Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide.

Background The hexapeptide 4A6 (Ac-Thr(tBu)-His(Bzl)-Thr(Bzl)-Nle-Glu(OtBu)-Gly-Bza) was isolated from a peptide library constructed to identify peptide-based transport inhibitors of multidrug resistance (MDR) efflux pumps including P-glycoprotein and Multidrug Resistance-associated Protein 1. 4A6 proved to be a substrate but not an inhibitor of these MDR efflux transporters. In fact, 4A6 and related peptides displayed potent cytotoxic activity via an unknown mechanism.

Cardiovascular risk management in rheumatoid arthritis patients still suboptimal: the Implementation of Cardiovascular Risk Management in Rheumatoid Arthritis project.

Objective: To assess the 10-year cardiovascular (CV) risk score and to identify treatment and undertreatment of CV risk factors in patients with established RA.

Methods: Demographics, CV risk factors and prevalence of cardiovascular disease (CVD) were assessed by questionnaire. To calculate the 10-year CV risk score according to the Dutch CV risk management guideline, systolic blood pressure was measured and cholesterol levels were determined from fasting blood samples.

One-year effects of glucocorticoids on bone density: a meta-analysis in cohorts on high and low-dose therapy.

Background: Bone loss during glucocorticoid (GC) therapy is poorly quantified.

Objective: Quantification of bone loss in GC-treated patients with chronic inflammatory diseases (CID; low dose) and transplants (high dose).

Methods: Meta-analysis of cohorts: PubMed, Cochrane, EMBASE and bibliographic searches (1995-2012).

Etanercept Increases Bone Mineral Density in Ankylosing Spondylitis, but Does Not Prevent Vertebral Fractures: Results of a Prospective Observational Cohort Study.

Objective: Ankylosing spondylitis (AS) is characterized by chronic inflammation leading to ankylosis, but also to low bone mineral density (BMD) and vertebral fractures (VFx). Treatment with tumor necrosis factor-α blockers decreases inflammation and has shown to be effective in increasing BMD. We studied the effects of etanercept (ETN) on BMD and VFx in patients with AS after 2 years of treatment.

Objective evaluation of physical functioning after tumor necrosis factor inhibitory therapy in patients with ankylosing spondylitis: a selection of 3 feasible performance-based tests.

Objective: (1) To select a limited number of performance-based tests that are reliable, show improvement in physical functioning after tumor necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS), and generate information equivalent to the full set of tests, and (2) are feasible for use in daily clinical practice.

Methods: Eight performance-based tests were evaluated. To eliminate redundant testing, the tests that showed adequate reliability, the highest standardized response mean (SRM), and the largest proportion of patients with an improved performance-based physical functioning were selected.

Imported Armillifer pentastomiasis: report of a symptomatic infection in The Netherlands and mini-review.

We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year-old female Liberian immigrant to The Netherlands. The patient was referred to the gynecologist because of lower abdominal pain. During laparotomy, multiple adhesions were seen in the lower pelvis and a hydrosalpinx with an encapsulated Armillifer nymph, most likely Armillifer armillatus, was found.

What do we miss? ASAS non-responders on anti-TNF therapy show improvement in performance-based physical function.

Objective: A prospective study was conducted in order to establish whether AS patients, who are defined as non-responders after 3 months of anti-TNF therapy, show improvement on performance-based tests of physical functioning.

Methods: At baseline and 3 months after the start of anti-TNF therapy, AS patients completed seven performance-based tests of physical functioning, questionnaires on self-reported physical functioning (BASFI) and disease activity (BASDAI), and a pain and a global patient assessment. The concordance between ≥ 20% intra-individual improvement on the performance-based test of physical functioning and (i) response to anti-TNF therapy [Assessment of SpondyloArthritis International Society 20% (ASAS20) response] and (ii) ≥ 20% intra-individual improvement on self-reported physical functioning (BASFI) was assessed.

The interferon type I signature towards prediction of non-response to rituximab in rheumatoid arthritis patients.

Introduction: B cell depletion therapy is efficacious in rheumatoid arthritis (RA) patients failing on tumor necrosis factor (TNF) blocking agents. However, approximately 40% to 50% of rituximab (RTX) treated RA patients have a poor response. We investigated whether baseline gene expression levels can discriminate between clinical non-responders and responders to RTX.

Bone formation rather than inflammation reflects ankylosing spondylitis activity on PET-CT: a pilot study.

Introduction: Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation.

Moving instead of asking? Performance-based tests and BASFI-questionnaire measure different aspects of physical function in ankylosing spondylitis.

Introduction: Ankylosing Spondylitis (AS) is characterised by limitations in physical function. The Bath Ankylosing Spondylitis Functional Index (BASFI) is considered to be the gold-standard to assess physical function in AS patients. However, the BASFI questionnaire is a self-reported outcome measure and susceptible to subjective interpretation (under- or over-estimation).

Parvovirus B19 in pregnancy: prenatal diagnosis and management of fetal complications.

Purpose Of Review: Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical importance. This review aims to raise awareness of recently discovered potentially devastating consequences of this infection in pregnancy, and provides updated guidelines on diagnosis and management.

Recent Findings: In contrast to previous beliefs, parvovirus B19 infection during any stage of pregnancy may not only cause fetal death, but may also result in severe and irreversible neurological sequelae in survivors.

Inactivating PSMB5 mutations and P-glycoprotein (multidrug resistance-associated protein/ATP-binding cassette B1) mediate resistance to proteasome inhibitors: ex vivo efficacy of (immuno)proteasome inhibitors in mononuclear blood cells from patients with rheumatoid arthritis.

Bortezomib (BTZ), a registered proteasome inhibitor (PI) for multiple myeloma, has also been proposed as a potential antirheumatic agent. Its reported side effects, however, make it unappealing for long-term administration, and resistance may also develop. To overcome this, second-generation PIs became available.

Pulmonary arterial hypertension in systemic sclerosis is associated with profound impairment of microvascular endothelium-dependent vasodilatation.

Objective: Impaired microvascular function may contribute to organ complications in patients with systemic sclerosis (SSc). We investigated whether SSc patients with and without pulmonary arterial hypertension (PAH) show a graded impairment of microvascular function compared to healthy controls.

Methods: Twenty-two patients with SSc and 22 controls were studied.

Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial.

Objective: To compare the effects of aggressive tight control therapy and conventional care on radiographic progression and disease activity in patients with early mild inflammatory arthritis.

Methods: Patients with two to five swollen joints, Sharp-van der Heijde radiographic score (SHS) <5 and symptom duration ≤2 years were randomized between two strategies. Patients with a definite non-RA diagnosis were excluded.

[From splint to smart syringe: the changing perspective of rheumatology].

Over the course of the past 30 years the outlook for patients with rheumatic arthritis (RA) has changed substantially. The careful "wait-and-see" attitude of rheumatologists of the past has been replaced by early and intensive intervention in patients with early RA. These days it is possible to bring about remission in half of all patients with, among others, the new medicines-- the "biologicals".

Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction.

Objective: To investigate the dose-related effects of glucocorticoid treatment on glucose tolerance, beta cell function, and insulin sensitivity in patients with early active rheumatoid arthritis (RA).

Methods: A randomized, controlled, single-blind trial was conducted in 41 patients with early active RA. At the beginning of the trial patients had not been treated for their RA, and were randomized to begin treatment with prednisolone at 60 mg/day or 30 mg/day.

Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study.

Objective: To conduct a prospective pilot study to determine whether macrophage targeting by 11C-(R)-PK11195 positron emission tomography (PET) can visualize subclinical synovitis in arthralgia patients who have anti-citrullinated protein antibodies (ACPAs).

Methods: Twenty-nine arthralgia patients who were positive for ACPAs but did not have clinical arthritis were studied. High (spatial)-resolution 11C-(R)-PK11195 PET scans of the hands and wrists were performed.

Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis.

Objective: To examine how anti-citrullinated protein antibody (ACPA) epitope spreading takes place prior to the onset of clinical rheumatoid arthritis (RA), and to analyze the pattern of autoantigen reactivity at the beginning of the immune response.

Methods: Multiple consecutive serum samples from 79 RA patients who had donated blood before disease onset were available for analysis. Fifty-three patients tested positive for ACPAs prior to the onset of clinical RA.

Bone turnover is adequately suppressed in osteoporotic patients treated with bisphosphonates in daily practice.

Background: Monitoring osteoporosis therapy by measurement of bone turnover markers (BTMs) might detect non-compliance in an earlier stage of anti-osteoporosis treatment and improve persistence.

Methods: BTMs were measured in two groups. The first group consisted of patients newly diagnosed with osteoporosis and starting treatment.

Effect of the application of trial inclusion criteria on the efficacy of adalimumab therapy in a rheumatoid arthritis cohort.

Objective: To evaluate the influence of inclusion criteria used in rheumatoid arthritis (RA) trials with adalimumab on clinical outcome and response.

Methods: The different inclusion criteria of published trials of adalimumab in RA were separately applied to a large prospective cohort of patients with RA treated with adalimumab (AdRA cohort), thereby mimicking patient selection for a clinical trial. Clinical response and outcome in the resulting 11 projection groups were compared using the 28-joint Disease Activity Score (DAS28) and time-averaged DAS28 as outcome measures of efficacy.

The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta-analysis.

Objectives: Changes in the lipid profile have been described in patients with rheumatoid arthritis (RA) following therapy with tumor necrosis factor (TNF)-alpha blocking agents. However, thus far, results have been inconsistent. Therefore, we investigated changes in lipid levels after TNF-alpha blocking therapy using meta-analysis of published data.

Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study.

Introduction: Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH.

Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up.

Context: Short-term data on the immunogenicity of monoclonal antibodies showed associations between the development of antidrug antibodies and diminished serum drug levels, and a diminished treatment response. Little is known about the clinical relevance of antidrug antibodies against these drugs during long-term follow-up.

Objective: To examine the course of antidrug antibody formation against fully human monoclonal antibody adalimumab and its clinical relevance during long-term (3-year) follow-up of patients with rheumatoid arthritis (RA).