Search

The idiopathic inflammatory myopathies (IIMs) are a group of connective tissue diseases that afect multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the most common and heterogeneous complication of IIMs, with its degree ranging from mild to fatal. Thus, it is critical to identify clinical features and validated biomarkers for predicting disease progression and prognosis, which could be beneficial for therapy adjustment. In this review, we discuss predictors for rapid progression of IIM-ILD and propose guidance for disease monitoring and implications of therapy. Systematic screening of myositis-specific antibodies, measuring serum biomarker levels, pulmonary function tests, and chest high-resolution computer tomography will be beneficial for the evaluation of disease progression and prognosis.

Introduction Community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are common complications in idiopathic inflammatory myopathy (IIM) patients, and are frequently associated with unfavorable outcome as well as prolonged antibiotic therapy. In this study, we intended to clarify whether clinical pulmonary infection score (CPIS) and multiple serum biomarkers are valuable in predicting unfavorable outcomes and prolonged antibiotic therapy in adult IIM patients complicated with CAP or HAP. Methods Data of IIM patients with CAP or HAP who were admitted to three tertiary centers from December 2010 to November 2019 were retrospectively collected. Cox proportional hazards regression analysis and logistic regression analysis were adopted to identify risk factors for unfavorable outcomes and prolonged antibiotic therapy in these patients. The predictive values of potential predictors were assessed using receiver operating characteristic analysis. Results The mortality rate was 60.6% in 109 IIM patients complicated with CAP or HAP. Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT) score, CPIS and timely adjustment to antibiotics based on drug susceptibility test (DST-based antibiotic) were significantly associated with long-term outcome in these patients. With an optimal cutoff value of 6.5 and area under the curve (AUC) of 0.813, CPIS was a more satisfying predictor compared with MYOACT score. The peak C-reactive protein (CRP) level, DST-based antibiotics, and complication of interstitial lung disease (ILD) were also significantly correlated with prolonged antibiotic therapy. Conclusions IIM patients complicated with CAP or HAP frequently suffer from unfavorable outcomes. Compared with IIM disease activity, CPIS worked as a better predictor of outcome in these patients. Also, the peak CRP level during hospitalization might be valuable in predicting prolonged antibiotic therapy. The existence of ILD might impede early discontinuation of antibiotics. Timely adjustment to antibiotics based on drug susceptibility testing would decrease the mortality rate and reduce the incidence of prolonged antibiotic therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-020-00268-7.

Objective. Iguratimod, a novel disease-modifying anti-rheumatic drug for the treatment of rheumatoid arthritis, has been approved in China and Japan. Here, we aimed to find whether iguratimod can inhibit the aggressive behavior and promote apoptosis of rheumatoid fibroblast-like synoviocytes (RA-FLSs). Methods. The proliferation of RA-FLSs was assessed by 5-ethynyl-2′-deoxyuridine test and Cell Counting Kit-8. Migration and invasion were determined by the wound test and a transwell assay. Apoptosis was tested by flow cytometry. The mRNA expression of matrix metalloproteinases (MMPs) and proinflammatory cytokines in RA-FLSs were measured by quantitative PCR and ELISA. To gain insight into the molecular signaling mechanisms, we determined the effect of iguratimod on the activation of mitogen-activated protein kinases (MAPK) signaling pathways by the cellular thermal shift assay (CETSA) and western blot. Results. Iguratimod treatment significantly reduced the proliferation, migration, and invasive capacities of RA-FLSs in a dose-dependent manner in vitro. MMP-1, MMP-3, MMP-9, Interleukin-6 (IL-6), and monocyte chemoattractant protein-1 mRNA and protein levels were all decreased after treatment with iguratimod. Furthermore, tumor necrosis factor-alpha- (TNF-α-) induced expression of phosphorylated c-Jun N-terminal kinases (JNK) and P38 MAPK were inhibited by iguratimod. Additionally, iguratimod promoted the apoptosis of RA-FLSs. Most importantly, iguratimod was shown to directly interact with JNK and P38 protein by CETSA assay. Moreover, activating transcription factor 2 (ATF-2), a substrate of both JNK and P38, was suppressed by iguratimod. Conclusions. Our findings suggested that the therapeutic effects of iguratimod on RA might be, in part, due to targeting the aggressive behavior and apoptosis of RA-FLSs.

Objective.To clarify the prevalence, risk factors, outcome, and outcome-related factors of hemophagocytic lymphohistiocytosis (HLH) in patients with dermatomyositis (DM), polymyositis (PM), or clinically amyopathic dermatomyositis (CADM).Methods.Data of patients with DM, PM, or CADM who were admitted to the First Affiliated Hospital of Zhejiang University from February 2011 to February 2019 were retrospectively collected. Patients diagnosed with HLH constituted the case group. A 1:4 case-control study was performed to identify risk factors for HLH in patients with DM, PM, or CADM through comparison, univariate, and multivariate logistic regression analysis. Intragroup comparison was made among patients with HLH to identify factors influencing unfavorable short-term outcome.Results.HLH was a rare (4.2%) but fatal (77.8%) complication in patients with DM, PM, or CADM. The retrospective case-control study revealed that higher on-admission disease activity (p = 0.008), acute exacerbation of interstitial lung disease (AE-ILD, p = 0.002), and infection (p = 0.002) were risk factors for complication of HLH in patients with DM, PM, or CADM. The following intragroup comparison showed that higher on-admission disease activity (p = 0.035) and diagnosis of CADM (p = 0.039) might influence the short-term outcome of patients with HLH. However, no risk factor was identified after false discovery rate correction.Conclusion.In this study, secondary HLH was a fatal complication, with higher on-admission disease activity, AE-ILD, and infection working as risk factors. The underlying role of infection and autoimmune abnormality in HLH in connective tissue disease was subsequently noted. Clinical factors influencing the short-term outcome of patients with secondary HLH require further study.

Objectives: To initially clarify the efficacy and tolerability of nintedanib in patients with idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD).Methods: A retrospective, real-world analysis was conducted in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to March 2020 in three centers. And the patients were divided into two groups depending on presence or absence of nintedanib therapy. Comparisons, Kaplan-Meier survival analysis and propensity score matching were made to identify difference in time to death from any cause, incidence of rapidly progressive interstitial lung disease (RP-ILD) and comorbidity of pulmonary infection between the two groups. The following logistic regression analyses and Cox proportional-hazard regression analyses were used to verify the therapeutic value of nintedanib as well as clinical significance of other factors. Adverse events were descriptively recorded.Results: Thirty-six patients receiving nintedanib therapy and 115 patients without use of nintedanib were included. Before and after propensity score matching, the primary comparisons revealed better survival (P = 0.015, P = 0016, respectively) and lower incidence of RP-ILD (P = 0.017, P = 0.014, respectively) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P < 0.001), percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.036), nintedanib therapy (P = 0.004, OR value = 0.072) and amyopathic dermatomyositis (ADM, P = 0.012) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis suggested that disease activity (P < 0.001), anti-MDA5 antibody (P < 0.001) and nintedanib therapy (P = 0.013, HR value=0.268) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses after propensity score matching. In the 36 patients with nintedanib therapy, diarrhea was the most common adverse event (44.4%) and hepatic insufficiency contributed to most dosage reduction (44.4% of nine patients) or therapy discontinuation (60.0% of five patients).Conclusions: Nintedanib was found to reduce incidence of RP-ILD and improve survival in IIM-ILD patients in a real-world setting. Anti-MDA5 antibody could be taken as a risk factor for unfavorable outcome. ADM was significantly correlated with occurrence of RP-ILD. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation.

Background Interstitial lung disease (ILD) is a common and frequently fatal extra-muscular complication in patients with idiopathic inflammatory myopathy (IIM), and is refractory to the conventional immunosuppressive medications. Nintedanib has previously been proven to be effective and tolerable in idiopathic pulmonary fibrosis, systemic-sclerosis-related ILD, etc. However, the efficacy and safety of nintedanib in idiopathic-inflammatory-myopathy-related ILD (IIM-ILD) remain unknown. The purpose of this study was to initially explore the efficacy and tolerability of nintedanib in IIM-ILD patients. Methods A real-world analysis was conducted to explore the efficacy and tolerability of nintedanib in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to October 2019 in one medical center. The primary end point was occurrence of rapid progression of interstitial lung disease (RP-ILD) in the follow-up. And time to death from any cause, complication of pulmonary infection and difference in immunosuppressive regimen were taken as secondary end points in this study. Adverse events were descriptively recorded. Results 22 patients receiving nintedanib therapy and 82 patients under conventional medications were included. After propensity score matching, the primary comparison revealed that better survival (P = 0.036) and prominently less RP-ILD (P = 0.031) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P = 0.032), anti-PM-Scl75 antibody (P = 0.027) and nintedanib therapy (P = 0.023, OR value = 0.063) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis demonstrated that disease activity (P = 0.007), anti-MDA5 antibody (P = 0.004) and nintedanib therapy (P = 0.027, HR value = 0.190) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses before propensity score matching. In the 22 patients with nintedanib therapy, diarrhea was the most common adverse event (54.5%) and hepatic insufficiency contributed to most dosage reduction (50%) or therapy discontinuation (50%). Conclusion Nintedanib therapy might reduce incidence of RP-ILD and improve survival in IIM-ILD patients. Anti-PM-Scl75 and anti-MDA5 antibodies could predict RP-ILD and survival respectively. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation. Trial registration: ISRCTN.com, ISRCTN 10507540. Retrospectively registered.

High-performance hierarchical cheese-like C-ZSM-5 nanocrystals are successfully prepared by acid–base treatment and are evaluated for oxidative desulfurization of dibenzothiophene. The acid–base treatment can generate a large number of Si-OH bonds and an open-mesoporous structure, which is conducive for the dispersion of TiO2 and also for the transport of dibenzothiophene and its oxidation products simultaneously. The catalytic results indicate that the hierarchical cheese-like C-ZSM-5 nanocrystals are highly active catalysts for the oxidative desulfurization of dibenzothiophene due to open mesoporosity. Complete conversion was obtained within 80 min at 338 K. The excellent performance is due to the large number of active framework sites and open mesopores generated by post-processing.

© 2018 Elsevier Ltd Porous carbon with high surface area and low cost has emerged as promising alternative electrode for supercapacitor. However, the poor electrical conductivity arising from the rich existence of sp3carbon remains a big challenge. Here, a novel strategy is reported for the nanographitic domains (sp2carbon) distributed in porous carbon via transition metal acetate (M(CH3COO)2M = Fe, Co, Ni) assistance and in situ N-doping during the activation process. The resultant different N-doped porous carbon foams (denoted as NCF (Fe), NCF (Co), NCF (Ni)) exhibit a localized graphitic structure and hierarchically porous framework with micropore integrating into macroporous scaffold. Whereas, the NCF (Fe) shows ultra-high BET surface areas of up to 2630 m2g−1, a large pore volume of up to 1.1 cm3g−1, notable nitrogen content of 5.34 wt %, optimal pore size and superior hydrophilicity. When adopted as supercapacitor electrode, the NCF (Fe) presents a reversible capacity of 273.7 F g−1in 6 M KOH aqueous electrolyte. Even at a high current of 10 A g−1, a capacity of 200.5 F g−1can also be achieved, which makes it a potential capacitive material for high-rate supercapacitor. Considering other advantages of the method such as cheap precursor, facile process et al., NCF (Fe) can be rendered to be a promising candidate for commercial supercapacitors.

Rationale: Dysregulated immune function in rheumatoid arthritis (RA) might lead to the development of myelodysplastic syndrome (MDS). Serum interleukin-6 (IL-6) concentrations are increased in both RA and MDS patients. Patient concerns: A 58-year-old woman presented with severe RA. During a recent 8-month period, the patient experienced swelling in multiple joints, dizziness, and severe anemia. The symptoms responded poorly to oral corticosteroids and methotrexate (MTX). Even treatment of the patient's anemia by transfusion of red blood cells was ineffective. Laboratory tests showed high levels of IL-6 (214.24 pg/mL). Diagnoses: Combining her medical history with clinical and laboratory parameters, especially those obtained by bone marrow aspiration, a diagnosis of RA with MDS was made. Interventions: MTX was discontinued and the patient was given tocilizumab intravenously at a dose of 8 mg/kg every 4 weeks and oral corticosteroids (15 mg/QD). Outcomes: The patient's serological, physical, and pathological abnormalities improved significantly. Lessons: We report a case of RA with MDS successfully treated with tocilizumab. To our knowledge, this is the first case of an RA patient with MDS that was successfully treated with tocilizumab. In addition, our case emphasizes that IL-6 plays a critical role in the pathogenesis of RA with MDS. Tocilizumab might be an effective treatment for RA with MDS, especially in those with high levels of IL-6, elevated C-reactive protein, and severe anemia.

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor ofκB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/εin patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε(pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/βand pIKKγwere both negative. And pIKKεpositively related to expression of p-p65. Furthermore, pIKKεand p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγand IκBαbetween pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKεexpression and deregulation of NF-κB pathway.

The present study describes the case of an 18-year-old adolescent male exhibiting acute lymphocytic leukemia (ALL), complicated by the onset of the symptom of sacroiliitis mimicking spondyloarthritis. Atypical features including an enlarged spleen, poor effects of non-steroidal anti-inflammatory drug therapy, low levels of hemoglobin, a low platelet count, a low neutrophil count and increased levels of monocytes, indicated the possibility of hematological malignancy. Bone marrow examination confirmed the diagnosis of ALL. The patient received chemotherapy and the symptoms were dramatically relieved. To the best of our knowledge, the current study reports the second published case of a patient with ALL presenting with sacroiliitis. Sacroiliitis as an onset manifestation of ALL may result in misdiagnosis, therefore, a differential diagnosis is essential when atypical features are present.

Development of facile, economic and green routes towards the synthesis of hierarchical zeolites with high catalytic activity still remains a challenge in modern industrial catalysis. In this paper, we report on a novel synthesis of house-of-cards-like ZSM-5 (HCL-ZSM-5) via the introduction of N-methyl-2-pyrrolidone into a template-free zeolite synthesis system. Importantly, the HCL-ZSM-5 presents much better catalytic performances in the cracking of cumene and 1,3,5-triisopropylbenzene (TIPB) than conventional porous catalysts (ZSM-5, Y zeolite and Al-MCM-41).