Optimal Combination of Effective ANtihypertensives (OCEAN) study: a prospective, randomized, open-label, blinded endpoint trial--rationale, design and results of a pilot study in Japan

There are limited clinical trials examining the efficacy of antihypertensive drug combinations aimed at preventing cardiovascular events. Therefore, we designed a randomized controlled trial using amlodipine as the base drug of a multi-drug regimen, the Optimal Combination of Effective ANtihypertensives (OCEAN) Study, to determine the drug combination that is most efficacious in the prevention of cardiovascular events, such as stroke. The OCEAN Study is a collaborative study between Japan and China, enrolling 20?000 patients and following them for 3 to 4 years. A pilot study was conducted before the full-scale study to confirm the feasibility of the protocol and that the study groups and infrastructures could function properly. A total of 279 Japanese patients were enrolled from 57 participating medical institutions between June and December 2004. Two hundred and sixty-six patients (mean age: 65.9 years) were treated with amlodipine alone. One hundred and fifty-four of these patients (57.9%) did not reach the treatment targets (<140/90?mm?Hg for the elderly and patients with cerebrovascular disease, <130/80?mm?Hg for those with diabetes mellitus, chronic kidney disease or prior myocardial infarction) and a second agent was added. They were randomly allocated into three different treatment groups using a diuretic, a β-blocker or an angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist. The pilot study showed that the protocol was appropriate, and the inclusion of patients with slightly higher blood pressures was necessary to increase the randomization rate. It also confirmed that we organized properly functioning study groups and infrastructures.     

Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: the effect of etanercept on the serum levels of IL-33

To investigate the role of interleukin (IL)-33 in rheumatoid arthritis (RA) patients, we measured the serum levels of IL-33 in RA patients before and after the administration of etanercept. Twenty-four patients with RA were treated with etanercept. Clinical and laboratory examinations, including serum levels of C-reactive protein (CRP) and hemoglobin (Hb); white blood cell (WBC) and red blood cell (RBC) counts; and the Disease Activity Score of 28 joints including CRP (DAS28-CRP), were performed at the baseline and at 3 and 6 months after the initial treatment with etanercept. The mean serum IL-33 levels had decreased significantly at 3 and 6 months after the initial treatment with etanercept. Serum IL-33 levels showed a significant correlation with the number of tender joints, CRP, DAS28-CRP, and the WBC count, and an inverse correlation with the RBC count and Hb level. These findings indicated that the decrease of serum IL-33 levels was a novel function of etanercept, shown for the first time in this study. Measurement of serum levels of IL-33 may become a useful control marker for RA treatment.     

Revised FIGO staging system for cancer of the ovary,fallopian tube,and peritoneum: important implications for radiologists

Ovarian cancer is the seventh most common cancer diagnosis among women worldwide. The International Federation of Gynecology and Obstetrics recently significantly revised staging criteria for cancer of the ovary. The latest revision was based on the concept that high-grade serous tubal intraepithelial carcinoma (STIC) may be the origin of some high-grade serous carcinomas of the ovary and peritoneum. Therefore, staging criteria for the ovary, fallopian tube, and peritoneum have been unified. Understanding this background and other important revised points are essential for radiologists concerned with imaging diagnosis in gynecologic oncology. Through this review, we introduce the STIC theory and show examples of diseases in accordance with the new staging criteria based on magnetic resonance imaging (MRI) and computed tomography (CT) results.     

Associations of radiographic degeneration and pain with daily cumulative hip loading in patients with secondary hip osteoarthritis

The purpose of this study was to investigate the associations of radiographic and clinical variables of hip osteoarthritis (OA) with alterations in gait and joint loading in patients with secondary hip OA. Fifty females with secondary hip OA were participated. The minimum joint space width (mJSW) of the hip as a degenerative sign and Sharp and center edge (CE) angles as morphological variables were measured radiographically. Hip joint pain was assessed using a visual analog scale. As gait variables, walking speed, range of hip motion, hip moment peak, and hip moment impulse were calculated. Daily cumulative hip loading was calculated as the hip moment impulse multiplied by the mean number of steps per day. After bivariate correlation analyses between dependent (mJSW and pain) and independent variables (age, body mass index, sharp/CE angles, steps per day, and gait variables), separate forward‐backward stepwise multiple regression analyses were performed for each dependent variable. Daily cumulative hip loading in the sagittal plane (β = 0.30, p = 0.021) and age (β = ?0.36, p = 0.007) were significantly associated with the mJSW. Walking speed (β = ?0.36, p = 0.008) and age (β = 0.29, p = 0.031) were significantly associated with hip joint pain. Decrease in daily cumulative hip loading in the sagittal plane was associated with mJSW independently of age. Although the causal relationship was not clear, patients with hip OA reduced total exposure to hip joint loading adaptively rather than lowering the hip moment peak concerning worsening of hip degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1977–1983, 2016.

     

Clinical Effect of Switching from a Luteinizing Hormone-Releasing Hormone Agonist to an Antagonist in Patients with Castration-Resistant Prostate Cancer and Serum Testosterone Level ≥ 20 ng/dl

Introduction

The efficacy of conversion from a luteinizing hormone-releasing hormone agonist to an antagonist was evaluated prospectively in patients with castration-resistant prostate cancer.

Materials and Methods

From October 2012 to December 2014, 8 cases with a serum testosterone level ≥ 20 ng/dl during following androgen deprivation therapy were enrolled and received degarelix monthly. The primary end-pointgoal was to determine the effective prostate-specific antigen response rate. The secondary end-pointgoal was to assess the proportion of cases with a decrease in serum testosterone level to < 20 ng/ml.

Results

One patient achieved a complete response, with a prostate-specific antigen level of 0.02 ng/ml at the nadirend of the study. The effective response rate was 25.0% (2/8), and the proportion of cases with prostate-specific antigen decline was 62.5% (5/8). In 5/8 cases (5/8, 62.5%), serum testosterone levels declined to < 20 ng/dl.

Conclusion

Switching to a luteinizing hormone-releasing hormone antagonist in patients with testosterone levels ≥ 20 ng/dl may be an option in sequential androgen deprivation therapy for some patients.Key Words: Castration-resistant, Degarelix, Prostatic neoplasms, Luteinizing hormone-releasing hormone, Testosterone     

Analysis of antigen-stimulated B cell migration into germinal centers during the early stage of a T-dependent immune response

The quasimonoclonal (QM) mouse provides a model to analyze B cell selection because major B cell antigen receptors (BCR) are composed of the knockin V(H)DJ(H) 17.2.25 (V(H)T) encoded H chain and the lambda1 or lambda2 L chain, thereby being specific for (4-hydoxy-3-nitrophenyl)acetyl (NP). We have reported that during a T-dependent antibody (Ab) response for a low-affinity NP analog p-nitrophenylacetyl (pNP), although V(H)T/lambda1 and V(H)T/lambda2 IgM were equally produced, V(H)T/lambda2 IgG almost exclusively underwent affinity maturation toward pNP. The initial affinity of V(H)T/lambda2 B cells for pNP was approximately 50-100-fold higher than that of V(H)T/lambda1 B cells, suggesting a role of BCR affinity in recruiting B cells to affinity maturation processes. Here, we investigated whether the intensity of BCR signals could contribute to the selection of V(H)T/lambda2 B cells for affinity maturation. V(H)T/lambda2 B cells were more responsive to pNP than V(H)T/lambda1 B cells in vitro. When CFSE-labeled QM B cells were transferred into the wild type mice where T cells had been primed with chicken gamma-globulin (CGG), QM B cells challenged by pNP-conjugated CGG could be observed to get activated and migrate to GCs in the early phase of the T-dependent response to pNP-CGG. Adoptive transfer of sorted populations revealed that the V(H)T/lambda2 B cell population was more potent in migration into GCs than the V(H)T/lambda1 counterpart. Thus, it is suggested that the higher BCR affinity of V(H)T/lambda2 B cells may be an initial cue for their recruitment to GCs during a T-dependent Ab response.