Imaging in early rheumatoid arthritis: roles of magnetic resonance imaging, ultrasonography, conventional radiography and computed tomography

Efficient methods for diagnosis, monitoring and prognostication are essential in early rheumatoid arthritis (RA). While conventional X-rays only visualize the late signs of preceding disease activity, there is evidence for magnetic resonance imaging (MRI) and ultrasonography being highly sensitive for early inflammatory and destructive changes in RA joints, and for MRI findings being sensitive to change and of predictive value for future progressive X-ray damage. Reviewing the data on X-ray, computed tomography, MRI and ultrasonography in RA, this paper discusses current and future roles of these imaging modalities in the management of early RA. The main focus is on recent advances in MRI and ultrasonography. Suggestions on clinical use and research priorities are provided.     

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 – a retrospective case series

Purpose: The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2-related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. Materials and methods: We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. Results: The median duration of therapy was 27 months (range 16–34) and 42 MR scans (median 8, range 4–11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range –4%–+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was –10% (range –3%––25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. Conclusions: Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects.     

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions,joint pathology definitions,and the OMERACT RA-MRI scoring system

This article describes the 2002 OMERACT rheumatoid arthritis magnetic resonance image scoring system (RAMRIS) for evaluation of inflammatory and destructive changes in RA hands and wrists, which was developed by an international MRI-OMERACT group. MRI definitions of important RA joint pathologies, and a "core set" of basic MRI sequences for use in RA are also suggested.     

Imaging in rheumatoid arthritis – status and recent advances for magnetic resonance imaging, ultrasonography, computed tomography and conventional radiography

Within the field of imaging in RA, large and exciting advances have been made during the last decade. Although X-ray is still the most widely used tool for monitoring disease progression, other methods offer clear advantages through more sensitive depiction of inflammatory and destructive disease manifestations. MRI and US are increasingly used in RA trials and practice. MRI can visualize all the features involved in inflammation and damage in RA patients, and have documented independent prognostic value and superior sensitivity to change compared with conventional methods. US offers sensitive assessment of joint damage and, particularly, inflammation, and can be used by practising rheumatologists as part of the clinical examination. CT provides high-resolution images of erosion, and may have potential for sensitive monitoring of erosive progression.Overall, these new imaging modalities already provide important benefits for the clinician, including: more sensitive detection of early disease manifestations; more sensitive monitoring of responses to therapeutic agents, including improved assessment of whether optimal disease control (remission) has been achieved; and improved prognostication. Many questions concerning the optimal use of these new imaging modalities require further research efforts, but as technical advances are still progressing rapidly, the clinical and research applications of these modern imaging modalities are also expected to increase markedly during the next decade.Imaging could be useful in practice for the following:

A. In routine clinical practice

• to establish a diagnosis of RA (ACR 1987 criteria): X-ray

• to assist with the diagnostic workout in suspected, but not definite, inflammatory joint disease and early, unclassified inflammatory joint disease (by detection of presence/absence of synovitis, enthesitis, bone erosions etc.): MRI, US

• to monitor structural joint damage: X-ray, MRI

• to monitor disease activity: MRI, US

• to assist with the prognostic stratification of patients with early RA: X-ray, MRI

• to help define the presence or absence of true remission: MRI, US

• to guide aspirations and injections in joints, bursae and tendon sheaths: US

B. In research

• to assess structural joint damage in phase III/IV RA trials: X-ray, MRI

• to assess the anti-inflammatory effectiveness of a new compound (‘proof of concept' studies): MRI, US

• for pretrial selection of the patients most likely to progress (‘enrichment'): X-ray, MRI

For the individual imaging modalities, further exploration of:

• clinical value of differential diagnosis in early and in early suspected, but not certain, inflammatory joint disease: MRI, US

• clinical value of monitoring disease activity by imaging: MRI, US

• defining imaging remission and/or an imaging ‘acceptable state’: MRI, US

• clinical value of monitoring joint damage by imaging: MRI, US, CT

• benefit of and optimal methods for using modern imaging in clinical trials: MRI, US, CT

• development and testing of new technical methods: US (e.g. three-dimensional, new transducers), MRI (e.g. 3 Tesla imaging, whole-body MRI), X-ray (e.g. software for automated image interpretation)

The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes

Aims

To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events.

Materials and Methods

In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the ⁵¹Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included.

Results

From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by −7.9 mL/min (95% confidence interval [CI] −11.1 to −4.7; P < 0.001), estimated ECV by −192.5 mL (95% CI −318.0 to −66.9; P = 0.003) and estimated PV by −128.9 mL (95% CI −218.0 to 39.8; P = 0.005) at Week 13.

Conclusions

Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.     

Prevalence and severity of groin problems in Spanish football: A prospective study beyond the time-loss approach

The time-loss definition of injury is commonly adopted in epidemiological groin-injury studies in football, with a significant risk of underestimating the impact of these injuries. This study investigated the extent of groin problems, beyond the time-loss approach, over a full Spanish football season. Players from 17 amateur male teams were followed over 39 consecutive weeks. Groin-injury time loss and self-reported groin pain, irrespective of time loss, were combined to calculate the average weekly prevalence of all groin problems with or without time loss. A subscale measuring hip- and groin-related sporting function from the Copenhagen Hip and Groin Outcome Score questionnaire (HAGOS, Sport/Rec) was registered every 4 weeks. In total, 407 players participated in the study. The average (range) weekly prevalence of all groin problems was 11.7% (7.2%-20.8%); 1.3% with time loss (0.0%-3.2%) and 10.4% without time loss (6.3%-17.6%). Players with groin problems reported lower scores (mean difference) on the HAGOS, Sport/Rec subscale compared with players without (−19.5 [95% CI: −20.7 to −18.4]), while there was no difference between players reporting groin problems with and without time loss (4.0 [95% CI: −1.1 to 9.1]). The traditional time-loss measure only captured 10% of all groin problems. Hip- and groin-related sporting function was not different between players reporting groin problems with or without time loss, suggesting the reason for continuing to play is not only related to the severity of symptoms. These findings question the judicious use of the time-loss approach in overuse conditions, such as groin pain in footballers.     

Health-related quality of life: validity, reliability, and responsiveness of SF-36, 15D, EQ-5D [corrected] RAQoL, and HAQ in patients with rheumatoid arthritis

OBJECTIVE: To compare validity, reliability, and responsiveness of generic and disease specific health-related quality of life (HRQOL) instruments in rheumatoid arthritis (RA). METHODS: Two samples of patients completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36), EuroQol (EQ)-5D, 15D, Rheumatoid Arthritis Quality of Life Scale (RAQoL), Health Assessment Questionnaire (HAQ), and visual analog scales (VAS) for pain, fatigue, and global RA. Validity (convergent, discriminant, and known-groups) was evaluated in a cross-section of 200 patients. Reliability was evaluated by agreement (intraclass correlation coefficient; baseline to 2 weeks) and internal consistency (Cronbach's alpha); and responsiveness by the standardized response mean stratified on improvement, status quo, or deterioration in health status after 6 months in 150 patients followed longitudinally. Followup questionnaires (at 2 weeks and 6 months) included questions about changes in health status since baseline. RESULTS: The cross-sectional sample included 77% women, median age 57 years (range 19-87), disease duration 6 years (0-58), with Disease Activity Score 28-joint count (DAS28) of 3.10 (1.21-6.47). The longitudinal sample included 80% women, median age 60 years (22-82). Validity: all instruments discriminated between low, moderate, and high DAS28. Reliability: RAQoL and HAQ displayed good repeatability (ICC > 0.95) and internal consistency (Cronbach's alpha > 0.90). Responsiveness: SF-36 bodily pain scale and VAS pain were responsive to both improvement and deterioration. CONCLUSION: All instruments were valid measures for HRQOL in RA. The RAQoL and HAQ displayed the best reliability, while the SF-36 bodily pain scale and VAS pain were the most responsive. The choice of instrument should depend on the study objectives.     

Selective matrix metalloproteinase inhibition increases breaking strength and reduces anastomotic leakage in experimentally obstructed colon

Purpose

Colonic obstruction causes loss of collagen and impairment of anastomotic integrity by matrix metalloproteinases (MMPs). Unexpectedly, pharmacological MMP inhibition increased anastomotic leakage (AL) in obstructed colon possibly due to the non-selective nature of these compounds and the experimental model applied. We therefore studied the effects of selective MMP inhibition on the healing of anastomoses in colon obstructed by a novel laparoscopic technique.

Methods

Left colon was obstructed in 38 male Sprague-Dawley rats (226–284 g). After 12 h, stenoses were resected and end-to-end anastomoses constructed. Baseline breaking strength was determined in 6 animals on day 0. The remaining 32 rats were randomized to daily treatment with the selective MMP-8, MMP-9, and MMP-12 inhibitor AZD3342 (n = 16) or vehicle (n = 16). On day 3, anastomoses were evaluated for AL and breaking strength. Isolated anastomotic wound tissue was analyzed on total collagen and pepsin-insoluble and pepsin-soluble collagen by hydroxyproline. The soluble collagens were further differentiated into native, measured by Sircol, and fragmented forms.

Results

Baseline breaking strength was maintained with AZD3342 but decreased by 25% (P = 0.023) in the vehicle group. The anastomotic breaking strength of AZD3342-treated rats was 44% higher (P = 0.008) than the vehicle-treated rats. Furthermore, the AL rate was reduced (P = 0.037) with AZD3342 compared with vehicle treatment. AZD3342 treatment influenced neither the total or insoluble collagen concentrations nor the degree of fragmentation of the soluble collagen triple helices.

Conclusion

Selective MMP inhibition increased anastomotic breaking strength and reduced AL after resection of colonic obstruction.

     

Is there a preferred method for scoring activity of the spine by magnetic resonance imaging in ankylosing spondylitis?

This report summarizes the discussion during a module update at OMERACT 8 on scoring methods for activity in the spine on magnetic resonance imaging. The conclusion was that the 3 available scoring methods are all very good with respect to discrimination and feasibility: the Ankylosing Spondylitis spine MRI score for activity (ASspiMRI-a), the Berlin method (a modification of the ASspiMRI-a), and the Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index for Assessment of Spinal Inflammation in AS (SPARCC). All 3 methods were judged to be similar with respect to responsiveness and discrimination, although the differences in between-reader intraclass correlation coefficients (ICC) were judged to be relevant (the SPARCC method provided consistently higher ICC). The Berlin and SPARCC methods were preferred most frequently. The development of a new method combining the best elements of all methods is an additional possibility.