Hikaru Matsuda

Therapeutic effect of a new immunosuppressive agent, everolimus, on interleukin-10 gene-deficient mice with colitis

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohns disease (CD) is not satisfactory and new approaches are needed. Interleukin‐10 gene‐deficient (IL‐10–/–) mice, a well‐characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL‐10–/– mouse model. Everolimus was administered orally for a period of 4u2003weeks to IL‐10–/– mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4‐week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4+ T cells in the colonic lamina propria as well as IFN‐γ production in colonic lymphocytes. Everolimus treatment of established colitis in IL‐10–/– mice ameliorated the colitis, probably as a result of decreasing the number of CD4+ T cells in the colonic mucosa and an associated reduction in IFN‐γ production.

Domestic and foreign trends in the prevalence of heart failure and the necessity of next-generation artificial hearts: a survey by the Working Group on Establishment of Assessment Guidelines for Next-Generation Artificial Heart Systems.

A series of guidelines for development and assessment of next-generation medical devices has been drafted under an interagency collaborative project by the Ministry of Health, Labor and Welfare and the Ministry of Economy, Trade and Industry. The working group for assessment guidelines of next-generation artificial hearts reviewed the trend in the prevalence of heart failure and examined the potential usefulness of such devices in Japan and in other countries as a fundamental part of the process of establishing appropriate guidelines. At present, more than 23 million people suffer from heart failure in developed countries, including Japan. Although Japan currently has the lowest mortality from heart failure among those countries, the number of patients is gradually increasing as our lifestyle becomes more Westernized; the associated medical expenses are rapidly growing. The number of heart transplantations, however, is limited due to the overwhelming shortage of donor hearts, not only in Japan but worldwide. Meanwhile, clinical studies and surveys have revealed that the major causes of death in patients undergoing long-term use of ventricular assist devices (VADs) were infection, thrombosis, and mechanical failure, all of which are typical of VADs. It is therefore of urgent and universal necessity to develop next-generation artificial hearts that have excellent durability to provide at least 2 years of event-free operation with a superior quality of life and that can be used for destination therapy to save patients with irreversible heart failure. It is also very important to ensure that an environment that facilitates the development, testing, and approval evaluation processes of next-generation artificial hearts be established as soon as possible.

In-patient step count predicts re-hospitalization after cardiac surgery

BACKGROUNDnClinical significance of in-patient step count after cardiac surgery remains unknown. The aim of this study was to determine whether the number of steps walked during the in-patient stay after cardiac surgery predicts the risk of cardiac re-hospitalization in the following year.nnnMETHODSnOne hundred and thirty-three patients who underwent cardiac surgery were included in this study. The number of steps was assessed using a triaxial accelerometer. One year after surgery, patients completed a postal survey to determine their health condition and occurrence of cardiac re-hospitalization.nnnRESULTSnThe mean number of steps walked during the last three in-patient days was 2460 ± 1549 (mean ± standard deviation). Of the 133 patients, there were 16 cases (12.0%) of cardiac re-hospitalization during the 1-year follow-up period. The average step count before discharge was significantly lower in the 16 patients who were re-hospitalized for cardiac causes (1297 ± 1232 versus 2620 ± 1524, p<0.01). The cut-off value that predicted the occurrence of cardiac re-hospitalization on the receiver operating curve was 1308 steps (area under the curve: 0.783, p<0.001, sensitivity: 0.814, specificity: 0.733). Cox proportional hazards analysis revealed that the strongest predictor of cardiac re-hospitalization was a low step count prior to discharge (≤1308 steps, hazard ratio: 7.58; 95% confidence interval: 2.04-28.22).nnnCONCLUSIONSnIn-patient step count appears to be a risk factor for cardiac re-hospitalization within the first year following cardiac surgery. Further studies are needed to clarify the clinical significance of step count both preoperatively and following discharge.

Japanese guidance for ventricular assist devices/total artificial hearts.

To facilitate research and development (R&D) and to expedite the review processes of medical devices, the Ministry of Health, Labor and Welfare (MHLW) and the Ministry of Economy, Trade and Industry (METI) founded a joint committee to establish guidance for newly emerging technology. From 2005 to 2007, two working groups held discussions on ventricular assist devices and total artificial hearts, including out-of-hospital programs, based on previous guidance documents and standards. Based on this discussion, the METI published the R&D Guidelines for innovative artificial hearts in 2007, and in 2008 the MHLW published a Notification by Director regarding the evaluation criteria for emerging technology.

Prediction of postoperative hepatic dysfunction after cardiac surgery in patients with chronic congestive heart failure

ObjectiveChronic congestive liver dysfunction in advanced valvular disease remains an important co-morbidity in open heart surgery. The objective of this study was to explore the prognostic value in patients with severe valvular disease associated with congestive liver dysfunction.MethodsFrom 1997 to 2004, a total of 63 patients who had valvular disease with moderate or severe tricuspid regurgitation were studied. In addition to the indocyanine green retention rate at 15 min (ICG15) and the Child-Pugh score, we measured serum total bilirubin (T-bil), asparate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), albumin (Alb) concentration, and prothrombin time. We compared these preoperative factors with postoperative liver dysfunction and mortality and attempted to develop a new liver function score.ResultsThere were eight in-hospital deaths (13%). Seventeen patients had postoperative liver dysfunction. The univariate analysis indicated there were significant differences in preoperative T-bil, Alb, ChE, ICG15, and Child-Pugh score between the patients with and without liver dysfunction. Multivariate logistic regression analysis also identified preoperative T-bil as a significant indicator of postoperative liver dysfunction and preoperative ChE as a predictor of mortality. Based on these findings, we introduced a liver function score to predict postoperative dysfunction and death.ConclusionIn addition to preoperative ChE, T-bil and Alb appeared to be valuable for producing obtainable prognostic information regarding postoperative liver dysfunction in patients with severe valvular disease. A new liver score, including T-bil, ChE, and Alb, is proposed for predicting postoperative hepatic dysfunction and outcome.

Where does the new regime of medical specialty certification go

The certification system of medical specialty is going to be changed to a new regime after the proposal of reorganization conducted by the Government in 2013. This review focuses on the issue of program-based accreditation of the training institution which is the core of the new regime. In particular, the strategy for surgical subspecialty such as thoracic surgery is discussed.

JATS’ role in a new era

We face a vital turning point in the basic organization of thoracic surgery having a long history of very cooperative relations among three core subgroups—cardiac, general thoracic, and esophageal surgery. The time has come for timely, drastic changes in our mission as a medical professional organization to cope with increasing burdens of quality control and risk management in our practice and in ongoing education including the establishment of reliable residency programs. Because of strong public demands to open up academic data related to quality assessment of institutions and for thoracic surgery specialists, we must make decisions on these issues by exchanging opinions and ideas among members and the Board to decide how to reorganize and restart efforts in a new era. In doing so, we welcome medical graduates and young surgeons to thoracic surgery fields by changing social and medical circumstances surrounding them and our medical profession. As the Director of the Japanese Association for Thoracic Surgery Board, I look forward to the cooperation of all members to make a breakthrough and open an exciting new era for thoracic surgery and surgeons.