Thromboembolic Events in the Hemodialysis Setting: Understanding Risk Profiles and Cumulative Incidences to Inform Clinical Trial Design.

Background: People with kidney failure have a high risk of cardiovascular morbidity/death, including thromboembolic events. Factor XIa inhibitors are a new class of anticoagulants in development that may offer antithrombotic benefits with a lower risk of incremental bleeding events than traditional therapies. We investigated major adverse vascular events (MAVEs), a relevant composite outcome for testing novel antithrombotic agents, in a large cohort of patients on hemodialysis, to better understand the key requirements to adequately design a phase 3 trial.

Unsupervised machine-learning algorithms for the identification of clinical phenotypes in the osteoarthritis initiative database.

Objectives: Osteoarthritis (OA) is a complex disease comprising diverse underlying patho-mechanisms. To enable the development of effective therapies, segmentation of the heterogenous patient population is critical. This study aimed at identifying such patient clusters using two different machine learning algorithms.

Seroprevalence and Factors Associated with Risk of Hepatitis B Virus Infection among Antenatal Attendees in ABUTH Zaria, Northwestern Nigeria.

Background: Nigeria is one of the sub-Saharan African countries within the World Health Organization's (WHO) hyperendemic region for hepatitis B virus infection with prevalence greater than 8%. In this region, mother-to-child transmission is the major route of infection and approximately 90% of newborns of mothers who are seropositive for HBsAg and HBeAg become chronic carriers with a 25% risk of developing chronic liver diseases. This study aimed to determine the seroprevalence, and factors associated with risk of hepatitis B virus infection among antenatal attendees in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria.

[Non-malignant, non-infectious lymphoproliferation: challenges in the diagnosis and treatment of autoimmune lymphoproliferative syndrome].

Összefoglaló. Az autoimmun lymphoproliferativ szindróma egy ritka, immundeficientiával járó genetikai betegség. Hátterében az extrinszik apoptotikus útvonal génjeinek örökletes vagy szerzett mutációi és a következményesen kialakuló, aktivált lymphocyták negatív szelekciójának a defektusa áll.

Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis.

Objective: To assess the long-term safety and tolerability and to monitor benefits of extended use of bimagrumab in individuals with sporadic inclusion body myositis (sIBM) who completed a single-dose core study.

Methods: In this multicenter, open-label extension study, 10 adults received bimagrumab 10 mg/kg IV every 4 weeks up to 2 years (104 weeks). Safety (primary endpoint) was assessed by recording adverse events (AEs).

Effect of bimagrumab on thigh muscle volume and composition in men with casting-induced atrophy.

Background: Patients experiencing disuse atrophy report acute loss of skeletal muscle mass which subsequently leads to loss of strength and physical capacity. In such patients, especially the elderly, complete recovery remains a challenge even with improved nutrition and resistance exercise. This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization.

Does Activin Receptor Blockade by Bimagrumab (BYM338) Pose Detrimental Effects on Bone Healing in a Rat Fibula Osteotomy Model?

Bimagrumab (BYM338) is a novel fully human monoclonal antibody that exerts strong promyogenic effects on skeletal muscle by blocking activin type II receptors (ActRII). We investigated whether such blockade of ActRII by bimagrumab manifests any detrimental effect on outcomes of bone healing in a rat fibula osteotomy model. Animals (n = 150) were divided into 11 groups and received weekly treatment with either bimagrumab (10 or 100 mg/kg) or vehicle.

Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.

Unlabelled: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent.

Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix.

Purpose: We investigated associations of baseline cardiovascular disease risk profile, dosing regimen and treatment duration with incident cardiovascular disease events during androgen deprivation therapy with degarelix in patients with prostate cancer.

Materials And Methods: Data on 1,704 men who participated in a total of 9 clinical trials were pooled for analysis. Patients received treatment with 1-month (20 to 240 mg) or 3-month (240 to 480 mg) doses of degarelix for an average of 22 months.

Metabolite profiles of degarelix, a new gonadotropin-releasing hormone receptor antagonist, in rat, dog, and monkey.

Degarelix is a novel competitive gonadotropin-releasing hormone receptor blocker (antagonist). In this study, the nonclinical metabolism and excretion of degarelix was investigated in Sprague-Dawley rat, beagle dog, and cynomolgus monkey. Degarelix was found to be stable when incubated in microsomes and cryopreserved hepatocytes from animal liver tissue.

Hot flushes in prostatic cancer patients during androgen-deprivation therapy with monthly dose of degarelix or leuprolide.

The aim of the study was to compare the onset, incidence and frequency/intensity of hot flushes during androgen-deprivation therapy with a gonadotropin-releasing hormone antagonist (GnRH) blocker versus an agonist using data from a randomized Phase 3 clinical trial. In total, 610 prostate cancer patients received monthly degarelix (s.c.

Degarelix, a novel GnRH antagonist, causes minimal histamine release compared with cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples.

Aims: Early studies on gonadotrophin-releasing hormone (GnRH) antagonists pointed out histamine-mediated anaphylactic reactions as a potential adverse effect of these drug candidates. In this study we have compared the histamine-releasing potential of four approved and marketed antagonists, degarelix, cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples.

Methods: Human skin samples were obtained during cosmetic plastic surgery and kept in oxygenated saline solution.

Lack of association of the serotonin transporter gene promoter region polymorphism, 5-HTTLPR, including rs25531 with cigarette smoking and alcohol consumption.

We addressed the question whether 5-HTTLPR, a variable number of tandem repeats located in the 5' end of the serotonin transporter gene, is associated with smoking or alcohol consumption. Samples of DNA from 1,365 elderly women with a mean age of 69.2 years were genotyped for this polymorphism using a procedure, which allowed the simultaneous determination of variation in the number of repeat units and single nucleotide changes, including the A > G variation at rs25531 for discrimination between the L(A) and L(G) alleles.

Automated effect-specific mammographic pattern measures.

We investigate the possibility to develop methodologies for assessing effect specific structural changes of the breast tissue using a general statistical machine learning framework. We present an approach of obtaining objective mammographic pattern measures quantifying a specific biological effect, such as hormone replacement therapy (HRT). We compare results using this approach to using standard density measures.

Higher physical activity is associated with increased androgens, low interleukin 6 and less aortic calcification in peripheral obese elderly women.

The presence of peripheral fat mass (PFM) appears to counteract the atherogenic trends of central fat mass through mechanisms presently poorly understood. In elderly women with distinct forms of body fat distribution, we wanted to study whether physical activity and aortic calcification are related to plasma levels of cortisol, 17-alpha-hydroxyprogesterone (17-alpha-OHP), dehydroepiandrosterone (DHEA), androstenedione (ASD), and interleukin 6 (IL6) accomplishing an anti-atherogenic milieu. A total of 276 well-defined generally healthy women aged 60-85 years were included.

Parallel assessment of the impact of different hormone replacement therapies on breast density by radiologist- and computer-based analyses of mammograms.

Objectives: First, to compare the impact of nasally and orally dosed estradiol on breast density; second, to investigate the utility of computer-based automated approaches to the assessment of breast density with reference to traditional methods.

Methods: Digitized images from two 2-year, randomized, placebo-controlled trials formed the basis of the present post hoc analysis. Active treatments were 1 mg estradiol continuously combined with 0.

An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage.

Objective: To review cellular mechanisms that have been proposed to mediate the indirect and direct effects of estrogen on articular cartilage, and to outline the remaining clinical questions that need to be clarified before utilizing the beneficial effects of estrogen for the prevention of osteoarthritis in early postmenopausal women.

Design: Summary of original research papers and reviews listed in Pubmed (1980-2007).

Results: Estrogen receptors have been identified in articular chondrocytes from various animals and humans.

Quantifying calcification in the lumbar aorta on X-ray images.

In this paper we propose to use inpainting to estimate the severity of atherosclerotic plaques from X-ray projections. Inpainting allows to "remove" the plaque and estimate what the background image for an uncalcified aorta would have looked like. A measure of plaque severity can then be derived by subtracting the inpainting from the original image.

Effect of RANKL-specific denosumab on osteoclast number and function: a potential friend or foe?

The antiresorptive effect of a single 60-mg injection of the RANKL (receptor activator of NFkappaB ligand)-specific mAb, denosumab, substantially exceeds the effects of alendronic acid (70 mg weekly) yet increases in bone mass at the lumbar spine are identical for both agents. Important experimental and clinical observations illustrating some of the potential consequences of osteoclast deficiency and low-rate bone resorption for osteoblast function, bone mineralization, bone quality and related mechanical properties are summarized. This review also discusses whether the benefits for bone health can be improved when aggressively pushing the limits with novel antiresorptive medications.

Quantitative vertebral morphometry using neighbor-conditional shape models.

A novel method for vertebral fracture quantification from X-ray images is presented. Using pairwise conditional shape models trained on a set of healthy spines, the most likely normal vertebra shapes are estimated conditional on the shapes of all other vertebrae in the image. The difference between the true shape and the reconstructed normal shape is subsequently used as a measure of abnormality.

Association of a dopamine beta-hydroxylase gene variant with depression in elderly women possibly reflecting noradrenergic dysfunction.

Background: Depression has a multifactorial etiology which involves genetic factors and comorbid diseases.

Methods: A cross-sectional sample of 1371 elderly women (mean age=69.2 years) was examined.

The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model.

Objective: To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.

Methods: Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-operated, ovariectomy, ovariectomy plus subcutaneously implanted 17beta-estradiol pellet, ovariectomy plus 2 mg/kg salmon calcitonin plus 50 mg/kg 5CNAC (carrier), or ovariectomy plus 50 mg/kg 5CNAC. Each treatment was administered for 9 weeks after the ovariectomy.