Faculty Bibliography

OBJECTIVES/OBJECTIVE:To provide a level-adjusted correction to the current standard relating anatomical cochlear place to characteristic frequency (CF) in humans, and to re-evaluate anatomical frequency mismatch in cochlear implant (CI recipients considering this correction. It is proposed that a level-adjusted place-frequency function may represent a more relevant tonotopic benchmark for CIs in comparison to the current standard. DESIGN/METHODS:The present analytical study compiled data from 15 previous animal studies that reported isointensity responses from cochlear structures at different stimulation levels. Extracted outcome measures were CFs and centroid-based best frequencies at 70 dB SPL input from 47 specimens spanning a broad range of cochlear locations. A simple relationship was used to transform these measures to human estimates of characteristic and best frequencies, and nonlinear regression was applied to these estimates to determine how the standard human place-frequency function should be adjusted to reflect best frequency rather than CF. The proposed level-adjusted correction was then compared with average place-frequency positions of commonly used CI devices when programmed with clinical settings. RESULTS:The present study showed that the best frequency at 70 dB SPL (BF70) tends to shift away from CF. The amount of shift was statistically significant (signed-rank test z = 5.143, p < 0.001), but the amount and direction of shift depended on cochlear location. At cochlear locations up to 600° from the base, BF70 shifted downward in frequency relative to CF by about 4 semitones on average. Beyond 600° from the base, BF70 shifted upward in frequency relative to CF by about 6 semitones on average. In terms of spread (90% prediction interval), the amount of shift between CF and BF70 varied from relatively no shift to nearly an octave of shift. With the new level-adjusted place-frequency function, the amount of anatomical frequency mismatch for devices programmed with standard-of-care settings is less extreme than originally thought and may be nonexistent for all but the most apical electrodes. CONCLUSIONS:The present study validates the current standard for relating cochlear place to CF, and introduces a level-adjusted correction for how best frequency shifts away from CF at moderately loud stimulation levels. This correction may represent a more relevant tonotopic reference for CIs. To the extent that it does, its implementation may potentially enhance perceptual accommodation and speech understanding in CI users, thereby improving CI outcomes and contributing to advancements in the programming and clinical management of CIs.

This study aimed to develop and evaluate a novel magnetization-prepared, ultra-short echo time (UTE)-capable, stack-of-spirals sequence (STFL) to quantify monoexponential and biexponential T_1ρ maps of the whole knee joint, addressing limitations of existing MRI techniques in assessing bone-patellar tendon-bone (BPTB) donor site healing and graft remodeling after anterior cruciate ligament (ACL) reconstruction (ACLR). Experiments were performed with agar-gel model phantoms, seven healthy volunteers (four males, average age 31.4 years old), and five ACLR patients (three males, average age 28.2 years old). Compared with a conventional Cartesian turbo fast low angle shot (CTFL) sequence, the STFL sequence demonstrated an improved signal-to-noise ratio (SNR), increasing from 16.5 for CTFL to 21.7 for STFL. In ACLR patients, the STFL sequence accurately detected increased fractions of short T_1ρ components within the ACL graft, rising from 0.15 to 0.38, compared with 0.11 to 0.18 with CTFL. Furthermore, the STFL sequence revealed significant decreases in the fraction of short T_1ρ components in the patellar tendon of ACLR patients (from 0.6 to 0.47) compared with healthy controls, whereas no significant changes were observed with the CTFL sequence. These findings suggest that the STFL sequence holds promise for noninvasive assessment of BPTB donor site healing and graft maturation following ACLR.

BACKGROUND:Recreational cannabis use is increasing in Mexico, where legalization is a possibility. The current area-level socioeconomic context of cannabis use has not been studied in the country, limiting our understanding and public health response. We aimed to analyze the association between the municipal socioeconomic environment and recreational cannabis use in Mexico. METHODS:We used data from the National Survey of Drug, Alcohol and Tobacco Consumption 2016-17, the National Health and Nutrition Survey 2023, the 2015 intercensal survey and the 2020 census to study the association of municipal income and municipal education with past-year recreational cannabis use. We fitted Poisson models with robust variance to obtain prevalence ratios and assessed for effect modification by individual-level sex and age, and household-level education. RESULTS:For every unit increase in municipal education, we observed a 1.5 % increase in the prevalence of recreational cannabis use in 2016-17, and a 2.9 % increase in 2023. For each unit increase in municipal income, we observed a 1.5 % increase in the prevalence of recreational cannabis use in 2016-17, and a 1.8 % increase in 2023. We found no effect modification except for a single age group (20- to 29-year-olds vs to 12- to 19-year-olds). CONCLUSION/CONCLUSIONS:Recreational cannabis use in Mexico is currently higher in more socioeconomically advantaged municipalities. Recreational cannabis use through socioeconomic areas should be monitored closely. Further research of the modifiable causes of this association could help inform current and future public health policies.

Lipid processing in the retinal pigment epithelium (RPE) is important for maintaining the health and function of the neural retina and the RPE itself. One mode of en mass lipid transport from the RPE is apolipoprotein B-containing lipoproteins (Blps), the assembly of which is regulated by microsomal triglyceride transfer protein (MTP). To gain an initial understanding of how the loss of MTP and, thereby, Blp secretion alters other lipid processing pathways in the RPE, we measured the expression of proteins associated with β-oxidation and lipid droplets in mice lacking MTP expression in the RPE (RPEΔMttp) and age-matched controls. Expression of perilipin 2, a lipid droplet-associated protein, nearly doubled in the RPE of RPEΔMttp, and its localization with neutral lipids also increased. Meanwhile, expression of CPT1A, which mediates the transport of fatty acids into the mitochondria for β-oxidation, was unaffected. These results suggest that the loss of Blp assembly alters intracellular lipid storage patterns. Future studies will examine the effects of the loss of RPE-specific MTP expression and Blp secretion on additional lipid processing pathways.

OBJECTIVE:The aim of the study was to investigate prognostic factors in context of neoadjuvant therapy (NAT) and develop tools that can allow for accurate and personalized patient prognostication. SUMMARY OF BACKGROUND DATA/BACKGROUND:NAT might impact the prognostic ability of well-established clinicopathological factors in resected pancreatic ductal adenocarcinoma (PDAC). METHODS:Patients after resection for PDAC were identified from the Dutch Pancreatic Cancer Group Recurrence Database and institutional databases at NYU Langone Health and the Johns Hopkins Hospital (2014-2019). Patients were stratified into NAT and chemo-naïve groups. Overall survival (OS), calculated from the time of resection, was estimated using Kaplan-Meier and compared using log-rank tests. Prognostic factors associated with OS were assessed in both groups using univariable and multivariable Cox-regression analyses and presented using hazard ratios (HR) with corresponding 95% confidence intervals (95%CI). Predictive models were developed and an interactive tool was created to predict survival independently in both groups. RESULTS:Of 2,760 patients with resected PDAC, 778 patients (28%) received NAT. Independent predictors for worse OS in chemo-naïve patients included age ≥65 years, markedly elevated CA19-9 (≥500 U/mL) at diagnosis, higher AJCC-T stage (T3/4 vs T1/2), worsening AJCC N-stage (N2 vs. N1 vs. N0), poor tumor differentiation, perineural invasion, and microscopically positive resection margin (R1 vs. R0). Contrastingly, predictors for worse OS in NAT patients included non-normalization of CA19-9 after NAT (<37 U/mL), presence of nodal disease (N1/2 vs. N0 given no statistical difference between N1 and N2 disease), and grade of treatment response (moderate/poor vs. complete/near complete). CONCLUSION/CONCLUSIONS:Prognostic factors for OS in patients with resected PDAC differ between chemo-naïve and NAT patients. Personalized prediction tools for OS in resected PDAC based on these specific factors are available online (www.pancpals.com/tools).

INTRODUCTION/UNASSIGNED:In response to accreditation bodies requiring health disparities curricula, medical educators are tasked with incorporating structural competency, the understanding of how social and structural barriers like structural racism impact health, into their teaching. Most have not received training in this area, yet there remains a scarcity of faculty development curricula to address this gap. We describe the creation, implementation, and evaluation of a faculty development workshop series rooted in the framework of structural competency. METHODS/UNASSIGNED:test. RESULTS/UNASSIGNED:< .001) incorporating structural competency. DISCUSSION/UNASSIGNED:Our application of structural competency to faculty workshops and teaching tools feasibly engages faculty in instruction to incorporate concepts of structural racism and the downstream effects of social determinants of health into clinical teaching. It represents an innovative tool as we seek to enhance clinical teaching to improve care for racially and ethnically minoritized communities.

PURPOSE/OBJECTIVE:To determine the robustness of randomized controlled trials (RCTs) supporting the current rhinosinusitis guideline; International Consensus Statement on Allergy and Rhinology: rhinosinusitis (ICAR-RS). MATERIALS & METHODS/METHODS:RCTs referenced by ICAR-RS with primary dichotomous outcomes were analyzed. The Fragility Index (FI) was calculated for trials with statistically significant findings. Trial characteristics, the FI, and FI minus number lost to follow-up (LTF) were assessed for associations. RESULTS:A total of 317 RCTs were identified, with 38 trials possessing a primary dichotomous outcome. Thirty-one percent evaluated surgical interventions and 24 % were industry-sponsored. The mean sample size was 116 with 9 patients, on average, LTF. Sixty-three percent were eligible for FI calculation and had a median FI of 2.5 (IQR 1, 4.25). Sixty-seven percent of trials had an FI ≤ 3, indicating low robustness. No difference in FI was observed between trials with and without industry support (p = 0.577). The FI was less than or equal to the number of patients LTF in 33 % of trials (n = 8). Higher FI was strongly correlated with higher sample size, total number of events, p-value, and grade of recommendation (p < 0.001). After adjusting for covariates, higher sample size and total number of events were associated with higher FI. CONCLUSION/CONCLUSIONS:The RCTs used to support the ICAR-RS have an overall low robustness and future rhinosinusitis trials should report FI measures to provide improved context of their results.

Hypertrophic cardiomyopathy is a common but underrecognized cardiac disorder characterized by a heterogenous phenotype that includes increased left ventricular thickness, outflow obstruction, diastolic dysfunction, and arrhythmia. Hypertrophic cardiomyopathy is often heritable and associated with pathogenic variants in sarcomeric genes. While not curable, an integrated approach involving medical, interventional, and surgical care can have a considerable impact on disease burden, quality of life, and mortality. This review provides a practical overview of important topics in hypertrophic cardiomyopathy, including evaluation of differential diagnosis, imaging, provocation of left ventricular outflow obstruction, treatment of obstructive and nonobstructive hypertrophic cardiomyopathy with negative inotropic therapy and myosin inhibition, as well as surgical and interventional approaches to septal reduction and mitral valve intervention.