Mikael Boesen

Comparing two low-energy diets for the treatment of knee osteoarthritis symptoms in obese patients: a pragmatic randomized clinical trial

OBJECTIVES To evaluate in a prospective, randomized clinical trial (RCT), symptom response among obese knee osteoarthritis (OA) patients following a feasible, intensive weight-loss program for 16 weeks. METHODS Eligible patients were obese [body mass index (BMI)>30 kg/m(2)]; >50 years old, with primary knee OA. Participants were randomized to either a very-low-energy diet (VLED) or a low-energy diet (LED) (415 kcal/day and 810 kcal/day, respectively), using commercially available formula foods - only for the first 8 weeks, managed by dieticians. The 8 weeks were followed by an additional 8-week period of a hypo-energetic diet consisting of normal food plus meal replacements (1200 kcal/day). The primary endpoint was the number of patients responding according to the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responder criterion. The statistical analysis was based on a non-responder intention-to-treat (ITT) population (baseline observation carried forward). RESULTS One hundred and ninety two patients (155 (80.7%) females) with a mean age 62.5 years [standard deviation (SD) 6.4; range 50-78 years]; average BMI 37.3 (SD 4.8) were included. At 16 weeks, similar proportions of the VLED and LED groups, 59 (61.5%), and 63 (65.6%) patients, respectively, met the OMERACT-OARSI responder criteria, with no statistical significant difference between the groups (P=0.55). Combining the groups the pooled estimate was 64% meeting the responder criteria [95% confidence interval (CI) 57%, 70%]. There was an overall reduction in pain, corresponding to an average pain reduction on the visual analogue scale (VAS) of 11.1 (95%CI 13.6, 8.5) in the combined groups. At week 16 weight loss in the combined groups was 12.8 kg (95%CI: 11.84-13.66; P<0.001). 71% lost > or =10% body weight in both diet groups, with a pooled estimate of 74% (95%CI: 68-80%). CONCLUSION No clinically significant differences were found between the 415 kcal/day and 810 kcal/day diets. A 16-week formula-diet weight-loss program resulted in a fast and effective weight loss with very few adverse events resulting in a highly significant improvement in symptoms in overweight patients with knee OA.

Weight loss is effective for symptomatic relief in obese subjects with knee osteoarthritis independently of joint damage severity assessed by high-field MRI and radiography

OBJECTIVE With an increasing prevalence of older and obese citizens, the problems of knee osteoarthritis (KOA) will escalate. Weight loss is recommended for obese KOA patients and in a majority of cases this leads to symptomatic relief. We hypothesized that pre-treatment structural status of the knee joint, assessed by radiographs, 1.5 T magnetic resonance imaging (MRI) and knee-joint alignment, may influence the symptomatic changes following a significant weight reduction. DESIGN Patients were recruited from a Department of Rheumatology. Eligibility criteria were age above 50 years, body mass index ≥ 30 kg/m(2), primary KOA diagnosed according to the American College of Rheumatology (ACR) criteria and having verified structural damage. Patients underwent a 16 weeks dietary programme with formula products and counselling. MRI and radiographs of the most symptomatic knee were obtained at baseline and assessed for structural damage using the Boston-Leeds Osteoarthritis of the Knee Score, minimum joint space width and Kellgren-Lawrence score. Imaging variables, muscle strength and degree of alignment, were examined as predictors of changes in Knee Osteoarthritis Outcome Score (KOOS) and Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) - Osteoarthritis Research Society International (OARSI) Responder Criterion. RESULTS Structural damage at baseline assessed by imaging, muscle strength or knee-joint alignment showed no statistically significant association to changes in KOOS pain and function in daily living (r ≤ 0.13; P>0.05) or the OMERACT-OARSI Responder Criterion (OR 0.48-1.68; P-values ≥ 0.13). CONCLUSIONS Presence of joint damage did not preclude symptomatic relief following a clinically relevant weight loss in older obese patients with KOA. Neither muscle strength nor knee-joint alignment was associated with the degree of symptomatic relief.

MRI quantification of rheumatoid arthritis: Current knowledge and future perspectives

The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method for detecting and quantifying joint damage in RA. However, radiographs only show late disease manifestations as joint space narrowing and bone erosions, whereas it cannot detect synovitis and bone marrow oedema, i.e., inflammation in the synovium or the bone, which may be visualized by magnetic resonance imaging (MRI) months to years before erosions develop. Furthermore, MRI allows earlier visualization of bone erosions than radiography. In order to allow early treatment initiation and optimal guidance of the therapeutic strategy, there is a need for methods which are capable of early detection of inflammatory joint changes. In this review, we will discuss available data, advantages, limitations and potential future of MRI in RA.

A randomized, controlled study of a single intra-articular injection of etanercept or glucocorticosteroids in patients with rheumatoid arthritis.

Objective: Glucocorticosteroids are used successfully for both systemic and intra‐articular treatment of arthritis. Inhibitors of tumour necrosis factor alpha (TNF‐α) are effective when administered systemically and this study was performed to compare the effect of intra‐articular injection of these two substances. Design: A randomized, parallel‐group, double‐blind study with an independent observer. Thirty‐eight patients with flare of arthritis in a single joint (wrist, elbow, or knee) were given intra‐articular 25 mg etanercept or 40 mg methylprednisolone guided by ultrasound. The primary end‐point was the 4‐week change in pain in the target joint. The study complied with Good Clinical Practice (GCP) and the Consolidated Standards for Reporting of Trials (CONSORT) statement. Results: At 4 weeks no difference in pain outcome between treatment groups was demonstrated by analysis of covariance (ANCOVA). Pain on the Visual Analogue Scale (VAS) for etanercept was baseline mean 40.9 (SD 19.6) mm, follow‐up 32.7 (29.1) mm (p = 0.29), methylprednisolone baseline mean 47.1 (29.6) mm, follow‐up 25.3 (24.7) mm (p<0.001). The investigators evaluation was for etanercept baseline 30.6 (21.2) mm, follow‐up 17.1 (15.5) mm (p = 0.054) and for methylprednisolone baseline 35.4 (26.4) mm, follow‐up 11.9 (14.6) mm (p = 0.012). Joint swelling was for etanercept baseline 1.78 (0.73), follow‐up 1.25 (0.77) (p = 0.015) and for methylprednisolone baseline 1.74 (0.73), follow‐up 0.71 (0.77) (p<0.001). One serious adverse event was seen in a patient treated with methylprednisolone injection. Conclusion: Although no difference between groups was demonstrated, the within‐group effect of methylprednisolone was more marked than that of etanercept. Injections with 25 mg etanercept were well tolerated. However, the cost of etanercept will presumably limit its use to patients with adverse reactions to steroid.

Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the wrist region. A descriptive interventional study

BackgroundThe wrist region is one of the most complex joints of the human body. It is prone to deformity and functional impairment in juvenile idiopathic arthritis (JIA), and is difficult to examine clinically. The aim of this study was to evaluate the role of ultrasonography (US) with Doppler in diagnosis of synovitis, guidance of steroid injections, and follow-up examinations of the wrist in JIA.MethodsIn 11 patients (median age 12.5 years, range 2-16), 15 wrists with clinically active arthritis were assessed clinically by US and color Doppler (Logiq 9, GE, 16-4 MHz linear transducer) prior to and 1 and 4 weeks after US-guided steroid injection.ResultsUS detected synovitis in the radio-carpal joints, the midcarpal joints, and the tendon sheaths in 87%, 53% and 33% of the wrists, respectively. Multiple compartments were involved in 67%. US-guidance allowed accurate placement of steroid in all 21 injected compartments, with a low rate of subcutaneous atrophy. Synovial hypertrophy was normalized in 86% of the wrists, hyperemia in 91%, and clinically active arthritis in 80%.ConclusionsUS enabled detection of synovial inflammation in compartments that are difficult to evaluate clinically and exact guidance of injections, and it was valuable for follow-up examinations. Normalization of synovitis was achieved in most cases, which supports the notion that US is an important tool in management of wrist involvement in JIA.

Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology

Objective: To determine whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluated using semi-automatic image processing software can accurately assess synovial inflammation in rheumatoid arthritis (RA) knee joints. Methods: In 17 RA patients undergoing knee surgery, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T1-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement (IRE), were generated by the software in three different areas: (I) the entire slice (Whole slice); (II) a manually outlined region of interest (ROI) drawn quickly around the joint, omitting large artefacts such as blood vessels (Quick ROI); and (III) a manually outlined ROI following the synovial capsule of the knee joint (Precise ROI). Intra- and inter-reader agreement was assessed using the intra-class correlation coefficient (ICC). Results: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman’s correlation coefficient (rho) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intra- and inter-reader ICCs were very high (0.93–1.00). No Whole slice parameters were correlated to histology. Conclusion: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint to omit large artefacts is necessary.

The role of cytotoxic T-lymphocytes in the prevention and immune surveillance of tumors— lessons from normal and immunodeficient mice

The idea of immunological surveillance against cancer has existed for nearly 100 years but as no conclusive evidence has yet been published the importance of the cellular immune defense in the detection and removal of incipient or existing tumors is still a hotly debated subject. However, in order to select a relevant immunotherapeutic strategy in the treatment of cancer, a fundamental understanding of the basic immunologic conditions under which a tumor develops and exists is a prerequisite. Therefore, a murine model was set up that we hoped would enable us to confirm or reject the theory of immunological surveillance. A large panel of methylcholanthrene induced tumors was established in T-cell immunodeficient nude mice and congenic normal mice to study the influence of the immune system on developing tumors. As nude mice developed tumors fastest and with the highest incidence, we concluded that in this model the immune system constituted a ‘tumor-suppressive factor’ delaying and sometimes abrogating tumor growth, i.e. performing immune surveillance. Immunogenicity of the tumors was assessed by transplantation back to normal histocompatible mice. Tumors originating from the immunodeficient nude mice turned out to be far more immunogenic than tumors from normal mice, resulting in a high rejection rate. CD8+cytotoxic T cells were found to be indispensable for this rejection, leading to the conclusion that the cytotoxic T cells perform immune selection in normal mice, eliminating immunogenic tumor cell variants in the incipient tumor.In this review, we discuss the difficulties facing immunotherapy when conclusions are drawn from the presented observations and hypotheses.

Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial 1

To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee‐exercise program (E), or “no attention” (C; control group).

MRI findings in soccer players with long-standing adductor-related groin pain and asymptomatic controls

Background Soccer players are commonly affected by long-standing adductor-related groin pain (ARGP), but the clinical significance of MRI findings in these athletes is largely unknown. Our aims were (1) to evaluate whether MRI findings are associated with long-standing ARGP in soccer players, (2) to assess MRI findings in asymptomatic soccer players and non-soccer playing controls. Methods This cross-sectional study included 28 male soccer players with long-standing ARGP, 17 male asymptomatic soccer players and 20 male asymptomatic non-soccer playing athletes of matching age and athletic exposure. Participants underwent identical standardised and reliable clinical examination, and MRI scans (3 T) of the pelvis performed by a blinded observer. Images were consensus rated by three blinded radiologists according to a standardised MRI evaluation protocol. The associations between clinical adductor-related findings and pathological MRI findings were investigated with χ2 statistics and OR. Results Central disc protrusion (p=0.027) and higher grades of pubic bone marrow oedema (BMO; p=0.027) were significantly more present in symptomatic players than asymptomatic players. However, up to 71% of asymptomatic soccer players displayed different positive MRI findings, and asymptomatic soccer players had significantly higher odds (OR ranging from 6.3 to 13.3) for BMO, adductor tendinopathy and degenerative changes than non-soccer players. Conclusions ARGP in soccer players was associated with central disc protrusion and higher grades of pubic BMO. Moreover, positive MRI findings were significantly more frequent in soccer players compared with non-soccer players irrespective of symptoms, suggesting that these MRI changes may be associated with soccer play itself rather than clinical symptoms.

Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in rheumatoid arthritis

Objectives: To investigate the responsiveness to treatment and the reliability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rheumatoid arthritis (RA) knee joints. Methods: DCE-MRI was performed in 12 clinically active RA knee joints before and 1, 7, 30, and 180 days after intra-articular injection with 80 mg methylprednisolone. Using semi-automated image processing software, DCE-MRI parameters, including the initial rate of enhancement (IRE) and maximal enhancement (ME), were generated for three regions of interest (ROIs): ‘Whole slice’, ‘Quick ROI’, and ‘Precise ROI’. The smallest detectable difference (SDD), the smallest detectable change (SDC), and intra- and inter-reader intraclass correlation coefficients (ICCs) were used to assess the reliability of DCE-MRI. Responsiveness to treatment was assessed by the standardized response mean (SRM). Results: In all patients clinical remission of the knee was achieved at day 7. All DCE-MRI parameters decreased from day 0 to day 7. Using the Quick and Precise ROI methods, respectively, IRE decreased by 63% and 69%, ME decreased by 11% and 11%, Nvoxel decreased by 55% and 57%, and IRE × Nvoxel decreased by 84% and 85%. The intra- and inter-reader ICCs were very high (0.96–1.00). The decrease in DCE-MRI parameters was larger than the SDC for all patients. SRM was large for all parameters, ranging from –1.04 to –2.40. When the Whole slice ROI method was used, no parameters were responsive to treatment. Conclusions: DCE-MRI analysed using semi-automatic software is a reliable and responsive tool for assessing treatment in RA knees joints. Rough manual delineation of the joint to omit enhancement artefacts is necessary.