Impact of Obstructive Sleep Apnea Syndrome on Time to Complete Recovery of Continence After Robot-Assisted Radical Prostatectomy: A Propensity Score Matching Analysis.

Background: Postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP) represents a bothersome side effect, which may permanently affect patient's quality of life. Several studies have demonstrated that obstructive sleep apnea syndrome (OSAS) is associated with urinary symptoms such as urge incontinence, overactive bladder, and nocturia. In this study, we sought to further explore the effect of OSAS on urinary continence after RARP. Methods: We queried our prospectively collected institutional RARP database and identified 82 patients with OSAS and 131 controls, which were matched for age and body mass index (BMI), with available follow-up data for continence. To minimize selection bias, we conducted a propensity score-matched analysis. Patient's characteristics and urinary continence outcomes were compared between the two groups before and after propensity-score matching. Kaplan-Meier curves were constructed to assess the difference in continence between the two groups. Results are presented as means with standard deviations and percentages with 95% confidence intervals (CIs). Results: A total of 213 patients were included in the analysis, of whom 82 with OSAS and 131 with non-OSAS (control group). The mean age of the total cohort was 61.7 ± 6.96 years, the mean BMI was 30.4 ± 5.36, and 52% of the cohort were classified as obese (BMI ≥30). In post-propensity score-matched analyses, there was no significant difference in baseline demographics and tumor characteristics between the two groups (included 82 cases in each group). The median time to continence was 6.6 months for the control group as compared with 13.0 months for the OSAS group (p < 0.001). At 12 months the continence rate for the OSAS group was 41.2% (95% CI: 28.9%-51.4%) as compared with 61.7% (95% CI: 28.5%-71.5%) for the control group. At 24 months the continence rate for the OSAS group was 68.7% (95% CI: 56%-77.7%) as compared with 90.8% (95% CI: 79%-96%) for the control group. Conclusion: On matched analysis, we found that patients with OSAS tended to demonstrate worse urinary continence recovery as compared with patients without OSAS. Additional investigation will be necessary to confirm these initial findings.

When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

PURPOSE: The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments. METHODS: We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model. RESULTS: The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome. CONCLUSIONS: The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

Oncological and Functional Outcomes of Robot-Assisted Radical Prostatectomy in Kidney Transplant Recipients.

OBJECTIVE: Management of prostate cancer in kidney transplant recipients presents a unique surgical challenge due to the risk of direct or indirect injury to the transplanted kidney. Herein, we report the largest single center study of Robot-assisted Radical prostatectomy (RARP) in kidney transplant recipients. METHODS: Between Jan 2014-2019, 14 kidney transplant recipients with prostate cancer underwent RARP. Clinical and pathological features, perioperative and postoperative complications were retrospectively evaluated. Continence was defined as by patient utilization of zero urinary pads postoperatively. RESULTS: The median (IQR) age at RARP was 60.2 (57.8-61.3) years, the interval between kidney transplant and RARP was 8.1 ± 7.5 years. The median (IQR) PSA was 6.9 (4-8.6); 10 of 14 patients had intermediate or high-risk prostate cancer. The median ASA score was 3, the mean (SD) operative time was 129.7 (26.3) minutes, and mean (SD) blood loss was 110 (44.6) ml. All cases were completed robotically, there was no graft loss or injury to transplanted ureter, and the mean length of stay was 1 (0.26) day.Final pathology demonstrated that 42.8% (6/14) of the patients had nonorgan confined disease (pT3a/T3b). 50% (7/14) of the patients were upgraded to higher risk Gleason disease on final surgical pathology. Post-RARP continence rate at 3 months, and 12 months were 45.5% (5/11) and 87.5% (7/8), respectively. CONCLUSION: RARP following kidney transplantation represents a safe and feasible operation which does not appear to compromise oncological or transplant outcomes.

Computationally Derived Cribriform Area Index from Prostate Cancer Hematoxylin and Eosin Images Is Associated with Biochemical Recurrence Following Radical Prostatectomy and Is Most Prognostic in Gleason Grade Group 2.

BACKGROUND: The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement. OBJECTIVE: To investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups. DESIGN, SETTING, AND PARTICIPANTS: A machine learning approach was developed for ICC segmentation using 70 RP patients and validated in a cohort of 749 patients from four sites whose median year of surgery was 2007 and with median follow-up of 28 mo. ICC was segmented on one representative hematoxylin and eosin RP slide per patient and the fraction of tumor area composed of ICC, the cribriform area index (CAI), was measured. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association between CAI and BCR was measured in terms of the concordance index (c index) and hazard ratio (HR). RESULTS AND LIMITATIONS: CAI was correlated with BCR (c index 0.62) in the validation set of 411 patients with ICC morphology, especially those with Gleason grade group 2 cancer (n = 192; c index 0.66), and was less prognostic when patients without ICC were included (c index 0.54). A doubling of CAI in the group with ICC morphology was prognostic after controlling for Gleason grade, surgical margin positivity, preoperative prostate-specific antigen level, pathological T stage, and age (HR 1.19, 95% confidence interval 1.03-1.38; p = 0.018). CONCLUSIONS: Automated image analysis and machine learning could provide an objective, quantitative, reproducible, and high-throughput method of quantifying ICC area. The performance of CAI for grade group 2 cancer suggests that for patients with little Gleason 4 pattern, the ICC fraction has a strong prognostic role. PATIENT SUMMARY: Machine-based measurement of a specific cell pattern (cribriform; sieve-like, with lots of spaces) in images of prostate specimens could improve risk stratification for patients with prostate cancer. In the future, this could help in expanding the criteria for active surveillance.

Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study.

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03-3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40-3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.

Urologic emergencies before and after COVID-19: a retrospective chart review.

INTRODUCTION During the coronavirus disease 2019 (COVID-19) pandemic, decreased presentations for various emergent conditions have been observed. Our objective was to compare the volume of patients with urologic emergencies presenting to emergency departments (EDs) within a single health system before and after the onset of the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective chart review was performed for 3 EDs within a single health system in the United States to identify all ED consults to urology from January 1, 2019 to May 31, 2020. For emergent consults, covariates were extracted, including demographic information, insurance status, Charlson Comorbidity Index (CCI) score, travel distance from home to the ED, and whether the patient had seen a provider in the hospital system before. Data were compared between COVID-19 months (March-May 2020) and corresponding months in 2019. RESULTS: The study period encompassed 1,179 consults and 373 urologic emergencies. We observed not only a 22% decrease in urologic presentations to the ED compared to corresponding months in 2019, but also a 54% decrease in the proportion of urologic presentations that were truly emergent. For patients with emergent diagnoses, April 2020 saw an increase in Medicare/Medicaid coverage and a decrease in private insurance, May 2020 saw a decreased travel distance from home to the ED, and March and May 2020 saw an increase in patients who had previously seen a health system provider outside of the ED. No changes were seen in demographic characteristics or CCI. CONCLUSIONS: During the early COVID-19 pandemic, urologic emergencies within a single health system decreased by 54% compared to the corresponding months pre-pandemic. Those who do present for care may be influenced by both locality and provider familiarity.

A novel imaging based Nomogram for predicting post-surgical biochemical recurrence and adverse pathology of prostate cancer from pre-operative bi-parametric MRI.

BACKGROUND: We developed and validated an integrated radiomic-clinicopathologic nomogram (RadClip) for post-surgical biochemical recurrence free survival (bRFS) and adverse pathology (AP) prediction in men with prostate cancer (PCa). RadClip was further compared against extant prognostics tools like CAPRA and Decipher. METHODS: A retrospective study of 198 patients with PCa from four institutions who underwent pre-operative 3 Tesla MRI followed by radical prostatectomy, between 2009 and 2017 with a median 35-month follow-up was performed. Radiomic features were extracted from prostate cancer regions on bi-parametric magnetic resonance imaging (bpMRI). Cox Proportional-Hazards (CPH) model warped with minimum redundancy maximum relevance (MRMR) feature selection was employed to select bpMRI radiomic features for bRFS prediction in the training set (D1, N = 71). In addition, a bpMRI radiomic risk score (RadS) and associated nomogram, RadClip, were constructed in D1 and then compared against the Decipher, pre-operative (CAPRA), and post-operative (CAPRA-S) nomograms for bRFS and AP prediction in the testing set (D2, N = 127). FINDINGS: "RadClip yielded a higher C-index (0.77, 95% CI 0.65-0.88) compared to CAPRA (0.68, 95% CI 0.57-0.8) and Decipher (0.51, 95% CI 0.33-0.69) and was found to be comparable to CAPRA-S (0.75, 95% CI 0.65-0.85). RadClip resulted in a higher AUC (0.71, 95% CI 0.62-0.81) for predicting AP compared to Decipher (0.66, 95% CI 0.56-0.77) and CAPRA (0.69, 95% CI 0.59-0.79)." INTERPRETATION: RadClip was more prognostic of bRFS and AP compared to Decipher and CAPRA. It could help pre-operatively identify PCa patients at low risk of biochemical recurrence and AP and who therefore might defer additional therapy. FUNDING: The National Institutes of Health, the U.S. Department of Veterans Affairs, and the Department of Defense.

Stepwise Description and Outcomes of Bladder Neck Sparing Robot-Assisted Simple Prostatectomy.

Background: To present a stepwise description and outcomes of bladder neck sparing (BNS) robot-assisted simple prostatectomy (RASP). Methods: Between March 2015 and December 2018, 30 consecutive patients with benign prostate hyperplasia underwent BNS RASP. Baseline characteristics, and intraoperative and postoperative variables were retrospectively abstracted. Descriptive statistics were used to report the variables. Results: The median age was 66.5 (59.3-72.3) years, and median body mass index was 27.6 (24.5-72.3) kg/m2. The median preoperative International Prostate Symptoms Score was 23 (17.5-27), and median prostate size was 97 (74-148.75) mL. The mean (standard deviation [SD]) operative time was 107.5 (22.2) minutes, and the mean (SD) estimated blood loss was 132.4 (35.4) mL. All cases were completed robotically without any intraoperative complications, and continuous bladder irrigation was not necessary for any patient postoperatively. All patients were able to void after catheter removal except one patient with a preexisting diagnosis of neurogenic bladder who resumed clean intermittent catheterization. All patients were continent as defined as using 0 pads postoperatively. Of the 19 patients who had antegrade ejaculation before the operation, 8 patients (42%) reported of continued antegrade ejaculation after the operation. Conclusions: In this report, we demonstrate a simplified approach of BNS RASP that is reproducible with a favorable perioperative complication rates and acceptable postoperative functional outcomes. This technique obviates the need for continuous bladder irrigation and intraperitoneal drain.

Outpatient Robot-Assisted Radical Prostatectomy: Are Patients Ready for Same-Day Discharge?

Purpose: Several case series have demonstrated the safety and feasibility of outpatient robot-assisted radical prostatectomy (RARP) in well-selected patients; however, the patient perspective of this practice has not been well explored. In this study, we explored patients' perspectives on the potential barriers and benefits of outpatient RARP. Materials and Methods: We developed a multidimensional questionnaire to assess socioeconomic status, presence of caretaker at home, preferred transportation to the emergency room in case of chest pain or postsurgical complications, readiness for discharge at postanesthesia care unit (PACU), and potential barriers for discharge. In addition, patients were asked to provide an estimate of overnight hospitalization costs and their willingness to pay out-of-pocket expenses for their overnight stay. Patients who underwent RARP between August 1, 2018, and April 30, 2019, were asked to fill the questionnaire within the first week following their operation. Results: During our study, 157/292 (53.8%) of men undergoing RARP from a single high-volume robotic surgeon completed the survey. Patients who completed <80% of the survey (n = 5) were excluded from the final analysis. Thirty-seven (24.3%) patients felt that they would have been ready for discharge immediately from PACU, and 48 (31.6%) patients after extended recovery and before midnight. Only 17.8% (n = 27) of the patients claim that they experienced a medical intervention in the hospital that could not have been managed at home. The main barriers for same-day discharge were pain (55.9%, 80/143), catheter discomfort (44.7%, 64/143), insufficient education about catheter care (31.4%, 45/143), postoperative nausea and vomiting (15.3%, 22/143), and medical complications (13.2%, 19/143). Conclusions: Two-thirds of patients following RARP did not feel ready to be discharged on the day of their surgery. Further research is necessary to identify patients who may benefit from this approach to reduce health care costs while minimizing patient postoperative morbidity.

Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids.

BACKGROUND: The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn's disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease. RESULTS: We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens, was associated with diet-induced remission in human pediatric Crohn's disease. CONCLUSIONS: These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn's disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets.

Childhood lead poisoning from domestic products in China: A case study with implications for practice, education, and policy.

OBJECTIVE: This study aimed to report three representative childhood lead poisoning cases in China from domestic products exposure and to highlight their critical implications for practice, education, and policy in prevention and treatment of childhood lead poisoning by health care providers, especially public health nurses. DESIGN AND SAMPLE: Three representative childhood lead poisoning cases occurring in 2017 were collected and analyzed. RESULTS: The lead exposure sources of three cases were evaluated by experts in the field and determined to be tin pots, home factories for tinfoil, and contamination of folk medicine, respectively. These cases demonstrated that the lack of lead exposure risk assessment, insufficient knowledge of potential lead exposure sources, underdeveloped policy, and regulations were areas for improvement. CONCLUSIONS: The best strategies for preventing lead poisoning include an appropriate risk assessment of lead exposure, implementation of comprehensive parental health education, conduction of further research by public health providers, and the application of policy strategies by the government. It was determined that public health nurses are at the frontline of prevention of lead poisoning in children.

Infection-Induced Intestinal Dysbiosis Is Mediated by Macrophage Activation and Nitrate Production.

Oral infection of C57BL/6J mice with Toxoplasma gondii results in a marked bacterial dysbiosis and the development of severe pathology in the distal small intestine that is dependent on CD4+ T cells and interferon gamma (IFN-γ). This dysbiosis and bacterial translocation contribute to the development of ileal pathology, but the factors that support the bloom of bacterial pathobionts are unclear. The use of microbial community profiling and shotgun metagenomics revealed that Toxoplasma infection induces a dysbiosis dominated by Enterobacteriaceae and an increased potential for nitrate respiration. In vivo experiments using bacterial metabolic mutants revealed that during this infection, host-derived nitrate supports the expansion of Enterobacteriaceae in the ileum via nitrate respiration. Additional experiments with infected mice indicate that the IFN-γ/STAT1/iNOS axis, while essential for parasite control, also supplies a pool of nitrate that serves as a source for anaerobic respiration and supports overgrowth of Enterobacteriaceae Together, these data reveal a trade-off in intestinal immunity after oral infection of C57BL/6J mice with T. gondii, in which inducible nitric oxide synthase (iNOS) is required for parasite control, while this host enzyme is responsible for specific modification of the composition of the microbiome that contributes to pathology.IMPORTANCEToxoplasma gondii is a protozoan parasite and a leading cause of foodborne illness. Infection is initiated when the parasite invades the intestinal epithelium, and in many host species, this leads to intense inflammation and a dramatic disruption of the normal microbial ecosystem that resides in the healthy gut (the so-called microbiome). One characteristic change in the microbiome during infection with Toxoplasma-as well as numerous other pathogens-is the overgrowth of Escherichia coli or similar bacteria and a breakdown of commensal containment leading to seeding of peripheral organs with gut bacteria and subsequent sepsis. Our findings provide one clear explanation for how this process is regulated, thereby improving our understanding of the relationship between parasite infection, inflammation, and disease. Furthermore, our results could serve as the basis for the development of novel therapeutics to reduce the potential for harmful bacteria to bloom in the gut during infection.