No positive effect of rhdnase on the pulmonary colonization in children with cystic fibrosis

Background. Long-term clinical trials have shown that daily treatment with recombinant human deoxyribonuclease (rhDNAse) in patients with mild to moderate cystic fibrosis (CF) improves lung function and decreases the number of respiratory exacerbations. The aim of this study was to analyze the effect of rhDNAse on the bacterial colonization of the airways in children with CF. Methods. This was a retrospective cohort study. From the database of the CF Center Utrecht, we selected two groups, an rhDNAse group (daily 2.5 mg rhDNAse) and a control group (no rhDNAse). Primary outcome parameter was the difference in change in bacterial colonization between the treatment and control group during 1.5-year. Secondary outcome parameters were changes in lung function (FEV1) and pulmonary exacerbations. Results. Children treated with rhDNAse showed no significant changes in bacterial colonization during the treatment period, apart from an increase of P. aeruginosa positive cultures, both compared to baseline (53.1% versus 25%, p<0.05) and control group (no change during study period, 37% versus 37%). The change in FEV1 after one year of treatment was +4.0% in the treatment group versus -0.3% in the control group (p=0.22). There were no significant changes in number of pulmonary exacerbations. Conclusions. This study showed no significant beneficial decrease in bacterial airway colonization during 1.5-year of treatment with rhDNAse. The positive effects of rhDNAse on the lung function can therefore not be explained by a change in airway colonization

Long-term follow-up of pericardium for the ventricular component in atrioventricular septal defect repair

Background: Despite the improved outcome in complete atrioventricular septal defect (AVSD) repair, reoperations for left atrioventricular valve (LAVV) dysfunction are common. The aim of this study was to evaluate the effect of fresh untreated autologous pericardium for ventricular septal defect (VSD) closure on atrioventricular valve function and compare the results with the use of treated bovine pericardial patch material. Methods: Clinical and echocardiographic data were collected of patients with complete AVSD with their VSD closed with either untreated autologous pericardial or treated bovine pericardial patch material between January 1, 1996, and December 31, 2003. Evaluation closed in September 2019. Results: A total of 77 patients were analyzed (untreated autologous pericardial VSD patch: 59 [77%], treated bovine pericardial VSD patch: 18 [23%]). Median age at surgery was 3.6 (interquartile range [IQR]: 2.7-4.5) months, and median weight was 4.5 (IQR: 3.9-5.1) kg. Trisomy 21 was present in 70 (91%) patients. Median follow-up time was 17.5 (IQR: 12.6-19.8) years. Death <30 days occurred in two (3%) patients. Reinterventions occurred in eight patients (early [within 30 days] in two, early and late in one, and late in five), all in the autologous pericardium group. Log-rank tests showed no significant difference in mortality (P = .892), LAVV reinterventions (P = .228), or LAVV regurgitation (P = .770). Conclusions: In AVSD, the VSD can safely be closed with either untreated autologous pericardium or xeno-pericardium. We found no difference in LAVV regurgitation or the need for reoperation between the two patches.Thoracic Surger

Mechanical Mitral Valve Replacement: A Multicenter Study of Outcomes with Use of 15- to 17-mm Prostheses

Background: The aim of this study was to evaluate early and mid-term outcomes (mortality and prosthetic valve reintervention) after mitral valve replacement with 15- to 17-mm mechanical pr

Patient information portal for congenital aortic and pulmonary valve disease:A stepped-wedge cluster randomised trial

Background In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted. Methods Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement. Results 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable. Conclusion Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice.Cardiolog

Systemic age-associated DNA hypermethylation of ELOVL2 gene : in vivo and in vitro evidences of a cell replication process

Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2 We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age. Interestingly, ELOVL2 hypermethylation was not found in tissues with very low replication rate. We demonstrated that ELOVL2 hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra-individual hypermethylation of ELOVL2 and FHL2 in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, ELOVL2 methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that ELOVL2 methylation is a marker of cell divisions occurring during human aging

Prognosis in Cystic Fibrosis: Trends and Predictors

Cystic fibrosis (CF) is a multisystem disease affecting the digestive system, sweat glands, and the reproductive tract, but progressive lung disease continues to be the major cause of morbidity and mortality. Patients develop chronic infection of the respiratory tract with a characteristic array of bacterial flora, leading to progressive respiratory insufficiency and eventual respiratory failure. Birth prevalence and survival in patients with CF in the Netherlands were last investigated over 30 years ago. We showed that the actual birth prevalence of CF in the Netherlands is clearly lower than it was 30 years ago and that survival in CF has dramatically improved. Furthermore, we demonstrated that young children with CF who have acute respiratory failure (ARF) have a good prognosis, but that ARF in adult CF patients is associated with high mortality. There is a wide range in the severity of CF lung disease and survival, with some patients facing death or lung transplantation during childhood while others have very mild disease well into adulthood. Furthermore, some CF patients suffer from complications such as CF-related liver disease (CFRLD) or nasal polyps early in life, whereas others will never develop these complications. A better understanding of risk factors for an adverse pulmonary course and for complications of CF is the basis for early diagnosis, and an important step in targeting populations for early intervention and prophylactic treatments. We showed that in families with 2 or more siblings with CF, younger siblings have a better lung function than their older counterparts, probably due to an earlier age at diagnosis. We also demonstrated that the presence of CFRLD or sinonasal polyps does not negatively influence pulmonary disease in children with CF, and that nasal polyps are even associated with better lung function. Finally, we found that, beside lung function and nutritional status, inflammatory status and P. aeruginosa colonization independently affect aerobic capacity in children and adolescents with CF. Increasing evidence suggests that phenotypic variation in CF can be attributed to genetic variation in genes other than the CFTR gene, the so-called modifier genes. Most of the recently investigated modifier genes are genes that are involved in the control of infection, immunity and inflammation. The majority of studies on modifier genes in CF have included rather small numbers of patients. Furthermore, they are mainly cross-sectional, mostly not replicated, and often show conflicting results. We performed a large single-center modifier gene study in a well-defined population consisting of over 300 CF patients and analyzed data both cross-sectionally and longitudinally. We found that genetic polymorphisms associated with decreased production of mannose-binding lectin, toll-like receptor 4 and interleukin-6 were associated with better lung function. We hypothesize that the decreased production of these proteins leads to a less intense inflammatory response in response to pathogens, and consequently less damage to the airways

Preserved Myocardial Deformation after Successful Coarctation Repair: A CMR Feature-Tracking Study

Contains fulltext : 190059.pdf (publisher's version ) (Open Access

Surgical Repair of Ventricular Septal Defect; Contemporary Results and Risk Factors for a Complicated Course

Surgical closure of the ventricular septal defect is the most commonly performed procedure in pediatric cardiac surgery. There are conflicting data on weight at operation as risk factor for a complicated course. We performed a retrospective evaluation of mortality and morbidity in all patients undergoing surgical ventricular septal defect closure at our institution between 2004 and 2012 to identify risk factor for a complicated course. Multivariate logistic regression modeling was performed to identify risk factors for a complicated course. 243 patients who underwent surgical ventricular septal defect closure were included. Median age at operation was 168.0 days (range 17-6898), the median weight 6.0 kg (range 2.1-102.0). No deaths occurred. Two patients (0.8%) required a pacemaker for permanent heart block. Five patients (2.1%) underwent reoperation for a hemodynamically important residual ventricular septal defect. No other major adverse events occurred. No risk factors for major adverse events could be established. Multivariate analysis identified a genetic syndrome, long bypass time and low weight at operation as independent risk factors for a prolonged intensive care stay (>1 day) and prolonged ventilation time (>6 h). Contemporary results of surgical VSD closure are excellent with no mortality and low morbidity in this series. Although it is associated with increased ventilation time and a longer hospital stay, low bodyweight at operation is not associated with an increased risk of complications or major adverse events in our series

Arterioventricular interaction after coarctation repair

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