Search

Exercise and dietary (EX+D) interventions could represent an optimal treatment for attenuating or reversing adverse effects of androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. The Individualized Diet and Exercise Adherence-Pilot (IDEA-P) trial compared the effects of an EX+D intervention relative to standard-of-care (SC) treatment among PCa patients undergoing ADT. The present study evaluated the effects of the EX+D intervention on body composition (BC) obtained via dual-energy X-ray absorptiometry (DXA) in a subsample of IDEA-P patients. A secondary objective was to explore the association of adiposity and lean mass with mobility performance and strength.Complete DXA data were acquired from a subsample of 22 PCa patients (EX+D:Intention-to-treat analysis revealed EX+D resulted in significant improvements in fat mass (Findings suggest the EX+D intervention resulted in superior preservation of lean tissue and improvement in adiposity relative to SC treatment. Results underscore the utility of implementing EX+D interventions for preserving muscle mass and reducing adiposity in PCa patients undergoing ADT.

Being overweight or obese is a primary modifiable risk factor that exacerbates disease progression and mobility disability in older knee osteoarthritis (OA) patients. Lifestyle interventions combining exercise with dietary weight loss (EX+DWL) yield meaningful improvements in mobility and weight loss that are superior to EX or DWL alone. Unfortunately, community access to practical, sustainable weight management interventions remains limited and places knee OA patients at increased risk of mobility disability. The Collaborative Lifestyle Intervention Program in Knee Osteoarthritis patients (CLIP-OA), was a two-arm, 18 month randomized-controlled, comparative effectiveness trial designed to contrast the effects of an evidence-based, theory-driven EX+DWL intervention, personalized to patient needs and delivered by our community partners, with those of the Arthritis Foundation’s Walk With Ease (WWE) standard of care self-management program in the treatment of knee OA patients with overweight or obesity. The primary outcome of the CLIP-OA trial was mobility performance assessed using the 400-m walk test (400MWT). Secondary outcomes included weight loss, pain, select quality of life and social cognitive variables, and cost-effectiveness of intervention delivery. Findings from the CLIP-OA trial will determine the comparative and cost-effectiveness of the EX+DWL and WWE interventions on key clinical outcomes and has the potential to offer a sustainable medium for intervention delivery that can promote widely accessible weight management among knee OA patients with overweight or obesity. Trial Registration: NCT02835326.

Background: Ketogenic diets (KDs) that elevate beta-hydroxybutyrate (BHB) promote weight and fat loss. Exogenous ketones, such as ketone salts (KS), also elevate BHB concentrations with the potential to protect against muscle loss during caloric restriction. Whether augmenting ketosis with KS impacts body composition responses to a well-formulated KD remains unknown.Purpose: To explore the effects of energy-matched, hypocaloric KD feeding (Methods: Overweight and obese adults were provided a precisely defined hypocaloric KD (~75% of energy expenditure) for 6 weeks. In a double-blind manner, subjects were randomly assigned to receive ~24 g/day of a racemic BHB-salt (KD + KS; n = 12) or placebo (KD + PL; n = 13). A matched comparison group (n = 12) was separately assigned to an isoenergetic/isonitrogenous low-fat diet (LFD). Body composition parameters were assessed by dual x-ray absorptiometry and magnetic resonance imaging.Results: The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study (p < 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks (p < 0.05). There were decreases in body mass, whole body fat and lean mass, mid-thigh muscle cross-sectional area, and both visceral and subcutaneous adipose tissues (p < 0.001), but no group differences between the two KDs or with the LFD. Urine nitrogen excretion was significantly higher in KD + PL than LFD (p < 0.01) and trended higher in KD + PL compared to KD + KS (p = 0.076), whereas the nitrogen excretion during KD + KS was similar to LFD (p > 0.05).Conclusion: Energy-matched hypocaloric ketogenic diets favorably affected body composition but were not further impacted by administration of an exogenous BHB-salt that augmented ketosis. The trend for less nitrogen loss with the BHB-salt, if manifested over a longer period of time, may contribute to preserved lean mass.

Introduction The caregiver role for patients with an LVAD is so critical that most LVAD programs in the United States will not implant the device if the patient has not identified a dedicated and capable caregiver. We aimed to describe caregiver characteristics and understand their unique experiences through a multicenter survey. Methods We designed an online and print survey consisting of 32 questions. Participants were recruited from 5 LVAD programs across the United States. Caregivers were eligible to participate if they were identified as providing care for a patient with an LVAD. Survey results were compiled and analyzed using descriptive statistics in SAS. Missing data were treated with pairwise deletion. Results From 11/2016 through 11/2017, 95 caregivers accessed or attempted the survey and 86 caregivers completed the survey. A total of 19 different states were represented. The average age of caregivers was 57.6 years old. The majority were female, white, married, and lived with the patient. Most caregivers had not provided care to the patient prior to the LVAD implant (n=41, 47.6%). The majority of caregivers provided care daily (n=57, 66.3%) with most reporting 1-5 hours per day (n=58, 68.3%). Caregivers reported moderate impacts of caregiving on emotional, financial, social, and physical domains, with the most impact on the emotional domain and least impact on the physical domain (Figure). Many caregivers had personal medical issues with the large majority taking ≥2 medications daily (n=56, 68.3%) and attending ≥2 medical appointments for themselves annually (n=48, 57.1%). ConclusionS Overall, caregivers of patients with an LVAD were mostly female, white, and spouses of the patient, with many reporting providing care for several hours per day. Most caregivers felt more emotional, financial, and social effects, and less so physical effects. Moreover, half of caregivers reported their own chronic health condition and took several medications regularly. Future research should focus on factors that cause the most burden as well as the health outcomes of these individuals so that appropriate support tools and interventions can be provided to these important members of the care team.

Objective. To compare the effects of a group-mediated cognitive behavioral (GMCB) exercise and dietary (EX+D) intervention with those of standard-of-care (SC) treatment on select social cognitive outcomes in prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Methods. In the single-blind, 2-arm, randomized controlled Individualized Diet and Exercise Adherence–Pilot (IDEA-P) trial, 32 PCa patients (mean age = 66.2 years; SD = 7.8) undergoing ADT were randomly assigned to a 12-week EX+D intervention (n = 16) or SC treatment (n = 16). The exercise component of the personalized EX+D intervention integrated a combination of supervised resistance and aerobic exercise performed twice per week. The dietary component involved counseling and education to modify dietary intake and composition. Blinded assessments of social cognitive outcomes were obtained at baseline and 2-month and 3-month follow-up. Results. Intent-to-treat analysis of covariance demonstrated that the EX+D intervention resulted in significantly greater improvements in scheduling ( P < .05), coping ( P < .01), and exercise self-efficacy ( P < .05), and satisfaction with function ( P < .01) at 3 months relative to SC. Results of partial correlation analysis also demonstrated that select social cognitive outcomes were significantly correlated with primary trial outcomes of mobility performance and exercise participation ( P < .05) at 3-month follow-up. Conclusions: The GMCB lifestyle intervention yielded more favorable improvements in relevant social cognitive outcomes relative to SC among PCa patients undergoing ADT. Additionally, more favorable social cognitive outcomes were associated with superior mobility performance and exercise participation following the independent maintenance phase of the EX+D intervention.

Friedreich’s ataxia (FA) is an inherited disease that causes degeneration of the nervous system. Features of FA include proprioceptive and cerebellar deficits leading to impaired muscle coordination and, consequently, dysmetria in force and time of movement. The aim of this study is to characterize dysmetria and its association to disease severity. Also, we examine the neural mechanisms of dysmetria by quantifying the EMG burst area, duration, and time-to-peak of the agonist muscle. Twenty-seven individuals with FA and 13 healthy controls (HCs) performed the modified Functional Ataxia Rating Scale and goal-directed movements with the ankle. Dysmetria was quantified as position and time error during dorsiflexion. FA individuals exhibited greater time but not position error than HCs. Moreover, time error correlated with disease severity and was related to increased agonist EMG burst. Temporal dysmetria is associated to disease severity, likely due to altered activation of the agonist muscle. NEW & NOTEWORTHY For the first time, we quantified spatial and temporal dysmetria and its relation to disease severity in Friedreich’s ataxia (FA). We found that FA individuals exhibit temporal but not spatial dysmetria relative to healthy controls. Temporal dysmetria correlated to disease severity in FA and was predicted from an altered activation of the agonist muscle. Therefore, these results provide novel evidence that FA exhibit temporal but not spatial dysmetria, which is different from previous findings on SCA6.

e24035 Background: Post-treatment weight gain places breast cancer (BCa) survivors at heightened risk for cardiovascular disease, metabolic syndrome, and functional decline. Lifestyle weight management (LWM) interventions combining exercise and dietary weight loss represents an effective approach to mitigating the adverse cardiometabolic and functional effects frequently observed in BCa survivors. Unfortunately, community access to cost-effective, sustainable, LWM interventions among BCa survivors remains limited. The purpose of this study is to determine the preliminary efficacy of a community-based LWM intervention in BCa survivors on select body composition (BC), physical function, and social cognitive outcomes of the first wave of participants in the Healthy New Albany Breast Cancer (HNABC) pilot trial. Methods: The 24-week, community-based pilot trial promotes lifestyle behavior changes through a group-mediated cognitive behavioral (GMCB) approach driven by Social Cognitive Theory. The measures analyzed were BC done via Dual-energy X-ray Absorptiometry, physical function via the 400m walk test, and social cognitive outcomes via satisfaction with function and appearance and perceived competence with exercise and diet at 6-months via effect size calculations using Cohen’s d. Results: Meaningful changes were observed in fat mass ( d= -0.46), percent lean mass ( d= 0.33), lean mass ( d= -0.45), and physical function ( d= -0.59), some of which reached clinical relevance. Select self-reported outcomes also saw meaningful improvements from this LWM intervention. Conclusions: Findings from this study demonstrate the preliminary efficacy of implementing a GMCB-based LWM intervention among overweight or obese BCa survivors. Given the meaningful impact that successful weight management has on reducing risk for chronic diseases, these results highlight the utility of implementing a LWM intervention in the community for BCa survivors in an effort to extend the access, reach, and scalability of supportive care approaches during BCa survivorship.

The objective of the present study was to compare a group-mediated cognitive behavioral (GMCB) physical activity intervention with traditional exercise therapy (TRAD) upon select social cognitive outcomes in sedentary knee osteoarthritis (knee OA) patients. A total of 80 patients (mean age = 63.5 years; 84% women) were recruited using clinic and community-based strategies to a 12-month, single-blind, two-arm, randomized controlled trial. Mobility-related self-efficacy, self-regulatory self-efficacy (SRSE), and satisfaction with physical function (SPF) were assessed at baseline, 3, and 12 months. Results of intent-to-treat 2 (Treatment: GMCB and TRAD) × 2 (Time: 3 and 12 month) analyses of covariance yielded significantly greater increases in SRSE and SPF (P < 0.01) relative to TRAD. Partial correlations revealed that changes in SRSE and SPF were significantly related (P < 0.05) to improvements in physical activity and mobility at 3 and 12-months. The GMCB intervention yielded more favorable effects on important social cognitive outcomes than TRAD; these effects were related to improvements in physical activity and mobility.

Background— Congenital heart disease (CHD) is the most common type of birth defect with family- and population-based studies supporting a strong genetic cause for CHD. The goal of this study was to determine whether a whole exome sequencing (WES) approach could identify pathogenic-segregating variants in multiplex CHD families. Methods and Results— WES was performed on 9 kindreds with familial CHD, 4 with atrial septal defects, 2 with patent ductus arteriosus, 2 with tetralogy of Fallot, and 1 with pulmonary valve dysplasia. Rare variants (GATA4 mutation in the transactivation domain, p.G115W, was identified in familial atrial septal defects and demonstrated decreased transactivation ability in vitro. A p.I263V mutation in TLL1 was identified in an atrial septal defects kindred and is predicted to affect the enzymatic functionality of TLL1. A disease-segregating splice donor site mutation in MYH11 (c.4599+1delG) was identified in familial patent ductus arteriosus and found to disrupt normal splicing of MYH11 mRNA in the affected individual. Conclusions— Our findings demonstrate the clinical utility of WES to identify causative mutations in familial CHD and demonstrate the successful use of a CHD candidate gene list to allow for a more streamlined approach enabling rapid prioritization and identification of likely pathogenic variants from large WES data sets. Clinical Trial Registration— URL: https://clinicaltrials.gov ; Unique Identifier: NCT0112048.

Myoepithelial carcinomas (MC) represent aggressive tumors that occur in a myriad of ages and anatomic locations. The rarity and histologic similarity with other tumors make them difficult to diagnosis. We report an extremely rare case of a right ventricular outflow tract mass identified to be an intracardiac MC in a 4-month-old male infant. Pathology revealed an EWS-KLF15 translocation. Treatment included gross total resection and intensive chemotherapy. Recurrent cardiac mass with brain metastasis was seen 16 months after primary diagnosis. We describe the rarity of intracardiac MC in pediatric patients and the challenges encountered in the multimodal management of this patient.

Summary This letter addresses the controversial issue of the use of oral corticosteroids during wheezing exacerbations in preschool-aged children by demonstrating findings of a prematurely terminated multi-center clinical trial, discussing lessons learned, and suggesting future directions.

Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals.

Bicuspid aortic valve (BAV) is the most common type of congenital heart defect (CHD) and is associated with clinically significant cardiovascular complications including valve calcification and ascending aortopathy (AscAo), predominantly occurring in adulthood. While a limited number of genetic etiologies for BAV have been defined, family members of affected individuals display BAV along with other left-sided CHD. This has led to guidelines from the American Heart Association and American College of Cardiology that recommend echocardiographic screening of first-degree relatives of affected adults. While potentially beneficial in adults, the yield of such screening in children is unknown. The purpose of this study was to investigate a cohort of children with familial BAV to determine the frequency of development of AscAo, and to identify risk factors that contribute to abnormal aortic growth. Echocardiograms over a 10-year follow-up period were reviewed on 26 patients with familial BAV [22 male, 4 female; 22 with isolated BAV, 6 with BAV and aortic coarctation (CoA)]. All had a family history of CHD and were recruited from 2005 to 2010 as part of a genetics research study. Four aortic segments (annulus, root, sinotubular junction, ascending aorta) on parasternal long-axis echocardiographic images were measured by a single observer. The mean age at first echocardiogram was 7.1 ± 5.5 and that was 13.8 ± 6.2 years at the last echocardiogram. Only patients with > 2 echocardiograms in the 10-year period were included. Z score measurements of the aorta were plotted over time and based on these the cohort was divided into two groups: Group 1 (abnormal)—Z score for any segment > 2 or a change in Z score > 2 over follow-up; Group 2 (normal)—Z score

This chapter reviews the normal path of electrical conduction in the heart. In the structurally normal heart, the cardiac impulse is automatically generated by the pacemaker of the heart, the sinus node, and terminates in the ventricular myocardium. The anatomy and physiology of the electrical conduction in a normal heart are reviewed in this chapter.

Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10-8 for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10-9, odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10-5, OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10-9 for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10-7 for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease.

Background: Recent advances in technology, and a greater demonstration of the genetic contributors to congenital heart disease (CHD), have resulted in an expansion of genetic screening among infants with CHD. However, the utility of this screening strategy has not been well studied. We aimed to