Evolution of Extracranial Internal Carotid Artery Disease in Children With Sickle Cell Anemia.

BACKGROUND: Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. METHODS: Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. RESULTS: Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1-9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT (P=0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and -0.18 (0.55) with CTT (P=0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. CONCLUSIONS: Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.

Anti-MDA5 juvenile idiopathic inflammatory myopathy: a specific subgroup defined by differentially enhanced interferon-α signalling.

OBJECTIVES: JDM and juvenile overlap myositis represent heterogeneous subtypes of juvenile idiopathic inflammatory myopathy (JIIM). Chronic evolution can occur in up to 60% of cases, and morbidity/mortality is substantial. We aimed to describe the clinical, biological, histological and type I IFN status in JIIM associated with anti-melanoma differentiation-associated protein 5 (anti-MDA5) autoantibodies at presentation (group 1) in comparison with other JIIM (group 2). METHODS: This was a retrospective and prospective study of patients with JIIM ascertained from three French paediatric rheumatology reference centres between 2013 and 2019. Muscle biopsies were reviewed. Type I interferon pathway activity was assessed by dosage of IFNα serum protein and the expression of IFN-stimulated genes. RESULTS: Sixty-four patients were included, 13 in group 1 (54% JDM and 46% juvenile overlap myositis) and 51 in group 2 (76% JDM and 24% juvenile overlap myositis). Group 1 patients demonstrated more arthritis, skin ulcerations, lupus features and interstitial lung disease, and a milder muscular involvement. Serum IFNα levels were higher in group 1 than 2, and decreased after treatment or improvement in both groups. Outcome was similar in both groups. Unconventional treatment (more than two lines) was required in order to achieve remission, especially when skin ulceration was reported. CONCLUSION: This study indicates a higher frequency of arthritis, skin ulcerations and interstitial lung disease, but milder muscular involvement, in JIIM with positive anti-MDA5 autoantibodies compared with other JIIM. Our data support an important role of systemic IFNα in disease pathology, particularly in the anti-MDA5 auto-antibody-positive subgroup. In severe and refractory forms of JIIM, IFNα may represent a therapeutic target.

Routine multi detector computed tomography evaluation of tracheal impairment compared to laryngo-tracheal endoscopy in children with vascular ring.

PURPOSE: The aim of this study is to compare free-breathing routine multi detector computed tomography (MDCT) and laryngo-tracheal (LT) flexible endoscopy in the evaluation of tracheal impairment in children with vascular ring (VR). MATERIALS AND METHODS: We performed a retrospective and monocentric study of all patients with VR from 1997 to 2014. Clinical data included: initial symptoms, type of surgery and clinical outcome. MDCT were blindly reviewed by two radiologists in consensus, independently of LT endoscopy results. Radiologic and endoscopic results were reviewed according to four criteria: percentage of tracheal narrowing, distance of the compression from carina, presence of bronchial compression and signs of tracheomalacia (TM). Concordance was evaluated for each criterion with a Spearman coefficient. RESULTS: From 1997 to 2016, 21 patients with a vascular ring were operated on, among which 57% by thoracoscopy: double aortic arch (n = 14), Neuhauser anomaly (n = 4) and Right aorta + aberrant right subclavian artery (n = 3). 90% of them presented with respiratory symptoms among which 43% of stridor. Chest X-ray was suggestive of VR in 87% of the cases. MDCT images and LT endoscopy results were available and analyzed for nine patients. Concordance (Spearman correlation coefficient) was excellent for percentage and level of tracheal narrowing (1) and good for TM (0.79). CONCLUSION: Free breathing routine MDCT is a reliable exam compared to LT endoscopy in the evaluation of tracheal impairment in children with VR. In case of respiratory symptoms (except stridor) and suggestive chest X-ray of VR, endoscopy could be avoided and routine MDCT alone performed.

Extracranial carotid arteriopathy in stroke-free children with sickle cell anemia: detection by submandibular Doppler sonography.

BACKGROUND: Cerebral vasculopathy is a serious complication of sickle cell anemia. Overt strokes are largely due to intracranial arteriopathy, detected by routine transcranial Doppler and largely prevented through chronic transfusions. As extracranial internal carotid artery arteriopathy was considered rare, it has not been routinely assessed in sickle cell anemia. Recent cases of overt strokes associated with stenosis/occlusion of the extracranial portion of the internal carotid artery prompted us to include extracranial internal carotid artery assessment to our transcranial Doppler sonography protocol. OBJECTIVE: The aim of the study was to perform a cross-sectional study in children with sickle cell anemia to evaluate Doppler flow patterns of the extracranial internal carotid arteries and to assess potential associated factors. MATERIALS AND METHODS: Between June 2011 and April 2012, 435 consecutive stroke-free children with sickle cell anemia (200/235 M/F, median age: 7.9 years) were assessed for extracranial internal carotid artery using a 2-MHz transcranial Doppler sonography probe via a submandibular window during routine transcranial Doppler sonography visits. The course of both extracranial internal carotid artery was assessed by color Doppler mapping, and the highest flow velocity was recorded after insonation of the entire length of the artery and analyzed. Intra- and extracranial MR angiographies were available in 104/435 subjects for comparison. RESULTS: Mean (SD) extracranial internal carotid artery time-averaged mean of maximum velocity was 96 (40) cm/s. Extracranial internal carotid artery tortuosities were echo-detected in 25% cases and were more frequent in boys (33% vs.18%; P < 0.001). Velocity ≥160 cm/s in at least one extracranial internal carotid artery was found in 45 out of 435 patients with sickle cell anemia (10.3%) and was highly predictive of MR angiography stenosis. Simultaneous abnormal intracranial velocity (≥200 cm/s) was recorded in 5/45 patients, while 40 patients had isolated extracranial internal carotid artery velocity ≥160 cm/s. Low hemoglobin (odds ratio: 1.9/g/dL, 95% confidence interval (CI): 1.3-2.9; P = 0.001) and tortuosities (odds ratio: 19.2, 95% CI: 7.1-52.6; P < 0.001) were significant and independent associated factors for isolated extracranial internal carotid artery velocities ≥160 cm/s. CONCLUSION: Adding extracranial internal carotid artery evaluation via the submandibular window to transcranial Doppler sonograpy allowed us to detect 10.3% patients at risk for extracranial internal carotid arteriopathy. Further studies are needed to evaluate the prognosis of these anomalies.

Whole pulmonary assessment 1 year after paediatric acute respiratory distress syndrome: prospective multicentre study.

BACKGROUND: Long-term pulmonary sequelae, including 1-year thoracic computed tomography (CT) sequelae of paediatric acute respiratory distress syndrome (ARDS) remain unknown. The purpose of the study was to determine pulmonary abnormalities in child survivors of pulmonary (p-ARDS) and extra-pulmonary ARDS (ep-ARDS) 1 year after paediatric intensive care unit discharge (PICUD). METHODS: Prospective multicentre study in four paediatric academic centres between 2005 and 2014. Patients with ARDS were assessed 1 year after PICUD with respiratory symptom questionnaire, thoracic CT and pulmonary function tests (PFT). RESULTS: 39 patients (31 p-ARDS) aged 1.1-16.2 years were assessed. Respiratory symptoms at rest or exercise and/or respiratory maintenance treatment were reported in 23 (74%) of children with p-ARDS but in 1 (13%) of those with ep-ARDS. Thoracic CT abnormalities were observed in 18 (60%) of children with p-ARDS and 4 (50%) of those with ep-ARDS. Diffuse and more important CT abnormalities, such as ground glass opacities or mosaic perfusion patterns, were observed in 5 (13%) of children, all with p-ARDS. PFT abnormalities were observed in 30 (86%) of patients: lung hyperinflation and/or obstructive pattern in 12 (34%) children, restrictive abnormalities in 6 (50%), mild decrease in diffusing capacity in 2 (38%) and 6-min walking distance decrease in 11 (73%). Important PFT abnormalities were observed in 7 (20%) children, all with p-ARDS. Increasing driving pressure (max plateau pressure-max positive end-expiratory pressure) was correlated with increasing CT-scan abnormalities and increasing functional residual capacity (more hyperinflation) (p < 0.005). CONCLUSIONS: Children surviving ARDS requiring mechanical ventilation present frequent respiratory symptoms, significant CT-scan and PFT abnormalities 1 year after PICUD. This highlights the need for a systematic pulmonary assessment of these children. Trial registration The study was registered on Clinical Trials.gov PRS (ID NCT01435889).

Pneumonia with pleural empyema caused by Salmonella Typhi in an immunocompetent child living in a non-endemic country.

Extra-intestinal complications of Salmonella Typhi (S. Typhi) infections usually occur in endemic countries and in patients with underlying risk conditions. A 14-year-old immunocompetent girl was admitted with respiratory distress owing to S. Typhi pneumonia and pleural empyema. She was a native of Ivory Coast but had lived in France for 4 years and had not travelled abroad for several years. There were no gastro-intestinal symptoms and no S. Typhi carriage was detected in her family. She recovered completely with ceftriaxone and ciprofloxacin and pleural drainage was not required. An atypical presentation of S. Typhi should be considered even in settings where there are no risk factors.

Central venous thrombosis and thrombophilia in cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thrombophilic tendency was described in cystic fibrosis (CF), the significance of which remains unclear. The aims of this study were to (1) document the frequency of catheter venous thrombosis detected by colour-Doppler-ultrasound (Doppler-US), (2) assess genetic and acquired thrombophilia risk factors for catheter venous thrombosis and hypercoagulability status and (3) provide recommendations on laboratory screening when considering insertion of a totally implantable vascular access device (TIVAD) in CF patients. METHODS: We designed a multicentre prospective study in patients selected at the time of catheter insertion. Doppler-US was scheduled at 1 and 6months after insertion and before insertion in case of a previous central line. Blood samplings were drawn at insertion and at 1 and 6months later. RESULTS: One-hundred patients received a TIVAD and 90 completed the 6-month study. Prevalence of thrombophilia abnormalities and hypercoagulability was found in 50% of the cohorts. Conversely, catheter venous thrombosis frequency was low (6.6%). CONCLUSION: Our data do not support biological screening at the time of a TIVAD insertion. We emphasise the contribution of a medical history of venous thromboembolism and prospective Doppler-US for identifying asymptomatic catheter venous thrombosis to select patients who may benefit from biological screening and possible anticoagulant therapy.

Is radical lobectomy required in congenital cystic adenomatoid malformation?

BACKGROUND: The extent of surgical resection in the management of congenital cystic adenomatoid malformation (CCAM) located in 1 pulmonary lobe remains controversial. Although lobectomy seems to be the best treatment to avoid recurrent pulmonary infection and neoplasia, neither retrospective nor prospective studies have been done to our knowledge. Besides, many reports claim that there are advantages of parenchyma-saving resections. The aim of our study was to determine whether it was necessary to perform an extended resection in these cases. MATERIALS AND METHODS: We retrospectively reviewed all patients who had undergone a thoracoscopic lobectomy for CCAM located to 1 pulmonary lobe between January 2007 and January 2009. A thoracic radiologist performed a single blind review of all preoperative computed tomographic (CT) scans, mentioning the presence or absence of distant lesions from the main cysts of CCAM within the pulmonary lobe. The pathologist who analyzed the pulmonary lobectomy specimen was aware of the diagnosis but not the CT report. RESULTS: Twenty-five patients underwent thoracoscopic lobectomy for congenital lung malformations, including 12 with CCAM. All had a positive prenatal sonogram. The median age at surgery was 12 months (range, 2-24 months). The preoperative CT showed only 2 cases with distant lesions within the affected pulmonary lobe, whereas the histologic study of the surgical specimen identified 6 cases. The sensitivity of the CT scan was low, 33%, whereas its specificity was high, 100%. Furthermore, the preoperative CT negative predictive value was 60%. The median time of follow-up was 7.5 months. CONCLUSION: Adequate treatment of CCAM in children requires a lobectomy because of poor sensitivity and very poor negative predictive value (60%) of the preoperative CT to determine distal adjacent lesions. A prospective study on a larger number of patients is required to confirm these observations.

Inter-observer variability in chest radiograph reading for diagnosing acute lung injury in children.

Acute lung injury (ALI), including its most serious form called acute respiratory distress syndrome (ARDS), is a devastating disease that can occur at any age. ALI/ARDS accounts for only 5-8% of admissions to pediatric intensive care units (PICUs) but is fatal in 30-60% of cases. International multicenter prospective studies are needed to better understand pediatric ALI/ARDS. However, a reproducible definition of ALI/ARDS is crucial to ensure that study populations are homogeneous. We designed a retrospective review to test the inter-observer variability of chest radiograph interpretation for presence of the American-European Consensus Conference (AECC) radiographic criterion for ALI/ARDS. The medical files of 24 children ventilated for ALI/ARDS in our PICU between January 1993 and December 2002 were reviewed. Five pediatric radiologists and five pediatric intensivists interpreted one frontal chest radiograph (FCR) per patient taken on the day of ALI/ARDS diagnosis. Each reader indicated whether the radiograph showed the AECC radiographic criterion for ALI/ARDS. Data analysis involved comparing each reader to all the others based on the raw agreement and Kappa coefficient (kappa). Features in the 24 patients were consistent with earlier studies. Global inter-observer agreement beyond chance was fair (kappa = 0.29 +/- 0.02) among the five radiologists (kappa = 0.26 +/- 0.05) and among the five intensivists (kappa = 0.29 +/- 0.05). Thus, considerable inter-observer variability occurred in assessing the radiographic criterion for ALI/ARDS, as previously shown in adults. Given the low incidence of ALI/ARDS in children, this variability may have a large impact in studies of pediatric ALI/ARDS.

Ultrasonography of Crohn disease in children.

US is increasingly performed in Crohn disease (CD) in children as a first line imaging modality. It reduces the use of other more invasive examinations such as endoscopy, CT or contrast enema. We describe bowel ultrasonography technique, normal bowel appearances on US and pathological patterns in CD. We discuss the current role and limitations of bowel US in CD in children including diagnosis, extent of disease, assessment of disease activity, follow-up and detection of complications. The diagnostic accuracy of US is discussed according to the literature and compared to other imaging modalities. US is currently used for screening in children with the suspicion of inflammatory bowel disease (IBD) with a good negative predictive value. In follow-up, US has a role in monitoring medical treatment by evaluating disease activity, extent of disease and for detecting complications.