Dysfunction In Pediatric Patients Research Articles

Evaluating dysphagia in infants with congenital heart disease using Fiberoptic Endoscopic Evaluation of Swallowing

ObjectiveDysphagia is common in infants with congenital heart disease (CHD). However, there is minimal published data regarding its management outside of the perioperative period. The objective of this study is to describe the role of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in the diagnosis and management of dysphagia in infants with CHD. MethodsInfants with CHD who underwent FEES exam for evaluation of swallowing dysfunction between February 2015 and February 2021 at a university-based, tertiary care urban pediatric hospital were studied. Demographic data, presenting symptoms, medical history, and dysphagia history were examined. The validated Dysphagia Outcome and Severity Scale (DOSS) was used to standardize and compare dysphagia severity. Results62 FEES exams were performed on 48 patients. All 48 patients were diagnosed with dysphagia and had a mean dysphagia severity score (DOSS) of 2.68. Patients with wet laryngeal congestion on presentation had worse mean DOSS score and were more likely to demonstrate aspiration on FEES exam (p < 0.01). There was no significant difference in mean DOSS or presence of aspiration when comparing infants who had cardiothoracic surgery, vocal cord paralysis, or lower respiratory tract illness with those who had not (p > 0.05). ConclusionA FEES exam is an effective and well-tolerated procedure for evaluating swallowing dysfunction in pediatric patients with CHD and its use reduces radiation exposure for this vulnerable population. Wet laryngeal congestion was found to be predictive of more severe dysphagia and aspiration. There is no significant association between severity of dysphagia or aspiration on FEES exam and history of cardiac surgery, vocal cord paralysis, or lower respiratory tract illness.

Total serum cortisol level is low in children with severe dengue shock syndrome.

Dengue shock syndrome (DSS) is a potentially critical and life-threatening concern, especially in children of tropical countries. The serum cortisol levels in severe DSS or later stages of DSS are limited references. We prospectively studied an association between of serum cortisol as well as interleukin levels and the severity of DSS in pediatric patients. A prospective cross-sectional study of 35 consecutive DSS cases (3 months to 16 years old) admitted to our institution from July 1, 2019, to June 30, 2020 was conducted. Serum cortisol, IL-6, and IL-10 were measured at T0 (shock recognition) and T12 (12 hours after T0); their values were presented as median and interquartile ranges (25%-75%). Severe DSS included patients with impalpable pulses or systolic blood pressure < 70 mmHg, recurrent shock, and prolonged shock. In contrast, non-severe DSS presented circulatory failure without any features of severe DSS. A total of 8 (22.8%) severe DSS patients expressed the cortisol (T0) significantly lower compared to the non-severe DSS group (7.3 μg/dl versus 14.3 μg/dl, p=0.008). In severe DSS, there was a minimal change in cortisol levels between T0 and T12 (7.3 μg/dl and 4.7 μg/dl p>0.05), whereas the decrease is significant in their counterparts (14.3 μg/dl to 5.6 μg/dl, p<0.005). Additionally, there were moderate correlations between IL-6 (T0), IL-10 (T0), IL-10 (T12) and total fluid requirement (Spearman's rho = 0.47, 0.4, and 0.36, respectively; p<0.05). Our study demonstrated that adrenal dysfunction was present in patients with severe and non-severe DSS, as noted by cortisol level at T12. In addition, IL-6 and IL-10 levels are correlated with the total fluid requirement, which is a marker of DSS severity. Further studies could reveal how adrenal dysfunction in pediatric patients with DSS can affect outcomes and the potential roles of interleukin levels in fluid management strategy.

Evaluation of Left Atrial Function and Cardiac Autonomic Dysfunction in Pediatric Patients with Type 1 Diabetes Mellitus

Type 1 Diabetes mellitus (DM) is associated with the development of cardiovascular disease. In this study we aimed to determine left atrial function with two-dimensional speckle tracking echocardiography (2D-STE) and to identify cardiac autonomic dysfunction with P wave analysis in pediatric patients with Type 1 Diabetes Mellitus (DM). 63 patients and 36 healthy controls were included in the study. Conventional transthoracic echocardiography, left atrial 2D-STE, and 12-lead surface electrocardiography were performed in all patients. The LA strain (LA S) parameters: systolic [LA S-S], early diastolic [LA S-E], and late diastolic [LA S-A] strains were assessed. The LAV index (LAVI) was calculated as LAV divided by body surface area. Maximum P wave duration (Pmax), minimum P wave duration (Pmin) and P wave dispersion (Pdis) were measured from the 12-lead electrocardiogram. The LA S-S ([39.91±9.08 vs 45.88±8.85], p= 0.018), LA S-E ([26.86±7.54 vs 29.77±7.65], p= 0.012 ), and LA S-A ([13.43±4.68 vs 15.82±5.02], p= 0.022), E/A wave ratio ([1.76±0.37 vs 2.11±0.34], p= 0.024) values were significantly lower, the mean LAVI (ml/m2) ([26.10±2.81 vs 23.53±2.04], p= 0.028) and mitral valve A wave velocity ([0.58±0.14 vs 0.50±0.10], p= 0.032) were found to be higher in the patient group compared to the control group. Pdis and Pmax intervals were significantly longer in the patient group. 2D-STE showed impaired atrial function in pediatric patients with type 1 DM, in this patients may develop cardiac autonomic dysfunction. This may be diagnosed on ECG even when the patients are asymptomatic.

Contractile and Structural Properties of Detrusor from Children with Neurogenic Lower Urinary Tract Dysfunction

Simple SummaryDisorders of bladder function can result from congenital spinal cord developmental defects and can remain in a significant number of patients despite surgical improvements to repair the primary defect. We studied the ability of bladder wall muscle from such patients to contract, a function essential to void collected urine and avoid urinary tract infections and potential damage to the kidneys. Tissue was taken when patients were several years old, at the time of surgical operations to improve bladder function. This tissue would otherwise have been discarded and was collected with the full ethical approval and consent of parents or guardians. We found that the ability of the bladder wall samples to contract was impaired and was generally stiffer; both of which would make it more difficult for the bladder to void urine. These functional changes were associated with a replacement of muscle with connective tissue (fibrosis). The experiments provide a pathway to devise strategies that might improve bladder function in these patients through reversal of the intrinsic tissue pathways that increase fibrosis.Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.

Correlation between Body Mass Index and Left Ventricular Remodeling and Function in Children with Sickle Cell Disease

Background:Cardiovascular complications play an important role in morbidity and mortality of patients with sickle cell disease (SCD). Historically, patients with SCD were underweight, but due to changes in the diet and advances in therapies there is a trend of increasing BMI, with some patients developing metabolic syndrome (MS). We hypothesized that obesity, MS, and SCD are associated with left ventricular (LV) remodeling and dysfunction and the presence of these conditions may increase the risk of cardiac disease.Objective:We aimed to evaluate the association between BMI and LV remodeling and dysfunction in pediatric patients with SCD, as well as the association with laboratory markers and clinical outcomes.Methods:We performed a retrospective study that included patients 10 to 22 years old with SCD followed at St. Christopher's Hospital for Children. Data collected included BMI, markers of MS, hemolysis, and inflammation, clinical outcomes and 2D and Doppler echocardiographic parameters. Echocardiogram parameters included those of cardiac structure, geometry, systolic function, and diastolic function. Analysis of variance (ANOVA) tests were performed to examine the differences between biomarkers and various weight categories. Pearson correlations were calculated to evaluate associations of BMI percentile with biomarkers and LV remodeling variables. A chi square test was used to assess differences in geometry by weight categories. Differences in BMI percentile associated with MS status was explored with a T-Test. ANOVA was used to assess differences in mean LV remodeling and functional variables associated with the various weight categories.Results:Demographic and laboratory data was collected on all 139 patients who met inclusion criteria, 35 had both pediatric cardiology evaluation and complete echocardiography. Of the 139 patients, 17 (12%) were obese, with 5 of them meeting the criteria for MS as defined by the International Diabetes Federation. Blood pressure was found to be significantly higher in obese patients when compared to non-obese patients (p = 0.026). Hemoglobin was statistically different among weight groups (underweight, normal weight, overweight, obese), with higher mean values being seen in the overweight and obese groups (p = 0.006). No significant correlations were found between cardiac biomarkers, BMI percentile and MS. In 35 patients with echocardiographic data, BMI percentile was positively correlated with relative wall thickness and negatively correlated with peak early LV filling and peak early LV filling/septal annuli early peak (E/Ea) velocities. Relative wall thickness was also positively associated with age. Partial correlations of BMI percentile with these variables were therefore calculated and remained significant in the same directions: Relative wall thickness (r = 0.345, p = 0.046), peak early LV filling velocity (r = -0.473, p = 0.011) and E/Ea (r = -0.415, p = 0.015). E/Ea was also significantly associated with weight category, with higher values in the normal and underweight groups (p = 0.020). Weight category and geometry were not significantly related.Conclusions:Obese patients were found to have significantly higher blood pressures and higher BMI percentiles were associated with LV remodeling, contributing to the risk of cardiac disease. Conversely, higher BMI percentile was associated with lower diastolic function measures (improved LV diastolic function) and the trend of higher mean hemoglobin values. This study suggests a complex relationship between BMI, hemoglobin and cardiovascular risks in children with SCD. Further prospective studies with larger sample size are necessary to validate our findings and to develop preventive strategies for cardiovascular risks in SCD. DisclosuresNo relevant conflicts of interest to declare.

Olfactory and Gustatory Dysfunction in Pediatric Patients With Coronavirus Disease (COVID-19).

Olfactory and Gustatory Dysfunction in Pediatric Patients With Coronavirus Disease (COVID-19).

Association of Calculated Area under the Curve or Cyclosporine C0 and C2 Level Monitoring in Pediatric Renal Transplant Patients

Cyclosporine A (CsA) is highly variable pharmacokinetically and has a narrow therapeutic window; the serum level of patients treated with CsA must be monitored carefully. We investigated the trough and second-hour serum levels of CsA, the calculated area under the curve (AUC), and their association of those factors with chronic allograft dysfunction in pediatric patients.

New PELOD-2 cut-off score for predicting death in children with sepsis

Background According to the most recent Sepsis-3 Consensus, the definition of sepsis is life-threatening organ dysfunction caused by dysregulated immune system against infection. Currently, one of the most commonly used prognostic scoring system is pediatric logistic organ damage-2 (PELOD-2) score.&#x0D; Objective To determine and validate the pediatric logistic organ dysfunction-2 (PELOD-2) cut-off score to predict mortality in pediatric sepsis patients.&#x0D; Methods A prospective cohort study was conducted in the intensive care units of Cipto Mangunkusumo Hospital, Jakarta. We assessed subjects with PELOD-2 and calculated the predicted death rate (PDR) using SFAR software. The Hosmer-Lemeshow goodness-of-fit test was used to evaluate calibration and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) to estimate discrimination.&#x0D; Results Of 2,735 children admitted to the emergency department, 52 met the inclusion criteria. Patients had various types of organ dysfunction: 53.8% respiratory, 28.8% neurological, 15.4% cardiovascular, 1.9% hematological. The mortality rate in this study was 38.5%. Mean PELOD-2 score was higher in patients who died than in those who survived [13.9 (SD 4.564) vs. 7.59 (SD 3.025), respectively, P=0.000]. The discrimination of PELOD-2 score with the lactate component had an AUC of 85.5% (95%CI 74.5 to 96.5), while PELOD-2 without lactate had an AUC of 85.4% (95%CI 74.5 to 96.3%). We propose a new PELOD-2 cut-off score to predict organ dysfunction and death of 10, with 75% sensitivity, 72% specificity, 62.5% PPV, and 82% NPV. PELOD-2 score &gt; 10 had a moderate, statistically significant correlation to mortality (r=0.599; P&lt;0.001).&#x0D; Conclusion A PELOD-2 score &gt; 10 is valid for predicting life-threatening organ dysfunction in pediatric patients with sepsis.

Cardiac functions in children with steroid-sensitive nephrotic syndrome.

The aim of the present study was to evaluate the presence of cardiac systolic and diastolic dysfunction in pediatric patients with steroid-sensitive nephrotic syndrome (NS). The study population consisted of 19 patients with debut-relapse of NS aged 1-18years and 30 sex and age-matched healthy controls. Blood and urine samples, two M-mode conventional echocardiograms and tissue Doppler velocity imaging were evaluated in both attack and remission periods. With regard to conventional pulse wave Doppler (cPWD), steroid-sensitive NS patients (both in debut / relapse and in remission periods) had a higher peak of late diastolic flow velocities (A peak), and patients in debut / relapse had a lower E/A ratio than the control group, indicating diastolic dysfunction (overall P = 0.003 and P = 0.006, respectively). Based on tissue Doppler velocity imaging echocardiography results, patients in debut/relapse had a higher A' and a lower E'/A' ratio (overall P < 0.001 and P = 0.001, respectively). There was also a significant difference in the cPWD E/TDI E' ratio between the patients showing an increased cPWD E/TDI E' ratio in remission periods compared to in debut/relapse periods (P = 0.09). The albumin levels were positively correlated with E'/A' and E/ E' ratio (r = 0.609; P = 0.007, r = 0.472; P = 0.041 respectively). Systolic cardiac functions are preserved but diastolic functions are affected in steroid-sensitive NS patients both in debut/relapse and in remission periods in a relatively short time. The persistence of left ventricular (LV) dysfunction during the remission period requires special attention during the follow up for early detection of cardiac abnormalities.

Progressive QRS Duration and Ventricular Dysfunction in Pediatric Patients with Chronic Ventricular Pacing.

Pacemakers are a mainstay of therapy for patients with congenital and acquired heart block, but ventricular pacing is related to ventricular dysfunction. We sought to evaluate patient and device characteristics associated with ventricular dysfunction in pediatric patients with chronic ventricular pacing. This was a retrospective cohort of pediatric patients with heart block and chronic ventricular pacing. Patient, ECG, and device characteristics were analyzed to determine factors associated with ventricular dysfunction. Longitudinal ECG and echocardiogram parameters were obtained to track changes in QRS and systemic ventricular systolic function over time. In total, 82 patients were included (median age at implant 0.81years). Over a follow-up time of 6.1years, 18% developed ventricular dysfunction. Patients with dysfunction had greater current QRS duration (p = 0.002) compared to those with preserved function with a similar time from device implantation. There was no difference between lead location or age at device implantation. QRS duration increased with time from implant and the resultant ΔQRS was associated with ventricular dysfunction (p = 0.01). QRS duration >162ms was associated with a 5.8 (2-9)-fold increased risk for dysfunction. Transvenous leads were associated with longer QRS duration with no difference compared to epicardial leads in development of ventricular dysfunction. This study demonstrated that the absolute paced QRS duration and Δpaced QRS were association with long-term ventricular dysfunction independent of how long a given patient was paced. Patients in high-risk categories may benefit from close echocardiographic monitoring. Whether permissive junctional rhythm or His bundle/biventricular pacing decreases the rate of dysfunction needs further study.

Right ventricular area strain from 3-dimensional echocardiography: Mechanistic insight of right ventricular dysfunction in pediatric pulmonary hypertension

Right ventricular (RV) function is a major contributor to the outcome of pulmonary arterial hypertension (PAH). Adult studies demonstrated that regional and global changes in RV deformation are prognostic in PAH using 3-dimensional echocardiography (3DE). However, regional and global dynamic changes in RV mechanics have not been described in pediatric PAH. We compared 3DE RV regional and global deformation between pediatric patients who had associated PAH with congenital heart disease (APAH-CHD), pediatric patients who had idiopathic PAH (IPAH), and normal controls, and evaluated the clinical outcomes. A total of 48 controls, 47 patients with APAH-CHD, and 45 patients with IPAH were evaluated. 3DE RV sequences were analyzed and post-processed to extract global and regional deformation (circumferential, longitudinal, and area strain). Statistical analyses compared the sub-groups on the basis of global and regional deformation, and outcome analysis was performed. Patients with PAH had significantl8y different global and regional deformation (p < 0.001) compared with controls. Patients with APAH-CHD and and those with IPAH significantly differed in global circumferential strain (p < 0.010), area strain (inlet septum, p = 0.041), and circumferential strain at the inlet septum (p < 0.019), apex free wall (p < 0.004), and inlet free wall (p < 0.004). Circumferential strain at the inlet free wall and circumferential, longitudinal, and area strain at the apex free wall were predictors of adverse events. RV regional and global strain differ between controls and pediatric patients with PAH. RV apical free-wall area strain provides insight into the mechanism of RV dysfunction in pediatric patients with PAH, with regional strain emerging as outcome predictors, suggesting that this novel measure may be considered as a future measure of RV function.

Frequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media- a long-term observational study.

Background The thyroid gland of patients with congenital heart disease may be exposed to large doses of iodine from various sources. We assessed the thyroid response after iodine exposure during conventional angiography in cardiac catheterization and angiographic computer tomography in childhood. Methods Retrospective mid- to long-term follow-up of 104 individuals (24% neonates, 51% infants, 25% children) with a median age and body weight of 104days [0-8 years] and 5.3kg [1.6-20]. Serum levels of thyroid-stimulating hormone, free triiodthyronine and free thyroxine were evaluated at baseline and after excess iodine. We also assessed risk factors that may affect thyroid dysfunction. Results Baseline thyroidal levels were within normal range in all patients. The mean cumulative iodinate contrast load was 6.6±1.6mL/kg. In fact, 75% had experienced more than one event involving iodine exposure, whose median frequency was three times per patient [1-12]. During the median three years follow-up period [0.5-10], the incidence of thyroid dysfunction was 15.4% (n=16). Those patients developed acquired hypothyroidism (transient n=14, long-lasting n=2 [both died]) with 10 of them requiring temporary replacement therapy for transient thyroid dysfunction, while four patients recovered spontaneously. 88 individuals (84.6%) remained euthyroid. Repeated cardiac interventions, use of drugs that interfere with the thyroid and treatment in the intensive care unit at the index date were strong predictors for acquired thyroid dysfunction. Conclusions The incidence of acquired hypothyroidism after iodine excess was 15.4%. However, most patients developed only transient hypothyroidism. Systemic iodine exposure seems to be clinically and metabolically well tolerated during long-term follow-up.

Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease.

We retrospectively reviewed the data of 140 female pediatric patients with rare mitochondrial diseases (MDs) confirmed using muscle biopsy. We evaluated patients who were diagnosed with central precocious puberty (PP) with early pubertal development to determine whether PP is a clinical manifestation of MDs. We also examined the clinical, auxiological, laboratory, and radiological parameters after 1year of gonadotropin-releasing hormone treatment for central PP. Among the 140 girls with MDs, 29 had early pubertal development and underwent endocrine evaluation. Ten (7.1%) patients were diagnosed with central PP; the prevalence of central PP was higher than was that previously thought. Patients with central PP exhibited bone age advancement over 1year and increased sex hormone levels despite their young age at diagnosis. Serum estradiol levels were significantly higher in younger patients than in older patients (P = 0.004). Patients with central PP treated with gonadotropin-releasing hormone had favorable outcomes, and their pubertal development was suppressed for 1year.Conclusion: Central PP may be a manifestation of endocrine dysfunction in young girls with MDs. What is Known: • The general characteristics of mitochondrial diseases include developmental delays and retarded growth. • Precocious puberty has rarely been suggested as a clinical manifestation of mitochondrial diseases. What is New: • Among the 140 girls with mitochondrial diseases, 10 (7.1%) were diagnosed with central precocious puberty. • Serum estradiol levels were significantly higher in younger patients than in older patients.

Predictors of behavioral dysregulation and social dysfunction in pediatric patients with epilepsy and obesity: Developmental timing matters

Childhood obesity has been associated with greater risks of psychopathology, including externalizing behaviors and social dysfunction. However, there has been limited research on the effect of obesity on psychosocial functioning among pediatric patients with epilepsy. Accordingly, this study aimed to examine the association between overweight/obesity and behavioral and social functioning among pediatric patients with epilepsy, as function of their developmental status. We completed a retrospective chart review of data (seizure factors, intellectual functioning, caregiver ratings of aggression/defiance and social problems, sex- and age-adjusted body mass index (BMI) percentile) from 30 school-age children and 30 adolescents with epilepsy evaluated through our institute. Body mass index percentile and overweight/obesity status were not associated with seizure variables. Despite controlling for intellectual functioning, overweight/obesity was associated with greater aggression/defiance among child patients but not adolescents. In contrast, adolescence, but not weight status, was associated with social dysfunction. In brief, while early interventions focused on behavior and weight management among children with epilepsy may mitigate risk of aggression and oppositional behavior, among adolescent patients, therapies directed towards promoting interpersonal skills, sense of social competency, and expansion of social support system may reduce psychosocial maladjustment. Findings highlight need to understand the developmental effects of common medical comorbidities on neurobehavioral functioning among youth with epilepsy.

Analysis of temporomandibular joint dysfunction in paediatric patients with unilateral crossbite using automatically generated finite element models

The evaluation of temporomandibular joint (TMJ) dysfunction using finite element models is a time consuming process that requires extensive technical knowledge. We combined a statistical active appearance model with automated modelling algorithms to biomechanically study the relationship between TMJ malformations and dysfunction in radiographs from 20 paediatric patients with unilateral crossbite. A fitting algorithm (fitting error < 4%) recognised the TMJ shape and adjusted the dimensions of each patient-specific 2D FE model, which was then used to compute 2 different joint movements. Significant functional differences were observed between the crossbite and non-cross bite sides, and the shape-function relation was verified.

Tilt-table Echocardiography Unmasks Early Diastolic Dysfunction in Patients With Hemoglobinopathies.

Individuals with hemoglobinopathy (sickle cell anemia and thalassemia major) are at risk for cardiac complications such as heart failure and cardiomyopathy. Diastolic dysfunction is known to precede systolic dysfunction in many cardiac diseases. This study sought to determine whether changes in left atrial (LA) function during manipulation of cardiac preload by tilt-table echocardiography can unmask subclinical diastolic dysfunction in pediatric patients with hemoglobinopathies. Eleven sickle cell anemia, 9 transfusion-dependent thalassemia major, and 10 control subjects underwent tilt-table echocardiogram in the supine (loading) and 30-degree upright (unloading) positions and cardiac magnetic resonance imaging (MRI). Echocardiography assessed LA and left ventricular (LV) strain, strain rate, mitral inflow, and annular velocities. MRI assessed LV function, myocardial T1 and T2* for iron deposition. Both thalassemia major and sickle cell anemia patients had normal LV function and no evidence of cardiac iron deposition on MRI T2* measurements. During cardiac loading, controls appropriately increased LA conduit (P=0.002) and reservoir strain (P=0.002), mitral e' velocity (P<0.0001) and medial e' velocity (P=0.002), while the hemoglobinopathy patients showed no change in these parameters. In pediatric sickle cell anemia and thalassemia, tilt-table echocardiography unmasked a failure to augment LA function in response to loading, suggesting altered myocardial relaxation is present, before evidence of iron overload or systolic dysfunction.

Pediatric CNS Tumor Patients Have Significantly Lower Requirement of Tissue Plasminogen Activator for Episodes of Central Venous Catheter Dysfunction Compared With Other Pediatric Oncology Patients: Results of a Population-based Cohort Study.

Central venous catheters (CVCs) are an important component of care delivery in pediatric oncology patients. However, CVC dysfunction is a common problem. Tissue plasminogen activator (tPA) is often administered to re-establish function, however, specific experience in pediatric patients with central nervous system (CNS) tumors is lacking. The goal of this study was to investigate the CVC experience and use of tPA for episodes of CVC dysfunction in pediatric patients with CNS tumors in comparison with other patients. Medical records of all pediatric oncology patients from the 4 Atlantic provinces in Canada (Nova Scotia, New Brunswick, Prince Edward Island, and Newfoundland and Labrador) were reviewed. Data collected included demographics, treatment, details of CVCs along with CVC dysfunction, and tPA use. The cohort consisted of 1152 pediatric oncology patients, 222 (19.3%) of whom had CNS tumors. CVC dysfunction requiring tPA administration occurred in 12 (5.4%) of patients with CNS tumors compared with 182 (19.6%) of patients with non-CNS tumors (P=0.0001). Multivariate logistic regression analysis showed that administration of tPA for CVC dysfunction was 2.5 times more likely in patients with non-CNS tumors than those with CNS tumors (P=0.012; 95% confidence interval, 1.3-4.9). Our study showed that pediatric patients with CNS tumors require significantly less frequent administration of tPA for episodes of CVC dysfunction than patients with non-CNS tumors after adjusting for confounding factors. Hypotheses for this include: potential biologic differences of tumors, the role of the blood-brain barrier, or systematic differences in intensity of treatments.

Abstract P3006: Angiotensin-(1-7) Prevents Doxorubicin-Induced Aortic Dysfunction Through Anti-Fibrotic Mechanisms in Juvenile Male and Female Sprague Dawley Rats

Doxorubicin (Dox) is an effective, anthracycline chemotherapeutic administered for a variety of malignancies, but clinical use of the drug is limited by a cumulative, dose-dependent cardiotoxicity. Thus, adjuvant therapies are needed to mitigate Dox-induced cardiovascular damage in cancer patients, especially in pediatric patients with decades of life ahead. Our group showed that angiotensin-(1-7) [Ang-(1-7)], an endogenous peptide hormone with anti-cancer properties, improved vascular dysfunction in coronary vessels and cremaster muscle microvessels in Ang II-infused rats. In this study, juvenile male and female Sprague Dawley rats (n = 8-10) were administered a clinically equivalent dose of Dox (21-24 mg/kg) over 6 weeks, in the presence or absence of Ang-(1-7) [24 μg/kg/h]. Aortic function was measured using echocardiography. In both sexes, Ang-(1-7) blocked the Dox-mediated increase in pulse wave velocity (PWV), a measure of arterial stiffness (75% in males and 179% in females, p&lt;0.05 and p&lt;0.001). Dox decreased aortic lumen diameter (by 18%, p&lt;0.01) and increased wall thickness at systole (p&lt;0.01) in males, which was attenuated by Ang-(1-7). In male but not female aortas, Dox increased media hypertrophy by 16% (p&lt;0.01) and reduced elastin content by 17% compared to control rats (p&lt;0.001), changes prevented by Ang-(1-7). Conversely, collagen deposition was increased 2.5-fold in the aortic arches of female rats treated with Dox (p&lt;0.001), which was blocked by Ang-(1-7). Dox increased nuclear ERK1/2 by 2-fold in the aortic media of male rats (p&lt;0.01) and Ang-(1-7) significantly attenuated nuclear ERK1/2 localization. In contrast, neither Dox nor Ang-(1-7) changed total or nuclear ERK1/2 in the aortic arches of female rats. Dox increased nuclear pSMAD2 4-fold in males (p&lt;0.05) and 3-fold in females (p&lt;0.05); prophylactic treatment with Ang-(1-7) reduced the Dox-induced increases in nuclear pSMAD2 while the heptapeptide hormone had no effect alone. These results demonstrate that Ang-(1-7) prevented Dox-induced aortic dysfunction in both sexes, albeit through different mechanisms, suggesting that treatment with Ang-(1-7) may serve as an effective adjuvant to improve Dox-induced vascular dysfunction in pediatric patients.

Evaluation of cardiac function in pediatric patients with mild to moderate bronchial asthma in the era of cardiac strain imaging.

Bronchial asthma is a common chronic inflammatory airway disease, which may be associated with pulmonary hypertension and cardiac dysfunction. The aim of this study was to evaluate the ability of 2D-speckle tracking echocardiography (2D-STE) and tissue doppler imaging (TDI) to detect subtle cardiac dysfunction in pediatric patients with mild to moderate bronchial asthma. The study included 30 children with mild to moderate bronchial asthma and 27 age-matched healthy controls. Both groups underwent pulmonary function tests, TDI and 2D-STE. Myocardial performance index (MPI), S', E', A' velocities, global strain of left ventricle (LV), right ventricle (RV), and right atrium (RA) were measured. RV diastolic function was impaired in the patient group, as the tricuspid E' velocity was significantly lower in the patients when compared with the controls (16 [14-17] vs 16 [17-19] cm/s, P = .044), while the RV-MPI was significantly higher in patients when compared to controls (0.30 [0.27-0.36] vs 0.30 [0.30-0.30], P = .001). The global RV longitudinal strain, RA strain, and LV strain did not show significant differences between the test and the control groups. RV systolic parameters and LV systolic and diastolic parameters did not differ significantly between the two groups. Pediatric patients with mild to moderate bronchial asthma may have early RV diastolic dysfunction with preserved other cardiac functions.

Endovascular treatment of surgical mesoportal and portosystemic shunt dysfunction in pediatric patients

Published data describing the endovascular treatment of dysfunctional mesoportal and portosystemic shunts in the pediatric population are limited. We sought to describe the treatment and follow-up of such shunts managed by interventional radiology at a single pediatric hospital. We hypothesized that stenotic and occluded pediatric portosystemic and mesoportal shunts can be maintained patent by interventional radiology in the moderate term. We conducted a single-center retrospective study at a tertiary pediatric hospital. We included children with surgical mesoportal (meso-Rex) or portosystemic (mesocaval, splenorenal or splenocaval) shunts treated with attempted angioplasty or stenting from 2010 to 2018. Technical success was defined as catheterization and intervention upon the shunt with venographic evidence of flow improvement. The primary outcome variables were shunt patency at 1month, 6months, 12months and 24months post-procedure and freedom from reintervention. Twenty pediatric patients (11 boys, 9 girls; mean age 8.25years, range 1.3-17years) met inclusion criteria. Fifty-two interventions (primary and reintervention) on 13 splenorenal, 3 meso-Rex, 2 mesocaval and 2 splenocaval shunts were performed because of evidence of shunt failure, including gastrointestinal bleeding, hypersplenism, or radiographic evidence of a flow defect. The 11 stenotic shunts were treated with 100% technical success, while the remaining 9 occluded shunts were treated with 66.7% technical success. The mean number of reinterventions was 1.9 (standard deviation [SD] = 3.1) per child, which did not differ between stenotic and occluded shunts (P=0.24). Primary patency at 1-month, 6-month, 12-month and 24-months follow-up visits was 17/17 (100%), 10/16 (62.5%), 7/15 (46.7%) and 4/10 (40%), respectively. However, 100% of shunts were either primary patent or primary-assisted patent by endovascular reintervention. There were no cases of shunt occlusion following initial technical success. Finally, the median freedom from reintervention duration was 387days (SD=821days). Dysfunctional portosystemic surgical shunts are effectively managed by endovascular methods. While many shunts require reintervention, combined primary patency and assisted primary patency rates are excellent.