Transcriptional profile of c-kit positive cardiac stem-progenitor cells (c-kitpos eCSCs) isolated from the four chambers of the adult human heart

Introduction: Our findings and those of others show that the adult myocardium, including human, harbours a population of resident (endogenous) cardiac stem cells (eCSCs). They express the stem cell factor receptor c-kit, are distributed throughout the myocardium, are clonogenic, self-renewing and multi-potent, in that they differentiate into the 3 main cardiac lineages; cardiomyocytes, smooth muscle and endothelial cells in vitro and in vivo. The objective of this study is to determine whether c-kitpos eCSCs isolated from the different cardiac chambers have a distinct transcriptional profile depending on the chamber of origin. Methods: Pieces of myocardium have been obtained from all the 4 chambers of the adult human heart. All patients were fully consented before undergone open heart surgery. They were suffered of various cardiac pathologies such as ischemic heart disease, aortic, mitral and tricuspid valve insufficiency or stenosis, and various aortic pathologies. Ethical approval for these procedures has been given by NREC (08/H1306/91).c-kitpos eCSCs were isolated by enzymatic digestion and purified by Magnetic Activated Cell Sorting (MACS) from samples taken from the right and left atria (RA, LA), right and left ventricle (RV, LV) of the adult human heart. mRNA was isolated using Qiagen® mRNA kit, and reverse transcribed using first strand cDNA synthesis with random hexamers. qRT-PCR was performed using SYBR Green on a MyIQ thermocycler Bio-Rad® of specific genes representative of the primary and secondary heart field, and the developmental program of their chamber of origin. Results: c-kitpos eCSCs isolated from 15 human samples (5LA, 1RV, 4LV, 5RA) were processed. c-kitpos eCSCs are distributed throughout the human myocardium and in all 4 chambers of the heart. Transmitted light microscopic observations of c-kitpos eCSCs revealed that the c-kitpos cells from the human biopsies were generally small and rounded, consistent with a stable c-kitpos eCSCs phenotype, regardless of the chamber of origin. The eCSCs c-kitpos cells could be cultured under hypoxic conditions between 7 and 12 days to attain full confluency. Expression of transcripts for c-kit, Foxh1, Hand1, Hand2, Pitx2, Tbx5, Tbx20, Hrt1, Hrt2, Fgf8, Fgf10, and Isl1 were found at differential levels in c-kitpos CSCs isolated from the four cardiac chambers. Conclusion: This study is the first to show that c-kitpos eCSCs derived from human adult cardiac samples, do not appear to have a ‘chamber-specific’ transcript footprint, and are therefore potentially interchangeable between cardiac chambers, raising the potential of their therapeutic application

Understanding nursing practice in stroke units: a Q-methodological study.

Abstract Purpose: Nurses represent the largest professional group working with stroke-survivors, but there is limited evidence regarding nurses' involvement in post-stroke rehabilitation. The purpose of this study was to identify and explore the perspectives of nurses and other multidisciplinary stroke team members on nurses' practice in stroke rehabilitation. Method: Q-methodological study with 63 multidisciplinary stroke unit team members and semi-structured interviews with 27 stroke unit team members. Results: Irrespective of their professional backgrounds, participants shared the view that nurses can make an active contribution to stroke rehabilitation and integrate rehabilitation principles in routine practice. Training in stroke rehabilitation skills was viewed as fundamental to effective stroke care, but nurses do not routinely receive such training. The view that integrating rehabilitation techniques can only occur when nursing staffing levels were high was rejected. There was also little support for the view that nurses are uniquely placed to co-ordinate care, or that nurses have an independent rehabilitation role. Conclusions: The contribution that nurses with stroke rehabilitation skills can make to effective stroke care was understood. However, realising the potential of nurses as full partners in stroke rehabilitation is unlikely to occur without introduction of structured competency-based multidisciplinary training in rehabilitation skills. Implications for Rehabilitation Multidisciplinary rehabilitation in stroke units is a cornerstone of effective stroke care. Views of stroke unit team members on nurses' involvement in rehabilitation have not been reported previously. Nurses can routinely incorporate rehabilitation principles in their care. Specialist competency-based stroke rehabilitation training needs to be provided for nurses as well as for allied health professionals

Study protocol for Women of Color and Asthma Control: A randomized controlled trial of an asthma-management intervention for African American women

<p>Abstract</p> <p>Background</p> <p>Among adults in the United States, asthma prevalence is disproportionately high among African American women; this group also experiences the highest levels of asthma-linked mortality and asthma-related health care utilization. Factors linked to biological sex (e.g., hormonal fluctuations), gender roles (e.g., exposure to certain triggers) and race (e.g., inadequate access to care) all contribute to the excess asthma burden in this group, and also shape the context within which African American women manage their condition. No prior interventions for improving asthma self-management have specifically targeted this vulnerable group of asthma patients. The current study aims to evaluate the efficacy of a culturally- and gender-relevant asthma-management intervention among African American women.</p> <p>Methods/Design</p> <p>A randomized controlled trial will be used to compare a five-session asthma-management intervention with usual care. This intervention is delivered over the telephone by a trained health educator. Intervention content is informed by the principles of self-regulation for disease management, and all program activities and materials are designed to be responsive to the specific needs of African American women. We will recruit 420 female participants who self-identify as African American, and who have seen a clinician for persistent asthma in the last year. Half of these will receive the intervention. The primary outcomes, upon which the target sample size is based, are number of asthma-related emergency department visits and overnight hospitalizations in the last 12 months. We will also assess the effect of the intervention on asthma symptoms and asthma-related quality of life. Data will be collected via telephone survey and medical record review at baseline, and 12 and 24 months from baseline.</p> <p>Discussion</p> <p>We seek to decrease asthma-related health care utilization and improve asthma-related quality of life in African American women with asthma, by offering them a culturally- and gender-relevant program to enhance asthma management. The results of this study will provide important information about the feasibility and value of this program in helping to address persistent racial and gender disparities in asthma outcomes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01117805">NCT01117805</a></p

Feasibility and effects of adapted cardiac rehabilitation after stroke: a prospective trial

Abstract Background Despite the cardiovascular etiology of stroke, exercise and risk factor modification programs akin to cardiac rehabilitation (CR) are not available. This study aimed to establish the feasibility of adapting a CR model for individuals with mild to moderate stroke disability. A secondary objective was to determine the program's effects on aerobic and walking capacity, and stroke risk factors. Methods A repeated measures design was used with a 3-month baseline period and 6-month adapted CR intervention (n = 43, mean ± SD age 65 ± 12 years, 30 ± 28 months post stroke). Feasibility was determined by the number of participants who completed the study, occurrence of adverse events and frequency, duration and intensity of exercise performed. To determine effectiveness of the program, outcomes measured included aerobic capacity (VO2peak, ventilatory threshold), 6-Minute Walk Test (6MWT) distance, and risk factors. Descriptive statistics characterized the classes attended and number and intensity of exercise sessions. Paired t-tests, one-factor repeated measures analyses of variance contrasts and chi-square analyses were used to compare changes over time. Results Two participants withdrew during the baseline period. Of the remaining 41 participants who commenced the program, 38 (93%) completed all aspects. No serious adverse effects occurred. Post-intervention, VO2peak improved relative to the stable baseline period (P = 0.046) and the increase in ventilatory threshold approached significance (P = 0.062). Conclusions CR is feasible after stroke and may be adapted to accommodate for those with a range of post-stroke disability. It is effective in increasing aerobic capacity. CR may be an untapped opportunity for stroke survivors to access programs of exercise and risk factor modification to lower future event risk. Trial registration ClinicalTrials.gov registration number: NCT0106749

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research