Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients’ disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity

Protective Role of HLA-DRB1*13:02 against Microscopic Polyangiitis and MPO-ANCA-Positive Vasculitides in a Japanese Population: A Case-Control Study

Among antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), granulomatosis with polyangiitis (GPA) and proteinase 3-ANCA-positive AAV (PR3-AAV) are prevalent in European populations, while microscopic polyangiitis (MPA) and myeloperoxidase-ANCA-positive AAV (MPO-AAV) are predominant in the Japanese. We previously demonstrated association of DRB1*09:01-DQB1*03:03 haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in HLA-class II plays a role in the epidemiology of this disease. To gain further insights, we increased the sample size and performed an extended association study of DRB1 and DPB1 with AAV subsets in 468 Japanese patients with AAV classified according to the European Medicines Agency algorithm (MPA: 285, GPA: 92, eosinophilic GPA [EGPA]: 56, unclassifiable: 35) and 596 healthy controls. Among these patients, 377 were positive for MPO-ANCA and 62 for PR3-ANCA. The significance level was set at α = 3.3x10-4 by applying Bonferroni correction. The association of DRB1*09:01 with MPO-AAV was confirmed (allele model, P = 2.1x10-4, odds ratio [OR] = 1.57). Protective association of DRB1*13:02 was detected against MPO-AAV (allele model, P = 2.3x10-5, OR = 0.42) and MPA (dominant model, P = 2.7x10-4, OR = 0.43). A trend toward increased frequency of DPB1*04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1*13:02 (Padjusted = 0.0021, ORadjusted = 3.48). In contrast, the frequency of DPB1*04:01 was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on DRB1*13:02 (Padjusted = 0.16), suggesting that DRB1*13:02 or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of DPB1*04:01 with PR3-AAV and MPO-AAV and difference in DPB1*04:01 allele frequencies between populations supported the hypothesis that the HLA-class II population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying DRB1*13:02 was suggested to be a shared protective factor against multiple autoimmune diseases

Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow

Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and can give rise to multiple mesenchymal lineages. Because MSCs have only been isolated from tissue in culture, the equivalent cells have not been identified in vivo and little is known about their physiological roles or even their exact tissue location. In this study, we used phenotypic, morphological, and functional criteria to identify and prospectively isolate a subset of MSCs (PDGFRα+Sca-1+CD45−TER119−) from adult mouse bone marrow. Individual MSCs generated colonies at a high frequency and could differentiate into hematopoietic niche cells, osteoblasts, and adipocytes after in vivo transplantation. Naive MSCs resided in the perivascular region in a quiescent state. This study provides the useful method needed to identify MSCs as defined in vivo entities

<原著>二酸化炭素気腹で抑制される豚の門脈血流量はドパミン投与によって回復する

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF) and systemic arterial pressure (SAP) were examined after dopamine (DA) injection into the jugular vein under carbon dioxide pneumoperitoneum in pigs. When intraabdominal pressure (IAP) was increased by 12 mmHg, PVF and HAF were reduced, but SAP was unchanged. When IAP was kept at 12 mmHg, the injection of DA at 10 μg/kg/min for 2 min produced an increase in PVF without causing any change in HAF or SAP. The response in PVF was dose-dependent. When IAP was increased to 16 mmHg, PVF response was diminished, and no change in HAF or SAP was seen at the same dose of DA. These observations suggest that DA is effective in increasing PVF under enhanced IAP conditions, but such circulatory improvement due to the agent would be prominent when IAP is below 12 mmHg.豚を用いて二酸化炭素気腹下でドパミンの頸静脈投与が門脈血流量, 肝動脈血流量, 体血圧に対する影響を調へた腹腔内圧を 12 mmHg まで高めると, 門脈と肝動脈血流量は減少したが, 体血圧には変化を認めなかった. 腹腔内圧を 12 mmHg で維持した状態で, ドパミン 10 μg/kg/min で2分間の投与は肝動脈血流量と体血圧に変化を与えることなく, 門脈血流量を増加させた. こうしたドパミンによる門脈血流量反応は用量依存性を示した. 腹腔内圧 16 mmHg では同用量のドパミンの投与で, 門脈血流量反応は低下したが, 肝動脈血流量と体血圧には変化を認めなかった. これらの観察から, ドパミンは腹腔内圧上昇時に肝門脈血流量を増加させること, しかしそうしたドパミンの肝循環改善効果は腹腔内圧 12 mmHg 以下で顕著であることを導いた

Right-sided Bochdalek hernia in an elderly adult: a case report with a review of surgical management

Abstract Background Bochdalek hernias are one of the most common types of diaphragmatic hernia, with most cases diagnosed during the neonatal period. In contrast, diagnosis of a Bochdalek hernia in an adult is rare and is typically observed on the left side of the diaphragm. Even more rare is the diagnosis of a right-sided Bochdalek hernia in an adult, where there is concurrent visceral malformation in most cases. Case presentation We describe a case of an 89-year-old female who presented with abdominal pain. An abdominal computed tomography (CT) scan showed decreased intravenous contrast uptake and thickening of the wall of herniated small intestine through the right side of the diaphragm, which led to the diagnosis of a strangulated diaphragmatic hernia. The patient underwent emergent laparotomy and required a partial resection of the necrotic ileum and a hernia repair with direct closure. Interestingly, in this case, organ malformation was not observed. The patient was discharged approximately 2 weeks after surgery without complication. Conclusions Adult right-sided Bochdalek hernia with strangulation in the absence of hepatic atrophy is a rare entity. Considering the severity of this condition, accurate diagnosis and proper treatment are needed. A tailored operative approach is required on an individual case basis

Breast Signet-ring Cell Lobular Carcinoma Presenting with Duodenal Obstruction and Acute Pancreatitis

We report here an extremely rare case of breast signet-ring cell carcinoma (SRCC) initially manifesting as duodenal metastasis and acute pancreatitis. A 62-year-old female presented with duodenal obstruction and swollen head of the pancreas, and the diagnosis of acute pancreatitis was initially made. Upper gastrointestinal endoscopy revealed duodenal stenosis with erosive mucosa, with signet-ring cells infiltrating the submucosal layer, suggesting duodenal metastasis of SRCC. Despite absence of a palpable mass in both breasts, computed tomography revealed diffuse enhancement of the left breast in addition to left axillary lymphadenopathy. Histological examination of mammary needle biopsy samples revealed SRCC with a non-invasive lobular carcinoma component. Primary breast SRCC with duodenal metastasis was therefore diagnosed. The patient underwent palliative surgery twice for intestinal obstruction due to peritoneal dissemination. She has remained alive without bowel obstruction for 18 months while being treated with cytotoxic chemotherapies