Abstract
Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and ...researchers. Both the pathogenesis and treatment of these disorders require further study. In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy. Sjogren's syndrome, which is a classical autoimmune disease, could serve as a disease model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may most benefit from the immunotherapy.
•Autoimmune aspects of CFS, POTS, CRPS and SIIS are discussed.•The common denominators of anti-GPCR AAb and SFN are identified for these syndromes.•A new concept of autoimmune neurosensory dysautonomia is suggested.•Sjogren's syndrome can illustrate the suggested concept.
Objective To retrospectively investigate the clinical manifestations of systemic amyloid light-chain (AL) amyloidosis in Japanese patients and the treatment strategy for the condition. Methods We ...conducted a survey of Japanese AL amyloidosis patients, who were treated between January 1, 2012, and December 31, 2014. Results A total of 741 AL amyloidosis patients were included in this study (436 men and 305 women; median age: 65 years old, range: 31-93). The most frequently affected organ was the kidneys (n=542), followed by the heart (n=252), gastrointestinal (GI) tract (n=164), autonomic nervous system (n=131), liver (n=71), and peripheral nervous system (n=71). Diagnostic findings were most commonly detected in the GI tract (upper GI tract: 350 cases, lower GI tract: 167 cases), followed by the bone marrow and kidneys. An abdominal fat-pad biopsy was only conducted in 128 patients. Autologous stem cell transplants (ASCTs) and bortezomib were used to treat 126 and 276 patients, respectively. Conclusion The clinical features of Japanese patients with systemic AL amyloidosis are similar to those reported previously for cases in the US and Europe. Regarding treatment, a significant number of ASCTs were performed in Japan as well as in Western countries. Surprisingly, a marked number of patients received bortezomib as a treatment for AL amyloidosis.
Our previous phase II trial for treating human T-lymphotropic virus type I-associated adult T-cell leukemia-lymphoma (ATLL) with vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP), ...doxorubicin, ranimustine, and prednisone (AMP), and vindesine, etoposide, carboplatin, and prednisone (VECP) showed promising results. To test the superiority of VCAP-AMP-VECP over biweekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), we conducted a randomized controlled trial exclusively for ATLL.
Previously untreated patients with aggressive ATLL were assigned to receive either six courses of VCAP-AMP-VECP every 4 weeks or eight courses of biweekly CHOP. Both treatments were supported with granulocyte colony-stimulating factor and intrathecal prophylaxis.
A total of 118 patients were enrolled. The complete response (CR) rate was higher in the VCAP-AMP-VECP arm than in biweekly CHOP arm (40% v 25%, respectively; P = .020). Progression-free survival rate at 1 year was 28% in the VCAP-AMP-VECP arm compared with 16% in the CHOP arm (P = .100, two-sided P = .200). Overall survival (OS) at 3 years was 24% in the VCAP-AMP-VECP arm and 13% in the CHOP arm (P = .085, two-sided P = .169). For VCAP-AMP-VECP versus biweekly CHOP, grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 or 4 infection rates were 98% v 83%, 74% v 17%, and 32% v 15%, respectively. There were three toxic deaths in the VCAP-AMP-VECP arm.
The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
Familial Mediterranean fever (FMF) is a well-known cause of secondary AA amyloidosis. Colchicine is generally considered to be the most effective treatment for FMF and FMF-associated amyloidosis, but ...the management of patients who are refractory to colchicine remains controversial. We encountered a 51-year-old Japanese man with suspected FMF, who had periodic fever with abdominal pain, polyarthritis, and nephropathy (serum creatinine of 1.9 mg/dL and 24-h protein excretion of 3.8 g). FMF was diagnosed by mutation analysis of the Mediterranean fever (MEFV) gene, which revealed that the patient was compound heterozygous for the marenostrin/pyrin variant E148Q/M694I. AA amyloidosis was diagnosed by renal and gastric biopsy. Colchicine was administered, but his arthritis persisted, and serum creatinine increased to 2.4 mg/dL. Therefore, a humanized anti-interleukin-6 receptor antibody (tocilizumab) was administered at a dose of 8 mg/kg on a monthly basis. Both arthritis and abdominal pain subsided rapidly, and C-reactive protein (CRP) decreased from 2.5 to 0.0 mg/dL. After 2 years, his serum creatinine was decreased to 1.5 mg/dL and proteinuria was improved to 0.3 g daily. In addition, repeat gastric biopsy showed a marked decrease of AA amyloidosis. This case suggests that tocilizumab could be a new therapeutic option for patients with FMF-associated AA amyloidosis if colchicine is not effective.
In recent years, the frequency of occurrence of natural disasters has increased around the world. ASEAN, especially, has often suffered serious human and economic damages from large scale disasters. ...Therefore, ASEAN leaders emphasize that the regional cooperation and capacity development for disaster prevention and response in the ASEAN region is essential. Japan, as a natural-disaster-prone country, has vast experience and knowledge of disaster response and disaster medicine, including deployment of international and domestic emergency medical teams (EMT) in affected areas. JICA conducted “the survey on the Current Situation of Disaster/Emergency Medicine System in the ASEAN Region” (November 2014–August 2015). Based on the results of this survey, JICA, in cooperation with the Thai government, has been conducting “the Project for Strengthening the ASEAN Regional Capacity on Disaster Health Management （ARCH project）” since July 2016, with a three-year project period. The ASEAN Regional Collaboration Committee (RCC) was established as a coordination platform under the ARCH project, and five RCC meetings were held in order to oversee the activities of the ARCH Project and make recommendations on regional collaboration mechanisms on disaster health management. As a framework for the practice of regional collaboration, a Regional Collaboration Drill (RCD) was conducted five times. The host countries of the RCD were able to test their systems and policies, including coordination mechanisms, among relevant disaster management organizations for disaster response, assuming a large scale disaster such as can be anticipated to happen in each host country. As tools for regional coordination, Standard Operation Procedures (SOP) for EMT Coordination in ASEAN, Minimum Requirements for personnel in EMTs, Health Needs Assessment Framework for EMT, and a Database of EMT were also developed. These tools were actively tested in the RCDs and the results were fed back to enable improvement. Training programs for the ASEAN Member States (AMS) were conducted four times in terms of medical knowledge/skills necessary for EMT members, systems/procedures for deploying and receiving international EMT, and EMT coordination mechanisms. At the 31st ASEAN Summit in 2017, the ASEAN Leader’s Declaration of Disaster Health Management was adopted, which included the results and outputs of this project. The three-year project has been extended for another 21 months to further strengthen the disaster medical cooperation mechanisms in the ASEAN region.
Southeast Asia is the second biggest region in the world in terms of the total number of natural disasters since 1900. Therefore, the Association of Southeast Asian Nations (ASEAN) initiated regional ...challenges toward strengthening regional collaboration for disaster prevention and response since the earthquake of Sumatra in Indonesia occurred in 2004. Moreover, ASEAN Leaders signed "the ASEAN Declaration on One ASEAN, One Response" in 2016. Under these circumstances, ASEAN decided to implement the Project for Strengthening the ASEAN Regional Capacity on Disaster Health Management (ARCH Project).
The objective of the ARCH Project is to strengthen coordination on disaster health management (DHM) for rapid and effective response to disasters occurring in the ASEAN region and to enhance the capacity of each ASEAN Member State (AMS) on DHM. This article aims to overview the outline and its strategy, and review the progress of the project.
ARCH Project is an ASEAN official project supported by Japan's official development assistance. Five outputs were launched for: (1) coordination platform on DHM; (2) framework of regional collaboration practices; (3) tools for effective regional collaboration; (4) enhancement of academic network on DHM; and (5) capacity development activities for each AMS. The Project was reviewed in terms of accomplishment and evaluation criteria.
Regional Coordination Committee on DHM was established as a coordination platform to: Oversee the implementation of the ARCH Project for the Output 1; Regional Collaboration Drill was developed and conducted for the Output 2; The standard operating procedure for coordination of emergency medical teams (EMTs) in ASEAN was developed for the Output 3; Various presentations on ARCH were made in academic conferences for the Output 4; and Several training programs and educational curricula were developed for the Output 5. The Project has accomplished its Project Purpose and satisfied all the indicators set. ARCH Project has high Relevance, Impact, Sustainability, and Effectiveness, while some improvements in Efficiency are needed.
ARCH Project is the first-ever successful regional cooperation mechanism and standardization of DHM in ASEAN, one of the most disaster-prone regions. It also contributes to the capacity building of AMS. The ARCH Project has a remarkable impact on the resilience and flexible medical response to disasters, although continuous efforts of stakeholders to make this initiative sustainable are necessary.
Although ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) therapy has been regarded as a standard of care for advanced-stage Hodgkin lymphoma (HL) since 1992, there has been no prospective ...data of ABVD therapy in Japan. To investigate the efficacy and safety of ABVd therapy with the lower dose of dacarbazine (250 mg/m
2
) in patients with newly diagnosed stage II–IV HL, Lymphoma Study Group of Japan Clinical Oncology Group conducted a phase II study. The primary endpoints were complete response rate (%CR) and progression-free survival (PFS). A total of 128 patients with age less than 70 years were enrolled and received 6–8 cycles of ABVd followed by radiation to initial bulky mass. The %CR in 118 eligible patients was 81.4% 95% confidence interval (CI) 73.1–87.9%. Major toxicity was grade 4 neutropenia (45.3%). Grade 3 nausea/vomiting was the most frequent non-hematological toxicity (10.9%). Transient grade 4 constipation, infection (abscess), hypoxemia and hyperbilirubinemia were observed in 4 patients. No treatment-related death was observed. PFS and overall survival at 5 years were 78.4% (95% CI 70.9–85.9%) and 91.3% (95% CI 86.1–96.5%), respectively. In conclusion, ABVd is effective in Japanese patients with stage II–IV HL with acceptable toxicities (UMIN-CTR Number: C000000092).
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