Faculty Bibliography

INTRODUCTION:As the utility of genomic sequencing increases, its use in healthcare will continue to expand beyond expert clinics toward nonspecialist practices such as primary care. At the same time, discordance in genetic variant identification and classification between laboratories remains a concern for the field. This research assesses how clinicians with and without genetics expertise understand and trust genetic test results, underscoring how variation in the handling of genetic test results can have real impact on patient care. METHODS:We conducted 40 interviews with genetics experts, including clinical geneticists and genetic counselors, and nonexpert clinicians including primary care providers and cardiologists. RESULTS:Clinical geneticists and genetic counselors reported spending significant time assessing the validity of results from genetic testing laboratories, conversing with laboratories about those results, and potentially reinterpreting results. Conversely, primary care providers and cardiologists without specific genetics expertise reported high levels of trust in laboratory accuracy and variant interpretation, and did not reassess results. CONCLUSION:We find significant variation in how genetics experts and nonexperts understand the trustworthiness of genetic laboratory reports. This variation could lead to differences in patient care between clinical settings and requires additional guidance for clinicians regarding the handling of genetic test results.

State and local health departments were responsible for ensuring equitable distribution of the COVID-19 vaccine. This qualitative study aimed to identify the challenges, strategies, disappointments, and successes in achieving equity for hard-to-reach and at-risk populations. Using a purposive sampling strategy, 16 individuals affiliated with health departments across nine states, each holding leadership roles in vaccine distribution, were interviewed between late 2021 and mid-2022. The key factors promoting vaccine equity included (1) inviting community members to serve on vaccine advisory groups to participate in decision-making; (2) utilizing pre-existing community relationships and spaces to facilitate the planning and distribution of the vaccine; and (3) establishing and building upon community outreach to support accessibility and uptake of the vaccine. The barriers included (1) a lack of clarity on vaccine prioritization criteria; (2) language/communication access; and (3) the initial focus on mass vaccination sites for vaccine delivery. The stakeholders also highlighted potential facilitators for increasing equity in future vaccine rollouts. Overall, community engagement emerged as a critical factor in ensuring equity during disaster response efforts.

Central body fat distribution affects kidney function. Abdominal fat measurements using computed tomography (CT) may prove superior in assessing body composition-related kidney risk in living kidney donors. This retrospective cohort study including 550 kidney donors aimed to determine the association between CT-measured abdominal fat areas and kidney function before and after donor nephrectomy. Donors underwent glomerular filtration rate measurements (¹²⁵I-Iothalamate, mGFR) before and 3 months after donation. Linear regression analyses with body surface area (BSA)-standardized and crude mGFR were performed to assess the association of height-indexed tomographic fat measurements with kidney function. In age-, and sex-adjusted analyses higher levels of total abdominal, visceral, subcutaneous, and intramuscular adipose tissue index were significantly associated with lower mGFR levels before donation (BSA-standardized mGFR: visceral adipose tissue index: Βeta=-0.11, p < 0.001, subcutaneous: Βeta=-0.10, p < 0.001, intramuscular: Βeta=-1.18, p < 0.001, total abdominal: Βeta=-0.07, p < 0.001). Higher tomographic abdominal fat is associated with lower BSA-standardized mGFR after donation and a greater decrease in mGFR between screening and 3 months post-donation. This study shows that CT-measured abdominal fat area is associated with kidney function before and after living kidney donation.

INTRODUCTION/UNASSIGNED:In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine. METHODS/UNASSIGNED:We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises. We assessed learner self-perceived confidence via workshop surveys. The target audience of this module was medical trainees, including medical students, residents, and fellows. RESULTS/UNASSIGNED:Forty-three workshop attendees across three sites submitted partial or complete survey evaluations. Respondents included medical students (77%), with the remainder self-identified as either postbaccalaureate students, residents/fellows, academic faculty, or physicians. A comparison of pre- and postresponses showed a statistically significant increase in confidence in addressing each of the four educational objectives. Participants felt the case presentations offered relevant applicable examples. DISCUSSION/UNASSIGNED:For many trainees, the role that diversity-related NMOs play in developing leadership competencies may be unclear and not articulated in traditional medical curricula. In this module, we provide examples of how NMOs facilitate leadership development and may encourage our diverse trainees to eventually become academic faculty.

BACKGROUND:Pretransplant functional, motor, cognitive, and academic deficits are common in pediatric patients requiring heart transplantation (HT); some persist post-HT. We assessed the association between these quality of life (QoL) deficits and post-HT outcomes. METHODS:Using SRTR data 2008-2023, we evaluated the functional, motor, cognitive, and academic status of pediatric HT recipients from listing to 15 years post-HT. We compared all-cause graft survival among patients with vs. without pre-HT deficits using Cox regressions. Among patients with a functioning graft at 1 year, we assessed the association between deficits at that time and subsequent graft failure. RESULTS:, p < 0.001). CONCLUSION/CONCLUSIONS:Pediatric HT recipients with decreased functional status are at higher risk for graft failure and mortality. These patients may benefit from early intervention aimed at improving functional status.

BACKGROUND:T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors. METHODS:This was a three-part, open-label, phase 1/2 study: part A, dose-escalation monotherapy, part B, dose-expansion monotherapy, and part C, combination therapy with pembrolizumab. The study was conducted at 32 sites in 7 countries. Adult patients with advanced solid tumors were enrolled and received intravenous nemvaleukin once daily on days 1-5 (21-day cycle) at 0.1-10 µg/kg/day (part A), or at the RP2D (part B), or with pembrolizumab (part C). Primary endpoints were RP2D selection and dose-limiting toxicities (part A), and overall response rate (ORR) and safety (parts B and C). RESULTS:T and natural killer cell expansion, and minimal regulatory T cell expansion were observed following nemvaleukin treatment. ORR with nemvaleukin plus pembrolizumab was 13% (19/144; 95% CI 8 to 20), with 5 complete and 14 partial responses; 6 responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types. Three responses were in patients with platinum-resistant ovarian cancer. The most common grade 3-4 treatment-related adverse events (TRAEs) in parts B and C, respectively, were neutropenia (49%, 21%) and anemia (10%, 11%); 4% of patients in each part discontinued due to TRAEs. CONCLUSIONS:Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT02799095.

PURPOSE/OBJECTIVE:Studies demonstrate similar long-term Total Knee Arthroplasty (TKA) outcomes in patients with significant versus minimal preoperative coronal plane deformity. Limited short-term outcomes data, which determine costs of care, exist. METHODS:We retrospectively explored the impact of preoperative coronal plane deformity on operative time, length of stay (LOS), and discharge to skilled nursing facility (SNF) in TKA. A total of 3,964 patients undergoing unilateral primary TKA at our institution from 2014 to 2019 were included (1,158 > 10˚ deformity: mean age 67.2 years, 47% male; 2,806 < 10˚ deformity: mean age 67 years, 37.4% male). The degree of coronal plane deformity (mechanical axis deviation on preoperative radiographs) was recorded. Patients with no knee radiographs ≤ 3 years preoperatively were excluded. Statistical analysis included Chi-Square tests, Student's t-tests, Mann-Whitney U tests, and uni- and multivariable linear and logistic regression analyses. RESULTS:The > 10˚ deformity cohort had a longer time from procedure start to finish (113.56 vs. 110.68 min; p = 0.020), greater deviation from surgeon mean operative time (+ 6.19 vs. + 0.69 min; p < 0.001), and higher proportion of cases requiring > 15 (26.8% vs. 22%;p = 0.001) and > 30 (12.3% vs. 7.8%;p < 0.001) additional minutes over their scheduled times. LOS was similar between cohorts (median 2 days, IQR 1-3). The deformity cohort more likely discharged to SNF (19.9% vs. 15.8%;p = 0.002). For every 1˚ increase in coronal plane deformity, operative time increased by 0.566 min (p = 0.000). The odds of SNF discharge increased with increasing coronal plane deformity (OR 1.029 [1.009,1.050]; p = 0.004). CONCLUSION/CONCLUSIONS:Greater preoperative coronal deformity is associated with increased operative time and odds of discharge to SNF in TKA.

We examined the impact of auditory stimuli and their methods on a dynamic balance task performance. Twenty-four young adults wore an HTC Vive headset and dodged a virtual ball to the right or left based on its color (blue to the left, red to the right, and vice versa). We manipulated the environment by introducing congruent (auditory stimuli from the correct direction) or incongruent (auditory stimuli played randomly from either side) and comparing a multimodal (visual and congruent auditory stimuli) to unimodal (visual or auditory stimuli) presentation. We tested four apparatuses: loudspeakers, headphones, passthrough, (wearing headphones while auditory stimuli come from loudspeakers) and room simulation (externalization via headphones). We quantified reaction time (RT) and accuracy (choosing the correct direction to dodge) from the head movement. We hypothesized that the weight of the headset will slow RT, and that externalization of the auditory stimuli will make it more usable when no visual cues are provided. Interestingly, both hypotheses were refuted. In silent conditions, RT was faster with headphones compared to loudspeakers, but this difference disappeared when auditory stimuli were introduced. Participants used congruent auditory stimuli to improve accuracy but disregarded incongruent auditory stimuli across all apparatuses except for room simulation. In conclusion, this study confirmed that healthy young adults can use congruent auditory stimuli to enhance accuracy and disregard incongruent auditory stimuli such that accuracy is not harmed. RT was either faster or the same with headphones compared to loudspeakers. Notably, this specific room simulation did not enhance performance.

BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a major driver of cirrhosis and liver-related mortality. However, therapeutic options for MASLD, including prevention of liver steatosis, are limited. We previously described that vasoactive intestinal peptide-producing neurons (VIP-neurons) regulate the efficiency of intestinal dietary fat absorption and IL-22 production by type 3 innate lymphoid cells (ILC3) in the intestine. Given the described hepatoprotective role of IL-22, we hypothesize that modulation of this neuroimmune circuit could potentially be an innovative approach for the control of liver steatosis. METHODS:We used a model of diet-induced MASLD by exposing mice to a high-fat diet (HFD) for 16 weeks, when the development of liver steatosis was first observed in our animals. We characterized IL-22 production by intestinal ILC3 at this dietary endpoint. We then evaluated whether communication between VIP-neurons and ILC3 affected IL-22 production and MASLD development by exposing mice with a conditional genetic deletion of Vipr2 in ILC3 (Rorc(t)CreVipr2fl/fl) to the HFD. We also performed intermittent global inhibition of VIP-neurons using a chemogenetic inhibitory approach (VipIres-CrehM4DiLSL) in HFD-fed mice. RESULTS:Production of IL-22 by intestinal ILC3 is reduced in steatotic mice that were exposed to an HFD for 16 weeks. Targeted deletion of VIP receptor 2 in ILC3 resulted in higher production of IL-22 in ILC3 and was associated with a significant reduction in liver steatosis in mice under HFD. Global inhibition of VIP-producing neurons also resulted in a significant reduction in liver steatosis. CONCLUSIONS:Modulating VIPergic neuroimmune signaling can ameliorate the development of hepatic steatosis induced by a surplus of fat ingestion in the diet. This neuroimmune pathway should be further investigated as a potential therapeutic avenue in MASLD.

BACKGROUND:Quitline counseling is an effective method for supporting smoking cessation, offering personalized and accessible assistance. Tobacco use is a significant public health issue among people living with HIV. In Vietnam, over 50% of men living with HIV use tobacco. However, there is limited research on Quitline use and retention rates in this population and a lack of research on factors associated with retention in Quitline counseling. The study aims to evaluate the factors associated with retention in Quitline counseling for smoking cessation among HIV-positive smokers receiving care at HIV outpatient clinics in Vietnam. METHOD/METHODS:The study analyzed data from a randomized controlled trial (RCT) that compared the effectiveness of three smoking cessation interventions for smokers living with HIV at 13 Outpatient Clinics in Ha Noi. A total of 221 smokers aged 18 and above living with HIV participated in Arm 1 of the RCT, which included screening for tobacco use (Ask), health worker-delivered brief counseling (Assist), and proactive referral to Vietnam's national Quitline (AAR), in which the Quitline reached out to the patient to engage them in up to 10 sessions of smoking cessation counseling. Retention in Quitline counseling was defined as participating in more than five counseling calls. The study used bivariate and logistic regression analyses to explore the associations between retention and other factors. RESULTS:Fifty-one percent of HIV-positive smokers completed more than five counseling sessions. Smokers living with HIV aged 35 or older (OR = 5.53, 95% CI 1.42-21.52), who had a very low/low tobacco dependence level (OR = 2.26, 95% CI 1.14-4.51), had a lower score of perceived importance of quitting cigarettes (OR = 0.87, 95% CI 0.76-0.99), had a household ban or partial ban on cigarettes smoking (OR = 2.58, 95% CI 1.39-4.80), and had chosen a quit date during the Quitline counseling (OR = 3.0, 95% CI 1.63-5.53) were more likely to retain in the Quitline counseling than those smokers living with HIV whose ages were less than 35, who had a high/very high tobacco dependence level, had a higher score of perception of the importance of quitting cigarettes, did not have a household ban on cigarettes smoking, and did not choose a quit date during counseling. CONCLUSION/CONCLUSIONS:There is a high retention rate in Quitline counseling services among PLWHs receiving care at HIV outpatient clinics. Tailoring interventions to the associated factors such as age, tobacco dependence, perceived importance of quitting, household smoking bans, and setting a quit date during counseling may improve engagement and outcomes, aiding in the reduction of smoking prevalence among HIV-positive individuals.