Association between pelvic lymph node dissection and survival among patients with prostate cancer treated with radical prostatectomy.

Introduction: Although the clinical benefits of pelvic lymph node dissection (PLND) at the time of radical prostatectomy for prostate cancer remain uncertain, major guidelines recommend PLND based on risk profile. Thus, the objective of this study was to examine the association between PLND and survival among patients undergoing RP stratified by Gleason grade group (GG) with the aim of allowing patients and physicians to make more informed care decisions about the potential risks and benefits of PLND. Materials and methods: From the SEER-17 database, we examined overall (OS) and prostate cancer-specific (PCSS) survival of prostate cancer patients who underwent RP from 2010 to 2015 stratified by GG. We applied propensity score matching to balance pre-operative characteristics including race, age, PSA, household income, and housing status (urban/rural) between patients who did and did not undergo PLND for each GG. Statistical analyses included log-rank test and Kaplan-Meier curves. Results: We extracted a matched cohort from 80,287 patients with GG1-5 who underwent RP. The median PSA value was 6.0 ng/mL, and the median age was 62-years-old. 49,453 patients underwent PLND (61.60%), while 30,834 (38.40%) did not. There was no difference in OS and PCSS between patients who received PLND and those who did not for all Gleason GG (OS-GG1: P = 0.20, GG2: P = 0.34, GG3: P > 0.05, GG4: P = 0.55, GG5: P = 0.47; PCSS-GG1: P = 0.11, GG2: P = 0.96, GG3: P = 0.81, GG4: P = 0.22, GG5: P = 0.14). Conclusions: In this observational study, PLND at the time of RP was not associated with improved OS or PCSS among patients with cGS of 3 + 3, 3 + 4, 4 + 3, 4 + 4, 4 + 5, and 5 + 4. These findings suggest that until definitive clinical trials are completed, prostate cancer patients who have elected RP should be appropriately counseled on the potential risks and lack of proven survival benefit of PLND.

High-Throughput Genotyping of Plasmodium vivax in the Peruvian Amazon via Molecular Inversion Probes.

Plasmodium vivax transmission occurs throughout the tropics and is an emerging threat in areas of Plasmodium falciparum decline, causing relapse infections that complicate treatment and control. Targeted sequencing for P. falciparum has been widely deployed to detect population structure and the geographic spread of antimalarial and diagnostic resistance. However, there are fewer such tools for P. vivax . Leveraging global variation data, we designed four molecular inversion probe (MIP) genotyping panels targeting geographically differentiating SNPs, neutral SNPs, putative antimalarial resistance genes, and vaccine candidate genes. We deployed these MIP panels on 866 infections from the Peruvian Amazon and identified transmission networks with clonality (IBD>0.99), copy number variation in Pvdbp and multiple Pvrbps , fixation of putative antimalarial resistance, and balancing selection in 13 vaccine candidate genes. Our MIP panels are the broadest genotyping panel currently available and are poised for successful deployment in other regions of P. vivax transmission.

Existing Psychiatric Diagnoses Among Breast Cancer Patients Interact with Outcomes After Autologous and Implant-Based Bilateral Breast Reconstruction: A Propensity Score Matched Analysis.

BACKGROUND: Breast reconstruction is an integral postoncologic procedure that has been associated with improved mental health and psychological outcomes. The possible interaction between existing psychiatric diagnoses hospital courses and postoperative complications warrants further exploration. METHODS: Bilateral breast reconstruction patients were identified from the 2016 to 2018 Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP - NIS). Number and type of psychiatric diagnoses within the cohort were then evaluated using a host of ICD-10 codes. A propensity score analysis was applied to control for confounding variables such as demographics, existing comorbidities, and hospital characteristics. A binary logistic regression model was then used to identify the prediction value of psychiatric diagnosis and its interaction with modality of reconstruction for objective outcomes like length of hospital stay, treatment charge, and postoperative complications. RESULTS: A total of 10,114 patients were identified as the final cohort of breast reconstruction patients. 2621 (25.9%) patients possessed an average of 1.4 ± 0.6 existing psychiatric diagnoses. Presence of at least 1 psychiatric diagnosis was a strong predictor alone for extended length of stay (OR: 1.34, 95% CI: 1.28-1.41, P < .001) and occurrence of postoperative complications (OR: 1.31, 95% CI: 1.21-1.41, P < .001). Psychiatric diagnosis displayed a significant interaction with modality of breast reconstruction and conferred a lower increase in risk of extended length of stay in autologous reconstruction when compared to implant-based reconstruction (OR: 0.80, 95% CI: 0.72-0.89, P < .001). CONCLUSION: Existing psychiatric diagnoses were shown to strongly predict and modulate risk of adverse postoperative outcomes depending on modality of reconstruction.

Characteristics of Medical Schools in the United States Associated With Successful Match into Urology Residency Programs: Analysis of the 2016-2021 Urology Resident Cohort.

OBJECTIVE: To determine the characteristics of US medical schools associated with successful urology match applicants. MATERIALS AND METHODS: Using publicly available data, demographics and bibliometrics were collected for 1814 current urology residents who attend a US-based Accreditation Council for Graduate Medical Education (ACGME) Accredited program, reflecting matched applicants over a 6-year period from 2016-2021. A generated list of US feeder medical schools for urology was analyzed for correlative and predictive factors. Statistical analyses to characterize these factors included Pearson's Correlation Coefficient (PCC) and univariable and multivariable linear regression, respectively, as needed. RESULTS: There were 516 (28.45%) female residents and 58 (3.20%) international medical graduates. The mean number of published papers and abstracts ± SD pre-residency was 5.54 ± 7.20 with a mean h-index of 1.97 ± 2.24. The Cleveland Clinic Lerner College of Medicine had the highest percentage of successful matches into urology (n = 7, 3.65%), while the State University of New York Downstate Medical Center College of Medicine produced the highest absolute number (n = 41, 3.30%). The presence of a home urology program and pre-residency h-index had the strongest correlation with producing urology residents (PCC = 0.5769 and 0.3709, respectively, P<.0001). CONCLUSION: Understanding the characteristics of a successful urology match applicant and the medical schools that produce them will be vital as USMLE Step 1 exam becomes pass/fail. Further research into these schools' curricula is required to better understand the effect of early exposure to urology on matching into urology.

Impact of medical school responses during the COVID-19 pandemic on student satisfaction: a nationwide survey of US medical students.

PURPOSE: Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students' satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises. METHODS: In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools' responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing. RESULTS: The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools' response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction. CONCLUSION: In future crises, schools can best improve student satisfaction by prioritizing timely communication.

Changes in prostate cancer survival among insured patients in relation to USPSTF screening recommendations.

BACKGROUND: To investigate the effects of the U.S. Preventive Services Task Force's (USPSTF) 2012 recommendation against prostate-specific antigen (PSA)-based screening for prostate cancer on survival disparities based on insurance status. Prior to the USPSTF's 2012 screening recommendation, previous studies found that insured patients with prostate cancer had better outcomes than uninsured patients. METHODS: Using the SEER 18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and insurance status. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010-2012 or post-USPSTF era if diagnosed in 2014-2016. PCSS was measured with the Kaplan-Meier method, while disparities were measured with the Cox proportional hazards model. RESULTS: During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.256, 95% CI 1.037-1.520, p = 0.020). This survival disparity was no longer observed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients (adjusted HR 0.946, 95% CI 0.642-1.394, p = 0.780). CONCLUSIONS: Although the underlying reasons are not clear, the USPSTF's 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without affecting the survival of uninsured patients.

Marginal improvement in survival among patients diagnosed with metastatic prostate cancer in the second-line antiandrogen therapy era.

Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer-specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre-2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second-line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small.

Abrogation of survival disparity between Black and White individuals after the USPSTF's 2012 prostate-specific antigen-based prostate cancer screening recommendation.

BACKGROUND: In May 2012, the US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), assigning it a grade D. This decision then was modified in 2018 to a grade C for men aged 55 to 69 years. The authors hypothesized that changes in screening practices would reduce survival outcomes for both Black and White men but maintain racial discrepancies in outcomes. METHODS: Using the Surveillance, Epidemiology, and End Results database, the authors examined PCa-specific survival based on race and year of diagnosis. The period between January 2010 and December 2012 was categorized as the pre-USPSTF era, whereas the period between January 2014 and December 2016 was classified as the post-USPSTF era. The year 2013 was considered the transition year and was excluded from the analysis. RESULTS: A total of 49,388 men were identified in the pre-USPSTF era who were diagnosed with PCa, approximately 83.7% of whom were White and 16.3% of whom were Black. In the post-USPSTF era, a total of 41,829 men were diagnosed with PCa, approximately 82.7% of whom were White and 17.3% of whom were Black. When compared with the pre-USPSTF era, men diagnosed in the post-USPSTF era were found to have more adverse clinical features. In the pre-USPSTF era, White men were less likely to die of PCa than Black men. This survival disparity between White and Black men was no longer observed in the post-USPSTF era. CONCLUSIONS: In men diagnosed with PCa between 2014 and 2016, a survival disparity between White and Black men was not observed due to a decrease in survival among White men while the survival of Black men remained steady.

Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract.

Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.

Opioid Epidemic in the United States: Empirical Trends, and A Literature Review of Social Determinants and Epidemiological, Pain Management, and Treatment Patterns.

OBJECTIVES: Dramatic increases in opioid and drug overdose mortality have occurred in the United States (US) over the past two decades. To address this national public health crisis and identify gaps in the literature, we analyzed recent empirical trends in US drug overdose mortality by key social determinants and conducted a selective review of the recent literature on the magnitude of the opioid crisis facing different racial/ethnic, socioeconomic, and rural-urban segments of the US population. METHODS: We used the 1999-2017 mortality data from the US National Vital Statistics System to analyze trends in drug overdose mortality by race/ethnicity, age, and geographic area. Log-linear regression was used to model mortality trends. Using various key words and their combinations, we searched PubMed and Google Scholar for select peer-reviewed journal articles and government reports published on the opioid epidemic between 2010 and 2018. RESULTS: Our original analysis and review indicate marked increases in drug overdose mortality overall and by race/ethnicity and geographic regions, with adolescents and young adults experiencing steep increases in mortality between 1999 and 2017. Our selective search yielded 405 articles, of which 39 publications were selected for detailed review. Suicide mortality from drug overdose among teens aged 12-19 increased consistently between 2009 and 2017, particularly among teen girls. The rise of efficient global supply chains has increased opioid prescription use and undoubtedly contributed to the opioid epidemic. Many other important contributing factors to the epidemic include lack of education and economic opportunities, poor working conditions, and low social capital in disadvantaged communities. CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: Our analysis and review indicate substantial disparities in drug overdoses and related mortality, pain management, and treatment outcomes according to social determinants. Increases in drug overdoses and resultant mortality are not only unique to the US, but have also been observed in other industrialized countries. Healthcare systems, community leaders, and policymakers addressing the opioid epidemic should focus on upstream structural factors including education, economic opportunity, social cohesion, racial/ethnic disadvantage, geographic isolation, and life satisfaction.

Racial Representation Disparity of Population-Level Genomic Sequencing Efforts.

To develop personalized treatments for diseases, it is essential that they reflect the population of individuals that may be affected by a given disease. Amidst claims that there may be racial disparities in research populations, there have been no direct studies to explore this disparity in disease incidence and research projects that involve genomic sequencing. The precise relationship between underrepresentation of certain races in genomic sequencing studies and health outcomes relative to these races is unknown. Here, we examine the disparities in racial representation of national datasets pertaining to clinical data, mortality rates, and a major initiative involving genomic sequence analysis (The Cancer Genome Atlas [TCGA]). The results suggest that black Americans are underrepresented for most cancers in TCGA compared to clinical and mortality datasets, whereas Asian Americans are overrepresented. These findings accentuate the importance of targeted efforts to recruit representative patient populations into studies involving genomic sequencing.

Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer.

BACKGROUND: In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. METHODS: TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. RESULTS: DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA > 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). CONCLUSIONS: Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.