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Interim PET provides limited prognostic value for diffuse large B-cell lymphoma
Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.
“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).
Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.
Patients underwent six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 100 mg/m2 for 5 days) every 14 days, followed by two cycles of rituximab.
Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.
“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.
The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.
“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).
Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.
Patients underwent six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 100 mg/m2 for 5 days) every 14 days, followed by two cycles of rituximab.
Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.
“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.
The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.
“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).
Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.
Patients underwent six cycles of R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 100 mg/m2 for 5 days) every 14 days, followed by two cycles of rituximab.
Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.
“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.
The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: After two cycles of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL), positive results from PET signaled worse 2-year event-free survival (EFS) than negative interim PET results, but overall survival was not significantly different.
Major finding: After two cycles of chemotherapy, 2-year EFS for PET-positive, compared with PET-negative patients was 48.2% vs. 74.2% (P = .004). Overall survival was 87.7% vs. 90.6% (P = .6).
Data source: The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).
Disclosures: The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.
Enoxaparin and Warfarin for Venous Thromboembolism Prophylaxis in Total Hip Arthroplasty: To Bridge or Not to Bridge?
According to the literature, the rate of deep venous thrombosis after total hip arthroplasty (THA) can be high (45%-63%) without prophylactic anticoagulation.1-6 A meta-analysis of 13 studies found a rate of 51%.7 As lower extremity deep venous thrombi are the initial source of symptomatic pulmonary emboli in about 90% of cases,8 THA patients are usually given medication postoperatively focused on prevention of these thromboembolic events.9 Chemoprophylaxis may involve warfarin, enoxaparin, or their combination in an anticoagulation bridge. Enoxaparin is one of many low-molecular-weight heparins (LMWHs). All LMWHs exert their anticoagulant effect by binding to antithrombin III.10 The binding of LMWH to antithrombin III catalyzes the inhibition of factor Xa by antithrombin III, disrupting clot formation.11
In its hydroquinone form, vitamin K is essential as a cofactor for carboxylation of the glutamic acid residues of the amino-terminals of the coagulation proteins II, VII, IX, and X, leading to their activation. Anticoagulation by warfarin is achieved by the inhibition of the reductase enzymes that produce vitamin K hydroquinone in the liver from vitamin K epoxide.12 This inhibition prevents activation of the clotting proteins.12,13 Prophylaxis with enoxaparin or warfarin can reduce the rate of venous thromboembolic disease to 3.6% and 3.7%, respectively.2 However, these medications inhibit the clotting cascade, and their use risks prolonging the healing process.9 The delay increases the risk for wound infection,14 which can lead to a longer hospital stay and therefore higher costs.
We conducted a study to compare patients who received warfarin only with patients who received warfarin bridged with enoxaparin as antithrombotic chemoprophylaxis after THA. Outcomes of interest were number of days until a dry wound was observed and length of hospital stay. We hypothesized that, compared with warfarin-only therapy, bridged therapy would increase the risk for prolonged wound healing and result in longer hospital stays.
Materials and Methods
At our 746-bed academic medical center, 121 THAs were performed between January 1, 2008 and December 31, 2009. This study was approved by the center’s Office for Human Subjects Protections institutional review board (IRB). The research involved collecting or studying existing data, documents, and records recorded anonymously by the investigator in such a manner that subjects could not be identified, directly or through identifiers linked to the subjects, and therefore patient consent was not needed. Therefore, the IRB waived the need for consent. Relevant data included in this study were extracted from patient medical records, given within 35 days of surgery. For each patient, discharge notes provided data on the hospital course, and nurses’ notes provided data on wound status after THA.
Propensity Score Matching
For accurate analysis, it was important to consider confounding factors in both patient groups. Some covariates that may influence accurate analysis are age,15 diabetes,16 sex,15,17 hypertension,18 and body mass index.15,19Propensity score, defined as the conditional probability of receiving treatment, given the observed background covariates, was initially defined by Rosenbaum20 and Rubin.21 The motivation behind propensity scores can be understood by considering an idealized situation in which the 2 groups are similar on all background characteristics. In nonexperimental studies, researchers aim to find for each treated individual a comparison individual who looks exactly the same as the treated individual with respect to observed pretreatment covariates. Thus, assuming no hidden bias, any difference in outcomes within these pairs can be attributed to the variable of interest and not to any other differences between the treated and comparison individuals. Our study is a typical nonexperimental retrospective study in which the 2 groups being compared are patients receiving warfarin only or warfarin bridged with enoxaparin. To minimize the influence of background covariates, we used matching procedures and present our results both with and without the use of matching techniques.
Data and Results
There are different matching algorithms aimed at matching groups. In our study, the optimal matching procedure alone could not produce adequately matched data, so we used both optimal matching20 and genetic matching.22,23 Genetic matching procedure with replacement22 can produce well-matched data—it matched each patient in the warfarin-only group with a patient in the bridged-therapy group and allowed different patients to be matched with 1 similar patient in the control group. However, as the same patients in the bridged-therapy group might be matched multiple times, it would complicate the after-matching analysis. We therefore used a 2-step matching procedure to obtain well-matched data, and a simplified analysis procedure after matching. In the first step, we implemented genetic matching with replacement, as introduced by Abadie and Imbens,22 to match each warfarin-only patient with 1 bridged-therapy patient. In the second step, we applied optimal matching to the 2 groups. This 2-step matching turned out to produce better matched pairs, as denoted by Rubin.21 Both matching steps were implemented using the MatchIt function in R.24
The balance of matching is checked using criteria suggested by Rubin21: (1) standardized difference of means of propensity score, (2) ratio of variances in propensity score in treated and control groups, and (3) for each covariate, ratio of variance in residuals orthogonal to propensity score in treated and control groups.
Table 1 lists the means of the background covariates for each group before and after matching. Table 2 lists the balance check results suggested by Rubin.21 After matching, all standardized differences of means are smaller than 0.25, and the variance ratios are between 0.5 and 2, which are the standards suggested21 for regression adjustment to be valid after matching.
After genetic matching, 31 bridged-therapy patients and 57 warfarin-only patients remained. After optimal matching, there were 31 patients in each group. Poisson regressions of datasets before and after matching adjustment were fitted.
Results
Wounds of bridged-therapy patients took longer to heal than wounds of warfarin-only patients both before (odds ratio, 2.16; P < .05) and after matching data (odds ratio, 2.39; P < .05) with respect to confounding factors. In addition, bridged-therapy patients had longer hospital stays both before (odds ratio 1.20; P < .05) and after matching data (odds ratio, 1.27; P < .05) with respect to confounding factors. Figures 1 and 2 are histograms displaying the 2 groups and their outcomes.
Discussion
For patients undergoing THA procedures, several important considerations should be taken into account. Colwell and colleagues2 showed that, compared with warfarin, enoxaparin offered a 0.1% higher rate of protection against venous thromboembolic disease after THA. However, patients given enoxaparin may face increased risks.25 Hallevi and colleagues26 demonstrated that, compared with warfarin, enoxaparin bridging increased the risk for serious bleeding in patients with cardioembolic stroke. In our review of the literature, we learned that the benefits of bridge therapy in thromboembolic disease have yet to be investigated in THA.
At our academic hospital, the extra costs associated with bridge therapy can be as much as about $200027 per day per patient. These costs can go much higher, depending on type of patient and types of resources used. Over the 2-year period covered by our study, the costs of using enoxaparin amounted to about $151,200 ($2000 × 1.2 days per patient). If bridging offers no significant protection against thromboembolic disease, then it would be more cost-effective to use a single anticoagulant, particularly enoxaparin, for high-risk patients.
There are significant risk factors associated with prolonged healing of surgical wounds. Protocols outlining these factors may help reduce costs. In addition, when deciding on the use of aggressive anticoagulation therapy, surgeons must consider the risks for prolonged leakage and infection in addition to the risk for thromboembolic disease. Protocols may aid in this process as well. Our study results showed that, compared with warfarin-only therapy, bridged therapy (enoxaparin and warfarin) was associated with longer hospital stays. Further research should examine whether there are advantages that justify the higher risks of delayed wound healing and subsequent infection. Improving our understanding of risk factors associated with anticoagulation therapy will make orthopedic surgery safer for patients.
1. Bergqvist D, Benoni G, Björgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335(10):696-700.
2. Colwell CW Jr, Collis DK, Paulson R, et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am. 1999;81(7):932-940.
3. Haake DA, Berkman SA. Venous thromboembolic disease after hip surgery. Risk factors, prophylaxis, and diagnosis. Clin Orthop Relat Res. 1989;(242):212-231.
4. Johnson R, Carmichael JH, Almond HG, Loynes RP. Deep venous thrombosis following Charnley arthroplasty. Clin Orthop Relat Res. 1978;(132):24-30.
5. Stamatakis JD, Kakkar VV, Sagar S, Lawrence D, Nairn D, Bentley PG. Femoral vein thrombosis and total hip replacement. Br Med J. 1977;2(6081):223-225.
6. Turpie AG, Levine MN, Hirsh J, et al. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315(15):925-929.
7. Clagett GP, Anderson FA Jr, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest. 1995;108(4 suppl):312S-334S.
8. Westrich GH, Sánchez PM. Prevention and treatment of thromboembolic disease: an overview. Instr Course Lect. 2002;51:471-480.
9. Colwell CW Jr, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535.
10. Fareed J, Jeske W, Hoppensteadt D, Clarizio R, Walenga JM. Low-molecular-weight heparins: pharmacologic profile and product differentiation. Am J Cardiol. 1998;82(5B):3L-10L.
11. Gerlach AT, Pickworth KK, Seth SK, Tanna SB, Barnes JF. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy. 2000;20(7):771-775.
12. Kamali F, Wood P, Ward A. Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety. Ann Hematol. 2009;88(2):141-149.
13. Choonara IA, Malia RG, Haynes BP, et al. The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin. Br J Clin Pharmacol. 1988;25(1):1-7.
14. Saleh K, Olson M, Resig S, et al. Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program. J Orthop Res. 2002;20(3):506-515.
15. Ridgeway S, Wilson J, Charlet A, Kafatos G, Pearson A, Coello R. Infection of the surgical site after arthroplasty of the hip. J Bone Joint Surg Br. 2005;87(6):844-850.
16. Lai K, Bohm ER, Burnell C, Hedden DR. Presence of medical comorbidities in patients with infected primary hip or knee arthroplasties. J Arthroplasty. 2007;22(5):651-656.
17. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee arthroplasty in the United States. J Arthroplasty. 2008;23(7):984-991.
18. Ahmed AA, Mooar PA, Kleiner M, Torg JS, Miyamoto CT. Hypertensive patients show delayed wound healing following total hip arthroplasty. PLoS One. 2011;6(8):e23224.
19. Lübbeke A, Stern R, Garavaglia G, Zurcher L, Hoffmeyer P. Differences in outcomes of obese women and men undergoing primary total hip arthroplasty. Arthritis Rheum. 2007;57(2):327-334.
20. Rosenbaum PR. A characterization of optimal designs for observational studies. J R Stat Soc Ser B. 1991;53(3):597-610.
21. Rubin DB. Using propensity scores to help design observational studies: application to the tobacco litigation. Health Serv Outcomes Res Methodol. 2001;2(1):169-188.
22. Abadie A, Imbens GW. Simple and Bias-Corrected Matching Estimators for Average Treatment Effects. Berkeley, CA: Department of Economics, University of California; 2002.
23. Diamond A, Sekhon J. Genetic matching for estimating causal effects: a new method of achieving balance in observational studies. Paper presented at: Annual Meeting of the Midwest Political Science Association; April 2005; Chicago, IL.
24. Imai K, King G, Lau O. logit: logistic regression for dichotomous dependent variables. In: Imai K, King G, Lau O. Zelig: Everyone’s Statistical Software. 2011; 238-244. http://gking.harvard.edu/zelig. Accessed May 26, 2015.
25. Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007;89(1):33-38.
26. Hallevi H, Albright KC, Martin-Schild S, et al. Anticoagulation after cardioembolic stroke: to bridge or not to bridge? Arch Neurol. 2008;65(9):1169-1173.
27. Henry J. Kaiser Family Foundation. Hospital adjusted expenses per inpatient day [2010]. http://kff.org/other/state-indicator/expenses-per-inpatient-day/#table. Accessed May 26, 2015.
According to the literature, the rate of deep venous thrombosis after total hip arthroplasty (THA) can be high (45%-63%) without prophylactic anticoagulation.1-6 A meta-analysis of 13 studies found a rate of 51%.7 As lower extremity deep venous thrombi are the initial source of symptomatic pulmonary emboli in about 90% of cases,8 THA patients are usually given medication postoperatively focused on prevention of these thromboembolic events.9 Chemoprophylaxis may involve warfarin, enoxaparin, or their combination in an anticoagulation bridge. Enoxaparin is one of many low-molecular-weight heparins (LMWHs). All LMWHs exert their anticoagulant effect by binding to antithrombin III.10 The binding of LMWH to antithrombin III catalyzes the inhibition of factor Xa by antithrombin III, disrupting clot formation.11
In its hydroquinone form, vitamin K is essential as a cofactor for carboxylation of the glutamic acid residues of the amino-terminals of the coagulation proteins II, VII, IX, and X, leading to their activation. Anticoagulation by warfarin is achieved by the inhibition of the reductase enzymes that produce vitamin K hydroquinone in the liver from vitamin K epoxide.12 This inhibition prevents activation of the clotting proteins.12,13 Prophylaxis with enoxaparin or warfarin can reduce the rate of venous thromboembolic disease to 3.6% and 3.7%, respectively.2 However, these medications inhibit the clotting cascade, and their use risks prolonging the healing process.9 The delay increases the risk for wound infection,14 which can lead to a longer hospital stay and therefore higher costs.
We conducted a study to compare patients who received warfarin only with patients who received warfarin bridged with enoxaparin as antithrombotic chemoprophylaxis after THA. Outcomes of interest were number of days until a dry wound was observed and length of hospital stay. We hypothesized that, compared with warfarin-only therapy, bridged therapy would increase the risk for prolonged wound healing and result in longer hospital stays.
Materials and Methods
At our 746-bed academic medical center, 121 THAs were performed between January 1, 2008 and December 31, 2009. This study was approved by the center’s Office for Human Subjects Protections institutional review board (IRB). The research involved collecting or studying existing data, documents, and records recorded anonymously by the investigator in such a manner that subjects could not be identified, directly or through identifiers linked to the subjects, and therefore patient consent was not needed. Therefore, the IRB waived the need for consent. Relevant data included in this study were extracted from patient medical records, given within 35 days of surgery. For each patient, discharge notes provided data on the hospital course, and nurses’ notes provided data on wound status after THA.
Propensity Score Matching
For accurate analysis, it was important to consider confounding factors in both patient groups. Some covariates that may influence accurate analysis are age,15 diabetes,16 sex,15,17 hypertension,18 and body mass index.15,19Propensity score, defined as the conditional probability of receiving treatment, given the observed background covariates, was initially defined by Rosenbaum20 and Rubin.21 The motivation behind propensity scores can be understood by considering an idealized situation in which the 2 groups are similar on all background characteristics. In nonexperimental studies, researchers aim to find for each treated individual a comparison individual who looks exactly the same as the treated individual with respect to observed pretreatment covariates. Thus, assuming no hidden bias, any difference in outcomes within these pairs can be attributed to the variable of interest and not to any other differences between the treated and comparison individuals. Our study is a typical nonexperimental retrospective study in which the 2 groups being compared are patients receiving warfarin only or warfarin bridged with enoxaparin. To minimize the influence of background covariates, we used matching procedures and present our results both with and without the use of matching techniques.
Data and Results
There are different matching algorithms aimed at matching groups. In our study, the optimal matching procedure alone could not produce adequately matched data, so we used both optimal matching20 and genetic matching.22,23 Genetic matching procedure with replacement22 can produce well-matched data—it matched each patient in the warfarin-only group with a patient in the bridged-therapy group and allowed different patients to be matched with 1 similar patient in the control group. However, as the same patients in the bridged-therapy group might be matched multiple times, it would complicate the after-matching analysis. We therefore used a 2-step matching procedure to obtain well-matched data, and a simplified analysis procedure after matching. In the first step, we implemented genetic matching with replacement, as introduced by Abadie and Imbens,22 to match each warfarin-only patient with 1 bridged-therapy patient. In the second step, we applied optimal matching to the 2 groups. This 2-step matching turned out to produce better matched pairs, as denoted by Rubin.21 Both matching steps were implemented using the MatchIt function in R.24
The balance of matching is checked using criteria suggested by Rubin21: (1) standardized difference of means of propensity score, (2) ratio of variances in propensity score in treated and control groups, and (3) for each covariate, ratio of variance in residuals orthogonal to propensity score in treated and control groups.
Table 1 lists the means of the background covariates for each group before and after matching. Table 2 lists the balance check results suggested by Rubin.21 After matching, all standardized differences of means are smaller than 0.25, and the variance ratios are between 0.5 and 2, which are the standards suggested21 for regression adjustment to be valid after matching.
After genetic matching, 31 bridged-therapy patients and 57 warfarin-only patients remained. After optimal matching, there were 31 patients in each group. Poisson regressions of datasets before and after matching adjustment were fitted.
Results
Wounds of bridged-therapy patients took longer to heal than wounds of warfarin-only patients both before (odds ratio, 2.16; P < .05) and after matching data (odds ratio, 2.39; P < .05) with respect to confounding factors. In addition, bridged-therapy patients had longer hospital stays both before (odds ratio 1.20; P < .05) and after matching data (odds ratio, 1.27; P < .05) with respect to confounding factors. Figures 1 and 2 are histograms displaying the 2 groups and their outcomes.
Discussion
For patients undergoing THA procedures, several important considerations should be taken into account. Colwell and colleagues2 showed that, compared with warfarin, enoxaparin offered a 0.1% higher rate of protection against venous thromboembolic disease after THA. However, patients given enoxaparin may face increased risks.25 Hallevi and colleagues26 demonstrated that, compared with warfarin, enoxaparin bridging increased the risk for serious bleeding in patients with cardioembolic stroke. In our review of the literature, we learned that the benefits of bridge therapy in thromboembolic disease have yet to be investigated in THA.
At our academic hospital, the extra costs associated with bridge therapy can be as much as about $200027 per day per patient. These costs can go much higher, depending on type of patient and types of resources used. Over the 2-year period covered by our study, the costs of using enoxaparin amounted to about $151,200 ($2000 × 1.2 days per patient). If bridging offers no significant protection against thromboembolic disease, then it would be more cost-effective to use a single anticoagulant, particularly enoxaparin, for high-risk patients.
There are significant risk factors associated with prolonged healing of surgical wounds. Protocols outlining these factors may help reduce costs. In addition, when deciding on the use of aggressive anticoagulation therapy, surgeons must consider the risks for prolonged leakage and infection in addition to the risk for thromboembolic disease. Protocols may aid in this process as well. Our study results showed that, compared with warfarin-only therapy, bridged therapy (enoxaparin and warfarin) was associated with longer hospital stays. Further research should examine whether there are advantages that justify the higher risks of delayed wound healing and subsequent infection. Improving our understanding of risk factors associated with anticoagulation therapy will make orthopedic surgery safer for patients.
According to the literature, the rate of deep venous thrombosis after total hip arthroplasty (THA) can be high (45%-63%) without prophylactic anticoagulation.1-6 A meta-analysis of 13 studies found a rate of 51%.7 As lower extremity deep venous thrombi are the initial source of symptomatic pulmonary emboli in about 90% of cases,8 THA patients are usually given medication postoperatively focused on prevention of these thromboembolic events.9 Chemoprophylaxis may involve warfarin, enoxaparin, or their combination in an anticoagulation bridge. Enoxaparin is one of many low-molecular-weight heparins (LMWHs). All LMWHs exert their anticoagulant effect by binding to antithrombin III.10 The binding of LMWH to antithrombin III catalyzes the inhibition of factor Xa by antithrombin III, disrupting clot formation.11
In its hydroquinone form, vitamin K is essential as a cofactor for carboxylation of the glutamic acid residues of the amino-terminals of the coagulation proteins II, VII, IX, and X, leading to their activation. Anticoagulation by warfarin is achieved by the inhibition of the reductase enzymes that produce vitamin K hydroquinone in the liver from vitamin K epoxide.12 This inhibition prevents activation of the clotting proteins.12,13 Prophylaxis with enoxaparin or warfarin can reduce the rate of venous thromboembolic disease to 3.6% and 3.7%, respectively.2 However, these medications inhibit the clotting cascade, and their use risks prolonging the healing process.9 The delay increases the risk for wound infection,14 which can lead to a longer hospital stay and therefore higher costs.
We conducted a study to compare patients who received warfarin only with patients who received warfarin bridged with enoxaparin as antithrombotic chemoprophylaxis after THA. Outcomes of interest were number of days until a dry wound was observed and length of hospital stay. We hypothesized that, compared with warfarin-only therapy, bridged therapy would increase the risk for prolonged wound healing and result in longer hospital stays.
Materials and Methods
At our 746-bed academic medical center, 121 THAs were performed between January 1, 2008 and December 31, 2009. This study was approved by the center’s Office for Human Subjects Protections institutional review board (IRB). The research involved collecting or studying existing data, documents, and records recorded anonymously by the investigator in such a manner that subjects could not be identified, directly or through identifiers linked to the subjects, and therefore patient consent was not needed. Therefore, the IRB waived the need for consent. Relevant data included in this study were extracted from patient medical records, given within 35 days of surgery. For each patient, discharge notes provided data on the hospital course, and nurses’ notes provided data on wound status after THA.
Propensity Score Matching
For accurate analysis, it was important to consider confounding factors in both patient groups. Some covariates that may influence accurate analysis are age,15 diabetes,16 sex,15,17 hypertension,18 and body mass index.15,19Propensity score, defined as the conditional probability of receiving treatment, given the observed background covariates, was initially defined by Rosenbaum20 and Rubin.21 The motivation behind propensity scores can be understood by considering an idealized situation in which the 2 groups are similar on all background characteristics. In nonexperimental studies, researchers aim to find for each treated individual a comparison individual who looks exactly the same as the treated individual with respect to observed pretreatment covariates. Thus, assuming no hidden bias, any difference in outcomes within these pairs can be attributed to the variable of interest and not to any other differences between the treated and comparison individuals. Our study is a typical nonexperimental retrospective study in which the 2 groups being compared are patients receiving warfarin only or warfarin bridged with enoxaparin. To minimize the influence of background covariates, we used matching procedures and present our results both with and without the use of matching techniques.
Data and Results
There are different matching algorithms aimed at matching groups. In our study, the optimal matching procedure alone could not produce adequately matched data, so we used both optimal matching20 and genetic matching.22,23 Genetic matching procedure with replacement22 can produce well-matched data—it matched each patient in the warfarin-only group with a patient in the bridged-therapy group and allowed different patients to be matched with 1 similar patient in the control group. However, as the same patients in the bridged-therapy group might be matched multiple times, it would complicate the after-matching analysis. We therefore used a 2-step matching procedure to obtain well-matched data, and a simplified analysis procedure after matching. In the first step, we implemented genetic matching with replacement, as introduced by Abadie and Imbens,22 to match each warfarin-only patient with 1 bridged-therapy patient. In the second step, we applied optimal matching to the 2 groups. This 2-step matching turned out to produce better matched pairs, as denoted by Rubin.21 Both matching steps were implemented using the MatchIt function in R.24
The balance of matching is checked using criteria suggested by Rubin21: (1) standardized difference of means of propensity score, (2) ratio of variances in propensity score in treated and control groups, and (3) for each covariate, ratio of variance in residuals orthogonal to propensity score in treated and control groups.
Table 1 lists the means of the background covariates for each group before and after matching. Table 2 lists the balance check results suggested by Rubin.21 After matching, all standardized differences of means are smaller than 0.25, and the variance ratios are between 0.5 and 2, which are the standards suggested21 for regression adjustment to be valid after matching.
After genetic matching, 31 bridged-therapy patients and 57 warfarin-only patients remained. After optimal matching, there were 31 patients in each group. Poisson regressions of datasets before and after matching adjustment were fitted.
Results
Wounds of bridged-therapy patients took longer to heal than wounds of warfarin-only patients both before (odds ratio, 2.16; P < .05) and after matching data (odds ratio, 2.39; P < .05) with respect to confounding factors. In addition, bridged-therapy patients had longer hospital stays both before (odds ratio 1.20; P < .05) and after matching data (odds ratio, 1.27; P < .05) with respect to confounding factors. Figures 1 and 2 are histograms displaying the 2 groups and their outcomes.
Discussion
For patients undergoing THA procedures, several important considerations should be taken into account. Colwell and colleagues2 showed that, compared with warfarin, enoxaparin offered a 0.1% higher rate of protection against venous thromboembolic disease after THA. However, patients given enoxaparin may face increased risks.25 Hallevi and colleagues26 demonstrated that, compared with warfarin, enoxaparin bridging increased the risk for serious bleeding in patients with cardioembolic stroke. In our review of the literature, we learned that the benefits of bridge therapy in thromboembolic disease have yet to be investigated in THA.
At our academic hospital, the extra costs associated with bridge therapy can be as much as about $200027 per day per patient. These costs can go much higher, depending on type of patient and types of resources used. Over the 2-year period covered by our study, the costs of using enoxaparin amounted to about $151,200 ($2000 × 1.2 days per patient). If bridging offers no significant protection against thromboembolic disease, then it would be more cost-effective to use a single anticoagulant, particularly enoxaparin, for high-risk patients.
There are significant risk factors associated with prolonged healing of surgical wounds. Protocols outlining these factors may help reduce costs. In addition, when deciding on the use of aggressive anticoagulation therapy, surgeons must consider the risks for prolonged leakage and infection in addition to the risk for thromboembolic disease. Protocols may aid in this process as well. Our study results showed that, compared with warfarin-only therapy, bridged therapy (enoxaparin and warfarin) was associated with longer hospital stays. Further research should examine whether there are advantages that justify the higher risks of delayed wound healing and subsequent infection. Improving our understanding of risk factors associated with anticoagulation therapy will make orthopedic surgery safer for patients.
1. Bergqvist D, Benoni G, Björgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335(10):696-700.
2. Colwell CW Jr, Collis DK, Paulson R, et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am. 1999;81(7):932-940.
3. Haake DA, Berkman SA. Venous thromboembolic disease after hip surgery. Risk factors, prophylaxis, and diagnosis. Clin Orthop Relat Res. 1989;(242):212-231.
4. Johnson R, Carmichael JH, Almond HG, Loynes RP. Deep venous thrombosis following Charnley arthroplasty. Clin Orthop Relat Res. 1978;(132):24-30.
5. Stamatakis JD, Kakkar VV, Sagar S, Lawrence D, Nairn D, Bentley PG. Femoral vein thrombosis and total hip replacement. Br Med J. 1977;2(6081):223-225.
6. Turpie AG, Levine MN, Hirsh J, et al. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315(15):925-929.
7. Clagett GP, Anderson FA Jr, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest. 1995;108(4 suppl):312S-334S.
8. Westrich GH, Sánchez PM. Prevention and treatment of thromboembolic disease: an overview. Instr Course Lect. 2002;51:471-480.
9. Colwell CW Jr, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535.
10. Fareed J, Jeske W, Hoppensteadt D, Clarizio R, Walenga JM. Low-molecular-weight heparins: pharmacologic profile and product differentiation. Am J Cardiol. 1998;82(5B):3L-10L.
11. Gerlach AT, Pickworth KK, Seth SK, Tanna SB, Barnes JF. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy. 2000;20(7):771-775.
12. Kamali F, Wood P, Ward A. Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety. Ann Hematol. 2009;88(2):141-149.
13. Choonara IA, Malia RG, Haynes BP, et al. The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin. Br J Clin Pharmacol. 1988;25(1):1-7.
14. Saleh K, Olson M, Resig S, et al. Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program. J Orthop Res. 2002;20(3):506-515.
15. Ridgeway S, Wilson J, Charlet A, Kafatos G, Pearson A, Coello R. Infection of the surgical site after arthroplasty of the hip. J Bone Joint Surg Br. 2005;87(6):844-850.
16. Lai K, Bohm ER, Burnell C, Hedden DR. Presence of medical comorbidities in patients with infected primary hip or knee arthroplasties. J Arthroplasty. 2007;22(5):651-656.
17. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee arthroplasty in the United States. J Arthroplasty. 2008;23(7):984-991.
18. Ahmed AA, Mooar PA, Kleiner M, Torg JS, Miyamoto CT. Hypertensive patients show delayed wound healing following total hip arthroplasty. PLoS One. 2011;6(8):e23224.
19. Lübbeke A, Stern R, Garavaglia G, Zurcher L, Hoffmeyer P. Differences in outcomes of obese women and men undergoing primary total hip arthroplasty. Arthritis Rheum. 2007;57(2):327-334.
20. Rosenbaum PR. A characterization of optimal designs for observational studies. J R Stat Soc Ser B. 1991;53(3):597-610.
21. Rubin DB. Using propensity scores to help design observational studies: application to the tobacco litigation. Health Serv Outcomes Res Methodol. 2001;2(1):169-188.
22. Abadie A, Imbens GW. Simple and Bias-Corrected Matching Estimators for Average Treatment Effects. Berkeley, CA: Department of Economics, University of California; 2002.
23. Diamond A, Sekhon J. Genetic matching for estimating causal effects: a new method of achieving balance in observational studies. Paper presented at: Annual Meeting of the Midwest Political Science Association; April 2005; Chicago, IL.
24. Imai K, King G, Lau O. logit: logistic regression for dichotomous dependent variables. In: Imai K, King G, Lau O. Zelig: Everyone’s Statistical Software. 2011; 238-244. http://gking.harvard.edu/zelig. Accessed May 26, 2015.
25. Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007;89(1):33-38.
26. Hallevi H, Albright KC, Martin-Schild S, et al. Anticoagulation after cardioembolic stroke: to bridge or not to bridge? Arch Neurol. 2008;65(9):1169-1173.
27. Henry J. Kaiser Family Foundation. Hospital adjusted expenses per inpatient day [2010]. http://kff.org/other/state-indicator/expenses-per-inpatient-day/#table. Accessed May 26, 2015.
1. Bergqvist D, Benoni G, Björgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335(10):696-700.
2. Colwell CW Jr, Collis DK, Paulson R, et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am. 1999;81(7):932-940.
3. Haake DA, Berkman SA. Venous thromboembolic disease after hip surgery. Risk factors, prophylaxis, and diagnosis. Clin Orthop Relat Res. 1989;(242):212-231.
4. Johnson R, Carmichael JH, Almond HG, Loynes RP. Deep venous thrombosis following Charnley arthroplasty. Clin Orthop Relat Res. 1978;(132):24-30.
5. Stamatakis JD, Kakkar VV, Sagar S, Lawrence D, Nairn D, Bentley PG. Femoral vein thrombosis and total hip replacement. Br Med J. 1977;2(6081):223-225.
6. Turpie AG, Levine MN, Hirsh J, et al. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315(15):925-929.
7. Clagett GP, Anderson FA Jr, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest. 1995;108(4 suppl):312S-334S.
8. Westrich GH, Sánchez PM. Prevention and treatment of thromboembolic disease: an overview. Instr Course Lect. 2002;51:471-480.
9. Colwell CW Jr, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535.
10. Fareed J, Jeske W, Hoppensteadt D, Clarizio R, Walenga JM. Low-molecular-weight heparins: pharmacologic profile and product differentiation. Am J Cardiol. 1998;82(5B):3L-10L.
11. Gerlach AT, Pickworth KK, Seth SK, Tanna SB, Barnes JF. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy. 2000;20(7):771-775.
12. Kamali F, Wood P, Ward A. Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety. Ann Hematol. 2009;88(2):141-149.
13. Choonara IA, Malia RG, Haynes BP, et al. The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin. Br J Clin Pharmacol. 1988;25(1):1-7.
14. Saleh K, Olson M, Resig S, et al. Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program. J Orthop Res. 2002;20(3):506-515.
15. Ridgeway S, Wilson J, Charlet A, Kafatos G, Pearson A, Coello R. Infection of the surgical site after arthroplasty of the hip. J Bone Joint Surg Br. 2005;87(6):844-850.
16. Lai K, Bohm ER, Burnell C, Hedden DR. Presence of medical comorbidities in patients with infected primary hip or knee arthroplasties. J Arthroplasty. 2007;22(5):651-656.
17. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee arthroplasty in the United States. J Arthroplasty. 2008;23(7):984-991.
18. Ahmed AA, Mooar PA, Kleiner M, Torg JS, Miyamoto CT. Hypertensive patients show delayed wound healing following total hip arthroplasty. PLoS One. 2011;6(8):e23224.
19. Lübbeke A, Stern R, Garavaglia G, Zurcher L, Hoffmeyer P. Differences in outcomes of obese women and men undergoing primary total hip arthroplasty. Arthritis Rheum. 2007;57(2):327-334.
20. Rosenbaum PR. A characterization of optimal designs for observational studies. J R Stat Soc Ser B. 1991;53(3):597-610.
21. Rubin DB. Using propensity scores to help design observational studies: application to the tobacco litigation. Health Serv Outcomes Res Methodol. 2001;2(1):169-188.
22. Abadie A, Imbens GW. Simple and Bias-Corrected Matching Estimators for Average Treatment Effects. Berkeley, CA: Department of Economics, University of California; 2002.
23. Diamond A, Sekhon J. Genetic matching for estimating causal effects: a new method of achieving balance in observational studies. Paper presented at: Annual Meeting of the Midwest Political Science Association; April 2005; Chicago, IL.
24. Imai K, King G, Lau O. logit: logistic regression for dichotomous dependent variables. In: Imai K, King G, Lau O. Zelig: Everyone’s Statistical Software. 2011; 238-244. http://gking.harvard.edu/zelig. Accessed May 26, 2015.
25. Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007;89(1):33-38.
26. Hallevi H, Albright KC, Martin-Schild S, et al. Anticoagulation after cardioembolic stroke: to bridge or not to bridge? Arch Neurol. 2008;65(9):1169-1173.
27. Henry J. Kaiser Family Foundation. Hospital adjusted expenses per inpatient day [2010]. http://kff.org/other/state-indicator/expenses-per-inpatient-day/#table. Accessed May 26, 2015.
Evaluation of 3 Fixation Devices for Tibial-Sided Anterior Cruciate Ligament Graft Backup Fixation
Restoration of stability with return to activity is generally expected after anterior cruciate ligament (ACL) reconstruction; long-term success rates range from 75% to 95%.1 However, graft failure occurs most frequently with soft-tissue grafts fixated only with interference screws.2,3 Fixation failure also occurs more frequently at the tibial site.2 This failure has been attributed to extensive graft slippage in cases of soft-tissue fixation with interference screws.2 Interference screw fixation alone, with a double-looped hamstring tendon graft, fails at 350 N in young human tibiae.4,5 However, failure is limited with use of a bone–tendon–bone graft or with backup fixation, particularly at the tibial site.3 The superiority of bicortical fixation has also been proven.5-7
In addition, as shown in a goat model, ACL graft fixation is a major cause of failure in the immediate postoperative period, before biological incorporation of the graft.8 Fixation techniques for soft-tissue grafts must withstand stresses during the healing period (grafts may take up to 12 weeks to incorporate).9 Failures may result from forces exerted on the graft—forces that may be as high as 450 to 700 N during daily activities.10,11 Within the tibial tunnel, various fixation devices are used, including interference screws, staples, pins, buttons, and interference screw/sheath constructs.12,13 Primary fixation is commonly achieved with interference screws because of their ease of insertion and greater stiffness. However, fixation of the soft-tissue graft is influenced by several variables, including bone density, insertion torque, thread geometry, and interference screw material.14-16 Many of these variables, which are a source of inconsistency and concern during the immediate postoperative period, have led surgeons to seek alternative methods of backup fixation at the tibial site. Nevertheless, good clinical and subjective results have been found after ACL reconstruction with a 4-stranded semitendinosus tendon at 10-year follow-up.17
An anchor used in rotator cuff repair is the SwiveLock system (Arthrex). Major advantages of this system include ease and speed of insertion, good strength, and reduced need for later hardware removal.
We conducted a study to biomechanically evaluate 3 methods of tibial-sided fixation for ACL reconstruction: fully threaded interference screw only, interference screw backed with 4.75-mm SwiveLock anchor, and fully threaded bio-interference screw backed with 4.5-mm bicortical screw. We hypothesized that a fully threaded bio-interference screw backed with a 4.75-mm SwiveLock anchor would provide mechanical strength no different from that provided by backup fixation with a bicortical post at the tibial site. We further hypothesized that SwiveLock backup fixation would provide more strength than fixation with bio-interference screw alone.
Materials and Methods
The design of this study was adapted from one used by Walsh and colleagues,3 who compared 3 fixation methods: retrograde interference screw, suture button, and combined fixation. Tibiae inspected before selection showed no signs of injury or abnormality. Bovine extensor tendons, which lacked any defects along their entire length, were stored in saline 0.9% solution. Both the tibiae and the extensor tendons were stored at –20°C before completion of the tibial-sided ACL reconstruction. Thirty fresh-frozen, skeletally mature porcine proximal tibiae were selected and thawed at 4°C before preparation. Specimens were prepared by potting the diaphysis in fiberglass resin, and a tunnel 9 mm in diameter was drilled through the anteromedial aspect of the tibia.
For consistency, one author (CAV) prepared all 30 specimens. Both tails of all 30 bovine extensor tendons were whip-stitched with No. 2 FiberLoop (Arthrex) 9 mm in diameter. Grafts and tibiae were randomly divided into 3 sample groups. The first group was prepared by antegrade graft fixation within the tibial tunnel using a fully threaded 9×28-mm BioComposite interference screw (Arthrex). The second and third groups used the same primary fixation within the tibial tunnel along with 2 types of secondary fixation. These backup fixation groups included a 4.5-mm titanium bicortical post (Arthrex) and a 4.75-mm BioComposite SwiveLock C anchor (Arthrex) (Figure 1). The FiberLoop at the ends of the distal graft tails for backup groups were fixated 1 cm distal to the tibial tunnel and tapped before insertion of backup devices (Figures 2A, 2B). Insertion was completed after 4.5-mm bicortical and 4.75-mm unicortical drilling and tapping of the anteromedial cortices for the titanium posts and SwiveLocks, respectively. The free ends of the whip-stitched No. 2 FiberLoop were tied to the proximal end of the titanium post with a single surgical knot followed by 5 square knots.3 The free ends of the No. 2 FiberLoop were inserted into the eyelet of the 4.75-mm SwiveLock and 1 cm directly inferior to the tibial tunnel. Interference fit of FiberLoop with SwiveLock was achieved within the corticocancellous bone of the tibiae. All samples retained a 30-mm tendon loop superior to the tibial plateau to simulate intra-articular ACL length. Specimens were then stored at –20°C and thawed at 4°C before biomechanical testing.
Each of the 30 tibiae was tested once. Each testing group consisted of 10 porcine tibiae. The tendons were kept moist during the entire testing procedure by spraying them thoroughly with saline 0.9% solution. Mechanical testing was performed with an Instron 8871 system with a 5-kN load cell secured to the crosshead. A fixed-angle aperture, attached to the testing surface, was adjusted so that the tendon would be pulled in line with the tibial tunnel. A hook fixture suspended from clevis and dowel was used to secure the tendon to the crosshead (Figure 3). A small preload of 5 N manually applied to each sample was followed by a precycling regimen of 10 cycles between 10 N and 50 N at 1 Hz. Precycling was performed to remove slack from the system. Mechanical testing consisted of 500 cycles between 50 N and 250 N at 1 Hz followed by pull to failure at 20 mm per minute. Load and displacement data were recorded at 500 Hz.
An a priori power analysis was not performed because 6 specimens per group in the study from which the testing protocol was adapted demonstrated sufficient power among 3 testing categories.3 In addition, other studies have demonstrated similar testing protocols using 10 specimens per testing group.7,12,13,18 The data for each sample were analyzed with OriginPro 8.0 software (OriginLab). Ultimate load, yield load, stiffness, and cyclic displacement of the 3 sample groups were compared with 1-way analysis of variance (α = 0.05). Holm-Sidak tests were used for post hoc analysis.19P < .05 was statistically significant.
Results
None of the 30 specimens failed during preloading. Modes of failure were consistent among groups. All 10 specimens in the interference-screw-only group failed by graft slippage past the screw in the tibial tunnel. Nineteen of the 20 specimens in the backup-fixation groups failed by graft slippage past the screw and suture cutout through the distal graft tail. In the bicortical-post backup group, 1 failure was attributed to tendon tearing proximal to whip-stitching. There were no instances of hardware breakage or failure of either titanium screw or SwiveLock anchor.
Mean (SD) cyclic displacement was higher in the interference-screw-only group, 3.5 (2.2) mm, than in the SwiveLock backup group, 2.6 (0.5) mm, and the bicortical-post backup group, 2.1 (0.6) mm; no statistical significance was demonstrated between any 2 of these groups alone (P = .12) (Figure 4). Mean (SD) pullout stiffness was higher in the bicortical-post backup group, 192 (48) N/mm, than in the SwiveLock backup group, 164 (53) N/mm, and the screw-only group, 163 (64) N/mm (P = .42) (Figure 5). Mean (SD) initial load at 5 mm of displacement was higher in the bicortical-post backup group, 482 (156) N, and the SwiveLock backup group, 423 (94) N, than in the screw-only group, 381 (169) N (P = .30).
Mean (SD) yield load was higher in the bicortical-post backup group, 829 (253) N, than in the SwiveLock backup group, 642 (172) N, and the interference-screw-only group, 496 (133) N (P = .003). Statistical significance was demonstrated between the screw-only and bicortical-post groups (P = .002) and between the screw-only and SwiveLock groups (P = .048). There was no statistical difference between the bicortical-post and SwiveLock groups (P = .07).
Mean (SD) ultimate load to failure was higher in the bicortical-post backup group, 1148 (186) N, than in the SwiveLock backup group, 1007 (176) N, and the interference-screw-only group, 778 (139) N (Figure 6). The difference was statistically significant, whereby the screw-only group failed at a lower load compared with the bicortical-post group (P < .001) and the SwiveLock group (P = .005). The 2 backup groups were not statistically different (P = .1).
Discussion
We investigated whether a fully threaded bio-interference screw backed with a 4.75-mm SwiveLock anchor would provide mechanically equivalent pullout strength within the tibial tunnel during ACL reconstruction with soft-tissue allografts in comparison either with a fully threaded bio-interference screw backed with a bicortical post or with a fully threaded bio-interference screw without backup fixation. The results of the study support this hypothesis. With SwiveLock used for backup fixation, there was no significant difference in stiffness or cyclic load displacement between the screw-only, SwiveLock, and bicortical-post groups. However, adding backup fixation could particularly help improve fixation consistency. Specifically, although after only 500 cycles there was no statistically significant difference in cyclic displacement, continued cycling may be clinically relevant if graft slippage exceeded limits to allow for healing within the tibial tunnel. Conversely, a significantly larger difference was found between the SwiveLock, bicortical-post, and screw-only groups in yield load and ultimate load to failure. However, there was no significant difference between the SwiveLock and bicortical-post groups.
In this study, interference screw with SwiveLock backup demonstrated a mean (SD) ultimate load to failure of 1007 (176) N, comparable to that found by Walsh and colleagues3 for retrograde bio-interference screw with suture button, 1027 (157.11) N. In a study comparing quadrupled hamstring tibial graft fixation, Intrafix (DePuy Mitek) and an 8×25-mm Bioscrew (Linvatec) demonstrated mean (SD) single-cycle yield loads of 1332 (304) N and 612 (176) N, respectively.13 These results are similar to the ultimate yield loads in the present study: bicortical-post group, 1148 (186) N; SwiveLock group, 1007 (176) N; screw-only group, 778 (139) N. Differences may be attributed to hamstring tendons used in a quadrupled manner in the aforementioned study.12,13 Last, mean (SD) ultimate load to failure in a study that used only a retrograde bio-interference screw (9×20 mm) was 679.00 (109.44) N,3 similar to the 778 (139) N found for interference-screw-only in the present study. The difference is likely attributable to the longer screw (9×28 mm) in our study. Using SwiveLock C in cortical bone, Barber and colleagues18 found mean (SD) loads to failure up to 711.9 (89.1) N.
Clinically, it has been shown that a statistically significant increase in anterior laxity occurred between 4 months and 2 years in 10.7% of patients who underwent hamstring ACL reconstruction.20 The knees were clinically categorized as unstable or severely abnormal. The authors concluded that the clinical outcome was more likely influenced by the methods used to fix the free ends of the graft, specifically with 2 staples or a washer. To simulate early postoperative rehabilitation in the present study, cyclic loading of the graft was performed. Ultimate load to failure was then determined in order to evaluate catastrophic failure strength of the backup fixation devices in comparison with the interference-screw-only group without supplementary fixation.
It has been shown in autologous hamstring ACL reconstruction that a centrally placed polyethylene screw with sheath (Intrafix) performed as well as a standard, eccentrically placed metal interference screw with staple.10 It is therefore logical that backup fixation with use of a similar device (eg, SwiveLock, bicortical post) is necessary to ensure comparable clinical outcomes in relation to a screw/sheath device that has been shown to endure the highest yield loads.2,9,12,13,21-23 Potential benefits of using SwiveLock anchors for backup fixation include a statistically significant increased mean (SD) ultimate yield load of 229 (176) N over interference screw only. These results are similar to those in comparable studies: 218.3 (59.7) N24 and 165 (24.15) N25 in healthy bone with a reported bone mineral density (BMD) of 1.39 g/cm2, similar to that of skeletally mature porcine tibia (1.220-1.675 g/cm²).3 In addition, ease of insertion of this device over a bicortical post was demonstrated. The titanium post required bicortical drilling as well as measurement with a depth gauge to ensure adequate screw length. This process appeared to require more time during specimen preparation and theoretically could prove to be more dangerous clinically.7 However, caution in using a SwiveLock anchor in osteoporotic bone is advised because of reduced pullout strength.26 In this case, bicortical-post backup fixation may be more suitable. Moreover, although not demonstrated in this study, hardware prominence and irritation with a post may cause postoperative morbidity necessitating future removal.20 Hardware removal was the most common reason for additional surgery using hamstring tendons as graft.20 A second surgery for hardware removal was required in 21% of these patients.20 This is unlikely to occur with a SwiveLock, as the anchor is buried within cortical bone.
Limitations
Regarding use of nonhuman tissues in a biomechanical model, porcine tibiae and bovine extensor tendons were used because of availability, consistency among specimens, and cost-effectiveness. However, bovine extensor tendons have been shown to exhibit stiffness and viscoelastic properties similar to those of a human hamstring graft.27 In addition, the BMD of the porcine tibiae used in this study was not tested because of time involved and cost-efficiency. However, it has been shown that average BMD of porcine tibiae, 1.220-1.675 g/cm², is similar to that in a young athletic population, 1.24-1.62 g/cm2.3,28-31 We therefore assumed similarity to a young athletic population and uniformity of BMD of the porcine tibiae used in this study.
In addition, the biomechanical testing protocol did not simulate physiologic loading within the tibial tunnel. Moreover, the testing protocol used loads of only 250 N during cyclic testing for 500 cycles. This simulates only the early rehabilitation period and not the healing period, which may last up to 12 weeks.9 In addition, as previously mentioned, forces on the graft may be as high as 450 to 700 N.11,32 Pullout testing in line with the long axis of the tibia was performed in order to compare mechanical testing results with those of similar studies.3,12,13 Last, the P of .07 for the comparison of ultimate load to failure between the 2 backup fixation groups suggests that this study may have been underpowered.
Conclusion
This study demonstrated an effective, alternative, and equivalent backup fixation device that can help prevent graft slippage within the tibial tunnel during soft-tissue ACL reconstruction. Potential benefits of using SwiveLock anchors for backup fixation include a significantly increased ultimate yield load (229 N) when supplementing an interference screw, ease of insertion compared with a bicortical post, and the improbable need for future hardware removal. We support using SwiveLock for supplementary fixation at the tibial tunnel site when using soft-tissue grafts in ACL reconstruction.
1. Wetzler MJ, Bartolozzi AR, Gillespie MJ, Rubenstein DL, Ciccotti MG, Miller LS. Revision anterior cruciate ligament reconstruction. Oper Tech Orthop. 1996;6(3):181-189.
2. Scheffler SU, Südkamp NP, Göckenjan A, Hoffmann RF, Weiler A. Biomechanical comparison of hamstring and patellar tendon graft anterior cruciate ligament reconstruction techniques: the impact of fixation level and fixation method under cyclic loading. Arthroscopy. 2002;18(3):304-315.
3. Walsh MP, Wijdicks CA, Parker JB, Hapa O, LaPrade RF. A comparison between a retrograde interference screw, suture button, and combined fixation on the tibial side in an all-inside anterior cruciate ligament reconstruction: a biomechanical study in a porcine model. Am J Sports Med. 2009;37(1):160-167.
4. Howell SM, Hull ML. Aggressive rehabilitation using hamstring tendons: graft construct, tibial tunnel placement, fixation properties, and clinical outcome. Am J Knee Surg. 1998;11(2):120-127.
5. Magen HE, Howell SM, Hull ML. Structural properties of six tibial fixation methods for anterior cruciate ligament soft tissue grafts. Am J Sports Med. 1999;27(1):35-43.
6. Beynnon BD, Meriam CM, Ryder SH, Fleming BC, Johnson RJ. The effect of screw insertion torque on tendons fixed with spiked washers. Am J Sports Med. 1998;26(4):536-539.
7. Post WR, King SS. Neurovascular risk of bicortical tibial drilling for screw and spiked washer fixation of soft-tissue anterior cruciate ligament graft. Arthroscopy. 2001;17(3):244-247.
8. Holden JP, Grood ES, Butler DL, et al. Biomechanics of fascia lata ligament replacements: early postoperative changes in the goat. J Orthop Res. 1988;6(5):639-647.
9. Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg Am. 1993;75(12):1795-1803.
10. Frank CB, Jackson DW. The science of reconstruction of the anterior cruciate ligament. J Bone Joint Surg Am. 1997;79(10):1556-1576.
11. Markolf KL, Willems MJ, Jackson SR, Finerman GA. In situ calibration of miniature sensors implanted into the anterior cruciate ligament. Part I: strain measurements. J Orthop Res. 1998;16(4):455-463.
12. Kousa P, Teppo LN, Jarvinen TL, Vihavainen M, Kannus P, Jarvinen M. The fixation strength of six hamstring tendon graft fixation devices in anterior cruciate ligament reconstruction: I. Femoral site. Am J Sports Med. 2003;3 (2)1:174-181.
13. Kousa P, Jarvinen TL, Vihavainen M, Kannus P, Jarvinen M. The fixation strength of six hamstring tendon graft fixation devices in anterior cruciate ligament reconstruction: II. Tibial site. Am J Sports Med. 2003;31(2):182-188.
14. Brand JC Jr, Pienkowski D, Steenlage E, Hamilton D, Johnson DL, Caborn DN. Interference screw fixation strength of a quadrupled hamstring tendon graft is directly related to bone mineral density and insertion torque. Am J Sports Med. 2000;28(5):705-710.
15. Weiler A, Hoffmann RF, Siepe CJ, Kolbeck SF, Südkamp NP. The influence of screw geometry on hamstring tendon interference fit fixation. Am J Sports Med. 2000;28(3):356-359.
16. Weiler A, Hoffmann RF, Stähelin AC, Bail HJ, Siepe CJ, Südkamp NP. Hamstring tendon fixation using interference screws: a biomechanical study in calf tibial bone. Arthroscopy. 1998;14(1):29-37.
17. Streich NA, Reichenbacher S, Barié A, Buchner M, Schmitt H. Long-term outcome of anterior cruciate ligament reconstruction with an autologous four-strand semitendinosus tendon autograft. Int Orthop. 2013;37(2):279-284.
18. Barber FA, Herbert MA, Beavis C, Barrera Oro F. Suture anchor materials, eyelets, and designs: update 2008. Arthroscopy. 2008;24(8):859-867.
19. Aickin M, Gensler H. Adjusting for multiple testing when reporting research results: the Bonferroni vs Holm methods. Am J Public Health. 1996;86(5):726-728.
20. Howell SM, Deutsch ML. Comparison of endoscopic and two-incision techniques for reconstructing a torn anterior cruciate ligament using hamstring tendons. Arthroscopy. 1999;15(6):594-606.
21. Gwynne-Jones DP, Draffin J, Vane A, Craig R, McMahon S. Failure strengths of concentric and eccentric implants for hamstring graft fixation. ANZ J Surg. 2008;78(3):177-181.
22. Hayes DA, Watts MC, Tevelen GA, Crawford RW. Central versus peripheral tibial screw placement in hamstring anterior cruciate ligament reconstruction: in vitro biomechanics. Arthroscopy. 2005;21(6):703-706.
23. Shino K, Pflaster DS. Comparison of eccentric and concentric screw placement for hamstring graft fixation in the tibial tunnel. Knee Surg Sports Traumatol Arthrosc. 2000;8(2):73-75.
24. Prevrhal S, Fuerst T, Fan B, et al. Quantitative ultrasound of the tibia depends on both cortical density and thickness. Osteoporosis Int. 2001;12(1):28-34.
25. Pietschmann MF, Gülecyüz MF, Fieseler S, et al. Biomechanical stability of knotless suture anchors used in rotator cuff repair in healthy and osteopenic bone. Arthroscopy. 2010;26(8):1035-1044.
26. Burns JP, Snyder SJ, Albritton M. Arthroscopic rotator cuff repair using triple-loaded anchors, suture shuttles, and suture savers. J Am Acad Orthop Surg. 2007;15(7):432-444.
27. Tetsumura S, Fujita A, Nakajima M, Abe M. Biomechanical comparison of different fixation methods on the tibial side in anterior cruciate ligament reconstruction: a biomechanical study in porcine tibial bone. J Orthop Sci. 2006;11(3):278-282.
28. Alfredson H, Nordstrom P, Lorentzon R. Total and regional bone mass in female soccer players. Calcif Tissue Int. 1996;59(6):438-442.
29. Nevill AM, Holder RL, Stewart AD. Modeling elite male athletes’ peripheral bone mass, assessed using regional dual x-ray absorptiometry. Bone. 2003;32(1):62-68.
30. Nordström P, Lorentzon R. Site-specific bone mass differences of the lower extremities in 17-year-old ice hockey players. Calcif Tissue Int. 1996;59(6):4443-4448.
31. Patzer T, Santo G, Olender GD, Wellmann M, Hurschler C, Schofer MD. Suprapectoral or subpectoral position for biceps tenodesis: biomechanical comparison of four different techniques in both positions. J Shoulder Elbow Surg. 2012;21(1):116-125.
32. De Wall M, Scholes CJ, Patel S, Coolican MR, Parker DA. Tibial fixation in anterior cruciate ligament reconstruction: a prospective randomized study comparing metal interference screw and staples with a centrally placed polyethylene screw and sheath. Am J Sports Med. 2011;39(9):1858-1864.
Restoration of stability with return to activity is generally expected after anterior cruciate ligament (ACL) reconstruction; long-term success rates range from 75% to 95%.1 However, graft failure occurs most frequently with soft-tissue grafts fixated only with interference screws.2,3 Fixation failure also occurs more frequently at the tibial site.2 This failure has been attributed to extensive graft slippage in cases of soft-tissue fixation with interference screws.2 Interference screw fixation alone, with a double-looped hamstring tendon graft, fails at 350 N in young human tibiae.4,5 However, failure is limited with use of a bone–tendon–bone graft or with backup fixation, particularly at the tibial site.3 The superiority of bicortical fixation has also been proven.5-7
In addition, as shown in a goat model, ACL graft fixation is a major cause of failure in the immediate postoperative period, before biological incorporation of the graft.8 Fixation techniques for soft-tissue grafts must withstand stresses during the healing period (grafts may take up to 12 weeks to incorporate).9 Failures may result from forces exerted on the graft—forces that may be as high as 450 to 700 N during daily activities.10,11 Within the tibial tunnel, various fixation devices are used, including interference screws, staples, pins, buttons, and interference screw/sheath constructs.12,13 Primary fixation is commonly achieved with interference screws because of their ease of insertion and greater stiffness. However, fixation of the soft-tissue graft is influenced by several variables, including bone density, insertion torque, thread geometry, and interference screw material.14-16 Many of these variables, which are a source of inconsistency and concern during the immediate postoperative period, have led surgeons to seek alternative methods of backup fixation at the tibial site. Nevertheless, good clinical and subjective results have been found after ACL reconstruction with a 4-stranded semitendinosus tendon at 10-year follow-up.17
An anchor used in rotator cuff repair is the SwiveLock system (Arthrex). Major advantages of this system include ease and speed of insertion, good strength, and reduced need for later hardware removal.
We conducted a study to biomechanically evaluate 3 methods of tibial-sided fixation for ACL reconstruction: fully threaded interference screw only, interference screw backed with 4.75-mm SwiveLock anchor, and fully threaded bio-interference screw backed with 4.5-mm bicortical screw. We hypothesized that a fully threaded bio-interference screw backed with a 4.75-mm SwiveLock anchor would provide mechanical strength no different from that provided by backup fixation with a bicortical post at the tibial site. We further hypothesized that SwiveLock backup fixation would provide more strength than fixation with bio-interference screw alone.
Materials and Methods
The design of this study was adapted from one used by Walsh and colleagues,3 who compared 3 fixation methods: retrograde interference screw, suture button, and combined fixation. Tibiae inspected before selection showed no signs of injury or abnormality. Bovine extensor tendons, which lacked any defects along their entire length, were stored in saline 0.9% solution. Both the tibiae and the extensor tendons were stored at –20°C before completion of the tibial-sided ACL reconstruction. Thirty fresh-frozen, skeletally mature porcine proximal tibiae were selected and thawed at 4°C before preparation. Specimens were prepared by potting the diaphysis in fiberglass resin, and a tunnel 9 mm in diameter was drilled through the anteromedial aspect of the tibia.
For consistency, one author (CAV) prepared all 30 specimens. Both tails of all 30 bovine extensor tendons were whip-stitched with No. 2 FiberLoop (Arthrex) 9 mm in diameter. Grafts and tibiae were randomly divided into 3 sample groups. The first group was prepared by antegrade graft fixation within the tibial tunnel using a fully threaded 9×28-mm BioComposite interference screw (Arthrex). The second and third groups used the same primary fixation within the tibial tunnel along with 2 types of secondary fixation. These backup fixation groups included a 4.5-mm titanium bicortical post (Arthrex) and a 4.75-mm BioComposite SwiveLock C anchor (Arthrex) (Figure 1). The FiberLoop at the ends of the distal graft tails for backup groups were fixated 1 cm distal to the tibial tunnel and tapped before insertion of backup devices (Figures 2A, 2B). Insertion was completed after 4.5-mm bicortical and 4.75-mm unicortical drilling and tapping of the anteromedial cortices for the titanium posts and SwiveLocks, respectively. The free ends of the whip-stitched No. 2 FiberLoop were tied to the proximal end of the titanium post with a single surgical knot followed by 5 square knots.3 The free ends of the No. 2 FiberLoop were inserted into the eyelet of the 4.75-mm SwiveLock and 1 cm directly inferior to the tibial tunnel. Interference fit of FiberLoop with SwiveLock was achieved within the corticocancellous bone of the tibiae. All samples retained a 30-mm tendon loop superior to the tibial plateau to simulate intra-articular ACL length. Specimens were then stored at –20°C and thawed at 4°C before biomechanical testing.
Each of the 30 tibiae was tested once. Each testing group consisted of 10 porcine tibiae. The tendons were kept moist during the entire testing procedure by spraying them thoroughly with saline 0.9% solution. Mechanical testing was performed with an Instron 8871 system with a 5-kN load cell secured to the crosshead. A fixed-angle aperture, attached to the testing surface, was adjusted so that the tendon would be pulled in line with the tibial tunnel. A hook fixture suspended from clevis and dowel was used to secure the tendon to the crosshead (Figure 3). A small preload of 5 N manually applied to each sample was followed by a precycling regimen of 10 cycles between 10 N and 50 N at 1 Hz. Precycling was performed to remove slack from the system. Mechanical testing consisted of 500 cycles between 50 N and 250 N at 1 Hz followed by pull to failure at 20 mm per minute. Load and displacement data were recorded at 500 Hz.
An a priori power analysis was not performed because 6 specimens per group in the study from which the testing protocol was adapted demonstrated sufficient power among 3 testing categories.3 In addition, other studies have demonstrated similar testing protocols using 10 specimens per testing group.7,12,13,18 The data for each sample were analyzed with OriginPro 8.0 software (OriginLab). Ultimate load, yield load, stiffness, and cyclic displacement of the 3 sample groups were compared with 1-way analysis of variance (α = 0.05). Holm-Sidak tests were used for post hoc analysis.19P < .05 was statistically significant.
Results
None of the 30 specimens failed during preloading. Modes of failure were consistent among groups. All 10 specimens in the interference-screw-only group failed by graft slippage past the screw in the tibial tunnel. Nineteen of the 20 specimens in the backup-fixation groups failed by graft slippage past the screw and suture cutout through the distal graft tail. In the bicortical-post backup group, 1 failure was attributed to tendon tearing proximal to whip-stitching. There were no instances of hardware breakage or failure of either titanium screw or SwiveLock anchor.
Mean (SD) cyclic displacement was higher in the interference-screw-only group, 3.5 (2.2) mm, than in the SwiveLock backup group, 2.6 (0.5) mm, and the bicortical-post backup group, 2.1 (0.6) mm; no statistical significance was demonstrated between any 2 of these groups alone (P = .12) (Figure 4). Mean (SD) pullout stiffness was higher in the bicortical-post backup group, 192 (48) N/mm, than in the SwiveLock backup group, 164 (53) N/mm, and the screw-only group, 163 (64) N/mm (P = .42) (Figure 5). Mean (SD) initial load at 5 mm of displacement was higher in the bicortical-post backup group, 482 (156) N, and the SwiveLock backup group, 423 (94) N, than in the screw-only group, 381 (169) N (P = .30).
Mean (SD) yield load was higher in the bicortical-post backup group, 829 (253) N, than in the SwiveLock backup group, 642 (172) N, and the interference-screw-only group, 496 (133) N (P = .003). Statistical significance was demonstrated between the screw-only and bicortical-post groups (P = .002) and between the screw-only and SwiveLock groups (P = .048). There was no statistical difference between the bicortical-post and SwiveLock groups (P = .07).
Mean (SD) ultimate load to failure was higher in the bicortical-post backup group, 1148 (186) N, than in the SwiveLock backup group, 1007 (176) N, and the interference-screw-only group, 778 (139) N (Figure 6). The difference was statistically significant, whereby the screw-only group failed at a lower load compared with the bicortical-post group (P < .001) and the SwiveLock group (P = .005). The 2 backup groups were not statistically different (P = .1).
Discussion
We investigated whether a fully threaded bio-interference screw backed with a 4.75-mm SwiveLock anchor would provide mechanically equivalent pullout strength within the tibial tunnel during ACL reconstruction with soft-tissue allografts in comparison either with a fully threaded bio-interference screw backed with a bicortical post or with a fully threaded bio-interference screw without backup fixation. The results of the study support this hypothesis. With SwiveLock used for backup fixation, there was no significant difference in stiffness or cyclic load displacement between the screw-only, SwiveLock, and bicortical-post groups. However, adding backup fixation could particularly help improve fixation consistency. Specifically, although after only 500 cycles there was no statistically significant difference in cyclic displacement, continued cycling may be clinically relevant if graft slippage exceeded limits to allow for healing within the tibial tunnel. Conversely, a significantly larger difference was found between the SwiveLock, bicortical-post, and screw-only groups in yield load and ultimate load to failure. However, there was no significant difference between the SwiveLock and bicortical-post groups.
In this study, interference screw with SwiveLock backup demonstrated a mean (SD) ultimate load to failure of 1007 (176) N, comparable to that found by Walsh and colleagues3 for retrograde bio-interference screw with suture button, 1027 (157.11) N. In a study comparing quadrupled hamstring tibial graft fixation, Intrafix (DePuy Mitek) and an 8×25-mm Bioscrew (Linvatec) demonstrated mean (SD) single-cycle yield loads of 1332 (304) N and 612 (176) N, respectively.13 These results are similar to the ultimate yield loads in the present study: bicortical-post group, 1148 (186) N; SwiveLock group, 1007 (176) N; screw-only group, 778 (139) N. Differences may be attributed to hamstring tendons used in a quadrupled manner in the aforementioned study.12,13 Last, mean (SD) ultimate load to failure in a study that used only a retrograde bio-interference screw (9×20 mm) was 679.00 (109.44) N,3 similar to the 778 (139) N found for interference-screw-only in the present study. The difference is likely attributable to the longer screw (9×28 mm) in our study. Using SwiveLock C in cortical bone, Barber and colleagues18 found mean (SD) loads to failure up to 711.9 (89.1) N.
Clinically, it has been shown that a statistically significant increase in anterior laxity occurred between 4 months and 2 years in 10.7% of patients who underwent hamstring ACL reconstruction.20 The knees were clinically categorized as unstable or severely abnormal. The authors concluded that the clinical outcome was more likely influenced by the methods used to fix the free ends of the graft, specifically with 2 staples or a washer. To simulate early postoperative rehabilitation in the present study, cyclic loading of the graft was performed. Ultimate load to failure was then determined in order to evaluate catastrophic failure strength of the backup fixation devices in comparison with the interference-screw-only group without supplementary fixation.
It has been shown in autologous hamstring ACL reconstruction that a centrally placed polyethylene screw with sheath (Intrafix) performed as well as a standard, eccentrically placed metal interference screw with staple.10 It is therefore logical that backup fixation with use of a similar device (eg, SwiveLock, bicortical post) is necessary to ensure comparable clinical outcomes in relation to a screw/sheath device that has been shown to endure the highest yield loads.2,9,12,13,21-23 Potential benefits of using SwiveLock anchors for backup fixation include a statistically significant increased mean (SD) ultimate yield load of 229 (176) N over interference screw only. These results are similar to those in comparable studies: 218.3 (59.7) N24 and 165 (24.15) N25 in healthy bone with a reported bone mineral density (BMD) of 1.39 g/cm2, similar to that of skeletally mature porcine tibia (1.220-1.675 g/cm²).3 In addition, ease of insertion of this device over a bicortical post was demonstrated. The titanium post required bicortical drilling as well as measurement with a depth gauge to ensure adequate screw length. This process appeared to require more time during specimen preparation and theoretically could prove to be more dangerous clinically.7 However, caution in using a SwiveLock anchor in osteoporotic bone is advised because of reduced pullout strength.26 In this case, bicortical-post backup fixation may be more suitable. Moreover, although not demonstrated in this study, hardware prominence and irritation with a post may cause postoperative morbidity necessitating future removal.20 Hardware removal was the most common reason for additional surgery using hamstring tendons as graft.20 A second surgery for hardware removal was required in 21% of these patients.20 This is unlikely to occur with a SwiveLock, as the anchor is buried within cortical bone.
Limitations
Regarding use of nonhuman tissues in a biomechanical model, porcine tibiae and bovine extensor tendons were used because of availability, consistency among specimens, and cost-effectiveness. However, bovine extensor tendons have been shown to exhibit stiffness and viscoelastic properties similar to those of a human hamstring graft.27 In addition, the BMD of the porcine tibiae used in this study was not tested because of time involved and cost-efficiency. However, it has been shown that average BMD of porcine tibiae, 1.220-1.675 g/cm², is similar to that in a young athletic population, 1.24-1.62 g/cm2.3,28-31 We therefore assumed similarity to a young athletic population and uniformity of BMD of the porcine tibiae used in this study.
In addition, the biomechanical testing protocol did not simulate physiologic loading within the tibial tunnel. Moreover, the testing protocol used loads of only 250 N during cyclic testing for 500 cycles. This simulates only the early rehabilitation period and not the healing period, which may last up to 12 weeks.9 In addition, as previously mentioned, forces on the graft may be as high as 450 to 700 N.11,32 Pullout testing in line with the long axis of the tibia was performed in order to compare mechanical testing results with those of similar studies.3,12,13 Last, the P of .07 for the comparison of ultimate load to failure between the 2 backup fixation groups suggests that this study may have been underpowered.
Conclusion
This study demonstrated an effective, alternative, and equivalent backup fixation device that can help prevent graft slippage within the tibial tunnel during soft-tissue ACL reconstruction. Potential benefits of using SwiveLock anchors for backup fixation include a significantly increased ultimate yield load (229 N) when supplementing an interference screw, ease of insertion compared with a bicortical post, and the improbable need for future hardware removal. We support using SwiveLock for supplementary fixation at the tibial tunnel site when using soft-tissue grafts in ACL reconstruction.
Restoration of stability with return to activity is generally expected after anterior cruciate ligament (ACL) reconstruction; long-term success rates range from 75% to 95%.1 However, graft failure occurs most frequently with soft-tissue grafts fixated only with interference screws.2,3 Fixation failure also occurs more frequently at the tibial site.2 This failure has been attributed to extensive graft slippage in cases of soft-tissue fixation with interference screws.2 Interference screw fixation alone, with a double-looped hamstring tendon graft, fails at 350 N in young human tibiae.4,5 However, failure is limited with use of a bone–tendon–bone graft or with backup fixation, particularly at the tibial site.3 The superiority of bicortical fixation has also been proven.5-7
In addition, as shown in a goat model, ACL graft fixation is a major cause of failure in the immediate postoperative period, before biological incorporation of the graft.8 Fixation techniques for soft-tissue grafts must withstand stresses during the healing period (grafts may take up to 12 weeks to incorporate).9 Failures may result from forces exerted on the graft—forces that may be as high as 450 to 700 N during daily activities.10,11 Within the tibial tunnel, various fixation devices are used, including interference screws, staples, pins, buttons, and interference screw/sheath constructs.12,13 Primary fixation is commonly achieved with interference screws because of their ease of insertion and greater stiffness. However, fixation of the soft-tissue graft is influenced by several variables, including bone density, insertion torque, thread geometry, and interference screw material.14-16 Many of these variables, which are a source of inconsistency and concern during the immediate postoperative period, have led surgeons to seek alternative methods of backup fixation at the tibial site. Nevertheless, good clinical and subjective results have been found after ACL reconstruction with a 4-stranded semitendinosus tendon at 10-year follow-up.17
An anchor used in rotator cuff repair is the SwiveLock system (Arthrex). Major advantages of this system include ease and speed of insertion, good strength, and reduced need for later hardware removal.
We conducted a study to biomechanically evaluate 3 methods of tibial-sided fixation for ACL reconstruction: fully threaded interference screw only, interference screw backed with 4.75-mm SwiveLock anchor, and fully threaded bio-interference screw backed with 4.5-mm bicortical screw. We hypothesized that a fully threaded bio-interference screw backed with a 4.75-mm SwiveLock anchor would provide mechanical strength no different from that provided by backup fixation with a bicortical post at the tibial site. We further hypothesized that SwiveLock backup fixation would provide more strength than fixation with bio-interference screw alone.
Materials and Methods
The design of this study was adapted from one used by Walsh and colleagues,3 who compared 3 fixation methods: retrograde interference screw, suture button, and combined fixation. Tibiae inspected before selection showed no signs of injury or abnormality. Bovine extensor tendons, which lacked any defects along their entire length, were stored in saline 0.9% solution. Both the tibiae and the extensor tendons were stored at –20°C before completion of the tibial-sided ACL reconstruction. Thirty fresh-frozen, skeletally mature porcine proximal tibiae were selected and thawed at 4°C before preparation. Specimens were prepared by potting the diaphysis in fiberglass resin, and a tunnel 9 mm in diameter was drilled through the anteromedial aspect of the tibia.
For consistency, one author (CAV) prepared all 30 specimens. Both tails of all 30 bovine extensor tendons were whip-stitched with No. 2 FiberLoop (Arthrex) 9 mm in diameter. Grafts and tibiae were randomly divided into 3 sample groups. The first group was prepared by antegrade graft fixation within the tibial tunnel using a fully threaded 9×28-mm BioComposite interference screw (Arthrex). The second and third groups used the same primary fixation within the tibial tunnel along with 2 types of secondary fixation. These backup fixation groups included a 4.5-mm titanium bicortical post (Arthrex) and a 4.75-mm BioComposite SwiveLock C anchor (Arthrex) (Figure 1). The FiberLoop at the ends of the distal graft tails for backup groups were fixated 1 cm distal to the tibial tunnel and tapped before insertion of backup devices (Figures 2A, 2B). Insertion was completed after 4.5-mm bicortical and 4.75-mm unicortical drilling and tapping of the anteromedial cortices for the titanium posts and SwiveLocks, respectively. The free ends of the whip-stitched No. 2 FiberLoop were tied to the proximal end of the titanium post with a single surgical knot followed by 5 square knots.3 The free ends of the No. 2 FiberLoop were inserted into the eyelet of the 4.75-mm SwiveLock and 1 cm directly inferior to the tibial tunnel. Interference fit of FiberLoop with SwiveLock was achieved within the corticocancellous bone of the tibiae. All samples retained a 30-mm tendon loop superior to the tibial plateau to simulate intra-articular ACL length. Specimens were then stored at –20°C and thawed at 4°C before biomechanical testing.
Each of the 30 tibiae was tested once. Each testing group consisted of 10 porcine tibiae. The tendons were kept moist during the entire testing procedure by spraying them thoroughly with saline 0.9% solution. Mechanical testing was performed with an Instron 8871 system with a 5-kN load cell secured to the crosshead. A fixed-angle aperture, attached to the testing surface, was adjusted so that the tendon would be pulled in line with the tibial tunnel. A hook fixture suspended from clevis and dowel was used to secure the tendon to the crosshead (Figure 3). A small preload of 5 N manually applied to each sample was followed by a precycling regimen of 10 cycles between 10 N and 50 N at 1 Hz. Precycling was performed to remove slack from the system. Mechanical testing consisted of 500 cycles between 50 N and 250 N at 1 Hz followed by pull to failure at 20 mm per minute. Load and displacement data were recorded at 500 Hz.
An a priori power analysis was not performed because 6 specimens per group in the study from which the testing protocol was adapted demonstrated sufficient power among 3 testing categories.3 In addition, other studies have demonstrated similar testing protocols using 10 specimens per testing group.7,12,13,18 The data for each sample were analyzed with OriginPro 8.0 software (OriginLab). Ultimate load, yield load, stiffness, and cyclic displacement of the 3 sample groups were compared with 1-way analysis of variance (α = 0.05). Holm-Sidak tests were used for post hoc analysis.19P < .05 was statistically significant.
Results
None of the 30 specimens failed during preloading. Modes of failure were consistent among groups. All 10 specimens in the interference-screw-only group failed by graft slippage past the screw in the tibial tunnel. Nineteen of the 20 specimens in the backup-fixation groups failed by graft slippage past the screw and suture cutout through the distal graft tail. In the bicortical-post backup group, 1 failure was attributed to tendon tearing proximal to whip-stitching. There were no instances of hardware breakage or failure of either titanium screw or SwiveLock anchor.
Mean (SD) cyclic displacement was higher in the interference-screw-only group, 3.5 (2.2) mm, than in the SwiveLock backup group, 2.6 (0.5) mm, and the bicortical-post backup group, 2.1 (0.6) mm; no statistical significance was demonstrated between any 2 of these groups alone (P = .12) (Figure 4). Mean (SD) pullout stiffness was higher in the bicortical-post backup group, 192 (48) N/mm, than in the SwiveLock backup group, 164 (53) N/mm, and the screw-only group, 163 (64) N/mm (P = .42) (Figure 5). Mean (SD) initial load at 5 mm of displacement was higher in the bicortical-post backup group, 482 (156) N, and the SwiveLock backup group, 423 (94) N, than in the screw-only group, 381 (169) N (P = .30).
Mean (SD) yield load was higher in the bicortical-post backup group, 829 (253) N, than in the SwiveLock backup group, 642 (172) N, and the interference-screw-only group, 496 (133) N (P = .003). Statistical significance was demonstrated between the screw-only and bicortical-post groups (P = .002) and between the screw-only and SwiveLock groups (P = .048). There was no statistical difference between the bicortical-post and SwiveLock groups (P = .07).
Mean (SD) ultimate load to failure was higher in the bicortical-post backup group, 1148 (186) N, than in the SwiveLock backup group, 1007 (176) N, and the interference-screw-only group, 778 (139) N (Figure 6). The difference was statistically significant, whereby the screw-only group failed at a lower load compared with the bicortical-post group (P < .001) and the SwiveLock group (P = .005). The 2 backup groups were not statistically different (P = .1).
Discussion
We investigated whether a fully threaded bio-interference screw backed with a 4.75-mm SwiveLock anchor would provide mechanically equivalent pullout strength within the tibial tunnel during ACL reconstruction with soft-tissue allografts in comparison either with a fully threaded bio-interference screw backed with a bicortical post or with a fully threaded bio-interference screw without backup fixation. The results of the study support this hypothesis. With SwiveLock used for backup fixation, there was no significant difference in stiffness or cyclic load displacement between the screw-only, SwiveLock, and bicortical-post groups. However, adding backup fixation could particularly help improve fixation consistency. Specifically, although after only 500 cycles there was no statistically significant difference in cyclic displacement, continued cycling may be clinically relevant if graft slippage exceeded limits to allow for healing within the tibial tunnel. Conversely, a significantly larger difference was found between the SwiveLock, bicortical-post, and screw-only groups in yield load and ultimate load to failure. However, there was no significant difference between the SwiveLock and bicortical-post groups.
In this study, interference screw with SwiveLock backup demonstrated a mean (SD) ultimate load to failure of 1007 (176) N, comparable to that found by Walsh and colleagues3 for retrograde bio-interference screw with suture button, 1027 (157.11) N. In a study comparing quadrupled hamstring tibial graft fixation, Intrafix (DePuy Mitek) and an 8×25-mm Bioscrew (Linvatec) demonstrated mean (SD) single-cycle yield loads of 1332 (304) N and 612 (176) N, respectively.13 These results are similar to the ultimate yield loads in the present study: bicortical-post group, 1148 (186) N; SwiveLock group, 1007 (176) N; screw-only group, 778 (139) N. Differences may be attributed to hamstring tendons used in a quadrupled manner in the aforementioned study.12,13 Last, mean (SD) ultimate load to failure in a study that used only a retrograde bio-interference screw (9×20 mm) was 679.00 (109.44) N,3 similar to the 778 (139) N found for interference-screw-only in the present study. The difference is likely attributable to the longer screw (9×28 mm) in our study. Using SwiveLock C in cortical bone, Barber and colleagues18 found mean (SD) loads to failure up to 711.9 (89.1) N.
Clinically, it has been shown that a statistically significant increase in anterior laxity occurred between 4 months and 2 years in 10.7% of patients who underwent hamstring ACL reconstruction.20 The knees were clinically categorized as unstable or severely abnormal. The authors concluded that the clinical outcome was more likely influenced by the methods used to fix the free ends of the graft, specifically with 2 staples or a washer. To simulate early postoperative rehabilitation in the present study, cyclic loading of the graft was performed. Ultimate load to failure was then determined in order to evaluate catastrophic failure strength of the backup fixation devices in comparison with the interference-screw-only group without supplementary fixation.
It has been shown in autologous hamstring ACL reconstruction that a centrally placed polyethylene screw with sheath (Intrafix) performed as well as a standard, eccentrically placed metal interference screw with staple.10 It is therefore logical that backup fixation with use of a similar device (eg, SwiveLock, bicortical post) is necessary to ensure comparable clinical outcomes in relation to a screw/sheath device that has been shown to endure the highest yield loads.2,9,12,13,21-23 Potential benefits of using SwiveLock anchors for backup fixation include a statistically significant increased mean (SD) ultimate yield load of 229 (176) N over interference screw only. These results are similar to those in comparable studies: 218.3 (59.7) N24 and 165 (24.15) N25 in healthy bone with a reported bone mineral density (BMD) of 1.39 g/cm2, similar to that of skeletally mature porcine tibia (1.220-1.675 g/cm²).3 In addition, ease of insertion of this device over a bicortical post was demonstrated. The titanium post required bicortical drilling as well as measurement with a depth gauge to ensure adequate screw length. This process appeared to require more time during specimen preparation and theoretically could prove to be more dangerous clinically.7 However, caution in using a SwiveLock anchor in osteoporotic bone is advised because of reduced pullout strength.26 In this case, bicortical-post backup fixation may be more suitable. Moreover, although not demonstrated in this study, hardware prominence and irritation with a post may cause postoperative morbidity necessitating future removal.20 Hardware removal was the most common reason for additional surgery using hamstring tendons as graft.20 A second surgery for hardware removal was required in 21% of these patients.20 This is unlikely to occur with a SwiveLock, as the anchor is buried within cortical bone.
Limitations
Regarding use of nonhuman tissues in a biomechanical model, porcine tibiae and bovine extensor tendons were used because of availability, consistency among specimens, and cost-effectiveness. However, bovine extensor tendons have been shown to exhibit stiffness and viscoelastic properties similar to those of a human hamstring graft.27 In addition, the BMD of the porcine tibiae used in this study was not tested because of time involved and cost-efficiency. However, it has been shown that average BMD of porcine tibiae, 1.220-1.675 g/cm², is similar to that in a young athletic population, 1.24-1.62 g/cm2.3,28-31 We therefore assumed similarity to a young athletic population and uniformity of BMD of the porcine tibiae used in this study.
In addition, the biomechanical testing protocol did not simulate physiologic loading within the tibial tunnel. Moreover, the testing protocol used loads of only 250 N during cyclic testing for 500 cycles. This simulates only the early rehabilitation period and not the healing period, which may last up to 12 weeks.9 In addition, as previously mentioned, forces on the graft may be as high as 450 to 700 N.11,32 Pullout testing in line with the long axis of the tibia was performed in order to compare mechanical testing results with those of similar studies.3,12,13 Last, the P of .07 for the comparison of ultimate load to failure between the 2 backup fixation groups suggests that this study may have been underpowered.
Conclusion
This study demonstrated an effective, alternative, and equivalent backup fixation device that can help prevent graft slippage within the tibial tunnel during soft-tissue ACL reconstruction. Potential benefits of using SwiveLock anchors for backup fixation include a significantly increased ultimate yield load (229 N) when supplementing an interference screw, ease of insertion compared with a bicortical post, and the improbable need for future hardware removal. We support using SwiveLock for supplementary fixation at the tibial tunnel site when using soft-tissue grafts in ACL reconstruction.
1. Wetzler MJ, Bartolozzi AR, Gillespie MJ, Rubenstein DL, Ciccotti MG, Miller LS. Revision anterior cruciate ligament reconstruction. Oper Tech Orthop. 1996;6(3):181-189.
2. Scheffler SU, Südkamp NP, Göckenjan A, Hoffmann RF, Weiler A. Biomechanical comparison of hamstring and patellar tendon graft anterior cruciate ligament reconstruction techniques: the impact of fixation level and fixation method under cyclic loading. Arthroscopy. 2002;18(3):304-315.
3. Walsh MP, Wijdicks CA, Parker JB, Hapa O, LaPrade RF. A comparison between a retrograde interference screw, suture button, and combined fixation on the tibial side in an all-inside anterior cruciate ligament reconstruction: a biomechanical study in a porcine model. Am J Sports Med. 2009;37(1):160-167.
4. Howell SM, Hull ML. Aggressive rehabilitation using hamstring tendons: graft construct, tibial tunnel placement, fixation properties, and clinical outcome. Am J Knee Surg. 1998;11(2):120-127.
5. Magen HE, Howell SM, Hull ML. Structural properties of six tibial fixation methods for anterior cruciate ligament soft tissue grafts. Am J Sports Med. 1999;27(1):35-43.
6. Beynnon BD, Meriam CM, Ryder SH, Fleming BC, Johnson RJ. The effect of screw insertion torque on tendons fixed with spiked washers. Am J Sports Med. 1998;26(4):536-539.
7. Post WR, King SS. Neurovascular risk of bicortical tibial drilling for screw and spiked washer fixation of soft-tissue anterior cruciate ligament graft. Arthroscopy. 2001;17(3):244-247.
8. Holden JP, Grood ES, Butler DL, et al. Biomechanics of fascia lata ligament replacements: early postoperative changes in the goat. J Orthop Res. 1988;6(5):639-647.
9. Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg Am. 1993;75(12):1795-1803.
10. Frank CB, Jackson DW. The science of reconstruction of the anterior cruciate ligament. J Bone Joint Surg Am. 1997;79(10):1556-1576.
11. Markolf KL, Willems MJ, Jackson SR, Finerman GA. In situ calibration of miniature sensors implanted into the anterior cruciate ligament. Part I: strain measurements. J Orthop Res. 1998;16(4):455-463.
12. Kousa P, Teppo LN, Jarvinen TL, Vihavainen M, Kannus P, Jarvinen M. The fixation strength of six hamstring tendon graft fixation devices in anterior cruciate ligament reconstruction: I. Femoral site. Am J Sports Med. 2003;3 (2)1:174-181.
13. Kousa P, Jarvinen TL, Vihavainen M, Kannus P, Jarvinen M. The fixation strength of six hamstring tendon graft fixation devices in anterior cruciate ligament reconstruction: II. Tibial site. Am J Sports Med. 2003;31(2):182-188.
14. Brand JC Jr, Pienkowski D, Steenlage E, Hamilton D, Johnson DL, Caborn DN. Interference screw fixation strength of a quadrupled hamstring tendon graft is directly related to bone mineral density and insertion torque. Am J Sports Med. 2000;28(5):705-710.
15. Weiler A, Hoffmann RF, Siepe CJ, Kolbeck SF, Südkamp NP. The influence of screw geometry on hamstring tendon interference fit fixation. Am J Sports Med. 2000;28(3):356-359.
16. Weiler A, Hoffmann RF, Stähelin AC, Bail HJ, Siepe CJ, Südkamp NP. Hamstring tendon fixation using interference screws: a biomechanical study in calf tibial bone. Arthroscopy. 1998;14(1):29-37.
17. Streich NA, Reichenbacher S, Barié A, Buchner M, Schmitt H. Long-term outcome of anterior cruciate ligament reconstruction with an autologous four-strand semitendinosus tendon autograft. Int Orthop. 2013;37(2):279-284.
18. Barber FA, Herbert MA, Beavis C, Barrera Oro F. Suture anchor materials, eyelets, and designs: update 2008. Arthroscopy. 2008;24(8):859-867.
19. Aickin M, Gensler H. Adjusting for multiple testing when reporting research results: the Bonferroni vs Holm methods. Am J Public Health. 1996;86(5):726-728.
20. Howell SM, Deutsch ML. Comparison of endoscopic and two-incision techniques for reconstructing a torn anterior cruciate ligament using hamstring tendons. Arthroscopy. 1999;15(6):594-606.
21. Gwynne-Jones DP, Draffin J, Vane A, Craig R, McMahon S. Failure strengths of concentric and eccentric implants for hamstring graft fixation. ANZ J Surg. 2008;78(3):177-181.
22. Hayes DA, Watts MC, Tevelen GA, Crawford RW. Central versus peripheral tibial screw placement in hamstring anterior cruciate ligament reconstruction: in vitro biomechanics. Arthroscopy. 2005;21(6):703-706.
23. Shino K, Pflaster DS. Comparison of eccentric and concentric screw placement for hamstring graft fixation in the tibial tunnel. Knee Surg Sports Traumatol Arthrosc. 2000;8(2):73-75.
24. Prevrhal S, Fuerst T, Fan B, et al. Quantitative ultrasound of the tibia depends on both cortical density and thickness. Osteoporosis Int. 2001;12(1):28-34.
25. Pietschmann MF, Gülecyüz MF, Fieseler S, et al. Biomechanical stability of knotless suture anchors used in rotator cuff repair in healthy and osteopenic bone. Arthroscopy. 2010;26(8):1035-1044.
26. Burns JP, Snyder SJ, Albritton M. Arthroscopic rotator cuff repair using triple-loaded anchors, suture shuttles, and suture savers. J Am Acad Orthop Surg. 2007;15(7):432-444.
27. Tetsumura S, Fujita A, Nakajima M, Abe M. Biomechanical comparison of different fixation methods on the tibial side in anterior cruciate ligament reconstruction: a biomechanical study in porcine tibial bone. J Orthop Sci. 2006;11(3):278-282.
28. Alfredson H, Nordstrom P, Lorentzon R. Total and regional bone mass in female soccer players. Calcif Tissue Int. 1996;59(6):438-442.
29. Nevill AM, Holder RL, Stewart AD. Modeling elite male athletes’ peripheral bone mass, assessed using regional dual x-ray absorptiometry. Bone. 2003;32(1):62-68.
30. Nordström P, Lorentzon R. Site-specific bone mass differences of the lower extremities in 17-year-old ice hockey players. Calcif Tissue Int. 1996;59(6):4443-4448.
31. Patzer T, Santo G, Olender GD, Wellmann M, Hurschler C, Schofer MD. Suprapectoral or subpectoral position for biceps tenodesis: biomechanical comparison of four different techniques in both positions. J Shoulder Elbow Surg. 2012;21(1):116-125.
32. De Wall M, Scholes CJ, Patel S, Coolican MR, Parker DA. Tibial fixation in anterior cruciate ligament reconstruction: a prospective randomized study comparing metal interference screw and staples with a centrally placed polyethylene screw and sheath. Am J Sports Med. 2011;39(9):1858-1864.
1. Wetzler MJ, Bartolozzi AR, Gillespie MJ, Rubenstein DL, Ciccotti MG, Miller LS. Revision anterior cruciate ligament reconstruction. Oper Tech Orthop. 1996;6(3):181-189.
2. Scheffler SU, Südkamp NP, Göckenjan A, Hoffmann RF, Weiler A. Biomechanical comparison of hamstring and patellar tendon graft anterior cruciate ligament reconstruction techniques: the impact of fixation level and fixation method under cyclic loading. Arthroscopy. 2002;18(3):304-315.
3. Walsh MP, Wijdicks CA, Parker JB, Hapa O, LaPrade RF. A comparison between a retrograde interference screw, suture button, and combined fixation on the tibial side in an all-inside anterior cruciate ligament reconstruction: a biomechanical study in a porcine model. Am J Sports Med. 2009;37(1):160-167.
4. Howell SM, Hull ML. Aggressive rehabilitation using hamstring tendons: graft construct, tibial tunnel placement, fixation properties, and clinical outcome. Am J Knee Surg. 1998;11(2):120-127.
5. Magen HE, Howell SM, Hull ML. Structural properties of six tibial fixation methods for anterior cruciate ligament soft tissue grafts. Am J Sports Med. 1999;27(1):35-43.
6. Beynnon BD, Meriam CM, Ryder SH, Fleming BC, Johnson RJ. The effect of screw insertion torque on tendons fixed with spiked washers. Am J Sports Med. 1998;26(4):536-539.
7. Post WR, King SS. Neurovascular risk of bicortical tibial drilling for screw and spiked washer fixation of soft-tissue anterior cruciate ligament graft. Arthroscopy. 2001;17(3):244-247.
8. Holden JP, Grood ES, Butler DL, et al. Biomechanics of fascia lata ligament replacements: early postoperative changes in the goat. J Orthop Res. 1988;6(5):639-647.
9. Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg Am. 1993;75(12):1795-1803.
10. Frank CB, Jackson DW. The science of reconstruction of the anterior cruciate ligament. J Bone Joint Surg Am. 1997;79(10):1556-1576.
11. Markolf KL, Willems MJ, Jackson SR, Finerman GA. In situ calibration of miniature sensors implanted into the anterior cruciate ligament. Part I: strain measurements. J Orthop Res. 1998;16(4):455-463.
12. Kousa P, Teppo LN, Jarvinen TL, Vihavainen M, Kannus P, Jarvinen M. The fixation strength of six hamstring tendon graft fixation devices in anterior cruciate ligament reconstruction: I. Femoral site. Am J Sports Med. 2003;3 (2)1:174-181.
13. Kousa P, Jarvinen TL, Vihavainen M, Kannus P, Jarvinen M. The fixation strength of six hamstring tendon graft fixation devices in anterior cruciate ligament reconstruction: II. Tibial site. Am J Sports Med. 2003;31(2):182-188.
14. Brand JC Jr, Pienkowski D, Steenlage E, Hamilton D, Johnson DL, Caborn DN. Interference screw fixation strength of a quadrupled hamstring tendon graft is directly related to bone mineral density and insertion torque. Am J Sports Med. 2000;28(5):705-710.
15. Weiler A, Hoffmann RF, Siepe CJ, Kolbeck SF, Südkamp NP. The influence of screw geometry on hamstring tendon interference fit fixation. Am J Sports Med. 2000;28(3):356-359.
16. Weiler A, Hoffmann RF, Stähelin AC, Bail HJ, Siepe CJ, Südkamp NP. Hamstring tendon fixation using interference screws: a biomechanical study in calf tibial bone. Arthroscopy. 1998;14(1):29-37.
17. Streich NA, Reichenbacher S, Barié A, Buchner M, Schmitt H. Long-term outcome of anterior cruciate ligament reconstruction with an autologous four-strand semitendinosus tendon autograft. Int Orthop. 2013;37(2):279-284.
18. Barber FA, Herbert MA, Beavis C, Barrera Oro F. Suture anchor materials, eyelets, and designs: update 2008. Arthroscopy. 2008;24(8):859-867.
19. Aickin M, Gensler H. Adjusting for multiple testing when reporting research results: the Bonferroni vs Holm methods. Am J Public Health. 1996;86(5):726-728.
20. Howell SM, Deutsch ML. Comparison of endoscopic and two-incision techniques for reconstructing a torn anterior cruciate ligament using hamstring tendons. Arthroscopy. 1999;15(6):594-606.
21. Gwynne-Jones DP, Draffin J, Vane A, Craig R, McMahon S. Failure strengths of concentric and eccentric implants for hamstring graft fixation. ANZ J Surg. 2008;78(3):177-181.
22. Hayes DA, Watts MC, Tevelen GA, Crawford RW. Central versus peripheral tibial screw placement in hamstring anterior cruciate ligament reconstruction: in vitro biomechanics. Arthroscopy. 2005;21(6):703-706.
23. Shino K, Pflaster DS. Comparison of eccentric and concentric screw placement for hamstring graft fixation in the tibial tunnel. Knee Surg Sports Traumatol Arthrosc. 2000;8(2):73-75.
24. Prevrhal S, Fuerst T, Fan B, et al. Quantitative ultrasound of the tibia depends on both cortical density and thickness. Osteoporosis Int. 2001;12(1):28-34.
25. Pietschmann MF, Gülecyüz MF, Fieseler S, et al. Biomechanical stability of knotless suture anchors used in rotator cuff repair in healthy and osteopenic bone. Arthroscopy. 2010;26(8):1035-1044.
26. Burns JP, Snyder SJ, Albritton M. Arthroscopic rotator cuff repair using triple-loaded anchors, suture shuttles, and suture savers. J Am Acad Orthop Surg. 2007;15(7):432-444.
27. Tetsumura S, Fujita A, Nakajima M, Abe M. Biomechanical comparison of different fixation methods on the tibial side in anterior cruciate ligament reconstruction: a biomechanical study in porcine tibial bone. J Orthop Sci. 2006;11(3):278-282.
28. Alfredson H, Nordstrom P, Lorentzon R. Total and regional bone mass in female soccer players. Calcif Tissue Int. 1996;59(6):438-442.
29. Nevill AM, Holder RL, Stewart AD. Modeling elite male athletes’ peripheral bone mass, assessed using regional dual x-ray absorptiometry. Bone. 2003;32(1):62-68.
30. Nordström P, Lorentzon R. Site-specific bone mass differences of the lower extremities in 17-year-old ice hockey players. Calcif Tissue Int. 1996;59(6):4443-4448.
31. Patzer T, Santo G, Olender GD, Wellmann M, Hurschler C, Schofer MD. Suprapectoral or subpectoral position for biceps tenodesis: biomechanical comparison of four different techniques in both positions. J Shoulder Elbow Surg. 2012;21(1):116-125.
32. De Wall M, Scholes CJ, Patel S, Coolican MR, Parker DA. Tibial fixation in anterior cruciate ligament reconstruction: a prospective randomized study comparing metal interference screw and staples with a centrally placed polyethylene screw and sheath. Am J Sports Med. 2011;39(9):1858-1864.
Risk Factors for Thromboembolic Events After Surgery for Ankle Fractures
Venous thromboembolic events (VTEs), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), are potentially fatal events that can occur after orthopedic surgery.1 In patients who do not receive prophylaxis, VTE incidence can be as high as 70% for total hip arthroplasty,2 26% for hip fracture,3 and 5% for ankle fracture.4 Based on the relatively low incidence of VTE after ankle fractures and insufficient evidence for VTE prophylaxis in this population, the American Orthopaedic Foot and Ankle Society and the American College of Chest Physicians do not recommend routine screening or prophylaxis for VTE in patients with ankle fractures.1,5 Nevertheless, certain patients may be at increased risk for VTE after open reduction and internal fixation (ORIF) of an ankle fracture. In such cases, further consideration for prophylaxis may be warranted.
Other studies of VTEs have identified general risk factors of increased age, obesity, prior thromboembolic disease, oral contraceptive use, multitrauma, varicose veins, and prolonged immobilization, among others.1,6,7 In orthopedics, most of this research comes from total joint arthroplasty and hip fracture studies. However, there is relatively limited data for ankle fracture. The best studies directly addressing VTE after ORIF of ankle fractures have had important limitations, including missing patient data and suboptimal capture of VTE occurrences,8-10 possibly leading to underestimates of the incidence of VTEs.
Given the limited data available, we conducted a retrospective national-cohort study to determine the incidence of and independent risk factors for VTEs after ankle fracture ORIF. If patients who are at higher risk for VTE can be identified, they can and should be carefully monitored and be considered for VTE prophylaxis. This information is needed for patient counseling and clinical decision-making.
Materials and Methods
This retrospective study used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which captures data from more than 370 participating US hospitals.11 In ACS-NSQIP, 150 patient variables are collected from operative reports, medical records, and patient interviews by trained clinical reviewers.11,12 Patients are identified prospectively and randomly sampled at participating hospitals. Routine auditing is performed to ensure high-quality data. Clinical data are collected for the entire 30-day postoperative period, regardless of discharge status during this time.
Patients who underwent ankle fracture ORIF between 2005 and 2012 were identified in the ACS-NSQIP database. They were initially selected by the postoperative diagnosis of ankle fracture (International Classification of Diseases, Ninth Revision codes 824.0-824.9). Of these patients, only those with primary Current Procedural Terminology codes 27766 (ORIF of medial malleolus fracture), 27769 (ORIF of posterior malleolus fracture), 27792 (ORIF of lateral malleolus fracture), 27814 (ORIF of bimalleollar fracture), and 27822/27823 (ORIF of trimalleollar fracture) were included in the analysis. Patients with incomplete perioperative data were excluded, leaving 4412 patients (out of the initial 4785) for analysis.
Patient characteristics, including sex, age, height, weight, and history of smoking, were collected from the ACS-NSQIP database. Body mass index (BMI) was calculated from each patient’s height and weight. Age was divided into approximately 20-year increments, beginning with age 18 years, in order to compare younger, middle-aged, and elderly groups of patients with ankle fractures. BMI was divided into categories based on the World Health Organization definitions of obesity: under 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or over (class II and class III obesity).13
Information about medical comorbidities is also available in the ACS-NSQIP database. History of pulmonary disease was defined as a history of dyspnea, severe chronic obstructive pulmonary disease, ventilator-assisted respiration within 48 hours before surgery, or current pneumonia. History of heart disease was defined as a history of congestive heart failure (CHF) or angina within 1 month before admission, myocardial infarction within 6 months before admission, cardiac surgery, or percutaneous coronary intervention. American Society of Anesthesiologists (ASA) classes 3 and above signify severe systemic disease. Steroid use was defined as requiring regular administration of corticosteroid medications within 1 month before surgery. Disseminated cancer was defined as a malignancy that has spread to 1 or more sites besides the primary site.
Functional status was defined as the ability to perform activities of daily living (ADLs) within 30 days before surgery. Best functional status during this period was recorded. ACS-NSQIP defines ADLs as the “activities usually performed in the course of a normal day in a person’s life,” including bathing, feeding, dressing, toileting, and mobility. An independent patient does not require assistance for any ADLs; a partially dependent patient requires assistance for some ADLs; and a totally dependent patient requires assistance in all ADLs. Partially and totally dependent patients were grouped for analysis. Anesthesia type was separated into general and nongeneral, which includes monitored anesthesia care, spinal anesthesia, and regional anesthesia.
ACS-NSQIP also records the occurrence of multiple events up to 30 days after surgery. For our study, VTE was defined as the occurrence of a DVT or a PE during this period. ACS-NSQIP defines DVT as a new blood clot or thrombus identified within a vein—with confirmation by duplex ultrasonography, venogram, or computed tomography (CT)—that required therapy (anticoagulation, placement of vena cava filter, and/or clipping of vena cava). PE is recorded if ventilation/perfusion (VQ) scan, CT examination, transesophageal echocardiogram, pulmonary arteriogram, CT angiogram, or any other definitive modality is positive.
Statistical analyses were performed with Stata Version 11.2 (StataCorp). Demographic and comorbidity variables were tested for association with occurrence of VTE using bivariate and multivariate logistic regression.
Final multivariate models were constructed with a backward stepwise process that initially included all potential variables and sequentially excluded variables with the highest P value until only those with P < .200 remained. Variables with .050 < P < .200 were left in the model to control for potential confounding but are not considered significantly associated with the outcome. Statistical significance was established at a 2-sided α of 0.050 (P < .050). The fitness of the final logistic regression model was assessed with the C statistic and the Hosmer-Lemeshow goodness-of-fit test.
Results
For the 4412 ankle fracture patients who met the inclusion criteria, mean (SD) age was 50.9 (18.2) years, and mean (SD) BMI was 30.4 (7.6) kg/m2. The cohort was 40.4% male. Surgery was performed on 235 patients (5.3%) with medial malleolus fracture, 1143 patients (25.9%) with lateral malleolus fracture, 1705 patients (38.6%) with bimalleollar fracture, and 1329 patients (30.1%) with trimalleollar fracture. Table 1 summarizes the patient characteristics.
Of the 33 patients (0.8%) with a VTE recorded within the first 30 postoperative days, 16 (0.4% of all patients) had a DVT recorded, 14 (0.3% of all patients) had a PE recorded, and 3 (0.1% of all patients) had both a DVT and a PE recorded. In 13 (39.4%) of the 33 patients with a VTE, the event occurred after discharge. VTEs were reported a mean (SD) of 11.5 (9.6) days after surgery. No patient in this study died of VTE.
Bivariate logistic regressions were performed to test the association of each patient variable with the occurrence of a VTE. Results are listed in Table 2. The bivariate analyses revealed significant associations between VTE after ankle fracture ORIF and the patient variables of age 60 years or older (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.01-5.72), class I obesity (BMI, 30-35 kg/m2: OR, 5.15, 95% CI, 1.14-23.28), class II and class III obesity (BMI, ≥35 kg/m2: OR, 6.33, 95% CI, 1.41-28.38), ASA classes 3 and 4 (OR, 3.05; 95% CI, 1.53-6.08), history of heart disease (OR, 5.10; 95% CI, 2.08-12.49), history of hypertension (OR, 2.81; 95% CI, 1.39-5.66), and dependent functional status (OR, 3.39; 95% CI, 1.52-7.56).
Multivariate logistic regression was used to control for potential confounding variables and determine which factors were independently associated with VTEs. Results of this analysis are listed in Table 2 as well. The multivariate analysis revealed that the patient variables of class I obesity (BMI, 30-35 kg/m2: OR, 4.77; 95% CI, 1.05-21.72; P = .044), class II and class III obesity (BMI, ≥35 kg/m2: OR, 4.71; 95% CI, 1.03-21.68; P = .046), history of heart disease (OR, 3.28; 95% CI, 1.20-8.97; P = .020), and dependent functional status (OR, 2.59; 95% CI, 1.11-6.04; P = .028) were independently associated with an increased rate of VTEs. Of note, anesthesia type was not significantly associated with occurrence of VTE on bivariate or multivariate analysis.
The C statistic of the final multivariate model was 0.76, indicating very good distinguishing ability. The Hosmer-Lemeshow goodness-of-fit test showed no evidence of lack of fit.
Discussion
Citing the lack of conclusive evidence and the low incidence of VTE after ankle fracture surgery, current recommendations are to avoid routine VTE prophylaxis in the postoperative management of patients who undergo this surgery.1,5 However, it is important to identify patients who are at increased risk, as some may benefit from VTE prophylaxis. In the present study, we used the large, high-quality ACS-NSQIP database collecting information from multiple US hospitals to examine risk factors for VTE after ankle fracture ORIF. We identified 4412 patients who underwent ankle fracture ORIF between 2005 and 2012, and found an overall VTE incidence of 0.8%. Multivariate analysis identified obesity, history of heart disease, and dependent functional status as independent risk factors for VTE after ankle fracture ORIF.
This study’s 0.8% incidence of VTE after ankle fracture ORIF is consistent with the range (0.29%-5%) reported in other ankle fracture studies.4,8-10,14-18 We found that VTEs occurred a mean of about 11 days after surgery, and no patient died of VTE.
Obesity (BMI, ≥30 kg/m2) had the strongest association with VTEs in this study. Obesity, which is a growing public health concern, can make postoperative care and mobilization more difficult.19 Obesity has previously been associated with VTEs after ankle fractures, and BMI of over 25 kg/m2 is one of the Caprini criteria for thrombosis risk factor assessment.6,10 In our study, however, BMI of 25 to 30 kg/m2 was not associated with an increased VTE rate, indicating that moderately overweight patients may not be at significantly higher risk for VTE (compared with patients with normal BMI) and may not need VTE prophylaxis. VTE prophylaxis after ankle fracture surgery may be considered in patients with BMI over 30 kg/m2.
History of heart disease was also associated with VTEs in this study. Patients with a history of heart disease were at 3 times the risk for VTE within 30 days of ankle fracture surgery. This association is also consistent with the Caprini criteria, which include acute myocardial infarction and CHF as risk factors for venous thrombosis.6 Other studies have found associations between CHF and VTE and between cardiovascular risk factors and VTE.7,20 The association between cardiovascular disease and VTE may derive from the decreased venous flow rate associated with CHF or an overall vascular disease state. These patients may benefit from heightened surveillance and postoperative prophylaxis for VTE.
Dependent functional status was the final risk factor found to be associated with VTE after ankle fracture ORIF. This association likely derives from an inability to mobilize independently, leading to increased venous stasis. Immobilization has been previously associated with increased risk for VTE after ankle surgery.7,14,16,20 Caretakers should be aware of this increased risk during the postoperative period and diligently monitor these patients for signs and symptoms of VTE. Prophylaxis may also be considered in this patient population.
Several risk factors that were significant on bivariate analysis (increased age; increased ASA class; history of diabetes, pulmonary disease, hypertension) were not significant in the final multivariate model. This finding suggests covariance between these factors and those that were significant in the final multivariate model. In particular, age and increased overall comorbidity (represented by increased ASA class) were not significant in our multivariate model—contrary to findings of other studies.8-10 It is possible that history of heart disease alone was responsible for the association between overall comorbidity and VTE in those studies. In the present study, separating and controlling for individual comorbidities could have allowed this association to be more precisely characterized.
The characteristics of the ACS-NSQIP database limited our study in several ways. First, although ACS-NSQIP makes significant efforts to collect as many patient variables as possible, some information is not captured. Data about additional factors that may affect VTE risk (eg, history of previous VTE, hypercoagulable state, history of malignancy other than disseminated cancer, tourniquet time, patient position in operating room) were not available. Second, data are collected only on those postoperative adverse events that occur within 30 days after surgery; data on VTEs that occur later are not captured. However, it has been shown that the majority of VTEs occur within the first 30 days after lower extremity trauma and surgery,21,22 so this follow-up interval was deemed adequate for capture of VTE data. Third, the database does not include information on the prophylactic regimens used for these patients—which may have weakened the associations between predictor variables and VTE risk and led to an underestimated effect size. VTE incidence, as well as the odds of developing a VTE with one of the identified risk factors, may actually be higher than reported in this study.
Conclusion
VTEs are serious complications that can occur after ORIF of ankle fractures. In this study, the overall incidence of VTE after ankle fracture ORIF was 0.8%. Although the American Orthopaedic Foot and Ankle Society and the American College of Chest Physicians do not recommend routine screening or prophylaxis for VTE in patients with ankle fractures,1,5 the results of this study showed there may be a benefit in emphasizing VTE prophylaxis after ankle fracture ORIF in patients with obesity, history of heart disease, or dependent functional status. At minimum, these patients should be more carefully monitored for development of VTEs.
1. American Orthopaedic Foot and Ankle Society. Position statement: the use of VTED prophylaxis in foot and ankle surgery. http://www.aofas.org/medical-community/health-policy/Documents/VTED-Position-Statement-Approv-7-9-13-FINAL.pdf. Updated 2013. Accessed May 10, 2015.
2. Grady-Benson JC, Oishi CS, Hanson PB, Colwell CW Jr, Otis SM, Walker RH. Routine postoperative duplex ultrasonography screening and monitoring for the detection of deep vein thrombosis. A survey of 110 total hip arthroplasties. Clin Orthop Relat Res. 1994;(307):130-141.
3. Salzman EW, Harris WH, DeSanctis RW. Anticoagulation for prevention of thromboembolism following fractures of the hip. New Engl J Med. 1966;275(3):122-130.
4. Patil S, Gandhi J, Curzon I, Hui AC. Incidence of deep-vein thrombosis in patients with fractures of the ankle treated in a plaster cast. J Bone Joint Surg Br. 2007;89(10):1340-1343.
5. Falck-Ytter Y, Francis CW, Johanson NA, et al; American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
6. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-78.
7. Mayle RE Jr, DiGiovanni CW, Lin SS, Tabrizi P, Chou LB. Current concepts review: venous thromboembolic disease in foot and ankle surgery. Foot Ankle Int. 2007;28(11):1207-1216.
8. Jameson SS, Augustine A, James P, et al. Venous thromboembolic events following foot and ankle surgery in the English National Health Service. J Bone Joint Surg Br. 2011;93(4):490-497.
9. SooHoo NF, Eagan M, Krenek L, Zingmond DS. Incidence and factors predicting pulmonary embolism and deep venous thrombosis following surgical treatment of ankle fractures. Foot Ankle Surg. 2011;17(4):259-262.
10. Shibuya N, Frost CH, Campbell JD, Davis ML, Jupiter DC. Incidence of acute deep vein thrombosis and pulmonary embolism in foot and ankle trauma: analysis of the National Trauma Data Bank. J Foot Ankle Surg. 2012;51(1):63-68.
11. American College of Surgeons National Surgical Quality Improvement Program. User Guide for the 2012 ACS NSQIP Participant Use Data File. http://site.acsnsqip.org/wp-content/uploads/2013/10/ACSNSQIP.PUF_.UserGuide.2012.pdf. Published October 2013. Accessed May 10, 2015.
12. Khuri SF, Henderson WG, Daley J, et al; Principal Investigators of Patient Safety in Surgery Study. Successful implementation of the Department of Veterans Affairs’ National Surgical Quality Improvement Program in the private sector: the Patient Safety in Surgery study. Ann Surg. 2008;248(2):329-336.
13. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999;282(16):1523-1529.
14. Mizel MS, Temple HT, Michelson JD, et al. Thromboembolism after foot and ankle surgery. A multicenter study. Clin Orthop Relat Res. 1998;(348):180-185.
15. Solis G, Saxby T. Incidence of DVT following surgery of the foot and ankle. Foot Ankle Int. 2002;23(5):411-414.
16. Hanslow SS, Grujic L, Slater HK, Chen D. Thromboembolic disease after foot and ankle surgery. Foot Ankle Int. 2006;27(9):693-695.
17. Pelet S, Roger ME, Belzile EL, Bouchard M. The incidence of thromboembolic events in surgically treated ankle fracture. J Bone Joint Surg Am. 2012;94(6):502-506.
18. Manafi Rasi A, Kazemian G, Emami Moghadam M, et al. Deep vein thrombosis following below knee immobilization: the need for chemoprophylaxis. Trauma Mon. 2013;17(4):367-369.
19. Sabharwal S, Root MZ. Impact of obesity on orthopaedics. J Bone Joint Surg Am. 2012;94(11):1045-1052.
20. Kadous A, Abdelgawad AA, Kanlic E. Deep venous thrombosis and pulmonary embolism after surgical treatment of ankle fractures: a case report and review of literature. J Foot Ankle Surg. 2012;51(4):457-463.
21. Forsythe RM, Peitzman AB, DeCato T, et al. Early lower extremity fracture fixation and the risk of early pulmonary embolus: filter before fixation? J Trauma. 2011;70(6):1381-1388.
22. Bjørnarå BT, Gudmundsen TE, Dahl OE. Frequency and timing of clinical venous thromboembolism after major joint surgery. J Bone Joint Surg Br. 2006;88(3):386-391.
Venous thromboembolic events (VTEs), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), are potentially fatal events that can occur after orthopedic surgery.1 In patients who do not receive prophylaxis, VTE incidence can be as high as 70% for total hip arthroplasty,2 26% for hip fracture,3 and 5% for ankle fracture.4 Based on the relatively low incidence of VTE after ankle fractures and insufficient evidence for VTE prophylaxis in this population, the American Orthopaedic Foot and Ankle Society and the American College of Chest Physicians do not recommend routine screening or prophylaxis for VTE in patients with ankle fractures.1,5 Nevertheless, certain patients may be at increased risk for VTE after open reduction and internal fixation (ORIF) of an ankle fracture. In such cases, further consideration for prophylaxis may be warranted.
Other studies of VTEs have identified general risk factors of increased age, obesity, prior thromboembolic disease, oral contraceptive use, multitrauma, varicose veins, and prolonged immobilization, among others.1,6,7 In orthopedics, most of this research comes from total joint arthroplasty and hip fracture studies. However, there is relatively limited data for ankle fracture. The best studies directly addressing VTE after ORIF of ankle fractures have had important limitations, including missing patient data and suboptimal capture of VTE occurrences,8-10 possibly leading to underestimates of the incidence of VTEs.
Given the limited data available, we conducted a retrospective national-cohort study to determine the incidence of and independent risk factors for VTEs after ankle fracture ORIF. If patients who are at higher risk for VTE can be identified, they can and should be carefully monitored and be considered for VTE prophylaxis. This information is needed for patient counseling and clinical decision-making.
Materials and Methods
This retrospective study used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which captures data from more than 370 participating US hospitals.11 In ACS-NSQIP, 150 patient variables are collected from operative reports, medical records, and patient interviews by trained clinical reviewers.11,12 Patients are identified prospectively and randomly sampled at participating hospitals. Routine auditing is performed to ensure high-quality data. Clinical data are collected for the entire 30-day postoperative period, regardless of discharge status during this time.
Patients who underwent ankle fracture ORIF between 2005 and 2012 were identified in the ACS-NSQIP database. They were initially selected by the postoperative diagnosis of ankle fracture (International Classification of Diseases, Ninth Revision codes 824.0-824.9). Of these patients, only those with primary Current Procedural Terminology codes 27766 (ORIF of medial malleolus fracture), 27769 (ORIF of posterior malleolus fracture), 27792 (ORIF of lateral malleolus fracture), 27814 (ORIF of bimalleollar fracture), and 27822/27823 (ORIF of trimalleollar fracture) were included in the analysis. Patients with incomplete perioperative data were excluded, leaving 4412 patients (out of the initial 4785) for analysis.
Patient characteristics, including sex, age, height, weight, and history of smoking, were collected from the ACS-NSQIP database. Body mass index (BMI) was calculated from each patient’s height and weight. Age was divided into approximately 20-year increments, beginning with age 18 years, in order to compare younger, middle-aged, and elderly groups of patients with ankle fractures. BMI was divided into categories based on the World Health Organization definitions of obesity: under 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or over (class II and class III obesity).13
Information about medical comorbidities is also available in the ACS-NSQIP database. History of pulmonary disease was defined as a history of dyspnea, severe chronic obstructive pulmonary disease, ventilator-assisted respiration within 48 hours before surgery, or current pneumonia. History of heart disease was defined as a history of congestive heart failure (CHF) or angina within 1 month before admission, myocardial infarction within 6 months before admission, cardiac surgery, or percutaneous coronary intervention. American Society of Anesthesiologists (ASA) classes 3 and above signify severe systemic disease. Steroid use was defined as requiring regular administration of corticosteroid medications within 1 month before surgery. Disseminated cancer was defined as a malignancy that has spread to 1 or more sites besides the primary site.
Functional status was defined as the ability to perform activities of daily living (ADLs) within 30 days before surgery. Best functional status during this period was recorded. ACS-NSQIP defines ADLs as the “activities usually performed in the course of a normal day in a person’s life,” including bathing, feeding, dressing, toileting, and mobility. An independent patient does not require assistance for any ADLs; a partially dependent patient requires assistance for some ADLs; and a totally dependent patient requires assistance in all ADLs. Partially and totally dependent patients were grouped for analysis. Anesthesia type was separated into general and nongeneral, which includes monitored anesthesia care, spinal anesthesia, and regional anesthesia.
ACS-NSQIP also records the occurrence of multiple events up to 30 days after surgery. For our study, VTE was defined as the occurrence of a DVT or a PE during this period. ACS-NSQIP defines DVT as a new blood clot or thrombus identified within a vein—with confirmation by duplex ultrasonography, venogram, or computed tomography (CT)—that required therapy (anticoagulation, placement of vena cava filter, and/or clipping of vena cava). PE is recorded if ventilation/perfusion (VQ) scan, CT examination, transesophageal echocardiogram, pulmonary arteriogram, CT angiogram, or any other definitive modality is positive.
Statistical analyses were performed with Stata Version 11.2 (StataCorp). Demographic and comorbidity variables were tested for association with occurrence of VTE using bivariate and multivariate logistic regression.
Final multivariate models were constructed with a backward stepwise process that initially included all potential variables and sequentially excluded variables with the highest P value until only those with P < .200 remained. Variables with .050 < P < .200 were left in the model to control for potential confounding but are not considered significantly associated with the outcome. Statistical significance was established at a 2-sided α of 0.050 (P < .050). The fitness of the final logistic regression model was assessed with the C statistic and the Hosmer-Lemeshow goodness-of-fit test.
Results
For the 4412 ankle fracture patients who met the inclusion criteria, mean (SD) age was 50.9 (18.2) years, and mean (SD) BMI was 30.4 (7.6) kg/m2. The cohort was 40.4% male. Surgery was performed on 235 patients (5.3%) with medial malleolus fracture, 1143 patients (25.9%) with lateral malleolus fracture, 1705 patients (38.6%) with bimalleollar fracture, and 1329 patients (30.1%) with trimalleollar fracture. Table 1 summarizes the patient characteristics.
Of the 33 patients (0.8%) with a VTE recorded within the first 30 postoperative days, 16 (0.4% of all patients) had a DVT recorded, 14 (0.3% of all patients) had a PE recorded, and 3 (0.1% of all patients) had both a DVT and a PE recorded. In 13 (39.4%) of the 33 patients with a VTE, the event occurred after discharge. VTEs were reported a mean (SD) of 11.5 (9.6) days after surgery. No patient in this study died of VTE.
Bivariate logistic regressions were performed to test the association of each patient variable with the occurrence of a VTE. Results are listed in Table 2. The bivariate analyses revealed significant associations between VTE after ankle fracture ORIF and the patient variables of age 60 years or older (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.01-5.72), class I obesity (BMI, 30-35 kg/m2: OR, 5.15, 95% CI, 1.14-23.28), class II and class III obesity (BMI, ≥35 kg/m2: OR, 6.33, 95% CI, 1.41-28.38), ASA classes 3 and 4 (OR, 3.05; 95% CI, 1.53-6.08), history of heart disease (OR, 5.10; 95% CI, 2.08-12.49), history of hypertension (OR, 2.81; 95% CI, 1.39-5.66), and dependent functional status (OR, 3.39; 95% CI, 1.52-7.56).
Multivariate logistic regression was used to control for potential confounding variables and determine which factors were independently associated with VTEs. Results of this analysis are listed in Table 2 as well. The multivariate analysis revealed that the patient variables of class I obesity (BMI, 30-35 kg/m2: OR, 4.77; 95% CI, 1.05-21.72; P = .044), class II and class III obesity (BMI, ≥35 kg/m2: OR, 4.71; 95% CI, 1.03-21.68; P = .046), history of heart disease (OR, 3.28; 95% CI, 1.20-8.97; P = .020), and dependent functional status (OR, 2.59; 95% CI, 1.11-6.04; P = .028) were independently associated with an increased rate of VTEs. Of note, anesthesia type was not significantly associated with occurrence of VTE on bivariate or multivariate analysis.
The C statistic of the final multivariate model was 0.76, indicating very good distinguishing ability. The Hosmer-Lemeshow goodness-of-fit test showed no evidence of lack of fit.
Discussion
Citing the lack of conclusive evidence and the low incidence of VTE after ankle fracture surgery, current recommendations are to avoid routine VTE prophylaxis in the postoperative management of patients who undergo this surgery.1,5 However, it is important to identify patients who are at increased risk, as some may benefit from VTE prophylaxis. In the present study, we used the large, high-quality ACS-NSQIP database collecting information from multiple US hospitals to examine risk factors for VTE after ankle fracture ORIF. We identified 4412 patients who underwent ankle fracture ORIF between 2005 and 2012, and found an overall VTE incidence of 0.8%. Multivariate analysis identified obesity, history of heart disease, and dependent functional status as independent risk factors for VTE after ankle fracture ORIF.
This study’s 0.8% incidence of VTE after ankle fracture ORIF is consistent with the range (0.29%-5%) reported in other ankle fracture studies.4,8-10,14-18 We found that VTEs occurred a mean of about 11 days after surgery, and no patient died of VTE.
Obesity (BMI, ≥30 kg/m2) had the strongest association with VTEs in this study. Obesity, which is a growing public health concern, can make postoperative care and mobilization more difficult.19 Obesity has previously been associated with VTEs after ankle fractures, and BMI of over 25 kg/m2 is one of the Caprini criteria for thrombosis risk factor assessment.6,10 In our study, however, BMI of 25 to 30 kg/m2 was not associated with an increased VTE rate, indicating that moderately overweight patients may not be at significantly higher risk for VTE (compared with patients with normal BMI) and may not need VTE prophylaxis. VTE prophylaxis after ankle fracture surgery may be considered in patients with BMI over 30 kg/m2.
History of heart disease was also associated with VTEs in this study. Patients with a history of heart disease were at 3 times the risk for VTE within 30 days of ankle fracture surgery. This association is also consistent with the Caprini criteria, which include acute myocardial infarction and CHF as risk factors for venous thrombosis.6 Other studies have found associations between CHF and VTE and between cardiovascular risk factors and VTE.7,20 The association between cardiovascular disease and VTE may derive from the decreased venous flow rate associated with CHF or an overall vascular disease state. These patients may benefit from heightened surveillance and postoperative prophylaxis for VTE.
Dependent functional status was the final risk factor found to be associated with VTE after ankle fracture ORIF. This association likely derives from an inability to mobilize independently, leading to increased venous stasis. Immobilization has been previously associated with increased risk for VTE after ankle surgery.7,14,16,20 Caretakers should be aware of this increased risk during the postoperative period and diligently monitor these patients for signs and symptoms of VTE. Prophylaxis may also be considered in this patient population.
Several risk factors that were significant on bivariate analysis (increased age; increased ASA class; history of diabetes, pulmonary disease, hypertension) were not significant in the final multivariate model. This finding suggests covariance between these factors and those that were significant in the final multivariate model. In particular, age and increased overall comorbidity (represented by increased ASA class) were not significant in our multivariate model—contrary to findings of other studies.8-10 It is possible that history of heart disease alone was responsible for the association between overall comorbidity and VTE in those studies. In the present study, separating and controlling for individual comorbidities could have allowed this association to be more precisely characterized.
The characteristics of the ACS-NSQIP database limited our study in several ways. First, although ACS-NSQIP makes significant efforts to collect as many patient variables as possible, some information is not captured. Data about additional factors that may affect VTE risk (eg, history of previous VTE, hypercoagulable state, history of malignancy other than disseminated cancer, tourniquet time, patient position in operating room) were not available. Second, data are collected only on those postoperative adverse events that occur within 30 days after surgery; data on VTEs that occur later are not captured. However, it has been shown that the majority of VTEs occur within the first 30 days after lower extremity trauma and surgery,21,22 so this follow-up interval was deemed adequate for capture of VTE data. Third, the database does not include information on the prophylactic regimens used for these patients—which may have weakened the associations between predictor variables and VTE risk and led to an underestimated effect size. VTE incidence, as well as the odds of developing a VTE with one of the identified risk factors, may actually be higher than reported in this study.
Conclusion
VTEs are serious complications that can occur after ORIF of ankle fractures. In this study, the overall incidence of VTE after ankle fracture ORIF was 0.8%. Although the American Orthopaedic Foot and Ankle Society and the American College of Chest Physicians do not recommend routine screening or prophylaxis for VTE in patients with ankle fractures,1,5 the results of this study showed there may be a benefit in emphasizing VTE prophylaxis after ankle fracture ORIF in patients with obesity, history of heart disease, or dependent functional status. At minimum, these patients should be more carefully monitored for development of VTEs.
Venous thromboembolic events (VTEs), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), are potentially fatal events that can occur after orthopedic surgery.1 In patients who do not receive prophylaxis, VTE incidence can be as high as 70% for total hip arthroplasty,2 26% for hip fracture,3 and 5% for ankle fracture.4 Based on the relatively low incidence of VTE after ankle fractures and insufficient evidence for VTE prophylaxis in this population, the American Orthopaedic Foot and Ankle Society and the American College of Chest Physicians do not recommend routine screening or prophylaxis for VTE in patients with ankle fractures.1,5 Nevertheless, certain patients may be at increased risk for VTE after open reduction and internal fixation (ORIF) of an ankle fracture. In such cases, further consideration for prophylaxis may be warranted.
Other studies of VTEs have identified general risk factors of increased age, obesity, prior thromboembolic disease, oral contraceptive use, multitrauma, varicose veins, and prolonged immobilization, among others.1,6,7 In orthopedics, most of this research comes from total joint arthroplasty and hip fracture studies. However, there is relatively limited data for ankle fracture. The best studies directly addressing VTE after ORIF of ankle fractures have had important limitations, including missing patient data and suboptimal capture of VTE occurrences,8-10 possibly leading to underestimates of the incidence of VTEs.
Given the limited data available, we conducted a retrospective national-cohort study to determine the incidence of and independent risk factors for VTEs after ankle fracture ORIF. If patients who are at higher risk for VTE can be identified, they can and should be carefully monitored and be considered for VTE prophylaxis. This information is needed for patient counseling and clinical decision-making.
Materials and Methods
This retrospective study used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which captures data from more than 370 participating US hospitals.11 In ACS-NSQIP, 150 patient variables are collected from operative reports, medical records, and patient interviews by trained clinical reviewers.11,12 Patients are identified prospectively and randomly sampled at participating hospitals. Routine auditing is performed to ensure high-quality data. Clinical data are collected for the entire 30-day postoperative period, regardless of discharge status during this time.
Patients who underwent ankle fracture ORIF between 2005 and 2012 were identified in the ACS-NSQIP database. They were initially selected by the postoperative diagnosis of ankle fracture (International Classification of Diseases, Ninth Revision codes 824.0-824.9). Of these patients, only those with primary Current Procedural Terminology codes 27766 (ORIF of medial malleolus fracture), 27769 (ORIF of posterior malleolus fracture), 27792 (ORIF of lateral malleolus fracture), 27814 (ORIF of bimalleollar fracture), and 27822/27823 (ORIF of trimalleollar fracture) were included in the analysis. Patients with incomplete perioperative data were excluded, leaving 4412 patients (out of the initial 4785) for analysis.
Patient characteristics, including sex, age, height, weight, and history of smoking, were collected from the ACS-NSQIP database. Body mass index (BMI) was calculated from each patient’s height and weight. Age was divided into approximately 20-year increments, beginning with age 18 years, in order to compare younger, middle-aged, and elderly groups of patients with ankle fractures. BMI was divided into categories based on the World Health Organization definitions of obesity: under 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or over (class II and class III obesity).13
Information about medical comorbidities is also available in the ACS-NSQIP database. History of pulmonary disease was defined as a history of dyspnea, severe chronic obstructive pulmonary disease, ventilator-assisted respiration within 48 hours before surgery, or current pneumonia. History of heart disease was defined as a history of congestive heart failure (CHF) or angina within 1 month before admission, myocardial infarction within 6 months before admission, cardiac surgery, or percutaneous coronary intervention. American Society of Anesthesiologists (ASA) classes 3 and above signify severe systemic disease. Steroid use was defined as requiring regular administration of corticosteroid medications within 1 month before surgery. Disseminated cancer was defined as a malignancy that has spread to 1 or more sites besides the primary site.
Functional status was defined as the ability to perform activities of daily living (ADLs) within 30 days before surgery. Best functional status during this period was recorded. ACS-NSQIP defines ADLs as the “activities usually performed in the course of a normal day in a person’s life,” including bathing, feeding, dressing, toileting, and mobility. An independent patient does not require assistance for any ADLs; a partially dependent patient requires assistance for some ADLs; and a totally dependent patient requires assistance in all ADLs. Partially and totally dependent patients were grouped for analysis. Anesthesia type was separated into general and nongeneral, which includes monitored anesthesia care, spinal anesthesia, and regional anesthesia.
ACS-NSQIP also records the occurrence of multiple events up to 30 days after surgery. For our study, VTE was defined as the occurrence of a DVT or a PE during this period. ACS-NSQIP defines DVT as a new blood clot or thrombus identified within a vein—with confirmation by duplex ultrasonography, venogram, or computed tomography (CT)—that required therapy (anticoagulation, placement of vena cava filter, and/or clipping of vena cava). PE is recorded if ventilation/perfusion (VQ) scan, CT examination, transesophageal echocardiogram, pulmonary arteriogram, CT angiogram, or any other definitive modality is positive.
Statistical analyses were performed with Stata Version 11.2 (StataCorp). Demographic and comorbidity variables were tested for association with occurrence of VTE using bivariate and multivariate logistic regression.
Final multivariate models were constructed with a backward stepwise process that initially included all potential variables and sequentially excluded variables with the highest P value until only those with P < .200 remained. Variables with .050 < P < .200 were left in the model to control for potential confounding but are not considered significantly associated with the outcome. Statistical significance was established at a 2-sided α of 0.050 (P < .050). The fitness of the final logistic regression model was assessed with the C statistic and the Hosmer-Lemeshow goodness-of-fit test.
Results
For the 4412 ankle fracture patients who met the inclusion criteria, mean (SD) age was 50.9 (18.2) years, and mean (SD) BMI was 30.4 (7.6) kg/m2. The cohort was 40.4% male. Surgery was performed on 235 patients (5.3%) with medial malleolus fracture, 1143 patients (25.9%) with lateral malleolus fracture, 1705 patients (38.6%) with bimalleollar fracture, and 1329 patients (30.1%) with trimalleollar fracture. Table 1 summarizes the patient characteristics.
Of the 33 patients (0.8%) with a VTE recorded within the first 30 postoperative days, 16 (0.4% of all patients) had a DVT recorded, 14 (0.3% of all patients) had a PE recorded, and 3 (0.1% of all patients) had both a DVT and a PE recorded. In 13 (39.4%) of the 33 patients with a VTE, the event occurred after discharge. VTEs were reported a mean (SD) of 11.5 (9.6) days after surgery. No patient in this study died of VTE.
Bivariate logistic regressions were performed to test the association of each patient variable with the occurrence of a VTE. Results are listed in Table 2. The bivariate analyses revealed significant associations between VTE after ankle fracture ORIF and the patient variables of age 60 years or older (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.01-5.72), class I obesity (BMI, 30-35 kg/m2: OR, 5.15, 95% CI, 1.14-23.28), class II and class III obesity (BMI, ≥35 kg/m2: OR, 6.33, 95% CI, 1.41-28.38), ASA classes 3 and 4 (OR, 3.05; 95% CI, 1.53-6.08), history of heart disease (OR, 5.10; 95% CI, 2.08-12.49), history of hypertension (OR, 2.81; 95% CI, 1.39-5.66), and dependent functional status (OR, 3.39; 95% CI, 1.52-7.56).
Multivariate logistic regression was used to control for potential confounding variables and determine which factors were independently associated with VTEs. Results of this analysis are listed in Table 2 as well. The multivariate analysis revealed that the patient variables of class I obesity (BMI, 30-35 kg/m2: OR, 4.77; 95% CI, 1.05-21.72; P = .044), class II and class III obesity (BMI, ≥35 kg/m2: OR, 4.71; 95% CI, 1.03-21.68; P = .046), history of heart disease (OR, 3.28; 95% CI, 1.20-8.97; P = .020), and dependent functional status (OR, 2.59; 95% CI, 1.11-6.04; P = .028) were independently associated with an increased rate of VTEs. Of note, anesthesia type was not significantly associated with occurrence of VTE on bivariate or multivariate analysis.
The C statistic of the final multivariate model was 0.76, indicating very good distinguishing ability. The Hosmer-Lemeshow goodness-of-fit test showed no evidence of lack of fit.
Discussion
Citing the lack of conclusive evidence and the low incidence of VTE after ankle fracture surgery, current recommendations are to avoid routine VTE prophylaxis in the postoperative management of patients who undergo this surgery.1,5 However, it is important to identify patients who are at increased risk, as some may benefit from VTE prophylaxis. In the present study, we used the large, high-quality ACS-NSQIP database collecting information from multiple US hospitals to examine risk factors for VTE after ankle fracture ORIF. We identified 4412 patients who underwent ankle fracture ORIF between 2005 and 2012, and found an overall VTE incidence of 0.8%. Multivariate analysis identified obesity, history of heart disease, and dependent functional status as independent risk factors for VTE after ankle fracture ORIF.
This study’s 0.8% incidence of VTE after ankle fracture ORIF is consistent with the range (0.29%-5%) reported in other ankle fracture studies.4,8-10,14-18 We found that VTEs occurred a mean of about 11 days after surgery, and no patient died of VTE.
Obesity (BMI, ≥30 kg/m2) had the strongest association with VTEs in this study. Obesity, which is a growing public health concern, can make postoperative care and mobilization more difficult.19 Obesity has previously been associated with VTEs after ankle fractures, and BMI of over 25 kg/m2 is one of the Caprini criteria for thrombosis risk factor assessment.6,10 In our study, however, BMI of 25 to 30 kg/m2 was not associated with an increased VTE rate, indicating that moderately overweight patients may not be at significantly higher risk for VTE (compared with patients with normal BMI) and may not need VTE prophylaxis. VTE prophylaxis after ankle fracture surgery may be considered in patients with BMI over 30 kg/m2.
History of heart disease was also associated with VTEs in this study. Patients with a history of heart disease were at 3 times the risk for VTE within 30 days of ankle fracture surgery. This association is also consistent with the Caprini criteria, which include acute myocardial infarction and CHF as risk factors for venous thrombosis.6 Other studies have found associations between CHF and VTE and between cardiovascular risk factors and VTE.7,20 The association between cardiovascular disease and VTE may derive from the decreased venous flow rate associated with CHF or an overall vascular disease state. These patients may benefit from heightened surveillance and postoperative prophylaxis for VTE.
Dependent functional status was the final risk factor found to be associated with VTE after ankle fracture ORIF. This association likely derives from an inability to mobilize independently, leading to increased venous stasis. Immobilization has been previously associated with increased risk for VTE after ankle surgery.7,14,16,20 Caretakers should be aware of this increased risk during the postoperative period and diligently monitor these patients for signs and symptoms of VTE. Prophylaxis may also be considered in this patient population.
Several risk factors that were significant on bivariate analysis (increased age; increased ASA class; history of diabetes, pulmonary disease, hypertension) were not significant in the final multivariate model. This finding suggests covariance between these factors and those that were significant in the final multivariate model. In particular, age and increased overall comorbidity (represented by increased ASA class) were not significant in our multivariate model—contrary to findings of other studies.8-10 It is possible that history of heart disease alone was responsible for the association between overall comorbidity and VTE in those studies. In the present study, separating and controlling for individual comorbidities could have allowed this association to be more precisely characterized.
The characteristics of the ACS-NSQIP database limited our study in several ways. First, although ACS-NSQIP makes significant efforts to collect as many patient variables as possible, some information is not captured. Data about additional factors that may affect VTE risk (eg, history of previous VTE, hypercoagulable state, history of malignancy other than disseminated cancer, tourniquet time, patient position in operating room) were not available. Second, data are collected only on those postoperative adverse events that occur within 30 days after surgery; data on VTEs that occur later are not captured. However, it has been shown that the majority of VTEs occur within the first 30 days after lower extremity trauma and surgery,21,22 so this follow-up interval was deemed adequate for capture of VTE data. Third, the database does not include information on the prophylactic regimens used for these patients—which may have weakened the associations between predictor variables and VTE risk and led to an underestimated effect size. VTE incidence, as well as the odds of developing a VTE with one of the identified risk factors, may actually be higher than reported in this study.
Conclusion
VTEs are serious complications that can occur after ORIF of ankle fractures. In this study, the overall incidence of VTE after ankle fracture ORIF was 0.8%. Although the American Orthopaedic Foot and Ankle Society and the American College of Chest Physicians do not recommend routine screening or prophylaxis for VTE in patients with ankle fractures,1,5 the results of this study showed there may be a benefit in emphasizing VTE prophylaxis after ankle fracture ORIF in patients with obesity, history of heart disease, or dependent functional status. At minimum, these patients should be more carefully monitored for development of VTEs.
1. American Orthopaedic Foot and Ankle Society. Position statement: the use of VTED prophylaxis in foot and ankle surgery. http://www.aofas.org/medical-community/health-policy/Documents/VTED-Position-Statement-Approv-7-9-13-FINAL.pdf. Updated 2013. Accessed May 10, 2015.
2. Grady-Benson JC, Oishi CS, Hanson PB, Colwell CW Jr, Otis SM, Walker RH. Routine postoperative duplex ultrasonography screening and monitoring for the detection of deep vein thrombosis. A survey of 110 total hip arthroplasties. Clin Orthop Relat Res. 1994;(307):130-141.
3. Salzman EW, Harris WH, DeSanctis RW. Anticoagulation for prevention of thromboembolism following fractures of the hip. New Engl J Med. 1966;275(3):122-130.
4. Patil S, Gandhi J, Curzon I, Hui AC. Incidence of deep-vein thrombosis in patients with fractures of the ankle treated in a plaster cast. J Bone Joint Surg Br. 2007;89(10):1340-1343.
5. Falck-Ytter Y, Francis CW, Johanson NA, et al; American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
6. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-78.
7. Mayle RE Jr, DiGiovanni CW, Lin SS, Tabrizi P, Chou LB. Current concepts review: venous thromboembolic disease in foot and ankle surgery. Foot Ankle Int. 2007;28(11):1207-1216.
8. Jameson SS, Augustine A, James P, et al. Venous thromboembolic events following foot and ankle surgery in the English National Health Service. J Bone Joint Surg Br. 2011;93(4):490-497.
9. SooHoo NF, Eagan M, Krenek L, Zingmond DS. Incidence and factors predicting pulmonary embolism and deep venous thrombosis following surgical treatment of ankle fractures. Foot Ankle Surg. 2011;17(4):259-262.
10. Shibuya N, Frost CH, Campbell JD, Davis ML, Jupiter DC. Incidence of acute deep vein thrombosis and pulmonary embolism in foot and ankle trauma: analysis of the National Trauma Data Bank. J Foot Ankle Surg. 2012;51(1):63-68.
11. American College of Surgeons National Surgical Quality Improvement Program. User Guide for the 2012 ACS NSQIP Participant Use Data File. http://site.acsnsqip.org/wp-content/uploads/2013/10/ACSNSQIP.PUF_.UserGuide.2012.pdf. Published October 2013. Accessed May 10, 2015.
12. Khuri SF, Henderson WG, Daley J, et al; Principal Investigators of Patient Safety in Surgery Study. Successful implementation of the Department of Veterans Affairs’ National Surgical Quality Improvement Program in the private sector: the Patient Safety in Surgery study. Ann Surg. 2008;248(2):329-336.
13. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999;282(16):1523-1529.
14. Mizel MS, Temple HT, Michelson JD, et al. Thromboembolism after foot and ankle surgery. A multicenter study. Clin Orthop Relat Res. 1998;(348):180-185.
15. Solis G, Saxby T. Incidence of DVT following surgery of the foot and ankle. Foot Ankle Int. 2002;23(5):411-414.
16. Hanslow SS, Grujic L, Slater HK, Chen D. Thromboembolic disease after foot and ankle surgery. Foot Ankle Int. 2006;27(9):693-695.
17. Pelet S, Roger ME, Belzile EL, Bouchard M. The incidence of thromboembolic events in surgically treated ankle fracture. J Bone Joint Surg Am. 2012;94(6):502-506.
18. Manafi Rasi A, Kazemian G, Emami Moghadam M, et al. Deep vein thrombosis following below knee immobilization: the need for chemoprophylaxis. Trauma Mon. 2013;17(4):367-369.
19. Sabharwal S, Root MZ. Impact of obesity on orthopaedics. J Bone Joint Surg Am. 2012;94(11):1045-1052.
20. Kadous A, Abdelgawad AA, Kanlic E. Deep venous thrombosis and pulmonary embolism after surgical treatment of ankle fractures: a case report and review of literature. J Foot Ankle Surg. 2012;51(4):457-463.
21. Forsythe RM, Peitzman AB, DeCato T, et al. Early lower extremity fracture fixation and the risk of early pulmonary embolus: filter before fixation? J Trauma. 2011;70(6):1381-1388.
22. Bjørnarå BT, Gudmundsen TE, Dahl OE. Frequency and timing of clinical venous thromboembolism after major joint surgery. J Bone Joint Surg Br. 2006;88(3):386-391.
1. American Orthopaedic Foot and Ankle Society. Position statement: the use of VTED prophylaxis in foot and ankle surgery. http://www.aofas.org/medical-community/health-policy/Documents/VTED-Position-Statement-Approv-7-9-13-FINAL.pdf. Updated 2013. Accessed May 10, 2015.
2. Grady-Benson JC, Oishi CS, Hanson PB, Colwell CW Jr, Otis SM, Walker RH. Routine postoperative duplex ultrasonography screening and monitoring for the detection of deep vein thrombosis. A survey of 110 total hip arthroplasties. Clin Orthop Relat Res. 1994;(307):130-141.
3. Salzman EW, Harris WH, DeSanctis RW. Anticoagulation for prevention of thromboembolism following fractures of the hip. New Engl J Med. 1966;275(3):122-130.
4. Patil S, Gandhi J, Curzon I, Hui AC. Incidence of deep-vein thrombosis in patients with fractures of the ankle treated in a plaster cast. J Bone Joint Surg Br. 2007;89(10):1340-1343.
5. Falck-Ytter Y, Francis CW, Johanson NA, et al; American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
6. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-78.
7. Mayle RE Jr, DiGiovanni CW, Lin SS, Tabrizi P, Chou LB. Current concepts review: venous thromboembolic disease in foot and ankle surgery. Foot Ankle Int. 2007;28(11):1207-1216.
8. Jameson SS, Augustine A, James P, et al. Venous thromboembolic events following foot and ankle surgery in the English National Health Service. J Bone Joint Surg Br. 2011;93(4):490-497.
9. SooHoo NF, Eagan M, Krenek L, Zingmond DS. Incidence and factors predicting pulmonary embolism and deep venous thrombosis following surgical treatment of ankle fractures. Foot Ankle Surg. 2011;17(4):259-262.
10. Shibuya N, Frost CH, Campbell JD, Davis ML, Jupiter DC. Incidence of acute deep vein thrombosis and pulmonary embolism in foot and ankle trauma: analysis of the National Trauma Data Bank. J Foot Ankle Surg. 2012;51(1):63-68.
11. American College of Surgeons National Surgical Quality Improvement Program. User Guide for the 2012 ACS NSQIP Participant Use Data File. http://site.acsnsqip.org/wp-content/uploads/2013/10/ACSNSQIP.PUF_.UserGuide.2012.pdf. Published October 2013. Accessed May 10, 2015.
12. Khuri SF, Henderson WG, Daley J, et al; Principal Investigators of Patient Safety in Surgery Study. Successful implementation of the Department of Veterans Affairs’ National Surgical Quality Improvement Program in the private sector: the Patient Safety in Surgery study. Ann Surg. 2008;248(2):329-336.
13. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999;282(16):1523-1529.
14. Mizel MS, Temple HT, Michelson JD, et al. Thromboembolism after foot and ankle surgery. A multicenter study. Clin Orthop Relat Res. 1998;(348):180-185.
15. Solis G, Saxby T. Incidence of DVT following surgery of the foot and ankle. Foot Ankle Int. 2002;23(5):411-414.
16. Hanslow SS, Grujic L, Slater HK, Chen D. Thromboembolic disease after foot and ankle surgery. Foot Ankle Int. 2006;27(9):693-695.
17. Pelet S, Roger ME, Belzile EL, Bouchard M. The incidence of thromboembolic events in surgically treated ankle fracture. J Bone Joint Surg Am. 2012;94(6):502-506.
18. Manafi Rasi A, Kazemian G, Emami Moghadam M, et al. Deep vein thrombosis following below knee immobilization: the need for chemoprophylaxis. Trauma Mon. 2013;17(4):367-369.
19. Sabharwal S, Root MZ. Impact of obesity on orthopaedics. J Bone Joint Surg Am. 2012;94(11):1045-1052.
20. Kadous A, Abdelgawad AA, Kanlic E. Deep venous thrombosis and pulmonary embolism after surgical treatment of ankle fractures: a case report and review of literature. J Foot Ankle Surg. 2012;51(4):457-463.
21. Forsythe RM, Peitzman AB, DeCato T, et al. Early lower extremity fracture fixation and the risk of early pulmonary embolus: filter before fixation? J Trauma. 2011;70(6):1381-1388.
22. Bjørnarå BT, Gudmundsen TE, Dahl OE. Frequency and timing of clinical venous thromboembolism after major joint surgery. J Bone Joint Surg Br. 2006;88(3):386-391.
Isolating Suture Slippage During Cadaveric Testing of Knotless Anchors
Knotless suture anchor fixation techniques continue to evolve as efficient, low-profile options for arthroscopic rotator cuff repair (RCR).1,2 Excellent outcomes have been reported for constructs that use knotless fixation laterally, typically in suture bridge-type configurations.2-4 Early comparative biomechanical and clinical studies have also demonstrated equivalent results for all-knotless versus conventional constructs for arthroscopic RCR.5-10 Given the increased use and availability of multiple implant designs, it is important to supplement our clinical knowledge of these devices with laboratory studies delineating the biomechanical properties of the anchors that are used to help guide appropriate clinical use of the implants in specific patient populations.
Several biomechanical studies have shown suture slippage to be the weak but crucial link in the design of knotless anchors and the most likely mode of in vivo failure.11,12 Other studies have demonstrated frequent anchor dislodgement from bone, but these analyses involved use of elderly cadaveric specimens and relatively high-force testing protocols.12,13 Because suture-retention force may have exceeded anchor resistance to pullout (imparted by weak cadaveric bone in such biomechanical settings), the focus on suture-retention properties was limited.11 It is thought that, in clinical practice, the majority of patients who undergo RCR tend not to generate the high forces (relative to resistance to bone pullout) used to cause the anchor pullouts observed in biomechanical studies, particularly in the early postoperative setting.11-15 Cadaveric testing, however, often involves use of specimens with diminished bone mineral density (BMD), relative to age, because of the illness and other factors leading to death and donation.
Using a novel testing apparatus, we isolated, analyzed, and compared suture slippage in 2 anchor designs, one with entirely press-fit suture clamping and the other reliant on an intrinsic suture-locking mechanism.
Materials and Methods
Six human cadaveric proximal humeri specimens were used for this biomechanical study. Mean (SD) age was 53.3 (5.7) years (range, 46-59 years). Middle-aged specimens were used in order to best represent the quality of bone typically encountered in RCR surgery. To approximate tissue in clinical use, we used fresh-frozen cadaver tissue. Specimens were maintained at –20°C until about 24 hours before use and then were thawed to room temperature for testing. Specimens were included only if they had a completely intact humeral head and no prior surgery or hardware placement. Before instrumentation, dual-energy x-ray absorptiometry with a QDR-1000 scanner (Hologic) was used to determine BMD of all proximal humeri.
Two knotless suture anchors were compared: PushLock (4.5×18.5 mm; Arthrex) and ReelX STT (5.5×19.4 mm; Stryker). These anchors have multiple surgical indications (including RCR), allow patient-specific tissue tensioning, and use polyetheretherketone eyelets. The clamping force for PushLock depends entirely on the interference fit achieved for the suture between the outside of the anchor and the surrounding trabecular/cortical bone after device insertion, whereas the suture in ReelX is secured within the anchor shaft entirely by an internal ratchet-locking mechanism.
For anchor insertion, shoulders were dissected down to the greater tuberosity of the proximal humerus, and all implants were inserted (by a fellowship-trained surgeon in accordance with manufacturer guidelines) at a 25° insertion angle with manufacturer-supplied instruments. One anchor of each type (Figure 1) was inserted into the center of the rotator cuff footprint on the greater tuberosity of each specimen. Anterior and posterior positions were randomized, and an anchor from the other group was inserted into the matching location on the contralateral matched-pair specimen. In all instances, distance between the anterior and posterior anchors was 2 cm, and anchors were placed midway between the articular margin and the lateral edge of the greater tuberosity (Figure 2). Two strands of size 2 ultrahigh-molecular-weight–polyethylene Force Fiber (Stryker) were loaded into all anchors.
A custom urethane fixture was secured over the center of each anchor to allow testing to focus on suture slippage by minimizing anchor migration (Figure 3). The small aperture of this device allowed suture tails to pass freely through the center of the fixture but prevented disengagement and proximal migration of the suture anchor from the underlying bone through contact of the urethane fixture with the anchor perimeter. Any system deformation observed during testing was restricted to the suture and/or the anchor’s suture-locking mechanism. Testing fixtures also oriented the suture anchor coaxial with the axis of tension, creating a worst-case loading scenario (Figure 3).
PushLock implants were inserted with 5 pounds of tension, as indicated, using a manufacturer-supplied suture tensioner, and ReelX devices were inserted and locked with 2 full rotations, as specified by the manufacturer. After one end of each suture was cut, as would be done in vivo, the 2 other suture ends, which would have been part of the RCR in vivo, were tied together to form an 8-cm circumference loop that was brought through the urethane fixture. Humeri were then mounted in a materials testing system (MTS 810; MTS Systems) servohydraulic load frame, and the suture loop was passed around a cross-bar on the actuator of the testing device. A mechanical testing protocol consisting of modest repetitive forces was carefully chosen to simulate expected activity during rehabilitation after RCR.15 In this protocol, a 60-second preload of 10 N was followed by tensile loading between 10 N and 90 N at a frequency of 0.5 Hz for 500 cycles.15 Cycle duration at 3 mm and 5 mm of suture slippage (threshold for clinical failure) was recorded.12,16,17 In addition, suture slippage was measured after 1, 10, 50, 100, 200, 300, 400, and 500 cycles. The first 5 test cycles were not counted in the analysis to control for initial knot slippage. Finally, after completion of dynamic testing, samples were loaded at a displacement rate of 0.5 mm/s for tension-to-failure testing in the custom fixtures. Maximum failure load, stiffness, and failure mode were recorded. Ultimate failure was defined as suture breakage or gross suture slippage.
Paired Student t test was used to determine significant differences in suture slippage distance between the 2 groups at various cycle durations. In addition, Kaplan-Meier survival test was used to determine statistical differences in sample survival during the dynamic loading test.
Results
Mean (SD) BMD of the cadaveric shoulder specimens was 0.55 (0.13) g/cm2 (range, 0.29-0.68 g/cm2). The testing fixtures isolated suture slippage from anchor–bone disengagement. All 6 PushLock implants demonstrated slippage of more than 3 mm, and 5 of the 6 demonstrated slippage of more than 5 mm. All 6 ReelX devices exhibited slippage of less than 3 mm. In addition, PushLock demonstrated more suture slippage at cycles 1, 10, and 100 (P < .05) and more maximum slippage after 500 cycles (mean, 11.2 mm; SD, 4.7 mm) compared with ReelX (mean, 1.9 mm; SD, 0.5 mm) (P = .004). Figure 4 shows mean suture slippage at each cycle.
Kaplan-Meier analysis revealed significantly (λ2 = 8.170; P = .0043) decreased survival after dynamic testing for PushLock versus ReelX (Figure 5). Survival was defined as suture slippage of less than 5 mm after completion of dynamic testing. Only 1 of the 6 PushLock anchors completed dynamic testing; the other 5 failed via complete suture slippage from the anchor before testing could be completed. All 6 ReelX devices survived dynamic testing.
Therefore, 1 PushLock implant and all 6 ReelX devices were available for subsequent load-to-failure testing. Failure in this setting was defined as suture slippage of more than 10 mm or suture breakage. The PushLock implant failed at a maximum force of 171.8 N with a stiffness of 74.4 N/mm and eventually exhibited gross suture slippage. All 6 ReelX devices failed at a mean (SD) maximum of 273.5 (20.2) N, with a mean (SD) stiffness of 74.1 (17) N/mm. Mechanism of failure for all ReelX devices was suture breakage during the tensile load-to-failure test.
Discussion
We evaluated a new technique designed to isolate suture slippage in knotless anchors used for RCR. The impetus for developing this new method was to provide a means for better analyzing the ability of a knotless anchor to resist suture slippage in the cadaveric biomechanical testing setting. Suture slippage is an important mode of failure during such analyses.11,12 Significant slippage occurred in a range of implants before half the anchor–bone pullout strength was reached in a study using young bovine femoral heads.11 In another study, using young, high-BMD cadaveric humeral heads, initial slippage and maximum failure loads were equivalent among numerous devices using various suture-retention mechanisms, and suture slippage was the most common failure mode.12 Nevertheless, other biomechanical studies have demonstrated frequent failure caused by anchor pullout in elderly human cadaveric specimens with diminished BMD, often with high-force testing protocols.12,13 In the more modest-force, in vivo rehabilitative environment, suture slippage rather than anchor dislodgement may be the main failure mode.11-15
We compared the PushLock implant and its entirely press-fit suture clamping design with the ReelX device, which relies on an intrinsic suture-locking mechanism. Middle-aged (mean, 53.3 years; SD, 5.7 years) cadaveric humeri were tested under physiologically relevant biomechanical conditions to begin to help identify how relatively osteopenic bone may affect suture-retention properties for a given implant. The results showed that the study methodology prevented implant failure via anchor–bone pullout. To our knowledge, this was the first study to exclusively analyze suture slippage in knotless anchors. The findings indicated that implants that rely heavily on a tight interference fit of the suture between the anchor and the surrounding bone may exhibit early slippage and failure after RCR in middle-aged patients with relative osteopenia.11,12 However, this study also demonstrated that devices with intrinsic clamping mechanisms that do not depend on the quality of surrounding bone may better resist suture slippage. It is not clear that all knotless anchors with intrinsic locking mechanisms function equivalently. For instance, Pietschmann and colleagues12 found that 2 of 10 implants with a different internal clamping device were unable to resist failure via suture slippage, even in healthy bone. Similarly, in a study comparing ReelX devices with implants having a different internal suture-retention mechanism, ReelX failed at higher ultimate loads, and typically via anchor dislodgement, versus suture slippage in the other implants.18
It is important to note that, in the present study, the loads at which sutures broke in the intrinsic clamping anchors approached the maximum contractile force of the supraspinatus muscle (302 N).19,20 In addition, these loads were above the resistance of the rotator cuff tendon to cut out with modern suture material.21
This study’s limitations include use of an in vitro human cadaveric model that precluded analysis of the effects of postoperative healing. Biomechanical testing was also performed in a single row-type suture configuration with the rotator cuff tendon removed. Fixtures used during testing oriented the load coaxially with the axis of tension, creating a worst-case loading scenario. Although this form of testing may limit its clinical applicability, its purpose was to critically isolate how well a knotless anchor could resist suture slippage. The methods we used were also limited because the stability of the bone–anchor interface was not assessed. For patients with osteopenia, anchor pullout rather than suture slippage could be the most limiting factor for knotless anchor construct failure, and therefore further testing of both failure modes is needed. Future biomechanical studies should compare various knotless anchors’ suture-slippage characteristics in other constructs in physiologic testing orientations, including double-row and suture-bridge configurations, as well as with intact rotator cuff tendons. In addition, use of labral tape as a substitute for polyblend suture has been suggested to limit suture slippage, and this technique theoretically could have changed the results of this study.22
Conclusion
An implant with an internal ratcheting mechanism for suture retention demonstrated significantly less suture slippage in an axial tension evaluation protocol than a device reliant on interference fit of the suture between the anchor and surrounding bone. In the clinical setting, this may allow for less gap formation during the healing phase following RCR with a knotless anchor. There was also increased maximum load to failure, demonstrating an increased load until catastrophic failure using a device with a ratcheting internal locking mechanism.
1. Thal R. A knotless suture anchor. Design, function, and biomechanical testing. Am J Sports Med. 2001;29(5):646-649.
2. Cole BJ, ElAttrache NS, Anbari A. Arthroscopic rotator cuff repairs: an anatomic and biomechanical rationale for different suture-anchor repair configurations. Arthroscopy. 2007;23(6):662-669.
3. Kim KC, Shin HD, Cha SM, Lee WY. Comparison of repair integrity and functional outcomes for 3 arthroscopic suture bridge rotator cuff repair techniques. Am J Sports Med. 2013;41(2):271-277.
4. Choi CH, Kim SK, Cho MR, et al. Functional outcomes and structural integrity after double-pulley suture bridge rotator cuff repair using serial ultrasonographic examination. J Shoulder Elbow Surg. 2012;21(12):1753-1763.
5. Brown BS, Cooper AD, McIff TE, Key VH, Toby EB. Initial fixation and cyclic loading stability of knotless suture anchors for rotator cuff repair. J Shoulder Elbow Surg. 2008;17(2):313-318.
6. Burkhart SS, Adams CR, Burkhart SS, Schoolfield JD. A biomechanical comparison of 2 techniques of footprint reconstruction for rotator cuff repair: the SwiveLock-FiberChain construct versus standard double-row repair. Arthroscopy. 2009;25(3):274-281.
7. Hepp P, Osterhoff G, Engel T, Marquass B, Klink T, Josten C. Biomechanical evaluation of knotless anatomical double-layer double-row rotator cuff repair: a comparative ex vivo study. Am J Sports Med. 2009;37(7):1363-1369.
8. Maguire M, Goldberg J, Bokor D, et al. Biomechanical evaluation of four different transosseous-equivalent/suture bridge rotator cuff repairs. Knee Surg Sports Traumatol Arthrosc. 2011;19(9):1582-1587.
9. Millar NL, Wu X, Tantau R, Silverstone E, Murrell GA. Open versus two forms of arthroscopic rotator cuff repair. Clin Orthop Relat Res. 2009;467(4):966-978.
10. Rhee YG, Cho NS, Parke CS. Arthroscopic rotator cuff repair using modified Mason-Allen medial row stitch: knotless versus knot-tying suture bridge technique. Am J Sports Med. 2012;40(11):2440-2447.
11. Wieser K, Farshad M, Vlachopoulos L, Ruffieux K, Gerber C, Meyer DC. Suture slippage in knotless suture anchors as a potential failure mechanism in rotator cuff repair. Arthroscopy. 2012;28(11):1622-1627.
12. Pietschmann MF, Gülecyüz MF, Fieseler S, et al. Biomechanical stability of knotless suture anchors used in rotator cuff repair in healthy and osteopenic bone. Arthroscopy. 2010;26(8):1035-1044.
13. Barber FA, Hapa O, Bynum JA. Comparative testing by cyclic loading of rotator cuff suture anchors containing multiple high-strength sutures. Arthroscopy. 2010;26(9 suppl):S134-S141.
14. Barber FA, Coons DA, Ruiz-Suarez M. Cyclic load testing of biodegradable suture anchors containing 2 high-strength sutures. Arthroscopy. 2007;23(4):355-360.
15. Bynum CK, Lee S, Mahar A, Tasto J, Pedowitz R. Failure mode of suture anchors as a function of insertion depth. Am J Sports Med. 2005;33(7):1030-1034.
16. Gerber C, Schneeberger AG, Beck M, Schlegel U. Mechanical strength of repairs of the rotator cuff. J Bone Joint Surg Br. 1994;76(3):371-380.
17. Schneeberger AG, von Roll A, Kalberer F, Jacob HA, Gerber C. Mechanical strength of arthroscopic rotator cuff repair techniques: an in vitro study. J Bone Joint Surg Am. 2002;84(12):2152-2160.
18. Efird C, Traub S, Baldini T, et al. Knotless single-row rotator cuff repair: a comparative biomechanical study of 2 knotless suture anchors. Orthopedics. 2013;36(8):e1033-e1037.
19. Wright PB, Budoff JE, Yeh ML, Kelm ZS, Luo ZP. Strength of damaged suture: an in vitro study. Arthroscopy. 2006;22(12):1270-1275.
20. Burkhart SS. A stepwise approach to arthroscopic rotator cuff repair based on biomechanical principles. Arthroscopy. 2000;16(1):82-90.
21. Bisson LJ, Manohar LM. A biomechanical comparison of the pullout strength of No. 2 FiberWire suture and 2-mm FiberWire tape in bovine rotator cuff tendons. Arthroscopy. 2010;26(11):1463-1468.
22. Burkhart SS, Denard PJ, Konicek J, Hanypsiak BT. Biomechanical validation of load-sharing rip-stop fixation for the repair of tissue-deficient rotator cuff tears. Am J Sports Med. 2014;42(2):457-462.
Knotless suture anchor fixation techniques continue to evolve as efficient, low-profile options for arthroscopic rotator cuff repair (RCR).1,2 Excellent outcomes have been reported for constructs that use knotless fixation laterally, typically in suture bridge-type configurations.2-4 Early comparative biomechanical and clinical studies have also demonstrated equivalent results for all-knotless versus conventional constructs for arthroscopic RCR.5-10 Given the increased use and availability of multiple implant designs, it is important to supplement our clinical knowledge of these devices with laboratory studies delineating the biomechanical properties of the anchors that are used to help guide appropriate clinical use of the implants in specific patient populations.
Several biomechanical studies have shown suture slippage to be the weak but crucial link in the design of knotless anchors and the most likely mode of in vivo failure.11,12 Other studies have demonstrated frequent anchor dislodgement from bone, but these analyses involved use of elderly cadaveric specimens and relatively high-force testing protocols.12,13 Because suture-retention force may have exceeded anchor resistance to pullout (imparted by weak cadaveric bone in such biomechanical settings), the focus on suture-retention properties was limited.11 It is thought that, in clinical practice, the majority of patients who undergo RCR tend not to generate the high forces (relative to resistance to bone pullout) used to cause the anchor pullouts observed in biomechanical studies, particularly in the early postoperative setting.11-15 Cadaveric testing, however, often involves use of specimens with diminished bone mineral density (BMD), relative to age, because of the illness and other factors leading to death and donation.
Using a novel testing apparatus, we isolated, analyzed, and compared suture slippage in 2 anchor designs, one with entirely press-fit suture clamping and the other reliant on an intrinsic suture-locking mechanism.
Materials and Methods
Six human cadaveric proximal humeri specimens were used for this biomechanical study. Mean (SD) age was 53.3 (5.7) years (range, 46-59 years). Middle-aged specimens were used in order to best represent the quality of bone typically encountered in RCR surgery. To approximate tissue in clinical use, we used fresh-frozen cadaver tissue. Specimens were maintained at –20°C until about 24 hours before use and then were thawed to room temperature for testing. Specimens were included only if they had a completely intact humeral head and no prior surgery or hardware placement. Before instrumentation, dual-energy x-ray absorptiometry with a QDR-1000 scanner (Hologic) was used to determine BMD of all proximal humeri.
Two knotless suture anchors were compared: PushLock (4.5×18.5 mm; Arthrex) and ReelX STT (5.5×19.4 mm; Stryker). These anchors have multiple surgical indications (including RCR), allow patient-specific tissue tensioning, and use polyetheretherketone eyelets. The clamping force for PushLock depends entirely on the interference fit achieved for the suture between the outside of the anchor and the surrounding trabecular/cortical bone after device insertion, whereas the suture in ReelX is secured within the anchor shaft entirely by an internal ratchet-locking mechanism.
For anchor insertion, shoulders were dissected down to the greater tuberosity of the proximal humerus, and all implants were inserted (by a fellowship-trained surgeon in accordance with manufacturer guidelines) at a 25° insertion angle with manufacturer-supplied instruments. One anchor of each type (Figure 1) was inserted into the center of the rotator cuff footprint on the greater tuberosity of each specimen. Anterior and posterior positions were randomized, and an anchor from the other group was inserted into the matching location on the contralateral matched-pair specimen. In all instances, distance between the anterior and posterior anchors was 2 cm, and anchors were placed midway between the articular margin and the lateral edge of the greater tuberosity (Figure 2). Two strands of size 2 ultrahigh-molecular-weight–polyethylene Force Fiber (Stryker) were loaded into all anchors.
A custom urethane fixture was secured over the center of each anchor to allow testing to focus on suture slippage by minimizing anchor migration (Figure 3). The small aperture of this device allowed suture tails to pass freely through the center of the fixture but prevented disengagement and proximal migration of the suture anchor from the underlying bone through contact of the urethane fixture with the anchor perimeter. Any system deformation observed during testing was restricted to the suture and/or the anchor’s suture-locking mechanism. Testing fixtures also oriented the suture anchor coaxial with the axis of tension, creating a worst-case loading scenario (Figure 3).
PushLock implants were inserted with 5 pounds of tension, as indicated, using a manufacturer-supplied suture tensioner, and ReelX devices were inserted and locked with 2 full rotations, as specified by the manufacturer. After one end of each suture was cut, as would be done in vivo, the 2 other suture ends, which would have been part of the RCR in vivo, were tied together to form an 8-cm circumference loop that was brought through the urethane fixture. Humeri were then mounted in a materials testing system (MTS 810; MTS Systems) servohydraulic load frame, and the suture loop was passed around a cross-bar on the actuator of the testing device. A mechanical testing protocol consisting of modest repetitive forces was carefully chosen to simulate expected activity during rehabilitation after RCR.15 In this protocol, a 60-second preload of 10 N was followed by tensile loading between 10 N and 90 N at a frequency of 0.5 Hz for 500 cycles.15 Cycle duration at 3 mm and 5 mm of suture slippage (threshold for clinical failure) was recorded.12,16,17 In addition, suture slippage was measured after 1, 10, 50, 100, 200, 300, 400, and 500 cycles. The first 5 test cycles were not counted in the analysis to control for initial knot slippage. Finally, after completion of dynamic testing, samples were loaded at a displacement rate of 0.5 mm/s for tension-to-failure testing in the custom fixtures. Maximum failure load, stiffness, and failure mode were recorded. Ultimate failure was defined as suture breakage or gross suture slippage.
Paired Student t test was used to determine significant differences in suture slippage distance between the 2 groups at various cycle durations. In addition, Kaplan-Meier survival test was used to determine statistical differences in sample survival during the dynamic loading test.
Results
Mean (SD) BMD of the cadaveric shoulder specimens was 0.55 (0.13) g/cm2 (range, 0.29-0.68 g/cm2). The testing fixtures isolated suture slippage from anchor–bone disengagement. All 6 PushLock implants demonstrated slippage of more than 3 mm, and 5 of the 6 demonstrated slippage of more than 5 mm. All 6 ReelX devices exhibited slippage of less than 3 mm. In addition, PushLock demonstrated more suture slippage at cycles 1, 10, and 100 (P < .05) and more maximum slippage after 500 cycles (mean, 11.2 mm; SD, 4.7 mm) compared with ReelX (mean, 1.9 mm; SD, 0.5 mm) (P = .004). Figure 4 shows mean suture slippage at each cycle.
Kaplan-Meier analysis revealed significantly (λ2 = 8.170; P = .0043) decreased survival after dynamic testing for PushLock versus ReelX (Figure 5). Survival was defined as suture slippage of less than 5 mm after completion of dynamic testing. Only 1 of the 6 PushLock anchors completed dynamic testing; the other 5 failed via complete suture slippage from the anchor before testing could be completed. All 6 ReelX devices survived dynamic testing.
Therefore, 1 PushLock implant and all 6 ReelX devices were available for subsequent load-to-failure testing. Failure in this setting was defined as suture slippage of more than 10 mm or suture breakage. The PushLock implant failed at a maximum force of 171.8 N with a stiffness of 74.4 N/mm and eventually exhibited gross suture slippage. All 6 ReelX devices failed at a mean (SD) maximum of 273.5 (20.2) N, with a mean (SD) stiffness of 74.1 (17) N/mm. Mechanism of failure for all ReelX devices was suture breakage during the tensile load-to-failure test.
Discussion
We evaluated a new technique designed to isolate suture slippage in knotless anchors used for RCR. The impetus for developing this new method was to provide a means for better analyzing the ability of a knotless anchor to resist suture slippage in the cadaveric biomechanical testing setting. Suture slippage is an important mode of failure during such analyses.11,12 Significant slippage occurred in a range of implants before half the anchor–bone pullout strength was reached in a study using young bovine femoral heads.11 In another study, using young, high-BMD cadaveric humeral heads, initial slippage and maximum failure loads were equivalent among numerous devices using various suture-retention mechanisms, and suture slippage was the most common failure mode.12 Nevertheless, other biomechanical studies have demonstrated frequent failure caused by anchor pullout in elderly human cadaveric specimens with diminished BMD, often with high-force testing protocols.12,13 In the more modest-force, in vivo rehabilitative environment, suture slippage rather than anchor dislodgement may be the main failure mode.11-15
We compared the PushLock implant and its entirely press-fit suture clamping design with the ReelX device, which relies on an intrinsic suture-locking mechanism. Middle-aged (mean, 53.3 years; SD, 5.7 years) cadaveric humeri were tested under physiologically relevant biomechanical conditions to begin to help identify how relatively osteopenic bone may affect suture-retention properties for a given implant. The results showed that the study methodology prevented implant failure via anchor–bone pullout. To our knowledge, this was the first study to exclusively analyze suture slippage in knotless anchors. The findings indicated that implants that rely heavily on a tight interference fit of the suture between the anchor and the surrounding bone may exhibit early slippage and failure after RCR in middle-aged patients with relative osteopenia.11,12 However, this study also demonstrated that devices with intrinsic clamping mechanisms that do not depend on the quality of surrounding bone may better resist suture slippage. It is not clear that all knotless anchors with intrinsic locking mechanisms function equivalently. For instance, Pietschmann and colleagues12 found that 2 of 10 implants with a different internal clamping device were unable to resist failure via suture slippage, even in healthy bone. Similarly, in a study comparing ReelX devices with implants having a different internal suture-retention mechanism, ReelX failed at higher ultimate loads, and typically via anchor dislodgement, versus suture slippage in the other implants.18
It is important to note that, in the present study, the loads at which sutures broke in the intrinsic clamping anchors approached the maximum contractile force of the supraspinatus muscle (302 N).19,20 In addition, these loads were above the resistance of the rotator cuff tendon to cut out with modern suture material.21
This study’s limitations include use of an in vitro human cadaveric model that precluded analysis of the effects of postoperative healing. Biomechanical testing was also performed in a single row-type suture configuration with the rotator cuff tendon removed. Fixtures used during testing oriented the load coaxially with the axis of tension, creating a worst-case loading scenario. Although this form of testing may limit its clinical applicability, its purpose was to critically isolate how well a knotless anchor could resist suture slippage. The methods we used were also limited because the stability of the bone–anchor interface was not assessed. For patients with osteopenia, anchor pullout rather than suture slippage could be the most limiting factor for knotless anchor construct failure, and therefore further testing of both failure modes is needed. Future biomechanical studies should compare various knotless anchors’ suture-slippage characteristics in other constructs in physiologic testing orientations, including double-row and suture-bridge configurations, as well as with intact rotator cuff tendons. In addition, use of labral tape as a substitute for polyblend suture has been suggested to limit suture slippage, and this technique theoretically could have changed the results of this study.22
Conclusion
An implant with an internal ratcheting mechanism for suture retention demonstrated significantly less suture slippage in an axial tension evaluation protocol than a device reliant on interference fit of the suture between the anchor and surrounding bone. In the clinical setting, this may allow for less gap formation during the healing phase following RCR with a knotless anchor. There was also increased maximum load to failure, demonstrating an increased load until catastrophic failure using a device with a ratcheting internal locking mechanism.
Knotless suture anchor fixation techniques continue to evolve as efficient, low-profile options for arthroscopic rotator cuff repair (RCR).1,2 Excellent outcomes have been reported for constructs that use knotless fixation laterally, typically in suture bridge-type configurations.2-4 Early comparative biomechanical and clinical studies have also demonstrated equivalent results for all-knotless versus conventional constructs for arthroscopic RCR.5-10 Given the increased use and availability of multiple implant designs, it is important to supplement our clinical knowledge of these devices with laboratory studies delineating the biomechanical properties of the anchors that are used to help guide appropriate clinical use of the implants in specific patient populations.
Several biomechanical studies have shown suture slippage to be the weak but crucial link in the design of knotless anchors and the most likely mode of in vivo failure.11,12 Other studies have demonstrated frequent anchor dislodgement from bone, but these analyses involved use of elderly cadaveric specimens and relatively high-force testing protocols.12,13 Because suture-retention force may have exceeded anchor resistance to pullout (imparted by weak cadaveric bone in such biomechanical settings), the focus on suture-retention properties was limited.11 It is thought that, in clinical practice, the majority of patients who undergo RCR tend not to generate the high forces (relative to resistance to bone pullout) used to cause the anchor pullouts observed in biomechanical studies, particularly in the early postoperative setting.11-15 Cadaveric testing, however, often involves use of specimens with diminished bone mineral density (BMD), relative to age, because of the illness and other factors leading to death and donation.
Using a novel testing apparatus, we isolated, analyzed, and compared suture slippage in 2 anchor designs, one with entirely press-fit suture clamping and the other reliant on an intrinsic suture-locking mechanism.
Materials and Methods
Six human cadaveric proximal humeri specimens were used for this biomechanical study. Mean (SD) age was 53.3 (5.7) years (range, 46-59 years). Middle-aged specimens were used in order to best represent the quality of bone typically encountered in RCR surgery. To approximate tissue in clinical use, we used fresh-frozen cadaver tissue. Specimens were maintained at –20°C until about 24 hours before use and then were thawed to room temperature for testing. Specimens were included only if they had a completely intact humeral head and no prior surgery or hardware placement. Before instrumentation, dual-energy x-ray absorptiometry with a QDR-1000 scanner (Hologic) was used to determine BMD of all proximal humeri.
Two knotless suture anchors were compared: PushLock (4.5×18.5 mm; Arthrex) and ReelX STT (5.5×19.4 mm; Stryker). These anchors have multiple surgical indications (including RCR), allow patient-specific tissue tensioning, and use polyetheretherketone eyelets. The clamping force for PushLock depends entirely on the interference fit achieved for the suture between the outside of the anchor and the surrounding trabecular/cortical bone after device insertion, whereas the suture in ReelX is secured within the anchor shaft entirely by an internal ratchet-locking mechanism.
For anchor insertion, shoulders were dissected down to the greater tuberosity of the proximal humerus, and all implants were inserted (by a fellowship-trained surgeon in accordance with manufacturer guidelines) at a 25° insertion angle with manufacturer-supplied instruments. One anchor of each type (Figure 1) was inserted into the center of the rotator cuff footprint on the greater tuberosity of each specimen. Anterior and posterior positions were randomized, and an anchor from the other group was inserted into the matching location on the contralateral matched-pair specimen. In all instances, distance between the anterior and posterior anchors was 2 cm, and anchors were placed midway between the articular margin and the lateral edge of the greater tuberosity (Figure 2). Two strands of size 2 ultrahigh-molecular-weight–polyethylene Force Fiber (Stryker) were loaded into all anchors.
A custom urethane fixture was secured over the center of each anchor to allow testing to focus on suture slippage by minimizing anchor migration (Figure 3). The small aperture of this device allowed suture tails to pass freely through the center of the fixture but prevented disengagement and proximal migration of the suture anchor from the underlying bone through contact of the urethane fixture with the anchor perimeter. Any system deformation observed during testing was restricted to the suture and/or the anchor’s suture-locking mechanism. Testing fixtures also oriented the suture anchor coaxial with the axis of tension, creating a worst-case loading scenario (Figure 3).
PushLock implants were inserted with 5 pounds of tension, as indicated, using a manufacturer-supplied suture tensioner, and ReelX devices were inserted and locked with 2 full rotations, as specified by the manufacturer. After one end of each suture was cut, as would be done in vivo, the 2 other suture ends, which would have been part of the RCR in vivo, were tied together to form an 8-cm circumference loop that was brought through the urethane fixture. Humeri were then mounted in a materials testing system (MTS 810; MTS Systems) servohydraulic load frame, and the suture loop was passed around a cross-bar on the actuator of the testing device. A mechanical testing protocol consisting of modest repetitive forces was carefully chosen to simulate expected activity during rehabilitation after RCR.15 In this protocol, a 60-second preload of 10 N was followed by tensile loading between 10 N and 90 N at a frequency of 0.5 Hz for 500 cycles.15 Cycle duration at 3 mm and 5 mm of suture slippage (threshold for clinical failure) was recorded.12,16,17 In addition, suture slippage was measured after 1, 10, 50, 100, 200, 300, 400, and 500 cycles. The first 5 test cycles were not counted in the analysis to control for initial knot slippage. Finally, after completion of dynamic testing, samples were loaded at a displacement rate of 0.5 mm/s for tension-to-failure testing in the custom fixtures. Maximum failure load, stiffness, and failure mode were recorded. Ultimate failure was defined as suture breakage or gross suture slippage.
Paired Student t test was used to determine significant differences in suture slippage distance between the 2 groups at various cycle durations. In addition, Kaplan-Meier survival test was used to determine statistical differences in sample survival during the dynamic loading test.
Results
Mean (SD) BMD of the cadaveric shoulder specimens was 0.55 (0.13) g/cm2 (range, 0.29-0.68 g/cm2). The testing fixtures isolated suture slippage from anchor–bone disengagement. All 6 PushLock implants demonstrated slippage of more than 3 mm, and 5 of the 6 demonstrated slippage of more than 5 mm. All 6 ReelX devices exhibited slippage of less than 3 mm. In addition, PushLock demonstrated more suture slippage at cycles 1, 10, and 100 (P < .05) and more maximum slippage after 500 cycles (mean, 11.2 mm; SD, 4.7 mm) compared with ReelX (mean, 1.9 mm; SD, 0.5 mm) (P = .004). Figure 4 shows mean suture slippage at each cycle.
Kaplan-Meier analysis revealed significantly (λ2 = 8.170; P = .0043) decreased survival after dynamic testing for PushLock versus ReelX (Figure 5). Survival was defined as suture slippage of less than 5 mm after completion of dynamic testing. Only 1 of the 6 PushLock anchors completed dynamic testing; the other 5 failed via complete suture slippage from the anchor before testing could be completed. All 6 ReelX devices survived dynamic testing.
Therefore, 1 PushLock implant and all 6 ReelX devices were available for subsequent load-to-failure testing. Failure in this setting was defined as suture slippage of more than 10 mm or suture breakage. The PushLock implant failed at a maximum force of 171.8 N with a stiffness of 74.4 N/mm and eventually exhibited gross suture slippage. All 6 ReelX devices failed at a mean (SD) maximum of 273.5 (20.2) N, with a mean (SD) stiffness of 74.1 (17) N/mm. Mechanism of failure for all ReelX devices was suture breakage during the tensile load-to-failure test.
Discussion
We evaluated a new technique designed to isolate suture slippage in knotless anchors used for RCR. The impetus for developing this new method was to provide a means for better analyzing the ability of a knotless anchor to resist suture slippage in the cadaveric biomechanical testing setting. Suture slippage is an important mode of failure during such analyses.11,12 Significant slippage occurred in a range of implants before half the anchor–bone pullout strength was reached in a study using young bovine femoral heads.11 In another study, using young, high-BMD cadaveric humeral heads, initial slippage and maximum failure loads were equivalent among numerous devices using various suture-retention mechanisms, and suture slippage was the most common failure mode.12 Nevertheless, other biomechanical studies have demonstrated frequent failure caused by anchor pullout in elderly human cadaveric specimens with diminished BMD, often with high-force testing protocols.12,13 In the more modest-force, in vivo rehabilitative environment, suture slippage rather than anchor dislodgement may be the main failure mode.11-15
We compared the PushLock implant and its entirely press-fit suture clamping design with the ReelX device, which relies on an intrinsic suture-locking mechanism. Middle-aged (mean, 53.3 years; SD, 5.7 years) cadaveric humeri were tested under physiologically relevant biomechanical conditions to begin to help identify how relatively osteopenic bone may affect suture-retention properties for a given implant. The results showed that the study methodology prevented implant failure via anchor–bone pullout. To our knowledge, this was the first study to exclusively analyze suture slippage in knotless anchors. The findings indicated that implants that rely heavily on a tight interference fit of the suture between the anchor and the surrounding bone may exhibit early slippage and failure after RCR in middle-aged patients with relative osteopenia.11,12 However, this study also demonstrated that devices with intrinsic clamping mechanisms that do not depend on the quality of surrounding bone may better resist suture slippage. It is not clear that all knotless anchors with intrinsic locking mechanisms function equivalently. For instance, Pietschmann and colleagues12 found that 2 of 10 implants with a different internal clamping device were unable to resist failure via suture slippage, even in healthy bone. Similarly, in a study comparing ReelX devices with implants having a different internal suture-retention mechanism, ReelX failed at higher ultimate loads, and typically via anchor dislodgement, versus suture slippage in the other implants.18
It is important to note that, in the present study, the loads at which sutures broke in the intrinsic clamping anchors approached the maximum contractile force of the supraspinatus muscle (302 N).19,20 In addition, these loads were above the resistance of the rotator cuff tendon to cut out with modern suture material.21
This study’s limitations include use of an in vitro human cadaveric model that precluded analysis of the effects of postoperative healing. Biomechanical testing was also performed in a single row-type suture configuration with the rotator cuff tendon removed. Fixtures used during testing oriented the load coaxially with the axis of tension, creating a worst-case loading scenario. Although this form of testing may limit its clinical applicability, its purpose was to critically isolate how well a knotless anchor could resist suture slippage. The methods we used were also limited because the stability of the bone–anchor interface was not assessed. For patients with osteopenia, anchor pullout rather than suture slippage could be the most limiting factor for knotless anchor construct failure, and therefore further testing of both failure modes is needed. Future biomechanical studies should compare various knotless anchors’ suture-slippage characteristics in other constructs in physiologic testing orientations, including double-row and suture-bridge configurations, as well as with intact rotator cuff tendons. In addition, use of labral tape as a substitute for polyblend suture has been suggested to limit suture slippage, and this technique theoretically could have changed the results of this study.22
Conclusion
An implant with an internal ratcheting mechanism for suture retention demonstrated significantly less suture slippage in an axial tension evaluation protocol than a device reliant on interference fit of the suture between the anchor and surrounding bone. In the clinical setting, this may allow for less gap formation during the healing phase following RCR with a knotless anchor. There was also increased maximum load to failure, demonstrating an increased load until catastrophic failure using a device with a ratcheting internal locking mechanism.
1. Thal R. A knotless suture anchor. Design, function, and biomechanical testing. Am J Sports Med. 2001;29(5):646-649.
2. Cole BJ, ElAttrache NS, Anbari A. Arthroscopic rotator cuff repairs: an anatomic and biomechanical rationale for different suture-anchor repair configurations. Arthroscopy. 2007;23(6):662-669.
3. Kim KC, Shin HD, Cha SM, Lee WY. Comparison of repair integrity and functional outcomes for 3 arthroscopic suture bridge rotator cuff repair techniques. Am J Sports Med. 2013;41(2):271-277.
4. Choi CH, Kim SK, Cho MR, et al. Functional outcomes and structural integrity after double-pulley suture bridge rotator cuff repair using serial ultrasonographic examination. J Shoulder Elbow Surg. 2012;21(12):1753-1763.
5. Brown BS, Cooper AD, McIff TE, Key VH, Toby EB. Initial fixation and cyclic loading stability of knotless suture anchors for rotator cuff repair. J Shoulder Elbow Surg. 2008;17(2):313-318.
6. Burkhart SS, Adams CR, Burkhart SS, Schoolfield JD. A biomechanical comparison of 2 techniques of footprint reconstruction for rotator cuff repair: the SwiveLock-FiberChain construct versus standard double-row repair. Arthroscopy. 2009;25(3):274-281.
7. Hepp P, Osterhoff G, Engel T, Marquass B, Klink T, Josten C. Biomechanical evaluation of knotless anatomical double-layer double-row rotator cuff repair: a comparative ex vivo study. Am J Sports Med. 2009;37(7):1363-1369.
8. Maguire M, Goldberg J, Bokor D, et al. Biomechanical evaluation of four different transosseous-equivalent/suture bridge rotator cuff repairs. Knee Surg Sports Traumatol Arthrosc. 2011;19(9):1582-1587.
9. Millar NL, Wu X, Tantau R, Silverstone E, Murrell GA. Open versus two forms of arthroscopic rotator cuff repair. Clin Orthop Relat Res. 2009;467(4):966-978.
10. Rhee YG, Cho NS, Parke CS. Arthroscopic rotator cuff repair using modified Mason-Allen medial row stitch: knotless versus knot-tying suture bridge technique. Am J Sports Med. 2012;40(11):2440-2447.
11. Wieser K, Farshad M, Vlachopoulos L, Ruffieux K, Gerber C, Meyer DC. Suture slippage in knotless suture anchors as a potential failure mechanism in rotator cuff repair. Arthroscopy. 2012;28(11):1622-1627.
12. Pietschmann MF, Gülecyüz MF, Fieseler S, et al. Biomechanical stability of knotless suture anchors used in rotator cuff repair in healthy and osteopenic bone. Arthroscopy. 2010;26(8):1035-1044.
13. Barber FA, Hapa O, Bynum JA. Comparative testing by cyclic loading of rotator cuff suture anchors containing multiple high-strength sutures. Arthroscopy. 2010;26(9 suppl):S134-S141.
14. Barber FA, Coons DA, Ruiz-Suarez M. Cyclic load testing of biodegradable suture anchors containing 2 high-strength sutures. Arthroscopy. 2007;23(4):355-360.
15. Bynum CK, Lee S, Mahar A, Tasto J, Pedowitz R. Failure mode of suture anchors as a function of insertion depth. Am J Sports Med. 2005;33(7):1030-1034.
16. Gerber C, Schneeberger AG, Beck M, Schlegel U. Mechanical strength of repairs of the rotator cuff. J Bone Joint Surg Br. 1994;76(3):371-380.
17. Schneeberger AG, von Roll A, Kalberer F, Jacob HA, Gerber C. Mechanical strength of arthroscopic rotator cuff repair techniques: an in vitro study. J Bone Joint Surg Am. 2002;84(12):2152-2160.
18. Efird C, Traub S, Baldini T, et al. Knotless single-row rotator cuff repair: a comparative biomechanical study of 2 knotless suture anchors. Orthopedics. 2013;36(8):e1033-e1037.
19. Wright PB, Budoff JE, Yeh ML, Kelm ZS, Luo ZP. Strength of damaged suture: an in vitro study. Arthroscopy. 2006;22(12):1270-1275.
20. Burkhart SS. A stepwise approach to arthroscopic rotator cuff repair based on biomechanical principles. Arthroscopy. 2000;16(1):82-90.
21. Bisson LJ, Manohar LM. A biomechanical comparison of the pullout strength of No. 2 FiberWire suture and 2-mm FiberWire tape in bovine rotator cuff tendons. Arthroscopy. 2010;26(11):1463-1468.
22. Burkhart SS, Denard PJ, Konicek J, Hanypsiak BT. Biomechanical validation of load-sharing rip-stop fixation for the repair of tissue-deficient rotator cuff tears. Am J Sports Med. 2014;42(2):457-462.
1. Thal R. A knotless suture anchor. Design, function, and biomechanical testing. Am J Sports Med. 2001;29(5):646-649.
2. Cole BJ, ElAttrache NS, Anbari A. Arthroscopic rotator cuff repairs: an anatomic and biomechanical rationale for different suture-anchor repair configurations. Arthroscopy. 2007;23(6):662-669.
3. Kim KC, Shin HD, Cha SM, Lee WY. Comparison of repair integrity and functional outcomes for 3 arthroscopic suture bridge rotator cuff repair techniques. Am J Sports Med. 2013;41(2):271-277.
4. Choi CH, Kim SK, Cho MR, et al. Functional outcomes and structural integrity after double-pulley suture bridge rotator cuff repair using serial ultrasonographic examination. J Shoulder Elbow Surg. 2012;21(12):1753-1763.
5. Brown BS, Cooper AD, McIff TE, Key VH, Toby EB. Initial fixation and cyclic loading stability of knotless suture anchors for rotator cuff repair. J Shoulder Elbow Surg. 2008;17(2):313-318.
6. Burkhart SS, Adams CR, Burkhart SS, Schoolfield JD. A biomechanical comparison of 2 techniques of footprint reconstruction for rotator cuff repair: the SwiveLock-FiberChain construct versus standard double-row repair. Arthroscopy. 2009;25(3):274-281.
7. Hepp P, Osterhoff G, Engel T, Marquass B, Klink T, Josten C. Biomechanical evaluation of knotless anatomical double-layer double-row rotator cuff repair: a comparative ex vivo study. Am J Sports Med. 2009;37(7):1363-1369.
8. Maguire M, Goldberg J, Bokor D, et al. Biomechanical evaluation of four different transosseous-equivalent/suture bridge rotator cuff repairs. Knee Surg Sports Traumatol Arthrosc. 2011;19(9):1582-1587.
9. Millar NL, Wu X, Tantau R, Silverstone E, Murrell GA. Open versus two forms of arthroscopic rotator cuff repair. Clin Orthop Relat Res. 2009;467(4):966-978.
10. Rhee YG, Cho NS, Parke CS. Arthroscopic rotator cuff repair using modified Mason-Allen medial row stitch: knotless versus knot-tying suture bridge technique. Am J Sports Med. 2012;40(11):2440-2447.
11. Wieser K, Farshad M, Vlachopoulos L, Ruffieux K, Gerber C, Meyer DC. Suture slippage in knotless suture anchors as a potential failure mechanism in rotator cuff repair. Arthroscopy. 2012;28(11):1622-1627.
12. Pietschmann MF, Gülecyüz MF, Fieseler S, et al. Biomechanical stability of knotless suture anchors used in rotator cuff repair in healthy and osteopenic bone. Arthroscopy. 2010;26(8):1035-1044.
13. Barber FA, Hapa O, Bynum JA. Comparative testing by cyclic loading of rotator cuff suture anchors containing multiple high-strength sutures. Arthroscopy. 2010;26(9 suppl):S134-S141.
14. Barber FA, Coons DA, Ruiz-Suarez M. Cyclic load testing of biodegradable suture anchors containing 2 high-strength sutures. Arthroscopy. 2007;23(4):355-360.
15. Bynum CK, Lee S, Mahar A, Tasto J, Pedowitz R. Failure mode of suture anchors as a function of insertion depth. Am J Sports Med. 2005;33(7):1030-1034.
16. Gerber C, Schneeberger AG, Beck M, Schlegel U. Mechanical strength of repairs of the rotator cuff. J Bone Joint Surg Br. 1994;76(3):371-380.
17. Schneeberger AG, von Roll A, Kalberer F, Jacob HA, Gerber C. Mechanical strength of arthroscopic rotator cuff repair techniques: an in vitro study. J Bone Joint Surg Am. 2002;84(12):2152-2160.
18. Efird C, Traub S, Baldini T, et al. Knotless single-row rotator cuff repair: a comparative biomechanical study of 2 knotless suture anchors. Orthopedics. 2013;36(8):e1033-e1037.
19. Wright PB, Budoff JE, Yeh ML, Kelm ZS, Luo ZP. Strength of damaged suture: an in vitro study. Arthroscopy. 2006;22(12):1270-1275.
20. Burkhart SS. A stepwise approach to arthroscopic rotator cuff repair based on biomechanical principles. Arthroscopy. 2000;16(1):82-90.
21. Bisson LJ, Manohar LM. A biomechanical comparison of the pullout strength of No. 2 FiberWire suture and 2-mm FiberWire tape in bovine rotator cuff tendons. Arthroscopy. 2010;26(11):1463-1468.
22. Burkhart SS, Denard PJ, Konicek J, Hanypsiak BT. Biomechanical validation of load-sharing rip-stop fixation for the repair of tissue-deficient rotator cuff tears. Am J Sports Med. 2014;42(2):457-462.
Second pathology review boosts diagnostic accuracy in lymphoma
In patients with newly diagnosed lymphoma and suspected lymphoma, a second pathological review found inaccuracies in the original diagnosis among 17% of more than 42,000 cases, based on data presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.
In more than 25% of all discrepancies, tumors were reclassified at the second pathology review as the result of findings from additional immunostaining and molecular studies – polymerase chain reaction and fluorescence in situ hybridization.
In 15% of cases, diagnostic changes were expected to result in a change in patient management.
“Our study highlights the importance of specialized centralized review of lymphoma diagnosis, not only in the setting of clinical trials but also in routine clinical practice, for optimal patient management,” reported Dr. Camille Laurent of the Institut Universitaire du Cancer Oncopole, Toulouse, France.
In 2010, the French National Cancer Agency (INCa) established the Lymphopath Network, comprising 33 reference centers, to provide a review by expert hematopathologists of every newly diagnosed lymphoma or suspected lymphoma prior to treatment. These new diagnoses were entered in a central national database. Between 2010 and 2015, 42,146 samples were reviewed: 35,753 were newly diagnosed as lymphomas, while the remaining 6,393 cases included 4,610 reactive lymphoid conditions and 1,783 nonlymphoid malignancies, including especially myeloma and leukemic disorders.
Discordant diagnoses among extra-cutaneous lymphomas were carefully examined by a hematologist and recorded as major or minor depending on the expected therapeutic impact. Dr. Laurent said.
The discordance rate between the referral diagnosis and the final diagnosis was 17.2%. Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis, Dr. Laurent stated.
Less than 2% of discrepancies were due to misclassifications of benign versus malignant lymphoid conditions and of Hodgkin lymphoma versus non-Hodgkin lymphoma. There were minor discrepancies (2.2%) in follicular lymphoma misgrading and diffuse large B-cell lymphoma subtypes.
Given the complexity of lymphoma classification, it is not surprising that expert hematopathologists can refine diagnoses. As we progress in understanding the specific pathogenesis of lymphoma subtypes and utility of targeted therapy, it becomes even more critical to make correct diagnoses. This study reiterates the importance of expert review for many, if not all, lymphoma samples, particularly any T-cell lymphoma and non—follicular small B-cell lymphoma.
Given the complexity of lymphoma classification, it is not surprising that expert hematopathologists can refine diagnoses. As we progress in understanding the specific pathogenesis of lymphoma subtypes and utility of targeted therapy, it becomes even more critical to make correct diagnoses. This study reiterates the importance of expert review for many, if not all, lymphoma samples, particularly any T-cell lymphoma and non—follicular small B-cell lymphoma.
Given the complexity of lymphoma classification, it is not surprising that expert hematopathologists can refine diagnoses. As we progress in understanding the specific pathogenesis of lymphoma subtypes and utility of targeted therapy, it becomes even more critical to make correct diagnoses. This study reiterates the importance of expert review for many, if not all, lymphoma samples, particularly any T-cell lymphoma and non—follicular small B-cell lymphoma.
In patients with newly diagnosed lymphoma and suspected lymphoma, a second pathological review found inaccuracies in the original diagnosis among 17% of more than 42,000 cases, based on data presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.
In more than 25% of all discrepancies, tumors were reclassified at the second pathology review as the result of findings from additional immunostaining and molecular studies – polymerase chain reaction and fluorescence in situ hybridization.
In 15% of cases, diagnostic changes were expected to result in a change in patient management.
“Our study highlights the importance of specialized centralized review of lymphoma diagnosis, not only in the setting of clinical trials but also in routine clinical practice, for optimal patient management,” reported Dr. Camille Laurent of the Institut Universitaire du Cancer Oncopole, Toulouse, France.
In 2010, the French National Cancer Agency (INCa) established the Lymphopath Network, comprising 33 reference centers, to provide a review by expert hematopathologists of every newly diagnosed lymphoma or suspected lymphoma prior to treatment. These new diagnoses were entered in a central national database. Between 2010 and 2015, 42,146 samples were reviewed: 35,753 were newly diagnosed as lymphomas, while the remaining 6,393 cases included 4,610 reactive lymphoid conditions and 1,783 nonlymphoid malignancies, including especially myeloma and leukemic disorders.
Discordant diagnoses among extra-cutaneous lymphomas were carefully examined by a hematologist and recorded as major or minor depending on the expected therapeutic impact. Dr. Laurent said.
The discordance rate between the referral diagnosis and the final diagnosis was 17.2%. Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis, Dr. Laurent stated.
Less than 2% of discrepancies were due to misclassifications of benign versus malignant lymphoid conditions and of Hodgkin lymphoma versus non-Hodgkin lymphoma. There were minor discrepancies (2.2%) in follicular lymphoma misgrading and diffuse large B-cell lymphoma subtypes.
In patients with newly diagnosed lymphoma and suspected lymphoma, a second pathological review found inaccuracies in the original diagnosis among 17% of more than 42,000 cases, based on data presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.
In more than 25% of all discrepancies, tumors were reclassified at the second pathology review as the result of findings from additional immunostaining and molecular studies – polymerase chain reaction and fluorescence in situ hybridization.
In 15% of cases, diagnostic changes were expected to result in a change in patient management.
“Our study highlights the importance of specialized centralized review of lymphoma diagnosis, not only in the setting of clinical trials but also in routine clinical practice, for optimal patient management,” reported Dr. Camille Laurent of the Institut Universitaire du Cancer Oncopole, Toulouse, France.
In 2010, the French National Cancer Agency (INCa) established the Lymphopath Network, comprising 33 reference centers, to provide a review by expert hematopathologists of every newly diagnosed lymphoma or suspected lymphoma prior to treatment. These new diagnoses were entered in a central national database. Between 2010 and 2015, 42,146 samples were reviewed: 35,753 were newly diagnosed as lymphomas, while the remaining 6,393 cases included 4,610 reactive lymphoid conditions and 1,783 nonlymphoid malignancies, including especially myeloma and leukemic disorders.
Discordant diagnoses among extra-cutaneous lymphomas were carefully examined by a hematologist and recorded as major or minor depending on the expected therapeutic impact. Dr. Laurent said.
The discordance rate between the referral diagnosis and the final diagnosis was 17.2%. Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis, Dr. Laurent stated.
Less than 2% of discrepancies were due to misclassifications of benign versus malignant lymphoid conditions and of Hodgkin lymphoma versus non-Hodgkin lymphoma. There were minor discrepancies (2.2%) in follicular lymphoma misgrading and diffuse large B-cell lymphoma subtypes.
FROM 13-ICML
Key clinical point: A second pathological review of newly-diagnosed lymphoma or suspected lymphoma found discrepancies in 17% of cases.
Major finding: Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis.
Data source: 42,146 samples from the French National Cancer Agency’s Lymphopath Network, comprising 33 reference centers.
Disclosures: Dr. Laurent had no relevant financial disclosures.
LISTEN NOW: Hospitalist, Edwin Lopez, PA-C, on Post-Acute Care in the U.S. Health System
Edwin Lopez, PA-C, of St. Elizabeth Hospital in Enumclaw, Wash., offers his views on post-acute care in the U.S. health system, and how his work as a hospitalist has expanded to the nursing home across the street.
Edwin Lopez, PA-C, of St. Elizabeth Hospital in Enumclaw, Wash., offers his views on post-acute care in the U.S. health system, and how his work as a hospitalist has expanded to the nursing home across the street.
Edwin Lopez, PA-C, of St. Elizabeth Hospital in Enumclaw, Wash., offers his views on post-acute care in the U.S. health system, and how his work as a hospitalist has expanded to the nursing home across the street.
Methotrexate could treat MPNs cheaply, team says
Photo courtesy of the
National Cancer Institute
Preclinical research suggests the antineoplastic agent methotrexate (MTX) could be used to treat patients with myeloproliferative neoplasms (MPNs).
Experiments in Drosophila and human cell lines showed that MTX reduces JAK/STAT pathway activity and MPN-associated pathway signaling.
Researchers therefore speculated that low doses of MTX might treat MPNs as effectively as the JAK1/2 inhibitor ruxolitinib, but for a lower cost.
“Given that a year’s course of low-dose MTX costs around £30, the potential to repurpose MTX could provide thousands of patients with a much-needed treatment option and also generate substantial savings for healthcare systems,” said study author Martin Zeidler, DPhil, of The University of Sheffield in the UK.
He and his colleagues noted that, in comparison, ruxolitinib costs more than £40,000 per year per patient.
The researchers made this comparison and described their work with MTX in PLOS ONE.
The team used cells from the fruit fly Drosophila to screen for small molecules that suppress the JAK/STAT signaling pathway, which is central to the development of MPNs in humans. The screen suggested that MTX and a related molecule, aminopterin, suppress STAT activation.
So the researchers conducted experiments in human cell lines and found that MTX suppresses human JAK/STAT signaling without affecting other phosphorylation-dependent pathways.
The team also found that MTX significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F. However, MTX-treated cells can still respond to physiological levels of erythropoietin.
The researchers are now looking to undertake clinical trials to examine the possibility of repurposing low-dose MTX for the treatment of MPNs.
“We have the potential to revolutionize the treatment of this group of chronic diseases—a breakthrough that may ultimately represent a new treatment option able to bring relief to both patients and health funders,” Dr Zeidler said. 
Photo courtesy of the
National Cancer Institute
Preclinical research suggests the antineoplastic agent methotrexate (MTX) could be used to treat patients with myeloproliferative neoplasms (MPNs).
Experiments in Drosophila and human cell lines showed that MTX reduces JAK/STAT pathway activity and MPN-associated pathway signaling.
Researchers therefore speculated that low doses of MTX might treat MPNs as effectively as the JAK1/2 inhibitor ruxolitinib, but for a lower cost.
“Given that a year’s course of low-dose MTX costs around £30, the potential to repurpose MTX could provide thousands of patients with a much-needed treatment option and also generate substantial savings for healthcare systems,” said study author Martin Zeidler, DPhil, of The University of Sheffield in the UK.
He and his colleagues noted that, in comparison, ruxolitinib costs more than £40,000 per year per patient.
The researchers made this comparison and described their work with MTX in PLOS ONE.
The team used cells from the fruit fly Drosophila to screen for small molecules that suppress the JAK/STAT signaling pathway, which is central to the development of MPNs in humans. The screen suggested that MTX and a related molecule, aminopterin, suppress STAT activation.
So the researchers conducted experiments in human cell lines and found that MTX suppresses human JAK/STAT signaling without affecting other phosphorylation-dependent pathways.
The team also found that MTX significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F. However, MTX-treated cells can still respond to physiological levels of erythropoietin.
The researchers are now looking to undertake clinical trials to examine the possibility of repurposing low-dose MTX for the treatment of MPNs.
“We have the potential to revolutionize the treatment of this group of chronic diseases—a breakthrough that may ultimately represent a new treatment option able to bring relief to both patients and health funders,” Dr Zeidler said.
Photo courtesy of the
National Cancer Institute
Preclinical research suggests the antineoplastic agent methotrexate (MTX) could be used to treat patients with myeloproliferative neoplasms (MPNs).
Experiments in Drosophila and human cell lines showed that MTX reduces JAK/STAT pathway activity and MPN-associated pathway signaling.
Researchers therefore speculated that low doses of MTX might treat MPNs as effectively as the JAK1/2 inhibitor ruxolitinib, but for a lower cost.
“Given that a year’s course of low-dose MTX costs around £30, the potential to repurpose MTX could provide thousands of patients with a much-needed treatment option and also generate substantial savings for healthcare systems,” said study author Martin Zeidler, DPhil, of The University of Sheffield in the UK.
He and his colleagues noted that, in comparison, ruxolitinib costs more than £40,000 per year per patient.
The researchers made this comparison and described their work with MTX in PLOS ONE.
The team used cells from the fruit fly Drosophila to screen for small molecules that suppress the JAK/STAT signaling pathway, which is central to the development of MPNs in humans. The screen suggested that MTX and a related molecule, aminopterin, suppress STAT activation.
So the researchers conducted experiments in human cell lines and found that MTX suppresses human JAK/STAT signaling without affecting other phosphorylation-dependent pathways.
The team also found that MTX significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F. However, MTX-treated cells can still respond to physiological levels of erythropoietin.
The researchers are now looking to undertake clinical trials to examine the possibility of repurposing low-dose MTX for the treatment of MPNs.
“We have the potential to revolutionize the treatment of this group of chronic diseases—a breakthrough that may ultimately represent a new treatment option able to bring relief to both patients and health funders,” Dr Zeidler said.
Healthcare professionals work while sick despite risk to patients
Photo by Logan Tuttle
Results of a small survey showed that many healthcare professionals reported to work while sick, despite recognizing that this could put their patients at risk.
About 95% of survey respondents acknowledged that working while sick puts patients at risk, but 83% of respondents said they had worked while sick at least once in the past year.
About 9% of respondents reported working while sick at least 5 times.
Julia E. Szymczak, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania, and her colleagues reported these results in JAMA Pediatrics alongside a related editorial.
The researchers administered an anonymous survey to attending physicians and advanced practice clinicians (APCs) at the Children’s Hospital of Philadelphia. APCs included certified registered nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives.
Overall, 280 attending physicians (61%) and 256 APCs (54.5%) responded. Most respondents (504, 95.3%) said working while sick put patients at risk.
However, 446 respondents (83.1%) reported working while sick at least once in the past year, and 50 respondents (9.3%) reported working while sick at least 5 times.
Respondents reported working with symptoms that included diarrhea, fever, and the onset of significant respiratory symptoms.
The reasons physicians and APCs worked while sick included not wanting to let colleagues down (98.7%), staffing concerns (94.9%), not wanting to let patients down (92.5%), fear of being ostracized by colleagues (64%), and concerns about the continuity of care (63.8%).
An analysis of written comments about why respondents work while sick highlighted 3 areas: challenges in identifying and arranging someone to cover their work and a lack of resources to accommodate sick leave, a strong cultural norm in the hospital to report for work unless one is extremely ill, and ambiguity about what symptoms constitute being too sick to work.
Dr Szymczak and her colleagues said this study suggests complex social and logistical factors cause healthcare workers to report to work sick. But these results could inform efforts to help workers make the right choice to keep their patients and colleagues safe while caring for themselves.
Photo by Logan Tuttle
Results of a small survey showed that many healthcare professionals reported to work while sick, despite recognizing that this could put their patients at risk.
About 95% of survey respondents acknowledged that working while sick puts patients at risk, but 83% of respondents said they had worked while sick at least once in the past year.
About 9% of respondents reported working while sick at least 5 times.
Julia E. Szymczak, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania, and her colleagues reported these results in JAMA Pediatrics alongside a related editorial.
The researchers administered an anonymous survey to attending physicians and advanced practice clinicians (APCs) at the Children’s Hospital of Philadelphia. APCs included certified registered nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives.
Overall, 280 attending physicians (61%) and 256 APCs (54.5%) responded. Most respondents (504, 95.3%) said working while sick put patients at risk.
However, 446 respondents (83.1%) reported working while sick at least once in the past year, and 50 respondents (9.3%) reported working while sick at least 5 times.
Respondents reported working with symptoms that included diarrhea, fever, and the onset of significant respiratory symptoms.
The reasons physicians and APCs worked while sick included not wanting to let colleagues down (98.7%), staffing concerns (94.9%), not wanting to let patients down (92.5%), fear of being ostracized by colleagues (64%), and concerns about the continuity of care (63.8%).
An analysis of written comments about why respondents work while sick highlighted 3 areas: challenges in identifying and arranging someone to cover their work and a lack of resources to accommodate sick leave, a strong cultural norm in the hospital to report for work unless one is extremely ill, and ambiguity about what symptoms constitute being too sick to work.
Dr Szymczak and her colleagues said this study suggests complex social and logistical factors cause healthcare workers to report to work sick. But these results could inform efforts to help workers make the right choice to keep their patients and colleagues safe while caring for themselves.
Photo by Logan Tuttle
Results of a small survey showed that many healthcare professionals reported to work while sick, despite recognizing that this could put their patients at risk.
About 95% of survey respondents acknowledged that working while sick puts patients at risk, but 83% of respondents said they had worked while sick at least once in the past year.
About 9% of respondents reported working while sick at least 5 times.
Julia E. Szymczak, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania, and her colleagues reported these results in JAMA Pediatrics alongside a related editorial.
The researchers administered an anonymous survey to attending physicians and advanced practice clinicians (APCs) at the Children’s Hospital of Philadelphia. APCs included certified registered nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives.
Overall, 280 attending physicians (61%) and 256 APCs (54.5%) responded. Most respondents (504, 95.3%) said working while sick put patients at risk.
However, 446 respondents (83.1%) reported working while sick at least once in the past year, and 50 respondents (9.3%) reported working while sick at least 5 times.
Respondents reported working with symptoms that included diarrhea, fever, and the onset of significant respiratory symptoms.
The reasons physicians and APCs worked while sick included not wanting to let colleagues down (98.7%), staffing concerns (94.9%), not wanting to let patients down (92.5%), fear of being ostracized by colleagues (64%), and concerns about the continuity of care (63.8%).
An analysis of written comments about why respondents work while sick highlighted 3 areas: challenges in identifying and arranging someone to cover their work and a lack of resources to accommodate sick leave, a strong cultural norm in the hospital to report for work unless one is extremely ill, and ambiguity about what symptoms constitute being too sick to work.
Dr Szymczak and her colleagues said this study suggests complex social and logistical factors cause healthcare workers to report to work sick. But these results could inform efforts to help workers make the right choice to keep their patients and colleagues safe while caring for themselves.
NICE supports use of apixaban for VTE
Photo courtesy of the CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending the anticoagulant apixaban (Eliquis) as an option for treating and preventing venous thromboembolism (VTE) in adults.
According to NICE, data from the AMPLIFY and AMPLIFY-EXT studies suggest apixaban is clinically effective for treating and preventing VTE.
And cost analyses indicate that apixaban is a cost-effective use of National Health Service (NHS) resources.
NICE said apixaban should be available on the NHS within 3 months of the guidance release date. The guidance was made available in June.
Dosing
To treat deep vein thrombosis (DVT) or pulmonary embolism (PE), 10 mg of apixaban should be taken twice a day for the first 7 days, followed by 5 mg twice a day for at least 3 months.
To prevent recurrent VTE, patients who have completed 6 months of treatment for DVT or PE should take apixaban at 2.5 mg twice a day.
“[A]pixaban is the only oral anticoagulant for which the licensed dose is lower for secondary prevention than for initial treatment of VTE,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“This could also be of potential benefit in terms of reducing the risk of bleeding where treatment is continued and therefore increase the chance that a person would take apixaban long-term.”
Clinical effectiveness
To assess the clinical effectiveness of apixaban, a committee advising NICE evaluated data from the AMPLIFY and AMPLIFY-EXT studies.
Results of the AMPLIFY study indicated that apixaban is noninferior to standard treatment for recurrent VTE—initial parenteral enoxaparin overlapped with warfarin. Apixaban was comparable in efficacy to standard therapy and induced significantly less bleeding.
In AMPLIFY-EXT, researchers compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.
Both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.
The NICE committee noted that there were limited data in these trials pertaining to patients who needed less than 6 months of treatment and for patients still at high risk of recurrent VTE after 6 months of treatment.
However, the committee concluded that, despite these limitations, the AMPLIFY trials were the pivotal trials that informed the marketing authorization for apixaban. As such, they were sufficient to inform a recommendation for the whole population covered by the marketing authorization.
The committee also pointed out that there were no head-to-head trials evaluating the relative effectiveness of apixaban compared with rivaroxaban and dabigatran etexilate for treating and preventing VTE.
In addition, there were insufficient data to assess the effectiveness and safety of apixaban in patients with active cancer who had VTE, so it was not possible to make a specific recommendation for this group.
Cost-effectiveness
The cost of apixaban is £1.10 per tablet for either the 2.5 mg or 5 mg dose (excluding tax). The daily cost of apixaban is £2.20. (Costs may vary in different settings because of negotiated procurement discounts.)
Analyses suggested that the incremental cost-effectiveness ratio of apixaban was less than £20,000 per quality-adjusted life-year gained for either 6 months or life-long treatment. Therefore, NICE concluded that apixaban is a cost-effective use of NHS resources.
Photo courtesy of the CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending the anticoagulant apixaban (Eliquis) as an option for treating and preventing venous thromboembolism (VTE) in adults.
According to NICE, data from the AMPLIFY and AMPLIFY-EXT studies suggest apixaban is clinically effective for treating and preventing VTE.
And cost analyses indicate that apixaban is a cost-effective use of National Health Service (NHS) resources.
NICE said apixaban should be available on the NHS within 3 months of the guidance release date. The guidance was made available in June.
Dosing
To treat deep vein thrombosis (DVT) or pulmonary embolism (PE), 10 mg of apixaban should be taken twice a day for the first 7 days, followed by 5 mg twice a day for at least 3 months.
To prevent recurrent VTE, patients who have completed 6 months of treatment for DVT or PE should take apixaban at 2.5 mg twice a day.
“[A]pixaban is the only oral anticoagulant for which the licensed dose is lower for secondary prevention than for initial treatment of VTE,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“This could also be of potential benefit in terms of reducing the risk of bleeding where treatment is continued and therefore increase the chance that a person would take apixaban long-term.”
Clinical effectiveness
To assess the clinical effectiveness of apixaban, a committee advising NICE evaluated data from the AMPLIFY and AMPLIFY-EXT studies.
Results of the AMPLIFY study indicated that apixaban is noninferior to standard treatment for recurrent VTE—initial parenteral enoxaparin overlapped with warfarin. Apixaban was comparable in efficacy to standard therapy and induced significantly less bleeding.
In AMPLIFY-EXT, researchers compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.
Both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.
The NICE committee noted that there were limited data in these trials pertaining to patients who needed less than 6 months of treatment and for patients still at high risk of recurrent VTE after 6 months of treatment.
However, the committee concluded that, despite these limitations, the AMPLIFY trials were the pivotal trials that informed the marketing authorization for apixaban. As such, they were sufficient to inform a recommendation for the whole population covered by the marketing authorization.
The committee also pointed out that there were no head-to-head trials evaluating the relative effectiveness of apixaban compared with rivaroxaban and dabigatran etexilate for treating and preventing VTE.
In addition, there were insufficient data to assess the effectiveness and safety of apixaban in patients with active cancer who had VTE, so it was not possible to make a specific recommendation for this group.
Cost-effectiveness
The cost of apixaban is £1.10 per tablet for either the 2.5 mg or 5 mg dose (excluding tax). The daily cost of apixaban is £2.20. (Costs may vary in different settings because of negotiated procurement discounts.)
Analyses suggested that the incremental cost-effectiveness ratio of apixaban was less than £20,000 per quality-adjusted life-year gained for either 6 months or life-long treatment. Therefore, NICE concluded that apixaban is a cost-effective use of NHS resources.
Photo courtesy of the CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending the anticoagulant apixaban (Eliquis) as an option for treating and preventing venous thromboembolism (VTE) in adults.
According to NICE, data from the AMPLIFY and AMPLIFY-EXT studies suggest apixaban is clinically effective for treating and preventing VTE.
And cost analyses indicate that apixaban is a cost-effective use of National Health Service (NHS) resources.
NICE said apixaban should be available on the NHS within 3 months of the guidance release date. The guidance was made available in June.
Dosing
To treat deep vein thrombosis (DVT) or pulmonary embolism (PE), 10 mg of apixaban should be taken twice a day for the first 7 days, followed by 5 mg twice a day for at least 3 months.
To prevent recurrent VTE, patients who have completed 6 months of treatment for DVT or PE should take apixaban at 2.5 mg twice a day.
“[A]pixaban is the only oral anticoagulant for which the licensed dose is lower for secondary prevention than for initial treatment of VTE,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“This could also be of potential benefit in terms of reducing the risk of bleeding where treatment is continued and therefore increase the chance that a person would take apixaban long-term.”
Clinical effectiveness
To assess the clinical effectiveness of apixaban, a committee advising NICE evaluated data from the AMPLIFY and AMPLIFY-EXT studies.
Results of the AMPLIFY study indicated that apixaban is noninferior to standard treatment for recurrent VTE—initial parenteral enoxaparin overlapped with warfarin. Apixaban was comparable in efficacy to standard therapy and induced significantly less bleeding.
In AMPLIFY-EXT, researchers compared 12 months of treatment with apixaban at 2 doses—2.5 mg and 5 mg—to placebo in patients who had previously received anticoagulant therapy for 6 to 12 months to treat a prior VTE.
Both doses of apixaban effectively prevented VTE, VTE-related events, and death. And the incidence of bleeding events was low in all treatment arms.
The NICE committee noted that there were limited data in these trials pertaining to patients who needed less than 6 months of treatment and for patients still at high risk of recurrent VTE after 6 months of treatment.
However, the committee concluded that, despite these limitations, the AMPLIFY trials were the pivotal trials that informed the marketing authorization for apixaban. As such, they were sufficient to inform a recommendation for the whole population covered by the marketing authorization.
The committee also pointed out that there were no head-to-head trials evaluating the relative effectiveness of apixaban compared with rivaroxaban and dabigatran etexilate for treating and preventing VTE.
In addition, there were insufficient data to assess the effectiveness and safety of apixaban in patients with active cancer who had VTE, so it was not possible to make a specific recommendation for this group.
Cost-effectiveness
The cost of apixaban is £1.10 per tablet for either the 2.5 mg or 5 mg dose (excluding tax). The daily cost of apixaban is £2.20. (Costs may vary in different settings because of negotiated procurement discounts.)
Analyses suggested that the incremental cost-effectiveness ratio of apixaban was less than £20,000 per quality-adjusted life-year gained for either 6 months or life-long treatment. Therefore, NICE concluded that apixaban is a cost-effective use of NHS resources.