洛约拉大学医学中心

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder caused by germline inactivation of the folliculin gene (FLCN). Approximately 25

ABSTRACT:Clinical trial eligibility criteria select a target population and reduce anticipated risks for participants but may unnecessarily limit participation both overall and differently across demographic groups. We previously abstracted eligibility criteria for 190 phase 2/3 acute myeloid leukemia (AML) trials and used US Food and Drug Administration and professional society guidance on modernizing criteria to develop alternative, safety-based eligibility criteria for each trial. In this analysis, these trial- and safety-based eligibility criteria sets were applied to a retrospective cohort of 2226 newly diagnosed patients across 8 hospitals to assess the impact on eligibility. Eligibility proportions increased from a median of 47.9% with trial-based criteria to 84.2% with safety-based criteria (median difference, 30.0%; P< .001); excluding age criteria, the increase was 11.5% (P< .001). Non-Hispanic (NH) Asian, NH Black, NH White, and Hispanic patients were eligible for median proportions of 41.1%, 44.0%, 47.9%, and 50.0%, respectively, with trial-based criteria, increasing by 27.9% to 31.6% when using safety-based criteria (within-group changes, all P< .001; between-group changes, all P> .05). Excluding age criteria, increases were between 10.0% and 11.9%. Moving from trial- to safety-based criteria decreased the proportion of trials with significant eligibility differences between NH White and NH Asian (-11.1%), NH Black (-4.2%), and Hispanic (-12.1%) patients. Criteria significantly associated with increased eligibility and decreased between-group differences in eligibility were coronary artery disease, congestive heart failure, aspartate transaminase level, upper age limits, and previous malignancy. These data suggest that modernization of eligibility for AML trials to focus on safety-based criteria can improve both overall enrollment and population representation.

Abstract Purpose The Ki-67 proliferation index (Ki-67 PI) has been associated with meningioma recurrence, yet its clinical utility remains debated. Whether Ki-67 PI provides prognostic information across subgroups defined by both WHO grade and extent of resection remains to be investigated. Methods We analyzed 5,050 patients with intracranial meningiomas from the international PERNS cohort (42 centers, diagnosed between 1989–2019) who underwent surgical resection without postoperative radiotherapy. Ki-67 PI prognostic accuracy was assessed up to 10 years postoperatively by using ROC analyses and estimating its association with the risk of recurrence. Results Results demonstrated that the prognostic value of Ki-67 PI differed by subgroups defined by WHO grade and Simpson grade. For patients with the same Simpson grade (1–3), the predictive accuracy of Ki-67 PI for 10-year recurrence risk was stronger in WHO-2 than in WHO-1. Within WHO-1 and WHO-2 meningiomas, the predictive accuracy of Ki-67 PI increased with higher Simpson grade (1–3). However, no predictive value was observed in Simpson grade 4 resections regardless of WHO grade. Conclusion These findings highlight that Ki-67 PI should be interpreted in the context of both WHO grade and extent of resection, and, if done so, may offer potential value to refine individualized surveillance strategies in meningioma patients with gross total resection in the initial 10-year postoperative timeframe. Findings cannot be extrapolated beyond 10 years, which may be particularly relevant for WHO-1 tumors with low Ki-67 PI and Simpson grade 1 resection.

INTRODUCTION:The purpose of this scoping review was to determine if there is an association between sleep patterns, as measured by sleep actigraphy, and athletic injuries and performance. METHODS:Studies were included from Pubmed, Embase, and SPORTDiscus, if they measured sleep using actigraphy, evaluated sports injuries and athletic performance. Systematic reviews, narrative reviews, and those not using actigraphy or which focused on concussions instead of other sports injuries were excluded. RESULTS:A total of 17 studies met inclusion criteria, examining athletes from 10 different sports. Of the seven studies evaluating the relationship between sleep metrics (sleep latency, efficiency, duration, wake after sleep onset) and injury occurrence, four studies (57%) found that decreased sleep correlated with increased injury occurrence in elite soccer, paralympic, and adolescent track and field athletes. Eight studies (47%) evaluated the relationship between sleep metrics and performance (reaction time, sports specific tasks, aerobic, and anaerobic capacity), finding that decreased sleep metrics correlated with decreased aerobic and anaerobic performance in rugby athletes, cyclists, triathletes, mixed martial arts (MMA), and Dutch elite youth athletes. CONCLUSION:Findings of this study show that there is no consensus on the relationship between the amount or quality of sleep and rates of sports-related injuries in adult athletes. Poor sleep metrics (total sleep time/duration, latency, and efficiency) were correlated with a decrease in response time in cyclists and Dutch elite youth athletes. Worsened sleep metrics were also found to decrease aerobic performance in physically active males, MMA fighters, rugby players, triathletes, and cyclists. In summary, these findings suggest that there is an association between poor sleep and worsened athletic performance, but the evidence for injury risk is inconclusive.