Effect of Tissue Processing on Clinical Outcomes of Primary ACL Reconstuction Using Allograft (SS-04)

Abstract

IntroductionConcerns with viral and bacterial disease transmission associated with allogenic tissue use have resulted in many tissue banks sterilizing allografts with gamma irradiation. The clinical implication of low-dose irradiation on primary allograft anterior cruciate ligament (ACL) reconstructions remains poorly understood. It is also unclear if other tissue-processing techniques affect the clinical outcome of ACL reconstructions using allograft.MethodsA computerized search of multiple electronic databases was conducted for both prospective and retrospective studies involving primary allograft ACL reconstructions between January 1980 and May 2012. Inclusion criteria were English-language publications with a minimum of two-year follow-up. Studies were excluded if they involved revision surgery, multiple ligament procedures, meniscal allograft or non-human graft use, skeletally immature patients, grafts treated with ethylene oxide or irradiation greater than 2.5 Mrad, or if the tissue processing methods were not specified. Tissue processing methods such as low-dose irradiation use (less than 2.5 Mrad), as well as preservation by fresh-frozen, freeze-dried, or cryopreserved techniques were identified within each study. Clinical outcomes were evaluated using the KT-1000 arthrometer score, Lachman test, Pivot Shift test, and the International Knee Documentation Committee (IKDC) score. Two sets of statistical analyses were performed. First, meta-analyzed irradiated allograft data was compared against meta-analyzed non-irradiated data. Second, statistical comparisons were performed between meta-analyzed data from fresh-frozen versus freeze-dried versus cryopreserved allograft. Sub-analyses were then performed to examine the effect of preservation method within the irradiated and non-irradiated data, and the effect of irradiation within each preservation technique. All the analyses were conducted using R (version 2.15) software. The metafor package (Wolfang Viechtbauer [2010]) in R was used for meta-analysis.ResultsThirty-three publications met the inclusion and exclusion criteria, involving a total of 1,948 patients, with 297 irradiated and 1,651 non-irradiated allografts. Non-irradiated allografts had a higher percentage of grade A and B IKDC outcomes (85.8% vs. 79.3%, p=0.0070), grade 1 and 2 KT-1000 (96.4% vs. 79.1%, p<0.0001), grade 0 and 1 Pivot Shift (98.6% vs. 94.0%, p=0.0037), and grade 0 and 1 Lachman (95.9% vs. 83.8%, p<0.0001) than irradiated grafts. With regards to preservation techniques, there were no statistically significant differences except for a higher percentage of IKDC grade A and B outcomes with cryopreserved allografts compared to fresh-frozen allografts (92.1% vs. 85.6%, p=0.0467). Within the non-irradiated group, there were no statistically significant differences between the three preservation techniques. There were insufficient numbers to analyze for differences within the irradiated group. Within the fresh-frozen preservation group, non-irradiated allografts had a higher percentage of grade 1 and 2 KT-1000 (96.1% vs. 78.0%, p<0.0001), grade 0 and 1 Pivot Shift (98.6% vs. 91.1%, p<0.0001), and grade 0 and 1 Lachman (95.5% vs. 78.0%, p<0.0001) than those treated with irradiation. There were insufficient numbers for comparison within the cryopreserved and freeze-dried groups.ConclusionThese results suggest that primary ACL reconstructions using non-irradiated allografts provide superior clinical outcomes than low-dose (less than 2.5 Mrad) irradiated grafts. Within the non-irradiated allografts, there were no differences in clinical outcomes based on graft preservation using fresh-frozen, cryopreserved, or freeze-dried techniques. IntroductionConcerns with viral and bacterial disease transmission associated with allogenic tissue use have resulted in many tissue banks sterilizing allografts with gamma irradiation. The clinical implication of low-dose irradiation on primary allograft anterior cruciate ligament (ACL) reconstructions remains poorly understood. It is also unclear if other tissue-processing techniques affect the clinical outcome of ACL reconstructions using allograft. Concerns with viral and bacterial disease transmission associated with allogenic tissue use have resulted in many tissue banks sterilizing allografts with gamma irradiation. The clinical implication of low-dose irradiation on primary allograft anterior cruciate ligament (ACL) reconstructions remains poorly understood. It is also unclear if other tissue-processing techniques affect the clinical outcome of ACL reconstructions using allograft. MethodsA computerized search of multiple electronic databases was conducted for both prospective and retrospective studies involving primary allograft ACL reconstructions between January 1980 and May 2012. Inclusion criteria were English-language publications with a minimum of two-year follow-up. Studies were excluded if they involved revision surgery, multiple ligament procedures, meniscal allograft or non-human graft use, skeletally immature patients, grafts treated with ethylene oxide or irradiation greater than 2.5 Mrad, or if the tissue processing methods were not specified. Tissue processing methods such as low-dose irradiation use (less than 2.5 Mrad), as well as preservation by fresh-frozen, freeze-dried, or cryopreserved techniques were identified within each study. Clinical outcomes were evaluated using the KT-1000 arthrometer score, Lachman test, Pivot Shift test, and the International Knee Documentation Committee (IKDC) score. Two sets of statistical analyses were performed. First, meta-analyzed irradiated allograft data was compared against meta-analyzed non-irradiated data. Second, statistical comparisons were performed between meta-analyzed data from fresh-frozen versus freeze-dried versus cryopreserved allograft. Sub-analyses were then performed to examine the effect of preservation method within the irradiated and non-irradiated data, and the effect of irradiation within each preservation technique. All the analyses were conducted using R (version 2.15) software. The metafor package (Wolfang Viechtbauer [2010]) in R was used for meta-analysis. A computerized search of multiple electronic databases was conducted for both prospective and retrospective studies involving primary allograft ACL reconstructions between January 1980 and May 2012. Inclusion criteria were English-language publications with a minimum of two-year follow-up. Studies were excluded if they involved revision surgery, multiple ligament procedures, meniscal allograft or non-human graft use, skeletally immature patients, grafts treated with ethylene oxide or irradiation greater than 2.5 Mrad, or if the tissue processing methods were not specified. Tissue processing methods such as low-dose irradiation use (less than 2.5 Mrad), as well as preservation by fresh-frozen, freeze-dried, or cryopreserved techniques were identified within each study. Clinical outcomes were evaluated using the KT-1000 arthrometer score, Lachman test, Pivot Shift test, and the International Knee Documentation Committee (IKDC) score. Two sets of statistical analyses were performed. First, meta-analyzed irradiated allograft data was compared against meta-analyzed non-irradiated data. Second, statistical comparisons were performed between meta-analyzed data from fresh-frozen versus freeze-dried versus cryopreserved allograft. Sub-analyses were then performed to examine the effect of preservation method within the irradiated and non-irradiated data, and the effect of irradiation within each preservation technique. All the analyses were conducted using R (version 2.15) software. The metafor package (Wolfang Viechtbauer [2010]) in R was used for meta-analysis. ResultsThirty-three publications met the inclusion and exclusion criteria, involving a total of 1,948 patients, with 297 irradiated and 1,651 non-irradiated allografts. Non-irradiated allografts had a higher percentage of grade A and B IKDC outcomes (85.8% vs. 79.3%, p=0.0070), grade 1 and 2 KT-1000 (96.4% vs. 79.1%, p<0.0001), grade 0 and 1 Pivot Shift (98.6% vs. 94.0%, p=0.0037), and grade 0 and 1 Lachman (95.9% vs. 83.8%, p<0.0001) than irradiated grafts. With regards to preservation techniques, there were no statistically significant differences except for a higher percentage of IKDC grade A and B outcomes with cryopreserved allografts compared to fresh-frozen allografts (92.1% vs. 85.6%, p=0.0467). Within the non-irradiated group, there were no statistically significant differences between the three preservation techniques. There were insufficient numbers to analyze for differences within the irradiated group. Within the fresh-frozen preservation group, non-irradiated allografts had a higher percentage of grade 1 and 2 KT-1000 (96.1% vs. 78.0%, p<0.0001), grade 0 and 1 Pivot Shift (98.6% vs. 91.1%, p<0.0001), and grade 0 and 1 Lachman (95.5% vs. 78.0%, p<0.0001) than those treated with irradiation. There were insufficient numbers for comparison within the cryopreserved and freeze-dried groups. Thirty-three publications met the inclusion and exclusion criteria, involving a total of 1,948 patients, with 297 irradiated and 1,651 non-irradiated allografts. Non-irradiated allografts had a higher percentage of grade A and B IKDC outcomes (85.8% vs. 79.3%, p=0.0070), grade 1 and 2 KT-1000 (96.4% vs. 79.1%, p<0.0001), grade 0 and 1 Pivot Shift (98.6% vs. 94.0%, p=0.0037), and grade 0 and 1 Lachman (95.9% vs. 83.8%, p<0.0001) than irradiated grafts. With regards to preservation techniques, there were no statistically significant differences except for a higher percentage of IKDC grade A and B outcomes with cryopreserved allografts compared to fresh-frozen allografts (92.1% vs. 85.6%, p=0.0467). Within the non-irradiated group, there were no statistically significant differences between the three preservation techniques. There were insufficient numbers to analyze for differences within the irradiated group. Within the fresh-frozen preservation group, non-irradiated allografts had a higher percentage of grade 1 and 2 KT-1000 (96.1% vs. 78.0%, p<0.0001), grade 0 and 1 Pivot Shift (98.6% vs. 91.1%, p<0.0001), and grade 0 and 1 Lachman (95.5% vs. 78.0%, p<0.0001) than those treated with irradiation. There were insufficient numbers for comparison within the cryopreserved and freeze-dried groups. ConclusionThese results suggest that primary ACL reconstructions using non-irradiated allografts provide superior clinical outcomes than low-dose (less than 2.5 Mrad) irradiated grafts. Within the non-irradiated allografts, there were no differences in clinical outcomes based on graft preservation using fresh-frozen, cryopreserved, or freeze-dried techniques. These results suggest that primary ACL reconstructions using non-irradiated allografts provide superior clinical outcomes than low-dose (less than 2.5 Mrad) irradiated grafts. Within the non-irradiated allografts, there were no differences in clinical outcomes based on graft preservation using fresh-frozen, cryopreserved, or freeze-dried techniques.