Program Signaling in Emergency Medicine: The 2022–2023 Program Director Experience

Introduction: Program signaling (PS), which enables residency applicants to signal their preference for a specific program, was introduced in emergency medicine (EM) in the 2022–2023 residency application cycle. In this study we evaluated EM program directors’ (PD) utilization of PS in application review and ranking. This study also explores the relationship between program characteristics and number of signals received as well as the relative importance and utilization of signals related to the number of signals received. Methods: This is an institutional review board-approved, cross-sectional study of PDs at Accreditation Council for Graduate Medical Education-accredited EM residency programs. We used descriptive statistics to describe the characteristics of residency programs and practices around PS. Measures of central tendency and dispersion summarized continuous variables. We used chi-square analysis or the Fisher exact test for comparisons between groups for categorical variables. Comparisons for continuous variables were made using the t-test for independent samples or analysis of variance. Results: The response rate was 41% (n = 113/277 EM programs). Most programs participated in PS(n = 261/277 EM programs, 94.2%). Mean number of signals received was 60 (range 2–203). Signals received varied based on program characteristics including geographic location and program type, duration, environment, and longevity. Most used PS in holistic review (52.2%), but other uses varied by proportion of applications that were signaled. The importance of PS in application review (mean 2.9; 1–5scale,1= not important, 5 = extremely important) and rank list preparation (2.1) was relatively low compared to other application elements such as standardized letters of evaluation (4.97 for review, 4.90 for ranking). Conclusion: The study provides insights into PS utilization in EM’s inaugural year. We have identified patterns of signal use based on program characteristics and number of signals received that can inform signal allocation and utilization on an individual applicant and program level. A more nuanced understanding of signal use can provide valuable insight as the specialty of EM grapples with fluctuations in its applicant numbers and shifting demographics of its applicant pool

Characterization of a Human Antibody Fragment Fab and Its Calcium Phosphate Nanoparticles that Inhibit Rabies Virus Infection with Vaccine

Recombinant antibody phage display technology has been used to mimic many aspects of the processes that govern the generation and selection of high-affinity natural human antibodies in the human immune system, especially for infectious disease prophylaxis. An anti-rabies virus immunized phage-display Fab library was constructed from peripheral blood lymphocytes from vaccinated volunteers. The immunized antibody library, with a diversity of 6.7×108, was used to select and produce antibodies that bound to rabies virus glycoprotein. After five rounds of immobilized fixed rabies virion panning, four unique DNA sequences were found in the higher binding clones, and only one, Fab094, showed neutralization activity. Fab094 components were analyzed by ELISA, immunoprecipitation and immunofluorescent staining. ELISA and immunofluorescence showed that Fab094 bound specifically to rabies virions. Immunoprecipitation and mass spectrometry showed that Fab094 reacted with rabies virus glycoprotein. To improve the penetration power of Fab094 antibodies, we developed Fab094 calcium phosphate nanoparticles (Fab094-CPNPs) and tested their efficacy. The rapid fluorescent focus inhibition test indicated that the neutralizing antibody titers of Fab094 and Fab094-CPNPs were reached at 200.17 IU/Kg and 246.12 IU/Kg, respectively. These findings were confirmed in vivo in a Kunming mouse challenge model. Our results demonstrate that human Fab094 and Fab094-CPNPs are efficacious candidate drugs to replace rabies immunoglobulin in post-exposure prophylaxis (PEP)

Surgical Resection of Native Viscera to Manage Persistent Ascites after Multivisceral Transplant

Multivisceral transplantation is the therapy of choice in patients with diffuse portomesenteric thrombosis. In the present case, we describe a patient who had persistent ascites after multivisceral transplant. The patient was initially diagnosed with a chyle leak which was cured via embolization. When this did not cure her ascites, reexploration proved the etiology to be at least partially attributable to persistent hypertension in the retained viscera. This was cured with the resection of her native viscera. This case highlights the importance of resection of all congested viscera at the time of transplantation in patients with diffuse portomesenteric thrombosis, the utility of preoperative embolization techniques in assisting this, and also the ability to perform delayed resection if necessary

Feedback in Medical Education: An Evidence-based Guide to Best Practices from the Council of Residency Directors in Emergency Medicine

Within medical education, feedback is an invaluable tool to facilitate learning and growth throughout a physician’s training and beyond. Despite the importance of feedback, variations in practice indicate the need for evidence-based guidelines to inform best practices. Additionally, time constraints, variable acuity, and workflow in the emergency department (ED) pose unique challenges to providing effective feedback. This paper outlines expert guidelines for feedback in the ED setting from members of the Council of Residency Directors in Emergency Medicine Best Practices Subcommittee, based on the best evidence available through a critical review of the literature. We provide guidance on the use of feedback in medical education, with a focus on instructor strategies for giving feedback and learner strategies for receiving feedback, and we offer suggestions for fostering a culture of feedback

Center variations in patient selection for simultaneous heart-kidney transplantation

There are no established regulations governing patient selection for simultaneous heart-kidney (SHK) transplantation, creating the potential for significant center-level variations in clinical practice.MethodsUsing the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) file, we examined practice trends and variations in patient selection for SHK at the center level between January 1, 2004 and March 31, 2019.ResultsOverall, SHK is becoming more common with most centers performing heart transplants also performing SHK. Among patients who underwent heart transplant who were receiving dialysis, the rate of SHK varied from 22% to 86% at the center level. Among patients not on dialysis, the median estimated glomerular filtration rate (eGFR) of patients receiving SHK varied between 19 and 59 mL/min/1.73 m2. When adjusting for other factors, the odds of SHK varied 57-fold between the highest and lowest SHK performing centers.ConclusionVariation in SHK at the center level suggests the need for national guidelines around the selection of patients for SHK.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172855/1/ctr14619.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172855/2/ctr14619_am.pd

Regulation of Endogenous Human Gene Expression by Ligand-Inducible TALE Transcription Factors

The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks

Kidney Donor Profile Index Is a Reliable Alternative to Liver Donor Risk Index in Quantifying Graft Quality in Liver Transplantation.

Background:The most established metric for estimating graft survival from donor characteristics in liver transplantation is the liver donor risk index (LDRI). The LDRI is calculated from donor and transplant-related variables, including cold ischemic time. Because cold ischemic time is unknown at the time of organ offer, LDRI is not available for organ acceptance decisions. In contrast, the kidney donor profile index (KDPI) is derived purely from donor variables known at the time of offer and thus calculated for every deceased donor in the United States. The similarity in donor factors included in LDRI and KDPI led us to hypothesize that KDPI would reliably approximate LDRI in estimating graft survival in liver transplantation. Methods:The United Network of Organ Sharing registry was queried for adults who underwent deceased donor liver transplantation from 2002 to 2016. The cohort was divided into quintiles of KDPI and LDRI, and graft survival was calculated according to Kaplan Meier. Hazard ratios for LDRI and KDPI were estimated from Cox proportional hazards models, and Uno's concordance statistic was compared. Results:In our analysis of 63 906 cases, KDPI closely approximated LDRI in estimating liver graft survival, with an equivalent concordance statistic of 0.56. Conclusions:We conclude that KDPI can serve as a reasonable alternative to LDRI in liver acceptance decisions