Large Cohort Of Pediatric Patients Research Articles

Electroclinical Features and Long-Term Photosensitivity Outcome in Patients With Photoparoxysmal Response With Epilepsy

BackgroundTo investigate electroclinical phenotypes and long-term photosensitivity outcome in a large pediatric cohort of patients with epilepsy with photosensitivity. MethodsPatients with epilepsy with photosensitivity with four or more years of follow-up were included. Sustained terminal remission (STR) of photosensitivity (≥3.5 years) and seizure control were investigated, as well as the prognostic factors of photosensitivity. Furthermore, a cluster analysis was used to study the different subgroups of photoparoxysmal responses (PPR). ResultsWe included 190 individuals with a median age at diagnosis of photosensitivity of 93.1 months (interquartile range [IQR] 62.8 to 120 months) and a median follow-up duration of 68.5 months (IQR 51.8 to 84 months). STR of photosensitivity was achieved in 97 (51.1%) patients, and the mean time from age at diagnosis of photosensitivity onset to STR was 16.5 months. Age at the last follow-up (9 to 18 years [P = 0.001]), a history of photoconvulsive response (PCR) (P = 0.009), and posterior epileptiform discharges (EDs) of PPRs (P = 0.05) were significantly associated with a lower chance of entering STR according to a Cox proportional hazards model. The subgroup of generalized epilepsy syndrome exhibited 46.2% of eye closure sensitivity and 47.7% of PCR. The rates of focal epilepsy syndrome (cluster 1), generalized epilepsy syndrome (cluster 2), and unclassified epilepsy (cluster 3) were similar and not statistically different in photosensitive outcome (P = 0.527). ConclusionsAge nine to 18 years, a history of PCR, and posterior EDs of PPRs were the adverse factors affecting photosensitivity, suggesting the effect of age-related brain changes in STR. There was no difference in the prognosis of photosensitivity in different epileptic syndromes.

Respiratory syncytial virus infection: survival experience in a cohort of children inpatients

ObjectiveThe objective of this study was to assess the survival experience of children hospitalized with laboratory-confirmed respiratory syncytial virus (RSV) infection due to bronchiolitis. Study designThis was a nationwide retrospective cohort study conducted in Mexico. MethodsWe analyzed data from 436 children aged 5 years and younger, with symptom onset between August 2021 and November 2022. The Kaplan–Meier method was used to compute survivor functions and their 95% confidence intervals (CI). ResultsHigh survival rates were observed, particularly within the first three weeks of hospital admission. The 3-day survival rate was 99.8% (CI 98.4–99.9%), which decreased to 98.9% (CI 96.5–99.7%), 97.5% (CI 91.9–99.3%), 86.7% (CI 48.2–97.2%), and 69.4% (CI 24.2–91.0%) on days 7, 14, 21, and 28 of hospital stay, respectively. We documented a total of 5 fatal outcomes, resulting in a mortality rate of 2.1 (95% CI 0.9–5.1) per 1,000 person-days. ConclusionsOur study analyzed a large cohort of pediatric patients with bronchiolitis caused by RSV infection, providing valuable insights into the in-hospital progression of this disease.

Peripherally inserted central venous catheter for pediatric acute leukemia: A retrospective 11-year single-center experience.

Peripherally inserted central catheters (PICCs) are successfully increasingly used in children in onco-hematologic setting. PICC insertion, especially in oncologic patients, can be associated with adverse events (thrombosis, mechanical complications, and infections). Data regarding the use of PICC, as long-term access in pediatric patients with severe hematologic diseases, are still limited. We retrospectively evaluated the safety and efficacy of 196 PICC, inserted in 129 pediatric patients with acute leukemia diagnosed and treated at Pediatric Hematology Unit, Sapienza University of Rome. The 196 PICC analyzed were in situ for a median dwell time of 190 days (range 12-898). In 42 children, PICC was inserted twice and in 10, three times or more due to hematopoietic stem cell transplant, disease recurrence, or PICC-related complications. The overall complication rate was 34%: catheter-related bloodstream infections (CRBSI) occurred in 22% of cases after a median time of 97 days; a catheter-related thrombosis (CRT) in 3.5% and mechanical complications in 9% of cases. Premature removal for complications occurred in 30% of PICC. One death from CRBSI was observed. To our knowledge, this study represents the largest cohort of pediatric patients who have inserted the PICC for acute leukemia. In our experience, PICC was a cheap, safe, and reliable device for long-term intravenous access in children with acute leukemia. This has been possible with the help of dedicated PICC team.

MDB-11. AN ONLINE CALCULATOR USING MACHINE LEARNING FOR PREDICTION OF SURVIVAL IN PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA

Abstract OBJECTIVE Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a >75% 5-year survival rate, children who survive often have substantial neurological and cognitive sequelae. The authors aimed to identify risk factors and develop a clinically friendly online calculator for prognostic estimation in pediatric medulloblastoma patients. METHODS Pediatric patients with a histopathologically confirmed medulloblastoma were extracted from the Surveillance Epidemiology and End Results database (2000-2019) and split into training and validation cohorts in an 80:20 ratio. The Cox proportional hazards model was used to identify the univariate and multivariate survival predictors. Subsequently, a calculator with those factors was developed to predict 2-, 5-, and 10-year overall survival as well as median survival months for pediatric medulloblastoma patients. The performance of the calculator was determined by discrimination, calibration, and decision curve analysis (DCA). RESULTS A total of 1,739 pediatric patients with medulloblastoma met the prespecified inclusion criteria. Fourteen variables, including age, sex, race, ethnicity, median household income, county attribute, laterality, histology, anatomical location, tumor grade, tumor size, surgery status, radiotherapy, and chemotherapy, were included in the calculator (https://spine.shinyapps.io/Peds_medullo/). The concordance index was 0.757 in the training cohort and 0.762 in the validation cohort, denoting clinically useful predictive accuracy. Good agreement between the predicted and observed outcomes was demonstrated by the calibration plots. The DCA curves indicated that the developed model has a good clinical prognostic benefit for pediatric medulloblastoma patients. CONCLUSION An easy-to-use prognostic calculator for a large cohort of pediatric patients with medulloblastoma was established. Future efforts should focus on improving granularity of population-based registries and externally validating the proposed calculator.

The prognostic value of HLA loss of heterozygosity after allogeneic hematopoietic stem cell transplantation in children with relapsed acute leukemia

The loss of a patient-specific HLA haplotype on the surface of the blast cell population is one of the ways a tumor can evade the immune surveillance of donor cells. This phenomenon is observed in approximately 30 % of relapses in patients with hematologic malignancies who underwent partially mismatched allogeneic hematopoietic stem cell transplantation (HSCT). In this study, for the first time, a large cohort of pediatric patients (n = 80) with relapsed acute myeloid (AML) or acute lymphoblastic (ALL) leukemia after allogeneic HSCT was analyzed with the help of the STR method (highlypolymorphic microsatellite marker analysis) using 6 HLA haplotype markers. The study was approved by the Independent Ethics Committee and the Scientific Council of the I. P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation. Loss of heterozygosity (LOH) was observed in 18 / 80 (22 %) relapsed patients with various types of acute leukemia: out of these, 8 / 44 (18 %) patients had B-cell ALL, 4 / 10 (40 %) patients – T-cell ALL and 6 / 25 (24 %) patients – AML. All relapses with LOH were observed in patients who had undergone haploidentical HSCT, and were found to occur later than relapses without loss of the HLA haplotype (median time to relapse: 8.8 months vs 6.2 months, p = 0.043). In the patients treated with haploidentical HSCT (n = 61), we assessed factors increasing the risk of LOH at relapse. The number of previous therapy lines in the patients with AML (n = 17) and acute or chronic graft-versus-host disease in the patients with ALL (n = 44) were associated with an increasedrisk of genetic loss of the HLA haplotype (p = 0.008 and p = 0.015 respectively). A relapse following the second allogeneic HSCT was associated with LOH in 4 / 5 (80 %) patients, p = 0.008. The prognosis of the patients with LOH was extremely poor. At a median follow-up of 6 months, the overall survival from relapse was 22 % in the LOH group and 37 % in the non-LOH group. The median overall survival was 4.5 months (95 % confidence interval 3–NA) and 10.3 months (95 % confidence interval 5.7–16.1) respectively, p = 0.063. Among the patients with LOH, the best survival rates were observed in those who had undergone a repeat allogeneic HSCT from a different donor. Thus, the analysis of LOH is an important tool for determining the prognosis and further treatment in pediatric patients with acute leukemias. We strongly recommend that this diagnostic test should be included into standard testing of patients after partially-mismatched allogeneic HSCT.

Characteristics of facial nerve palsy in 112 children and risk factors for ocular complications

To report the ophthalmic findings and ocular complications in a large cohort of pediatric patients with facial nerve palsy (FNP). Ocular data of children (≤16 years of age) diagnosed with FNP presenting to an eye care network from 2012 to 2021 were analyzed. Study parameters were etiology of FNP, ocular and imaging findings, degree of lagophthalmos, and degree of vision loss. Clinical characteristics were compared between those with and without moderate-to-severe vision impairment (best-corrected visual acuity <20/50) and those with and without exposure keratopathy at presentation. A total of 112 patients were included. Mean age at presentation was 8.3 ± 5.0 years. The most common etiology was idiopathic (57%) followed by congenital (22.3%) and traumatic (13.4%). There was bilateral involvement in 8% of children, multiple cranial nerve involvement in 15.2%, and exposure keratopathy at presentation in 38.4%. One-fifth (20.5%) of children (29.6% of affected eyes with known visual acuity) had moderate-to-severe visual impairment. Multiple cranial nerve involvement was present in 31% of eyes with visual impairment compared with 14% of those without. Corneal scarring and strabismic amblyopia were both frequent causes of visual impairment. Most children with exposure keratopathy had lagophthalmos (76.6%), whereas it was less common in those without keratopathy (49.2%). Pediatric FNP was most commonly idiopathic, secondarily congenital. Strabismic amblyopia and corneal scarring were the most common causes of visual impairment in our cohort.

Tickle Me ECMO…Differences and Outcomes Unearthed for Kids Requiring Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Syndrome Coronavirus 2-Associated Disease.

Tickle Me ECMO…Differences and Outcomes Unearthed for Kids Requiring Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Syndrome Coronavirus 2-Associated Disease.

High Rates of Pediatric Venous Thromboembolism After Elective Laparoscopic Splenectomy Suggest Need for Perioperative Prophylaxis

IntroductionIn adult populations, postoperative venous thromboembolism (VTE) is a reported complication of up to 8% of elective laparoscopic splenectomy (LS) cases. VTE is a rare event in the pediatric population, affecting less than 1% of all pediatric surgical patients. We hypothesized that pediatric patients are at a higher risk of postoperative VTE after undergoing elective LS relative to other laparoscopic procedures and may warrant prophylactic treatment. Materials and methodsWe queried the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database from 2012 to 2020. Patients were identified using the Current Procedural Terminology code 38120 and only elective cases were analyzed. ResultsThe incidence of VTE in all pediatric patients undergoing surgery in the American College of Surgeons NSQIP-P database was 0.13%. The incidence of VTE in pediatric patients undergoing elective laparoscopic abdominopelvic procedures was 0.17%. There were seven total cases of VTE (0.41%) in pediatric patients undergoing elective LS, more than twice the rate of the general population (P = 0.001). Eighty percent of pediatric patients undergoing elective LS had an underlying hematological disorder. ConclusionsBy analyzing the NSQIP-P database, we evaluated the largest cohort of pediatric patients undergoing elective LS to date. We identified a higher incidence of VTE following this procedure relative to the rate of VTE in the overall population in the NSQIP-P database, as well as those undergoing elective laparoscopic abdominopelvic operations. The relatively higher incidence of VTE after elective LS is likely due to the presence of underlying hematological conditions. Given the low incidence of complications associated with pharmacologic VTE prophylaxis, the results of this study suggest that further research is warranted to establish the efficacy of perioperative pharmacological VTE prophylaxis in pediatric patients undergoing elective LS.

Phenotyping mitochondrial DNA-related diseases in childhood: A cohort study of 150 patients.

Mitochondrial diseases (MDs) are heterogeneous disorders caused by mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) associated with specific syndromes. However, especially in childhood, patients often display heterogeneity. Several reports on the biochemical and molecular profiles in children have been published, but studies tend not to differentiate between mtDNA- and nDNA-associated diseases, and focus is often on a specific phenotype. Thus, large cohort studies specifically focusing on mtDNA defects in the pediatric population are lacking. We reviewed the clinical, metabolic, biochemical, and neuroimaging data of 150 patients with MDs due to mtDNA alterations collected at our neurological institute over the past 20 years. mtDNA impairment is less frequent than nDNA impairment in pediatric MDs. Ocular involvement is extremely frequent in our cohort, as is classical Leber hereditary optic neuropathy, especially with onset before 12 years of age. Extraneurological manifestations and isolated myopathy appear to be rare, unlike adult phenotypes. Deep gray matter involvement, early disease onset, and specific phenotypes, such as Pearson syndrome and Leigh syndrome, represent unfavorable prognostic factors. Phenotypes related to single large scale mtDNA deletions appear to be very frequent in the pediatric population. Furthermore, we report for the first time an mtDNA pathogenic variant associated with cavitating leukodystrophy. We report on a large cohort of pediatric patients with mtDNA defects, adding new data on the phenotypical characterization of mtDNA defects and suggestions for diagnostic workup and therapeutic approach.

Children with functional gastrointestinal disorders with and without co-existing nausea: A comparison of clinical and psychological characteristics.

Nausea co-existing with functional gastrointestinal disorders (FGIDs) has been suggested to negatively impact physical and psychological factors in children. This study aims to compare clinical and psychological characteristics of a large cohort of pediatric patients with an FGID with and without nausea. Patients of two previous randomized controlled trials were included, the first assessing the effect of hypnotherapy (HT) in 260 children fulfilling Rome criteria of irritable bowel syndrome (IBS) or functional abdominal pain (FAP), the second examining the effect of HT in 100 children with nausea in children with either functional nausea (FN) or functional dyspepsia (FD). At inclusion, demographics, clinical features, including the presence of nausea, depression and anxiety, somatization, and health-related quality of life (QoL) were assessed in patients. In total, 355 patients with IBS (n = 131), FAP (n = 127), FN (n = 62), and FD (n = 35) were included, of which 255 (72%) patients experienced nausea versus 100 (28%) without nausea. Age at onset of symptoms was higher in children experiencing nausea (12.0y vs. 9.0y, p = 0.000). Significantly higher somatization, anxiety and depression scores, and lower health-related QoL were reported for children with nausea. There were no significant differences between children with only nausea and children with nausea and abdominal pain. Children with nausea, either with or without abdominal pain, report higher somatization scores, increased anxiety and depression, and lower overall QoL, compared to children with pain-related FGIDs without accompanying nausea. Addressing the presence of nausea in children with FGIDs seems essential to customize their treatment and improve overall quality of life.

Genotype-phenotype correlation in a large cohort of pediatric patients with heterozygous and homozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease (CVD). Both the heterozygous form and the very severe homozygous form can be diagnosed by genetic testing and by clinical criteria. Genetic testing can discern FH in a form caused by complete absence of the LDL-receptors, the negative variant and a form leading to reduced activity of the LDL receptors, the defective variant. The aim of this study is to provide more insight in the genotype-phenotype correlation in children and adolescents diagnosed with heterozygous FH (HeFH) and with homozygous FH (HoFH), specifically in relation to the clinical and therapeutic consequences of the negative and defective variant of FH. Data of 5904 children with a tentative diagnosis of FH referred to our center for genetic testing were collected. A lipid-profile was present in 3494 children, who became the study cohort. In this large cohort of children, which includes 2714 HeFH and 41 HoFH patients, it is shown that receptor negative variants are associated with significant higher LDL-C levels in HeFH patients than receptor defective variants (6.0 versus 4.9 mmol/L; p < 0.001). A negative/negative variant is associated with a significant higher LDL-C level jn HoFH patients than a negative/defective variant, which in itself has a higher LDL-C level than a defective/defective variant. Significantly more premature CVD is present in close relatives of children with HeFH with negative variants compared to close relatives of HeFH children with defective variants (75% vs 59%; p < 0.001). Performing genetic testing and identifying the type of underlying genetic variant is of added value in order to distinguish between pediatric patients with higher risks of premature CVD and to identify those that will benefit most from new types of lipid-lowering therapies. Since in children the phenotype of FH is less affected by environmental factors, the study substantiates the genotype-phenotype correlation in this large pediatric population.

A molecular study of pediatric pilomyxoid and pilocytic astrocytomas: Genome-wide copy number screening, retrospective analysis of clinicopathological features and long-term clinical outcome.

Pilocytic Astrocytoma (PA) is the most common pediatric brain tumors. PAs are slow-growing tumors with high survival rates. However, a distinct subgroup of tumors defined as pilomyxoid astrocytoma (PMA) presents unique histological characteristics and have more aggressive clinical course. The studies on genetics of PMA are scarce. In this study, we report one of the largest cohort of pediatric patients with pilomyxoid (PMA) and pilocytic astrocytomas (PA) in Saudi population providing a comprehensive clinical picture, retrospective analysis with long-term follow-up, genome-wide copy number changes, and clinical outcome of these pediatric tumors. We examined and compared genome-wide copy number aberrations (CNAs) and the clinical outcome of the patients with PA and PMA. The median progression free survival for the whole cohort was 156 months and it was 111 months for the PMA, however, not statistically significantly different between the groups (log-rank test, P = 0.726). We have identified 41 CNAs (34 gains and 7 losses) in all tested patients. Our study yielded the previously reported KIAA1549-BRAF Fusion gene in over 88% of the tested patients (89% and 80% in PMA and PA, respectively). Besides the fusion gene, twelve patients had additional genomic CNAs. Furthermore, pathway and gene network analyses of genes in the fusion region revealed alterations in retinoic acid mediated apoptosis and MAPK signaling pathways and key hub genes that may potentially be involved in tumor growth and progression, including BRAF, LUC7L2, MKRN1, RICTOR, TP53, HIPK2, HNF4A, POU5F, and SOX4. Our study is the first report of a large cohort of patients with PMA and PA in the Saudi population that provides detailed clinical features, genomic copy number changes, and outcome of these pediatric tumors and may help better diagnosis and characterization of PMA.

Newborn Hearing Screening Results in Patients with Enlarged Vestibular Aqueduct.

Enlarged vestibular aqueduct (EVA) is the most common anatomic abnormality contributing to permanent hearing loss (HL) in children. Although the association between EVA and HL is well-documented, the pass rate for the newborn hearing screening (NBHS) for patients with EVA-related HL is not. Our objective was to investigate the association between NBHS results and audiologic and clinical outcomes in a large cohort of pediatric patients with EVA. This was a retrospective chart review of patients seen in the Boston Children's Hospital (BCH) Department of Otolaryngology and Communication Enhancement with confirmed HL, known NBHS results, and confirmed EVA. Demographic, clinical, audiologic, and imaging data were collected from the medical record. Frequency-specific data points from pure-tone audiograms and/or automated auditory brainstem response tests were recorded, and four-frequency pure tone average was calculated using air conduction thresholds at 500, 1000, 2000, and 4000 Hz. Of the 183 patients included in the study, 84 (45.9%) passed their NBHS, whereas 99 (54.1%) did not pass. Compared with patients who did not pass, patients who passed were more likely to have unilateral EVA and unilateral HL, whereas they were less likely to undergo cochlear implantation and to have causative SLC26A4 variants. EVA-associated HL may be identified at birth or during childhood, with nearly half the patients in this cohort passing their NBHS. Our results provide prognostic information for patients with EVA who pass their NBHS and highlight the importance of regular hearing monitoring for children not initially suspected of having HL. 4 Laryngoscope, 133:2786-2791, 2023.

Quadratus Lumborum Blockade for Postoperative Analgesia in Infants and Children Following Colorectal Surgery.

Adult studies have indicated that the quadratus lumborum block (QLB) may provide superior analgesia compared to single-shot neuraxial and other truncal peripheral nerve blocks. The technique is being increasingly used for postoperative analgesia in children undergoing lower abdominal surgery. To date, these pediatric reports have been limited by small sample sizes, which may hinder the interpretation of results and assessment of safety. In this study, we retrospectively examined QLBs performed at a large tertiary care hospital for evidence of effectiveness and safety in the pediatric colorectal surgery population. Patients less than 21 years of age who underwent abdominal surgery and received a unilateral or bilateral QLB over a 4-year period were identified in the electronic medical record. Patient demographics, surgery type, and QLB characteristics were retrospectively examined. Pain scores and opioid consumption were tabulated over the first 72-h postoperative period. QLB procedural complications or adverse events attributable to the regional anesthetic were obtained. The study cohort included 204 QLBs in 163 pediatric-aged patients (2 days to 19 years of age, median age of 2.4 years). The most common indication was unilateral blockade for ostomy creation or reversal. The majority of QLBs were performed using ropivacaine 0.2% with a median volume of 0.6 mL/kg. The median opioid requirement in oral morphine milligram equivalents (MMEs) was 0.7, 0.5, and 0.3 MME/kg on the first, second, and third postoperative days, respectively. Median pain scores were less than 2 over each time period. Aside from block failure (incidence 1.2%), there were no complications or postoperative adverse events related to the QLBs. This retrospective review in a large cohort of pediatric patients demonstrates that the QLB can be performed safely and efficiently in children undergoing colorectal surgery. The QLB provides adequate postoperative analgesia, has a high success rate, may limit postoperative opioid consumption, and is associated with a limited adverse effect profile.

Timing of Tracheostomy in Critically Ill Infants and Children With Respiratory Failure: A Pediatric Health Information System Study.

Tracheostomy placement in infants and children with respiratory failure has steadily increased over time, yet there is no consensus for optimal timing. We sought to: 1) describe tracheostomy timing and associated demographic and clinical characteristics in a large ICU cohort and 2) compare clinical outcomes between subgroups based on tracheostomy timing. Retrospective observational study using the Pediatric Health Information System (PHIS). Neonatal ICUs and PICUs in the United States. PHIS was queried for patients less than 18 years who underwent tracheostomy from 2010 to 2020. Patients were included if admitted to an ICU with need for mechanical ventilation (MV) prior to tracheostomy in the same hospitalization. Patients were categorized as early tracheostomy (ET) (placement at MV day ≤ 14), late tracheostomy (LT) (MV days 15-60), and extended tracheostomy (ExT) (MV day > 60). Primary endpoints included demographic and clinical characteristics. Secondary endpoints included patient outcomes: in-hospital mortality, length of stay (LOS), hospital-acquired pneumonia (HAP), and hospital costs. None. Sixteen thousand one hundred twenty-one patients underwent tracheostomy at 52 children's hospitals. Ten thousand two hundred ninety-five had complete data and were included in the analysis. Thirty-nine percent (4,006/10,295) underwent ET, 40% (4,159/10,295) underwent LT, and 21% (2,130/10,295) underwent ExT. Majority of patients in all subgroups had complex chronic conditions. Median age was significantly different between subgroups with ET being the oldest ( p < 0.001). A multivariable regression analysis showed that ET was associated with lower in-hospital mortality ( p < 0.001), shorter hospital LOS ( p < 0.001), shorter ICU LOS ( p < 0.001), shorter post-tracheostomy LOS ( p < 0.001), decreased HAP ( p < 0.001), and lower hospital costs ( p < 0.001) compared with those who underwent LT or ExT. In a large cohort of pediatric patients with respiratory failure, tracheostomy placement within 14 days of MV was associated with improved in-hospital outcomes. ET was independently associated with decreased mortality, LOS, HAP, and hospital costs.

FDXR Gene Expression after in Vivo Radiation Exposure of Pediatric Patients Undergoing Interventional Cardiology Procedures.

Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

HGG-11. Clinical characteristics and clinical evolution of a large cohort of pediatric patients with primary central nervous system (CNS) tumors and tropomyosin receptor kinase (TRK) fusion.

BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHODS: We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULTS: Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0–17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSIONS: We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.

Multiple Breath Washout for Early Assessment of Pulmonary Complications in Patients With Primary Antibody Deficiencies: An Observational Study in Pediatric Age.

BackgroundIn primary antibody deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations, and respiratory physiotherapy. Current Italian recommendations for surveillance of PADs respiratory complications include an annual assessment of spirometry and execution of chest high-resolution computed tomography (HRCT) every 4 years.ObjectiveThis study aimed to evaluate the effectiveness of the lung clearance index (LCI) as an early marker of lung damage in patients with PADs. LCI is measured by multiple breath washout (MBW), a non-invasive and highly specific test widely used in patients with cystic fibrosis (CF).MethodsPediatric patients with PADs (n = 17, 10 male, 7 female, and age range 5–15 years) underwent baseline assessment of lung involvement with chest HRCT, spirometry, and multiple breath nitrogen washout. Among them, 13 patients were followed up to repeat HRCT after 4 years, while performing pulmonary function tests annually. Their baseline and follow-up LCI and forced expiratory volume at 1 s (FEV1) values were compared, taking HRCT as the gold standard, using logistic regression analysis.ResultsLung clearance index [odds ratio (OR) 2.3 (confidence interval (CI) 0.1–52) at baseline, OR 3.9 (CI 0.2–191) at follow-up] has a stronger discriminating power between altered and normal HRCT rather than FEV1 [OR 0.6 (CI 0.2–2) at baseline, OR 1.6 (CI 0.1–13.6) at follow-up].ConclusionWithin the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting non-uniform ventilation in the absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.

Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model.

We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than -2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R2 87.2%). This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies.

Paediatric tracheobronchomalacia: Incidence, patient characteristics, and predictors of surgical intervention

ObjectivesTracheobronchomalacia (TBM), a condition where an abnormality of the tracheal walls causes collapse during the respiratory cycle, is a common cause of airway obstruction in childhood. TBM can present with a large spectrum of disease severity and underlying pathologies that may be managed medically and surgically, and it is not always clear which patients would most benefit from surgical intervention. We aim to describe the incidence, patient characteristics, and predictors of surgical intervention in a large cohort of paediatric patients. MethodsWe performed a retrospective review of all children diagnosed with TBM to a paediatric Otolaryngology unit in the west of Scotland between 2010 and 2020. Odds ratios for clinical predictors of surgery were calculated using logistic regression with uni- and multivariate analysis. Results249 patients were identified of which 219 proceeded to data collection. Primary malacia was noted in 161 (73.5%) and secondary in 58 (26.5%). Causes of secondary malacia included compression by the innominate artery (11%) and vascular rings (7.8%). Surgical interventions were performed in 28 patients (12.8%) including division of vascular ring, aortopexy, and surgical tracheostomy. Multivariate analysis showed secondary TBM, acute life-threatening events, and difficulty weaning from mechanical ventilation were independent risk factors for surgical intervention. ConclusionsTBM can present with a myriad of airway symptoms and is frequently associated with other airway and mediastinal pathologies necessitating multiple interventions. Children aged <1 year present with a more severe form of the disease and the presence of particular independent risk factors may indicate a need for surgical intervention. Level of evidence4