Aims. It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. Materials and Methods. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium. RNA sequencing analysis was performed using sorted CD31. hi. EMCN. hi. endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. Results. Flow cytometry revealed that anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. Conclusion. VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31. hi. EMCN. hi. endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108–114

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors.

Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Cite this article: Bone Joint J 2014;96-B:1319–24.

Abstract. Introduction. Knee dislocations (KDs) are complex injuries which are often associated with damage to surrounding soft tissues or neurovascular structures. A classification system for these injuries should be simple and reproducible and allow communication among surgeons for surgical planning and outcome prediction. The aim of this study was to formulate a list of factors, prioritised by high-volume knee surgeons, that should be included in a KD classification system. Methods. A global panel of orthopaedic knee surgery specialists participated in a Delphi process. A list of factors to be included in a KD classification system was formulated by 91 orthopaedic surgeons, which was subsequently prioritised by 27 experts from 6 countries. The items were analysed to find factors that had at least 70% consensus for inclusion in a classification system. Results. The four factors that reached consensus agreement and thus deemed critical for inclusion in a classification system were vascular injuries (89%), common peroneal nerve injuries (78%), number of torn ligaments (78%), and open injuries (70%). Conclusion. The wide geographic distribution of participants provides diverse insight and makes the results of the study globally applicable. The most important factors to include in a classification system as determined by the Delphi technique were vascular injuries, common peroneal nerve injuries, number of torn ligaments, and open injuries. The Schenck anatomic classification system most accurately identifies these patient variables with the addition of open injuries. The authors propose to update the Schenck classification system with the inclusion of open injuries as an additional modifier

Abstract. Background. Fracture dislocation of the knee involves disruption of knee ligaments with associated tibial plateau fracture. If these injuries are not evaluated swiftly, can result in a limb-threatening injury. The aim of this study is to look at the clinical outcomes of a single surgeon case series at a major trauma centre. Methods. Prospectively collected data was analysed for a 5-year period. Primary outcome measures used were International Knee Documented Committee (IKDC) score and Knee Injury & Osteoarthritis Outcome Score (KOOS). The secondary outcome measures include Tegner activity scale, knee range of movements and complications. Results. 32 patients were presented with the mean age was 34 years (range 17–74). 14% of patients sustained vascular injury and 19% had common peroneal nerve injury. Priority was given for early total repair/reconstruction with fracture fixation within three weeks where feasible (90% of patients), and if not, a staged approach was adopted. The mean IKDC score was 67 (35–100) & KOOS was 74 (40–100). The mean preoperative Tegner Activity Scale was 6.5 whereas post-operative Tegner Activity Scale was 3.6 The mean flexion achieved postoperative was 115 (90–130). The two common patterns of injuries seen were Anterio-medial rim fractures (52%) with avulsion injuries of posterio-lateral corner structures and posteriomedial plateau fractures with ACL avulsion injuries. The first pattern was commonly associated with vascular and common peroneal nerve injury (90% of patients). Conclusion. To our knowledge, this is the first kind of study to report some fracture patterns that can be associated with particular ligamentous injuries

Abstract. The radiographic or bony landmark techniques are the two most common methods to determine Medial patellofemoral ligament (MPFL) femoral tunnel placement. Their intra/inter-observer reliability is widely debated. The palpation technique relies on identifying the medial epicondyle (ME) and adductor Tubercle (AT). The central longitudinal artery and associated vessels (CLV) are consistently seen in the surgical dissection during MPFL reconstruction. The aim of this study was to investigate the anatomic relationship of CLV to ME-AT and thereby use CLV as an important vascular landmark during MPFL reconstruction. A retrospective review of MRI scans in skeletally mature patients presenting to a tertiary referral knee clinic was undertaken. Group-N consisted of any presentation without patellofemoral instability or malalignment (PFI). Group-P with PFI. MRI's were reviewed and measured by two Consultant Radiologists for the CLV-ME-AT anatomy and relationship. Following exclusions 50 patients were identified in each group. The CLV passed anterior to the AT and ME in all patients. ME morphology did not differ greatly between the groups except in the tubercle height, where there was a statically but not clinically significant difference (larger in the non-PFI group, 2.95mm vs 2.52mm, p=0.002). The CLV to ME Tip distance was consistent between the groups (Group PFI group 3.8mm & ‘normal’ non-PFI Group 3.9mm). The CLV-ME-AT relationship remained consistent despite patients presenting pathology. The CLV consistently courses anterior to ME and AT. The CLV could be used as a vascular landmark assisting femoral tunnel placement during MPFL reconstruction

Abstract. Introduction. Traumatic knee dislocations are devastating injuries and there is no single best accepted treatment. This study looked at functional outcome of a single surgeon case series of patients who underwent surgical management of their knee dislocation. Methods. Eighty-seven patients with knee dislocation were treated at a major trauma centre. Acute surgical repair and reconstruction with fracture fixation within 4 weeks was preferred unless the patient was too unstable (Injury severity score>16). The collaterals were repaired and augmented using a variety of autografts, allografts or synthetic grafts. PCL was primarily braced and reconstructed subsequently, if required. Outcome was collected prospectively using IKDC score, KOOS and Tegner score. Results. The mean age of the patients was 33.6yrs (SD 11.9), 66 males and 21 females. According to Schenck classification, 26 were KD-I (30%), 6 KD-II (7%), 13 were KD-III (15%), 7 were KD-IV (8%) and 35 were KD-V (40%). 7 patients had CPN injury (8%), 3 had vascular injury (3.4%), 2 had combined CPN and vascular injury (2.3%). Acute surgical treatment was done in 62 patients while 10 had staged reconstruction. 22 patients had delayed reconstruction. The mean follow-up period was 5.8 years (1- 12 yrs), mean IKDC score was 57.6 (SD 23.6). The mean Tegner activity scale postoperatively was 4.5(SD 2) and the mean KOOS score was 74.9 (SD 19.6). Conclusion. A large proportion of cases were KD-V but still had a good outcome with surgical management. Current classification systems do not cover all dislocation patterns and a modification is proposed

Introduction. In the setting of periprosthetic joint infection, the complete removal of implants and cement can be challenging with well-fixed, cemented implants about the knee. This can get especially complex in the setting of long cemented femoral stems. Osteotomies are well described in the proximal femur and tibia for removal of implants and cement. There is little information available on distal femoral osteotomies to facilitate knee implant and retained cement removal. Methods. We describe a novel anterolateral oblique distal femoral osteotomy for the removal of well-fixed, cemented components during resection knee arthroplasty that preserves vascularity to the osteotomized segment. Cadaveric anatomic vascular injection studies were performed to document vascularity of the osteotomized segment. Clinical examples, and results will be presented. Results. Anatomic vascular studies documented preserved vascularity to the osteotomized segment. In two patients intramedullary infected implant and cement was completely removed. At reimplantation and final followup the osteotomy was radiographically healed, implants well fixed, and no recurrent infections were noted. Conclusions. This osteotomy appears to be useful when removing well fixed, cemented femoral components during periprosthetic infection. Vascularity and union was preserved and obtained in all patients. For figures, tables, or references, please contact authors directly

We have investigated iatrogenic popliteal artery injuries (PAI) during non arthroplasty knee surgery regarding mechanism of injury, treatment and outcomes, and to identify successful strategies when injury occurs. In all, 21 iatrogenic popliteal artery injuries in 21 patients during knee surgery other than knee arthroplasty were identified from the Swedish Vascular Registry (Swedvasc) between 1987 and 2011. Prospective registry data were supplemented with case-records, including long-term follow-up. In total, 13 patients suffered PAI during elective surgery and eight during urgent surgery such as fracture fixation or tumour resection. Nine injuries were detected intra-operatively, five within 12 to 48 hours and seven > 48 hours post-operatively (two days to 23 years). There were 19 open vascular and two endovascular surgical repairs. Two patients died within six months of surgery. One patient required amputation. Only six patients had a complete recovery of whom had the vascular injury detected at time of injury and repaired by a vascular surgeon. Patients sustaining vascular injury during elective procedures are more likely to litigate (p = 0.029). We conclude that outcomes are poorer when there is a delay of diagnosis and treatment, and that orthopaedic surgeons should develop strategies to detect PAI early and ensure rapid access to vascular surgical support. Cite this article: Bone Joint J 2015;97-B:192–6

Aims. Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm. 2. , 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. Results. ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells’ capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion. ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis. Cite this article: Bone Joint Res 2020;9(8):457–467

Introduction. Poor osseointegration of cementless implants is the leading clinical cause of implant loosening, subsidence, and replacement failure, which require costly and technically challenging revision surgery. The mechanism of osseointegration requires further elucidation. We have recently developed a novel titanium implant for the mouse tibia that maintains in vivo knee joint function and allows us to study osseointegration in an intra-articular, load-bearing environment. Vascular endothelial growth factor (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. It also plays critical roles in skeletal development and bone repair and regeneration. A specialized subset of vascular endothelium, CD31. hi. EMCN. hi. cells displaying high cell surface expression of CD31 and Endomucin, has been reported to promote osteoblast maturation and may be responsible for bone formation during development and fracture healing. Because of their potential role in osseointegration, the aim of this study was to use our mouse implant model to investigate the role of VEGF and CD31. hi. EMCN. hi. endothelium in osseointegration. Methods. Under an IACUC-approved protocol, the implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (N = 38). The mice were then randomized into 2 groups: Control group (N=19) and Anti-VEGFR group (N=19). A cocktail of VEGFR-1 antibody (25mg/kg) and VEGFR-2 antibody (25mg/kg) was given to the mice in the Anti-VEGFR group by intraperitoneal injection every third day starting immediately after surgery until euthanasia. An equivalent amount of an isotype control antibody was given to the control group. Flow cytometric (N = 4/group) and immunofluorescencent (N = 3/group) analyses were performed at 2 weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium in the peri-implant bone. Pull-out testing was used at 4 weeks post-implantation to determine the strength of the bone-implant interface. Results. Flow cytometry revealed that Anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium percentage in the peri-implant bone vs. control (p = 0.039) at 2 weeks post-implantation (Fig. 1). This was confirmed by the decrease of CD31 and EMCN double positive cells detected with immunofluorescence at the same time point (Fig. 2). More importantly, anti-VEGFR treatment decreased the maximum load of pullout testing compared with control (p = 0.042) (Fig. 3). Conclusion. VEGF is a key mediator of osseointegration and the development of CD31. hi. EMCN. hi. endothelium. This may provide a new drug target for the enhancement of osseointegration. We have also developed a system to run flow cytometric analysis and perform fluorescent staining on the limited tissue around the implant in this mouse model. This will be a powerful platform for future mechanistic studies on osseointegration. For any figures or tables, please contact authors directly

Popliteal artery injury (PAI) is a feared complication during knee replacement. Our aim was to investigate those injuries that occurred in association with knee replacement in terms of the type of injury, treatment and outcomes. From our national vascular registry (Swedvasc) and the Swedish Patient Insurance databases a total of 32 cases were identified. Prospective data from the registries was supplemented with case-records, including long-term follow-up. We estimated the incidence during 1998 to 2010 to be 0.017%. In our series of 32 patients with PAI occurring between 1987 and 2011, 25 (78%) were due to penetrating trauma and seven were caused by blunt trauma. The patients presented in three ways: bleeding (14), ischaemia (7) and false aneurysm formation (11), and five occurred during revision surgery. A total of 12 injuries were detected intra-operatively, eight within 24 hours (3 to 24) and 12 at more than 24 hours post-operatively (2 to 90 days). Treatment comprised open surgery in 28 patients. Patency of the vascular repair at 30 days was 97% (31 of 32, one amputation). At the time of follow-up (median 546 days, mean 677 days (24 to 1251)), 25 patients had residual symptoms. Of seven patients with a complete recovery, six had had an early diagnosis of the PAI during the procedure, and were treated by a vascular surgeon in the same hospital. PAI is a rare adverse event during knee replacement surgery. The outcome following such events is often adversely affected by diagnostic and therapeutic delay. Bleeding and false aneurysm were the most common clinical presentations. Cite this article: Bone Joint J 2013;95-B:1645–9

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This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.

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To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration.

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Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

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The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

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Tibial tubercle osteotomy (TTO) facilitates surgical exposure and protects the extensor mechanism during revision total knee arthroplasty (rTKA). The purpose of this study was to determine the rates of bony union, complications, and reoperations following TTO during rTKA, to assess the functional outcomes of rTKA with TTO at two years’ minimum follow-up, and to identify the risk factors of failure.

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To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Purpose. To study the initial presentation and subsequent investigation and management of acute knee dislocations at a regional trauma centre. Introduction. Knee dislocation requires high energy trauma, and often affects young working adults. The high incidence of associated arterial, neurological, ligamentous, and other soft tissue injuries, can produce potentially devastating outcomes. Rapid mobilisation of traditionally distinct surgical teams, with urgent vascular imaging and emergency surgery are often necessary. The extent and severity of ligamentous damage may require multiple operations to repair. Methods. A retrospective nine-year study of knee dislocations managed in the Trauma and Orthopaedic Department of the Royal Hospitals, Belfast was performed using a Fractures Outcomes Research Database (FORD), a chart review, and a review of relevant radiology. Demographic data, mechanisms of injury, associated neurovascular injuries, ligamentous damage, and operative intervention were recorded. Results. 15 patients were identified over 9 years (2000-2008 inclusive). Mean age at injury was 38 years, median 37. 14 (93%) of patients were male, 1 (7%) was female. 6 injuries (40%) were sport-related, 3 (20%) occurred as a result of road traffic collisions, 5 (33%) were accidents in the workplace, and 1 (7%) was a result of a fall while intoxicated with alcohol. 5 (33%) patients experienced a common peroneal nerve palsy. 10 (67%) received vascular imaging, and 2 (13%) underwent vascular surgery as part of the initial theatre episode. All 15 dislocations led to some degree of structural soft tissue knee injuries. These included 12 (80%) anterior cruciate ligaments, 8 (53%) posterior cruciate ligaments, 7 (47%) lateral collateral ligaments, and 5 (33%) medial collateral ligaments. 3 posterolateral corner injuries required repair. Of the 15 patients, 2 (13%) underwent no operative procedures following closed reduction, and the remaining 13 patients had 21 distinct theatre episodes recorded between them. 2 fasciotomies for compartment syndrome, and 2 common peroneal nerve decompression/explorations were performed in the initial theatre episode. 3 patients (20%) were managed with an external fixator initially. 1 patient (7%) developed complications and required trans-femoral amputation. Conclusions. Knee dislocation remains uncommon, and even major centres may receive only a few injuries per year. Orthopaedic, Vascular and Plastic surgeons, as well as Emergency Physicians and Radiologists must remain vigilant to the challenge which this injury can present, and the opportunity for excellent outcomes through a coordinated approach with close communication, awareness of injury patterns, and availability of theatre and imaging resources

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Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

Introduction. Active robotics for total knee Arthroplasty (TKA) uses a CAD-CAM approach to plan the correct size and placement of implants and to surgically achieve planned limb alignment. The TSolution One Total Knee Application (THINK Surgical Inc., Fremont, CA) is an open-implant platform, CT-based active robotic surgical system. A multi-center, prospective, non-randomized clinical trial was performed to evaluate the safety and effectiveness of robotic-assisted TKA using the TSolution One Total Knee Application. This report details the findings from the IDE. Methods. Inclusion criteria for patients receiving robotic TKA were: primary unilateral TKA; Kellgren-Lawrence OA grade 3 or 4; BMI < 40 kg/m2; coronal plane deformity < 20° varus; sagittal flexion contracture < 15°. In addition to monitoring all adverse events (AE), a pre-defined list of relevant major AEs were specifically identified to evaluate safety (Healy et al, 2013): medial collateral ligament injury; extensor mechanism disruption; neural deficit; periprosthetic fracture; patellofemoral dislocation; tibiofemoral dislocation; and vascular injury. Bleeding complications were also assessed. Malalignment rate, defined as the percentage of patients with more than a ± 3° difference in varus-valgus alignment from the preoperative plan, was used to determine accuracy of the active robotic system. Knee Society Scores (KSS) and Short Form 12 (SF-12) Health Surveys were assessed as clinical outcome measures. For each outcome, results were compared to published values associated with manual TKA. Results. A total of 115 patients were enrolled at 6 US centers and followed for a maximum of 12 months after surgery. Mean surgical time (incision to close) improved consistently as the technique evolved (first 10 cases = 131.5 min, first 20 cases = 122.4 min), with mean robot time = 45.8 min. The incidence of pre-defined AEs identified was 0%, serving as a measure of safety of the procedure. Outside of the pre-defined list, only one AE was definitely associated with the use of the device; a metal pin was left inside the knee joint but no reoperation was performed. No patients required a blood transfusion. Alignment outside of the ± 3° goal was 11.2% with a difference of 0.5° ± 1.9° (mean ± STD), which represents a 45% statistically significant (posterior probability > 0.95) reduction in malalignment compared to the literature (Mason et al, 2007). Mean KSS Functional scores improved from 40.5 at baseline to 65.3 at 3 months, mean KSS Objective scores improved from 36.8 to 81.0, mean KSS Patient Satisfaction scores improved from 14.4 to 30.6, and mean SF-12 Physical Component scores improved from 32.9 to 43.5. Discussion. The TSolution One Total Knee Application is descended from an active robotic system used in >8000 cases outside the United States since 2002. This trial represents the first US based study of this technology for primary TKA. The clinical study demonstrated positive safety outcomes as none of the seven pre-defined AEs were observed and there were no cases requiring transfusion. A positive effectiveness outcome was also demonstrated as the malalignment rate found in this study showed a substantial reduction from the 32% malalignment rate published in the literature for conventional instruments. KSS and SF-12 scores were comparable to other published TKA series. For figures, tables, or references, please contact authors directly