LOWER EXTREMITY JOINT LOADING IS ALTERED IN PEOPLE WITH MARFAN SYNDROME DURING A SIT-TO-STAND TASK

Justin Pol, Christopher McLouth, Mariana Jacobs, Mary Sheppard, Michael A. Samaan. University of Kentucky, Lexington, KY. BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that negatively impacts the musculoskeletal system. Previous work has shown decreased quadricep/hamstring strength in people with MFS compared to healthy individuals. However, the impact of MFS on activities of daily living such as a sit-to-stand (STS) are not well understood. The purpose of this study was to evaluate joint loading in people with MFS during a STS task. We hypothesize that people with MFS will perform the STS task with abnormal knee joint loading. METHODS: Ten people with MFS (20 limbs, 9F, age:36.5±7.54 yrs) were age, sex and BMI-matched to 10 healthy asymptomatic individuals (20 limbs, 9F, age:29.5±7.34 yrs). Participants were asked to perform 5 repetitions of the STS task at a self-selected pace starting from a seated position. Peak internal hip, knee and ankle joint extensor moments (Nm•kg-1), the total support moment (TSM; Nm•kg-1) and the hip, knee and ankle joint percent contributions to the TSM during the STS task were assessed. In order to account for the correlation between right and left limbs (bilateral samples), a linear mixed model was used to assess group differences in lower extremity joint loading parameters (p\u3c0.05). RESULTS: Compared to healthy individuals, people with MFS exhibit 1.12x higher peak ankle plantarflexor moment (p=0.002), 1.34x higher TSM (p=0.002), 6.3% less hip contribution to TSM, and 9.6% higher ankle contribution to TSM (p=0.007). No differences were observed in hip and knee joint moments or the percent knee joint contribution to the TSM (p\u3e0.05). CONCLUSIONS: People with MFS perform the STS task utilizing altered joint loading patterns compared to healthy individuals. The overall increase in TSM in people with MFS indicates a higher lower extremity muscular demand to successfully perform the STS task. In order to successfully perform the STS task, the MFS group utilized a larger ankle joint contribution to the TSM and higher plantarflexor moment to compensate for the lower hip joint contribution to the TSM. Our study results suggest altered lower extremity mechanics during a STS task in people with MFS that may be associated with abnormal hip and ankle muscle function. Future work will focus on understanding the role of the hip and ankle joint musculature on lower extremity joint loading patterns in people with MFS

VAERS reported new-onset seizures following use of Covid 19 vaccinations as compared to influenza vaccinations

The incidence of new-onset seizures, which we defined as de novo seizures occurring within four weeks of receiving any of the FDA-approved Covid 19 vaccinations as reported in patient-reported data compiled in the US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data (CDC VAERS) has not been explored. The VAERS database contains de-identified patient-reported adverse events following vaccinations and represents post-marketing surveillance and analysis of vaccine safety. After adjusting for time at risk, this resulted in estimated incidence rates of 3.19 seizures per 100,000 persons per year for the Covid 19 vaccine and 0.090 seizures per 100,000 persons per year. A data-driven, individualized dataset that is comprehensive and coupled with a longitudinal follow-up in larger numbers of vaccinated individuals is needed to expand on our preliminary findings of vaccine-related seizures

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer

Purpose: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. Experimental design: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/− salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. Results: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1–2), 25% nausea (grade 1–2), and 20% fatigue (grade 1–2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). Conclusion: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies