Persistent neuroinflammation of the right insular cortex in children with juvenile idiopathic arthritis: a proton MRS study.

OBJECTIVE: The aim of this study of children with juvenile idiopathic arthritis (JIA) was to use proton magnetic resonance spectroscopy (1H-MRS) to compare the levels of five neurometabolites in the right and left insular cortexes of subjects in three groups: JIA-active, JIA-inactive, and healthy controls (HCs). METHODS: Two inflammation markers and five psychometric scores were determined. 1H-MRS was used to measure the levels of total N-acetylaspartate (NAA), total choline (Cho), myo-inositol (mI), and glutamate (Glu), and the complex of glutamine and glutamate (Glx) relative to total creatine (tCr) in the right and left insular cortexes of participants. RESULTS: Intra-group comparisons indicated that each group had higher levels of NAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. Inter-group comparisons of the right insula indicated that the JIA-active and JIA-inactive groups had higher levels of Cho/tCr than the HC group, but none of the other inter-group differences were statistically significant. The score of the Sleep Disturbance Scale for Children (SDCD) had an inverse correlation with the level of Cho/tCr in the right insular cortex of patients in the JIA-inactive group. CONCLUSIONS: Relative to the HC group, the right insular cortex of subjects in the JIA-active and the JIA-inactive groups had greater levels of Cho/tCr, suggesting increased inflammation in this region. The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group. Key Points • Healthy controls and JIA patients had higher levels of tNAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. • A greater level of Cho/tCr in the right insula of JIA-active and JIA-inactive patients indicated neuroinflammation in this region. • The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group.

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study.

Background: Etanercept biosimilar recombinant human TNF-α receptor II: IgG Fc fusion protein (rhTNFR-Fc) has showed its efficacy and safety in Chinese patients with rheumatoid arthritis. However, data on rhTNFR-Fc's application in juvenile idiopathic arthritis (JIA) is limited. Methods: A prospective, observational, multicenter study was performed at 6 institutes in China from July 2020 to December 2021. In a 24-week follow-up, patients with JIA including polyarticular JIA and enthesitis related arthritis received rhTNFR-Fc plus methotrexate (MTX) treatment. The primary outcome parameters were improvements of cJADAS-10 (clinical Juvenile Arthritis Disease Activity Score), and the secondary outcome parameter was an inactive disease. Results: 60 patients completed at least 12-week follow-up, and 57 completed 24-week follow-up. They had high C reactive protein values (11.6 mg/L) and cJADAS-10 (14.6) at baseline. Thirteen patients had morning stiffness. 33 patients showed synovial thickening, and 34 showed bone marrow edemas on MRI. Ultrasonography demonstrated significant joint effusions in 43 patients. The cJADAS-10 sharply decreased from 14.66 at the baseline to 2.4 at 24 weeks of rhTNFR-Fc therapy, respectively (P < 0.01). About half of patients achieved inactive disease at 24 weeks of therapy. Compared with the baseline, the number of patients with morning stiffness, joint effusions, bone marrow edema and synovial thickening on MRI significantly decreased at 24 weeks. Adverse events were consistent with known side effects of biologic agents. Conclusions: The present study indicated that the combination of rhTNFR-Fc and MTX significantly improve symptoms and disease activity of children with JIA. This study suggests etanercept biosimilar rhTNFR-Fc as an effective and safe therapy for children with JIA.

[Research progress in mechanism of necroptosis in acute pancreatitis].

Acute pancreatitis (AP) is a common and potentially threatening disease of the pancreas, and some patients eventually develop to severe acute pancreatitis (SAP). Symptomatic support therapies such as rehydration therapy and anti-infection are still the main treatments. Lacking specific therapies is the main reason for the high mortality of AP patients, especially those with SAP. Premature trypsinogen activation is the most important pathologic cellular event in the pathogenesis of AP. The release of trypsin can cause self-digestion inside and outside of acinar cells, especially the release of cathepsin B can also cause a caspase-unrelated regulatory cell death (RCD) known as necroptosis, which is closely related to the development and prognosis of AP. Therefore, it is necessary to further study the mechanism of necroptosis in the occurrence and development of AP. This article reviews the mechanism of necroptosis and the research progress related to AP, in an attempt to provide a new understanding of the pathogenesis and treatment of AP, and promote the better target drug development.

The Brain Structural-Functional Vulnerability in Drug-Naive Children With Juvenile Idiopathic Arthritis: Insights From the Hippocampus.

Objective: Leveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis (JIA) and to explore potential correlations within the "joint-inflammation-brain" axis during the period of central neural system (CNS) development. Methods: Twenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model (SPHARM-PDM) and the ROI-to-voxel functional connectivity (FC) to measure the hippocampal shape and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices. Results: Compared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately. Conclusion: As with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA.

Familial chilblain lupus due to a novel mutation in TREX1 associated with Aicardi-Goutie'res syndrome.

BACKGROUND: Familial chilblain lupus (FCL) is a rare, chronic form of cutaneous lupus erythematosus, which is characterized by painful bluish-red inflammatory cutaneous lesions in acral locations. Mutations in TREX1, SAMHD1 and STING have been described in FCL patients. Less than 10 TREX1 mutation positive FCL families have been described in the literature. CASE PRESENTATION: Genetic study was performed in a large, nonconsanguineous Chinese family with 13 members over 4 generations affected by chilblain lupus. Whole exome sequencing was performed for the index patient. Significant variant detection was subsequently validated by resequencing using Sanger sequencing in the index patient and other family members. A novel pathogenic mutation TREX1 p.Asp18His was iditified in the index patient. The mutation was present in affected individuals and was absent in non-affected individuals in the familiy. CONCLUSIONS: We present a four-generation Chinese family with FCL caused by a novel heterozygous mutation TREX1 p.Asp18His, which had been reported in a patient with Aicardi-Goutie'res syndrome. This is the first reported Chinese family with FCL based on mutation in TREX1.

Clinical and laboratory features, treatment, and outcomes of macrophage activation syndrome in 80 children: a multi-center study in China.

BACKGROUND: Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. METHODS: A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. RESULTS: 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P < 0.05), but no difference in alanine aminotransferase, ferritin, and ratio of ferritin/erythrocyte sedimentation rate (ESR) at onset of MAS when compared to pre-MAS stages of the disease. In addition, ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage. Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD. Receiver-operating characteristic analysis showed that 12,217.5 µg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity (80.0% and 90.5%) and specificity (88.2% and 86.7%), respectively, for predicting full-blown SJIA-MAS. The majority of the patients received corticosteroids (79/80), while biologic agents were used in 12.5% (10/80) of cases. Tocilizumab was the most commonly selected biologic agent. The overall mortality rate was 7.5%. CONCLUSIONS: About half of MAS occurred when the underlying autoimmune diseases (SJIA, KD, and CTD) were first diagnosed. Hypotension could be an important manifestation before MAS diagnosis. Decreased albumin and increased AST, LDH, ferritin, and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

The value of ultrasound for detecting hand fractures: A meta-analysis.

BACKGROUNDS: Hand fractures are the second most common upper-extremity fractures. The standard X-ray has shortcomings, such as exposure to radiation. Ultrasound has been reported as an alternative method of detecting hand fractures. In this study, we used meta-analysis to assess the diagnostic value of ultrasound for hand fractures. METHODS: Web of Science, PubMed, Embase, and Cochrane Library databases were searched for relative citations up to June 2019. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUC), and summary receiver operating characteristic (SROC) curve were estimated. RESULTS: Seven studies including 842 participants (845 examined hands) met our inclusion criteria. The pooled sensitivity, specificity, PLR, and NLR of ultrasound for detecting hand fractures were 91%, 96%, 20.66, and 0.09, respectively. The pooled DOR was 231.17, indicating a very powerful diagnostic ability of ultrasound. Meta-regression showed that there was no heterogeneity with respect to age, cut-off, the performer of the ultrasound, and the types of hand fractures. CONCLUSIONS: Our results showed that ultrasound had an excellent diagnostic value for hand fractures. In clinic, we proposed using ultrasound as a first-line and radiation-free modality in detecting hand fractures, including phalanx and metacarpal fractures.