Faculty Bibliography

BACKGROUND/UNASSIGNED:In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting. OBJECTIVES/UNASSIGNED:The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial. DESIGN/UNASSIGNED:RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC. METHODS/UNASSIGNED:Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03. RESULTS/UNASSIGNED:The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm. CONCLUSION/UNASSIGNED:The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC. TRIAL REGISTRATION/UNASSIGNED:NCT03981796.

BACKGROUND/UNASSIGNED:A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. METHODS/UNASSIGNED:Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. RESULTS/UNASSIGNED:significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. CONCLUSIONS/UNASSIGNED:The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.

The 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) updated the indications for Metabolic and Bariatric Surgery (MBS), replacing the previous guidelines established by the NIH over 30 years ago. The evidence supporting these updated guidelines has been strengthened to assist metabolic and bariatric surgeons, nutritionists, and other members of multidisciplinary teams, as well as patients. This study aims to assess the level of evidence and the strength of recommendations compared to the previously published criteria.

BACKGROUND/UNASSIGNED:Continuous glucose monitoring (CGM) systems allow detailed assessment of postprandial glucose responses (PPGR), offering new insights into food choices' impact on dysglycemia. However, current approaches to analyze PPGR using a CGM require manual meal logging, limiting the scalability of CGM-driven applications like personalized nutrition and at-home diabetes risk assessment. OBJECTIVE/UNASSIGNED:We propose a machine learning (ML) framework to automatically identify and characterize breakfast-related PPGRs from CGM profiles in adults at risk of or living with noninsulin-treated type 2 diabetes (T2D). METHODS/UNASSIGNED:Our PPGR estimation framework uses a random forest ML algorithm trained on 15 adults without diabetes who wore a CGM for up to four weeks. The algorithm performance was evaluated on a held-out subset of the participants' CGM data as well as on an external validation data set of 36 individuals at risk for or with noninsulin-treated T2D. RESULTS/UNASSIGNED:= .18). CONCLUSIONS/UNASSIGNED:We designed an ML framework to automatically estimate the timing of meal events from CGM data in individuals without diabetes and in individuals at risk or with T2D. This could provide a more scalable approach for analyzing postprandial glycemia, increasing the feasibility of CGM-based precision nutrition and diabetes risk assessment applications.

Carcinoid heart disease (CHD) is a rare cardiac complication that occurs most commonly in patients with advanced neuroendocrine tumors and is a known sequela of carcinoid syndrome. Neuroendocrine tumors most widely associated with CHD include tumors in the small bowel, followed by lung, large bowel, pancreatic, appendiceal, and ovarian neoplasms. Carcinoid syndrome is a paraneoplastic syndrome caused by the release of serotonin and other substances from neuroendocrine tumors. It results in a spectrum of symptoms, including diarrhea, flushing, bronchospasm, and symptoms of congestive heart failure. Without treatment and for patients with advanced heart failure, the prognosis of CHD can be less than a year. Management of CHD is often challenging as patients typically present late, and the disease can progress rapidly. Therefore, optimal management of these patients requires close collaboration among various specialties to quantify disease burden, delay the progression of valvular disease, and determine the most effective surgical and medical management strategies depending on the cardiac manifestations to improve quality of life and reduce mortality. This involves a collaborative team, including cardiology and oncology, and often involves many other disciplines, including hepatobiliary and cardiovascular surgeons, endocrinologists, anesthesiologists, and gastroenterologists.

BACKGROUND:Biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) is a minimally invasive surgical technique for treating degenerative lumbar spine conditions. It offers advantages such as reduced soft tissue trauma and lower infection rates, but certain technical aspects may be challenging. The current study aims to identify strategies to enhance the fusion rate in BE-TLIF by addressing these specific challenges. METHODS:A literature review was conducted on techniques to improve fusion rates in BE-TLIF. RESULTS:The review suggests that lateral-based portals supplemented with medial portals allowed for safe insertion of interbody cages with large footprint. Direct visualization of the disc space with a 30° endoscope assisted with better disc space preparation. Facetectomies performed with osteotomes, rather than burrs, ensured maximum retrieval of autologous bone graft. Utilizing bone morphogenetic proteins with sustained release carriers such as hydroxyapatite can be useful to increase fusion rates of BE-TLIF. CONCLUSIONS:To our knowledge, the current literature is the first comprehensive review of strategies to enhance fusion rates in BE-TLIF. The proposed techniques and biological adjuncts are effective means to address key challenges associated with the procedure, and such strategies would potentially shorten the learning curve and improve clinical outcomes. Further clinical studies are required to validate these findings and establish standardized protocols. CLINICAL RELEVANCE/CONCLUSIONS:These findings provide practical solutions to overcome common challenges in BE-TLIF. The suggested techniques would reduce the incidence of pseudarthrosis, improve patient outcomes, and ultimately offer a safer and more reliable option for lumbar interbody fusion patients.

OBJECTIVE/UNASSIGNED:To better characterize the cochlear apex in relation to surgically relevant landmarks to guide surgeons and improve procedural success of apical electrode placement. STUDY DESIGN/UNASSIGNED:Retrospective image analysis. SETTING/UNASSIGNED:Tertiary referral center. PATIENTS/UNASSIGNED:Cochlear implant recipients with available preoperative computed tomography (CT) imaging. INTERVENTION/UNASSIGNED:None. MAIN OUTCOME MEASURE/UNASSIGNED:Cochlear dimensions and cochlear apex distance measures to surgically relevant middle ear landmarks and critical structures. RESULTS/UNASSIGNED:Eighty-two temporal bone CT scans were analyzed utilizing multiplanar reformats. The average lateral width of promontory bone over the cochlear apex was 1.2 mm (standard deviation [SD], 0.3). The anteroposterior distance from the round window (avg, 4.2 mm; SD, 0.5), oval window (avg, 3.3 mm; SD, 0.3), cochleariform process (avg, 2.3; SD, 0.5), and superior-inferior distance from the cochleariform process (avg, -0.9; SD, 0.8) to the cochlear apex were measured. The relationship of the cochlear apex to critical structures was highly variable.A newly developed stapes vector was created and found to mark the posterior/superior boundary of the apex in 94% of patients. When a vector parallel to the stapes vector was drawn through the round window, it marked the anterior/inferior boundary of the cochlear apex in 89% of patients. CONCLUSIONS/UNASSIGNED:This study assists in characterizing cochlear apex anatomy and its relation to surrounding structures as a means of improving procedural accuracy and reducing trauma during apical cochleostomy. Understanding both distance relationships and expected boundaries of the apex could help to inform future surgical approaches.

OBJECTIVE/UNASSIGNED:To evaluate for equivalence in postoperative changes of speech recognition scores in a veteran patient population undergoing cochlear implantation (CI) compared to matched nonveteran patients. STUDY DESIGN/UNASSIGNED:Retrospective chart review. SETTING/UNASSIGNED:Tertiary referral center. PATIENTS/UNASSIGNED:A total of 83 veteran patients who underwent CI at a single Veterans Affairs Medical Center (VA cohort) were matched to 83 nonveteran patients from the Health Insurance Portability and Accountability Act-secure, Encrypted, Research, Management and Evaluation Solution database (HERMES cohort) based on age, sex, and baseline Consonant-Nucleus-Consonant (CNC) scores. INTERVENTION/UNASSIGNED:Patients underwent CI. MAIN OUTCOME MEASURES/UNASSIGNED:Comparison of postoperative CNC and Arizona Biomedical Institute recognition scores. RESULTS/UNASSIGNED:The mean difference and lower confidence interval of CNC scores between matched Veterans Affairs and HERMES cohorts were within a -ΔNI boundary of -15% at the 3-month (mean = 6.15, lower confidence interval = -2.38), 6-month (mean = 7.36, lower confidence interval = -2.21), and 12-month (mean = 4.03, lower confidence interval = -4.88) postoperative time points. The mean difference and lower confidence interval of Arizona Biomedical Institute scores between cohorts were within the -ΔNI boundary of -30% at 3 months (mean = 1, lower confidence interval = -8.71), 6 months (mean = 0.31, lower confidence interval = -12.30), and 12 months (mean = 0.72, lower confidence interval = -10.48). CONCLUSION/UNASSIGNED:Our veteran population demonstrated improvements in speech recognition scores after CI comparable to a matched nonveteran population. Although veterans face unique factors that affect their hearing, access to medical care, and baseline general health, these findings affirm appropriate veteran candidates should be offered CI.

RATIONALE & OBJECTIVE/UNASSIGNED:In 2021, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) updated the creatinine-based estimated glomerular filtration rate (eGFR) equation and removed the coefficient for race. The development and validation of this equation involved binarizing race into African American and non-African American, involving few Asian participants. This study aimed to examine the difference between the 2021 equation and the previous 2009 equation on CKD prevalence estimates in 2 Asian populations. STUDY DESIGN/UNASSIGNED:Observational study using 2 national surveys. SETTING & PARTICIPANTS/UNASSIGNED:Participants from the 2019 Korea National Health and Nutrition Survey and participants self-reported as Asian from the 2011-2020 US National Health and Nutrition Survey. EXPOSURE/UNASSIGNED:eGFR using 2009 and 2021 CKD-EPI creatinine equation. OUTCOMES/UNASSIGNED:or urine albumin-creatinine ratio ≥30 mg/g). ANALYTICAL APPROACH/UNASSIGNED:Sampling-weighted prevalence estimated using the 2009 and 2021 equations as well as the percentage of individuals with CKD G3+ using the 2009 equation being reclassified as not having CKD G3+ using the 2021 equation. RESULTS/UNASSIGNED:The prevalence of CKD estimated using the 2021 equation was 9.75% (95% confidence intervals [CI], 8.80-10.80%) in Koreans and 11.60% (95% CI, 10.23-13.13%) in US Asians. The prevalence of CKD estimated using the 2021 equation was slightly lower than that using the 2009 equation in both Korean and US Asian populations by 0.63% (95% CI, 0.44-0.90%) and 0.84% (95% CI, 0.52-1.34%), respectively. Furthermore, 32.8% and 30.2% of Koreans and US Asians with CKD G3-5, respectively, estimated using the 2009 equation were reclassified as not having CKD G3-5 when the eGFR was calculated using the 2021 equation. LIMITATIONS/UNASSIGNED:Measured GFR was not available. CONCLUSIONS/UNASSIGNED:Use of the 2021 CKD-EPI creatinine equation leads to a small decrease in CKD prevalence in both Korean and US Asian populations, and of similar magnitude, resulting in significant reclassification among those originally classified as having CKD G3+.

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.