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Early radiological results after total knee arthroplasty using patient-specific instruments and implants (iTotal™)
S518
Abstracts / Osteoarthritis and Cartilage 24 (2016) S63eS534
894 EFFECT OF TOURNIQUET USE ON BLOOD LOSS AND POST-OPERATIVE FUNCTION IN TOTAL KNEE ARTHROPLASTY C. Yan, P. Chan, C. Fu, K. Chiu. The Univ. of Hong Kong, Hong Kong, Hong Kong Purpose: The effectiveness of tourniquet in total knee arthroplasty in reducing blood loss and their influence on the postoperative course remain unclear. We performed a prospective randomized controlled trial to clarify its effect. Methods: 24 patients undergoing total knee arthroplasty were randomly allocated to 3 groups regarding the application of tourniquet: from skin to cement hardening, only during cementation and from skin to skin. Post-operative lower limb mechanical axis and individual component position were measured on radiographs. Blood loss and changes serological indicators of soft tissue damage were monitored peri-operatively. Thigh pain, knee pain, limb swelling, and rehabilitation progress were also recorded. Results: The mean age of the patients was 72 ± 7.5 years. There was no difference in terms of patients’ pre-operative demographic data between 3 groups. The mean tourniquet time in 3 groups was 34 ± 6.6, 8.5 ± 0.7 and 65.8 ± 25.8 minutes respectively (p ¼ 0.014). There was no significant difference in intra-operative blood loss, drain output, change in haemoglobin & haematocrit, thigh & knee pain, thigh & leg swelling, change in CRP & LDH between 3 groups. The only difference was found in post-operative increase in creatine kinase on day 1 and day 2. There was also no difference in terms of the lower limb mechanical axis and individual components position on post-operative radiographs. In terms of early complication, there was 1 case of transient common peroneal nerve palsy in skin to cement group and 1 case of transient deranged liver function in skin to skin group. Conclusions: Early results did not show any significant difference in majority of the parameters between different tourniquet application methods. 895 EARLY RADIOLOGICAL RESULTS AFTER TOTAL KNEE ARTHROPLASTY USING PATIENT-SPECIFIC INSTRUMENTS AND IMPLANTS (ITOTAL™) A.F. Steinert y, Y. Kamawal y, J. Arnholdt y, B. Holzapfel y, A. Ripp z, M. Rudert y. y Julius-Maximilians-Univ. Würzburg, Würzburg, Germany; z Elbandklinik Radebeul, Radebeul, Germany Purpose: Numerous studies using historic TKA implants suggest up to 18% of primary TKA patients are not satisfied. (Bourne, Chesworth, Davis, Mahomed, & Charron, 2010) The patient-specific cruciate retaining knee replacement system iTotal™ utilizes custom-made implants and instruments and represents a novel technique for the treatment of patients with gonarthrosis in the medial and lateral compartment. The current retrospective radiological analysis was designed to determine in an initial series whether treatment with iTotal™ would correct the hip-knee-ankle angle (HKA) toward an ideal alignment of 180 and to see the impact on the patella height. Methods: Long-leg X-Ray analysis of the knee was performed pre- and post- operatively in 133 patients (73 females, 60 males) in two centers receiving a patient-specific total knee arthroplasty using the iTotal™ technology (ConforMIS Inc.) for gonarthrosis in the medial and lateral compartment. Additionally to HKA, the zone of the mechanical axis (ZMA; zone of the tibial base plate where the mechanical axis of the limb intersects with the tibial base plate) was analysed, with the ideal intersection being located centrally. The patellar height was measured, by means of two ratios, on the pre- and post-operative lateral radiographs of the patients, using the Insall-Salvati and the modified InsallSalvati ratio. Results: The average HKA changed from 174.5 ± 4.9 preoperatively to 178.9 ± 2.1 postoperatively. The rate of ±3 and ±5 HKA outliers changed from 75.9% and 60.9% preoperatively, to 16.5% and 3% postoperatively, respectively. With respect to the ZMA, the course of mechanical axis corrected from 26.3% within the central third of the knee preoperatively, to 89.4% postoperatively. Patella height measured with Insall-Salvati ratio and modified Insall-Salvati ratio changed from 0,99 and 0,75 preoperatively to 0,98 and 0,76 postoperatively. There were no intra-operative complications with the use of iTotal™. Conclusions: The use of the patient-specific iTotal™ total knee replacement system was able to correct the mechanical axis towards
neutral alignment in the majority of the patients undergoing BKA. The patella height was not affected after the operation. Further clinical follow-up studies are necessary to determine the long-term impact of these findings.
Therapy- Intraarticular 896 INTRAARTICULAR INJECTION OF LIPID NANOPARTICLE-SIRNA, A NOVEL CARTILAGE DELIVERY SYSTEM TO ATTENUATE CARTILAGE DEGENERATION IN RAT ANTERIOR CRUCIATE LIGAMENT TRANSECTION OSTEOARTHRITIS MODEL S. Wang y, X. Wei z, Y. Chang z, J. Zhou y, C. Chen y, Y. Zhang y, L. Wei y. y Brown Univ., Providence, RI, USA; z The Second Hosp., Shanxi Med. Univ., Taiyuan, China Purpose: Osteoarthritis (OA) is a degenerative disease of the articular joints characterized by slow but progressive loss of cartilage. Our previous study showed that conditional deletion of Indian Hedgehog (Ihh) in chondrocytes attenuates OA progression, suggesting the possibility that blocking Ihh signaling can be used as a therapeutic approach to prevent or delay cartilage degeneration. However, Ihh gene deletion is currently not a therapeutic option as it is lethal in animals. RNA interference (RNAi) provides a means to knockdown Ihh without the severe side effects caused by chemical inhibitors. However, cartilage siRNA delivery is not available because the cartilage is avascular and very dense tissue. Thus, development of a specific delivery system for RNAibased therapies that addresses this issue is highly desirable. Recently, we modified an attractive ionizable cationic lipid nanoparticle (LNP) that showed an exciting and promising silencing effect in vitro. The objective of this study is to determine whether the LNP-siRNA delivery system can be used to knock down Ihh in vivo and attenuate surgery induced OA model as a specific therapy for cartilage diseases. Methods: In vitro, transfection efficiency of siRNA or beacon delivered by LNPs was evaluated by fluorescence or confocal microscope using cultured chicken chondrocytes or pig cartilage. In vivo, LNP beacon/IhhsiRNA complexes were injected into the mouse/rat right knee joints, and the left knee joints were injected with free beacon/Ihh-siRNA without LNP as control. The beacan/siRNA positive signals in the mice and rats were evaluated by fluorescence molecular tomography (FMT) in vivo and confocal microscope after sacrifice. Total mRNA was isolated fron rats knee cartilage 7 day after injection and quantitative polymerase chain reaction (qPCR) was performed to assess the Ihh gene and downstream related genes. In vivo effects of LNP Ihh-siRNA complexes on cartilage degeneration were evaluated in rat surgery induced anterior cruciate ligament transection (ACLT) OA models. Male rats (N ¼ 120) were randomized into four treatments: (a) Sham surgery þ Ihh-siRNA (0.2 nmol), (b) ACLT þ LNP Ihh-siRNA (0.2 nmol), (c) ACLT þ LNP Ihh-siRNA (0.4 nmol) or (d) ACLT þ Ihh siRNA (0.2 nmol). Intraarticular injections were given weekly for 8 weeks. The animals were sacrificed at 9 weeks after surgery. OA-related gene expression was quantified by qPCR. The extent of OA progression was graded by Osteoarthritis Research Society International Osteoarthritis Cartilage Histopathology Assessment System (OOCHAS) scores. Results: In the cell culture, almost 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group; whereas no chondrocyte was transfected in the free-siRNA group (Fig1A) and 3D image shows all the transfected siRNA were located in the cytoplasm (Fig1B). In accordance with cell culture, red fluorescence, a positive signal for beacan/siRNA determined by confocal microscopy could be detected in the cartilage organ culture (Fig1C). In vivo study shows fluorescence from LNP-beacon injected joint could be detected by FMT (Fig2A) and confocal microscope at 680 nm (Fig2B). Real-time qPCR results showed Ihh mRNA level decreased by more than 40% after 7 days of LNP IhhsiRNA treatment, and type II collagen mRNA level was enhanced, while MMP-13, type X collagen and runx2 mRNA levels were depressed (Fig3C). In the rat model of ACLT OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression (Fig3AB). The mRNA levels of type II collagen and aggrecan were increased in the ACLTþLNP Ihh-siRNA (0.2 nmol) group and ACLTþ LNP Ihh-siRNA (0.4 nmol) group compared with the ACLT þ Ihh-siRNA (0.2 nmol) group, suggesting the positive impact of LNP-Ihh siRNA on anabolic metabolism and the reliability of LNP in vivo delivery. In contrast, MMP-3,-13, Runx2 and type X collagen showed the opposite pattern (Fig3C).
Abstracts / Osteoarthritis and Cartilage 24 (2016) S63eS534
894 EFFECT OF TOURNIQUET USE ON BLOOD LOSS AND POST-OPERATIVE FUNCTION IN TOTAL KNEE ARTHROPLASTY C. Yan, P. Chan, C. Fu, K. Chiu. The Univ. of Hong Kong, Hong Kong, Hong Kong Purpose: The effectiveness of tourniquet in total knee arthroplasty in reducing blood loss and their influence on the postoperative course remain unclear. We performed a prospective randomized controlled trial to clarify its effect. Methods: 24 patients undergoing total knee arthroplasty were randomly allocated to 3 groups regarding the application of tourniquet: from skin to cement hardening, only during cementation and from skin to skin. Post-operative lower limb mechanical axis and individual component position were measured on radiographs. Blood loss and changes serological indicators of soft tissue damage were monitored peri-operatively. Thigh pain, knee pain, limb swelling, and rehabilitation progress were also recorded. Results: The mean age of the patients was 72 ± 7.5 years. There was no difference in terms of patients’ pre-operative demographic data between 3 groups. The mean tourniquet time in 3 groups was 34 ± 6.6, 8.5 ± 0.7 and 65.8 ± 25.8 minutes respectively (p ¼ 0.014). There was no significant difference in intra-operative blood loss, drain output, change in haemoglobin & haematocrit, thigh & knee pain, thigh & leg swelling, change in CRP & LDH between 3 groups. The only difference was found in post-operative increase in creatine kinase on day 1 and day 2. There was also no difference in terms of the lower limb mechanical axis and individual components position on post-operative radiographs. In terms of early complication, there was 1 case of transient common peroneal nerve palsy in skin to cement group and 1 case of transient deranged liver function in skin to skin group. Conclusions: Early results did not show any significant difference in majority of the parameters between different tourniquet application methods. 895 EARLY RADIOLOGICAL RESULTS AFTER TOTAL KNEE ARTHROPLASTY USING PATIENT-SPECIFIC INSTRUMENTS AND IMPLANTS (ITOTAL™) A.F. Steinert y, Y. Kamawal y, J. Arnholdt y, B. Holzapfel y, A. Ripp z, M. Rudert y. y Julius-Maximilians-Univ. Würzburg, Würzburg, Germany; z Elbandklinik Radebeul, Radebeul, Germany Purpose: Numerous studies using historic TKA implants suggest up to 18% of primary TKA patients are not satisfied. (Bourne, Chesworth, Davis, Mahomed, & Charron, 2010) The patient-specific cruciate retaining knee replacement system iTotal™ utilizes custom-made implants and instruments and represents a novel technique for the treatment of patients with gonarthrosis in the medial and lateral compartment. The current retrospective radiological analysis was designed to determine in an initial series whether treatment with iTotal™ would correct the hip-knee-ankle angle (HKA) toward an ideal alignment of 180 and to see the impact on the patella height. Methods: Long-leg X-Ray analysis of the knee was performed pre- and post- operatively in 133 patients (73 females, 60 males) in two centers receiving a patient-specific total knee arthroplasty using the iTotal™ technology (ConforMIS Inc.) for gonarthrosis in the medial and lateral compartment. Additionally to HKA, the zone of the mechanical axis (ZMA; zone of the tibial base plate where the mechanical axis of the limb intersects with the tibial base plate) was analysed, with the ideal intersection being located centrally. The patellar height was measured, by means of two ratios, on the pre- and post-operative lateral radiographs of the patients, using the Insall-Salvati and the modified InsallSalvati ratio. Results: The average HKA changed from 174.5 ± 4.9 preoperatively to 178.9 ± 2.1 postoperatively. The rate of ±3 and ±5 HKA outliers changed from 75.9% and 60.9% preoperatively, to 16.5% and 3% postoperatively, respectively. With respect to the ZMA, the course of mechanical axis corrected from 26.3% within the central third of the knee preoperatively, to 89.4% postoperatively. Patella height measured with Insall-Salvati ratio and modified Insall-Salvati ratio changed from 0,99 and 0,75 preoperatively to 0,98 and 0,76 postoperatively. There were no intra-operative complications with the use of iTotal™. Conclusions: The use of the patient-specific iTotal™ total knee replacement system was able to correct the mechanical axis towards
neutral alignment in the majority of the patients undergoing BKA. The patella height was not affected after the operation. Further clinical follow-up studies are necessary to determine the long-term impact of these findings.
Therapy- Intraarticular 896 INTRAARTICULAR INJECTION OF LIPID NANOPARTICLE-SIRNA, A NOVEL CARTILAGE DELIVERY SYSTEM TO ATTENUATE CARTILAGE DEGENERATION IN RAT ANTERIOR CRUCIATE LIGAMENT TRANSECTION OSTEOARTHRITIS MODEL S. Wang y, X. Wei z, Y. Chang z, J. Zhou y, C. Chen y, Y. Zhang y, L. Wei y. y Brown Univ., Providence, RI, USA; z The Second Hosp., Shanxi Med. Univ., Taiyuan, China Purpose: Osteoarthritis (OA) is a degenerative disease of the articular joints characterized by slow but progressive loss of cartilage. Our previous study showed that conditional deletion of Indian Hedgehog (Ihh) in chondrocytes attenuates OA progression, suggesting the possibility that blocking Ihh signaling can be used as a therapeutic approach to prevent or delay cartilage degeneration. However, Ihh gene deletion is currently not a therapeutic option as it is lethal in animals. RNA interference (RNAi) provides a means to knockdown Ihh without the severe side effects caused by chemical inhibitors. However, cartilage siRNA delivery is not available because the cartilage is avascular and very dense tissue. Thus, development of a specific delivery system for RNAibased therapies that addresses this issue is highly desirable. Recently, we modified an attractive ionizable cationic lipid nanoparticle (LNP) that showed an exciting and promising silencing effect in vitro. The objective of this study is to determine whether the LNP-siRNA delivery system can be used to knock down Ihh in vivo and attenuate surgery induced OA model as a specific therapy for cartilage diseases. Methods: In vitro, transfection efficiency of siRNA or beacon delivered by LNPs was evaluated by fluorescence or confocal microscope using cultured chicken chondrocytes or pig cartilage. In vivo, LNP beacon/IhhsiRNA complexes were injected into the mouse/rat right knee joints, and the left knee joints were injected with free beacon/Ihh-siRNA without LNP as control. The beacan/siRNA positive signals in the mice and rats were evaluated by fluorescence molecular tomography (FMT) in vivo and confocal microscope after sacrifice. Total mRNA was isolated fron rats knee cartilage 7 day after injection and quantitative polymerase chain reaction (qPCR) was performed to assess the Ihh gene and downstream related genes. In vivo effects of LNP Ihh-siRNA complexes on cartilage degeneration were evaluated in rat surgery induced anterior cruciate ligament transection (ACLT) OA models. Male rats (N ¼ 120) were randomized into four treatments: (a) Sham surgery þ Ihh-siRNA (0.2 nmol), (b) ACLT þ LNP Ihh-siRNA (0.2 nmol), (c) ACLT þ LNP Ihh-siRNA (0.4 nmol) or (d) ACLT þ Ihh siRNA (0.2 nmol). Intraarticular injections were given weekly for 8 weeks. The animals were sacrificed at 9 weeks after surgery. OA-related gene expression was quantified by qPCR. The extent of OA progression was graded by Osteoarthritis Research Society International Osteoarthritis Cartilage Histopathology Assessment System (OOCHAS) scores. Results: In the cell culture, almost 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group; whereas no chondrocyte was transfected in the free-siRNA group (Fig1A) and 3D image shows all the transfected siRNA were located in the cytoplasm (Fig1B). In accordance with cell culture, red fluorescence, a positive signal for beacan/siRNA determined by confocal microscopy could be detected in the cartilage organ culture (Fig1C). In vivo study shows fluorescence from LNP-beacon injected joint could be detected by FMT (Fig2A) and confocal microscope at 680 nm (Fig2B). Real-time qPCR results showed Ihh mRNA level decreased by more than 40% after 7 days of LNP IhhsiRNA treatment, and type II collagen mRNA level was enhanced, while MMP-13, type X collagen and runx2 mRNA levels were depressed (Fig3C). In the rat model of ACLT OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression (Fig3AB). The mRNA levels of type II collagen and aggrecan were increased in the ACLTþLNP Ihh-siRNA (0.2 nmol) group and ACLTþ LNP Ihh-siRNA (0.4 nmol) group compared with the ACLT þ Ihh-siRNA (0.2 nmol) group, suggesting the positive impact of LNP-Ihh siRNA on anabolic metabolism and the reliability of LNP in vivo delivery. In contrast, MMP-3,-13, Runx2 and type X collagen showed the opposite pattern (Fig3C).