Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to develop the novel analytical approach and to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Transrectal ultrasound guided prostate biopsy performed by supervised junior and senior residents is safe and does not result in inferior outcomes.

PURPOSE: To compare transrectal ultrasound guided prostate biopsy (TRUSBx) cancer detection and complication rates between residents at different levels of training and attending physicians at a single academic center. METHODS: We performed a retrospective review of consecutive series of 623 men undergoing TRUSBx from June 2014 to February 2017. The procedure was performed either by resident physicians under direct supervision by an attending physician or by an attending physician. In total, junior residents, senior residents and attending physicians performed 244, 212, and 167 biopsies, respectively. Prostate cancer detection, 30-day complications, and 30-day hospitalizations rates were the outcomes of interest. We performed multivariable logistic regression analysis to identify predictors of these outcomes and examined the hypothesis that TRUSBx performed by trainees would not be associated with inferior outcomes. RESULTS: There was no statistically significant difference in patient populations between the three groups when stratified by age, BMI, Charleston co-morbidity index, aspirin use, PSA level and palpable nodule on DRE. Prostate cancer was detected in 43.8% of the biopsies and there was no difference in detection rates (P = 0.53), Gleason score (P = 0.11), number of positive cores (P = 0.95), 30-day hospitalization (P = 0.86), and 30-day complication rates (P = 0.67) between TRUSBx performed by trainees and attending physicians. CONCLUSIONS: TRUSBx performed by residents and attending physicians yielded equivalent rates of cancer detection with no significant difference in 30-day complications or 30-day hospitalizations rates. There was no difference in outcomes between junior and senior residents suggesting that with adequate faculty supervision, it is safe for trainees at all levels to perform prostate biopsies.

Comprehensive non-invasive analysis of lower urinary tract anatomy using MRI.

PURPOSE: Anatomic changes that coincide with aging including benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) negatively impact quality of life. Use of MRI with its exquisite soft tissue contrast, full field-of-view capabilities, and lack of radiation is uniquely suited for quantifying specific lower urinary tract features and providing comprehensive measurements such as total bladder wall volume (BWV), bladder wall thickness (BWT), and prostate volume (PV). We present a technique for generating 3D anatomical renderings from MRI to perform quantitative analysis of lower urinary tract anatomy. METHODS: T2-weighted fast-spin echo MRI of the pelvis in 117 subjects (59F;58 M) aged 30-69 (49.5 ± 11.3) without known lower urinary tract symptoms was retrospectively segmented using Materialise software. Virtual 3D models were used to measure BWV, BWT, and PV. RESULTS: BWV increased significantly between the 30-39 and 60-69 year age group in women (p = 0.01), but not men (p = 0.32). BWV was higher in men than women aged 30-39 and 40-49 (p = 0.02, 0.05, respectively) ,but not 50-59 or 60-69 (p = 0.18, 0.16, respectively). BWT was thicker in men than women across all age groups. Regional differences in BWT were observed both between men and women and between opposing bladder wall halves (anterior/posterior, dome/base, left/right) within each sex in the 50-59 and 60-69 year groups. PV increased from the 30-39 to 60-69 year groups (p = 0.05). BWT was higher in subjects with enlarged prostates (> 40cm3) (p = 0.05). CONCLUSION: Virtual 3D MRI models of the lower urinary tract reliably quantify sex-specific and age-associated changes of the bladder wall and prostate.

Second-harmonic generation microscopy analysis reveals proteoglycan decorin is necessary for proper collagen organization in prostate.

Collagen remodeling occurs in many prostate pathologies; however, the underlying structural architecture in both normal and diseased prostatic tissues is largely unexplored. Here, we use second-harmonic generation (SHG) microscopy to specifically probe the role of the proteoglycan decorin (Dcn) on collagen assembly in a wild type (wt) and Dcn null mouse (Dcn - / - ). Dcn is required for proper organization of collagen fibrils as it regulates size by forming an arch-like structure at the end of the fibril. We have utilized SHG metrics based on emission directionality (forward-backward ratio) and relative conversion efficiency, which are both related to the SHG coherence length, and found more disordered fibril organization in the Dcn - / - . We have also used image analysis readouts based on entropy, multifractal dimension, and wavelet transforms to compare the collagen fibril/fiber architecture in the two models, where all these showed that the Dcn - / - prostate comprised smaller and more disorganized collagen structures. All these SHG metrics are consistent with decreased SHG phase matching in the Dcn - / - and are further consistent with ultrastructural analysis of collagen in this model in other tissues, which show a more random distribution of fibril sizes and their packing into fibers. As Dcn is a known tumor suppressor, this work forms the basis for future studies of collagen remodeling in both malignant and benign prostate disease.

Potency Analysis of Mesenchymal Stromal Cells Using a Phospho-STAT Matrix Loop Analytical Approach.

Potency assays for mesenchymal stromal cells (MSCs) need to be defined in advanced clinical trials. Here, we have developed an assay matrix approach that captures the signal transducer and activator of transcription (STAT) phosphorylation of MSCs upon stimulation with their combined secretome that arose with the interaction of activated peripheral blood mononuclear cells (PBMCs). Secretome of heat-inactivated (HI) MSCs cocultured with and without activated PBMCs was used as an internal reference. We have compared the short-term phosphorylation status of STAT1, STAT3, STAT4, STAT5, and STAT6 on MSCs derived from human bone marrow, adipose tissue, and umbilical cord using phosflow technology. Secretome of live MSCs cocultured with activated PBMCs downregulate STAT1 and STAT3 phosphorylation on MSCs, whereas the secretome of HI-MSCs or PBMCs do not. Thus, investigation of the combined secretome of MSC and PBMC interaction on MSCs determine the potency of MSCs as the generator and sensor of the secretome. Bone marrow, adipose, and umbilical cord MSCs are comparable in modulating STAT1 and STAT3 responses. Measurements of STAT1 and STAT3 phosphorylation on MSCs as responder cells correlate and predict allogeneic T-cell suppression. Our comparative phosphomatrix approach between live and reference HI-MSCs defines the potency of MSCs as both stimulators and responders as part of a robust platform for predictive potency analysis. Stem Cells 2019;37:1119-1125.

Effectiveness of a transrectal prostate needle biopsy protocol with risk-tailored antimicrobials in a veterans cohort.

PURPOSE: To prospectively implement a prostate biopsy protocol to identify high-risk patients for bleeding or infectious complications and use risk-tailored antimicrobials, patient education, and postbiopsy monitoring with the objective of reducing complications. MATERIALS AND METHODS: Overall, 637 consecutive patients from June 2014 to August 2016 underwent prostate biopsy at our Veterans Affairs hospital. In the protocol cohort, patients were screened before biopsy and prophylaxis was tailored (high risk = ceftriaxone; low risk = ciprofloxacin). Patients were also provided additional education about bleeding and monitored for up to 1-hour. We defined complications as any deviation from normal postbiopsy activities. Comparisons were made between preprotocol/postprotocol cohorts. Logistic regression was used to identify risk factors for admissions or complications. RESULTS: Median age was 67 years (IQR: 64-69, P = 0.29) in both groups (pre n = 334, post n = 303). Preprotocol, 99% patients received ciprofloxacin; postprotocol, 86% received ciprofloxacin and 14% received ceftriaxone (P<0.001). There were no deaths in either group. There were decreased 30-day complication and hospitalization rates in the postprotocol group (pre 15% vs. post 8.9%, P = 0.025; 3.3% vs. 1.0%, P = 0.048). Sepsis occurred in 2 patients preprotocol and no patients postprotocol. Postprotocol group was associated with decreased 30-day complications on multivariable logistic regression (OR = 0.58, 95% CI: 0.35-0.95, P = 0.031). CONCLUSIONS: A screening protocol before prostate biopsy is a targeted approach for selecting prophylactic antimicrobials and closer monitoring postbiopsy for bleeding. Our results suggest that the protocol has a favorable effect on complication and hospitalization rates.

The role of prostate inflammation and fibrosis in lower urinary tract symptoms.

Lower urinary tract symptoms (LUTS) in aging men are extremely common. They have historically been attributed to benign prostatic hyperplasia (BPH), enlargement of the prostate, and bladder outlet obstruction. However, recent studies have revealed acute and chronic inflammation to be highly associated with LUTS, correlated with prostatic enlargement, and implicated as a cause of prostatic fibrosis that contributes to bladder outlet obstruction. This review examines the evidence implicating inflammation and fibrosis in BPH/LUTS. It identifies potential mechanisms by which inflammation may drive nociceptive signaling as well as hyperplastic growth and fibrosis and identifies targets for pharmacological intervention. This is a promising area for research and development of novel therapies to prevent or more effectively treat LUTS in aging men.