Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.

The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.

Ductal stenting to improve pulmonary blood flow in pulmonary atresia with intact ventricular septum and critical pulmonary stenosis after balloon valvuloplasty.

OBJECTIVE: To assess the feasibility, safety, and efficiency of ductal stenting in pulmonary atresia with intact ventricular septum or critical pulmonary stenosis after balloon pulmonary valvuloplasty. BACKGROUND: Ductal stenting in pulmonary atresia with intact ventricular septum is a re-emerging and promising technique. There is little data available on its outcomes after establishing prograde pulmonary blood flow. METHODS: We retrospectively reviewed all neonates with pulmonary atresia with intact ventricular septum or critical pulmonary stenosis who underwent ductal stenting after balloon valvuloplasty. Ductal stenting was performed either in the same setting (group A) or a few days later after balloon valvuloplasty (group B). We compared the two groups. RESULTS: Eighteen coronary stents were transvenously delivered and successfully deployed in 18 newborns. There was no procedure-related mortality. The median hospital stay post-intervention was 6 days with a mean discharge oxygen saturation of 94%. Group A had a shorter overall hospital stay with a shorter overall time of irradiation but with a longer overall procedural time. On a follow-up of 18 months, no re-intervention for stent failure or overflow was undertaken. The median stent patency based on echocardiography was 12 months. CONCLUSION: Stenting the arterial duct in pulmonary atresia with intact ventricular septum or critical pulmonary stenosis is a feasible, safe, and efficient technique. It avoids surgery or long hospital stay with prostaglandin infusion. The minimal 6 months stent longevity provides a period of time long enough to decide whether the right ventricular diastolic function is normalised or Glenn surgery is still needed.

PULMONARY ARTERY ACCELERATED FLOW REVEALING HODGKIN'S LYMPHOMA.

We present a case in which transthoracic echocardiography was the first diagnostic tool to suspect mediastinal Hodgkin's lymphoma by revealing a change in the hemodynamic of left pulmonary artery flow, and it was used as a follow-up method for monitoring treatment efficacy by demonstrating a normalization of pulmonary artery hemodynamics.

[Supravalvular aortic stenosis with and without coronary lesions in pediatrics. A Lebanese study]. / STÉNOSE SUPRAVALVULAIRE AORTIQUE AVEC OU SANS LÉSIONS CORONAIRES EN PÉDIATRIE--ÉTUDE LIBANAISE.

OBJECTIVE: This study aims to analyze several parameters concerning the supravalvular aortic stenosis (SVAS) in children such as age of diagnosis, place of residence, the existence of a metabolic disorder or dysmorphic syndrome and possible damage to the coronary ostia, the means of diagnosis and outcome of these patients. MATERIALS AND METHODS: A large group of patients (2868) with congenital heart disease enrolled between 1 May 1999 and 30 April 2010 at the National Register of Pediatric and Congenital Heart Disease, Lebanese Society of Cardiology. RESULTS: SVAS were found in 14 patients (0.5%) aged 8.5 months to 15 years. The Williams Beuren syndrome was the most common etiology (6 cases) without ostial stenosis, asymptomatic and not treated, followed by forms without dysmorphic syndrome (5 cases) and without ostial stenosis, one patient was operated because of severe SVAS; finally, 3 cases of homozygous familial hypercholesterolemia treated differently: a patient had a successful liver transplantation at age of 4.5 years but has developed, despite the normalization of cholesterol level, a SVAS associated with severe ostial lesions 10 years after transplantation, another treated by coronary artery bypass graft surgery and the latter treated medically. CONCLUSION: SVAS is a very rare disease, but its discovery must lead to search for coronary lesions especially in presence of homozygous familial hypercholesterolemia. The ultrasound monitoring is mandatory and is designed to detect this anomaly and early coronary lesions. The slightest suspicion should carry out more extensive explorations to detect ostial stenosis.

FALSE AND TRUE ACUTE RHEUMATIC FEVER: A Lebanese Experience.

OBJECTIVES: The main aim of this study is to evaluate the significance of several clinical and laboratory findings presented by a large number of pediatric patients who were suspected to have acute rheumatic fever (ARF) by physicians who ordered echocardiogram for confirmation and for avoiding overuse of unnecessary antibiotics. These suspecting reasons include elevated ASO titers and recurrent tonsillitis. Another aim is to stress the role of Doppler echocardiogram in confirming the diagnosis of ARF by detecting rheumatic heart disease (RHD) in suspected cases. MATERIALS AND METHODS: 401 patients were registered in the National Registry of the Pediatric and Congenital Heart Disease (RNCPC) from April 1, 2002 until the end of March 2013 as suspected cases of ARF. The clinical reasons that brought suspicion are discussed and evaluated in accordance to modified Jones criteria. The patients are distributed into two groups: 1) confirmed ARF and 2) different diagnosis. All patients underwent echocardiogram. Patients came from different geographic areas and were referred by a variety of physicians. RESULTS: 48 patients out of 401 suspected cases turned to have confirmed ARF (12%). In this group, the predominant suspecting reasons are reported as heart murmur in 29/48 (60.4%), arthritis in 28/48 (58.3%), arthralgia with reduced physical activity in 15/48 (31%) and chorea in 5/48 (10%). In the different diagnosis group with a high ASO titer 174/353 (49.3%), isolated arthralgia 91/353 (25.8%) and combined elevated ASO with arthralgia in 44/353 (12.5%) were the predominant suspecting reasons. Doppler echocardiography could detect 38/48 cases of active carditis and subclinical carditis (SCC). CONCLUSION: Heart murmur, arthritis, arthralgia with reduced physical activity and chorea are the main clinical reasons that lead to suspicion in the ARF group. High ASO titers, arthralgia, and combination of high ASO titers with arthralgia are the main presenting symptoms in the group with a different diagnosis. We concluded that elevated ASO titer and normal ESR with arthralgia not reducing physical activity can exclude ARF. Doppler echocardiography is found to be a gold standard key to confirm acute rheumatic heart disease and ARF.

[Spontaneous regression of coarctation of the aorta in infants]. / Régression spontanée de la coarctation de l'aorte chez le nourrisson.

Coarctation of the aorta in neonates and small infants is, in most cases, a severe congenital malformation and requires a rapid surgical treatment or interventional catheterization. To our knowledge, and so far, no cases of coarctation of the aorta have spontaneously improved. We report three cases of coarctation diagnosed in young infants and considered as moderate forms on physical exam and/or ultrasound study which evolved to partial or complete regression without any treatment.

[Linear insertion of atrioventricular valves in children with and without Down's syndrome]. / Insertion linéaire des valves auriculo-ventriculaires chez les enfants avec et sans syndrome de Down.

OBJECTIVE: Study various parameters encountered in the linear insertion of the atrioventricular valves (LIAVV) in patients with and without Down's syndrome (DS). MATERIAL: A group of patients (n = 6240) aged from 0 to 16 years with and without congenital heart disease (CHD) registered over 6 years (1.07.2005-30.06.2011) in the National Registry of the Pediatric and Congenital Heart Disease of the Society of Cardiology in Lebanon. METHOD: Children were divided in two groups; Group I: children with DS and group II: children without DS. In the two groups, the frequency of LIAVV whether isolated or associated with other CHD (excluding the atrioventricular canal), the distribution boy-girl and the various associated cardiac anomalies were studied. We used nonparametric tests for comparing the two groups. The p value < 0.05 was considered significant. RESULTS: Group I consists of 155 patients including 31 (20%) with LIAVV, isolated in 22 cases (14.2%) and associated with CHD in 9 cases (5.8%). Group II was composed of 5995 patients; the incidence of LIAVV was 0.2% (14 patients) with apvalue < 0.00001. Regarding sex, there was a marked male predominance: respectively 78% and 56% in groups I and II. In patients with isolated LIAVV, 86% of patients were males. Family history of DS is found in 3/7 children without T21 with isolated LIAVV. A patient, in whom an atrial septal defect ostium primum type with LIAVV was diagnosed during the first month of life, has seen his septal defect closed spontaneously five months later. CONCLUSION: Encountered predominantly among a male population, the isolated LIAVV is less frequent in children without DS but often with family history of Down's syndrom.

Pilot-based assessment of the economics of recycling construction demolition waste.

The significant amount of waste generated from construction demolition has become a chronic problem in many developing countries. Using data obtained from demolition contractors and various other sources, this paper proposes a framework for proper handling of construction demolition waste (CDW) to serve as a decision support tool in countries suffering from the lack of national CDW management guidelines. The framework is then demonstrated through a case study in the city of Beirut, Lebanon, and a sensitivity analysis is carried out to examine the economic feasibility of developing a recycling facility. The analysis showed that in order for a facility to be feasible, a gate fee should be charged in the presence of a market for recycled aggregates. The results confirm the significance of instigating and implementing legislation to control illegal dumping, constructing, and managing engineered landfills, and establishing markets for recycled CDW.

Analyzing the failures of percutaneous closure of the patent ductus arteriosus in patients over 5 kg.

UNLABELLED: Percutaneous closure of the patent ductus is the gold standard therapy. Our aim was to analyze our failures between 2001 and 2010. METHODS: All patients over 5 kg benefited from a transcatheter attempt at duct closure. Coils and Amplatzer duct occluder (ADO) I were used before 2008, and ADO I and ADO II afterward. The failure was recovered when another percutaneous attempt was successful and definite when surgery was needed. RESULTS: There were 138 patients. Coils were used in 22 patients (16%), ADO I in 74 (54%), and ADO II in 42 (30%). Immediate and 6-month closure rates were 55% and 100% for coils, 40% and 96% for the ADO I, and 74% and 93% for the ADO II, respectively. There were no failures in the coil group, and 3 failures in each of the ADO I and ADO II groups. Among the 3 ADO I failures, 1 was recovered after device migration into the abdominal aorta. The 2 other failures were definite, due to immediate device protrusion, once in the aorta and once in the pulmonary artery. One of the 3 ADO II failures was definite, due to protrusion into the aorta, 10 days following the procedure. The two other failures were due to immediate device migration into the pulmonary artery, and were both recovered. CONCLUSIONS: 97% of ducts can be closed percutaneously. The combination of coil and ADO I gives excellent results. Failed attempts with the ADO II were bailed out by the ADO I.

[The percutaneous treatment of pulmonary atresia with intact ventricular septum]. / Traitement percutané de l'atrésie pulmonaire à septum interventriculaire intact.

OBJECTIVE: Describe a mechanical method of perforation-dilatation of the pulmonary valve in pulmonary atresia with intact interventricular septum (PA-IVS), with or without stenting the patent ductus arteriosus (PDA) and medium-term results. METHOD: Since 2007, all patients with PA-IVS and a right ventricle adequate for biventricular repair, benefited from a transcatheter attempt to perforate-dilate the valve with or without stenting the PDA, and were included in this retrospective study. TECHNIQUE: A catheter was percutaneously introduced through the femoral vein and positionned in front of the atretic pulmonary valve. A lasso catheter was introduced through the femoral artery to the other side of the pulmonary valve. The tip of a rigid guidewire was then pushed through the atretic valve and taken with the lasso, creating a loop that allowed for balloon valvuloplasty. If the child remained ductal dependant following PGE1 withdrawal, a stent is placed in the ductus arteriosus. RESULTS: Five patients were included in this series. Four patients were successfully dilated, and two patients necessitated stents. The procedure had to be interrupted in one patient. FOLLOW-UP: One patient with a patent stent was operated at the age of one year and died in the postoperative period. The other patient with a stent is now 16 months old with a patent stent and an oxygen saturation of 98%. The two remaining patients without stent are now 3- and 18-month-old with oxygen saturation of 85% and 96% respectively. CONCLUSION: The percutaneous treatment of PA-IVS is feasible and avoids early high risk surgery. Stenting the ductus arteriosus may replace a Blalock shunt. However, the prognosis is still related to the severity of the anomaly.

[Parental smoking during early pregnancy and congenital heart defects]. / Tabagisme parental en début de grossesse et cardio- pathies congénitales.

OBJECTIVES: Analyze the possible role that can play parental smoking during early pregnancy on the occurrence of different types of congenital heart defects (CHD). MATERIALS AND METHODS: Over a period of 4.5 years (between January 1, 2006 and June 30, 2010), data on all children who had an echocardiography were collected and entered in the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology, Beirut. Patients were divided into two groups: group I without CHD, and group II with CHD. Variables recorded were: age of mother, place of residence, parental smoking, the type of CHD, the sex of the child and consanguinity of the parents. We used nonparametric tests for comparing the two populations. The p value was considered significant when inferior to 0.05. RESULTS: Group I consisted of 2466 patients and group II of 793 patients. Only valvar pulmonary stenosis (VPS) was highly associated with mothers who smoked 20 cigarettes or more per day (p = 0.03). When the mother and father consumed at least 20 cigarettes per day, VPS and coarctation of the aorta were associated with a significant p-value (0.03 and 0.02 respectively). CONCLUSION: Parental smoking in early pregnancy can be considered a risk factor for valvar pulmonary stenosis and coarctation of the aorta. Cessation of smoking by the parents before pregnancy could reduce the risk of their occurrence.

Fatal cardiac atherosclerosis in a child 10 years after liver transplantation: a case report and a review.

We hereby review liver transplantation for homozygous familial hypercholesterolemia and report the case of a 14-year-old girl presenting with severe bilateral coronary ostial stenosis and tight supra-valvular aortic narrowing 10 years after liver transplantation. Despite normalization of the lipids after liver transplantation, the patient showed evidence of severe cardiac atherosclerosis 10 years later and died of apparent sepsis.

[Epidemiology of mitral valve disease in pediatrics: a Lebanese study]. / Epidémiologie des pathologies mitrales en pédiatrie: étude libanaise.

OBJECTIVES: To study the incidence, etiology, clinical signs and treatment of children with mitral valve disease in Lebanon. PATIENTS AND METHODS: This is a retrospective study on a period of 9 years (between May 1, 1999 and April 30, 2008), including a group of children with congenital and acquired heart disease, consecutively enrolled in the National Register of Pediatric and Congenital Heart Disease, Lebanese Society of Cardiology. RESULTS: 2586 new patients aged 0-18 years were recorded. Among them, 128 (4.9%) had mitral disease. The causes were congenital in 65% of the cases (28% were associated with other congenital heart anomalies, especially a double outlet right ventricle) and acquired in 35% of the cases (91% were secondary to rheumatic fever). The diagnosis of the disease was fortuitous in 24% of the cases, and a murmur was discovered on auscultation in 53% of the cases. The majority of children showed mitral regurgitation (86%). The regurgitation was severe in 12% of the cases. Half of the children received medical or surgical treatment. The mortality of this disease reached 2%. CONCLUSION: Congenital anomalies of the mitral valve are the most common cause of mitral regurgitation in children. Rheumatic disease remains another important cause of mitral disease in Lebanon. A high index of suspicion must exist, since the vast majority of diseases are found fortuitously or during simple auscultation.

[Atrioventricular septal defect characteristics in infants with and without Down's syndrome: a Lebanese study]. / Caractéristiques du canal atrioventriculaire chez les enfants avec et sans syndrome de Down: étude libanaise.

OBJECTIVES: Analyze the demographic and clinical characteristics of complete atrioventricular septal defect (AVSD), its association with Down's syndrome, with other cardiac and extra-cardiac anomalies, and finally the impact of consanguineous marriages on the incidence of AVSD. PATIENTS & METHODS: The sample consisted of 2195 consecutive patients with congenital heart defect, entered in the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology, Beirut, between Jan 1999 and Dec 2007. 120 patients with AVSD were analyzed. The gathered data included age, sex, type of AVSD, mother's age, 1st and 2nd degree cousins, and other associated cardiac or extra-cardiac anomalies. RESULTS: AVSD was diagnosed in 5.5% of all patients with congenital heart disease, with 81.7% (n = 98) being complete AVSD. Male sex was predominant (58%). More than half (57.5%) were also diagnosed with Down's syndrome. The mean maternal age was 30.4 years (+/- 4.7 years) and consanguinity found in 16.7% of the cases. Cardiac and extra-cardiac anomalies (all in the esophagus and intestine) were associated in 15% and 6.7% respectively. Complete AVSD was significantly associated with Down's syndrome: 94% of patients with Down's syndrome had a complete AVSD. Digestive anomalies were also significantly more frequent with Down's syndrome (10% versus 2%, p = 0.02). Other cardiac anomalies, however, were less frequent with Down's syndrome (33% versus 7.7%, p = 0.02). CONCLUSION: Down's syndrome is more frequently associated with isolated and complete AVSD. Other anomalies may complicate the management of these patients. The cause of this probable genetic anomaly is still debated.

The Amplatzer Duct Occluder II: a new device for percutaneous ductus arteriosus closure.

OBJECTIVE: Study the new Amplatzer Duct Occluder II (ADO II). Limitations were encountered with the preexisting devices in nonconical ducts, large ducts, or in small infants. These include failure, residual shunts, protrusion, migration, and vascular damage. METHODS: Between June 2008 and March 2009, 20 consecutive patients were enrolled. In cases where different devices were applicable, we favored the use of the ADO II to maximize our experience with this device and prove its superiority. No coils were required in these 20 patients. RESULTS: There were 15 females and 5 males (median age 2 years). ADO II group (n = 16): Immediate complete closure in 75% of the patients, rising to 93.7% at 24 hours. A residual shunt persisted at 3 months in one child. Aortic narrowing from device protrusion was noted in two type E ducts, without any significant gradient, however. ADO I group (n = 4): In two adolescents and in one adult patient, the duct was successfully closed. In a 2-year-old patient with a 6.6 mm type B duct, the ADO I totally obstructed the aortic flow and was retrieved before releasing. The child was sent for surgery. CONCLUSION: Even though we did not compare the ADO II to other devices, we feel that it has the capacity to substitute most of the coils, and some of the original ADO I indications. Arterial access was sufficient in most patients, but venous delivery is advised in small infants with large or long ducts, to avoid aortic protrusion and residual shunts.

Development of catheter-based treatment of patent ductus arteriosus: a medium-sized centre experience.

BACKGROUND: Despite the availability of effective devices, percutaneous closure of patent ductus arteriosus (PDA) can be challenging in some situations. AIM: To describe our initial experience of percutaneous PDA closure. METHODS: Between 2001 and 2007, 73 consecutive patients aged 3 months to 70 years underwent transcatheter PDA closure. An Amplatzer duct occluder (ADO) was chosen for ducts greater than 2 mm (n=50) and a Detachable coil (DC) for smaller ducts (n=23). RESULTS: The diameter of the ducts ranged from 1 to 7.2 (mean 2.9+/-1.3) mm. The prostheses were implanted successfully in all patients. The complete closure rate reached 98% in the ADO group and 100% in the DC group at 12 months. Four (5.4%) patients showed asymptomatic device protrusion: three patients (5, 6 and 10 kg) into the aortic isthmus and one patient (7 kg) into the pulmonary artery (PA). One patient (7 kg) experienced transient severe bradycardia due to pulmonary air embolism. Another patient (3.3 kg) had a permanent asymptomatic occlusion of the femoral artery. In a third patient (17 kg), the ADO migrated asymptomatically into the descending aorta and was discovered 12 months later. CONCLUSION: Even during the learning curve, percutaneous PDA closure can give excellent results. Strict adherence to protocols and careful follow-up assessments are mandatory. In small infants, the use of the ADO may lead to obstruction in the aorta or PA, or to device migration. Cautious surveillance for untoward events is essential, especially in small infants with large ducts.

The silent patent ductus arteriosus.

OBJECTIVES: To describe the characteristics and outcome of children with an isolated silent patent ductus arteriosus (SPDA), with comparison to non-silent ducts. PATIENTS AND METHODS: Between 1999 and 2004, all consecutive cases of isolated silent and non-silent-patent ductus were recorded at the National Register of Pediatric and Congenital Heart Disease, Lebanese Society of Cardiology. Patients with a SPDA were followed clinically and by Doppler echocardiography while all non-SPDA were percutaneously or surgically closed. RESULTS: Twenty-four cases of isolated SPDA and 50 cases of isolated non-SPDA ducts were recorded. Male sex was significantly predominant in the silent group (70%). First-cousin consanguinity rates were not different between both groups, with 20.4% for the silent group versus 22% for the non-silent group. Down's syndrome was associated in three cases of SPDA. No cases of endocarditis were noted during a mean follow-up of 33.3 months. Four patients with a SPDA experienced spontaneous closure at the age of 25, 30, 36 and 58 months. CONCLUSION: SPDA is a relatively benign disease. The risk of endocarditis cannot be totally ignored, but the systematic closure of the SPDA is not warranted. Larger series and longer follow-up are needed in order to draw conclusions. Spontaneous closure occurred in four patients with SPDA.

[Congenital heart disease, maternal age and parental consanguinity in children with Down's syndrome]. / Cardiopathie congenitale, age maternel et consanguinite parentale chez les enfants avec syndrome de Down.

OBJECTIVE: Analyze the role of parental consanguinity and/or maternal age on the occurrence of congenital cardiac anomalies in infants with Down's syndrome (DS). MATERIAL AND METHODS: A large group of patients with or without congenital heart disease, registered between May 1st, 1999 and June 30th, 2006, at the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology. 217 children with DS have been enrolled over this period. Group I: DS with cardiac anomalies (n:119). Group II: DS without cardiac anomalies (n:98). The consanguinity rate was compared to a study made in 2000 by UNICEF in Lebanon, in which the consanguinity rate was 14.9% of 1st degree cousins and 25% of all degrees together. RESULTS: Congenital cardiac anomalies were found in 54.2% of babies with DS. First degree cousins in both groups I and II was 143% (close to the general population), and it was lower in group I compared to group II (11.8% and 17.3% respectively ; p = 0.205) ; this difference was not statistically significant for all degrees together. Maternal age ranged from 20 to 47 years, with a mean of 29.5 +/- 5.3 years. The risk of congenital cardiac anomaly was greater (p < 0.05) when maternal age was equal or below 32 years. As in the international literature, complete atrioventricular canal and ventricular septal defect were the most frequent cardiac anomalies. CONCLUSION: In children with DS, the risk of congenital cardiac anomalies was not associated with the parents consanguinity. Maternal age above 32 years seem to be associated with a lesser occurrence of congenital cardiac anomaly in children with DS.