ABSTRACT
Objective:To investigate the prevalence, distribution, and prognosis of knee joint bone marrow edema (BME) in children with juvenile idiopathic arthritis (JIA).Methods:From January 2017 to December 2019, 128 JIA children in the Children′s Hospital, Capital Institute of Pediatrics were analyzed retrospectively, and 136 knees were included totally. BME was evaluated and counted from eight regions according to the juvenile arthritis MRI scoring system (JAMRIS). Chi-square test, independent sample t test or Mann-Whitney U test were used to compare the clinical characteristics between BME group (36 cases) and non-BME group (92 cases). The prognosis of BME were observed. Results:BME was found in 37 of 136 knee joints (27.2%). The ages of the children in BME group and non-BME were (8±4) and (6±4) years old, and the disease duration were 9 (3, 22) and 4 (2, 18) months, respectively, both with statistically significant differences (age: t=-2.63, P=0.010; duration: Z=-5.78, P=0.013). In 23 joints (62.2%,23/37), BME occurred at multiple locations simultaneously in the knee. Locations with BME, according to the frequency of involvement from most to least, were the lateral tibial plateau with 17, the lateral weight-bearing femur with 16, the medial tibial plateau and the medial femoral condyle both with 15, the medial weight-bearing femur with 12, the lateral femoral condyle with 8, the lateral patella with 7, and the medial patella with 5. The MRI score of most of medial femoral conclyle was 1(7/15). Of the 15 BME joints with the MRI follow-up data with interval (7±3) months, BME disappeared in 10 joints, improved in 3 joints and progressed in 2 joints within 12 months after the treatments. Conclusions:There is a low incidence of BME in JIA affected knee joint. Older children and the children with long disease duration have a higher risk for BME, and more likely involved the weight-bearing surfaces of the joint. The overall prognosis is satisfactory after the standard treatments.
ABSTRACT
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic [~]0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
ABSTRACT
BackgroundRespiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients. MethodsWe included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a meta-analysis of both case-control panels. ResultsWe detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5x10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14x10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95x10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48x10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06x10-5). ConclusionsWe herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid-19 pathophysiology.
ABSTRACT
Objective: To observe intracranial imaging manifestations of PHACES syndrome. Methods: Imaging data of 9 children with PHACES syndrome who met the diagnostic criteria were retrospectively analyzed, including craniocerebral MRI of 4 cases, enhanced CT of 3 cases as well as enhanced CT and MRI of 2 cases, and whether there were abnormal intracranial vessels, brain structures and other accompanying abnormalities were observed. Results: Six cases were found with intracranial vascular abnormalities, including 2 cases of unilateral internal carotid artery dysplasia, 1 case of unilateral internal carotid artery dysplasia with ipsilateral middle cerebral artery stenosis, 1 case of unilateral internal carotid artery absence with cystic aneurysm in the origin of posterior cerebral artery, 1 case of proatlantal intersegmental artery and 1 case of primitive ophthalmic artery. Abnormal brain structures in the posterior cranial fossa were detected in 8 cases, including 6 cases of unilateral cerebellar dysplasia and 2 cases of Dandy-Walker malformation, while intracranial hemangioma located in the cerebellopontine angle but not associated with subcutaneous hemangioma were noticed in 6 cases. There were 6 cases of intraorbital hemangioma, 5 of which were accompanied by ipsilateral intracranial hemangioma but not connected. Supratentorial hydrocephalus was found in 3 cases. Conclusion: Unilateral cerebellar dysplasia and abnormal internal carotid artery are the most common intracranial manifestations of PHACES syndrome. Intracranial hemangioma is not uncommon among children with PHACES syndrome.
ABSTRACT
Objective: To examine the efficacy and safety of pemetrexed plus apatinib for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in elderly patients. Methods: Between January 2016 and June 2017, 38 elderly patients with ad-vanced non-squamous NSCLC from Qingdao Municipal Hospital were examined. All patients received first-or second-line therapy. The inclusion criteria were an age of≥65 years, physical status score of 0-2, and expected survival time of>3 months. Eighteen patients were assigned to the test group, and the remaining 20 patients were assigned to the control group. The patients in the test group were treated with pemetrexed plus apatinib, pemetrexed 500 mg/m2 on day 1 and apatinib 250 mg/d on days 1-21. The control group re-ceived pemetrexed in a 21-day cycle until the disease progressed or intolerable adverse reactions developed. The study was reviewed and approved by the medical ethics committee of Qingdao Municipal Hospital. Results: The disease control rates in the test and con-trol groups were 72.2% and 35%, respectively, with a statistically significant difference (χ2=5.265, P=0.022). The median progression-free survival time (PFS) in the test and control groups were 5.7 months [95% confidence interval (CI): 2.8-8.6] and 3.1 months (95% CI:2.7-3.5), with a statistically significant difference (χ2=4.01, P=0.045). The difference in the incidence of hand-foot syndrome and hyper-tension between the two groups was statistically significant (P=0.007 and P=0.016, respectively), with side effects of 1 or 2 degree in most cases, which was acceptable. Conclusions: Pemetrexed plus apatinib has a definite curative effect on advanced NSCLC, with con-trollable adverse reactions.
ABSTRACT
Objective To analyze the clinical characteristics and genetic variation of megalencephalic leu-koencephalopathy with subcortical cysts(MCL),then to explore the genetic characteristics so as to help families by pro-viding genetic counseling. Methods The clinical data of the children and their family members were collected,and the peripheral blood DNA of the children and family members were extracted. Then,the MLC1 gene mutation in the children was detected by using the target sequence capture high-throughput sequencing technology and Sanger sequencing tech-nology. Results (1)MCL often presented abnormal head circumference in infants as the first symptom. The main clini-cal manifestations were hypoevolutism in motor development,retrogression of early school age,then the movement disor-der progressed and finally paralyzed;epilepsy was common in early childhood;head magnetic resonance imaging showed white matter in bilateral cerebral hemisphere diffusing abnormal signal with temporal lobe cystic change in the early stage,and then showed brain atrophy. (2)The gene results showed that the 2 girls with MLC had both c. 368C >T (p. Thr123Ile)and c. 353C > T (p. Thr118Met)complex heterozygous variation,which existed in the MLC1 gene. The girls′ father and a sister carried c. 368C > T (p. Thr123Ile),while the mother carried c. 353C > T (p. Thr118Met) heterozygous variation,all of whom were normal phenotypes. Conclusions MCL is one cause of hypoevolutism in motor development in children and abnormal head circumference of infants is usually the first symptom. The MLC1 gene c. 368C> T(p. Thr123Ile)is a pathogenic mutation for MLC,and may be another new pa-thogenic mutation.
ABSTRACT
Objective To detect the differences of grey matter volume between the patients with mental retardation (MR) presented clinically as operation deficit (OD) or as language deficit (LD) and the children with typical normal development using optimal VBM.The developmental connections between brain gray matter and language or operation skills were examined.Methods Magnetic resonance imaging was obtained from 9 children with mental retardation presented as OD predominantly and 11 children with mental retardation presented as LD mainly,as well as the age-matched control group (11 and 14 normal children,respectively) on a 1.5 T scanner.Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the volume of grey matter between the two groups (OD VS.control; LD VS.control).Statistically,the total and local gray matter volumes were compared between the two groups with t test.Results The total gray matter volume of OD group was [(1.030 ± 0.078) × 106 mm3].Compared to that of controls [(0.984 ± 0.058) × 106 mm3],it was increased significantly (t =-2.6,P ＜ 0.05).And the gray matter volume in the posterior cingulated gyrus,left superior prefrontal gyrus,left cuneus,left middle prefrontal gyrus and the body of left caudate nucleus showed significantly increased.Meanwhile,the total gray matter volume of the MR children presented as LD [(1.002 ± 0.068) × 106 mm3] showed significantly increased(t =-3.0,P ＜ 0.05) compared with that of control group [(0.957 ±0.057) × 106 mm3].The gray matter volume in bilateral thalami,the left inferior temporal gyrus,the left inferior frontal gyrus,and the left cerebellum of the LD group was more than that of normal children.Conclusion As revealed by VBM,there are differences in alterations of gray matter volume between MR children presented with OD and with LD relative to control.
ABSTRACT
Objective To detect brain structural difference between children with unexplained mental retardation and children with typically normal development. Methods The high-resolution magnetic MR imaging were obtained from 21 children with unexplained mental retardation and 30 age-matched control children without intellectual disabilities. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures were applied to compare differences of gray matter volume between the two groups. The total and regional gray matter volume were compared between the two groups with independent t test. Meanwhile, correlation was conducted to analyze the relationship between the total gray matter volume and intelligence quotient (IQ) with partial correlation test. Results The total gray matter volume was significantly increased in the mental retardation children [(1. 012 ±0. 079) × 106 mm3]in relative to the controls [(0. 956 ± 0. 059) × 106 mm3, t = - 2. 80, P ＜ 0. 05]. Compared to controls,children with unexplained mental retardation showed significantly increased gray matter volume in different regions, including the bilateral thalami, the bilateral superior frontal gyri, the bilateral gyri rectus, the bilateral temporal poles, the right inferior frontal gyrus, right parahippocampal gyrus and the right cerebellum. No correlation was detected between the total gray matter volume and IQ in children with mental retardation (r = 0. 078 ,P ＞ 0. 05). Conclusions VBM would detect the gray matter abnormalities that were not founded in routine MR scanning. The increase of gray matter volume in the frontal-thalamus network might indicate the delayed maturation of the brain development. This might be one of the causations of mental retardation in children.
