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The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor–tezacaftor–deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor–tezacaftor–deutivacaftor compared with standard of care elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older.

In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor–tezacaftor–deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor–tezacaftor–deutivacaftor in children with cystic fibrosis aged 6–11 years.

Le nombre de grossesses chez les femmes atteintes de mucoviscidose a considérablement augmenté au cours de ces dernières années, avec pour corollaire une hausse du nombre de fœtus sains exposés à la trithérapie par élexacaftor-tézacaftor-ivacaftor. Pour l’instant, les éléments concernant le devenir immédiat de ces enfants sont rassurants, mais des anomalies des tests hépatiques et des cas de cataracte ont été rapportés chez quelques nouveau-nés exposés in uteroet allaités. Sur le plus long terme, l’aspect neurodéveloppemental doit également être surveillé. Des recommandations d’un groupe de travail de la Société française de la mucoviscidose sont en cours d’élaboration pour le suivi de ces enfants au cours des deux premières années et au-delà.

Endovascular treatment of abdominal aortic aneurysms (endovascular aneurysm repair [EVAR]) has been shown to be effective, with lower perioperative mortality and morbidity than open surgical treatment in patients with compatible anatomy. This benefit is lost after 3 years of follow-up. This could be explained by the higher rate of reintervention in EVAR patients due to endoleaks. Around half of patients with a persistent type 2 endoleak (T2EL) have an increase in aneurysm size. Either endovascular or conventional surgery techniques have been described to treat this type of endoleak. The aim of this study was to measure the long-term success rate of embolization of T2EL in a pragmatic retrospective series.

Late open conversion (LOC) following endovascular aneurysm repair (EVAR) is a rare complication with a high morbidity and mortality and is often proposed as the last line of treatment after failure of endovascular reintervention of any type. This study aimed to highlights the limitations of EVAR follow-up imaging in characterizing endoleaks, which may contribute to the failure of endovascular reinterventions and lead to LOC.

Elexacaftor–tezacaftor–ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTRvariant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor–tezacaftor–ivacaftor for people with cystic fibrosis without a F508del CFTRvariant in France and to determine CFTRvariant responsiveness to elexacaftor–tezacaftor–ivacaftor based on the observed clinical response.

L’histoire des soins palliatifs au Liban est marquée par la résilience et la persévérance. Portés par des initiatives personnelles, des combats législatifs et des donations privées, les soins palliatifs ont réussi à s’ancrer petit à petit dans le paysage médical, malgré les maigres moyens proposés par l’État. La délivrance des soins palliatifs au Liban a la particularité d’être soutenue principalement par des ONG à but non lucratif, dont le fonctionnement est à mi-chemin entre HAD et EMSP françaises et qui offrent des soins gratuits aux patients. Plus de 30 % des patients suivis par l’ONG BALSAM souffrent de maladies chroniques non cancéreuses. Les soins palliatifs pédiatriques sont quasi-inexistants, BALSAM étant la seule ONG assurant un accompagnement des enfants à leur domicile. Face aux difficultés financières majeures que connaît le pays, ces ONG se tournent aujourd’hui vers des partenariats internationaux, à la fois pour s’assurer les moyens de poursuivre leurs missions, et pour se réserver une place sur la scène mondiale. Le modèle libanais développé par BALSAM est présenté dans les pays en voie de développement comme un exemple possible de fonctionnement en contexte de crise. Une délégation du centre médicochirurgical de réadaptation des massues (CMCR) à Lyon est par ailleurs intervenue au centre hospitalier Rafik Hariri de Beyrouth pour échanger sur trois thématiques : management, rééducation et soins palliatifs. Les mêmes difficultés que nous rencontrons en France concernant la temporalité d’intervention dans une prise en charge ont pu être relevées : il est peu courant pour les confrères médecins libanais de solliciter les soins palliatifs précocement. La place des soins palliatifs au sein de l’institution hospitalière est encore nouvelle, et les moyens alloués trop faibles, autant en temps soignants qu’en locaux adaptés. La route reste longue, mais tout est mis en œuvre pour que les soins palliatifs continuent de faire parler d’eux et de s’étendre toujours plus profondément au sein du système sanitaire libanais.

IntroductionInterstitial lung disease in children (chILD) are rare and mostly severe lung diseases. Very few epidemiological data are available in limited series of patients. The aim of this study was to assess the prevalence and incidence of chILD in France.MethodsWe performed within the RespiRare network a multicentre retrospective observational study in patients with chILD from 2000 to 2022 and a prospective evaluation of chILD’s incidence between February 2022 and 2023.ResultschILD was reported in 790 patients in 42 centres. The estimated 2022 prevalence in France was 44 /million children (95% CI 40.76 to 47.46) and the computed incidence was 4.4 /million children (95% CI 3.44 to 5.56). The median age at diagnosis was 3 months with 16.9% of familial forms. Lung biopsy and genetic analyses were performed in 23.4% and 76.9%, respectively. The most frequent chILD aetiologies in the <2 years group were surfactant metabolism disorders (16.3%) and neuroendocrine cell hyperplasia of infancy (11.8%), and in the 2–18 years group diffuse alveolar haemorrhage (12.2%), connective tissue diseases (11.4%), hypersensitivity pneumonitis (8.8%) and sarcoidosis (8.8%). The management included mainly oxygen therapy (52%), corticosteroid pulses (56%), oral corticosteroids (44%), azithromycin (27.2%), enteral nutrition (26.9%), immunosuppressants (20.3%) and hydroxychloroquine (15.9%). The 5-year survival rate was 57.3% for the patients diagnosed before 2 years and 86% between 2 and 18 years.ConclusionThis large and systematic epidemiological study confirms a higher incidence and prevalence of chILD than previously described. In order to develop international studies, efforts are still needed to optimise the case collection and to harmonise diagnostic and management practices.

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8–15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < −1.645; n= 12), restrictive defects (TLC < 80% predicted, FEV1and FVC z-scores < −1.645; n= 7) and non-specific pattern (FEV1and FVC z-score< −1.645, FEV1/FVC z-score > −1.645, and TLC > 80% predicted; n= 8). HCT for malignant disease was the only factor associated with LONIPC (P= 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

For complex extensive TASC-II D lesions, the standard of care remains conventional surgery. Nevertheless, guidelines tend to broaden endovascular surgery indications in expert centers for patients at high surgical risk with TASC-II D lesions. Due to the increasing use of endovascular surgery in this setting, we planned to evaluate the patency rate of this approach.

Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftrgene in vivoin a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout the body. The ability of DAP to correct various endogenous UGA nonsense mutations in the CFTRgene and to restore its function in mice, in organoids derived from murine or patient cells, and in cells from patients with cystic fibrosis reveals the potential of such readthrough-stimulating molecules in developing a therapeutic approach. The fact that correction by DAP of certain nonsense mutations reaches a clinically relevant level, as judged from previous studies, makes the use of this compound all the more attractive.

L’apparition de troubles du sommeil (TS) chez l’adulte atteint de mucoviscidose (MV) sous ELEXACAFTOR-TEZACAFTOR-IVACAFTOR (ETI) a été rapportée. Aucune étude sur le chronotype n’a été réalisée sous ETI ni chez l’enfant ni chez l’adulte. L’objectif de l’étude était d’évaluer la nature du chronotype des enfants traités par ETI et leur qualité de sommeil.

L’apparition de troubles du sommeil (TS) chez l’adulte atteint de mucoviscidose (MV) sous elexacaftor-tezacaftor-ivacaftor (ETI) a été rapportée. Aucune étude sur le chronotype n’a été réalisée sous ETI ni chez l’enfant ni chez l’adulte. L’objectif de l’étude était d’évaluer la nature du chronotype des enfants traités par ETI et leur qualité de sommeil.

Cette étude présente les coûts des soins associés à la mucoviscidose (MV) chez les enfants diagnostiqués soit en anténatal (ANT), par dépistage néonatal (DNS), suite à un iléus méconial (IM), ou sur symptômes tardifs (ST).

Peu de données existent en vie réelle sur les effets de l’elexacaftor-tezacaftor-ivacaftor (ETI) sur l’inhomogénéité de ventilation et sur la fonction des petites voies aériennes. L’étude a pour objectif d’évaluer l’effet de l’ETI sur les petites voies aériennes, en utilisant différents paramètres fonctionnels respiratoires : rinçage en cycles respiratoires multiples (RCM), spirométrie et pléthysmographie.

In the Saline Hypertonic in Preschoolers (SHIP) study, inhaled 7% hypertonic saline improved the lung clearance index in children aged 3–6 years with cystic fibrosis, but it remained unclear whether improvement is also seen in structural lung disease. We aimed to assess the effect of inhaled hypertonic saline on chest CT imaging in children aged 3–6 years with cystic fibrosis.

« Kipal, le jeu du qui quoi comment en soins palliatifs » est un outil ludopédagogique élaboré par une infirmière et un médecin membres d’une équipe mobile de soins palliatifs au centre hospitalier de Vienne. Grâce à la création de cas patients fictifs et évolutifs au cours du jeu, les soignants participants peuvent appréhender des thèmes variés concernant les soins palliatifs de façon interactive. Les bénéfices attendus sont, une implication des apprenants devenant acteurs de leur formation, la dédramatisation du thème des soins palliatifs, la définition d’une démarche palliative et la découverte de la variété des prises en soin par la richesse des scénarios possibles. Pour cela, le jeu propose 16 situations cliniques brèves, issues de diverses spécialités, 46 cartes dites « évènement » (clinique, psychologique, social ou familial) et 62 cartes « suggestion » (ressources humaines et techniques disponibles) qui pourront être associées à l’infini à chaque partie. Cet outil est réservé aux professionnels des soins palliatifs lors de formations destinées à des soignants non spécialisés, mais exerçant auprès de personnes nécessitant des soins palliatifs. En perspective, des extensions pourront être développées pour s’adapter à un public plus large (pédiatrie, domicile). Soutenu par le Fonds pour les soins palliatifs et approuvé par la Société française d’accompagnement et de soins palliatifs (SFAP), 250 jeux Kipal ont été attribués lors du congrès francophone de soins palliatifs organisé par la SFAP et la Fédération francophone internationale de soins palliatifs en 2019.

Common femoral artery (CFA) stenting appears as a promising alternative treatment to the open surgery for de novo CFA stenosis. The stenting of lesions just located at the CFA is simple, whereas stenting of CFA bifurcation lesions is more complex, and outcomes are still matter of debate. The aim of this study was to describe and to compare clinical outcomes of techniques used to treat simple over complex lesions for the stenting of CFA lesions.

Le vieillissement de la population a entraîné une augmentation du nombre de patients de 80ans et plus admis en réanimation et aux soins continus. L’objectif de cette étude est d’analyser les caractéristiques de ces patients âgés, ainsi que leur devenir en termes de mortalité et d’autonomie à trois mois.

Évaluer les résultats en termes d’efficacité au cours du temps des ballons latéro-urétraux ACT® chez la femme dans le traitement de l’incontinence urinaire d’effort (IUE) par insuffisance sphinctérienne (IS).

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Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results.

Cardiovascular disease is the leading cause of morbidity and mortality in developed countries. Stroke is associated with a marked disability burden and has a major economic impact; this is especially true for carotid artery stroke. Major advances in primary and secondary prevention during the last few decades have helped to tackle this public health problem. However, better knowledge of the physiopathology of stroke and its underlying genetic mechanisms is needed to improve diagnosis and therapy. miRNAs are an important, recently identified class of post-transcriptional regulators of gene expression and are known to be involved in cerebrovascular disease. These endogenous, small, noncoding RNAs may have applications as noninvasive biomarkers and therapeutic tools in practice. Here, we review the involvement of several miRNAs in cell-based and whole-animal models of stroke, with a focus on human miRNA profiling studies of carotid artery stroke. Lastly, we describe the miRNAs’ potential role as a biomarker of stroke.

Lumacaftor and ivacaftor combination treatment showed efficacy in patients aged 12 years or older with cystic fibrosis homozygous for F508del-cystic fibrosis transmembrane conductance regulator (CFTR)in placebo-controlled studies and patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTRin an open-label study. We report efficacy and safety of lumacaftor and ivacaftor in patients with cystic fibrosis aged 6–11 years homozygous for F508del-CFTR.

•Dengue fever is an arbovirosis expanding worldwide and in Reunion Island, whose main treatment is oral hydration in primary care.•Oral hydration of Reunionese patients was higher than the recommendations of the World Health Organization.•Drinking at least 5 glasses of liquid in the previous 24 hours was significantly associated with fewer clinical warning signs (p = 0.044).•Adequate hydration could reduce the severity of dengue in primary care.

•Phase IV study on 2014/2015 Northern Hemisphere Vaxigrip.•Compared rates of solicited reactions in individuals ⩾6months with historical data.•No clinically significant increases in frequencies of solicited reactions.•No specific concerns identified for the 2014/2015 Northern Hemisphere formulation.•The 2014/2015 Northern Hemisphere formulation of Vaxigrip meets EU requirements.

We report three cases of pulmonary disease suggesting fibrosis in two familial and one sporadic case. Pulmonary symptoms were associated with various clinical features of systemic inflammation and vasculitis involving the skin, and appeared at different ages. A strong interferon signature was found in all three cases. Disease was not responsive to corticosteroids, and lung transplantation was considered for all three subjects at an early age. One of them underwent double-lung transplantation, but she immediately experienced a primary graft dysfunction and died soon after. Recognized causes of familial interstitial lung disease were all excluded. All three subjects had a mutation in the previously described autoinflammatory disease called SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy). These cases emphasize the need to consider this possibility in children and young adults with lung fibrosis after common causes have been ruled out.

Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZhomozygous status and is favored by smoking. Liver fibrosis is due to the ZZhomozygous status and is favored by obesity and excessive chronic alcohol intake, with a risk of liver cancer. Diagnosis is based on serum level and either isoelectric focusing determination of the biochemical phenotype or PCR detection of some variants. SERPINA1gene sequencing is necessary in case of discrepancies between the results of these tests. No treatment is available for the liver disease in AATD. Although no specific trial has been performed, COPD in AATD should be treated as per COPD recommendations. Based on a randomized clinical trial, augmentation therapy is indicated in non-smoking adults less than 70 years of age with emphysema at chest CT, confirmed homozygous AATD, and FEV1 between 35% and 70% of predicted. In contrast Z heterozygosis (MZ or SZ) brings a risk of lung or liver disease only in association with further risk factors. Early detection, in all patients with COPD and chronic liver disease, is critical for the correct information of Z variant carriers. News ways of correcting the liver production of alpha1-antitrypsin will modify the care of AATD patients.

La mélatonine est une hormone somnogène utilisée comme chronothérapie. Sa régulation par la lumière a été bien étudiée, cependant, l’interaction entre lumière et dette de sommeil sur la sécrétion de mélatonine et sur l’endormissement reste encore mal connue.

Les mutations du gène SFTPC sont responsables de pathologies interstitielles diffuses et représentent la plus fréquente des pathologies du surfactant chez l’enfant. Notre objectif était de décrire le mode de présentation et l’évolution de la pathologie en fonction du génotype dans une large cohorte de patients porteurs d’une mutation SFTPC.

Longtemps considérée comme cliniquement normale à la naissance, les données actuelles montrent que l’atteinte respiratoire fonctionnelle et structurale s’installe précocement chez les nourrissons atteints de mucoviscidose. Les modèles animaux développés dans les années 2000 ont montré l’étroitesse des voies aériennes dès la naissance, associée à des phénomènes inflammatoires et infectieux. Les données issues des cohortes de nourrissons dépistés pour la mucoviscidose montrent que 25 % d’entre eux, bien qu’asymptomatiques et suivis dans des centres spécialisés, ont des anomalies fonctionnelles respiratoires dès 3mois de vie. Sur le plan structural, des dilatations des bronches sont retrouvées au même âge chez 28 % des enfants, un trappage aérique chez 68 %. La présence d’élastase des polynucléaires neutrophiles à 3mois dans le lavage broncho-alvéolaire triple le risque de survenue de dilatations des bronches à 3ans. Les outils actuellement disponibles (exploration fonctionnelle du nourrisson par technique de la jaquette, mesure de l’inhomogénéité de ventilation par rinçage à l’azote, imagerie par scanner thoracique en volume contrôlé, imagerie par résonance magnétique fonctionnelle) devraient faciliter, dans un avenir proche, la mise en place d’essais cliniques interventionnels précoces. La place de ces outils en pratique clinique quotidienne et la capacité des interventions précoces à modifier l’histoire de la maladie restent à préciser.

The main aim of this study was to compare the 5 years rates of secondary patency of above-knee femoropopliteal revascularizations with autologous veins or prosthetic grafts. The secondary objectives were to compare the rates of primary patency, limb salvage, morbidity, and mortality between the 2 groups.

Malgré une incidence en lente décroissance, la morbi-mortalité de la tuberculose (TB) reste importante. L’émergence et la diffusion de souches multi-résistantes (MR) constituent actuellement un problème mondial majeur de santé publique. Les cas pédiatriques de TB-MR sont un évènement sentinelle indiquant une circulation de souches au sein d’une communauté. L’infection tuberculeuse latente (ITL) précède les cas de TB-MR. La détection et le suivi des sujets contacts sont des axes clés de la lutte anti-TB.

Cette étude monocentrique, prospective, a comme objectif d’explorer le bénéfice global de l’acupuncture chez des patients atteints de cancer.

ABSTRACTGlycopeptides are known to select for heterogeneous vancomycin-intermediate Staphylococcus aureus(h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant Staphylococcus aureus(MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days in vitro. Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of ≥90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance (vraSR, yvqF, SA1703, graRS, walKR, and rpoB) were PCR sequenced; no de novomutations were observed upon beta-lactam exposure. To determine whether trfA, a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a trfA-knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance in vitro. This induction required an intact trfAlocus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.

Closed dislocation of the knee with complete popliteal rupture is an uncommon injury. It requires prompt recognition and treatment to prevent limb loss. We describe a case of acute ischemia caused by complete knee dislocation with rupture of the popliteal artery that was successfully repaired with superficial femoral artery transposition. To the best of our knowledge, this is the first reported clinical experience of the use of an arterial autograft for revascularization of traumatic popliteal artery rupture.

The purpose of this study was to evaluate short-term results of endovascular treatment of common iliac artery (CIA) aneurysms without a distal neck by using iliac branch devices (IBDs), which enable maintenance of antegrade perfusion to the internal iliac artery (IIA).

An improved animal model of obstructive sleep apnea (OSA) is needed for the development of effective pharmacotherapies. In humans, flexion of the neck and a supine position, two main pathogenic factors during human sleep, are associated with substantially greater OSA severity. We postulated that these two factors might generate OSA in animals.

The morphology of the digestive system in fasting and refed Burmese pythons was determined, as well as the localization of the proton (H+, K+-ATPase) and sodium (Na+, K+-ATPase) pumps. In fasting pythons, oxyntopeptic cells located within the fundic glands are typically non-active, with a thick apical tubulovesicular system and numerous zymogen granules. They become active immediately after feeding but return to a non-active state 3 days after the ingestion of the prey. The proton pump, expressed throughout the different fasting/feeding states, is either sequestered in the tubulovesicular system in non-active cells or located along the apical digitations extending within the crypt lumen in active cells. The sodium pump is rapidly upregulated in fed animals and is classically located along the baso-lateral membranes of the gastric oxyntopeptic cells. In the intestine, it is only expressed along the lateral membranes of the enterocytes, i.e., above the lateral spaces and not along the basal side of the cells. Thus, solute transport within the intestinal lining is mainly achieved through the apical part of the cells and across the lateral spaces while absorbed fat massively crosses the entire height of the cells and flows into the intercellular spaces. Therefore, in the Burmese python, the gastrointestinal cellular system quickly upregulates after feeding, due to inexpensive cellular changes, passive mechanisms, and the progressive activation and synthesis of key enzymes such as the sodium pump. This cell plasticity also allows anticipation of the next fasting and feeding periods. [ABSTRACT FROM AUTHOR]