Citations

e18518 Background: Initiatives enhancing equitable oncologic care are an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage status. Methods: We performed a retrospective, case control study consisting of 39 Hispanic ethnicity uninsured patients (UP) with newly diagnosed BC at federally qualified health centers and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, ER and HER2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients ultimately received their cancer treatment at MCA. Results: Similar treatment patterns with chemotherapy, surgery, and radiation treatment were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p ˂ 0.001, percent of high school or lower (53.0 % v 23.2 %, p ˂ 0.001), and lower income for UP (33733.5 v 64728.0 p values ˂ 0.001). UP BMI was significantly higher (30.6 V 24.7, p=0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p ˂ 0.001), hypertension (35.9 % v 20.2%, p= 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p= 0.013), and tobacco use (17.9% v 2.5%, p ˂ 0.001). IP had higher alcohol use (52.9% v 5.3%, p ˂ 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p=0.004), lower acceptance of oncology nutrition consultation for UP (29.4% vs 7.4%, p= 0.024) Median time from abnormal mammogram to biopsy (25.5 days vs. 14 days, p=0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p=0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP (primarily Hispanic, Spanish-speaking) and IP (primarily non-Hispanic White, English-speaking) with newly diagnosed BC we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling services, access to oncology nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations can allow development of tailored interventions to achieve greater equity in delivery of BC care.

AbstractCSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow‐up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

Abstract Objective: Fibromuscular dysplasia (FMD) is an arteriopathy that presents mainly by hypertension, stroke or dissection. Diagnosis is often made in middle-aged women with few cardiovascular risk factors. We aim at identifying common genetic variants associated to FMD. Design and method: We tested ∼6.5 million common genetic variants (MAF > 0.01) in 1962 cases and 7100 controls from 6 studies using variants and gene-based association analyses. Participants were of European ancestry, with similar characteristics (91% multifocal, 88% women), diagnosis methods and inclusion/exclusion criteria. Transcriptome-wide association (TWAS), eQTL, gene expression by sex and colocalization analyses used expression data in arteries from GTEx and/or FMD patients and matched controls. Open chromatin regions were defined using ATAC-Seq on primary human fibroblasts, smooth muscle and endothelial cells. Genetic correlations were assessed using summary statistics from UKBiobank and/or published studies by linkage disequilibrium score regression and multi-trait-based conditional and joint analyses (mtCOJO). Results: We confirmed the previously identified PHACTR1 locus and identified three new loci (LRP1, ATP2B1, and LIMA1) associated with FMD. TWAS in arteries identified one additional locus (SLC24A3). Through integration of annotation datasets, we provided prioritization of variants and genes. These are consistently and specifically expressed in fibroblasts, smooth muscle cells, and arterial tissues. PHACTR1 and SLC24A3 showed sex differences in gene expressions consistent with the direction of effects of FMD risk alleles. FMD genes are involved in regulatory mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, two mechanisms central to vascular contraction. We found significant genetic overlaps between FMD and blood pressure traits, for the associated loci and globally at the genome level, but demonstrated that hypertension is not driving the genetic association with FMD. We also found positive genetic correlations with migraine and intracranial aneurysm, and an inverse correlation with coronary artery disease, independently from the genetics of blood pressure. Conclusions: We describe robustly associated loci and genes with FMD and provide several new leads toward understanding biological mechanisms of stenosis and dissection in young women in the absence of atherosclerosis, which shares part of its genetic basis with more common cardiovascular and neurovascular diseases.

Abstract Introduction: Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously described AREG as a circulating biomarker of late-onset aGVHD, but its relevance combined with clinical risk factors has not yet been tested in a large cohort of patients with aGVHD occurring prior to day 100 post-transplant. We therefore tested samples from two aGVHD first-line treatment trials, Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0302 and 0802, and identified a clinically relevant threshold level of circulating AREG at aGVHD onset. We then investigated whether incorporating AREG into the refined Minnesota Risk Score could further risk-stratify patients. Patients and Methods: Blood samples were obtained at the onset of systemic aGVHD treatment within BMT CTN 0302 (serum) and BMT CTN 0802 (plasma). All patients with response data and samples for analysis from both trials were included (N=251). We determined the association of AREG with clinical outcomes, including risk stratification by the refined Minnesota criteria, day 28 complete/partial response (CR/PR) to first-line therapy, 2-year overall survival (OS) and 6-month and 2-year non-relapse mortality (NRM). We investigated the effect of AREG on clinical endpoints per a doubling in the value of AREG, defined a clinically relevant threshold level in the AREG values using two-fold cross-validation, and confirmed the clinical relevance of this cut-point in independent samples (N=92) from pooled from drawn from the Chronic GVHD Consortium and the Mount Sinai Acute GVHD International Consortium (MAGIC). Results: In patients enrolled in BMT CTN 0302/0802, AREG levels were 1.7-fold higher in patients with Minnesota high-risk (HR) compared to standard-risk (SR) aGVHD (HR median 53.4 vs SR 31 pg/ml, p<0.01). Every 2-fold increase in AREG was associated with a 33% decrease in the likelihood of day 28 CR/PR (odds ratio [OR] 0.67, p<0.01, table). Clinical factors alone, as determined by the refined Minnesota Risk Score, were associated with day 28 CR/PR (p=0.02, table). Adding AREG to the Minnesota Risk Score could further risk-stratify patients. Minnesota SR patients with elevated AREG ≥ 33 pg/mL showed a 59% lower odds of day 28 CR/PR than SR patients with low AREG (OR 0.41, p=0.02). Patients with Minnesota HR aGVHD with AREG ≥ 33 pg/mL had the worst outcomes, with an 82% lower odds of day 28 CR/PR in comparison to HR with low AREG (OR 0.18, p<0.01). High AREG was associated with worse OS and NRM in both Minnesota SR (hazard ratios 2-year OS 2.3, p<0.01 and 6 month NRM 2.95, p=0.01, respectively) and HR patients (hazard ratios 2-year OS 3.35, p<0.01 and 6-month NRM 9.38, p<0.01 respectively, figure). Finally, in independent samples from the Chronic GVHD Consortium/MAGIC we confirmed that high AREG was associated with worse day 28 CR/PR (55.2% vs. 79.4%, p=0.02) and significantly worse 6-month survival after the onset of aGVHD (57.1% vs. 82.5%, p=0.01). Conclusion: AREG is elevated in patients with poor aGVHD outcomes and adds to the accuracy of risk stratification when combined with the refined Minnesota Risk Score. AREG ≥33 pg/mL at aGVHD onset is associated with lower day 28 CR/PR and higher mortality in samples from 4 multicenter cohorts. The mechanism of elevated circulating AREG in severe aGVHD is not yet known, although we hypothesize the degree of AREG elevation reflects the intensity of immune-mediated tissue injury resulting in AREG release. With accumulating evidence of altered EGFR ligands in aGVHD, further investigation into epithelial repair pathways involving AREG may lead to new adjunctive therapies to overcome poor steroid response in high-risk aGVHD. Disclosures Holtan: Incyte: Other: One-time advisory board member. Khera: Novartis: Consultancy. Lee: Mallinckrodt: Honoraria; Amgen: Other: One-time advisory board member; Bristol-Myers-Squibb: Other: One-time advisory board member; Kadmon: Other: One-time advisory board member. Chen: Immudex: Research Funding. Arora: Takeda Oncology: Consultancy. Flowers: Pharmacyclics: Consultancy. Cutler: Pfizer: Consultancy; Kite: Consultancy; Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Pharmacyclics: Consultancy; Astellas: Consultancy. Jagasia: Janssen: Consultancy, Research Funding; Therakos: Consultancy, Research Funding; Mallinckrodt: Consultancy. Hexner: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Levine: Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. MacMillan: Magenta Therapeutics: Research Funding.

Abstract Background: DNIV accounts for 6%–10% of newly diagnosed breast cancer cases. Despite widespread mammography screening, its incidence is increasing in the United States and survival of this disease has only modestly improved since the late 1970s. As patient data accumulates in EHR, it’s promising to generate practice-based evidence through utilization of observational data sources. However, assembly of a DNIV cohort based on EHR data is challenging, as key pathologic and staging information are stored in unstructured clinical narratives and not available as structured data. In this study, we developed a rule-based algorithm to phenotype DNIV using natural language processing (NLP) techniques, and implemented the algorithm on our institutional EHR to extract potential DNIV cases. Methods and Results: We defined DNIV as those with either (1) M1 disease identified at time of initial presentation or M1 disease identified within 4 months after definitive surgery. We first developed a reference case list of DNIV verified by physician chart review of the EHR. We next refined the algorithm on a training dataset containing 51 positive and 38 negative reference cases. Next we tested the performance on the testing data containing 23 positive and 55 negative cases. The phenotyping algorithm identified key data elements using NLP, i.e., stage IV breast cancer, definitive surgery, stage 0-III, recurrent breast cancer and associated dates. To identify DNIV cases, phenotyping algorithm integrated temporal relations among the key data elements. The following steps were conducted in the following sequential order: (1) Identification of patients with breast cancer diagnosis using ICD-9 and ICD-10 codes. (2) Patients are positive cases if there are explicit mentions that delineate DNIV from recurrent metastatic breast cancer, such as “de novo stage IV” or “primary intact” detected by NLP at time of diagnosis. (3) Otherwise, patients with definitive surgery are selected if stage IV was within 5 years before definitive surgery or within 4 months after definitive surgery, along with patients with stage IV but without definitive surgery. (4) We further excluded patients with stage 0-III detected within 5 years after stage IV. (5) We further excluded patients with recurrent breast cancer detected before or at time of detection of stage IV. The remaining patients were left as positive cases. Precision of the algorithm was 70%, recall was 87% and F1, the weighted average of precision and recall, was 77%. We implemented our algorithm to interrogate 10 million clinical documents in a cohort of 56,548 patients with breast cancer diagnosis codes who presented to our institution between 2004 and 2018 and had research authorization. We identified 1918 potential DNIV cases. Conclusion: Our future focus is on algorithm refinement. An algorithm-generated cohort could serve as a data source for further study on outcomes related to DNIV and ideally as automated data abstractor and staging process. Citation Format: Liwei Wang, Karthik Giridhar, Kimberly Corbin, Brenda Ernst, Sadia Choudhery, Emmanuel Gabriel, Feichen Shen, Hongfang Liu, James Jakub. Identifying de novo stage IV breast cancer (DNIV) cases in Electronic Health Records (EHR) using natural language processing [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-050.

Abstract Background: Contrast-enhanced mammography (CEM) is an emerging breast imaging technique utilizing iodinated contrast to highlight areas of neovascularity. The role of CEM in patients with breast implants has not yet been characterized. We report our clinical experience of CEM in patients with breast augmentation surgery to better understand the potential diagnostic utility and limitations of CEM in the setting of breast implants. Materials and Methods: A HIPPA compliant, IRB exempt single-institution review of prospective CEM cases who had “breast implants” in their report between 01/2015 and 03/2020. Medical records were reviewed to supplement database information. Results: Forty-six patients were included with a mean age of 52 years (range 33-72). Clinical indications included: high risk research screen 3 (6%), diagnostic evaluation for abnormal imaging 24 (52%), further evaluation of newly diagnosed breast cancer 12 (26%) or assessment of neoadjuvant treatment response 7 (15%). Thirty patients had malignant lesions. Histology was invasive ductal carcinoma (90%), invasive lobular carcinoma (7%), and ductal carcinoma in situ (3%). CEM identified the index cancer and extent of disease in 28/30 (93%) of malignant cases. In two patients (7%), the malignant lesion was not included in the field-of-view due to its location. One of these lesions was a far medial mass within the breast which was detected by ultrasound alone. The other false negative CEM was a palpable axillary mass negative on both mammogram (MG) and MRI but seen by ultrasound. Twenty-three (50%) underwent additional breast MRI of which 20 had an already diagnosed cancer. the findings on CEM were concordant with MR imaging for the index lesion in 19/20 (95%) cases (kappa=0.86; p <0.001). Six additional lesions were found by CEM and confirmed by MRI. Of these lesions, 33% were found to be malignant and changed the surgical procedure. Four were only seen on CEM (no MRI comparison was available) and 75% were found to be malignant. One was only seen on MRI and was benign. One additional lesion was only seen as an asymmetry on MG without CEM or MRI correlate. This was benign on both the biopsy and surgical pathology. Conclusions: CEM appears to be a valuable breast imaging modality for diagnostic evaluations and surgical staging, including patients with breast implants. Due to technical artifacts and positioning limitations for posterior lesions, we recommend performing CEM with implant displaced views. Breast centers that use CEM, should be aware of field of view as a potential limitation when evaluating extent of disease in patients with breast augmentation. Citation Format: Molly Carnahan, Barbara Pockaj, Victor Pizzitola, Marina Giurescu, Roxanne Lorans, William Eversman, Richard Sharpe, Patricia Cronin, Donald Northfelt, Karen Anderson, Brenda Ernst, Bhavika Patel. Experience of contrast-enhanced mammography in patients with breast augmentation surgery [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 PS3-23.

Abstract Objective and Rationale: To investigate the utility of screening Contrast Enhanced Mammography (CEM) imaging as a supplemental screening tool in women at elevated risk for breast cancer. Materials and Methods: This prospective, single institution, IRB approved observational study was conducted in asymptomatic women 35 years of age or older who were deemed at elevated risk of breast cancer, defined as IBIS v.8.0 lifetime risk of breast cancer score >15% or a prior personal history of breast cancer. Enrollment started in January 2019 and is on-going. An interim data analysis was performed. Women were invited to undergo supplemental CEM screening within 180 days of negative (BI-RADS 1 or 2) conventional 2D/3D screening mammography (MG). Patients with prior screening MBI, ultrasound or MR imaging within 12 months were excluded from study participation. Outcome measures were supplemental cancer detection rates, sensitivity, specificity, positive predictive value, and negative predictive value of CEM, along with their 95% confidence intervals, as well as the biologic profiles of MG-occult, CEM detected cancers. Results: A total of 351 women were enrolled in this prospective study over a 20-month period. To date, we have 1 year follow up on 106 cases with negative follow-up MG. Average age of the participants was 56 years ± 9.44 (standard deviation); 11 patients had screening 2D MG, 333 had combined 3-D and 2-D screening MG; 309 dense and 37 non-dense breasts based on ACR BI-RADS categories. CEM depicted 8 additional breast cancers (table 1), which were otherwise MG occult, for an overall supplemental cancer detection rate of 22.7 per 1000 patients, 95% CI (9.9, 44.3). 1 false negative cancer on CEM imaging which was further detected on MR imaging only. Biopsy revealed 16 benign changes (16/28=57%), 4 high-risk lesions (4/28=14%), and 8 breast cancers (8/28=29%) (table 2). CEM imaging screening offered high specificity (0.942, 95% CI (0.917, 0.967), high NPV 0.997, 95% CI (0.991, 1.000) and moderate PPV (0.286, 95% CI (0.118, 0.453) and sensitivity (0.889, 95% CI (0.684, 1.000)). Size of CEM detected cancers ranged from 7 to 57 mm. Conclusion: This pilot trial demonstrates a supplemental cancer detection rate of 22.7 per 1000 during prevalence round of CEM screening in women at an elevated risk for breast cancer. These initial results are comparable to results reported for high-risk surveillance MR imaging. Larger, multi-institutional high-risk CEM trials are needed for those patients who are not otherwise undergoing regular supplemental surveillance MR imaging. Citation Format: Bhavika K. Patel, Victor Pizzitola, Donald Northfelt, Karen Anderson, Marina Giurescu, Gina Mazza, Roxanne Lorans, William Eversman, Richard Sharpe, Juliana Kling, Denise Millstine, Ernst Brenda, Patricia Cronin, Heidi Apsey, Jennifer Palmieri, Barbara Pockaj, Michele Halyard. Supplemental contrast enhanced mammography screening of women with elevated risk of breast cancer [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 PS2-41.

Abstract Background: Hereditary factors play a key role in the risk of developing breast cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and testing for family members. Aim: To determine the prevalence of pathogenic or likely pathogenic germline mutations (P/LP) using a “universal” testing approach and uptake of no-cost cascade family testing in patients with breast cancer. Methods: We undertook a prospective multi-site study of germline genetic alterations among breast cancer patients receiving care at Mayo Clinic cancer centers in Rochester, MN; Eau Claire, WI; Jacksonville, FL and Phoenix, AZ between April 1, 2018 and March 31, 2020. Patients with a new or active breast cancer diagnosis (all stages) irrespective of cancer family history were tested with a >80-gene next generation sequencing panel.Results: Of 390 patients, the median age was 58 years (SD 12.3), 1% were male, 85% were white and 28% had advanced (stage 3-4) disease. P/LP were found in 12.1% (n=47) of patients, including 29 in moderate and high penetrance cancer susceptibility genes. 13 (3.3%) patients had mutations in BRCA1 or 2, while 33 (8.4%) had mutations in BRCAness (ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C, RAD51D, WRN) associated genes. Of the P/LP findings the most frequent aberrations were in BRCA2 (13.5%), BRCA1 (11.5%), CHEK2 (11.5%), MUTYH (11.5%), and WRN (9.6%). Variants of uncertain significance were found in 209 (53.6%) including 26 (6.6%) with concurrent P/LP and VUS. 37 (9.4%) patients had mutations associated with published management recommendations, precision therapies and/or clinical trial eligibility. 10 (2.6%) patients had P/LP that would not have met current screening guidelines, including 4 with moderate or high penetrance mutations. Patients with younger age of diagnosis were less likely than patients with older age of diagnosis to have a P/LP mutation (OR= 0.47, 95%CI: 0.25-0.90 p = 0.020). Only 10 (21%) patients with P/LP had family members undergo familial site- specific testing at no cost.Conclusions: In this prospective multi-center study of unselected breast cancer patients, universal multi-gene panel testing found that 1 in 8 patients harbor P/LP germline variants. Current guidelines were able to identify the majority of patients with P/LP mutations. Familial site specific testing is greatly under-utilized even when cost is not a barrier. Multigene panels impact cancer patient care by identifying precision medicine treatment interventions, and guiding long-term medical management and preventive surveillance. Citation Format: Brenda Ernst, Natalie Ertz-Archambault, Deborah J Rhodes, Donald W Northfelt, Myra Wick, Douglas L Riegert-Johnson, Scott Okuno, Katie Kunze, Michael Golafshar, Cindy M Azevedo, PLS Uson Junior, ED Esplin, Robert Nussbaum, Margaret Klint, Sarah Mantia, Megan Hager, Keith Stewart, Niloy Jewel Samadder. Universal genetic testing in breast cancer patients: A multi-center prospective study [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 PD10-05.

Abstract Steroid-refractory (SR) acute graft-versus-host disease (GVHD) remains a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT), but its occurrence is not accurately predicted by pre-HCT clinical risk factors. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP) identifies patients who are at high risk for developing SR GVHD as early as 7 days after HCT based on the extent of intestinal crypt damage as measured by the concentrations of 2 serum biomarkers, suppressor of tumorigenesis 2 and regenerating islet-derived 3α. We conducted a multicenter proof-of-concept “preemptive” treatment trial of α-1-antitrypsin (AAT), a serine protease inhibitor with demonstrated activity against GVHD, in patients at high risk for developing SR GVHD. Patients were eligible if they possessed a high-risk MAP on day 7 after HCT or, if initially low risk, became high risk on repeat testing at day 14. Thirty high-risk patients were treated with twice-weekly infusions of AAT for a total of 16 doses, and their outcomes were compared with 90 high-risk near-contemporaneous MAGIC control patients. AAT treatment was well tolerated with few toxicities, but it did not lower the incidence of SR GVHD compared with controls (20% vs 14%, P = .56). We conclude that real-time biomarker-based risk assignment is feasible early after allogeneic HCT but that this dose and schedule of AAT did not change the incidence of SR acute GVHD. This trial was registered at www.clinicaltrials.gov as #NCT03459040.

AbstractCOVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.