Citations

Abstract Objective This study was conducted to review and synthesize current evidence on anti‐calcitonin gene‐related peptide (CGRP) therapies in women with menstrual‐related migraine, during pregnancy and lactation, and while using hormonal contraception. Background Migraine disproportionately affects women, with prevalence peaking during reproductive years when hormonal fluctuations modulate neurovascular and nociceptive pathways, including CGRP signaling, that contribute to migraine susceptibility. Despite the established efficacy of anti‐CGRP therapies—including monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) and gepants (ubrogepant, rimegepant, atogepant, and zavegepant)—evidence regarding their use across critical reproductive health contexts remains limited. Methods A systematic search of MEDLINE and Embase was conducted using MeSH terms and keywords related to migraine, CGRP‐targeted therapies, and reproductive health contexts. Studies were screened independently by two reviewers. Data were extracted using standardized forms and synthesized narratively by clinical domain. Results Sixteen studies met inclusion criteria. For menstrual‐related migraine, post hoc analyses and observational studies demonstrate that CGRP monoclonal antibodies reduce migraine frequency both during and outside the perimenstrual window (galcanezumab: −5.1 vs. −3.2 days, p < 0.001), although the perimenstrual period remains a time of relatively higher headache burden despite treatment. Pregnancy data are limited to pharmacovigilance analyses and case reports of unintended exposures, which have not identified specific patterns of maternal, fetal, or neonatal toxicity. Phase 1 pharmacokinetic studies demonstrate minimal gepant transfer into breast milk (relative infant doses, 0.04%–0.19%), well below the 10% safety threshold, although no human lactation data exist for CGRP monoclonal antibodies. No studies specifically evaluated anti‐CGRP therapies in women using hormonal contraceptives. Conclusion Substantial evidence gaps exist across all reproductive health contexts examined. Prospective trials in menstrual‐related migraine, pregnancy registries, lactation studies assessing infant outcomes, and research examining interactions with hormonal contraceptives are needed to optimize migraine care for women.

Objective This study aimed to compare longitudinal cephalometric growth, speech outcomes, and secondary surgeries after 1-stage versus 2-stage palatoplasty in patients with non-syndromic unilateral cleft lip and palate (UCLP). Design Retrospective single-institution cohort study. Setting Tertiary academic craniofacial center. Patients/Participants Sixty-eight patients with non-syndromic UCLP treated between 1992 and 2015 who underwent primary palatal repair and had long-term clinical and radiographic follow-up. Forty-eight underwent 1-stage palatoplasty, and 20 underwent 2-stage palatoplasty. Interventions One-stage palatoplasty versus staged palatoplasty with initial soft palate repair followed by delayed hard palate closure. Main Outcome Measures Longitudinal cephalometric measurements at approximately 10 and 16 years, speech outcomes at 5, 10, 13, and 16 years, oronasal fistula, velopharyngeal insufficiency surgery, and need for continued speech follow-up after age 10. Results Mean follow-up was 15.2 ± 4.4 years. Linear fixed-effects modeling showed significant age-related worsening in sagittal skeletal relationships in both groups, including decreases in sella-nasion-A point angle (SNA), A point-nasion-B point angle (ANB), and Wits appraisal, without significant effects of palatoplasty strategy or age-by-strategy interaction for key sagittal outcomes. Speech outcomes were comparable between groups across all timepoints, including hypernasality, nasal emission, compensatory articulation, intelligibility, and Cleft Audit Protocol for Speech-Augmented (CAPS-A) scores. Rates of secondary velopharyngeal surgery and continued speech follow-up after age 10 did not differ significantly. Oronasal fistula occurred more frequently after 2-stage palatoplasty than 1-stage palatoplasty (30% vs 9%, P = .02). Conclusion One-stage and 2-stage palatoplasty demonstrated similar long-term growth and speech outcomes through adolescence. Two-stage repair was associated with a higher oronasal fistula rate but not greater secondary velopharyngeal or speech burden.

ABSTRACT Melanoma in skin of color (SOC), defined as Fitzpatrick skin tones IV‐VI, presents unique epidemiologic, diagnostic, and therapeutic challenges compared to non‐Hispanic White (NHW). Although SOC patients have a lower incidence of melanoma, they experience higher melanoma‐specific fatality rates, which may be attributable to later‐stage diagnoses, differences in the distribution patterns of melanoma subtypes, and systemic barriers to care. SOC patients, particularly non‐Hispanic Black individuals, have a higher proportion of acral lentiginous and mucosal melanomas, which arise in non‐sun‐exposed areas, carry lower mutational burdens, and respond less favorably to immunotherapy and BRAF/MEK‐targeted therapies. These anatomic and biological differences contribute to delayed recognition and reduced treatment efficacy. Concurrently, the rising incidence of melanoma in situ across racial and ethnic groups without corresponding decreases in invasive disease or similarly increased mortality rates raises concern for overdiagnosis. Artificial intelligence‐based diagnostic tools show promise in NHW populations but are limited by the underrepresentation of SOC in training datasets and diminished positive predictive value in low‐prevalence populations. The estimated number needed to screen to prevent one melanoma death in SOC populations ranges from approximately 46,000 to 201,000, underscoring the challenge of melanoma screening in this group. Suggested solutions and improvements include expanding healthcare access through patient navigators, developing culturally tailored education programs focused on identifying early invasive disease, diversifying AI training datasets to include acral and mucosal melanoma, biobanking rare melanoma subtypes, and decentralizing clinical trials into community settings. A multifaceted approach is essential to addressing overdiagnosis and improving melanoma outcomes in the SOC populations. image

ABSTRACT Background Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are rare, chronic cholestatic liver diseases with heterogeneous progression and limited biomarkers of disease biology. Epigenetic age acceleration has been demonstrated in PSC and PBC, suggesting accelerated biological aging. DNA methylation–derived telomere length (DNAmTL) reflects replicative aging and cellular turnover, but its role in PSC and PBC remains unclear. We aimed to evaluate DNAmTL in PSC and PBC and its association with disease severity. Methods We analysed and compared DNAmTL and age‐adjusted DNAmTL among patients with PSC ( n = 474) versus PSC controls ( n = 484) and patients with PBC ( n = 291) versus PBC controls ( n = 291). Associations with clinical outcomes were assessed using nonparametric tests and multivariable logistic regression models. Correlations with primary sclerosing cholangitis Risk Estimate Tool (PREsTO) score and epigenetic age acceleration (AgeAccelGrim) were evaluated using linear regression. Results Patients with PSC demonstrated significantly shorter age‐adjusted DNAmTL compared with controls (median −0.036 vs. 0.016, p < 0.001). Patients with PBC also exhibited reduced DNAmTL relative to controls (median 6.814 vs. 6.885, p < 0.001). Within PSC, shorter DNAmTL was associated with cirrhosis (OR 0.21, 95% CI 0.06–0.69, p = 0.013) and advanced disease (OR 0.20, 95% CI 0.06–0.67, p = 0.009). Shorter DNAmTL was also observed in hepatic decompensation and hepatobiliary malignancy, including cholangiocarcinoma. DNAmTL inversely correlated with PReSTO score ( p < 0.001). DNAmTL was strongly inversely correlated with AgeAccelGrim in both PSC and PBC ( p < 0.001). Conclusion Cholestatic liver diseases are associated with shortened DNAmTL, which independently correlates with disease severity in PSC. Together with epigenetic age acceleration, these findings support a model of accelerated biological aging in PSC and PBC characterized by converging signatures of accelerated biological aging that may contribute to progressive biliary injury and fibrosis.

Introduction Extracranial internal carotid artery (ICA) aneurysms are rare (<1% of arterial aneurysms) yet clinically significant due to risks of distal embolization, local compressive symptoms, and, less commonly, rupture. High-quality evidence is limited, and no consensus guidelines exist, management is therefore individualized to aneurysm morphology, cervical segment involvement, vessel tortuosity, and operator expertise. Flow diversion with Pipeline Embolization Device (PED) achieves aneurysm exclusion while reconstructing the parent artery and is especially useful in tortuous cervical segments. Clinical Summary A 60-year-old woman with incidentally discovered bilateral cervical ICA aneurysms (left 2.3 cm mid-ICA; right 0.5 cm) and a type III bovine arch underwent PED diversion of the lesion. Via femoral access, a long 6-F Fubuki sheath (Asahi Intecc, Irvine, USA) with Sofia catheter (Micro-Vention, Tustin, USA) support and systemic heparinization (ACT >250 s) enabled deployment of a 5.0 × 25 mm Pipeline Flex (Medtronic Neurovascular, Irvine, USA) across the aneurysm neck. Immediate angiography showed intra-aneurysmal stasis while preserving parent-artery flow . At 12 months, she is asymptomatic with a 70% reduction in the contrast-opacified aneurysm component to 7 mm, and the contralateral small aneurysm remains stable. Conclusion Flow diversion with a PED provided an effective, artery-preserving solution for a mid-cervical ICA aneurysm in tortuous anatomy, achieving immediate flow stasis with parent-artery patency. At 12 months, the patient is asymptomatic with a contrast-opacified component reduced to 7 mm. This case supports using flow diversion for extracranial ICA aneurysms when anatomy is favorable, alongside careful antiplatelet therapy and planned imaging follow-up.

Background: Operative decision-making in gastric gastrointestinal stromal tumor (GIST) surgery is strongly influenced by tumor anatomy. Although surgeons routinely consider anatomic features such as proximity to the gastroesophageal junction, posterior wall location, and endophytic growth during operative planning, their combined association with operative strategy has not been systematically evaluated. Methods: We evaluated whether commonly recognized anatomic features of gastric GISTs were associated with operative strategy in a contemporary minimally invasive surgical cohort. Tumors were characterized according to the presence of three predefined anatomic features: proximal location near the gastroesophageal junction, posterior wall involvement, and endophytic growth pattern. Cases were grouped as lower (0–1 features) or higher (2–3 features) complexity. The primary outcome was operative strategy, categorized as simple (wedge resection or enucleation) or complex (partial gastrectomy or transgastric resection). Associations between anatomic complexity and operative approach were evaluated. Results: A total of 83 patients were included, with 50 (60.2%) classified as lower complexity and 33 (39.8%) as higher complexity. Operative strategy varied significantly by complexity group. Tumors in the higher complexity group were more frequently managed with complex operative techniques, including partial gastrectomy and transgastric resection ( P = .002). This association remained significant after adjustment for tumor size (odds ratio 2.87, 95% CI: 1.12–7.65, P = .031). A graded relationship was observed, with increasing use of complex techniques as the number of anatomical features increased. The robotic platform was used more frequently in higher complexity cases ( P = .03). Perioperative outcomes were comparable between groups. Conclusions: Recognized anatomical features of gastric GISTs were associated with operative strategy and reflected real-world surgical decision-making. Systematically describing these features may facilitate preoperative assessment and improve consistency in reporting operative approaches.

Abstract INTRODUCTION Plasma phosphorylated tau 217 (p‑tau217) immunoassays are increasingly being used to assess Alzheimer's disease (AD) pathology despite limited data affirming test reliability over time. METHODS Clinical performance of the Fujirebio Lumipulse G p‑tau217 assay was assessed in 744 Mayo Clinic patients presenting for evaluation of cognitive impairment between July 2024 and December 2025. Cerebrospinal fluid p‑tau181/amyloid beta 42 or amyloid positron emission tomography, within 1 year of p‐tau217 testing, were used as reference. Analytical robustness was evaluated by tracking result frequencies over time, conducting quality control checks, performing 10 lot‑to‑lot comparisons, and comparing two versions of reagents. RESULTS Diagnostic accuracy for detection of AD pathology was 93% (95% confidence interval 91–95) with 23% intermediate results. Reduced estimated glomerular filtration rate was associated with increased intermediate results among amyloid‐negative individuals. Result frequencies remained stable, average imprecision was 8%, and analytical bias between lots and version changes were ≤ 11%. DISCUSSION The findings support plasma p‐tau217 reliability in clinical practice for evaluation of cognitively impaired individuals.

This Perspective discusses whether secondary genomic findings in the clinical context of diagnostic genomic sequencing tests should be sought and reported.