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Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C- and C-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

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In a histologic re‐examination and reclassification of a series of 1678 tumors of the parotid gland, 63 (3.7%) exhibited the structures characteristic of mucoepidermoid carcinoma. A long‐term follow‐up study showed that mucoepidermoid carcinoma differs from acinic cell and adenoid cystic carcinoma in that the determinate survival rate does not fall markedly when the follow‐up exceeds 5 years. This implies that the prognosis based on the determinate survival rate can be evaluated after a 5‐year follow‐up study. Histologically, the 63 tumors have been divided into two subgroups, one consisting of 20 tumors exhibiting invasive growth (high grade malignant) and the other of 43 without invasive growth (low grade malignant). The follow‐up study showed the difference between the prognosis in the two groups. In order to improve the poor prognosis in high grade malignant mucoepidermoid carcinoma, the authors recommend that parotidectomy should be routinely combined with radical neck dissection in high grade malignant tumors.