ObjectivesTo collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis.MethodsFifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.ResultsThe study population comprised 26 males and 24 females aged 0–61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.ConclusionsIn patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.

We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1–10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16; VGIH, n = 15); 31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.

BackgroundIntrauterine inflammation has been associated with preterm birth and neonatal complications. Few reports have comprehensively investigated multiple cytokine profiles in cord blood and precisely identified surrogate markers for intrauterine inflammation.AimTo identify the cytokines and surrogate markers associated with intrauterine inflammation and subsequent neonatal complications.Patients and methodsWe analyzed cord blood samples from 135 patients admitted to the neonatal intensive care unit at Sasebo City General Hospital. We retrospectively determined the associations between the presence of neonatal complications and cord blood cytokines, prenatal factors, and laboratory data at birth. A total of 27 cytokines in the cord blood were measured using a bead-based array sandwich immunoassay.ResultsBoth Th1 and Th2 cytokine levels were low, whereas the levels of growth factors and chemokines were high. In particular, chemokines IL-8, MCP-1, and MIP-1α were significantly higher in very premature neonates when compared with more mature neonates. In addition, some have been shown to be associated with multiple neonatal complications, including patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Similarly, the levels of N-terminal pro-brain natriuretic peptide, nucleated RBC, and urinary β2-microglobulin were associated with these complications and chemokine levels.ConclusionsOur results suggest the association of inflammatory chemokines IL-8, MCP-1, and MIP-1α with intrauterine inflammation, premature birth, and neonatal complications in these perinatal subjects. Furthermore, the association of the aforementioned biomarkers with PDA, RDS, and CLD may help establish early diagnostic measures to predict such neonatal complications following intrauterine inflammation.

In this study, plaque‐like lesions, epithelial hyperplasias, and papillary invasive carcinomas were produced in the tongues of hamsters by the application of DMBA combined with trauma for 16 weeks. The junction between the neoplastic epithelial cells and the connective tissue was studied ultrastructurally. In plaque‐like lesions, the basal lamina was partially decreased in both thickness and density or partially discontinuous. In epithelial hyperplasias, cytoplasmic projections were observed in the portion of the basal cell near the intercellular space, and the basal lamina was absent around these cytoplasmic projections. In papillary invasive carcinomas, however, numerous cytoplasmic projections extended from various portions of the basal surface of the basal cells into the underlying connective tissue. The basal lamina was also absent around these projections. In epithelial hyperplasias and papillary invasive carcinomas, some of the cytoplasmic projections appeared almost empty, some contained a small number of tonofilaments and ribosomes, and others were filled with a large number of ribosomes but did not contain the tonofilaments. The collagen fibrils were markedly reduced in number in the area around cytoplasmic projections. The cytoplasm of some fibroblasts in that area contained many intracellular collagen fibrils.