Publications by authors named "Lauren Howard"

150 Publications

Dutasteride Improves Nocturia but Does Not Lead to Better Sleep: Results from the REDUCE Clinical Trial.

J Urol 2021 Feb 19:101097JU0000000000001640. Epub 2021 Feb 19.

Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: In men, complaints of nocturia causing poor sleep are often attributed to benign prostatic hyperplasia (BPH) and treated with BPH medications. We assessed whether treating lower urinary tract symptoms (LUTS) with dutasteride altered either nocturia or sleep quality using data from REDUCE.

Materials And Methods: REDUCE was a 4-year randomized, multi-center trial comparing dutasteride 0.5mg/day vs. placebo for prostate cancer chemoprevention. Study participants were men considered at increased risk of prostate cancer. Eligibility included age 50-75 years, PSA 2.5-10 ng/mL, and one negative prostate biopsy. At baseline, 2-years and 4-years, men completed the International Prostate Symptom Score (IPSS) and MOS Sleep Scale (MOSSS), a 6-item scale assessing sleep. To test differences in nocturia and MOSSS over time, we used linear mixed models adjusted for baseline confounders. Subanalyses were conducted in men symptomatic from LUTS, nocturia, poor sleep, or combinations thereof.

Results: Of 6,914 men with complete baseline data, 80% and 59% were assessed at 2- and 4-year follow-up. Baseline characteristics were balanced between treatment arms. Dutasteride improved nocturia at 2 (-0.15, [-0.21,-0.09]) and 4 years (-0.24, [-0.31,-0.18]), but did not improve sleep. When limited to men symptomatic from LUTS, nocturia, poor sleep or combinations thereof, results mirrored findings from the full cohort.

Conclusions: In men with poor sleep who complain of nocturia, treatment of LUTS with dutasteride modestly improves nocturia but has no effect on sleep. These results suggest men with poor sleep who complain of nocturia may not benefit from oral BPH treatment.
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http://dx.doi.org/10.1097/JU.0000000000001640DOI Listing
February 2021

Family history of prostate cancer and prostate tumor aggressiveness in black and non-black men;results from an equal access biopsy study.

Cancer Causes Control 2021 Feb 2. Epub 2021 Feb 2.

Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, 97 Lisburn Road, Room 2.15, Belfast, BT9 7AE, UK.

Purpose: To test for racial differences in associations between family history (FH) of prostate cancer (PC) and prostate cancer aggressiveness in a racially diverse equal access population undergoing prostate biopsy.

Subjects/patients And Methods: We prospectively enrolled men undergoing prostate biopsy at the Durham Veterans Administration from 2007 to 2018 and assigned case or control status based on biopsy results. Race and FH of PC were self-reported on questionnaires. Logistic regression was used to test the association between FH and PC diagnosis overall and by tumor aggressiveness [high- (Grade Group 3-5) or low-grade (Grade Group 1-2) vs. no cancer], overall, and stratified by race. Models were adjusted for age and year of consent, race, PSA level, digital rectal exam findings, prostate volume, and previous (negative) biopsy receipt.

Results: Of 1,225 men, 323 had a FH of PC and 652 men were diagnosed with PC on biopsy. On multivariable analysis, FH was associated with increased odds of high-grade PC in black (OR 1.85, p = 0.041) and all men (OR 1.56, p = 0.057) and was unrelated to overall or low-grade PC diagnosis, overall, or stratified by race (all p ≥ 0.325). In sensitivity analyses among men without a previous biopsy, results were slightly more pronounced.

Conclusion: In this setting of equal access to care, positive FH of PC was associated with increased tumor aggressiveness in black men, but not non-black men undergoing prostate biopsy. Further research is required to tease apart the contribution of genetics from increased PC awareness potentially influencing screening and biopsy rates in men with FH.
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http://dx.doi.org/10.1007/s10552-020-01389-8DOI Listing
February 2021

Individual differences in gesture interpretation predict children's propensity to pick a gesturer as a good informant.

J Exp Child Psychol 2021 May 11;205:105069. Epub 2021 Jan 11.

Department of Psychology, Franklin & Marshall College, Lancaster, PA 17604, USA.

To learn from others, children rely on cues (e.g., familiarity, confidence) to infer who around them will provide useful information. We extended this research to ask whether children will use an informant's inclination to gesture as a marker of whether or not the informant is a good person to learn from. Children (N = 459, ages 4-12 years) watched short videos in which actresses made statements accompanied by meaningful iconic gestures, beat gestures (which act as prosodic markers with speech), or no gestures. After each trial, children were asked "Who do you think would be a good teacher?" (good teacher [experimental] condition) or "Who do you think would be a good friend?" (good friend [control] condition). Results show that children do believe that someone who produces iconic gesture would make a good teacher compared with someone who does not, but this is only later in childhood and only if children have the propensity to see gesture as meaningful. The same effects were not found in the good friend condition, indicating that children's responses are not just about liking an adult who gestures more. These findings have implications for how children attend to and learn from instructional gesture.
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http://dx.doi.org/10.1016/j.jecp.2020.105069DOI Listing
May 2021

Monocyte counts and prostate cancer outcomes in white and black men: results from the SEARCH database.

Cancer Causes Control 2021 Feb 4;32(2):189-197. Epub 2021 Jan 4.

Center for Integrated Research On Cancer and Lifestyle, Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8631 West 3rd Street Suite 430W, Los Angeles, CA, 90048, USA.

Purpose: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men.

Methods: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders.

Results: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP.

Conclusion: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.
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http://dx.doi.org/10.1007/s10552-020-01373-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856261PMC
February 2021

Do Hispanic Men Have Worse Outcomes After Radical Prostatectomy? Results From SEARCH.

Urology 2020 Nov 12. Epub 2020 Nov 12.

Section of Urology, Division of Surgery, Durham VA Medical Center, Durham, North Carolina; Center for Integrated Research in Cancer and Lifestyle, Division of Urology, Department of Surgery, and the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Objective: To examine the associations between ethnicity and outcomes after radical prostatectomy (RP) among Hispanics. While non-Hispanic Black men have worse prostate cancer (PC) outcomes, there are limited data on outcomes of Hispanic men, especially after RP.

Methods: We identified 3789 White men who underwent RP between 1988 and 2017 in the Shared Equal Access Regional Cancer Hospital database. Men were categorized as Hispanic or non-Hispanic. Logistic regression was used to test the association between ethnicity and PC adverse features. Cox models were used to test the association between ethnicity and biochemical recurrence (BCR), metastases, and castration-resistant PC (CRPC). All models were adjusted for age, prostate-specific antigen, clinical stage, biopsy grade group, surgery year, and surgical center.

Results: Of 3789 White men, 236 (6%) were Hispanic. Hispanic men had higher prostate-specific antigen, but all other characteristics were similar between ethnicities. On multivariable analysis, there was no difference between ethnicities in odds of extracapsular extension, seminal vesicle invasion, positive margins, positive lymph nodes, or high-grade disease (odds ratio 0.62-0.89, all P > .07). A total of 1168 men had BCR, 182 developed metastasis, and 132 developed CRPC. There was no significant association between Hispanic ethnicity and risk of BCR, metastases, or CRPC (hazards ratio 0.39-0.85, all P > .06).

Conclusion: In an equal access setting, we found no evidence Hispanic White men undergoing RP had worse outcomes than non-Hispanic White men. In fact, all hazard ratios were <1 and although they did not achieve statistical significance, suggest perhaps slightly better outcomes for Hispanic men. Larger studies are needed to confirm findings.
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http://dx.doi.org/10.1016/j.urology.2020.10.043DOI Listing
November 2020

The application of noninvasive, restraint-free eye-tracking methods for use with nonhuman primates.

Behav Res Methods 2020 Sep 15. Epub 2020 Sep 15.

Department of Psychology, Nottingham Trent University, Nottingham, UK.

Over the past 50 years there has been a strong interest in applying eye-tracking techniques to study a myriad of questions related to human and nonhuman primate psychological processes. Eye movements and fixations can provide qualitative and quantitative insights into cognitive processes of nonverbal populations such as nonhuman primates, clarifying the evolutionary, physiological, and representational underpinnings of human cognition. While early attempts at nonhuman primate eye tracking were relatively crude, later, more sophisticated and sensitive techniques required invasive protocols and the use of restraint. In the past decade, technology has advanced to a point where noninvasive eye-tracking techniques, developed for use with human participants, can be applied for use with nonhuman primates in a restraint-free manner. Here we review the corpus of recent studies (N=32) that take such an approach. Despite the growing interest in eye-tracking research, there is still little consensus on "best practices," both in terms of deploying test protocols or reporting methods and results. Therefore, we look to advances made in the field of developmental psychology, as well as our own collective experiences using eye trackers with nonhuman primates, to highlight key elements that researchers should consider when designing noninvasive restraint-free eye-tracking research protocols for use with nonhuman primates. Beyond promoting best practices for research protocols, we also outline an ideal approach for reporting such research and highlight future directions for the field.
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http://dx.doi.org/10.3758/s13428-020-01465-6DOI Listing
September 2020

Problem solving flexibility across early development.

J Exp Child Psychol 2020 Dec 26;200:104966. Epub 2020 Aug 26.

Department of Psychology, Franklin & Marshall College, Lancaster, PA 17603, USA.

Cognitive flexibility allows individuals to adapt to novel situations. However, this ability appears to develop slowly over the first few years of life, mediated by task complexity and opacity. We used a physically simple novel task, previously tested with nonhuman primates, to explore the development of flexible problem solving in 2-, 3-, and 4-year-old children from a developmental and comparative perspective. The task goal was to remove barriers (straws) from a clear tube to release a ball. The location of the ball, and therefore the number of straws necessary to retrieve it, varied across two test phases (four of five straws and two of five straws, respectively). In Test Phase 1, all children retrieved the ball in Trial 1 and 83.61% used the most efficient method (removing only straws below the ball). Across Phase 1 trials, 4-year-olds were significantly more efficient than 2-year-olds, and solve latency decreased for all age groups. Test Phase 2 altered the location of the ball, allowing us to explore whether children could flexibly adopt a more efficient solution when their original (now inefficient) solution remained available. In Phase 2, significantly more 4-year-olds than 2-year-olds were efficient; the older children showed greater competency with the task and were more flexible to changing task demands than the younger children. Interestingly, no age group was as flexible in Phase 2 as previously tested nonhuman primates, potentially related to their relatively reduced task exploration in Phase 1. Therefore, this causally clear task revealed changes in cognitive flexibility across both early childhood and species.
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http://dx.doi.org/10.1016/j.jecp.2020.104966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449664PMC
December 2020

Sleep quality and prostate cancer aggressiveness: Results from the REDUCE trial.

Prostate 2020 11 24;80(15):1304-1313. Epub 2020 Aug 24.

Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.

Background: Disrupted sleep has been associated with increased risk of certain cancers. Little data exist in prostate cancer. We tested the association between sleep quality and prostate cancer diagnosis overall and by tumor grade in the Reduction by Dutasteride of Prostate Cancer Events chemoprevention trial. We hypothesized that worse sleep quality would be associated with increased tumor aggressiveness.

Methods: At baseline, 5614 men completed a validated six-item questionnaire on sleep quality. We generated a composite score categorized into tertiles to measure overall sleep quality and assessed each sleep quality question individually. Logistic regression was used to test associations between baseline sleep quality and overall, low-grade and high-grade prostate cancer diagnosis at 2-year study-mandated biopsy. Models were stratified by nocturia.

Results: Overall sleep quality was unrelated to overall or low-grade prostate cancer. Worse overall sleep quality was associated with elevated odds of high-grade prostate cancer (odds ratio [OR] 1.15; 95% confidence interval [CI]: 0.83-1.60 and OR 1.39; 95% CI: 1.01-1.92). Men reporting trouble falling asleep at night sometimes vs never had elevated odds of high-grade prostate cancer (OR: 1.51; 95% CI: 1.08-2.09) while trouble staying awake during the day was associated with decreased odds of low-grade prostate cancer (OR: 0.65; 95% CI: 0.49-0.86). Results were similar within strata of nocturia severity.

Conclusions: Overall, associations between sleep quality and prostate cancer were inconsistent. However, there was some evidence for a positive association between insomnia and high-grade prostate cancer, and an inverse relationship between daytime sleepiness and low-grade prostate cancer; findings that should be validated by future studies.
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http://dx.doi.org/10.1002/pros.24052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780858PMC
November 2020

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy.

Prostate 2020 10 7;80(14):1244-1252. Epub 2020 Aug 7.

Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK.

Background: Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI.

Materials And Methods: We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation-treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable-adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT).

Results: Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow-up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87-3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24-1.03; P-interaction = .002), though neither association reached statistical significance. Similar patterns of ADT-stratified associations were observed for PPAT and SFA.

Conclusions: Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.
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http://dx.doi.org/10.1002/pros.24054DOI Listing
October 2020

Obese men undergoing radical prostatectomy: Is robotic or retropubic better to limit positive surgical margins? Results from SEARCH.

Int J Urol 2020 10 17;27(10):851-857. Epub 2020 Jul 17.

Section of Urology, Veterans Affairs Medical Center, Durham, North Carolina, USA.

Objectives: To evaluate the association between obesity and positive surgical margins in patients undergoing retropubic radical prostatectomy versus robotic-assisted laparoscopic prostatectomy.

Methods: We retrospectively reviewed the data of 3141 men undergoing retropubic radical prostatectomy and 1625 undergoing robotic-assisted laparoscopic prostatectomy between 1988 and 2017 at eight Veterans Health Administration hospitals. The positive surgical margin location (peripheral, apical, bladder neck, overall) was determined from pathology reports. We adjusted for age, race, prostate-specific antigen, surgery year, prostate weight, pathological grade group, extracapsular extension, seminal vesicle invasion, hospital surgical volume and surgical method (in analyses not stratified by surgical method). Interactions between body mass index and surgical approach were tested.

Results: Among all patients, higher body mass index was associated with increased odds of overall, peripheral and apical positive surgical margins (OR 1.02-1.03, P ≤ 0.02). Although not statistically significant, there was a trend between higher body mass index and increased odds of bladder neck positive surgical margins (OR 1.03, P = 0.09). Interactions between body mass index and surgical method were significant for peripheral positive surgical margins only (P = 0.024). Specifically, there was an association between body mass index and peripheral positive surgical margins among men undergoing retropubic radical prostatectomy (OR 1.04, P < 0.001), but not robotic-assisted laparoscopic prostatectomy (OR 1.00, P = 0.98). Limitations include lacking individual surgeon data and lacking central pathology review.

Conclusions: In this multicenter cohort, higher body mass index was associated with increased odds of positive surgical margins at all locations except the bladder neck. Furthermore, there was a significant association between obesity and peripheral positive surgical margins in men undergoing retropubic radical prostatectomy, but not robotic-assisted laparoscopic prostatectomy. Long-term clinical significance requires further study.
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http://dx.doi.org/10.1111/iju.14307DOI Listing
October 2020

NONINVASIVE SAMPLING FOR DETECTION OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS AND GENOMIC DNA IN ASIAN () AND AFRICAN () ELEPHANTS.

J Zoo Wildl Med 2020 Jun;51(2):433-437

School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.

Elephant endotheliotropic herpesvirus (EEHV) hemorrhagic disease (EEHV-HD) threatens Asian elephant () population sustainability in North America. Clusters of cases have also been reported in African elephants (). Risk to range country elephant populations is unknown. Currently, EEHV detection depends upon sampling elephants trained for invasive blood and trunk wash collection. To evaluate noninvasive sample collection options, paired invasively collected (blood, trunk wash and oral swabs), and noninvasively collected (chewed plant and fecal) samples were compared over 6 wk from 9 Asian elephants and 12 African elephants. EEHV shedding was detected simultaneously in a paired trunk wash and fecal sample from one African elephant. Elephant γ herpesvirus-1 shedding was identified in six chewed plant samples collected from four Asian elephants. Noninvasively collected samples can be used to detect elephant herpesvirus shedding. Longer sampling periods are needed to evaluate the clinical usefulness of noninvasive sampling for EEHV detection.
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http://dx.doi.org/10.1638/2019-0112DOI Listing
June 2020

Obesity, race, and long-term prostate cancer outcomes.

Cancer 2020 Aug 4;126(16):3733-3741. Epub 2020 Jun 4.

Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California.

Background: The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race.

Methods: Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25 kg/m ), overweight (25-29.9 kg/m ), and obese (≥30 kg/m ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders.

Results: Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30 kg/m , seminal vesicle invasion, and positive surgical margins (all P ≤ .032). During a median follow-up of 7.4 years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P = .035]). No interaction was found between BMI and race in predicting PCSM (P ≥ .88), BCR (P ≥ .81), CRPC (P ≥ .88), or metastasis (P ≥ .60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P ≥ .18).

Conclusions: Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race.
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http://dx.doi.org/10.1002/cncr.32906DOI Listing
August 2020

Race does not predict skeletal-related events and all-cause mortality in men with castration-resistant prostate cancer.

Cancer 2020 Jul 6;126(14):3274-3280. Epub 2020 May 6.

Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: The impact of race on prostate cancer skeletal-related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration-resistant prostate cancer (mCRPC).

Methods: The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan-Meier method. Cox models tested the association between race and SREs and overall mortality.

Results: Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate-specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P < .01). On multivariable analysis, there were no differences noted with regard to SRE risk (hazard ratio [HR], 0.80; 95% CI, 0.59-1.07) or overall mortality (HR, 0.87; 95% CI, 0.73-1.04) between black and nonblack people, although the HRs were <1, which suggested the possibility of better outcomes.

Conclusions: No significant association between black race and risk of SREs and overall mortality was observed in the current study. These data have suggested that efforts to understand the basis for the excess risk of aggressive prostate cancer in black men should focus on cancer development and progression in individuals with early-stage disease.
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http://dx.doi.org/10.1002/cncr.32933DOI Listing
July 2020

Competing Risks of Mortality among Men with Biochemical Recurrence after Radical Prostatectomy.

J Urol 2020 Sep 3;204(3):511-517. Epub 2020 Apr 3.

Division of Urology, Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: Men with biochemical recurrence after radical prostatectomy need information on competing risks of mortality to inform prognosis and guide treatment. We quantified the risk of prostate cancer metastasis and mortality, and other cause mortality across key clinical predictors.

Materials And Methods: We analyzed 1,225 men with biochemical recurrence after radical prostatectomy from 2001 to 2017 in the VA SEARCH database. Multivariable competing risks regression was used to identify predictors and quantify cumulative incidence of metastasis, prostate cancer specific mortality and other cause mortality. Recursive partitioning analysis was used to identify optimum variable cut points for prediction of prostate cancer specific mortality and other cause mortality.

Results: During a median followup of 5.6 years after biochemical recurrence (IQR 2.7-9.1), 243 (20%) men died of other causes and 68 (6%) died of prostate cancer. Multivariable competing risks regression showed that high D'Amico tumor risk and prostate specific antigen doubling time at biochemical recurrence less than 9 months were associated with metastasis and prostate cancer specific mortality (p ≤0.001). Ten-year prostate cancer specific mortality was 14% and 9% for those with high risk tumors and prostate specific antigen doubling time less than 9 months, respectively. Advanced age and worse comorbidity were associated with other cause mortality (p ≤0.001). Ten-year other cause mortality was higher among men 70 years old or older with any Charlson comorbidity (1-3+) (40% to 49%) compared to those with none (20%). Recursive partitioning analysis identified optimal variable cut points for prediction of prostate cancer specific mortality and other cause mortality, with 10-year prostate cancer specific mortality ranging from 3% to 59% and 10-year other cause mortality ranging from 17% to 50% across risk subgroups.

Conclusions: Among men with biochemical recurrence after radical prostatectomy, there is significant heterogeneity in prognosis that can be explained by available clinical variables. Men in their 70s with any major comorbidity are 2 to 10 times more likely to die of other causes than of prostate cancer.
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http://dx.doi.org/10.1097/JU.0000000000001036DOI Listing
September 2020

Soluble Endoglin (sCD105) as a Novel Biomarker for Detecting Aggressive Prostate Cancer.

Anticancer Res 2020 Mar;40(3):1459-1462

Division of Hematology/Oncology, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A.

Background/aim: We have previously found elevated levels of endoglin (CD105) in the prostate cancer (PC) tissue of men with poor prognosis, compared to men with indolent disease. Herein, we examined whether plasma levels of the soluble form of CD105 (sCD105) differ according to the PC grade at diagnosis.

Patients And Methods: We measured sCD105 in 73 subjects with biopsy-confirmed PC at the Durham, North Carolina, Veteran Affairs Health System. The association between sCD105 and intermediate/high-grade PC risk [Gleason Group (GG) 2-5 vs. 1] was examined using regression models.

Results: Of 73 men, 27 had low-grade PC and 46 high-grade PC. Higher GG was linked to lower sCD105 (GG1: 6938 pg/ml, GG2-3: 6150 pg/ml, GG4-5: 5554 pg/ml; p=0.012). On multivariable analysis, lower sCD105 was associated with increased high-grade PC risk (OR=1.33, p=0.028).

Conclusion: Lower sCD105 levels were associated with intermediate and high-risk PC. Further investigation is warranted in a larger PC cohort.
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http://dx.doi.org/10.21873/anticanres.14088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768804PMC
March 2020

A Randomized Controlled Trial of a 6-Month Low-Carbohydrate Intervention on Disease Progression in Men with Recurrent Prostate Cancer: Carbohydrate and Prostate Study 2 (CAPS2).

Clin Cancer Res 2020 06 27;26(12):3035-3043. Epub 2020 Feb 27.

Duke University School of Medicine, Durham, North Carolina.

Purpose: Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer.

Experimental Design: We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m and PSADT 3 to 36 months. The LCD arm was instructed to eat [Formula: see text]20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet.

Results: Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-seven LCD and 18 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (-117 vs. 8 g, < 0.001) and lost weight (-12.1 vs. -0.50 kg, < 0.001). The LCD arm reduced HDL, triglycerides, and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (21 months) and control (15 months, = 0.316) arms. In a exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (28 vs. 13 months, = 0.021) arms. Adverse events were few, usually mild, and returned to baseline by 6 months.

Conclusions: Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3873DOI Listing
June 2020

Partial Validation of the Sleep Health Construct in the Medical Outcomes Study Sleep Questionnaire.

J Clin Psychol Med Settings 2021 Mar;28(1):168-173

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.

Sleep health is postulated as a multi-dimensional construct comprised of sleepiness/alertness, timing, duration, efficiency, and satisfaction. New questionnaires for its measurement have been proposed. We performed secondary data analyses and analyzed responses on a widely used, well-established sleep questionnaire to determine whether the construct might be detectable with an existing questionnaire. Healthy men (n = 7604) aged 55-75 completed the six-item Medical Outcomes Study Sleep Questionnaire (MOSSQ) at baseline in a large, randomized clinical trial [the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial). Two components clearly emerged from a Principal Components Analysis, suggesting that both sleep disturbance and sleep satisfaction are differentiated by the MOSSQ. Selected elements of sleep health are accessible with relatively few questionnaire items. Widespread previous usage of the MOSSQ in both descriptive and interventional research suggests that many previously collected databases could address at least two components of this construct.
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http://dx.doi.org/10.1007/s10880-020-09699-4DOI Listing
March 2021

REPEATED USE OF A THIAFENTANIL-BASED ANESTHESIA PROTOCOL IN AN OKAPI ().

J Zoo Wildl Med 2020 Jan;50(4):993-996

Harter Veterinary Medical Center, San Diego Zoo Safari Park, Escondido, CA 92027, USA.

Seven anesthesia events were performed over 6 wk on a 1.5-yr-old female okapi () being managed for a fetlock injury. A combination of butorphanol (B) (median; range) (0.045; 0.031-0.046 mg/kg), medetomidine (M) (0.037; 0.031-0.037 mg/kg), ketamine (K) (0.553; 0.536-1.071 mg/kg), and thiafentanil (T) (0.0045; 0.0040-0.0046 mg/kg) was administered in a padded stall. One dart containing all drugs was used for the first two anesthesias. Subsequently, BM was administered 10 min prior to KT using two darts. Time (median; range) from initial injection to first effects (6; 3-7 min) and recumbency (14; 4-20 min) were recorded. Induction quality with the one-dart protocol was poor or fair and was good or excellent with the two-dart protocol. Following recumbency, the okapi was intubated and ventilated, and physiological parameters were recorded. Anesthesia was consistently achieved with BMKT, but induction was smoother with the staged two-dart approach. Neither resedation nor renarcotization was observed post-reversal.
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http://dx.doi.org/10.1638/2019-0037DOI Listing
January 2020

Validation of a genomic classifier for prediction of metastasis and prostate cancer-specific mortality in African-American men following radical prostatectomy in an equal access healthcare setting.

Prostate Cancer Prostatic Dis 2020 09 16;23(3):419-428. Epub 2019 Dec 16.

Department of Surgery, Division of Urology, Veteran Affairs Healthcare System, Durham, NC, USA.

Background: The Decipher 22-gene genomic classifier (GC) may help in post-radical prostatectomy (RP) decision making given its superior prognostic performance over clinicopathologic variables alone. However, most studies evaluating the GC have had a modest representation of African-American men (AAM). We evaluated the GC within a large Veteran Affairs cohort and compared its performance to CAPRA-S for predicting outcomes in AAM and non-AAM after RP.

Methods: GC scores were generated for 548 prostate cancer (PC) patients, who underwent RP at the Durham Veteran Affairs Medical Center between 1989 and 2016. This was a clinically high-risk cohort and was selected to have either pT3a, positive margins, seminal vesicle invasion, or received post-RP radiotherapy. Multivariable Cox models and survival C-indices were used to compare the performance of GC and CAPRA-S for predicting the risk of metastasis and PC-specific mortality (PCSM).

Results: Median follow-up was 9 years, during which 37 developed metastasis and 20 died from PC. Overall, 55% (n = 301) of patients were AAM. In multivariable analyses, GC (high vs. intermediate and intermediate vs. low) was a significant predictor of metastasis in all men (all p < 0.001). Consistent with prior studies, relative to CAPRA-S, GC had a higher C-index for 5-year metastasis (0.78 vs. 0.72) and 10-year PCSM (0.85 vs. 0.81). There was a suggestion GC was a stronger predictor in AAM than non-AAM. Specifically, the 5-year metastasis risk C-index was 0.86 in AAM vs. 0.69 in non-AAM and the 10-year PCSM risk C-index was 0.91 in AAM vs. 0.78 in non-AAM. However, the test for interaction of race and the performance of the GC in the Cox model was not significant for either metastasis or PCSM (both p ≥ 0.3).

Conclusions: GC was a very strong predictor of poor outcome and performed well in both AAM and non-AAM. Our data support the use of GC for risk stratification in AAM post-RP. While our data suggest that GC may actually work better in AAM, given the limited number of events, further validation is needed.
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http://dx.doi.org/10.1038/s41391-019-0197-3DOI Listing
September 2020

Pregnancies following long luteal phases in southern white rhinoceros (Ceratotherium simum simum).

Zoo Biol 2020 Mar 3;39(2):141-144. Epub 2019 Dec 3.

San Diego Zoo Global, Escondido, California.

All extant species in the Rhinocerotidae family are experiencing escalating threats in the wild, making self-sustaining captive populations essential genetic reservoirs for species survival. Assisted reproductive technologies (ARTs) will become increasingly important for achieving and maintaining ex situ population sustainability and genetic diversity. Previous reports have shown that a large proportion of captive southern white rhinoceros (SWR) females are irregularly cyclic or acyclic, and that cycling females display two different estrous cycle lengths of approximately 30 or 70 days. It has been suggested that the longer estrous cycle length is infertile or subfertile, as no term pregnancies have been observed following long cycles. Here we report the achievement of two pregnancies following long luteal phases, using ovulation induction and artificial insemination with either fresh or frozen-thawed semen. One female SWR conceived on the first insemination attempt and gave birth to a live offspring. A second female conceived twice in consecutive long cycles although the first embryo was resorbed by 33 days post-insemination. A pregnancy from this female's second insemination is ongoing with expected parturition in November 2019. Whether prolonged estrous cycles in SWR are subfertile or infertile in natural breeding situations remains unclear. However, our findings demonstrate that the application of ARTs following prolonged cycles can result the successful establishment of pregnancies in SWR. Therefore, with ARTs, female SWR otherwise considered nonreproductive due to long estrous cycles may still have the potential for representation and contribution to the ex situ population.
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http://dx.doi.org/10.1002/zoo.21529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187308PMC
March 2020

Reply by Authors.

J Urol 2020 01 14;203(1):127. Epub 2019 Oct 14.

Division of Urology, Veterans Affairs Medical Center, Durham, North Carolina.

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http://dx.doi.org/10.1097/01.JU.0000604076.44320.a0DOI Listing
January 2020

Statin use and longitudinal changes in prostate volume; results from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

BJU Int 2020 02 27;125(2):226-233. Epub 2019 Sep 27.

Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Objective: To test the association between statin use and prostate volume (PV) change over time using data from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, a 4-year randomised controlled trial testing dutasteride for prostate cancer chemoprevention.

Subjects/patients And Methods: We identified men with a baseline negative prostate biopsy from REDUCE who did not undergo prostate surgery or develop prostate cancer over the trial period. Men reported statin use at baseline. PV was determined from transrectal ultrasonography performed to guide prostate biopsy at baseline, and 2- and 4-years after randomisation. Multivariable generalised estimating equations tested differences in PV change over time by statin use, overall and stratified by treatment arm. We tested for interactions between statins and time in association with PV using the Wald test.

Results: Of 4106 men, 17% used statins at baseline. Baseline PV did not differ by statin use. Relative to non-users, statin users had decreasing PVs over the trial period (P = 0.027). Similar patterns were seen in the dutasteride and placebo arms, although neither reached statistical significance. The mean estimated PV was modestly but significantly lower in statin users relative to non-users in the dutasteride arm at 2-years (4.5%, P = 0.032) and 4-years (4.0%, P = 0.033), with similar (3-3.3%) but non-significant effects in the placebo arm.

Conclusion: If confirmed, our present findings support a role for statins in modestly attenuating PV growth, with a magnitude of effect in line with previously reported prostate-specific antigen-lowering effects of statins (~4%). Future studies are needed to assess whether this putative role for statins in PV growth could impact lower urinary tract symptom development or progression.
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http://dx.doi.org/10.1111/bju.14905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980161PMC
February 2020

Racial Discrepancies in Overall Survival among Men Treated with Radium.

J Urol 2020 02 3;203(2):331-337. Epub 2019 Sep 3.

Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Purpose: Several recent studies on metastatic castration resistant prostate cancer demonstrated improved overall survival in black vs white men. Radium is Food and Drug Administration approved for metastatic castration resistant prostate cancer based on a survival benefit in the ALSYMPCA (A Phase III Study of Radium-223 Dichloride in Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal Metastases) trial, in which 94% of participants were white. We identified a real world population of patients with metastatic castration resistant prostate cancer who received radium to compare differences in baseline characteristics and outcomes in black vs nonblack men.

Materials And Methods: We reviewed the charts of all men who received radium in the entire Veterans Affairs system. We compared treatment patterns and baseline characteristics between black and nonblack men. We used Cox models to analyze predictors of time from radium start to overall survival and time to skeletal related events.

Results: We identified 318 patients treated with radium, including 87 (27%) who were black. Median followup after radium initiation was 25.3 months (IQR 13.8-37.1). Black men were younger than nonblack men when starting radium (median age 67 vs 70 years, p <0.001) and they had higher prostate specific antigen (median 159.9 vs 90.2 ng/ml, p=0.014) and alkaline phosphatase (median 163 vs 135 IU/l, p=0.017). A greater proportion of black men received docetaxel prior to radium (77% vs 55%, p <0.001). On multivariable analysis black race was associated with a decreased risk of mortality from the time of radium initiation (HR 0.75, 95% CI 0.57-0.99, p=0.045).

Conclusions: Black men had longer overall survival than nonblack men, although they appeared to receive radium later in the disease course. Further studies are required to verify our findings and explore biological differences between black and nonblack men with metastatic castration resistant prostate cancer.
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http://dx.doi.org/10.1097/JU.0000000000000524DOI Listing
February 2020

Serum Lipids prior to Starting Androgen Deprivation Therapy and Risk of Castration Resistant Prostate Cancer and Metastasis: Results from the SEARCH Database.

J Urol 2020 01 20;203(1):120-127. Epub 2019 Aug 20.

Division of Urology, Veterans Affairs Medical Center, Durham, North Carolina.

Purpose: We tested the association of serum lipid levels prior to androgen deprivation therapy with the risk of castration resistant prostate cancer and metastasis.

Materials And Methods: We identified 302 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who received androgen deprivation therapy after radical prostatectomy for nonmetastatic disease, had never received statins before androgen deprivation therapy and had available serum lipid data within 2 years prior to androgen deprivation therapy. Cox proportional hazards models were used to test associations between total cholesterol (less than 200 vs 200 mg/dl or greater), low density lipoprotein (less than 130 vs 130 mg/dl or greater), high density lipoprotein (40 or greater vs less than 40 mg/dl) and triglycerides (less than 150 vs 150 mg/dl or greater) and the risk of castration resistant prostate cancer and metastasis after androgen deprivation therapy while adjusting for potential confounders. Subanalyses were restricted to men who remained statin nonusers after androgen deprivation therapy.

Results: Median followup after androgen deprivation therapy was 67 months. Castration resistant prostate cancer and metastasis developed in 42 and 44 men, respectively. Men with elevated cholesterol received androgen deprivation therapy in an earlier year and had longer followup and a higher rate of statin use after androgen deprivation therapy. On multivariable analysis total cholesterol and low density lipoprotein were unrelated to castration resistant prostate cancer. Low high density lipoprotein (less than 40 vs 40 mg/dl or greater) was suggestively linked to an increased risk of castration resistant prostate cancer (HR 1.86, 95% CI 0.99-3.48). The association was stronger in men who remained statin nonusers after androgen deprivation therapy (HR 3.64, 95% CI 1.45-9.17). Results for metastasis were similar to those for castration resistant prostate cancer.

Conclusions: Among men with nonmetastatic prostate cancer who started androgen deprivation therapy serum cholesterol was unrelated to castration resistant prostate cancer or metastasis. Low high density lipoprotein was suggestively associated with risks of increased castration resistant prostate cancer and metastasis, particularly in statin never users. Further studies are needed to explore a potential role for lipids in prostate cancer progression after androgen deprivation therapy.
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http://dx.doi.org/10.1097/JU.0000000000000494DOI Listing
January 2020

Learning From Others: The Effects of Agency on Event Memory in Young Children.

Child Dev 2020 07 9;91(4):1317-1335. Epub 2019 Aug 9.

University of Chicago.

Little is known about the influence of social context on children's event memory. Across four studies, we examined whether learning that could occur in the absence of a person was more robust when a person was present. Three-year-old children (N = 125) viewed sequential events that either included or excluded an acting agent. In Experiment 1, children who viewed an agent recalled more than children who did not. Experiments 2a and 2b utilized an eye tracker to demonstrate this effect was not due to differences in attention. Experiment 3 used a combined behavioral and event-related potential paradigm to show that condition effects were present in memory-related components. These converging results indicate a particular role for social knowledge in supporting memory for events.
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http://dx.doi.org/10.1111/cdev.13303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326290PMC
July 2020

Predictors of skeletal-related events and mortality in men with metastatic, castration-resistant prostate cancer: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

Cancer 2019 11 7;125(22):4003-4010. Epub 2019 Aug 7.

Division of Urology, Department of Surgery, The University of Texas Medical Branch, Galveston, Texas.

Background: Although skeletal-related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all-cause mortality among men with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Data were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality.

Results: Of the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow-up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25-3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85-0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91-0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18-3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72-2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61-0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94-0.99), older age (HR, 1.03; 95% CI, 1.02-1.04), higher prostate-specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14-1.28), bone pain (HR, 1.44; 95% CI, 1.23-1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23-2.39) were associated with an increased mortality risk.

Conclusions: Among men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.
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http://dx.doi.org/10.1002/cncr.32414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819222PMC
November 2019

Natural killer cell activity and prostate cancer risk in veteran men undergoing prostate biopsy.

Cancer Epidemiol 2019 10 1;62:101578. Epub 2019 Aug 1.

Department of Surgery, Division of Urology, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Surgery Section, Durham VA Health Care System, Durham, NC, USA.

Background: A previous pilot study found that men with a positive prostate biopsy had low numbers of circulating natural killer (NK) cells, compared to biopsy negative men.

Methods: To confirm these data, we analyzed differences in NK cells from 94 men undergoing prostate biopsy to determine whether NK cells could predict for a positive biopsy. NK cells activity (NKA) was measured by an in vitro diagnostic system, with a pre-defined cut-off value for NKA at 200 pg/mL. Logistic regression and receiver operator characteristics (Area Under the Curve (AUC)) analyses were used to test the diagnostic value of NKA.

Results: The NKA test performance showed specificity of 88%, positive predictive value of 84%, sensitivity of 34%, and a negative predictive value of 41%. Among the 94 men analyzed, NKA was not significantly linked with age, race, digital rectal examination (DRE), prostate volume, PSA or biopsy grade group (all P ≥ 0.14). In multivariable logistic regression analysis, the odds ratio (OR) of low NKA (<200 pg/mL) for the detection of PC was 4.89, 95%CI 1.34-17.8, with a ROC area under the curve of 0.79 in all participants and increasing to 0.83 and 0.85 for the detection of PC and high-grade PC, respectively, among men with a normal DRE.

Conclusions: Men with a low NKA value had five-times higher odds of PC at biopsy. The implementation of this NKA assay in the clinic together with PSA may help to advise patients with the highest risk of PC whether, or not, to undergo a prostate biopsy.
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http://dx.doi.org/10.1016/j.canep.2019.101578DOI Listing
October 2019

The misdiagnosis of interstitial cystitis/bladder pain syndrome in a VA population.

Neurourol Urodyn 2019 09 14;38(7):1966-1972. Epub 2019 Jul 14.

Samuel Oschin Comprehensive Cancer Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.

Aims: The complexity of Interstitial Cystitis/bladder Pain Syndrome (IC/BPS) has led to a great deal of uncertainty around the diagnosis and prevalence of the condition. Under the hypothesis that IC/BPS is frequently misdiagnosed, we sought to assess the accuracy of the ICD-9/ICD-10 code for IC/BPS using a national data set.

Methods: Using the Veterans Affairs Informatics and Computing Infrastructure, we identified a random sample of 100 patients with an ICD-9/ICD-10 diagnosis of IC/BPS (595.1/N30.10) by querying all living patients in the Veterans Affairs (VA) system. We purposely sampled men and women equally to better understand gender-specific practice patterns. Patients were considered a correct IC/BPS diagnosis if they had two visits complaining of bladder-centric pain in the absence of positive urine culture at least 6 weeks apart. Patients were considered not to have IC/BPS if they had a history of pelvic radiation, systemic chemotherapy, metastatic cancer, or bladder cancer.

Results: Of the 100 patients, 48 were female and 52 were male. Five had prior radiation, one had active cancer, and 10 had bladder cancer (all male), and an additional fifteen had insufficient records. Of the remaining 69 patients, 43% did not have IC/BPS. Of these patients who did not have IC/BPS, 43% complained only of overactive bladder (OAB) symptoms, which was more common in women (63%) than men (21%), P = .003.

Conclusions: In our small sample from a nationwide VA system, results indicate that IC/BPS has a high misdiagnosis rate. These findings shed light on the gender-specific diagnostic complexity of IC/BPS.
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http://dx.doi.org/10.1002/nau.24100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169430PMC
September 2019

Practice patterns and outcomes of equivocal bone scans for patients with castration-resistant prostate cancer: Results from SEARCH.

Asian J Urol 2019 Jul 18;6(3):242-248. Epub 2019 Jan 18.

Urology Section, Department of Surgery, Veterans Affairs Medical Center, Durham, NC, USA.

Objective: To review follow-up imaging after equivocal bone scans in men with castration resistant prostate cancer (CRPC) and examine the characteristics of equivocal bone scans that are associated with positive follow-up imaging.

Methods: We identified 639 men from five Veterans Affairs Hospitals with a technetium-99m bone scan after CRPC diagnosis, of whom 99 (15%) had equivocal scans. Men with equivocal scans were segregated into "high-risk" and "low-risk" subcategories based upon wording in the bone scan report. All follow-up imaging (bone scans, computed tomography [CT], magnetic resonance imaging [MRI], and X-rays) in the 3 months after the equivocal scan were reviewed. Variables were compared between patients with a positive negative follow-up imaging after an equivocal bone scan.

Results: Of 99 men with an equivocal bone scan, 43 (43%) received at least one follow-up imaging test, including 32/82 (39%) with low-risk scans and 11/17 (65%) with high-risk scans ( = 0.052). Of follow-up tests, 67% were negative, 14% were equivocal, and 19% were positive. Among those who underwent follow-up imaging, 3/32 (9%) low-risk men had metastases 5/11 (45%) high-risk men ( = 0.015).

Conclusion: While 19% of all men who received follow-up imaging had positive follow-up imaging, only 9% of those with a low-risk equivocal bone scan had metastases versus 45% of those with high-risk. These preliminary findings, if confirmed in larger studies, suggest follow-up imaging tests for low-risk equivocal scans can be delayed while high-risk equivocal scans should receive follow-up imaging.
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http://dx.doi.org/10.1016/j.ajur.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595156PMC
July 2019

Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?

Clin Genitourin Cancer 2019 10 24;17(5):e930-e938. Epub 2019 May 24.

Cedars-Sinai Medical Center, Los Angeles, CA.

Purpose: In order to better time salvage radiotherapy (SRT) for post-radical prostatectomy biochemical failure, we examined the association between pre-SRT prostate-specific antigen (PSA) and PSA control as a function of the new prognostic grade group (PGG) system.

Patients And Methods: Using the Shared Equal Access Regional Cancer Hospital database, we identified men after radical prostatectomy with PSA > 0.2 ng/mL and without cancer involvement of lymph nodes who underwent SRT alone. SRT failure was defined as post-SRT PSA nadir + 0.2 ng/mL or receipt of post-SRT hormone therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99, and ≥ 1.0 ng/mL). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by PGG.

Results: A total of 358 men met the inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. A total of 174 men (49%) had pre-SRT PSA 0.2-0.49 ng/mL, 97 (27%) PSA 0.5-0.99 ng/mL, and 87 (24%) PSA ≥ 1.0 ng/mL. On multivariable analysis among men with PGG 1-2, pre-SRT PSA 0.2-0.49 ng/mL had similar outcomes as PSA 0.5-0.99 ng/mL; those with PSA ≥ 1.0 ng/mL had higher recurrence risks (hazard ratio = 2.78, P < .001). Among PGG 3-5, PSA 0.5-0.99 ng/mL or ≥ 1.0 ng/mL had a higher recurrence risk (hazard ratio = 2.15, P = .021; and hazard ratio = 2.49, P = .010, respectively) versus PSA 0.2-0.49 ng/mL.

Conclusion: In men with higher-grade prostate cancer (PGG 3-5), SRT should be provided earlier (PSA < 0.5 ng/mL), while among men with lower-grade disease (PGG 1-2), SRT results in equal PSA control up to PSA 1.0 ng/mL.
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http://dx.doi.org/10.1016/j.clgc.2019.05.007DOI Listing
October 2019