Prostate cancer genetic alterations in Hispanic men.

BACKGROUND: Differences in DNA alterations in prostate cancer among White, Black, and Asian men have been widely described. This is the first description of the frequency of DNA alterations in primary and metastatic prostate cancer samples of self-reported Hispanic men. METHODS: We utilized targeted next-generation sequencing tumor genomic profiles from prostate cancer tissues that underwent clinical sequencing at academic centers (GENIE 11th). We decided to restrict our analysis to the samples from Memorial Sloan Kettering Cancer Center as it was by far the main contributor of Hispanic samples. The numbers of men by self-reported ethnicity and racial categories were analyzed via Fisher's exact test between Hispanic-White versus non-Hispanic White. RESULTS AND LIMITATIONS: Our cohort consisted of 1412 primary and 818 metastatic adenocarcinomas. In primary adenocarcinomas, TMPRSS2 and ERG gene alterations were less common in non-Hispanic White men than Hispanic White (31.86% vs. 51.28%, p = 0.0007, odds ratio [OR] = 0.44 [0.27-0.72] and 25.34% vs. 42.31%, p = 0.002, OR = 0.46 [0.28-0.76]). In metastatic tumors, KRAS and CCNE1 alterations were less prevalent in non-Hispanic White men (1.03% vs. 7.50%, p = 0.014, OR = 0.13 [0.03, 0.78] and 1.29% vs. 10.00%, p = 0.003, OR = 0.12 [0.03, 0.54]). No significant differences were found in actionable alterations and androgen receptor mutations between the groups. Due to the lack of clinical characteristics and genetic ancestry in this dataset, correlation with these could not be explored. CONCLUSION: DNA alteration frequencies in primary and metastatic prostate cancer tumors differ among Hispanic-White and non-Hispanic White men. Notably, we found no significant differences in the prevalence of actionable genetic alterations between the groups, suggesting that a significant number of Hispanic men could benefit from the development of targeted therapies.

Defining the Expression, Production, and Signaling Roles of Specialized Metabolites during Bacillus subtilis Differentiation.

Bacterial specialized (or secondary) metabolites are structurally diverse molecules that mediate intra- and interspecies interactions by altering growth and cellular physiology and differentiation. Bacillus subtilis, a Gram-positive model bacterium commonly used to study biofilm formation and sporulation, has the capacity to produce more than 10 specialized metabolites. Some of these B. subtilis specialized metabolites have been investigated for their role in facilitating cellular differentiation, but only rarely has the behavior of multiple metabolites been simultaneously investigated. In this study, we explored the interconnectivity of differentiation (biofilm and sporulation) and specialized metabolites in B. subtilis. Specifically, we interrogated how development influences specialized metabolites and vice versa. Using the sporulation-inducing medium DSM, we found that the majority of the specialized metabolites examined are expressed and produced during biofilm formation and sporulation. Additionally, we found that six of these metabolites (surfactin, ComX, bacillibactin, bacilysin, subtilosin A, and plipastatin) are necessary signaling molecules for proper progression of B. subtilis differentiation. This study further supports the growing body of work demonstrating that specialized metabolites have essential physiological functions as cell-cell communication signals in bacteria. IMPORTANCE Bacterially produced specialized metabolites are frequently studied for their potential use as antibiotics and antifungals. However, a growing body of work has suggested that the antagonistic potential of specialized metabolites is not their only function. Here, using Bacillus subtilis as our model bacterium, we demonstrated that developmental processes such as biofilm formation and sporulation are tightly linked to specialized metabolite gene expression and production. Additionally, under our differentiation-inducing conditions, six out of the nine specialized metabolites investigated behave as intraspecific signals that impact B. subtilis physiology and influence biofilm formation and sporulation. Our work supports the viewpoint that specialized metabolites have a clear role as cell-cell signaling molecules within differentiated populations of bacteria.

Insurer coverage of prostate cancer biomarkers.

INTRODUCTION: Several recently-developed prostate cancer (CaP) biomarkers are recommended per national guidelines, yet feasibility of obtaining these tests is unknown. We used a national database to assess insurance coverage of CaP biomarkers. MATERIALS AND METHODS: Insurance policies regarding 4K Score, ExoDx, My Prostate Score, Prostate Cancer Antigen 3, Prostate Health Index, and SelectMDx as of January 1, 2022 were extracted from the policy reporter database. Coverage was defined as a biomarker being deemed medically necessary, conditionally covered, or covered with prior authorization. Overall rates of biomarker coverage were compared by insurance type and region using Chi-squared test. SelectMDx was not covered by any queried policies and was omitted from analysis. RESULTS: A total of 186 insurance plans were identified among 131 payers. Of the 186 plans, 109 (59%) covered at least one biomarker, with prior authorization required for 38 (35%) of these plans. Prostate Cancer Antigen 3 and 4K Score had higher rates of coverage compared to ExoDx, Prostate Health Index, and My Prostate Score (52% and 43% vs. 26%, 26%, and 5%, respectively, P < 0.01). Medicare plans had higher rates of coverage compared to non-Medicare plans (80% Medicare vs. 17% commercial, 15% federal employer, and 13% Medicaid, P < 0.01), and nationwide plans had higher coverage rates compared to regional plans (43% nationwide vs. 32% midwest, 27% northeast, 25% south, 24% west, P < 0.01). Covered biomarkers under Medicare plans were less likely to require prior authorization compared to those covered by non-Medicare plans (12% Medicare vs. 63% commercial, 100% federal employer, 70% Medicaid, P < 0.01). CONCLUSIONS: Coverage of novel CaP biomarkers are relatively robust for Medicare plans but sparse for non-Medicare plans, with the majority of non-Medicare plans requiring prior authorization. Non-Medicare eligible men may face significant barriers to obtaining these tests.

Adoption and Outcomes of Holmium Laser Enucleation of the Prostate in the United States.

OBJECTIVE: To investigate the utilization of holmium laser enucleation of the prostate (HoLEP) using a large real-world cohort. We compare the safety, readmission, and retreatment rates of HoLEP to other widely used endoscopic surgical interventions for benign prostatic hyperplasia (BPH) including transurethral resection of the prostate (TURP), photoselective vaporization of the prostate, and prostatic urethral lift. METHODS: Men who underwent endoscopic treatments for BPH from 2000 to 2019 were identified in the Premier Healthcare Database (n = 218,793). We compared the relative proportion of each procedure performed and annual physician volume data to identify trends in adoption and utilization. Readmission and retreatment rates were determined at both 30- and 90-days postoperation. Multivariable logistic regression was used to assess the association between procedure type and outcomes. RESULTS: HoLEP accounted for 3.2% (n = 6967) of all the BPH procedures performed between 2000 and 2019 and increased from 1.1% of the procedures in 2008 to 4% in 2019. Patients undergoing HoLEP had lower odds of 90-days readmission compared to TURP (Odds ratio (OR) 0.87, p = 0.025). HoLEP had similar odds of retreatment compared to TURP at both 1-year (OR 0.96, p = 0.7) and 2-years (OR 0.98, p = 0.9), while patients undergoing photoselective vaporization of the prostate and prostatic urethral lift were more likely to retreat within 2-years (OR 1.20, P < 0.001; OR 1.87, P < 0.001). CONCLUSION: HoLEP is a safe therapy for BPH with lower readmission and comparable retreatment rates to the gold standard TURP. Despite this, the utilization of HoLEP has lagged behind other endoscopic procedures and remains low.

Impact of Magnetic Resonance Imaging Targeting on Pathologic Upgrading and Downgrading at Prostatectomy: A Systematic Review and Meta-analysis.

CONTEXT: The evidence supporting multiparametric magnetic resonance imaging (MRI) targeting for biopsy is nearly exclusively based on biopsy pathologic outcomes. This is problematic, as targeting likely allows preferential identification of small high-grade areas of questionable oncologic significance, raising the likelihood of overdiagnosis and overtreatment. OBJECTIVE: To estimate the impact of MRI-targeted, systematic, and combined biopsies on radical prostatectomy (RP) grade group concordance. EVIDENCE ACQUISITION: PubMed MEDLINE and Cochrane Library were searched from July 2018 to January 2022. Studies that conducted systematic and MRI-targeted prostate biopsies and compared biopsy results with pathology after RP were included. We performed a meta-analysis to assess whether pathologic upgrading and downgrading were influenced by biopsy type and a net-benefit analysis using pooled risk difference estimates. EVIDENCE SYNTHESIS: Both targeted only and combined biopsies were less likely to result in upgrading (odds ratio [OR] vs systematic of 0.70, 95% confidence interval [CI] 0.63-0.77, p < 0.001, and 0.50, 95% CI 0.45-0.55, p < 0.001), respectively). Targeted only and combined biopsies increased the odds of downgrading (1.24 (95% CI 1.05-1.46), p = 0.012, and 1.96 (95% CI 1.68-2.27, p < 0.001) compared with systematic biopsies, respectively. The net benefit of targeted and combined biopsies is 8 and 7 per 100 if harms of up- and downgrading are considered equal, but 7 and -1 per 100 if the harm of downgrading is considered twice that of upgrading. CONCLUSIONS: The addition of MRI-targeting results in lower rates of upgrading as compared to systematic biopsy at RP (27% vs 42%). However, combined MRI-targeted and systematic biopsies are associated with more downgrading at RP (19% v 11% for combined vs systematic). Strong heterogeneity suggests further research into factors that influence the rates of up- and downgrading and that distinguishes clinically relevant from irrelevant grade changes is needed. Until then, the benefits and harms of combined MRI-targeted and systematic biopsies cannot be fully assessed. PATIENT SUMMARY: We reviewed the ability of magnetic resonance imaging (MRI)-targeted biopsies to predict cancer grade at prostatectomy. We found that combined MRI-targeted and systematic biopsies result in more cancers being downgraded than systematic biopsies.

Serial prostate magnetic resonance imaging fails to predict pathological progression in patients on active surveillance.

INTRODUCTION: Limited data guide urological practice when employing prostate magnetic resonance imaging (MRI) in active surveillance (AS) protocols. To determine the ability of prostate MRI to predict pathological progression in AS patients, we correlated findings of serial MRI with results of surveillance biopsies. METHODS: Patients on AS with ≥2 prostate MRI and ≥2 prostate biopsies were included. Prostate Imaging-Reporting and Data System (PI-RADS) score upgrade, as assigned by experienced radiologists, was used to assess the ability of imaging to predict pathological biopsy progression. Imaging test statistics and the odds ratio of pathological progression according to MRI upgrade were calculated. RESULTS: Of 121 patients meeting criteria, 36 (30%) demonstrated MRI upgrade. Biopsy progression was noted in 55 patients (46%). Of these, 20 patients (37%) had biopsy progression predicted by MRI upgrade, while the remaining (n=35) had no lesion upgrade on prostate MRI. Conversely, among those with no biopsy progression (n=66), 16 patients (24%) had a false-positive upgrade on serial MRI. We report a sensitivity and specificity of MRI change for pathological progression of 36% and 76%, respectively. Although MRI change was associated with a positive predictive value of 56% for pathological progression, patients with a high-suspicion lesion (PI-RADS >3) at any time were more likely to experience disease progression, (odds ratio 3.3, 95% confidence interval 1.6-8.0, p<0.01). CONCLUSIONS: Given its modest sensitivity/specificity, serial prostate MRI should be used judiciously as a surveillance tool. However, when prostate MRI demonstrates a PI-RADS >3 lesion, a high index of suspicion should be maintained, as these patients are more likely to progress on AS.

Pre-surgical chronic kidney disease continues to drive outcomes in the modern era of minimally invasive renal surgery, despite advances in technology.

PURPOSE: To assess the impact of preoperative chronic kidney disease (CKD) on perioperative morbidity and mortality in a contemporary cohort undergoing renal surgery in an era of increased prevalence of minimally invasive surgery and partial nephrectomy. METHODS: The National Surgery Quality Improvement Program dataset was queried to identify patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) between 2010 and 2018. CKD staging was assigned based on creatinine clearance calculated using the Cockcroft-Gault formula. Multivariable logistic regression was performed to assess the effect of preoperative CKD stage on postoperative outcomes, including a composite variable encompassing multiple major complications. RESULTS: We analyzed 19,545 patients with CKD undergoing renal surgery. CKD stage ≥ 2 predicted an increase in major perioperative complications, OR 1.54 (95% CI 1.46-1.63); p < 0.01. The risk of perioperative morbidity increased linearly with increasing CKD stage. Patients with CKD stage > 2 also demonstrated increased 30-day mortality, OR 1.87 (95% CI 1.26-2.48); p < 0.01. Adjusting for surgery type, CKD staging predicted perioperative mortality in patients undergoing RN only, and perioperative morbidity in RN and PN. CONCLUSIONS: Here, we demonstrate a statistically significant increase in the risk of major postoperative complications following RN and PN with increasing CKD stage. Amongst patients undergoing RN, we also demonstrate increasing 30-day mortality with increasing CKD stage. Importantly, we highlight the ability of CKD staging to predict major perioperative outcomes with greater magnitude of effect than surgery type alone. Thus, we provide a model for translating CKD staging into operative risk amongst patients undergoing surgery for a renal mass.

Predictors and Trends of Opioid-Sparing Radical Prostatectomy From a Large National Cohort.

OBJECTIVE: To examine the use of pain medications after radical prostatectomy using a large national database. METHODS: The Premier Hospital Database was queried to identify all robotic and laparoscopic radical prostatectomies from January 2015 to March 2020 with length of stay more than or equal to 1 day. "Opioid-sparing" was defined as absence of intravenous opioid use after post-operative day 0 and absence of oral opioid use throughout admission. Comparisons were made between opioid-sparing and non-opioid-sparing prostatectomy. Logistic multivariable regression was used to identify predictors of opioid-sparing prostatectomy. RESULTS: A total of 62,660 patients were included, of whom 14,806 (23.6%) underwent opioid-sparing prostatectomy. Opioid-sparing prostatectomy was associated with older age (65 vs 63 years, P <.01), white versus black race (76.3% vs 73.4%, P <.01), high-volume surgeons (75.2% vs 70.0%, P <.01), and use of intravenous ketorolac (62.2% vs 48.0%, P <.01), intravenous acetaminophen (32.5% vs 30.1%, P <.01), and liposomal bupivacaine (5.4% vs 4.9%, P <.01). On multivariable regression, ketorolac was the strongest predictor of opioid-sparing prostatectomy (odds ratio: 1.86, 95% confidence interval: 1.79-1.93, P <.01), and black race was predictive of non-opioid sparing prostatectomy (odds ratio: 0.75, 95% confidence interval: 0.71-0.80, P <.01). Ketorolac was not associated with increased risk of postoperative bleeding (0.3% vs 0.3%, P =1.0) or dialysis requirement (<0.1% vs <0.1%, P =.91). CONCLUSION: Opioid-sparing radical prostatectomy was feasible and associated with administration of each of the non-opioid pain medications assessed. Ketorolac was the strongest predictor of opioid-sparing prostatectomy and was not associated with increased risk of bleeding or dialysis.

Establishing a Virtual Global Health Education Partnership: The Cleveland-Cusco Connection.

Introduction: The Cleveland-Cusco Connection (CCC) elective was created during the COVID-19 pandemic to continue global health (GH) education for Case Western Reserve University (CWRU) and Universidad Nacional de San Antonio Abad del Cusco (UNSAAC) medical students. The CCC elective was held over Zoom and aimed to promote international collaboration, knowledge about health systems, and perspectives in GH with synchronous and asynchronous learning. Methods: Peruvian and US medical students participated in six monthly sessions consisting of student presentations and large and small group discussions. The elective was led collaboratively by CWRU and UNSAAC students. We evaluated students' experience using pre- and post-course surveys. Results: Nineteen students (76%) completed the post-course survey. The median rating for meeting each course objective was "somewhat effective" on a 5-point scale ranging from "very ineffective" to "very effective." All respondents would recommend the course to a friend. Common barriers included language challenges, fatigue from other coursework, and technology issues. Seven students' pre- and post-course surveys could be linked. The number of students who agreed with the statements assessing course objectives increased for all questions between the pre- and post-test, with only the number agreeing that they understood the Peruvian healthcare system increasing significantly (p < 0.05). Discussion: The CCC elective provides a valuable GH educational opportunity via a virtual platform. Students reported that learning from their peers was effective and enjoyable. Conclusion: Virtual GH electives like the CCC may offer benefits in terms of cost, equity, and flexibility and merit further investigation. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01626-6.

Race and prostate cancer: genomic landscape.

In the past 20 years, new insights into the genomic pathogenesis of prostate cancer have been provided. Large-scale integrative genomics approaches enabled researchers to characterize the genetic and epigenetic landscape of prostate cancer and to define different molecular subclasses based on the combination of genetic alterations, gene expression patterns and methylation profiles. Several molecular drivers of prostate cancer have been identified, some of which are different in men of different races. However, the extent to which genomics can explain racial disparities in prostate cancer outcomes is unclear. Future collaborative genomic studies overcoming the underrepresentation of non-white patients and other minority populations are essential.

Selective Bacterial Community Enrichment between the Pitcher Plants Sarracenia minor and Sarracenia flava.

The interconnected and overlapping habitats present in natural ecosystems remain a challenge in determining the forces driving microbial community composition. The cuplike leaf structures of some carnivorous plants, including those of the family Sarraceniaceae, are self-contained ecological habitats that represent systems for exploring such microbial ecology questions. We investigated whether Sarracenia minor and Sarracenia flava cultivate distinct bacterial communities when sampled at the same geographic location and time. This sampling strategy eliminates many abiotic environmental variables present in other studies that compare samples harvested over time, and it could reveal biotic factors driving the selection of microbes. DNA extracted from the decomposing detritus trapped in each Sarracenia leaf pitcher was profiled using 16S rRNA amplicon sequencing. We identified a surprising amount of bacterial diversity within each pitcher, but we also discovered bacteria whose abundance was specifically enriched in one of the two Sarracenia species. These differences in bacterial community representation suggest some biotic influence of the Sarracenia plant on the bacterial composition of their pitchers. Overall, our results suggest that bacterial selection due to factors other than geographic location, weather, or prey availability is occurring within the pitchers of these two closely related plant species. This indicates that specific characteristics of S. minor and S. flava may play a role in fostering distinct bacterial communities. These confined, naturally occurring microbial ecosystems within Sarracenia pitchers may provide model systems to answer important questions about the drivers of microbial community composition, succession, and response to environmental perturbations. IMPORTANCE This study uses amplicon sequencing to compare the bacterial communities of environmental samples from the detritus of the leaf cavities of Sarracenia minor and Sarracenia flava pitcher plants. We sampled the detritus at the same time and in the same geographic location, eliminating many environmental variables present in other comparative studies. This study revealed that different species of Sarracenia contain distinct bacterial members within their pitchers, suggesting that these communities are not randomly established based on environmental factors and the prey pool but are potentially enriched for by the plants' chemical or physical environment. This study of these naturally occurring, confined microbial ecosystems will help further establish carnivorous pitcher plants as a model system for answering important questions about the development and succession of microbial communities.