Differences in serum and plasma levels of microRNAs and their time-course changes after blood collection.

Background: Serum and plasma are used for measurements of microRNAs (miRNAs) as biomarkers of various diseases. However, no consistent findings have been obtained regarding differences in serum and plasma levels of miRNAs. The purpose of this study was to clarify differences in serum and plasma levels of total miRNAs and their time-course changes after blood collection.

Nocturnal Hypertension and Left Ventricular Diastolic Dysfunction in Patients With Diabetes With the Absence of Heart Failure: Prospective Cohort HSCAA Study.

Background: Diabetes is an important risk factor for heart failure (HF) and is associated with left ventricular (LV) diastolic dysfunction. However, diabetic comorbid conditions, such as nocturnal hypertension, as predictors of diastolic dysfunction are not known in the absence of an HF period. The present study was conducted as the longitudinal examination of the predictive value of nocturnal hypertension profiles on the progression of LV diastolic dysfunction in patients with and without diabetes without HF.

Resection of positive tissue on methionine-PET is associated with improved survival in glioblastomas.

Background And Purpose: The volume of excised tumor in contrast-enhanced areas evaluated via magnetic resonance imaging is known to have a strong influence on the survival of patients with glioblastoma (GBM). In this study, we investigated the effect of tumor resection on the survival of patients with GBM in the C-methionine (MET) accumulation area using MET-positron emission tomography (MET-PET).

Methods: A total of 26 patients (median age, 69 years; 15 males) who had undergone tumor resection and MET-PET before and after surgery, after being newly diagnosed with GBM, were included in the study.

A randomized phase III study of docetaxel alone versus docetaxel plus S-1 in patients with previously treated non-small cell lung cancer: JMTO LC09-01.

Background: This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S-1 in patients with previously treated non-small cell lung cancer (NSCLC) compared to docetaxel alone.

Methods: Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S-1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS).

Hematometabolic Index as a New Discriminator of Cardiometabolic Risk in Middle-Aged Men with Polycythemia and High Leukocyte Count in Peripheral Blood.

Both polycythemia and high leukocyte count are associated with the risk of cardiovascular disease. However, it remains to be determined whether polycythemia and high leukocyte count show synergistic increasing effects on cardiometabolic risk. Cardiometabolic risk was evaluated by cardiometabolic index (CMI) and metabolic syndrome in a cohort of middle-aged men ( = 11,140) who underwent annual health check-up examinations.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT.

Methods: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan.

Peritransplantation Glucocorticoid Haploidentical Stem Cell Transplantation Is a Promising Strategy for AML Patients With High Leukemic Burden: Comparison With Transplantations Using Other Donor Types.

Using a murine haploidentical bone marrow transplantation (BMT) model, we recently showed that peritransplantation administration of glucocorticoid (GC) redistributed donor T cells from the gastrointestinal tract to bone marrow, which resulted in a significant reduction of graft-versus-host disease (GVHD) while promoting graft-versus-leukemia effects. Furthermore, in a retrospective clinical study of patients with acute myelogenous leukemia (AML) undergoing transplantation in non-remission, we also showed that haploidentical stem cell transplantation (haplo-SCT) using peritransplantation GC administration led to a significantly lower relapse rate and better overall survival rate compared with haplo-SCT using post-transplantation cyclophosphamide. In the present study, using the same dataset of patients undergoing GC haplo-SCT, we retrospectively compared with patients with AML undergoing transplantation in non-remission using 3 other donor types: matched sibling donor (MSD), matched unrelated donor (MUD), and umbilical cord blood (UCB).

Usefulness of the placebo lead-in design for clinical trials with binary outcomes.

Background: In placebo-controlled clinical trials to develop new drugs for the treatment of psychiatric or neurological disorders, a high and sometimes greater-than-expected placebo response makes it difficult to show the superiority of an investigational drug over a corresponding placebo. To avoid such difficulty, a placebo lead-in design has been presented, but its usefulness has been open to discussion. Although the statistical properties of the placebo lead-in design are investigated in the context of continuous outcomes, whether these properties can be generalized for binary or ordinal cases remains unclear.

Clinical Efficacy and Safety of Nivolumab in Malignant Non-Pleural Mesothelioma: A Multicenter, Open-Label, Single-Arm, Japanese Phase II Trial (Viola) Protocol.

Background: There is no authorized treatment for malignant non-pleural mesothelioma (MNPM) worldwide. In contrast to malignant pleural mesothelioma, MNPM has not been investigated, and no treatment has been established due to its rarity.

Objectives: This multicenter, open-label, single-arm, Japanese phase II trial aims at evaluating the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in advanced or metastatic MNPM treatment.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

Purpose: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model.

Attenuation by habitual alcohol drinking of the associations of obesity with blood pressure and pulse pressure.

Background: Obesity and alcohol drinking are known to be risk factors for hypertension. However, it remains to be determined whether alcohol affects the relationships of obesity with blood pressure and pulse pressure.

Methods: The participants in this study were 29 171 men who had received annual health checkups.

Sleep Apnea and Physical Movement During Sleep, But Not Sleep Duration, Are Independently Associated With Progression of Left Ventricular Diastolic Dysfunction: Prospective Hyogo Sleep Cardio-Autonomic Atherosclerosis Cohort Study.

Background Although co-occurrence of sleep disorder with heart failure is known, it is not clear whether that condition is a cause or consequence of heart failure. The present study was conducted as a longitudinal examination of the predictive value of sleep parameters on progression of left ventricular diastolic dysfunction. Methods and Results Four-hundred fifty-two subjects were followed for a mean of 34.

Intratumor hemodynamics using contrast-enhanced MRI in intra-arterial chemotherapy for head and neck cancer.

Objective: The objectives of the study were to estimate the perfusion of tumors by drugs used in intra-arterial chemotherapy for head and neck cancer with magnetic resonance imaging and to establish the factors involved in determining the optimal dose.

Study Design: Contrast agent was administered intra-arterially into either the lingual or maxillary artery in 43 patients. Triple-phase continuous fast spin echo magnetic resonance imaging was performed.

Regulatory issues and the potential use of Bayesian approaches for early drug approval systems in Japan.

Bayesian methods quantify and interpret the therapeutic effects of investigational drugs based on probability statements of the posterior distribution. However, the basic principle underlying the use of Bayesian methods in registration trials for new drug applications in Japan has not been adequately discussed. Motivated by the two drug approval systems for early approval recently enacted in Japan, we present our perspectives on the application of the Bayesian approach in registration trials in Japan.

Associations of Blood Urate Level with Glycemic Status and Other Cardiometabolic Risk Factors in Middle-Aged Women.

Hyperuricemia is a risk factor of cardiovascular disease. It remains to be elucidated how blood urate level is associated with hyperglycemia in women. The participants were 4612 middle-aged Japanese female workers.

Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT.

Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes, with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities, but it typically requires intensive immunosuppression with posttransplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here, we demonstrate in preclinical models that glucocorticoid administration from days -1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T cell priming and subsequent expansion therein.

Ethnic Differences in Serum Levels of microRNAs Potentially Regulating Alcohol Dehydrogenase 1B and Aldehyde Dehydrogenase 2.

Ethnic difference is known in genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B), which cause Asian flushing by blood vessel dilation due to accumulation of acetaldehyde. We investigated ethnic differences in microRNAs (miRNAs) related to ALDH2 and ADH1B. miRNA levels in serum were totally analyzed by using miRNA oligo chip arrays and compared in Austrian and Japanese middle-aged men.

Neoadjuvant pemetrexed plus cisplatin followed by pleurectomy for malignant pleural mesothelioma.

Purpose: Despite becoming the preferred surgical technique for malignant pleural mesothelioma, pleurectomy/decortication has received few prospective clinical trials. Therefore, the Japan Mesothelioma Interest Group conducted a prospective multi-institutional study to evaluate the feasibility of neoadjuvant chemotherapy followed by pleurectomy/decortication.

Methods: Patients with histologically confirmed, resectable malignant pleural mesothelioma underwent neoadjuvant chemotherapy comprising pemetrexed 500 mg/m plus cisplatin 75 mg/m for 3 cycles, followed by pleurectomy/decortication.

Heterogeneous reduction in regional wall stress after aortic valve replacement for aortic regurgitation: a distinct feature from aortic stenosis.

Geometric changes caused by volume reduction early after aortic valve replacement (AVR) for aortic regurgitation (AR) may not be uniform, resulting in varying regional end-systolic wall stress (ESS). This study compared changes in regional ESS between AR and aortic stenosis (AS) patients in the early phase following AVR. Computer-tomographic left ventricular (LV) angiography was performed for 10 patients with AR and 13 with AS before and three months after AVR.

Detrimental effects of elevated transpulmonary gradient on outcomes following restrictive mitral annuloplasty in patients with pre-existing pulmonary hypertension.

Background: This study retrospectively examined the association between elevated trans-pulmonary gradient (TPG), which reflects pre-capillary contribution to pulmonary hypertension (PH), and postoperative pulmonary hemodynamics and outcomes following restrictive mitral annuloplasty (RMA) in patients with pre-existing PH.

Methods: Pre- and postoperative (1 month) cardiac catheterization was performed in 64 patients with severely impaired left ventricular function (i.e.

Efficacy and Safety of Landiolol in Patients With Ventricular Tachyarrhythmias With or Without Renal Impairment - Subanalysis of the J-Land II Study.

Post hoc analysis was used to investigate the effects of renal function on the efficacy and safety of landiolol using data from the J-Land II study, which evaluated landiolol in patients with hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) who were refractory to Class III antiarrhythmic drugs. Patient data from the J-Land II study (n=29) were stratified by renal function (estimated glomerular filtration rate [eGFR] <45 and ≥45 mL/min/1.73 m) and analyzed.

Tibial Tubercle-Midepicondyle Distance Can Be a Better Index to Predict the Outcome of Medial Patellofemoral Ligament Reconstruction Than Tibial Tubercle-Trochlear Groove Distance.

Purpose: To compare the clinical utility of tibial tubercle-midepicondyle (TT-ME) and tibial tubercle-trochlear groove (TT-TG) distances in predicting the risk for recurrent instability after isolated MPFL reconstruction.

Methods: A consecutive series of patients with recurrent patellar dislocation who underwent isolated MPFL reconstruction made up the study population. The patients were followed for a minimum of 2 years.

A Comparison Between a Meta-analytic Approach and Power Prior Approach to Using Historical Control Information in Clinical Trials With Binary Endpoints.

Background: In the process of research and development of a new treatment, clinical trials are conducted to evaluate its safety and efficacy. Key to streamlining the process is to utilize appropriate historical information on an outcome of a control treatment when designing and analyzing a clinical trial.

Methods: For the use of such historical control information, there exist a meta-analytic approach and power prior approach.