Faculty Bibliography

BACKGROUND:Parastomal hernia repair is technically complex and associated with substantial morbidity, yet disparities in outcomes among racial groups have not been evaluated. Identifying inequalities in this population may inform strategies to improve access and perioperative care. METHODS:The ACS-NSQIP database from 2013 to 2023 was queried for adults undergoing parastomal hernia repair. Demographics, comorbidities, and operative details were compared among White patients, Black patients, and Hispanic patients. Primary outcomes included 30-day morbidity, infectious complications, and length of stay (LOS). Multivariable logistic and linear regression models were performed using a two step forward selection model adjusting for comorbidities and surgical details. RESULTS:A total of 3,513 patients were included (White 85, Black 8, Hispanic 7%). Black patients had higher unadjusted rates of morbidity (38 vs 30 White, 32% Hispanic; p = 0.023), serious complications (20 vs 13% white vs 13% Hispanic, p = 0.008), infectious complications (20 vs 13 White, 15% Hispanic; p = 0.004), and longer median LOS (6 vs 5 days White, 6 days Hispanic; p = 0.005). On multivariable analysis, Black race remained independently associated with increased odds of overall morbidity (aOR 1.31, 95% CI 1.01-1.70; p = 0.043), serious complications (aOR 1.65; CI 1.15-2.34, p = 0.006), and infectious complications (OR 1.44, 95% CI 1.04-1.98, p = 0.026) compared to white patients. CONCLUSION/CONCLUSIONS:This is the first national study to characterize racial disparities in parastomal hernia repair. Black patients experienced higher morbidity, infectious complications, and length of stay compared to White patients, while Hispanic patients did not differ from White patients. Disparities were emphasized in emergent cases, suggesting that barriers to timely elective repair possible drive imbalances in parastomal hernia repair, warranting interventions for underserved populations, with early referral, equal access, and tailored perioperative support.

In mesial temporal lobe epilepsy, resection or ablation-typically of anterior temporal structures-is highly successful in achieving seizure freedom. However, in a substantial proportion of patients, seizures recur for unclear reasons. Invasive hippocampal recordings suggest that, in some patients, hippocampal seizures are highly focal, often restricted to the anterior or posterior hippocampus. This led us to hypothesize that resection or ablation limited to the hippocampal subregion(s) involved at seizure onset is more likely to control seizures than surgery that does not address the specific onset locations. We present a case in which seizures were successfully controlled after posterior hippocampal ablation, as well as a retrospective case series of 18 patients in which 10 cases demonstrated focal onsets within the anterior or posterior hippocampus. Better outcomes occurred when surgery was concordant with the onset region(s) versus discordant (n = 7 concordant vs. 11 discordant patients, P = 0.046, Barnard Exact test). These data suggest that mesial temporal lobe epilepsy can be subdivided according to whether the hippocampal onset pattern is focal or nonfocal, and that targeting localized seizure onset zones within the hippocampus can be effective for seizure control, while limiting surgical morbidity and potentially the risk of adverse cognitive outcomes.

Dostarlimab in combination with carboplatin-paclitaxel was approved for primary advanced or recurrent endometrial cancer (pA/rEC). The first interim analysis (IA1) of RUBY Part 1 (NCT03981796) showed no significant exposure-response (ER) relationship for progression-free survival or for the five most common dostarlimab-related adverse events (AEs), except rash. Herein, we report the ER relationship between dostarlimab exposure and overall survival (OS) and between dostarlimab exposure and dostarlimab-related AEs. Population pharmacokinetic model was based on IA1, and the predicted exposure metrics from Cycle 1 were used to perform ER analysis at the second interim analysis (IA2). AE analysis was completed for three periods: Cycles 1-6 (chemotherapy phase), Cycle 7 and beyond (monotherapy phase), and all cycles. Included in the OS analysis were 232 patients treated with dostarlimab + carboplatin-paclitaxel. Cox regression of OS showed no significant ER relationship based on dostarlimab Cycle 1 exposure, except for rash and arthralgia. The increase in predicted probabilities for rash and arthralgia for patients with high versus low exposure was limited, ranging from 5.6% to 10.4% for rash and 4.3% to 17.7% for arthralgia (deemed not clinically relevant). These data support the risk/benefit profile at the selected dose of dostarlimab + carboplatin-paclitaxel as standard of care in patients with pA/rEC.

IMPORTANCE/UNASSIGNED:Black women have twice the endometrial cancer mortality of White women, and studies suggest that differences in ultrasound diagnostic accuracy partially contribute to this disparity. OBJECTIVE/UNASSIGNED:To evaluate racial and ethnic differences in the diagnostic performance of transvaginal ultrasound for detecting endometrial neoplasia. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A prospective cohort study of 1833 women aged 50 years or older at risk of endometrial neoplasia, conducted at a large urban academic medical center from February 2014 to August 2022, with follow-up through March 2023. The statistical analyses were conducted from March 2024 to December 2025. INTERVENTIONS/UNASSIGNED:Women underwent endometrial assessment via transvaginal ultrasound followed by sonohysterogram-directed biopsy and follow-up observation to establish final outcome. MAIN OUTCOME AND MEASURES/UNASSIGNED:Assessment of transvaginal ultrasound diagnostic performance for detecting endometrial cancer and hyperplasia across racial and ethnic groups, measured by: (1) completion rate (endometrial accessibility) and (2) accuracy of completed scans. To assess any association with fibroids, analyses were repeated after excluding women with fibroids. Subgroup analyses were conducted among women with endometrial cancer, those with postmenopausal bleeding, and those without prior exposure to estrogen or tamoxifen. RESULTS/UNASSIGNED:A total of 1833 women met inclusion criteria (mean [SD] age, 60.3 [8.1] years). Most were postmenopausal (1218 women [87.4%]), and 832 (45.4%) were Black, 705 (38.5%) were Hispanic, and 253 (13.8%) were White. Black women had significantly lower completion rates (adequate endometrial visibility) for transvaginal ultrasound compared with White women (75.7% vs 88.9%; relative risk, 0.85; 95% CI, 0.80-0.90; P < .001). Accuracy of completed transvaginal ultrasound was slightly lower among Black women compared with White women (sensitivity, 96.3%; 95% CI, 91.3%-100% vs 100%; negative predictive value, 97.9%; 95% CI, 95.0%-100% vs 100%). After excluding women with fibroids, differences in completion and accuracy between Black and White women disappeared. Similar findings were observed in subgroup analyses of women with a final diagnosis of endometrial cancer, those presenting with postmenopausal bleeding, and those without prior exposure to estrogen or tamoxifen. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of a diverse population of women, ultrasound completion rates were lower among Black women, primarily due to fibroids impairing endometrial visibility. Nevertheless, transvaginal sonography demonstrated a 76% completion rate and retained excellent ability to exclude cancer in Black women, regardless of fibroid presence.

OBJECTIVES/OBJECTIVE:The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS:Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS:In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS:Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

INTRODUCTION/BACKGROUND:Skeletal muscle loss is associated with cognitive decline, but whether neuroimaging-derived muscle characteristics predict incident dementia remains unclear. METHODS:We evaluated associations of deep learning-derived temporalis muscle (TM) cross-sectional area (CSA) and radiomic texture features from baseline T1-weighted magnetic resonance imaging (MRI) with incident dementia in dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 750) and the Atherosclerosis Risk in Communities (ARIC) study (n = 532). TM was segmented using a convolutional neural network trained in ADNI and externally validated in ARIC. Radiomic features were reduced using least absolute shrinkage and selection operator-penalized Cox models to generate a composite score. Multivariable Cox regression adjusted for demographics, apolipoprotein E ε4, baseline cognition, body mass index, and physical performance. RESULTS:Higher TM radiomic scores were associated with increased dementia risk in ADNI (hazard ratio per SD, 1.32) and ARIC (1.64). Smaller TM CSA predicted dementia in ADNI but not ARIC. DISCUSSION/CONCLUSIONS:TM texture patterns from routine brain MRI are associated with dementia risk, supporting TM phenotyping as a scalable marker of systemic biological vulnerability.

BACKGROUND:The United States-based Early Access Program (US EAP) provided access to arimoclomol for individuals with Niemann-Pick disease Type C (NPC) ineligible or unable to enroll in clinical trials, generating 4 years of real-world safety and effectiveness data. METHODS:Participants were enrolled at 14 US sites. Investigators collected adverse events (AEs) and assessed disease severity using the 5-domain NPC Clinical Severity Scale (5DNPCCSS) at Baseline and follow-up visits as part of routine clinical care. RESULTS:Among 109 participants, 53 (48.6%) were adults (≥18 years) and 71 (65.1%) received miglustat alongside arimoclomol. Mean (SD) arimoclomol exposure was 820 (539) days. Of 248 reported AEs, 17 events in 13 participants (12.8%) were treatment related. 5DNPCCSS scores remained relatively stable throughout the program, with mean (SD) total scores of 11.0 (6.15) at Baseline (n = 100) and 12.0 (7.32) at Year 4 (n = 22). Among participants with Baseline and Year 1 assessments, mean (SD) scores were 11.2 (6.33) at Baseline and 11.1 (6.63) at Year 1 (n = 78). Similar patterns were observed for those with Baseline and Year 2, Year 3, or Year 4 assessments. Rescored 4-domain NPCCSS (R4DNPCCSS) scores (calculated based on 5DNPCCSS data) showed comparable longitudinal trends. CONCLUSION/CONCLUSIONS:The US EAP provides robust real-world evidence data up to 4 years, supporting the tolerability and effectiveness of arimoclomol in a broad NPC population, including adults and those not treated with miglustat. These findings complement and extend clinical trials results, reinforcing the role of arimoclomol, especially in combination with miglustat, as an important therapeutic option in routine clinical practice.

BACKGROUND:Chronic low back pain (cLBP) is often managed conservatively, but it is vital to rule out certain causes before pursuing targeted treatment. A thorough evaluation, including medication reconciliation, ensures appropriate care and may prevent costly or invasive treatments for many ubiquitous conditions, including patients taking statin medications. CASE REPORT/METHODS:We present a series of 3 cases in which patients on statin medication presented to a pain management clinic with symptoms initially resembling mechanical and/or radicular chronic LBP (cLBP). In all 3 cases, medication reconciliation revealed high-dose statin medication, and supervised dose reduction or discontinuation was temporally linked with the alleviation of symptoms. CONCLUSION/CONCLUSIONS:This is the first known case series reporting suspected statin-associated muscle symptoms that mimic lumbar radiculopathy. These cases underscore the importance of comprehensive clinical evaluation, including medication reconciliation. Clinicians should consider medication-related side effects in the differential diagnosis of new or atypical musculoskeletal pain.