Pediatric Disease Research Articles

Alterations of brain structural and functional connectivity networks topology and decoupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

ObjectiveTo investigate the alteration in structural and functional connectivity networks (SCN and FCN) as well as their coupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and determine if these properties could serve as potential biomarkers for the disease. Materials and methodsIn total of 32 children with MOGAD and 30 age- and sex-matched healthy controls (HC) were employed to construct the SCN and FCN, respectively. The graph-theoretical analyses of the global properties, node properties of the 90 brain nodes, and the structural-functional connectivity (SC-FC) coupling of the two networks were performed. The graph-theoretical properties that exhibited significant differences were analyzed using partial correlation analysis in conjunction with the clinical scales, including the expanded disability status scale (EDSS), modified Rankin scale (mRS), and pediatric cerebral performance category (PCPC) of the MOGAD group. Subsequently, a machine learning model was developed to discriminate between MOGAD and the HC group, aiming to explore the potential of these properties as biomarkers. ResultsThe SCN of the MOGAD group exhibited aberrant global properties, including an increased characteristic path length (Lp) and a decreased global efficiency (Eg), along with reduced nodal properties such as degree centrality (Dc), nodal efficiency (Ne), and local efficiency in multiple nodes. The FCN of the MOGAD group only exhibited decreased Dc, Ne, and betweenness centrality in two nodes of nodal properties. Besides, MOGAD showed a significant decrease in SC-FC coupling compared to the HC group. The analysis of partial correlation revealed significant correlations between several properties and the scales of EDSS and mRS in the MOGAD group. The machine learning method was used to extract six features and establish the model, achieving a classification accuracy of 82.3% for MOGAD. ConclusionsPediatric MOGAD showed a more pronounced impairment in the SCN along with decoupling of SC-FC. Both partial correlation analysis and discriminant modeling suggest that alterations in brain network properties have the potential as biomarkers for assessing brain damage in MOGAD.

Nodding syndrome: A role for environmental biotoxins that dysregulate MECP2 expression?

Nodding syndrome is an epileptic encephalopathy associated with neuroinflammation and tauopathy. This initially pediatric brain disease, which has some clinical overlap with Methyl-CpG-binding protein 2 (MECP2) Duplication Syndrome, has impacted certain impoverished East African communities coincident with local civil conflict and internal displacement, conditions that forced dependence on contaminated food and water. A potential role in Nodding syndrome for certain biotoxins (freshwater cyanotoxins plus/minus mycotoxins) with neuroinflammatory, excitotoxic, tauopathic, and MECP2-dysregulating properties, is considered here for the first time.

Diagnosis and treatment strategy of pediatric nonalcoholic fatty liver disease

Diagnosis and treatment strategy of pediatric nonalcoholic fatty liver disease

Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

The clinical application and laboratory management of molecular genetic diagnosis in children's hospital

AbstractBackgroundMolecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high‐quality development of the discipline requires careful consideration by relevant management and professionals.MethodsThis study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.ResultsThis study highlights the importance of molecular diagnostic technology in providing information and decision‐making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross‐discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.ConclusionsMolecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.

Child Oral Health Management: Prevention, Early Diagnosis, and Intervention Strategies

This paper explores various aspects of childhood oral health management, including prevention, early diagnosis, and intervention strategies. This paper reviews the epidemiological data of pediatric oral diseases, highlighting the high incidence of dental caries and periodontal disease in the pediatric population. This paper details multiple preventive measures, such as the use of fluoride and the importance of oral health education, which can help to reduce the incidence of oral diseases. This paper analyzes early diagnostic techniques and therapeutic approaches, including digital imaging and laser diagnostic techniques, highlighting the key role of these techniques in early detection and intervention in oral diseases. This paper presents a series of intervention strategies to improve the oral health of children through integrated management. The results show that systematic prevention and early intervention measures have significant effects in controlling and reducing oral diseases in children.

Metabolomics analysis of bronchoalveolar lavage fluid predicts unique features of the lower airway in pediatric cystic fibrosis

BackgroundProgressive, obstructive lung disease resulting from chronic infection and inflammation is the leading cause of morbidity and mortality in persons with cystic fibrosis (PWCF). Metabolomics and next -generation sequencing (NGS) of airway secretions can allow for better understanding of cystic fibrosis (CF) pathophysiology. In this study, global metabolomic profiling on bronchoalveolar lavage fluid (BALF) obtained from pediatric PWCF and disease controls (DCs) was performed and compared to lower airway microbiota, inflammation, and lung function. MethodsBALF was collected from children undergoing flexible bronchoscopies for clinical indications. Metabolomic profiling was performed using a platform developed by Metabolon Inc. Total bacterial load (TBL) was measured using quantitative polymerase chain reaction (qPCR), and bacterial communities were characterized using 16S ribosomal RNA (rRNA) sequencing. Random Forest Analysis (RFA), principal component analysis (PCA), and hierarchical clustering analysis (HCA) were performed. ResultsOne hundred ninety-five BALF samples were analyzed, 142 (73 %) from PWCF. Most metabolites (425/665) and summed categories (7/9) were significantly increased in PWCF. PCA of the metabolomic data revealed CF BALF exhibited more dispersed clustering compared to DC BALF. Higher metabolite concentrations correlated with increased inflammation, increased abundance of Staphylococcus, and decreased lung function. ConclusionsThe lower airway metabolome of PWCF was defined by a complex expansion of metabolomic activity. These findings could be attributed to heightened inflammation in PWCF and aspects of the CF airway polymicrobial ecology. CF-specific metabolomic features are associated with the unique underlying biology of the CF airway.

Object detection for caries or pit and fissure sealing requirement in children's first permanent molars

AbstractDental caries, a common oral disease, poses serious risks if untreated, necessitating effective preventive measures like pit and fissure sealing. However, the reliance on experienced dentists for pit and fissures or caries detection limits accessibility, potentially leading to missed treatment opportunities, especially among children. To bridge this gap, we leverage deep learning in object detection to develop a method for autonomously identifying caries and determining pit and fissure sealing requirements using smartphone oral photos. We test several detection models and adopt a tiling strategy to reduce information loss during image pre‐processing. Our implementation achieves 72.3 mAP.5 with the YOLOXs model and tiling strategy. We enhance accessibility by deploying the pre‐trained network as a WeChat applet on mobile devices, enabling in‐home detection by parents or guardians. In addition, our data set of children's first permanent molars will also aid in the broader study of pediatric oral disease.

Early predictors of intestinal complications in pediatric-onset Crohn's disease: A long-term cohort study in Taiwan

PurposeIdentifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan. MethodsThis was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications. ResultsAmong 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17–9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively. ConclusionsECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy.

The Primary Nutritional Approach in Pediatric Cystic Fibrosis: A Mini-Review

In recent decades, diets for Pediatric Diseases have gained increasing acceptance, with disease-specific diets recommended in various international guidelines. This Mini-Review, a crucial resource for medical professionals, researchers, and students specializing in pediatric gastroenterology and nutrition, highlights the basic principles of diet in Cystic Fibrosis. The text will focus on primary dietary interventions that will benefit by removing, adding, supplementing, and restricting diets.

Endoscopic combined intrarenal surgery versus percutaneuos nephrolithotomy for complex pediatric stone disease: A comparative analysis of efficacy and safety

INTRODUCTIONDecision-making for complex pediatric urinary system stone disease is still a challenge for pediatric urologists. The interest in supine percutaneous nephrolithotomy (PCNL) is increasing among centers to achieve high surgical success rates with less morbidity. Despite advanced retrograde intrarenal surgery armamentarium, percutaneous approaches remain the first-line surgical treatment modality for >2 cm and complex renal stones. There are no comparative studies yet in the literature for pediatric endoscopic combined intrarenal surgery (ECIRS) OBJECTIVEIn this study, we aimed to contribute to the literature by evaluating the safety and efficacy of ECIRS by comparing it with PCNL. STUDY DESIGNPatients under 18 years of age who underwent PCNL and ECIRS for urinary tract stone disease at our Pediatric Urology department between 2012 and 2024 were included. Preoperative (demographic characteristics, stone characteristics, biochemical parameters), perioperative (duration of surgery, number of accesses, lasing and fluoroscopy times, endoscopic and fluoroscopic stone-free rates) and postoperative (hospital stay, urinary tract infection, complication and radiological stone-free rates) parameters were retrospectively evaluated. RESULTSA total of 68 children [28 (41%) girls and 40 (59%) boys] aged 5 (0-17) years were included in the study. ECIRS was performed in 19 (28%), supine in 28 (41%) and prone PCNL in 21 (30%) patients. Age (p = 0.029), Guy's stone score (p<0.001), S.T.O.N.E. (p<0.001), and Seoul National University Renal Stone Complexity (S-ReSC) scores (p=0.001) for preoperative parameters were found to be higher in ECIRS group over both PCNL methods (Summary Table). However, Clinical Research Office of the Endourological Society (CROES) score was seen lower for ECIRS group patients compared to other groups (p=0.028).Surgery time (in favor of supine over prone PCNL), fluoroscopy time (in favor of ECIRS and Supine PCNL over Prone PCNL), preferred laser type (prone PCNL group was mostly performed with holmium laser, whereas other groups were balanced between Holmium and Thulium Fiber Laser) and exit strategy (the preferred exit strategy was DJ Stent in most of the ECIRS patients, whereas nephrostomy tube was used in some of the PCNL group) showed significant difference among the groups as perioperative parameters (p=0.042, <0.001, <0.001, <0.001, respectively). Surgery time was lower for supine PCNL compared to prone PCNL. For postoperative parameters, stone-free rates, complication rates and urinary tract infections were similar between the 3 groups, while a difference was detected in terms of length of hospital stay in favor of ECIRS over both supine and prone PCNL (p = 0.006). DISCUSSIONThe current trial suggests that stone-free and complication rates of ECIRS and supine PCNL were similar in the pediatric complex stone patients. Although, the stones in the ECIRS group we found to be more complex. Also, ECIRS was superior to PCNL in terms of fluoroscopy exposure and hospital stay. CONCLUSIONWith the widespread use of new generation ureteral access sheaths and flexible ureterorenoscopes, ECIRS may have an important role in treatment of complex pediatric kidney stones.

Developing a Novel Deep Learning Model for Pediatric Chest Radiograph Analysis

Pediatric thoracic diseases pose significant challenges to healthcare systems worldwide, particularly in regions with limited access to specialized medical resources. Lower respiratory infections, in particular, contribute significantly to childhood morbidity and mortality. This research aims to address the diagnostic challenges associated with pediatric thoracic diseases by harnessing the power of artificial intelligence. The study utilizes the PediCXR dataset, composed of pediatric chest radiographs, and employs a Faster R-CNN model pretrained on ImageNet data for lesion detection and classification. The model is trained to identify abnormal lesions indicative of various thoracic diseases, with a focus on achieving high accuracy and minimizing loss. Experimental results demonstrate the model's capability to achieve an accuracy exceeding 90% and a loss under 0.1, meeting predefined objectives.

Genetic and radiological aspects of pediatric renal cystic disease: A case series

Renal cystic diseases are common conditions whose etiology can be highly heterogeneous. They require a correct approach for adequate diagnosis and management. We aimed to illustrate part of the spectrum of renal cystic diseases through some clinical cases managed in our service. We describe 11 clinical cases including clinical entities such as renal multicystic dysplasia, and autosomal dominant and autosomal recessive polycystic renal disease, among other pathologies. Renal cystic diseases are heterogeneous in their clinical presentation, natural history, radiological findings, and genetic and pathophysiological basis. An integral clinical approach is needed to get a clear etiological diagnosis and offer adequate individualized care and follow-up for patients.

Highlights of the 2023 Bethesda System for Reporting Thyroid Cytopathology, 3rd Edition

The Bethesda System for Reporting Thyroid Cytopathology (TBSRCT) is crucial for cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations and is effective for clear communication with the referring physicians. The new Bethesda System for Reporting Thyroid Cytopathology, the third edition in 2023, provides several key updates. The most important update is the assignment of only single name for each of the six diagnostic categories: (I) nondiagnostic; (II) benign; (III) atypia of undetermined significance; (IV) follicular neoplasm; (V) suspicious for malignancy; and (VI) malignant. An implied risk of malignancy (ROM) for each of six categories has been updated based on extensively published data since the second edition of TBSRTC in 2017 and offers both an average ROM for each category and the expected range of cancer risk. Estimated final ROM after excluding “Noninvasive Follicular Thyroid Neoplasm with Papillary Like Nuclear Features (NIFTP)” for each of six categories has been updated based on the reported mean decreases in the ROM if excluding NIFTP. For atypia of undetermined significance (AUS) category, the subcategorization is simplified and more formalized into 2 subgroups, AUS-nuclear atypia or AUS-other, based on the implied ROM and molecular profiling. For the pediatric thyroid disease, pediatric ROMs and management algorithms are newly added for the same six reporting categories for this age group. New or revised disease nomenclatures including high-grade follicular-derived carcinoma has been updated according to the recently published 2022 World Health Organization Classification of Thyroid Neoplasms. Brand new two chapters are added including clinical perspectives and imaging studies (Chap. 13) and the use of molecular and other ancillary tests (Chap. 14). The atlas is updated with new images to illustrate more effectively for new disease entity and diagnostic criteria.

Utilization of Indocyanine Green (ICG) Fluorescence in Patients with Pediatric Colorectal Diseases: The Current Applications and Reported Outcomes.

In pediatric colorectal surgery, achieving and visualizing adequate perfusion during complex reconstructive procedures are paramount to ensure postoperative success. However, intraoperative identification of proper perfusion remains a challeng. This review synthesizes findings from the literature spanning from January 2010 to March 2024, sourced from Medline/PubMed, EMBASE, and other databases, to evaluate the role of indocyanine green (ICG) fluorescence imaging in enhancing surgical outcomes. Specifically, it explores the use of ICG in surgeries related to Hirschsprung disease, anorectal malformations, cloacal reconstructions, vaginal agenesis, bladder augmentation, and the construction of antegrade continence channels. Preliminary evidence suggests that ICG fluorescence significantly aids in intraoperative decision-making by improving the visualization of vascular networks and assessing tissue perfusion. Despite the limited number of studies, initial findings indicate that ICG may offer advantages over traditional clinical assessments for intestinal perfusion. Its application has demonstrated a promising safety profile in pediatric patients, underscoring the need for larger, prospective studies to validate these observations, quantify benefits, and further assess its impact on clinical outcomes. The potential of ICG to enhance pediatric colorectal surgery by providing real-time, accurate perfusion data could significantly improve surgical precision and patient recovery.

The first translation on pediatrics: Er Ke Cuo Yao

Er Ke Cuo Yao(The Pediatric Summary) is the first monograph on pediatrics of Western medicine translated and introduced in the late Qing Dynasty. It occupies an important position in the history of the development of modern pediatrics and modern Western medicine in China. Edited by American missionary Mary Hannah Fulton and translated by Chinese Western medicine scholar Yin Duanmo, the book consists of 2 volumes and 14 books, including general discussion of pediatrics, diagnosis of pediatric diseases, and discussion on teething, throat diseases, gastrointestinal diseases, worms, liver diseases, abdominal epimesis, and new infectious diseases, etc. covering the diagnosis, treatment, maintenance and other knowledge of Western medical pediatrics. The source of Er Ke Cuo Yao is not yet available, but it may be a synthesis of various materials, and the translation uses paraphrasing, transliteration, and traditional Chinese medicine terminology, and the language is easy to understand. Er Ke Cuo Yao reflects the level of development of pediatrics in Western medicine in the early modern period, makes up for the lack of pediatrics knowledge of traditional Chinese medicine, and plays an active role in the diagnosis and treatment of common pediatric diseases, epidemiological diseases, surgical diseases, and malnutrition prevention.

Written communication of whole genome sequencing results in the NHS Genomic Medicine Service: a multi-centre service evaluation.

Whole genome sequencing (WGS) is being used in diagnostic testing for certain clinical indications within the NHS Genomic Medicine Service (GMS) in England. Letter writing is an integral part of delivering results. However, no national guidelines for writing results from WGS exist. This multi-centre service evaluation used mixed methods to understand the content and readability of letters returning diagnostic, variant of uncertain significance (VUS), and no-finding results to paediatric rare disease patients. Eight Regional Genetics Services (response rate 47%) in England provided a total of 37 letters returning diagnostic (n = 13), VUS (n = 10), and no-finding (n = 14) results. Diagnostic and VUS results were usually delivered during an appointment; no-finding results were typically delivered by letter only. Letters were diverse in which content topics they covered and level of detail. No-finding letters (14/14) explained the result but were less likely to cover other topics. Diagnostic letters discussed the result (13/13), the condition (13/13), clinical genetics follow-up (13/13), clinical management (10/13), and adapting to the result (9/13). VUS letters explained the result (10/10), diagnostic uncertainty (10/10), and clinical genetics follow-up (10/10). Uncertainty was a common component of letters (33/37), irrespective of the result. Reanalysis or review after one or more years was suggested in 6/13 diagnostic, 7/10 VUS, and 6/14 no-finding letters. The mean reading level of letters corresponded to 15-17 years. Understanding how WGS results are conveyed to families during appointments, as well as how families interpret that information, is needed to provide a more comprehensive overview of results communication and inform best practices.

Celiac disease in North America: What is the current practice of pediatric gastroenterology providers?

While guidelines exist for the diagnosis and management of pediatric celiac disease (CeD), current practices in North America are not well-described. This study aimed to explore current practice patterns to identify gaps and direct future clinical, training and research initiatives. A 23-item survey designed by the Celiac Disease Special Interest Group was distributed electronically to its members. Questions explored four themes: (1) screening and diagnosis pre and post the coronavirus disease (COVID)-19 pandemic, (2) treatment and monitoring, (3) family screening and transition of care, and (4) CeD focused training. The survey response rate was 10.8% (278/2552). Most respondents were from the United States (89.9%, n = 250) and Canada (8.6%, n = 24). While endoscopy remained the gold standard, serology-based diagnosis was accepted by 47.5% (132/278). In response to the COVID-19 pandemic, 37.4% of providers changed their diagnostic practice. Barriers to care included: lack of insurance coverage for dietitians, wait times, and lack of CeD focused training. During fellowship 69.1% (192/278) reported no focused CeD training. Survey results revealed practice variation regarding the diagnosis and management of CeD in North America including a substantial proportion accepting non-biopsy, serology-based diagnosis, which increased during the COVID-19 pandemic. Variations in screening, diagnosis, interval surveillance, and family screening were also identified. Dedicated CeD education in pediatric gastroenterology fellowship may be an opportunity for standardizing practice and advancing research. Future North American guidelines should take current care patterns into consideration and develop new initiatives to improve care of children with CeD.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

JAK inhibitors in refractory juvenile rheumatic diseases: Efficacy, tolerance and type-I interferon profiling, a single center retrospective study

Objectives– Janus Kinase inhibitors (JAKi) are a new class of drugs available for pediatric rheumatic diseases.This study aimed to describe the safety and effectiveness of JAKi in these diseases, with a focus on longitudinal interferon-stimulated genes (ISG) assessment. Methods– We present a single-center retrospective study of children with refractory pediatric rheumatic diseases including connective tissue diseases, monogenic type I interferonopathies or juvenile idiopathic arthritis, receiving JAKi. According to physicians’ assessment, treatment effectiveness was classified at 12 months as a complete response in the total absence of disease activity, partial response in case of significant (>50%) but incomplete improvement or no response in the case of non-response or improvement of less than 50% of the clinical and biological parameters. ISG were monitored longitudinally using Nanostring technology. Results- 22 children were retrospectively included in this study, treated either by baricitinib or ruxolitinib. Complete response was achieved at 12 months in 9/22 (41%) patients. 6/22 (27%) patients were non-responders and treatment had been discontinued in five of them. Within the interferon (IFN)-related diseases group, ISG-score was significantly reduced 12 months after JAKi onset (p = 0.0068). At 12 months, daily glucocorticoid doses had been reduced with a median dose of 0.16 mg/kg/day (IQR 0.11; 0.33) (p = 0.0425). 7/22 (32%) patients had experienced side effects, infections being the most common. Increase of the body mass index was also recorded in children in the first 6 months of treatment. Conclusion– JAKi represent a promising treatment of immune-mediated pediatric diseases, enabling to decrease type-I IFN transcriptomic signature in responding patients, especially in the context of juvenile dermatomyositis. JAKi represent steroid-sparing drugs but they induce metabolic changes linked to weight gain, posing a concern in the treatment of young patients and teenagers. More data are required to define the efficacy and safety of JAKi in the management of refractory pediatric rheumatic diseases.