Independent Risk Factors for Impaired Early Outcome after Isolated Ankle Fracture - A Multivariate Analysis and Prognostic Models. / Unabhängige Risikofaktoren für komplizierte Frühverläufe nach isolierter Sprunggelenksfraktur ­ eine multivariate Analyse und prognostische Modellierung.

BACKGROUND: Ankle fractures are common operative indications in orthopedic surgery. Their incidence is increasing. OBJECTIVES: To identify independent risk factors and to develop prognostic models for the prediction of prolonged length of hospital stay (LOS) and the onset of postoperative complications. MATERIALS AND METHODS: This is a single-center, retrospective, observational study analyzing data of 154 consecutive, isolated, surgically treated ankle fractures. Multivariate binary logistic regression analysis was applied to identify significant independent risk factors. The validity and clinical applicability of the developed prognostic models was assessed with ROC-curve analysis (ROC: Receiver Operating Characteristic). Internal validation of prognostic models was performed with randomized backwards bootstrapping. RESULTS: The median LOS was 7 days. 50 patients (33%) had a longer LOS. 13% of operated patients had a postoperative complication (n = 20). Independent preoperative risk factors for prolonged length of stay were leukocytosis (p = 0.020; OR: 1.211), an increased CRP-level (p = 0.005; OR: 1.901), as well as a bi- (p = 0.002; OR: 15.197) or trimalleolar (p = 0.001; OR: 10.678) fracture type. Immediate operative therapy was an independent beneficial factor (p < 0.001; OR: 0.070). The onset of complications was associated significantly with diabetes mellitus (p = 0.004; OR: 9.903) and an elevated ASA score (p = 0,004; OR: 3.574). The developed prognostic models for the prediction of prolonged LOS (AUROC: 0.736) and postoperative complications (AUROC: 0.724) had a good clinical validity and were internally validated. CONCLUSION: The current data pronounce the importance of preoperative laboratory works. Furthermore, co-morbidities play a major role in the prognosis of outcome. The developed prognostic models are able to reliably predict the outcome and enable the preoperative identification of high-risk patients.

Identification of candidate genes for susceptibility to reactive arthritis.

This study was undertaken to evaluate the gene expression profile in monocytes from three patients with reactive arthritis (ReA) in remission in order to identify candidate genes accounting for a potential susceptibility to ReA. Gene expression analyses revealed eight differentially expressed mRNA transcripts in monocytes of ReA patients. The major part of genes encoded cytokines, growth factors and chemokines. There was a remarkably high proportion of proangiogenic factors, in particular IP10, ENA-78, and IL-8 accounting for a genetically determined susceptibility to ReA at the host cell level.

Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis.

INTRODUCTION: We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF). METHODS: mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant. RESULTS: SF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro. CONCLUSIONS: Neurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthritis.

Identification of interleukin-7 as a candidate disease mediator in spondylarthritis.

OBJECTIVE: Understanding of the molecular pathophysiology of spondylarthritis (SpA) remains largely elusive. This is related both to the complexity of the disease (axial versus peripheral disease, inflammation versus tissue remodeling) and to the difficulty in obtaining samples from primary disease sites. This study was undertaken to explore a gene expression approach for identifying novel candidate mediators of SpA. METHODS: Sacroiliac joint fluid aspirates from 3 SpA patients with active sacroiliitis were studied by microarray analysis. The expression of selected candidate molecules in peripheral synovitis was confirmed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Microarray analysis identified 4 sacroiliitis gene clusters, containing a total of 47 messenger RNA (mRNA) transcripts. Two clusters contained genes expressed in all sacroiliitis samples, corresponding to both known and unsuspected candidate mediators of SpA pathology. These included proinflammatory molecules as well as molecules involved in tissue remodeling, such as transforming growth factor beta2. Of the novel candidate genes selected for confirmation, interleukin-7 (IL-7) mRNA expression was higher in SpA peripheral synovial fluid and synovial tissue samples than in osteoarthritis samples, and similar to expression in rheumatoid arthritis (RA) samples. At the protein level, synovial fluid IL-7 levels were even higher in SpA than in RA, despite lower levels of tumor necrosis factor alpha and IL-1beta. CONCLUSION: In the present study, both known and unsuspected candidate mediators of SpA pathogenesis were identified, including IL-7. The specific overexpression of IL-7 at sites of peripheral synovitis in SpA suggests that further functional investigations of the role of this cytokine in SpA pathogenesis are warranted.