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A delay in the diagnosis and treatment of an occult femoral neck fracture (OFNF) can negatively affect the subsequent quality of life. We investigated the diagnostic accuracy of ultrasonography for OFNF in patients confirmed with this condition by magnetic resonance imaging (MRI), and compared these results with other clinical findings.Ninety-four outpatients aged above 70 years with acute hip pain but without radiographic abnormal findings who were suspected of having an occult femoral neck fracture (11 men and 83 women with a mean age of 81.8 ± 6.0 years) were enrolled. Both ultrasonography and MRI were performed in all cases within 24 h. The ultrasonographic distance between the anterior aspect of the femoral neck and the anterior joint capsule (ultrasound joint swelling) was measured.By MRI findings, 27 patients were assigned to an occult femoral neck fracture (OFNF) group (1 man, 26 women) and 67 patients to a non-OFNF group (10 men, 57 women). The mean ultrasound joint swelling in both groups was 7.53 ± 1.52 mm and 3.45 ± 0.89 mm, respectively (Ultrasonography shows very high diagnostic accuracy for occult femoral neck fracture. This modality can thus contribute to initial bed-side examinations for this condition in patients over 70 years with acute hip pain.

Objectives To describe the treatment patterns and determine the effectiveness and safety of nivolumab treatment for non-small cell lung cancer (NSCLC) in real-world setting in Japan. Materials and methods Japanese patients with NSCLC who received nivolumab were analyzed retrospectively. Patients who had started nivolumab treatment between April 2016 and December 2016 were enrolled. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness and safety of nivolumab treatment and that of treatments just before and after nivolumab treatment, and programmed death-ligand 1 (PD-L1) expression status, if available, were collected. Factors associated with nivolumab effectiveness identified by univariate and multivariate analyses were further investigated for plotting Kaplan-Meier curves of epidermal growth factor receptor (EGFR) gene mutation status, PD-L1 expression status, and Eastern Cooperative Oncology Group performance status (ECOG PS). Results In this study, 901 NSCLC patients were enrolled. Nivolumab was used the most as a second line treatment with a median number of nivolumab doses of five. The median overall survival (OS) was 14.6 months, one-year survival rate was 54.3 %, and median progression-free survival (PFS) was 2.1 months. The objective response rate was 20.5 % and disease control rate was 57.4 %. According to multivariate analyses, better OS and PFS were associated with favorable ECOG PS and absence of liver metastasis. Better PFS was observed in patients without EGFR mutation and patients with smoking history. PFS and best overall response in PD-L1 expression subgroups were expression level-dependent. The overall incidence of irAEs was 45.8 %, and the incidence of adverse events of grade 3 or higher was 14.0 %. Conclusion The real-world effectiveness and safety of nivolumab is consistent with that reported by previous clinical trials and other real-world data. Subgroup analysis showed that ECOG PS, EGFR mutation status, smoking status, and PD-L1 were associated with the effectiveness of nivolumab.

Objectives: The purpose of this study was to clarify the diagnostic accuracy of the mobile assessment of varus thrust using inertial measurement units (IMUs). Methods: A total of 80 knees in 49 patients were enrolled in this study. On visual analysis of gait to determine the presence or absence of varus thrust, 23 knees were assigned to the Present group, 17 to the Ambiguous group, and 40 to the Absent group. The peak knee varus angular velocities (PVVs), measured by quantitative gait analysis using nine-axis IMUs, were compared between these three groups. A receiver operating characteristic curve for the relationship between the visual assessment of varus thrust (Present and Ambiguous) and the measured PVV was created, and the cut-off PVV for visualized varus thrust was determined as the highest point for both sensitivity and specificity. Results: The mean PVVs were significantly different between the three groups (Present, 47.7 ± 8.2 degree/s, Ambiguous, 34.1 ± 10.5 degree/s, and Absent, 28.1 ± 8.3 degree/s, respectively, ANOVA P=0.000). The PVV cut-off value for visualized varus thrust was 28.1 degree/s, yielding a sensitivity of 0.957 and a specificity of 0.579. Conclusions: A PVV

Background Since its approval in December 2015, nivolumab has been widely used as a second-line treatment for non-small cell lung cancer (NSCLC) patients regardless of tumor PD-L1 expression or histology. However, the relationship between nivolumab effectiveness and PD-L1 expression using 22C3 PharmDx in the real-world setting is unclear. Methods Data from patient who initiated nivolumab treatment from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan. Tumor PD-L1 expression was determined using PD-L1 IHC 22C3 PharmDx or 28-8 PharmDx assays. Here, we report the relationship between nivolumab effectiveness/safety and PD-L1 expression using 22C3 PharmDx, from a multicenter, observational study; CA209-9CR (NCT03273790). Results PD-L1 expression in 348 cases of NSCLC was determined using the 22C3 PharmDx assay. The propotion of cases with PD-L1 negative ( Conclusion These real-world data show relationship of nivolumab effectiveness and PD-L1 expression using 22C3 PharmDx.

Background In December 2015, nivolumab was approved as treatment for previously treated NSCLC irrespective of PD-L1 expression or histology in Japan. There are few reports that include real-world data on large cohorts of patients from Japan. Method Data from patients who initiated nivolumab treatment from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan. Here we report a retrospective data analysis accessing effectiveness and safety of nivolumab in 901 Japanese NSCLC pts from a multicenter, observational study; CA209-9CR (NCT03273790). Result Among 901 pts, median age of the pts treated with nivolumab was 67 ys old and proportion of 75 ys or over was 19.8%. Pts with ECOG PS 0 or 1 account for 75.8%, and pts with SQ and adeno histology were 24.5% and 67.7%, respectively. Pts with EGFR mutation account for 12.9%. Median numbers of nivolumab dose was five and nivolumab was most frequently used at 2nd line (46.8%) and followed by at 3rd line (26.5%). Rate of 1 yr overall survival (OS) was 54.3% and, median PFS was 2.1 months and overall ORR was 20.6%. There was no significant difference in effectiveness among histology. Although there was no difference in effectiveness of nivolumab by age, ECOG PS status significantly influence effectiveness of nivolumab. Analysis is ongoing to access various factors that may be associated with the effectiveness of nivolumab. Overall irAE incidence for all grade and grade 3-4 will be reported as well as categorized irAE. Further analysis is planned for safety management of irAEs and prognosis. Conclusion The effectiveness and safety of nivolumab observed in real-world data from NSCLC patients in Japan was comparable to results observed in clinical trials. ECOG PS status was identified as a factor influencing effectiveness of nivolumab.

Background In December 2015, nivolumab was approved for previously treated advanced NSCLC irrespective of PD-L1 expression or histology in Japan. Real-world data can provide insights beyond the clinical trial, and in this analysis we study a large Japanese patient cohort. Methods Data for 901 patients who initiated nivolumab treatment for advanced NSCLC from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan, including clinical laboratory data before and all the available data during nivolumab treatment. Here we report an exploratory analysis on the association of nivolumab effectiveness with the clinical laboratory data of the Japanese advanced NSCLC patients from a multicenter, observational study; CA209-9CR (NCT03273790). Results Analysis on association of objective response rate (ORR) with each clinical laboratory data at baseline among responders and non-responders suggested that neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), albumin, sodium, CYFRA, and uric acid at baseline were associated with significantly improved ORR. Further analyses on those multiple factors are planned to identify associations with improved outcome of with nivolumab treatment beyond ORR.

Background In December 2015, nivolumab was approved as treatment for previously treated NSCLC irrespective of PD-L1 expression or histology in Japan. There are few reports that include real-world data on large-scale cohorts of patients with special backgrounds from Japan. Method Data from patients who initiated nivolumab treatment from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan. Here we report retrospective analysis of all 901 pts data and focus on effectiveness and safety in special subgroups of the Japanese NSCLC patients, from a multicenter, observational study; CA209-9CR (NCT03273790). Result Patients with EGFR mutations showed significantly shorter PFS as compared to EGFR wild-type patients. Among other special groups, 316 pts with high blood pressure, in which 272 pts was on antihypertensive, showed superior ORR as compared to 585 pts with normal pressure at baseline. Safety analysis showed higher pulmonary toxicity in patients with pulmonary infection at baseline and higher hepatotoxicity in a group of pts infected with hepatitis virus. In this presentation, further analysis on the other subgroups will be presented.

Background: Bronchial occlusion therapy using silicon spigots is effective for intractable pneumothorax. However, sometimes the pneumothorax is refractory to bronchial occlusion because of collateral ventilation. For such difficult pneumothoraces, we attempted an intrabronchial infusion of autologous blood plus thrombin to control collateral ventilation and stop air leaks. Methods: We performed bronchial occlusions using silicon spigots in patients with spontaneous pneumothorax secondary to emphysema and refractory to chest drainage, but which was inoperable owing to each patient’s poor surgical candidacy and poor overall health condition. When bronchial occlusion proved ineffective, we undertook intrabronchial infusion of autologous blood plus thrombin, 2 to 4 days after bronchial occlusion. A catheter was inserted into the subpleural area, through a gap between the silicon spigot and the bronchial wall, using a flexible bronchoscope under fluoroscopic guidance. Autologous blood, followed by a thrombin solution, was infused using the catheter. We repeated the same infusion a total of 4 to 6 times while changing the target bronchi. All interventions were performed under local anesthesia. Results: The subjects were 9 men, aged from 61 to 88 years, with smoking histories. Three patients also had interstitial pneumonia, and 6 patients had undergone pleurodesis in vain before bronchial occlusion. For 4of the 9 patients, autologous blood plus thrombin infusions successfully stopped air leaks, and in 3 patients, intrabronchial infusions and pleurodesis halted leaks altogether. Conclusion: Intrabronchial infusion of autologous blood plus thrombin was effective for intractable pneumothoraces that could not be clinically managed, even by bronchial occlusion using silicon spigots.

Polarized Raman spectra of a β-FeSi2(100)//Si(001) epitaxial film grown by molecular beam epitaxy were measured to identify the Raman mode of the observed Raman active lines. Twelve of the observed 18 Raman lines showed a clear dependence of the Raman intensity on the crystal rotation angle. By factor group analysis using the orthorhombic symmetry D2h18 of β-FeSi2, five Raman lines (193, 200, 249, 401, 494 cm-1) and seven lines (175, 277, 284, 298, 327, 410, 442 cm-1) were completely assigned to the Ag and B3g modes, respectively. The depolarization ratio of Raman scattering intensities was obtained from polarized Raman spectra measured in two polarization configurations. The values of the depolarization ratio also support the assignment of the Ag and B3g modes in β-FeSi2.

Effects of lattice deformations on Raman spectra were investigated in β-FeSi2 epitaxial films grown on Si substrates. The lattice of the epitaxial film was deformed depending on thermal-annealing temperature (Ta). In Raman spectra, Raman lines of Ag-mode (iron displacements) showed a frequency shift with increasing Ta. The shift of Raman lines showed that the residual strain in the epitaxial films was changed by the lattice deformation. In the temperature dependence of Raman spectra, the temperature shifts of the Raman lines were found to be different between β-FeSi2(100)//Si(001) and β-FeSi2(110)(101)//Si(111) epitaxial films.

To explore the implications of the structure/ function relationships in factor XIII. a patient with severe A subunit deficiency was examined at the DNA and RNA levels. Nucleotide sequence analysis of the patient's DNA amplified by PCR revealed that the patient had a replacement of C by T in the codon for Arg260. RT-PCR analysis demonstrated that only one kind of mRNA coding for the Arg260-Cys mutation was expressed in the patient at a normal level. Another possible defective allele of the A subunit gene with a G-A polymorphism was not expressed (null allele). The substitution of Arg260 by Cys located on the interface of two A subunits would preclude the reciprocal ionic interaction (salt bridge) between Arg260 and Asp404. Molecular modelling and, for the first time, molecular mechanics calculated that Cys260 changed the local conformation of the A subunit and reduced the electrostatic interaction between two monomers, suggesting destabilization of the molecule's dimer.

To determine ligand-binding sites of a platelet-activating factor (PAF) receptor, alanine-scanning mutagenesis was carried out. All 23 polar amino acids in the putative 7-transmembrane (TM) domains of a guinea pig PAF receptor were individually replaced with alanine. The ligand-binding properties of mutant receptors were determined after transient expression in COS-7 cells. Mutants in TM II (N58A, D63A), TM III (N100A, T101A, S104A) and TM VII (D289A) displayed higher PAF-binding affinities than seen with the wild-type receptor. In contrast, mutants in TM V (H188A), TM VI (H248A, H249A, Q252A), and TM VII (Q276A, T278A) showed lower affinities. Representative mutants were then stably expressed in Chinese hamster ovary cells to observe PAF-induced cellular signals (arachidonate release, phosphatidylinositol hydrolysis, adenylyl cyclase inhibition). An N100A mutant with the highest affinity was constitutively active and was responsive to lyso-PAF, an inactive derivative of PAF. One nanomolar PAF induced no signals in low affinity mutants, an EC50 value for the wild-type receptor. Three histidines (His-188, His-248, His-249) might form a binding pocket for the phosphate group of PAF, since zinc effectively inhibited ligand binding. Based on these results, a three-dimensional molecular model of PAF and its receptor was generated using bacteriorhodopsin as a reference protein.

CASE 1: A 74-year-old man having a week's fever and diagnosed with a liver abscess was treated with several antibiotics and percutaneous liver drainage. His respiration gradually worsened and chest computed tomography (CT) showed right pleural effusion and a left-lung mass. Percutaneous fine needle aspiration of the pulmonary mass detected Entamoeba histolytica. CASE 2: A 44-year old, zoo office worker admitted for fever and right chest pain was found in CT to have right pleural effusion and a mass with a liver abscess necessitating abscess drainage. Injected contrast medium detected a fistula connected to the right. Following surgical drainage, E. histolytica was detected from the resected lung. Both cases responded well to metronidazole.

We have previously reported a mutated protein C, designated protein C Nagoya (PCN), characterized by the deletion of a single guanine residue (8857G). This frameshift mutation results in the replacement of the carboxyl-terminal 39 amino acids of wild-type protein C (G381-P419) by 81 abnormal amino acids. This elongated mutant was not effectively secreted, and was retained in the endoplasmic reticulum. To determine why PCN is not secreted, we constructed a series of mutants from which some or all of the 81 amino acids were deleted. None of these shortened proteins were secreted from producing cells, indicating that the carboxyl-terminal extension is not mainly responsible for the intracellular retention of PCN, and that the 39 carboxyl-terminal amino acids of wild-type protein C are required for secretion. To determine which residues are essential for the secretion of protein C, deletion mutants of the carboxyl-terminal region (D401-P419) were prepared. Metabolic labeling showed that mutants of protein C truncated before W417, Q414, E411, or K410 were efficiently secreted. On the other hand, the mutants truncated before D409 were retained and degraded intracellularly. Immunofluorescence and immunoelectron microscopy showed that truncation before D409 blocks the movement from rough endoplasmic reticulum to the Golgi apparatus. To understand the conformational change in the carboxyl-terminal region, two models of truncated activated protein C were constructed using energy optimization and molecular dynamics with water molecules.