A novel colorectal cancer test combining microsatellite instability and BRAF/RAS analysis: Clinical validation and impact on Lynch syndrome screening.

Background: Lynch syndrome (LS) is under-diagnosed. UK National Institute for Health and Care Excellence guidelines recommend multistep molecular testing of all colorectal cancers (CRCs) to screen for LS. However, the complexity of the pathway has resulted in limited improvement in diagnosis. Methods: One-step multiplex PCR was used to generate sequencing-ready amplicons from 14 microsatellite instability (MSI) markers and 22 BRAF, KRAS, and NRAS mutation hotspots. MSI and BRAF/RAS variants were detected using amplicon-sequencing and automated analysis. The assay was clinically validated and deployed into service in northern England, followed by regional and local audits to assess its impact. Results: MSI analysis achieved 99.1% sensitivity and 99.2% specificity and was reproducible (r = 0.995). Mutation hotspot analysis had 100% sensitivity, 99.9% specificity, and was reproducible (r = 0.998). Assay-use in service in 2022-2023 increased CRC testing (97.2% (2466/2536) versus 28.6% (601/2104)), halved turnaround times, and identified more CRC patients at-risk of LS (5.5% (139/2536) versus 2.9% (61/2104)) compared to 2019-2020 when a multi-test pathway was used. Conclusion: A novel amplicon-sequencing assay of CRCs, including all biomarkers for LS screening and anti-EGFR therapy, achieved >95% testing rate. Adoption of this low cost, scalable, and fully automatable test will complement on-going, national initiatives to improve LS screening.

Hawks and Doves in Standardized Letters of Evaluation: 6 Years of Rating Distributions and Trends in Emergency Medicine.

Background Standardized Letters of Evaluation (SLOEs) are an important part of resident selection in many specialties. Often written by a group, such letters may ask writers to rate applicants in different domains. Prior studies have noted inflated ratings; however, the degree to which individual institutions are "doves" (higher rating) or "hawks" (lower rating) is unclear. Objective To characterize institutional SLOE rating distributions to inform readers and developers regarding potential threats to validity from disparate rating practices. Methods Data from emergency medicine (EM) SLOEs between 2016 and 2021 were obtained from a national database. SLOEs from institutions with at least 10 letters per year in all years were included. Ratings on one element of the SLOE-the "global assessment of performance" item (Top 10%, Top Third, Middle Third, and Lower Third)-were analyzed numerically and stratified by predefined criteria for grading patterns (Extreme Dove, Dove, Neutral, Hawk, Extreme Hawk) and adherence to established guidelines (Very High, High, Neutral, Low, Very Low). Results Of 40 286 SLOEs, 20 407 met inclusion criteria. Thirty-five to 50% of institutions displayed Neutral grading patterns across study years, with most other institutional patterns rated as Dove or Extreme Dove. Adherence to guidelines was mixed and fewer than half of institutions had Very High or High adherence each year. Most institutions underutilize the Lower Third rating. Conclusions Despite explicit guidelines for the distribution of global assessment ratings in the EM SLOE, there is high variability in institutional rating practices.

Greater Disease Severity and Worse Clinical Outcomes in Patients Hospitalised with COVID-19 in Africa.

Background: COVID-19 cardiovascular research from Africa is limited. This study describes cardiovascular risk factors, manifestations, and outcomes of patients hospitalised with COVID-19 in the African region, with an overarching goal to investigate whether important differences exist between African and other populations, which may inform health policies. Methods: A multinational prospective cohort study was conducted on adults hospitalised with confirmed COVID-19, consecutively admitted to 40 hospitals across 23 countries, 6 of which were African countries. Of the 5,313 participants enrolled globally, 948 were from African sites (n = 9). Data on demographics, pre-existing conditions, clinical outcomes in hospital (major adverse cardiovascular events (MACE), renal failure, neurological events, pulmonary outcomes, and death), 30-day vitality status and re-hospitalization were assessed, comparing African to non-African participants. Results: Access to specialist care at African sites was significantly lower than the global average (71% vs. 95%), as were ICU admissions (19.4% vs. 34.0%) and COVID-19 vaccination rates (0.6% vs. 7.4%). The African cohort was slightly younger than the non-African cohort (55.0 vs. 57.5 years), with higher rates of hypertension (48.8% vs. 46.9%), HIV (5.9% vs. 0.3%), and Tuberculosis (3.6% vs. 0.3%). In African sites, a higher proportion of patients suffered cardiac arrest (7.5% vs. 5.1%) and acute kidney injury (12.7% vs. 7.2%), with acute kidney injury (AKI) appearing to be one of the strongest predictors of MACE and death in African populations compared to other populations. The overall mortality rate was significantly higher among African participants (18.2% vs. 14.2%). Conclusions: Overall, hospitalised African patients with COVID-19 had a higher mortality despite a lower mean age, contradicting literature that had previously reported a lower mortality attributed to COVID-19 in Africa. African sites had lower COVID-19 vaccination rates and higher AKI rates, which were positively associated with increased mortality. In conclusion, African patients were hospitalized with more severe COVID-19 cases and had poorer outcomes.

Measuring Emergency Department Workload Perception Using Electronic Medical Record Measures of Patient Volume and Acuity.

BACKGROUND: Workload in the emergency department (ED) fluctuates and there is no established model for measurement of clinician-level ED workload. OBJECTIVE: The aim of this study was to measure perceived ED workload and assess the relationship between perceived workload and objective measures of workload from the electronic medical record (EMR). METHODS: This study was conducted at a tertiary care, academic ED from July 1, 2020 through April 13, 2021. Attending workload perceptions were collected using a 5-point scale in three care areas with variable acuity. We collected eight EMR measures thought to correlate with perceived workload. EMR values were compared across areas of the department using ANOVA and correlated with attending workload ratings using linear regression. RESULTS: We collected 315 unique workload ratings, which were normally distributed. For the entire department, there was a weak positive correlation between reported workload perception and mean percentage of inpatient admissions (r = 0.23; p < 0.001), intensive care unit admissions (r = 0.2; p < 0.001), patient arrivals per shift (r = 0.14; p = 0.017), critical care billed visits (r = 0.22; p < 0.001), cardiopulmonary resuscitation code activations (r = 0.2; p < 0.001), and level 5 visits (r = 0.13; p = 0.02). There was weak negative correlation for ED discharges (r = -0.23; p < 0.001). Several correlations were stronger in individual care areas, including percent admissions in the lowest-acuity area (r = 0.43; p = 0.033) and patient arrivals in the highest-acuity area (r = 0.44; p < .01). No significant correlation was found in any area for observation admissions or trauma activations. CONCLUSIONS: In this study, EMR measures of workload were not closely correlated with ED attending physician workload perception. Future study should examine additional factors contributing to physician workload outside of the EMR.

The utility of an online discussion board for reflective writing in an emergency medicine rotation.

Background: Narrative analysis and reflection have been found to support professional identity formation (PIF) and resilience among medical students. In the emergency department, students have used reflective practice to process challenging clinical experiences, such as ethical dilemmas or moral distress. An online discussion board, however, has not been described as a curricular component of emergency medicine (EM) rotations. The objective of this educational innovation was to support medical students in an EM clinical rotation via an online discussion board for reflecting on and debriefing clinical experiences with faculty and peers. Methods: Fifty-two medical students enrolled in the pass/fail EM elective between May 13, 2019, and October 30, 2020. Each cohort of six students took part in a cohort-specific discussion using the Canvas learning management system. Students were encouraged to post about any observations, reflections, or emotions after their shifts. Faculty course directors responded to each post using concepts of debriefing, coaching, and trauma-informed teaching. Results: Over 18 months, 49 of 52 (94%) students participated in the discussion board. Of 346 total posts, half were by students, and the other half were faculty responses. Students posted 3.27 times each, on average. Students rarely raised questions about scientific knowledge content, fact-based aspects of patient care, or specific skills. Rather, they often posted about intensely affective reactions to experiences that left them with complex emotions. Upon review of posts by the course directors, the majority (54%) of students' posts contained a range of affective responses. Students appreciated faculty responses and supported each other in their written responses to peers. Conclusions: An online discussion board can be used successfully for asynchronous reflective practice to debrief clinical experiences during an EM rotation, if designed incorporating faculty and peer support using trauma-informed teaching principles to bolster well-being and PIF.

Variability in Emergency Department Procedure Rates and Distributions in a Regional Health System: A Cross-Sectional Observational Study.

STUDY OBJECTIVE: Procedural competency is essential to the practice of emergency medicine. However, there are limited data quantifying emergency department procedural volumes to inform the work of educators and credentialing bodies. In this study, we characterize procedural scope and volume in a regional health care system and compare rates between practice settings and over time. METHODS: Cross-sectional data were acquired from electronic medical records of a regional health care system from March 2017 through February 2022. Nonspecific entries, esoteric procedures, and nonprocedural clinical skills were excluded. Procedural rates were compared: (1) between academic and community hospitals, (2) across study years, and (3) across seasons. Analyses were repeated for pediatric encounters, and with study year 4 removed to assess the influence of the first year of the coronavirus disease 2019 pandemic on results. RESULTS: There were 131,976 instances of 40 qualifying procedures in 1,979,935 unique visits across 9 EDs. Several high-acuity procedures had similar rates in academic and community settings, including cardiac pacing, cricothyrotomy, and lateral canthotomy. Year-over-year procedural rates were stable or increasing for most procedures, with a notable exception of lumbar puncture. Most procedures did not have significant seasonal variation, and most findings were stable when study year 4 was removed from the analysis. CONCLUSION: All procedures were performed in all settings and rates of several emergent procedures were similar in both settings, underscoring the importance of broad procedural competence for all emergency physicians. Educators and credentialing organizations can use these data to inform decisions regarding curriculum design and certification requirements.

The Emergency Medicine Resident Retreat: Creating and Sustaining a Transformative and Reflective Experience.

Introduction  Burnout rates for emergency medicine residents are high. One intervention and initiative to enhance wellness and address burnout is the resident retreat. Retreats have multiple formats and are often designed with an emphasis on social events. This longitudinal retreat curriculum for a three-year residency training program was designed emphasizing rest, a step away from what is familiar, and reflection.  Methods Individual resident retreats were designed for each year of postgraduate training. The agenda for each is organized and intentional. Activities focused on personal well-being, self-reflection, team building, professional development, and physical activities are coupled with topics unique to class year roles and responsibilities. Retreats are held away from the hospital establishing a separation from the workplace. Results The retreat program has been sustainable for almost decades with trainees evaluating it highly. Faculty and residents enthusiastically participate in the program and consider it a fundamental part of the residency; 93.75% of residents surveyed strongly agreed that the retreats benefit their training while 94.2% strongly agreed that retreats increased their enthusiasm for training. Conclusions An emergency medicine resident retreat program focusing on unique elements for each post-graduate year is achievable and sustainable in an emergency medicine residency program. Over time, the retreat has become an integral part of the residency experience with positive experiences for both faculty and trainees.

The role of adjuvant chemotherapy in the management of acute promyelocytic leukemia differentiation syndrome.

Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone. We conducted a three-institution retrospective study, aiming to evaluate the role of short-term adjuvant chemotherapy in managing moderate DS for patients with low- or intermediate-risk APL initially treated with ATRA/ATO only protocols. We evaluated the difference in incidence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy. 57 low- or intermediate-risk APL patients were retrospectively identified and included for this study; 36 patients received ATRA/ATO only induction treatment, and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy. Similar proportions of patients experienced DS in both groups (66.7% vs. 81.0%, P = 0.246). The median duration of DS resolution in patients receiving ATRA/ATO only was 17 days (n = 23), and in patients receiving combination therapy was 8 days (n = 16) (P = 0.0001). The lengths of hospital stay in patients receiving ATRO/ATO only was 38 days (n = 7), and in patients receiving combination therapy was 14 days (n = 17) (P = 0.0007). In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and the length of hospital stay during APL induction treatment.

Block by block: Building on our knowledge to better care for LGBTQIA+ patients.

Background: Emergency physicians need to recognize the diversity of identities held by sexual and gender minorities, as well as the health implications and inequities experienced by these communities. Identities such as lesbian, gay, bisexual, transgender, queer, questioning, intersex, asexual, aromantic, and many others fall under the LGBTQIA+ acronym. This wide spectrum is seldom discussed in emergency medicine but nonetheless impacts both patient care and patient experience in acute and critical care settings. Aims: This commentary aims to provide a brief but nonexhaustive review of LGBTQIA+ identities and supply a critical framework for applying this understanding to patient encounters in the emergency department, as well as describe the challenges and educational aims at the level of medical school, residency, and postresidency. Materials and Methods: The commonly used and widely accepted definitions of LGBTQIA+ terms are described, as well as implications for patient care and emergency physician education. The authors of this writing group represent the Society for Academic Emergency Medicine, LGBTQ Task Force of the Academy of Diversity Inclusion in Medicine. Results: LGB terms are addressed, with LGBTQIA+ adding "intersex," "asexual," and "+," to include other gender identities and sexual orientations which are not already included. This paper also addresses the terms "transition," "nonbinary," "polyamorous." "two-spirit," "queer," and others. These acronyms and terms continually expand and evolve in the pursuit of inclusivity. Additionally, with some health issues potentially related to medications, hormones, surgery, or to internal or external genitalia, important EM physician tools include gathering an "organ inventory," asking about sexual history, and conducting a physical exam. Discussion: Most persons have congruent biological sex, gender identity, and attraction to the "opposite" gender. However, humans can have every imaginable variation and configuration of chromosomes, genitalia, gender identities, sexual attractions, and sexual behaviors. Terms and definitions are constantly changing and adapting; they may also vary by local culture. Obtaining relevant medical history, conducting an "organ inventory," asking about sexual history in a nonjudgmental way, and conducting a physical exam when warranted can all be important in delivering best possible medical care. Although there has been increased focus on education at the medical school, residency, and faculty level on LGBTQIA+ patient care in the ED, much work remains to be done. Conclusion: Emergency physicians should feel confident in providing a model of care that affirms the sexual and gender identities of all the patient populations we serve. Optimal patient-centric care requires a deeper understanding of the patient's biology, gender identity, and sexual behavior encapsulated into the ever-growing acronym LGBTQIA+.

Emergency care of LGBTQIA+ patients requires more than understanding the acronym.

Emergency physicians (EPs) frequently deliver care to members of the LGBTQIA+ community in the emergency department. This community suffers from many health disparities important to understand as part of comprehensive care, and these disparities are infrequently discussed in emergency medicine education. Previous data also suggest a need for broader education to increase the comfort of EPs caring for LGBTQIA+ patients. A group of content experts identified key disparities, opportunities for expanded education, and strategies for more inclusive care of LGBTQIA+ patients.

United States 2020 Emergency Medicine Resident Workforce Analysis.

STUDY OBJECTIVE: To characterize the emergency medicine resident physician workforce and the residency programs training them. METHODS: We identified emergency medicine residents in the 2020 American Medical Association (AMA) Physician Masterfile, analyzed demographic information, mapped both county-level population-adjusted and hospital referral region densities, and compared 2020 versus 2008 resident physician densities. We also analyzed all Accreditation Council for Graduate Medical Education (ACGME)-accredited emergency medicine residency programs from 2013 to 2020, mapped state-level population-adjusted densities, and identified temporal trends in program location and state-level program densities. All population-adjusted densities were calculated using the US Census Bureau resident population estimates. RESULTS: There were 6,993 emergency medicine residents in the 2020 AMA dataset with complete information. Most of them (98%) were in urban areas. Compared with 2008, per 100,000 US population, this represents disproportionate increases in urban areas (total [0.5], urban [0.5], large rural [0.2] and small rural [0.05]). We further identified 160 (2013) to 265 (2020) residency programs using the ACGME data. The new programs were 3-year training programs that were disproportionately added to states with an already higher number of programs (Florida [5 to 19], Michigan [11 to 25], New York [21 to 31], Ohio [9 to 18], Pennsylvania [12 to 21], California [14 to 22]). CONCLUSION: The number of emergency medicine residency programs has increased; most new programs were added to the states that already had emergency medicine residency programs. There is an emergency physician "desert" in the rural United States, lacking both residents and residency training programs. This analysis provides essential context to the ongoing conversation about the future of the emergency physician workforce.

Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency.

Designing effective antileukemic immunotherapy will require understanding mechanisms underlying tumor control or resistance. Here, we report a mechanism of escape from immunologic targeting in an acute myeloid leukemia (AML) patient, who relapsed 1 year after immunotherapy with engineered T cells expressing a human leukocyte antigen A*02 (HLA-A2)-restricted T cell receptor (TCR) specific for a Wilms' tumor antigen 1 epitope, WT1126-134 (TTCR-C4). Resistance occurred despite persistence of functional therapeutic T cells and continuous expression of WT1 and HLA-A2 by the patient's AML cells. Analysis of the recurrent AML revealed expression of the standard proteasome, but limited expression of the immunoproteasome, specifically the beta subunit 1i (ß1i), which is required for presentation of WT1126-134. An analysis of a second patient treated with TTCR-C4 demonstrated specific loss of AML cells coexpressing ß1i and WT1. To determine whether the WT1 protein continued to be processed and presented in the absence of immunoproteasome processing, we identified and tested a TCR targeting an alternative, HLA-A2-restricted WT137-45 epitope that was generated by immunoproteasome-deficient cells, including WT1-expressing solid tumor lines. T cells expressing this TCR (TTCR37-45) killed the first patients' relapsed AML resistant to WT1126-134 targeting, as well as other primary AML, in vitro. TTCR37-45 controlled solid tumor lines lacking immunoproteasome subunits both in vitro and in an NSG mouse model. As proteasome composition can vary in AML, defining and preferentially targeting these proteasome-independent epitopes may maximize therapeutic efficacy and potentially circumvent AML immune evasion by proteasome-related immunoediting.

A Case of Bleeding During Infection With COVID-19.

Dr. Patrick Lowe: Our case today is that of a 47-year-old woman who was referred to our emergency department (ED) due to bloody urine, dark tarry stools, red spots on her skin, and bruising throughout her body. Fourteen days prior to presentation, she began exhibiting intermittent fevers, headache, shortness of breath, and a dry cough, and she tested positive for SARS-CoV-2 (the virus that causes COVID-19 pneumonia). Over the 3 days prior to her ED presentation, she experienced a headache that was more intense than the headaches she had been having in the preceding 2 weeks. She reported episodes of both dark urine as well as bright red blood in her urine. In addition, she had multiple dark stools described as tar-like when asked. On the day of her ED presentation, the patient noted a red rash throughout her body. In addition, earlier in the day, she had atraumatic self-limited epistaxis. She denied any falls or head strikes, vision changes, focal weakness or numbness, shortness of breath, chest pain, abdominal pain, or peripheral swelling.

Gender-based Barriers to the Advancement of Women in Academic Emergency Medicine: A Multi-Institutional Survey Study.

INTRODUCTION: Leadership positions occupied by women within academic emergency medicine have remained stagnant despite increasing numbers of women with faculty appointments. We distributed a multi-institutional survey to women faculty and residents to evaluate categorical characteristics contributing to success and differences between the two groups. METHODS: An institutional review board-approved electronic survey was distributed to women faculty and residents at eight institutions and were completed anonymously. We created survey questions to assess multiple categories: determination; resiliency; career support and obstacles; career aspiration; and gender discrimination. Most questions used a Likert five-point scale. Responses for each question and category were averaged and deemed significant if the average was greater than or equal to 4 in the affirmative, or less than or equal to 2 in the negative. We calculated proportions for binary questions. RESULTS: The overall response rate was 55.23% (95/172). The faculty response rate was 54.1% (59/109) and residents' response rate was 57.1% (36/63). Significant levels of resiliency were reported, with a mean score of 4.02. Childbearing and rearing were not significant barriers overall but were more commonly reported as barriers for faculty over residents (P <0.001). Obstacles reported included a lack of confidence during work-related negotiations and insufficient research experience. Notably, 68.4% (65/95) of respondents experienced gender discrimination and 9.5% (9/95) reported at least one encounter of sexual assault by a colleague or supervisor during their career. CONCLUSION: Targeted interventions to promote female leadership in academic emergency medicine include coaching on negotiation skills, improved resources and mentorship to support research, and enforcement of safe work environments. Female emergency physician resiliency is high and not a barrier to career advancement.