Citations

AbstractIntroductionPhospholipids are altered in brains of patients with dementia and some studies suggest their plasma levels may be useful in the detection of mild cognitive impairment (MCI) and dementia.MethodsWe measured 188 plasma metabolites in participants who underwent a detailed neuropsychological assessment and classified as normal (n = 153), MCI (n = 145), or dementia (n = 143) by expert adjudication.ResultsAmong 10 phospholipids recently implicated as altered in dementia, higher concentration of PC aa C36:6 was significantly associated with decreased prevalence of dementia (odds ratio = 0.71, 95% confidence interval = 0.50–1.00 per 1−SD increase). Adding these phospholipids to a model including multiple predictors of dementia led to only minimal improvement in detection (C statistic changed from 0.702 to 0.71).DiscussionSome phospholipids and metabolites were altered in MCI and dementia but cross‐sectional association was relatively weak and did not improve detection of MCI and dementia beyond information provided by clinical variables.

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1 + CD11a hi CD8 + ) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8 + T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility.

AbstractIntroductionThe impact of blood pressure on brain volumes may be time‐dependent or pattern‐dependent.MethodsOf 1678 participants from the Atherosclerosis Risk in Communities Neurocognitive Study, we quantified the association between measures and patterns of blood pressure over three time points (∼24 or ∼15 years prior and concurrent with neuroimaging) with late life brain volumes.ResultsHigher diastolic blood pressure ∼24 years prior, higher systolic and pulse pressure ∼15 years prior, and consistently elevated or rising systolic blood pressure from ∼15 years prior to concurrent with neuroimaging, but not blood pressures measured concurrent with neuroimaging, were associated with smaller volumes. The pattern of hypertension ∼15 years prior and hypotension concurrent with neuroimaging was associated with smaller volumes in regions preferentially affected by Alzheimer's disease (e.g., hippocampus: −0.27 standard units, 95% CI: −0.51, −0.03).DiscussionHypertension 15 to 24 years prior is relevant to current brain volumes. Hypertension followed by hypotension appears particularly detrimental.

Objectives/HypothesisTo present an overview of the barriers to the implementation of clinical practice guidelines (CPGs) in thyroid cancer management and to introduce a computer‐based clinical support system.Data SourcesPubMed.Review Methods: A review of studies on adherence to CPGs was conducted.ResultsAwareness and adoption of CPGs is low in thyroid cancer management. Barriers to implementation include unfamiliarity with the CPGs and financial concerns. Effective interventions to improve adherence are possible, especially when they are readily accessible at the point of care delivery. Computerized clinical support systems show particular promise. The authors introduce the clinical decision making modules (CDMMs) of the Thyroid Cancer Care Collaborative, a thyroid cancer‐specific electronic health record. These computer‐based modules can assist clinicians with implementation of these recommendations in clinical practice.ConclusionComputer‐based support systems can help clinicians understand and adopt the thyroid cancer CPGs. By integrating patient characteristics and guidelines at the point of care delivery, the CDMMs can improve adherence to the guidelines and help clinicians provide high‐quality, evidence‐based, and individualized patient care in the management of differentiated thyroid cancer. Laryngoscope, 126:2640–2645, 2016

AbstractGenetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high‐ (≥7 Gleason score) versus low‐grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916‐T variant in 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.

Background: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. Materials and Methods: Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. Results: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. Conclusions: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

The legacy of human-Neandertal interbreeding Non-African humans are estimated to have inherited on average 1.5 to 4% of their genomes from Neandertals. However, how this genetic legacy affects human traits is unknown. Simonti et al. combined genotyping data with electronic health records. Individual Neandertal alleles were correlated with clinically relevant phenotypes in individuals of European descent. These archaic genetic variants were associated with medical conditions affecting the skin, the blood, and the risk of depression. Science , this issue p. 737