Resistance to thyroid hormone induced tachycardia in RTHα syndrome.

Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.

Trends in, and predictors of, swallowing and social eating outcomes in head and neck cancer survivors: A longitudinal analysis of head and neck 5000.

OBJECTIVE: To investigate the recovery trajectory and predictors of outcome for swallowing difficulties following head and neck cancer treatment in a large prospective cohort. MATERIALS AND METHODS: Data from 5404 participants of the Head and Neck 5000 study were collected from 2011 to 2014. Patient-reported swallowing was measured using the EORTC HN35, recorded at baseline (pre-treatment) and 4 and 12 months post-baseline. Mixed-effects linear multivariable regression was used to investigate time trends, compare cancer sites, and identify associations between clinical, socio-demographic and lifestyle variables. RESULTS: 2458 participants with non-recurrent oral (29%) oropharyngeal (46%) and laryngeal (25%) cancer were included in the analysis. There was a clinically significant deterioration in scores between baseline and four months for swallowing (11.7 points; 95% CI 10.7-12.8) and trouble with social eating (17.9 points; 95% CI 16.7-19.2), but minimal difference between baseline and 12 months. Predictors of better swallowing and social eating were participants with larynx cancer, early-stage disease, treatment type, age, gender, co-morbidity, socio-economic status, smoking behaviour and cohabitation. CONCLUSION: Swallowing problems persist up to a year after head and neck cancer treatment. These findings identify disease and demographic characteristics for particularly vulnerable groups, supporting the need for holistic interventions to help improve swallowing outcomes. People diagnosed with head and neck cancer at risk of severe eating and drinking problems following treatment can be identified earlier in the pathway, receive more accurate information about early and late post-treatment side-effects, which can inform shared decision-making discussions.

ACR Appropriateness Criteria® Movement Disorders and Neurodegenerative Diseases.

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. This document summarizes the imaging appropriateness data for rapidly progressive dementia, chorea, Parkinsonian syndromes, suspected neurodegeneration with brain iron accumulation, and suspected motor neuron disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Diabetes Self-Management Education and Medical Nutrition Therapy: A Multisite Study Documenting the Efficacy of Registered Dietitian Nutritionist Interventions in the Management of Glycemic Control and Diabetic Dyslipidemia through Retrospective Chart Review.

BACKGROUND: Diabetes self-management education (DSME) and medical nutrition therapy (MNT) improve glycemic control and reduce risk of chronic comorbid disease. OBJECTIVE: Document outcomes for patients with type 2 diabetes (T2D) completing DSME and MNT through American Diabetes Association-recognized programs. DESIGN: Descriptive, retrospective chart review. PARTICIPANTS/SETTING: Four random samples of 100 records of patients with T2D completing DSME and MNT at each of four regional centers in Alabama, June 2013 to 2014, were chosen for review; after exclusions, 392 records were retained. OUTCOME MEASURES: Weight, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol, low-density lipoprotein, high-density lipoproteins (HDL), triglycerides (TG), and TG-to-HDL ratio. ANALYSIS: Mixed-model analysis of variance was used to determine differences between continuous variables. McNemar test was used to assess frequency of patients reaching glycemic targets. Paired t tests were used to determine significance of lipid parameters. RESULTS: Significant reductions were observed at end of program and 1 year in weight (2.67±5.54 kg, P<0.001; 2.25±5.45 kg, P=0.001), BMI (0.93±1.91, P<0.001; 0.76±1.93, P=0.001), and HbA1c (1.82%±2.23%, P<0.001; 1.22%±2.15%, P<0.001). Patients managed by diet alone had a mean baseline HbA1c of 6.95% and exhibited a 0.8% reduction in HbA1c (P<0.001) at end of program. Those managed with diet plus drug therapy had a baseline HbA1c of 9% and exhibited a 2.09% reduction in HbA1c (P<0.001). Following DSME and MNT, 62% of patients reached glycemic targets (HcA1c≤7%), as compared with 32% at baseline (P<0.001). Significant reductions in TG were observed from baseline (162±74 mg/dL [4.19±1.91 mmol/L]) to follow-up (109±36 mg/dL [2.82±0.92 mmol/L]) (P<0.001). HDL increased from baseline (45±13 mg/dL [1.16±0.34 mmol/L]) to follow-up (48±11 mg/dL [1.24±0.28 mmol/L]) (P=0.05). The TG-to-HDL ratio improved from a baseline of 4.07±2.41 to 2.48±1.26 at follow-up (P<0.001). CONCLUSIONS: Reductions were observed in weight, BMI, HbA1c, TG, and TG-to-HDL ratio. Improved patient outcomes were achieved in the clinical setting and support universal coverage to increase patient access to DSME and MNT.