Feasibility and acceptability of a physical activity behavioural modification tele-coaching intervention in lung transplant recipients.

BACKGROUND: Despite improvements in pulmonary function following lung transplantation (LTx), physical activity levels remain significantly lower than the general population. To date, there is little research investigating interventions to improve daily physical activity in LTx recipients. This study assessed the feasibility and acceptability of a novel, 12-weeks physical activity tele-coaching (TC) intervention in LTx recipients. METHODS: Lung transplant recipients within 2 months of hospital discharge were recruited and randomised (1:1) to TC or usual care (UC). TC consists of a pedometer and smartphone app, allowing transmission of activity data to a platform that provides feedback, activity goals, education, and contact with the researcher as required. Recruitment and retention, occurrence of adverse events, intervention acceptability and usage were used to assess feasibility. RESULTS: Key criteria for progressing to a larger study were met. Of the 15 patients eligible, 14 were recruited and randomised to TC or UC and 12 completed (67% male; mean ± SD age; 58 ± 7 years; COPD n = 4, ILD n = 6, CF n = 1, PH n = 1): TC (n = 7) and UC (n = 5). TC was well accepted by patients, with 86% indicating that they enjoyed taking part. Usage of the pedometer was excellent, with all patients wearing it for over 90% of days and rating the pedometer and telephone contact as the most vital aspects. There were no adverse events related to the intervention. After 12 weeks, only TC displayed improvements in accelerometry steps/day (by 3475 ± 3422; p = .036) and movement intensity (by 153 ± 166 VMU; p = .019), whereas both TC and UC groups exhibited clinically important changes in physical SF-36 scores (by 11 ± 14 and 7 ± 9 points, respectively). CONCLUSION: TC appears to be a feasible, safe, and well-accepted intervention in LTx.

Lung Transplant With Cardiopulmonary Bypass: Impact of Blood Transfusion on Rejection, Function, and Late Mortality.

BACKGROUND: Allogeneic blood transfusion has been associated with immune modulation in other solid organ transplants. Within cardiothoracic surgery, allogeneic blood transfusion is associated with greater postoperative morbidity and mortality. We investigated the impact of allogeneic blood transfusion on rejection, function, and late mortality within lung transplantation. METHODS: A retrospective review was made of 311 adult patients who underwent bilateral lung transplantation with cardiopulmonary bypass from 2003 to 2013. Patients were stratified based on the amount of blood products transfused within 24 hours of transplantation. Kaplan-Meier methods and multivariate Cox proportional hazards models were used for time to first rejection/death and all-cause mortality analyses. RESULTS: In all, 174 men and 137 women (mean age 41.4 ± 14.0 years) utilized a median number of 3 units (range, 0 to 40) of red blood cells (RBC), 2 units (range, 0 to 26) of fresh frozen plasma (FFP), and 1 unit (range, 0 to 7) of platelets within the first 24 hours of transplantation. Time to first treated rejection/death was not statistically different whether patients were transfused with more or less than the median number of units of RBC (unadjusted p = 0.233, adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI]: 0.75 to 1.40, p = 0.177), FFP (unadjusted p = 0.146, adjusted HR 1.29, 95% CI: 0.95 to 1.76, p = 0.108), or platelets (unadjusted p = 0.701, adjusted HR 0.74, 95% CI: 0.47 to 1.15, p = 0.177). Rate of rejection and number of rejection episodes per patient at 1 year after transplant were not statistically different. Forced expiratory volume in 1 second expressed as percentage of forced vital capacity at 3 and 6 months was similar for all groups. Unadjusted early all-cause mortality was not influenced by RBC (p = 0.162) or FFP (p = 0.298) but was significantly different with more platelets (p = 0.032). Adjusted 10-year mortality showed no significant differences for RBC (HR 1.12, 95% CI: 0.70 to 1.79, p = 0.645), FFP (HR 1.24, 95% CI: 0.78 to 1.97, p = 0.356), or platelets (HR 1.49, 95% CI: 0.84 to 2.64, p = 0.172.). CONCLUSIONS: All blood products administration regardless of amount transfused did not appear to affect early rejection outcomes or forced expiratory volume in 1 second expressed as percentage of forced vital capacity at 3 and 6 months. Use of RBC and FFP had no effect on survival. However, greater platelet usage appeared to adversely affect early but not late mortality.

Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality.

OBJECTIVES: Blood transfusion is associated with higher morbidity and mortality after general cardiothoracic surgery but its impact within the transplant population is unclear. We investigated the profile of blood product transfusion in the bilateral lung transplant population and its impact on function and mortality. METHODS: Three hundred and eleven adult patients who underwent bilateral lung transplant between 2003 and 2013 were retrospectively reviewed. Patients were stratified according to pretransplant diagnoses and amount of blood products transfused within 24 h of transplant. All-cause mortality at the 1-year follow-up was analysed using a Cox proportional hazards regression model. RESULTS: One hundred and seventy-four male patients and 137 female patients (mean age = 41.4 ± 14.0 years) underwent bilateral lung transplant using cardiopulmonary bypass for cystic fibrosis (48.9%), fibrotic lung disease (12.2%), emphysema (27.0%), bronchiectasis (5.8%), pulmonary hypertension (1.3%) and others (4.5%). The median number of red blood cells in the first 24 h was 3 (0-40) units, fresh frozen plasma (FFP) = 2 (0-26) units and platelets = 1 (0-7) units. The unadjusted all-cause mortality at the 1-year follow-up did not appear to be different between patient subgroups stratified by the median number of units of red blood cells (P = 0.827) or FFP transfused (P = 0.456). However, 1-year mortality was adversely affected when more than the median number of units of platelets was transfused (P = 0.010). Upon adjustment for confounding variables, 1-year mortality was noted to be greater among patients transfused more than the median unit of platelets (adjusted hazard ratios: 2.3, 95% confidence interval: 1.15-4.61, P = 0.019) and those with longer bypass times (P = 0.046). No significant difference in the number of units transfused was noted when patients were stratified by pretransplant diagnosis. Predicted lung function at 3 and 6 months was not significantly affected by greater blood product use. CONCLUSIONS: Unlike general cardiothoracic surgery, blood transfusion had no effect on all-cause mortality, whereas a greater administration of platelets was observed to be associated with higher adjusted 1-year mortality. Transfusion rates were not significantly influenced by pretransplant diagnoses. Interestingly, lung function at 3 and 6 months was similar for patients who received more blood product transfusion.

Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development.