Large Series Of Pediatric Patients Research Articles

Auxological and endocrine findings in narcolepsy type 1: seventeen-year follow-up from a pediatric endocrinology center.

Narcolepsy Type 1 (NT1) is a rare hypersomnia of central origin linked to hypocretin deficiency, most frequently arising at pediatric age. NT1 could be associated with endocrine comorbidities involving the neuroendocrine axis, predominantly obesity, and Central Precocious Puberty (CPP). The primary aim of this study is the evaluation of endocrine and auxological parameters at diagnosis and during follow-up in patients with NT1, treated with Sodium Oxybate (SO) or not. We retrospectively evaluated the auxological, biochemical, and radiological parameters of 112 patients referred to our Center between 2004-2022. The design of our study is cross-sectional at the time of diagnosis followed by a longitudinal follow-up. Our study confirms an increased frequency of CPP and obesity in patients with NT1. At first evaluation, obesity was found in 31.3% of patients, while overweight was found in 25.0%. A diagnosis of CPP was made in 19.6% of patients. Interestingly, this group showed a significantly lower level of CSF-hypocretin (hrct-1) at diagnosis compared to others. We found an improvement in BMI SDS in the SO-treated group compared to untreated patients, and this trend persisted also at 36 months of follow-up (0.0 ± 1.3 vs 1.3 ± 0.4; p<0.03). Sixty-three patients reached their final height, with a median SDS of 0.6 ± 1.1 in boys and 0.2 ± 1.2 in girls. To our knowledge, these are the first results regarding the final height in a large series of pediatric patients with NT1, with a normal range of IGF1-SDS levels and stature SDS.

Vasospasm following brain tumor resection in children: institutional experience and systematic review.

Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data. The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children's Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis. Six patients treated at Montreal Children's Hospital were identified, with an average age of 9.5 years (range 6-15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours-10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children's Hospital. Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.

Comprehensive Radiotherapy For Pediatric Ewing Sarcoma: Outcomes of a Prospective Proton Study

<h3>Objectives</h3> Patients with Ewing Sarcoma (EWS) are treated with multimodal therapy, with radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) for localized and metastatic EWS. <h3>Methods</h3> Fifty children with EWS (39 localized, 11 metastatic) treated between 2007 and 2020 were enrolled on a prospective IRB-approved protocol for pediatric patients undergoing PRT. Median age at time of PRT was 11.5y (range 0.9-19.6y); 62% were male. Median tumor size was 6.4cm (range 2.5-21cm). All patients received induction chemotherapy; 38 patients had definitive PRT and 12 had surgery followed by PRT. PRT was delivered by passive scatter (74%), pencil-beam scanning (12%) or mixed technique (14%). Treated sites included the spine (40%), pelvis/sacrum (26%), skull (18%), extraosseous (10%), and axial-skeleton (6%). Median radiation dose was 51Gy-RBE (range 39.6-55.8Gy-RBE). All patients with metastatic disease received consolidative RT to metastatic sites (5 at the time of local control [LC], 6 after completion of chemotherapy). Long-term follow-up data was available for 41 patients and median follow-up time was 47m after PRT. <h3>Results</h3> The 4-year LC, progression-free survival (PFS), and overall survival (OS) rates were 83.2%, 71.4%, and 86.3%, respectively. All local failures (n=6) were in-field failures. Tumor size ≥8cm predicted both inferior 4-year LC and PFS (69% vs 95%, p=0.04; 55% vs 86%, p=0.03, respectively). The 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72% vs 67%, p=0.70; 89% vs 78%, p=0.38, respectively). Long-term toxicity included a grade 3 esophageal stricture in 1 patient. <h3>Conclusion</h3> We report one of the largest series of pediatric patients with EWS treated with PRT. LC was comparable to that of historical patients who received photon-RT and there were no marginal failures. Larger initial tumor size predicted increased risk of local failure and disease progression, which supports current efforts to dose-escalate treatment of tumors ≥8cm. Finally, patients with metastatic disease had survival outcomes comparable to those of patients with localized disease, suggesting a benefit to using RT for consolidation in metastatic EWS.

Comprehensive Radiotherapy for Pediatric Ewing Sarcoma: Outcomes of a Prospective Proton Study

<h3>Purpose/Objective(s)</h3> Patients with Ewing Sarcoma (EWS) are treated with multimodal therapy, with radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) for localized and metastatic EWS. <h3>Materials/Methods</h3> Fifty children with EWS (39 localized, 11 metastatic) treated between 2007 and 2020 were enrolled on a prospective IRB-approved protocol for pediatric patients undergoing PRT. Median age at time of PRT was 11.5 years (range 0.9-19.6 years); 62% were male. Median tumor size was 6.4cm (range 2.5-21cm). All patients received induction chemotherapy prior to PRT; 38 patients had definitive PRT and 12 had surgery followed by PRT. PRT was delivered by passive scatter (74%), pencil-beam scanning (12%) or mixed technique (14%). Treated sites included the spine (40%), pelvis/sacrum (26%), skull (18%), extraosseous (10%), and axial-skeleton (6%). Median radiation dose was 54Gy-RBE (range 36.9-55.8Gy-RBE). All patients with metastatic disease (n=11) received consolidative RT to metastatic sites (5 at the time of local control [LC], 6 after completion of chemotherapy). Long-term follow-up data was available for 41 patients which comprise the subjects included in this report. Local failures were classified as in-field (>80% of relapse volume within the 95% isodose line [IDL]), marginal (>20% to ≤80% within the 95% IDL), or out-of-field (≤20% within the 95% IDL). Median follow-up time was 47 months after PRT. <h3>Results</h3> The 4-year LC, progression-free survival (PFS), and overall survival (OS) rates were 83.2%, 71.4%, and 86.3%, respectively. All local failures (n=6) were in-field failures. Tumor size ≥8cm predicted both inferior 4-year LC and PFS (69% vs 95%, p=0.04; 55% vs 86%, p=0.03, respectively). The 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72% vs 67%, p=0.70; 89% vs 78%, p=0.38, respectively). Long-term toxicity included a grade 3 esophageal stricture in 1 patient. <h3>Conclusion</h3> We report one of the largest series of pediatric patients with EWS treated with PRT. LC was comparable to that of historical patients who received photon-RT and there were no marginal failures. Larger initial tumor size predicted increased risk of local failure and disease progression, which supports current efforts to dose-escalate treatment of tumors ≥8cm. Finally, patients with metastatic disease received radiation therapy to all metastatic sites and had survival outcomes comparable to those of patients with localized disease, suggesting a benefit to using RT for consolidation in metastatic EWS.

Investigation into the ophthalmic artery and its branches by superselective angiography.

The vascular anatomy of orbit is highly complex, and the main blood supply to the orbit is via the ophthalmic artery, which is a branch of the internal carotid artery. The purpose of this study was to determine the morphometry of the ophthalmic artery and its branches by superselective angiography in a large series of pediatric patients. We evaluated 134 angiographies performed on children with intraocular retinoblastoma undergoing intra-arterial chemotherapy. The origin, diameter, and angiographic visibility percentages of the ophthalmic artery and its branches were examined according to age group and sex. The ophthalmic artery originated 97.8% from the internal carotid artery and 2.2% from the middle meningeal artery. The mean diameter of ophthalmic artery was measured 0.76 ± 0.14 mm in girls, 0.80 ± 0.15 mm in boys and 0.79 ± 0.15 mm in general. The posterior ciliary, lacrimal, inferior muscular, and anterior ethmoidal arteries had a higher angiographic visibility percentages (> 85%) than the other OA branches. Only the diameter of the dorsal nasal artery showed a significant correlation with age. The supratrochlear and posterior ciliary arteries showed statistically significant relationship with sex. Present study will make a substantial contribution to the pediatric literature about the ophthalmic artery and its branches. A better understanding of ophthalmic artery morphology can help surgeons and neurointerventional radiologists to avoid possible severe complications during embolization, intra-arterial chemotherapy, cosmetic procedures, endonasal and orbital surgeries.

KMT2A Rearrangements Are Associated with Lineage Switch Following CD19 Targeting CAR T-Cell Therapy

KMT2A Rearrangements Are Associated with Lineage Switch Following CD19 Targeting CAR T-Cell Therapy

Is ABO-Incompatible Living Donor Liver Transplantation Really a Good Alternative for Pediatric Recipients?

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. Methods: A retrospective case–control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. Results: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). Conclusions: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation.

16-OR: Endocrine Manifestations of Pediatric HNF1B-MODY (MODY 5)

Objective: Mutations in hepatocyte nuclear factor 1B (HNF1B), are often identified based on a history of renal disease and diabetes mellitus, but other endocrine manifestations including dyslipidemia and hyperparathyroidism have not been well-defined in the literature. Given HNF1B-MODY is rare, there have been few case series defining the disease spectrum. This study analyzes the clinical characteristics of HNF1B-related endocrine disorders in 9 pediatric patients identified at a single pediatric tertiary care center. Methods: Data was collected through the Atypical Diabetes Registry and Biorepository at the Children’s Hospital of Philadelphia. Results: Of the 9 pediatric patients with HNF1B mutations or deletions, 7/9 (78%) have diabetes mellitus, 8/9 (89%) have renal disease, 8/9 (89%) have dyslipidemia, and 5/9 (55%) have hyperparathyroidism. Over half (55%) initially presented with diabetes mellitus, while the remaining 45% were diagnosed either based on family history or a genetic workup secondary to renal disease. No patients presented with diabetic ketoacidosis and only two presented with ketosis. Of the 4/9 with previously identified HNF1B-mutations, two have subsequently developed diabetes mellitus. Lipid profiles demonstrated: 7/9 with total cholesterol &amp;gt;170 mg/dL, 8/9 with triglycerides &amp;gt;100 mg/dL, 3/9 with LDL &amp;gt; 110 mg/dL and 3/9 with HDL &amp;lt; 40 mg/dL. In regards to calcium homeostasis, 55% have an elevated PTH (&amp;gt;65 pg/mL) with high-normal calcium levels. Autism spectrum disorder was diagnosed in 3/9 patients (2 with 17q12 deletion and 1 with HNF1B mutation). Conclusion: This study represents one of the largest series of pediatric patients with HNF1B-MODY at a single center. The majority of patients have had progressively declining beta-cell function resulting in diabetes mellitus. Nearly all had elevated lipids with hypertriglyceridemia predominating. Over half of the patients had elevated PTH levels preceding the decline in renal function concerning for primary hyperparathyroidism. Disclosure M. E. Craven: None. V. Bamba: None. A. C. Calabria: None. S. E. Pinney: None.

Prevalence of joint hypermobility syndromes in pediatric postural orthostatic tachycardia syndrome.

Patients with postural orthostatic tachycardia syndrome (POTS) have been shown to exhibit comorbid joint hypermobility manifested as Ehlers-Danlos syndrome (EDS) or hypermobility spectrum disorder (HSD). The prevalence of EDS and HSD in POTS has been demonstrated in smaller studies combining adult and pediatric patients. We examined a large series of pediatric patients to determine their prevalence in children with POTS. Patients 18years old, or less, at initial evaluation at our clinic were included. POTS was diagnosed based on at least six months of frequent debilitating symptoms of orthostatic intolerance, plus a consistent heart rate increase of at least 40 beats per minute without orthostatic hypotension on standing test. Patients with a Beighton score of at least 5/9 plus other systemic findings suggestive of EDS were further evaluated in Connective Tissue Disorders clinics. There were 362 patients meeting inclusion criteria, of which 82 patients had EDS (22.7%) and 141 patients had HSD (39.0%). Patients with EDS had an earlier median age at symptom onset (12.1 vs. 13.5years, p=0.004) and longer median symptom duration (2.5 vs. 1.5years, p=0.0008) compared to patients without hypermobility. Our evaluation of a large series of pediatric patients with POTS revealed that over one-fifth of patients had EDS and over one-third of patients had HSD. The awareness of the prevalence of comorbidities such as hypermobility disorders may help inform providers diagnosing and caring for these patients.

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke: A Multi-Institutional Experience of Technical and Clinical Outcomes.

Endovascular thrombectomy is a promising treatment for acute ischemic stroke in children, but outcome and technical data in pediatric patients with large-vessel occlusions are lacking. To assess technical and clinical outcomes of thrombectomy in pediatric patients. We undertook a retrospective cohort study of pediatric patients who experienced acute ischemic stroke from April 2017 to April 2019 who had immediate, 30-, and 90-d follow-up. Patients were treated with endovascular thrombectomy at 5US pediatric tertiary care facilities. We recorded initial and postprocedural modified Thrombolysis in Cerebral Infarction (mTICI) grade≥2b, initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and pediatric modified Rankin scale (mRS) score 0 to 2 at 90 d. There were 23 thrombectomies in 21 patients (mean age 11.6±4.9 yr, median 11.5, range 2.1-19; 52% female). A total of 19 (83%) thrombectomies resulted in mTICI grade≥2b recanalization. The median PedNIHSS score was 13 on presentation (range 4-33) and 2 (range 0-26) at discharge (mean reduction 11.3±6.1). A total of 14 (66%) patients had a mRS score of 0 to 2 at 30-d follow-up; 18/21 (86%) achieved that by 90 d. The median mRS was 1 (range 0-4) at 30 d and 1 (range 0-5) at 90 d. One patient required a blood transfusion after thrombectomy. In this large series of pediatric patients treated with endovascular thrombectomy, successful recanalization was accomplished via a variety of approaches with excellent clinical outcomes; further prospective longitudinal study is needed.

Frequency and antimicrobial susceptibility of bacteria causing bloodstream infections in pediatric patients from United States (US) medical centers (2014–2018): therapeutic options for multidrug-resistant bacteria

Studies evaluating large series of pediatric patients with bloodstream infections (BSIs) are scarce. We evaluated the frequency and antimicrobial susceptibility of organisms isolated from pediatric patients with BSI and therapeutic options for BSI caused by multidrug-resistant (MDR) organisms. A total of 2423 organisms were consecutively collected from 33 US medical centers between 2014 and 2018, and susceptibility was tested by reference broth microdilution methods. Isolates with an extended-spectrum β-lactamase phenotype were screened for β-lactamase genes. Overall, 40.2% of organisms were Gram-negative bacteria, 57.0% Gram-positives, and 2.8% Candida spp. The 5 most common organisms were Staphylococcus aureus (26.0%), Escherichia coli (13.0%), coagulase-negative staphylococci (8.3%), Enterococcus faecalis (7.1%), and Klebsiella pneumoniae (6.9%). Among S. aureus, 26.0% were oxacillin-resistant and 99.8% were susceptible to ceftaroline (MIC50/90, 0.25/0.5 mg/L). Enterobacterales and Pseudomonas aeruginosa isolates combined represented >85% of Gram-negative bacteria, and all isolates (100.0%) were susceptible to ceftazidime-avibactam.

Value of Exercise Stress Echocardiography in Children with Hypertrophic Cardiomyopathy

Exercise stress echocardiography (ESE) is a valuable diagnostic and prognostic tool in adults with hypertrophic cardiomyopathy (HCM). Inducible and resting left ventricular outflow tract gradients are important predictors of heart failure. However, there are minimal data on the utility of this modality in children. Retrospective review of all pediatric HCM patients who underwent ESE at Boston Children's Hospital (January 2007-June 2018) was carried out. Patients were assigned to one of three categories based on left ventricular outflow tract gradients: group 1: <30mm Hg at rest and exercise; group 2: <30mm Hg at rest and ≥30mm Hg with exercise; and group 3: ≥ 30mm Hg at rest and exercise. Records were reviewed for earliest occurrence of composite endpoint of any one of the following: cardiac syncope, chest pain, nonsustained and sustained ventricular tachycardia, aborted cardiac arrest, heart failure class≥II, or HCM-related death/transplantation. A total of 91 children (67% males) with median age 12years (6-24years) at first ESE and median left ventricle wall thickness of 20mm formed the cohort. Median follow-up duration was 3years. During ESE, only one child experienced an event and was resuscitated. Of the 91 children, 25 were classified as group 1, 40 as group 2, and 26 as group 3. Twenty-six patients met the composite endpoint, including two heart transplant, one aborted cardiac arrest, and one sudden cardiac death. Group 3 patients had a 5 times higher risk of developing symptoms and/or serious clinical outcome at any age (hazard ratio=5.18; 95% CI, [1.39-19.2]; P=.014). During our short follow-up time, group 2 patients had a higher risk of outcome, but this did not achieve statistical significance (hazard ratio=1.95; 95% CI, [0.5-7.6]; P=.33). In this large series of pediatric patients with HCM, ESE can be performed safely and served as an effective tool to identify the lowest risk patients for cardiac outcome.

Busulfan, Cyclophosphamide and Melphalan As Conditioning Regimen for Pediatric Patients with AML in 1st or 2nd CR: A Retrospective Analysis from the AIEOP HSCT Registry

Allogeneic stem cell transplantation (HSCT) is largely adopted as post-remissional therapy in children with acute myeloid leukemia (AML) in first complete remission (CR1) but with high-risk characteristics (including high-risk cytogenetics or high levels of minimal residual disease at the end of induction therapy) or to rescue patients reaching CR2 after a previous relapse.Busulfan-based regimens represent the standard of care for these patients in association with alkylating agents. One of the most frequent drugs combination used in Europe in pediatric patients is Busulfan, Cyclophosphamide and Melphan (BuCyMel), which provide a potent anti-leukemic effect, despite remarkable extramedullary toxicities, especially in adolescents.We aimed at analyzing the results of children with AML receiving BuCyMel and reported to the AIEOP registry from 2008 to 2015. A total of 182 patients were reported by 15 transplant centers. Median age at HSCT was 9 years (range 0.3-18); 100 patients (55%) were male. Disease status at HSCT was CR1 in 159 (88%) patients and CR2 in the remaining 23 (12%). All patients received the same myeloablative conditioning regimen with BuCyMel and GVHD prophylaxis was mainly based on calcineurin inhibitors, with the addition of methotrexate in unrelated donors recipients. In vivo T-cell depletion/modulation with ATG was used in 90 cases (49.5%). In almost all cases, pharmacokinetics monitoring of Busulfan was performed, with the drug dosage adjusted according to the systemic exposure evaluated after the first dose.Donor type was an HLA-matched family donor (MFD) in 82 (45%) patients and an unrelated donor (UD) in 100 (55%); 154 (85%) patients received bone marrow (BM) as stem cell source, while the remaining patients (15%) were transplanted with peripheral blood stem cells (PBSCs).Median follow up for surviving patients was 39 months (range 1-111).All patients achieved neutrophil engraftment. The cumulative incidence (CI) of grade II-IV and grade III-IV aGVHD was 35% (95%CI 28-42) and 11% (95% CI 7-16), respectively. The CI of aGVHD was not different according to the type of donor, being 37% (95%CI 28-50) and 32% (95%CI 24-46) in MFD and UD, respectively (p=0.38). The CI of chronic GVHD at 3 years was 17% (95%CI 12-24), while that of extensive cGVHD was 6% (95%CI 3-10). No difference was found in the CI of CGVHD according to the donor employed (MFD 15% and UD 19%, p=0.49).Overall, the CI of relapse and non-relapse mortality (NRM) at 3 years was 18% (95%CI 12-26) and 15% (95%CI 10-22), respectively. The CI of relapse and NRM was significantly different according to age at HSCT (using 12 years as cut-off): (Relapse age<12y: 21% (95%CI 15-32) and age>12y: 11% (95%CI 3-32), (p=0.003); NRM age<12y: 10% (95%CI 5-20) and age>12y: 24% (95%CI 15-37), (p=0.005).According to disease status at HSCT the CI of relapse and NRM were as follows: Relapse: CR1: 18% (95%CI 18-26), CR2 15% (95%CI 5-41) p=0.90) and NRM CR1: 14% (95%CI 9-21), CR2 19% (95%CI 8-46) p=0.38).Also, there was no difference in relapse and NRM by donor type, relapse: MFD 16% (95%CI 9-28), UD 19% (95%CI 11-32) p=0.38) NRM: MFD 19% (95%CI 11-34), UD 11% (95%CI 7-20) p=0.62).Causes of deaths were disease recurrence (39%), infections (27%), and GVHD (12%).Three- years overall survival (OS) and disease-free survival (DFS) were 74% (95%CI 67-81) and 68% (95%CI 60-70). DFS was 70% (95%CI 60-77) and 67% (95%CI 47-87) for patients transplanted in CR1 and CR2 respectively, (p=0.39); and was 70% (95%CI 59-81) and 65% (95%CI 53-78), p=0.77, for UD and MFD HSCT recipients, respectively.In conclusion, our results confirm the efficacy of BuCyMel in preventing relapse in a large series of pediatric patients affected by AML in CR1 and CR2. Adolescents represent a population of more fragile patients at risk of developing transplant-related fatalities. Optimization of toxicity profile and supportive care could further improve outcomes. Prospective randomized clinical trials are warranted to assess the best conditioning regimen for children and adolescents with AML. DisclosuresZecca:Chimerix: Honoraria. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Management and outcomes of pediatric vocal cord paresis in Chiari malformation

IntroductionPediatric vocal cord paresis (VCP) has a variety of etiologies, including congenital neurologic disease. Arnold-Chiari Malformation (ACM) is one such disease with known VCP association. However, the natural history, need for tracheostomy, and rate of decannulation in this patient population is not well characterized. ObjectiveTo provide prognostic information on infants with ACM and VCP. MethodsA retrospective chart review was conducted of patients with both ACM and VCP at a single institution. Clinical outcomes and disease progression were determined using flexible laryngoscopy, serial clinical exams, and operative reports from otolaryngology and neurosurgery services. ResultsEighteen patients were included in this study, four with ACM Type I and 14 with ACM Type II. These groups were analyzed separately. For ACM I, the average age at diagnosis was 25 months and two (50%) required tracheostomy. Three subjects (75%) achieved VCP resolution, with two doing so after neurosurgical decompression. For ACM II, the average age at diagnosis was eight months and 12 patients (86%) underwent tracheostomy. Four subjects with tracheostomy (33%) achieved decannulation, with three of these demonstrating VCP resolution. In total, six ACM II patients had complete and one had partial VCP resolution, all of whom underwent decompression. Two patients initially had normal endoscopic exams despite stridor and VCP was only noted on serial exams. DiscussionThis study represents the largest series of pediatric patients with VCP and ACM. The majority needed decompression (80%) and tracheotomy (78%). Tracheostomy decannulation typically occurred only after decompression and resolution of VCP. No children diagnosed at age <1 month were decannulated. Early decompression was associated with successful avoidance of tracheostomy in majority of Chiari I but not Chiari II patients. Serial endoscopies were required to confirm VCP in some patients. This information could potentially aid in management and counseling parents of children with VCP and CM.

Cardiac MRI in evaluation and management of pediatric pericarditis

BackgroundEvaluation of pediatric pericarditis depends on the physical examination, electrocardiography and echocardiography. However, a multimodality imaging approach which includes cardiac magnetic resonance imaging (MRI) has been adopted in the adult population. The use of such an approach in the pediatric population has not been studied well. ObjectiveThe present study was intended to describe a single institution's experience with the use of cardiac MRI in the evaluation of pericarditis in the pediatric population. Study DesignA retrospective review of patients who had a cardiac MRI before the age of 21 years, between 2005 and 2014, to evaluate for pericardial pathology including pericarditis, constrictive pericarditis, recurrent pericarditis and pericardial effusion was performed. Patients were excluded if the cardiac MRI was done for evaluation of pathologies other than those related to the pericardium. Patients with predominant myocarditis were also excluded. The cardiac MRI and the echocardiograms were reviewed by a single blinded investigator. ResultsTwenty-one patients satisfied the inclusion criteria. The study population were predominantly male (81%) older adolescents (mean age: 17 ± 3 years). The major indications for cardiac MRI included evaluation of myocardial involvement in acute pericarditis, modulation of therapy in recurrent pericarditis and confirmation of constriction. Cardiac MRI was comparable to echocardiogram in detecting constrictive physiology and was useful in determining the presence of active pericardial inflammation. Systemic inflammatory diseases demonstrated higher values on quantification of late gadolinium enhancement. ConclusionWe have reported on a relatively large series of pediatric patients with pericarditis evaluated by cardiac MRI. Cardiac MRI may be a useful adjunct to conventional imaging in selected pediatric patients with pericarditis.

Embolie pulmonaire bilatérale mimant un syndrome thoracique aigu chez un adolescent drépanocytaire

Pulmonary embolism is a life-threatening and potentially lethal disease. Its incidence in children with sickle cell disease is probably underestimated and pediatric case reports in the literature are rare. Moreover, symptoms can mimic an acute chest syndrome. We report on the case of a 17-year-old boy with SS sickle cell disease, admitted for chest pain with dyspnea and tachycardia. Pulmonary angiography revealed a partial bilateral obstructive pulmonary embolism. We did not find any deep venous thrombosis or thrombophilia. The progression was rapidly favorable with anticoagulant therapy. We recommend a pulmonary angiography for any chest pain that does not evolve favorably in a child with sickle cell disease. Large series of pediatric patients would be useful to establish diagnostic and therapeutic guidelines.

Pediatric Tibial Osteomyelitis.

Osteomyelitis shows a strong predilection for the tibia in the pediatric population and is a significant source of complications. The purpose of this article is to retrospectively review a large series of pediatric patients with tibial osteomyelitis. We compare our experience with that in the literature to determine any factors that may aid diagnosis and/or improve treatment outcomes. A 10-year retrospective review was performed of clinical records of all cases of pediatric tibial osteomyelitis managed at the 2 children's orthopaedic departments in the Auckland region. The Osteomyelitis Database was used to identify all cases between 1997 and 2007, at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital. One hundred ninety-one patients fulfilled the inclusion criteria, and had a review of clinical notes and relevant investigations. The average duration of symptoms before presentation to hospital was 5.7 days. Less than 40% of patients had a recent episode of trauma. Almost 60% of patients could not bear weight on admission. Over 40% of patients had a temperature above 38°C. Erythrocyte sedimentation rate was elevated in 78% and the C-reactive protein was elevated in 90% of patients. In total, 42% of blood cultures and almost 75% of tissue cultures were positive, with Staphylococcus aureus being the most commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging were all used to aid the diagnosis. About 43% of patients had surgery. Treatment length was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2 days of oral treatment. Six postsurgical complications and 46 readmissions were noted: 25 for relapse, with the remainder due to social and antibiotic-associated complications. Although generally diagnosed on presentation, pediatric tibial osteomyelitis can require more sophisticated investigations and prolonged management. Treatment with intravenous and oral antibiotics and surgical debridement where indicated can lead to a good clinical outcome, although complications are often noted. Level IV-Prognostic study.

The Impact of Targeted Therapies for Pulmonary Hypertension on Pediatric Intraoperative Morbidity or Mortality

Pulmonary hypertension (PHT) is a significant risk factor for major adverse events during anesthesia, with a reported incidence of 5% to 7%, secondary to acute pulmonary hypertensive crises or right ventricular ischemia. Newer therapies for treating PHT have reduced mortality. In this single-center study, we investigated the frequency of major and minor events during anesthesia under the current strategies to manage PHT. We reviewed the records of children with PHT who underwent noncardiopulmonary bypass procedures from 2008 to 2012. Clinically important symptoms, physical signs, and results of investigations present before anesthesia were recorded. The incidence and type of intraoperative complications and death (up to 7 days) were collected. Data were collected for 122 patients undergoing 284 procedures. Minor (3.9%) and major (3.2%) complication rates were unchanged from previous publications. The etiology of PHT was not significant for complications (P = 0.14). Disease-modifying agents were not associated with reduced complications: 4.1% in treated versus 8.6% untreated (all P > 0.14). Patients receiving home oxygen had more complications (P = 0.02). Multiple logistic regression identified age and degree of PHT as significant predictors of complications (all P ≤ 0.03). The risk for adverse events during anesthesia in patients with PHT remains high, despite newer disease-modifying treatments. Risk factors for complications include age and severity of PHT.

Incidence of platinum-induced ototoxicity in pediatric patients in Quebec.

The antineoplastic agents cisplatin and carboplatin are widely-used and highly-effective against a variety of pediatric cancers. Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy. There is currently no treatment or prevention for platinum-induced ototoxicity and development of hearing loss may lead to devastating consequences on the quality of life of pediatric cancer survivors. The objective of this study is to determine the incidence of platinum-induced ototoxicity in a large series of pediatric patients and to evaluate the incidence of progression of ototoxicity after completion of treatment. A retrospective chart review of pediatric patients treated with cisplatin or carboplatin between 2000 and 2012 was conducted. The incidence of ototoxicity was determined based on the American-Speech-Language-Hearing Association (ASHA) criteria and severity was based on the Chang classification. Four hundred and sixty-six patients received platinum-based chemotherapy. Patients were excluded due to congenital hearing loss (n = 1) and insufficient data for calculating the platinum dose (n = 24) or for assessing ototoxicity (n = 135). Three hundred and six patients were included in the analysis. Post-chemotherapy ototoxicity was detected in 148 (48%) patients, and clinically-significant ototoxicity was present in 91 (30%). In addition, based on the ASHA criteria, 48% of patients (97/204) with long-term follow-up had further deterioration of their hearing after completion of treatment. Ototoxicity following chemotherapy with cisplatin or carboplatin is common and can frequently progress after the completion of treatment. Long-term follow-up is strongly recommended.

Outcome after anterior callosal section that spares the splenium in pediatric patients with drop attacks

We report on the efficacy and safety of extended, one-stage anterior callosal section that spares the splenium, which is performed in a large series of pediatric patients with drop attacks. Twenty-nine pediatric patients with drop attacks were studied (19 males and 10 females; mean age: 9.9years). As presurgical factors, the age at surgery, age at seizure onset, age at drop attack onset, sex, hemiparesis, severe mental retardation, electroencephalograph abnormalities, magnetic resonance imaging abnormalities, and 18fluorodeoxyglucose positron emission tomography abnormalities were analyzed. All patients had multiple seizure types, including drop attacks, atypical absence seizures, complex partial seizures, tonic seizures, and generalized tonic–clonic seizures. All patients were developmentally impaired and had electroencephalograph results showing marked secondary bilateral synchrony. All patients received an extended, one-stage callosal section, leaving only the splenium intact. The mean follow-up time was 5.2years. Seizure outcome (cessation of seizures or ≥90% seizure reduction) was achieved in 79.3% of patients with drop attacks. The families assessed the overall daily function as improved in 62.1% of the patients, unchanged in 24.1%, and worse in 13.8%. Family satisfaction with callosotomy was achieved in 82.8% of the patients. The majority of the patients had some degree of a transient acute postoperative disconnection syndrome that disappeared within 3weeks. Postoperatively, patients showed a consistent increase in attention levels. We conclude that extended callosal sectioning that leaves the splenium intact should be considered a good palliative surgical option for pediatric patients with drop attacks and that diminishment of epileptic discharge synchrony is a good prognostic sign following callosotomy. We also found that the postoperative increase in attention levels was as useful as seizure control in improving the quality of life of these patients.