Epidemiology, treatment patterns, and clinical outcomes in de novo oligometastatic hormone-sensitive prostate cancer.

BACKGROUND: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. METHODS: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status. RESULTS: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively. CONCLUSIONS: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies.

Seeing the unseen: how can we best identify transgender women within the Veterans Affairs healthcare system's electronic medical record?

BACKGROUND: One challenge in transgender research is reliably identifying patients through electronic medical records data, as there is no universal transgender International Classification of Diseases (ICD) code, but rather multiple ICD codes that can be used. AIM: To explore the sensitivity and specificity of 5 commonly used ICD codes to identify transgender patients overall and transgender women specifically (assigned male sex at birth) by using data from the Veterans Affairs (VA), the largest integrated health system in the United States. METHODS: Patients aged ≥18 years were identified via ICD-9 codes 302.5 and 302.6 (Ninth Revision) and ICD-10 codes F64.0, F64.8, and F64.9 (Tenth Revision) using VA health records from 2000 to 2021 and stratified by bilateral orchiectomy status. OUTCOMES: Detailed chart review was performed on 32 randomly selected patients for each code (half with and half without orchiectomy) to confirm transgender status and to perform descriptive analyses. RESULTS: For each ICD code, rates of confirmed transgender status ranged from 88% to 100% for those with and without an orchiectomy, with the majority being transgender women (consistent with most veterans being assigned male sex at birth). Most transgender women (66%-100%) were undergoing estrogen gender-affirming therapy. The majority of provider-driven entries of transgender status took place from 2011 to 2020, with 75% of entries made from 2011 to 2020, consistent with increased recognition and societal acceptance of this population. False negatives were detected at a rate of 15%. Based upon these 5 ICD codes alone, we estimate that the VA has records for 9,449 to 10,738 transgender individuals. CLINICAL IMPLICATIONS: All 5 codes are very sensitive in identifying transgender patients, and the combination of these codes with orchiectomy is extremely sensitive in identifying transgender women, specifically. STRENGTHS AND LIMITATIONS: Major strengths of the study are the use of universal ICD codes and a large patient sample size that spans health records nationally and across multiple decades, potentially making our data more generalizable. The main limitation of this study is that subanalyses were performed on a limited number of patients, which prevented us from capturing all false positives and thus from calculating specificity for each code. Similarly, our true negatives were derived from a small, random subset of the population; as such, our calculation for specificity is an estimate. CONCLUSION: This study highlights a novel method to identify transgender women and paves the way for further research.

DNA mismatch repair and microsatellite instability in colorectal tumors: an observational study in the Veterans Affairs Health Care System.

Background: Challenges in identifying microsatellite instability (MSI)/mismatch repair (MMR)-tested colorectal carcinoma (CRC) patients in electronic health records have led to gaps in the understanding of MSI-high/deficient mismatch repair prevalence. Methods: An algorithm to identify MSI-/MMR-tested Veterans Affairs patients was developed and an observational study of adult CRC patients with MSI/MMR testing from 2010 to 2018 was undertaken. Results: An optimized model to identify MSI-/MMR-tested patients yielded high positive predictive value (89.0%) and specificity (97.8%). The authors observed MSI-high/deficient mismatch repair CRC in 54 of 291 patients (18.6%); highest frequencies were observed in stages II (25.9%) and III (22.6%) and lowest in stage IV (5.8%). Conclusions: In this real-world study, the authors proposed a novel method of identifying MSI-/MMR-tested patients. Further validation and refinement of this model, and study in a larger CRC cohort, is warranted.

Plasma Apelin Unchanged With Acute Exercise Insulin Sensitization.

Blood glucose and insulin responses to aerobic exercise are well defined yet the mechanisms effecting post-exercise insulin sensitization remain incomplete. Apelin has been reported to enhance glucose uptake and insulin sensitivity in vivo, but its role as a regulator of insulin sensitivity following acute aerobic exercise has not been investigated. Therefore, the purpose of this study was to investigate apelin's response to acute bouts of maximal and submaximal aerobic exercise and to elucidate apelin's influence on insulin sensitivity. Twelve (22.8 ± 2.9 yrs) healthy male (n = 7) and female (n = 5) subjects completed a graded to maximal (VO2max) and submaximal (70-75% VO2max) treadmill running bouts, as well as a 50g glucose challenge (GC). Blood was obtained at four time points (pre, post, 1hr post and 24hrs post) and assessed for glucose, insulin and apelin. Hepatic insulin sensitivity was assessed at rest and at 1hr and 24hrs via HOMA-IR and QUICKI indices. Results demonstrated that plasma apelin did not significantly change by condition (p = 0.324) or time (p = 0.633). Blood glucose and plasma insulin were significantly elevated immediately after VO2max and GC, but remained stable after submaximal exercise. Insulin sensitivity was significantly improved 1hr post-submaximal exercise, per HOMA-IR (p = 0.034) and QUICKI (p = 0.018) indices. Plasma apelin was significantly correlated with plasma insulin (r = 0.699, p = 0.011), HOMA-IR (r = 0.626, p = 0.029) and QUICKI (r = 0.660, p = 0.019) at rest. We conclude that, although hepatic insulin sensitivity was improved 1hr post-submaximal exercise, this exercise-induced insulin sensitization occurred independent of plasma apelin changes.

Effects of stimulation technique, anatomical region, and time on human sweat lipid mediator profiles.

Few studies compare sampling protocol effect on sweat composition. Here we evaluate the impact of sweat stimulation mode and site of collection on lipid mediator composition. Sweat from healthy males (n=7) was collected weekly for three weeks from the volar forearm following either pilocarpine iontophoresis or exercise, and from the forearm, back and thigh following pilocarpine iontophoresis only. Sweat content of over 150 lipid mediators were measured by liquid chromatography-tandem mass spectrometry. Seventy lipid mediators were routinely detected, including prostanoids, alcohols, diols, epoxides, ketones, nitrolipids, N-acylethanolamides, monoacylglycerols, and ceramides. Detected lipid mediators appeared unaffected by sampling site, though the forearm was the most consistent source of sweat. Pilocarpine-induced sweat showed increased concentrations of most detected compounds. Moreover, lipid mediator concentrations and profiles were temporally stable over the study duration. Sweat therefore appears to be a consistent and anatomically-stable source of lipid mediators, but care must be taken in comparing results obtained from different stimulation techniques.

Association of the COVID-19 Pandemic With Rates of Prostate Cancer Biopsies and Diagnoses in Black vs White US Veterans.

Importance: Several studies have assessed the negative effect of the COVID-19 pandemic on cancer screening and diagnosis rates. However, this has not been evaluated for prostate biopsy and prostate cancer (PC) diagnosis in an equal-access health care system. Objective: To determine the association of the pandemic with prostate biopsy and PC diagnosis rates among Black vs White patients in the Veterans Affairs Health Care System (VAHCS). Design, Setting, and Participants: This cohort study included a retrospective analysis of all prostate biopsies performed on patients in the VAHCS without a preexisting PC diagnosis between January 2018 and March 2021. The base population included all living male patients who had at least 1 visit to the VAHCS during the 3 years prior to each month of the study. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: The main outcomes were the number of prostate biopsies and PC diagnoses by month. The influence of the pandemic on prostate biopsy volume and the incidence of PC diagnoses was modeled using an interrupted time-series analysis. Poisson generalized linear models were fitted to project the expected number of prostate biopsies and PC diagnoses had there been no pandemic interruption. Additional models were used to test for differences by race. Results: Prior to the pandemic (January 2018 through February 2020), monthly biopsy numbers among 51 606 included men ranged between 1230 and 1695, of which 56% to 60% of results were positive for PC. The estimated number of missed PC diagnoses from March 2020 through March 2021 ranged from 97 cases (October 2020: 752 cases expected, 655 cases observed) to 573 cases (April 2020: 794 cases expected, 221 cases observed). Prior to the pandemic, biopsy rates were statistically significantly higher among Black vs White men (incidence rate ratio, 2.25; 95% CI, 2.06-2.46; P < .001). There was no change in biopsy rates associated with race at the onset of the pandemic nor during the recovery period from March 2020 to March 2021. Similar trends were observed for PC diagnosis rates. Conclusions and Relevance: Results of this cohort study demonstrate that during the COVID-19 pandemic, prostate biopsy and PC diagnosis rates decreased, particularly during the peak of the pandemic. However, there were no statistically significant changes in rates by race.

A novel method for intratracheal injection of infectious agents into mice.

Intratracheal injection is a traditional technique used in small animal studies of highly contagious airborne pathogens such as Mycobacterium tuberculosis. However, current techniques of intratracheal injection generally involve procedures that pose a risk of incident injury and infection for researchers, and may also cause collateral damage to experimental animals during the installation process. Here we describe an intratracheal injection method that was enabled by a three dimensional printing of a custom platform. This updated technique improved the overall ergonomics of intratracheal injection in mice, minimizing the risk of human injury and implementing the 3R (replacement, reduction and refinement) principle in mouse infection studies.