Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.

The role of CagA status in gastric and extragastric complications of Helicobacter pylori.

Two major markers of virulence have been described in H. pylori. The first is a secreted protein (VacA) that is toxic to human cells in tissue culture. This cytotoxin causes vacuolation of epithelial cells in vitro and induces epithelial cell damage in mice. The second is a 40-Kb pathogenicity island for which the gene cagA (cytotoxin-associated gene A) is a marker. Approximately 60% of H. pylori isolates in Western countries are cagA+. The protein encoded by cagA+ has a molecular weight of 120-140 kDa and exhibits sequence heterogeneity among strains isolated from Western and Eastern countries. Although no specific function has been identified for CagA, there is increasing evidence that cagA+ strains are associated with increased intensity of gastric inflammation and increased mucosal concentration of particular cytokines including interleukin 8. Inactivation of picB (Hp 0544) or any of several other genes in the cag island ablates the enhanced IL-8 secretion of human gastric epithelial cells in tissue culture. Furthermore, persons colonized with cagA+ strains have an increased risk of developing more severe gastric diseases such as peptic ulcer and distal (non-cardia) gastric cancer than those harboring cagA- strains. We investigated the role of cagA status in both gastroduodenal and extragastroduodenal disease with H. pylori. Among the diseases limited to the antrum and body of the stomach and the duodenum, we demonstrated a correlation between CagA seropositivity and peptic ulcer disease. We also showed correlation between distal gastric cancer rated and CagA prevalence in populations in both developed and developing countries. In addition, we found that for several Asian populations, the relationship between CagA seropositivity and gastroduodenal diseases was complex. For extragastroduodenal diseases, our results confirmed previous reports that demonstrated that CagA status did not play a role in diseases such as rheumatoid arthritis and hyperemesis gravidarum. However, we found a clear negative association between the presence of a positive response to CagA and esophageal diseases. Therefore, CagA seropositivity (and thus gastric carriage) is associated with increased risks of certain diseases (involving the lower stomach and duodenum) and decreased risks of GERD and its sequelae. This apparent paradox can best be explained by differences in the interaction of cagA+ and cagA- strains with their hosts.

Different patterns of Helicobacter pylori adherence to gastric mucosa cells in children and adults. An ultrastructural study.

BACKGROUND: Infection with Helicobacter pylori in childhood may be the initiation of a lifelong coexistence between microorganisms and epithelial cells resulting in chronic inflammation. The adhesion pattern of H. pylori found in antral biopsies from a group of H. pylori-infected children with recurrent abdominal pain was compared with a group of H. pylori-infected adults suffering from dyspepsia, in an attempt to reveal differences in the type of adhesion. METHODS: The histology of antrum biopsies and the ultrastructure of adherent H. pylori in biopsies from 26 children (median age, 10.1 years) were compared with organisms in biopsies from 19 adults (median age, 54.4 years). RESULTS: More than 1000 adherent H. pylori were studied and divided into four types of adhesion: 1) contact to microvilli; 2) connection to the plasma membrane via filamentous material; 3) adhesive pedestal formation; and 4) abutting or making a depression in the plasma membrane. Contact to microvilli was significantly higher (69% versus 39%; P = 0.002) in children compared with adults and comprised two-thirds of all adherent organisms in children. The more intimate adhesion types as abutting or adhesive pedestals dominated in adults. CONCLUSIONS: These results indicate a change in contact types between H. pylori and gastric epithelial cells in adults compared with children and this may be a natural development in the lifelong infection of humans.

Magnetic resonance imaging of the wrist and finger joints in patients with inflammatory joint diseases.

OBJECTIVE: To study magnetic resonance imaging (MRI) features in the wrist and metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints in 4 patient groups: early rheumatoid arthritis (RA) (< 3 yrs); established RA (> 3 yrs); other arthritis; arthralgia. METHODS: MRI was obtained before and after contrast (gadodiamide) injection of the wrist and finger joints in 103 patients and 7 controls. The study included: (1) 28 patients with disease duration < 3 yrs who fulfilled the American College of Rheumatology (ACR) criteria for RA; (2) 25 patients with RA disease duration > 3 yrs who fulfilled the ACR criteria. (3) 25 patients with reactive arthritis, psoriatic arthritis, or mixed connective tissue disease; and (4) 25 patients with arthralgia. The following MRI variables were assessed: number of joints with enhancement after contrast injection, number of joints with joint fluid, and number of bones with edema in the wrist and fingers. The volume of the enhancing synovial membrane after contrast injection in the MCP, PIP, and DIP joints was manually outlined. MR images were scored independently under blinded conditions. RESULTS: Bone marrow edema was found in 68% of the patients with established RA, and the number of bones with edema was significantly higher in patients with established RA compared to patients with early RA, other arthritis, and arthralgia (Mann-Whitney p < 0.04). Bone edema was not found in patients with arthralgia. There was marked overlap within and between the patient groups. No differences in MRI features were found between patients with early RA and patients with other arthritis. The volumes of the synovial membrane in the MCP, PIP, and DIP joints were significantly higher in patients with arthritis compared to patients with arthralgia. CONCLUSION: Although there was marked overlap between the arthritis patient groups, MRI determined bone marrow edema and synovial membrane volumes provided additional information about disease activity and may be used as a marker of it. Bone marrow edema appeared with the highest percentage in patients with long duration of RA (> 3 yrs) and is probably secondary to changes in inflammatory activity.

MRI of the arthritic small joints: comparison of extremity MRI (0.2 T) vs high-field MRI (1.5 T).

The aim of this study was to compare the diagnostic capabilities of extremity MRI (E-MRI) with high-field MRI in arthritic small joints, and to evaluate the patients' acceptance and perceptions of the two MR systems. One hundred three patients (group 1 = 28 patients with RA < 3 years, group 2 = 25 patients with reactive and psoriatic arthritis and mixed connective tissue disease, group 3 = 25 patients with rheumatoid arthritis (RA) more than 3 years and group 4 = 25 patients with arthralgia) underwent dedicated E-MRI and high-field MRI of the wrist and finger joints. Coronal short tau inversion recovery and transversal 3D T1-weighted images before and after gadodiamide (Gd) were performed in both cases to outline the volume of the synovial membrane (Vsm) and to evaluate joints with enhancement, effusion, bone edema, and erosions. Investigators blinded to the clinical findings evaluated the images. Patients' compliance and acceptance of E-MRI and high-field MRI were evaluated. The median Vsm obtained on E-MRI did not differ significantly from that obtained on high-field MRI. Vsm = 1 ml (E-MRI) and 1.1 ml (high-field MRI) before Gd and Vsm = 0.1 ml (E-MRI) and 0 ml (high-field MRI) after Gd (Wilcoxon test, p > 0.05). The difference in agreement was 8% for joint enhancement, 2% for joint effusion, 3% for bone edema, and 4% for bone erosions. Of the patients, 64% preferred E-MRI due to more comfortable positioning and less claustrophobia and noise. Extremity MRI of the small arthritic joints is comparable to high-field MRI and more readily accepted than high-field MRI by this patient group.