Integrated analysis of DNA copy number and gene expression microarray data using gene sets

Background: Genes that play an important role in tumorigenesis are expected to show association between DNA copy number and RNA expression. Optimal power to find such associations can only be achieved if analysing copy number and gene expression jointly. Furthermore, some copy number changes extend over larger chromosomal regions affecting the expression levels of multiple resident genes.

Long-term results of balloon angioplasty for native coarctation of the aorta in childhood in comparison with surgery

OBJECTIVES: Coarctation of the aorta (CoA) can be treated either surgically or with balloon angioplasty (BA). Long-term follow-up for either treatment has been limited. Our objective was to compare long-term results of BA and surgery for treatment of native CoA in childhood. METHODS: Retrospective cohort study of patients with native CoA treated with BA or surgery between 3 months and 16 years of age. Forty-eight patients filled out questionnaires and approved review of their medical records. Twenty-four patients underwent additional testing, including 24-h ambulatory blood pressure measurement, cardiopulmonary exercise testing and cardiac magnetic resonance imaging. Results were analysed cross-sectionally and longitudinally. RESULTS: Nineteen and 29 patients received BA and surgery, respectively. Prevalence of hypertension and aneurysms was similar in both groups. Fifty percent of patients were hypertensive. Two-thirds of patients demonstrating hypertension were not receiving antihypertensive medication. Aneurysm formation occurred in 1 BA (5%) and 1 surgery (3%) patient. The BA group had a significantly higher risk of recoarctation (47% vs 24%) and reintervention (hazard ratio 2.95, 95% confidence interval 1.04-8.32). Exercise capacity and global left ventricular function were preserved in both groups and not significantly different after correction for age. Quality of life was good to excellent in the majority of the patients. CONCLUSIONS: After CoA repair in childhood, most patients perform well in daily life. However, on the long term, more than half of the patients develop hypertension and many develop re-CoA, especially in those who underwent BA. Therefore, we do not recommend BA for the treatment of native CoA in children

Fifth decennium after the arterial switch operation for transposition of the great arteries

Background: From 1977 onwards, patients with both simple and complex transposition of the great arteries (TGA) have been treated with the arterial switch operation (ASO) in the Wilhelmina Children's Hospital/University Medical Center Utrecht the Netherlands. In this study, we compared mortality and morbidity between two patient groups: A. operated before and B. after 1991, specifically focusing on late ventricular function and reinterventions. Methods: A single institution retrospective cohort study was performed on patients who had an ASO for either simple or complex TGA. Data were collected from medical records. The entire patient cohort (n = 283) was divided in a group with more than 30 years of follow-up (A) and a group with less than 30 years of follow-up (B). Clinical and standardized echocardiographic follow-up was evaluated. Results: Group A consisted of 79 patients, of whom follow-up was available in 59 patients (median follow-up 34.8 years, IQR 33.0–36.9). Group B consisted of 204 patients, of whom 195 long-term survivors (median follow-up 14.9 years, IQR 10.0–21.2). Early survival was best in group B (A: 67.8% vs. B: 96.6%, p < 0.001), whereas late mortality (in total 1.8%) was similar for both groups. Reinterventions, corrected for follow-up time, were more frequent in group A (p = 0.005). In total 65 patients (25.1%) required 105 late reinterventions including 4 late aortic valve replacements. The mode of reinterventions has shifted over time, from surgical to more catheter-based (p = 0.03). The vast majority of patients functioned in NYHA class I. In contrast to the recent cohort, who have a normal average LVEF (%), the average LVEF in the oldest cohort was in the bottom percentile of normal range. Conclusion: The majority of patients in their fifth decade after ASO are in functional class I. Early outcome improved showing reduced mortality and need for reoperation. However, a trend towards reduced left ventricular function and late aortic valve replacements justify further research

Patients with a congenital heart defect and Type D personality feel functionally more impaired, report a poorer health status and quality of life, but use less healthcare

Background: Type D personality, characterized by high levels of negative affectivity and social inhibition, is related to mortality, morbidity, poor health status, quality of life (QoL) and less healthcare utilization in various cardiovascular patient groups. To date, studies in patients with congenital heart disease (CHD) are lacking. Aims: (1) To examine the prevalence of Type D personality in CHD patients; (2) to compare Type D to non-Type D patients with regard to disease severity, functional status, health status and QoL; and (3) to examine the extent to which Type D personality is independently related to healthcare utilization. Methods: A total of 1109 adult CHD patients were included in a questionnaire survey. Due to missing data, 302 patients were excluded. Results: The prevalence of Type D personality was 20.4%. Type D patients reported a poorer functional status, health status and QoL than non-Type D patients (p <0.05). Type D patients reported less healthcare use than non-Type D patients (primary and cardiac outpatient healthcare: adjusted OR=0.56, 95% CI=0.35-0.90; inpatient healthcare: adjusted OR=0.38, 95% CI=0.17-0.83). Results of a post-hoc analysis showed a high prevalence of Type D personality in patients with a poor functional status who did not consult their cardiologist. Conclusion: Type D patients report a poorer functional status, health status and QoL, but less healthcare utilization. In clinical practice, patients should be screened for Type D personality, since social inhibition may prevent them from contacting a healthcare provider in the event of symptom aggravatio

Patients with a congenital heart defect and Type D personality feel functionally more impaired, report a poorer health status and quality of life, but use less healthcare.

Contains fulltext : 108996.pdf (publisher's version ) (Closed access)Background: Type D personality, characterized by high levels of negative affectivity and social inhibition, is related to mortality, morbidity, poor health status, quality of life (QoL) and less healthcare utilization in various cardiovascular patient groups. To date, studies in patients with congenital heart disease (CHD) are lacking. Aims: (1) To examine the prevalence of Type D personality in CHD patients; (2) to compare Type D to non-Type D patients with regard to disease severity, functional status, health status and QoL; and (3) to examine the extent to which Type D personality is independently related to healthcare utilization. Methods: A total of 1109 adult CHD patients were included in a questionnaire survey. Due to missing data, 302 patients were excluded. Results: The prevalence of Type D personality was 20.4%. Type D patients reported a poorer functional status, health status and QoL than non-Type D patients (p<0.05). Type D patients reported less healthcare use than non-Type D patients (primary and cardiac outpatient healthcare: adjusted OR=0.56, 95% CI=0.35-0.90; inpatient healthcare: adjusted OR=0.38, 95% CI=0.17-0.83). Results of a post-hoc analysis showed a high prevalence of Type D personality in patients with a poor functional status who did not consult their cardiologist. Conclusion: Type D patients report a poorer functional status, health status and QoL, but less healthcare utilization. In clinical practice, patients should be screened for Type D personality, since social inhibition may prevent them from contacting a healthcare provider in the event of symptom aggravation.1 september 201

Temsirolimus does not impact the levels of reactive oxygen species and superoxide in HGPS cells.

<p>(A) Immunochemistry was performed on control (GMO3349C) and HGPS (HGADFN003) fibroblasts mock-treated or temsirolimus-treated for the indicated periods. Live cells were stained with an oxidative stress detection reagent for ROS and a superoxide detection reagent. The negative control was treated with N-acetyl-L-cysteine to quench the signal intensity. The positive control was treated with pycocyanin to induce ROS production. DNA was stained with Hoechst 33342. Representative images are shown (n = 4). Scale-bar: 20 μm. (B) The same cells and detection reagents as in (A) were used to perform a 96-well microplate assay as described in Methods. The percentage of activity was calculated relative to mock-treated control cells. Data are expressed as the mean ± S.D. (*p-value ≤ 0.05; n = 4).</p

Incidence, Risk Factors and Outcome of Suspected Central Venous Catheter-related Infections in Critically Ill COVID-19 Patients: A Multicenter Retrospective Cohort Study

BACKGROUND: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. METHODS: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic healthrecord database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. RESULTS: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1000 catheter indwelling days, respectively. Prone ventilation for more than five days was associated with increased risk of suspected catheter-related infection; odds ratio: 5.05 (95 CI: 2.12 - 11.0). Risk of death was significantly higher in patients with suspected catheter-related infection; hazard ratio: 1.78 (95% CI: 1.25 - 2.53). CONCLUSION: This study shows that in critically ill patients with COVID-19 prevalence and incidence of suspected catheter-related infection is high, prone ventilation is a risk factor and mortality is higher in case of catheter-related infection