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Abstract Background Interstitial lung disease (ILD) is a serious complication in systemic juvenile idiopathic arthritis (SJIA). This study aimed to identify the clinical characteristics and prognosis of SJIA-ILD. Methods A two-center retrospective cohort study was conducted on patients newly diagnosed with SJIA in China from October 2010 to December 2021. Clinical characteristics, laboratory parameters, outcomes, and relapse rates were compared between ILD and non-ILD groups. Results A total of 176 children with SJIA were included, including 35 in ILD group and 141 in non-ILD group. The median age at onset of SJIA was 5.8 years (range 4.4–9.5) in patients with SJIA-ILD. It exhibited higher incidences of cervical spine (28.6%) and hip involvement (40.0%) in ILD group (P = 0.031 and P = 0.029, respectively). The incidence of macrophage activation syndrome (MAS) in ILD group reached up to 40%, significantly elevated than that in non-ILD group (P = 0.047). Children with ILD demonstrated a stronger inflammatory response and were more prone to developing lymphopenia (P = 0.009), requiring more combination therapy (P = 0.006) to control disease activity. 54.3% of patients received biologic therapies, with only three patient receiving biologics (one with IL-6 blockade, two with TNF inhibitor) prior to ILD onset and none receiving IL-1 blockade. The median follow-up duration was 6.0 years (range 3.9–9.5). The proportions of patients with SJIA-ILD achieving clinical inactive disease without glucocorticoids within 6 to 12 months of the treatment were significantly lower than control group (45.7% vs. 70.2%, P = 0.006). In ILD group, only 54.3% of patients achieved complete remission, and 17.1% were in a non-remission state, among whom two deaths from respiratory failure. There was no significant difference in disease relapse rates between the two groups (P > 0.05). Conclusions Patients with SJIA-ILD exhibited heightened inflammation, increased hip joint and cervical spine involvement, and were more susceptible to developing lymphopenia and MAS, suggesting a relatively poor prognosis. They required a prolonged time to control inflammation and more aggressive treatment strategies to achieve inactive status. The unsatisfactory rate of complete remission highlighted an urgent need for focused clinical strategies.

BackgroundCurrently, no established integrated treatment regimen exists for anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive juvenile dermatomyositis (JDM) complicated by rapidly progressive interstitial lung disease (RP-ILD). We present a case of refractory anti-MDA5-positive JDM with RP-ILD that was successfully treated using a combination of tocilizumab and plasma exchange, along with a review of the relevant literature.MethodsA literature review was conducted to gain insights into the clinical features and treatment strategies for managing refractory anti-MDA5-positive JDM complicated by RP-ILD.ResultsWe report a case of successful management of anti-MDA5-positive JDM complicated by RP-ILD using a combination of immunosuppressive agents, plasma exchange, and tocilizumab.ConclusionTocilizumab may serve as an effective adjunctive treatment option for patients with refractory anti-MDA5-positive JDM complicated by RP-ILD who do not respond to conventional intensive immunosuppressive therapies.

Abstract Background Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. Methods Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. Results Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. Conclusions Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

Under the dual-carbon target, hydrogen energy, as a zero-carbon secondary energy source, has great scope for replacing fossil feedstocks in the fields of energy, transportation and industry. However, the current research on the competitiveness of hydrogen energy in various fields is not sufficiently addressed. In this paper, we use the LEAP model to predict the future scale of hydrogen use and the two-factor learning curve to predict the trend of hydrogen price change from 2025 to 2050, using Qinghai Province as the research background. At the same time, considering the carbon emission reduction benefits and raw material costs, the competitiveness of hydrogen energy in energy, transportation, industry and other fields in the future is compared. The results show that: 1) The hydrogen load scale in Qinghai Province will grow fast from 2025 to 2030. From 2030 to 2040, it slows under the steady and basic scenarios but remains high under the accelerated one. By 2040, the consumption scales are 1.057 million, 649,000 and 442,000 tons respectively. 2) The price of hydrogen energy will drop rapidly from the current 28 CNY/kg to about 20 CNY/kg in the next 5 years. By 2040, the price of hydrogen energy will be reduced to about 17 CNY/kg. 3) In terms of hydrogen energy competitiveness, when carbon emissions are not taken into account, hydrogen energy is currently competitive in the transportation field. During 2032–2038, it will be competitive in the field of methanol synthesis. By 2040, hydrogen energy will not be competitive in the fields of ammonia synthesis and power/heating. When considering carbon emissions, the competitiveness of hydrogen energy in the transportation field will become greater. The competitive year in the field of methanol synthesis will be 1–2 years ahead. By 2040, it will not be competitive in the field of synthetic ammonia and power/heating, but the gap will be significantly reduced due to the consideration of carbon emissions.

ObjectiveIt has been recognized that there is a nexus among Trisomy 8 (T8), Behcet's disease (BD), and myelodysplastic syndrome (MDS). We reported a series of inflammatory features in 2 children with T8 without hematological involvement.Methods2 children with trisomy 8 who were excluded from MDS were retrospectively collected from the Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing.ResultsPatients developed a range of inflammatory manifestations before a diagnosis of T8. The clinical manifestations of T8 patients vary from normal to severely disabled. Glucocorticoids and thalidomide can effectively relieve inflammation in patients with T8.ConclusionThe early clinical manifestations of T8 in children lack specificity, and the diagnosis is mainly based on karyotype analysis, gastrointestinal endoscopy and bone marrow aspiration findings. Active and effective immunoregulatory therapy and long-term follow-up can improve the prognosis of patients with T8.

Abstract Background Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data. Methods We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment. Results Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P

ObjectiveTakayasu artery (TAK) is a chronic inflammatory disease that mainly affects the aorta and its major branches and is rarely reported in infants. We aimed to summarize the clinical features of infant TA (I-TA) in a tertiary care center.MethodsWe performed a retrospective study involving 10 infants diagnosed with TAK. A comprehensive evaluation of clinical, laboratory, radiographic features, disease activity, treatment and outcomes was carried out.ResultsA consecutive cohort was composed of 8 girls and 2 boys, with an age at diagnosis of 11.1 (1.7–36) months. The median time to diagnosis and the average time to follow-up were 9.5 days (2–235 days) and 10.9 (1–21) months, respectively. The most common initial manifestations were malaise (80%), fever (70%), hypertension (50%) and rash (30%). The mean Pediatric Vasculitis Activity Score (PVAS), Takayasu Clinical Activity Score (ITAS-2010) and ITAS-A scores were 2.8/63, 2.6/51, and 5.6/54, respectively. All patients had aberrant laboratory parameters. The most common lesions were in the thoracic aorta (60%) and abdominal aorta (60%). Corticosteroids combined with cyclophosphamide followed by long-term mycophenolate mofetil were initiated in most cases (70%). Biologics were attempted in 5 cases. Mortality was 40%.ConclusionsIt is challenging to diagnose TAK in infants in a timely manner. Considering the more vessels involved, more severe inflammation and higher mortality, aggressive treatment is warranted in infants. GCs and CYC treatment seem to be effective.

Abstract Background Axial involvement in children with enthesitis-related arthritis (ERA) has characteristics that differ from those of peripheral involvement. This study characterized their clinical characteristics and treatment. Methods Patients with ERA at the Children’s Hospital of Nanjing Medical University between January 2018 and December 2020 were included. The ERA cohort was divided into two based on the presence or absence of axial joint involvement. Demographic characteristics, clinical features, and treatments were described and compared. Results In total, 105 children with ERA were enrolled (axial ERA, n = 57; peripheral ERA, n = 48). The age at disease onset of the axial group tended to be higher (11.93 ± 1.72 vs. 11.09 ± 1.91 years) and the diagnosis delay was bigger in patients with axial ERA (10.26 ± 11.66 months vs. 5.13 ± 7.92 months). The inflammatory marker levels were significantly higher in patients with axial. There were no differences in HLA-B27 positivity between the groups (34 [59.65%] vs. 28 [58.33%], P > 0.05). Hip involvement was more frequent in the axial group (52.63% vs 27.08%; X2 = 7.033). A total of 38 (66.67%) and 10 (20.83%) patients with axial and peripheral ERA, respectively, were treated with biological disease-modifying anti-rheumatic drugs (DMARDs) at diagnosis. The administration of biologics increased gradually in the axial ERA group, peaking at 18 months and decreasing thereafter, whereas that in the peripheral ERA group peaked at 6 months and began to decline thereafter. Conclusions Axial ERA is a persistent active disease and requires a more aggressive treatment. Classification and early recognition of axial involvement may help with timely diagnosis and appropriate management.

ObjectiveIn children with enthesitis-related arthritis (ERA), the hip and sacroiliac joint function might be impaired if not properly treated. We sought to evaluate the effectiveness of anti-tumor necrosis factor-α (TNF-α) therapy using the inflammatory indicators, Juvenile Arthritis Disease Activity Score 27 (JADAS27) and magnetic resonance imaging (MRI).MethodsWe conducted a single-center retrospective study of 134 patients with ERA. We evaluated the effect of anti-TNF therapy on the inflammatory indicators, active joint count, MRI quantitative score, and JADAS27 over 18 months. We used the Spondyloarthritis Research Consortium of Canada (SPARCC) and the Hip Inflammation MRI Scoring System (HIMRISS) scoring systems for hip and sacroiliac joints scoring.ResultsThe average age of onset of children with ERA was 11.62 ± 1.95 years, and they were treated with disease-modifying antirheumatic drugs (DMARDs) combined with biologics (n = 87, 64.93%). There were no differences in HLA-B27 positivity between the biologics and non-biologics treatment groups [66 (49.25%) vs. 68 (50.75%), P > 0.05]. Children who received anti-TNF (71 received etanercept, 13 adalimumab, 2 golimumab, and 1 infliximab) therapy improved significantly. Children with ERA used DMARDs and biologics at baseline (Group A) were followed up to 18 months, and their active joint count (4.29 ± 1.99 vs. 0.76 ± 1.33, P = 0.000), JADAS27 (13.70 ± 4.80 vs. 4.53 ± 4.52, P = 0.000) and MRI quantitative scores (P = 0.001) were significantly lower than those at baseline. Some of the patients (n = 13, 9.70%) were treated with DMARDs at the onset of the disease, but did not show significant improvement (Group B). After 6−18 months of switching to anti-TNF therapy, related indicators of the children were significantly lower than at baseline and 1 month (P

Abstract Objective The aim of this study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO). Methods Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China. Results Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7–13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0–72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1–7). Most frequently affected bones were tibiofibula (88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate (MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect. Conclusions The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications.

Background. Approximately 10%–20% of patients with Kawasaki disease (KD) are nonresponsive to intravenous immunoglobulin (IVIG) treatment, placing them at higher risk of developing coronary heart lesions. Early detection of nonresponsiveness is crucial to curtail this risk; however, the applicability of existing predictive scoring systems is limited to the Japanese population. Our study aimed to identify a predictive scoring system for IVIG resistance in KD specific to the Chinese population. We aimed to assess the utility of three commonly used risk-scoring systems in predicting IVIG resistance and compare them to the newly developed predictive scoring system. Methods. A total of 895 patients with KD were enrolled in this retrospective review and divided into two groups: IVIG responders and nonresponders. Clinical and laboratory variables were compared between the two groups. Multivariable logistic regression models were used to construct a new scoring system. The utility of the existing and new scoring systems was assessed and compared using the area under the receiver operating characteristic curve. Results. Albumin levels, percentage of neutrophils, and hemoglobin were independent predictors of resistance by logistic regression analysis. The new predictive scoring system was derived with improved sensitivity (60.5%) and specificity (87.8%). The area under the receiver operating characteristic curve was 0.818. Conclusion. This study developed a novel risk-scoring system for predicting resistance to IVIG treatment in KD specific to the Chinese population. Although this new model requires further validation, it may be useful for improving prognostic outcomes and reducing the risk of complications associated with KD.

Current treatments cannot significantly alleviate the radiographic progression in ankylosing spondylitis (AS), which results in joints stiffness and bony fusion of AS. Smo inhibitor sonidegib retards the pathological new bone formation in AS through targeting dysfunctional chondrogenesis.

Inherited autosomal dominant gain-of-function (GOF) mutations of signal transducer and activator of transcription 1 (STAT1) cause a wide range of symptoms affecting multiple systems, including chronic mucocutaneous candidiasis (CMC), infections, and autoimmune disorders. We describe a rare case of STAT1 mutation with recurrent CMC, lung infections, and anemia. According to the whole-exome sequencing (WES), the patient was genetically mutated in STAT1 GOF (c.854A>G, p.Q285R), and bone marrow biopsy suggested pure red cell aplasia (PRCA). As a functional verification, STAT1 levels and phosphorylation (p-STAT1) of peripheral blood mononuclear cells (PBMCs) following IFN-γ stimulation in STAT1 GOF patient was higher than in the healthy control. Combination therapy of blood transfusion, antimicrobials, intravenous immunoglobulin, methylprednisolone, and the Janus Kinase (JAK) specific inhibitor ruxolitinib was used during treatment of patients. The patient also received a hematopoietic stem cell transplant (HSCT) to help with infections and anemia. This is the first reported case of STAT1 GOF disease complicated with PRCA. This complication might be attributed to immune disorders caused by STAT1 GOF. Furthermore, ruxolitinib may be a viable therapeutic option before HSCT to improve disease management.

Background: X-linked agammaglobulinemia (XLA) is a rare inherited disease characterized by recurrent bacterial infections, a paucity or absence of peripheral lymphoid tissue, an absence of circulating B cells, and marked depression of serum IgG, IgA, and IgM. Germline mutation of the BTK gene has been identified as a cause of XLA. These mutations cause defects in early B cell development. Case presentation: In this study, we report a variant form of XLA with partial B cell function that results from a missense mutation (c.1117C > G) in exon 13 of the BTK gene. A genetic analysis of the family revealed an affected male sibling with a c.1117C > G mutation. He was observed with low level of serum immunoglobulin and CD19+ B cell and received the IVIG replacement therapy regularly in follow up. Four female carriers were found. Conclusion: BTK mutation analysis is necessary in the diagnosis of XLA and may be used for subsequent genetic counseling, carrier detection and prenatal diagnosis. [ABSTRACT FROM AUTHOR]