Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Cardiac strangulation following epicardial pacemaker implantation: a rare pediatric complication.

OBJECTIVES: The aim of our study was 2-fold: to determine the incidence of cardiac strangulation (CS) and to develop a clinical pathway to aid in the diagnosis and prognosis of CS. In <2 years, 2 cases of CS occurred in our institution, which caused much alarm and led to the study's objectives. METHODS: All patients who underwent implantation of an epicardial pacemaker from January 1992 to March 2012 were included. There were no exclusion criteria. Health records were used to locate all subjects and gather all retrospective data. Prospectively, subjects without a chest radiograph from the previous 2 years were approached for imaging. RESULTS: This study included 86 patients retrospectively, and 84 patients prospectively. There was a 2.3% incidence, and a 1.2% mortality, related to CS. A pattern of posterior looping of the ventricular lead was seen in radiographs of both CS-diagnosed patients. Five variables were significantly associated with an outcome of CS (P = .0153). CONCLUSIONS: Our data indicate that the 2 cases of CS were not caused by a lack of follow-up but by a lack of consistent imaging for diagnosis. This conclusion is supported by the 8 cases of CS found in the English-language literature. If the patient is age ≤6 months at the time of implantation, particular attention should be given to the placement of leads and follow-up.

Cardiac strangulation from epicardial pacemaker: early recognition and prevention.

Cardiac strangulation from epicardial pacemaker leads is a rare event that can be difficult to recognise and can cause serious complications such as cardiac failure or death. We describe a 3-year-old girl who received an epicardial pacing system as a neonate for complete congenital cardiac block and developed cardiac strangulation from the leads. The clinical presentation modes are reviewed and technical aspects for lead and generator positioning are discussed.

Echocardiographic tools for pacemaker optimization of ventricular function in an infant following surgical repair for double outlet right ventricle.

A case of an infant, following surgical repair for double outlet right ventricle, who developed low cardiac output syndrome and complete heart block that required insertion of a pacemaker is presented. The infant underwent optimization of his ventricular function to determine whether pacing the right ventricle or left ventricle or both would improve cardiac function. Using standard two-dimensional echocardiography and Doppler imaging, tissue synchronization imaging, and two-dimensional speckle-tracking strain analysis, improvement in cardiac output and function was demonstrated. The present case highlights the usefulness of newer echocardiographic techniques in pacemaker optimization in the acute postoperative setting.

Imaging of a carotid aneurysm in two patients following extracorporeal membrane oxygenation therapy.

Following extracorporeal membrane oxygenation (ECMO), two patients subsequently developed carotid aneurysms at the site of cannulation. Given the invasive nature of ECMO, vascular ultrasound and/or computerized tomographic imaging should be considered to rule out cannulation-site complications post-ECMO.

A criss-cross heart with twisted atrioventricular connections, "perfect streaming," and double discordance.

At 24 weeks gestational age, a term female infant was diagnosed with complex congenital heart disease. The antenatal cardiac diagnosis was uncertain and included univentricular heart. Following delivery, the child remained well and was normally saturated. Echocardiography and angiocardiography revealed an unusual relationship between atria and ventricles.

Intra-atrial thrombus in a neonate with coarctation of the aorta.

It is uncommon for thrombus to form within the heart of neonates with congenital cardiac disease. We describe a newborn with coarctation of the aorta, in whom a left atrial thrombus was discovered on the second day of life, and was thought to have been present before birth.

Is the nuchal index increased in fetuses with congenital structural heart defects?

OBJECTIVES: To determine if the Nuchal index (NIx) is increased in euploid fetuses with structural congenital heart defects (CHD). METHODS: Euploid fetuses with CHD between 18 and 24 weeks gestation were identified. The next fetus meeting the same criteria with a normal fetal echocardiogram were selected as a control. The NIx [(mean nuchal thickness /mean biparietal diameter) x 100] and cardiac axis (CA; degrees) were calculated for each fetus. Standard descriptive tests and two-tailed t test were used. RESULTS: The NIx in the abnormal (n = 20) and control (n = 20) groups were 9.10 (2.35) and 7.54 (p = 0.04) and CA was 55.8 degrees and 48.6 degrees (p = 0.02), respectively. CONCLUSIONS: The NIx and CA were significantly different in fetuses with CHD. A prospective study to confirm these findings and determine clinical utility is warranted.

Intraoperative rescue by placement of a stent following a surgical coronary arterial injury in a child.

An acute injury to a coronary artery was recognized during the surgical construction of the Fontan circulation. Surgical manipulation of the site of injury was not successful in restoring normal myocardial blood flow. A stent was therefore placed intraoperatively under direct vision, with restoration of normal coronary arterial flow acutely and at short-term follow-up.

Unguarded tricuspid valvar orifice in the fetus.

The unguarded tricuspid valve is uncommon. We describe herein a fetus with a grossly dilated right ventricle and atrium, with severe tricuspid and pulmonary valvar regurgitation. The right ventricle was akinetic, and no tricuspid tissue or valvar apparatus was identified. Colour Doppler showed a highly unusual retrograde flow of blood through the right heart. The pregnancy was terminated, and necropsy examination confirmed the gross dilation of the right heart chambers, with severely dysplastic valvar tissue at the right atrioventricular junction effectively giving an unguarded orifice. There was no valvar displacement, and the left heart was normal. The fetus had a normal karyotype, albeit with absent kidneys.

Pulmonary atresia with intact ventricular septum and antenatal left ventricular failure.

Pulmonary atresia with intact ventricular septum has been described extensively, and it is recognized that associated abnormalities of the coronary arteries may cause ischemia. We describe a fetus, diagnosed antenatally as having pulmonary atresia with intact ventricular septum and severe hypoplasia of the right ventricle, who developed severe left ventricular dysfunction. We hypothesize that this is due to reduced coronary blood flow because of falling right ventricular volume in the presence of complete right ventricular coronary arterial dependence.

Clipped tube fenestration after extracardiac Fontan allows for simple transcatheter coil occlusion.

BACKGROUND: Expensive devices are increasingly used to close a patent fenestration after a modified Fontan operation. We report our 5-year institutional experience of clipped tube fenestration after extracardiac Fontan operation, which allows for simple transcatheter coil occlusion. METHODS: We retrospectively reviewed 30 children, median age of 4.0 years (range, 2.4 to 8.8 years) who underwent extracardiac Fontan operation between May 1996 and May 2001, and were fenestrated using a 4- to 8-mm diameter clipped tube graft. RESULTS: Ten children had a patent fenestration occluded by transcatheter placement of 15 detachable coils (5- to 8-mm diameter). Aortic oxygen saturations increased on average by 5.5% (2% to 14%) and mean pressures in the Fontan circuit by 2.5 mm Hg (0 to 3 mm Hg). Four had immediate complete occlusion angiographically and 6 had trivial residual shunt, but complete occlusion by echocardiography at follow-up. There have been no immediate complications, late coil embolizations, thromboembolic events, or documented hemolysis within a follow-up after coil implantation of 1.7 years (0.4 to 4.5 years). Spontaneous fenestration closure was documented in 8 patients at cardiac catheterization and 9 patients by echocardiography with consistent improvement in resting transcutaneous oxygen saturation. Two children with a patent fenestration have been considered inappropriate for closure, and there was one early surgical death. There have been no complications related to the tube fenestration modification within a follow-up postoperation of 2.6 years (0.1 to 5.5 years). CONCLUSIONS: Clipped tube fenestration after extracardiac Fontan operation is a useful surgical modification that allows for simple transcatheter coil occlusion.

Supravalvar aortic stenosis with supravalvar pulmonary stenosis and peripheral vascular stenoses.

A non-dysmorphic 10 month old female was discovered at surgery to have severe vasculopathy of both the systemic and pulmonary arteries. These findings were confirmed by pathologic examination. Follow-up angiography has confirmed multiple sites of vascular obstruction which appear to be worsening. Angioplasty has only partially relieved these obstructions. The pathology and possible etiology are reviewed.

Pulmonary arterial and intracranial calcification in the recipient of a twin-twin transfusion.

Pulmonary arterial and intracranial calcifications are rarely found in children. A female infant, the recipient of a twin-twin transfusion syndrome was found, by ultrasound and computed tomography, to have both pulmonary arterial and intracerebral calcification. A rare condition, termed idiopathic arterial calcification of infancy, is the likely cause. This condition carries a poor prognosis and is usually fatal.