based on in vitro experiments.

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1ß, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T-H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

The influence of Potentilla chinensis aqueous extract on urinary bladder function in retinyl acetate-induced detrusor overactivity in rats.

INTRODUCTION & OBJECTIVES: In overactive bladder (OAB) therapy several herbal medicines presented promising effects, however the results are sparse to provide their efficacy. Herbals may become a popular alternative for OAB therapy. Therefore, we investigated whether Potentilla chinensis extract (PCE) would reverse retinyl acetate (RA)-induced detrusor overactivity (DO). MATERIAL & METHODS: 60 rats were divided into 4 groups, as follows: I - control, II - rats with RA-induced DO, III - rats received PCE in dose of 500 mg/kg, and IV - rats with RA-induced DO which received PCE. PCE or vehicle were administered orally for 14 days. The cystometry and bladder blood flow assessment were performed 3 days after the last dose of the PCE. Then the rats were put into the metabolic cages for 24 h. Next, urothelium thickness measurement and biochemical analyses were performed. < /p>

Results. Intravesical infusion of RA solution induced DO. PCE had no influence on the urinary bladder function and  micturition cycles in normal rats. PCE diminished the severity of RA-induced DO. In the urothelium the RA induced the elevation of ATP, CGRP, substance P, VEGF-A, OTC3, and ERK1/2. The concentration of NOS2, CDH1, and ZO1 decreased. Moreover, RA affected the concentration of SNARE proteins (increased concentration of SNAP23, SNAP25, and SV2A). Also in detrusor the elevated level of ROCK1 and VAChT were observed. In turn, PCE in RA-induced DO caused a reversal of the described biochemical changes within urothelium, detrusor muscle and urine. < /p>

Conclusions. PCE attenuates detrusor overactivity. The potential mechanisms of action of PCE in the urinary bladder seem to be multifactorial and complex. PCE seems to become a reasonable novel OAB therapy.

Frailty, geriatric assessment and prehabilitation in elderly patients undergoing urological surgery - is there a need for change of the daily clinical practice? Synthesis of the available literature.

INTRODUCTION: The population of older people is heterogeneous and constantly growing. Over 50% of urological operations are performed in elderly patients. Some elderly patients present with frailty syndrome - a state of increased vulnerability to external stressors resulting in increased risk of hospitalizations, adverse treatment outcomes and death. Currently, there is no widely accepted system of qualification and preparation for surgical treatment developed specifically for elderly patients. MATERIAL AND METHODS: We searched Medline/Pubmed, Embase and Cochrane Libraries databases from 2000-2020 (week 5). The following medical subject headings (MeSH) terms were used to ensure the sensitivity of the searches: geriatric assessment, frailty, urology, and prehabilitation. Relevant articles were also identified through a manual search of the reference lists of potentially relevant articles. RESULTS: A total of 23 papers met the criteria and were included in the current study. Screening for frailty seems to be promising in predicting adverse outcomes, but frail patients should undergo detailed geriatric assessment (GA) which may indicate a need for preoperative intervention which can be unavailable during the hospitalization. The concept of prehabilitation is becoming increasingly discussed in thoracic and abdominal surgery, but only a few studies are available in the field of urology. CONCLUSIONS: Geriatric assessment seems to be a valuable tool for urologists in daily clinical practice. A proper form of prehabilitation may provide enhanced recovery after surgery.

Health-related quality of life is not related to laparoscopic or robotic technique in radical cystectomy.

BACKGROUND: Evaluating health-related quality of life (HR-QoL) is important in urological oncology. OBJECTIVES: To evaluate the impact of minimally invasive radical cystectomy (RC) on the patients' QoL depending on the surgical strategy (laparoscopic compared to robotic). MATERIAL AND METHODS: The study involved 110 patients divided into 2 groups: group 1 (n = 65), qualified for robotic-assisted RC (RARC), and group 2 (n = 45), qualified for laparoscopic RC (LRC). A prospective analysis of QoL was performed. In the study, we used sociodemographic data taken from the patients' medical records, and data from standardized questionnaires of QoL surveys entitled Functional Assessment of Cancer Therapy - General (FACT-G) and Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-Bl). RESULTS: In the patients who had undergone LRC, a statistically significant difference in HR-QoL was noted only for the subjective well-being (SWB) domain regarding family and social life: The patients had higher SWB values before surgery than after it. In the patients who had undergone RARC, statistically significant differences in HR-QoL were noted in 3 domains: 1) SWB - family and social life, 2) FACT-Bl assessment and 3) FACT-G assessment. Both before and after surgery, no statistically significant differences were found between the 2 groups for any of the HR-QoL domains. CONCLUSIONS: The surgical technique of minimally invasive endoscopic RC used (laparoscopic or robotic) does not affect HR-QoL domains.

The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease.

The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.