Citations

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC–associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC–related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

Context.— Misdiagnosis of antiphospholipid syndrome can occur owing to the wide diversity of antiphospholipid (aPL) assays and a lack of international calibrators and harmonized reference intervals. Objective.— To assess laboratory practices regarding reporting and establishing reference intervals for immunoglobulin (Ig) G/IgM anti-cardiolipin (aCL) and anti–beta-2 glycoprotein I (anti-β2GPI) assays. Design.— Supplemental questions related to reporting and establishing reference ranges for aPL assays were sent as part of the Antiphospholipid Antibody (ACL)-B 2019 College of American Pathologists (CAP) proficiency testing survey. The response rate and methods assessment details were determined, as well as qualitative and quantitative results for 3 test samples. Results.— The number of participants reporting results for IgG aCL (n = 489), IgM aCL (n = 476), IgG anti-β2GPI (n = 354), and IgM anti-β2GPI (n = 331) varied by antibody type. The enzyme-linked immunosorbent assay (ELISA) (up to 58.6%, 260 of 444) was the most used method; others included multiplex (from 18.9% to 23.9%), fluorescence enzyme immunoassay (14.4%–17.6%), and chemiluminescence immunoassay (6.5%–9.0%). More respondents reported quantitative than qualitative results, and manufacturer cutoff ranges were used by 92.9% and 94.2% of respondents for aCL and anti-β2GPI, respectively. Despite variation in the use of semiquantitative ranges, qualitative negative/positive reporting of the test samples achieved almost 100% consensus. Qualitative consensus was met in contrast to the wide range of quantitative results obtained for each analyte across different kits. Conclusions.— ELISA remains the most used method for detecting aPL antibodies, with most laboratories reporting quantitative results based on manufacturers' suggested reference ranges. The categorization of quantitative results as equivocal, weak positive, or positive for responders using kits from the same manufacturer was variable.

Objective To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. Methods This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real‐world patient scenarios, and weighting via consensus‐based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators’ consensus as the gold standard. Results The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL‐associated clinical criterion, followed by additive weighted criteria (score range 1–7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid‐phase enzyme‐linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti–β 2 ‐glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versu s 86%, and a sensitivity of 84% versus 99%. Conclusion These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk‐stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Abstract Objectives Inflatable penile prosthesis (IPP) placement on active anticoagulation (AC) is controversial. Techniques utilized to decrease complications include use of malleable implant, partial inflation of IPP for hemostasis, and placement of drain; however risk and benefits must be weighed. We sought to assess outcomes of IPP in men on AC in a multi-institutional study. Methods Data from 3 high-volume implant centers was retrospectively analyzed. Demographics, comorbidities, secondary procedures, drain placement/output, and complications were recorded. Aspirin was excluded as it is not routinely held. Center 1 utilizes a penoscrotal approach without drain placement, center 2 a penoscrotal approach with drain placement (removal when output <50 mL/8 hours), and center 3 an infra-pubic approach with drain for 3 days. Results 202 patients were continued on AC throughout surgery: 112 on clopidogrel, 35 warfarin, 38 apixaban, 1 enoxaparin, 15 rivaroxaban, and 1 combination therapy with clopidogrel and enoxaparin. AC was most continued for peripheral vascular disease (55%), cardiac stents (11.6%), CHF (11%), and atrial fibrillation (11%). Nine patients (3.98%) experienced complications. Four significant events (1 retropubic bleed requiring transfusion, 3 IPP infections) and 5 minor events (3 hematomas, 1 wound dehiscence,1 CT-negative stroke) occurred. Average drain output for center 1 was 223 mL with no hematomas or infections noted. Average drain output for center 2 was 121 mL with most drains removed postoperative day 1. Drain output was significantly higher than historical non-AC controls (p=0.001), however complication rates were not significantly different (p>0.05). AC type, revision surgery, scrotoplasty, or reservoir technique did not affect outcomes or drainage. Conclusions In high-volume implant centers, major complication rate of 1.9% occurred in IPP patients on AC. Although IPP is feasible in this patient population, drain for 3 days and submuscular reservoir placement may be indicated. In most, elective IPP surgery should be delayed until it is safe to discontinue anticoagulation. Conflicts of Interest None

Abstract Introduction Penile prosthesis placement in men on active anti-coagulation (AC) is controversial. The bleeding risk of continued blood thinners must be weighed against the increased thrombotic risk for patients when stopping them. Previously utilized techniques to decrease complication rates from AC include the use of a malleable implant only, leaving the IPP partially inflated for hemostasis, and placement of a drain. Objective We sought to assess outcomes of penile implant placement in men on clopidogrel, warfarin, apixaban, enoxaparin, and rivaroxaban in a multi-institutional study. Methods Data from 3 high volume implant centers were retrospectively obtained. Demographic characteristics, comorbidities, case information including secondary procedures, placement of drain, drain output, and complications were recorded. Data on patients with aspirin any dose alone were not included as all 3 centers do not routinely discontinue ASA at time of penile implant. One center never placed drains and used a penoscrotal approach, one center left a drain at least one day and removed when output was < 50 ml/8 hours and used a penoscrotal approach, and the last center placed a drain for 3 days and utilized an infra-pubic approach. Results 202 patients were continued on AC throughout surgery. 112 patients were on clopidogrel, 35 warfarin, 38 apixaban, 1 enoxaparin, 15 rivaroxaban, and 1 on combination therapy with clopidogrel and enoxaparin. AC requirement included peripheral vascular disease (55%), CHF (11%), cardiac stents (11.6%), DVT/PE/history of thrombosis (7%), atrial fibrillation (11%), cardiac valves (2.2%), stroke (1.3%), and preventive (0.9%). Nine patients on AC (3.98%) experienced complications including 4 significant events (1.9%): 1 major retropubic bleed requiring transfusion, 3 IPP infections and 5 minor events: 3 minor hematomas, 1 minor wound dehiscence and 1 CT negative stroke event. Drain outputs for the 3 day center averaged 113 ml, 81 ml and 30 ml of output per day respectively with a total average output average of 223 ml and experienced no hematomas nor infections. Drain output for the center with removal when < 50 ml/8 hours averaged 121 ml with the majority or patients having the drain for only one day. Drain output was significantly higher than historical non AC controls (121 vs. 72 ml p=.001) but there was no difference in hematoma rate. Three hematomas and 1 infection occurred in this group. AC type, revision surgery, scrotoplasty, or reservoir technique did not affect outcomes nor drainage (P>.05). Complication rate (IPP infection and hematoma rate) where not different when compared to large cohorts from respective institutions. Conclusions Our data shows a 1.9% rate of major complications in patients undergoing IPP placement on anticoagulation in high volume implant centers. Although this approach appears feasible and similar in complication rates in men not on AC, careful consideration of the risk benefit ratio should be undertaken. Our data indicate closed suction draining for 3 days may be warranted. Additionally, the retropubic bleed case argues for only submuscular reservoirs placed under direct vision which minimizes occult bleeding risk. In the majority of cases, elective IPP surgery should be delayed until it is safe to discontinue anticoagulation therapy. Disclosure No

Abstract Introduction: The lack of representation of minoritized and marginalized (MaM) populations in Clinical Trials (CTs) has been noted as one of the key factors that contribute to cancer health disparities. The challenges of CT diversity are multifactorial, including barriers at the personal, provider, health systems and protocol levels. Guided by a vision of developing and implementing inclusive CTs that address the priorities identified by our communities, we created a Community Research Registry (CoRR) with three primary aims: 1. Maintaining a CoRR database of participants who may be eligible for participation in future CTs; 2. Using the database, facilitate matching of MaM populations to Clinical Trials; and 3. Facilitating access of MaM populations to CTs. Methodology: The Mayo Clinic CoRR is IRB-approved and was implemented in 2022 through bidirectional engagement of communities, partnership with community leaders to foster community input, dissemination of CT information to high-risk communities, and use of evidence-based education materials for community outreach. Participants are recruited in MaM communities (including clinics, churches, health events) and through effective use of social media. Organized events for recruitment include: 1. CT education; 2. provision of culturally tailored CT educational materials and T-shirts; and 3. data collection from those who consent to be part of the registry. The inclusion criteria for the registry are adults and ability to read and write in English or Spanish. Informed consent is obtained prior to completion of the registry form and participants receive $10 incentive. The data is collected using REDCap, and includes name and contact information of participants, demographic information, chronic disease status and explicit consent to be contacted for future research studies (with option to state type of study). New Unpublished Data: Within 7 months of CoRR implementation, 184 MaM participants signed up with 92% Black (including 10% African immigrants), 7% Hispanic, 69% female, median age of 64 years, 24% rural residents, and most of the participants had high school level education. Over 30% of participants reported medical history of hypertension, high cholesterol, arthritis and/or diabetes. 8% reported cancer. Approved investigators (with appropriate community engagement training) have direct access to de-identified CoRR information though Tableau for the purpose of estimating participants for their study. Tableau has been found to be effective for investigators to explore the database for CT/research match. All requests for participants matching are approved by a CoRR Board that includes community representatives, prior to matching. CoRR CT matching is now in its pilot phase, with Mayo Clinic studies identified for matching. Conclusion: The feasibility of the CT CoRR has been established, and has led to over 20 CoRR Champion organizations, including churches, sororities, fraternities, and the American Legion Post. Citation Format: Folakemi T. Odedina, Floyd Willis, Jennifer Crook, Emelina Asto-Flores, Kim Barbel Johnson, Chad Workman, Mayo Clinic Comprehensive Cancer Center CommunityOutreach and Engagement. Increasing clinical trials diversity through Community Research Registry (CoRR): The Community Champions for clinical trials program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB112.