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A novel approach to patients with acute odontoid fractures: atlantoaxial instability as a prognostic variable
The Spine Journal 15 (2015) 1161–1163
Commentary
A novel approach to patients with acute odontoid fractures: atlantoaxial instability as a prognostic variable Nathan Evaniew, MDa,*, Blake Yarascavitch, MD, FRCSCb, Kim Madden, BScc, Michelle Ghert, MD, FRCSCa, Brian Drew, MD, FRCSCa, Mohit Bhandari, MD, PhD, FRCSCa,c, Desmond Kwok, MD, FRCSCa a Division of Orthopaedics, Department of Surgery, McMaster University, 293 Wellington St N, Suite 110, Hamilton, Ontario, Canada L8L 8E7 Division of Neurosurgery, Department of Surgery, McMaster University, Hamilton General Hospital 8N-01, 237 Barton St E, Hamilton, Ontario, Canada L8L 2X2 c Department of Clinical Epidemiology and Biostatistics, McMaster University, 293 Wellington St N, Suite 110, Hamilton, Ontario, Canada L8L 8E7 Received 12 November 2014; accepted 20 November 2014 b
COMMENTARY ON: Liu S, Liu L. Re: Evaniew N, Yarascavitch B, Madden K, Ghert M, Drew B, Bhandari M, et al. Atlantoaxial instability in acute odontoid fractures is associated with nonunion and mortality. Spine J 2015;15:1160 (in this issue).
Odontoid fractures are part of an emerging geriatric spine fracture health-care crisis and their clinical management has proven particularly challenging [1]. In the United States alone, the economic burden of treating patients with C2 fractures rose nearly fivefold from 2001 to an estimated $1.5 billion in 2010 [2]. Approximately, one-third patients with acute odontoid fractures experience treatment-related complications and one-third die within 1 year [3]. Surgical indications and management strategies for patients with acute odontoid fractures remain controversial, and the identification of reliable prognostic factors is critical to optimize patient care and guide future research.
FDA device/drug status: Not applicable. Author disclosures: NE: Nothing to disclose. BY: Nothing to disclose. KM: Nothing to disclose. MG: Grant: Canadian Institutes of Health Research (G, Research grant), Canadian Cancer Society (F, Research grant); Personal Fees: Wright Medical (C, Consultant ad hoc). BD: Nothing to disclose. MB: Consultancy: Smith & Nephew (C), Stryker (C), Amgen (C), Zimmer (C), Moximed (C), Bioventus (C), Merck, Eli Lilly, Sanofi (F); Grants/grants pending: Smith & Nephew (E, paid directly to institution), DePuy, Eli Lily, Bioventus (C), Stryker (F, Paid directly to institution), Zimmer, Amgen (F, Paid directly to institution). DK: Nothing to disclose. The disclosure key can be found on the Table of Contents and at www.TheSpineJournalOnline.com. * Corresponding author. Division of Orthopaedics, Department of Surgery, McMaster University, 293 Wellington St N, Suite 110, Hamilton, Ontario, Canada L8L 8E7. Tel.: (905) 521-2100 ext 6449; fax: (905) 523-8781. E-mail address: [email protected] (N. Evaniew) http://dx.doi.org/10.1016/j.spinee.2014.11.013 1529-9430/Ó 2015 Elsevier Inc. All rights reserved.
In this issue of The Spine Journal, we report a retrospective cohort analysis of 124 consecutive patients with acute odontoid fractures that were treated at our institution over a 10-year period. We hypothesized that atlantoaxial instability (AAI) would be a marker of increased injury severity in patients with acute odontoid fractures, and the objective of our study was to determine whether severe AAI was associated with increased rates of nonunion or mortality, regardless of the treatment strategy [4]. This issue of The Spine Journal also includes a letter to the editor about our article and we thank the authors of this letter for their interest in our research and their insightful comments [5]. They have raised several critical issues that deserve further elaboration. We defined AAI as the mean subluxation across both C1–C2 facet joints in each patient, and patients were classified as having either ‘‘severe’’ or ‘‘minimal’’ AAI on the basis of greater versus #50% mean subluxation across both joints. One hundred seven patients in our cohort had minimal AAI and 17 had severe AAI, and the mean follow-up was 4.4 months (standard deviation 4.6). In comparison with patients with minimal AAI, patients with severe AAI experienced significantly higher rates of nonunion (29% vs. 10%; p5.03) and mortality (35% vs. 14%; p5.03). Our risk-adjusted regression models failed to generate statistically significant odds ratios, but we saw trends toward worse risk-adjusted outcomes with severe AAI and this effect was preserved in the subgroup of patients with Type-II fractures. The authors of this letter highlight our relatively small sample size, a limitation that we acknowledged in our discussion. Although our results were statistically significant
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N. Evaniew et al. / The Spine Journal 15 (2015) 1161–1163
by conventional standards (p!.05 for Fisher’s exact test), studies with relatively small sample sizes are at risk of producing spurious or misleading results and ours is of course no exception [6]. Walsh et al. [7] recently proposed the Fragility Index as a metric that complements p values and 95% confidence intervals to help to identify studies with less robust findings. The Fragility Index for a given study is the minimum number of patients in the treatment group with fewer events whose status would have to change from a nonevent to an event to change a statistically significant result to a nonsignificant result. Walsh et al. [7] found a median Fragility Index of just eight events among 399 randomized trials from high-impact medical journals, with 25% of the trials having a Fragility Index of three or less events and 53% having a Fragility Index less than the number of patients lost to follow-up. The Fragility Index for each of nonunion and mortality in our study was just one event, which clearly supports our conclusion that further investigation with a large prospective study is justified. The authors of this letter commented that many other factors likely contribute to the risk of nonunion in patients with acute odontoid fractures and we agree that this is an important consideration. In fact, we noted in our article that patient age, amount of linear fracture displacement, and Anderson and D’Alonzo fracture subtype have the greatest established prognostic importance and we performed multivariable binary logistic regression analyses to adjust for these factors. The effects of different surgical approaches versus nonoperative treatments remain controversial [8,9], but there were no significant differences in the rates of nonunion and mortality between patients treated operatively versus nonoperatively in our study. The authors of this letter also suggested that the timing of surgery may be important, and they referred to a single retrospective study of 41 patients, only five of whom experienced nonunion [10]. We did not examine the effect of timing to surgery in our study, but others have shown that delays in surgical management can negatively impact the outcomes of patients with traumatic spinal cord injuries or geriatric hip fractures [11–15], and this is probably a variable that demands further research in patients with odontoid fractures. Finally, the authors of this letter suggest the possibility that postinjury AAI might not correlate with posttreatment AAI, and they draw attention to the potential importance of achieving anatomical reduction. Our results support a theoretical framework in which severe AAI could be evaluated at initial presentation to identify those injuries with greater severity and a worse prognosis, a framework that was strengthened by positive correlations between postinjury AAI and linear fracture displacement (p!.01) and between postinjury AAI and rates of associated C1 fractures (p!.01). Further highquality prospective studies are required to reliably establish whether the effects of severe postinjury AAI on rates of nonunion and mortality are modifiable and whether treatment aimed at restoring normal atlantoaxial alignment might improve outcomes. None of the patients in our study underwent
traction before their postinjury computed tomography scans, but traction was sometimes used to achieve anatomical reduction intraoperatively. Evidence-based medicine describes the judicious integration of clinical expertise and patient preferences with the best available external clinical evidence, and clinicians are often are faced with the task of managing their patients despite uncertain evidence [16]. We are hopeful that our research will assist surgeons and patients considering the possible risks and anticipated benefits of various treatment options for patients with odontoid fractures, but we recognize that many questions remain. Further work is necessary to confirm our findings, narrow our adjusted estimates of risk, and clarify the effect of AAI in specific patient subgroups. The validity, reliability, and measurement accuracy of determining AAI from sagittal computed tomography scans remain unknown, as does the role of axial alignment and rotatory subluxation [17]. Given the substantial morbidity and mortality associated with acute odontoid fractures, an evidence-based approach is paramount. We again thank the authors of this letter for their attention to our work and for drawing attention to the potential value of AAI as a prognostic variable. References [1] Chapman J, Bransford R. Geriatric spine fractures: an emerging healthcare crisis. J Trauma 2007;62(6 Suppl):S61–2. [2] Daniels AH, Arthur M, Esmende SM, Vigneswaran H, Palumbo MA. Incidence and cost of treating axis fractures in the United States from 2000 to 2010. Spine 2014;39:1498–505. [3] Vaccaro AR, Kepler CK, Kopjar B, Chapman J, Shaffrey C, Arnold P, et al. Functional and quality-of-life outcomes in geriatric patients with type-II dens fracture. J Bone Joint Surg Am 2013;95:729–35. [4] Evaniew N, Yarascavitch B, Madden K, Ghert M, Drew B, Bhandari M, et al. Atlantoaxial instability in acute odontoid fractures is associated with nonunion and mortality. Spine J 2015;15:910–7. [5] Liu S, Liu L. Re: Evaniew N, Yarascavitch B, Madden K, Ghert M, Drew B, Bhandari M, et al. Atlantoaxial instability in acute odontoid fractures is associated with nonunion and mortality. Spine J 2015;15: 1160. [6] SPRINT InvestigatorsBhandari M, Tornetta P 3rd, Rampersad SA, Sprague S, Heels-Ansdell D, et al. (Sample) size matters! An examination of sample size from the SPRINT trial study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures. J Orthop Trauma 2013;27:183–8. [7] Walsh M, Srinathan SK, McAuley DF, Mrkobrada M, Levine O, Ribic C, et al. The statistical significance of randomized controlled trial results is frequently fragile: a case for a fragility index. J Clin Epidemiol 2014 Jun;67(6):622–8. [8] Denaro V, Papalia R, Di Martino A, Denaro L, Maffulli N. The best surgical treatment for type II fractures of the dens is still controversial. Clin Orthop 2011;469:742–50. [9] Harrop JS, Hart R, Anderson PA. Optimal treatment for odontoid fractures in the elderly. Spine 2010;35(21 Suppl):S219–27. [10] Cho DC, Sung JK. Analysis of risk factors associated with fusion failure after anterior odontoid screw fixation. Spine 2012;37:30–4. [11] Dvorak MF, Noonan V, Fallah N, Fisher CG, Finkelstein J, Kwon BK, et al. The influence of time from injury to surgery on motor recovery and length of hospital stay in acute traumatic spinal cord injury: an observational Canadian cohort study. J Neurotrauma 2014 Nov 19. [Epub ahead of print].
N. Evaniew et al. / The Spine Journal 15 (2015) 1161–1163 [12] Fehlings MG, Vaccaro A, Wilson JR, Singh A, W Cadotte D, Harrop JS, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the surgical timing in acute spinal cord injury study (STASCIS). PLoS One 2012;7:e32037. [13] Carreon LY, Dimar JR. Early versus late stabilization of spine injuries: a systematic review. Spine 2011;36:E727–33. [14] Simunovic N, Devereaux PJ, Sprague S, Guyatt GH, Schemitsch E, Debeer J, et al. Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis. CMAJ 2010;182:1609–16.
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[15] Hip Fracture Accelerated Surgical Treatment and Care Track (HIP ATTACK) Investigators. Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial. CMAJ 2014;186:E52–60. [16] Guyatt G, Cook D, Haynes B. Evidence based medicine has come a long way. BMJ 2004;329:990–1. [17] Monckeberg JE, Tome CV, Matias A, Alonso A, Vasquez J, Zubieta JL. CT scan study of atlantoaxial rotatory mobility in asymptomatic adult subjects: a basis for better understanding C1-C2 rotatory fixation and subluxation. Spine 2009;34:1292–5.
Commentary
A novel approach to patients with acute odontoid fractures: atlantoaxial instability as a prognostic variable Nathan Evaniew, MDa,*, Blake Yarascavitch, MD, FRCSCb, Kim Madden, BScc, Michelle Ghert, MD, FRCSCa, Brian Drew, MD, FRCSCa, Mohit Bhandari, MD, PhD, FRCSCa,c, Desmond Kwok, MD, FRCSCa a Division of Orthopaedics, Department of Surgery, McMaster University, 293 Wellington St N, Suite 110, Hamilton, Ontario, Canada L8L 8E7 Division of Neurosurgery, Department of Surgery, McMaster University, Hamilton General Hospital 8N-01, 237 Barton St E, Hamilton, Ontario, Canada L8L 2X2 c Department of Clinical Epidemiology and Biostatistics, McMaster University, 293 Wellington St N, Suite 110, Hamilton, Ontario, Canada L8L 8E7 Received 12 November 2014; accepted 20 November 2014 b
COMMENTARY ON: Liu S, Liu L. Re: Evaniew N, Yarascavitch B, Madden K, Ghert M, Drew B, Bhandari M, et al. Atlantoaxial instability in acute odontoid fractures is associated with nonunion and mortality. Spine J 2015;15:1160 (in this issue).
Odontoid fractures are part of an emerging geriatric spine fracture health-care crisis and their clinical management has proven particularly challenging [1]. In the United States alone, the economic burden of treating patients with C2 fractures rose nearly fivefold from 2001 to an estimated $1.5 billion in 2010 [2]. Approximately, one-third patients with acute odontoid fractures experience treatment-related complications and one-third die within 1 year [3]. Surgical indications and management strategies for patients with acute odontoid fractures remain controversial, and the identification of reliable prognostic factors is critical to optimize patient care and guide future research.
FDA device/drug status: Not applicable. Author disclosures: NE: Nothing to disclose. BY: Nothing to disclose. KM: Nothing to disclose. MG: Grant: Canadian Institutes of Health Research (G, Research grant), Canadian Cancer Society (F, Research grant); Personal Fees: Wright Medical (C, Consultant ad hoc). BD: Nothing to disclose. MB: Consultancy: Smith & Nephew (C), Stryker (C), Amgen (C), Zimmer (C), Moximed (C), Bioventus (C), Merck, Eli Lilly, Sanofi (F); Grants/grants pending: Smith & Nephew (E, paid directly to institution), DePuy, Eli Lily, Bioventus (C), Stryker (F, Paid directly to institution), Zimmer, Amgen (F, Paid directly to institution). DK: Nothing to disclose. The disclosure key can be found on the Table of Contents and at www.TheSpineJournalOnline.com. * Corresponding author. Division of Orthopaedics, Department of Surgery, McMaster University, 293 Wellington St N, Suite 110, Hamilton, Ontario, Canada L8L 8E7. Tel.: (905) 521-2100 ext 6449; fax: (905) 523-8781. E-mail address: [email protected] (N. Evaniew) http://dx.doi.org/10.1016/j.spinee.2014.11.013 1529-9430/Ó 2015 Elsevier Inc. All rights reserved.
In this issue of The Spine Journal, we report a retrospective cohort analysis of 124 consecutive patients with acute odontoid fractures that were treated at our institution over a 10-year period. We hypothesized that atlantoaxial instability (AAI) would be a marker of increased injury severity in patients with acute odontoid fractures, and the objective of our study was to determine whether severe AAI was associated with increased rates of nonunion or mortality, regardless of the treatment strategy [4]. This issue of The Spine Journal also includes a letter to the editor about our article and we thank the authors of this letter for their interest in our research and their insightful comments [5]. They have raised several critical issues that deserve further elaboration. We defined AAI as the mean subluxation across both C1–C2 facet joints in each patient, and patients were classified as having either ‘‘severe’’ or ‘‘minimal’’ AAI on the basis of greater versus #50% mean subluxation across both joints. One hundred seven patients in our cohort had minimal AAI and 17 had severe AAI, and the mean follow-up was 4.4 months (standard deviation 4.6). In comparison with patients with minimal AAI, patients with severe AAI experienced significantly higher rates of nonunion (29% vs. 10%; p5.03) and mortality (35% vs. 14%; p5.03). Our risk-adjusted regression models failed to generate statistically significant odds ratios, but we saw trends toward worse risk-adjusted outcomes with severe AAI and this effect was preserved in the subgroup of patients with Type-II fractures. The authors of this letter highlight our relatively small sample size, a limitation that we acknowledged in our discussion. Although our results were statistically significant
1162
N. Evaniew et al. / The Spine Journal 15 (2015) 1161–1163
by conventional standards (p!.05 for Fisher’s exact test), studies with relatively small sample sizes are at risk of producing spurious or misleading results and ours is of course no exception [6]. Walsh et al. [7] recently proposed the Fragility Index as a metric that complements p values and 95% confidence intervals to help to identify studies with less robust findings. The Fragility Index for a given study is the minimum number of patients in the treatment group with fewer events whose status would have to change from a nonevent to an event to change a statistically significant result to a nonsignificant result. Walsh et al. [7] found a median Fragility Index of just eight events among 399 randomized trials from high-impact medical journals, with 25% of the trials having a Fragility Index of three or less events and 53% having a Fragility Index less than the number of patients lost to follow-up. The Fragility Index for each of nonunion and mortality in our study was just one event, which clearly supports our conclusion that further investigation with a large prospective study is justified. The authors of this letter commented that many other factors likely contribute to the risk of nonunion in patients with acute odontoid fractures and we agree that this is an important consideration. In fact, we noted in our article that patient age, amount of linear fracture displacement, and Anderson and D’Alonzo fracture subtype have the greatest established prognostic importance and we performed multivariable binary logistic regression analyses to adjust for these factors. The effects of different surgical approaches versus nonoperative treatments remain controversial [8,9], but there were no significant differences in the rates of nonunion and mortality between patients treated operatively versus nonoperatively in our study. The authors of this letter also suggested that the timing of surgery may be important, and they referred to a single retrospective study of 41 patients, only five of whom experienced nonunion [10]. We did not examine the effect of timing to surgery in our study, but others have shown that delays in surgical management can negatively impact the outcomes of patients with traumatic spinal cord injuries or geriatric hip fractures [11–15], and this is probably a variable that demands further research in patients with odontoid fractures. Finally, the authors of this letter suggest the possibility that postinjury AAI might not correlate with posttreatment AAI, and they draw attention to the potential importance of achieving anatomical reduction. Our results support a theoretical framework in which severe AAI could be evaluated at initial presentation to identify those injuries with greater severity and a worse prognosis, a framework that was strengthened by positive correlations between postinjury AAI and linear fracture displacement (p!.01) and between postinjury AAI and rates of associated C1 fractures (p!.01). Further highquality prospective studies are required to reliably establish whether the effects of severe postinjury AAI on rates of nonunion and mortality are modifiable and whether treatment aimed at restoring normal atlantoaxial alignment might improve outcomes. None of the patients in our study underwent
traction before their postinjury computed tomography scans, but traction was sometimes used to achieve anatomical reduction intraoperatively. Evidence-based medicine describes the judicious integration of clinical expertise and patient preferences with the best available external clinical evidence, and clinicians are often are faced with the task of managing their patients despite uncertain evidence [16]. We are hopeful that our research will assist surgeons and patients considering the possible risks and anticipated benefits of various treatment options for patients with odontoid fractures, but we recognize that many questions remain. Further work is necessary to confirm our findings, narrow our adjusted estimates of risk, and clarify the effect of AAI in specific patient subgroups. The validity, reliability, and measurement accuracy of determining AAI from sagittal computed tomography scans remain unknown, as does the role of axial alignment and rotatory subluxation [17]. Given the substantial morbidity and mortality associated with acute odontoid fractures, an evidence-based approach is paramount. We again thank the authors of this letter for their attention to our work and for drawing attention to the potential value of AAI as a prognostic variable. References [1] Chapman J, Bransford R. Geriatric spine fractures: an emerging healthcare crisis. J Trauma 2007;62(6 Suppl):S61–2. [2] Daniels AH, Arthur M, Esmende SM, Vigneswaran H, Palumbo MA. Incidence and cost of treating axis fractures in the United States from 2000 to 2010. Spine 2014;39:1498–505. [3] Vaccaro AR, Kepler CK, Kopjar B, Chapman J, Shaffrey C, Arnold P, et al. Functional and quality-of-life outcomes in geriatric patients with type-II dens fracture. J Bone Joint Surg Am 2013;95:729–35. [4] Evaniew N, Yarascavitch B, Madden K, Ghert M, Drew B, Bhandari M, et al. Atlantoaxial instability in acute odontoid fractures is associated with nonunion and mortality. Spine J 2015;15:910–7. [5] Liu S, Liu L. Re: Evaniew N, Yarascavitch B, Madden K, Ghert M, Drew B, Bhandari M, et al. Atlantoaxial instability in acute odontoid fractures is associated with nonunion and mortality. Spine J 2015;15: 1160. [6] SPRINT InvestigatorsBhandari M, Tornetta P 3rd, Rampersad SA, Sprague S, Heels-Ansdell D, et al. (Sample) size matters! An examination of sample size from the SPRINT trial study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures. J Orthop Trauma 2013;27:183–8. [7] Walsh M, Srinathan SK, McAuley DF, Mrkobrada M, Levine O, Ribic C, et al. The statistical significance of randomized controlled trial results is frequently fragile: a case for a fragility index. J Clin Epidemiol 2014 Jun;67(6):622–8. [8] Denaro V, Papalia R, Di Martino A, Denaro L, Maffulli N. The best surgical treatment for type II fractures of the dens is still controversial. Clin Orthop 2011;469:742–50. [9] Harrop JS, Hart R, Anderson PA. Optimal treatment for odontoid fractures in the elderly. Spine 2010;35(21 Suppl):S219–27. [10] Cho DC, Sung JK. Analysis of risk factors associated with fusion failure after anterior odontoid screw fixation. Spine 2012;37:30–4. [11] Dvorak MF, Noonan V, Fallah N, Fisher CG, Finkelstein J, Kwon BK, et al. The influence of time from injury to surgery on motor recovery and length of hospital stay in acute traumatic spinal cord injury: an observational Canadian cohort study. J Neurotrauma 2014 Nov 19. [Epub ahead of print].
N. Evaniew et al. / The Spine Journal 15 (2015) 1161–1163 [12] Fehlings MG, Vaccaro A, Wilson JR, Singh A, W Cadotte D, Harrop JS, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the surgical timing in acute spinal cord injury study (STASCIS). PLoS One 2012;7:e32037. [13] Carreon LY, Dimar JR. Early versus late stabilization of spine injuries: a systematic review. Spine 2011;36:E727–33. [14] Simunovic N, Devereaux PJ, Sprague S, Guyatt GH, Schemitsch E, Debeer J, et al. Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis. CMAJ 2010;182:1609–16.
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[15] Hip Fracture Accelerated Surgical Treatment and Care Track (HIP ATTACK) Investigators. Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial. CMAJ 2014;186:E52–60. [16] Guyatt G, Cook D, Haynes B. Evidence based medicine has come a long way. BMJ 2004;329:990–1. [17] Monckeberg JE, Tome CV, Matias A, Alonso A, Vasquez J, Zubieta JL. CT scan study of atlantoaxial rotatory mobility in asymptomatic adult subjects: a basis for better understanding C1-C2 rotatory fixation and subluxation. Spine 2009;34:1292–5.