Antibiotic use, best practice statement adherence, and UTI rate for intradetrusor onabotulinumtoxin-A injection for overactive bladder: A multi-institutional collaboration from the SUFU Research Network (SURN).

INTRODUCTION: Onabotulinumtoxin A (BTX-A) is a well-established treatment for overactive bladder (OAB). The American Urological Association (AUA) 2008 Antibiotic Best Practice Statement (BPS) recommended trimethoprim-sulfamethoxazole or fluoroquinolone for cystoscopy with manipulation. The aim of the study was to evaluate concordance with antibiotic best practices at the time of BTX-A injection and urinary tract infection (UTI) rates based on antibiotic regimen. METHODS: Men and women undergoing first-time BTX-A injection for idiopathic OAB with 100 units in 2016, within the SUFU Research Network (SURN) multi-institutional retrospective database were included. Patients on suppressive antibiotics were excluded. The primary outcome was concordance of periprocedural antibiotic use with the AUA 2008 BPS antimicrobials of choice for "cystoscopy with manipulation." As a secondary outcome we compared the incidence of UTI among women within 30 days after BTX-A administration. Each outcome was further stratified by procedure setting (office vs. operating room; OR). RESULTS: Of the cohort of 216 subjects (175 women, 41 men) undergoing BTX-A, 24 different periprocedural antibiotic regimens were utilized, and 98 (45%) underwent BTX-A injections in the OR setting while 118 (55%) underwent BTX-A injection in the office. Antibiotics were given to 86% of patients in the OR versus 77% in office, and 8.3% of subjects received BPS concordant antibiotics in the OR versus 82% in office. UTI rates did not vary significantly among the 141 subjects who received antibiotics and had 30-day follow-up (8% BPS-concordant vs. 16% BPS-discordant, CI -2.4% to 19%, p = 0.13). A sensitivity analysis of UTI rates based on procedure setting (office vs. OR) did not demonstrate any difference in UTI rates (p = 0.14). CONCLUSIONS: This retrospective multi-institutional study demonstrates that antibiotic regimens and adherence to the 2008 AUA BPS were highly variable among providers with lower rates of BPS concordant antibiotic use in the OR setting. UTI rates at 30 days following BTX-A did not vary significantly based on concordance with the BPS or procedure setting.

A Prospective Observational Study of Posterior Tibial Nerve Stimulation in Multiple Sclerosis.

INTRODUCTION AND HYPOTHESIS: The objective was to examine the outcomes of posterior tibial nerve stimulation (PTNS) on bladder, bowel, and sexual health-related quality of life among a cohort of patients with multiple sclerosis (MS) with refractory lower urinary tract symptoms (LUTS). METHODS: Patients with MS and refractory LUTS were recruited for a prospective, observational study using PTNS to treat their symptoms. Patients underwent 12 weekly 30-min PTNS sessions and bladder, bowel, and sexual symptoms were evaluated at baseline, 3, 12, and 24 months with voiding diaries, visual analog scales (VAS), and validated patient-reported questionnaires, including the American Urological Association Symptom Score (AUA-SS), Neurogenic Bladder Symptom Score (NBSS), Michigan Incontinence Symptom Index (M-ISI), Health Status Questionnaire, Sexual Satisfaction Scale, and Bowel Control Scale. RESULTS: A total of 23 patients were recruited: 18 started PTNS and 14 completed 3 months of PTNS. Of the 18 who started PTNS, the mean age was 52 years (SD 12), 61% were female, 83% were white, and most patients had relapsing remitting (39%) MS. Baseline (n=18) and 3-month voiding (n=11) outcomes showed no significant change in number of voids or incontinence episodes. The median VAS symptom improvement was 49 (IQR 26.5, 26) and 9 (53%) patients elected for monthly maintenance PTNS. On paired analysis, there was a significant improvement in median change in NBSS, AUA-SS, and M-ISI. There was no significant change in bowel or sexual dysfunction. CONCLUSIONS: This prospective, observational study of PTNS in patients with MS with refractory LUTS shows improvement in patient-reported bladder outcomes, but not in number of voids per day or bowel or bladder function.

What Is the Optimal Stenting Duration After Ureteroscopy and Stone Intervention? Impact of Dwell Time on Postoperative Emergency Department Visits.

PURPOSE: AUA stone management guidelines recommend stenting duration following ureteroscopy be minimized to reduce morbidity; stents with extraction strings may be used for this purpose. However, an animal study demonstrated that short dwell time results in suboptimal ureteral dilation, and a pilot clinical study showed this increases postprocedure events. Using real-world practice data we examined stent dwell time after ureteroscopy and its association with postoperative emergency department visits. MATERIALS AND METHODS: We used the Michigan Urological Surgery Improvement Collaborative registry to identify ureteroscopy and stenting procedures (2016-2019). Pre-stented cases were excluded. Stenting cohorts with and without strings were analyzed. Using multivariable logistic regression we evaluated the risk of an emergency department visit occurring on the day of, or day after, stent removal based on dwell time and string status. RESULTS: We identified 4,437 procedures; 1,690 (38%) had a string. Median dwell time was lower in patients with a string (5 vs 9 days). Ureteroscopy in younger patients, smaller stones, or renal stone location had a higher frequency of string use. The predicted probability of an emergency department visit was significantly greater in procedures with string, compared to without string, when dwell times were less than 5 days (P < .01) but were not statistically significant after. CONCLUSIONS: Patients who had ureteroscopy and stenting with a string have short dwell times. Patients are at increased risk of a postoperative emergency department visit around the time of stent removal if dwell time is ≤4 days. We recommended stenting duration of at least 5 days in nonpre-stented patients.

A Phase 2 Trial of Nab-paclitaxel in Combination With Anti-PD1 Therapy in Advanced Urothelial Cancer.

PURPOSE: Immune checkpoint inhibitor therapy and nab-paclitaxel have each shown efficacy in platinum-refractory advanced urothelial cancer. We conducted a single-arm phase 2 trial of the combination of nab-paclitaxel and pembrolizumab in platinum-refractory or cisplatin-ineligible advanced urothelial cancer (NCT03240016). MATERIALS AND METHODS: Eligible patients had RECIST 1.1 measurable and cisplatin-ineligible or platinum-refractory advanced urothelial cancer. Patients received nab-paclitaxel at starting dose of 125 mg/m2 intravenously on days 1 and 8 and pembrolizumab 200 mg intravenously on day 1 in 21-day cycles until progression, intolerable toxicity, or death. Nab-paclitaxel was permitted to be discontinued after 6 cycles. The nab-paclitaxel starting dose was reduced to 100 mg/m2 after planned interim analysis. Primary end point was overall response rate by RECIST 1.1. Secondary end points included safety/toxicity, duration of response, progression-free survival), and overall survival. RESULTS: Between February 2018 and April 2021, 36 response-evaluable patients were enrolled. There was an equal split of platinum-refractory and cisplatin-ineligible patients. Confirmed overall response rate was 50.0% (18/36) including 3 complete and 15 partial responses; 31/36 patients experienced some tumor shrinkage. At a median follow-up of 19.7 months, median duration of response was 4.4 months (95% CI: 4.0-8.6), median progression-free survival 6.8 months (95% CI: 4.4-not reached), and median overall survival 18.2 months (95% CI: 10.6-not reached). Grade ≥3 adverse events occurred in 21/36 patients including fatigue (n=6) and anemia (n=4). Ten patients had immune-mediated adverse events. CONCLUSIONS: The combination of nab-paclitaxel and pembrolizumab exhibited promising activity in advanced urothelial cancer and warrants further study in this population. After reduction in nab-paclitaxel starting dose, no unanticipated or unexpected toxicities emerged.

Improving the Quality of Upper Urinary Tract Stone Surgery: External Validation of a Statewide Collaborative's Efforts to Reduce Emergency Department Visits After Ureteroscopy.

PURPOSE: The ROCKS (Reducing Operative Complications from Kidney Stones) program in MUSIC (Michigan Urological Surgery Improvement Collaborative) was created to optimize ureteroscopy outcomes. Through data collection, distribution of reports, patient education, and standardization of medication, post-ureteroscopy emergency department visits in Michigan have declined. It is unclear whether this is because of statewide quality efforts or due to national trends. We therefore sought to understand emergency department visit rates in Michigan compared to a national data set. MATERIALS AND METHODS: We compared the MUSIC ROCKS clinical registry in Michigan against a national cohort, Optum's de-identified Clinformatics Data Mart, from 2016-2021 (excluding Michigan). We identified patients who underwent ureteroscopy and the proportion who had a postoperative emergency department visit within 30 days. Emergency department rates were modeled over time, adjusting for age, gender, comorbidity, and ureteral stenting. RESULTS: We identified 24,688 patients in MUSIC ROCKS and 99,340 in the Clinformatics Data Mart database who underwent ureteroscopy. The risk-adjusted emergency department visit rate in MUSIC ROCKS significantly declined over the study period (10.5% in 2016 to 6.9% in 2021, P < 0.001) while the mean emergency department visit rate in the Clinformatics Data Mart cohort was 9.9% and did not change over time (9.6% in 2016 to 10% in 2021). Comparing emergency department visits between the cohorts, the MUSIC ROCKS rate significantly declined relative to the Clinformatics Data Mart (P < 0.001) over the study period. CONCLUSIONS: Postoperative emergency department visit rates in Michigan have declined significantly after ureteroscopy since the establishment of MUSIC ROCKS. This decline outpaced national rates, providing evidence that systematic quality initiatives can improve urological care.

Practice patterns and outcomes of urgent versus elective ureteroscopy in a statewide surgical collaborative.

PURPOSE: Urgent indications for nephrolithiasis treatment include obstruction with intractable pain or renal impairment without untreated infection. Patients and hospitals may benefit from urgent primary ureteroscopy. We aimed to examine variation in urgent ureteroscopy utilization and associated outcomes. METHODS: Using Reducing Operative Complications from Kidney Stones (ROCKS), we identified all ureteroscopy's between 2016 and 2019. Cases were classified by acuity (elective versus urgent). We assessed practice/urologist variation in urgent ureteroscopy performance. We characterized patients demographic, operative and outcomes data, making bivariate comparisons with elective ureteroscopy to understand implications of urgent surgery. We performed multilevel modeling to understand factors associated with unplanned healthcare encounters after urgent ureteroscopy. RESULTS: 12,859 cases were identified from 33 practices and 204 urologists, 10,854 (84.4%) elective and 2005 (15.6%) urgent. Urgent ureteroscopy was performed on younger patients (53 vs 57, p < 0.001), with higher rates of ureteral stones (72.8% vs 56.8%, p < 0.001). Urgent ureteroscopy rates varied widely by practice (2-70%) and urologist (0-98%). Urgent ureteroscopy had higher stenting rates (77.4% vs 72.5%, p < 0.001), stone free rates (66% vs 58.4%, p < 0.001), and postoperative ED visits (11% vs 7.2%, p < 0.001). There were no differences in intraoperative complications or unplanned hospitalizations. Factors predictive of ED visits in urgent ureteroscopy included concomitant ureteral/renal stone location (OR = 1.53, CI = 1.05-2.23, p = 0.035). CONCLUSIONS: In Michigan elective ureteroscopy is performed 5 times more frequently than urgent ureteroscopy with wide variation. Urgent ureteroscopy demonstrated low morbidity. Urgent ureteroscopy produced modestly higher stone free rates with a slightly increased frequency of unscheduled ED visits particularly for ureteral stones.

TrueNTH Sexual Recovery Intervention for couples coping with prostate cancer: Randomized controlled trial results.

BACKGROUND: Despite significant sexual dysfunction and distress after localized prostate cancer treatment, patients typically receive only physiologic erectile dysfunction management. The authors performed a randomized controlled trial of an online intervention supporting couples' posttreatment recovery of sexual intimacy. METHODS: Patients treated with surgery, radiation, or combined radiation and androgen deprivation therapy who had partners were recruited and randomized to an online intervention or a control group. The intervention, tailored to treatment type and sexual orientation, comprised 6 modules addressing expectations for sexual and emotional sequelae of treatment, rehabilitation, and guidance toward sexual intimacy recovery. Couples, recruited from 6 sites nationally, completed validated measures at the baseline and 3 and 6 months after treatment. Primary outcome group differences were assessed with t tests for individual outcomes. RESULTS: Among 142 randomized couples, 105 patients (mostly surgery) and 87 partners completed the 6-month survey; this reflected challenges with recruitment and attrition. There were no differences between the intervention and control arms in Patient-Reported Outcomes Measurement Information System Global Satisfaction With Sex Life scores 6 months after treatment (the primary outcome). Three months after treatment, intervention patients and partners reported more engagement in penetrative and nonpenetrative sexual activities than controls. More than 73% of the intervention participants reported high or moderate satisfaction with module content; more than 85% would recommend the intervention to other couples. CONCLUSIONS: Online psychosexual support for couples can help couples to connect and experience sexual pleasure early after treatment despite patients' sexual dysfunction. Participants' high endorsement of the intervention reflects the importance of sexual health support to couples after prostate cancer treatment. LAY SUMMARY: This study tested a web-based program supporting couples' sexual recovery of sexual intimacy after prostate cancer treatment. One hundred forty-two couples were recruited and randomly assigned to the program (n = 60) or to a control group (n = 82). The program did not result in improvements in participants' satisfaction with their sex life 6 months after treatment, but couples in the intervention group engaged in sexual activity sooner after treatment than couples in the control group. Couples evaluated the program positively and would recommend it to others facing prostate cancer treatment.

What Is a Normal Testosterone Level for Young Men? Rethinking the 300 ng/dL Cutoff for Testosterone Deficiency in Men 20-44 Years Old.

PURPOSE: There is an age-related decline in male testosterone production. It is therefore surprising that young men are evaluated for testosterone deficiency with the same cutoff of 300 ng/dL that was developed from samples of older men. Our aim is to describe normative total testosterone levels and age-specific cutoffs for low testosterone levels in men 20 to 44 years old. MATERIALS AND METHODS: We analyzed the 2011-2016 National Health and Nutrition Examination Surveys, which survey nationally representative samples of United States residents. Men 20 to 44 years old with testosterone levels were included. Men on hormonal medications, with a history of testicular cancer or orchiectomy, and with afternoon/evening laboratory values were excluded. We separated men into 5-year intervals and evaluated the testosterone levels of each age group, and for all men 20 to 44 years old. We used the American Urological Association definition of a "normal testosterone level" (the "middle tertile") to calculate age-specific cutoffs for low testosterone levels. RESULTS: Our final analytic cohort contained 1,486 men. Age-specific middle tertile levels were 409-558 ng/dL (20-24 years old), 413-575 ng/dL (25-29 years old), 359-498 ng/dL (30-34 years old), 352-478 ng/dL (35-39 years old), and 350-473 ng/dL (40-44 years old). Age-specific cutoffs for low testosterone levels were 409, 413, 359, 352, and 350 ng/dL, respectively. CONCLUSIONS: Diagnosis of testosterone deficiency has traditionally been performed in an age-indiscriminate manner. However, young men have different testosterone reference ranges than older men. Accordingly, age-specific normative values and cutoffs should be integrated into the evaluation of young men presenting with testosterone deficiency.

Incomplete bladder emptying and urinary tract infections after botulinum toxin injection for overactive bladder: Multi-institutional collaboration from the SUFU research network.

INTRODUCTION: Onabotulinumtoxin A (BTX-A) is an effective therapy for overactive bladder (OAB), however, adverse events may prevent patients from initiating therapy. The study objective was to report real-world rates of incomplete emptying and urinary tract infection (UTI) in men and women undergoing BTX-A for OAB. METHODS: Eleven clinical sites performed a retrospective study of adults undergoing first-time BTX-A injection (100 units) for idiopathic OAB in 2016. Exclusions included: postvoid residual (PVR) > 150 ml, prior BTX-A, pelvic radiation, or need for preprocedure catheterization. Primary outcomes at 6 months were incomplete emptying (clean intermittent catheterization [CIC] or PVR ≥ 300 ml without the need for CIC); and UTI (symptoms with either positive culture or urinalysis or empiric treatment). We compared rates of incomplete emptying and UTI within and between sexes, using univariate and multivariable models. RESULTS: 278 patients (48 men and 230 women) met inclusion criteria. Mean age was 65.5 years (range: 24-95). 35% of men and 17% of women had incomplete emptying. Men had 2.4 (95% CI: 1.04-5.49) higher odds of incomplete emptying than women. 17% of men and 23.5% of women had ≥1 UTI, the majority of which occurred within the first month following injection. The strongest predictor of UTI was a history of prior UTI (OR: 4.2 [95% CI: 1.7-10.3]). CONCLUSIONS: In this multicenter retrospective study, rates of incomplete emptying and UTI were higher than many previously published studies. Men were at particular risk for incomplete emptying. Prior UTI was the primary risk factor for postprocedure UTI.

SIMPLifying Urology Residency Operative Assessments: A Pilot Study in Urology Training.

PURPOSE: The Society for Improving Medical Professional Learning (SIMPL) app is an innovative, convenient and validated smartphone-based tool to evaluate residents' operative performance. In this study, we describe the initial implementation of SIMPL in our program's pediatric urology rotation-the first among urology residencies-and provide preliminary data on its adoption by residents and faculty. MATERIALS AND METHODS: Residents and faculty in our pediatric urology division submitted SIMPL evaluations following surgical cases from August 2019 to July 2020. Evaluations consisted of ratings in 3 domains: resident autonomy, resident operative performance and patient-related case complexity. An online survey was also used to gauge attitudes towards SIMPL, describe patterns of use and solicit feedback on areas for improvement. RESULTS: Eight residents and 6 faculty submitted 141 evaluations, with 76.6% of evaluated cases having both faculty and resident ratings. Verbal feedback was included in 94.2%. Faculty-resident agreement ranged from 68.6% to 75.2% (kappa=0.47 to 0.61). Faculty rated postgraduate year (PGY)-4 residents as more autonomous (p=0.040) and higher performing (p=0.028) than PGY-3 residents. All participants agreed that SIMPL was easy to use and compared favorably to existing avenues of feedback. Barriers to implementation included lack of reminders for evaluations and evaluation fatigue. CONCLUSIONS: The SIMPL application improved both frequency and quality of resident operative feedback. Among participants, SIMPL was preferred over the existing feedback system at our institution.

Ureteral Stent Placement following Ureteroscopy Increases Emergency Department Visits in a Statewide Surgical Collaborative.

PURPOSE: Ureteral stents are commonly placed after ureteroscopy. Although studies indicate that stents are associated with patient discomfort, their impact on downstream health services use is unclear. We examined patterns of stent utilization in Michigan and their association with unplanned health care encounters. MATERIALS AND METHODS: We used the Michigan Urological Surgery Improvement Collaborative's Reducing Operative Complications from Kidney Stones (MUSIC ROCKS) clinical registry to identify ureteroscopy cases between 2016 and 2019. Factors associated with stent placement were examined using bivariate and multivariable statistics. Using multivariable logistic regression, we evaluated whether stent placement was associated with emergency department visits and hospitalizations within 30 days. RESULTS: We identified 9,662 ureteroscopies and a stent was placed in 7,025 (73%) of these. Frequency of stent use across the 137 urologists varied (11%-100%, p <0.001) and was not associated with total case volume. Factors associated with stent use included age and stone size. Pre-stented cases and renal stones had a decreased odds of stent placement. On multivariable analysis after adjusting for risk factors, stent placement was associated with a 1.25 higher odds of emergency department visit (OR 1.25, 95% CI 1.01-1.54, p=0.043) but not hospitalization (OR 1.28, 95% CI 0.94-1.76, p=0.12). In a single high volume practice, 0.5% of cases that omitted a stent required urgent stenting postoperatively. CONCLUSIONS: There is substantial variation in the use of stents in Michigan, irrespective of case volume. Stent placement significantly increased the odds of an emergency department visit after surgery. Importantly, stent omission rarely required subsequent urgent stent placement.

Long-term follow-up after radiotherapy for prostate cancer with and without rectal hydrogel spacer: a pooled prospective evaluation of bowel-associated quality of life.

OBJECTIVE: To evaluate the long-term bowel-associated quality of life (QOL) in men after radiotherapy (RT) for prostate cancer with and without the use of rectal hydrogel spacer. PATIENTS AND METHODS: The patients' QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) and mean changes from baseline in EPIC domains were evaluated. A total of 215 patients from a randomised multi-institutional trial of RT, with or without hydrogel spacer, with a QOL endpoint were pooled with 165 non-randomised patients from a single institution with prospective QOL collection in patients with or without hydrogel spacer. The proportions of men with minimally important differences (MIDs) relative to pre-treatment baseline in the bowel domain were tested using repeated measure logistic models with a pre-specified threshold for clinically significant declines (≥5 equivalent to MIDx1 and ≥10 equivalent to MIDx2). RESULTS: A total of 380 men were evaluated (64% with spacer and 36% without) with QOL data being available for 199 men with >24 months of follow-up [median (range) 39.5 (31-71.4) months]. Treatment with spacer was associated with less decline in average long-term bowel QOL (89.4 for control and 94.7 for spacer) with differences at >24 months meeting the threshold of a MID difference between cohorts (bowel score difference from baseline: control = -5.1, spacer = 0.3, difference = -5.4; P < 0.001). When evaluated over time men without spacer were more likely to have MIDx1 (5 points) declines in bowel QOL (P = 0.01). At long-term follow-up MIDx1 was 36% without spacer vs 14% with spacer (P <0.001; odds ratio [OR] 3.5, 95% CI 1.7-6.9) while MIDx2 was seen in 19% vs 6% (P = 0.008; OR 3.6, 95% CI 1.4-9.1). The use of spacer was associated with less urgency with bowel movements (P = 0.002) and fewer loose stools (P = 0.009), as well as less bother with urgency (P = 0.007) and frequency of bowel movements (P = 0.009). CONCLUSIONS: In this pooled analysis of QOL after prostate RT with up to 5 years of follow-up, use of a rectal spacer was associated with preservation of bowel QOL. This QOL benefit was preserved with long-term follow-up.

Real-world comparison of immune checkpoint inhibitors in non-small cell lung cancer following platinum-based chemotherapy.

PURPOSE: Immunotherapy is a relatively new treatment modality for advanced non-small cell lung cancer following platinum-based chemotherapy. Nivolumab, pembrolizumab, and atezolizumab demonstrated superior outcomes and improved tolerability compared to standard treatment in randomized controlled trials; however, these studies vary significantly in inclusion criteria and study design. To our knowledge, the efficacy and safety of nivolumab and atezolizumab following platinum-based chemotherapy have not been directly compared to one another in a real-world clinic setting. METHODS: We retrospectively compared immunotherapy response rates and toxicity in patients with stage IV or recurrent non-small cell lung cancer following progression during or after platinum-based chemotherapy. RESULTS: Among 124 eligible patients, the objective response rate was 14.8% in the nivolumab group (n = 81) vs. 13.9% in the atezolizumab group (n = 43) (p = 0.897). Median overall survival was 8.4 months with nivolumab (95% confidence interval (CI), 6.3 to 11.2) vs. 6.5 months with atezolizumab (95% CI, 4.7 to not reached). Median progression free survival was 2.2 months (95% CI, 1.7 to 2.8) and 2.0 months (95% CI, 1.8 to 2.7) in the nivolumab and atezolizumab groups, respectively. Treatment-related adverse events occurred in 70.4% of patients in the nivolumab group and 65.1% in the atezolizumab group. CONCLUSIONS: There was no statistically significant difference in efficacy outcomes in patients with non-small cell lung cancer who received atezolizumab or nivolumab after progression during or after platinum-based chemotherapy. Response rates in this study were numerically lower than response rates observed in the landmark randomized controlled trials leading to approval of immunotherapy in this setting. Rates of treatment-related adverse events were similar between groups.

Characterization of glycine-N-acyltransferase like 1 (GLYATL1) in prostate cancer.

BACKGROUND: Recent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine-N-acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen. METHOD: We performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high-density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA-sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways. RESULTS: Our in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers had higher GLYATL1 expression compared to high-grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways. CONCLUSIONS: In summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings.

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma.

Background Pazopanib is approved for metastatic renal cell carcinoma (RCC). We assessed the safety and efficacy of pazopanib with a low fat meal (LFM): <400 cal and < 20% fat or 10 g per meal. Methods A single arm study of pazopanib with a LFM in 16 adult patients with metastatic RCC with a clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤ 2, and ≤ 3 prior therapies. Pazopanib at 400 mg daily given with LFM for 12 weeks. Incremental dose increases up to 800 mg, or irreversible decreases to 200 mg, allowed every 2 weeks. Primary study endpoint was safety; adverse events (AE) measured per CTCAE version 4.0. Secondary endpoints of RECIST 1.1 response with assessment as 12 weeks; pharmacokinetic (PK) analysis at nine time points, and CYP3A4 polymorphism evaluation. Results Pazopanib with a LFM was well tolerated; 13 of 16 subjects completed all 12 weeks. Three patients withdrew due to adverse events (AEs), with five occurrences of grade 3 AEs. Conclusions Pazopanib with a LFM has acceptable safety and comparable efficacy to fasting administration. Total median pazopanib dose per subject for the study duration was 63.5% of maximum possible conventional dose. A larger study is warranted. Clinical Trial Registration Number: NCT02729194.

Epididymectomy Is an Effective Treatment for Chronic Epididymal Pain.

INTRODUCTION: Chronic scrotal pain is difficult to manage, and epididymectomy is a treatment option for a subset of men with pain localized to the epididymis. We sought to evaluate the efficacy of epididymectomy at our institution. METHODS: Between 2000 and 2020, 225 men underwent epididymectomy at our institution for pain localized to the epididymis and not part of a greater constellation of pelvic pain or urinary symptoms. Our primary outcome measure was change in pain after epididymectomy, categorized as cured/improved or no change/worsened. Multivariable logistic regression compared the impact of pain duration, and surgical and psychiatric histories on postoperative pain. RESULTS: Patients in both outcome categories-cured/improved and no change/worsened-were similar in age and BMI. Overall, 162 patients (72%) reported cured/improved pain at the last documented follow-up visit. Median follow-up time was 12 (IQR 1-364) weeks. About half of the cohort (n = 117, 52%) had a prior vasectomy, and there was no difference in outcome based on vasectomy history on multivariate analysis (OR 0.625, P = .3). Men with pain duration > 1 year (OR 0.46, P = .03), diagnosed psychiatric conditions (OR 0.44, P = .04), or prior scrotal/inguinal/abdominal surgeries other than vasectomy (OR 0.47, P = .03) had decreased odds of pain relief after epididymectomy. CONCLUSIONS: This 20-year analysis is the largest review of postepididymectomy outcomes reported. Among carefully screened men, 72% had resolution or improvement of scrotal pain. Epididymectomy is most effective for men with < 1 year of focal epididymal pain, with no history of psychiatric conditions or scrotal/inguinal/abdominal surgery other than vasectomy.

Poor Glycemic Control Increases Dental Risk in a Sri Lankan Population.

Introduction: The aim of our study was to investigate the impact of diabetes-related factors on the dental disease outcomes of diabetes patients in Trincomalee, Sri Lanka. Materials and Methods: Dental data were collected from 80 type-2-diabetic individuals. A dental risk score was calculated based on the frequency of dental outcomes observed and categorized as low risk (≤3 dental outcomes) and high risk (>3 dental outcomes). Results: In this cohort of men and women with type 2 diabetes, there was a high frequency of periodontal related outcomes, including missing teeth (70%), gingival recessions (40%), tooth mobility (41%), and bleeding (20%). Thirty-nine (39%) of participants had high dental risk, while forty-nine (61%) had low risk. Conclusions: After controlling for age, participants with higher capillary blood glucose levels had 3-fold greater odds of a high dental risk score (OR = 2.93, 95%CI = 1.13, 7.61). We found that poor glycemic control indicated by elevated capillary blood glucose was associated with increased dental risk.