Acute and midterm outcomes of the post-approval MELODY Registry: a multicentre registry of transcatheter pulmonary valve implantation

AIMS The post-approval MELODY Registry aimed to obtain multicentre registry data after transcatheter pulmonary valve implantation (TPVI) with the Melody™ valve (Medtronic plc.) in a large-scale cohort of patients with congenital heart disease (CHD). METHODS AND RESULTS Retrospective analysis of multicentre registry data after TPVI with the Melody™ valve. Eight hundred and forty-five patients (mean age: 21.0 ± 11.1 years) underwent TPVI in 42 centres between December 2006 and September 2013 and were followed-up for a median of 5.9 years (range: 0-11.0 years). The composite endpoint of TPVI-related events during follow-up (i.e. death, reoperation, or reintervention >48 h after TPVI) showed an incidence rate of 4.2% per person per year [95% confidence interval (CI) 3.7-4.9]. Transcatheter pulmonary valve implantation infective endocarditis (I.E.) showed an incidence rate of 2.3% per person per year (95% CI 1.9-2.8) and resulted in significant morbidity and in nine deaths. In multivariable Cox proportional hazard models, the invasively measured residual right ventricle (RV)-to-pulmonary artery (PA) pressure gradient (per 5 mmHg) was associated with the risk of the composite endpoint (adjusted hazard ratio: 1.21, 95% CI 1.12-1.30; P 2 improved significantly from 36 [interquartile range (IQR) 24-47] to 12 (IQR 7-17) mmHg and 47 to 1%, respectively (P < 0.001 for each). CONCLUSION The post-approval MELODY Registry confirms the efficacy of TPVI with the Melody™ valve in a large-scale cohort of CHD patients. The residual invasively measured RV-to-PA pressure gradient may serve as a target for further improvement in the composite endpoint and TPVI I.E. However, TPVI I.E. remains a significant concern causing significant morbidity and mortality

AN EMPIRICAL ANALYSIS OF ASYMMETRIC DUOPOLY IN THE INDONESIAN CRUDE PALM OIL INDUSTRY

The apparent increase in market concentration and vertical integration in the Indonesian crude palm oil (CPO) industry has led to concerns about the presence of market power. For the Indonesian CPO industry, such concerns attract more attention because of the importance of this sector to the Indonesian economy. CPO is used as the main raw material for cooking oil (which is an essential commodity in Indonesia) and it contributes significantly to export earnings and employment. However, dominant producers argue that the increase in economies of scale and scope lead to an increase in the efficiency, which eventually will be beneficial for the end consumers and export earnings. This research seeks to examine whether the dominant producers do behave competitively and pass the efficiency gains to the end consumers, or they enhance inefficiency through market power instead. In order to identify the most suitable model to measure market power in the Indonesian CPO industry, different market power models are explored. These models can be divided into static and dynamic models. In general, all of them accept the price–cost margins as a measure of market power. However, static models fail to reveal the dynamic behaviour that determines market power; hence the dynamic models are likely to be more appropriate to modelling market power. Among these dynamic models, the adjustment model with a linear quadratic specification is considered to be a more appropriate model to measure market power in the Indonesian CPO industry. In the Indonesian CPO industry, producers can be divided into three groups, namely the public estates, private companies and smallholders. However, based on their ability to influence market price, smallholders are not considered as one of the dominant groups. By using the adjustment cost model, the market power of the dominant groups is estimated. The model is estimated using a Bayesian technique annual data spanning 1968–2003. The public estates and private companies are assumed to engage in a noncooperative game. They are assumed to use Markovian strategies, which permit firms to respond to changes in the state vector. In this case, the vector comprises the firms and their rivals’ previous action, implying that firms respond to changes in their rivals’ previous action. The key contribution of this thesis is the relaxation of the symmetry assumption in the estimation process. Although the existence of an asymmetric condition often complicates the estimation process, the different characteristics of the public estates and private companies lead to a need for relaxing such an assumption. In addition, the adjustment system—which can be seen as a type of reaction function—is not restricted to have downward slopes. Negative reaction functions are commonly assumed for a quantity setting game. However, the reverse may occur in particular circumstances. Without such restrictions, the analysis could reveal the type of interaction between the public estates and private companies. In addition, it provides insights into empirical examples of conditions that might lead to the positive reaction function. Furthermore, the analysis adds to the understanding of the impact of positive reaction functions to avoid the complicated estimation of the asymmetric case. As expected, the public estates act as the leader, while the private companies are the follower. Interestingly, results indicate that as well as the private companies, public estates do exert some degree of market power. Moreover, the public estates enjoy even higher market power than the private companies, as indicated by market power indices of -0.46 and -0.72, respectively. The exertion of market power by both the public estates and the private companies cast some doubts about the effectiveness of some current policies in the Indonesian CPO industry. With market power, the underlying assumption of a perfectly competitive market condition—that serves as the basis for the government interventions—is no longer applicable. Hence, many government interventions are unlikely to have the desired effect. The Indonesian competition law that has been imposed since 1999 might be effective in preventing firms to sign collusive contracts. In fact, even without such an agreement, firms in the CPO industry are likely to exert some degree of market power. As an alternative, eliminating the ‘sources’ of market power might be a better solution. If the public estates have the aim of maximising welfare, privatisation might improve their efficiency, hence they have ability to suppress the private companies’ market power. However, if in fact, the public estates deliberately reduce output to gain higher profit, privatisation might increase the degree of market power of both groups of companies even further. In such a condition, addressing the long term barriers of entry stemming from the requirement of high investment might be a better alternative to address the market power problem in the CPO industry

The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant

Background: The arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin‑2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. Methods: Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C &gt; T (p.Arg79*), c.397C &gt; T (p.Gln133*) and c.2489+1G &gt; A (p.?)). Results: Of the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p &lt; 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia–free survival between 4 PKP2 founder variants, including c.1211dup. Conclusions: The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.</p

Differential Temporal and Spatial Progerin Expression during Closure of the Ductus Arteriosus in Neonates

Closure of the ductus arteriosus (DA) at birth is essential for the transition from fetal to postnatal life. Before birth the DA bypasses the uninflated lungs by shunting blood from the pulmonary trunk into the systemic circulation. The molecular mechanism underlying DA closure and degeneration has not been fully elucidated, but is associated with apoptosis and cytolytic necrosis in the inner media and intima. We detected features of histology during DA degeneration that are comparable to Hutchinson Gilford Progeria syndrome and ageing. Immunohistochemistry on human fetal and neonatal DA, and aorta showed that lamin A/C was expressed in all layers of the vessel wall. As a novel finding we report that progerin, a splicing variant of lamin A/C was expressed almost selectively in the normal closing neonatal DA, from which we hypothesized that progerin is involved in DA closure. Progerin was detected in 16.2%±7.2 cells of the DA. Progerin-expressing cells were predominantly located in intima and inner media where cytolytic necrosis accompanied by apoptosis will develop. Concomitantly we found loss of α-smooth muscle actin as well as reduced lamin A/C expression compared to the fetal and non-closing DA. In cells of the adjacent aorta, that remains patent, progerin expression was only sporadically detected in 2.5%±1.5 of the cells. Data were substantiated by the detection of mRNA of progerin in the neonatal DA but not in the aorta, by PCR and sequencing analysis. The fetal DA and the non-closing persistent DA did not present with progerin expressing cells. Our analysis revealed that the spatiotemporal expression of lamin A/C and progerin in the neonatal DA was mutually exclusive. We suggest that activation of LMNA alternative splicing is involved in vascular remodeling in the circulatory system during normal neonatal DA closure

Correction to: Putting genome-wide sequencing in neonates into perspective

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article

Stenting of the vertical vein in obstructed total anomalous pulmonary venous return as rescue procedure in a neonate

A newborn girl with progressive respiratory distress and cyanosis was found to have severely obstructed supracardiac total pulmonary venous return (TAPVR). Stenting of the stenosis provided immediate and effective relief of the obstruction until corrective surgery was performed. Catheter intervention should be considered in high-risk infants with obstructed supracardiac TAPVR as part of the strategy for preoperative cardiovascular stabilizatio

Fifteen years' experience with the use of artificial chords for valve reconstruction in children

OBJECTIVES: To retrospectively review our experience with artificial chords in mitral and tricuspid reconstructive surgery in children. METHODS: All consecutive paediatric ( <18 years) patients who underwent mitral or tricuspid valve reconstruction with the use of artificial chords in our centre in the past 15 years were retrospectively analysed. RESULTS: Thirty-nine patients (age 3 days to 17 years) underwent reconstruction of the mitral (n = 27) or tricuspid (n = 12) valve using artificial chords. Mean number of chords was 3.5 +/- 1.7. In 26 of 27 mitral valve patients, chords were placed on the anterior leaflet, in one on the posterior leaflet. In 10 of the 12 tricupid valve, patients chords were placed on the anterior leaflet and in 2 on the septal leaflet. All mitral patients underwent annuloplasty (10 bilateral Wooler-Kay and 17 rigid ring annuloplasty). Ten of the 12 tricuspid patients underwent annuloplasty (1 rigid ring and 9 commissural plication). Follow-up was after 8.7 +/- 5.5 years. There was no early or late mortality. The actuarial freedom from reoperation rates at 1, 5 and 10 years were 95%, 91% and 81%, respectively. No reoperations occurred in the tricuspid group. In the mitral group, there were 2 early failures and 3 late reoperations due to mitral stenosis. Restricted leaflet motion probably caused by the artificial chords was seen in only 1 patient. CONCLUSIONS: Our data show that long-term durability of mitral and tricuspid valve reconstruction using artificial chords in children is good. Despite patient growth, restricted leaflet motion by the artificial chords does not seem to form a major proble