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Summary: Background: Infants with Down syndrome (DS) are at high risk of obstructive sleep apnoea (OSA) which is associated with neurocognitive dysfunction and behaviour problems. The aim of our study was to evaluate the effect of early OSA treatment in infants with DS on neurocognitive development and behaviour. Methods: In this prospective, interventional, non-randomised study, 40 infants with DS underwent polysomnography (PSG) every 6 months in room air between 6 and 36 months of age (Screened Group) and were compared to a control group of 40 infants with DS receiving standard of care and a single, systematic PSG in room air at 36 months of age (Standard Care Group). When present, OSA was treated. The primary endpoint was the total score of the Griffiths Scales of Child Development, Third Edition (Griffiths III) and its subscores at 36 months. Secondary endpoints included a battery of neurocognitive and behaviour questionnaires, and PSG outcomes. Findings: On the Griffiths III, the total score was significantly higher in the Screened Group compared to the Standard Care Group (difference: 4.1; 95%CI: 1.3; 7.6; p = 0.009). Results in Griffiths III subscores and secondary endpoints were in support of better neurocognitive outcomes in the Screened Group compared with the Standard Care Group. At 36 months, median (Q1; Q3) apnoea-hypopnea index was higher in the Standard Care Group (4.0 [1.5; 9.0] events/hour) compared to the Screened Group (1.0 [1.0; 3.0] events/hour, p = 0.006). Moderate and severe OSA were more frequent in the Standard Care Group as compared to the Screened Group (18.9% versus 3.7% for moderate OSA and 27.0% versus 7.4% for severe OSA). Interpretation: Early diagnosis and treatment of OSA in infants with DS may contribute to a significantly better neurocognitive outcome and behaviour at the age of 36 months. Funding: The study was funded by the Jérôme Lejeune Foundation.

Objective: To study the efficiency of lingual tonsillectomy (LT) as part of multilevel surgery in children with complex obstructive sleep apnea (OSA). To evaluate the safety and the outcomes of LT. Study Design: Retrospective case series. Setting: Pediatric tertiary care academic center. Methods: We included all children operated for LT to treat complex OSA, from January 2018 to June 2022. All patients underwent a protocolized drug‐induced sleep endoscopy (DISE) followed by a coblation LT, associated with the treatment of all other obstructive sites. Patient demographics, medical history, surgery, and outcomes were reviewed. The efficiency of LT was analyzed exclusively in patients with a preoperative and postoperative sleep study. Results: One hundred twenty‐three patients were included. Median age was 8 years (interquartile range, IQR [3‐12]). Sixty‐five (53%) patients had Down syndrome, 22 (18%) had a craniofacial malformation, and 8 (7%) were obese. LT was associated with adenoidectomy (n = 78, 63%), partial tonsillectomy (n = 70, 57%), inferior turbinoplasty/turbinectomy (n = 59, 48%), epiglottoplasty (n = 92, 75%), and/or expansion pharyngoplasty (n = 2, 2%). Eighty‐nine patients underwent a sleep study before and after surgery. The median apnea‐hypopnea index (AHI) decreased from 18 events/h (IQR [9‐36]) before surgery to 3 events/h (IQR [1‐5]) after surgery (P <.001) (patients with a postoperative AHI <1.5 events/h, n = 31, 35%, and an AHI <5 events/h, n = 32, 36%). Seventeen out of 30 (57%) patients could be weaned from continuous positive airway pressure after surgery. Two patients had a postoperative hemorrhage and 2 patients required a transient postoperative reintubation. Conclusion: In children with complex OSA, LT as part of a DISE‐directed multilevel upper airway surgery, was a very efficient and safe procedure. [ABSTRACT FROM AUTHOR]

BackgroundThe definition of a great surgeon is usually reported by surgeons themselves. The objective of the study was to define a multifaceted definition of a great surgeon, by confronting patients', healthcare workers', and surgeons' perspectives.Study designAn online open-ended questionnaire was created to identify three qualities and three shortcomings defining a great surgeon. Age, gender, and profession of respondents were collected. Responses with a similar meaning were combined into word groups and labeled within four themes: human qualities, technical surgical skills (TSS), non-technical skills (NTS), and knowledge. Multivariate analyses were conducted between themes and respondent characteristics.ResultsFour thousand seven hundred and sixty qualities and 4,374 shortcomings were obtained from 1,620 respondents including 385 surgeons, 291 patients, 565 operating theater (OT) health professionals, and 379 non-OT health professionals. The main three qualities were dexterity (54% of respondents), meticulousness (18%), and empathy (18%). There was no significant difference between professional categories for TSS. Compared with surgeons, non-OT health professionals and patients put more emphasis on human qualities (29 vs. 39% and 42%, respectively, p < .001). OT health professionals referred more to NTS than surgeons (35 vs. 22%, p < 0.001). Knowledge was more important for surgeons (19%) than for all other professional categories (p < 0.001).ConclusionsThis survey illustrates the multifaceted definition of a great surgeon. Even if dexterity is a major quality, human qualities are of paramount importance. Knowledge seems to be underestimated by non-surgeons, although it essential to understand the disease and preparing the patient and OT team for the procedure.

A supernumerary marker chromosome (SMC) is a structurally abnormal chromosome that cannot be characterized by conventional banding cytogenetics. Marker chromosomes are present in 0.075% of prenatal cases. They are associated with variable phenotypes, ranging from normal to severely abnormal, and the prognosis is largely dependent on the results of further cytogenomic analysis. Here, we report the identification and characterization of a marker chromosome following prenatal screening in a 39-year-old pregnant patient. The patient had a normal first trimester ultrasound but was high-risk for fetal chromosome anomalies based on the results of maternal serum parameters. Chorionic villus sampling was performed, and analysis of chorionic villi revealed the presence of two identical marker chromosomes. In the interest of a rapid identification of the markers, we performed noninvasive prenatal testing (NIPT) together with chorionic villus sampling. A pericentromeric 29 Mb duplication of chromosome 20: dup (20) (p13q11.21) was identified and thereafter confirmed by targeted metaphasic FISH. Whole-genome sequencing-based NIPT was instrumental in rapid characterization of the SMCs and allowed us to obviate the need for multiple expensive and time-consuming FISH analyses.

IntroductionThe head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities.MethodsThe study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed.ResultsForty-eight patients (median age 6 years; range 4 months−21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor locations included the following: orbit (n = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity (n = 16), deep facial spaces (n = 10), nasolabial fold (n = 8), and other non-parameningeal HN sites (n = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.With a median follow-up of 7 years (range 2–13 years), 5-year OS and EFS were 78% (95% CI, 63–88%) and 66% (95% CI, 51–78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age (p = 0.002), while FOXO1-negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS.ConclusionOur study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings.

Abstract Background Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95–0.99]), high education (OR = 1.64 [1.23–2.17]), male sex (OR = 1.56 [1.19–2.04]), and positive family history of dementia (OR = 1.66 [1.19–2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02–1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81–4.94]). These results were similar across prescreen settings. Conclusions Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.

Abstract The tumor suppressor gene neurofibromin 1 (NF1) is a major regulator of the RAS‐MAPK pathway. NF1 mutations occur in lung cancer but were not extensively explored. We hypothesized that NF1‐mutated tumors could define a specific population with a distinct clinical and molecular profile. We performed NF1 sequencing using next generation sequencing (NGS) in 154 lung adenocarcinoma surgical specimens with known KRAS, EGFR, TP53, BRAF, HER2, and PIK3CA status, to evaluate the molecular and clinical specificities of NF1‐mutated lung cancers. Clinical data were retrospectively collected, and their associations with molecular profiles assessed. In this series, 24 tumors were NF1 mutated (17.5%) and 11 were NF1 deleted (8%). There was no mutation hotspot. NF1 mutations were rarely associated with other RAS‐MAPK pathway mutations. Most of patients with NF1 alterations were males (74.3%) and smokers (74.3%). Overall survival and disease‐free survival were statistically better in patients with NF1 alterations (N = 34) than in patients with KRAS mutations (N = 30) in univariate analysis. Our results confirm that NF1 is frequently mutated and represents a distinct molecular and clinical subtype of lung adenocarcinoma.

Neurologic manifestations associated with Covid-19 are increasingly reported, especially stroke and acute cerebrovascular events. Beyond cardiovascular risk factors associated with age, some young adults without medical or cardiovascular history had stroke as a presenting feature of Covid-19. Suggested stroke mechanisms in this setting are inflammatory storm, subsequent hypercoagulability, and vasculitis. To date, a handful of pediatric stroke cases associated with Covid-19 have been reported, either with a cardioembolic mechanism or a focal cerebral arteriopathy. We report the case of an adolescent who presented with febrile meningism and stupor. Clinical, biological, and radiological features favored the diagnosis of Lemierre syndrome (LS), with Fusobacterium necrophorum infection (sphenoid sinusitis and meningitis) and intracranial vasculitis. The patient had concurrent SARS-CoV-2 infection. Despite medical and surgical antimicrobial treatment, stroke prevention, and venous thrombosis prevention, he presented with severe cerebrovascular complications. Venous thrombosis and stroke were observed, with an extension of intracranial vasculitis, and lead to death. As both F. necrophorum and SARS-CoV-2 enhance inflammation, coagulation, and activate endothelial cells, we discuss how this coinfection may have potentiated and aggravated the usual course of LS. The potentiation by SARS-CoV-2 of vascular and thrombotic effects of a bacterial infection may represent an underreported cerebrovascular injury mechanism in Covid-19 patients. These findings emphasize the variety of mechanisms underlying stroke in this disease. Moreover, in the setting of SARS-CoV-2 pandemic, we discuss in what extent sanitary measures, namely, lockdown and fear to attend medical facilities, may have delayed diagnosis and influenced outcomes. This case also emphasizes the role of clinical assessment and the limits of telemedicine for acute neurological condition diagnosis.