Faculty Bibliography

Mismatch repair-deficient (dMMR) endometrial cancer is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase 3 ENGOT-en11/GOG-3053/KEYNOTE-B21 study (NCT04634877) in newly-diagnosed, high-risk endometrial cancer after surgery with curative intent. Patients were randomized to pembrolizumab 200mg or placebo (6 cycles) plus carboplatin-paclitaxel (4-6 cycles) Q3W, then pembrolizumab 400mg or placebo Q6W (6 cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary endpoint. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31; 95%CI, 0.14-0.69); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95%CI, 84.4%-96.4%) and 80.2% (95%CI, 70.8%-86.9%), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis based on the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

Due to femoral head-neck deformities and hip joint incongruence, patients with Legg-Calvé-Perthes Disease (LCPD) commonly require total hip arthroplasty (THA) in the fifth and sixth decades of life. These patients present additional challenges to arthroplasty surgeons not only because of their complicated hip anatomy but also because patients may have undergone prior operative procedures in childhood and thus present with pre-existing proximal femoral deformities. THA in LCPD patients can be associated with peri-operative complications such as fracture or nerve injury, and the rate of reoperation has been reported to be higher in the LCPD population as compared to the general population undergoing THA. Despite this, multiple case reports and studies have shown the relative long-term success of THA in patients with history of LCPD. In particular, uncemented modular stems are a commonly used implant choice in such cases. This article reviews and discusses the technical considerations for THA in patients with LCPD and highlights three such cases.

RATIONALE & OBJECTIVE/UNASSIGNED:Understanding national attitudes about living kidney donation will enable us to identify and address existing disincentives to living kidney donation. We performed a national survey to describe living kidney donation perceptions, perceived factors that affect the willingness to donate, and analyzed differences by demographic subgroups. STUDY DESIGN/UNASSIGNED:The survey items captured living kidney donation awareness, living kidney donation knowledge, willingness to donate, and barriers and facilitators to living kidney donation. SETTING & POPULATION/UNASSIGNED:We surveyed 802 US adults (aged 25-65 years) in June 2021, randomly selected from an online platform with diverse representation. ANALYTICAL APPROACH/UNASSIGNED:and Fisher exact tests. We inductively evaluated free-text responses to identify additional barriers and facilitators to living kidney donation. RESULTS/UNASSIGNED:Most (86.6%) of the respondents reported that they might or would definitely consider donating a kidney while they were still living. Barriers to living kidney donation included concerns about the risk of the surgery, paying for medical expenses, and potential health effects. Facilitators to living kidney donation included having information on the donation surgery's safety, knowing that the donor would not have to pay for medical expenses related to the donation, and hearing living kidney donation success stories. Awareness of the ability to participate in kidney-paired donation was associated with a higher willingness to donate. LIMITATIONS/UNASSIGNED:Potential for selection bias resulting from the use of survey panels and varied incentive amounts, and measurement error related to respondents' attention level. CONCLUSIONS/UNASSIGNED:Most people would consider becoming a living kidney donor. Increased rates of living kidney donation may be possible with investment in culturally competent educational interventions that address risks associated with donating, policies that reduce financial disincentives, and communication campaigns that raise awareness of kidney-paired donation and living kidney donation.

We present a variant of the immersed boundary (IB) method that implements acoustic perturbation theory to model acoustically levitated fluid droplets. Instead of resolving sound waves numerically, our hybrid method solves acoustic scattering semi-analytically to obtain the corresponding time-averaged acoustic forces on the droplet. This framework allows the droplet to be simulated on inertial timescales of interest, and therefore works with much larger time steps than traditional compressible flow solvers. To benchmark this technique and demonstrate its utility, we implement the hybrid IB method for a single droplet in a standing wave. Simulated droplet shape deformations and streaming profiles agree with available theoretical predictions. Our simulations also yield insights into the streaming profiles for elliptical droplets, for which a comprehensive analytic solution does not yet exist.

BACKGROUND:This review outlines clinical data and characteristics of current Food and Drug Administration (FDA)-approved implants in cervical disc replacement/cervical disc arthroplasty (CDR/CDA) to provide a centralized resource for spine surgeons. METHODS:Randomized controlled trials (RCTs) on CDR/CDA were identified using a search of the PubMed, Web of Science, and Google Scholar databases. The initial search identified 69 studies. Duplicates were removed, and the following inclusion criteria were applied when determining eligibility of RCTs for the current review: (1) discussing CDR/CDA prosthesis and (2) published within between 2010 and 2020. Studies without clinical data or that were not RCTs were excluded. All articles were reviewed independently by 2 authors, with the involvement of an arbitrator to facilitate consensus on any discrepancies. RESULTS:A total of 34 studies were included in the final review. Findings were synthesized into a comprehensive table describing key features and clinical results for each FDA-approved CDR/CDA implant and are overall suggestive of expanding indications and increasing utilization. CONCLUSIONS:RCTs have provided substantial evidence to support CDR/CDA for treating single- and 2-level cervical degenerative disc disease in place of conventional anterior cervical discectomy and fusion. CLINICAL RELEVANCE/CONCLUSIONS:This review provides a resource that consolidates relevant clinical data for current FDA-approved implants to help spine surgeons make an informed decision during preoperative planning.

BACKGROUND/UNASSIGNED:Anterior retroperitoneal lumbar spinal exposure has traditionally been performed in the supine position (SUP) to access the L4-L5 and L5-S1 disc spaces where lateral approaches may be unsafe. However, advancements in lateral single position surgery have resulted in advocacy for anterior L4-5 disc access in the lateral decubitus position (LAT). While L5-S1 access in the lateral position is well-described, no series of L4-5 anterior access in the lateral position has been published. The study aims to evaluate the safety of anterior lumbar exposure at the L4-5 disc level in the LAT compared to the SUP. METHODS/UNASSIGNED:A multi-center retrospective study of patients who underwent anterior retroperitoneal lumbar exposure involving the L4-5 disc level were classified according to patient positioning: (I) LAT or (II) SUP. RESULTS/UNASSIGNED:10.70%, P=0.09) were similar between groups. CONCLUSIONS/UNASSIGNED:Anterior lumbar spinal exposure of the L4-5 disc in the LAT is safe compared to supine exposure, despite higher case complexity in the lateral position.

OBJECTIVE/UNASSIGNED:Young Latinas and Black women drink less than women of other racial/ethnic groups but experience more alcohol-related problems in midlife. This study aims to identify modifiable factors to prevent adult onset of alcohol use disorder (AUD) in this population. METHODS/UNASSIGNED:Data were collected at six time points as part of the Harlem Longitudinal Development Study from 365 Latinas (47%) and Black (53%) women (mean age at time 1 = 14, standard deviation 1.3). Structural equation modeling was used to test hypothesized pathways from childhood physical and sexual abuse to AUD via depressive mood, anxiety disorders, and somatic complaints in the 20s. We also tested the moderation effect of the high school academic environment by including in the structural equation model two latent variable interaction terms between the school environment and each of the abuse variables. RESULTS/UNASSIGNED: = -9.56, 95% CI [-13.95, -5.17]) in the early 20s. CONCLUSIONS/UNASSIGNED:Our findings underscore the need to invest in early violence prevention interventions and in education to ensure equitable access to quality, academically oriented, and safe schools.

BACKGROUND/UNASSIGNED:The burden of Alzheimer's disease and related dementias (AD/ADRD) in Costa Rica is expected to become one of the highest in the region. Early detection will help optimize resources and improve primary care interventions. The Montreal Cognitive Assessment (MoCA) has shown good sensitivity for detecting mild cognitive impairment (MCI), but specificity varies depending on the population. This motivated the analysis of different cutoffs to minimize false-positive classifications in a Costa Rican sample for its use in clinical settings. METHODS/UNASSIGNED:Data was analyzed from 516 memory clinic outpatients (148 cognitively normal, 260 MCI, 108 mild AD/ADRD; mean age 66.3 ± 10.8 years) who underwent complete neurological and neuropsychological assessment and were diagnosed by consensus. Optimal MoCA cutoff scores were identified using a multiple cutoff approach. RESULTS/UNASSIGNED:Overall, a cutoff score of ≥ 23 showed better accuracy to distinguish between normal cognition (NC) and MCI (sensitivity 73%, specificity 83%). When analyzed by educational levels, a cutoff score of ≥ 21 showed better accuracy for ≤ 6 years (sensitivity 80%, specificity 76%), ≥23 for 7-12 years (sensitivity 86%, specificity 76%) and ≥ 24 for > 12 years (sensitivity 70%, specificity 85%). For distinguishing MCI from mild AD/ADRD, the optimal overall cutoff score was ≥ 15 (sensitivity 66%, specificity 85%). When stratified by years of education, cutoff scores of ≥ 14 showed better accuracy for ≤ 6 years (sensitivity 70%, specificity 88%), ≥15 for 7-12 years (sensitivity 46%, specificity 95%) and ≥ 17 for > 12 years (sensitivity 67%, specificity 93%). CONCLUSIONS/UNASSIGNED:A MoCA cutoff score of ≥ 23 in the Costa Rican population showed better diagnostic accuracy for detecting MCI and may reduce the false positive rate. Our findings may be helpful for primary care clinical settings and further referral criteria.