Faculty Bibliography

BACKGROUND:Pain during intrauterine device (IUD) insertion is a significant patient concern. Current pharmacologic strategies inadequately address procedural pain, highlighting the need for rigorous evaluation of novel approaches. OBJECTIVE:To evaluate whether high-frequency transcutaneous electrical nerve stimulation (TENS) reduces pain with IUD insertion. STUDY DESIGN/METHODS:We conducted a double-blind randomized controlled trial in which 98 participants undergoing LNG 52 mg or CuT380A IUD insertion received either active high-frequency TENS or sham TENS. We measured pain using a 100-mm visual analog scale (VAS) at multiple time points during the procedure. The primary outcome was pain at the time of IUD insertion. Participants completed a pre-procedure survey asking about demographic and reproductive characteristics, anticipated pain, and anxiety. We asked participants post-procedure about satisfaction with pain during procedure and the TENS device. Clinicians completed a post-procedure survey asking about their perception of participant pain and ease of insertion. We estimated a total sample size of 98 to achieve 80% power to detect a 20 mm difference in pain scores, with 10% attrition/protocol deviation and 15% inflation to account for nonparametric distribution. We performed an intention-to-treat analysis and calculated mean pain scores and standard deviations. We used t-tests to compare mean pain scores at the time of IUD insertion and chi-square tests to compare categorical variables. We dichotomized parity as nulliparous (no prior delivery) vs. parous (any delivery greater than 20 weeks). RESULTS:Between March 2024 and April 2025, we screened 150 participants and enrolled 99 individuals (active n=49; sham n=50) with one post-randomization exclusion. Baseline characteristics were similar, with a median age of 29 years and just over half having had a previous birth (53.1%). Pain at the time of IUD insertion did not differ between active and sham TENS groups (50.8 ± 26.9 mm vs 50.6 ± 29.2 mm; p=0.97). We also observed no differences in procedure duration. Nulliparous participants reported higher pain scores overall compared to parous individuals, but we detected no difference in pain scores relative to treatment intervention within groups (nulliparous - active 58.8 ± 28.7 mm, sham 59.3 ± 25.5 mm, p=0.95; parous - active 43.5 ± 23.3 mm vs. sham 43.2 ± 30.6, p=0.97). While clinician estimates and participant-reported maximum-pain scores were mildly correlated (Pearson's correlation coefficient = 0.41), there was a significant difference between mean clinician-estimated and participant-reported maximum pain scores (p<0.001), 48.9 ± 26.8 mm vs. 60.5 ± 25.2 mm, respectively. Participants undergoing IUD insertions perceived as difficult by clinicians reported higher mean pain scores than those perceived as easy (71.6 ± 24.2 mm vs. 56.0 ± 24.4 mm, respectively; p=0.006). CONCLUSION/CONCLUSIONS:High-frequency active TENS did not reduce pain during IUD insertion compared with sham TENS. These findings were not affected by parity.

BACKGROUND:Folate receptor alpha (FRα) is overexpressed in most high-grade ovarian cancers (HGOC), but use of the FRα-targeting drug mirvetuximab soravtansine-gynx (MIRV) is limited by expression-level restrictions and toxicity profile. Sofetabart mipitecan (Sofe-M) is a novel FRα-targeting antibody-drug conjugate designed to overcome these barriers. Here we report safety, efficacy, and pharmacokinetics from the first-in-human phase 1 study. PATIENTS AND METHODS/METHODS:This multicenter, open-label, phase 1 trial evaluated Sofe-M in patients with HGOC, regardless of FRα expression level. Prior MIRV treatment was permitted. RESULTS:One-hundred-five patients with HGOC, the majority of whom were platinum resistant, received Sofe-M at 2, 3, 4 or 6 mg/kg every 21 days. Median age was 63.0 years, median number of prior treatments was 5.0 (1-11), 19 (18.1%) patients had prior MIRV, and 54 (51.4%) had tumor FRα expression <75% at ≥2+ intensity. Overall response rate was 50.5% (95% CI 40.5, 60.4) for all patients, 58.8% (95% CI 32.9, 81.6) at 3 mg/kg, 44.4% (95% CI 30.9, 58.6) for FRα <75%, 56.5% (95% CI, 41.1, 71.1) for FRα ≥75%, and 57.9% (95% CI 33.5, 79.7) for patients with prior MIRV exposure. Median progression-free survival was 8.1 months (95% CI 6.4, 8.5) and median follow-up was 12.9 months (95% CI 10.6, 15.2). Most common treatment-emergent adverse events (TEAEs) were nausea (64.8%), fatigue (56.2%), and anemia (47.6%). No keratopathies or grade ≥3 neuropathy were observed. At 3 and 4 mg/kg, the rate of Grade ≥3 treatment-related TEAEs was 35.3% and 56.4%, respectively. Treatment discontinuation due to TEAEs occurred in 11 patients (10.5%). CONCLUSIONS:Sofe-M demonstrated a favorable tolerability profile, notably absent of keratopathy and high-grade neuropathy, with durable clinical activity in heavily pretreated HGOC patients regardless of FRα expression level or prior MIRV. These data support 3 mg/kg as the recommended phase 3 dose and provide the basis for the FRAmework-01 trial. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:Phase 1 (NCT06400472); FRAmework-01 (NCT07213804).

INTRODUCTION/UNASSIGNED:Urogynecology and Reconstructive Pelvic Surgery (URPS) became an accredited fellowship in 2013. Our objective was to assess the landscape of URPS procedures performed by URPS fellowship-trained (FT) and non-FT urologists (NFT) since accreditation. MATERIALS AND METHODS/UNASSIGNED:A retrospective cohort study of American Board of Urology case logs of urologists performing URPS procedures from January 2013 through August 2024 was conducted. The annual case volumes of FT and NFT urologists were compared. Multivariable mixed-effects Poisson regression models assessed the impact of covariates on annual case volume. RESULTS/UNASSIGNED:5,816 urologists (393 FT, 5,423 NFT) performing URPS procedures were included, with 513 FT and 5,818 NFT case log submissions. Compared to NFT, FT urologists were predominantly female (48% vs 13%, p<0.01), practiced in metropolitan areas (52% vs 23%, p<0.01) and academic settings (41% vs 7%, p<0.01). FT performed 24% of annual URPS cases on average, rising to 34% when excluding benign prostate hypertrophy (BPH) procedures. Modelling demonstrated that FT performed URPS cases at 4.2 times the annual rate of NFT (RR 4.2, 95% CI 3.6-4.6) on average, rising to 7.6 times when BPH was excluded (RR 7.6, 95% CI 6.7-8.6), controlling for other covariates. Independent of FT status, women performed non-BPH URPS at a 62% higher rate than men, with higher rates also seen among urologists that are younger, recertifying and outside the Northeast. CONCLUSIONS/UNASSIGNED:Although NFT outnumber FT by 14 to one, FT performed eight times more non-BPH URPS cases annually on average and accounted for 34% of total non-BPH volume.

PURPOSE/OBJECTIVE:Adolescent and young adult (AYA) patients (18-39) with cancer experience psychosocial challenges upon being diagnosed with cancer. AYAs are also at risk of potential infertility due to certain cancer treatments. We examined factors associated with desire for future children among AYAs. Among those interested in having future children or were unsure if they wanted children, we examined factors associated with interest in fertility consultations. METHODS:Patients completed an electronic patient questionnaire (EPQ) which included items assessing physical/mental health, desire for future children, and interest in fertility consultations. Cancer registry data comprised cancer characteristics (e.g., cancer and treatment type). Multinomial regression analysis examined factors associated with desire for future children. Binary regression examined factors associated with interest in fertility consultations. RESULTS:AYAs (n = 4847) were majority female (62%) and on average, 32 years old. In multinomial analysis, females (vs. males) (OR [95% CI] = 0.56 [0.48-0.71]), older AYAs (OR [95% CI] = 0.81 [0.80-0.83]), and those with children (OR [95% CI] = 0.34 [0.26-0.45]) were less likely to report wanting future children. Among AYAs wanting children, older patients (OR [95% CI] = 1.04 [1.01-1.06]), females (OR [95% CI] = 1.39 [1.00-1.94]), breast cancer (OR [95% CI = 2.65 [1.38-5.10]) or lymphoma patients (OR [95% CI] = 1.99 [1.12-3.56]), and receiving hormone therapy (OR [95% CI] = 1.73 [1.06-2.81]) or transfusions (OR [95% CI] = 3.23 [0.86-12.21]) were more likely to desire consultations. CONCLUSIONS:There is a need to systematically address and offer fertility consultation for all AYA patients prior to treatment initiation. Sociodemographic, clinical, and psychosocial factors warrant additional study and future intervention development to ensure fertility needs are met.

Lynch syndrome and BRCA-mutation associated malignancies are fortunately rare. Affected patients have an increased risk of cancer diagnosis at a young age, often significantly overlapping with their reproductive years. In helping these patients, oncologists must navigate the following areas of care: cancer prevention, impact of cancer prevention strategies on fertility, impact of cancer treatment on fertility, effective cancer therapies, and preservation of fertility without compromising oncologic outcomes. This intersectionality between fertility preservation and effective cancer prevention/therapy makes the care of these patients extremely complex. With the utility of multidisciplinary care models, careful employment of evolving new treatment strategies, it is possible for patients to achieve their fertility desires while at the same time being protected from the risks imposed by their genetic mutations.

Hypertensive disorders of pregnancy arise from early placental and systemic vascular dysfunction, yet current first-trimester screening remains imprecise, biologically opaque and logistically challenging. Here we present Visionary AI, an interpretable platform that integrates retinal imaging with graph-based vascular modeling to predict hypertensive disorders before clinical onset. Visionary AI converts retinal images into topological and geometric representations of microvascular structure, enabling risk prediction from biologically grounded vascular features rather than generic image embeddings or clinical variables. In a prospective development cohort of 1,267 pregnancies, Visionary AI achieved strong performance for preeclampsia across population-wide control settings (area under the curve (AUC) = 0.91, average precision (AP) = 0.81). A stability-optimized model transferred without retraining to an independent external validation cohort, achieving AUC = 0.81 and AP = 0.68 and outperforming clinical and deep learning benchmarks. Recurrent features involving retinal vascular topology, geometry, network complexity and hierarchical organization position the maternal retina as a minimally invasive biosensor of systemic vascular health and Visionary AI as a biologically interpretable framework for pregnancy risk stratification.

BACKGROUND:Although gliomas during pregnancy are rare, they present significant clinical and ethical challenges due to the potential effects of pregnancy on tumor behavior and the risks associated with the standard of care. Given the peak incidence of IDH-mutant glioma in the 3rd and 4th decades of life, clinicians face a challenge in balancing maternal oncological outcomes with fetal safety, while navigating the uncertainty surrounding the effects of standard treatment modalities on fetal development. OBSERVATIONS/METHODS:A 31-year-old woman at 23 weeks of gestation with a history of IDH-mutant glioma presented to the authors' institution with worsening neurological symptoms. MRI indicated tumor progression, and re-resection was performed via awake craniotomy with functional mapping. The maternal-fetal medicine team was consulted to guide the selection of anesthesia and optimize intraoperative positioning, ensuring the safety of both the patient and fetus. Postoperative recovery was uneventful, with stable maternal and fetal outcomes. Pathological analysis confirmed progression to a grade 4 astrocytoma. LESSONS/CONCLUSIONS:This case highlights the feasibility of awake craniotomy with functional mapping during pregnancy. Management of gliomas in pregnancy requires a multidisciplinary approach, balancing maternal health and fetal safety, with careful consideration of treatment timing and anesthetic strategies. https://thejns.org/doi/10.3171/CASE2696.

INTRODUCTION/UNASSIGNED:Hereditary cancer testing can identify individuals with a significant risk of cancer, and provide an opportunity for early risk management, prevention, precision treatment strategies, and family cascade testing. Medical professional organizations have developed guidance on genetic testing criteria based on personal and family histories. However, many individuals with cancer-predisposing pathogenic germline variants remain unidentified. The objective of this study was to determine the utility of a multi-cancer, clinically actionable cancer syndrome gene panel in identifying pathogenic variants among individuals both meeting and not meeting national genetic testing criteria. METHODS/UNASSIGNED:This retrospective cohort study analyzed 153,767 unrelated consecutive women and men, unselected for personal or family cancer history, who were referred for genetic testing across multiple sites from June 2020 to August 2023. Positivity rates were evaluated and compared according to testing guideline eligibility and cancer site-specific recommended gene sets. RESULTS/UNASSIGNED:(met: 0.8%, not met: 0.36%) among those meeting only Lynch syndrome criteria. DISCUSSION/UNASSIGNED:These findings indicate that strict testing criteria may miss 22% of individuals with an actionable hereditary cancer gene variant. The use of comprehensive multi-cancer panels, alongside broader eligibility criteria, can identify individuals with hereditary cancer syndromes and improve opportunities for targeted screening, clinical management, and cascade testing for relatives.

OBJECTIVE:To evaluate a GABAergic, melatonergic, and glutamatergic supplement for enhancing sleep quality in perimenopausal and postmenopausal women with low vasomotor symptom (VMS) burden. METHODS:A randomized, double-blind, placebo-controlled, decentralized trial (NCT07375095) was performed in healthy perimenopausal and postmenopausal women with moderate-to-severe sleep disturbance (patient-reported outcome measure information system sleep disturbance [PROMIS SD] SF 8b T-score ≥60) and minimal VMS (≤5 hot flashes and ≤2 night sweats/wk). Participants were randomized to a neurotransmitter-modulating supplement (NMS; L-theanine, gamma-aminobutyric acid, magnesium, S-adenosyl methionine, propyl gallate) or placebo for three weeks. Primary outcomes were changes in PROMIS SD and sleep-related impairment T-scores and responder rates. Secondary outcomes included diary-based total sleep time, sleep efficiency, and visual analog ratings of sleepiness and daytime functioning. RESULTS:Of 128 randomized participants, 127 completed the trial (NMS, n = 65; placebo, n = 62). Baseline characteristics and VMS frequency were similar between groups (3.0 ± 4.0 hot flashes and 1.9 ± 1.7 night sweats/wk). At week 3, NMS significantly improved PROMIS SD T-score (LS mean difference: -11.1 [95% CI, -13.6 to -8.6]; P = 0.0012) and responder rate (90.9% vs. 45.2%; P < 0.001) versus placebo. PROMIS sleep-related impairment T-score (-4.8 [95% CI, -7.3 to -2.3]; P < 0.001) and responder rate (50.8% vs. 32.2%; P = 0.047) also improved. All primary endpoints reached significance by week 2. NMS increased total sleep time by 40.9 minutes versus a 14.9-minute decrease with placebo (P < 0.001), and sleep efficiency improved by 7.4% versus 3.4% (P = 0.021). No between-group differences in adverse events were observed. CONCLUSION/CONCLUSIONS:In perimenopausal and postmenopausal women with disrupted sleep but minimal VMS, a NMS significantly improved sleep quality and duration.