Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol.

INTRODUCTION: Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood. METHODS AND ANALYSIS: A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF. ETHICS AND DISSEMINATION: Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children's NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

Solitary pulmonary nodule in an early adolescent.

An early adolescent boy presented with 1-week history of left-sided chest pain, localised to the anterior aspect of seventh intercostal space. A chest radiograph revealed a round opacity measuring 2.6×2.4 cm in the left mid zone. A CT scan of the chest confirmed a solitary well-circumscribed pulmonary nodule measuring 2.7×2.4 cm in the central left upper lobe, adjacent to the anterior segmental bronchus. Positron emission tomography scan showed mild to moderate fluorodeoxyglucose uptake (maximum standardized uptake value 5.2) in the nodule. He underwent a video-assisted left upper lobectomy. Histology of the nodule was consistent with sclerosing pneumocytoma, a rare benign lung neoplasm that occurs predominantly in middle-aged women of Asian descent. This case highlights the challenges in diagnosis and management of solitary pulmonary nodules in children, especially those who remain symptomatic or only have minimal symptoms and provides a pragmatic approach to this condition.

Gastrointestinal transit time of radiopaque ingested foreign bodies in children: experience of two paediatric tertiary centres.

Introduction: Foreign body (FB) ingestion is a common paediatric emergency. While guidelines exist for urgent intervention, less is known of the natural progress of FBs passing through the gastrointestinal tract (GIT). We reviewed these FB transit times in an outpatient cohort. Methods: A retrospective review was performed on all children (≤18 years) treated for radiopaque FB ingestion at two major tertiary paediatric centres from 2015 to 2016. Demographic data, FB types, outcomes and hospital visits (emergency department [ED] and outpatient) were recorded. All cases discharged from the ED with outpatient follow-up were included. We excluded those who were not given follow-up appointments and those admitted to inpatient wards. We categorised the outcomes into confirmed passage (ascertained via abdominal X-ray or reported direct stool visualisation by patients/caregivers) and assumed passage (if patients did not attend follow-up appointments). Results: Of the 2,122 ED visits for FB ingestion, 350 patients who were given outpatient follow-up appointments were reviewed (median age 4.35 years [range: 0.5-14.7], 196 [56%] male). The largest proportion (16%) was aged 1-2 years. Coins were the most common ingested FB, followed by toys. High-risk FB (magnets or batteries) formed 9% of cases (n=33). The 50th centile for FB retention was 8, 4 and 7 days for coins, batteries and other radiopaque FBs, respectively; all confirmed passages occurred at 37, 7 and 23 days, respectively. Overall, 197 (68%) patients defaulted on their last given follow-up. Conclusion: This study provides insight into the transit times of FB ingested by children, which helps medical professionals to decide on the optimal time for follow-up visits and provide appropriate counsel to caregivers.

Covid-19 Pandemic Strategy for Treatment of Acute Uncomplicated Appendicitis with Antibiotics- Risk Categorization and Shared Decision-Making.

BACKGROUND: During the Coronavirus disease 2019 (COVID-19) pandemic, a protocol was adopted by our department on antibiotics treatment for Acute Uncomplicated Appendicitis (AUA). Our study aimed to determine the feasibility and safety of non-operative treatment (NOT), compared to upfront laparoscopic appendectomy (LA), for AUA in children during the pandemic. METHOD: Our prospective comparative study was conducted from May 1, 2020 to January 31, 2021. Patient selection criteria included: age ≥5 years, abdominal pain duration ≤48 h, ultrasound (US)/Computered Tomography scan confirmation of AUA, US appendiceal diameter 6-11 mm with no features of perforation/abscess collection and no faecolith. For NOT patients, intravenous antibiotics were administered for 24-48 h followed by oral for 10-day course. Comparison was performed between patients whose parents preferred NOT to those who opted for up-front appendectomy. Primary outcomes were NOT success at index admission, early and late NOT failure rates till 27 months. Secondary outcomes were differences in complication rate, hospital length of stay (LOS) and cost between groups. RESULTS: 77 patients were recruited: 43 (55.8%) underwent NOT while 34 (44.2%) patients opted for LA. Success of NOT at index admission was 90.7% (39/43). Overall, NOT failure rate at 27 months' follow-up was 37.2% (16/43). Of the NOT failures, 1 appendix was normal on histology while only 1 was perforated. There were no significant differences in secondary outcomes between both groups except for LOS of late NOT failure. Cost for upfront LA was nearly thrice that of NOT. CONCLUSION: Our stringent COVID protocol together with shared decision-making with parents is a safe and feasible treatment option during a crisis situation. LEVEL OF EVIDENCE: Treatment study, Level II.

Management of acute testicular pain in children: changing trends with improvements in scrotal ultrasonography over 18 years.

Introduction: Doppler scrotal ultrasonography (US) is the modality of choice in diagnosing testicular torsion. We aimed to evaluate the performance of scrotal US in diagnosing testicular torsion over the past 18 years in our institution and determine the factors contributing to the length of wait times for it. Methods: A retrospective review was conducted of boys who presented with acute scrotal pain from 2014 to 2015. US reports, operative findings, final diagnosis and key time points of the patients' journey (time to emergency department consultation, time to admission, time to US and time to operating theatre [OT]) were collected. US performance results were compared with those observed in a historical cohort from 1998 to 2004. Wait times were compared between operated and non-operated patients. Results: Data from 519 boys with a mean age of 9.15 years was collected. Of these, 438 (84.4%) boys had undergone initial scrotal US; of these scrotal US cases, 28 were surgically explored, with 23 confirmed to have torsion. Another five cases were explored without prior US, and all were confirmed to have torsion. Performance analysis of US showed a sensitivity of 100% and a specificity of 98.8%. There was no significant difference between wait times of operated and non-operated patients. Time to US (P < 0.0001, r = 0.96) and time to OT (P < 0.0001, r = 0.64) correlated significantly with the total time from presentation to surgery. Conclusion: There has been an improvement in the diagnostic performance of scrotal US for testicular torsion over the past 18 years. Quality improvement programmes targeted at reducing wait times for patients presenting with acute scrotum should target time to US and time to OT.

Conservative antibiotic treatment of pediatric acute uncomplicated appendicitis during the COVID-19 pandemic: a prospective comparative cohort study.

BACKGROUND: Our study aimed to compare the clinical outcomes and cost-efficiency of antibiotic management versus laparoscopic appendectomy for acute uncomplicated appendicitis (AUA) in children during the COVID-19 pandemic when resources were limited and transmission risks uncertain. METHOD: In this prospective comparative cohort study, we analyzed the data of 139 children diagnosed with AUA meeting the following inclusion criteria: 5-18 years of age, symptoms duration of ≤ 48 h, appendix diameter ≤ 11 mm and no appendicolith. Treatment outcomes between non-operative management group (78/139) and upfront laparoscopic appendectomy group (61/139) were compared. Antibiotic regimes were intravenous ceftriaxone/metronidazole or amoxicillin/clavulanic acid for 48 h, followed by oral antibiotics to complete total 10-days course. RESULTS: 8/78 (10.3%) children had early failure (within 48 h) requiring appendectomy. 17/70 (24.3%) patients experienced late recurrence within mean follow-up time of 16.2 ± 4.7 months. There were no statistical differences in peri-operative complications, negative appendicectomy rate, and incidence of perforation and hospitalization duration between antibiotic and surgical treatment groups. Cost per patient in upfront surgical group was significantly higher ($6208.5 ± 5284.0) than antibiotic group ($3588.6 ± 3829.8; p = 0.001). CONCLUSION: Despite 24.3% risk of recurrence of appendicitis in 16.2 ± 4.7 months, antibiotic therapy for AUA appears to be a safe and cost-effective alternative to upfront appendectomy.

Extravesical vs. intravesical ureteric reimplantation for primary vesicoureteral reflux: A systematic review and meta-analysis.

Purpose: This study aims to compare the outcomes of extravesical (EVUR) and intravesical (IVUR) ureteric reimplantation for primary vesicoureteral reflux (VUR) via systematic review and meta-analysis. Methods: Literature review from Medline, Embase, and Cochrane since inception to March 2022 was performed. Meta-analysis was conducted on eligible randomized controlled trials (RCT) and observational cohort studies (OCS) comparing outcomes between EVUR and IVUR. Results: Twelve studies were included, comprising 577 patients (778 ureters) operated by EVUR and 395 patients (635 ureters) by IVUR. Pre-operative VUR grade, postoperative VUR persistence and hydronephrosis was not statistically significant. EVUR had shorter operative time [mean differences (MD) -22.91 min; 95% confidence interval (CI), -44.53 to -1.30, P = 0.04] and hospital stay (MD -2.09 days; 95% CI, -2.82 to -1.36, P < 0.00001) compared to IVUR. Bilateral EVUR had higher risk of postoperative acute urinary retention (ARU) (8.1%) compared to bilateral IVUR (1.7%) (OR = 4.40; 95% CI, 1.33-14.58, P = 0.02). No patient undergoing unilateral EVUR or IVUR experienced ARU. Conclusion: Both EVUR and IVUR are equally effective in correcting primary VUR. Operative time and hospital stay are shorter after EVUR compared to IVUR. However, bilateral EVUR is associated with higher risk of postoperative ARU.

Meckel's Diverticulum - Clinical Presentation and Pitfalls in Diagnosis in the Pediatric Age Group in Singapore.

Purpose: The purpose of this study was to study the presentation of patients who underwent Meckel's diverticulectomy (MD) and utility of pertechnetate Meckel's scan in the diagnosis of MD. Methods: The clinical presentation of a retrospective cohort of patients who underwent MD from January 2007 to December 2019 was studied. The modes of presentation, treatment, and the diagnostic utility of pertechnetate Meckel's scans were evaluated. False-positive and false-negative scans were reviewed. The presence of gastric mucosa on histology of Meckel's was correlated with presentation as gastrointestinal bleeding and positive scan results. Results: Ninety-nine patients underwent MD. Thirty-five out of 263 (13.3%) Meckel's scans done were positive. There was a male preponderance (86.9%). The peak age of presentation was 0-4 years (rectal bleeding or intestinal obstruction). Only a third of the patients with Meckel's diverticulum Meckel's had a preoperative diagnosis of Meckel's. The sensitivity/specificity of Meckel's scan was higher in patients presenting with painless rectal bleeding. Seven patients were false positive (weak tracer uptake or ectopic uptake) and five were false negative. Two patients with false-negative Meckel's scan, having gastrointestinal bleeding had gastric mucosa on histology of Meckel's. Conclusion: Meckel's diverticulum has a male predominance. Meckel's scan has a high sensitivity in the children presenting with fresh painless rectal bleeding but is of limited use in the diagnosis of Meckel's diverticulum in other forms of presentations. False-positive scans can be anticipated in the presence of weak or ectopic uptake. False-negative scans can occur even in the presence of bleeding and in spite of the presence of gastric mucosa in the Meckel's diverticulum. Laparoscopy is a useful tool in diagnosis and treatment.

Outcome of boys with posterior urethral valves from a single tertiary hospital in Singapore.

INTRODUCTION: Posterior urethral valve (PUV) is the most common congenital cause of bladder outflow obstruction in male infants. Despite timely treatment, renal damage can still occur in the long-term leading to chronic kidney disease (CKD). METHODS: A retrospective review of all PUV patients in a single tertiary institution between April 1998 and July 2019 was conducted to analyze their presentations, management and outcomes. Long-term renal function, radiologic scans and somatic growth were evaluated. RESULTS: A total of 16 patients were included in this study. Two patients who defaulted all follow-ups were excluded. Seven patients (43.7%) presented in the antenatal period; four patients (25%) presented in the neonatal period and five patients (31.3%) presented in the post-neonatal period. Primary transurethral fulguration of valves was done in 13 patients, while three had vesicostomies as the primary procedure. Three patients had associated anterior urethral valves (AUV), which were treated endoscopically. Nine boys had additional procedures for diversion and undiversion, VUR, non-functioning kidney and clean intermittent catheterization. Ten patients had urodynamic studies performed, of which eight patients received anticholinergic therapy. Eleven patients had DMSA scans, of which three patients had a normal study and eight patients showed unilateral reduced function. Four patients were diagnosed with CKD on long-term follow-up duration over 5 years. All patients were shown to have good somatic growth. CONCLUSION: Patients with PUV can suffer from complications despite primary treatment. In our small cohort, a quarter of our patients developed CKD on follow-up. Thus, patients need long-term follow-up to optimize bladder and renal function.

Association of anesthetic and surgical risk factors with outcomes of initial diagnostic biopsies in a current cohort of children with anterior mediastinal masses.

Background: Diagnostic biopsies of pediatric anterior mediastinal masses (AMMs) are high-risk procedures in which general anesthesia (GA) is traditionally avoided. However, awareness of historically recognized risk factors and corresponding perioperative management have improved over time and may now no longer strictly preclude the use of GA. Therefore, in this study, we examined the association of anesthetic and surgical risk factors and modalities with resulting procedural and survival outcomes in a current patient cohort. Methods: We retrospectively reviewed charts of 35 children with AMMs who underwent initial diagnostic biopsies between January 2001 and August 2019, and determined tracheal compression and deviation from archival CT scans and procedural and disease outcomes. Results: Twenty-three (65%) patients underwent GA while 12 (35%) received sedation. Among patients with available CT measurements, 13 of 25 (52%) had >50% anteroposterior tracheal diameter reduction. Patients with >50% anteroposterior tracheal compression received sedation more frequently (p=0.047) and were positioned upright (p=0.015) compared with patients with ≤50% compression, although 4 of 13 and 9 of 12, respectively, still received GA. Intraoperative adverse events (AEs) occurred in four (11.4%) patients: three received GA, and all were positioned supine or lateral. AEs were not associated with radiographic airway risk factors but were significantly associated with morphine and sevoflurane use (p<0.001) and with thoracoscopic biopsies (p=0.035). There were no on-table mortalities, but four delayed deaths occurred (three related to disease and one from late procedural complications). Conclusions: In a current cohort of pediatric AMM biopsies, patients with >50% anteroposterior tracheal compression were more frequently managed with a conservative perioperative management strategy, though not completely excluding GA. The corresponding reduction in frequency of procedural AEs in this traditionally high-risk group suggests that increased awareness of procedural risk factors and appropriate risk-guided perioperative management choices may obviate the procedural mortality historically associated with pediatric AMM biopsies.

Salivary biomarker for acute appendicitis in children: a pilot study.

PURPOSE: Assays of salivary biomarkers for diagnosis are gaining popularity in pediatric diseases due to their non-invasive nature. Our pilot project aims to evaluate the utility of salivary leucine-rich-alpha-2-glycoprotein (LRG) in the diagnosis of pediatric acute appendicitis (AA). METHODS: We prospectively recruited 34 patients, aged between 4 and 16 years, admitted with acute abdominal pain suspicious of appendicitis. The patients' demography, clinical characteristics, laboratory investigations, imaging examination results, operative findings, and discharge diagnoses were recorded. We compared the diagnostic performance of the patients' total white counts, neutrophil percentages, C-reactive protein, and saliva LRG levels. Saliva samples were obtained using the SalivaBio Children's Swab and LRG levels were quantified using a commercially available LRG enzyme-linked immunosorbent assay (ELISA) kit. IRB approval was obtained. RESULTS: Seventeen patients had a confirmed diagnosis of appendicitis on histology. Another 17 were confirmed not to have appendicitis after a minimum of 24 h of hospitalization, with further verification via telephone interview 2 weeks later. The median levels of saliva LRG were elevated in patients with AA as compared to those without (P = 0.008). At a cutoff of LRG 0.33 ng/µg, we obtained a diagnostic specificity of 100% and sensitivity of 35.3%. CONCLUSION: Our proof-of-concept study demonstrated the diagnostic potential of saliva LRG for appendicitis in children. The distinct advantage of saliva LRG assays is that the procedure is simple, pain-free, and requires no specialized skill. Further study with a larger cohort is needed to verify our results.

Primary spontaneous pneumothorax in children: factors predicting recurrence and contralateral occurrence.

BACKGROUND: The risk factors for recurrence in primary spontaneous pneumothorax (PSP) in children are not well known. We aimed to identify possible risk factors, and to evaluate the utility of computerised tomography (CT) scans in predicting future episodes. METHODS: We reviewed children aged < 18 years admitted to our institution for PSP from 2008 to 2017, excluding those with malignancies. Basic demographic data were extracted. Clinical data collected include pneumothorax laterality, CT results, treatment protocols and recurrences. RESULTS: 63 patients were included, 19 (30.2%) of whom had CT scans. A total of 41 surgeries were performed. The median (interquartile range) age was 15.4 years (14.9-15.9), and body-mass index was 17.9 kg/m2 (15.8-19.3). 56 (88.9%) patients were male. Median follow-up duration was 19.8 months (11.6-35.9). Multivariate logistic regression analyses identified surgery in the first episode as a predictor for a subsequent contralateral occurrence (odds ratio [95% confidence interval] 32.026 [1.685-608.518], p = 0.021). No predictors for ipsilateral recurrence were found. CT scans were 76.5% sensitive for bleb detection, and predicted poorly for occurrence (positive predictive value 14.3%, likelihood ratio 1.1). CONCLUSION: This is the first study demonstrating that surgery at first presentation appears to predict for occurrence of PSP on the contralateral lung. CT appears to be ineffective in detecting blebs and predicting PSP occurrence.

Mechanical versus Chemical Pleurodesis after Bullectomy for Primary Spontaneous Pneumothorax: A Systemic Review and Meta-Analysis.

INTRODUCTION: Primary spontaneous pneumothorax (PSP) and its high recurrence rate pose a therapeutic challenge to both patients and their managing surgeons. Mechanical or chemical pleurodesis can be used to prevent recurrence, but the optimal treatment often remains a matter of debate. This meta-analysis aims to compare the outcomes between mechanical and chemical pleurodesis following bullectomy for PSP. MATERIALS AND METHODS: Studies published up to 2019 were searched from Medline, Embase, Google Scholar, and Cochrane databases. A meta-analysis of randomized controlled trials (RCTs) and observational cohort studies (OCSs) comparing outcomes between mechanical and chemical pleurodesis for PSP was performed. RESULTS: Seven studies (one RCT and six OCSs) were included, comprising 1,032 cases of mechanical (799 abrasions, 202 pleurectomies, and 31 unspecified abrasions/pleurectomies/both), and 901 cases of chemical (643 talc, 69 minocycline, and 189 unspecified talc/kaolin) pleurodesis. The recurrence rate of pneumothorax after chemical pleurodesis (1.2%) was significantly lower than mechanical pleurodesis (4.0%) (pooled odds ratio [OR] = 3.00; 95% confidence interval [CI] = 1.59-5.67; p = 0.0007; I 2 = 19%). Hospital stay was also slightly shorter in the chemical pleurodesis group (pooled mean difference [MD] = 0.42 days; 95% CI = 0.12-0.72; p = 0.005; I 2 = 0%). There was no statistically significant difference in postoperative complications (pooled OR = 1.18; 95%CI = 0.40-3.48; p = 0.76; I 2 = 71%) and operative time (pooled MD = 3.50; 95%CI = -7.28 to 14.28; p = 0.52; I 2 = 99%) between these two groups. CONCLUSION: Chemical pleurodesis is superior to mechanical pleurodesis following bullectomy for PSP in reducing hospital stay and recurrence rate. However, more RCTs with longer follow-up are necessary to demonstrate the benefit of chemical pleurodesis for PSP.

Anorectal malformation & Hirschsprung's disease: A cross-sectional comparison of quality of life and bowel function to healthy controls.

BACKGROUND: Patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) face long-term disturbance in bowel function even after definitive surgery. This study evaluates the quality of life (QOL) of patients with ARM and HD, and compares them to healthy controls using self-report questionnaires. METHODOLOGY: A prospective study was performed recruiting patients with ARM or HD from September 2013 to December 2014 who had primary surgery done in our institution at least 2 years prior to participation. Age-matched and gender-matched controls were enrolled from our patients with minor outpatient complaints. All participants completed the following PedsQL™ scales (maximum score 100): 4.0 Generic Core Scales, 3.0 General Well-Being (GWB) Scale and 2.0 Family Impact (FI) Module. All were also scored on bowel function (BFS), with a maximum score 20. Appropriate statistical analysis was performed, with significance level <0.05. RESULTS: There were 193 participants: 87 controls, 62 ARM, 44 HD. When comparing Core, GWB and FI scores, there were no significant differences between groups although controls had best scores indicating best QOL and general wellbeing, with least impact of the child's health on the family. BFS was significantly different with controls having best and ARM worst scores. There were no significant differences in scores between parent and child indicating intradyad consistency. There was significant positive correlation between BFS and Core (p<0.0001), and between BFS and GWB scores (p<0.005); and significant negative correlation between BFS and FI scores (p<0.0001). CONCLUSIONS: Bowel function impacts quality of life. Those with ARM and HD can achieve good quality of life comparable to controls, based on patient and caregiver self-reported outcomes. TYPE OF STUDY: Prospective comparative study LEVEL OF EVIDENCE: Level II.

Congenital diaphragmatic hernia associated with oesophageal atresia and tracheo-oesophageal fistula in a low birth weight infant.

The cooccurrence of congenital diaphragmatic hernia and oesophageal atresia with distal tracheo-oesophageal fistula is very rare and carries high mortality. Very few anecdotal case reports and one case series have been reported in the literature. We report a case of a late preterm, low birth weight infant with this rare association who was successfully managed by staged surgical approach and had good outcome.

Cap polyposis: a rare cause of rectal bleeding in children.

AIM: To evaluate the clinicopathological features and treatment outcomes of cap polyposis in the pediatric population. METHODS: All pediatric patients with histologically proven diagnosis of cap polyposis were identified from our endoscopy and histology database over a 12 year period from 2000-2012 at our tertiary pediatric center, KK Women's and Children's Hospital in Singapore. The case records of these patients were retrospectively reviewed. The demographics, clinical course, laboratory results, endoscopic and histopathological features, treatments, and outcomes were analyzed. The study protocol was approved by the hospital institutional review board. The histological slides were reviewed by a pediatric histopathologist to confirm the diagnosis of cap polyposis. RESULTS: Eleven patients were diagnosed with cap polyposis. The median patient age was 13 years (range 5-17 years); the sample included 7 males and 4 females. All of the patients presented with bloody stools. Seven patients (63%) had constipation, while 4 patients (36%) had diarrhea. All of the patients underwent colonoscopy and polypectomies (excluding 1 patient who refused polypectomy). The macroscopic findings were of polypoid lesions covered by fibrinopurulent exudates with normal intervening mucosa. The rectum was the most common involvement site (n = 9, 82%), followed by the rectosigmoid colon (n = 3, 18%). Five (45%) patients had fewer than 5 polyps, and 6 patients (65%) had multiple polyps. Histological examination of these polyps showed surface ulcerations with a cap of fibrin inflammatory exudate. Four (80%) patients with fewer than 5 polyps had complete resolution of symptoms following the polypectomy. One patient who did not consent to the polypectomy had resolution of symptoms after being treated with sulphasalazine. All 6 patients with multiple polyps experienced recurrence of bloody stools on follow-up (mean = 28 mo). CONCLUSION: Cap polyposis is a rare and under-recognised cause of rectal bleeding in children. Our study has characterized the disease phenotype and treatment outcomes in a pediatric cohort.