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Michael J McNicholas,1 Stefan M Gabriel,2 Anton G Clifford,2 Evelyne M Hasler2 1Aintree University Hospital, Teaching Hospital, Major Trauma Centre, NHS Foundation Trust, Liverpool, UK; 2Moximed, Hayward, CA, USA Introduction: The KineSpring implant system has been shown to provide load reductions at the medial compartment of the knee, and has demonstrated clinical success in reducing pain and increasing function in patients with medial knee osteoarthritis. These results depend on the ability of the KineSpring to rotate, lengthen, and shorten to accommodate knee motions, and in response to knee position and loading. Purpose: The present study was undertaken to determine length changes of the implanted KineSpring in response to a range of knee positions, external knee loads, and placements by different orthopedic surgeons. Materials and methods: KineSpring system components were implanted in ten cadaver leg specimens by ten orthopedic surgeons, and absorber-length changes were measured under combined loading and in different positions of the knee. Results and conclusion: Spring compression consistent with knee-load reduction, and device lengthening and shortening to accommodate knee loads and motions were seen. These confirm the functionality of the KineSpring when implanted medially to the knee. Keywords: KineSpring, knee, function, preservation, offloading, osteoarthritis

Anton G Clifford,1 Stefan M Gabriel,1 Mary O’Connell,1 David Lowe,1 Larry E Miller,2,3 Jon E Block31Moximed, Inc, Hayward, CA, USA; 2Miller Scientific Consulting, Inc, Arden, NC, USA; 3The Jon Block Group, San Francisco, CA, USAAbstract: Symptomatic medial compartment knee osteoarthritis (OA) is the leading cause of musculoskeletal pain and disability in adults. Therapies intended to unload the medial knee compartment have yielded unsatisfactory results due to low patient compliance with conservative treatments and high complication rates with surgical options. There is no widely available joint-unloading treatment for medial knee OA that offers clinically important symptom alleviation, low complication risk, and high patient acceptance. The KineSpring® Knee Implant System (Moximed, Inc, Hayward, CA, USA) is a first-of-its-kind, implantable, extra-articular, extra-capsular prosthesis intended to alleviate knee OA-related symptoms by reducing medial knee compartment loading while overcoming the limitations of traditional joint-unloading therapies. Preclinical and clinical studies have demonstrated excellent prosthesis durability, substantial reductions in medial compartment and total joint loads, and clinically important improvements in OA-related pain and function. The purpose of this report is to describe the KineSpring System, including implant characteristics, principles of operation, indications for use, patient selection criteria, surgical technique, postoperative care, preclinical testing, and clinical experience. The KineSpring System has potential to bridge the gap between ineffective conservative treatments and irreversible surgical interventions for medial compartment knee OA.Keywords: KineSpring, knee, medial, osteoarthritis, prosthesis

Background: TBX3 is a T-box transcription factor repressor that is elevated in metastatic breast cancer and is believed to promote malignancy of tumor cells, possibly by promoting cell survival and epithelial-mesenchymal transition., Methods: The relative expression of TBX3 was assessed in the 21T cell lines which were derived from an individual patient and represent three distinct stages of breast cancer progression: 21PT, atypical ductal hyperplasia; 21NT, ductal carcinoma in situ; and 21MT-1, invasive mammary carcinoma. Two different isoforms of TBX3 (TBX3iso1 and TBX3iso2) were overexpressed to evaluate cell survival/colony forming ability, growth, and invasion in the ductal carcinoma in situ-like 21NT cell line using an in vitro Matrigel model of cancer progression. In addition, TBX3 expression was knocked down to evaluate the effects of downregulating TBX3 on the invasive mammary carcinoma-like 21MT-1 cell line. Finally, PCR array profiling was used to assess alterations in gene expression due to TBX3 overexpression in the 21NT cells., Results: TBX3 is abundant in the invasive 21MT-1 cell line, while being minimally expressed in the non-invasive 21NT and 21PT cell lines. Overexpression of either TBX3iso1 or TBX3iso2 in 21NT cells resulted in increased cell survival/colony forming ability, growth vs. apoptosis and invasion in Matrigel. In contrast, short hairpin RNA-mediated knockdown of TBX3 in the 21MT-1 cells resulted in smaller colonies, with a more regular, less dispersed (less infiltrative) morphology. Array profiling of the 21NT TBX3 iso1 and iso2 transfectants showed that there are common alterations in expression of several genes involved in signal transduction, cell cycle control/cell survival, epithelial-mesenchymal transition and invasiveness., Conclusions: Overall, these results indicate that TBX3 (isoform 1 or 2) expression can promote progression in a model of early breast cancer by altering cell properties involved in cell survival/colony formation and invasiveness, as well as key regulatory and EMT/invasiveness-related gene expressions.

Medial knee osteoarthritis (OA) is a common disorder often associated with pathologic joint loading. Insoles, braces, and high tibial osteotomy are OA treatments aimed at reducing medial joint loads, but their use and effectiveness are limited. The KineSpring System implant also intends to reduce knee loads in OA patients while overcoming those limitations. The current study was undertaken to test the implant's effect on loads at the knee. Six cadaver knees with Outerbridge Grade I-II medial OA were subjected to simulated gait using a kinematic test system. Knees were tested with and without the medial knee implant while thin film sensors measured medial and lateral femorotibial contact pressures. Significant medial compartment load reductions (134 ± 53 N [P = .002]) were found throughout the stance phase of gait in the treated knee. Significant total joint load decreases (91 ± 40 N [P = .002]) were also observed without substantial changes in lateral compartment loads. These significant reductions of medial and total intra-articular loads are also within clinically effective ranges of other unloading systems. This suggests that the KineSpring System could be a viable treatment for medial knee OA.

Objective: The clinical results after stenting in the coronary and peripheral circulations are vastly different. Possible explanations for this discrepancy include generally longer and more complex lesions in the periphery, variable vascular responses to injury according to anatomic location, disparate blood flow rates, and impedance in coronary vs skeletal smooth muscle beds, or phenotypic differences in neointimal hyperplasia and remodeling. This study examined the long-term results (6 months) after implantation of phosphorylcholine-coated balloon-expandable stents in a porcine model of experimental in-stent coronary and peripheral arterial restenosis., Methods: Forty-eight stainless steel-tantalum-stainless steel composite balloon-expandable stents coated with phosphorylcholine (TriMaxx stent, Abbott Laboratories, Abbott Park, Ill) were implanted in the coronary (3.0 x 15 mm) or larger femoral arteries (4.0 x 38 mm) of Yorkshire crossbred swine to achieve a 1.1:1 stent-to-artery ratio. After 28, 90, or 180 days, the arteries were excised, perfusion-fixed at 100 mm Hg, sectioned, and stained with hematoxylin and eosin for morphometric evaluation., Results: One animal did not survive to euthanasia; all arteries in surviving animals were patent. No significant differences were found in mean injury or inflammation scores among the groups or time points. The larger femoral arteries generated more neointimal area over time than the coronary arteries. The neointimal area in coronary arteries was 2.76 +/- 0.71, 1.75 +/- 0.42, and 1.83 +/- 0.19 mm(2) at 28, 90, and 180 days, respectively, and 5.20 +/- 0.97, 3.11 +/- 0.53, and 5.10 +/- 0.80 mm(2) in the femoral arteries (P < .05 coronary vs femoral at 180 days). This led to statistically significantly increased percent area stenosis at 180 days (coronary 27% +/- 4% vs femoral 45% +/- 5%; P < .05)., Conclusions: The vascular response to balloon-expandable stenting in the coronary and peripheral circulations is different. After 6 months, neointimal hyperplasia and stent-induced stenosis were increased in peripheral porcine arteries compared with coronary arteries.