Citations

Abstract Background Patients taking chronic opioids are at high risk of opioid induced adrenal insufficiency (OIAI). Previously, we showed that the prevalence of OIAI was 9% based on low morning cortisol, corticotropin (ACTH), and dehydroepiandrosterone sulfate (DHEAS). Data on the overnight metyrapone test to diagnose OIAI are sparse. We aimed to determine the prevalence of OIAI using overnight metyrapone test and identify changes in the steroid metabolome of patients treated with opioids. Methods Cross-sectional study of adult patients treated with opioid therapy of at least 20 morphine milligram equivalents (MME)/day for at least 3 months. Measurements included ACTH, cortisol, and DHEAS. Overnight metyrapone test was administered in all patients, and 24h urine steroid profiling was optional (25 steroids measured by liquid chromatography mass spectrometry1). All patients completed the quality-of-life survey (AddiQoL). Prevalence of OIAI was defined as sum of post-metyrapone 11-deoxycortisol and cortisol of <15 mcg/dL. Result: In 22 patients (median age 59 years [range, 38-74], 9, 41% women), median MME was 33 (20-161) mg, and median cumulative opioid exposure was 245 (10-2550) mg*years. Following the overnight metyrapone test, 7 (32%) patients were diagnosed with OIAI. Patients with OIAI had lower DHEAS concentrations (median of 21 mcg/dL[ 5-113] vs 54 [22-173], p =0. 03), but not cortisol (median 10[5.3-16] mcg/dL vs 13[5.3-22], p=0. 06) or ACTH (median 27[8.1-51] pg/mL vs 26[5.9-55], p=0.8). Patients with OIAI were treated with higher daily MME (100 mg[30-150] vs 30[20-161], p=0. 03) and had a higher cumulative exposure to opioids (median, 660 mg*years [250-2250] vs 150 [10-1288], p =0. 01). AddiQol scores were similar between groups (median of 68[56-84] vs 73[48-83], p= 0.97). Urine steroid profiling was performed in 18 patients. Patients with OIAI demonstrated 4 times lower total urine glucocorticoids (16334 mcg/24h vs 4377 mcg/24h, p=0. 003), all <10% of the reference range, and 3 times lower total urinary androgens (median of 805 mcg/24h vs 2320 mcg/24h, p=0.14). Conclusion Prevalence of OIAI using overnight metyrapone test is high at 32%. Patients diagnosed with OIAI were treated with higher doses of MME/day and had a higher cumulative exposure to opioids when compared to those without OIAI. Applying 24h urine steroid profiling we showed that total glucocorticoids are 4 times lower in those with OIAI (and all <10% of reference ranges) as opposed to those without OIAI. We showed that baseline measurements of ACTH, DHEAS, and cortisol may incorrectly exclude OIAI, and a dynamic test, such as overnight metyrapone test is needed when suspicion for OIAI is high. | 1. Hines JM, Bancos I, Bancos C, et al. High-Resolution, Accurate-Mass (HRAM) Mass Spectrometry Urine Steroid Profiling in the Diagnosis of Adrenal Disorders. Clin Chem. 2017;63(12): 1824-1835. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

AbstractBackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer–related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types.ConclusionsCNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

AbstractBackground and objectivesPrevious studies have identified racial‐ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial‐ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT.MethodsWe performed an 11‐institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence‐free survival according to race‐ethnicity.ResultsWomen of non‐White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non‐Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence‐free survival in our cohort.ConclusionsDifferences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race‐ethnicity. These conclusions are supported by our finding that there were no differences in recurrence‐free survival.

AbstractBackgroundIn 2016, the IDWeek program committee was charged with ensuring gender equity in speaker sessions. Whether this charge also resulted in more opportunities for historically underrepresented speakers is unknown.MethodsWe conducted a retrospective analysis of trends in the demographic composition of IDWeek speakers and program committee members between 2013 and 2021. We used descriptive statistics to summarize data, χ2 tests to compare speaker demographics between 2013–2016 (before 2016) and 2017–2021 (after 2016), and Cochran–Armitage tests for trend. Each speaker slot was considered an independent event.ResultsA total of 5482 speaker slots were filled by 3389 individuals from 2013 to 2021. There was a linear increase in female speakers from 38.6% in 2013 to 58.4% in 2021 (P < .001). The proportion of white speakers decreased overall from 84.9% in 2013 to 63.5% in 2021. Compared with white speakers, more slots were filled by Asian speakers after 2016 versus before 2016 (20.1% vs 14.8%, respectively; P < .001). Program committee members from 2013–2021 were >80% non-Hispanic white; <5% of committee members identified as black, American Indian, Alaska Native, Native Hawaiian, Pacific Islander, or Hispanic. More program committee slots were filled by women after 2016 than before 2016 (52.7% vs 33.9%; P = .004).ConclusionsIntentional consideration of gender equity by the program committee was associated with equitable gender representation of invited speakers at IDWeek after 2016. Gradually, the proportions of IDWeek speakers from historically excluded racial/ethnic approached their respective proportions in the IDSA membership. White speakers remained overrepresented relative to membership proportions until 2021, and gaps in program committee racial/ethnic demographic representation highlights opportunities for continued inclusion, diversity, access, and equity at IDWeek.

Summary The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo‐HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo‐HCT between 2008 and 2019. Non‐relapse mortality (NRM), disease relapse/progression (REL), progression‐free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow‐up of survivors was 62 (3–148) months. The 1‐year NRM was 18%. The 5‐year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6–4.8; p < 0.001) and refractory disease at allo‐HCT (HR 3.2, 95% CI 1.6–6.2; p < 0.001) were predictive of inferior OS. Similarly, African‐American race (HR 2.1, 95% CI 1.3–3.4; p = 0.003), other minority race (HR 2.5, 95% CI 1.2–5.3; p = 0.02) and refractory disease (HR 2.2, 95% CI 1.2–4.3; p = 0.01) were predictive of inferior PFS. These data, demonstrate that allo‐HCT can result in durable disease control in a sizable proportion of patients with R/R ALCL. Refractory disease and racial minority status predicted inferior allo‐HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL after allo‐HCT are driven by differences in disease biology or disparities in post allo‐HCT care, or both, requires further investigation.

Antiplatelet therapy is used in the treatment of patients with acute coronary syndromes, stroke, and those undergoing percutaneous coronary intervention. Clopidogrel is the most widely used antiplatelet P2Y12 inhibitor in clinical practice. Genetic variation in CYP2C19 may influence its enzymatic activity, resulting in individuals who are carriers of loss-of-function CYP2C19 alleles and thus have reduced active clopidogrel metabolites, high on-treatment platelet reactivity, and increased ischemic risk. Prospective studies have examined the utility of CYP2C19 genetic testing to guide antiplatelet therapy, and more recently published meta-analyses suggest that pharmacogenetics represents a key treatment strategy to individualize antiplatelet therapy. Rapid genetic tests, including bedside genotyping platforms that are validated and have high reproducibility, are available to guide selection of P2Y12 inhibitors in clinical practice. The aim of this review is to provide an overview of the background and rationale for the role of a guided antiplatelet approach to enhance patient care.

Background: The extent to which concussions affect Women’s National Basketball Association (WNBA) athletes has not been thoroughly examined. Purpose: To evaluate the incidence and impact of concussion injuries occurring in the WNBA. Study Design: Descriptive epidemiology study. Methods: Publicly available records were searched to identify all documented basketball-related concussions from WNBA seasons 1997 to 2020. Player demographics, injury details, and basketball career information were collected. Concussion incidence and return-to-play (RTP) timing were evaluated before and after the institution of the WNBA concussion protocol in 2012. Minutes per game and game score per minute were compared 5 games before and 5 games after the concussion was sustained. Player game availability and RTP performance were also compared with an age-, body mass index–, position-, and experience-matched control group of players who did not sustain any injuries during the index season. Results: A total of 70 concussions among 55 players were reported in the WNBA from 1997 to 2020, with a mean incidence of 2.9 ± 2.3 concussions per season. After the implementation of the WNBA concussion protocol, the incidence significantly increased from 1.7 to 5.0 concussions per season ( P < .001). All players returned after a first-time concussion, missing a mean of 3.8 ± 4.7 games and 17.9 ± 20.7 days. After the adoption of the concussion protocol, the time to RTP significantly increased with games missed ( P = .006) and days missed ( P = .006). Minutes per game and game score per minute were not significantly affected by sustaining a concussion ( P = .451 and P = .826, respectively). Conclusion: Since the adoption of the WNBA concussion protocol in the 2012 season, the incidence of concussions increased significantly. Athletes retained a high rate of RTP after missing a median of 4 games, and the time to RTP increased after the institution of the concussion protocol. Player game availability and performance within the same season were not significantly affected by concussion injuries after a successful RTP.