Disentangling the genetics of lean mass.

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.

Genetic polymorphisms in ABCG2 and CYP1A2 are associated with imatinib dose reduction in patients treated for gastrointestinal stromal tumors.

Imatinib has a mild toxicity profile, although severe adverse events may develop. In this pharmacogenetic pathway analysis the need for dose reduction and cessation of therapy was tested for an association with single nucleotide polymorphisms (SNPs) in genes related to imatinib pharmacology. Retrospective data from 315 patients with a gastrointestinal stromal tumor who received imatinib 400 mg o.

Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

A correction to this article has been published and is linked from the HTML version of this article.

Genetic polymorphisms in angiogenesis-related genes are associated with worse progression-free survival of patients with advanced gastrointestinal stromal tumours treated with imatinib.

Background: Imatinib 400 mg per day is first-line therapy for patients with gastrointestinal stromal tumours (GISTs). Although clinical benefit is high, progression-free survival (PFS) is variable. This study explores the relationship of single nucleotide polymorphisms (SNPs) in genes related to imatinib pharmacokinetics and pharmacodynamics and PFS in imatinib-treated patients with advanced GIST.

[Focal lesions in whole-body MRI in multiple myeloma : Quantification of tumor mass and correlation with disease-related parameters and prognosis].

Background And Objectives: In this study, we evaluated methods of quantification of tumor mass in whole-body MRI (wb-MRI) in multiple myeloma and correlated these with disease-related parameters in serum and bone marrow.

Materials And Methods: We retrospectively evaluated wb-MRIs of 52 patients with focal infiltration pattern and a total of 700 focal lesions (subsequently called lesions). We determined the longest diameter (LD), the segmented volume (SV), and the morphology (spherical or non-spherical).

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10) or suggestively genome wide (p < 2.

Genetic polymorphisms as predictive biomarker of survival in patients with gastrointestinal stromal tumors treated with sunitinib.

This study aimed to identify single-nucleotide polymorphisms (SNPs) that are associated with outcome to treatment with sunitinib in patients with advanced gastrointestinal stromal tumors (GIST). Forty-nine SNPS involved in the pharmacokinetic and pharmacodynamic pathway of sunitinib were associated with progression-free survival (PFS) and overall survival (OS) in 127 patients with advanced GIST who have been treated with sunitinib. PFS was significantly longer in carriers of the TT genotype in POR rs1056878 (hazards ratio (HR) 4.

Feasibility of FDG-PET in myocarditis: Comparison to CMR using integrated PET/MRI.

Objective: Besides cardiac sarcoidosis, FDG-PET is rarely used in the diagnosis of myocardial inflammation, while cardiac MRI (CMR) is the actual imaging reference for the workup of myocarditis. Using integrated PET/MRI in patients with suspected myocarditis, we prospectively compared FDG-PET to CMR and the feasibility of integrated FDG-PET/MRI in myocarditis.

Methods: A total of 65 consecutive patients with suspected myocarditis were prospectively assessed using integrated cardiac FDG-PET/MRI.

Prospective Analysis in GIST Patients on the Role of Alpha-1 Acid Glycoprotein in Imatinib Exposure.

Background: For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time, for which several mechanisms have been suggested. In this study, we investigated if a decrease in alpha-1 acid glycoprotein (AGP) is the main cause of the lowering in imatinib exposure over time.

Macrocytosis as a potential parameter associated with survival after tyrosine kinase inhibitor treatment.

Aim Of The Study: As a rise in mean corpuscular volume (MCV) of the erythrocyte is frequently seen during treatment with imatinib and sunitinib, we investigated whether macrocytosis (MCV > 100 fl) also occurs as a class effect in other tyrosine kinase inhibitors (TKIs) and whether occurrence of macrocytosis is associated with outcome.

Materials And Methods: In 533 patients, using 5 TKIs, we investigated if macrocytosis and an increase in MCV were associated with progression-free survival and overall survival (OS) in specific tumour-treatment combinations.

Results: Macrocytosis as well as an increase in MCV from baseline of >10 fl (ΔMCV +10 fl), when included as a time-dependent covariate, were associated with improved OS in patients with renal cell cancer (RCC) treated with sunitinib (macrocytosis, hazard ratio [HR] = 0.

Association between magnetic resonance imaging patterns and baseline disease features in multiple myeloma: analyzing surrogates of tumour mass and biology.

Objective: To assess associations between bone marrow infiltration patterns and localization in magnetic resonance imaging (MRI) and baseline clinical/prognostic parameters in multiple myeloma (MM).

Methods: We compared baseline MM parameters, MRI patterns and localization of focal lesions to the mineralized bone in 206 newly diagnosed MM patients.

Results: A high tumour mass (represented by International Staging System stage III) was significantly associated with severe diffuse infiltration (p = 0.

Quality-controlled dose-reduction of pelvic X-ray examinations in infants with hip dysplasia.

Background: Digital plain radiography (DR) examinations of the pelvis are frequently performed in infants with hip dysplasia.

Objective: The purpose was to reduce the radiation dose and to determine objective quality control criteria to ensure accurate assessment. This seems feasible because of higher quantum efficiency of DR and easy assessable anatomical structures for most orthopaedic measurements.

Radiation Dose Reduction in Digital Plain Radiography of the Knee after Total Knee Arthroplasty.

Purpose: To reduce radiation exposure of frequently performed radiographs of the knee in follow-up of total-knee arthroplasty ensuring accurate assessment by using objective quality control criteria.

Materials And Methods: In this prospective randomized study 278 radiographs of the knee in follow-up of total-knee arthroplasty were performed with standard and 37% reduced radiation dose. The evaluation of the plain-radiographs was conducted using the following criteria: bone-implant interface, implant-surface character, implant-implant discrimination and periarticular heterotopic ossification.

Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients.

The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Pharmacokinetic analysis was performed in mice, dosed at six different times (24-h period).

A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma.

Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated.

Modern Radiological Postoperative Diagnostics of the Hip Joint in Children and Adults.

Unlabelled: The assessment of bone healing and loosening of endoprosthesis material was long the primary indication for postoperative projection radiography and CT imaging of the hip joint following trauma and endoprosthesis implantation. With the increasing number of joint-preserving surgery, e. g.

Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors.

Background: Tyrosine kinase inhibitors (TKIs) are associated with prolongation of the QTc interval on the electrocardiogram (ECG). The QTc-interval prolongation increases the risk of life-threatening arrhythmias. However, studies evaluating the effects of TKIs on QTc intervals are limited and only consist of small patient numbers.

Pelvic X-ray examinations in follow-up of hip arthroplasty or femoral osteosynthesis--dose reduction and quality criteria.

Objective: Digital plain radiographs of the pelvis are frequently performed in follow-up examinations of patients who received total hip arthroplasty (THA) or osteosynthesis (OS). Thus, the purpose was to reduce the radiation dose and to determine objective quality control criteria to ensure accurate assessment.

Materials And Methods: Institutional review board approval was obtained.

[Clinical or radiological diagnosis of impingement].

Clinical/methodical Issue: Shoulder impingement syndrome is a clinically common entity involving trapping of tendons or bursa with typical clinical findings.

Standard Radiological Methods: Important radiological procedures are ultrasound, magnetic resonance imaging (MRI) and MR arthrography. Projection radiography and computed tomography (CT) are ideal to identify bony changes and CT arthrography also serves as an alternative method in cases of contraindications for MRI.

Relationship Between Sunitinib Pharmacokinetics and Administration Time: Preclinical and Clinical Evidence.

Background And Objective: Circadian rhythms may influence the pharmacokinetics of drugs. This study aimed to elucidate whether the pharmacokinetics of the orally administered drug sunitinib are subject to circadian variation.

Methods: We performed studies in male FVB-mice aged 8-12 weeks, treated with single-dose sunitinib at six dosing times.

Quality-controlled dose reduction of full-leg radiography in patients with knee malalignment.

Objective: Digital plain radiographs of the full leg are frequently performed examinations of children and young adults. Thus, the objective of this work was to reduce the radiation exposure dependent on specific indications, and to determine objective quality-control criteria to ensure accurate assessment.

Materials And Methods: Institutional review board approval and informed consent of all participants were obtained.

Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662.

Aims: Previously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between sunitinib and its metabolite. The current study aimed to develop an improved PK model that circumvented these limitations and to prove the utility of the PK model in treatment optimization in clinical practice.

Methods: One thousand two hundred and five plasma samples from 70 cancer patients were collected from three PK studies with sunitinib and SU12662.

Comparison of 3D turbo spin-echo SPACE sequences with conventional 2D MRI sequences to assess the shoulder joint.

Purpose: To determine the accuracy and reliability of three-dimensional (3D) T1- and proton density (PD)-weighted turbo spin-echo (TSE) sampling perfection with application-optimized contrasts using different flip-angle evolution (SPACE) compared with conventional 2D sequences in assessment of the shoulder-joint.

Materials And Methods: Ninety-three subjects were examined on a 3-T MRI system with both conventional 2D-TSE sequences in T1-, T2- and PD-weighting and 3D SPACE sequences in T1- and PD-weighting. All examinations were assessed independently by two reviewers for common pathologies of the shoulder-joint.

Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with advanced solid tumours.

Background: Plasma exposure of sunitinib shows large inter-individual variation. Therefore, a pharmacokinetic (PK) study was performed to determine safety and feasibility of sunitinib dosing based on PK levels.

Methods: Patients were treated with sunitinib 37.

Appearance of monoclonal plasma cell diseases in whole-body magnetic resonance imaging and correlation with parameters of disease activity.

The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in whole-body (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb-MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n=138), smoldering myeloma (SMM, n=157) and multiple myeloma (MM, n=252) on two 1.