From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone.

Many features of extracellular matrices, e.g., self-healing, adhesiveness, viscoelasticity, and conductivity, are associated with the intricate networks composed of many different covalent and non-covalent chemical bonds. Whereas a reductionism approach would have the limitation to fully recapitulate various biological properties with simple chemical structures, mimicking such sophisticated networks by incorporating many different functional groups in a macromolecular system is synthetically challenging. Herein, we propose a strategy of convergent synthesis of complex polymer networks to produce biomimetic electroconductive liquid metal hydrogels. Four precursors could be individually synthesized in one to two reaction steps and characterized, then assembled to form hydrogel adhesives. The convergent synthesis allows us to combine materials of different natures to generate matrices with high adhesive strength, enhanced electroconductivity, good cytocompatibility in vitro and high biocompatibility in vivo. The reversible networks exhibit self-healing and shear-thinning properties, thus allowing for 3D printing and minimally invasive injection for in vivo experiments.

Objectives To compare the effect of respiratory muscle stretch gymnastics (RMSG),proposed as a possible additional form of rehabilitation for patients with chronic obstructive pulmonary disease (COPD), with that of inspiratory muscle training (IMT).Patients Twelvenaive outpatients with COPD at a university hospital.Method The patients performed IMT (2 sessions of 10 minutes of training at 30% of PImax, daily) for 4 weeks and RMSG(3 sessions of 5 RMSGpatterns 4 times each, daily) for 4 weeks, in randomized order, with a 4-week washout period between the two interventions.Measurements and Results PImax increased with IMT (mean 66.1 to 79.1 cmH2O), but not with RMSG(mean 66.0 to 69.4 cmH2O). RMSGand IMT similarly increased maximumchest wall expansion. FRCwas significantly decreased by 158 ml with RMSG,but not with IMT. There were no significant changes in VC, FEV19or PEF nor in arterial blood gases with either form of rehabilitation. Six-minute walking distance was more significantly increased with RMSG(mean 383 to 430 m), than with IMT (mean 386 to 412m).Conclusions RMSGmay have clinically significant benefits, which may be somewhat different from the benefits of IMT, in patients with COPD. (Internal Medicine 41: 805-812, 2002)

CXCL13, a chemokine for B cells, follicular T cells, T helper 17 cells, and regulatory T cells, is reported to contribute to the development of systemic sclerosis (SSc), reflecting aberrant activation of immune system. To better understand the role of CXCL13 in SSc, we investigated the influence of Fli1 deficiency, a potential predisposing factor of this disease, on CXCL13 expression and assessed the clinical correlation of serum CXCL13 levels by multivariate regression analysis. Haploinsufficient loss of Fli1 remarkably induced CXCL13 expression in murine peritoneal macrophages, while gene silencing of FLI1 did not affect the expression of CXCL13 in human dermal fibroblasts and human dermal microvascular endothelial cells. Serum CXCL13 levels were elevated in SSc patients compared with healthy controls and correlated positively with skin score and negatively with pulmonary function test results. SSc patients with elevated serum CXCL13 levels had longer disease duration, diffuse cutaneous involvement, interstitial lung disease (ILD), heart involvement, pulmonary arterial hypertension, Raynaud's phenomenon, pitting scars, digital ulcers, telangiectasia, and high serum IgG levels more frequently than the other patients. In particular, serum CXCL13 levels were associated with ILD and digital ulcers by multivariate regression analysis. Taken together, these results indicate that CXCL13 expression is upregulated by Fli1 deficiency in macrophages, potentially contributing to the development of tissue fibrosis, vasculopathy and immune activation in SSc, especially ILD and digital ulcers.

BackgroundInternational clinical trials are now rapidly expanding into Asia. However, the proportion of global trials is higher in South Korea compared to Japan despite implementation of similar governmental support in both countries. The difference in clinical trial environment might influence the respective physicians’ attitudes and experience towards clinical trials. Therefore, we designed a questionnaire to explore how physicians conceive the issues surrounding clinical trials in both countries.MethodsA questionnaire survey was conducted at Kyoto University Hospital (KUHP) and Seoul National University Hospital (SNUH) in 2008. The questionnaire consisted of 15 questions and 2 open-ended questions on broad key issues relating to clinical trials.ResultsThe number of responders was 301 at KUHP and 398 at SNUH. Doctors with trial experience were 196 at KUHP and 150 at SNUH. Among them, 12% (24/196) at KUHP and 41% (61/150) at SUNH had global trial experience. Most respondents at both institutions viewed clinical trials favorably and thought that conducting clinical trials contributed to medical advances, which would ultimately lead to new and better treatments. The main reason raised as a hindrance to conducting clinical trials was the lack of personnel support and time. Doctors at both university hospitals thought that more clinical research coordinators were required to conduct clinical trials more efficiently. KUHP doctors were driven mainly by pure academic interest or for their desire to find new treatments, while obtaining credits for board certification and co-authorship on manuscripts also served as motivation factors for doctors at SNUH.ConclusionsOur results revealed that there might be two different approaches to increase clinical trial activity. One is a social level approach to establish clinical trial infrastructure providing sufficient clinical research professionals. The other is an individual level approach that would provide incentives to encourage doctors to participate in and conduct clinical trials.

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With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular-targeted agents, has drastically changed the nature of treatment for adjuvant and advanced-stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach.

We report a case of a 65-year-old man with rare prostatic stromal sarcoma in which suprapubital radical prostatectomy was performed, but neither chemotherapy nor radiation therapy were administered before or after the operation. The well-circumscribed tumor, measuring 5 cm in diameter, showed a homogeneous white grayish cut surface with a hard consistency. Histopathologically, the tumor consisted mainly of medium-sized rounded cells with a sarcomatous and epithelioid appearance intermingled with collagen fiber. Hyalinized foci were also noted in the tumor. Immunohistochemistry revealed that the tumor cells were diffusely positive for vimentin and focally positive for progesterone receptor and CD34, but not for EMA, cytokeratin or estrogen receptor. No recurrence or distant metastasis of the tumor has occurred in 8 years of follow up. The tumor was diagnosed as prostatic stromal sarcoma (PSS) showing epithelioid differentiation and of a progesterone-dependent nature. Possible favorable nature of the PSS might be expected after complete resection.