Case report: Transition from anti-CD20 therapy to inebilizumab for 14 cases of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system characterized by recurrent, disabling attacks that affect the optic nerve, spinal cord, and brain/brainstem. While rituximab, targeting CD20-positive B-cells, is used as an off-label therapy for NMOSD, some patients continue to exhibit breakthrough attacks and/or adverse reactions. Inebilizumab, a humanized and glycoengineered monoclonal antibody targeting CD19-positive B-cells, has been FDA approved for the treatment of NMOSD in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. Given the limited real-world data on the efficacy and safety of inebilizumab, especially in those transitioning from rituximab, a retrospective chart review was conducted on 14 NMOSD patients from seven centers. Of these, 71.4% (n = 10) experienced a combined 17 attacks during rituximab treatment, attributed to either breakthrough disease (n = 10) or treatment delay (n = 7). The mean duration of rituximab treatment was 38.4 months (3.2 years). Notably, no subsequent attacks were observed during inebilizumab treatment [mean duration of inebilizumab treatment was 19.3 months (1.6 years)], underscoring its potential as an effective treatment for NMOSD. Our data suggest that inebilizumab provides clinical benefit with effective disease control and a favorable safety profile for patients transitioning from rituximab.

DNA methylation episignature and comparative epigenomic profiling for Pitt-Hopkins syndrome caused by TCF4 variants.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by pathogenic variants in TCF4, leading to intellectual disability, specific morphological features, and autonomic nervous system dysfunction. Epigenetic dysregulation has been implicated in PTHS, prompting the investigation of a DNA methylation (DNAm) "episignature" specific to PTHS for diagnostic purposes and variant reclassification and functional insights into the molecular pathophysiology of this disorder. A cohort of 67 individuals with genetically confirmed PTHS and three individuals with intellectual disability and a variant of uncertain significance (VUS) in TCF4 were studied. The DNAm episignature was developed with an Infinium Methylation EPIC BeadChip array analysis using peripheral blood cells. Support vector machine (SVM) modeling and clustering methods were employed to generate a DNAm classifier for PTHS. Validation was extended to an additional cohort of 11 individuals with PTHS. The episignature was assessed in relation to other neurodevelopmental disorders and its specificity was examined. A specific DNAm episignature for PTHS was established. The classifier exhibited high sensitivity for TCF4 haploinsufficiency and missense variants in the basic-helix-loop-helix domain. Notably, seven individuals with TCF4 variants exhibited negative episignatures, suggesting complexities related to mosaicism, genetic factors, and environmental influences. The episignature displayed degrees of overlap with other related disorders and biological pathways. This study defines a DNAm episignature for TCF4-related PTHS, enabling improved diagnostic accuracy and VUS reclassification. The finding that some cases scored negatively underscores the potential for multiple or nested episignatures and emphasizes the need for continued investigation to enhance specificity and coverage across PTHS-related variants.

Air leak test in the Paediatric Intensive Care Unit (ALTIPICU): rationale and protocol for a prospective multicentre observational study.

INTRODUCTION: In children, respiratory distress due to upper airway obstruction (UAO) is a common complication of extubation. The quantitative cuff-leak test (qtCLT) is a simple, rapid and non-invasive test that has not been extensively studied in children. The objective of the ongoing study whose protocol is reported here is to investigate how well the qtCLT predicts UAO-related postextubation respiratory distress in paediatric intensive care unit (PICU) patients. METHODS AND ANALYSIS: Air Leak Test in the Paediatric Intensive Care Unit is a multicentre, prospective, observational study that will recruit 900 patients who are aged 2 days post-term to 17 years and ventilated through a cuffed endotracheal tube for at least 24 hours in any of 19 French PICUs. Within an hour of planned extubation, the qtCLT will be performed as a sequence of six measurements of the tidal volume with the cuff inflated then deflated. The primary outcome is the occurrence within 48 hours after extubation of severe UAO defined as combining a requirement for intravenous corticosteroid therapy and/or ventilator support by high-flow nasal cannula and/or by non-invasive ventilation or repeat invasive mechanical ventilation with a Westley score ≥4 with at least one point for stridor at each initiation. The results of the study are expected to identify risk factors for UAO-related postextubation respiratory distress and extubation failure, thereby identifying patient subgroups most likely to require preventive interventions. It will also determine whether qtCLT appears to be a reliable method to predict an increased risk for postextubation adverse events as severe UAO. ETHICS AND DISSEMINATION: The study was approved by the Robert Debré University Hospital institutional review board (IRB) on September 2021 (approval #2021578). The report of Robert Debré University Hospital IRB is valid for all sites, given the nature of the study with respect to the French law. The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05328206.

Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.

Single-Stage Endoscopic Repair of Pediatric Basal Encephalocele: A Comprehensive Multimedia Case Report.

BACKGROUND AND IMPORTANCE: Basal encephaloceles are the result of a concomitant cranial and dural defect that allows for inferior displacement of cerebral tissue, meninges, and cerebrospinal fluid into the paranasal sinuses and outside the cranial vault. This work illustrates a step-by-step surgical approach of a successful single-stage, endoscopic repair of a congenital basal encephalocele in a 10-year-old child, using a free mucosal middle turbinate graft that provided effective results without utilization of traditional open reconstructive techniques or vascularized flaps. CLINICAL PRESENTATION: A previously healthy 10-year-old male with a history of unilateral clear rhinorrhea was admitted as an inpatient because of an acute episode of nausea, vomiting, and confusion, accompanied by fever, diplopia, and bilateral abducens nerve palsies. Preoperative imaging revealed a 2-cm right-sided intranasal mass accompanied by a subcentimeter skull base defect spanning the lateral lamella. After completing a course of intravenous antibiotic therapy for 1 week after a negative lumbar puncture to ensure clearance of intracranial infection, the decision was made to proceed with definitive endoscopic skull base repair to obviate recurrent bacterial meningitis episodes and potential neurological complications. CONCLUSION: This study demonstrates technical feasibility of a single-stage endoscopic endonasal approach for pediatric basal encephalocele resection and repair which minimizes craniofacial morbidity associated with traditional open approaches and sinonasal morbidity associated with local pedicle-based flaps for small cranial base defects in this unique patient population.

Special Considerations in Pediatric Endoscopic Skull Base Surgery.

Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams.

Endoscopic Ultrasound-based Shear Wave Elastography for Detection of Advanced Liver Disease.

BACKGROUND AND AIMS: Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort. METHODS: EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation. RESULTS: Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P<0.001; median right lobe: 24.8 vs. 11.0 kPa, P<0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P=0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D. CONCLUSIONS: SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

Excessive pickle consumption: beware of adrenal crisis.

Adrenal insufficiency (AI) is one of the most life-threatening disorders resulting from adrenal cortex dysfunction. Symptoms and signs of AI are often nonspecific, and the diagnosis can be missed and lead to the development of AI with severe hypotension and hypovolemic shock. We report the case of a 13-year-old child admitted for cardiac arrest following severe hypovolemic shock. The patient initially presented with isolated mild abdominal pain and vomiting together with unexplained hyponatremia. He was discharged after an initial short hospitalization with rehydration but with persistent hyponatremia. After discharge, he had persistent refractory vomiting, finally leading to severe dehydration and extreme asthenia. He was admitted to pediatric intensive care after prolonged hypovolemic cardiac arrest with severe anoxic encephalopathy leading to brain death. After re-interviewing, the child's parents reported that he had experienced polydipsia, a pronounced taste for salt with excessive consumption of pickles lasting for months, and a darkened skin since their last vacation 6 months earlier. A diagnosis of autoimmune Addison's disease was made. Primary AI is a rare life-threatening disease that can lead to hypovolemic shock. The clinical symptoms and laboratory findings are nonspecific, and the diagnosis should be suspected in the presence of unexplained collapse, hypotension, vomiting, or diarrhea, especially in the case of hyponatremia.

Factors associated with adverse outcome among children with sickle cell disease admitted to the pediatric intensive care unit: an observational cohort.

BACKGROUND: Sickle cell disease (SCD) is one of the most frequent inherited diseases in the world. Over the last decades, in high-income countries, an important decrease in mortality have been observed due to the improvement of care. However, children with SCD can become critically ill and require admission in Pediatric Intensive Care Units (PICU). The purpose of this study was to describe the epidemiology of children with SCD admitted to PICU for acute crisis and to identify factors associated with adverse outcome (AO). METHODS: We conducted a retrospective study in a Tertiary Hospital in France including all consecutive children with SCD admitted to PICU between January 1st, 2009 and December 31, 2019. We collected baseline patient's characteristics, clinical and biological data as well as treatments and life sustaining therapies used in the PICU. Patients were defined as experiencing AO in case of death during stay and/or need for invasive mechanical ventilation (MV) and/or for non-invasive ventilation (NIV) for more than 3 days and/or need for vasopressors and/or need for renal replacement therapy. RESULTS: We included 579 admissions in 395 patients, mainly of SS genotype (90%) with a median age of 9.2 years [5.5-13.4] and a median baseline hemoglobin of 8.0 g/dl (7.5-8.8). The two main reasons for admission were acute chest syndrome (ACS) (n = 331, 57%) and vaso-occlusive crisis refractory to first line therapy (n = 99, 17%). Half of patients required NIV and 47 (8%) required MV. The overall length of stay was 3 days [1-4] and seven (1%) patients died during PICU stay.There was a total of 113 (20%) admissions with AO and on multivariable analysis, baseline hemoglobin < 8 g/dL, history of bronchial obstruction and admission for ACS were associated with AO. There was no difference in the proportion of hydroxyurea treatment or exchange transfusion program between patients with AO and the other patients. CONCLUSIONS: Baseline hemoglobin < 8 g/dL, history of bronchial obstruction and admission for ACS were the strongest risk factors for severe evolution in SCD children admitted to PICU. These factors could be taken into consideration when choosing the adequate therapeutic options.

Celiac artery mesenteric fat measurement with endosonography (CAMEUS) reliably correlates with obesity and related comorbidities.

Background: Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden. Methods: This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon. Results: CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P < 0.001) than BMI (R2 = 0.153, P < 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (-6.4 ± 5.2 mm, P < 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P < 0.05). Conclusions: CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.

Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children: results from the French pediatric national registry.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for an important mortality rate worldwide. We aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit (PICU). Secondary objectives were to identify risk factors for death. METHODS: This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions (PCRs) [acute corona virus disease 2019 (COVID-19) or incidental SARS-CoV-2 infection] and/or pediatric inflammatory multisystem syndrome (PIMS) recorded in the French PICU registry (PICURe) between September 1, 2021, and August 31, 2022. Included patients were classified and compared according to their living status at the end of their PICU stay. Deceased patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive care. The imputability of SARS-CoV-2 as the cause of death was classified into four categories: certain, very probable, possible, or unlikely, and was defined by any of the first three categories. RESULTS: There were 948 patients included of which 43 died (4.5%). From this, 26 deaths (67%) could be attributed to SARS-CoV-2 infection, with an overall mortality rate of 2.8%. The imputability of death to SARS-CoV-2 was considered certain in only one case (0.1%). Deceased patients suffered more often from comorbidities, especially heart disease, neurological disorders, hematological disease, cancer, and obesity. None of the deceased patients were admitted for pediatric inflammatory multisystem syndrome (PIMS). Mortality risk factors were male gender, cardiac comorbidities, cancer, and acute respiratory distress syndrome. CONCLUSIONS: SARS-CoV-2 mortality in the French pediatric population was low. Even though the imputability of SARS-CoV-2 on mortality was considered in almost two-thirds of cases, this imputability was considered certain in only one case.

[Pediatric necrotizing soft-tissue infections]. / Infections cutanées nécrosantes de l'enfant.

PEDIATRIC NECROTIZING SOFT-TISSUE INFECTIONS. Necrotizing soft-tissue infections (NSTI) include necrotizing forms of fasciitis, myositis, and cellulitis. In children, these are extremely rare conditions with an estimated annual incidence of less than 0.1/100,000 patients aged 0-18 years in France. Nevertheless, the evolution can be very serious (6% mortality, higher than the mortality observed in paediatric intensive care units [PICU]), whereas the initial local symptoms are poor and can be falsely reassuring. The monitoring of a skin infection must be close in order not to ignore the evolution towards a NSTI. In this case, prompt transfer to a PICU with all the necessary technical facilities and used to the management of these rare conditions must be done. Early initiation of antibiotic treatment and aggressive haemodynamic resuscitation according to the latest Surviving Sepsis Campaign guidelines should be a priority. The paediatric surgeon should be called upon as soon as clinical suspicion arises and participate in the frequent clinical reassessment to determine the optimal time to perform the surgical treatment.

INFECTIONS CUTANÉES NÉCROSANTES DE L'ENFANT. Les infections cutanées nécrosantes comprennent les dermo- hypodermites bactériennes nécrosantes (DHBN) et les fasciites nécrosantes (FN). Chez l'enfant, ce sont des pathologies extrêmement rares, avec une incidence annuelle en France estimée inférieure à 0,1/100 000 patients âgés de 0 à 18 ans. Néanmoins, leur évolution peut être gravissime (mortalité de 6 %, supérieure à la mortalité observée habituellement dans les unités de réanimation pédiatrique [URP]) alors que la symptomatologie locale initiale est pauvre et peut faussement rassurer. La surveillance d'une infection cutanée doit être rapprochée afin de ne pas méconnaître l'évolution vers une DHBN-FN. Dans ce cas, une orientation vers une URP disposant de l'ensemble du plateau technique nécessaire, et surtout habituée à gérer ces situations cliniques, est justifié. L'initiation précoce du traitement antibiotique et la prise en charge hémodynamique agressive en suivant les dernières recommandations de la Surviving Sepsis Campaign doivent être une priorité. Le chirurgien pédiatrique doit être appelé dès la suspicion clinique et participer à la réévaluation pluriquotidienne afin de déterminer le moment optimal pour réaliser le traitement chirurgical.

Assessment of adherence to the 2020 Surviving Sepsis Campaign guidelines for fluid resuscitation in children with suspected septic shock in paediatric emergency departments: a prospective multicentre study.

BACKGROUND: Paediatric sepsis is the leading cause of death in children under 5 years. No studies have evaluated the application of the Surviving Sepsis Campaign 2020 (SSC-2020) guidelines in paediatric emergency departments (PEDs). OBJECTIVE: To assess physician adherence to the SSC-2020 fluid resuscitation guidelines in children with suspected septic shock in PEDs. METHODS: This was a prospective multicentre observational study conducted in 21 French hospitals over 5 sequential weeks, between November 2021 and March 2022. Children with suspected septic shock and who received antimicrobial therapy within 72 hours were included. Primary outcome was SSC-2020 fluid resuscitation guidelines adherence (low 0-24%; moderate 25-74%; high 75-100%) according to: bolus volume of 10-20 mL/kg each, exclusive administration of balanced crystalloids at 1 and 24 hours of management, and initiation of fluid resuscitation within 1 hour of septic shock recognition. RESULTS: 63 children were included. 10 (16%) children had severe sepsis and 2 (3%) met the definition of septic shock. Compared with the SSC-2020 guidelines, 43 (68%) patients received boluses of 10-20 mL/kg; fluid resuscitation was initiated within 1 hour of septic shock recognition in 42 (76%) cases; balanced crystalloids were the only fluids administrated in 35 (56%) and 34 (55%) children at 1 and 24 hours of management, respectively. Main barriers reported by physicians were difficult intravenous access (43%), lack of team training (29%), workload constraints (28%), and absence or out-of-date protocols (24%). CONCLUSIONS: This study found high adherence for fluid resuscitation initiation but moderate adherence for bolus volume and fluid choice. TRIAL REGISTRATION NUMBER: NCT05066464.

Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.

CREB-binding protein (CBP, encoded by CREBBP) and its paralog E1A-associated protein (p300, encoded by EP300) are involved in histone acetylation and transcriptional regulation. Variants that produce a null allele or disrupt the catalytic domain of either protein cause Rubinstein-Taybi syndrome (RSTS), while pathogenic missense and in-frame indel variants in parts of exons 30 and 31 cause phenotypes recently described as Menke-Hennekam syndrome (MKHK). To distinguish MKHK subtypes and define their characteristics, molecular and extended clinical data on 82 individuals (54 unpublished) with variants affecting CBP (n = 71) or p300 (n = 11) (NP_004371.2 residues 1,705-1,875 and NP_001420.2 residues 1,668-1,833, respectively) were summarized. Additionally, genome-wide DNA methylation profiles were assessed in DNA extracted from whole peripheral blood from 54 individuals. Most variants clustered closely around the zinc-binding residues of two zinc-finger domains (ZZ and TAZ2) and within the first α helix of the fourth intrinsically disordered linker (ID4) of CBP/p300. Domain-specific methylation profiles were discerned for the ZZ domain in CBP/p300 (found in nine out of 10 tested individuals) and TAZ2 domain in CBP (in 14 out of 20), while a domain-specific diagnostic episignature was refined for the ID4 domain in CBP/p300 (in 21 out of 21). Phenotypes including intellectual disability of varying degree and distinct physical features were defined for each of the regions. These findings demonstrate existence of at least three MKHK subtypes, which are domain specific (MKHK-ZZ, MKHK-TAZ2, and MKHK-ID4) rather than gene specific (CREBBP/EP300). DNA methylation episignatures enable stratification of molecular pathophysiologic entities within a gene or across a family of paralogous genes.

Numerical flow experiment for assessing predictors for cerebrovascular accidents in patients with PHACES syndrome.

There is an increased risk of cerebrovascular accidents (CVA) in individuals with PHACES, yet the precise causes are not well understood. In this analysis, we aimed to examine the role of arteriopathy in PHACES syndrome as a potential contributor to CVA. We analyzed clinical and radiological data from 282 patients with suspected PHACES syndrome. We analyzed clinical features, including the presence of infantile hemangioma and radiological features based on magnetic resonance angiography or computed tomography angiography, in individuals with PHACES syndrome according to the Garzon criteria. To analyze intravascular blood flow, we conducted a simulation based on the Fluid-Structure Interaction (FSI) method, utilizing radiological data. The collected data underwent statistical analysis. Twenty patients with PHACES syndrome were included. CVAs were noted in 6 cases. Hypoplasia (p = 0.03), severe tortuosity (p < 0.01), absence of at least one main cerebral artery (p < 0.01), and presence of persistent arteries (p = 0.01) were associated with CVAs, with severe tortuosity being the strongest predictor. The in-silico analysis showed that the combination of hypoplasia and severe tortuosity resulted in a strongly thrombogenic environment. Severe tortuosity, combined with hypoplasia, is sufficient to create a hemodynamic environment conducive to thrombus formation and should be considered high-risk for cerebrovascular accidents (CVAs) in PHACES patients.

Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice.

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disorders (MOGAD) is an autoimmune central nervous system disease. Antigen-specific immune tolerance using nanoparticles such as Polylactic-co-glycolic acid (PLGA) have recently been used as a new therapeutic tolerization approach for CNS autoimmune diseases. We examined whether MOG1-125 conjugated with PLGA could induce MOG-specific immune tolerance in an experimental autoimmune encephalitis (EAE) mouse model. EAE was induced in sixty C57BL/6 J wild-type mice using MOG1-125 peptide with complete Freund's Adjuvant. The mice were divided into 12 groups (n = 5 each) to test the ability of MOG1-125 conjugated PLGA intervention to mitigate the severity or improve the outcomes from EAE with and without rapamycin compared to antigen alone or PLGA alone. EAE score and serum MOG-IgG titers were compared among the interventions.Kindly check and confirm the processed Affiliation “4” is appropriate.I confirmed the Aff 4.Affiliation: Corresponding author information have been changed to present affiliation. Kindly check and confirm.I checked and confirmed the Corresponding author's information. RESULTS: Mice with EAE that were injected intraperitoneally with MOG1-125 conjugated PLGA + rapamycin complex showed dose-dependent mitigation of EAE score. Intraperitoneal and intravenous administration resulted in similar clinical outcomes, whereas 80% of mice treated with subcutaneous injection had a recurrence of clinical score worsening after approximately 1 week. Although there was no significant difference in EAE scores between unconjugated-PLGA and MOG-conjugated PLGA, serum MOG-IgG tended to decrease in the MOG-conjugated PLGA group compared to controls. CONCLUSION: Intraperitoneal administration of PLGA resulted in dose-dependent and longer-lasting immune tolerance than subcutaneous administration. The induction of immune tolerance using PLGA may represent a future therapeutic option for patients with MOGAD.

The pediatric intensive care unit in France: What happens afterwards?

Although pediatric post-intensive care syndrome is frequent and impacts the child's quality of life in various aspects, there are currently no guidelines regarding post-pediatric intensive care unit (PICU) follow-up. The aim of this study was to describe post-PICU follow-up in France. Among the 37 French PICUs, only 67 % had a consultation service, mostly performed by pediatric intensivists (95 %). Post-intensive care evaluation was the main objective for 46 % of these centers, whereas others focused on specific patient populations. Post-intensive care follow-up is highly heterogeneous and developing such consultation services appears to be a main challenge for PICU teams.