Faculty Bibliography

BACKGROUND:Osteoporosis is a significant cause of morbidity and mortality in the aging population. Individuals with type 2 diabetes mellitus (T2D) typically have higher bone density yet also a higher rate of fractures. Blacks, meanwhile, have a lower incidence of osteoporosis compared to European Americans. Serum bicarbonate may be a risk factor for bone loss, but studies are conflicting, and little is known about this relationship in T2D or Blacks. METHODS:We examined the longitudinal relationship between serum bicarbonate and change in bone density in 300 participants with T2D in the African American-Diabetes Heart Study (AA-DHS). Serum bicarbonate was measured at baseline, and bone density was assessed using CT volumetric bone mineral density (vBMD) scans of the thoracic and lumbar vertebrae at baseline and after five years of follow-up. Multivariate linear regression models assessed associations between baseline serum bicarbonate and longitudinal change in vBMD, adjusted for multiple confounders. RESULTS:, p < 0.001), without a clear threshold effect or differences by sex. CONCLUSIONS:In this cohort of Blacks with T2D, higher baseline serum bicarbonate levels were associated with improved changes in bone density over time. Further studies are needed to determine if alkali supplementation would ameliorate loss of bone density in this population.

PURPOSE OF REVIEW/OBJECTIVE:Fiber restriction has been a long-standing strategy for patients with inflammatory bowel disease (IBD), ostensibly to improve symptoms and reduce complications. Fiber though has a well-documented trophic effect on gut barrier defenses and the intestinal microbiome. This report discusses how texture modification may allow the safe and effective provision of much needed fiber to this patient population. RECENT FINDINGS/RESULTS:The effect of dietary fiber is characterized by maintenance of gut integrity, support of the microbiome, and immune modulation. Low-fiber diets in patients with IBD result in greater dysbiosis, intestinal permeability, and mucosal inflammation. New recommendations from international IBD guidelines now promote texture modification to allow for inclusion of fiber in certain conditions of IBD. For patients flaring with acute inflammation, or those with ileostomy, intestinal stricture, or ileal pouch anastomosis, continued fiber intake with softer textures and mechanical modification should be prioritized when feasible. For patients recovering from surgery, diet advancement should include reintroduction of soluble and insoluble fibers, while those in remission should have little or no dietary restrictions. Texture modification of high fiber foods may be accomplished by a variety of strategies involved in the selection, preparation, and cooking of fruits and vegetables. Greater effort to include dietary soluble and insoluble fiber should result in clinical benefit to the IBD patient, avoiding the adverse consequences of a low-fiber diet.

INTRODUCTION/BACKGROUND:Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes. METHODS:We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax (Tg-SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances. RESULTS:Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (Aβ) load in 9- to 10-month-old Tg-SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced Aβ load. DISCUSSION/CONCLUSIONS:These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD. HIGHLIGHTS/CONCLUSIONS:Uncovered early capillary dysfunction in a presymptomatic Alzheimer's disease (AD) mouse model. Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD. Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.

PURPOSE/UNASSIGNED:This study examined the impact of socioeconomic status (SES) on medical education in the context of person-environment fit (PE fit) theory, and specifically focused on the medical school experiences of students from lower-SES backgrounds. METHOD/UNASSIGNED:A constructivist approach was used in this qualitative study of 48 medical students from 27 US medical schools, all of whom self-identified as first-generation college graduates and/or being from a lower-income background (30 were both). Semi-structured audio-only interviews were conducted with these demographically and geographically diverse students from November 2021 through April 2022. Themes were identified using open coding and content analysis software. RESULTS/UNASSIGNED:Almost all, 44 of 48, interviews included themes related to PE fit. Medical students indicated three interacting domains in which PE fit is relevant for them: (1) school, (2) clinical, and (3) professional environments. Learners from lower-SES backgrounds describe struggling to navigate multiple environments that are unfamiliar, culturally complex, and both personally and financially costly. They also describe ways they are addressing gaps, generating positive changes, supporting underserved patients, and broadening the perspectives of peers and educators. CONCLUSIONS/UNASSIGNED:PE fit theory provides a lens to understand unique aspects of lower-SES medical student experiences, including navigation of professional identity formation. It is critical for medical schools, funders, peers, and professional communities to sustain learning environments that support the flourishing of medical students from lower-SES backgrounds. This support includes transferring the burden of addressing fit from individual learners and marginalized classes of learners to educational, clinical, and professional organizations. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s40670-024-02174-x.

OBJECTIVES/OBJECTIVE:We aimed to assess inter-radiologist agreement when interpreting pelvic MRI in children with newly diagnosed perianal Crohn's disease (CD). MATERIALS AND METHODS/METHODS:In this retrospective multi-reader study, we identified pediatric patients (< 18 years of age) who underwent a pelvic MRI examination for newly diagnosed perianal CD. Images were de-identified and uploaded to a cloud-based image platform for review by 13 fellowship-trained pediatric radiologists The reviewers assessed for the presence of a fistula and abscess, categorization of different imaging findings, and classification using the Parks and St James' University Hospital systems. Fleiss' kappa (κ) statistics and intra-class correlation coefficients (ICC) were used to measure inter-reader agreement, along with 95% confidence intervals (CI). RESULTS:Forty-six patients were included in our study (median age = 13.0 years [IQR: 10.5 to 16.0 years]); thirty-five (76.1%) were boys. Most imaging features showed fair agreement (κ = 0.21 to 0.35). There was moderate agreement for categorical fistula length (κ = 0.42 [95% CI: 0.32 to 0.53]), involvement of the genitalia (κ = 0.45 [95% CI: 0.26 to 0.63]), and presence of an abscess/collection (κ = 0.52 [95% CI: 0.31 to 0.73]). Maximum abscess/collection length had good agreement (ICC = 0.81 [95% CI: 0.41, 1.00]). There was an almost equal split (yes vs. no: 50.7% vs. 49.3%) regarding whether postcontrast T1-weighted images added value compared to T2-weighted images alone across all radiologists and examinations. CONCLUSION/CONCLUSIONS:Inter-radiologist agreement when interpreting pelvic MRI for perianal CD in children is fair for most imaging features, with fewer features demonstrating moderate or good agreement. KEY POINTS/CONCLUSIONS:Question Pelvic magnetic resonance imaging (MRI) is used for diagnosing and monitoring children with perianal Crohn's disease (CD). Limited information is known about inter-radiologist agreement. Findings Agreement between pediatric radiologists when interpreting MRI for perianal CD in children is only fair for most imaging features (κ = 0.21 to 0.35). Clinical relevance Understanding MRI inter-radiologist agreement is crucial to improve the reliability of pelvic MRI in children with perianal Crohn's disease since it may affect patient management (e.g., surgery); further radiologist education and improved imaging feature definitions may help improve inter-radiologist agreement.

Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are at increased risk of atherosclerosis, including peripheral arterial disease (PAD). Critical limb ischemia (CLI) may complicate PAD and is associated with significant mortality and morbidity. Despite the increased risk of thrombosis with MPN, outcomes of CLI in MPN patients are unclear. We conducted an analysis utilizing the 2017-2020 National Readmission Database (NRD) of patients hospitalized for CLI with and without MPN. Patients with MPN were propensity score matched (PSM) with patients without MPN. Primary outcome was composite outcome of major adverse cardiovascular and limb events (MACLE). Logistic regression was utilized to estimate risk of MACLE in patients with MPN vs. without MPN. Inverse-probability treatment weighted (IPTW) analysis was performed to evaluate the effect of revascularization on MACLE in patients with MPN. A total of 102,598 patients were included, 931 (0.9%) had MPN. After PSM, MPN was associated with increased risk of MACLE (47.3% vs. 39.1%; OR 1.40, 95% CI 1.21-1.62). After IPTW, revascularization was associated with decreased risk of MACLE among patients with MPN (45.0% vs. 50.7%; OR 0.80, 95% CI 0.66-0.96). Among patients admitted with CLI, MPN was associated with increased risk of MACLE especially ET and MF phenotypes. Revascularization was associated with decreased risk of MACLE among patients with MPN. Further investigation is needed in order to improve outcomes in patients with MPN and CLI.

BACKGROUND:Ultrasound-based devices have been developed to improve various cosmetic indications, including fines lines, wrinkles, eyebrow laxity, and submental laxity. Ultrasound waves of high intensity targeting the dermis can induce neocollagenesis, neoelastogenesis, and subsequent remodeling to improve the clinical appearance of these indications. OBJECTIVE:To examine the utility of a novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams to improve the clinical appearance of skin laxity on the upper arms. MATERIALS AND METHODS/METHODS:A prospective, multicenter, clinical study investigated this novel ultrasound device using two treatments. RESULTS:Forty-six subjects were enrolled and underwent treatment. Mean age was 59 years, and 100% were women. Fitzpatrick skin types I-IV were represented. Assessments compared baseline to 3-month follow-up. Two out of 3 blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 88.9% of subjects (p < .0001), who were considered responders. Blinded reviewers rated significant improvements in skin crepiness and laxity scale (1.97 vs 2.95; p < .0001) and also in Global Aesthetic Improvement Scale in 93.3% of photographs. No device-related adverse events occurred. CONCLUSION/CONCLUSIONS:A novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams can safely and effectively improve skin laxity of the upper arms.

BACKGROUND/UNASSIGNED:Whether prolonged and excessive alcohol consumption contributes to dilated cardiomyopathy (DCM) remains uncertain. This study aimed to describe the prevalence of alcohol use in patients with DCM and their first-degree relatives (FDRs) and determine if cumulative alcohol exposure associates with DCM/partial DCM or modifies the association of DCM with DCM-relevant rare variants. METHODS/UNASSIGNED:All probands had DCM; FDRs were classified as with or without DCM or partial DCM. Alcohol exposure was measured with the Alcohol Use Disorder Identification Test-Consumption questionnaire and years of drinking. Rare variants in 36 DCM genes were classified as pathogenic, likely pathogenic, or variants of uncertain significance (pathogenic, likely pathogenic, variant of uncertain significance). Generalized linear mixed models were used to assess the association of DCM/partial DCM with alcohol use among FDRs. RESULTS/UNASSIGNED:=0.55). CONCLUSIONS/UNASSIGNED:Alcohol use was frequent among probands and FDRs. This study did not provide evidence supporting an association of cumulative alcohol exposure with DCM/partial DCM or a modifying effect of alcohol use on the association of DCM with DCM-relevant rare variants. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.