Study protocol subacromial impingement syndrome: the identification of pathophysiologic mechanisms (SISTIM)

<p>Abstract</p> <p>Background</p> <p>The Subacromial Impingement Syndrome (SIS) is the most common diagnosed disorder of the shoulder in primary health care, but its aetiology is unclear. Conservative treatment regimes focus at reduction of subacromial inflammatory reactions or pathologic scapulohumeral motion patterns (<it>intrinsic </it>aetiology). Long-lasting symptoms are often treated with surgery, which is focused at enlarging the subacromial space by resection of the anterior part of the acromion (based on <it>extrinsic </it>aetiology). Despite that acromionplasty is in the top-10 of orthopaedic surgical procedures, there is no consensus on its indications and reported results are variable (successful in 48-90%). We hypothesize that the aetiology of SIS, i.e. an increase in subacromial pressure or decrease of subacromial space, is multi-factorial. SIS can be the consequence of pathologic scapulohumeral motion patterns leading to humerus cranialisation, anatomical variations of the scapula and the humerus (e.g. hooked acromion), a subacromial inflammatory reaction (e.g. due to overuse or micro-trauma), or adjoining pathology (e.g. osteoarthritis in the acromion-clavicular-joint with subacromial osteophytes).</p> <p>We believe patients should be treated according to their predominant etiological mechanism(s). Therefore, the objective of our study is to identify and discriminate etiological mechanisms occurring in SIS patients, in order to develop tailored diagnostic and therapeutic strategies.</p> <p>Methods</p> <p>In this cross-sectional descriptive study, applied clinical and experimental methods to identify intrinsic and extrinsic etiologic mechanisms comprise: MRI-arthrography (eligibility criteria, cuff status, 3D-segmented bony contours); 3D-motion tracking (scapulohumeral rhythm, arm range of motion, dynamic subacromial volume assessment by combining the 3D bony contours and 3D-kinematics); EMG (adductor co-activation) and dynamometry instrumented shoulder radiographs during arm tasks (force and muscle activation controlled acromiohumeral translation assessments); Clinical phenotyping (Constant Score, DASH, WORC, and SF-36 scores).</p> <p>Discussion</p> <p>By relating anatomic properties, kinematics and muscle dynamics to subacromial volume, we expect to identify one or more predominant pathophysiological mechanisms in every SIS patient. These differences in underlying mechanisms are a reflection of the variations in symptoms, clinical scores and outcomes reported in literature. More insight in these mechanisms is necessary in order to optimize future diagnostic and treatment strategies for patients with SIS symptoms.</p> <p>Trial registration</p> <p>Dutch Trial Registry (Nederlands Trial Register) <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2283">NTR2283</a>.</p

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Quantitative assessment of morphology, T1ρ, and T2 of shoulder cartilage using MRI

OBJECTIVES: To assess the feasibility of quantifying shoulder cartilage morphology and relaxometry in a clinically feasible scan time comparing different pulse sequences and assessing their reproducibility at 3 Tesla. METHODS: Three pulse sequences were compared for morphological assessments of shoulder cartilage thickness and volume (SPGR, MERGE, FIESTA), while a combined T1ρ-T2 sequence was optimized for relaxometry measurements. The shoulders of six healthy subjects were scanned twice with repositioning, and the cartilage was segmented and quantified. The degree of agreement between the three morphological sequences was assessed using Bland-Altman plots, while the morphological and relaxometry reproducibility were assessed with root-mean-square coefficients of variation (RMS-CVs) RESULTS: Bland-Altman plots indicated good levels of agreement between the morphological assessments of the three sequences. The reproducibility of morphological assessments yielded RMS-CVs between 4.0% and 17.7%. All sequences correlated highly (R>0.9) for morphologic assessments with no statistically significant differences. For relaxometry assessments of humeral cartilage, RMS-CVs of 6.4% and 10.6% were found for T1ρ and T2, respectively. CONCLUSIONS: The assessment of both cartilage morphology and relaxometry is feasible in the shoulder with SPGR, humeral head, and T1ρ being the more reproducible morphological sequence, anatomic region, and quantitative sequence, respectively

The diagnostic test accuracy of magnetic resonance imaging, magnetic resonance arthrography and computer tomography in the detection of chondral lesions of the hip

BACKGROUND: The purpose of this study was to assess the diagnostic test accuracy of magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA) and multidetector arrays in CT arthrography (MDCT) for assessing chondral lesions in the hip joint. MATERIALS AND METHODS: A review of the published and unpublished literature databases was performed to identify all studies reporting the diagnostic test accuracy (sensitivity/specificity) of MRI, MRA or MDCT for the assessment of adults with chondral (cartilage) lesions of the hip with surgical comparison (arthroscopic or open) as the reference test. All included studies were reviewed using the quality assessment of diagnostic accuracy studies appraisal tool. Pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratios were calculated with 95 % confidence intervals using a random-effects meta-analysis for MRI, MRA and MDCT imaging. RESULTS: Eighteen studies satisfied the eligibility criteria. These included 648 hips from 637 patients. MRI indicated a pooled sensitivity of 0.59 (95 % CI: 0.49-0.70) and specificity of 0.94 (95 % CI: 0.90-0.97), and MRA sensitivity and specificity values were 0.62 (95 % CI: 0.57-0.66) and 0.86 (95 % CI: 0.83-0.89), respectively. The diagnostic test accuracy for the detection of hip joint cartilage lesions is currently superior for MRI compared with MRA. There were insufficient data to perform meta-analysis for MDCT or CTA protocols. CONCLUSIONS: Based on the current limited diagnostic test accuracy of the use of magnetic resonance or CT, arthroscopy remains the most accurate method of assessing chondral lesions in the hip joint