Prognostic impact of reduced connexin43 expression and gap junction coupling of neoplastic stromal cells in giant cell tumor of bone

Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in alpha-smooth muscle actin positive than alpha-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in neoplastic stromal cells are associated with the clinical progression and worse prognosis in GCTB

Revision Total Hip Arthroplasty Using the Cement-in-Cement Technique

The cement-in-cement technique is useful in the setting of revision total hip arthroplasty (THA), especially to gain acetabular exposure, change a damaged or loose femoral component, or change the version, offset, or length of a fixed femoral component. The goal of this retrospective study was to assess the clinical and radiographic characteristics of revision THA using the cement-incement technique. Between 1971 and 2013, a total of 63 revision THAs used an Omnifit (Osteonics, Mahwah, New Jersey) or Exeter (Howmedica, Mahwah, New Jersey) stem and the cement-in-cement technique at the senior author’s institution. Aseptic loosening (74%) was the predominant preoperative diagnosis followed by periprosthetic fracture (14%), instability (8%), and implant fracture (6%). Mean clinical follow-up was 5.5 +/- 3.8 years. The Harris Hip Score had a statistically significant increase of 18.5 points (P<.001) after revision THA using the cement-in-cement technique. There were 13 returns to the operating room, resulting in an overall failure rate of 21%. Eleven (18%) cases required revision THA, but only 1 (2%) revision THA was for aseptic removal of the femoral component. All other femoral implants had no evidence of component migration, cement mantel fracture, or circumferential lucent lines at final follow-up. The patients who underwent cement-in-cement revision THA at the senior author’s institution had good restoration of function but a high complication rate

Reproducibility and Precision of CT Scans to Evaluate Tibial Component Rotation.

Place: United StatesBACKGROUND: Component rotation likely plays a greater role on the survivorship and outcomes of total knee arthroplasties than is currently known. Our goal was to evaluate the precision, interobserver reliability, and intrarater reliability of tibial component rotation as measured by computed tomography (CT) scan, regardless of measurement technique. METHODS: Three fellowship-trained, academic arthroplasty surgeons independently measured tibial component rotation on CT scans of 62 total knee arthroplasties using their methods of choice. Measurements were repeated at least 2 weeks after the initial measurement. The precision of the measurements was assessed using a formal 8-step protocol as the gold standard. Intraclass correlation coefficients (ICCs) were calculated to evaluate precision, interobserver agreement, and intrarater reliability RESULTS: The interobserver agreement between the 3 surgeons for tibial component rotation was also moderate (ICC = 0.52). The intrarater reliability of tibial rotation was excellent (ICC = 0.81). Comparison of surgeons' measurement to a validated gold standard revealed only moderate precision for tibial component rotation (ICC = 0.64). CONCLUSION: Practicing surgeons measuring tibial rotation were internally consistent, but failed to demonstrate satisfactory precision and interobserver agreement. We support the adoption of standardized criteria for the measurement of tibial component rotation on CT scans

Experience Influences the Agreement and Reliability of Tibial Component Positioning in Total Knee Arthroplasty.

Place: United StatesBACKGROUND: Poor rotation of the tibial component is associated with unfavorable total knee arthroplasty outcomes. Some surgeons utilize the tibial tubercle (TT method), while others utilize the femoral cam (Box method) as a rotational landmark during total knee arthroplasty. Our purpose is to determine the reproducibility of 2 methods for establishing intra-operative tibial component rotation, while also comparing the effect of level of training. METHODS: Twelve surgeons positioned and sized a symmetric tibial component on 7 cadaver knees. Surgeons were allowed to utilize their preferred method for establishing tibial component rotation. Seven surgeons selected the TT method, 4 utilized the Box method, and 1 used both methods depending on the specimen. Repeat measurements were completed by each surgeon after a rest period. The differences between tibial tray positions were assessed using computer-assisted optoelectronic measurements. Intra-class correlation coefficients were calculated to determine inter-observer agreement (IOA) and intra-rater reliability (IRR). RESULTS: Overall, both the Box method and the TT method demonstrated high IRR for tibial component rotation. Experienced surgeons were more consistent at establishing component rotation regardless of technique. Trainees were more consistent when utilizing the Box method (IRR 0.96, IOA 0.94) than the TT method (IRR 0.71, IOA 0.72). CONCLUSION: Surgeon experience influences the agreement and reliability of tibial component position. For less experienced surgeons, the Box method was more effective than the TT method for consistently reproducing tibial component rotation