A nomogram based on clinical factors and CT radiomics for predicting anti-MDA5+ DM complicated by RP-ILD.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) DM complicated by rapidly progressive interstitial lung disease (RP-ILD) has a high incidence and poor prognosis. The objective of this study was to establish a model for the prediction and early diagnosis of anti-MDA5+ DM-associated RP-ILD based on clinical manifestations and imaging features. METHODS: A total of 103 patients with anti-MDA5+ DM were included. The patients were randomly split into training and testing sets of 72 and 31 patients, respectively. After image analysis, we collected clinical, imaging and radiomics features from each patient. Feature selection was performed first with the minimum redundancy and maximum relevance algorithm and then with the best subset selection method. The final remaining features comprised the radscore. A clinical model and imaging model were then constructed with the selected independent risk factors for the prediction of non-RP-ILD and RP-ILD. We also combined these models in different ways and compared their predictive abilities. A nomogram was also established. The predictive performances of the models were assessed based on receiver operating characteristics curves, calibration curves, discriminability and clinical utility. RESULTS: The analyses showed that two clinical factors, dyspnoea (P = 0.000) and duration of illness in months (P = 0.001), and three radiomics features (P = 0.001, 0.044 and 0.008, separately) were independent predictors of non-RP-ILD and RP-ILD. However, no imaging features were significantly different between the two groups. The radiomics model built with the three radiomics features performed worse than the clinical model and showed areas under the curve (AUCs) of 0.805 and 0.754 in the training and test sets, respectively. The clinical model demonstrated a good predictive ability for RP-ILD in MDA5+ DM patients, with an AUC, sensitivity, specificity and accuracy of 0.954, 0.931, 0.837 and 0.847 in the training set and 0.890, 0.875, 0.800 and 0.774 in the testing set, respectively. The combination model built with clinical and radiomics features performed slightly better than the clinical model, with an AUC, sensitivity, specificity and accuracy of 0.994, 0.966, 0.977 and 0.931 in the training set and 0.890, 0.812, 1.000 and 0.839 in the testing set, respectively. The calibration curve and decision curve analyses showed satisfactory consistency and clinical utility of the nomogram. CONCLUSION: Our results suggest that the combination model built with clinical and radiomics features could reliably predict the occurrence of RP-ILD in MDA5+ DM patients.

Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA. METHODS: Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16. RESULTS: In total, 147 patients were randomized to receive placebo (n = 73) or IXEQ4W (n = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n = 66; 40.9%) than the placebo group (n = 64, 7.8%; p < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest. CONCLUSIONS: IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04285229.

Interplay between COVID-19 and Secukinumab treatment in Spondylarthritis patients during the omicron surge: a retrospective cohort study.

The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366-1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.

Case report: IgG4-related intracranial lesions mimicking multiple sclerosis in a 14-year-old girl.

Objectives: IgG4-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs. Even so, central nervous system lesions associated with IgG4-RD are scarce. We present a case of IgG4-related brain parenchymal lesions that mimics multiple sclerosis in a young girl. Methods: The patient was followed by our neurology and rheumatology teams. Clinical information was recorded, and the brain was screened using magnetic resonance imaging (MRI). During follow-up, we examined serum IgE, IgG and IgG4 and lymph node biopsy. Results: Here, we presented details of a 14-year-old Chinese girl suffering from diplopia, left eyelid ptosis, right facial numbness, and right lower limb weakness admitted to our institute. Brain MRI revealed multiple sclerosis-like lesions in the brain parenchyma and spinal cord. During the follow-up, she developed lymphadenopathy. Elevation of serum, IgG, IgG4 and IgE and lymph node biopsy favors a diagnosis of IgG4-RD. The patient had a good response to glucocorticoids and mycophenolate mofetil. The literature review summarized eight previously reported IgG4-RD involving brain parenchyma. Discussion: Our case expands the known age spectrum of IgG4-RD. The intracranial IgG4-RD is rare and could mimic multiple sclerosis. Careful examination and dynamic review of disease history are crucial in the differential diagnosis.

Significance of Serum Markers and Urinary Microalbumin in the Diagnosis of Early Renal Damage in Patients with Gout.

BACKGROUND: To explore the diagnostic value of changes in serum C-X-C Motif Chemokine Ligand 16 (CXCL16), cystatin C (CysC), cyclooxygenase-2 (COX-2), and urinary microalbumin (mALB) in patients with gout complicated by early renal damage. METHODS: A retrospective analysis of 47 patients with gout without complications and 48 patients with gout complicated by early renal damage was conducted in our hospital. A retrospective analysis was performed with 50 healthy people as controls. Serum IL-8, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), CXCL16, CysC, COX-2, and urine mALB levels were detected and analyzed, and the diagnostic efficacy of single factor and multifactor combined detection for early renal damage in patients with gout was analyzed and compared. RESULTS: Serum interleukin-8 (IL-8), TNF-α, IL-1ß, CXCL16, CysC, COX-2, and urine mALB/Cr levels of patients with gout were significantly higher than those of healthy people (p < 0.01). Serum IL-8, TNF-α, IL-1ß, CXCL16, CysC, COX-2 and urinary mALB/Cr levels in patients with gout complicated by early renal damage were significantly higher than those in patients with gout but without complications (p < 0.01). The sensitivity of CXCL16, CysC, COX-2, and mALB in diagnosing gout patients with early renal damage can reach 91.7%. CXCL16 and COX-2 were positively correlated with CysC and mALB/Cr, respectively, p < 0.01. The area under the ROC curve of CXCL16, CysC, COX-2, and mALB in the diagnosis of gout patients with early renal damage was 0.763, 0.832, 0.518, and 0.895, respectively. CONCLUSIONS: CysC and mALB are sensitive indicators for the diagnosis of early renal damage. The combined diagnosis of CXCL16 and COX-2 can effectively improve the detection sensitivity of early renal damage in patients with gout.

Primary Central Nervous System Angiosarcoma.

BACKGROUND: Primary angiosarcoma of the brain is an extremely rare malignant tumor that that arises from vascular endothelial cells of the brain or meninges. The presentation, characteristics, and prognosis of this disease are not well understood. Here we report such a case. CASE DESCRIPTION: A 68-year-old Chinese man presented with confusion and progressive impairment of right limb movement. Magnetic resonance imaging (MRI) revealed a hemorrhagic lesion in the left frontal lobe. Exploratory surgery revealed a hematoma-like lesion and extensive superficial hemosiderin deposition. The postoperative pathological diagnosis was angiosarcoma. The tumor recurred at 1 month after the operation, with extensive tumor regrowth in the left hemisphere. The patient died after 4 weeks. CONCLUSIONS: Although accurate preoperative diagnosis of angiosarcoma of the brain is difficult, radiologists and neurosurgeons need to be aware of this rare entity. The prognosis of intracranial angiosarcoma is heterogenous. Intraoperatively, the presence of extensive superficial hemosiderosis may aid in its diagnosis.

Bilateral and symmetric C1-C2 dumbbell ganglioneuromas associated with neurofibromatosis type 1: A case report.

BACKGROUND: Ganglioneuroma (GN) is a rare and benign tumor that originates from autonomic nervous system ganglion cells. The most frequently involved sites are the posterior mediastinum, the abdominal cavity, and the retroperitoneal space. It rarely occurs in the cervical area, compressing the spinal cord. Neurofibromatosis type 1 (NF-1) is an autosomal dominant inheritance disorder, whose prevalence rate approximates one per 3000. CASE SUMMARY: We report an extremely rare case of bilateral and symmetric dumbbell GNs of the cervical spine with NF-1. A 27-year-old man with NF-1 presented with a one-year history of gradually progressive right upper extremity weakness and numbness in both hands. Magnetic resonance imaging showed bilateral and symmetric dumbbell lesions at the C1-C2 levels compressing the spinal cord. We performed total resection of bilateral tumors, and the postoperative histopathological diagnosis of the resected mass was GN. After operation, the preoperative symptoms were gradually relieved without complications. To our knowledge, this is the sixth report of cervical bilateral dumbbell GNs. CONCLUSION: In some cases, cervical bilateral dumbbell GNs could be associated with NF-1. The exact diagnosis cannot be obtained before operation, and pathological outcome is the current gold standard. Surgical resection is the most effective option, and disease outcome is generally good after treatment.

HLA-B27 Correlates with the Intracellular Elimination, Replication, and Trafficking of Salmonella Enteritidis Collected from Reactive Arthritis Patients.

BACKGROUND The aim of this study was to explore the correlation between HLA-B27 and the intracellular elimination, replication, and trafficking of Salmonella enteritidis (S. enteritidis) collected from patients with reactive arthritis. MATERIAL AND METHODS Confocal microscopy, flow cytometry, and sandwich enzyme-linked immunosorbent assay (ELISA) were employed in this study to evaluate the localization of proteins of interest, to assess the intracellular trafficking of S. enteritidis, and to measure the production of cytokines of interest. RESULTS HLA-B27 was negatively associated with intracellular S. enteritidis elimination in healthy human monocytes/macrophages. In S. enteritidis infected monocytes/macrophages, HLA-27B was also negatively correlated with bacteria elimination but positively related to bacteria replication. S. enteritidis did not co-localize with NRAMP1 and LAMP1/2 in HLA-B27 cells. S. enteritidis did not co-exist with transferrin or dextran within HLA-B27 and A2 cells. CONCLUSIONS HLA-B27 is closely associated with the intracellular elimination and replication of S. enteritidis. Replicated bacteria in HLA-B27 monocytic cells were located within unique vacuoles rather than disturbing host endocytosis.

IL-1ß and IL-6 Are Highly Expressed in RF+IgE+ Systemic Lupus Erythematous Subtype.

Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with great heterogeneity in pathogenesis and clinical symptoms. Rheumatoid factor (RF) is one key indicator for rheumatoid arthritis (RA) while immunoglobulin E (IgE) is associated with type I hypersensitivity. To better categorize SLE subtypes, we determined the dominant cytokines based on familial SLE patients. Methods. RF, IgE, and multiple cytokines (i.e., IL-1ß, IL-6, IL-8, IL-10, IL-17, IFN-γ, IP-10, MCP-1, and MIP-1ß) were measured in sera of familial SLE patients (n = 3), noninherited SLE patients (n = 108), and healthy controls (n = 80). Results. Three familial SLE patients and 5 noninherited SLE cases are with features of RF+IgE+. These RF+IgE+ SLE patients expressed significantly higher levels of IL-1ß and IL-6 than the other SLE patients (P < 0.05). IL-6 correlated with both IgE and IL-1ß levels in RF+IgE+ SLE patients (r2 = 0.583, P = 0.027; r2 = 0.847, P = 0.001), and IgE also correlated with IL-1ß (r2 = 0.567, P = 0.031). Conclusion. Both IL-1ß and IL-6 are highly expressed cytokines in RF+IgE+ SLE subtype which may be related to the pathogenesis of this special SLE subtype and provide accurate treatment strategy by neutralizing IL-1ß and IL-6.

[Effects of altered IFNAR expression on CD4+ CD25+ treg cell dysfunction in patients with systemic lupus erythematosus].

OBJECTIVE: To explore the role of type I interferon (IFNalpha) on the function of CD4+ CD25+ regulatory T (Treg) cells in patients with systemic lupus erythematosus (SLE). METHODS: Twenty patients with newly-onset active SLE and 20 healthy controls were recruited in this study. The expressions of type I interferon a receptor (IFNAR) on Treg cells were analyzed using flow cytometry. CD4+ CD25+ Treg cells were purified by magnetic-activated cell sorter (MACS). The function of these cells was assessed in vitro with or without IFNalpha (500 U/mL). The effect of exogenous IFNalpha on the apoptosis of Treg cells and the expression level of FOXP3, CTLA-4, and pAKT in Treg cells were analyzed using flow cytometry. Results The expression levels of IFNAR1 on CD4+ CD25+ Treg cells were significantly higher in the SLE patients than in the healthy controls (P=0.0006). There was a positive correlation between the expression levels of IFNAR on Treg cells and the SLEDAI scores in the SLE patients. Exogenous IFNalpha impaired the suppressive capacity of Treg cells in the SLE patients. However, neither the apoptosis of Treg cells nor the expression levels of FOXP3 and CTLA-4 on Treg cells were influenced by IFNalpha stimulation. IFNalpha enhanced AKT phosphorylation in Treg cells in the SLE patients. CONCLUSION: Altered IFNAR expression may contribute to Treg cell dysfunction in SLE patients through enhancing AKT phosphorylation in Treg cells.

A case of isolated aorta occlusion caused by Takayasu arteritis.

PURPOSE: We report a rare case of Takayasu arteritis causing isolated complete obliteration of the aorta. A 24-year-old woman with night sweats, weight loss, and claudication was hospitalized because of refractory hypertension. Laboratory tests showed increased inflammatory indexes. Imaging studies revealed isolated complete occlusion of thoracic and abdominal aorta. Takayasu arteritis was diagnosed. Glucosteroids and revascularization surgery were given. Clinical symptoms were relieved immediately without relapse after operation. Revascularization surgery was the effective therapy for the patient.

Atrial myxoma with metastasis misdiagnosed as Takayasu arteritis.

The objective of the study is to report a case of atrial myxoma with bloodstream metastasis misdiagnosed to be Takayasu arteritis. A 23-year-old woman manifested with fever, repetitive vasocerebral events and extremities ischemic signs (claudication, difference of BP in arms and absence of pulse) for 5 years. Imaging studies revealed multiple cerebral infarction, bilateral iliac artery stenosis and as thrombosis formation. Takayasu arteritis was diagnosed according to American College of Rheumatology criteria. Glucosteroids and immunosuppressants were given; however, symptoms were not relieved even after treatment. Echocardiography suggested a mass in left atrium, which was surgically removed and pathologically confirmed to be atrial myxoma. Clinical symptoms completely relieved after operation. In conclusion, atrial myxoma with bloodstream metastasis sometimes presented with similar clinical symptoms of Takayasu arteritis and may lead to misdiagnosis of these two diseases. Usually, accepted diagnosis criteria are not enough in distinguishing these diseases. Echocardiography should be considered in these patients.