Body composition, lung function, and prevalent and progressive bone deficits among adults with cystic fibrosis.

Introduction: Cystic fibrosis (CF) is associated with osteoporosis and incident fracture. This study assessed independent predictors of baseline and 2-year changes in bone mineral density (BMD) in adults with CF.

Methods: Sixty-four adult patients with CF, ages 18-57, were recruited from the Massachusetts General Hospital Cystic Fibrosis Care Center.

Trends in bone mineral density in young adults with cystic fibrosis over a 15 year period.

Background: Improvements in clinical care have led to increased life expectancy in patients with cystic fibrosis (CF) over the past several decades. Whether these improvements have had significant effects on bone health in patients with CF is unclear.

Methods: This is a cross-sectional study comparing clinical characteristics and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in adults with CF evaluated in 1995-1999 to age-, race-, and gender-matched patients with CF evaluated in 2011-2013 at the same center on calibrated DXA machines.

Doubled prevalence rates of ANCA-associated vasculitides and giant cell arteritis between 1994 and 2006 in northern Germany.

Objectives: The aim of this study was to investigate the period prevalences of ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic GPA (EGPA)/Churg-Strauss and GCA, in an urban and rural population in northern Germany in 2006 and to compare the data with our previous study performed in 1994.

Methods: We identified of all patients with AAV or GCA via questionnaires to all hospital departments, physicians, health insurance providers, pension funds, reference laboratories for autoimmune diseases and death registries in Luebeck (city) and the rural region of Segeberg (population 468 962) between January and December 2006. The type of vasculitis, gender, year of birth, postal code and death were documented and re-evaluated.

Toll-like receptor TLR2 and TLR9 ligation triggers neutrophil activation in granulomatosis with polyangiitis.

Objective: The aim of the study was to characterize the expression of TLR2, TLR4 and TLR9 in PMNs of patients with granulomatosis with polyangiitis (GPA) and to elucidate the role of these receptors in GPA with respect to neutrophil activation.

Methods: The expression of TLR2, TLR4 and TLR9 was determined on ex vivo PMNs in whole blood samples of GPA patients (n = 35) and healthy controls (HCs) (n = 24). Isolated PMNs were stimulated in vitro with TLR agonists and assessed for degranulation, membrane proteinase 3 (mPR3) expression, soluble l-selectin shedding and cytokine production (IL-8) in five GPA patients and five HCs.

Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations.

Objective: First, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA.

Patients And Methods: This study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010.

The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis.

There has been a marked increase in the past 15 years in the number and quality of clinical trials in the idiopathic inflammatory vasculitides, especially the small-vessel vasculitides known as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis [AAV; granulomatosis, with polyangiitis (Wegener's)]. These trials have been conducted by multicenter, international groups in Europe and the United States with financial support provided by government agencies and biopharmaceutical companies. This increased clinical trial activity in vasculitis has been accompanied by the development and validation of new outcome measures--a challenging process for these complex, multiorgan system diseases.

Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda.

Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms.

Health-related quality of life in patients with newly diagnosed antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) can present with a broad spectrum of signs and symptoms. The relative effects of different manifestations on health-related quality of life (HRQOL) are unknown.

Methods: We conducted an individual patient data meta-analysis of baseline Short Form 36 (SF-36) scores from 4 randomized controlled trials of patients with newly diagnosed AAV.

Patient-reported outcome assessment in vasculitis may provide important data and a unique perspective.

Objective: To assess patients' self-estimates of the burden of disease in vasculitis and to compare data across patient populations from the US, Germany, and the UK. Outcome assessment in vasculitis primarily focuses on physician evaluations of disease activity and damage. Little is known about the patients' perspectives regarding the burden of disease.

Progress towards a core set of outcome measures in small-vessel vasculitis. Report from OMERACT 9.

The past decade has seen a substantial increase in the number and quality of clinical trials of new therapies for vasculitis, including randomized, controlled, multicenter trials that have successfully incorporated measures of disease activity and toxicity. However, because current treatment regimens for severe disease effectively induce initial remission and reduce mortality, future trials will focus on any of several goals including: (a) treatment of mild-moderate disease; (b) prevention of chronic damage; (c) reduction in treatment toxicity; or (d) more subtle differences in remission induction or maintenance. Thus, new trials will require outcome measure instruments that are more precise and are better able to detect effective treatments for different disease states and measure chronic manifestations of disease.

Stable incidence of systemic vasculitides in schleswig-holstein, Germany.

Introduction: The authors present data on the incidence of primary systemic vasculitides (PSV) in the northern German state of Schleswig-Holstein from 1998 to 2005.

Methods: Population-based study of all new cases of PSV from 1 January 1998 onward in a region with a population of 2.83 million.

Expansion of circulating NKG2D+ effector memory T-cells and expression of NKG2D-ligand MIC in granulomaous lesions in Wegener's granulomatosis.

Expansion of circulating CD28- T-cells reminiscent of effector memory T-cells (T(EM)) has been reported in Wegener's granulomatosis (WG) recently. To investigate the role of T(EM) in WG, we analyzed the expression of the activating NK-receptor NKG2D and its ligand MIC on circulating T(EM) and in granulomatous lesions, respectively. NKG2D was anomalously expressed and preferentially detected on circulating CD4+CD28- T(EM) in WG.

Nutrient status of adults with cystic fibrosis.

Nutrition is thought to influence disease status in patients with cystic fibrosis (CF). This cross-sectional study sought to evaluate nutrient intake and anthropometric data from 64 adult outpatients with cystic fibrosis. Nutrient intake from food and supplements was compared with the Dietary Reference Intakes for 16 nutrients and outcomes influenced by nutritional status.

The future of damage assessment in vasculitis.

Damage denotes the aspects of chronic disease that do not reverse with therapy. This concept is particularly important for the primary systemic vasculitides, since the careful differentiation between activity and damage may help avoid unnecessary exposure to cytotoxic medications. Damage significantly influences both longterm prognosis and quality of life.

Stable incidence of primary systemic vasculitides over five years: results from the German vasculitis register.

Objective: To register all newly diagnosed patients with primary systemic vasculitides (PSV) in a large region in northern Germany.

Methods: Between January 1, 1998 and December 31, 2002 all newly diagnosed cases of PSV were identified in a large mixed rural/urban northern German region consisting of 2,777,275 habitants in a population-based prospective study. The following sources were used: departments of all hospitals, including their outpatient clinics; all departments of pathology; and the reference immunologic labs serving the catchment area.

Autoantibodies against the bactericidal/permeability-increasing protein from inflammatory bowel disease patients can impair the antibiotic activity of bactericidal/permeability-increasing protein.

Bactericidal/permeability-increasing protein (BPI) is an antineutrophil cytoplasmic autoantibody (ANCA) target antigen in inflammatory bowel disease (IBD). The aim of this study was to characterize binding regions of BPI-autoantibodies and to analyze their ability to block the antibiotic effect of BPI. Sera of 24 ulcerative colitis and Crohn's disease patients were examined in indirect immuno-fluorescence, ANCA enzyme-linked immunosorbent assay (ELISA), and by epitope mapping with 13mer peptides and Western blot for presence of BPI-autoantibodies.

BPI-ANCA of pediatric cystic fibrosis patients can impair BPI-mediated killing of E. coli DH5alpha in vitro.

Gram-negative bacterial lung infections and chronic bacterial colonization are major threats for pediatric cystic fibrosis (CF) patients. Besides impeded mucociliary clearance, other mechanisms that contribute to increased susceptibility to infections are presumed. The bactericidal/permeability-increasing protein (BPI), which is delivered by neutrophil granulocytes and mucosal epithelial cells, is one of the most potent innate antibiotics against Gram-negative bacteria and endotoxin.

Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon.

Objective: To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients.

Methods: Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated.

High rate of renal relapse in 71 patients with Wegener's granulomatosis under maintenance of remission with low-dose methotrexate.

Objective: To examine the long-term efficacy of low-dose intravenous methotrexate (MTX) with and without concomitant glucocorticoids (GC) for remission maintenance in patients with generalized Wegener's granulomatosis (WG) in an open-label, prospective, standardized trial.

Methods: After induction of remission by cyclophosphamide and GC, 71 patients (41 males, 30 female) with initially generalized WG received low-dose methotrexate at 0.3 mg/kg body weight once weekly.

Effect of Wegener's granulomatosis on work disability, need for medical care, and quality of life in patients younger than 40 years at diagnosis.

Objectives: To evaluate the effects of Wegener's granulomatosis (WG) on employment status, work disability, and need for medical care of 60 consecutive WG patients aged < or = 40 years at diagnosis.

Methods: Sixty WG patients (26 male, 34 female) with a median age of 36 years (range 17-48 years) and a median duration of disease of 39 months (range 0-228 months) completed self-administered questionnaires on hospitalization, medical care, and employment status plus the Medical Outcomes Study-Short Form-36 (SF-36) estimating their health-related quality of life.

Results: Thirty-two of the 60 patients reported full- or part-time employment more than 3 years after diagnosis.