Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.     

Braden scale for pressure ulcer risk predicts rehabilitation placement after pancreatic resection

BackgroundPatients undergoing pancreatic resection frequently require rehabilitation facilities after hospital discharge. We evaluated the predictive role of validated markers of frailty on rehabilitation facility placement to identify patients who may require this service.MethodsSingle-center retrospective cohort study of patients who underwent pancreatic resection from 2010 to 2015. 90-day morbidity and mortality were calculated. Postoperative validated markers of frailty (Activities of Daily Living scale, Braden scale [assesses pressure ulcer risk, lower scores = higher risk] and Morse fall scale) were evaluated via multivariate regression to identify predictors of discharge to rehabilitation facility.Results470 patients with complete data were included. Mean age was 62 and 49.2% were male. Postoperative median length of stay (LOS) was 8 (IQR 7–10). 92 (19.66%) patients were discharged to rehabilitation facilities and 138 (29.49%) patients were readmitted within 90 days. On multivariate analysis, age, sex, LOS > 8 days, inpatient Comprehensive Complication Index (CCI) and initial Braden scale were predictive of rehabilitation placement.ConclusionA marker of frailty routinely collected daily by nursing staff, the Braden scale, is available to help surgeons predict the need for postoperative rehabilitation placement after pancreatic resection. Engaging discharge planning services for at-risk patients may help prevent delayed hospital discharge and should be further evaluated.     

Slower Skeletal Muscle Oxygenation Kinetics in Adults With Complex Congenital Heart Disease

BackgroundAdults with complex congenital heart disease (CHD) show reduced aerobic exercise capacity and impaired skeletal muscle function compared with healthy peers. Peripheral muscle factors are presumed to be important contributors to the aerobic capacity, but the mechanisms are poorly understood. The aim of the present study was to investigate differences between adults with CHD and controls in muscle oxygenation kinetics at rest, and during and after exercise.MethodsSeventy-four patients with complex CHD (mean age 35.6 ± 14.3 years, female n = 22) were recruited. Seventy-four age- and sex-matched subjects were recruited as controls. Muscle oxygenation was successfully determined on the anterior portion of the deltoid muscle using near-infrared spectroscopy in 65 patients and 71 controls. Measurements were made at rest, during isotonic shoulder flexions (0-90°) to exhaustion, and during recovery.ResultsThe patients with CHD performed fewer shoulder flexions (40 ± 17 vs 69 ± 40; P < 0.001), had lower muscle oxygen saturation (StO₂) at rest (58 ± 18% vs 69 ± 18%; P < 0.001), slower desaturation rate at exercise onset (?9.7 ± 5.9 vs ?15.1 ± 6.5% StO₂ × 3.5 s^?1, P <0.001), and slower resaturation rate post exercise (4.0 ± 2.7 vs 5.4 ± 3.6% StO₂ × 3.5 s^?1; P = 0.009) compared with the controls.ConclusionsIn comparison with age- and sex-matched controls, adults with complex CHD had slower oxygenation kinetics. This altered skeletal muscle metabolism might contribute to the impaired skeletal muscle endurance capacity shown and thereby also to the reduced aerobic capacity in this population.