Application of novel burst wave lithotripsy and ultrasonic propulsion technology for the treatment of ureteral calculi in a bottlenose dolphin (Tursiops truncatus) and renal calculi in a harbor seal (Phoca vitulina).

Marine mammals may develop kidney stones, which can be challenging to treat. We describe burst wave lithotripsy (BWL) and ultrasonic propulsion to treat ureteral calculi in a 48-year-old female bottlenose dolphin (Tursiops truncatus) and to reduce renal stone burden in a 23-year-old male harbor seal (Phoca vitulina). BWL and ultrasonic propulsion were delivered transcutaneously in sinusoidal ultrasound bursts to fragment and reposition stones. Targeting and monitoring were performed with real-time imaging integrated within the BWL system. Four dolphin stones were obtained and fragmented ex vivo. The dolphin case received a 10-min and a 20-min BWL treatment conducted approximately 24 h apart to treat two 8-10 mm partially obstructing right mid-ureteral stones, using oral sedation alone. For the harbor seal, while under general anesthesia, retrograde ureteroscopy attempts were unsuccessful because of ureteral tortuosity, and a 30-min BWL treatment was targeted on one 10-mm right kidney stone cluster. All 4 stones fragmented completely to < 2-mm fragments in < 20 min ex vivo. In the dolphin case, the ureteral stones appeared to fragment, spread apart, and move with ultrasonic propulsion. On post-treatment day 1, the ureteral calculi fragments shifted caudally reaching the ureteral orifice on day 9. On day 10, the calculi fragments passed, and the hydroureter resolved. In the harbor seal, the stone cluster was observed to fragment and was not visible on the post-operative computed tomography scan. The seal had gross hematuria and a day of behavior indicating stone passage but overall, an uneventful recovery. BWL and ultrasonic propulsion successfully relieved ureteral stone obstruction in a geriatric dolphin and reduced renal stone burden in a geriatric harbor seal.

Access and Representation: A Narrative Review of the Disparities in Access to Clinical Trials and Precision Oncology in Black men with Prostate Cancer.

OBJECTIVE: To provide commentary on the disparities in access to clinical trials and precision oncology specific to Black men with Prostate Cancer (PCa) in the United States and lend a general framework to aid in closing these gaps. MATERIALS AND METHODS: The ideas, commentaries and data presented in this narrative review were synthesized by utilizing qualitative and quantitative studies, reviews, and randomized control trials performed between 2010 and 2021. We searched PubMed using the key words "Medicaid", "Medicare", "clinical trials", "African Americans", "Black", "underrepresentation", "access", "Prostate Cancer", "minority recruitment", "racial disparities", "disparity", "genomics", "biomarkers", "diagnostic" "prognostic", "validation", "precision medicine", and "precision oncology" to identify important themes, trends and data described in the current review. Keywords were used alone and combination with both "AND" and "OR" terms. RESULTS: Black men with prostate cancer (PCa) in the United States have earlier onset of disease, present with more advanced stages, and worse prostate cancer-specific survival than their White counterparts. Potential causative factors vary from disparities in health care access to differences in tumor immunobiology and genomics along with disparate screening rates, management patterns and underrepresentation in clinical and translational research such as clinical trials and precision oncology. CONCLUSION: To avoid increasing the racial disparity in PCa outcomes for Black men, we must increase inclusion of Black men into precision oncology and clinical trials, using multilevel change. Underrepresentation in clinical and translational research may potentiate poorly validated risk calculators and biomarkers, leading to poor treatment decisions in high-risk populations. Relevant actions include funding to include minority-serving institutions as recruitment sites, and inclusion of evidence based recruitment methods in funded research to increase Black representation in clinical trials and translational research.

Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma.

BACKGROUND: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes. METHODS: Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition. RESULTS: Of 245 treatment-naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P = .003), including none in 71 of 177 patients (40.1%); fewer metastases (P = .011); and higher proportions of clear cell histology (P = .012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13-2.19; P = .007; HR, 2.52; 95% CI, 1.74-3.65; P < .001). CONCLUSIONS: IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications.

Time of peak nocturnal diuresis rate between men with secondary nocturnal polyuria versus nocturnal polyuria syndrome.

AIM: Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. METHODS: Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (≥2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] ≥90 mL/hour or nocturnal polyuria index [NPi] ≥0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. RESULTS: The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP ≥ 90 mL/hour and 1.96 (0.87-4.42) at NPi ≥ 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. CONCLUSIONS: A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP ≥ 90 mL/hour, with similar odds ratios at NPi ≥ 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. PATIENT SUMMARY: Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.

Development and Initial Testing of the FLOW Instrument: Novel Assessment of Lower Urinary Tract Symptoms in Men.

PURPOSE: We sought to develop a method to assess lower urinary tract symptoms regardless of literacy and numeracy. MATERIALS AND METHODS: We convened focus groups and developed a questionnaire based on 4 identified domains of urinary function, including frequency, incontinence (leakage), nocturia (overnight voiding) and weak stream. We pilot tested the novel FLOW (frequency, leakage, overnight voiding and weak stream) questionnaire in 64 men and performed quantitative analysis to determine internal consistency. Criterion validity was established via direct comparison to the AUA (American Urological Association) symptom score in a larger cohort of 161 men. RESULTS: Median time to complete the FLOW questionnaire was 18.0 seconds (IQR 15.8-21.0). The mean number of positive responses to the FLOW instrument was 1.7. Test-retest reliability was 0.91 and the Cronbach α was 0.67. In the validation cohort there was a significant correlation between FLOW scores and AUA symptom score (r = 0.63, p <0.001). All men regardless of health literacy completed FLOW. However, fewer men with low health literacy completed the AUA symptom score compared to men with adequate health literacy (81% vs 100%, p <0.001). For FLOW health literacy was unrelated to the median completion time (21.5 seconds), the median number of prompts needed (0) or the median score (2). CONCLUSIONS: A critical analysis of the AUA symptom score using valid health literacy scales revealed that it is frequently not completed, requires prompting and takes longer to complete for men with low health literacy. The FLOW instrument represents a novel method to assess lower urinary tract symptoms in all men. It represents a valid alternative to the AUA symptom score.