OBJECTIVE:To assess the impact of selective supra-aortic trunk (SAT) stenting on aortic remodeling in patients with chronic type A aortic dissection (cTAAD). METHODS:Patients treated from 2017 to 2024 with aortic arch repair using double-fenestrated physician-modified endografts (PMEGs) for cTAAD were retrospectively analyzed. The objectives are to compare aortic treatment and remodeling, SAT evolution, and overall outcomes according to SAT dissection status (before and after), total aortic arch repair using a double-fenestrated PMEG. RESULTS:Among 42 cTAAD patients treated, 30 had SAT dissection. Thirty-five patients received a standard PMEG, while 7 underwent additional selective SAT stenting (3 LCCA, 1 brachiocephalic trunk (BT), 4 right subclavian artery (RSA), and 3 right common carotid artery (RCCA)). Technical success was 100%. At 30 days, 1 patient died from stroke, 1 from pneumonia post-discharge. During a median follow-up of 18.5 months (IQR: 38.8), no type Ia endoleaks occurred. Six type Ic endoleaks were observed; 3 patients underwent reintervention, while the remaining 3 were monitored with follow-up CT scans showing no evidence of aortic growth. Complete SAT dissection resolution occurred in 12 patients (40%), including 9 with standard PMEG. Positive aortic remodeling was seen in 32 patients (76%) with a median diameter reduction of -1% (IQR: 5.5%). Five patients died during mid-term follow-up, with no deaths related to the procedure. Positive aortic remodeling rates are 73% vs. 83% (p=0.7) between patients with and without initial SAT dissection, 83% vs 92% (p=1) between patients with initially no SAT dissection and those who healed, 61% vs 88% (p=0.07) between patients with persistent SAT dissection and the others. Patients on curative anticoagulation or dual antiplatelet therapy showed reduced positive remodeling. CONCLUSION:Double-fenestrated PMEGs are effective for treating residual cTAADs, with high SAT healing and favorable remodeling. Persistent SAT dissection may hinder remodeling and require additional intervention.Clinical ImpactAortic arch repair using fenestrated physician-modified endografts without systematic SAT stenting reduces SAT manipulation and may lower stroke risk, while promoting a high rate of SAT and aortic dissection healing. In cases where SAT dissection persists and aortic growth is reported, secondary complementary SAT intervention can be performed to enhance aortic remodeling.
BACKGROUND: Recent advances in sequencing technologies have enhanced patient diagnosis; however, causal pathogenic variants remain unidentified for a significant number of patients due to limited understanding of certain variants, regulatory sequences, or sequencing challenges, such as complex rearrangements. Investigating the epigenetic landscape has become essential to improve the diagnostic yield. Diseases caused by pathogenic variants in epigenetic regulators, often associated with growth abnormalities, intellectual disability, and facial dysmorphism, are prime models for studying episignatures. Among them, Snijders Blok-Campeau syndrome (ORPHA:599082), caused by pathogenic variants in the CHD3 gene, remains largely understudied. METHODS: A European cohort of 23 patients displaying typical Snijders Blok-Campeau syndrome traits and carrying pathogenic/likely pathogenic CHD3 variants was analysed using the Illumina EPIC array, identifying 270 differentially methylated positions distinguishing patients from 62 healthy matched controls. A subset of these regions serves as diagnostic tools for complex cases or variants of uncertain significance and helps uncover deregulated pathways linked to this syndrome. Four patients carrying pathogenic/likely pathogenic variants but with atypical clinical presentation, as well as 10 patients with variants of uncertain significance, were analysed as the testing set. RESULTS: Comparing methylomes of patients carrying pathogenic variants in CHD3, CHD7 (CHARGE syndrome, ORPHA:138), and CHD8 (Intellectual developmental disorder with autism and macrocephaly, ORPHA:642675) genes allows us to identify distinct subgroups with unique methylation profiles. This CHD3 DNA methylation signature aids in reclassifying variants and diagnosing atypical cases. CONCLUSIONS: Our findings advance the field of epigenetic signatures in rare diseases. We have opened new avenues for further investigation into subtypes defined by methylome assays (such as in the context of chromatinopathies), which could refine the phenotype spectrum and help predict patient outcomes.
Importance: Prone positioning has been shown to improve respiratory mechanics and oxygenation, but its clinical benefit in infants with acute viral bronchiolitis receiving high-flow nasal cannula (HFNC) support remains unknown. Objective: To investigate whether prone positioning in infants with moderate to severe acute bronchiolitis and HFNC support reduces escalation to noninvasive or invasive ventilation. Design, Setting, and Participants: Multicenter, randomized, open-label trial conducted in 15 pediatric intermediate or intensive care units in France. Infants aged 6 months or younger admitted for 24 hours or less with a diagnosis of acute bronchiolitis with moderate to severe respiratory distress requiring HFNC support were enrolled between January 2021 and November 2023 and followed up until hospital discharge (last patient discharged on December 11, 2023). Interventions: Participants were randomly assigned to the prone position (n = 221) or supine position (n = 230). Infants in the prone position group received prone positioning for 24 hours or longer during the first 48 hours. All participants received standardized HFNC support at 2 L/kg/min. Main Outcomes and Measures: The primary outcome was the need for escalation of care to noninvasive or invasive ventilation within the first 72 hours, according to prespecified criteria. Secondary outcomes included treatment failure, determined by an independent clinical adjudication committee; tolerance of prone positioning; length of hospital stay; duration of respiratory support; infant comfort; and adverse events. Results: Among 451 infants randomized, 446 were included in the primary analysis (median age, 41 [IQR, 19-72] days; 54% male). Escalation of care occurred in 80 infants (17.9%), with no significant difference between the prone position (33/220 [15.0%]) and supine position (47/226 [20.8%]) groups (adjusted odds ratio, 0.66 [95% CI, 0.40-1.07]; P = .09). Secondary outcomes did not differ significantly between the 2 groups. In the safety analysis, serious adverse events occurred in 2 of 180 infants (1.1%) in the prone position group and 2 of 264 (0.8%) in the supine position group. Conclusions and Relevance: Prone positioning in infants with moderate to severe bronchiolitis receiving HFNC support did not significantly reduce escalation of care. However, the wide 95% confidence interval around the observed odds ratio suggests that this study was not definitive and further research is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03976895.
Purpose To describe the epidemiology of pediatric community-onset severe bacterial infections (COSBIs) in France between 2015 and 2018 and evaluate changes over the 2010–2020 decade. Methods We conducted a prospective, observational study in 12 French pediatric intensive care units (PICUs) between 2015 and 2018, including children younger than 18 years admitted with a COSBI. Clinical characteristics, microbiological findings, and outcomes were reported. Age-standardized incidence, disability, and mortality rates were estimated in three administrative divisions of western France and compared with those from a 2009–2014 study. Results Among 493 children included, the median age (interquartile range [IQR]) was 2.1 (0.4–6.8) years, and 21% had underlying comorbidities. The most frequently identified pathogens were Neisseria meningitidis (19%) and Streptococcus pneumoniae (19%). Overall in-hospital mortality was 5.3% (95% CI, 3.6–7.8), and 15.8% (95% CI, 12.6–19.5) of survivors had moderate-to-severe disability at PICU discharge. The age-standardized incidence of COSBIs increased from 3.0 (95% CI, 2.7–3.2) to 4.8 (95% CI, 3.8–5.7) per 100,000 child-years between 2009–2014 and 2015–2018 (rate difference, 1.8; 95% CI, 0.8 to 2.8), corresponding to a 60% relative increase. Mortality remained unchanged, whereas the rate of moderate-to-severe disability increased by 270% (rate difference, 0.8; 95% CI 0.3 to 1.2). Conclusion The incidence of pediatric COSBIs increased in western France during the 2010–2020 decade, before the implementation of mandatory childhood vaccination. The marked increase in disability among survivors highlights the need for continued epidemiological surveillance and research into the long-term consequences of pediatric severe bacterial infections.
