The Clinical Effects of Febuxostat Alone or Combined with Arthroscopic Surgery for Gout: A Single-Center Retrospective Study.

PURPOSE: The purpose of the study was to retrospectively analyze the effects of febuxostat combined with arthroscopic debridement of monosodium urate crystal deposition and febuxostat treatment alone on uric acid levels and acute flares in gout patients. PATIENTS AND METHODS: We retrospectively analyzed gout patients who were treated from February 2016 to December 2020. Patients were divided into a control group (febuxostat treatment alone) or a combined group (febuxostat combined with arthroscopic surgery). We recorded and analyzed clinical data including age, sex, body mass index, comorbidities, lesion affected joints, acute flare times, medications history, febuxostat side effects, arthroscopic complications, and serum creatinine and uric acid levels changes. RESULTS: There were 80 patients in the control group and 93 patients in the combined group. At the beginning of treatment, the combined group had significantly higher disease severity (higher serum uric acid levels and more acute gout flare times). Arthroscopy was performed in 61 knees and 38 ankles, and 86 joints showed crystals deposition. Compared with baseline, follow-up results showed that serum creatinine significantly decreased in the combined group, and serum uric acid and acute gout flare times significantly decreased in both groups (all p < 0.05). In the comparison between the two groups at the follow-up endpoint, acute gout flare times did not differ significantly (p > 0.05), however, serum creatinine and uric acid levels were lower in the combined group compared with those in the control group (ps < 0.05). CONCLUSION: Febuxostat combined with arthroscopic debridement of monosodium urate crystal deposition or tophi had a superior effect on lowering uric acid levels and acute flare times in gout patients than did febuxostat alone.

Arg972 insulin receptor substrate-1 polymorphism and risk and severity of rheumatoid arthritis.

AIM: To explore the association between the Arg(972) insulin receptor substrate (IRS)-1 polymorphism (rs1801278) and the risk and disease activity/severity of rheumatoid arthritis (RA). METHOD: We genotyped the Arg(972) IRS-1 polymorphism in 871 pairs of age-, sex-, body mass index-, residence area- and current smoking status-matched RA patients and controls. We assessed RA severity using the disease activity score of 28 joints (DAS28). RESULTS: The AA (homozygous Arg(972) IRS-1) and GA (heterozygous Arg(972) IRS-1) genotypes were significantly associated with high risk of RA with or without adjustment for comorbidities (P < 0.001). The A allele was significantly associated with high risk of RA (P < 0.001). The AA genotype was significantly associated with high/severe RA activity (P < 0.001), while the GG genotype (wild type IRS-1) had protective effects. CONCLUSION: The Arg(972) IRS-1 polymorphism is associated with increased risk and disease activity/severity of RA, and therefore may be a potential prognostic factor for RA. This study adds novel insights into the pathogenesis of RA.

Arg972 insulin receptor substrate-1 enhances tumor necrosis factor-α-induced apoptosis in osteoblasts.

The presence of Arg972 insulin receptor substrate-1 (IRS-1) is associated with impaired insulin/IRS-1 signaling to activate phosphatidylinositol-3 kinase (PI3K). Tumor necrosis factor-α (TNF-α), an inflammatory cytokine with a central role in the pathogenesis of rheumatoid arthritis (RA), induces apoptosis in osteoblasts, which are the principal cell type responsible for bone loss in RA. In our previous study, an association between Arg972 IRS-1 and a high risk and severity of RA was identified. In the present study, the effects of Arg972 IRS-1 and IRS-1 on TNF-α-induced apoptosis in human osteoblasts were examined. Normal and RA osteoblasts were stably transfected with Arg972 IRS-1 and IRS-1. In addition, cells were stably transduced with IRS-1-shRNA to knock down IRS1. Following stimulation with 10 nM insulin for 30 min, the stable overexpression of Arg972 IRS-1 and knock down of IRS-1 significantly decreased IRS-1-associated PI3K activity and Akt activation/phosphorylation at serine 473 (ser473) and enhanced TNF-α-induced apoptosis in normal and in RA osteoblasts. By contrast, the stable overexpression of IRS-1 significantly increased the levels of IRS-1-associated PI3K activity and Akt phosphorylation (ser473) and inhibited TNF-α-induced apoptosis, which was eliminated by pretreatment with 50 µn BJM120, a selective PI3K inhibitor, for 30 min. In conclusion, the present study provided the first evidence, to the best of our knowledge, that insulin stimulation of Arg972 IRS-1 and IRS-1 enhanced and inhibited TNF-α-induced apoptosis, respectively in normal and RA osteoblasts by a PI3K­dependent mechanism. These findings suggest that insulin/IRS-1 signaling is important in the pathogenesis of RA.

[Clinical study of invasive fungal infection secondary to systemic lupus erythematosus].

OBJECTIVE: To study the clinical characteristics of invasive fungal infection secondary to systemic lupus erythematosus (SLE). METHODS: We observed the clinical features and experimental examination in 91 patients treated in Xiangya Hospital in recent years, of which 48 patients with invasive fungal infection and 41 patients without invasive fungal infection. RESULTS: The invasive fungal infection secondary to SLE mainly occurred in the lungs, nervous system, and urinary system. The fungi were mainly Candida albins and Aspergillus. The rate of invasive fungal infection in SLE patients and the level of CRP and TNF-α in these patients were significantly increased. The occurrence of invasive fungal infection was positively correlated with the prolonged course of disease, long-term use of immunosuppressants and antibiotics, and occurrence of complications, such as hypoproteinemia, leukocytopenia, and so on. The levels of C-reactive protein (CRP) and tumor necrosis factor-α(TNF-α) were increased in SLE patients with invasive fungal infection. CONCLUSION: The clinical features of SLE patients with invasive fungal infections are long course of disease, long-time use of immunosuppressants or antibiotics, and occurrence of complications, such as hypoproteinemia or leukopenia. The level of CRP and TNF-α can be used as an important reference index for diagnosing invasive fungal infections.