Lucas Research

Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare metabolic encephalopathy caused by pathogenic SLC2A1 variants. Ketogenic dietary therapy (KDT) is the mainstay of treatment. In Latin America, Glut1DS remains underdiagnosed due to limited awareness and restricted access to genetic testing. This study describes the clinical and genetic features, management, and response to KDT in an Argentine cohort. A retrospective multicenter study was conducted including patients with a clinical and/or genetic diagnosis of Glut1DS. Clinical data, seizure types, neurodevelopmental features, treatment response, and KDT characteristics were collected from medical records using a standardized form. Genetic confirmation was obtained by SLC2A1 sequencing. Descriptive and comparative analyses were performed. Thirty-nine patients with Glut1DS (64% males) were included. Mean age at evaluation was 13.7 years. Median ages at symptom onset and diagnosis were 6 and 55 months, respectively, with a median diagnostic delay of 49 months. Cognitive impairment was present in two-thirds of patients, and movement disorders in 79%. Epilepsy occurred in 74%. Of 39 patients, all but one received KDT, with MCT oil in 64%. Thirty patients remained on KDT, achieving seizure freedom in 86% and >50% reduction in four others. Improvements were reported in motor coordination (38%), cognition and attention (10%), energy (10%), and behavior (8%). No major adverse effects were reported. This first national report underscores the clinical diversity of Glut1DS in Argentina and a positive trend toward earlier KDT initiation. Strengthening early diagnosis, systematic follow-up, and equitable access to therapy remains essential.

BackgroundUsing unguided podcast narratives offers a unique and original opportunity to access patient experiences and understand what patient’s value in their care journey in developing true patient-centered oncology models. Online health communities contain a wealth of information, including unsolicited patient experiences that may go beyond what is captured by guided surveys or patient-reported outcome instruments. This study describes patient experiences reported in a peer support community to gain insight into what patients share amongst each other and what they value.MethodsA purposive sample of 31 unguided, French-speaking self-reported patient narratives were collected from the podcast “Naitre princesse, devenir guerrière” registered between 2021 and 2024. Episodes included patient (n = 30) and tandem patient-professional (n = 1) voices, reflecting diverse cancer types, treatment stages, and lived experiences. A transdisciplinary team, including the podcast founder, conducted the thematic analysis to identify patterns of patient values across narratives.ResultsFrom patient narratives, six core themes of patient value emerged: (peer) support, empowerment, relationship with healthcare professionals, quality of life, cancer as an opportunity, and individuality. Narratives underscored patient value as rooted in reclaiming agency, redefining life priorities, and engaging in meaningful action. Participants revealed the irreplaceable role of peers in providing mutual understanding and solidarity, alongside ambivalent but pivotal relationships with healthcare professionals.ConclusionSelf-reported narratives from peer communities offer empirical evidence into patients’ priorities and lived realities, revealing what patients identify as meaningful in their cancer pathways. These findings accentuate the importance of transdisciplinary analysis of patient experiences beyond clinical outcomes and physician reports. Online health communities represent a promising but underexplored arena for understanding and integrating patient values into care, research, and policy. Future research should further examine their role in shaping participatory and value-driven health systems.

Objective is to investigate the potential of DMMO to restore a harmonious forefoot morphotype according to Maestro criteria. Retrospective study investigated 51 feet in 48 patients with central primary metatarsalgia between the 2nd and 4th metatarsal. Associated procedures included hallux valgus and lesser toe corrections. Patients were evaluated radiographically with comparison of their forefoot morphotypes after the DMMO procedure to their preoperative state regarding the Maestro criteria. A subgroup of 17 patients was evaluated for union in 3 months and functionally by the AOFAS and VAS scale. Ten percent of the 48 patients were male and ninety percent were female with a mean age of 52.1 ± 11.7 (range 23 to 70) years. In total 148 DMMOs were performed in 51 feet. Osteotomies were localized on M2 and M3 in 10% and on three metatarsals (M2-M3-M4) in 90%). In 84% associated procedures were performed. All radiographic parameters of the Maestro criteria were significantly different preoperative compared to postoperative (p<0.05). In 94% patients of the subgroup there was a bony consolidation at three months. There was a mean AOFAS-score of 76.8 ± 15.1 (range 49-95) and a mean VAS-score of 2.7 ± 1.7 (range 1-6). There were late complications in 8% of the patients. DMMO is effective for treating primary central metatarsalgia unless the ideal harmonious forefoot was not restored. For DMMO the Maestro criteria have no predictive value for clinical outcome in preoperative planning. Further studies are necessary to correlate the functional improvement. Level of evidence: Level IV retrospective case series.

Esta investigación explora la aplicación de motores de pulsos para controlar un péndulo de masas múltiples, o N-péndulo, bajo forzamiento paramétrico que modela el oleaje marino. El N-péndulo, una alternativa más práctica al péndulo simple para la generación eléctrica impulsada por olas, exhibe una dinámica no lineal con un comportamiento estacionario fuertemente influenciado por las condiciones iniciales. Un par de motores de pulsos, posicionados simétricamente respecto a la posición de reposo del péndulo y modelados mediante elementos finitos, generan un par útil incluso desde el reposo, alterando las cuencas de atracción rotacionales. El estudio se centra en cómo los motores de pulso cambian estas cuencas para diferentes condiciones de forzamiento, con el objetivo de aumentar el rango de condiciones iniciales que conducen a rotaciones en estado estacionario.

Abstract Disclosure: R.J. Auchus: Consulting Fee; Self; Corcept Therapeutics, H Lundbeck A/S, Quest Diagnostics, Sparrow Pharmaceuticals, Neurocrine Biosciences, Novo Nordisk, Recordati Rare Diseases, Diurnal, Xeris Pharmaceuticals. Research Investigator; Self; Corcept Therapeutics, Adrenas Therapeutics, Neurocrine Biosciences, Diurnal, Spruce Biosciences. P.J. Trainer: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc.. K.J. Lucas: None. D. Bruera: None. J. Marko: Consulting Fee; Self; Crinetics Pharmaceuticals, Inc. A. Ayala: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. Y. Wu: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. C.T. Ferrara-Cook: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. E. De La Torre: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. A. Krasner: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. H. Lagast: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. R. Luo: Employee; Self; Crinetics Pharmaceuticals Inc.. Stock Owner; Self; Crinetics Pharmaceuticals Inc. T.A. Bachega: Research Investigator; Self; Spruce Biosciences. R.S. Struthers: Employee; Self; Crinetics Pharmaceuticals Inc.. Stock Owner; Self; Crinetics Pharmaceuticals Inc. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. U. Srirangalingam: Consulting Fee; Self; Diurnal, H Lundbeck A/S. Atumelnant (CRN04894) is a potent, once-daily, orally bioavailable, nonpeptide, first-in-class competitive and selective melanocortin type 2 receptor (MC2R, or ACTH receptor) antagonist being developed for the treatment of CAH and ACTH-Dependent Cushing’s Syndrome. Here we report initial results from an open-label, dose-finding phase 2 study of atumelnant in patients with CAH (NCT05907291). Patients (aged ≥18-75, ≥16 years in USA) with classical CAH on a stable dose of GC replacement for at least 6 months were enrolled and received once daily, oral atumelnant for 12 weeks. Key efficacy endpoints include early morning androstenedione (A4) and 17-hydroxyprogesterone (17-OHP) levels. Ten (10) participants have been enrolled and dosed. Data from the first 4 participants (3 females, median age 34 [range 25-42] years, methylprednisone 8 mg/day [hydrocortisone equivalent {HCeq} 32 mg/day, n=2], prednisone 10 mg/day [HCeq 40 mg/day, n=2]) who received 80 mg once daily, oral atumelnant are available. Baseline morning A4 levels in these participants ranged from 116 to 604 ng/dL (reference range [RR]: females 30-200 ng/dL; males 40-150 ng/dL). In these 4 participants, treatment with atumelnant resulted in rapid and profound A4 reductions within 2 weeks which were maintained for the duration of therapy. A4 reductions ranged from 74% to 99% throughout the study. There have been no instances of A4 being above the upper limit of normal on treatment with atumelnant. Baseline 17-OHP levels in these participants ranged from 4740 to 6905 ng/dL (RR: females &amp;lt;80 ng/dL [follicular], &amp;lt;285 ng/dL [luteal]; males &amp;lt;220 ng/dL). In these 4 participants, treatment with atumelnant resulted in rapid and profound 17-OHP reductions within 2 weeks which were maintained for the duration of therapy. 17-OHP reductions ranged from 68% to &amp;gt;99% throughout the study. Two female participants in this cohort menstruated for the first time in over 2 years. Mean baseline morning ACTH ranged from 155 to 1009 pg/mL (RR: 7.2-63 pg/mL), and while modest variations were seen with atumelnant, no consistent directional trend was observed. In conclusion, these data demonstrate rapid, profound, and sustained suppression of A4 and 17-OHP with 80 mg once daily, oral atumelnant. There were no serious or treatment-related adverse events and atumelnant was generally well-tolerated. This ongoing study will explore further the safety and efficacy of various doses of atumelnant. Support: Crinetics Pharmaceuticals, Inc. Presentation: 6/3/2024

Comprehensive and multidisciplinary discharge planning can improve trauma patient throughput, decrease length of hospitalization, increase family and patient support, and expedite hospital discharge. This study aimed to assess the feasibility and acceptability of implementing a patient-centered discharge plan form for adult trauma patients. A single-center pilot study was conducted with adult trauma patients on a neurosurgical medical-surgical floor at a Level II trauma center in the Western United States from January to February 2023. The study had three phases: observation, pilot intervention, and follow-up. The key pilot intervention was the development of a standardized patient-centered discharge plan form, pilot tested by a trauma advanced practice provider and an inpatient discharge nurse. The primary outcome was the frequency of discharge orders being written before noon on the day of discharge. Qualitative and quantitative outcomes are reported. The discharge form was used for eight patients during the pilot intervention phase; an advanced practice provider and an inpatient discharge nurse each completed the forms for four patients. Five of eight observed patients had discharge orders before noon; the incidence of orders before noon was slightly higher when the form was completed by the discharge nurse (three of four patients) than by the advanced practice provider (two of four patients). The pilot study found that the patient-centered discharge plan form was feasible and acceptable to help improve the discharge process for trauma patients. Additional work to further refine the form's content and administration is warranted.

ABSTRACTWe show theoretically that variable production costs reduce systematic risk of firms' cash flows if capital and variable inputs are complementary in firms' production and input prices are procyclical. In our dynamic model, this operating hedge effect is weaker for more profitable firms, giving rise to a gross profitability premium. Moreover, gross profitability and value factors are distinct and negatively correlated, and their premia are not captured by the capital asset pricing model (CAPM). We estimate the model by simulated method of moments, and find that its main implications for stock returns and cash flow dynamics are quantitatively consistent with the data.