Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.
BACKGROUND:The MAP2K1 K57T mutation is known to be a potential mechanism of primary and secondary resistance to EGFR inhibitors in metastatic colorectal cancer (CRC) and has also been reported to promote resistance to BRAF and MEK inhibitors. It is important to overcome therapeutic resistance to EGFR inhibitors to improve the treatment outcomes of metastatic CRC.METHODS: We established patient-derived tumor cells (PDCs) from metastatic lesions that newly appeared during treatment with a BRAF inhibitor (LGX-818) plus an EGFR inhibitor (cetuximab) in a patient with BRAF-mutant CRC. To investigate therapeutic options to overcome acquired resistance due to MAP2K1 mutation in BRAF-mutant CRC, we performed cell viability assays using the PDCs.RESULTS:We tested whether the PDCs were resistant to an EGFR inhibitor (cetuximab) and a BRAF inhibitor (sorafenib) as these cells were established at the time of resistance to the EGFR plus BRAF inhibitors. Moreover, the anti-tumor effect of AZD6244 (MEK inhibitor) was evaluated because PDCs harbored a MAP2K1 mutation at the time of resistance to the EGFR plus BRAF inhibitors. MTT proliferation assays showed that monotherapy with cetuximab, sorafenib, or AZD6244 did not suppress cell viability. We next tested viability of the PDCs to combination treatment with cetuximab plus AZD6244 and sorafenib plus AZD6244. Proliferation of PDCs was significantly inhibited by sorafenib and AZD6244, but not by cetuximab plus AZD6244. Investigation of the combined effect of sorafenib and AZD6244 using the calculated combination index (CI) showed synergistic effects of sorafenib and AZD6244 in combination therapy applied to PDCs with the MAP2K1 K57T mutation.CONCLUSION:Our results suggest that combination treatment with BRAF and MEK inhibitors might be a novel treatment strategy for MAP2K1 K57T-mutant CRC. This finding will be helpful to guide treatment of patients with CRC that is resistant to EGFR inhibitors.
Background Although pharmacokinetic profile of subcutaneous infliximab (SC IFX) is superior to conventional intravenous infliximab (IV IFX), long-term efficacy and safety of SC IFX have not been compared with those of IV IFX in patients with inflammatory bowel disease (IBD). This cohort study aimed to evaluate the loss of response (LOR) and durable remission in IBD patients treated with SC IFX after switching from IV IFX compared with those in IBD patients who continued IV IFX. Methods This prospective cohort study enrolled 61 IBD patients with clinical remission who received scheduled IFX maintenance therapy from May to September 2022. Of them, 38 patients were switched to SC IFX with a shared decision-making between patients and physician. After dose optimization, they were followed up for one year. Clinical remission was defined as HBI < 5 in in patients with Crohn's disease (CD) and partial Mayo ≥ 2 in in patients with ulcerative colitis (UC). Biochemical relapse was defined as CRP ≥ 0.5 mg/dL in patients with CD and UC. Results LOR occurred in three (8%) patients of the SC IFX group and 5 (22%) patients of the IV IFX group, showing no significant difference between both groups (p = 0.140). The clinical and biochemical remission were not significantly different between the SC and IV groups (clinical remission: 20/23, 87% vs 33/38, 87%, p = 1.000; biochemical remission: 22/23, 96% vs. 34/38 89%, p = 0.641). The patients with IFX trough level < 3 μg/mL was significantly lower in the SC IFX group (0/38, 0%) than in the IV IFX group (10/23, 43%; p < 0.001). The incidence of IFX-related adverse events did not differ significantly between both groups (26% vs. 39%; p = 0.446). Conclusion SC IFX switch induced similar 1-year durable remission rate and safety profile with continuing IV IFX in patients with IBD during maintenance therapy. Pharmacokinetic profile was superior in patients treated with SC IFX compared with IV IFX.
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