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Objective To describe an expanded phenotypic spectrum and longitudinal outcome in 256 LGI1‐IgG–seropositive and/or CASPR2‐IgG–seropositive patients. Methods Patients were identified through service neural autoantibody evaluation. Ninety‐five had longitudinal follow‐up (7–456 months; median = 35). Results Among 3,910 patients tested, 196 were LGI1‐IgG positive, 51 were CASPR2‐IgG positive, and 9 were dual positive. Cerebrospinal fluid testing was less sensitive than serum testing, detecting only 24 of 38 (63%) LGI1‐IgG–positive and 5 of 6 (83%) CASPR2‐IgG–positive patients. LGI1‐IgG–positive specimens had higher voltage‐gated potassium channel–IgG immunoprecipitation values (0.33nmol/l, range = 0.02–5.14) than CASPR2‐IgG–positive specimens (0.10nmol/l, range = 0.00–0.45, p < 0.001). Of patients presenting with pain or peripheral nervous system (PNS) manifestations, 39% were LGI1‐IgG seropositive (7% had solely neuropathy or pain). Multivariate analysis identified age as the only significant predictor of central nervous system (CNS) versus PNS involvement (>50 years; odds ratio = 15, p < 0.001). Paroxysmal dizziness spells (PDS), a unique LGI1‐IgG accompaniment (14% of patients), frequently delayed the diagnosis. T2‐mesiotemporal hyperintensity was more common in LGI1‐IgG–positive (41%) than in CASPR2‐IgG–positive patients ( p = 0.033). T1‐bright basal ganglia were confined to LGI1‐IgG–positive patients with faciobrachial–dystonic seizures (9 of 39, 31%). Cancer was found in 44% of LGI1‐IgG/CASPR2‐IgG dual seropositive patients (one‐third thymoma). Response to initial immunotherapy was favorable in 97%; mean modified Rankin score was 3 (range = 1–5) at onset and 1.74 (range = 0–6) at last follow‐up, with 9% having severe refractory disability, 20% being asymptomatic, 28% receiving immunotherapy, and 58% receiving antiepileptic medication. Interpretation Older age is a strong predictor of CNS involvement in patients seropositive for CASPR2‐IgG or LGI1‐IgG. Pain, peripheral manifestations, and stereotypic paroxysmal dizziness spells are common with LGI1‐IgG. Response to initial immunotherapy is often favorable, but some patients remain severely disabled, requiring long‐term immunotherapy and/or antiepileptic medications. Ann Neurol 2017;82:79–92

Purpose The purpose of this pilot feasibility project was to examine the potential effectiveness of a digital storytelling intervention designed through a community-based participatory research (CBPR) approach for immigrants and refugees with type 2 diabetes mellitus (T2DM). Methods The intervention was a 12-minute culturally and linguistically tailored video consisting of an introduction, 4 stories, and a concluding educational message. A structured interview was used to assess the intervention for acceptability, interest level, and usefulness among 25 participants with T2DM (15 Latino, 10 Somali) across 5 primary care clinical sites. After watching the video, participants rated their confidence and motivation about managing T2DM as a result of the intervention. Baseline A1C and follow-up values (up to 6 months) were abstracted from medical records. Results All participants reported that the intervention got their attention, was interesting, and was useful; 96% reported that they were more confident about managing their T2DM than before they watched the video, and 92% reported that the video motivated them to change a specific behavior related to T2DM self-management. The mean baseline A1C level for the intervention participants was 9.3% (78 mmol/mol). The change from baseline to first follow-up A1C level was −0.8% (−10 mmol/mol) ( P < .05). Conclusions Implementation of a digital storytelling intervention for T2DM among immigrant populations in primary care settings is feasible and resulted in self-rated improvement in psychosocial constructs that are associated with healthy T2DM self-management behaviors, and there was some evidence of improvement in glycemic control. A large-scale efficacy trial of the intervention is warranted.

Abstract OBJECTIVES: Mutations in ESR1 that are acquired following treatment with aromatase inhibitors commonly underlie resistance to endocrine therapy in breast cancer. ERa-LBD mutations, especially at ESR1 Y537 and D538, confer constitutive activity and partial resistance to selective estrogen receptor modulators (SERMs), such as tamoxifen, and degraders (SERDs) such as fulvestrant in transcription assays. Some ovarian tumors also respond to anti-hormone therapy, and a subset which initially respond subsequently become resistant. The mechanisms of resistance to hormone therapy in ovarian cancer have not been previously described. Comprehensive genomic profiling (CGP) of ovarian tumors was used to analyze ESR1 and correlate responsiveness to aromatase inhibitors in a subset of these patients. METHODS: DNA was extracted from tumor specimens and sequenced using hybridization-capture (FoundationOne) targeting up to 315 genes, plus select introns frequently rearranged in cancer. Demographic and clinicopathologic data will be presented for a subset of patients whose tumors harbor ERa-LBD mutations associated with activation and resistance.. RESULTS: CGP of 3,641 ovarian and peritoneal carcinomas revealed 31 (0.9%) samples with amplification of ESR1 and 16 (0.4%) samples with acquired or de novo mutations affecting the ERa-LBD: Y537S (10), Y537N (1), D638G (4), and S341L (1). Within the 16 samples, ovarian serous carcinoma (10), ovarian endometrioid adenocarcinoma (3), ovarian epithelial carcinoma NOS (2), and peritoneal serous carcinoma (1) were represented. In cases of acquired mutations following prior hormone therapy, there was evidence of clinical benefit to SERM/SERDs. CaseAgeDiseaseESR1 MutationPrior HRTAcquiredSERM/SERD (*post mut if acquired)Clinical Benefit SERM/SERD159Ov serousY537SYYNN/A258Papillary serousY537NNNYY344Endometrioid ov adenoY537SNNYY445HG ov serousD538GNUYU564Endometrioid ov adenoY537SYUNU646LG ov serousY537SYUYU739Papillary serousY537SYUNN/A827LG ov serousY537SYYYY CONCLUSIONS: Acquired activating mutations in ESR1, previously described in breast cancer, can occur in ovarian serous carcinomas and endometrioid carcinomas initially responsive to hormone therapy and suggest a similar mechanism for acquired aromatase inhibitor resistance. However, ERa mutations can occur in gynecologic malignancies even in the absence of prior endocrine therapy. Tumors harboring these mutations may remain responsive to SERM/SERDs. Citation Format: J. A. Elvin, L. Gay, G. Colon-Otero, M. Jorgensen, L. Havrilesky, D. Zajchowski, L Shawver, F. A. Valea, S Aithal, J. S. Ross, M. Markman, S. Gaillard. CONSTITUTIVELY ACTIVE ESTROGEN RECEPTOR–ALPHA LIGAND BINDING DOMAIN (ERA–LBD) MUTATIONS IN OVARIAN CARCINOMA [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-056.