Faculty Bibliography

BACKGROUND:This study evaluated differences in surgical and clinical outcomes among patients who have identical versus different implant sizes in sequential total knee arthroplasty (TKA) surgeries. METHODS:We retrospectively reviewed patients who underwent primary, elective, staged, bilateral, same-surgeon, same-prosthesis TKA between 2011 and 2024 at a large academic health system. Patients were grouped by femoral and tibial implant size consistency: same femoral and tibial (SS), different femoral, same tibial, different tibial, same femoral, and different femoral and tibial (DD). RESULTS:A total of 4,536 TKAs were performed in 2,268 patients. The SS had the shortest length of stay compared to DD (51.8 versus 58.2 hours, P < 0.001). The majority had the same femoral (75.6%) and tibial (76.6%) sizes in both knees, whereas polyethylene thickness varied. Undergoing contralateral surgery within one year was associated with receiving the same implant sizes (P < 0.001). The DD were more common in manual surgery, and the SS were more common using navigation assistance (P < 0.001). Different assistance modalities between surgeries increased different femoral, same tibial and DD, whereas the same navigation assistance increased SS (P < 0.001). Complication and revision rates were not significantly different between the groups. All groups showed improvement in their Knee injury and Osteoarthritis Outcome Score for Joint Replacement and Patient-Reported Outcomes Measurement Information System Pain Intensity and Interference scores with no significant intergroup differences (P > 0.05). CONCLUSIONS:Over one-third of patients (37.3%) undergoing staged, bilateral TKA received different implant sizes for at least one component, and over half had different polyethylene thicknesses. Although implant size consistency was influenced by factors such as time between surgeries and assistance modality, these variations did not significantly affect length of stay, complications, or patient-reported outcomes. Surgeons should be aware that minor implant size differences between knees are common, even when using the same prosthesis.

PURPOSE/UNASSIGNED:Vesicourethral anastomotic stenosis (VUAS) occurs after 1 to 3% of robotic-assisted radical prostatectomies (RARPs). Pelvic fascia-sparing techniques preserve more native anatomy and may reduce stenoses, but evidence is lacking. The aim of this study was to compare stenosis incidence, management, and outcomes after standard vs pelvic fascia-sparing RARP. MATERIALS AND METHODS/UNASSIGNED:We conducted a multi-institutional retrospective study of 910 standard, 409 Retzius-sparing, and 272 hood RARP during February 2012-September 2025. Standard and hood techniques used 18Fr urethral catheters, and the Retzius-sparing technique used 18Fr suprapubic catheters. The primary end point was cystoscopically confirmed VUAS requiring intervention within 12 months. Urinary continence was assessed using the validated Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Multivariable logistic regression assessed factors associated with VUAS. RESULTS/UNASSIGNED:= .046). CONCLUSIONS/UNASSIGNED:There were no VUAS after Retzius-sparing RARP, and Retzius-sparing vs standard approach was associated with lower odds of stenosis. Endoscopic management with structured self-catheterization achieved high success without worsening incontinence. Prospective studies are needed to validate our findings.

Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.

BACKGROUND:The impact of body mass index (BMI) extremes on the outcomes after head and neck cancer (HNC) reconstruction remains uncertain. Herein, we investigate the influence of low and high BMI on the intraoperative and postoperative outcomes of oncologic head and neck microvascular reconstruction. METHODS:We analyzed a prospective institutional database (09/2019-12/2024). Patients were stratified into underweight, normal weight, overweight, and obesity I, II, and III. Flaps were categorized by donor site (thigh, back, fibula, or forearm). Demographics, intraoperative events, and donor, recipient, and systemic postoperative complications were assessed. RESULTS:BMI extremes relate to perioperative risk in HNC microvascular reconstruction. Underweight status is associated with higher perioperative complications across flaps, while obesity-related risk concentrates in class II/III patients undergoing thigh-based flaps. Findings support BMI-informed preoperative optimization and flap selection strategies.

PURPOSE/UNASSIGNED:To compare a strategy utilizing testing to guide treatment, also known as selective therapy, to a strategy of initiating interventions without testing, termed empiric therapy, on urinary supersaturation of calcium oxalate and calcium phosphate. MATERIALS AND METHODS/UNASSIGNED:In this single-center trial, adult individuals with recurrent idiopathic calcium stone disease were randomized to either an empiric or selective strategy. Participants received 24-hour urine testing at baseline, 4 weeks, and 8 weeks. Treatment in the empiric arm was comprised of dietary and fluid counseling and pharmacologic treatment with indapamide and potassium citrate irrespective of 24-hour urine results. For the selective arm, diet and pharmacologic treatments, which included indapamide, potassium citrate, and/or allopurinol, were tailored based on urine testing at baseline and 4 weeks. The primary outcome was urinary supersaturation of calcium oxalate and calcium phosphate at 8 weeks. RESULTS/UNASSIGNED:= 0.58). Similarly, there were no significant differences at 8 weeks in urine volume and pH, or in excretion of calcium, oxalate, citrate, uric acid, and sodium. CONCLUSIONS/UNASSIGNED:In this short-term trial among individuals at high-risk for stone recurrence, there was no statistically significant difference in the urinary stone risk comparing an empiric versus selective strategy for kidney stone prevention.

BACKGROUND/UNASSIGNED:Racial and ethnic disparities are a concern in lung cancer screening. OBJECTIVE/UNASSIGNED:To investigate the performance of risk prediction models to define screening eligibility across 4 U.S. racial and ethnic groups. DESIGN/UNASSIGNED:Cohort study. SETTING/UNASSIGNED:United States, Lung Cancer Cohort Consortium. PARTICIPANTS/UNASSIGNED:641 830 participants aged 50 to 80 years with a smoking history from 12 U.S. cohorts, including 6390 Asian, 9781 Hispanic, 39 872 non-Hispanic Black, and 585 787 non-Hispanic White participants. MEASUREMENTS/UNASSIGNED:Calibration and discrimination were quantified for 16 lung cancer prediction models. Then, screening-related metrics were calculated after applying model thresholds to select the same number of eligible participants as the 2021 criteria from the U.S. Preventive Services Task Force (USPSTF-2021). These included eligibility, sensitivity, and efficiency measured as estimated number needed to screen (NNS; the ratio between participants and lung cancer cases) for each strategy or prediction model in each racial and ethnic group. RESULTS/UNASSIGNED:General patterns across the 16 models included substantial underestimation of lung cancer risk in non-Hispanic Black participants (expected-observed ratio < 0.75 for 11 of 16 models), lower discrimination in Asian participants than all other groups (13 of 16 models), and lower discrimination in non-Hispanic Black than non-Hispanic White participants (15 of 16 models). When a same-sized screening-eligible population as USPSTF-2021 (38.0%) was enforced, all risk-based strategies achieved better average estimated screening efficiency and reduced racial and ethnic differences in efficiency compared with USPSTF-2021. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOm2012) and Life Years gained From Screening-Computed Tomography model (LYFS-CT) performed best (mean estimated NNS, 36.5 [SD, 8.8] and 40.1 [SD, 8.2], respectively). However, no strategy could simultaneously optimize eligibility, sensitivity, and efficiency while also reducing racial and ethnic differences. LIMITATION/UNASSIGNED:Smaller sample for Asian and Hispanic participants. CONCLUSION/UNASSIGNED:To optimize efficiency and minimize its variation across racial and ethnic groups, risk-based strategies were superior to USPSTF criteria. Further optimization of prediction models for the diverse U.S. population is needed. PRIMARY FUNDING SOURCE/UNASSIGNED:U.S. National Cancer Institute, Lung Cancer Research Foundation, and Cancer Research UK.

OBJECTIVE/UNASSIGNED:To evaluate the safety of alopecia treatments during pregnancy, in-vitro fertilization (IVF), and polycystic ovary syndrome (PCOS) workup, with a focus on potential maternal and fetal risks. DATA SOURCES/UNASSIGNED:A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus from November 2024 to December 2024. Search terms included medication names in combination with "pregnancy," "IVF," "in-vitro fertilization," and "PCOS." STUDY SELECTION/UNASSIGNED:Peer-reviewed studies addressing the use of therapies for androgenetic alopecia, alopecia areata, and scarring alopecias in the contexts of pregnancy, IVF, and PCOS were included. Articles evaluating maternal safety, fetal risks, and treatment timing were prioritized. Only English-language publications were reviewed. RESULTS/UNASSIGNED:Despite increasing therapeutic options for alopecia, significant knowledge gaps remain regarding their safety during pregnancy. Pregnant women are often excluded from clinical trials, leading to a reliance on older treatments with limited data on dosing or pharmacokinetics in the pregnant population. Unfortunately, there are few alopecia medications with robust safety data in pregnancy, and many medications are contraindicated during this period. Some medications may be used with caution, while others require additional investigation. During IVF, there are alopecia medications with potential benefit in women experiencing implantation failure or PCOS. For patients undergoing PCOS workup, some alopecia medications may impact hormonal labs or mask PCOS symptoms. CONCLUSION/UNASSIGNED:There is a critical need for more targeted research on alopecia treatments in pregnancy, IVF, and PCOS contexts. This review provides current evidence to guide clinicians and support informed, individualized treatment decisions during this vulnerable period.

INTRODUCTION/UNASSIGNED:Innovative strategies are crucial to meet the World Health Organization's 90/70/90 cervical cancer elimination targets and to prevent millions of deaths by 2030. Women in low-and middle-income countries (LMICs) bear the greatest burden of cervical cancer yet have limited access to cervical precancer treatment. Scalable solutions, such as self-administered intravaginal therapies, can help close this treatment gap. In an ongoing Phase 1 trial of intravaginal artesunate pessaries as primary treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3), we evaluated the acceptability of this intervention among trial participants. METHODS/UNASSIGNED:Seventeen participants completed in-depth interviews in their preferred language, focusing on their experiences with artesunate self-administration and contextual factors that impacted acceptability. We conducted a thematic analysis using the socioecological framework to analyze product, individual, partner, community, and cultural factors related to acceptability of intravaginal artesunate. RESULTS/UNASSIGNED:Participants in this Phase 1 trial were primarily low-income women with limited formal education, and the majority were also living with HIV and had been on antiretrovirals for over a decade. Despite minimal prior experience with vaginal self-administration of medication, participants found the pessary acceptable and were highly motivated to get treatment for cervical precancer. Social support, educational interventions, and faith were crucial in enabling participants to complete the treatment protocol successfully. CONCLUSION/UNASSIGNED:Kenyan women found self-administered intravaginal artesunate for treating CIN2/3 to be highly acceptable. Randomized studies of intravaginal artesunate and other topical therapies are needed to further evaluate their efficacy and acceptability in LMICs. CLINICAL TRIALS REGISTRATION/UNASSIGNED:Clinicaltrials.gov NCT06165614.

BACKGROUND/UNASSIGNED:Alterations in microtubule dynamics have been shown to affect cardiomyocyte membrane stiffness and modulate ion channels, including the cardiac sodium channel. While conditions, such as heart failure and Duchenne muscular dystrophy, are associated with increased detyrosination of microtubules and reduced sodium current, a potential role for microtubule detyrosination in arrhythmogenic cardiomyopathy has not been explored. We here investigated the impact of microtubule detyrosination on membrane stiffness, cardiac sodium channel distribution, and function in mouse and human models of arrhythmogenic cardiomyopathy. METHODS/UNASSIGNED:-c.2013delC, and isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes were incubated for 2 to 4 hours with compounds known to decrease microtubule detyrosination (parthenolide, 10 µmol/L; EpoY, 20 µmol/L) or vehicle (dimethyl sulfoxide). Immunocytochemistry, mechano-scanning ion conductance microscopy, patch-clamp analysis, and stochastic optical reconstruction microscopy were performed. RESULTS/UNASSIGNED:-c.2013delC human-induced pluripotent stem cell-derived-cardiomyocytes displayed increased microtubule detyrosination and reduced sodium current compared with isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes, which were both prevented by parthenolide and EpoY. CONCLUSIONS/UNASSIGNED:Increased microtubule detyrosination secondary to loss of PKP2 impacts cardiomyocyte (dys)function beyond the desmosome, contributing to both electrical and mechanical alterations in the setting of arrhythmogenic cardiomyopathy. Our findings identify microtubule detyrosination as a novel therapeutic target in pathophysiological conditions, such as arrhythmogenic cardiomyopathy, aimed at improving both contractile and electrical function.

The September 11, 2001, terrorist attacks on the World Trade Center (9/11) exposed both disaster responders and community members to a complex mixture of environmental contaminants, resulting in long-term health consequences. While clinical and research efforts have characterized health effects among adult survivors (community members) and responders, less is known about individuals who were exposed in utero, during childhood, adolescence, or young adulthood. Recognizing this gap, Congress amended the Public Health Service Act (42 U.S.C. § 300mm-51(c)) to establish a Research Cohort for Emerging Health Impacts on Youth to promote research on those individuals who were 21 years of age or younger at the time of exposure. This Commentary reviews the historical development of post-9/11 monitoring, treatment, and research programs, and discusses the unique challenges of conducting research in such a youth cohort 25 years after the event. A central coordinating center supported by community-based field sites offers a promising approach to promoting research among this cohort and addressing critical gaps in understanding the lifelong impacts of 9/11 exposures.