Omega-3 fatty acid ethyl esters improve low-density lipoprotein subclasses without increasing low-density lipoprotein-cholesterol levels: A phase 4, randomized study.

BACKGROUND AND AIMS: We aimed to investigate blood lipid and lipoprotein profiles in patients with dyslipidemia receiving hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) after 8 weeks of omega-3 fatty acid ethyl esters (Omega-3) treatment, using high-performance liquid chromatography with highly-sensitive gel filtration columns. METHODS: In this phase 4, randomized, open-label study, patients with dyslipidemia receiving statins were randomized 1:1 to Omega-3 treatment (oral Omega-3 2 g twice daily) or Control (no Omega-3). Primary endpoint was change in mean particle size of low-density lipoprotein (LDL) and small dense LDL (cholesterol monitoring) in the specific 20-lipoprotein fraction assay. Secondary endpoints included changes in lipids, apolipoproteins, and lipoprotein concentrations in fasting blood. Changes were compared between treatments using analysis of covariance, adjusted by baseline fasting triglycerides and age. RESULTS: Fifty-three patients were randomized (Omega-3, n = 24; Control, n = 29). The difference in LDL particle size between Omega-3 and Control groups was significant at week 8 (p = 0.0040). Differences in least squares mean change in concentration from baseline to week 8 between Omega-3 and Control groups were significant for total cholesterol (p = 0.0009), LDL-C (p = 0.0442), non-high-density lipoprotein cholesterol (p = 0.0009), and remnant lipoprotein-cholesterol (p = 0.0396). Differences were significant for apolipoproteins AI, AII, B, B-48, B-100, CII, CIII, and CII/III, but not apolipoprotein E. CONCLUSIONS: Significant increases in LDL particle sizes and significant decreases in blood lipid, lipoprotein and apolipoprotein concentrations were observed with Omega-3 compared with Control. Omega-3 may improve blood lipid profile and increase LDL particle size, resulting in an anti-atherogenic profile.

Randomized Multicenter Evaluation of Quality of Life and Treatment Satisfaction in Type 2 Diabetes Patients Receiving Once-Weekly Trelagliptin Versus a Daily Dipeptidyl Peptidase-4 Inhibitor.

INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors are an established treatment in type 2 diabetes mellitus (T2DM). The objective of this study was to investigate differences in quality of life (QOL) and treatment satisfaction among treatment-naïve T2DM patients receiving once-weekly trelagliptin or a daily DPP-4 inhibitor. METHODS: In this multicenter, randomized, open-label, parallel-group, phase IV study conducted in Japan, 218 patients were randomized to trelagliptin 100 mg once weekly or a once- or twice-daily DPP-4 inhibitor for 12 weeks (NCT03014479; JapicCTI-173482). QOL and treatment satisfaction were assessed using the Diabetes Therapy-Related QOL (DTR-QOL) Questionnaire and Diabetes Treatment Satisfaction Questionnaire (DTSQ), respectively. The primary endpoint was change from baseline in DTR-QOL total score at week 12. Secondary endpoints included further analysis of the DTR-QOL and DTSQ components. Other endpoints included glycemic control, treatment adherence, and safety. RESULTS: The between-group difference in the change from baseline to week 12 in DTR-QOL total score was 2.418 (95% confidence interval - 1.546, 6.382; P = 0.2305). Analysis of the DTR-QOL and DTSQ results by subscales and stratification generally showed a numerical improvement with trelagliptin over daily DPP-4 inhibitors. QOL and treatment satisfaction improved with a reduction in frequency of concurrent and study drug dosing. Treatment adherence was > 97% for both groups. The effect of trelagliptin on glycemic control was similar to that seen with daily DPP-4 inhibitors. Trelagliptin and daily DPP-4 inhibitors were well-tolerated and demonstrated similar safety profiles. CONCLUSIONS: Once-weekly trelagliptin 100 mg administered for 12 weeks resulted in a numerically, but not statistically, greater improvement in QOL and treatment satisfaction versus daily DPP-4 inhibitors. The decision to administer once-weekly or daily DPP-4 inhibitor treatment is likely to depend on patient preferences and the treatment policies of physicians. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03014479) and JAPIC (JapicCTI-173482). FUNDING: Takeda Pharmaceutical Company Ltd.

Giant serous cystadenoma of the pancreas appearing sonographically as a remote pararenal mass.

Macrocystic serous cystadenoma (MSC) of the pancreas is a rare benign neoplasm with varied imaging appearances. We describe an intriguing case of a surgically resected and histologically proven giant MSC, developed in the pararenal space. Ultrasonography (US) revealed a large, oligocystic mass around the lower pole of right kidney. Like US, computed tomography, and magnetic resonance imaging were unable to detect the origin of the lesion, which was only verified at surgical exploration. A bizarre finding was the unusual location of the pancreatic tumor growing seemingly apart from the pancreas itself, with no obvious connection to it.

Effect of Trelagliptin on Quality of Life in Patients with Type 2 Diabetes Mellitus: Study Protocol.

INTRODUCTION: Long-term glycemic control in type 2 diabetes is critical to prevent or delay the onset of macrovascular and microvascular complications. Medication adherence is an integral component of type 2 diabetes management. Minimizing the dosing frequency of antidiabetic drugs may reduce treatment burden for patients and improve medication adherence. This study has been proposed to assess the reduction in treatment burden during 12 weeks' administration of trelagliptin, a weekly dosing dipeptidyl peptidase-4 (DPP-4) inhibitor, compared with a daily dosing DPP-4 inhibitor in patients with type 2 diabetes. METHODS: This is a multicenter, randomized, open-label, parallel-group, comparative study to be conducted at approximately 15 sites across Japan. A total of 240 patients are to be randomized 1:1 to receive trelagliptin or a daily DPP-4 inhibitor for 12 weeks. Efficacy and safety will be compared between the two groups. The primary endpoint is the change in total score for all items of the diabetes-therapy-related QOL questionnaire from treatment start to treatment end. The study will be conducted with the highest respect for the individual participants in accordance with the protocol, the Declaration of Helsinki, the Ethical Guidelines for Clinical Research, the ICH Consolidated Guideline for Good Clinical Practice, and applicable local laws and regulations. FUNDING: Takeda Pharmaceutical Company Limited. TRIAL REGISTRATION NUMBER: Japic CTI-173482.

Efficacy and safety of a 60-week treatment with candesartan in Japanese patients with mild to moderate chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is an increasingly common cardiovascular disease despite recent advances in its diagnosis and management. METHODS AND RESULTS: A multicenter, open-label study was designed to assess the efficacy and safety of 60-week treatment with candesartan in Japanese patients with mild to moderate CHF. Primary efficacy endpoints were changes from baseline in plasma brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), end-diastolic dimension, and New York Heart Association (NYHA) functional class. Two hundred and eighty-nine eligible patients were divided into 2 groups based on the daily dose at the end of treatment: high-dose (HD, 8mg, N=170) and low-dose (LD, 2 or 4mg, N=119). Neither plasma BNP levels nor LVEF changed from the baseline to the end of treatment in the LD group, whereas BNP significantly improved from 61.6 to 50.1pg/mL (p=0.0005) and LVEF from 57.2 to 60.1% (p=0.0005) in the HD group. The changes in NYHA functional class were comparable between groups: 21.2% improved and 76.3% unchanged in the LD group and 20.6% improved and 79.4% unchanged in the HD group. No safety concerns were observed in either group. CONCLUSIONS: HD candesartan was more effective in improving plasma BNP levels and cardiac function than LD in Japanese CHF patients. Both LD and HD candesartan were well tolerated in CHF patients.

Evaluation of the efficacy and tolerability of combination therapy with candesartan cilexetil and amlodipine besilate compared with candesartan cilexetil monotherapy and amlodipine besilate monotherapy in Japanese patients with mild-to-moderate essential hypertension: a multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-group study.

BACKGROUND: Blood pressure is reported to be insufficiently controlled in >50% of patients with hypertension. Guidelines for the management of hypertension recommend using drugs with different mechanisms of action when >1 agent is needed to achieve the blood pressure target. The combination of an angiotensin II receptor blocker and a calcium channel blocker is recommended as the preferred antihypertensive medication combination, and candesartan cilexetil (CC) and amlodipine besilate (AML) are commonly used in Japan. OBJECTIVE: The objective of our study was to determine if the combination of CC 8 mg and AML 5 mg has a greater blood pressure-lowering effect than monotherapy with either component, and if the combination of CC 4 mg and AML 2.5 mg has a greater blood pressure-lowering effect than placebo. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in Japanese patients with mild-to-moderate essential hypertension. After receiving placebo during a 4-week run-in period in a single-blind manner, patients were randomized to receive the combination of CC 4 or 8 mg with AML 2.5 or 5 mg, CC 8 mg monotherapy, AML 5 mg monotherapy, or placebo once daily in the fasting or fed state for 12 weeks. The primary end point was change from baseline in trough diastolic blood pressure, and the secondary end point was change from baseline in trough systolic blood pressure at the end of treatment. Tolerability was assessed based on adverse events, vital signs, and physical findings. RESULTS: Of 548 patients who received placebo during the run-in period, 444 were randomized to receive CC 8 mg/AML 5 mg (CC/AML 8/5 mg) (n = 101), 8/2.5 mg (n = 36), 4/5 mg (n = 36), 4/2.5 mg (n = 35), CC 8 mg (n = 100), AML 5 mg (n = 100), or placebo (n = 36). These 444 patients included 272 men and 172 women. The mean (SD) age was 56.9 (10.7) years and the mean baseline BP was 153.4/95.7 mm Hg. The antihypertensive effect in the CC/AML 8/5 mg group (-27.4/-16.3 mm Hg) was significantly higher than in the CC 8 mg group (-13.9/-7.8 mm Hg) or the AML 5 mg group (-19.9/-11.2 mm Hg) in terms of reduction in the seated trough diastolic blood pressure and systolic blood pressure (both P < 0.0001). The incidence and severity of adverse events in the CC/AML combination groups did not differ significantly from those in the monotherapy and placebo groups. CONCLUSIONS: In Japanese adult patients with mild-to-moderate essential hypertension, CC/AML 8/5 mg combination therapy was more effective in lowering blood pressure than CC 8 mg or AML 5 mg monotherapy. These combinations were also well tolerated. Japan Pharmaceutical Information Center registration number: Japic CTI-101054.

FDG PET for rheumatoid arthritis: basic considerations and whole-body PET/CT.

[(18) F]Fluorodeoxyglucose (FDG) is a tracer for glucose metabolism. Its distribution is not specific to cancer cells but is also observed in inflammatory tissue, including macrophages, capillaries, and fibroblasts. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. The disease is characterized by fibrovascular proliferation leading to the formation of a pannus and causing high FDG uptake. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between uptake and various clinical parameters having been noted. Furthermore, the use of FDG PET for the sensitive detection and monitoring of the response to RA therapy has been reported. FDG PET/computed tomography (CT) enables the detailed evaluation of disease in large joints throughout the whole body, which is a unique advantage of PET/CT. FDG PET/CT can also be used to detect high-risk disease complications, such as atlanto-axial joint involvement, at an early stage. The possible contribution of FDG PET to the management of patients with RA remains to be studied in detail.

Spontaneous spinal subarachnoid hemorrhage associated with subdural hematoma at different spinal levels.

We describe the clinical features and MR-imaging findings of spontaneous spinal subarachnoid hemorrhage located in the lumbar spine associated with subdural hematoma at a higher, thoracic level in a 66-year-old man without neurological deficit. The sequential MR-imaging changes of hemorrhage at various stages in its evolution are portrayed. The possible pathogenetic mechanism for these very unusual, combined hemorrhages in both spinal compartments is discussed.

Growing porcine oocyte-granulosa cell complexes acquired meiotic competence during in vitro culture.

The aim of this study was to establish a culture system to improve the meiotic competence of porcine oocyte-granulosa cell complexes (OGCs) obtained from preantral or early antral follicles. Porcine OGCs were recovered from follicles with diameters of 230-300 (preantral follicles), 300-500, and 500-700 mum (early antral follicles) using scalpels. The OGCs were cultured for 2 weeks in culture medium. We examined the effects of the sizes of the follicles from which OGCs were recovered, the concentrations of polyvinylpyrrolidone (PVP, 0-8%) in the culture medium, and 2 types of culture dish (Falcon 3002 vs 1007) on formation of the antrum of OGCs. After culture, the oocytes were matured for 44 h to assess their meiotic competence. OGCs recovered from small follicles (230-500 microm) required longer (P<0.05) than larger follicles to form the antrum structure. The percentage of OGCs forming the antrum structure that were cultured in 2% PVP (31%) was higher (P<0.05) than for those cultured in other PVP concentrations (0-11%). The percentages of antrum-structure formation for OGCs cultured on Falcon 3002 (83% for 2% PVP and 60% for 4% PVP) were higher (P<0.05) than those cultured on Falcon 1007 (47% for 2% PVP and 9% for 4% PVP). Furthermore, all of the intact oocytes that were obtained from culture of OGCs and that formed an antrum were in the GV stage (n=28). When these immature oocytes were cultured for 44 h, the percentage of oocytes that reached the metaphase II stage (25%, n=68) was higher (P<0.0001) than that of oocytes matured without culture (0.7%, n=137). The results of the present study show that porcine OGCs obtained from preantral or early antral follicles acquire meiotic competence in vitro.