An Obstetrician-Gynecologist's Review of Hernias: Risk Factors, Diagnosis, Prevention, and Repair.

Management of obstetric and gynecologic patients with hernias pose challenges to their providers caring for them. Risks for hernia development include well described factors that impair surgical wound healing and increase abdominal pressure. Among the diverse populations cared for by obstetricians and gynecologists, pregnant patients and those with gynecologic malignancies are at the highest risk for hernia formation. This article provides an overview of the existing literature with a focus on patients cared for by OB/Gyns and commonly encountered pre-operative and intra-operative scenarios. We highlight scenarios when a hernia repair is not commonly performed including those for patients undergoing non-elective surgeries with known or suspected gynecologic cancers. Finally, we offer multidisciplinary recommendations on the timing of elective hernia repair with obstetric and gynecologic procedures, with attention to the primary surgical procedure, the type of pre-existing hernia and patient characteristics.

To Target or Not to Target Schistosoma mansoni Cyclic Nucleotide Phosphodiesterase 4A?

Schistosomiasis is a neglected tropical disease with high morbidity. Recently, the Schistosoma mansoni phosphodiesterase SmPDE4A was suggested as a putative new drug target. To support SmPDE4A targeted drug discovery, we cloned, isolated, and biochemically characterized the full-length and catalytic domains of SmPDE4A. The enzymatically active catalytic domain was crystallized in the apo-form (PDB code: 6FG5) and in the cAMP- and AMP-bound states (PDB code: 6EZU). The SmPDE4A catalytic domain resembles human PDE4 more than parasite PDEs because it lacks the parasite PDE-specific P-pocket. Purified SmPDE4A proteins (full-length and catalytic domain) were used to profile an in-house library of PDE inhibitors (PDE4NPD toolbox). This screening identified tetrahydrophthalazinones and benzamides as potential hits. The PDE inhibitor NPD-0001 was the most active tetrahydrophthalazinone, whereas the approved human PDE4 inhibitors roflumilast and piclamilast were the most potent benzamides. As a follow-up, 83 benzamide analogs were prepared, but the inhibitory potency of the initial hits was not improved. Finally, NPD-0001 and roflumilast were evaluated in an in vitro anti-S. mansoni assay. Unfortunately, both SmPDE4A inhibitors were not effective in worm killing and only weakly affected the egg-laying at high micromolar concentrations. Consequently, the results with these SmPDE4A inhibitors strongly suggest that SmPDE4A is not a suitable target for anti-schistosomiasis therapy.

Intravitreal Nesvacumab (Anti-Angiopoietin-2) Plus Aflibercept in Neovascular AMD: Phase 2 ONYX Randomized Trial.

Purpose: To compare intravitreal nesvacumab (anti-angiopoietin-2) + aflibercept vs intravitreal aflibercept injection (IAI) in neovascular age-related macular degeneration (nAMD). Methods: Eyes were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, week 4, and week 8. The LD combo was continued every 8 weeks (q8w). At week 12, the HD combo was re-randomized to q8w or every 12 weeks (q12w) and IAI was re-randomized to q8w, q12w, or HD combo q8w through week 32. Results: The study comprised 365 eyes. At week 12, the mean best-corrected visual acuity (BCVA) gains from baseline were similar in the LD combo group, HD combo group, and IAI group (5.2 letters, 5.6 letters, and 5.4 letters, respectively); the mean central subfield thickness (CST) reductions were similar (182.2 µm, 200.0 µm, and 178.6 µm, respectively). The mean changes in BCVA and CST through week 36 were similar across groups. At week 12, complete retinal fluid resolution was observed in 49.1% (LD combo), 50.8% (HD combo), and 43.6% (IAI) of eyes; the proportions with a CST of 300 µm or less were similar across groups. Numerical trends at week 32 toward complete retinal fluid resolution with combination treatment were not maintained at week 36. Serious ocular adverse events were infrequent and comparable across groups. Conclusions: In nAMD, nesvacumab + aflibercept showed no additional BCVA or CST benefit over IAI monotherapy.

A Consensus Approach for Targeted Muscle Reinnervation in Amputees.

Amputations have been performed with few modifications since the dawn of surgery. Blood vessels are ligated, bones are shortened, and nerves are cut. In a percentage of people, this can result in severe neuropathic, residual limb, and phantom limb pain. Targeted muscle reinnervation is a surgical procedure initially conceived to optimize function for myoelectric prostheses in amputees. Recently, it has been adopted more widely by surgeons for the prevention and treatment of neuropathic pain. Perhaps as a function of its relatively recent development, many authors perform this operation differently, and there has been no overall agreement regarding the principles, indications, technical specifics, and postoperative management guidelines. This article is written as a consensus statement by surgeons focused on the treatment of neuropathic pain and those with extensive experience performing targeted muscle reinnervation. It is designed to serve as a roadmap and template for extremity surgeons to consider when performing targeted muscle reinnervation.

Two-Year Outcomes After Pediatric In-Office Tympanostomy Using Lidocaine/Epinephrine Iontophoresis and an Automated Tube Delivery System.

OBJECTIVE: Evaluate 2-year outcomes after lidocaine/epinephrine iontophoresis and tympanostomy using an automated tube delivery system for pediatric tube placement in-office. STUDY DESIGN: Prospective, single-arm. SETTING: Eighteen otolaryngology practices. METHODS: Children age 6 months to 12 years indicated for tympanostomy were enrolled between October 2017 and February 2019. Local anesthesia of the tympanic membrane was achieved via lidocaine/epinephrine iontophoresis and tympanostomy was completed using an automated tube delivery system (the Tula® System). An additional Lead-In cohort of patients underwent tube placement in the operating room (OR) under general anesthesia using only the tube delivery system. Patients were followed for 2 years or until tube extrusion, whichever occurred first. Otoscopy and tympanometry were performed at 3 weeks, and 6, 12, 18, and 24 months. Tube retention, patency, and safety were evaluated. RESULTS: Tubes were placed in-office for 269 patients (449 ears) and in the OR for 68 patients (131 ears) (mean age, 4.5 years). The median and mean times to tube extrusion for the combined OR and In-Office cohorts were 15.82 (95% confidence interval [CI]: 15.41-19.05) and 16.79 (95% CI: 16.16-17.42) months, respectively. Sequelae included ongoing perforation for 1.9% of ears (11/580) and medial tube displacement for 0.2% (1/580) observed at 18 months. Over a mean follow-up of 14.3 months, 30.3% (176/580) of ears had otorrhea and 14.3% (83/580) had occluded tubes. CONCLUSION: In-office pediatric tympanostomy using lidocaine/epinephrine iontophoresis and automated tube delivery results in tube retention within the ranges described for similar grommet-type tubes and complication rates consistent with traditional tube placement in the OR.

Sociodemographic circumstances, health, and life experience shape posttraumatic distress trajectories among individuals exposed to smoke during a large-scale coal mine fire.

The 2014 Hazelwood coal mine fire in the Latrobe Valley, Australia, distributed toxic smoke into surrounding communities over 45 days. This study investigated risk and protective factors associated with four trajectories of posttraumatic distress (resilient, recovery, delayed-onset, chronic) among exposed adults. Participants (N = 709) completed surveys in 2016-2017 and 2019-2020 assessing mine fire-related particulate matter (PM2.5 ) exposure; sociodemographic, physical, and mental health variables; and exposure to other traumatic and recent stressful events. Mine fire-related posttraumatic distress was measured using the IES-R; trajectories were determined according to established clinical significance thresholds. Relative risk ratios (RRRs) were generated from multivariate multinomial regressions. The resilient trajectory was most common (77.0%). The chronic trajectory (8.5%) was associated with loneliness, RRR = 2.59, 95% CI [1.30, 5.16], and physical health diagnoses, RRR = 2.31, 95% CI [1.32, 4.02]. The delayed-onset trajectory (9.1%) was associated with multiple recent stressful events, RRR = 2.51, 95% CI [1.37, 4.59]; mental health diagnoses, RRR = 2.30, 95% CI [1.25, 4.24]; loneliness, RRR = 2.05, 95% CI [1.09, 3.88]; and male gender, RRR = 2.01, 95% CI [1.18, 3.44]. Socioeconomic advantage protected against chronic, RRR = 0.68, 95% CI [0.53, 0.86], and delayed-onset trajectory membership, RRR = 0.68, 95% CI [0.50, 0.94]; social support protected against chronic trajectory membership, RRR = 0.67, 95% CI [0.49, 0.92]. PM2.5 exposure did not determine trajectory. These findings enhance understanding of longer-term posttraumatic responses to large-scale smoke events and can inform mental health initiatives within at-risk communities.

Primate-conserved carbonic anhydrase IV and murine-restricted LY6C1 enable blood-brain barrier crossing by engineered viral vectors.

The blood-brain barrier (BBB) presents a major challenge for delivering large molecules to study and treat the central nervous system. This is due in part to the scarcity of targets known to mediate BBB crossing. To identify novel targets, we leverage a panel of adeno-associated viruses (AAVs) previously identified through mechanism-agnostic directed evolution for improved BBB transcytosis. Screening potential cognate receptors for enhanced BBB crossing, we identify two targets: murine-restricted LY6C1 and widely conserved carbonic anhydrase IV (CA-IV). We apply AlphaFold-based in silico methods to generate capsid-receptor binding models to predict the affinity of AAVs for these identified receptors. Demonstrating how these tools can unlock target-focused engineering strategies, we create an enhanced LY6C1-binding vector, AAV-PHP.eC, that, unlike our prior PHP.eB, also works in Ly6a-deficient mouse strains such as BALB/cJ. Combined with structural insights from computational modeling, the identification of primate-conserved CA-IV enables the design of more specific and potent human brain-penetrant chemicals and biologicals, including gene delivery vectors.

Prophylactic Muscle Flaps in Patients with Oncologic Spine Disease Decrease Wound Complication Rates: A single institution cohort study.

BACKGROUND: Patients with oncologic spine disease face a high systemic illness burden and often require surgical intervention to alleviate pain and maintain spine stability. Wound healing complications are the most common reason for reoperation in this population and are known to impact quality of life and initiation of adjuvant therapy. Prophylactic muscle flap (MF) closures are known to reduce wound healing complications in high risk patients, but the efficacy in oncologic spine patients is not well established. METHODS: A collaboration at our institution presented an opportunity to study the outcomes of prophylactic MF closure. We performed a retrospective cohort study of patients who underwent MF closure versus a cohort who underwent non-MF closure in the preceding time. Demographic and baseline health data were collected, as well as postoperative wound complication data. RESULTS: A total of 166 patients were enrolled, including 83 patients in the MF cohort and 83 control patients. Patients in the MF group were more likely to smoke (p=0.005) and had a higher incidence of prior spine irradiation (p=0.002). Postoperatively, 5 (6%) patients in the MF group developed wound complications, compared to 14 (17%) patients in the control group (p=0.028). The most common overall complication was wound dehiscence requiring conservative therapy, which occurred in 6 (7%) control patients and 1 (1%) MF patient (p=0.053). CONCLUSIONS: Prophylactic MF closure during oncologic spine surgery significantly reduces the wound complication rate. Future studies should examine the precise patient population that stands to benefit most from this intervention.

Virtual Subinternships in the COVID Era: Lessons Learned from Three Institutional Experiences.

After the cessation of all in-person visiting rotations during the coronavirus 2019 pandemic, many programs developed virtual rotations as an alternative for the recruitment and education of prospective applicants. In this study, we developed a consortium of three institutions each with a unique virtual subinternship and prospectively surveyed participating students in order to reflect and improve upon future rotations. All students participating in virtual subinternships at three institutions were administered the same pre subinternship and post subinternship electronic surveys. Subinternship curricula were developed independently at each respective institution. Fifty-two students completed both surveys, for an overall response rate of 77.6%. Students' primary objectives were to evaluate their fit with the program (94.2%), interact with residents (94.2%), gain faculty mentorship (88.5%), and improve didactic knowledge (82.7%). Postrotation surveys revealed that over 73% of students reported having met all of these objectives over the course of the rotation. On average, students ranked programs 5% higher overall after the rotation (P = 0.024). Postrotation results showed that the majority (71.2%) of students perceived the virtual subinternship as slightly less valuable than in-person subinternships but that all students would participate in a virtual subinternship again. Student objectives can be successfully met using the virtual format for subinternships. The virtual format is also effective in enhancing the overall perception of a program and its residents. Although students still prefer in-person subinternships, our results suggest that virtual rotations are more accessible and very capable of meeting student goals.

Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.

Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials. One-Sentence Summary: Human genetic variation can modulate the strength of vaccine-induced broadly neutralizing antibody precursor B cell responses.

Human Performance Optimization: A Framework for the Military Health System.

The Department of Defense (DoD) is increasingly dependent on highly technological weapon systems, but the human is still at the heart of our war-fighting efforts. In order to maintain an effective fighting force, we must optimize and sustain human performance, which is defined as the successful completion of a specified task within an available performance capacity that meets or exceeds the mission demands. When health and performance are optimized and sustained, the costs of warfighter care and disability compensation are reduced and the quality of life is enhanced. Therefore, we propose that the Military Health System (MHS) reshape its focus on disease and injury treatment and prevention to embrace health enhancement for optimal human performance in a technology-rich battle space. This commentary develops a high-level strategy and policy framework to enable the MHS to optimize health and human performance for all DoD warfighters. We conducted a review of human performance literature, assessed existing health programs across the services, and conducted interviews with MHS and Line representatives. We found that the MHS has thus far met warfighter needs in a haphazard fashion. We propose an orchestrated approach to warfighter health and performance across the DoD and a more substantial partnership between Total Force Fitness and the MHS. We provide a notional concept for how the parts of this system could interact and a strategic framework for the delivery of health and performance to the warfighter.

Framework to Guide Health Professions Faculty Towards Increased Scholarship: Recommendations from the ASAHP Research, Discovery & Innovation Committee.

The Research, Discovery, and Innovation Publications (RDI-P) Task Force met from October 2020 to March 2022 to discuss ways in which the Association of Schools Advancing Health Professions (ASAHP) can help to guide institutional leaders to assign faculty effort and resources to enable success with the scholarship mission. The purpose of this White Paper is to propose a guiding framework for institutional leaders to determine their faculty's individual or team scholarly goals, assign appropriate percent efforts (funded/unfunded), and guide an overall faculty mix that balances required teaching loads with scholarly activities. The Task Force identified seven modifiable factors that can influence workload allocation for scholarship: 1. Limited range of the spectrum for effort distribution; 2. Matching expectations with reality; 3. Clinical training undervalued as adequate prep for translational or implementation research; 4. Limited support for mentorship availability; 5. Richer collaborations needed; 6. Finding resources and matching them to individual faculty needs; and 7. Further time for training needed. We then provide a set of recommendations to address the seven issues described. Finally, we describe four foci of scholarly activity (evidence-based educator; evidence-based clinical application; evidence-based collaborator; and evidence-based principal leader) with which a leader can develop strategies to align faculty interests and growth opportunities towards advancing scholarship.

Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade.

Paired single-cell RNA and T cell receptor sequencing (scRNA/TCR-seq) has allowed for enhanced resolution of clonal T cell dynamics in cancer. Here, we report a scRNA/TCR-seq analysis of 187,650 T cells from 31 tissue regions, including tumor, adjacent normal tissues, and lymph nodes (LN), from three patients with non-small cell lung cancer after immune checkpoint blockade (ICB). Regions with viable cancer cells are enriched for exhausted CD8+ T cells, regulatory CD4+ T cells (Treg), and follicular helper CD4+ T cells (TFH). Tracking T cell clonotypes across tissues, combined with neoantigen specificity assays, reveals that TFH and tumor-specific exhausted CD8+ T cells are clonally linked to TCF7+SELL+ progenitors in tumor draining LNs, and progressive exhaustion trajectories of CD8+ T, Treg, and TFH cells with proximity to the tumor microenvironment. Finally, longitudinal tracking of tumor-specific CD8+ and CD4+ T cell clones reveals persistence in the peripheral blood for years after ICB therapy.

Extreme Elevation of Baseline Intraoperative Parathyroid Hormone Measurements: Should Usual Protocols Apply?

INTRODUCTION: Intraoperative parathyroid hormone (IOPTH) monitoring is routinely used to facilitate minimally invasive parathyroidectomy. Many IOPTH protocols exist for predicting biochemical cure. Some patients are found to have extremely high baseline IOPTH levels (defined in this study as >500 pg/mL), which may affect the likelihood of satisfying certain final IOPTH criteria. We aimed to discover whether clinically significant differences exist in patients with extremely high baseline IOPTH and which IOPTH protocols are most appropriately applied to these patients. MATERIALS AND METHODS: This is a retrospective review of 237 patients who underwent parathyroidectomy with IOPTH monitoring for primary hyperparathyroidism (pHPT) from 2016 to 2020. Baseline IOPTH levels, drawn prior to manipulation of parathyroid glands, were grouped into categories labeled "elevated" (>65-500 pg/mL) and "extremely elevated" (>500 pg/mL). Final IOPTH levels were analyzed to determine whether there was a >50% decrease from baseline and whether a normal IOPTH value was achieved. 6-wk postoperative calcium levels were also examined. RESULTS: Of the patients in this cohort, 76% were in the elevated group and 24% in the extremely elevated group. Male sex and higher preoperative PTH levels were correlated with higher baseline IOPTH levels. Patients with extremely elevated baseline IOPTH were less likely to have IOPTH fall into normal range at the conclusion of the case (P = 0.019), and final IOPTH levels were higher (P < 0.001), but the IOPTH was equally likely to decrease >50% from baseline. There was no difference in the mean postoperative calcium levels between the two groups at 6-wk or at longer term follow-up (mean 525 d). CONCLUSIONS: Detection of baseline IOPTH levels >500 pg/mL during parathyroidectomy performed for pHPT is not uncommon. IOPTH in patients with extremely elevated baseline levels were less likely to fall into normal range, but follow-up calcium levels were equal, suggesting that applying more stringent IOPTH criteria for predicting biochemical cure may not be appropriate for this population.

FasterRib: A Deep Learning Algorithm to Automate Identification and Characterization of Rib Fractures on Chest Computed Tomography Scans.

OBJECTIVE: Characterizing and enumerating rib fractures is critical to informing clinical decisions, yet in-depth characterization is rarely performed due to the manual burden of annotating these injuries on computed tomography (CT) scans. We hypothesized that our deep learning model, FasterRib, could predict the location and percentage displacement of rib fractures using chest CT scans. METHODS: The development and internal validation cohort comprised over 4,700 annotated rib fractures from 500 chest CT scans within the public RibFrac. We trained a convolutional neural network to predict bounding boxes around each fracture per CT slice. Adapting an existing rib segmentation model, FasterRib outputs the three-dimensional locations of each fracture (rib number and laterality). A deterministic formula analyzed cortical contact between bone segments to compute percentage displacements. We externally validated our model on our institution's dataset. RESULTS: FasterRib predicted precise rib fracture locations with 0.95 sensitivity, 0.90 precision, 0.92 f1-score, with an average of 1.3 false positive fractures per scan. On external validation, FasterRib achieved 0.97 sensitivity, 0.96 precision, and 0.97 f1-score, and 2.24 false positive fractures per scan. Our publicly-available algorithm automatically outputs the location and percent displacement of each predicted rib fracture for multiple input CT scans. CONCLUSION: We built a deep learning algorithm that automates rib fracture detection and characterization using chest CT scans. FasterRib achieved the highest recall and the second highest precision among known algorithms in literature. Our open source code could facilitate FasterRib's adaptation for similar computer vision tasks and further improvements via large-scale external validation. LEVEL OF EVIDENCE: Level III. Diagnostic tests/criteria.

USE OF OPTICAL COHERENCE TOMOGRAPHY IN DETECTING RETINAL TEARS IN ACUTE, SYMPTOMATIC POSTERIOR VITREOUS DETACHMENT.

PURPOSE: To evaluate the association of posterior vitreous opacities (PVOs) on optical coherence tomography with retinal tears identified on examination in patients with acute, symptomatic posterior vitreous detachment (PVD). METHODS: Data were retrospectively collected from the medical records of 388 patients with acute, symptomatic PVD between January 1, 2021, and June 30, 2021. Included patients had received a primary diagnosis of PVD and presented with flashes and/or floaters. Optical coherence tomography scans were reviewed by two separate readers for the presence of PVOs. The primary outcome was the presence of retinal tear on fundus photograph and on examination. RESULTS: Of 388 patients who presented with acute PVD symptoms, 90 (23.2%) were found to have a retinal tear on dilated fundus examination. Among these patients, 78 (86.7%) were found to have PVOs on optical coherence tomography. Statistical analysis demonstrated a significant relationship between the presence of PVOs and retinal tear ( P < 0.01). The sensitivity and specificity of this finding was 86.7% and 72.5%, respectively. Further analysis included area under the curve from receiver operating characteristic curve which was found to be 0.80. CONCLUSION: The presence of PVOs on optical coherence tomography is suggestive of a retinal tear in patients with acute, symptomatic PVD.

Basic emergency care course and longitudinal mentorship completed in a rural Neno District, Malawi: A feasibility, acceptability, and impact study.

BACKGROUND: Frontline providers mostly outside specific emergency areas deliver emergency care around the world, yet often they do not receive dedicated training in managing emergency conditions. When designed for low-resource settings, emergency care training has been shown to improve provider skills, facilitate efficient use of available resources, and reduce death and disability by ensuring timely access to life-saving care. METHODS: The WHO/ICRC Basic Emergency Care (BEC) Course with follow up longitudinal mentorship for 6 months was implemented in rural Neno District Malawi from September 2019-April 2020. We completed a mixed-methods analysis of the course and mentorship included mentor and participant surveys and feedback, mentorship quantification, and participant examination results. Simple descriptive statistics and boxplot visuals were used to describe participant demographics and mentorship quantification with a Wilcoxon signed-rank test to evaluate pre- and post-test scores. Qualitative feedback from participants and mentors were inductively analyzed using Dedoose. RESULTS: The median difference of BEC course examination percentage score between participants before the BEC course and immediately following the course was 18.0 (95% CI 14.0-22.0; p<0.001). Examination scores from the one-year post-test was lower but sustained above the pre-course test score with a median difference of 11.9 (95% CI 4.0-16.0; p<0.009). There were 174 mentorship activities with results suggesting that a higher number of mentorship touches and hours of mentor-mentee interactions may assist in sustained knowledge test scores. Reported strengths included course delivery approach leading to improved knowledge with mentorship enhancing skills, learning and improved confidence. Suggestions for improvement included more contextualized training and increased mentorship. CONCLUSION: The BEC course and subsequent longitudinal mentorship were feasible and acceptable to participants and mentors in the Malawian low resource context. Follow-up longitudinal mentorship was feasible and acceptable and is likely important to cementing the course concepts for long-term retention of knowledge and skills.

Entrustable professional activities as a training and assessment framework in undergraduate medical education: A case study of a multi-institutional pilot.

In 2014, the Association of American Medical Colleges (AAMC) published 13 Core Entrustable Professional Activities (EPAs) that graduating students should be able to perform with indirect supervision when entering residency. A ten-school multi-year pilot was commissioned to test feasibility of implementing training and assessment of the AAMC's 13 Core EPAs. In 2020-21, a case study was employed to describe pilot schools' implementation experiences. Teams from nine of ten schools were interviewed to identify means and contexts of implementing EPAs and lessons learned. Audiotapes were transcribed then coded by investigators using conventional content analysis and a constant comparative method. Coded passages were organized in a database and analyzed for themes. Consensus among school teams regarding facilitators of EPA implementation included team commitment to piloting EPAs; agreement that: proximal EPA adoption with curriculum reform facilitates EPA implementation; EPAs 'naturally fit' in clerkships and provided opportunity for schools to reflect on and adjust curricula and assessments; and inter-school collaboration bolstered individual school progress. Schools did not make high-stakes decisions about student progress (e.g., promotion, graduation), yet EPA assessment results complemented other forms of assessment in providing students with robust formative feedback about their progress. Teams had varied perceptions of school capability to implement an EPA framework, influenced by various levels of dean involvement, willingness, and capability of schools to invest in data systems and provide other resources, strategic deployment of EPAs and assessments, and faculty buy-in. These factors affected varied pace of implementation. Teams agreed on the worthiness of piloting the Core EPAs, but substantial work is still needed to fully employ an EPA framework at the scale of entire classes of students with enough assessments per EPA and with required data validity/reliability. Recommendations stemming from findings may help inform further implementation efforts across other schools adopting or considering an EPA framework.

Measurable residual disease in adult acute myeloid leukaemia: evaluation of a multidimensional 'radar' flow cytometric plot analysis method.

Measurable residual disease (MRD) monitoring in acute myeloid leukaemia (AML) is becoming increasingly important and is predominantly performed by multiparameter flow cytometry (MFC) or quantitative polymerase chain reactions (RT-qPCR). We investigated the use of multidimensional plots (MD-MFC) for AML MRD monitoring in an adult cohort. AML MRD was determined using a novel MD-MFC method for 115 MRD samples. Results were correlated with traditional two-dimensional MFC (2D-MFC) and molecular methods. Using the standard cut-off of 0.1% CD45+ cells, concordance was 99/115 (p=0.332). Eighty-four of 115 were concordant using a very low reporting limit of 0.01% (p=0.216). MRD <0.1% by either method was present in 40 of 115 samples. Fifteen of 40 were MD-MFC positive and 2D-MFC negative. Of these two of 15 had a molecular MRD marker and both were positive. Molecular MRD markers were available in 36 of 115 cases. Twenty-one of 36 (58%) were concordant with MD-MFC. Eight of 36 had detectable molecular MRD only and eight of 36 had positive MD-MFC only. There was no correlation between either the MFC method and the molecular results. In summary, there is good correlation between MD- and 2D-MFC-MRD and no correlation between the MFC and molecular methods.