Scoring inflammatory activity of the spine by magnetic resonance imaging in ankylosing spondylitis: a multireader experiment

OBJECTIVE: Magnetic resonance imaging (MRI) of the spine is increasingly important in the assessment of inflammatory activity in clinical trials with patients with ankylosing spondylitis (AS). We investigated feasibility, inter-reader reliability, sensitivity to change, and discriminatory ability of 3 different scoring methods for MRI activity and change in activity of the spine in patients with AS. METHODS: Thirty sets of spinal MRI at baseline and after 24 weeks of followup, derived from a randomized clinical trial comparing a tumor necrosis factor (TNF)-blocking drug (n = 20) with placebo (n = 10) and selected to cover a wide range of activity at baseline and change in activity, were presented electronically in a partial latin-square design to 9 experienced readers from different countries (Europe, Canada). Readers scored each set of MRI 3 times, using 3 different methods including the Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a, grading activity (0-6) per vertebral unit in 23 units]; the Berlin modification of the ASspiMRI-a; and the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system, which scores the 6 vertebral units considered by the reader as the most abnormal, with additional scores for "depth" and "intensity." Both the order of the methods used by each reader and the timepoints (before/after treatment) were randomized. Feasibility of each scoring system was evaluated by measuring the mean time needed to score each set of MRI, and inter-reader reliability was evaluated by smallest detectable change (SDC) and by intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs separately. Sensitivity to change was investigated by calculating Guyatt's effect size on change scores. Discriminatory ability was assessed using Z-scores (Mann-Whitney test) comparing change in score between patients treated with TNF-blocking drug and placebo. RESULTS: The mean time to score one set of MRI was shortest for the Berlin method. SDC was lowest for the Berlin method and highest for SPARCC. Overall inter-reader ICC per method were between 0.49 and 0.77 for scoring activity status, and between 0.46 and 0.72 for scoring activity change. ICC for all possible reader pairs showed much more fluctuation per method, with lowest observed values of about 0.05 (very low agreement) and highest observed values over 0.90 (excellent agreement). In general, ICC for SPARCC were consistently higher than for other systems. Sensitivity to change differed per reader, and was more consistent with SPARCC than with the other methods, but was in general excellent for all 3 methods. Discrimination between groups (TNF-blocker vs placebo) assessed by Z-scores was good and comparable among methods. CONCLUSION: This experiment demonstrates the feasibility of multiple-reader MRI scoring exercises for method comparison, provides evidence for the feasibility, reliability, sensitivity to change, and discriminatory capacity of all 3 tested scoring systems to be used in assessing spinal activity on MRI in patients with AS in clinical trials. On the basis of these results it is not possible to prioritize one of the 3 methods.     

Reliability of the Cardiac Patients Learning Needs Inventory (CPLNI) for use in Portugal

Aims and objectives.  To perform the semantic validation and to evaluate the reliability and the presence of ceiling and floor effects of the Cardiac Patients Learning Needs Inventory in Portuguese patients with coronary artery disease. Background.  Information should be selected based on what patients know and need to learn, which means that the teaching process should be based on each person’s needs. The Cardiac Patients Learning Needs Inventory is aimed at identifying the cardiac patients’ individual learning needs. Design.  Methodological research design. Methods.  Two hundred patients hospitalised at the coronary intensive care unit or at the cardiothoracic surgery unit of a public hospital in Lisbon answered the adapted version of the Cardiac Patients Learning Needs Inventory. Internal consistency was estimated based on Cronbach’s alpha. Scores above 0·50 were considered acceptable. Stability was measured through test–retest and calculated using student’s t test. Significance was set at 0·05. Results.  Patients’ mean age was 65 years (SD = 11·8), and most were men (152; 76%). Cronbach’s alpha for the total scale was high in the first and second measurement (0·91), and for seven domains, it was acceptable in the first and second measurement (range from 0·50–0·89). No statistically significant difference was found between mean scores on the first and second measurement. Lower diversity was observed in the answers, most of which ranged between important and very important (ceiling‐effect). Conclusion.  The adapted version for use in Portugal maintained the conceptual, semantic and idiomatic equivalences of the original version and showed adequate reliability. Relevance to clinical practices.  Owing to the lack of validated instruments translated into Portuguese, to measure cardiac patients’ learning needs, this study entails important clinical and theoretical implications.     

Characterization of novel akermanite:poly‐ϵ‐caprolactone scaffolds for human adipose‐derived stem cells bone tissue engineering

In this study, three different akermanite:poly‐?‐caprolactone (PCL) composite scaffolds (wt%: 75:25, 50:50, 25:75) were characterized in terms of structure, compression strength, degradation rate and in vitro biocompatibility to human adipose‐derived stem cells (hASC). Pure ceramic scaffolds [CellCeram^TM, custom‐made, 40:60 wt%; β‐tricalcium phosphate (β‐TCP):hydroxyapatite (HA); and akermanite] and PCL scaffolds served as experimental controls. Compared to ceramic scaffolds, the authors hypothesized that optimal akermanite:PCL composites would have improved compression strength and comparable biocompatibility to hASC. Electron microscopy analysis revealed that PCL‐containing scaffolds had the highest porosity but CellCeram^TM had the greatest pore size. In general, compression strength in PCL‐containing scaffolds was greater than in ceramic scaffolds. PCL‐containing scaffolds were also more stable in culture than ceramic scaffolds. Nonetheless, mass losses after 21 days were observed in all scaffold types. Reduced hASC metabolic activity and increased cell detachment were observed after acute exposure to akermanite:PCL extracts (wt%: 75:25, 50:50). Among the PCL‐containing scaffolds, hASC cultured for 21 days on akermanite:PCL (wt%: 75:25) discs displayed the highest viability, increased expression of osteogenic markers (alkaline phosphatase and osteocalcin) and lowest IL‐6 expression. Together, the results indicate that akermanite:PCL composites may have appropriate mechanical and biocompatibility properties for use as bone tissue scaffolds. Copyright © 2012 John Wiley & Sons, Ltd.     

Inflammatory bowel disease in the Hubei Province of China

AIM: To analyze clinical features and response to treatment in inflammatory bowel disease (IBD) patients from the Hubei Province of China.METHODS: Clinical data was collected retrospectively from 74 patients with IBD [66 with ulcerative colitis (UC) and 8 with Crohn’s disease (CD)] admitted to The Second Hospital, Hubei Medical University from 1986 to 1995.RESULTS: The most common symptoms in IBD patients were abdominal pain, diarrhea, blood and mucus in stool, and constipation. Extraintestinal manifestations of IBD were not common. In these patients, inflammation was predominantly located in the sigmoid and left colon in UC cases, and in the ileum and colon in CD cases. Treatment with sulphasalazine and corticosteroids was effective in 95% of UC cases; However, about 42% of UC patients showed disease recurrence during the follow-up period of 1.11 years. Five out of eight CD patients had part of their intestine removed, whereas three were treated with anti-tuberculosis drugs or the antibiotic metronidazole. Out of four patients we followed up for 1-8 years, one died of severe complications after surgery, two experienced recurrence while in treatment with drugs, and one remained in remission under sulphasalazine treatment after surgery.CONCLUSION: Five percent of the patients reported a family history of IBD. About 34% of the patients were smokers and 32% of the patients were alcoholic. Epidemiological studies are urgently needed in the Hubei Province of China to assess the role that genetics and environmental factors play in the pathogenesis of inflammatory bowel diseases.     

Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia

We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.     

Thalidomide as salvage therapy for chronic graft-versus-host disease

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.