Citations

AbstractBackgroundIt is important to determine the natural history of sporadic and familial frontotemporal lobar degeneration (FTLD) and generate clinical, neuropsychological, neuroimaging and biofluid data for planning disease‐modifying trials.MethodAs part of the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD; U19 AG063911) protocol, investigators at 19 centers in North America will enroll 2100 participants with FTLD over the next 5 years beginning in early 2020.ResultAs of 1/20/20, the ARTFL/LEFFTDS (A/L) Consortium had enrolled 1832 participants, including 850 in kindreds with familial FTLD (239 associated with mutations in MAPT, 192 in GRN, 370 in C9orf72, 4 with mutations in both GRN and C9orf72, and 45 with a mutation in a different gene or no mutation in any known FTLD‐associated gene). Over 500 participants have undergone 2 or more annual visits to date. MRI has been performed in 1105. Biofluid samples have also been collected, with blood (DNA, plasma, serum, mRNA, PBMC) in 1413 and CSF in 303. Over 60 manuscripts using A/L data or samples have been published to date. Five clinical trials involving A/L and ALLFTD participants are in progress or planned. The longitudinal arm in ALLFTD will enroll 500 of existing A/L and 600 future participants for annual assessments with similar methodology to A/L. An additional 1000 FTLD patients will undergo focused one‐time clinical evaluations and biofluid collection.ConclusionThe data/samples from already‐enrolled and planned participants in ALLFTD and findings published to date underscore the utility of evaluating FTLD subjects. The absence of identifiable mutations in some with familial FTLD suggests that other genes are yet to be discovered. ALLFTD data will inform clinical trial design, and many participants will be eligible for future trials. The key data and samples in ALLFTD are available to interested investigators worldwide. Supported by: AG063911, AG045390, NS092089, AG016976, AG21886.

ObjectiveThe purpose of this study was to investigate the impact of obesity on disease activity and disease outcome in patients with inflammatory bowel disease.Patients and methodsThe impact of obesity on inflammatory bowel disease disease activity and outcome was retrospectively assessed in 3075 patients enrolled in the prospective nation‐wide Swiss inflammatory bowel disease cohort between July 2006 and September 2018. Baseline characteristics, disease activity and disease course in 325 obese inflammatory bowel disease patients (body mass index ≥30 kg/m2) were compared to 1725 normal weight inflammatory bowel disease individuals (body mass index 18.5‐24.9).ResultsAmong 3075 patients in the prospective Swiss inflammatory bowel disease cohort, 325 patients (10.6%) were obese, namely, 194 Crohn’s disease patients, 131 ulcerative colitis, and inflammatory bowel disease‐unclassified patients. Disease activity scores were elevated in obese Crohn’s disease (Crohn’s Disease Activity Index 33 vs 20, p = 0.001), but not ulcerative colitis patients. Obese Crohn’s disease, but not ulcerative colitis patients were less likely to be in remission based on a Crohn’s Disease Activity Index less than 100 and a calprotectin less than 100 ug/g. In a multivariate regression model, obesity was negatively associated with disease remission in Crohn’s disease (odds ratio 0.610, 95% confidence interval 0.402–0.926, p = 0.020), but not ulcerative colitis. Increased soft stool frequency was observed in both obese Crohn’s disease and ulcerative colitis patients. Adjusted Cox regression models revealed increased risk of complicated disease course in obese Crohn’s disease patients (hazard ratio 1.197, 95% confidence interval 1.046–1.370, p = 0.009). No association between obesity and disease progression, index treatment failure was seen neither in Crohn’s disease nor ulcerative colitis.ConclusionObesity is associated with decreased rates of disease remission and increased risk of complicated disease course in Crohn’s disease over a six‐year follow‐up period. No effects were seen on disease progression and index treatment failure neither in Crohn’s disease nor ulcerative colitis.

Abstract Background Recurrent pleomorphic adenoma (PA) can be a lifelong disease, and rates of subsequent recurrence are high. Methods Patients between 2000 and 2015 were identified. Primary outcome was subsequent recurrence after surgical salvage. Results Twenty‐seven of 84 patients developed a subsequent recurrence. Risk factors for subsequent recurrence included a higher number of previous recurrences ( P < .01), worse preoperative facial nerve function ( P < .01), and deep parotid lesion(s) ( P < .01). Interval since last surgery was protective ( P < .01), specifically >10 years since last surgery ( P < .01). For patients with a >10‐year interval since their last surgery, the subsequent recurrence‐free rate at 10 years follow‐up was 80.2% vs 31.8%. Conclusions For patients presenting with a >10‐year interval since their last surgery, subsequent recurrence rates are low, which may allow for as needed surveillance recommendations. For patients presenting with recurrent PA and ≤10 years since their last surgery, a closer surveillance is warranted.

Zebrafish are being increasingly used as animal models for human diseases such as cardiomyopathy and neuroblastoma because zebrafish have a nearly fully sequenced genome to humans. One pilot study is to develop zebrafish echocardiography. Because the heart of a zebrafish is small, a high frequency ultrasound system (50–80 MHz) is used for imaging. B-Mode imaging is analyzed for quantification of ejection fraction (EF), end-systolic volume (ESV), and end-diastolic volume (EDV). Pulse-wave Doppler (PWD) is used to calculate the E/A ratio (the peak velocities of E and A waves) and myocardial performance index (MPI). Techniques for improving image quality and repeatability of zebrafish echocardiography are discussed. Another pilot study is to develop zebrafish ultrasound vibro-elastography (ZUVE) for measuring the elastic properties of zebrafish. An adult female zebrafish is anesthetized for 3 min. A 0.1-s gentle harmonic vibration is generated on the tail of a zebrafish using a sphere tip indenter with a 3 mm diameter. Shear wave propagation in the zebrafish is measured using a high frequency 18 MHz ultrasound linear array probe. We conclude that ZUVE is safe, fast, and noninvasive and feasible for testing the elastic properties of zebrafish.

AbstractObjectiveMAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach.MethodsWe studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel‐based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype.ResultsSymptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers.InterpretationA subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.

Objective: To assess the efficacy and safety of closed-loop control (CLC) insulin delivery system in adolescents and young adults with type 1 diabetes. Research Design and Methods: Prespecified subanalysis of outcomes in adolescents and young adults aged 14–24 years old with type 1 diabetes in a previously published 6-month multicenter randomized trial. Participants were randomly assigned 2:1 to CLC (Tandem Control-IQ) or sensor augmented pump (SAP, various pumps+Dexcom G6 CGM) and followed for 6 months. Results: Mean age of the 63 participants was 17 years, median type 1 diabetes duration was 7 years, and mean baseline HbA1c was 8.1%. All 63 completed the trial. Time in range (TIR) increased by 13% with CLC versus decreasing by 1% with SAP (adjusted treatment group difference = +13% [+3.1 h/day]; 95% confidence interval [CI] 9–16, P < 0.001), which largely reflected a reduction in time >180 mg/dL (adjusted difference −12% [−2.9 h/day], P < 0.001). Time <70 mg/dL decreased by 1.6% with CLC versus 0.3% with SAP (adjusted difference −0.7% [−10 min/day], 95% CI −1.0% to −0.2%, P = 0.002). CLC use averaged 89% of the time for 6 months. The mean adjusted difference in HbA1c after 6 months was 0.30% in CLC versus SAP (95% CI −0.67 to +0.08, P = 0.13). There was one diabetic ketoacidosis episode in the CLC group. Conclusions: CLC use for 6 months was substantial and associated with improved TIR and reduced hypoglycemia in adolescents and young adults with type 1 diabetes. Thus, CLC has the potential to improve glycemic outcomes in this challenging age group. The clinical trial was registered with ClinicalTrials.gov (NCT03563313).