Faculty Bibliography

BACKGROUND:The purpose of this systematic review was to evaluate the clinical and radiological outcomes at short-term follow-up following suture button fixation for the management of ligamentous Lisfranc injuries. AIM/OBJECTIVE:To assess the effectiveness of suture button fixation in managing ligamentous Lisfranc injuries through a systematic evaluation of short-term clinical and radiological outcomes. METHODS:During March 2024, the PubMed, EMBASE, and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following suture button fixation for the management of ligamentous Lisfranc injuries. Data regarding patient demographics, pathological characteristics, subjective clinical outcomes, radiological outcomes, complications, and failure rates were extracted and analyzed. RESULTS:Eight studies were included. In total, 94 patients (94 feet) underwent suture button fixation for the management of ligamentous Lisfranc injuries at a weighted mean follow-up of 27.2 ± 10.2 months. The American Orthopaedic Foot and Ankle Society score improved from a weighted mean pre-operative score of 39.2 ± 11.8 preoperatively to a post-operative score of 82.8 ± 5.4. The weighted mean visual analogue scale score improved from a weighted mean pre-operative score of 7.7 ± 0.6 preoperatively to a post-operative score of 2.0 ± 0.4. In total, 100% of patients returned to sport at a mean time of 16.8 weeks. The complication rate was 5%, the most common complication of which was residual midfoot stiffness (3.0%). No failures nor secondary surgical procedures were recorded. CONCLUSION/CONCLUSIONS:This systematic review demonstrated that suture button fixation for ligamentous Lisfranc injuries produced improved clinical outcomes at short-term follow-up. In addition, there was an excellent return-to-sport rate (100%) at a weighted mean time of 16.8 weeks. This review highlights that suture button fixation is a potent surgical treatment strategy for ligamentous Lisfranc injuries; however, caution should be taken when evaluating this data in light of the lack of high quality, comparative studies, and short-term follow-up.

The goal of the MRI4ALL hackathon, which took place in October 2023, was to develop a functional low-field MRI scanner in just one week and to release all created source code and resources as open-source packages. The event was attended by 52 participants from 16 institutions who assembled the scanner on the last day of the hackathon. The scanner's magnetic B₀ field with a strength of 43 mT and a target field-of-view size of 11 cm³ was created with a Halbach array made from 990 N40UH permanent magnets, held in place using 3D printed ring formers. Gradient coils were fabricated by gluing enameled copper wire onto 3D printed holders with imprinted wire patterns. A solenoid coil for RF transmission and reception was built by winding 20 turns of Litz wire around a 3D printed cylinder. A Red Pitaya FPGA prototyping board running the MaRCoS framework was used to control the scanner components, and a GPA-FHDO amplifier board was used to drive the gradients. To simplify the scanner's operation, console software with an intuitive graphical user interface was developed in Python using the PyPulseq package for sequence calculations. Furthermore, the scanner was equipped with a cooling system, as well as options for passive and active shimming. After resolving several technical issues that arose during the assembly, the scanner is now able to acquire MR images with different sequences. While not suitable for real-world clinical applications, it can be utilized for educational purposes or as a low-cost prototyping platform. Moreover, it may serve as a reference design for future MRI development projects. All source code and resources are available on the project website mri4all.org, allowing other groups to replicate the scanner. EVIDENCE LEVEL: n/a TECHNICAL EFFICACY: Stage 1.

Oropharyngeal dysphagia is an independent predictor of poor outcomes in many health conditions and can be targeted directly through swallowing therapy. This study aims to explore the outcomes of outpatient swallowing therapy in clinical practice across a diverse cohort of patients. This was a retrospective, single-site longitudinal cohort study. Patients 18 years or older with dysphagia who completed 7-8 weeks of outpatient swallowing therapy with a pre- and post-treatment videofluoroscopy were included. Therapy employed a progressive swallowing exercise regimen based on the Systematic Exercise for Treatment of Swallowing (SETS) protocol. Outcome measures included the pharyngeal components of the Modified Barium Swallow Impairment Profile, penetration-aspiration scale scores, and diet recommendations using the International Dysphagia Diet Standardization Initiative. 152 patients were included. Swallowing therapy improved all MBSImP component scores except 1, 7, and 13. Therapy improved total pharyngeal impairment scores by 2.66 points (p < .001) and total oral impairment score by 1.41 points (p < .001). Odds of elevated aspiration risk were reduced by 49% (p < .001). Patients were more likely to be on an unmodified food consistency after completion of therapy (OR 26, p = .004), but liquid consistency was not altered (OR 2.0, p = .57). Overall, 44% of patients in the cohort with an efficiency issue improved, and 50% of patients at risk for aspiration pre-therapy improved. Completing a 7-8 week course of exercise-based outpatient swallowing therapy is effective at improving multiple measures of swallowing physiology, safety and efficiency. It can also enable relaxation of diet consistency restrictions based on the IDDSI framework.

BACKGROUND/UNASSIGNED:For patients with alpha-1 antitrypsin (AAT) deficiency, AAT augmentation therapy can be an important part of care. However, for those who require a lung transplant (LT), there is currently only limited information to guide the use of AAT augmentation therapy post-LT. METHODS/UNASSIGNED:We identified all LT recipients from 2011-2021 in the Scientific Registry of Transplant Recipients with an AAT deficiency diagnosis. We categorized recipients by use of AAT augmentation therapy post-LT and compared their baseline characteristics using Fisher's exact test and Wilcoxon rank-sum tests. We used Kaplan-Meier analyses and estimated the average treatment effect (ATE) of post-LT AAT augmentation therapy on mortality and all-cause graft failure (ACGF). The ATE measures the observed effect we would see if everyone in the population received the intervention as opposed to just a subset. RESULTS/UNASSIGNED: = 0.02, log-rank test). CONCLUSIONS/UNASSIGNED:In our study, the use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.

INTRODUCTION/UNASSIGNED:Patients with oral cancer often experience intense functional pain due to mechanical stimulation at the cancer site. The role of mechanosensitive ion channels in oral cancer pain, such as TRPV4, is not fully understood. OBJECTIVES/UNASSIGNED:Our objective was to investigate the role of Schwann cell TRPV4 in oral cancer pain. METHODS/UNASSIGNED:imaging, and patch-clamp electrophysiology. The effect of TRPV4 activation on Schwann cell responses to mechanical stimulation was evaluated using a piezo stimulator. Conditioned media (CM) from TRPV4-activated Schwann cells were injected into the mouse paw to evaluate the contribution of TRPV4 in Schwann cells to mechanical hypersensitivity. RESULTS/UNASSIGNED:responses and whole-cell membrane currents in human Schwann cells. Mechanoactivated currents in human Schwann cells were inhibited by the TRPV4 antagonist HC-067047. Schwann cell CM induced mechanical hypersensitivity in mice, which was blocked by pre-treatment with HC-067047. CONCLUSION/UNASSIGNED:TRPV4 activation plays a role in mediating mechanically induced pain of oral cancer.

Understanding the "fit" of models designed to predict binary outcomes has been a long-standing problem across the social sciences. We propose a flexible, portable, and intuitive metric for quantifying the change in accuracy between two predictive systems in the case of a binary outcome: the InterModel Vigorish (IMV). The IMV is based on an analogy to weighted coins, well-characterized physical systems with tractable probabilities. The IMV is always a statement about the change in fit relative to some baseline model-which can be as simple as the prevalence-whereas other metrics are stand-alone measures that need to be further manipulated to yield indices related to differences in fit across models. Moreover, the IMV is consistently interpretable independent of baseline prevalence. We contrast this metric with alternatives in numerous simulations. The IMV is more sensitive to estimation error than many alternatives and also shows distinctive sensitivity to prevalence. We consider its performance using examples spanning the social and natural sciences. The IMV allows for precise answers to questions about changes in model fit in a variety of settings in a manner that will be useful for furthering research and the understanding of social outcomes.

OBJECTIVE/UNASSIGNED:To investigate potential disparities in hearing aid use among urban and rural populations with hearing loss. STUDY DESIGN/UNASSIGNED:Cross-sectional analysis. METHODS/UNASSIGNED:We used pooled data from the 2017 and 2018 rounds of the Medicare Current Beneficiary Survey (MCBS). Our analytic sample was restricted to 8107 participants with hearing loss (those who reported little to a lot of trouble hearing) and with a full set of covariates. Multivariate logistic regression models for the probability of hearing aid use were estimated using a participant's place of residence (rural/urban) and household income relative to the Federal Poverty Level (low and middle income ≤ 200% of Federal Poverty Level (FPL); high income > 200% FPL) as main exposures. RESULTS/UNASSIGNED:In models using place of residence as the main exposure, we found no statistically significant difference in hearing aid use between rural and urban populations. In models combining place of residence with income, we found that respondents in the rural high-income group were at the highest odds for hearing aid use (odds ratio (OR): 1.99, 95% confidence interval (CI): 1.52-2.59) when compared to the rural low and middle-income group and, similarly, for the urban high-income (OR: 1.57, 95% CI: 1.26-1.96) and urban low and middle-income groups (OR: 1.31, 95% CI: 1.02-1.69). CONCLUSIONS/UNASSIGNED:There are potential interactions of metro status and income regarding hearing aid use that are more pronounced in rural populations. This might allow policymakers to target interventions for hearing loss to rural and low-income populations. LEVEL OF EVIDENCE/UNASSIGNED:3.

BACKGROUND:The US Food and Drug Administration approved satralizumab for use in adult patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) in 2020, but real-world data are limited. The objective of this case series is to describe the experience with satralizumab in adult patients with AQP4-IgG+ NMOSD who previously received rituximab. METHODS:Case information for patients with AQP4-IgG+ NMOSD who had received satralizumab for ≥6 months was obtained from US healthcare providers from April 1, 2022, to September 30, 2023. Patient characteristics, examination findings, diagnostic tests, treatment response and adverse events were recorded. Patients who received satralizumab after discontinuing treatment with rituximab were included in this case series. RESULTS:Twenty patients were included, and their ages ranged from 19 to 70 years. Overall, 45 % of patients self-identified as Black/African American, 40 % as White, 10 % as Asian and 5 % as multiracial. Time since confirmed NMOSD diagnosis ranged from 4 to 17 years. Median (range) duration of rituximab treatment was 50 (12-162) months. The main reasons for switching to satralizumab were intolerance (60 %) to and inadequate disease control (25 %) with rituximab. The majority of patients (70 %) received satralizumab for ≥24 months and as monotherapy (90 %). All 20 patients were free from radiographically confirmed relapses with satralizumab. Overall, patients maintained disease control with satralizumab, and adverse events primarily included asymptomatic laboratory abnormalities. Two patients permanently discontinued satralizumab due to adverse events. CONCLUSIONS:In this retrospective case series, satralizumab was effective and well tolerated in patients with NMOSD who switched due to ineffectiveness and/or poor tolerability of rituximab. These outcomes align with the long-term efficacy and safety outcomes with satralizumab in the Phase III SAkura clinical trials.

PURPOSE OF REVIEW/OBJECTIVE:Chylomicron biosynthesis plays a vital role in supplying essential lipids and lipid soluble vitamins to peripheral tissues for various functions. Despite this, the intracellular synthesis, trafficking, and secretion of chylomicrons remains only partly understood. The purpose of this review is to summarize the role of established proteins in this process and bring attention to recently identified proteins to provide an up-to-date model of chylomicron biosynthesis. RECENT FINDINGS/RESULTS:Recently, several proteins have been shown to play a role in the initial formation and lipidation of chylomicrons at the endoplasmic reticulum (ER), which include: TM6SF2, PLA2G12B, PRAP1, and SURF4. In addition, mitochondria have been implicated in chylomicron metabolism, but mechanistic insight is missing. The trafficking of chylomicrons from the ER to the Golgi, and the subsequent trafficking from the Golgi to the basolateral side of enterocytes, however, remains a mystery. SUMMARY/CONCLUSIONS:Progress in the chylomicron biosynthesis field is largely associated with findings in VLDL biosynthesis. In addition, increased insight in events after prechylomicrons leave the ER is needed. Given the important role of chylomicron biosynthesis in whole-body lipid metabolism, further research into the molecular mechanisms is warranted.

OBJECTIVE:The videofluoroscopic swallow study (VFSS) is an evaluation of the anatomy and physiology of swallowing, and often includes a screening evaluation of the esophagus. How the esophageal screen translates to esophageal pathology remains unknown. The purpose of this study was to determine if abnormal esophageal clearance (EC) on VFSS correlates with esophageal function on high-resolution esophageal manometry (HREM). MATERIALS AND METHODS/METHODS:This is a retrospective review of 115 adult patients who underwent both VFSS with esophageal screen and HRM. EC on VFSS was scored with the modified barium swallow impairment profile (MBSImP) component 17. Motility was characterized using HRM metrics according to the Chicago Classification Version 4.0 (CCv4.0). Predictive metrics were calculated for the esophageal screen. RESULTS:An EC score o greater than or equal to 1 had a sensitivity of 66%, specificity of 57%, PPV of 52%, NPV of 70%, and OR of 2.55 (p = 0.027). EC weakly correlated with incomplete bolus clearance (rho = 0.331, p = 0.0004) and did not correlate with bolus transit time (rho = 0.17, p = 0.105). CONCLUSIONS:The esophageal screen as characterized by the MBSImP is not an effective predictor of esophageal function on HREM as defined by the CCv4.0. Future work may focus on a defining a standardized VFSS protocol for the esophageal screen and potentially a more nuanced assessment of esophageal findings on VFSS that may enhance the sensitivity of the modality to motility disorders.