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Empirical evidence for physicians' knowledge gaps in bleeding disorders is limited to self-reported surveys, yet often cited as a leading cause of diagnostic and management delays.Our aim was to assess internal medicine (IM) residents' competence, based on their training level, in evaluating a patient with a bleeding disorder, and knowledge gaps in their clinical approach.Content experts developed patient case presenting with abnormal bleeding, bruising, and an isolated prolonged PTT. We administered the hemostasis case as part of an objective structured clinical examination (OSCE). We performed a descriptive analysis. One-way anova was conducted to compare the effect of training level on performance. Item difficulty level for the hemostasis case was also determined.Sixty-seven IM residents participated in the OSCE. The hemostasis case had the highest failure rate at 41.8% with a mean score for the station of 57.96% (SD 13.04). Senior residents scored significantly higher than junior residents on this case (F(2,64) = 4.604, p = .014,We demonstrated important knowledge gaps in IM residents' approach to the bleeding patient. Innovative strategies for hemostasis education should be a priority to address physician-related factors in the diagnostic and management delays of patients with bleeding disorders.

Introduction: Despite having a lower incidence of breast cancer, African American (AA) women suffer disproportionately worse outcomes; with more aggressive cancer and higher mortality rates, as well as higher incidence of triple negative breast cancer (TNBC). The cause of these disparities is unclear, but may be driven by different biologic and molecular features. Information about targetable molecular profiles for breast cancer in AAs is limited, and may not be representative of racial minorities. A better understanding of actionable targets is needed to improve treatment and outcomes of breast cancer for AA women. Materials and methods: This study utilized molecular data from three TCGA Breast Invasive Carcinoma studies (Cell 2015, Firehose Legacy, and PanCancer Atlas) on CBioPortal. Data was stratified by C/White and AA/Black to identify the most commonly affected genes, the most significantly differentially affected genes between the two populations, and 35 actionable genes. Genes were compared between racial subgroups (455 AA cases, 2103 C cases) for analysis of mutation types (point mutations, splice site, deletions, and amplifications) mutation load, overall survival, and mRNA expression vs. copy number variation (CNV). Data was assessed for differences, with p-value set at Citation Format: Genevra Magliocco, Roy Khalife, Anthony Magliocco. Distinct and targetable molecular features of breast cancer in African American women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-12.

Competency-based assessment of learners may benefit from a more holistic, inclusive, approach for determining readiness for unsupervised practice. However, despite movements towards greater patient partnership in health care generally, inclusion of patients in postgraduate medical learners' assessment is largely absent.We conducted a scoping review to map the nature, extent and range of literature examining the inclusion (or exclusion) of patients within the assessment of postgraduate medical learners. Guided by Arskey and O'Malley's framework and informed by Levac et al. and Thomas et al., we searched two databases (MEDLINE® and Embase®) from inception until February 2021 using subheadings related to assessment, patients and postgraduate learners. Data analysis examined characteristics regarding the nature and factor influencing patient involvement in assessment.We identified 41 papers spanning four decades. Some literature suggests patients are willing to be engaged in assessment, however choose not to engage when, for example, language barriers may exist. When stratified by specialty or clinical setting, the influence of factors such as gender, race, ethnicity or medical condition seems to remain consistent. Patients may participate in assessment as a stand-alone group or part of a multi-source feedback process. Patients generally provided high ratings but commented on the observed professional behaviours and communication skills in comparison with physicians who focused on medical expertise.Factors that influence patient involvement in assessment are multifactorial including patients' willingness themselves, language and reading-comprehension challenges and available resources for training programmes to facilitate the integration of patient assessments. These barriers however are not insurmountable. While understudied, research examining patient involvement in assessment is increasing; however, our review suggests that the extent which the unique insights will be taken up in postgraduate medical education may be dependent on assessment systems readiness and, in particular, physician readiness to partner with patients in this way.

[Voir la version anglaise de l’article ici: www.cmaj.ca/lookup/doi/10.1503/cmaj.210169][1] Une femme de 34 ans a consulte aux urgences pour des regles abondantes depuis 1 journee. Elle a dit utiliser des serviettes hygieniques epaisses ou meme des couches et devoir les changer toutes les

Segmental duplications (i.e., highly homologous DNA fragments greater than 1 kb in length that are present within a genome at more than one site) are typically found in genome regions that are prone to rearrangements. A noticeable fraction of the human genome (∼5%) includes segmental duplications (or duplicons) that are assumed to play a number of vital roles in human evolution, human-specific adaptation, and genomic instability. Despite their importance for crucial events such as synaptogenesis, neuronal migration, and neocortical expansion, these segmental duplications continue to be rather poorly characterized. Of particular interest are the core duplicon gene (CDG) families, which are replicates sharing common "core" DNA among the randomly attached pieces and which expand along single chromosomes and might harbor newly acquired protein domains. Another important feature of proteins encoded by CDG families is their multifunctionality. Although it seems that these proteins might possess many characteristic features of intrinsically disordered proteins, to the best of our knowledge, a systematic investigation of the intrinsic disorder predisposition of the proteins encoded by core duplicon gene families has not been conducted yet. To fill this gap and to determine the degree to which these proteins might be affected by intrinsic disorder, we analyzed a set of human proteins encoded by the members of 10 core duplicon gene families, such as NBPF, RGPD, GUSBP, PMS2P, SPATA31, TRIM51, GOLGA8, NPIP, TBC1D3, and LRRC37. Our analysis revealed that the vast majority of these proteins are highly disordered, with their disordered regions often being utilized as means for the protein-protein interactions and/or targeted for numerous posttranslational modifications of different nature.

Introduction: Triple-negative breast cancer (TNBC) is an aggressive disease that lacks well-defined molecular targets. It accounts for 15-20% of all breast cancers and disproportionately affects women of color due to both limited access to treatment and genetic variation. Recent studies identified BRCA1(or 2) and the PIK3CA/AKT1/PTEN axis as targets for treatment, but these studies neglected to account for genetic variations between race. Here, we present molecular differences between African American/Black (AA) and White (W) women with TNBC to highlight the importance of accounting for race to develop effective therapy and improve long-term outcomes. Methods: This study utilized the TCGA Firehose Legacy Breast Carcinoma dataset on cBioPortal. Subjects with breast cancer and negative ER, PR, and HER2 scores were stratified into AA (n=32) and W (n=69) subgroups. Data was analyzed to compare the most altered genes, copy number variation (CNV), and survival rates between the subgroups. The logrank test was used to obtain the hazard rate. The GISTIC2 model was used to assess CNV and G-scores (G; amplitude of aberration x frequency of occurrence). Results: The main genetic differences were in PIK3CA and BRCA1(or 2) genes. PIK3CA was detected as one of the ten most altered genes in TNBC, but this alteration was found in less than 10% of the TNBC cases. Of the 10%, PIK3CA was altered in 19% of W and 9% of AA subgroup. BRCA1(2) were altered in 10%(7%) of W but 0%(3%) of AA. Additionally, structural differences in chromosomes contributed to different survival outcomes. Both groups had co-amplification in 8q, but a significant hazard rate difference (z = 5.32, p < 0.001) was found for the W compared to the AA for the MYC gene. Further, the W had significantly higher amplification at 3q (G = 0.8 in W; 0.45 in AA). It is important to note that the PIK3CA gene lies in the 3q.26 region, meaning this gene is amplified significantly in the W subgroup. The AA group had a significant deletion at 8p.23 (G=0.5 in W; 0.8 in AA). Deletion of 8p causes MYC amplification, a targetable alteration. Conclusion: Our analysis reveals critical differences between AA and W subgroups with TNBC. Thus, it is clear that targeting the PIK3CA or BRCA1(2) gene benefits the W more than the AA population. To alleviate the disproportionate burden that AA women with TNBC face, more effort must be geared to find solutions specific to the AA subgroup. A greater sample size will help determine whether MYC amplification is unique to the AA subgroup, and if so, it could be targeted to improve outcomes of AA women with TNBC. Nevertheless, more data and research is needed to understand causes and decrease the rate of disparate outcomes in patients with TNBC. Citation Format: So Hyeon Park, Roy Khalife, Evan White, Anthony Magliocco. Distinct molecular differences between African American/Black and White women with Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-05.

A 34-year-old woman presented to the emergency department with a 1-day history of heavy menstrual bleeding. She described needing to use thick pads or diapers that required changing hourly because of the heavy flow of blood. One month previously, she had had sudden onset pelvic pain resulting from

Introduction The virtual learning environment has become increasingly important due to physical distance requirements put in place during the COVID-19 pandemic. The transition to a virtual format has been challenging for case-based teaching sessions, which involve substantial audience participation. We developed a faculty development workshop aimed at teaching health professions educators how to use various interactive virtual tools within videoconferencing platforms to facilitate virtual case-based sessions. Methods Two 90-minute workshops were piloted as a faculty development initiative. The facilitators demonstrated interactive teaching tools that could be used within virtual case-based sessions. Then, participants discussed how to incorporate these tools into case-based teaching sessions of different class sizes in small-group breakout sessions. Participants completed an online survey following each workshop to evaluate the sessions. Results A total of 18 and 26 subjects participated in the first and second workshops, respectively. Survey response rates were 100% (n = 18) and 65% (n = 17) for the first and second workshops, respectively. Both groups provided overall high ratings and reported that the workshop was clear, organized, and relevant. Participants were more familiar and comfortable with the use of various interactive tools for online teaching. Discussion Distance online teaching will be increasingly required for an undetermined time. Faculty development efforts are crucial to facilitate effective interactive teaching sessions that engage learners and maximize learning. This virtual teaching workshop is a simple and straightforward way to introduce a more interactive format to virtual case-based teaching in the health professions.

Introduction: Although the risk of colorectal cancer is roughly equal between sexes (slightly higher in males), the molecular profile between the two varies significantly. Many genes identified have a distinctive effect on outcome between these two subgroups, including actionable genes, the most frequently altered genes, and the most significantly altered genes. The molecular basis is important for understanding etiology and treatment options. Uncovering these molecular differences could help optimize screening and treatment and improve outcomes for colorectal cancer for both sexes. Materials and Methods: This study used molecular data from three TCGA Colorectal Adenocarcinoma studies (Firehose Legacy, Nature 2012, and PanCancer Atlas) on cBioPortal. The two subgroups, males and females, were separated and analyzed for molecular differences. 1496 cases (790 male, 706 female) were analyzed on cBioPortal for molecular characteristics including alterations (mutations, deletions, amplifications), overall survival, and mRNA expression vs. copy number variation (CNV). Significant differences were noted, and OncoPrints and survival curves were generated. Results: The genes analyzed on cBioPortal showed similar alteration rates between males and females, although differences were depicted between sex and specific genes. Out of the 17 actionable genes, four had a significant effect on one sex, but not the other. ARID1A alterations increased the probability of male survival (p-value = 0.0219), ERRB2 (0.0467) and NRAS (1.118e-3) decreased survival odds for males, and NF1 (0.0107) decreased survival odds for females. CDK12 and ERBB2 co-amplification was identified for both sexes, but more prominent in males. Multiple altered genes also had a lower probability of survival in only females. Of the most altered genes, RBFOX1 (0.0312), CSDM1 (8.631e-3), TTN (4.374e-4), WWOX (2.226e-4), CCSER1 (5.048e-3), MACROD2 (0.0366), and a 20q co-amplification cluster of CHD6 (7.313e-3), PREX1 (5.422e-3), and ZNF335 (0.0439) were significant in females. Also, among the most significant genes between males and females, TENM1 alteration (found in 11% of females and 4% of males) lowered the probability of survival in females (1.384e-6). Lastly, 75% of females remained disease free after 70 months, compared to 45% of males (8.849e-3). Conclusion: Molecular differences in colorectal cancer between males and females are significant. TTN is important to note due to its comparison to tumor mutational burden (TMB); TTN, combined with MUC4 and MUC16, can predict TMB and may be used as a convenient biomarker for effective immunotherapy in females. ERBB2 is potentially targetable with anti HER2 therapeutics, thus may improve the worse outcome observed in males with ERBB2 alterations. Colorectal cancer has different targetable genes expressed differentially among males and females. This needs to be considered when developing screening and treatment strategies. Citation Format: Roy Khalife, Genevra Magliocco, So Hyeon Park, Anthony Magliocco. Colorectal cancer and its molecular differences between sexes [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 5779.

5597 Background: Among women with endometrial cancer (EC), African American or Black (AAoB) population share a disproportionate burden of cancer deaths. Previous research exploring genetic and molecular explanations revealed White (W) women with EC are more likely to have mutations in PTEN, while AAoB women have higher rates of mutations in p53. However, these studies did not stratify EC by subtype, which occur at different rates among racial groups. Here, we aim to focus on molecular differences between racial groups, specifically in Type 1 EC (T1EC). Methods: Molecular data from TCGA Uterine Corpus Endometrial Carcinoma datasets on cBioPortal was used. Cancer type was filtered to Uterine Endometrioid Carcinoma Type 1 and separated by race. A total of 711 cases were analyzed for gene alterations, expression versus copy number variations, survival curves, and OncoPrints; significant findings and differences between racial groups were noted. The Surveillance, Epidemiology, and End Results (SEER) database was used to access the frequency, rate, and survival of AAoB and W with EC. Results: The genes analyzed on cBioPortal (575 W, 136 AAoB) depicted a similar alteration rate between the two groups, except for the most altered gene, PTEN (66% altered in W, 38% in AAoB). W women with a PTEN and PIK3CA alterations had significantly increased 5-year survival periods (P-value = 1.573e-3), while these alterations had no effect survival in AAoB. Six of the ten most altered genes between the two subgroups, and 6 of the 17 most actionable genes, were statistically significant for W but not for AAoB. SEER analyses depicted a frequency of 51,677 W and 3,915 AAoB, with a rate of 5.7% and 3.9%, respectively. The observed survival was 96.1% after 1 year and 85.6% after 5 years for W, compared to 92.8% after 1 year and 76.9% after 5 years for AAoB. Conclusions: Based on 5 years of data, overall survival (OS) rates among W women with T1EC are better than AAoB. PTEN mutation confers a survival advantage in W but not in AAoB, indicating that in AAoB, PTEN may play a different role or other factors may override the PTEN advantage. Additional analyses revealed non-remarkable findings, suggesting that molecular factors play a minor role in T1EC disparities or that a larger AAoB sample size is necessary. A better understanding of the downstream signaling pathways of common mutations in T1EC is necessary to further elucidate factors that contribute to racial disparities in T1EC. [Table: see text]

Introduction: African American (AA) women have a lower incidence of breast cancer (BC), however experience higher rates of more aggressive subtypes, mortality, and worse outcomes compared to Caucasian (C) women. Data also points to disparities among treatment access and response in AA women. Most existing genetic research and clinical trials have been conducted with majority C women, thus our existing knowledge about molecular profiles and effective treatments may not be accurate for AA women. The aim of this study is to uncover the biological and social factors related to treatment that may be causing this disparity in BC outcomes between AA and C women. Materials and Methods: Data from Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas Program (TCGA) was analyzed for differences in etiology, incidence, and prevalence of BC between AA and C. Prevalence of molecular aberrations and subtypes of BC were assessed to gain insight into potential causes of this disparity. FDA's Drug Trials Snapshots data was assessed for clinical trial enrollment by race. Results: SEER data from 2000-2018 reveals AA patients have higher incidences of TNBC and HER2 enriched BC compared to C, with luminal A incidence being higher in C patients. Within all subtypes of BC, 5-year survival rates were significantly lower for AA compared to C. TCGA data found 2282 genes that were significantly differentially altered in C vs. AA subgroups. Among the most commonly altered and significantly different genes, CSMD1 and TP53 were more prevalent among AA (19.78% AA vs. 10.79% in C for CSMD1, and 40.09% AA vs. 28.58% C for TP53), and PIK3CA among C (36.28% (C) vs. 22.47% (AA)). Survival analysis revealed AA women with PIK3CA alterations had lower rates of disease-free survival compared to C women. Clinical trials for oncology drugs approved in 2020 enrolled 5% AAs, with AAs also being underrepresented for BC specific drugs. The recent NCT02492711 trial of MARGENZA, for metastatic HER2 positive BC, had 5% AA compared to 80% C, the NCT01631552 trial of TRODELVY, for metastatic triple negative BC (TNBC), had 7% AA vs. 76% C, and the NCT02614794 trial of TUKYSA, for advanced HER2+ BC, had 9% AA vs. 73% C. Conclusion: Most existing treatments are for luminal A BC; with fewer approved drugs for subtypes more common among AA women, including the more aggressive TNBC. Recent data indicates that AA women continue to be underrepresented in clinical trials, despite having higher incidence of both HER2 and TNBC, resulting in a poor understanding of effective treatment for this subgroup. These factors may perpetuate disparities in outcomes for AA women with BC. Additionally, TCGA data uncovered underlying molecular differences in BC between AA and C women, some that are actionable. Disparities are multifactorial and can include both biological and socioeconomic factors. Thus, as we move towards more personalized medicine, it is increasingly important to improve representation of AA women in precision oncology trials. Citation Format: Genevra Magliocco, Roy Khalife, Anthony Magliocco. African American women with breast cancer have unique molecular features and reduced clinical trial enrollment [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-099.

Introduction: Pregnant women with bleeding disorders (WBD) are at higher risk of postpartum hemorrhage (PPH) compared to women without bleeding disorders. Multidisciplinary care is essential to minimize bleeding and optimize maternal outcomes in pregnant WBD. The safest mode of delivery for pregnant WBD remains debated with variable clinical practices and guideline recommendations. Studies are needed to inform decision-making for pregnant WBD and their multidisciplinary team. Objectives: To describe the maternal and neonatal outcomes in pregnant WBD by mode of delivery, including spontaneous vaginal delivery (SVD), induction of labor (IOL), planned C-section (CS) and emergent CS. Methods: We performed a retrospective analysis of all pregnant WBD who delivered at our institution between 2010-2020. The comprehensive hemostasis program offered at our institution has been providing multi-disciplinary care for patients with bleeding disorders since 1985 and coordinates care for 5-10 pregnant WBD a year. Patient/disease characteristics, mode of delivery, peripartum hemostatic management, and maternal outcomes were collected. PPH was defined according to the American College of Obstetrics and Gynecology (ACOG) (doi:10.1097/AOG.0000000000002351). Primary PPH was defined as blood loss of ≥ 1000 mL or blood loss with signs and symptoms of hypovolemia within 24h delivery regardless of route of delivery, or blood loss of > 500 mL in a vaginal delivery. Secondary PPH was defined as any abnormal or excessive vaginal bleeding beyond 24h of delivery to 12 weeks postpartum as documented by healthcare professionals' clinical notes. Data is presented using descriptive statistics. Fisher's Exact test was used to measure association between the mode of delivery and PPH. Results: A total of 73 pregnancies in 50 WBD were included. The incidence of primary PPH and secondary PPH were 6.8% (5/73, 95% CI [2.5, 14.5]) and 19.0% (12/63, 95% CI [10.8, 30.1]), respectively (Table 1). According to mode of delivery, primary PPH occurred in 1/34 for SVD, 3/21 for IOL, 0/11 for planned CS and 1/7 for emergent CS, and secondary PPH occurred in 6/31 for SVD, 5/19 for IOL, 0/6 for planned CS and 1/7 for emergent CS (Table 1). When comparing combined vaginal deliveries to CS, we found a numerically higher rate of both primary PPH (4/55, 7.2% vs. 1/18, 5.6%, p = 1.0) and secondary PPH (11/50, 22.0% vs. 1/13, 7.7%, p = 0.431), but both were not statistically significant (Table 1). Discussion: Our cohort of pregnant WBD showed rates of primary PPH (6.8%) comparable to those in a 2014 study of all Canadian deliveries (6.2%) (doi:10.1016/S1701-2163(15)30680-0). This likely reflected efforts for multidisciplinary and coordinated care for WBD within a hemophilia treatment centre with readily available clinical and laboratory monitoring as well as universal access to hemostatic therapies for Canadian WBD. In our cohort, planned CS did not result in any PPH which may reflect the ability to ensure clinical and laboratory expertise in hemostasis available (like recommendations for perioperative care in hemophilia) as opposed to spontaneous or unplanned deliveries that may occur outside of regular operating hours. Rates of secondary PPH remained high and problematic especially following vaginal deliveries. Several factors may explain these delayed bleeding events such as wound healing defects inherent to some bleeding disorders and decline in factor levels back to baseline in the early postpartum period. Our study was limited by its retrospective and single-centred design, small sample size, missing secondary PPH data in 10 pregnancies, and potential confounding variables that were unaccounted for by the study. Nevertheless, we reported incidence rates of primary and secondary PPH according to the mode of delivery in women with bleeding disorders, which can be important to inform clinical practices. Conclusion: Women with bleeding disorders are at high risk of PPH. Although we did not find statistically significance correlation by mode of delivery, these findings are clinically relevant in supporting patient-centered care and shared decision-making between WBD, obstetricians and hematologists. Close monitoring and follow-up are of utmost importance and further larger prospective research focused on postpartum outcomes is much needed. Figure 1 Figure 1. Disclosures Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding. Khalife: Canadian Hemophilia Society: Research Funding; Pfizer Canada: Honoraria, Research Funding.

Background: Cardiovascular disorders (CVD) and venous thromboembolism (VTE) are increasingly reported in people with hemophilia (PWH) whose life expectancy has improved dramatically over the past decades. While management of thrombotic events among PWH requires navigating the delicate balance between recurrent ischemic events and hemorrhage, current practices are highly variable and largely informed by expert opinion. Objective: We sought to examine and summarize what is known about the management, practice variation and outcomes of PWH requiring antithrombotic therapy (ATT) for cardiovascular disorders (CVD) or venous thromboembolism (VTE). We also aimed to identify current knowledge and practice gaps in the management of CVD and VTE in PWH. Methods: We conducted a scoping review guided by Arksey and O'Malley (2002), and Levac et al.'s (2010) methodological frameworks. We also adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A search strategy, developed iteratively in collaboration with a medical librarian, was performed on MEDLINE, EMBASE, and Scopus from inception to May 3, 2021. Studies of any design, published in English or French, in full-text or abstract, were included if they reported on more than two patients with inherited hemophilia A or B requiring ATT for CVD or VTE. Following eligibility assessment in duplicate, data from each study was charted by two independent reviewers to report the type of research designs, population, geographical location, interventions, and outcomes. Conflicts were resolved by consensus. We conducted a descriptive analysis and narrative synthesis to identify common themes and knowledge gaps. Results: We screened 3929 articles and selected 38 studies for inclusion (23 full-text and 15 abstracts). Published studies were largely retrospective (28/38, 73.7%), single center (25/38, 65.8%), and from Europe (25/38, 65.8%). A total of 567 patients with hemophilia A or B were reported. Common indications for ATT use included: coronary artery disease (26/38, 68.4%), including a history of percutaneous coronary intervention or coronary artery bypass procedures (14/38, 36.8%), atrial fibrillation (13/38, 34.2%), VTE treatment or prevention (10/38, 26.3%), cerebrovascular disease (9/38, 23.7%) and valvular heart disease (7/38, 18.4%). ATT included single antiplatelet therapy (28/38, 73.7%), heparins (21/38, 55.3%), dual antiplatelet therapy (19/38, 50%), vitamin K antagonists (10/38, 26.3%), and direct oral anticoagulants (5/38, 13.2%). The use of hemostatic therapies, either on-demand or prophylactically, was reported in 36 studies (94.7%). Clotting factors concentrates were used in 35 studies (92.1%). Other agents included desmopressin (2/38, 5.2%) and emicizumab (1/38, 2.6%). Only 19 studies (50%) reported target factor levels (peak and/or trough) while on ATT. Outcomes related to bleeding while on ATT were described in 36 studies (94.7%). Bleeding events resulting in a change in hemostatic regimen occurred in 9 studies (25%), while bleeding resulting in a change or discontinuation of ATT occurred in 10 studies (27.8%). In 10 studies (26.3%), no pathologic bleeding was observed in PWH on ATT. Four key themes were generated iteratively to describe the observed wide practice variation in the management of PWH requiring ATT: (1) Deviation from established and evolving CVD/VTE-related standards of care; (2) Difficulty weighing competing bleeding and thrombotic risks; (3) Advocacy for individualized strategies and multidisciplinary care; and (4) Absence of high-quality and long-term data for PWH. Discussion and Conclusion: Our scoping review highlights unmet needs in the management of an aging population of PWH with increasing prevalence of CVD and VTE. Management patterns are inconsistent and diverge from those of non-hemophilic patients. Current literature provides limited information on key issues such as hemostatic regimen, target factor levels, bleeding events and long-term outcomes. Prospective, clinically actionable data are needed to inform optimal and evidence-based management strategies of CVD and VTE in PWH. Higher quality data should culminate in much needed guidelines co-produced with patient partners and medical experts in hemophilia, CVD, and VTE. Disclosures Khalife: Pfizer Canada: Honoraria, Research Funding; Canadian Hemophilia Society: Research Funding.

Microangiopathic hemolytic anemia and thrombocytopenia (MAHA-T) is a rare complication of acute pancreatitis (AP). Treatment with therapeutic plasma exchange (TPE) is used at many centers. The natural history of this disease is not well understood. We report a case of acute pancreatitis induced MAHA-T with end organ dysfunction and a normal ADAMTS13 level. Following three TPEs, the patient's clinical status, blood counts and hemolytic markers stabilized. Improvement occurred even after TPE was discontinued. The optimal management of AP-induced MAHA-T is poorly understood. Many centres are reporting good outcomes with the early initiation of TPE. MAHA-T associated with acute pancreatitis is often treated with early initiation of TPE. However, the value of TPE in altering the natural history of the condition is not well understood. Further study is required to understand the role of ADAMTS13 testing to guide treatment, and the role of TPE in management.

Background Scurvy is a rare entity in developed countries and the diagnosis may often be delayed resulting in unnecessary investigations and/or potentially severe complications. A recent increase in the number of patients diagnosed with scurvy in our hematology clinics indicated the need to review the literature on the diagnosis and optimal management of similar patients. Methods We conducted a retrospective chart review of patients referred to hematology at our tertiary care centre between 2010 and 2018, who were ultimately diagnosed with scurvy. Data collected from electronic medical records included baseline characteristics, clinical features on presentation, bloodwork results from initial consultation, treatment plan as well as response to treatment. Findings Twenty-two adults patient had a diagnosis of scurvy with a mean vitamin C level of 6 μmol/L. Iron deficiency anemia (54%) and gastrointestinal disorders (54%) were the most common comorbidities noted in our cohort. Proton-pump inhibitors use was noted in 54% of patients. Bleeding (45%) and bruising (45%) were the most commonly reported clinical features. Eleven patients received oral supplementation, five had intravenous (IV) vitamin C and six were not treated. Two patients required a transition from oral to IV supplementation. Vitamin C dosing ranged between 250 and 2000 mg and the frequency varied from daily for oral therapy to every few weeks or months for IV. Interpretation Awareness of scurvy and its associated risk factors and clinical presentation is important in the evaluation of a patient with bleeding tendency. Treatment plan should be individualized, and a careful review of patients' diet, medial history and medications is warranted.

Among the realm of repeat containing proteins that commonly serve as &ldquo, scaffolds&rdquo, promoting protein-protein interactions, there is a family of proteins containing between 2 and 20 tetratricopeptide repeats (TPRs), which are functional motifs consisting of 34 amino acids. The most distinguishing feature of TPR domains is their ability to stack continuously one upon the other, with these stacked repeats being able to affect interaction with binding partners either sequentially or in combination. It is known that many repeat-containing proteins are characterized by high levels of intrinsic disorder, and that many protein tandem repeats can be intrinsically disordered. Furthermore, it seems that TPR-containing proteins share many characteristics with hybrid proteins containing ordered domains and intrinsically disordered protein regions. However, there has not been a systematic analysis of the intrinsic disorder status of TPR proteins. To fill this gap, we analyzed 166 human TPR proteins to determine the degree to which proteins containing TPR motifs are affected by intrinsic disorder. Our analysis revealed that these proteins are characterized by different levels of intrinsic disorder and contain functional disordered regions that are utilized for protein-protein interactions and often serve as targets of various posttranslational modifications.

Background: Residency programs are facing significant restructuring through the “Competence by Design” (CBD) framework proposed by the Royal College of Physicians and Surgeons of Canada (RCPSC). Our goal was to establish the competencies to be acquired during the transition to a senior role within Internal Medicine (IM) training. Methods: Using a modified Delphi technique, practicing IM physicians and recent graduates were polled to develop consensus on the required competencies to effectively transition from junior to senior medical resident. Participants rated each competency on a three-point Likert scale. Each competency was linked to an Entrustable Professional Activity (EPA) identified by the RCPSC IM Specialty Committee.Results: A total of eighteen participants took part in item generation (16% response rate) and nineteen in the initial ranking with seventeen completing all three iterations (89% completion rate). Eighty-three competencies were identified during questionnaire development. A final list of seventy-seven competencies reached consensus after three rounds. Most competencies matched to core of discipline EPAs.Conclusion: This consensus-based list of competencies will help create a framework and tools for the assessment of junior residents as they prepare to transition to the role of senior in the new CBD curricula for IM trainees at our institution.

Introduction: The prognosis of relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) remains poor in adults. Response rates and survival following anti-CD19 chimeric antigen receptor (CAR) T-cells in r/r ALL have exceeded those of other available agents, but comparative studies are still lacking. Although this therapy shows great promise, it involves complex and expensive manufacturing and administration. Our study seeks to understand the response and survival outcomes of a cohort of Canadian patients with ALL treated with current standard therapies to help the Canadian health care system build capacity for anti-CD19 CART therapies for r/r ALL. Methods: We conducted a retrospective chart review of all patients diagnosed with ALL at 2 large Canadian academic hospitals between 2010 and 2015 (Ottawa and Vancouver). All patient, therapy and outcome-based factors were extracted. Included patients were then cross-checked against the eligibility criteria for completed anti-CD19 CART cell trials in r/r ALL, but with an upper age cut-off of 75. Results: 173 patients were diagnosed with ALL over a 5-year period, with median age of 50 (range 16-88). 159 (92%) patients had CD19 reported by flow cytometry, of which 141 were positive at diagnosis. 124 patients (72%) achieved complete remission with induction chemotherapy and 74 patients (43%) relapsed after a median of 11.8 months (range 1-85.6) from diagnosis, of which 29 patients (17%) experienced a second relapse. A total of 63 patients (36%) had an allogeneic stem cell transplant, of which 22 (13%) relapsed after transplant. Patients who relapsed at any point in time survived 5.4 months (range 0.2-55.4). A total number of 62 patients (35.8%) would have been eligible for currently approved anti-CD19 CAR T cell therapy. Reasons for ineligibility were not limited to remission status, but also included CNS involvement, previous solid malignancy, undocumented CD19 status or CD19 negativity, and evidence of kidney or liver dysfunction. The median event-free and overall survival for patients who would have been eligible for FDA-approved anti-CD19 CART cells were 10.3 months (range 0.4-52.3) and 17.3 months (range 0.4-72.6), respectively. Conclusion: Anti-CD19 CAR T cell therapy has shown very promising results based on early phase data in patients with r/r ALL. Canadian patients are expecting this therapeutic option to be available soon, but our health care system needs to prepare for the complexity of this therapy. Our study helps provide "real-world" eligibility and outcomes of adult patients with r/r ALL. This data suggests that about one-third of cases of ALL could be eligible for this new therapy and should help centers build capacity according to how many new cases of ALL are seen per year. Disclosures No relevant conflicts of interest to declare.