Background and Purpose-We conducted this study to determine, through use of multivariate analyses, the independent predictors of hematoma enlargement occurring after hospital admission in patients with spontaneous intracerebral hemorrhage (ICH). Methods-We reviewed 627 patients with ICH admitted within 24 hours of onset. The first CT was performed at admission and the second within 24 hours of admission, and a blood sample was taken for laboratory examinations. Univariate and multivariate analyses were performed to assess the relationships between hematoma enlargement and time from onset, consciousness level, CT findings, amount of alcohol consumption, systolic blood pressure at and after admission, clinical outcome, and hematologic parameters. Hematoma enlargement was an independent factor increasing the mortality rate in the ICH patients (OR, 1.57; PϽ0.001). Conclusions-A particularly high likelihood of hematoma enlargement was observed in patients who (in order of importance) were admitted shortly after onset, who were heavy drinkers; who had an irregularly shaped hematoma, whose consciousness was disturbed, and who had a low level of fibrinogen.

Background IgG4-related disease (IgG4-RD) is a systemic condition of unknown etiology, characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4+ T cells constitute the major inflammatory cell population in IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T cell subsets in IgG4-RD subjects based on their clonal expansion and their ability to infiltrate affected tissue sites. Methods We used flow cytometry to identify CD4+ effector/memory T cells (TEM) in a cohort of 101 IgG4-related disease (IgG4-RD) patients. These expanded cells were characterized by gene expression analysis and flow cytometry. Next-generation sequencing of the T cell receptor β chain gene was performed on CD4+SLAMF7+ CTLs and CD4+GATA3+ TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined using quantitative multi-color imaging. Results CD4+ effector/memory T cells with a cytolytic phenotype were expanded in IgG4-RD patients. Next-generation sequencing revealed prominent clonal expansions of these CD4+CTLs but not CD4+GATA3+ memory TH2 cells in subjects with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally-expanded CD4+CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B cell depletion was associated with a reduction in disease-associated CD4+ CTLs Conclusions IgG4-RD is prominently linked to clonally-expanded, IL-1β, and TGF- β1 secreting, CD4+ CTLs in peripheral blood as well as in inflammatory tissue lesions. These active, terminally-differentiated, cytokine-secreting effector CD4+ T cells are now linked to a human disease characterized by chronic inflammation and fibrosis.

In order to evaluate the incidence and risk factors of hematoma enlargement in spontaneous intracerebral hemorrhage (ICH), 419 cases of ICH were reviewed. The first computerized tomography (CT) scan was performed within 24 hours of onset and the second within 24 hours of admission; a blood sample was taken for laboratory examination within 1 hour of admission. In 60 patients (14.3%) the second CT scan showed an enlarged hematoma. The incidence of enlargement significantly decreased with time (p < 0.05) and significantly increased with the severity of liver dysfunction and the volume of the hematoma on the first CT scan. Patients with an irregularly shaped hematoma had a higher risk of hematoma growth than those with a round hematoma. In addition, patients with hematoma enlargement were more likely to have coagulation abnormalities (low platelet counts and low levels of fibrinogen, alpha 2-antiplasmin activity and platelet aggregation). Moreover, hematoma growth was associated with a poor clinical outcome. It is concluded that patients admitted to a hospital within 6 hours of onset of ICH, especially those admitted within 2 hours, and patients with liver dysfunction or irregularly shaped large hematomas should be closely observed for at least 6 hours after onset in preparation for emergency surgery, since the risk of hematoma growth in these circumstances is high.

To determine the incidence of, and risk factors for, the occurrence of rebleeding between admission and early operation (ultra-early rebleeding) in patients with spontaneous subarachnoid hemorrhage (SAH), the authors reviewed the cases of 179 patients admitted within 24 hours after their last attack of SAH. Thirty-one (17.3%) of these patients had ultra-early rebleeding despite scheduling of early operation (within 24 hours after admission). The incidence of rebleeding significantly decreased as the time interval between the last attack and admission increased. Patients with rebleeding before admission, high systolic blood pressure, intracerebral or intraventricular hematoma, those in poor neurological condition on admission, and those who underwent angiography within 6 hours of the last SAH were significantly more likely to have ultra-early rebleeding than those without these factors. The incidence of rebleeding also significantly increased as levels of enhancement of platelet sensitivity and thrombin-antithrombin complex increased. Multivariate analysis revealed that the following three factors were independently associated with ultra-early rebleeding: the level of enhancement of platelet sensitivity; the time interval between the last attack and admission; and the level of thrombin-antithrombin complex. On the basis of these findings, the authors suggest that many of the risk factors for ultra-early rebleeding are interrelated. A particularly high risk of ultra-early rebleeding was observed in those patients 1) who had platelet hypoaggregability; 2) who were admitted shortly after their last SAH; and 3) whose thrombin-antithrombin complex levels were extremely high and were thus in severe clinical condition.

Objective Mikulicz disease has been considered to be a subtype of Sjögren's syndrome (SS). However, recent studies have suggested that Mikulicz disease is an IgG4‐related disease and is distinguishable from SS. In addition, it has been reported that both interleukin‐4 (IL‐4) and IL‐10 induce IgG4 production and inhibit IgE. This study was undertaken to examine the expression of these cytokines in patients with Mikulicz disease and patients with SS. Methods Labial salivary gland (LSG) sections from 15 patients with Mikulicz disease and 18 patients with SS were examined for subsets of the infiltrating lymphocytes, expression patterns of messenger RNA (mRNA) for cytokines/chemokines, and relationships between the IgG4:IgG ratio and the expression of mRNA for IL‐4 or IL‐10. Results Immunohistochemical analysis showed lymphocyte infiltration of various subsets in the LSGs of SS patients, and the selective infiltration of IgG4‐positive plasma cells and Treg cells in the LSGs of Mikulicz disease patients. The levels of mRNA for both Th1 and Th2 cytokines and chemokines in LSGs from patients with SS were significantly higher than in controls, while the expression of both Th2 and Treg cells was significantly higher in the patients with Mikulicz disease than in controls. Furthermore, the expression of IL‐4 or IL‐10 in the LSGs was correlated with the IgG4:IgG ratio. Conclusion These results suggest that the pathogenesis of Mikulicz disease is different from that of SS. Mikulicz disease is a unique inflammatory disorder characterized by Th2 and regulatory immune reactions that might play key roles in IgG4 production.

Objectives IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. Methods Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren’s syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. Results In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. Conclusions The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+GZMA+ CTLs that secrete IFN-γ.

Objectives Interleukin (IL)-21 is mainly produced by CD4 T helper (Th) cells including Th2, Th17 and follicular helper T (Tfh) cells. Recent studies have reported that IL-21 is involved in the formation of germinal centres (GCs) and class switching of IgG4. It has been suggested that IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease (MD), is distinct from Sjögren's syndrome (SS) and shows a high frequency of GC formation in salivary glands. In this study the expression of IL-21 in IgG4-DS and SS patients was examined. Methods Twelve patients with IgG4-DS, 15 with SS and 15 healthy subjects were screened for (1) ectopic GC formation in formalin-fixed labial salivary gland (LSG) biopsy samples; (2) expression of IL-21, Th2-, Th17-and Tfh-related molecules (cytokines, chemokine receptors and transcription factors) in LSGs; (3) relationship between IgG4/IgG ratio and mRNA expression of IL-21 in LSGs.Results mRNA expression of IL-21 and Bcl-6 in LSGs from patients with IgG4-DS was significantly higher than in patients with SS and controls. IL-21 and CXCR5 were detected by immunohistochemistry in or around GC in patients with SS and those with IgG4-DS. IL-21 was detected in infiltrating lymphocytes outside GC only in patients with IgG4-DS. Expression of IL-21 was consistent with that of Th2-related molecules while IL-17 was rarely seen in IgG4-DS. Furthermore, the expression of IL-21 in LSGs was correlated with the number of GC formations and the IgG4/IgG ratio in patients with IgG4-DS. Conclusions These results suggest that overexpression of IL-21 by Th2 cells might play a key role in GC formation and IgG4 production in IgG4-DS.

The incidence of uterine scar defects 1 month after cesarean sections varies with the method applied for myometrial suture and perioperative variables. The data suggest that methods for myometrium closure as well as other factors influence the condition of myometrial healing.