Nationwide patient registry for GNE myopathy in Japan

BACKGROUND: GNE myopathy is a slowly progressive autosomal recessive myopathy caused by mutations in the GNE (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) gene. This study aimed to (1) develop a nationwide patient registry for GNE myopathy in order to facilitate the planning of clinical trials and recruitment of candidates, and (2) gain further insight into the disease for the purpose of improving therapy and care. METHODS: Medical records of genetically-confirmed patients with GNE myopathy at the National Center Hospital of the National Center of Neurology and Psychiatry (NCNP) were retrospectively reviewed in order to obtain data reflecting the severity and progression of the disease. We also referred to items in the datasheet of the nationwide registry of dystrophinopathy patients in the Registry of Muscular Dystrophies (Remudy). Items selected for the registration sheet included age, sex, age at onset, past history and complications, family history, body weight and height, pathological findings of muscle biopsy, grip power, walking ability, respiratory function, cardiac function, willingness to join upcoming clinical trials, and participation in patient associations. A copy of the original genetic analysis report was required of each patient. RESULTS: We successfully established the Remudy-GNE myopathy. Currently, 121 patients are registered nationwide, and 93 physicians from 73 hospitals collaborated to establish the registry. The mean age at onset was 27.7 ± 9.6 years, and 19.8% (24/121) of patients could walk without assistance. Mean presumed durations from onset to use of assistive devices (cane and/or braces) and a wheelchair, and loss of ambulation were 12.4, 15.2, and 21.1 years, respectively. Three patients had a past history and/or complication of idiopathic thrombocytopenia. To share the progress of this study with the community, newsletters were published on a regular basis, and included information regarding new phase I clinical trials for GNE myopathy. The newsletters also served as a medium to bring attention to the importance of respiratory evaluation and care for respiratory insufficiency. CONCLUSION: The Japanese Remudy-GNE myopathy is useful for clarifying the natural history of the disease and recruiting patients with genetically-confirmed GNE myopathy for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-014-0150-4) contains supplementary material, which is available to authorized users

The Risk of Cytotoxic Chemotherapy-Related Exacerbation of Interstitial Lung Disease with Lung Cancer

IntroductionIt is unknown what type of interstitial lung disease (ILD) has high risk for chemotherapy-related exacerbation of ILD. We investigated the risk of exacerbation of ILD for patients with lung cancer with ILD.MethodsOne hundred nine patients with lung cancer with ILD treated with cytotoxic chemotherapy at Shizuoka Cancer Center between August 2002 and April 2010 were retrospectively reviewed.ResultsOn pretreatment computed tomography (CT) of the chest, 69 patients (63%) were identified with usual interstitial pneumonia (UIP) pattern, and 40 patients (37%) had non-UIP pattern. Patients with UIP pattern developed cytotoxic chemotherapy-related exacerbation of ILD more frequently than those with non-UIP pattern (30 versus 8%, p = 0.005). The incidence of grade 5 pulmonary toxicities was 9% in patients with UIP pattern, compared with 3% in those with non-UIP pattern. Multivariate analyses demonstrated that age (<70 years) and CT pattern (UIP) were significant independent risk factors for cytotoxic chemotherapy-related exacerbation of ILD. In small cell lung cancer, overall survival (OS) from the start of first-line chemotherapy was significantly shorter in UIP pattern than non-UIP pattern (median OS: 9 versus 16 months, p = 0.0475), whereas there was no significant difference in patients with non-small cell lung cancer (median OS: 12 versus 9 months, p = 0.2529).ConclusionsOur results indicated that the incidence of exacerbation of ILD was significantly higher in patients with lung cancer with UIP pattern on CT findings than in those with non-UIP pattern. Therefore, great care is required when administering cytotoxic chemotherapy agents for patients with lung cancer with UIP pattern

Detection and management of cardiomyopathy in female dystrophinopathy carriers

Regular health checkups for mothers of patients with Duchenne muscular dystrophy have been performed at National Hospital Organization Tokushima Hospital since 1994. Among 43 mothers participated in this study, 28 dystrophinopathy carriers were identified. Skeletal and cardiac muscle functions of these subjects were examined. High serum creatine kinase was found in 23 subjects (82.1%). Obvious muscle weakness was present in 5 (17.8%) and had progressed from 1994 to 2015. Cardiomyopathy was observed in 15 subjects (60.0%), including dilated cardiomyopathy-like damage that was more common in the left ventricular (LV) posterior wall. Late gadolinium enhancement on cardiac MRI was found in 5 of 6 subjects, suggesting fibrotic cardiac muscle. In speckle tracking echocardiography performed seven years later, global longitudinal strain was decreased in these subjects, indicating LV myocardial contractile abnormality. These results suggest that female dystrophinopathy carriers should receive regular checkups for detection and treatment of cardiomyopathy, even if they have no cardiac symptoms

Multiplexed Molecular Profiling of Lung Cancer Using Pleural Effusion

Introduction:Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated.Methods:Between July 2011 and April 2013, pleural effusion samples were obtained from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET, FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes using pyrosequensing and/or capillary electrophoresis, quantitative reverse-transcriptase polymerase chain reaction, and reverse-transcriptase polymerase chain reaction, respectively.Results:One hundred and two samples from 84 patients were analyzed. Adenocarcinoma was the most common histological subtype (82%). Genetic abnormalities were detected in 42% of patients. The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each). Concordance rates between pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%. Among 11 patients who provided samples at multiple time points, changes in molecular profile over the course of treatment were observed in five patients.Conclusions:The use of pleural effusion for multiplexed molecular testing and real-time monitoring in lung cancer was demonstrated

Multicenter questionnaire survey for sporadic inclusion body myositis in Japan

Background: Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disease in the elderly. sIBM is an intractable and progressive disease of unknown cause and without effective treatment. The etiology of sIBM is still unknown; however, genetic factors, aging, lifestyles, and environmental factors may be involved. The purpose of this study is to elucidate the cross-sectional profile of patients affected by sIBM in Japan. Methods: We surveyed patient data for 146 cases diagnosed at a number of centers across Japan. We also issued a questionnaire for 67 patients and direct caregivers to further elucidate the natural history of the disease. Results: The mean age at the onset was 63.4 ± 9.2 years. The mean length of time from the onset to diagnosis was 55.52 ± 49.72 months, suggesting that there is a difficulty in diagnosing this disease with long-term consequences because of late treatment. 73 % described the psychological/mental aspect of the disease. The most popular primary caregiver was the patient’s spouse and 57 % patients mentioned that they were having problems managing the finances. Conclusions: Through these surveys, we described the cross-sectional profiles of sIBM in Japan. Many patients described psychological/mental and financial anxiety because of the aged profile of sIBM patients. The profiles of sIBM patients are similar to those in Western countries

The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan

Background: Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was partly covered by the government. This study aimed to examine the changes in the number of patients with sIBM over the last 10 years and to elucidate the cross-sectional profile of Japanese patients with sIBM. Methods: The number of sIBM patients was estimated through a reply-paid postcard questionnaire for attending physicians. Only patients diagnosed as “definite” or “probable” sIBM by clinical and biopsy sIBM criteria were included in this study (Lancet Neurol 6:620-631, 2007, Neuromuscul Disord 23:1044-1055, 2013). Additionally, a registered selfadministered questionnaire was also sent to 106 patients who agreed to reply via their attending physician, between November 2016 and March 2017. Results: The number of patients diagnosed with sIBM for each 5-year period was 286 and 384 in 2011 and 2016, respectively. Inability to stand-up, cane-dependent gait, inability to open a plastic bottle, choking on food ingestion, and being wheelchair-bound should be included as sIBM milestones. Eight patients were positive for anti-hepatitis C virus antibody; three of them were administered interferon before sIBM onset. Steroids were administered to 33 patients (31.1%) and intravenous immunoglobulin to 46 patients (43.4%). From 2016 to 2017, total of 70 patients applied for the designated incurable disease medical expenses subsidy program. Although the treatment cost was partly covered by the government, many patients expressed psychological/mental and financial anxieties. Conclusions: We determined the cross-sectional profile of Japanese patients with sIBM. Continuous support and prospective surveys are warranted

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray