Permanent urethral catheter - a good servant, but bad master: Guidelines for prevention, diagnosis, and treatment of catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTI) are among the most common healthcare-associated infections, which increase morbidity, mortality, prolong the length of hospitalization and have a significant impact on the cost of treatment. The most efficient preventive method is removing catheters as soon as possible and avoid unnecessary catheterizations. Treatment of asymptomatic bacteriuria is not recommended. In cases of serious CAUTI, vigorous antibiotic therapy covering multidrug-resistant uropathogens should be initiated. These recommendations are intended for all medical specialties to improve the care of patients with indwelling catheters in the prevention, diagnosis, and treatment of CAUTI in primary care and subsequent long-term care.

The prevalence of antibiotic-resistant and multidrug-resistant bacteria in urine cultures from inpatients with spinal cord injuries and disorders: an 8-year, single-center study.

BACKGROUND: Patients, especially inpatients, with spinal cord lesions and disorders (SCI/D) have an elevated risk of recurrent urinary tract infections with multidrug resistant (MDR) bacteria. This study evaluated antimicrobial resistance and the prevalence of multidrug resistance and determined the risk factors for multidrug resistance. METHODS: In this retrospective cohort study, urine culture results were used to calculate the antimicrobial resistance rate and the incidence of infection with MDR bacteria in the SCI/D population. MDR was defined as acquired nonsusceptibility to at least one agent from three or more antimicrobial categories. The cohort included 402 inpatients from 2013 to 2020, with 1385 urine isolates. We included only the first isolate; duplicate isolates, defined as positive cultures of the same strain within 14 days, were excluded from the evaluation. RESULTS: The most common MDR strains were Klebsiella spp. (29%) and Escherichia coli (24%). MDR isolates were detected in 50% of the samples and extended spectrum beta-lactamase (ESBL)-producing isolates were detected in 26%, while carbapenem resistance was found in 0.1%. Significantly higher rates of infection with MDR bacteria were identified in groups of patients with indwelling urethral/suprapubic catheters (p = 0.003) and severity scores of C1-C4/AIS A-C (p = 0.01). We identified age (OR: 0.99, 95% CI; 0.98-0.99, p = 0.000), sex (OR: 1.55, 95% CI; 1.16-2.06, p = 0.003), management with urethral/suprapubic catheters (OR: 2.76, 95% CI; 2.04-3.74, p = 0.000), and spontaneous voiding (OR: 1.84, 95% CI; 1.03-3.29, p = 0.038) as independent predictors of multidrug resistance in our study population. CONCLUSIONS: We identified a high antibiotic resistance rate and an increasing prevalence of infection with MDR bacteria in the SCI/D inpatient population. Particular attention should be given to bladder management, with an emphasis on minimizing the use of indwelling catheters.

Multidrug-resistant bacteria in urine culture among patients with spinal cord injury and disorder: Time to first detection and analysis of risk factors.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The aim of this study was to assess the time to first detection of multidrug-resistant bacteria (MDRB) in urine culture and identify risk factors associated with the first detection of MDRB (1st MDRB). SETTING: Spinal Care Ward and Department of Microbiology, Regional Hospital Liberec a.s., Liberec, Czech Republic. METHOD: We cultured urine samples from patients in the acute phase of spinal cord injury or disorder (SCI/D). Multidrug resistance (MDR) was defined as acquired nonsusceptibility to at least one agent from three or more antimicrobial categories. Multivariate logistic regression was used to assess the association of bladder management, broad-spectrum antibiotic exposure, mechanical ventilation, pressure ulcers, positive urine culture on admission, and other risk factors with 1st MDRB. We used only the first urine culture with MDRB for evaluation. RESULTS: A total of 655 urine cultures from 246 individuals were evaluated, and 829 isolates were obtained. The MDRB prevalence among all isolates was 40.2%. MDRB was detected in 146 (59.3%) patients for the first time, and 76.0% of these isolates were from patients with asymptomatic bacteriuria. The median time to 1st MDRB was 37 days (95% CI, 33-41). According to multivariate logistic regression, 1st MDRB was associated with bladder management with urethral or suprapubic catheterization (OR: 2.8, 95% CI, 1.1-7.2). CONCLUSION: The prevalence of infections caused by MDRB was high among the SCI/D population, with three-quarters from patients with asymptomatic bacteriuria. Bladder management with an indwelling catheter is associated with an increased risk of 1st MDRB.

Efficacy and Safety of Autologous Dendritic Cell-Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer: The VIABLE Phase 3 Randomized Clinical Trial.

IMPORTANCE: DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. OBJECTIVE: To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). DESIGN, SETTING, AND PARTICIPANTS: The VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020. INTERVENTIONS: Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status. RESULTS: A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21; P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]). CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02111577.

Urachal yolk sac tumor penetrating the bladder as a diagnostic challenge: a case report and review of the literature.

BACKGROUND: Yolk sac tumor (YST) is a germ cell tumor. It is primarily located in the gonads but can also occur extragonadally (extragonadal yolk sac tumor - EGYST), most commonly in the pelvis, retroperitoneum or mediastinum. Only a few YSTs of the urachus have been described. CASE REPORT: We present a rare case report of a 37-year-old male with episodes of macroscopic hematuria. The histological specimen obtained by transurethral resection showed a solid, and in some parts papillary infiltrative, high-grade tumor with numerous areas of marked nuclear atypia and clear invasion between the detrusor bundles. Glandular pattern has been observed in only minority of the tumor. Immunohistochemistry showed significant positivity for GPC3, SALL4 and cytokeratins AE1/AE3, while KRT7 and GATA3 were negative. We concluded that the biopsy findings were consistent with urothelial carcinoma with infrequent YST differentiation. In definitive surgical specimens we found a malignant epithelial, glandular and cystically arranged tumor of germinal appearance arising from urachus. The surrounding urothelium was free of invasive or in situ tumor changes. We reclassified the tumor as a urachal YST. CONCLUSION: EGYST was suspected because glandular and hepatoid structures were found, but the presence of these structures should be verified by immunohistochemistry.

Patients with metastatic renal cell carcinoma treated with cabozantinib in the Czech Republic: analysis of four cancer centers.

AIM: The aim of this study was to retrospectively analyze treatment outcomes and tolerance in patients in whom cabozantinib was used after previous targeted therapy. PATIENTS AND METHODS: Cabozantinib was administered in dose 60 mg/day, a subset of patients received initial dose of 40 mg/day. The treatment was administered until to progression or unacceptable toxicity. CT scans were assessed according to the RECIST 1.1 and toxicity of treatment was assessed based on the CTCAE (version 4). Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. All statistics were evaluated at the significance level alpha = 0.05. RESULTS: 54 patients with metastatic renal cell carcinoma (mRCC) were evaluated. Median PFS in all patients treated with cabozantinib was 9.3 months (95% CI 5.3 - 13.3). One-year survival was 85.2% (95% CI 72.9 - 93.4%). Treatment response was observed in 45.9% of cases, including one complete remission. Cox regression analysis demonstrated that presence of subsequent treatment was the only factor with a significant effect on OS (P=0.008). Adverse events occurred in 88.9% of patients, grade 3 - 4 in 46.3%. CONCLUSION: The analysis of our cohort of patients treated with cabozantinib in the second or higher lines of treatment showed that cabozantinib represents an effective and safe therapy and contributes to longer survival of our mRCC patients.

Intravesical Loss of OnabotulinumtoxinA During Endoscopic Intradetrusor Injection - A Multicenter Experience.

PURPOSE: To evaluate intravesical loss of onabolunumtoxinA (onaBTA) during endoscopic injection into the bladder wall for treatment of neurogenic detrusor overactivity (NDO). The intraluminal loss of onaBTA cannot be determined directly, therefore we added methylene blue (MB) to reconstitute onaBTA. Subsequently we used spectrophotometry to determine the total amount of MB in the irrigation fluid, which allowed us to calculate total intraluminal loss of onaBTA. METHODS: The study population was consisted of 48 patients with NDO. The mean age was 36.6±8.9 years. Forty-two patients suffered from NDO due to spinal cord injury and 6 patients suffered from multiple sclerosis. Each patient received 200 units of onaBTA administered by 30 endoscopic injections (1 mL per injection) using a 23-G needle. The entire volume of irrigation fluid was collected and spectrophotometry was used to determine the MB concentration. The total amount of injected onaBTA, total amount of irrigation solution and the known amount of MB used during reconstitution, allowed for the determination of intravesical loss of onaBTA. RESULTS: Forty-five patients were included in the final analysis. The mean volume of irrigation fluid was 603.33±400.14 mL. The mean absorbance was 0.14±0.12 with the mean MB concentration 0.19±0.18 mg/L. The mean calculated loss of onaBTA was 4.14±4.11 units. CONCLUSION: The endoscopic injection of onaBTA marked by MB into the bladder wall is associated with minimal intravesical loss of the agent, representing less than 3% of the administered dose of MB. This may reflect the amount of the onaBTA detected in the irrigation fluid.

The expression of PD-L1 in patients with castrate prostate cancer treated with enzalutamide.

PURPOSE: The purpose of our retrospectively study was to evaluate the PD-L1 expression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. METHODS: A total of 33 patients with mCRPC were treated with enzalutamide. All patients were previously treated by one or two lines of chemotherapy. Enzalutamide was administered in the standard dose (160 mg orally once daily as four 40 mg capsules). No corticosteroids were concomitantly administered. PD-L1 expression was determined semiquantitavely by immunohistochemistry. RESULTS: Enzalutamide was well tolerated with predominantly G1-2 toxicity. G3-4 anaemia was found in 6 patients and G3-4 thrombocytopenia in 2 patients. One patient had cerebral hemorrhage. The median progression free survival (PFS) was 7.0 months (95% CI 6.1-7.9). The median overall survival (OS) was 8.4 months (95% CI: 5.1-11.7). The shorter OS was noted in the subgroup of patients with decreasing hemoglobin levels during enzalutamide treatment with hazard ratio (HR) 0.155 (95% CI 0.053-0.449) and in patients with Gleason score 8-10 with HR 0.334 (95% CI 0.12-0.927) according to the regression analysis. All tissue samples were scored as negative in the detection of PD-L1. CONCLUSIONS: The expression of PD-L1 in prostate cancer cells as potential new predictive biomarker was not confirmed. Further studies are needed to clarify this topic.

Submucosal administration of onabotulinumtoxinA in the treatment of neurogenic detrusor overactivity: pilot single-centre experience and comparison with standard injection into the detrusor.

INTRODUCTION: Apart from the standard intramural administration of botulinum neurotoxin A (BoNT/A) to the detrusor, intense research is taking place into new means of administration in view of the complex mechanism of action of BoNT/A. METHODS: An open, randomised, prospective study was performed on a total of 23 patients with neurogenic detrusor overactivity. Following randomisation, patients were treated with 300 U of onabotulinumtoxinA (onaBoNT/A) in either the submucosa or the detrusor. Urodynamic examinations were carried out, and a bladder diary was kept both prior to and 12 weeks after the treatment. All patients stopped taking anticholinergics 1 week prior to the treatment. RESULTS: In both the submucosa and detrusor groups, we recorded a significant improvement in the monitored urodynamic parameters and significant decreases in the frequency of urinary incontinence episodes following the treatment. A comparison of the two groups showed no significant difference between the two forms of application, with the exception of voided volume (p = 0.007). CONCLUSION: A comparison of the two administration methods did not show any significant difference between onaBoNT/A administration to the submucosa and to the detrusor. Thus, the submucosal injection of onaBoNT/A represents an equally effective approach for its administration to patients.