Faculty Bibliography

BACKGROUND:Survival rates for highly invasive bladder cancer (BC) patients have been very low, with a 5-year survival rate of 6%. Accurate prediction of tumor progression and survival is important for diagnosis and therapeutic decisions for BC patients. Our study aims to develop an autophagy-related-gene (ARG) signature that helps to predict the survival of BC patients. METHODS:RNA-seq data of 403 BC patients were retrieved from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) database. Univariate Cox regression analysis was performed to identify overall survival (OS)-related ARGs. The Lasso Cox regression model was applied to establish an ARG signature in the TCGA training cohort (N = 203). The performance of the 11-gene ARG signature was further evaluated in a training cohort and an independent validation cohort (N = 200) using Kaplan-Meier OS curve analysis, receiver operating characteristic (ROC) analysis, as well as univariate and multivariate Cox regression analysis. RESULTS:. The ARGs-derived high-risk bladder cancer patients exhibited significantly poor OS in both training and validation cohorts. The prognostic model showed good predictive efficacy, with the area under the ROC curve (AUCs) for 1-year, 3-year, and 5-year overall survival of 0.702 (0.695), 0.744 (0.640), and 0.794 (0.658) in the training and validation cohorts, respectively. A prognostic nomogram, which included the ARGs-derived risk factor, age and stage for eventual clinical translation, was established. CONCLUSION/CONCLUSIONS:We identified a novel ARG signature for risk-stratification and robust prediction of overall survival for BC patients.

BACKGROUND:Although falls are common, costly, and often preventable, emergency department (ED)-initiated fall screening and prevention efforts are rare. The Geriatric Emergency Medicine Applied Research Falls core (GEAR-Falls) was created to identify existing research gaps and to prioritize future fall research foci. METHODS:GEAR's 49 transdisciplinary stakeholders included patients, geriatricians, ED physicians, epidemiologists, health services researchers, and nursing scientists. We derived relevant clinical fall ED questions and summarized the applicable research evidence, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. The highest priority research foci were identified at the GEAR Consensus Conference. RESULTS:We identified two clinical questions for our review (1) fall prevention interventions (32 studies) and (2) risk stratification and falls care plan (19 studies). For (1) 21/32 (66%) of interventions were a falls risk screening assessment and 15/21 (71%) of these were combined with an exercise program or physical therapy. For (2) eleven fall screening tools were identified, but none were feasible and sufficiently accurate for ED patients. For both questions, the most frequently reported study outcome was recurrent falls, but various process and patient/clinician-centered outcomes were used. Outcome ascertainment relied on self-reported falls in 18/32 (56%) studies for (1) and 9/19 (47%) studies for (2). CONCLUSION/CONCLUSIONS:Harmonizing definitions, research methods and outcomes is needed for direct comparison of studies. The need to identify ED-appropriate fall risk assessment tools and role of Emergency Medical Services (EMS) personnel persists. Multifactorial interventions, especially involving exercise, are more efficacious in reducing recurrent falls, but more studies are needed to compare appropriate bundle combinations. GEAR prioritizes Five research priorities: (1) EMS role in improving fall-related outcomes, (2) identifying optimal ED fall assessment tools, (3) clarifying patient-prioritized fall interventions and outcomes, (4) standardizing uniform fall ascertainment and measured outcomes, and (5) exploring ideal intervention components.

We studied mortality in tuberous sclerosis complex (TSC) by analyzing data from the Tuberous Sclerosis Alliance Natural History Database of 2233 patients from 18 United States TSC centers. Among 31 decedents with data; mean age of death was 29 years. Cause of death could be determined in 26 cases: 11 definitely related to TSC, 14 possibly related to TSC, and 1 unrelated to TSC. Causes of death included SUDEP in 11 (35.5%; Definite (5), Probable (4), Possible (2)), respiratory conditions in 6 (23.1%; lymphangiomyelomatosis in one), tumors in 3 (11.5%), suicide in 2 (7.7%), cardiopulmonary in 2 (7.7%), shunt malfunction in one, and drowning in one. For SUDEP cases, mean age of epilepsy onset was 7 months and 10/11 were treated with multiple anti-seizure medications (ASMs) at death; 7 had intractable epilepsy and 3 were controlled with ASMs. Patients with TSC and their families should be counseled about ASM adherence and lifestyle factors, and the potential role of nocturnal supervision or seizure detection devices to prevent SUDEP.

Rett syndrome (RTT) is a rare neurodevelopmental disorder that is usually caused by mutations of the MECP2 gene. Patients with RTT suffer from severe deficits in motor, perceptual and cognitive domains. Electroencephalogram (EEG) has provided useful information to clinicians and scientists, from the very first descriptions of RTT, and yet no reliable neurophysiological biomarkers related to the pathophysiology of the disorder or symptom severity have been identified to date. To identify consistently observed and potentially informative EEG characteristics of RTT pathophysiology, and ascertain areas most worthy of further systematic investigation, here we review the literature for EEG abnormalities reported in patients with RTT and in its disease models. While pointing to some promising potential EEG biomarkers of RTT, our review identify areas of need to realize the potential of EEG including (1) quantitative investigation of promising clinical-EEG observations in RTT, e.g., shift of mu rhythm frequency and EEG during sleep; (2) closer alignment of approaches between patients with RTT and its animal models to strengthen the translational significance of the work (e.g., EEG measurements and behavioral states); (3) establishment of large-scale consortium research, to provide adequate Ns to investigate age and genotype effects.

INTRODUCTION/BACKGROUND:STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. METHODS:Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. RESULTS:In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7-63.4%) and 73.6% (95% CI 66.2-80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0-89.9%) and 91.9% (95% CI 86.4-95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54-9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15-0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05-0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. CONCLUSION/CONCLUSIONS:These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier NCT01485003.

Axial disorders, including postural deformities, postural instability, and gait disturbances, are among the most disabling symptoms of Parkinson's disease (PD). Equistasi®, a wearable proprioceptive stabilizer device, has been proposed as neurological rehabilitative device for this set of symptoms. To investigate the effects of the device on gait and balance, 24 participants affected by PD were enrolled in this crossover double-dummy, randomized, controlled study. Subjects were assessed four times before and after 8 weeks treatment with either active or placebo device; one-month wash-out was taken between treatments, in a 20-week timeframe. Gait analysis and instrumented Romberg test were performed with the aid of a sterofotogrammetric system and two force plates. Joint kinematics, spatiotemporal parameters of gait and center of pressure parameters were extracted. Paired T-test (p < 0.05) was adopted after evidence of normality to compare the variables across different acquisition sessions; Wilcoxon was adopted for non-normal distributions. Before and after the treatment with the active device, statistically significant improvements were observed in trunk flexion extension and in the ankle dorsi-plantarflexion. Regarding balance assessment, significant improvements were reported at the frequencies corresponding to vestibular system. These findings may open new possibilities on PD's rehabilitative interventions. Research question, tailored design of the study, experimental acquisition overview, main findings, and conclusions.

Virtual portion tasks have been used to predict food intake in healthy individuals, severity of illness in individuals with anorexia nervosa, and weight loss in bariatric surgery patients. Whether portion creation in response to a recalled interpersonal stress ("recalled stress portions") could be used as a proxy for ad lib intake, after a stressor, remains untested, and the mechanism supporting this relationship is unclear. The present study's goals were: 1) to validate virtual portion tasks as proxies for actual food intake in a stressful context and 2) to test a causal pathway in which these virtual stress portions predict ad lib intake after stress. We proposed that this relationship is mediated by virtual portions created the moment after laboratory stress or rest manipulation (momentary portions), and before the participant actually ate food. At screening, 29 healthy undergraduate white women created virtual portions of eight snacks (apples, olives, potato chips, pretzels, caramel popcorn, milk chocolate) that they typically eat and also portions they recall eating in response to a stressful interpersonal situation. In addition, after a Trier Social Stress Test, or a rest period, on separate days in counterbalanced order, participants created 'momentary' virtual portions of the same snacks presented during screening, and then were given potato chips, mini golden Oreos, and M&Ms to eat. Recalled stress (b = 0.07 ± 0.02, p = 0.003), and momentary stress (b = 0.12 ± 0.02, p = 0.00001), portions of milk chocolate accounted for 29% and 51%, respectively, of the variance in ad lib stress intake of M&Ms. Typical (b = 0.15 ± 0.07, p = 0.03), and momentary rest (b = 0.21 ± 0.06, p = 0.002), portions of chips accounted for 16% and 31%, respectively, of the variance in ad lib rest intake of chips. The causal pathway from recalled stress portion to ad lib stress snack intake was completely mediated by momentary stress portion for milk chocolate and M&Ms (β = 0.04 ± 0.02, z = 2.4, p = 0.0154). These findings illustrate the planning and recall components of eating in response to stress, but not necessarily under rest conditions. This recalled stress virtual portion paradigm has clinical and research value in that it can detect those who overconsume in response to stress.

INTRODUCTION/BACKGROUND:Flow diverters such as the pipeline embolization device (PED) cause hemodynamic changes of the treated vessel segment. In posterior communicating artery (PcomA), aneurysms' unique anatomic consideration have to be taken in account due to the connection between the anterior and posterior circulation. We hypothesize that in conjunction with PcomA remodeling, there will also be remodeling of the ipsilateral P1 segment of the posterior cerebral artery (PCA) after PED treatment for PcomA aneurysms. METHODS:We retrospectively collected radiological as well as clinical data of PcomA aneurysm patients treated with PED including PcomA and P1 vessel diameters before and after treatment as well as patient and aneurysm characteristics. RESULTS:= 0.042). There were no neurologic complications on LFU. CONCLUSION/CONCLUSIONS:In the treatment of PcomA aneurysms with PED, the P1 segment of the PCA increases in diameter while the PcomA diameter decreases. Our results suggest that this remodeling effect is associated with aneurysm occlusion and decrease of PcomA is hemodynamically compensated for by an increase in the ipsilateral P1 diameter.