The American Journal of Sports Medicine http://ajs.sagepub.com/
Paving the Way for Future Research in Autologous Chondrocyte Implantation: Response Thomas R. Niethammer, Elem Safi, Andreas Ficklscherer, Annie Horng, Markus Feist, Isa Feist-Pagenstert, Volkmar Jansson, Matthias F. Pietschmann and Peter E. Müller Am J Sports Med 2014 42: NP51 DOI: 10.1177/0363546514554366 The online version of this article can be found at: http://ajs.sagepub.com/content/42/11/NP51.2
Published by: http://www.sagepublications.com
On behalf of: American Orthopaedic Society for Sports Medicine
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REFERENCES
Paving the Way for Future Research in Autologous Chondrocyte Implantation: Letter to the Editor
1. Niethammer TR, Safi E, Ficklscherer A, et al. Graft maturation of autologous chondrocyte implantation: magnetic resonance investigation with T2 mapping. Am J Sports Med. 2014;42(9):2199-2204. 2. Roos EM, Davis A, Beynnon BD. IKDC or KOOS? Which measures symptoms and disabilities most important to postoperative articular cartilage repair patients? [letter]. Am J Sports Med. 2009;37(5):10421043. 3. de Windt TS, Welsch GH, Brittberg M, et al. Is magnetic resonance imaging reliable in predicting clinical outcome after articular cartilage repair of the knee? A systematic review and meta-analysis. Am J Sports Med. 2013;41(7):1695-1702.
DOI: 10.1177/0363546514554365
Dear Editor: I read with great interest the recently published case series study with 13 patients by Niethammer and colleagues,1 which suggested that graft maturation after autologous chondrocyte implantation (ACI) in the knee joint needs at least 1 year, with ongoing adjustment of the T2 relaxation time values compared with native surrounding cartilage, and found no correlation between increasing ACI graft maturation and clinical outcomes (International Knee Documentation Committee [IKDC] score). This is a very important study, adding to the studies on evaluating ACI graft maturation in osteochondral lesions. It would have been interesting if the authors—because of obvious heterogeneity of defect locations as well as serious methodological limitations inherent in case series studies (eg, lack of comparative cohort or control group)—could have improved their study assessment tools (such as also using histological findings or the Short Form–36 [SF-36] questionnaire as secondary outcomes) to determine the contributing factors that affected clinical outcomes. Mental factors, which could be assessed by the SF-36 questionnaire, or other variables that are not visible on magnetic resonance imaging (MRI), such as inflammation, increased vascular penetration, and nerve growth, may influence clinical outcomes. Moreover, the complexity of the knee injury and the patient history can make it difficult for any of the used outcome questionnaires to reflect the exact areas that are important to patients.2 Particularly with respect to the IKDC, the score reflects an overall outcome of different items such as pain, activity, and function, which may confound correlation with MRI. I therefore agree with de Windt et al3 that reported evidence to determine whether morphological MRI is reliable in predicting clinical outcomes after cartilage repair is lacking. Future research using more reliable clinical outcome tools after articular cartilage repair could be of great importance to the field.
Paving the Way for Future Research in Autologous Chondrocyte Implantation: Response DOI: 10.1177/0363546514554366
Authors’ Response: Thank you for your response to the recently published article regarding the graft maturation of ACI in the knee using MRI evaluation with T2 relaxation time values. We agree with your concerns that a case series has a limited validity because of the small number of patients. We also share your concern that a homogeneous cohort of either the same localization or the control group to analyze different methods of cartilage repair would be helpful. But the purpose of our study was to evaluate the graft maturation of ACI in the knee. Regarding your recommendation to analyze histological findings of the implanted ACI grafts, it should be noted that biopsies of the ACI grafts in the postoperative course cannot be performed for ethical reasons. Therefore we did not include this interesting point in this study. Instead, we have established a standardized MRI followup with T2 relaxation time measurement to get more information about the content of collagen and water in the ACI grafts. With regard to your proposed evaluation of mental factors using the Short Form–36 questionnaire, we would like to respond with the following. Mental factors might be a proper study assessment tool to interpret individual results. In a case series with a heterogeneous study population however, it is not helpful. For clinical evaluation, the subjective IKDC score and the visual analog scale for pain at rest and during activities were used. These scores are established and validated scores in the follow-up examination of cartilage regeneration procedures, and they have been used in several studies.2-4 To date, correlation of MRI after ACI and clinical scores are established and part of several performed studies.1,4,5 A careful analysis of radiological parameters such as the T2 relaxation time values are promising to improve the knowledge of this field. Further study into this topic is
Hamidreza Shemshaki, MD Tu¨ bingen, Germany
Address correspondence to Hamidreza Shemshaki, MD (e-mail: [email protected]). The author has declared no conflicts of interest in the authorship and publication of this contribution.
The American Journal of Sports Medicine, Vol. 42, No. 11 Ó 2014 The Author(s)
NP51 Downloaded from ajs.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 4, 2015
NP52 Letter to the Editor
The American Journal of Sports Medicine
clearly warranted, and we thank you for your kind words. Thomas R. Niethammer, MD Elem Safi, MD Andreas Ficklscherer, MD Annie Horng, MD Markus Feist, MD Isa Feist-Pagenstert, MD Volkmar Jansson, MD Matthias F. Pietschmann, MD Peter E. Mu ¨ ller, MD Munich, Germany ¨ ller, MD (e-mail: Address correspondence to Peter E. Mu [email protected]). The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.
REFERENCES 1. Blackman AJ, Smith MV, Flanigan DC, Matava MJ, Wright RW, Brophy RH. Correlation between magnetic resonance imaging and clinical outcomes after knee cartilage repair: author’s response [letter]. Am J Sports Med. 2013;41(11):NP49-NP50. 2. Henderson I, Gui J, Lavigne P. Autologous chondrocyte implantation: natural history of postimplantation periosteal hypertrophy and effects of repair-site debridement on outcome. Arthroscopy. 2006;22(12): 1318-1324 e1311. 3. Niemeyer P, Pestka JM, Kreuz PC, et al. Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med. 2008;36(11):2091-2099. 4. Pietschmann MF, Niethammer TR, Horng A, et al. The incidence and clinical relevance of graft hypertrophy after matrix-based autologous chondrocyte implantation. Am J Sports Med. 2012;40(1):68-74. 5. Salzmann GM, Erdle B, Porichis S, et al. Long-term T2 and qualitative MRI morphology after first-generation knee autologous chondrocyte implantation: cartilage ultrastructure is not correlated to clinical or qualitative MRI outcome. Am J Sports Med. 2014;42(8):18321840.
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Paving the Way for Future Research in Autologous Chondrocyte Implantation: Response Thomas R. Niethammer, Elem Safi, Andreas Ficklscherer, Annie Horng, Markus Feist, Isa Feist-Pagenstert, Volkmar Jansson, Matthias F. Pietschmann and Peter E. Müller Am J Sports Med 2014 42: NP51 DOI: 10.1177/0363546514554366 The online version of this article can be found at: http://ajs.sagepub.com/content/42/11/NP51.2
Published by: http://www.sagepublications.com
On behalf of: American Orthopaedic Society for Sports Medicine
Additional services and information for The American Journal of Sports Medicine can be found at: Email Alerts: http://ajs.sagepub.com/cgi/alerts Subscriptions: http://ajs.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> Version of Record - Oct 30, 2014 What is This?
Downloaded from ajs.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 4, 2015
REFERENCES
Paving the Way for Future Research in Autologous Chondrocyte Implantation: Letter to the Editor
1. Niethammer TR, Safi E, Ficklscherer A, et al. Graft maturation of autologous chondrocyte implantation: magnetic resonance investigation with T2 mapping. Am J Sports Med. 2014;42(9):2199-2204. 2. Roos EM, Davis A, Beynnon BD. IKDC or KOOS? Which measures symptoms and disabilities most important to postoperative articular cartilage repair patients? [letter]. Am J Sports Med. 2009;37(5):10421043. 3. de Windt TS, Welsch GH, Brittberg M, et al. Is magnetic resonance imaging reliable in predicting clinical outcome after articular cartilage repair of the knee? A systematic review and meta-analysis. Am J Sports Med. 2013;41(7):1695-1702.
DOI: 10.1177/0363546514554365
Dear Editor: I read with great interest the recently published case series study with 13 patients by Niethammer and colleagues,1 which suggested that graft maturation after autologous chondrocyte implantation (ACI) in the knee joint needs at least 1 year, with ongoing adjustment of the T2 relaxation time values compared with native surrounding cartilage, and found no correlation between increasing ACI graft maturation and clinical outcomes (International Knee Documentation Committee [IKDC] score). This is a very important study, adding to the studies on evaluating ACI graft maturation in osteochondral lesions. It would have been interesting if the authors—because of obvious heterogeneity of defect locations as well as serious methodological limitations inherent in case series studies (eg, lack of comparative cohort or control group)—could have improved their study assessment tools (such as also using histological findings or the Short Form–36 [SF-36] questionnaire as secondary outcomes) to determine the contributing factors that affected clinical outcomes. Mental factors, which could be assessed by the SF-36 questionnaire, or other variables that are not visible on magnetic resonance imaging (MRI), such as inflammation, increased vascular penetration, and nerve growth, may influence clinical outcomes. Moreover, the complexity of the knee injury and the patient history can make it difficult for any of the used outcome questionnaires to reflect the exact areas that are important to patients.2 Particularly with respect to the IKDC, the score reflects an overall outcome of different items such as pain, activity, and function, which may confound correlation with MRI. I therefore agree with de Windt et al3 that reported evidence to determine whether morphological MRI is reliable in predicting clinical outcomes after cartilage repair is lacking. Future research using more reliable clinical outcome tools after articular cartilage repair could be of great importance to the field.
Paving the Way for Future Research in Autologous Chondrocyte Implantation: Response DOI: 10.1177/0363546514554366
Authors’ Response: Thank you for your response to the recently published article regarding the graft maturation of ACI in the knee using MRI evaluation with T2 relaxation time values. We agree with your concerns that a case series has a limited validity because of the small number of patients. We also share your concern that a homogeneous cohort of either the same localization or the control group to analyze different methods of cartilage repair would be helpful. But the purpose of our study was to evaluate the graft maturation of ACI in the knee. Regarding your recommendation to analyze histological findings of the implanted ACI grafts, it should be noted that biopsies of the ACI grafts in the postoperative course cannot be performed for ethical reasons. Therefore we did not include this interesting point in this study. Instead, we have established a standardized MRI followup with T2 relaxation time measurement to get more information about the content of collagen and water in the ACI grafts. With regard to your proposed evaluation of mental factors using the Short Form–36 questionnaire, we would like to respond with the following. Mental factors might be a proper study assessment tool to interpret individual results. In a case series with a heterogeneous study population however, it is not helpful. For clinical evaluation, the subjective IKDC score and the visual analog scale for pain at rest and during activities were used. These scores are established and validated scores in the follow-up examination of cartilage regeneration procedures, and they have been used in several studies.2-4 To date, correlation of MRI after ACI and clinical scores are established and part of several performed studies.1,4,5 A careful analysis of radiological parameters such as the T2 relaxation time values are promising to improve the knowledge of this field. Further study into this topic is
Hamidreza Shemshaki, MD Tu¨ bingen, Germany
Address correspondence to Hamidreza Shemshaki, MD (e-mail: [email protected]). The author has declared no conflicts of interest in the authorship and publication of this contribution.
The American Journal of Sports Medicine, Vol. 42, No. 11 Ó 2014 The Author(s)
NP51 Downloaded from ajs.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 4, 2015
NP52 Letter to the Editor
The American Journal of Sports Medicine
clearly warranted, and we thank you for your kind words. Thomas R. Niethammer, MD Elem Safi, MD Andreas Ficklscherer, MD Annie Horng, MD Markus Feist, MD Isa Feist-Pagenstert, MD Volkmar Jansson, MD Matthias F. Pietschmann, MD Peter E. Mu ¨ ller, MD Munich, Germany ¨ ller, MD (e-mail: Address correspondence to Peter E. Mu [email protected]). The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.
REFERENCES 1. Blackman AJ, Smith MV, Flanigan DC, Matava MJ, Wright RW, Brophy RH. Correlation between magnetic resonance imaging and clinical outcomes after knee cartilage repair: author’s response [letter]. Am J Sports Med. 2013;41(11):NP49-NP50. 2. Henderson I, Gui J, Lavigne P. Autologous chondrocyte implantation: natural history of postimplantation periosteal hypertrophy and effects of repair-site debridement on outcome. Arthroscopy. 2006;22(12): 1318-1324 e1311. 3. Niemeyer P, Pestka JM, Kreuz PC, et al. Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med. 2008;36(11):2091-2099. 4. Pietschmann MF, Niethammer TR, Horng A, et al. The incidence and clinical relevance of graft hypertrophy after matrix-based autologous chondrocyte implantation. Am J Sports Med. 2012;40(1):68-74. 5. Salzmann GM, Erdle B, Porichis S, et al. Long-term T2 and qualitative MRI morphology after first-generation knee autologous chondrocyte implantation: cartilage ultrastructure is not correlated to clinical or qualitative MRI outcome. Am J Sports Med. 2014;42(8):18321840.
For reprints and permission queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav
Downloaded from ajs.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 4, 2015
