Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with Duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (ε_cc).</p> <p>Methods</p> <p>We used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (ε_cc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results.</p> <p>Results</p> <p>Patients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although ε_ccmagnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, ε_ccworsened regardless of treatment group.</p> <p>Conclusions</p> <p>These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.</p

“Taking your place at the table”: an autoethnographic study of chaplains’ participation on an interdisciplinary research team

BACKGROUND: There are many potential benefits to chaplaincy in transforming into a “research-informed” profession. However little is known or has been documented about the roles of chaplains on research teams and as researchers or about the effects of research engagement on chaplains themselves. This report describes the experience and impact of three chaplains, as well as tensions and challenges that arose, on one particular interdisciplinary team researching a spiritual assessment model in palliative care. Transcripts of our research team meetings, which included the three active chaplain researchers, as well as reflections of all the members of the research team provide the data for this descriptive, qualitative, autoethnographic analysis. METHODS: This autoethnographic project evolved from the parent study, entitled “Spiritual Assessment Intervention Model (AIM) in Outpatient Palliative Care Patients with Advanced Cancer.” This project focused on the use of a well-developed model of spiritual care, the Spiritual Assessment and Intervention Model (Spiritual AIM). Transcripts of nine weekly team meetings for the parent study were reviewed. These parent study team meetings were attended by various disciplines and included open dialogue and intensive questions from non-chaplain team members to chaplains about their practices and Spiritual AIM. Individual notes (from reflexive memoing) and other reflections of team members were also reviewed for this report. The primary methodological framework for this paper, autoethnography, was not only used to describe the work of chaplains as researchers, but also to reflect on the process of researcher identity formation and offer personal insights regarding the challenges accompanying this process. RESULTS: Three major themes emerged from the autoethnographic analytic process: 1) chaplains’ unique contributions to the research team; 2) the interplay between the chaplains’ active research role and their work identities; and 3) tensions and challenges in being part of an interdisciplinary research team. CONCLUSIONS: Describing the contributions and challenges of one interdisciplinary research team that included chaplains may help inform chaplains about the experience of participating in research. As an autoethnographic study, this work is not meant to offer generalizable results about all chaplains’ experiences on research teams. Research teams that are interdisciplinary may mirror the richness and efficacy of clinical interdisciplinary teams. Further work is needed to better characterize both the promise and pitfalls of chaplains’ participation on research teams

Effect of ventricular size and function on exercise performance and the electrocardiogram in repaired tetralogy of Fallot with pure pulmonary regurgitation

Background: In repaired tetralogy of Fallot (TOF), exercise test parameters like peak oxygen uptake and ventilatory efficiency predict mortality. Studies have also suggested cardiac magnetic resonance (CMR)-derived right ventricular (RV) size threshold values for pulmonary valve replacement in repaired TOF. However, effects of proposed RV size on exercise capacity and morbidity are not known. Methods: The relationship between CMR-derived ventricular size, function, and pulmonary regurgitation (PR) and NYHA class, exercise performance, and electrocardiogram (ECG) was studied in patients of repaired TOF with pure PR in a retrospective review of records. Results: 46 patients (22 females), mean age 14 years (8−30.8), were studied. There was no relationship between CMR-derived ventricular size, function, or PR and exercise test parameters, or NYHA class. RV end systolic and end diastolic volume correlated positively with the degree of PR. QRS duration on ECG correlated positively with RV end-diastolic volume (P < 0.01, r2 = 0.34) and PR (P < 0.01, r2 = 0.52). Conclusions: In repaired TOF and pure PR, there is no correlation between ventricular size or function and exercise performance. RV size increases with increasing PR. Timing of pulmonary valve replacement in TOF with pure PR needs further prospective evaluation for its effect on morbidity and mortality

Model of Human Fetal Growth in Hypoplastic Left Heart Syndrome: Reduced Ventricular Growth Due to Decreased Ventricular Filling and Altered Shape

Introduction: Hypoplastic left heart syndrome (HLHS) is a congenital condition with an underdeveloped left ventricle (LV) that provides inadequate systemic blood flow postnatally. The development of HLHS is postulated to be due to altered biomechanical stimuli during gestation. Predicting LV size at birth using mid-gestation fetal echocardiography is a clinical challenge critical to prognostic counseling. Hypothesis: We hypothesized that decreased ventricular filling in utero due to mitral stenosis may reduce LV growth in the fetal heart via mechanical growth signaling. Methods: We developed a novel finite element model of the human fetal heart in which cardiac myocyte growth rates are a function of fiber and cross-fiber strains, which is affected by altered ventricular filling, to simulate alterations in LV growth and remodeling. Model results were tested with echocardiogram measurements from normal and HLHS fetal hearts. Results: A strain-based fetal growth model with a normal 22-week ventricular filling (1.04 mL) was able to replicate published measurements of changes between mid-gestation to birth of mean LV end-diastolic volume (EDV) (1.1–8.3 mL) and dimensions (long-axis, 18–35 mm; short-axis, 9–18 mm) within 15% root mean squared deviation error. By decreasing volumetric load (−25%) at mid-gestation in the model, which emulates mitral stenosis in utero, a 65% reduction in LV EDV and a 46% reduction in LV wall volume were predicted at birth, similar to observations in HLHS patients. In retrospective blinded case studies for HLHS, using mid-gestation echocardiographic data, the model predicted a borderline and severe hypoplastic LV, consistent with the patients’ late-gestation data in both cases. Notably, the model prediction was validated by testing for changes in LV shape in the model against clinical data for each HLHS case study. Conclusion: Reduced ventricular filling and altered shape may lead to reduced LV growth and a hypoplastic phenotype by reducing myocardial strains that serve as a myocyte growth stimulus. The human fetal growth model presented here may lead to a clinical tool that can help predict LV size and shape at birth based on mid-gestation LV echocardiographic measurements.This article is published as Dewan, Sukriti, Adarsh Krishnamurthy, Devleena Kole, Giulia Conca, Roy Kerckhoffs, Michael D. Puchalski, Jeffrey H. Omens, Heather Sun, Vishal Nigam, and Andrew D. McCulloch. "Model of human fetal growth in hypoplastic left heart syndrome: reduced ventricular growth due to decreased ventricular filling and altered shape." Frontiers in Pediatrics 5 (2017): 25. doi: https://doi.org/10.3389/fped.2017.00025. Copyright © 2017 Dewan, Krishnamurthy, Kole, Conca, Kerckhoffs, Puchalski, Omens, Sun, Nigam and McCulloch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)

Optimization and Validation of a Multiplex, Electrochemiluminescence-Based Detection Assay for the Quantitation of Immunoglobulin G Serotype-Specific Antipneumococcal Antibodies in Human Serum▿

Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of Streptococcus pneumoniae. Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti-human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL assay exhibits a wide dynamic range and provides the ability to read concentrations down to the minimum reported concentration in the Merck ELISA (0.1 μg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies showed no cross talk between antigen spots within a well. By use of the WHO Pn sample reference panel, the results obtained with the Pn ECL assay were compared to the results obtained with the international Pn ELISA. The results for the Pn ECL assay satisfied the WHO-recommended acceptance criterion for concordance for all seven serotypes with published Pn ELISA values, and the overall correlation (r value) across the seven serotypes was 0.994. The MSD methodology has great potential to be extremely useful for simultaneously quantitating IgG responses to several Pn serotypes while conserving serum volumes and laboratory testing time