The usefulness of ultrasound in predicting outcomes in patients with shoulder pain: a prospective observational study

Objectives Shoulder pain is common but current clinical classification has limited utility. We aimed to determine whether groups of ultrasound-based shoulder pathologies exist and to evaluate outcomes according to identified groups and individual pathologies. Methods This was a prospective study of a community-based cohort with shoulder pain referred for their first ultrasound scan at a single radiology unit, with subsequent routine clinical care. Patient-reported outcomes were collected at baseline, 2 weeks and 6 months; standardized ultrasound reporting was employed. Latent class analysis (LCA) identified ultrasound pathology–based groups. Multiple linear regression analysis explored associations between baseline pathologies, subsequent treatment and Shoulder Pain and Disability Index (SPADI). Short-term response to corticosteroid injections was investigated. Results Of 500 participants (mean age 53.6 years; 52% female), 330 completed follow-up. LCA identified four groups: bursitis with (33%) or without (27%) acromioclavicular joint degeneration, rotator cuff tear (21%) and no bursitis/tear (19%). Total SPADI was higher at baseline for cuff tears (mean 55.1 vs 49.7–51.3; overall P = 0.005), but accounting for this, groups did not differ at 6 months (43.5 vs 38.5–40.5; P = 0.379). Baseline SPADI was the only predictor of 6-month SPADI retained by penalized modelling; neither LCA-derived ultrasound groups nor individual pathologies were selected. Response to baseline injection at week 2 did not differ between groups (mean SPADI 40.1–43.8; P = 0.423). Conclusion Ultrasound-based classification (groups or individual pathologies) of shoulder pain did not predict medium-term outcomes using current treatments. The role of routine diagnostic ultrasound for shoulder pain needs consideration; it may be useful to establish evidence-based therapies for specific pathologies

Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis

Objectives: To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. Methods: Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. Results: 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (−2.35 vs −0.68, −2.58 vs −0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (−1.34 vs −0.49 −2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. Conclusions: Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity

Exercise therapy after corticosteroid injection for moderate to severe shoulder pain: large pragmatic randomised trial

Objective To compare the effectiveness of subacromial corticosteroid injection combined with timely exercise and manual therapy (injection plus exercise) or exercise and manual therapy alone (exercise only) in patients with subacromial impingement syndrome

Targeted killing of colorectal cancer cell lines by a humanised IgG1 monoclonal antibody that binds to membrane-bound carcinoembryonic antigen

The distribution of carcinoembryonic antigen (CEA) in colorectal cancer (CRC) differs from that in normal colorectal tissue, being found on all borders of the cell membrane and hence enabling access to intravenous antibody, making CEA a good target for antibody-based therapy. The distinctive anti-CEA antibody, PR1A3, binds only membrane-bound CEA. Humanised PR1A3 (hPR1A3) was assessed both in vitro cytotoxicity and binding assays with colorectal cancer cell lines expressing varying levels of CEA. Human peripheral blood mononuclear cells (PBMCs) and purified natural killer (NK) cells were used as effectors. The in vitro assays demonstrated hPR1A3 CEA-specific binding and antibody-dependent and CEA-specific killing of human colorectal cancer cell lines by human PBMCs. The effect increased with increasing concentration of antibody and surface CEA, and was lost by using the parent murine IgG1 PR1A3. Killing was also blocked by antibody to the Fc-γIIIA receptor. Purified human NK cells were effective at much lower effector:target ratios than unfractionated PBMCs, indicating that NK cells were the main mediators of hPR1A3-based CEA-specific killing. The results support the development of hPR1A3 for therapy of colorectal cancer

Assessment of the radioanatomic positioning of the osteoarthritic knee in serial radiographs: comparison of three acquisition techniques

SummaryObjectiveRecent studies using various standardized radiographic acquisition techniques have demonstrated the necessity of reproducible radioanatomic alignment of the knee to assure precise measurements of medial tibiofemoral joint space width (JSW). The objective of the present study was to characterize the longitudinal performance of several acquisition techniques with respect to long-term reproducibility of positioning of the knee, and the impact of changes in positioning on the rate and variability of joint space narrowing (JSN).MethodsEighty subjects were randomly selected from each of three cohorts followed in recent studies of the radiographic progression of knee osteoarthritis (OA): the Health ABC study (paired fixed-flexion [FF] radiographs taken at a 36-month interval); the Glucosamine Arthritis Intervention Trial (GAIT) (paired metatarsophalangeal [MTP] radiographs obtained at a 12-month interval), and a randomized clinical trial of doxycycline (fluoroscopically assisted semiflexed anteroposterior (AP) radiographs taken at a 16-month interval).Manual measurements were obtained from each radiograph to represent markers of radioanatomic positioning of the knee (alignment of the medial tibial plateau and X-ray beam, knee rotation, femorotibial angle) and to evaluate minimum JSW (mJSW) in the medial tibiofemoral compartment. The effects on the mean annualized rate of JSN and on the variability of that rate of highly reproduced vs variable positioning of the knee in serial radiographs were evaluated.ResultsParallel or near-parallel alignment was achieved significantly more frequently with the fluoroscopically guided positioning used in the semiflexed AP protocol than with either the non-fluoroscopic FF or MTP protocol (68% vs 14% for both FF and MTP protocols when measured at the midpoint of the medial compartment; 75% vs 26% and 34% for the FF and MTP protocols, respectively, when measured at the site of mJSW; P<0.001 for each). Knee rotation was reproduced more frequently in semiflexed AP radiographs than in FF radiographs (66% vs 45%, P<0.01). In contrast, the FF technique yielded a greater proportion of paired radiographs in which the femorotibial angle was accurately reproduced than the semiflexed AP or MTP protocol (78% vs 59% and 56%, respectively, P<0.01 for each). Notably, only paired radiographs with parallel or near-parallel alignment exhibited a mean rate of JSN (±SD) in the OA knee that was more rapid and less variable than that measured in all knees (0.186±0.274mm/year, standardized response to mean [SRM]=0.68 vs 0.128±0.291mm/year, SRM=0.44).ConclusionThis study confirms the importance of parallel radioanatomic alignment of the anterior and posterior margins of the medial tibial plateau in detecting JSN in subjects with knee OA. The use of radiographic methods that assure parallel alignment during serial X-ray examinations will permit the design of more efficient studies of biomarkers of OA progression and of structure modification in knee OA

The reliability of musculoskeletal ultrasound in the detection of cartilage abnormalities at the metacarpo-phalangeal joints

Objective: To assess the reliability of ultrasound (US) in detecting cartilage abnormalities at the metacarpo-phalangeal (MCP) joints in people with cartilage pathology. Methods: Nine expert ultrasonographers initially achieved consensus on definitions and scanning protocols. They then examined the second to fifth MCP joints of the dominant hand of eight people with hand osteoarthritis (OA). US examinations were conducted in two rounds, with independent blinded evaluations of cartilage lesions. Global cartilage abnormalities were assessed by applying a dichotomous (presence/absence) score; in addition, the following lesions were evaluated using the same scoring system: loss of anechoic structure and/or thinning of the cartilage layer, and irregularities and/or loss of sharpness of at least one cartilage margin. Reliability was assessed using kappa (k) coefficients. Results: Thirty-two joints were examined. Intra-observer k values ranged from 0.52 to 1 for global cartilage abnormalities; k values ranged from 0.54 to 0.94 for loss of anechoic structure and/or thinning of cartilage layer and from 0.59 to 1 for irregularities and/or loss of sharpness of at least one cartilage margin. Values of k for inter-observer reliability were 0.80 for global cartilage abnormalities, 0.62 for loss of anechoic structure and/or thinning of cartilage layer, and 0.39 for irregularities and/or loss of sharpness of at least one cartilage margin. Conclusion: US is a reliable imaging modality for the detection of cartilage abnormalities in patients with cartilage pathology in the MCP joints. The analysis of specific cartilage measures showed more variable results that may be improved by modifying definitions and further standardization of US techniques. © 2012 Osteoarthritis Research Society International

A Simple Molecular Design Strategy for Delayed Fluorescence toward 1000 nm.

Harnessing the near-infrared (NIR) region of the electromagnetic spectrum is exceedingly important for photovoltaics, telecommunications, and the biomedical sciences. While thermally activated delayed fluorescent (TADF) materials have attracted much interest due to their intense luminescence and narrow exchange energies (ΔEST), they are still greatly inferior to conventional fluorescent dyes in the NIR, which precludes their application. This is because securing a sufficiently strong donor-acceptor (D-A) interaction for NIR emission alongside the narrow ΔEST required for TADF is highly challenging. Here, we demonstrate that by abandoning the common polydonor model in favor of a D-A dyad structure, a sufficiently strong D-A interaction can be obtained to realize a TADF emitter capable of photoluminescence (PL) close to 1000 nm. Electroluminescence (EL) at a peak wavelength of 904 nm is also reported. This strategy is both conceptually and synthetically simple and offers a new approach to the development of future NIR TADF materials

EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis

The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA

Enhanced Expression of Human Type 11a Secretory Phospholipase A2 Antigen in Arthritic Synovium

To determine the localisation and level of expression of human type IIa secretory phospholipase A2 (sPLA2) in the synovium of rheumatoid arthritis (RA), osteoarthritis (OA), and non-arthritic (NA) patients and to examine the relation between sPLA2 and histological features of inflammation. METHODS: Immunoperoxidase staining using the anti-sPLA2 monoclonal antibody 9C1 was performed on frozen sections of knee synovium of 10 RA, 10 OA, and 10 NA patients. sPLA2 positive cells were scored on a scale of 0-3 in 10 fields of a representative tissue section from each case. Double labelling immunofluorescence confocal microscopy with antibodies to CD14 or CD45 and 9C1 was used to determine cell type specificity. Inflammation was assessed by emiquantitative scoring of lining layer thickness and mononuclear cell infiltrates (MC) and a cumulative inflammation score, generated by summing the two parameters. Scores in each group were compared using non-parametric statistical analysis. RESULTS: sPLA2 was localised to endothelium (EC), vascular smooth muscle (VSM), and mast cells (M) in all tissue sections. In RA and OA sections, staining was seen in both macrophage-like and fibroblast-like cells in the synovial lining layer (LL) and subsynovial lining layer (SLL). Perineural cells stained positively. Subintimal lymphoid aggregates (LA) were negative in all sections. The RA group showed significantly greater staining in extravascular synovial tissue (median 3.6, range 1.5-6.0) than the OA (median 1.95, range 0-5.3) or NA (median 0, range 0-5.9) groups (p < 0.05). LL staining was significantly higher in RA than both OA and NA sections (p < 0.05). The OA group showed a trend to higher staining scores than the NA group that did not reach significance. There was a significant correlation between the sPLA2 staining score and inflammation score within the RA patient group (p < 0.05). CONCLUSIONS: The synovium is a site of increased expression of sPLA2 antigen in both RA and OA relative to NA. Its presence in both fibroblast and macrophage-like cells in the LL and SLL of synovial tissue in RA and OA, but not NA, indicates that the enzyme is specifically induced in these regions in both conditions with expression in the LL being particularly characteristic of RA. The widespread expression of sPLA2 in synovium suggests it is likely to play a significant part in synovial pathology