Citations

Abstract Study Objective To determine whether there is a drug‐drug interaction precluding the concomitant use of levetiracetam and high‐dose methotrexate (HDMTX). Design Retrospective analysis. Setting Large academic tertiary care medical center. Patients Adult lymphoma patients who received HDMTX as a 4‐h infusion with or without concomitant levetiracetam. Measurements and Main Results Generalized estimating equations clustered on patient were used to assess each outcome. The primary outcome was the incidence of delayed MTX elimination (MTX level >1 µmol/L at 48 h). Secondary outcomes included incidence of acute kidney injury (AKI) and hospital length of stay (LOS). The 430 included patients receiving 1993 doses of HDMTX had a median (IQR) age of 66 (57.5, 72.6) years, 88 (20.5%) received concomitant levetiracetam with at least one dose of MTX, 267 (62.1%) were male, and 397 (92.3%) were Caucasian. HDMTX doses ranged from 1 to 8 g/m 2 . The most common lymphoma diagnoses were systemic diffuse large B‐cell lymphoma (DLBCL; 58.5%) and systemic DLBCL with central nervous system (CNS) involvement (32.8%). Rates of delayed elimination with and without levetiracetam were 13.4% and 16.3%, respectively (OR = 0.80, 95% CI 0.47–1.34, p = 0.39). AKI occurred in 15.6% and 17.0% of patients with and without concomitant levetiracetam, respectively (OR = 0.83, 95% CI 0.52–1.33, p = 0.28). The median LOS with and without levetiracetam was 4.2 and 4.1 days, respectively ( p = 0.039). On multivariable analyses, only age, body surface area, diagnosis of systemic DLBCL with CNS involvement, serum creatinine, hemoglobin, total bilirubin, and dose of HDMTX were associated with delayed elimination. Conclusions High‐dose methotrexate administered with concomitant levetiracetam was not associated with increased risk for delayed MTX elimination or AKI. These results support that levetiracetam and HDMTX are safe for coadministration.

428 Background: Trimodality therapy (TMT) with maximal TURBT followed by chemoradiation(CRT) is a standard of care for select patients with muscle invasive bladder cancer (MIBC). This trial evaluates the activity of atezolizumab (atezo) in MIBC in combination with TMT. This trial was designed with pre-specified safety analyses of the first 80 patients (40 in each arm). At the time of SWOG fall 2020 DSMC report deadline we had enrolled 84 patients but data on only 73 patients were available. The same data are being submitted to ASCO GU meeting. Methods: This trial is testing atezo every 3 weeks for 6 months given concurrently and adjuvantly with CRT vs. CRT alone in 475 patients with MIBC T2-T4aN0M0 disease. Patients are stratified based on PS; T2 vs T3 or T4; choice of chemotherapy; and radiation field (bladder only vs small pelvis). Patients undergo biopsy 3 months after finishing CRT to assess treatment response. Patients are followed for 5 years for recurrence or survival. This trial was not preceded by a phase I study but was designed with a safety run in of 80 patients. Study team agreed on the study design based on available data from other tumor types and initial experience from investigators running smaller similar trials. It was pre-specified that if we observe more than 25% patients having grade 3-5 colitis or cystitis in the atezo arm or any other toxicity which is deemed clinically significant and related to atezo, the trial investigators and DSMC would consider stopping further enrollment. Results: 36 patients were enrolled on the TMT alone arm and 37 patients on the TMT + atezo arm. No grade 3 or higher colitis was reported in the atezo arm. Only one patient had treatment related grade 3 radiation cystitis which was diagnosed after finishing atezo treatment. No steroids were given. Overall 23 grade 3 or higher toxicity events were reported in the atezo arm vs 11 in non- atezo arm. Most common toxicity was hematological which was considered non-immune related. None of the grade 3 or higher toxicities were considered to be immune related by the treating investigator. Conclusions: There is no evidence of increased immune related grade 3-5 AEs.DSMC has recommended to continue enrollment. Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed Clinical trial information: NCT03775265 . [Table: see text]

Abstract Objectives We investigated the impact of our laboratory’s reflex testing process for resolving ERBB2 (HER2) status on breast cancer samples that require additional workup after fluorescence in situ hybridization (FISH), per guideline recommendations published in 2018 by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP). Methods In total, 500 breast cancer specimens with ERBB2 FISH results in groups 2 through 4 (all reported as immunohistochemistry [IHC] equivocal [2+] at external laboratories) were resubmitted for IHC testing in our laboratory. Per the ASCO/CAP guideline, FISH was rescored when internal IHC was also equivocal (2+), targeted to tumor areas demonstrating more intense IHC staining, if observed. Results Reflex IHC/FISH testing changed the final reported ERBB2 status in 185 of 500 (37.0%) samples. Result changes included discordant IHC (n = 4 score 0, n = 132 score 1+, and n = 16 score 3+) and discordant FISH (n = 33). Numerical differences in FISH scores were comparable for targeted vs nontargeted FISH rescoring (P = .086 for ERBB2 copy number; P = .49 for ERBB2 ratio). Two cases showed larger differences in FISH scores, suggesting heterogeneity. Conclusions Retesting of breast cancer samples with equivocal IHC frequently changes IHC results, but targeted reanalysis of borderline FISH results rarely identifies significant differences in ERBB2 copy number or ratio.

Background: The sustainability of health benefits in response to lifestyle-based interventions remains unclear in children with overweight and obesity, and cardiometabolic disease (CMD). We determined the changes in novel biomarkers of CMD in a 1-year family-based intervention (FBI) program, during 6-month active monitoring phase and at 12-month follow-up. Methods: Children with an age-adjusted body mass index (BMI) percentile ≥85 ( N = 130; age 8–11 years) were recruited for a 1-year (6-month monitored and 6-month unmonitored) randomized controlled FBI program. Anthropometry and selected biomarkers of CMD were measured in 87 participants, randomly allocated to intervention (INT) and education-only (EDU) groups, at baseline, immediately after a 6-month active intervention or control period, and at 12-month unmonitored follow-up. Results: Samples from 87 participants (age 10.00 ± 0.11 years and Tanner stage ≤3) with obesity (BMI%ile = 97.45 ± 0.15) were available. Overall intervention effect (between groups), was observed for total (T) and high molecular weight (HMW) adiponectin, ratio of total to HMW adiponectin, fibrinogen, and interleukin (IL)-6 ( P < 0.05 for all). However, between-group beneficial changes after adjusting for baseline levels were limited to BMI percentile, T and HMW adiponectin and their ratio, IL-6, and fibrinogen ( P < 0.05 for all) mainly during the 6-month period of monitored intervention. Changes in traditional risk factors such as lipids and triglycerides were inconsistent. During the 6-month follow-up period, the changes in biomarkers leveled-off, except for T and HMW adiponectin, IL-6, and fibrinogen that continued to show benefits ( P < 0.05) from the 6- to 12-month follow-up. Conclusions: The FBI program beneficially altered novel biomarkers of CMD during the monitored intervention phase in school-age children with obesity, but they mostly moved back toward baseline during the unmonitored follow-up phase. The changes in novel biomarkers of CMD appear to be more sensitive compared to the traditional risk factors. The study implies the need for refinements in lifestyle-based approaches in the preservation of cardiovascular health and calls for robust biomarkers to monitor the changes. The study was registered at ClinicalTrials.gov (NCT01146314).

Abstract Background Microsurgery is being increasingly utilized across surgical specialties, including plastic surgery. Microsurgical techniques require greater time and financial investment compared with traditional methods. This study aimed to evaluate 20-year trends in Medicare reimbursement and utilization for commonly billed reconstructive microsurgery procedures from 2000 to 2019. Methods Microsurgical procedures commonly billed by plastic surgeons were identified. Reimbursement data were extracted from The Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services for each current procedural terminology (CPT) code. All monetary data were adjusted for inflation to 2019 U.S. dollars. The average annual and total percentage changes in reimbursement were calculated based on these adjusted trends. To assess utilization trends, CMS physician/supplier procedure summary files were queried for the number of procedures billed by plastic surgeons from 2010 to 2018. Results After adjusting for inflation, the average reimbursement for all procedures decreased by 26.92% from 2000 to 2019. The greatest mean decrease was observed in CPT 20969 free osteocutaneous flaps with microvascular anastomosis (−36.93%). The smallest mean decrease was observed in repair of blood vessels with vein graft (−9.28%). None of the included procedures saw an increase in reimbursement rate over the study period. From 2000 to 2019, the adjusted reimbursement rate for all procedures decreased by an average of 1.35% annually. Meanwhile, the number of services billed to Medicare by plastic surgeons across the included CPT codes increased by 42.17% from 2010 to 2018. Conclusion This is the first study evaluating 20-year trends in inflation-adjusted Medicare reimbursement and utilization in reconstructive microsurgery. Reimbursement for all included procedures decreased over 20% during the study period, while number of services increased. Increased consideration of these trends will be important for U.S. policymakers, hospitals, and surgeons to assure continued access and reconstructive options for patients.

Background: This study aimed to explore clinicians’ perspectives on the current practice of perinatal mood and anxiety disorder (PMAD) management and strategies to improve future implementation. Methods: This study had a cross-sectional, descriptive design. A 35-item electronic survey was sent to clinicians (N = 118) who treated perinatal women and practiced at several community clinics at an academic medical center in the United States. Results: Among clinicians who provided care for perinatal women, 34.7% reported never receiving PMAD management training and 66.3% had less than 10 years of experience. Out of 10 patients who reported psychiatric symptoms, 47.8% of clinicians on average reported providing PMAD management to 1 to 3 patients and 40.7% noted that they conducted screening only when patient expresses PMAD symptoms. Suggested future improvements were providing training, developing a referral list, and establishing integrated behavioral health services. Conclusions: Results from this study indicated that while PMAD screening and management was implemented, improvements are warranted to meet established guidelines. Additionally, clinicians endorsed providing PMAD management to a small percentage of perinatal patients. Suggested strategies to increase adoption and implementation of PMAD management should be explored to improve access to behavioral health services for perinatal women.

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic has required swift implementation of innovative practices in health care across the globe. We describe a nurse practitioner (NP) and physician assistant (PA)–led initiative to implement telemonitoring (TM) of noncritical patients with COVID-19 by critical care NPs and PAs (C19TM) for early detection of decompensation and early transfer to the intensive care unit (ICU). Every hospitalized patient with suspected or confirmed COVID-19 received an initial telemedicine consult with a critical care NP or PA. Patients were subsequently monitored via electronic health record once every 12-hour shift for the following indicators: oxygen modality and flow, increase in oxygen requirements, sustained tachypnea, and hemodynamic instability. If signs of decompensation were noted, the NP/PA would remotely reassess the patient, provide recommendations to the hospital internal medicine team, and transfer the patient to the ICU. The primary goal was to avoid cardiopulmonary deterioration requiring aerosol-generating procedures outside of the ICU. Over 65 days, 113 patients (86 suspected and 27 confirmed) were enrolled in C19TM. As a result, there were 13 transfers to the ICU, none of which required an aerosol-generating procedure outside of the ICU.

ObjectiveThe aim of this systemic review is to compare different treatments for patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) to inform evidence‐based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) Vasculitis Management Guidelines.MethodsA systemic review was conducted by searching articles in English using OVID Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing PICO questions, with studies presenting the highest level of evidence given preference.ResultsA total of 729 full‐text articles addressing GPA and MPA PICO questions were reviewed. For remission induction, rituximab was shown to be noninferior to cyclophosphamide (CYC) (odds ratio [OR]: 1.55, moderate certainty of evidence). The addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease (hazard ratio [HR]: 0.86 [95% confidence interval CI: 0.65, 1.13], moderate certainty of evidence). In nonsevere disease, methotrexate was noninferior to CYC for induction of remission (remission at 6 months of 90% vs. 94%). For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse over a mean follow‐up of 29 months (HR: 0.92, [95% CI: 0.52, 1.65]low certainty of evidence). As maintenance therapy, rituximab was superior to a tapering azathioprine strategy in major relapse‐free survival at 28 months (HR: 6.61, [95% CI: 1.56, 27.96], moderate certainty of evidence). In two randomized trials, longer‐term azathioprine maintenance therapy (>24 months) is associated with fewer relapses without an increase in adverse events.ConclusionThis comprehensive systematic review synthesizes and evaluates the benefits and toxicities of different treatment options for GPA and MPA.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

Abstract Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast cancer (BC) risk by 50-65%. Despite this significant reduction, a small proportion of high risk women take ET, due to attitudes toward medications, inaccurate risk perception and drug side-effects. The addition of a polygenic risk score (PRS), comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)), to the standard risk calculator estimates, can be used to improve BC risk estimation. We previously reported on the influence of the PRS-adjusted BC risk estimates on the intent to use ET (Abstract, SABCS, 2019). Here we report on the influence of PRS-adjusted BC risk estimates on ET adherence at 1 and 2 year follow –up. We also report on ET side effects over this same time period. Methods: Women older than age 35 were eligible if they were deemed at high risk for BC by either a 5 year Gail Model risk of ≥3% or 10 year Tyrer-Cuzick risk (IBIS) of ≥5%. We excluded women with a personal history of BC or hereditary BC syndromes. At baseline, participants were counseled on their BC risk using standard risk calculators: Gail and IBIS risk scores (5 yr, 10 yr, & lifetime) and ET options were discussed, including benefits and risks. Blood samples were obtained and genotyped for 77 SNPs, and an updated BC -PRS risk report was shared with study participants that reflected the IBIS and Gail risk predictions for 5 yr, 10 yr, & lifetime BC risk with and without the PRS. A baseline self-reported questionnaire assessed understanding of BC risk and decision to take ET. Follow-up questionnaires at 1 and 2 years assessed self-reported ET adherence and ET side effects (vasomotor symptoms, vaginal symptoms, sexual dysfunction, weight gain, GI symptoms, headaches, breast sensitivity, mood changes, and joint pain). Adherence to ET at 1 and 2 year follow-up was stratified by three categories of lifetime PRS-BC risk: 0-20%; 20-40%; 40-100%. Results: 151 women at Mayo Clinic Rochester and CancerCare Manitoba were enrolled in the study from 2016 to 2017. Of the 149 participants with evaluable data at 1 and 2 year follow-up, 57 (38%) started on ET therapy, all within 1 year of the baseline visit; 43 (29%) were taking ET at 1 year and 33 (22%) were taking ET at 2 year follow-up, representing a discontinuation rate of 26% at 1 year and 42% at 2 year follow-up. Adherence to ET use at 1 year and 2 year follow-ups correlated significantly with the category of PRS-BC risk estimation: at 1 year follow up, 17% of those in the lowest PRS-IBIS risk category, 23% in the middle risk category and 50% of those in the highest risk category were taking ET (p=0.001). At 2 year follow up, 12% of those in the lowest PRS-IBIS risk category, 18% in the middle risk category and 38% of those in the highest risk category were taking ET (p=0.008). At 1 year follow up, participants taking ET reported significantly more bothersome symptoms of vaginal itching (p=0.010), weight gain (p=0.015) and joint pain (p=0.044), compared with those not on ET. There was a trend towards increased irritability and mood swings on those taking ET (p=0.059). At year 2 there was no significant difference in side effects between those taking and not taking ET. Conclusion: Adherence to ET in a population of women at high risk for BC decreased overtime and strongly correlated with the level of risk, with 38% of those at highest risk of breast cancer taking ET at 2 year follow up. Side effects of vaginal itching, weight gain and body aches were more common on those taking ET versus not taking ET at the 1 year follow-up, but did not differ at 2 year follow-up, possibly due to the fact that those with the most bothersome symptoms have discontinued ET by the 2 year follow up. Citation Format: Daniela Stan, Julian Kim, Daniel Schaid, Erin Carlson, Andrew Cooke, Christina A. Kim, Benjamin Goldenberg, Jason Sinnwell, Debjani Grenier, Amy Degnim, Fergus Couch, Celine Vachon, Sandhya Pruthi. Influence of a breast cancer polygenic risk score on adherence to preventive endocrine therapy in high risk women at 1 and 2 year follow-up: The genetic risk estimate (GENRE) trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-02.