Citations

Background Health disparities among minority groups, especially African Americans, can limit their access to quality medical care and lead to disproportionate medical management and disease outcomes. The aim of this study was to compare the COVID-19-related change in mammogram volumes and cancer detection at two affiliated academic breast centers, one that serves a predominantly African American patient population and one that serves a predominantly non-African American patient population. Materials and methods For the purpose of anonymity, racial demographics were collected and the center with a higher African American patient population was designated as institution A, while the center with a higher non-African American patient population was designated as institution B. Careful selection of the two breast centers was instituted in order to limit the impact of potential confounders other than race. An Institutional Review Board (IRB) exemption was obtained and two Mammography Quality Standards Act (MQSA) reports were generated; one for March 2020 through September 2020, during the height of the COVID-19 pandemic, and one for March 2019 through September 2019 to serve as the pre-pandemic control group. The i2b2 Query Analysis Tool® was used to obtain racial demographic data and compare the percent change in screening and diagnostic mammograms, image-guided biopsies, total cancers diagnosed by imaging, and percent of minimal cancers for both institutions. Results Screening mammograms and breast cancer detection decreased in 2020 compared to 2019 at both institutions. However, the percent change from 2019 to 2020 was greater at institution A than at institution B. Percent minimal cancers, an indicator of early-stage breast cancer also decreased more drastically at institution A than at institution B. Interestingly, the total number of diagnostic exams and image-guided biopsies increased in 2020 at institution B, whereas both decreased at institution A. Conclusion The COVID-19 pandemic may lead to worsening racial disparities in breast cancer screening. In an effort to narrow future disparity, it is crucial for radiologists and other health care providers to be aware of this inequality and educate all women on the importance of obtaining routine screening mammography. More studies are needed.

Abstract Background: Constitutive MEK-ERK activation induced by BRAFV600E or RAS mutation promotes tumor metastasis in CRC that is mediated by transcription factors regulating epithelial-to-mesenchymal transition (EMT). We determined the role of ZEB1, an EMT master transcription factor, and its potential regulation by the ubiquitin specific peptidase 10 (USP10), in tumor metastasis mediated by MEK-ERK. Materials and Methods: Isogenic RKO [BRAFV600E or wild-type (wt)] and Colo320 (BRAF/KRAS wt/wt) human CRC cells were utilized. Colo320 cells were transfected with mutant KRASG12D. In addition to parental cells, we generated USP10 shRNA expressing RKO and Colo320 cells. Cells were treated with the MEK1/2 inhibitor cobimetinib or BRAF inhibitor encorafenib. Cell migration was analyzed by wound healing and transwell assays. Protein/protein interaction was analyzed by immunoprecipitation. Protein ubiquitination level was determined by ubiquitination assay. In an orthotopic model, lung metastases in mice were generated by tail vein injection of RKO cells. Results: We demonstrate MEK-ERK activation, induced by BRAFV600E, promotes CRC metastasis through inhibition of the USP10-ZEB1 axis. USP10 is shown to interact with ZEB1 and to remove its K27 linkage ubiquitination chain, thus increasing K48 ubiquitination of ZEB1 protein that results in proteosome-mediated degradation of ZEB1. MEK-ERK induced the phosphorylation of USP10 that is shown to attenuate the USP10-ZEB1 interaction and results in ZEB1 stabilization in RKO and Colo320 cell lines. Increased ZEB1 expression promotes tumor cell migration in vitro and metastasis in a murine xenograft model that could be suppressed by cobimetinib or BRAFV600E-directed therapy with encorafenib and cetuximab. Conclusions: Targeting RAF/RAS-driven MEK/ERK signaling can suppress ZEB1 stabilization to inhibit tumor metastasis. Suppression of metastasis occurs by a novel mechanism of ZEB1 stabilization that is regulated by an atypical USP10 deubiquitinase activity. Citation Format: Bo Qin, Lei Sun, Frank A. Sinicrope. MEK/ERK induces the EMT transcription factor ZEB1 that is regulated by USP10 and promotes colorectal cancer metastasis that can be inhibited by BRAFV600E-directed therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 953.

ABSTRACT Introduction Women in healthcare are faced with unique challenges that may increase their risk of infertility including irregular work hours, occupational hazards due to radiation or chemicals, and advanced maternal age. Objective We sought to investigate live birth rates of female healthcare workers presenting with infertility compared to their non-healthcare counterparts. Methods After obtaining IRB approval, a retrospective review of all hospital employees (and their partners) presenting for a fertility evaluation between 2013-2019 was conducted. Patient age, BMI, history of previous live birth, occupation, use of assisted reproductive technology and female fertility factor were recorded. Couples with at least 12 months of follow up from initial presentation as well as a documented semen analysis were included in the study. Normal semen parameters were defined by the World Health Organization 2010 criteria. Logistic regression analysis was conducted to identify factors associated with increased likelihood of live birth. Results Of the 934 female partners identified, 445 were healthcare workers and 489 non-healthcare workers. Female age, female BMI, smoking status, and history of previous live birth were not statistically significant between groups. No differences in male partner age, male BMI, semen parameters and presence of male factor were noted. Live birth rate was greater in female health care workers compared to non-healthcare workers, 76.1 vs. 69.6%, respectively, p=0.042. Conclusions In this cohort of hospital employees, female healthcare workers had a higher live birth rate despite no differences in age, BMI, rate of female factor infertility, use of assisted reproductive technology, or male partner factors. While no differences in fertility were noted for female health care workers in this study, further research is needed to identify subgroups within the healthcare population that may be at greater risk for infertility. Disclosure No

Objective: This article aims to illustrate the design considerations of team-based primary care clinics in response to the pandemic. Background: Due to COVID-19, physical distancing became a critical practice in our daily life, especially in healthcare settings where healthcare professionals must continue providing care to patients despite the manifold risks. Many healthcare facilities are implementing physical distancing in their clinic layouts, and healthcare professionals are adjusting their behaviors, so they can stay away from each other. Methods: A total of four team-based primary care clinics were studied to identify their lessons learned regarding safety measures and space usage during the pandemic. Results: The four team-based primary care clinics made changes to the clinic design (e.g., waiting areas, exam rooms, team workspaces), operational protocols (e.g., in-person huddles, social gatherings, staff work locations), and usage of spaces (e.g., outdoor spaces, utility rooms). Such changes enabled the implementation of safety measures during the pandemic. However, healthcare professionals also reported challenges regarding their team communication and coordination due to physical distancing and separation. Conclusions: Our findings suggest that the physical distancing may in fact contribute to less effective teamwork and patient care and negatively affect staff well-being. In this article, we ask healthcare system leaders and designers to continue supporting both safety and teamwork by paying attention to the flexibility and spatial relationships among healthcare professionals rather than fully sacrificing teamwork for safety. Also, now is the time when multidisciplinary collaborations are needed to establish and validate guidelines that can improve both factors.

Background: We have previously reported that carotid artery stenting (CAS) carries a higher stroke risk than carotid endarterectomy (CEA) in patients over the age of 70. The question arises if advanced age is a surrogate for other factors? If so, can those factors be separately identified such that advanced chronological age alone would not be considered a contra-indication for CAS? Here we consider whether the CAS/CEA choice could be guided by other factors known in the clinical center at the time of patient evaluation, independent of age, in order to provide optimal 4-year outcomes. Methods: Demographic factors (age, sex and race), symptomatic status, patient risk factors (hypertension, diabetes, dyslipidemia, smoking), and arterial characteristics (percent stenosis) were available on 2,502 patients. Additional detailed arterial characteristics (ulcerated plaque, distal tortuosity, sequential lesions, circumferential calcification) were available on 1141 CAS and 438 CEA patients. Potential differential treatment efficacy was assessed by the addition of factor-by-treatment interaction terms to a proportional hazard model containing established predictors of outcome (treatment, symptomatic status, sex, age and age-by-treatment interaction). Results: No other factor was found to mitigate advanced age with evidence of additional treatment effect modification of 4-year outcome (p > 0.10). Discussion: Beyond the previously described differential treatment efficacy by age, there were no other patient or arterial characteristic detected to identify patient subgroups that would differentially benefit from the choice of CAS versus CEA. Our inability to identify factors to guide treatment choices could be due to the low number of stroke and death events, incomplete information regarding arterial characteristics in the CEA population, or the potential exclusion of “high risk” groups (such as those with severe arterial tortuosity) from the study.

Introduction: Advanced or “Stage D” heart failure (Adv HF) patients are at high risk of poor outcomes. However, recognition of Adv HF is limited as diagnostic criteria are complex. Administrative algorithms to identify Adv HF could enable better understanding of who has advanced HF and lead to enhanced therapeutics development, dissemination, and outcomes. Methods: In a population-based cohort of all Olmsted County, Minnesota residents with ≥1 HF billing code 2007-2017 (n=9881), we identified all patients with Adv HF (n=753) by applying the gold standard European Society of Cardiology Adv HF criteria via manual medical review by a HF cardiologist. The Adv HF index date was the date the patient first met all ESC criteria. We then developed candidate algorithms to identify Adv HF using only administrative data (billing codes and HF prescriptions or comorbidities known to affect HF outcomes), applied them to the entire HF cohort and assessed their ability to identify patients with Adv HF on or after their Adv HF index date. Results: A single hospitalization (Hsp) for HF or ventricular arrhythmias (VA, 2007-2017) identified all patients with Adv HF (sensitivity 100%), but the PPV was low (36.4%). Requiring more Hsp, other signs of Adv HF such as hyponatremia, acute kidney injury, hypotension or high-dose diuretic use decreased the sensitivity but improved specificity and PPV. As Adv HF was relatively uncommon, negative predictive values (NPV) were high regardless of algorithm characteristics. Conclusions: Algorithms using administrative data can identify patients with Adv HF with clinically useful accuracy.