Real-World Evidence of Aripiprazole Tablets with Sensor: Treatment Patterns and Impacts on Psychiatric Healthcare Resource Utilization.

Purpose: Maintaining adherence to antipsychotic (AP) medication is often challenging. Aripiprazole tablets with sensor (AS) contain an ingestible event marker and communicate with wearable patches and a smartphone app to provide objective medication ingestion data. This study evaluated real-world treatment patterns of AS usage and its impact on psychiatric healthcare resource utilization (HCRU). Patients and Methods: This retrospective, observational cohort study identified individuals who initiated AS between 1/1/2019 and 6/30/2020 with 3 months baseline and 6 months of follow-up data using a commercial medical and pharmacy claims database (Clarivate). Controls were propensity score-matched (4:1) to AS initiators based on age (±2 years), sex, diagnosis (major depressive disorder [MDD], schizophrenia, bipolar I disorder [BP-I], other), insurance, and baseline oral AP use (yes/no). Days of AP supply were evaluated using a general regression model. The frequency of psychiatric HCRU during follow-up was compared between groups using a zero-inflated regression model. Results: Most AS initiators were diagnosed with MDD (61.2%) and were women (61.2%); mean age was 37.7 years (standard deviation: 14.1). Most AS initiators (53.1%) continued treatment for >60 days (mean days of supply = 77). After adjusting for covariates, AS initiators had 41% more days of AP supply during follow-up compared with controls (P <0.0001) and significantly lower adjusted odds ratios (ORs) for psychiatric outpatient visits (adjusted OR = 0.80; P <0.05), emergency department visits (adjusted OR = 0.11; P <0.05), inpatient visits (adjusted OR = 0.42; P <0.05), and other medical services (adjusted OR = 0.25; P <0.05). Conclusion: Participants who implemented AS had significantly more days of AP supply and fewer psychiatric care visits. These preliminary results suggest AS usage can help build regular medication-taking habits and holds promise for reducing psychiatric HCRU. Additional studies with larger sample sizes are warranted to inform clinical practice and coverage decisions.

Association between Surgical Technical Skills and Clinical Outcomes: A Systematic Literature Review and Meta-Analysis.

Background: A systematic literature review and meta-analysis was conducted to assess the association between intraoperative surgical skill and clinical outcomes. Methods: Peer-reviewed, original research articles published through August 31, 2021 were identified from PubMed and Embase. From the 1,513 potential articles, seven met eligibility requirements, reporting on 151 surgeons and 17,932 procedures. All included retrospective assessment of operative videos. Associations between surgical skill and outcomes were assessed by pooling odds ratios (OR) using random-effects models with the inverse variance method. Eligible studies included pancreaticoduodenectomy, gastric bypass, laparoscopic gastrectomy, prostatectomy, colorectal, and hemicolectomy procedures. Results: Meta-analytic pooling identified significant associations between the highest vs. lowest quartile of surgical skill and reoperation (OR: 0.44; 95% confidence interval [CI]: 0.23, 0.83), hemorrhage (OR: 0.66; 95% CI, 0.65, 0.68), obstruction (OR: 0.33; 95% CI, 0.30, 0.35), and any medical complication (OR: 0.23, 95% CI, 0.19, 0.27). Nonsignificant inverse associations were noted between skill and readmission, emergency department visit, mortality, leak, infection, venous thromboembolism, and cardiac and pulmonary complications. Conclusions: Overall, surgeon technical skill appears to predict clinical outcomes. However, there are surprisingly few articles that evaluate this association. The authors recommend a thoughtful approach for the development of a comprehensive surgical quality infrastructure that could significantly reduce the challenges identified by this study.

Metabolic syndrome is associated with aggressive prostate cancer regardless of race.

PURPOSE: Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race. METHODS: Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested. RESULTS: Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25). CONCLUSION: Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.

Predicting Poor Outcomes Among Individuals Seeking Care for Major Depressive Disorder.

Objective: To develop and validate algorithms to identify individuals with major depressive disorder (MDD) at elevated risk for suicidality or for an acute care event. Methods: We conducted a retrospective cohort analysis among adults with MDD diagnosed between January 1, 2018 and February 28, 2019. Generalized estimating equation models were developed to predict emergency department (ED) visit, inpatient hospitalization, acute care visit (ED or inpatient), partial-day hospitalization, and suicidality in the year following diagnosis. Outcomes (per 1000 patients per month, PkPPM) were categorized as all-cause, psychiatric, or MDD-specific and combined into composite measures. Predictors included demographics, medical and pharmacy utilization, social determinants of health, and comorbid diagnoses as well as features indicative of clinically relevant changes in psychiatric health. Models were trained on data from 1.7M individuals, with sensitivity, positive predictive value, and area-under-the-curve (AUC) derived from a validation dataset of 0.7M. Results: Event rates were 124.0 PkPPM (any outcome), 21.2 PkPPM (psychiatric utilization), and 7.6 PkPPM (suicidality). Among the composite models, the model predicting suicidality had the highest AUC (0.916) followed by any psychiatric acute care visit (0.891) and all-cause ED visit (0.790). Event-specific models all achieved an AUC >0.87, with the highest AUC noted for partial-day hospitalization (AUC = 0.938). Select predictors of all three outcomes included younger age, Medicaid insurance, past psychiatric ED visits, past suicidal ideation, and alcohol use disorder diagnoses, among others. Conclusions: Analytical models derived from clinically-relevant features identify individuals with MDD at risk for poor outcomes and can be a practical tool for health care organizations to divert high-risk populations into comprehensive care models.

Measuring Response to Adjunctive Therapy Among Individuals with Major Depressive Disorder.

Background: Incomplete or inadequate response to first-line antidepressant therapy (ADT) for major depressive disorder (MDD) is common. Response to adjunctive therapy is less understood. Objective: To estimate response to adjunctive pharmacotherapy or psychotherapy among individuals with MDD on an antidepressant using the PHQ-9 questionnaire. Methods: This was a retrospective cohort analysis using medical and pharmacy insurance claims among individuals with MDD or ADT who initiated adjunctive pharmacotherapy, psychotherapy, or both (dual). Eligible individuals initiated adjunctive therapy between 7/1/2014-12/31/2018. Symptom severity was measured by PHQ-9 score in the 6-month baseline and 12-month follow up. Multivariate logistic regression identified factors associated with improved symptom severity. Results: Most (81.8%) of the 2389 participants initiated adjunctive pharmacotherapy, followed by psychotherapy (12.7%) and dual adjunctive (5.5%). Only 30.2% had both a baseline and follow-up PHQ-9 score. Among those with mild or more severe PHQ-9 baseline scores, 36.7% had the same or worse MDD severity during follow-up. Among those with moderate or more severe baseline scores, 28.1% had the same or worse MDD severity during follow-up. Conclusion: Most individuals with moderate-to-severe MDD did not receive a follow-up questionnaire, suggesting incomplete monitoring of treatment response. Among those with a PHQ-9 following initiation of adjunctive therapy, many continued to report impactful symptoms. Future studies should explore alternate treatment approaches and methods to support the utilization of the PHQ-9 for monitoring treatment response.

Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities.

INTRODUCTION: The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race. METHODS: Plasma SHLP2, humanin, and MOTS-c were measured in 198 men (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) undergoing biopsy. Logistic and multinomial regression models tested associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5). Models were adjusted for age, body mass index, digital rectal examination, and prostate specific antigen (PSA). We tested interactions between MDPs and race. RESULTS: Among controls, humanin was similar by race (p = 0.60), but both SHLP2 (p = 0.007) and MOTS-c (p = 0.026) were lower in AAM controls versus EAM controls. Among EAM, higher MDP values were associated with lower PC risk (all p ≤ 0.001), with null associations in AAM (all p-interactions ≤ 0.01). Similarly, higher MDP expression was associated with decreased risk of low- and high-grade PC in EAM (all p ≤ 0.005) with null associations in AAM. CONCLUSIONS: Higher MDP levels were associated with lower PC risk in EAM but not AAM. Generally, AAM controls had lower MDP levels. These data support MDPs and mitochondrial dysfunction in PC, suggesting greater dysfunction in AAM may contribute to excess PC risk. Future larger studies are needed to confirm these results.

Lifestyle and sociodemographic factors associated with treatment choice of clinically localized prostate cancer in an equal access healthcare system.

Sociodemographic and lifestyle factors may play a role in determining whether patients with clinically localized prostate cancer (PC) are managed with active surveillance (AS), radical prostatectomy (RP), or radiation therapy (RT); however, these relationships have not been well examined. In a cross-sectional study conducted within an equal access healthcare system, multivariable adjusted regression analysis revealed that living with a spouse or partner was associated with a 65% lower chance of being managed by RT (P = 0.001) and 57% lower risk of being managed by AS (P = 0.042) compared with RP. No other sociodemographic or lifestyle factors were independently associated with treatment modality.

The impact of the social construct of race on outcomes among bacille Calmette-Guérin-treated patients with high-risk non-muscle-invasive bladder cancer in an equal-access setting.

BACKGROUND: The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. METHODS: A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guérin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. RESULTS: A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. CONCLUSIONS: In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

Diagnostic Utility of Serum and Urinary Metabolite Analysis in Patients with Interstitial Cystitis/Painful Bladder Syndrome.

OBJECTIVE: To identify the potential biomarkers of interstitial cystitis/painful bladder syndrome (IC), a chronic syndrome of bladder-centric pain with unknown etiology that has an adverse impact on quality of life, we analyzed the urine and serum metabolomes of a cohort of IC patients and non-disease controls (NC). METHODS: Home collection of serum and urine samples was obtained from 19 IC and 20 NC females in the Veterans Affairs (VA) Health Care System. IC was diagnosed independently by thorough review of medical records using established criteria. Biostatistics and bioinformatics analyses, including univariate analysis, unsupervised clustering, random forest analysis, and metabolite set enrichment analysis (MSEA), were then utilized to identify potential IC biomarkers. RESULTS: Metabolomics profiling revealed distinct expression patterns between NC and IC. Random forest analysis of urine samples suggested discriminators specific to IC; these include phenylalanine, purine, 5-oxoproline, and 5-hydroxyindoleacetic acid. When these urinary metabolomics-based analytes were combined into a single model, the AUC was 0.92, suggesting strong potential clinical value as a diagnostic signature. Serum-based metabolomics did not provide potential IC discriminators. CONCLUSION: Analysis of serum and urine revealed that women with IC have distinct metabolomes, highlighting key metabolic pathways that may provide insight into the pathophysiology of IC. The findings from this pilot study suggest that integrated analyses of urinary metabolites, purine, phenylalanine, 5-oxoproline, and 5-HIAA, can lead to promising IC biomarkers for pathophysiology of IC. Validation of these results using a larger dataset is currently underway.

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

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.

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

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]T3vsT1 1.15; 95% confidence interval [CI]: 0.83-1.60 and ORT2vsT1 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.

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

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 (ORper 1000 units=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.

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).

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/m2 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, P < 0.001) and lost weight (-12.1 vs. -0.50 kg, P < 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, P = 0.316) arms. In a post hoc exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (28 vs. 13 months, P = 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.

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

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.

Facilitators and Barriers to the Implementation of the HPV VACs (Vaccinate Adolescents Against Cancers) Program: A Consolidated Framework for Implementation Research Analysis.

PURPOSE AND OBJECTIVES: The human papillomavirus (HPV) vaccine is an effective but underused method for preventing multiple cancers, particularly cervical cancer. Although interventions have successfully targeted barriers to HPV vaccine uptake in various clinical settings, few studies have explored their implementation. Our study examines the delivery of the HPV VACs (Vaccinate Adolescents Against Cancer) Program and elicits information on barriers and facilitators to implementation. INTERVENTION APPROACH: The VACs Program pilot was a multilevel, evidence-based intervention conducted by the American Cancer Society in 30 federally qualified health centers (FQHCs) in the United States. EVALUATION METHODS: We conducted in-depth interviews (N = 32) by telephone with representatives of 9 FQHC partners. We structured the interview guides on Consolidated Framework for Implementation Research (CFIR) domains. We asked about project start-up activities, implementation strategy selection, policy- and practice-level changes, staffing structure, challenges, and key factors leading to project success. At least 2 researchers coded each interview transcript verbatim. RESULTS: Participants most frequently identified the electronic health record system, training and education, concrete tools and resources, and provider champions as facilitators to implementing HPV VACs. Limited staff resources, challenges of electronic health records, issues with state immunization registries, patient misinformation about vaccines and vaccine stigma, cultural/language barriers, competing priorities, levels of funding, staff buy-in, training needs, and low health literacy were identified as barriers. IMPLICATIONS FOR PUBLIC HEALTH: Providing appropriate training for FQHC staff members and providers along with technical assistance and facilitation tools were critical for increasing provider confidence in recommending HPV vaccine. Addressing capacity-building and implementation barriers in FQHCs can increase effective implementation of evidence-based interventions to increase HPV vaccination uptake and reduce the burden of future cancers.

Low circulating levels of the mitochondrial-peptide hormone SHLP2: novel biomarker for prostate cancer risk.

CONTEXT: Mitochondrial DNA mutations and dysfunction are associated with prostate cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial-encoded peptide and an important mitochondrial retrograde signaling molecule. OBJECTIVE: To determine whether serum SHLP2 concentration is associated with PCa risk and whether associations are race-specific.Design, Setting and Participants: Patients undergoing prostate biopsy were recruited from the Durham Veterans Affairs hospital. Serum was collected prior to biopsy and SHLP2 measured by ELISA. We selected 200 men for analysis (100 negative biopsies and 100 PCa cases; 100 black and 100 white). RESULTS: Mean SHLP2 levels were significantly higher in white controls versus black controls and SHLP2 was significantly higher in white controls versus white PCa cases. In contrast, there was no significant difference in SHLP2 levels between black controls and black cases. SHLP2 levels > 350-pg/ml ruled out PCa with ≥ 95% accuracy in both races. CONCLUSIONS: Lower SHLP2 was linked with increased PCa risk in white men, but no significant association was observed in black men. While SHLP2 > 350-pg/ml ruled out PCa in both races with high accuracy, SHLP2 was unrelated to PCa grade. These data suggest the circulating mitochondrial-derived peptide hormone, SHLP2 plays a key role in the development and racial disparity of prostate cancer.

UDP-glucuronosyltransferases and biochemical recurrence in prostate cancer progression.

BACKGROUND: Uridine 5'-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients. METHODS: We determined the expression of UGT2B15, UGT2B17, and UGT2B28 enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center. The association between each protein's percent positive and H-score, a weighted score of staining intensity, and the risk of biochemical recurrence (BCR) was tested using separate Cox proportional hazards models. In an exploratory analysis, UGT2B17 total positive and H-score were divided at the median and we tested the association between UGT2B17 group and risk of BCR. RESULTS: The median follow-up for all patients was 118 months (IQR: 85-144). Of 190, 83 (44%) patients developed BCR. We found no association between UGT2B15 or UGT2B28 and risk of BCR. However, there was a trend for an association between UGT2B17 and BCR (HR = 1.01, 95% CI 1.00-1.02, p = 0.11), though not statistically significant. Upon further investigation, we found that patients with UGT2B17 higher levels of expression had a significant increased risk of BCR on univariable analysis (HR = 1.57, 95% CI 1.02-2.43, p = 0.041), although this association was attenuated in the multivariable model (HR = 1.50, 95% CI 0.94-2.40, p = 0.088). CONCLUSIONS: Our findings suggest that UGT2B17 overexpression may be associated with a significant increased risk of BCR. These results are consistent with previous reports which showed UGT2B17 significantly expressed in advanced prostate cancer including prostate tumor metastases.