Feasibility study of micronutrient status and body mass index of newly diagnosed pediatric oncology patients: Research commentary.

We conducted a feasibility study to evaluate micronutrients and body mass index (BMI). Fat soluble vitamins A, D, E and trace elements copper (Cu), selenium (Se), and zinc (Zn) levels were evaluated. Weight, height, BMI, and Z-scores were recorded. Side effects or specific adverse events were documented. No patient had a Z-score for height, weight, or BMI of less than 2 SD or greater than 2 SD. Ninety percent of patients had one or more micronutrient levels below normal. These results suggest that micronutrient abnormalities are common despite no obvious evidence of malnutrition. Side effects of chemotherapy may be exacerbated by micronutrient depletion.

An 8-Week Virtual Exercise Training Program for Pediatric Solid Organ Transplant Recipients.

PURPOSE: Musculoskeletal strength can be impaired in pediatric solid organ transplant recipients. Exercise training programs can be beneficial but in-person delivery can be challenging; virtual exercise programs can alleviate some of these challenges. This feasibility study aimed to deliver an 8-week virtual exercise program in pediatric solid organ transplant recipients. METHOD: Program delivery occurred 3 times per week for 30 minutes. An exercise stress test was completed prior to program start. The Bruininks-Oseretsky Test of Motor Proficiency strength subtest and self-report surveys were used to assess musculoskeletal strength, quality of life, fatigue, and physical activity. Contact was maintained through a text messaging platform. Z scores were calculated using standardized normative data. Medians (interquartile range) are reported for all other data. RESULTS: Eleven participants completed the program (2 liver, 5 kidney, 4 heart; 58% females; median age = 11.5 [10.3-13.8] y). Six participants attended ≥60% of classes, 5 participants attended <50% of classes. After 8 weeks, strength scores improved (Z score, Pre: -1.0 [-1.65 to -0.60] to Post: -0.2 [-1.30 to 0.40]; P = .007) with no change in other outcome measures. CONCLUSION: The virtual exercise program was delivered without technical issues and received positive participant feedback. Engagement and costs need to be considered.

Effect of distance to tertiary centre on enrolment of paediatric patients with relapsed or refractory cancer on early phase clinical trials in British Columbia.

Objectives: Access to early phase trials for children with relapsed, refractory or progressive (RRPD) cancer is limited in Canada. Patients and families face barriers to access trials, which are poorly understood. The aims of this study were to assess availability of early phase trials and examine the impact of distance from home to study centre on trial enrolment among paediatric oncology patients with RRPD. Methods: Oncology patients ≤18 years at diagnosis who later had RRPD were identified retrospectively via registry at the only quaternary paediatric oncology centre in British Columbia (BC). We determined if distance to home, as calculated using geocoding software, was predictive of trial offer or enrolment. Results: Between January 2015 and July 2021, 266 patients experienced 396 RRPD events. Seventy-five patients (28.2%) were eligible for an early phase trial at least once. At first eligible event, 61 patients (22.9%) were offered trial (median age 11.8 years; 69.0% male; 46.0% with CNS tumour) and thirty patients (11.3%) enrolled. Distance was not associated with odds of offer (OR 1.01, CI 0.98 to 1.05) or enrolment (OR 0.99, CI 0.95 to 1.03) on univariate or multivariable analysis adjusted for sex and disease (OR 0.93, CI 0.86 to 1.00). For offered patients, 2-year event-free survival (EFS) and overall survival (OS) were 39.1% (CI 28.0% to 54.8%) and 51.8% (CI 39.9% to 67.2%), respectively. EFS/OS did not differ with distance or enrolment, but varied by disease (EFS P = 0.002, OS P < 0.0001). Conclusions: Children in BC with cancer and RRPD have limited access to early phase trials. Distance was not predictive of enrolment, suggesting that families travel to access therapy.

Ductus arteriosus: more than just the patent ductus arteriosus.

The ductus arteriosus is important to fetal circulation. Failure to close at birth is a common event. In this educational pictorial essay, we illustrate the association of the ductus arteriosus with a variety of congenital cardiac, vascular and pulmonary lesions. These lesions can impact the systemic circulation, the pulmonary circulation or the airway and include coarctation of the aorta, ductal origin of the pulmonary artery and vascular rings.

Association between in-line filtration and Type I hypersensitivity reactions in pediatric oncology patients receiving intravenous etoposide.

The objective of this study was to describe hypersensitivity reactions with and without the use of in-line filters during intravenous etoposide therapy in pediatric oncology patients. This was a retrospective review of all patients treated in the Division of Oncology/Hematology/Bone Marrow Transplant at British Columbia Children's Hospital with intravenous etoposide between December 1, 2013 and February 1, 2018. Hypersensitivity reactions and anaphylaxis associated with etoposide infusions were compared over time, including 12 months prior to, 27 months during the use of, and for 12 months after the discontinuation of in-line filtration. There were 192 patients (median age 6.0 (IQR 2.8-13.0) years treated with etoposide and 486 etoposide infusions including 137 (28%) before, 261 (54%) during and 88 (18%) after use of in-line filters at our center. Twenty-six of 486 (5%) and 13/486 (3%) of infusions resulted in a type I hypersensitivity reaction and anaphylaxis, respectively. There were 2/137 (1%), 36/261 (14%) and 1/88 (1%) infusion reactions prior to, during and after in-line filter use, respectively. Infusion reactions during the in-line filter period were higher than during the pre-filter (Z = 3.978; p < 0.001) and post-filter (Z = 3.335; p < 0.001) periods of the study. These data suggest that the use of in-line filtration may be associated with increased frequency of hypersensitivity reactions to etoposide in pediatric cancer patients.

The relative incidence of cardiogenic and septic shock in neonates.

OBJECTIVE: To evaluate the relative incidence of cardiogenic and septic shock in term neonates and identify findings that help differentiate the two entities. STUDY DESIGN: We conducted a retrospective chart review of term neonates presenting to British Columbia Children's Hospital (BCCH) with decompensated shock of an undiagnosed etiology between January 1, 2008 and January 1, 2013. Charts were reviewed to determine the underlying diagnoses of all neonates meeting our inclusion criteria. Patients were categorized as having septic, cardiogenic, or other etiologies of shock. We then evaluated potential demographic, clinical, and biochemical parameters that could help differentiate between septic and cardiogenic shock. RESULTS: Cardiogenic shock was more common than septic shock (relative risk=1.53). A history of cyanosis was suggestive of cardiogenic shock (positive likelihood ratio, LR+=3.2 and negative likelihood ratio, LR-=0.4). Presence of a murmur or gallop (LR+=5.4, LR-=0.3), or decreased femoral pulses (LR+=5.1, LR-=0.5) on physical exam were also suggestive of cardiogenic shock as was cardiomegaly on chest x-ray (LR+=4.9, LR-=0.5). Notably, temperature instability (LR+=0.7, LR-=1.8) and white blood cell count elevation or depression (LR+=0.8, LR-=1.1) were all poor predictors of septic shock. CONCLUSION: Cardiogenic shock is a more common cause of decompensated shock than septic shock. A history of cyanosis, murmur or gallop, or decreased femoral pulses on exam and cardiomegaly on chest x-ray are useful indicators of cardiogenic shock. In evaluating the neonate with decompensated shock, early consideration for Cardiology consultation and interventions to treat the underlying condition is warranted.

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.

BACKGROUND: Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. METHODS AND RESULTS: Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026). CONCLUSIONS: Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa.

An Echocardiographic Study of Left Ventricular Size and Cardiac Function in Adolescent Females with Anorexia Nervosa.

OBJECTIVE: This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. METHODS: Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). RESULTS: Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. DISCUSSION: Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group.

Postnatal outcome in patients with fetal tachycardia.

The diagnosis and management of prenatal tachyarrhythmias is well established; however, the postnatal course and outcomes are not. The purpose of our study was to review the natural history of patients with fetal tachycardia, determine the incidence of postnatal arrhythmias, and determine whether there are factors to predict which fetuses will develop postnatal arrhythmias. A retrospective chart review of patients with fetal tachyarrhythmias investigated at British Columbia Children's and Women's Hospitals between 1983 and 2010 was conducted. Sixty-nine mother-fetus pairs were eligible for the study. Fifty-two had fetal supraventricular tachycardia, and 17 had fetal atrial flutter. Conversion to sinus rhythm occurred prenatally in 52 % of patients. Postnatal arrhythmia occurred in two thirds of patients, with 82 % of those cases occurring within the first 48 h of life. Hydrops fetalis, female sex, and lack of conversion to sinus rhythm was predictive of postnatal arrhythmia (P = 0.01, P = 0.01, and P = 0.001, respectively). Conversion to sinus rhythm prenatally did not predict postnatal arrhythmia. Median duration of treatment was 9 months. Two postnatal deaths of unknown etiology occurred. Two thirds of all patients with prenatal tachycardia will develop postnatal arrhythmia. Prenatal factors that predict postnatal arrhythmia include hydrops, sex, and whether or not conversion to sinus rhythm occurred prenatally. The majority of patients with postnatal arrhythmia present within 48 h of life, which has clinical implications for monitoring. Postnatal outcome is generally very good with most patients being weaned off medication in 6-12 months.

Physical activity recommendations for patients with electrophysiologic and structural congenital heart disease: a survey of Canadian health care providers.

Determining safe levels of physical activity for children and adolescents with electrophysiologic and structural congenital heart disease is a challenging clinical problem. The body of evidence for making these recommendations is limited and likely based on expert opinion, medicolegal concerns, and perceived risks of sudden cardiac death (SCD) with activity. The Bethesda Conference has established consensus guidelines for determining the eligibility of athletes with cardiovascular abnormalities for competitive sports and their disqualification from them. However, literature on guidelines for noncompetitive physical activity is not available. A survey was designed to determine practice patterns for patients with electrophysiologic and structural congenital heart disease. Between July 2011 and December 2011, approximately 350 health care providers working with this group of patients were recruited by email or while attending professional meetings. The survey received 81 responses, primarily from pediatric cardiologists (70 %). The findings indicate that the majority of Canadian cardiac care providers surveyed are only partially implementing current recommendations. Areas of variance included physical activity recommendations for hypertrophic cardiomyopathy, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and heart transplantation, among others. The development of comprehensive consensus guidelines for activity recommendations was supported by 96 % of the respondents. The heterogeneity of responses may be attributable to conflicting and poorly evidenced information in the literature, a lack of emphasis on recreational activity, an entrenched tendency toward bed rest in the cardiology community, and a lack of awareness by cardiac care providers regarding the actual risk associated with physical activity in electrophysiologic and structural congenital heart disease. A balanced discussion is required in considering both the significant benefit of physical activity in reducing cardiovascular risk factors and the small possibility of SCD in children and young adults with electrophysiologic and structural congenital heart disease.

Echo-Doppler assessment of the biophysical properties of the aorta in children with chronic kidney disease.

Chronic kidney disease (CKD) is known to cause increased arterial stiffness, which is an important independent risk factor for adverse cardiovascular events. The purpose of this study was to assess the vascular properties of the aorta (AO) in a group of children with CKD using a noninvasive echocardiography (echo)-Doppler method. We studied 24 children with stages 2 through 5 CKD and 48 age-matched controls. Detailed echocardiographic assessment and echo-Doppler pulse wave velocity (PWV) was performed. Indices of arterial stiffness, including characteristic (Zc) and input (Zi) impedances, elastic pressure-strain modulus (Ep), and arterial wall stiffness index, were calculated. CKD patients underwent full nephrology assessment, and an iohexol glomerular filtration rate was performed, which allowed for accurate assignment of the CKD stage. CKD patients had greater median systolic blood pressure (114 vs. 110 mmHg; p < 0.04) and pulse pressure (51 vs. 40 mmHg; p < 0.001) compared with controls. PWV was similar between groups (358 vs. 344 cm s(-1); p = 0.759), whereas Zi (182 vs. 131 dyne s cm(-5); p < 0.001), Zc (146 vs. 138 dyne s cm(-5); p = 0.05), and Ep (280 vs. 230 mmHg; p < 0.02) were significantly greater in CKD than in controls. Although load-dependent measures of arterial stiffness were greater in non-dialysis dependent CKD patients, PWV was not increased compared with controls. This suggests that the increased arterial stiffness may not be permanent in these pediatric patients with kidney disease.

Serial measurements of exercise performance in pediatric heart transplant patients using stress echocardiography.

Heart transplantation is an increasingly acceptable therapeutic option for children with end-stage and complex congenital heart disease. With advances in surgery, immunosuppression, and follow-up care, functional outcomes need to be evaluated. We report the results of serial exercise testing performed using stress echocardiography in a cohort of pediatric HTP. HTP (n = 7) exercised on a semi-recumbent ergometer to volitional fatigue. Echocardiography-Doppler measurements, HR, and blood pressure were taken at rest and during staged exercise. Results were compared with healthy CON (n = 12). HTP did significantly less work during exercise (940 vs. 1218 J/kg, p < 0.03). Their SVI (33 vs. 49 mL/m(2), p < 0.003), CI (5.16 vs. 9.25 L/min/m(2), p < 0.0005), and HR (162 vs. 185 bpm, p < 0.02) were lower at peak exercise. HTP had a lower SF at peak exercise (48% vs. 52%, p < 0.03) and an abnormal relationship between the MVCFc and σPS. During follow-up, hemodynamics and left ventricular function remained relatively constant in HTP. HTP are able to exercise safely; however, their exercise tolerance is reduced, and hemodynamics and contractility are diminished. Over time, their hemodynamics and left ventricular function have remained relatively constant.

Aortic Dimensions, Biophysical Properties, and Plasma Biomarkers in Children and Adults with Marfan or Loeys-Dietz Syndrome.

BACKGROUND: Aortic dilation, stiffening, and dissection are common and potentially lethal complications of Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), which involve abnormal transforming growth factor beta (TGF-ß) signalling. The relation of aortic dimensions, stiffness, and biomarker levels is unknown. The objective of this study was to measure aortic dimensions, stiffness, TGF-ß and matrix metalloproteinase (MMP) levels, and endothelial function in patients with MFS, and to compare TGF-ß levels in patients with MFS receiving different therapeutic regimens. METHODS: This was a cohort study of 40 MFS and 4 LDS patients and 87 control participants. Aortic dimension and stiffness indexes, including pulse wave velocity (PWV), were measured using echocardiography and Doppler. Total and free TGF-ß and MMP blood levels were measured using Quantikine (R&D Systems, Inc, Minneapolis, MN) and Quanterix (Billerica, MA) kits. Endothelial function was measured using brachial artery flow-mediated dilation. RESULTS: PWV was increased in patients with MFS. There were increased MMP-2 levels in those with MFS but no increase in free or total TGF-ß or MMP-9 levels compared with control participants. There was no difference in TGF-ß levels between MFS patients receiving no medications, angiotensin receptor blockers, and ß-blockers. PWV correlated most strongly with age. Endothelial function showed premature gradual decline in patients with MFS. CONCLUSIONS: Despite the increased PWV, monitoring aortic stiffness or TGF-ß levels would not be helpful in patients with MFS. TGF-ß levels were not increased and the increased MMP-2 levels suggest consideration of a different therapeutic target.

CONTEXTE: La dilatation, la rigidification et la dissection de l'aorte sont des complications fréquentes et parfois mortelles du syndrome de Marfan (SM) et du syndrome de Loeys-Dietz (SLD), qui sont tous deux dûs à une anomalie de la voie de signalisation du facteur de croissance transformant bêta (TGF-ß). On ne connaît pas la relation entre les dimensions et la rigidité de l'aorte et la présence de biomarqueurs. Notre étude visait à mesurer les dimensions et la rigidité de l'aorte, les taux de TGF-ß et de métalloprotéases matricielles (MMP) et la fonction endothéliale chez des patients atteints du SM, et à les comparer aux taux de TGF-ß observés chez des patients également atteints de SM, mais recevant un autre traitement. MÉTHODOLOGIE: Il s'agissait d'une étude de cohorte menée auprès de 40 patients atteints du SM et de quatre patients atteints du SLD, ainsi que de 87 témoins. Les indices des dimensions et de la rigidité aortiques, y compris la vitesse d'onde de pouls (VOP), ont été mesurés par échocardiographie et par échographie Doppler. Les taux sanguins de TGF-ß et de MMP totaux et libres ont été mesurés à l'aide de trousses Quantikine (R&D Systems, Inc, Minneapolis, MN) et Quanterix (Billerica, MA). La fonction endothéliale a été mesurée par dilatation liée au flux dans l'artère brachiale. RÉSULTATS: La VOP était plus élevée chez les patients atteints du SM. On a aussi observé une hausse des taux de MMP-2 chez les patients atteints de SM, mais aucune augmentation des taux de TGF-ß ou de MMP-9 libres ou totaux comparativement aux témoins. Il n'y avait pas de différence entre les taux de TGF-ß chez les patients atteints de SM ne recevant aucun traitement, ceux qui prenaient un antagoniste des récepteurs de l'angiotensine et ceux qui prenaient un bêtabloquant. La VOP été plus fortement corrélée avec l'âge. La fonction endothéliale a affiché un déclin progressif prématuré chez les patients atteints du SM. CONCLUSIONS: Malgré l'augmentation de la VOP, il ne semble pas utile de surveiller la rigidité aortique ni les taux de TGF-ß en cas de SM. Les taux de TGF-ß n'étaient pas plus élevés chez les patients atteints du SM, et la hausse des taux de MMP-2 indique qu'il conviendrait de choisir une autre cible thérapeutique.

Early changes in the biophysical properties of the aorta in pre-adolescent children born small for gestational age.

OBJECTIVE: To assess the biophysical properties of the aorta in children born small for gestational age (SGA) with an echo-Doppler method and to determine associations with known perinatal risk factors. STUDY DESIGN: In this cross-sectional study, 39 SGA and 41 control subjects aged 8 to 13 years were recruited. Perinatal risk factors were recorded. The aortic diameters and pulse wave transit time around the aortic arch were measured with echo-Doppler and the blood pressure recorded. Pulse wave velocity, aortic input impedance (Zi), characteristic impedance (Zc), arterial pressure-strain elastic modulus (Ep), and arterial wall stiffness index (beta-index) were calculated. RESULTS: Pulse wave velocity (374 +/- 46 vs 348 +/- 47 cm/sec, P < .02); Zi (177 +/- 39 vs 142 +/- 27 dynes x sec/cm(5), P < .0001); Zc (185 +/- 29 vs 152 +/- 37 dynes x sec/cm(5), P < .0001); Ep (286 +/- 101 vs 216 +/- 41 mm Hg, P < .0001); and beta-index (2.43 +/- 0.32 vs 2.17 +/- 0.15, P < .0001) were all higher in SGA. We found negative associations between the following: birth weight and Zi, Zc, Ep, and beta-index; as well as body mass index and Zi, Zc. CONCLUSION: This simple echo-Doppler method demonstrated abnormal biophysical properties of the aorta in a cohort of pre-adolescent patients born SGA who remain small in stature and continue to have normal blood pressure.

Vitamin A is systemically bioavailable after intratracheal administration with surfactant in an animal model of newborn respiratory distress.

Chronic lung disease (CLD) is a major cause of long-term morbidity in extremely LBW infants with respiratory distress syndrome. Parenteral vitamin A administration decreases the risk of CLD. We tested the hypothesis that intratracheal vitamin A administration with surfactant is systemically bioavailable without interfering with the functional properties of exogenous surfactant. Newborn piglets were ventilated with 100% FiO2 and sequential saline lavage induced respiratory distress syndrome. During lung injury induction, ventilator changes were allowed, but none were made following treatment allocation. Animals were assigned by chance in a blinded control trial to three groups: I=control; II=surfactant; III=surfactant+vitamin A. Hemodynamics, lung mechanics, and blood gases were measured following instrumentation, pre- and posttreatment for 4 h, at which time the liver was sampled for retinol determination. All parameters improved in animals receiving surfactant. A significant interaction existed between time and group for PaO2 and alveolar-arterial oxygen difference (A-aDO2). Hepatic levels of retinol were higher (p<0.001) in animals receiving retinyl acetate. Intratracheal administration of surfactant+vitamin A did not alter the beneficial effects of surfactant on lung compliance and gas exchange. Intratracheal Vitamin A was associated with rapid hepatic uptake. Further studies are warranted.

Primary pulmonary arterial hypertension and autoimmune polyendocrine syndrome in a pediatric patient.

Both primary pulmonary artery hypertension (PPAH) and autoimmune polyendocrine syndrome (APS) are rare disorders in children. We report a boy who was diagnosed with severe PPAH at 12 years of age. He was treated with prostacyclin for 6 years, briefly with adjunct bosentan, and eventually sildenafil was added. Six years later, after his diagnosis of PPAH, he developed APS in the form of hyperthyroidism and type 1 diabetes mellitus. No mutations were identified through genetic testing of bone morphogenetic protein receptor type II and the autoimmune-regulator gene. To our knowledge this is the first description of the combination of these two extremely rare diseases in a child.

Does biventricular pacing improve hemodynamics in children undergoing routine congenital heart surgery?

Biventricular (BiV) pacing or cardiac resynchronization therapy (CRT) is an established therapy for heart failure in adults. In children, cardiac dyssynchrony occurs most commonly following repair of congenital heart disease (CHD) where multisite pacing has been shown to improve both hemodynamics and ventricular function. Determining which patient types would specifically benefit has not yet been established. A prospective, repeated measures design was undertaken to evaluate BiV pacing in a cohort of children undergoing biventricular repair for correction of their CHD. Hemodynamics, arterial blood gas, electrocardiographic (ECG), and echocardiographic data were collected. Pacing protocol was undertaken prior to the patient's extubation with 20 min of conventional right ventricular (RV) or BiV pacing, preceded and followed by 10 min of recovery time. Multivariate statistics were used to analyze the data with p values <0.05 considered significant. Twenty-five (14 female) patients underwent surgery at a median (range) age of 5.2 (0.1-37.4) months with no early mortality. The Risk-adjusted classification for Congenital Heart Surgery (RACHS) scores were 2 in 14 patients, 3 in eight patients, and 4 in three patients. None had pre-existing arrhythmias, dyssynchrony, or required pacing pre-operatively. No patient required implantation of a permanent pacemaker post-operatively. The median cardio-pulmonary bypass time was 96 (55-236) min. RV and BiV pacing did not improve cardiac index from baseline (3.23 vs. 3.42 vs. 3.39 L/min/m2; p > 0.05). The QRS duration was not changed with pacing (100 vs. 80 vs. 80 ms; p > 0.05). On echocardiography, the time-to-peak velocity difference between the septal and posterior walls (synchrony) during pacing was similar to baseline and was also not statistically significant. BiV pacing did not improve cardiac output when compared to intrinsic sinus rhythm or RV pacing in this cohort of patients. Our study has shown that BiV pacing is not indicated in children who have undergone routine BiV congenital heart surgery. Further prospective studies are needed to assess the role of multisite pacing in children with ventricular dyssynchrony such as those with single ventricles, those undergoing reoperation or those with high RACHS scores.

Are implantable loop recorders useful in detecting arrhythmias in children with unexplained syncope?

INTRODUCTION: Syncope and presyncope are symptoms that occur infrequently in children, are unpredictable, and represent a diagnostic challenge to the physician. Conventional diagnostic investigations are often unable to establish a diagnosis, making it difficult to determine patient risk and direct appropriate therapy. The implantable loop recorder (ILR) is a medical device that was created for prolonged monitoring of heart rate and rhythm and has been used in a limited number of pediatric studies in which the cause of the syncope is unknown. METHODS: This is a retrospective review of the clinical, surgical, and follow-up data of patients who had ILR devices implanted after conventional testing failed to identify a cause for their symptoms. RESULTS: The diagnostic yield of the ILR device in unmasking the cause for symptoms in our patient cohort was 64%. In our study, manually activated events accounted for 71% of all documented episodes and 68% of the cases involving hemodynamically important arrhythmias or transient rhythm changes. The ILR device can be safely implanted and explanted in children without significant morbidity, in most cases. None of our patients experienced any long-term adverse events associated with placement of the device and all were alive at last follow-up. CONCLUSIONS: The use of the ILR device is a useful tool to help unmask arrhythmias as a cause of unexplained syncope in children. Patient selection for who should and should not have an ILR device implanted will continue to influence its diagnostic utility and generate controversy among stakeholders.

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.