Summary: Combination chemotherapy with platinum preparations is the standard first-line treatment for stage IIIB/IV non-small-cell lung cancer. However, the median survival in patients receiving this therapy is 8 to 10 months, and it is essential to improve the results of chemotherapy in non-small-cell lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors hinder EGFR signal transmission by binding to the adenosine triphosphate binding site of intracellular tyrosine kinase and inhibiting the autophospholylation of EGFR. They are a standard initial treatment option in EGFR gene mutation-positive patients. In Japan, gefitinib is routinely used. A combination of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and another antineoplastic drug may be a strategy to further improve treatment outcomes. We planned a randomized phase 2 trial to assess the efficacy and safety of gefitinib plus bevacizumab in such patients. In this study, subjects will be assigned to receive monotherapy with gefitinib (GEF group) or combination therapy with gefitinib and beva cizumab (GEF+BEV group) as the initial treatment at a ratio of 1:1. EGFR gene mutations are frequently detected in Asian patients with non-small-cell lung cancer. This study may be significant for establishing a new standard treatment.
Summary: In total hip arthroplasty (THA), it is generally accepted that the bones of the acetabular cup and femur of hip joint must be accurately cut and components (artificial joint parts) be implanted in exact positions at exact angles to achieve improvement of daily living (ADL) and quality of life (QOL). However, with the conventional surgical method, it is difficult to grasp and measure the acetabular cup and femoral stem precisely during surgery, making some kind of reliable guide necessary. Although it was reported that an accurate angle was achieved in acetabular cup implantation by support instruments for surgical planning, an effective support instrument is now being developed for stem implantation on the out-of-reach femur side. This is the first clinical study to assess the efficacy and safety of anterolateral approach THA using an extracorporeal patient-specific femoral guide (PSG) for stem implantation with three-dimensional (3D) surgical support software in patients with hip joint disease.
Summary: Introduction: The gall bladder (GB) is a storage reservoir that allows bile acids to be delivered in a high concentration. The quadrate (QL) and caudate lobes (CL) are functional parts of the liver. The knowledge of the gross and developmental anatomy of GB and CL and QL of liver is important for surgeons who operate in this region. The present study was conducted to examine the developmental sequence and morphometry of the GB, and CL and QL of liver.
Materials and Methods: In the present cross sectional study the parameters measured were length of GB from the neck to the lowest point on the fundus, and the length and width of QL and CL measured at the midpoint. The data was analyzed statistically and the various parameters were correlated using Pearson’s correlation.
Results: There was a statistically significant correlation indicating that the growth of GB, QL and CL was proportional to the gestational age (GA). The variations in the morphology of the GB were also noted. In two specimens it was found that the GB was embedded partially in the substance of the liver and failed to reach the inferior border of the liver.
Conclusion: The regression equations calculated in the study provide a tool to estimate the lengths of GB, QL and CL prenatally.
Summary: Objectives: Relapsing polychondritis (RP) is a very rare autoimmune disorder characterized by recurrent episodes of inflammation and destruction of cartilaginous tissues. We examined the clinical characteristics, management, and outcomes of Japanese RP patients.
Methods: We identified 8 RP cases in our department between 2003 and 2017. Detailed clinical features, testing, treatment, and outcomes were recorded.
Results: The mean time from symptom onset to diagnosis was 9 months. Four cases presented with auricular chondritis and laryngotracheal involvement and 3 cases presented with a saddle nose deformity. Anti-type II collagen antibody was positive in 5 of 6 cases. Of 3 cases with associated diseases (rheumatoid arthritis, ulcerative colitis, and Sjögren’s syndrome), 2 died of respiratory failure.
Conclusions: When RP is diagnosed, early computed tomography or pulmonary function testing is essential to enable early treatment. Undiagnosed airway involvement can cause tracheobronchial wall fibrosis, leading to fixed stenosis.
Summary: The SEM Glove developed by Bioservo Technologies AB is a new device that increases grip and pinch force. The purpose of this study was to evaluate the effectiveness of the device on the grip and pinch strength of patients with functional disorders of the fingers.
Materials and Method: 30 hospitalized patients with upper limb functional disorder were enrolled. The assistance of the device for the grip and pinch strength of each subject were assessed by the difference between the measured values with and without the SEM Glove. The 95% confidence interval of the difference was calculated across the subjects, and statistical significance was defined as when the lower limit was a positive value (corresponding with a paired t-test at a significance level of 0.05). The odds ratio was calculated in the study of subject adaptation, with statistical significance set using Fisher’s exact test at a significance level of 0.05.
Results: Grip strength significantly decreased (worn-not worn difference (kg): mean = –3.7, CI95 (–5.4, –2.1)). Pinch strength (thumb - middle finger) significantly increased (worn-not worn difference (N): mean = -4.1, CI95 (1.6, 6.6)). Analysis of factors related to improvement in hand function when wearing the SEM Glove extracted manual muscle tests (MMTs) of the upper extremity 4 or higher. The odds ratio was 6.11.
Conclusions: Use of the SEM Glove improved the pinch strength of patients with functional disorders of the hands.
Summary: Aims/Introduction: Several lines of evidence suggest that dysregulation of the WNT signaling pathway is involved in the pathogenesis of type 2 diabetes. This study was performed to elucidate the effects of a high-fat/high-sucrose (HF/HS) diet on pancreatic islet functions in relation to modulation of WNT ligand expression in β-cells.
Materials and Methods: Mice were fed either standard mouse chow or a HF/HS diet from 8 weeks of age. At 20 weeks of age, intraperitoneal glucose tolerance tests were performed in both groups of mice, followed by euthanasia and isolation of pancreatic islets. WNT-related gene expression in islets and MIN6 cells was measured by quantitative real-time RT-PCR. To explore the direct effects of WNT signals on pancreatic β-cells, MIN6 cells were exposed to recombinant mouse WNT4 protein (rmWNT4) for 48 h, and glucose-induced insulin secretion was measured. Furthermore, Wnt4 siRNAs were transfected into MIN6 cells, and cell viability and insulin secretion were measured in control and Wnt4 siRNA-transfected MIN6 cells.
Results: Mice fed the HF/HS diet were heavier and their plasma glucose and insulin levels were higher compared with mice fed standard chow. Wnt4, Wnt5b, Ror1, and Ror2 expression was upregulated, while Fzd4, Fzd5, Fzd6, Lrp5, and Lrp6 expression was downregulated in the islets of mice fed the HF/HS diet. Wnt4 was the most abundantly expressed WNT ligand in β-cells, and its expression was increased by the HF/HS diet. Although exposure to recombinant mouse WNT4 protein for 48 h did not alter glucose-induced insulin secretion, it was significantly reduced by knockdown of Wnt4 in MIN6 cells.
Conclusions: We demonstrated that the HF/HS diet-induced increase of WNT4 signaling in β-cells is involved in augmentation of glucose-induced insulin secretion and impaired β-cell proliferation. These results strongly indicate an essential role of WNT4 in the regulation of β-cell functions in mouse pancreatic islets.
Summary: Background: The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed.
Methods: The numbers of eosinophils and neutrophils, and levels of IL-5, IL-13 and IL-17A protein and mRNA in bronchoalveolar lavage fluid (BALF) and lung tissue were compared between wild-type (WT) and IL-38-KO mice after OVA sensitization and challenge. The effects of additional purified recombinant mouse (rm) IL-38 protein were investigated in the IL-38-KO murine asthma model.
Results: The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p<0.05). The number of airway eosinophils in IL-38-KO mice was significantly lower than in WT mice after OVA challenge (p<0.01). BALF analysis confirmed the lower number of airway eosinophils in IL-38-KO mice and showed that this was significantly associated with lower IL-5 protein levels (r=0.92, p<0.0001). However, the additional rm IL-38 protein did not neutralize airway eosinophilia in IL-38-KO mice.
Conclusion: IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction.