Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial.

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Scoring magnetic resonance imaging (MRI) inflammation and structural lesions in sacroiliac joints of patients with axial spondyloarthritis: assessment of all MRI slices of the cartilaginous compartment versus standardized six or five slices.

Objectives: The Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint (SIJ) scoring system assesses six or five (6/5) semicoronal magnetic resonance imaging (MRI) slices for inflammation/structural lesions in patients with axial spondyloarthritis (axSpA). However, the cartilaginous SIJ compartment may be visible in a few additional slices. The objective was to investigate interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types using an 'all slices' approach versus standard SPARCC scoring of 6/5 slices.Method: Fifty-three axSpA patients were treated with the tumour necrosis factor inhibitor golimumab and followed with serial MRI scans at weeks 0, 4, 16, and 52. The most anterior and posterior slices covering the cartilaginous compartment and the transitional slice were identified. Scores for inflammation, fat metaplasia, erosion, backfill, and ankylosis in the cartilaginous SIJ compartment were calculated for the 'all slices' approach and the 6/5 slices standard.Results: By the 'all slices' approach, three readers scored mean 7.2, 7.7, and 7.0 slices per MRI scan. Baseline and change scores for the various lesion types closely correlated between the two approaches (Pearson's rho ≥ 0.95). Inflammation score was median 13 (interquartile range 6-21, range 0-49) for 6/5 slices versus 14 (interquartile range 6-23, range 0-69) for all slices at baseline. Interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types were similar.Conclusion: The standardized 6/5 slices approach showed no relevant differences from the 'all slices' approach and, therefore, is equally suited for monitoring purposes.

Monitoring total-body inflammation and damage in joints and entheses: the first follow-up study of whole-body magnetic resonance imaging in rheumatoid arthritis.

OBJECTIVE: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab. METHODS: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated. RESULTS: The readability of peripheral and axial joints was 82-100%, being less for elbows and small joints of the feet. For entheses, 72-100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80-100%), and enthesitis (77-100%), and slightly lower for synovitis and soft tissue inflammation (50-100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions. CONCLUSIONS: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.

Pattern of bone erosion and bone proliferation in psoriatic arthritis hands: a high-resolution computed tomography and radiography follow-up study during adalimumab therapy.

OBJECTIVES: To investigate the pattern and development of bone erosion and proliferation in patients with psoriatic arthritis (PsA) during treatment with adalimumab, using high-resolution computed tomography (CT) and conventional radiography. METHOD: Forty-one biologic-naïve PsA patients were initiated with adalimumab 40 mg subcutaneously every other week. CT and radiography of the 2nd-5th metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints were conducted at baseline (n = 41) and after 24 weeks (n = 32). Changes in bone erosion and proliferation are described and the imaging modalities compared. RESULTS: Ninety percent of bone erosions detected by CT were located in the metacarpal heads, and most frequently in the 2nd-3rd MCP joints. Radial (37%) and ulnar (31%) surfaces were more frequently eroded than dorsal (10%) and palmar (22%) sites. Using CT, bone proliferations were located primarily on the sides of the distal part of the DIP joints (43% of all proliferations), but also proximally in DIP (17%) and MCP joints (27%). For bone erosions and proliferations, respectively, radiography showed a low sensitivity (17% and 26%), but a high specificity (98% and 95%) and accuracy (93% and 87%), with CT as the gold standard reference. Neither CT nor radiography revealed statistically significant changes in bone erosion or proliferation scores between baseline and follow-up. CONCLUSIONS: Patterns of bone erosion and proliferation in PsA hands were revealed in more detail by CT than by radiography. No overall progression or repair could be detected during adalimumab treatment with either of the methods.

Detection of meticillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae in Danish emergency departments - evaluation of national screening guidelines.

BACKGROUND: Multi-resistant bacteria (MRB) are an emerging problem. Early identification of patients colonized with MRB is mandatory to avoid in-hospital transmission and to target antibiotic treatment. Since most patients pass through specialized emergency departments (EDs), these departments are crucial in early identification. The Danish National Board of Health (DNBH) has developed exposure-based targeted screening tools to identify and isolate carriers of meticillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE). AIM: To assess the national screening tools for detection of MRSA and CPE carriage in a cohort of acute patients. The objectives were to investigate: (i) if the colonized patients were detected; and (ii) if the colonized patients were isolated. METHODS: This was a multi-centre cross-sectional survey of adults visiting EDs. The patients answered the DNBH questions, and swabs were taken from the nose, throat and rectum. The collected samples were examined for MRSA and CPE. Screening performances were calculated. FINDINGS: Of the 5117 included patients, 16 were colonized with MRSA and four were colonized with CPE. The MRSA screening tool had sensitivity of 50% [95% confidence interval (CI) 25-75%] for carrier detection and 25% (95% CI 7-52%) for carrier isolation. The CPE screening tool had sensitivity of 25% (95% CI 1-81%) and none of the CPE carriers were isolated. CONCLUSION: The national screening tools were of limited use as the majority of MRSA and CPE carriers passed unidentified through the EDs, and many patients were isolated unnecessarily.

Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arthritis treated with adalimumab. A 1 year investigator-initiated follow-up study using high-resolution computed tomography as the primary outcome measure.

OBJECTIVE: With computed tomography (CT) and radiography, to investigate if repair of bone erosions, defined as regression of erosion scores, occurs during adalimumab treatment of patients with rheumatoid arthritis (RA). METHODS: Fifty-two patients with RA, naïve to biological agents, with at least two low-grade radiographic erosions in the wrist or metacarpophalangeal (MCP) joints in the same (index) hand, initiated adalimumab 40 mg subcutaneously every other week. Thirty-five patients completed the study (median age 61 years (interquartile range 46-68), disease duration 8 years (3-15)). CT of the index wrist and MCP joints 2-5 and radiographs of hands and forefeet were obtained at baseline, 6 and 12 months. Images were evaluated by investigators blinded to chronology and clinical data, and assessed according to Sharp/van der Heijde (radiographs) and OMERACT RA MRI scoring (CT) methods. RESULTS: Disease activity score, C-reactive protein, tender and swollen joints count and Health Assessment Questionnaire score had all decreased at 6 and 12 months (wilcoxon signed-ranks test p<0.001). No significant change in any imaging parameters of joint destruction was observed at 6 and 12 months. High intrareader agreements were reached (mean intraobserver intraclass coefficients: 0.96 (CT) and 0.97 (radiography)). The number of patients with change scores exceeding the smallest detectable change (SDC) was comparable on CT and radiography, as were the proportions of patients progressing/regressing. Decreased erosion scores at 12 months were registered in 1.6% and 1.8% of sites assessed on CT and radiography, respectively. CONCLUSION: Repair of erosions in adalimumab-treated patients with RA is rare, but erosive regression, exceeding the SDC, on CT and radiography occurred. The very limited overall erosive progression supports the view that joint destruction is minimal during adalimumab treatment of patients with RA.

Neutral particle analyzer measurements on the SSPX spheromak.

A neutral particle analyzer is used to measure the time-resolved energy spectrum of neutral hydrogen leaving a spheromak plasma. A gas cell filled with 10-50 mTorr of helium is used to strip electrons from incoming neutral hydrogen, lowering the minimum detectable energy well below that obtained with thin foils. Effective neutral particle temperature is calculated by fitting a Maxwellian energy distribution to the measured energy spectrum above and below approximately 300 eV. A computational model with approximated profiles of plasma density and neutral density is used with the measured neutral hydrogen flux to estimate the ion temperature. Measurement of the power flux due to neutral hydrogen emitted at the measurement location is extended to the whole plasma surface to estimate the total charge exchange power loss from the plasma. The initial results indicate that the charge exchange power loss represents only 2% of the total input gun power during the sustainment phase of the discharge.

Homocysteine in Greenland Inuits.

Patients with homozygous homocystinuria are at greatly increased risk for development of atherosclerosis and thrombosis (1). Elevated plasma levels of homocysteine (HCY) are caused by reduced enzymatic catabolism or reduced enzymatic remethylation of HCY, due to either hereditary enzyme defects or to nutritional deficiencies of vitamins functioning as cofactors. However, several recent studies have suggested that persons with mildly elevated plasma levels of HCY also are at increased risk for coronary heart disease. (2-4). There are some indications that dietary n-3 polyunsaturated fatty acids (PUFAs) may offer protection against coronary heart disease (5-6). Several mechanisms may be involved, including beneficial effects of n-3 PUFAs on plasma lipids, platelet and leukocyte reactivity, blood pressure and vasoreactivity (7). Interestingly, Olszewski el al. recently found HCY-levels to be lowered 36% in 15 type IIa or IIb hyperlipemic men by n-3 PUFA supplementation. A possible beneficial effect of n-3 PUFA on the incidence of coronary heart disease was initially suggested from studies in Greenland Inuits by our group (8). We therefore investigated plasma levels of homocysteine in a group of traditionally living Greenland Inuits with a diet consisting mainly of marine food and with a very high content of n-3 PUFAs.

The acute effect of a single very high dose of N-3 fatty acids on coagulation and fibrinolysis.

The objective of the study was to investigate the acute effect of a single very high dose of n-3 PUFA on coagulation and fibrinolysis. Forty healthy volunteers were randomized into two groups to receive either 20 grams of n-3 PUFA or 20 grams of n-6 PUFA as a single dose at 6 p.m. with their evening meal. Coagulation and fibrinolysis were evaluated in the fasting state at 8 a.m. the next morning and compared to values obtained at 8 a.m. the day before, when the participants were on their habitual diets. PAI-1 activity in plasma increased by a mean of 62% in subjects randomized to receive n-3 PUFA despite that no changes could be demonstrated in t-PA antigen levels. PAI-1 activity was unaltered in the 20 controls receiving n-6 PUFA. Plasma fibrinogen, coagulation factor VII, thrombin-antithrombin complexes and D-dimer did not significantly change after either supplement. The substantial increase in levels of PAI-1 activity in plasma after a single very high dose of n-3 PUFA may limit the usefulness of single very high doses of n-3 PUFA in acute clinical conditions.

The acute effects of a single very high dose of n-3 fatty acids on plasma lipids and lipoproteins in healthy subjects.

Forty healthy volunteers were allocated in a double blind, randomized study to receive either 20 g of n-3 polyunsaturated fatty acids (PUFA) or 20 g of n-6 PUFA at their evening meal. The effect on plasma lipids and lipoproteins of this single dose of fish oil vs. corn oil was studied the next morning, 14 h after ingestion. Plasma triglycerides and very low density lipoprotein-cholesterol significantly decreased (33%) after n-3 PUFA (P < 0.001), and significantly (P < 0.01) more than after intake of n-6 PUFA. The decrease in plasma triglycerides after n-3 PUFA ingestion was more pronounced in subjects with higher baseline levels of triglycerides (P < 0.001). Total cholesterol decreased after both supplements, but did not differ between the supplements. Low density lipoprotein-cholesterol did not change, and high density lipoprotein-cholesterol significantly decreased in subjects given n-3 PUFA compared to baseline, but not when compared to subjects receiving n-6 PUFA. In conclusion, we have shown that a single very high dose of n-3 PUFA has a pronounced hypotriglyceridemic effect, which is directly related to the initial plasma level.

Morbidity from parotid sialography.

OBJECTIVE: Sialography is commonly used for the diagnosis of Sjögren's syndrome, although its invasive nature is often regarded as a serious drawback for routine usage. The aim of this study was to evaluate the morbidity and acceptability of parotid sialography using oil-based contrast fluid. STUDY DESIGN: Twenty-four consecutive sialographic procedures were evaluated in terms of morbidity and the patient's acceptance of the procedure, assessed with a standardized questionnaire. Information was also obtained by recording relevant physical parameters during the procedure. RESULTS: There was good acceptance of the sialographic procedure, and the morbidity was low. No signs of overfilling or false route were observed in any of the sialograms. On average, 0.74 mL of contrast fluid was infused with a velocity of 0.01 mL/s. The whole procedure was completed within 12 minutes. CONCLUSIONS: Parotid sialography appears less invasive than is often thought. It had a low morbidity rate and was well accepted by the patients.

[A hypersensitive reaction after radiography of the colon]. / Hypersensitivitetsreaktion ved røntgenundersøgelse af colon.

A case of systemic allergic reaction following barium enema is described. The reaction was most probably provoked by a latex balloon on the rectal catheter.

[n-3 polyunsaturated fatty acids, heart rate variability and ventricular arrhythmias in post-AMI-patients. A clinical controlled trial]. / n-3 polyumaettede fedtsyrer, hjertefrekvensvariabilitet og ventrikulaere arytmier hos post-AMI-patienter. Et klinisk kontrolleret studie.

There is evidence for an antiarrhythmic effect of n-3 polyunsaturated fatty acids (n-3 PUFA) in animals. The aim of the present study was to investigate the effect of dietary n-3 PUFA on ventricular arrhythmias and heart rate variability (HRV) in patients with a previous myocardial infarction. Fifty-five patients were randomized to receive either 5.2 g of n-3 PUFA daily for 12 weeks or placebo in a double blind, placebo-controlled study. Prior to randomization a 24-hour Holter recording was obtained, and this was repeated at the end of the study. The major end-points were the number of ventricular extrasystoles (VE)/24 hours and the 24-hour HRV. A non-significant decrease in VE/24 hours was found in both the n-3 PUFA group and among controls after dietary supplementation, whereas HRV significantly increased after n-3 PUFA compared to both baseline values (p = 0.04) and to controls (p = 0.01). The present study therefore supports the hypothesis that n-3 PUFA may have an anti-arrhythmic effect in humans.

Bioavailability of marine n-3 fatty acid formulations.

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

An ion Doppler spectrometer instrument for ion temperature and flow measurements on SSPX.

A high-resolution ion Doppler spectrometer (IDS) has been installed on the sustained spheromak plasma experiment to measure ion temperatures and plasma flow. The system is composed of a 1 m focal length Czerny-Turner spectrometer with a diffraction grating line density of 2400 lines/mm, which allows for first order spectra between 300 and 600 nm. A 16-channel photomultiplier tube detection assembly combined with output coupling optics provides a spectral resolution of 0.0126 nm/channel. We calculate in some detail the mapping of curved slit images onto the linear detector array elements. This is important in determining the wavelength resolution and setting the optimum vertical extent of the slit. Also, because of the small wavelength window of the IDS, a miniature fiber-optic survey spectrometer sensitive to a wavelength range 200-1100 nm and having a resolution of 0.2 nm is used to obtain a time-integrated spectrum for each shot to verify specific impurity line radiation. Several measurements validate the systems operation. Doppler broadening of C III 464.72 nm line in the plasma shows time-resolved ion temperatures up to 250 eV for hydrogen discharges, which is consistent with neutral particle energy analyzer measurements. Flow measurements show a sub-Alfvenic plasma flow ranging from 5 to 45 kms for helium discharges.

Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis.

Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

Is 0.6T magnetic resonance mammography adequate in the detection of breast cancer?

PURPOSE: To evaluate whether relevant diagnostic information can be achieved when using magnetic resonance mammography (MRM) on mid-field as a supplement to conventional imaging and clinical examination in women with primary breast cancer. MATERIAL AND METHODS: 30 women (55 breasts containing 49 malignant tumors) planned for uni- or bilateral mastectomy were examined with dynamic MRM on mid-field, 0.6T. The women were examined with mammography (M) and ultrasonography (US) prior to MRM. The descriptions of the conventional examinations were evaluated retrospectively, whereas the MRM was evaluated prospectively, with knowledge of the M+US findings. Imaging findings suggesting malignancy were registered and correlated with pathology after mastectomy. A home-made rating system for evaluation of the detected lesions was tested. RESULTS: MRM detected seven additional malignant tumors, failed to detect three lesions and characterized four as gray-zone lesions according to the rating system. Sensitivity of finding the tumors with M+US was 79.0%, with a PPV for malignant tumors of 84.4%. One breast in which MRM found a malignant tumor had not initially been examined with US. Sensitivity with MRM was 91.6%, with a positive predictive value of malignant tumors of 97.7%. CONCLUSION: MRM on mid-field seems to improve the detection of cancers when used as a supplement to M+US in women with primary breast cancer. We believe that the results are fair compared to MRM on high-field, although further research and refinement are needed.