ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.

HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10(-6) and 0.0011, OR: 1.57 (1.28-1.91) and 1.37 (1.13-1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21-1.89) and 3.08 (1.68-5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote

Multiple fusiform aneurysms of the distal middle cerebral artery showing different radiological courses: A case report

Middle cerebral artery (MCA) fusiform aneurysms may occur in the proximal MCA, and distal MCA fusiform aneurysms are rare. Here we present a rare case of subarachnoid hemorrhage (SAH) with multiple fusiform aneurysms in the M3 portion, which showed different morphological changes. A 43-year-old left-handed man with sudden aphasia and left-side hemiparesis had SAH with intraparenchymal hemorrhage in the right parietal lobe. Digital subtraction angiography (DSA) revealed multiple fusiform aneurysms in the M3 portion. Repeat DSA performed on day 29 demonstrated morphological changes in one fusiform aneurysm. We performed aneurysm trapping, and pathological examination indicated a dissecting aneurysm. Three-dimensional computed tomography angiography performed 4 months after onset revealed a decrease in other fusiform aneurysmal dilatations. This case showed two different clinical courses of fusiform aneurysms (regrowth and reduction). Frequent and close radiological examinations are necessary for ruptured multiple fusiform aneurysms. Keywords: fusiform aneurysm, middle cerebral artery, dissecting aneurys

Effects of tofacitinib on the clinical features of periodontitis in patients with rheumatoid arthritis: two case reports

Abstract Background The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines play an important pathologic role. There is evidence to suggest that inhibitors of tumor necrosis factor (TNF) and interleukin-6 (IL-6) receptor for the treatment of RA ameliorated periodontal inflammation. However, no study has evaluated the effect of tofacitinib, an oral Janus kinase inhibitor for the treatment of RA, on periodontitis. Case presentation The present report cases are 51- and 43-year-old non-smoking women with RA who demonstrated localized moderate chronic periodontitis. Both cases showed improvement in the periodontal inflammatory condition after 3 months of tofacitinib therapy, although the teeth count and supragingival bacterial plaque level were relatively unchanged. Improvements were also observed in the serum levels of IL-6 in both cases as well as in the serum levels of TNF-α and anti-cyclic citrullinated peptide immunoglobulin G in one case and of rheumatoid factor and matrix metalloproteinase-3 in the other case. Patients who received tofacitinib exhibited an inconsistent clinical response, likely due to the low disease activity of RA at the start of the administration. Conclusions These are the first reported cases in which tofacitinib may have a beneficial effect on periodontitis. However, more research is required to understand the relationship between periodontitis and tofacitinib therapy

Relationship between normalized distributional pattern and functional outcome in patients with acute cardiogenic cerebral embolism.

This study aimed to elucidate spatial characteristics for magnetic resonance imaging (MRI) of cardiogenic cerebral embolism, to determine imaging biomarkers predicting patient outcome and cerebral herniation in cardioembolic stroke. This retrospective study assessed 90 patients with cardiogenic cerebral embolism. All images from MRI were normalized using a voxel-based symptom lesion mapping technique. Patients were categorized into two subgroups based on the outcome and presence of cerebral herniation. Each subgroup was assessed individually. The distribution map of all analyzed patients revealed accumulated ischemic lesions in bilateral middle cerebral artery areas. Ischemic lesions for the poor outcome group accumulated at the corona radiata on the right side and throughout the entire left hemisphere. Receiver operating characteristic (ROC) analysis suggested that a normalized ischemic volume of 62.8 mL allowed optimal differentiation between good and poor outcomes (sensitivity, 0.923; specificity, 0.923; area under the curve (AUC), 0.91) for left-side-dominant infarction. The distribution map for the cerebral herniation group revealed large ischemic areas in the left hemisphere. The analysis of differential involvement map with random permutation analysis showed that left anterior circulation infarcts were associated with midline shift. Receiver operating characteristic analysis revealed that a normalized infarction volume of 192.9 mL was highly predictive of cerebral herniation (sensitivity, 0.929; specificity, 0.750; AUC, 0.895). The medial frontal and occipital lobes, caudate head and basal ganglia were significantly involved in those patients who developed cerebral herniation. Ischemic volume contributed to outcomes and cerebral herniation. Ischemic lesions of the anterior and posterior cerebral arteries and basal ganglia in addition to middle cerebral artery area were identified as differences on MRI images between with and without cerebral herniation patients