Large Cohort Of Pediatric Patients Research Articles

A significant increase in anthropometric indices during long-term follow-up of pediatric patients with celiac disease, with no endocrine disorders.

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups. Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

Pulmonary Artery Wedge Pressure Can Underestimate Direct Pulmonary Vein Pressure in Pediatric Pulmonary Vein Stenosis

BackgroundPulmonary artery wedge pressure (PAWP) can underestimate directly measured pulmonary vein pressure (PVP) as demonstrated in animal studies and human case reports. This concept has not been validated in a larger cohort of pediatric patients with pulmonary vein stenosis (PVS). MethodsPediatric patients who underwent cardiac catheterization for PVS at a single center from January 1, 2018, to March 31, 2023, were retrospectively reviewed. Mismatch between the PAWP and directly measured PVP or LA pressure was defined as >3 mm Hg. Preintervention angiography was reviewed and percent stenosis calculated. ResultsTwenty-six patients met inclusion criteria; 51 lower pulmonary veins (34 left, 17 right) from 42 catheterizations were evaluated. Significant PVS (≥30% stenosis) was seen in 38/51 (75%) veins, and 9/51 (18%) veins had no angiographic narrowing (0% stenosis). PAWP-PVP mismatch occurred in 37/51 (73%) veins with a median difference of 8 mm Hg (IQR, 6-12). Of these, PAWP was equal to LA pressure in 26 instances, all of which had significant PVS (median % stenosis 54 [IQR, 45-60]). Six of the cases with PAWP-PVP mismatch, PVS (range, 41%-70% stenosis), and no PAWP-LA mismatch reported both a proximal and distal segmental PAWP. In all 6 instances, there was no distal PAWP-PVP mismatch (median difference 1 mm Hg [range, 0-3]). ConclusionsIn this single-center study of pediatric patients with PVS, PAWP significantly underestimated directly measured PVP in lower pulmonary veins. Balloon wedge or end hole catheter position in a distal lobar segment may more accurately estimate the PVP.

P395 The frequency of SARS-CoV-2 infection and the impact of vaccination on the disease morbidity in Polish pediatric patients with Inflammatory Bowel Disease treated with biologic therapies

Abstract Background Little is known about morbidity of Covid-19 infection in pediatric patients with inflammatory bowel diseases (IBD) treated with biologic medications. The aim of this study was to evaluate the frequency of SARS-CoV-2 infection in children with IBD who received biologic therapies. Methods A prospective, observational cohort study to evaluate coronavirus disease 2019 (COVID-19) vaccination state, and its effect on the disease course among pediatric patients with IBD. The questionnaire included information concerning numbers of vaccine doses, patients’ medication and disease activity. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 320 children with IBD, 169 with Crohn’s disease (CD)-52,8%, 150 with ulcerative colitis (UC) - 46,9%, 1 unclassified -0,3%, responded to the questionnaire concerning COVI-19 vaccination. In our cohort 141 (49,7%) patients received biologic therapy: 13 patients (9,2%) adalimumab (ADA), 54 (38,3%) infliximab (IFX), 27 (19,1%) vedolizumasb (vedo), 29 (20,6%) ustekinumab (ust), 6 - vedo + ADA (4,3%), 1 - IFX + vedo (0,7%), 11 - ust + ADA (7,8%). 32 (22,7%) patients had COVID-19 infection during biological therapy (ust 6- 4,3%, vedo 7- 5,0%, ada 2-1,4%, ifx 12- 8,5%, ust + ada 2- 1,4%, vedo + ada 3- 2,1%). Among the patients on biologic treatment suffering from COVID-19, 25 (78,1%) children had mild course of the infection, 4 moderate (12,5%), 2 severe (6,3%), and 1 unknown (3,1%). A total of 127 (39,7%) patients received at least 1 COVID-19 vaccine, and among them 8 (6,3%) patients who received 1 dose of COVID-19 vaccine got the infection during biologic therapy. In our group, 193 (60,3%) patients have not been vaccinated against COVI-19, and 24 (12,4%) suffered from the disease during biologic therapy. Conclusion Based on the outcomes from our questionnaire concerning COVID-19 vaccination state on the large cohort of pediatric patients with IBD, we conclude that unvaccinated patients get sick more often than vaccinated ones, and that the use of biological treatment has no impact the frequency of covid infections or their course.

P393 The frequency of COVID-19 infection and the impact of vaccination on the disease morbidity in Polish pediatric patients with Inflammatory Bowel Disease

Abstract Background Little is known about morbidity of Covid-19 infection in pediatric patients with inflammatory bowel diseases (IBD). The aim of this study was to evaluate the frequency of SARS-CoV-2 infection in children with IBD. Methods A prospective, observational cohort study to evaluate morbidity of coronavirus disease 2019 (COVID-19) among pediatric patients with IBD. The questionnaire included information concerning numbers of vaccine doses, patients’ medication and disease activity. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Results A total of 320 children with IBD, 169 with Crohn’s disease (CD)-52,8%, 150 with ulcerative colitis (UC) - 46,9%, 1 unclassified -0,3%, responded to the questionnaire concerning COVI-19 vaccination. Among the participants 114 (35,6%) patients have suffered from COVID19 (62 CD- 54,4%, 51 UC- 44,7%, 1 unclassified - 0,9%). In 79 cases (69,3%) COVID-19 course was mild, in 31 (27,2%) it was moderate, and 3 (2,6%) children had severe disease. There was no statistically significant difference in morbidity among patients with CD and UC. A total of 127 (39,7%) patients received at least 1 COVID-19 vaccine, and among them 22 (17,3%) children got COVID-19 infection after vaccination. 91 (47.2%) of unvaccinated patients got COVID 19 infection. Following SARS-CoV-2 disease, 22 (19.3%) patients reported exacerbation of IBD during or after COVID 19. In 82 (71.9%) patients COVID-19 infection had no effect on the course of their IBD. Among patients with exacerbation during/after SARS-CoV-2 disease, 3 (13.6%) were vaccinated and 19 (86.4%) of them were not vaccinated. Conclusion Based on the outcomes from our questionnaire concerning COVID-19 vaccination state on the large cohort of pediatric patients with IBD, we conclude that unvaccinated patients get sick more often than vaccinated ones, and there is no difference in the frequency of SARS-CoV-2 infection between children with CD and UC. Also, there is no statistically significant difference in the severity of COVID-19 infection between vaccinated and unvaccinated patients. Vaccination against COVID-19 has no effect on the exacerbation of IBD during/after infection.

Population Pharmacokinetic Modeling for Twice-Daily Intravenous Busulfan in a Large Cohort of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation-A 10-Year Single-Center Experience.

Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children's Hospital Zurich between October 2010 and February 2020. Clinical data and busulfan plasma levels after twice-daily intravenous administration were analyzed retrospectively by population pharmacokinetic modeling. The volume of distribution correlated with total body water. The elimination rate constant followed an age-dependent maturation function, as previously suggested, and correlated with the levels of serum albumin. Acute lymphoblastic leukemia reduced busulfan clearance by 20%. Clearance significantly decreased by 17% on average from the start to the third day of busulfan administration, in agreement with other studies. An average reduction of 31% was found in patients with hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. In conclusion, we demonstrate that in addition to known factors, underlying disease and serum albumin significantly impact busulfan pharmacokinetics in pediatric patients; yet, substantial unexplained variability in some patients remained. Thus, we consider repeated pharmacokinetic assessment essential to achieve the desired target exposure in twice-daily busulfan administration.

Uncovering the Genetic Etiology of Inherited Bone Marrow Failure Syndromes Using a Custom-Designed Next-Generation Sequencing Panel

Inherited bone marrow failure syndromes (IBMFS) are a group of heterogeneous disorders that account for approximately 30% of pediatric bone marrow failure cases and are often associated with developmental abnormalities and cancer predisposition. We report the laboratory validation and clinical utility of a large custom-designed NGS panel, CHOP IBMFS panel, for the diagnosis of IBMFS in a large cohort of pediatric patients. This panel demonstrated excellent analytic accuracy with 100% sensitivity, ≥99.99% specificity, and 100% reproducibility on validation samples. Two hundred sixty-nine patients suspected to have IBMFS were investigated using this NGS panel to identify single nucleotide variants (SNVs), small insertions/deletions (indels) and copy number variations (CNVs) in mosaic or non-mosaic status. Sixty-one pathogenic/likely pathogenic (P/LP) variants (54 SNVs/indels and 7 CNVs), and 24 hypomorphic variants were identified, resulting in the molecular diagnosis of IBMFS in 21 cases (7.8%) and exclusion of IBMFS with a diagnosis of another blood disorder in 10 cases (3.7%). Secondary findings including evidence of early hematologic malignancies and other hereditary cancer-predisposition syndromes were observed in 9 cases (3.3%). CHOP IBMFS panel displays high sensitivity and specificity and has resulted in a significant increase in the diagnostic yield of IBMFS. This study demonstrates that NGS-based panel testing should be part of the routine diagnostic workup for suspected IBMFS patients.

Paediatric Cushing syndrome: a prospective, multisite, observational cohort study

Paediatric endogenous Cushing syndrome is a rare condition with variable signs and symptoms of presentation. We studied a large cohort of paediatric patients with endogenous Cushing syndrome with the aim of describing anthropometric, clinical, and biochemical characteristics as well as associated complications and outcomes to aid diagnosis, treatment, and management. In this prospective, multisite cohort study, we studied children and adolescents (≤18 years at time of presentation) with a diagnosis of Cushing syndrome. Patients had either received their initial diagnosis and evaluation at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Bethesda, MD, USA) or been referred from other centres in the USA or outside the USA. We collected participants' clinical, biochemical, and imaging findings and recorded their post-operative course until their latest appointment. Of 342 paediatric patients with a diagnosis of Cushing syndrome, 193 (56%) were female and 149 (44%) male. 261 (76%) patients had corticotroph pituitary neuroendocrine tumours (Cushing disease), 74 (22%) had adrenal-associated Cushing syndrome, and seven (2%) had ectopic Cushing syndrome. Patients were diagnosed at a median of 2 years (IQR 1·0-3·0) after the first concerning sign or symptom, and patients with adrenal-associated Cushing syndrome were the youngest at diagnosis (median 10·4 years [IQR 7·4-13·6] vs 13·0 years [10·5-15·3] for Cushing disease vs 13·4 years [11·0-13·7] for ectopic Cushing syndrome; p<0·0001). Body-mass index z-scores did not differ between the diagnostic groups (1·90 [1·19-2·34] for adrenal-associated Cushing syndrome vs 2·18 [1·60-2·56] for Cushing disease vs 2·22 [1·42-2·35] for ectopic Cushing syndrome; p=0·26). Baseline biochemical screening for cortisol and adrenocorticotropin at diagnosis showed overlapping results between subtypes, and especially between Cushing disease and ectopic Cushing syndrome. However, patients with ectopic Cushing syndrome had higher urinary free cortisol (fold change in median cortisol concentration from upper limit of normal: 15·5 [IQR 12·7-18·0]) than patients with adrenal-associated Cushing syndrome (1·5 [0·6-5·7]) or Cushing disease (3·9 [2·3-6·9]; p<0·0001). Common complications of endogenous Cushing syndrome were hypertension (147 [52%] of 281 patients), hyperglycaemia (78 [30%] of 260 patients), elevated alanine transaminase (145 [64%] of 227 patients), and dyslipidaemia (105 [48%] of 219 patients). Long-term recurrence was noted in at least 16 (8%) of 195 patients with Cushing disease. This extensive description of a unique cohort of paediatric patients with Cushing syndrome has the potential to inform diagnostic workup, preventative actions, and follow-up of children with this rare endocrine condition. Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health.

Clinical Characteristics and Treatment Outcomes of Idiopathic Multicentric Castleman Disease: Data from a Pediatric Cohort

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare, atypical hematologic disorder characterized by diffuse lymphadenopathy and systemic inflammation causing potentially fatal multi-organ system dysfunction. Though the etiology remains unknown, interleukin-6 (IL-6) has been implicated in disease pathogenesis and siltuximab, a monoclonal antibody that antagonizes IL-6, is the only FDA-approved iMCD treatment. Despite substantial morbidity for children with iMCD, the pediatric experience has not been well characterized. It is unclear whether insights gleaned from adults apply to children or whether siltuximab, which was never prospectively studied in a pediatric population, achieves similar response rates in children. We sought to correct this knowledge gap and better characterize pediatric iMCD. Methods: The ACCELERATE longitudinal Castleman disease (CD) natural history registry was interrogated for patients under 18 years of age at time of diagnosis. For each patient, complete medical history and lymph node biopsy slides were collected and extracted, and a panel of clinicians and pathologists performed independent adjudication of the diagnosis. Demographics - including age at diagnosis, histopathologic subtype, clinical subtype, clinical symptoms, and most severe laboratory parameters present within ± 90 days from date of pathological diagnosis were aggregated. Lastly, treatments administered to the cohort of pediatric patients were inventoried and both clinical response (defined as at least 50% reduction in abnormal clinical and laboratory criteria) and durable response (defined as a positive clinical response lasting ≥ 365 days with no other CD treating drug administered in between) were determined. Results: Nineteen pediatric patients were confirmed to have iMCD, of which 14 (74%) were male and 5 (26%) were female (Table 1A). The mean (standard deviation [SD]) age at diagnosis was 13.6 (4.3), with the youngest patient diagnosed at 2 years of age. Much of the cohort demonstrated hypervascular lymph node histology (89.5%). Clinically, 84% of the patients demonstrated the severe TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly) subtype while 16% were not otherwise specified. 95% of patients presented with constitutional symptoms and all but one patient presented with fatigue and fevers. All 19 patients presented with organomegaly and fluid retention (anasarca, ascites, pleural effusions, and/or peripheral edema). No patients demonstrated CD-specific skin abnormalities (violaceous lymphocytic papules or cherry hemangiomata) or interstitial lymphocytic pneumonitis. Labs indicated significant systemic inflammation, with mean (SD) C-reactive protein, erythrocyte sedimentation rates, and albumin values of 128.3 (102.7) mg/L, 74.5 (42.5) mm/hr, and 2.7 (0.6) g/dL, respectively. Eighteen (95%) patients presented with anemia, with a mean (SD) hemoglobin value of 9.5 (2.2) g/dL. Sixteen (84%) patients demonstrated platelet abnormalities, with 13 patients presenting with thrombocytopenia and three with thrombocytosis. No patient demonstrated hypergammaglobulinemia. Nine patients received three unique siltuximab regimens: siltuximab ± CS (corticosteroids), siltuximab + sirolimus ± CS, and siltuximab + other (other being defined as all other treatments such as rituximab, eculizumab, and ravulizumab) (Table 1B). Siltuximab ± CS was administered to six patients; 83% (n=5) had a positive response, and 60% of responders achieved a durable response. Lastly, two patients with TAFRO died from their disease. Conclusions: Overall, real-world medical record data from a cohort of pediatric iMCD patients enrolled in ACCELERATE reveals high disease burden within this population. A notable degree of TAFRO, the most severe iMCD subtype, was observed within this pediatric cohort, with clinical manifestations and laboratory abnormalities commonly observed in adult iMCD. This makes this population particularly vulnerable and highlights the need for prompt and accurate treatment. We also observed a high response rate to siltuximab ± CS in this small cohort, supporting its use in pediatric iMCD. Further research examining the effectiveness of siltuximab in a larger cohort of pediatric patients as well as other treatments is needed to identify optimal treatment approaches.

Clinical Implementation and Value of Plasma Metagenomic Sequencing in Immunocompromised Pediatric Patients

Abstract Background Metagenomic next-generation sequencing (mNGS) of cell-free DNA from plasma is emerging as a promising diagnostic tool in immunocompromised hosts but its performance characteristics in specific patient populations and clinical syndromes have not been systematically compared. Here, we describe the implementation and clinically utility of plasma mNGS in a large cohort of pediatric patients who are immunocompromised. Methods We performed retrospective review of all plasma mNGS testing (Karius®) performed at University of Minnesota between December 2017 – December 2022. Study design was reviewed by UMN IRB and determined to be nonhuman subjects research. For this study, we performed a nested subgroup secondary analysis of all patients aged &amp;lt;18 years at time of mNGS test who had underlying conditions that included hematologic malignancy, solid organ malignancy, hematopoietic stem cell transplantation or solid organ transplantations. Electronic medical records were reviewed for each mNGS test, recording patient demographics, underlying conditions, indications, and conventional microbiological results within 30 days of mNGS. The primary endpoint was change in clinical management as defined by Hogan et al and adjudicated by 2 independent reviewers. Secondary end points included sensitivity, time to mNGS order and time to diagnosis. Results We identified 71 unique pediatric patients with an immune compromised state who had 104 plasma mNGS tests performed between them. Fever was the most common indication for plasma mNGS (66%, 69/104), followed by Pulmonary Syndrome/Infiltrate/Lesion (23%, 22/104). The median time to plasma mNGS ordering from symptom onset was 8 days (IQR 3-17). Pediatric Infectious Diseases was consulted 70% (73/104) of the time. In cases where a microbiological cause(s) were identified, plasma mNGS identified the organism 48% of the time compared to 74% in conventional testing. Plasma mNGS led to a change in clinical management in 14 cases (13%,14/104) ordered in 13 unique patients. In 8 cases this led to a new diagnosis not confirmed by conventional microbiological testing or an earlier diagnosis, later confirmed by conventional testing. The new or earlier diagnoses cases included detection of invasive fungal/mold infections, anaerobic infections, and parasitic infections and were ordered on average within 2 days of symptom onset. Negative or DNA virus results on the plasma mNGS led to de-escalation of antimicrobials in 28% (4/13) of the positive impact cases. Conclusions Here, we describe the implementation of plasma mNGS in large immunocompromised pediatric cohort. Plasma mNGS led to a change in clinical management in a minority of cases (13%). However, these cases demonstrate that when ordered early in the clinical syndromes, plasma mNGS testing can detect difficult to diagnose organisms and promote antimicrobial stewardship. More prospective studies with early implementation of plasma mNGS in immunocompromised pediatric patients will be informative of the clinical value of this powerful diagnostic tool.

BIOS-05. USING DATA-DRIVEN ANALYTICS TO PREDICT SURVIVAL IN PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA: THE UTILITY OF MACHINE LEARNING IN NEXT-GENERATION NEURO-ONCOLOGY PROGNOSTICATION

Abstract Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a &amp;gt;75% 5-year survival rate, children who survive often have substantial neurological and cognitive sequelae. We aimed to identify risk factors and develop a clinically friendly online calculator for prognostic estimation in pediatric medulloblastoma patients. Pediatric patients with a histopathologically confirmed diagnosis of 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 (Figure 1). 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). 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 (). 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, and could aid prognostication efforts in the clinical setting. 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.

An online calculator using machine learning for predicting survival in pediatric patients with medulloblastoma.

Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a 5-year survival rate > 75%, 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 patients with medulloblastoma. Pediatric patients with a histopathologically confirmed medulloblastoma were extracted from the Surveillance, Epidemiology, and End Results database (2000-2018) 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 patients with medulloblastoma. The performance of the calculator was determined by discrimination and calibration. One thousand seven hundred fifty-nine pediatric patients with medulloblastoma met the prespecified inclusion criteria. Age, sex, race, ethnicity, median household income, county attribute, laterality, anatomical location, tumor grade, tumor size, surgery status, radiotherapy, and chemotherapy were variables included in the calculator (https://spine.shinyapps.io/Peds_medullo/). The concordance index was 0.769 in the training cohort and 0.755 in the validation cohort, denoting clinically useful predictive accuracy. Good agreement between the predicted and observed outcomes was demonstrated by the calibration plots. 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.

Juvenile Dermatomyositis in Afro-Caribbean children: a cohort study in the French West Indies

IntroductionThe epidemiology of Juvenile Dermatomyositis (JDM) in non-Caucasian population is poorly described. We performed a study of patients followed up in the French West Indies for JDM. We aimed to describe clinical and biological specificities during childhood.MethodsRetrospective study covering the period from Januarys 2000–2023. Listings of patients were obtained from multiple sources, namely computerized hospital archives, registry of referent pediatricians and adult specialists in internal medicine and the French National Registry for rare diseases. JDM and organ involvement were defined according to the international ILAR criteria.ResultsTwenty-one patients were included over a 23 year-period. Median age at onset was 8.1 years (Range: 2.5—13.9) with a median follow up of 8 years (Range: 2—19). Two-thirds (14/21) had dysphagia at onset and 33% had respiratory involvement. Thirteen had specific autoantibodies (58%), most frequently anti-Mi-2. The median number of flares during childhood was three (1—9). During childhood, 76% had calcinosis lesions. Clinical evolution seemed to be more aggressive for boys than girls (respectively 4.2 versus 2.2 flares (p = 0.04) and 50% vs 18% needing more than one background therapy, p = 0.03).ConclusionThis retrospective study is the largest cohort of pediatric patients of Afro-Caribbean and Black African descent treated for JDM in a high-income health system, and the first to describe the incidence and immunological profile in a population of African descent. They had higher rate of calcinosis and similar respiratory involvement. Overall outcomes during childhood were similar to North America and European countries.

FRI591 Association Of TSH Levels And NAFLD Severity In Children And Adolescents

Abstract Disclosure: M. Untalan: None. N.A. Crimmins: None. A. Mencin: None. K. Yates: None. X. Stavra: None. V. Thaker: None. Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation and is now the most common form of chronic liver disease in children and adolescents. Recent studies have indicated an association between subclinical hypothyroidism (SH) and NAFLD. An underactive thyroid gland produces insufficient T3 and T4 involved in hepatic fat metabolism that could contribute to NAFLD. While increased TSH has been documented in individuals with NAFLD, its independent role with NAFLD disease severity is yet to be clarified. Objective: To study the relationship of TSH levels and the severity of NAFLD/NASH, as well as determine whether changes in TSH levels are associated with changes in NAFLD/NASH among children. Methods: This retrospective study used data from two cohorts within the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). TSH, free and total T4, total T3, TPO antibodies and thyroglobulin (TBG) levels were assessed in samples obtained first at baseline and then at 52-96 weeks. Individuals with overt hypothyroidism, abnormal TPO antibody levels, and those receiving thyroid treatment were excluded from analysis. SH was defined as TSH &amp;gt; 4.4 mIU/L. Linear and multinomial regression models were used to identify the association between TSH, SH and NAFLD severity measured by NAFLD activity score (NAS), fibrosis stage, steatosis level, lobular and portal inflammation and ballooning while adjusting for potential confounders (sex, age, race, BMI-z, HOMA-IR and non-HDL levels). Longitudinal analysis was conducted by mixed-effects model. Analyses were performed with SAS and R statistical software. Results: 218 individuals and 421 observations were included in the cross-sectional and longitudinal analyses, respectively. Children with more severe grades of steatosis were more likely to be younger (p = 0.03) and male (p = 0.02). At baseline, TSH was not significantly associated with any NAFLD histological measures. Longitudinal analyses revealed a positive association of change in TSH and steatosis level after adjusting for covariates, and follow-up time (p = 0.03). Change in SH was associated with change in fibrosis stage (p = 0.01). Adding HOMA-IR and non-HDL levels to the models did not change this relationship. The positive relationship of total T3 and T4 with NAS was explained by TBG. Conclusion: In a large cohort of pediatric patients with biopsy-confirmed NAFLD, high TSH levels correlated with increasing steatosis grade and NAS, and SH with increased liver fibrosis. Markers of impaired thyroid function may help predict disease severity in pediatric patients with NAFLD. Presentation: Friday, June 16, 2023

Hyperbaric oxygen treatment in children: experience in 329 patients.

Paediatric patients, like adults, may undergo hyperbaric oxygen treatment (HBOT) in both life-threatening situations and chronic diseases. There are particular challenges associated with managing paediatric patients for HBOT. This paper documents the indications, results, complications, and difficulties that occur during HBOT for a large cohort of paediatric patients and compares them with adult data in the literature. Methods used to reduce these difficulties and complications in children are also discussed. This was a 15-year retrospective review of paediatric patients treated with HBOT at two hyperbaric centres. Between January 2006 and June 2021, patients under the age of 18 who received at least one session of HBOT were included. Three hundred and twenty-nine paediatric patients underwent a total of 3,164 HBOT exposures. Two-hundred and fifty-four patients (77.2%) completed treatment as planned and 218 (66.5%) achieved treatment goals without complications. Two patients treated for carbon monoxide poisoning exhibited neurological sequelae. Amputation was performed in one patient with limb ischaemia. Middle ear barotrauma events occurred in five treatments. No central nervous system oxygen toxicity was recorded during the treatments. This patient series indicates that HBOT can be safely performed in pediatric patients with low complication rates by taking appropriate precautions. The cooperation of hyperbaric medicine physicians and other physicians related to paediatric healthcare is important in order for more patients to benefit from this treatment. When managing intubated patients an anaesthesiologist may need to participate in the treatment in order to perform necessary interventions.

The majority of pediatric Fontan patients have excellent post-transplant survival

ObjectiveMany pediatric Fontan patients require heart transplant, but this cohort is understudied given the difficulty in identifying these patients in national registries. We sought to characterize survival post-transplant in a large cohort of pediatric patients undergoing the Fontan. MethodsThe United Network for Organ Sharing and Pediatric Health Information System were used to identify Fontan heart transplant recipients aged less than 18 years (n = 241) between 2005 and 2022. Decompensation was defined as the presence of extracorporeal membrane oxygenation, ventilation, hepatic/renal dysfunction, paralytics, or total parenteral nutrition at transplant. ResultsMedian age at transplant was 9 (interquartile range, 5-12) years. Median waitlist time was 107 (37-229) days. Median volume across 32 center was 8 (3-11) cases. Approximately half (n = 107, 45%) of recipients had 1A/1 initial listing status. Sixty-four patients (28%) were functionally impaired at transplant, 10 patients (4%) were ventilated, and 18 patients (8%) had ventricular assist device support. Fifty-nine patients (25%) had hepatic dysfunction, and 15 patients (6%) had renal dysfunction. Twenty-one patients (9%) were dependent on total parenteral nutrition. Median postoperative stay was 24 (14-46) days, and in-hospital mortality was 7%. Kaplan–Meier analysis showed 1- and 5-year survivals of 89% (95% CI, 85-94) and 74% (95% CI, 81-86), respectively. Kaplan–Meier of Fontan patients without decompensation (n = 154) at transplant demonstrated 1- and 5-year survivals of 93% (95% CI, 88-97) and 88% (95% CI, 82-94), respectively. In-hospital mortality was higher in decompensated patients (11% vs 4%, P = .023). Multivariable analysis showed that decompensation predicted worse post-transplant survival (hazard ratio, 2.47; 95% CI, 1.16-5.22; P = .018), whereas older age at transplant predicted superior post-transplant survival (hazard ratio, 0.89/year; 95% CI, 0.80-0.98; P = .019). ConclusionsPediatric Fontan post-transplant outcomes are promising, although early mortality remains high. For nondecompensated pediatric patients at transplant without end-organ disease (>63% of cohort), early mortality is circumvented and post-transplant survival is excellent and similar to all pediatric transplantation.

Solid pseudopapillary neoplasms of the pancreas in childhood and adolescence—an analysis of the German Registry for Rare Pediatric Tumors (STEP)

Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1–0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regarding diagnostics, treatment, and outcome of children aged 0–18 years with SPN recorded in the German Registry for Rare Pediatric Tumors (STEP) were analyzed. Thirty-eight patients were identified with a median age of 14.5 years at diagnosis (range: 8–18) and a female preponderance (81.6%). The most frequent location of the tumor was the pancreatic tail. In histopathological and immunohistochemical examination, pseudopapillary, solid, and cystic lesions as well as expression of beta-catenin, progesterone receptors, and cyclin D1 were the most common findings. All patients underwent surgical resection. Most patients underwent open resection, predominantly tail resection for tumors in the tail region and pylorus-preserving pancreaticoduodenectomy for tumors in the head region. The main postoperative sequela was exogenous pancreatic insufficiency (23.7%), especially with SPN in the pancreatic head. No recurrence occurred during follow-up, although two patients underwent resection with microscopic residue.Conclusion: SPN of the pancreas in childhood are low-grade malignancies with usually favorable treatment outcomes. However, therapy can lead to relevant long-term sequelae. To prevent recurrence, complete surgical resection is recommended, sparing as much healthy pancreatic tissue as possible. Interdisciplinary collaboration between specialists is essential to optimize treatment. Molecular genetic analysis of these tumors could improve understanding of their genesis.What is Known:• Solid pseudopapillary neoplasms (SPNs) of the pancreas are very rare tumors in childhood.• Little is known about tumorigenesis, and there are no specific guidelines for treatment and follow-up in pediatric patients.What is New:• Characteristics, treatment, and outcome were comprehensively assessed in a large cohort of pediatric patients with SPN.• We propose recommendations for diagnosis, treatment, and follow-up of children with SPN, based on our analysis and considering published experience.

Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery.

Identification of biological molecules related to post cardiopulmonary bypass (CPB) lung injury could help diagnose, predict and potentially impact patient's clinical course after cardiac surgery. Proteoglycan 4 (PRG4) initially identified as potential biomarker for patients with prolonged mechanical ventilation following CPB in a prior study. To further validate these findings, we sought to understand the association of lower plasma PRG4 with prolonged mechanical ventilation and worse lung compliance in a larger cohort of pediatric patients post CPB. Retrospective chart review study. Pediatric Cardiac Intensive Care Unit, Tertiary Hospital. Infants <1 year old with tetralogy of Fallot, ventricular septal defect, or atrioventricular septal defect who underwent surgical repair 2012-2020 and had stored plasma samples in our biorepository were screened for inclusion. Patients with mechanical ventilation before surgery were excluded. Patients were divided into quartiles based on postoperative duration of mechanical ventilation (control <25th percentile, study >75th percentile). Preoperative and 48-hour postoperative samples for each cohort (20 patients each) were tested for PRG4 level using enzyme-linked immunosorbent assay (ELISA) technique. Study group had lower lung compliance, higher mean airway pressure and higher oxygen need postoperative when compared to control group. Plasma PRG4 levels before surgery and 48 hours postoperative were lower in study group compared to control group (P=0.0232 preoperative; P=0.0016 postoperative). Plasma PRG4 levels were compared preoperative to PRG4 levels postoperative in both group, there was no statistically significant difference (study group: P=0.0869; control group: P=0.6500). Lower levels of plasma PRG4 is associated with longer duration of mechanical ventilation, worse ventilator compliance and higher oxygen requirement after cardiac surgery in our patient population. Further validation of this finding in a larger and more diverse patient population is necessary prior to its application at the bedside.

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.