Restoration of leg length and offset correlates with trochanteric pain syndrome in total hip arthroplasty

Persistent pain around the greater trochanter is a common complication after total hip arthroplasty. Restoration of biomechanics such as leg length, femoral und acetabular offset is crucial in THA. The purpose of this study was to evaluate postoperative differences of these parameters after THA and to analyze their association to greater trochanteric pain syndrome. Furthermore, we aimed to evaluate the clinical relevance of trochanteric pain syndrome compared to patient reported outcome measures. 3D-CT scans of 90 patients were analyzed after minimalinvasive total hip arthroplasty and leg length, femoral and acetabular offset differences were measured. Clinical evaluation was performed three years after THA regarding the presence of trochanteric pain syndrome and using outcome measures. Furthermore, the patients' expectation were evaluated. Patients with trochanteric pain syndrome showed a higher absolute discrepancy of combined leg length, femoral and acetabular offset restoration compared to the non-operated contralateral side with 11.8 +/- 6.0mm than patients without symptoms in the trochanteric region with 7.8 +/- 5.3mm (p=0.01). Patients with an absolute deviation of the combined parameters of more than 5mm complained more frequently about trochanteric symptoms (29.2%, 19/65) than patients with a biomechanical restoration within 5mm compared to the non-affected contralateral side (8.0%, 2/25, p=0.03). Clinical outcome measured three years after THA was significantly lower in patients with trochanteric symptoms than without trochanteric pain (p<0.03). Similarly, fulfillment of patient expectations as measured by THR-Survey was lower in the patients with trochanteric pain (p<0.005). An exact combined restoration of leg length, acetabular and femoral offset reduces significantly postoperative trochanteric pain syndrome and improves the clinical outcome of the patients

IL‐12‐polarized Th1 cells produce GM‐CSF and induce EAE independent of IL‐23

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115966/1/eji3410.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115966/2/eji3410-sup-0002-PRC.pd

Clarifying the Critical Factors for Th1 and Th17 Pathogenicity in an Animal Model of CNS-Targeted Autoimmune Disease.

Experimental autoimmune encephalitomyelitis (EAE) is a CD4+ T cell-mediated CNS-targeted autoimmune disease and a model of multiple sclerosis (MS). IL-12-polarized IFN-γ-producing Th1 cells and IL-23-polarized IL-17-producing Th17 cells have been implicated in EAE and MS pathogenesis. However, current dogma states that IL-23, and not IL-12, is absolutely critical for T cell encephalitogenicity. Furthermore, few reports measuring Th1 or Th17 cells in EAE have considered Th17 cell plasticity. IL-23-polarized Th17 cells can downregulate IL-17 and upregulate IFN-γ, which makes them indistinguishable from Th1 cells. This conversion to an “exTh17” is T-bet-dependent and promoted by IL-23. Though we have previously demonstrated that IL-12- or IL-23-polarized T cells can each induce EAE via distinct mechanisms, the contribution of IL-23 to IL-12-polarized disease, and vice versa, is unexamined. Therefore, we questioned whether IFN-γ-producing CD4+ T cells found during MS and EAE are actually IL-23-driven exTh17 cells and whether bona fide Th1 or stable Th17 cells are encephalitogenic independently of exTh17 cells. We also questioned whether distinctions seen between IL-12- and IL-23-mediated EAE could be found in MS patients. Here, we used adoptive transfer models of EAE to demonstrate that IL-12-polarized Th1 cell encephalitogenicity can be IL-23-independent. IL-23-independent Th1-mediated disease and IL-12-independent Th17-mediated disease had distinct cellular infiltration patterns and cytokine and chemokine expression profiles. Furthermore, we saw distinct cytokine and chemokine profiles in MS patients grouped by relative IL-12 and IL-23 expression. We also investigated the contribution of plasticity to Th17 pathogenicity. We demonstrated that IL-23-polarized T-bet-/- cells were stable Th17 cells. They induced EAE following adoptive transfer into wild-type and RAG2-/- hosts, though disease was milder and delayed relative to wild type Th17 cells. We also determined that the reduced potency of stable Th17 cells is not a result of poor proliferation or survival, rather due to altered trafficking molecules on stable Th17 cells. These data contribute to the understanding to the critical factors for CD4+ T cell encephalitogenicity, and suggest that Th1, Th17, and exTh17 cells are distinct effector lineages in EAE. These data have translational implications, which could result in the discovery of biomarkers in MS patient populations and targeted therapies.PHDImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108991/1/hgrifka_1.pd

Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target.

BACKGROUND: The proinflammatory and anti-inflammatory role of the sympathetic nervous system in early and late inflammation is an unresolved paradox. A drastic loss of sympathetic nerve fibres in the synovial tissue of patients with rheumatoid arthritis (RA) has previously been demonstrated. The presence of tyrosine hydroxylase (TH)-positive cells in RA and osteoarthritis (OA) has been determined, but the role of these cells in inflammation is still unclear. OBJECTIVE: To characterise TH-positive cells in inflamed RA and OA synovial tissue and to study their role in inflammation. METHODS: Synovial samples were obtained from 32 patients with OA and 19 patients with RA and from 10 control patients. Synovial tissue samples were used for immunofluorescence staining. Synovial cells were isolated by tissue digestion and immediately used for cell culture. For in vivo experiments, collagen type-II arthritis in DBA/1J mice was induced. RESULTS: TH+ cells were present only in inflamed tissue and not in controls. Catecholamine-storing vesicles and vesicular monoamine transporter 2 (VMAT2) were identified in the synovial tissue. Experimental increase of cytoplasmic catecholamines by VMAT2 blockade strongly reduced tumour necrosis factor (TNF) independently of canonical extracellular \u3b2-adrenergic signalling. In addition, VMAT2 blockade increased cyclic AMP (cAMP) and cAMP responsive element binding protein, responsible for TNF inhibition. In vivo, appearance of VMAT2 positive cells was confirmed. VMAT2 blockade ameliorated inflammation also in vivo. CONCLUSIONS: This study demonstrates that local catecholamine-producing cells start to replace sympathetic nerve fibres around the onset of disease, and modulation of locally produced catecholamines has strong anti-inflammatory effects in vivo and in vitro

Genauigkeit eines bildfreien Navigationssystemes für die Hüftpfannenimplantation – eine anatomische Studie

The position of the acetabular cup is of decisive importance for. the function of a total hip replacement (THR). Using the conventional surgical technique, correct placement of the cup often fails due to a lack of information about pelvic tilt. With CT-based and fluoroscopically-assisted navigation procedures the accuracy of implantation has been significantly improved. However, additional radiation exposure, high cost and the increased time requirement have hampered the acceptance of these techniques. The present anatomical study evaluates the accuracy of an alternative procedure-image-free navigation. This method requires little extra effort, does not substantially delay surgery, and needs no additional imaging. Press-fit cups were implanted in 10 human cadaveric hips with the help of the image-free navigation system, and the position of the cups was checked intraoperatively with a CT-based navigation system and postoperatively by computed tomography. All cups were implanted within the targeted safe zone with an average inclination of 44degrees (range 40degrees-48degrees, SABW 2.7degrees) and an average anteversion of 18degrees (range 12-24degrees, SABW 4.1degrees). Analysis of accuracy of the image-free navigation software revealed only a small, clinically tolerable deviation in cup anteversion and cup inclination in comparison with the CT-based navigation system and the post operative CT scans. The evaluated image-free navigation system appears to be a practicable and reliable alternative to the computer-assisted implantation of acetabular cups in total hip arthroplasty

Prospective Single-Arm, Multi-Center Trial of a Patient-Specific Interpositional Knee Implant: Early Clinical Results

Within narrow indication of patients with unicompartmental disease, the iForma device can provide improvement in knee function and reduction in pain, however, with a significant higher risk of early revision compared to traditional arthroplasty. Respecting this limitation it may be an alternative option for arthritic patients with unicompartmental disease who have contraindications to High Tibial Osteotomy or are too young for knee replacement; the iForma device further has the distinct advantage of time and cost saving compared to those procedures