Leveraging a global, federated, real-world data network to optimize investigator-initiated pediatric clinical trials: the TriNetX Pediatric Collaboratory Network.

Objective: Clinical research networks facilitate collaborative research, but data sharing remains a common barrier. Materials and Methods: The TriNetX platform provides real-time access to electronic health record (EHR)-derived, anonymized data from 173 healthcare organizations (HCOs) and tools for queries and analysis. In 2022, 4 pediatric HCOs worked with TriNetX leadership to found the Pediatric Collaboratory Network (PCN), facilitated via a multi-institutional data-use agreement (DUA). The DUA enables collaborative study design and execution, with institutional review board-approved transfer of complete datasets for further analyses on a per-protocol basis. Results and Discussion: Of the 41.2 million children with TriNetX records, the PCN represents nearly 10%. The PCN assisted several early-career investigators to bring study concepts from conception to an international scientific meeting presentation and journal submission. Conclusion: The PCN facilitates EHR vendor-agnostic multicenter pediatric research on the global TriNetX platform. Continued growth of the PCN will advance knowledge in pediatric health.

Infant With Recurrent Vomiting and Poor Weight Gain Secondary to an Aberrant Subclavian Artery.

Failure to thrive (FTT) is a term commonly used to characterize slower-than-expected weight gain. While inadequate caloric intake is the predominant cause, failure to thrive is a manifestation of undernutrition often resulting from the interplay of multiple etiologies. This case highlights the diagnosis and management of an infant who presented with recurrent large-volume emesis and poor weight gain secondary to esophageal compression from an aberrant right subclavian artery (ARSA).

Facial Nerve Palsy in a Five-Month-Old Infant.

Facial nerve palsy is a common neurological disorder, and the etiology is categorized as either congenital or acquired. Even after extensive workup, a vast majority of cases are deemed idiopathic. Treatment of acquired facial nerve palsy in pediatrics is essential to prevent long-term aesthetic and functional complications. The prognosis is favorable in pediatric patients and those treated with corticosteroids.

Inability to Ambulate in a Pediatric Patient Secondary to an Aneurysmal Bone Cyst With Associated Pathological Fracture.

Bone pain in pediatric patients is exceedingly common, with etiologies ranging from benign lesions such as fibrous dysplasia and enchondromas to potentially devastating, life-threatening malignancies such as Ewing's sarcoma or osteosarcoma. Given the low yield of physical examination and routine laboratory workup, pediatric patients with bone pain or an inability to ambulate warrant further workup. The initial workup should consist of imaging with radiography. A large majority of patients will have a resolution of symptoms without intervention and will have normal imaging. When radiographic imaging has suspicious findings, expert consultation is warranted because differentiating between benign and malignant processes on imaging can be challenging. Here we present a case of a six-year-old male with progressive worsening leg pain who was found to have a rare aneurysmal bone cyst with an associated pathologic fracture requiring open reduction and internal fixation.

Investigation of Genetic Causes in Patients with Congenital Heart Disease in Qatar: Findings from the Sidra Cardiac Registry.

Congenital heart disease (CHD) is one of the most common forms of birth defects worldwide, with a prevalence of 1-2% in newborns. CHD is a multifactorial disease partially caused by genetic defects, including chromosomal abnormalities and single gene mutations. Here, we describe the Sidra Cardiac Registry, which includes 52 families and a total of 178 individuals, and investigate the genetic etiology of CHD in Qatar. We reviewed the results of genetic tests conducted in patients as part of their clinical evaluation, including chromosomal testing. We also performed whole exome sequencing (WES) to identify potential causative variants. Sixteen patients with CHD had chromosomal abnormalities that explained their complex CHD phenotype, including six patients with trisomy 21. Moreover, using exome analysis, we identified potential CHD variants in 24 patients, revealing 65 potential variants in 56 genes. Four variants were classified as pathogenic/likely pathogenic based on the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification; these variants were detected in four patients. This study sheds light on several potential genetic variants contributing to the development of CHD. Additional functional studies are needed to better understand the role of the identified variants in the pathogenesis of CHD.

Tipping the Balance: Vitamin D Inadequacy in Children Impacts the Major Gut Bacterial Phyla.

Vitamin D inadequacy appears to be on the rise globally, and it has been linked to an increased risk of osteoporosis, as well as metabolic, cardiovascular, and autoimmune diseases. Vitamin D concentrations are partially determined by genetic factors. Specific single nucleotide polymorphisms (SNPs) in genes involved in vitamin D transport, metabolism, or binding have been found to be associated with its serum concentration, and these SNPs differ among ethnicities. Vitamin D has also been suggested to be a regulator of the gut microbiota and vitamin D deficiency as the possible cause of gut microbial dysbiosis and inflammation. This pilot study aims to fill the gap in our understanding of the prevalence, cause, and implications of vitamin D inadequacy in a pediatric population residing in Qatar. Blood and fecal samples were collected from healthy subjects aged 4-14 years. Blood was used to measure serum metabolite of vitamin D, 25-hydroxycholecalciferol 25(OH)D. To evaluate the composition of the gut microbiota, fecal samples were subjected to 16S rRNA gene sequencing. High levels of vitamin D deficiency/insufficiency were observed in our cohort with 97% of the subjects falling into the inadequate category (with serum 25(OH)D < 75 nmol/L). The CT genotype in rs12512631, an SNP in the GC gene, was associated with low serum levels of vitamin D (ANOVA, p = 0.0356) and was abundant in deficient compared to non-deficient subjects. Overall gut microbial community structure was significantly different between the deficient (D) and non-deficient (ND) groups (Bray Curtis dissimilarity p = 0.049), with deficient subjects also displaying reduced gut microbial diversity. Significant differences were observed among the two major gut phyla, Firmicutes (F) and Bacteroidetes (B), where deficient subjects displayed a higher B/F ratio (p = 0.0097) compared to ND. Vitamin D deficient children also demonstrated gut enterotypes dominated by the genus Prevotella as opposed to Bacteroides. Our findings suggest that pediatric vitamin D inadequacy significantly impacts the gut microbiota. We also highlight the importance of considering host genetics and baseline gut microbiome composition in interpreting the clinical outcomes related to vitamin D deficiency as well as designing better personalized strategies for therapeutic interventions.

Chest compression by two-thumb encircling method generates higher carotid artery blood flow in swine infant model of cardiac arrest.

OBJECTIVE: Two-Thumb(TT) technique provides superior quality chest compressions compared with Two-Finger(TF) in an instrumented infant manikin. Whether this translates to differences in blood flow, such as carotid arterial blood flow(CABF), has not been evaluated. We hypothesized that TT-CPR generates higher CABF and Coronary Perfusion Pressure(CPP) compared with TF-CPR in a neonatal swine cardiac arrest model. METHODS: Twelve anesthetized & ventilated piglets were randomized after 3 min of untreated VF to receive either TT-CPR or TF-CPR by PALS certified rescuers delivering a compression rate of 100/min. The primary outcome, CABF, was measured using an ultrasound transonic flow probe placed on the left carotid artery. CPP was calculated and end-tidal CO2(ETCO2) was measured during CPR. Data(mean ± SD) were analyzed and p-value ≤0.05 was considered statistically significant. RESULTS: Carotid artery blood flow (% of baseline) was higher in TT-CPR (66.2 ± 35.4%) than in the TF-CPR (27.5 ± 10.6%) group, p = 0.013. Mean CPP (mm Hg) during three minutes of chest compression for TT-CPR was 12.5 ± 15.8 vs. 6.5 ± 6.7 in TF-CPR, p = 0.41 and ETCO2 (mm Hg) was 29.0 ± 7.4 in TT-CPR vs. 20.7 ± 5.8 in TF-CPR group, p = 0.055. CONCLUSION: TT-CPR achieved more than twice the CABF compared with TF-CPR in a piglet cardiac arrest model. Although CPP and ETCO2 were higher during TT-CPR, these parameters did not reach statistical significance. This study provides direct evidence of increased blood flow in infant swine using TT-CPR and further supports that TT chest compression is the preferred method for CPR in infants.

Effect of alternative chest compression techniques in infant and child on rescuer performance.

OBJECTIVE: Current chest compression (CC) guidelines for an infant recommend a two-finger (TF) technique with lone rescuer and a two- thumb (TT) technique with two rescuers, and for a child either an one hand (OH) or a two hand (TH) technique with one or two rescuers. The effect of a 30:2 compression:ventilation ratio using these techniques on CC quality and rescuer fatigue is unknown. We hypothesized that during lone rescuer CC, TT technique, in infant and TH in child achieve better compression depth (CD) without additional rescuer fatigue compared with TF and OH, respectively. DESIGN: Randomized observational study. SETTING: University-affiliated pediatric hospital. SUBJECTS: Adult healthcare providers certified in basic life support or pediatric advanced life support. INTERVENTIONS: Laerdal baby advanced life support trainer and Resusci junior manikin were modified to digitally record CD, compression pressure (CP) and compression rate. Sixteen subjects were randomized to each of the four techniques to perform 5 minutes of lone rescuer 30:2 compression:ventilation cardiopulmonary resuscitation. Rescuer heart rate (HR) and respiratory rate were recorded continuously and the recovery time interval for HR/respiratory rate to return to baseline was determined. Subjects were blinded to data recording. Groups were compared using two-sample, two-sided Student's t tests. MEASUREMENTS AND MAIN RESULTS: Two-thumb technique generated significantly higher CD and peak CP compared with TF (p < 0.001); there was no significant difference between OH vs. TH. TF showed decay of CD and CP over time compared with TT. Compression rate (per minute) and actual compressions delivered were not significantly different between groups. No significant differences in fatigue and recovery time were observed, except the TT group had greater increase in the rescuer's HR (bpm) from baseline compared with TF group (p = 0.04). CONCLUSIONS: Two-thumb compression provides higher CD and CP compared with TF without any evidence of decay in quality and additional rescuer fatigue over 5 minutes. There was no significant difference in child CC quality or rescuer fatigue between OH and TH. Two-thumb technique is preferred for infant CC and our data support the current guidelines for child CC.

Chest compression quality and rescuer fatigue with increased compression to ventilation ratio during single rescuer pediatric CPR.

OBJECTIVE: The effects of the recommended 30:2 compression:ventilation (C:V) ratio on chest compression rate (CR), compression depth (CD), compression pressure (CP) and rescuer fatigue is unknown during pediatric CPR. We hypothesized that a 30:2 C:V ratio will decrease compression depth and compression pressure and increase rescuer fatigue compared with a 15:2 ratio. DESIGN: Randomized crossover observational study. METHODS: Adolescent, child and infant manikins were modified to digitally record compression rate, compression depth, compression pressure and total compression cycles (CC). BLS or PALS certified volunteers were randomized to five CPR groups: adolescent (AD), child 1-hand (OH), child 2-hand (TH), infant two-finger (TF) and infant two-thumb (TT). Each rescuer performed each ratio for 5 min with the order randomized. Rescuer heart rate (HR) and respiratory rate (RR) were recorded continuously during CPR and used to determine the recovery time (RT) for HR/RR to return to baseline. Data (mean+/-S.D.) were contrasted by paired differences for quantitative data and the sign rank test for ordinal data. RESULTS: Eighty subjects (16 per group) were randomized. The peak compression pressure and compression rate were not different within any group, but total compression cycle were higher in all 30:2 groups. Compression depth (mm) was not significantly different within any group. The rescuer's HR (bpm) increased significantly during 30:2 CPR in AD and OH group with no significant differences in RR and recovery time. Subjects reported that 15:2 CPR was easier to perform (P<0.001). CONCLUSION: During single rescuer pediatric BLS, more compression cycles were achieved with 30:2 C:V ratio without effect on compression depth, pressure and rate. Increased HR with 30:2 C:V ratio was noted during larger manikin CPR without subjective difference of reported fatigue. Most rescuers in AD and TF group did not achieve recommended compression depth regardless of C:V ratio.

Ventricular Fibrillation-Induced Cardiac Arrest Results in Regional Cardiac Injury Preferentially in Left Anterior Descending Coronary Artery Territory in Piglet Model.

Objective. Decreased cardiac function after resuscitation from cardiac arrest (CA) results from global ischemia of the myocardium. In the evolution of postarrest myocardial dysfunction, preferential involvement of any coronary arterial territory is not known. We hypothesized that there is no preferential involvement of any coronary artery during electrical induced ventricular fibrillation (VF) in piglet model. Design. Prospective, randomized controlled study. Methods. 12 piglets were randomized to baseline and electrical induced VF. After 5 min, the animals were resuscitated according to AHA PALS guidelines. After return of spontaneous circulation (ROSC), animals were observed for an additional 4 hours prior to cardiac MRI. Data (mean ± SD) was analyzed using unpaired t-test; p value ≤ 0.05 was considered statistically significant. Results. Segmental wall motion (mm; baseline versus postarrest group) in segment 7 (left anterior descending (LAD)) was 4.68 ± 0.54 versus 3.31 ± 0.64, p = 0.0026. In segment 13, it was 3.82 ± 0.96 versus 2.58 ± 0.82, p = 0.02. In segment 14, it was 2.42 ± 0.44 versus 1.29 ± 0.99, p = 0.028. Conclusion. Postarrest myocardial dysfunction resulted in segmental wall motion defects in the LAD territory. There were no perfusion defects in the involved segments.

Use of impedance threshold device in conjunction with our novel adhesive glove device for ACD-CPR does not result in additional chest decompression.

OBJECTIVE: To evaluate the hemodynamic effects of using an adhesive glove device (AGD) to perform active compression-decompression CPR (AGD-CPR) in conjunction with an impedance threshold device (ITD) in a pediatric cardiac arrest model. DESIGN: Controlled, randomized animal study. METHODS: In this study, 18 piglets were anesthetized, ventilated, and continuously monitored. After 3min of untreated ventricular fibrillation, animals were randomized (6/group) to receive either standard CPR (S-CPR), active compression-decompression CPR via adhesive glove device (AGD-CPR) or AGD-CPR along with an ITD (AGD-CPR+ITD) for 2min at 100-120compressions/min. AGD is delivered using a fingerless leather glove with a Velcro patch on the palmer aspect and the counter Velcro patch adhered to the pig's chest. Data (mean±SD) were analyzed using one-way ANOVA with pair wise multiple comparisons to assess differences between groups. p-Value≤0.05 was considered significant. RESULTS: Both AGD-CPR and AGD-CPR+ITD groups produced lower intrathoracic pressure (IttP, mmHg) during decompression phase (-13.4±6.7, p=0.01 and -11.9±6.5, p=0.01, respectively) in comparison to S-CPR (-0.3±4.2). Carotid blood flow (CBF, % of baseline mL/min) was higher in AGD-CPR and AGD-CPR+ITD (respectively 64.3±47.3%, p=0.03 and 67.5±33.1%, p=0.04) as compared with S-CPR (29.1±12.5%). Coronary perfusion pressure (CPP, mmHg) was higher in AGD-CPR and AGD-CPR+ITD (respectively 19.7±4.6, p=0.04 and 25.6±12.1, p=0.02) when compared to S-CPR (9.6±9.1). There was no statistically significant difference between AGD-CPR and AGD-CPR+ITD groups with reference to intra-thoracic pressure, carotid blood flow and coronary perfusion pressure. CONCLUSION: Active compression decompression delivered by this simple and inexpensive adhesive glove device resulted in improved cerebral blood flow and coronary perfusion pressure. There was no statistically significant added effect of ITD use along with AGD-CPR on the decompression of the chest.

Novel adhesive glove device (AGD) for active compression-decompression (ACD) CPR results in improved carotid blood flow and coronary perfusion pressure in piglet model of cardiac arrest.

OBJECTIVE: ACD-CPR improves coronary and cerebral perfusion. We developed an adhesive glove device (AGD) and hypothesized that ACD-CPR using an AGD provides better chest decompression resulting in improved carotid blood flow as compared to standard (S)-CPR. DESIGN: Prospective, randomized and controlled animal study. METHODS: Sixteen anesthetized and ventilated piglets were randomized after 3 min of untreated VF to receive either S-CPR or AGD-ACD-CPR by a PALS certified single rescuer with compressions of 100 min(-1) and C:V ratio of 30:2. AGD consisted of a modified leather glove exposing the fingers and thumb. A wide Velcro patch was sewn to the palmer aspect of the glove and the counter Velcro patch was adhered to the pig's chest wall. Carotid blood flow was measured using ultrasound. Data (mean±SD) was analyzed using one way ANOVA and unpaired t-test; p-value ≤ 0.05 was considered statistically significant. RESULTS: Right atrial pressure (mmHg) during the decompression phase was lower during AGD-ACD-CPR (-3.32±2.0) when compared to S-CPR (0.86±1.8, p=0.0007). Mean carotid blood flow was 53.2±27.1 (% of baseline blood flow in ml/min) in AGD vs. 19.1±12.5% in S-CPR, p=0.006. Coronary perfusion pressure (CPP, mmHg) was 29.9±5.8 in AGD vs. 22.7±6.9 in S-CPR, p=0.04. There was no significant difference in time to ROSC and number of epinephrine doses. CONCLUSION: Active chest decompression during CPR using this simple and inexpensive adhesive glove device resulted in significantly better carotid blood flow during the first 2 min of CPR.

Two-thumb technique is superior to two-finger technique during lone rescuer infant manikin CPR.

OBJECTIVE: Infant CPR guidelines recommend two-finger chest compression with a lone rescuer and two-thumb with two rescuers. Two-thumb provides better chest compression but is perceived to be associated with increased ventilation hands-off time. We hypothesized that lone rescuer two-thumb CPR is associated with increased ventilation cycle time, decreased ventilation quality and fewer chest compressions compared to two-finger CPR in an infant manikin model. DESIGN: Crossover observational study randomizing 34 healthcare providers to perform 2 min CPR at a compression rate of 100 min(-1) using a 30:2 compression:ventilation ratio comparing two-thumb vs. two-finger techniques. METHODS: A Laerdal Baby ALS Trainer manikin was modified to digitally record compression rate, compression depth and compression pressure and ventilation cycle time (two mouth-to-mouth breaths). Manikin chest rise with breaths was video recorded and later reviewed by two blinded CPR instructors for percent effective breaths. Data (mean+/-SD) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as p< or =0.05. RESULT: Mean % effective breaths were 90+/-18.6% in two-thumb and 88.9+/-21.1% in two-finger, p=0.65. Mean time (s) to deliver two mouth-to-mouth breaths was 7.6+/-1.6 in two-thumb and 7.0+/-1.5 in two-finger, p<0.0001. Mean delivered compressions per minute were 87+/-11 in two-thumb and 92+/-12 in two-finger, p=0.0005. Two-thumb resulted in significantly higher compression depth and compression pressure compared to the two-finger technique. CONCLUSION: Healthcare providers required 0.6s longer time to deliver two breaths during two-thumb lone rescuer infant CPR, but there was no significant difference in percent effective breaths delivered between the two techniques. Two-thumb CPR had 4 fewer delivered compressions per minute, which may be offset by far more effective compression depth and compression pressure compared to two-finger technique.

Improved chest recoil using an adhesive glove device for active compression-decompression CPR in a pediatric manikin model.

OBJECTIVE: We developed an adhesive glove device (AGD) to perform ACD-CPR in pediatric manikins, hypothesizing that AGD-ACD-CPR provides better chest decompression compared to standard (S)-CPR. DESIGN: Split-plot design randomizing 16 subjects to test four manikin-technique models in a crossover fashion to AGD-ACD-CPR vs. S-CPR. Healthcare providers performed 5min of CPR with 30:2 compression:ventilation ratio in the four manikin models: (1) adolescent; (2) child two-hand; (3) child one-hand; and (4) infant two-thumb. METHODS: Modified manikins recorded compression pressure (CP), compression depth (CD) and decompression depth (DD). The AGD consisted of a modified oven mitt with an adjustable strap; a Velcro patch was sewn to the palmer aspect. The counter Velcro patch was bonded to the anterior chest wall. For infant CPR, the thumbs of two oven mitts were stitched together with Velcro. Subjects were asked to actively pull up during decompression. Subjects' heart rate (HR), respiratory rate (RR) and recovery time (RT) for HR/RR to return to baseline were recorded. Subjects were blinded to data recordings. Data (mean+/-SEM) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as P< or =0.05. RESULTS: Mean decompression depth difference was significantly greater with AGD-ACD-CPR compared to S-CPR; 38-75% of subjects achieved chest decompression to or beyond baseline. AGD-ACD-CPR provided 6-12% fewer chest compressions/minute than S-CPR group. There was no significant difference in CD, CP, HR, RR and RT within each group comparing both techniques. CONCLUSION: A simple, inexpensive glove device for ACD-CPR improved chest decompression with emphasis on active pull in manikins without excessive rescuer fatigue. The clinical implication of fewer compressions/minute in the AGD group needs to be evaluated.