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Yamada R.,Osaka University | Hiramatsu N.,Osaka University | Oze T.,Osaka University | Morishita N.,Osaka University | And 24 more authors.
Journal of Gastroenterology

Background: Entecavir (ETV) is one of the first-line nucleoside analogs for treating patients with chronic hepatitis B virus (HBV) infection. However, the hepatocellular carcinoma (HCC) risk for ETV-treated patients remains unclear. Methods: A total of 496 Japanese patients with chronic HBV infection undergoing ETV treatment were enrolled in this study. The baseline characteristics were as follows: age 52.6 ± 12.0 years, males 58 %, positive for hepatitis B e antigen 45 %, cirrhosis 19 %, and median HBV DNA level 6.9 log copies (LC) per milliliter. The mean treatment duration was 49.9 ± 17.5 months. Results: The proportions of HBV DNA negativity (below 2.6 LC/mL) were 68 % at 24 weeks and 86 % at 1 year, and the rates of alanine aminotransferase (ALT) level normalization were 62 and 72 %, respectively. The mean serum alpha-fetoprotein (AFP) levels decreased significantly at 24 weeks after ETV treatment initiation (from 29.0 ± 137.1 to 5.7 ± 27.9 ng/mL, p < 0.001). The cumulative incidence of HCC at 3, 5, and 7 years was 6.0, 9.6, and 17.2 %, respectively, among all enrolled patients. In a multivariate analysis, advanced age [55 years or older, hazard ratio (HR) 2.84; p = 0.018], cirrhosis (HR 5.59, p < 0.001), and a higher AFP level (10 ng/mL or greater) at 24 weeks (HR 2.38, p = 0.034) were independent risk factors for HCC incidence. HCC incidence was not affected by HBV DNA negativity or by ALT level normalization at 24 weeks. Conclusions: The AFP level at 24 weeks after ETV treatment initiation can be the on-treatment predictive factor for HCC incidence among patients with chronic HBV infection. © 2014, Springer Japan. Source

Hayashi T.,Osaka General Medical Center | Hayashi T.,Rinku General Medical Center | Kimura T.,Osaka University | Yasuda K.,Osaka University | And 9 more authors.
Circulation Journal

Background: There is a paucity of studies on whether early referral (ER) to nephrologist could reduce cardiovascular mortality on dialysis, and the length of pre-dialysis nephrological care needed to reduce mortality on dialysis. Methods and Results: A total of 604 consecutive patients who started dialysis between 2001 and 2009 in Senshu region, Osaka, Japan were analyzed. Non-linear associations between mortality and pre-dialysis duration of nephrological care were assessed using restricted cubic spline function, and predictors for death analyzed on Cox modeling. A total of 31.6%, 18.2%, 11.3% and 6.1% of patients had >12, 24, 36 and 48 months of pre-dialysis care, respectively. A total of 258 patients (42.7%) were categorized as ER (≥6 months pre-dialysis duration). During the follow-up period (median, 31.1 months), 218 patients died (cardiovascular, n=70; infection, n=69). Although patients with late referral (LR) had a proxy of inappropriate pre-dialysis care compared with the ER group, Cox multivariate analysis failed to show a favorable association between ER and cardiovascular outcome. In contrast, a deleterious effect of LR on overall survival was observed but was limited only to the first 12 months of dialysis (HR, 1.957; 95% CI: 1.104–3.469; P=0.021), but not observed thereafter. Conclusions: Current pre-dialysis nephrological care may reduce short-term mortality but may not improve cardiovascular mortality after dialysis initiation. © 2016, Japanese Circulation Society. All rights reserved. Source

Temporin K.,Japan Community Health care Organization Osaka Hospital | Namba J.,Toyonaka Municipal Hospital | Okamoto M.,Toyonaka Municipal Hospital | Yamamoto K.,Toyonaka Municipal Hospital
Revue de Chirurgie Orthopedique et Traumatologique

Introduction: In minimally displaced pediatric lateral humeral condyle fractures, plain radiography cannot be used for accurate differential diagnosis of the cartilage lesion, and other imaging methods have demerits in their accuracy and their accessibility. The purpose of this study was to investigate the usefulness of arthroscopy to diagnose cartilage displacement in minimally displaced fractures. Materials and methods: Nine children with minimally displaced lateral humeral condyle fractures, an average of 6.6 years old, underwent combined arthroscopy and fixation surgery. Percutaneous fixation was performed with non-displaced articular surface according to the arthroscopic findings, while in case of displaced fracture under arthroscopy, open fixation was prefered. The difference between the arthroscopic and radiographic findings was investigated. Results: Articular surface could be arthroscopically visualized in all patients. Under arthroscopy, cartilage hinges were maintained in seven cases and disrupted in two. Non-displaced cartilage disruption was noted in one of these two cases, and percutaneous fixation was performed. A displaced articular surface was noted in the other one, where the patient underwent open surgery. At the last follow-up, an average of 14.7 months postoperatively, union and wide range of motion had been achieved without any complications. Conclusion: Diagnosis of fracture displacement by merely using plain radiography was considered to be insufficient for minimally displaced cases. Diagnostic arthroscopy aided in the appropriate selection of either a percutaneous or open fixation method. Level of evidence: Level IV, therapeutic case series. © 2015 Elsevier Masson SAS. Source

Kaneshiro S.,Japan Community Health care Organization Osaka Hospital | Kaneshiro S.,Osaka University | Otsuki D.,Osaka University | Yoshida K.,Osaka University | And 2 more authors.
Biochemical and Biophysical Research Communications

Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. © 2015 Elsevier Inc. All rights reserved. Source

Fuji T.,Japan Community Health care Organization Osaka Hospital | Wang C.-J.,Chang Gung University | Fujita S.,Takarazuka Daiichi Hospital | Kawai Y.,International University of Health and Welfare | And 2 more authors.
Journal of Arthroplasty

Edoxaban, an oral direct factor Xa inhibitor, has proven antithrombotic efficacy. In a multicenter, phase II study, 264 total hip arthroplasty (THA) patients randomly received edoxaban 15 or 30 mg once daily or enoxaparin 2000. IU (20-mg) twice daily for 11-14 days. Thromboembolic event incidences were 3.8% (3/78), 2.8% (2/72), and 4.1% (3/74) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively (P= 1.00). Edoxaban-induced prolongation of prothrombin time, international normalized ratio, and activated partial thromboplastin time were proportional to plasma edoxaban concentration. Major or clinically relevant non-major bleeding incidences were 2.2% (2/89), 1.2% (1/85), and 2.3% (2/87) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively (P= 1.00). Once-daily edoxaban showed similar efficacy and safety to enoxaparin for prevention of thromboembolic events in patients undergoing THA. © 2014 The Authors. Source

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