Publications by authors named "Claire D Eliasberg"

21 Publications

  • Page 1 of 1

Complications Following Biologic Therapeutic Injections: A Multicenter Case Series.

Arthroscopy 2021 Apr 17. Epub 2021 Apr 17.

Hospital for Special Surgery, New York, New York, U.S.A.

Purpose: To describe the complications that occur following biologic therapeutic injections.

Methods: We queried physician members of the Biologic Association, a multidisciplinary organization dedicated to providing a unified voice for all matters related to musculoskeletal biologics and regenerative medicine. Patients included in this study must have (1) received a biologic injection, (2) sustained an adverse reaction, and (3) had a minimum of 1-year follow-up after the injection. Patient demographic information, medical comorbidities, diagnoses, and previous treatments were recorded. The type of injection, injection setting, injection manufacturers, and specific details about the complication and outcome were collected.

Results: In total, 14 patients were identified across 6 institutions in the United States (mean age 63 years, range: 36-83 years). The most common injections in this series were intra-articular knee injections (50%), followed intra-articular shoulder injections (21.4%). The most common underlying diagnosis was osteoarthritis (78.5%). Types of injections included umbilical cord blood, platelet-rich plasma, bone marrow aspirate concentrate, placental tissue, and unspecified "stem cell" injections. Complications included infection (50%), suspected sterile inflammatory response (42.9%), and a combination of both (7.1%). The most common pathogen identified from infection cases was Escherichia coli (n = 4). All patients who had isolated infections underwent treatment with at least one subsequent surgical intervention (mean: 3.6, range: 1-12) and intravenous antibiotic therapy.

Conclusions: This study demonstrates that serious complications can occur following treatment with biologic injections, including infections requiring multiple surgical procedures and inflammatory reactions.

Level Of Evidence: Level IV, case series.
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http://dx.doi.org/10.1016/j.arthro.2021.03.065DOI Listing
April 2021

Mitochondrial dysfunction and potential mitochondrial protectant treatments in tendinopathy.

Ann N Y Acad Sci 2021 04 11;1490(1):29-41. Epub 2021 Apr 11.

Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York.

Tendinopathy is a common musculoskeletal condition that affects a wide range of patients, including athletes, laborers, and older patients. Tendinopathy is often characterized by pain, swelling, and impaired performance and function. The etiology of tendinopathy is multifactorial, including both intrinsic and extrinsic mechanisms. Various treatment strategies have been described, but outcomes are often variable, as tendons have poor intrinsic healing potential compared with other tissues. Therefore, several novel targets for tendon regeneration have been identified and are being explored. Mitochondria are organelles that generate adenosine triphosphate, and they are considered to be the power generators of the cell. Recently, mitochondrial dysfunction verified by increased reactive oxygen species (ROS), decreased superoxide dismutase activity, cristae disorganization, and decreased number of mitochondria has been identified as a mechanism that may contribute to tendinopathy. This has provided new insights for studying tendinopathy pathogenesis and potential treatments via antioxidant, metabolic modulation, or ROS inhibition. In this review, we present the current understanding of mitochondrial dysfunction in tendinopathy. The review summarizes the potential mechanism by which mitochondrial dysfunction contributes to the development of tendinopathy, as well as the potential therapeutic benefits of mitochondrial protectants in the treatment of tendinopathy.
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http://dx.doi.org/10.1111/nyas.14599DOI Listing
April 2021

Algorithm for Treatment of Focal Cartilage Defects of the Knee: Classic and New Procedures.

Cartilage 2021 Mar 20:1947603521993219. Epub 2021 Mar 20.

Hospital for Special Surgery, New York, NY, USA.

Objective: To create a treatment algorithm for focal grade 3 or 4 cartilage defects of the knee using both classic and novel cartilage restoration techniques.

Design: A comprehensive review of the literature was performed highlighting classic as well as novel cartilage restoration techniques supported by clinical and/or basic science research and currently being employed by orthopedic surgeons.

Results: There is a high level of evidence to support the treatment of small to medium size lesions (<2-4 cm) without subchondral bone involvement with traditional techniques such as marrow stimulation, osteochondral autograft transplant (OAT), or osteochondral allograft transplant (OCA). Newer techniques such as autologous matrix-induced chondrogenesis and bone marrow aspirate concentrate implantation have also been shown to be effective in select studies. If subchondral bone loss is present OAT or OCA should be performed. For large lesions (>4 cm), OCA or matrix autologous chondrocyte implantation (MACI) may be performed. OCA is preferred over MACI in the setting of subchondral bone involvement while cell-based modalities such as MACI or particulated juvenile allograft cartilage are preferred in the patellofemoral joint.

Conclusions: Numerous techniques exist for the orthopedic surgeon treating focal cartilage defects of the knee. Treatment strategies should be based on lesion size, lesion location, subchondral bone involvement, and the level of evidence supporting each technique in the literature.
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http://dx.doi.org/10.1177/1947603521993219DOI Listing
March 2021

The Ideal Hinge Axis Position to Reduce Tibial Slope in Opening-Wedge High Tibial Osteotomy Includes Proximalization-Extension and Internal Rotation.

Arthroscopy 2021 05 24;37(5):1577-1584. Epub 2020 Dec 24.

Hospital for Special Surgery, New York, New York, U.S.A.

Purpose: To evaluate the effect of the hinge axis position on the posterior tibial slope (PTS) in medial opening-wedge high tibial osteotomy.

Methods: This study included adults with medial-compartment osteoarthritis who had computed tomography (CT) scans available that were amenable to Bodycad Osteotomy software analysis. Virtual osteotomies modeling a 10-mm medial opening-wedge gap were performed. The hinge axis was rotated internally and externally and was proximalized-extended and distalized-flexed with respect to the anterior tibial cortex for 5°, 10°, 15°, and 20°. Each resultant PTS was recorded and compared with the results obtained from the true lateral hinge position and with the preoperative PTS.

Results: Computed tomography scans from 10 patients were used. Strong linear correlations were found with each hinge axis position change and the resultant PTS. The trend-line differences were statistically significant by single-factor analysis of variance (P < .001). The PTS decreased for an anterolateral hinge, whereas it increased for a posterolateral hinge. Linear regression analysis showed that rotating the hinge axis by 9.0° externally or angulating the hinge axis by 21.8° of distalization-flexion would result in increasing the tibial slope by 1° whereas rotating the hinge axis by 8.7° internally or angulating the hinge axis by 21.6° of proximalization-extension would decrease the tibial slope by 1°.

Conclusions: Distalization-flexion and external rotation of the hinge axis position led to stepwise increases in the PTS, whereas proximalization-extension and internal rotation led to decreases in the PTS.

Clinical Relevance: Our findings suggest that when performing medial opening-wedge high tibial osteotomy and aiming to decrease the PTS, the surgeon should aim to achieve maximal internal rotation (producing an anterolateral hinge), as well as proximalization-extension, of the hinge axis. This study quantifies and provides a model for the effect of the hinge axis position for a predetermined angular correction on the PTS.
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http://dx.doi.org/10.1016/j.arthro.2020.12.203DOI Listing
May 2021

Shoulder and elbow pathology in the female athlete: sex-specific considerations.

J Shoulder Elbow Surg 2021 May 18;30(5):977-985. Epub 2020 Nov 18.

Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA. Electronic address:

Unique biologic and biomechanical aspects of the female body make women more prone to certain orthopedic injuries. Sex differences are well understood with regard to certain orthopedic pathologies such as anterior cruciate ligament injury, hallux valgus, carpal tunnel, and carpometacarpal joint arthritis; however, sex differences are less commonly discussed with regard to shoulder and elbow pathology. The purpose of this review is to elucidate sex differences specific to sports-related shoulder and elbow injuries in the female athlete population.
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http://dx.doi.org/10.1016/j.jse.2020.10.020DOI Listing
May 2021

Development of Parsonage-Turner Syndrome After Heat Stroke in Firefighters: A Report of 2 Cases.

JBJS Case Connect 2020 Apr-Jun;10(2):e19.00462

Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York.

Case: Two firefighters developed Parsonage-Turner syndrome (PTS) shortly after sustaining episodes of heat stroke. Patient 1 was a 40-year-old man who presented with shoulder pain and supraspinatus and infraspinatus weakness. Patient 2 was a 35-year-old man who presented with shoulder pain and absent external rotation strength. Both had electrodiagnostic testing and magnetic resonance imaging findings consistent with PTS. Both demonstrated partial but incomplete recovery at 1- and 2.5-year follow-ups, respectively.

Conclusions: PTS should remain on the differential diagnosis for any patient presenting with sudden onset shoulder pain and neurological deficits after an episode of heat-related illness.
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http://dx.doi.org/10.2106/JBJS.CC.19.00462DOI Listing
February 2021

Development of a Meniscal Ossicle After a Meniscal Root Repair Augmented with Bone Marrow Aspirate Concentrate: A Case Report.

JBJS Case Connect 2020 Jan-Mar;10(1):e0419

Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York.

Case: A 17-year-old boy had persistent knee pain 1 year after medial meniscal root repair augmented with bone marrow aspirate concentrate injection. Radiographs and magnetic resonance imaging (MRI) demonstrated an intrameniscal ossicle which was not present on MRI performed before 6 months. He underwent arthroscopic excision of the meniscal ossicle. At the 7-month follow-up, he had complete relief of his pain.

Conclusions: It is possible that the meniscal ossicle developed because of osteoinductive cells and cytokines from the injected bone marrow or the drill hole for root repair and should be considered as a possible complication of this procedure.
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http://dx.doi.org/10.2106/JBJS.CC.19.00419DOI Listing
January 2021

The role of the macrophage in tendinopathy and tendon healing.

J Orthop Res 2020 08 30;38(8):1666-1675. Epub 2020 Mar 30.

Orthopaedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York.

The role of the macrophage is an area of emerging interest in tendinopathy and tendon healing. The macrophage has been found to play a key role in regulating the healing process of the healing tendon. The specific function of the macrophage depends on its functional phenotype. While the M1 macrophage phenotype exhibits a phagocytic and proinflammatory function, the M2 macrophage phenotype is associated with the resolution of inflammation and tissue deposition. Several studies have been conducted on animal models looking at enhancing or suppressing macrophage function, targeting specific phenotypes. These studies include the use of exogenous biological and pharmacological substances and more recently the use of transgenic and genetically modified animals. The outcomes of these studies have been promising. In particular, enhancement of M2 macrophage activity in the healing tendon of animal models have shown decreased scar formation, accelerated healing, decreased inflammation and even enhanced biomechanical strength. Currently our understanding of the role of the macrophage in tendinopathy and tendon healing is limited. Furthermore, the roles of therapies targeting macrophages to enhance tendon healing is unclear. Clinical Significance: An increased understanding of the significance of the macrophage and its functional phenotypes in the healing tendon may be the key to enhancing tendon healing. This review will present the current literature on the function of macrophages in tendinopathy and tendon healing and the potential of therapies targeting macrophages to enhance tendon healing.
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http://dx.doi.org/10.1002/jor.24667DOI Listing
August 2020

Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model.

J Orthop Res 2019 12 13;37(12):2575-2582. Epub 2019 Aug 13.

Department of Orthopaedic Surgery, Laboratory for Joint Tissue Repair and Regeneration, Orthopedic Soft Tissue Research Program, The Hospital for Special Surgery, New York, New York, 10021.

Subacromial impingement is associated with a spectrum of disorders-including rotator cuff disease-but their relationship is complex. We have established a novel murine model of subacromial impingement to study supraspinatus tendinopathy. The purpose of this study was to evaluate changes in gene expression in this murine shoulder impingement model to further elucidate the mechanisms underlying the development of tendinopathy. Twenty-eight C57BL/6 mice were used in this study. All mice underwent bilateral surgery with insertion of a small metal clip in the subacromial space or a sham procedure. The supraspinatus tendons underwent histological analyses, biomechanical testing, and RNA extraction for multiplex gene expression analysis (NanoString, Seattle, WA). Histology demonstrated increased cellularity and disorganized collagen fibers of the supraspinatus tendon in the clip impingement group. Mean load to failure (5.20 vs. 1.50 N, p < 0.001) and mean stiffness (4.95 vs. 1.47 N/mm, p < 0.001) were lower in the impingement group than the sham group. NanoString analyses revealed 111 differentially expressed genes (DEGs) between the impingement and sham groups. DEGs of interest included Mmp3 (expression ratio [ER]: 2.68, p = 0.002), Tgfb1 (ER: 1.76, p = 0.01), Col3a1 (ER: 1.66, p = 0.03), and Tgfbr2 (ER: 1.53, p = 0.01). Statement of clinical significance: We identified 111 DEGs that may contribute to the development of tendinopathy in this model. Further studies of these specific genes will allow identification of their roles in the initiation and regulation of tendon damage, and their potential to serve as novel therapeutic targets in the treatment of rotator cuff disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2575-2582, 2019.
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http://dx.doi.org/10.1002/jor.24434DOI Listing
December 2019

Perioperative Use of Novel Oral Anticoagulants in Orthopaedic Surgery: A Critical Analysis Review.

JBJS Rev 2019 07;7(7):e4

Departments of Orthopaedic Surgery (C.D.E., A.E.L., E.B.G., and A.M.K.), Anesthesiology (S.G.), and Medicine (L.A.R.), Hospital for Special Surgery, New York, NY.

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http://dx.doi.org/10.2106/JBJS.RVW.18.00148DOI Listing
July 2019

Contingent Valuation Studies in Orthopaedic Surgery: A Health Economic Review.

HSS J 2018 Oct 9;14(3):314-321. Epub 2018 Apr 9.

1Department of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA.

Background: A greater emphasis on providing high-value orthopaedic interventions has resulted in increased health economic reporting. The contingent-valuation method (CVM) is used to determine consumer valuation of the benefits provided by healthcare interventions. CVM is an important value-based health economic tool that is underutilized in orthopaedic surgery.

Questions/purposes: The purpose of this study was to (1) identify previously published CVM studies in the orthopaedic literature, (2) assess the methodologies used for CVM research, and (3) understand how CVM has been used in the orthopaedic cost-benefit analysis framework.

Methods: A systematic review of the literature using the MEDLINE database was performed to compile CVM studies. Search terms incorporated the phrase (WTP) or (WTA) in combination with orthopaedic clinical key terms. Study methodology was appraised using previously defined empirical and conceptual criteria for CVM studies.

Results: Of the 160 studies retrieved, 22 (13.8%) met our inclusion criteria. The economics of joint arthroplasty ( 6, 27.3%) and non-operative osteoarthritis care ( 4, 18.2%) were the most common topics. Most studies used CVM for pricing and/or demand forecasting ( 16, 72.7%); very few studies used CVM for program evaluation ( 6). WTP was used in all included studies, and one study used both WTP and WTA. Otherwise, there was little consistency among included studies in terms of CVM methodology. Open-ended questioning was used by only ten studies (45.5%), a significant number of studies did not perform a sensitivity analysis ( 9, 40.9%), and none of the studies accounted for the risk preference of subjects. Only two of the included studies applied CVM within a cost-benefit analysis framework.

Conclusion: CVM is not commonly reported in orthopaedic surgery and is seldom used in the context of cost-benefit analysis. There is wide variability in the methods used to perform CVM. We propose that CVM is an appropriate and underappreciated method for understanding the value of orthopaedic interventions. Increased attention should be paid to consumer valuations for orthopaedic interventions.
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http://dx.doi.org/10.1007/s11420-018-9610-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148581PMC
October 2018

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.

Clin Orthop Relat Res 2018 10;476(10):2091-2100

S. K. Devana, B. V. Kelley, O. J. McBride, N. Kabir, A. R. Jensen, S. J. Park, C. D. Eliasberg, A. Dar, G. M. Mosich, T. J. Kowalski, B. Péault, F. A. Petrigliano, N. F. SooHoo, Department of Orthopaedic Surgery, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA C. D. Eliasberg, Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA T. J. Kowalski, Department of Orthopaedic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK B. Péault, University of Edinburgh, MRC Center for Regenerative Medicine, Edinburgh, UK.

Background: Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use.

Questions/purposes: The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection.

Methods: Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining.

Results: Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005).

Conclusions: Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing.

Clinical Relevance: This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.
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http://dx.doi.org/10.1097/CORR.0000000000000461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259872PMC
October 2018

Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor β-positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff.

J Shoulder Elbow Surg 2018 Jul 10;27(7):1149-1161. Epub 2018 Apr 10.

Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Background And Hypothesis: After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor β (PDGFRβ) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRβ progenitor cells that contribute to fibroadipogenesis of the rotator cuff.

Methods: We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRβ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP PDGFRβ PDGFRα cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition.

Results: GFP PDGFRβ PDGFRα cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRβ PDGFRα cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRβ PDGFRα cells were highly adipogenic and significantly more fibrogenic than PDGFRβ PDGFRα cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRβ PDGFRα cells.

Conclusion: PDGFRβ PDGFRα cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRβ PDGFRα cells in vitro. Clinically, perioperative PDGFRβ PDGFRα cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears.
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http://dx.doi.org/10.1016/j.jse.2018.02.040DOI Listing
July 2018

Reoperation and complications after anterior cervical discectomy and fusion and cervical disc arthroplasty: a study of 52,395 cases.

Eur Spine J 2018 06 31;27(6):1432-1439. Epub 2018 Mar 31.

Department of Orthopedic Surgery, University of California, Los Angeles, CA, USA.

Purpose: The aim of this study was to analyze rates of perioperative complications and subsequent cervical surgeries in patients treated for cervical degenerative disc disease with anterior cervical discectomy and fusion (ACDF) and those treated with artificial cervical disc arthroplasty (ACDA) for up to 5-year follow-up.

Methods: California's Office of Statewide Health Planning and Development discharge database was analyzed for patients aged 18-65 years undergoing single-level ACDF or ACDA between 2003 and 2010. Medical comorbidities were identified with CMS-Condition Categories. Readmissions for short-term complications of the procedure were identified and rates of subsequent cervical surgeries were calculated at 90-day and 1-, 3-, and 5-year follow-up. Multivariate regression modeling was used to identify associations with complications and subsequent cervical surgeries correcting for patient and provider characteristics.

Results: A total of 52,395 eligible cases were identified: 50,926 ACDF and 1469 ACDA. Readmission was less common in the ACDA group (OR: 0.69, 95% CI: 0.48-1.0, p = 0.048). Subsequent cervical spine surgery was more common in the ACDF group in the immediate perioperative period (within 90 days of surgery) (ACDF 3.35% vs. ACDA 2.04%, OR: 0.63, 95% CI: 0.44-0.92, p = 0.015). At 1-, 3-, and 5-year postoperatively, rates of subsequent cervical surgeries were similar between the two cohorts.

Conclusions: We found no protective benefit for ACDA versus ACDF for single-level disease at up to 5-year follow-up in the largest cohort of patients examined to date. Early complications were rare in both cohorts stressing the value of large cohort studies to study risk factors for rare events. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-018-5570-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488512PMC
June 2018

Osteochondral Allograft Transplantation of the Knee in Patients Aged 40 Years and Older.

Am J Sports Med 2018 03 29;46(3):581-589. Epub 2017 Nov 29.

Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York, USA.

Background: Treatment of large chondral defects of the knee among patients aged ≥40 years remains a difficult clinical challenge owing to preexisting joint degeneration and the lack of treatment options short of arthroplasty.

Purpose: To characterize the survivorship, predictors of failure, and clinical outcomes of osteochondral allograft transplantation (OCA) of the knee among patients aged ≥40 years.

Study Design: Case series; Level of evidence, 4.

Methods: Prospectively collected data were reviewed for 54 consecutive patients aged ≥40 years who were treated with OCA. Preoperative levels of osteoarthritis (according to Kellgren-Lawrence classification) and meniscal volume and quality were graded from review of radiographs and magnetic resonance imaging. Complications, reoperations, and patient responses to validated outcome measures were reviewed. A minimum follow-up of 2 years was required for analysis. Failure was defined by any removal or revision of the allograft or conversion to arthroplasty.

Results: Among 51 patients (mean age, 48 years; range, 40-63 years; 65% male), a total of 52 knees had symptomatic focal cartilage lesions (up to 2 affected areas) that were classified as Outerbridge grade 4 at the time of OCA and did not involve substantial bone loss requiring shell allografts or additional bone grafting. Mean duration of follow-up was 3.6 years (range, 2-11 years). After OCA, 21 knees (40%) underwent reoperation, including 14 failures (27%) consisting of revision OCA (n = 1), unicompartmental knee arthroplasty (n = 5), and total knee arthroplasty (n = 8). Mean time to failure was 33 months, and 2- and 4-year survivorship rates were 88% and 73%, respectively. Male sex (hazard ratio = 4.18, 95% CI = 1.12-27.13) and a higher number of previous ipsilateral knee operations (hazard ratio = 1.70 per increase in 1 surgical procedure, 95% CI = 1.03-2.83) were predictors of failure. A higher Kellgren-Lawrence osteoarthritis grade on preoperative radiographs was associated with higher failure rates in the Kaplan-Meier analysis but not the multivariate model. At final follow-up, clinically significant improvements were noted in the pain (mean score, 47.8 to 67.6) and physical functioning (56.8 to 79.1) subscales of the Short Form-36, as well as the International Knee Documentation Committee subjective form (45.0 to 63.6), Knee Outcome Survey-Activities of Daily Living (64.5 to 80.1), and overall condition statement (4.5 to 6.8) ( P < .001). No significant changes were noted for the Marx Activity Rating Scale (5.1 to 3.9, P = .789).

Conclusion: A higher failure rate was found in this series of patients aged ≥40 years who were treated with OCA as compared with other studies of younger populations. However, for select older patients, OCA can be a good midterm treatment option for cartilage defects of the knee.
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http://dx.doi.org/10.1177/0363546517741465DOI Listing
March 2018

Condyle-Specific Matching Does Not Improve Midterm Clinical Outcomes of Osteochondral Allograft Transplantation in the Knee.

J Bone Joint Surg Am 2017 Oct;99(19):1614-1620

1Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, NY 2Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California.

Background: Condyle-specific matching for osteochondral allograft transplantation (OCA) pairs donor and recipient condyles in an attempt to minimize articular incongruity. While the majority of cartilage defects are located on the medial femoral condyle, lateral femoral condyles are more commonly available as a graft source. The purpose of this study was to compare the clinical outcomes of patients treated with non-orthotopic (lateral-to-medial condyle or medial-to-lateral condyle) OCA with those treated with traditional orthotopic (medial-to-medial condyle or lateral-to-lateral condyle) OCA. We hypothesized that clinical outcomes would be similar between groups at midterm follow-up.

Methods: A retrospective review of prospectively collected data on patients treated with OCA from 2000 to 2014 was conducted. Seventy-seven patients with a full-thickness cartilage defect of a femoral condyle were treated with either orthotopic (n = 50) or non-orthotopic (n = 27) OCA. A minimum follow-up of 2 years was required for analysis. Patients in each group were matched according to sex, age, and total chondral defect size. Reoperations and patient responses to validated outcome measures were reviewed. Failure was defined as any revision cartilage procedure or conversion to knee arthroplasty.

Results: The mean duration of follow-up was 4.0 years (range, 2 to 16 years). The orthotopic and non-orthotopic OCA groups were comparable in terms of demographics, the mean number of prior ipsilateral knee operations, and the percentage of concomitant procedures at baseline. Reoperation (p = 0.427) and failure (p = 0.917) rates did not differ significantly between groups. Both groups demonstrated significant increases in the Short Form-36 (SF-36) physical functioning and pain, International Knee Documentation Committee (IKDC), and Knee Outcome Survey-Activities of Daily Living (KOS-ADL) scores compared with baseline (p < 0.004). Outcome scores (baseline and postoperative) and change scores did not differ significantly between groups.

Conclusions: Clinical outcomes do not differ between patients treated with orthotopic OCA and those treated with non-orthotopic OCA, suggesting that condyle-specific matching may not be necessary.

Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.16.01542DOI Listing
October 2017

Similar Outcomes After Osteochondral Allograft Transplantation in Anterior Cruciate Ligament-Intact and -Reconstructed Knees: A Comparative Matched-Group Analysis With Minimum 2-Year Follow-Up.

Arthroscopy 2017 Dec 8;33(12):2198-2207. Epub 2017 Aug 8.

Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York, U.S.A.

Purpose: To compare failure rates and clinical outcomes of osteochondral allograft transplantation (OCA) in anterior cruciate ligament (ACL)-intact versus ACL-reconstructed knees at midterm follow-up.

Methods: After a priori power analysis, a prospective registry of patients treated with OCA for focal chondral lesions ≥2 cm in size with minimum 2-year follow-up was used to match ACL-reconstructed knees with ACL-intact knees by age, sex, and primary chondral defect location. Exclusion criteria included meniscus transplantation, realignment osteotomy, or other ligamentous injury. Complications, reoperations, and patient responses to validated outcome measures were reviewed. Failure was defined by any procedure involving allograft removal/revision or conversion to arthroplasty. Kaplan-Meier analysis and multivariate Cox regression were performed to evaluate the association of ACL reconstruction (ACLR) with failure.

Results: A total of 50 ACL-intact and 25 ACL-reconstructed (18 prior, 7 concomitant) OCA patients were analyzed. The mean age was 36.2 years (range, 14-62 years). Mean follow-up was 3.9 years (range, 2-14 years). Patient demographics and chondral lesion characteristics were similar between groups. ACL-reconstructed patients averaged 2.2 ± 1.9 prior surgeries on the ipsilateral knee compared with 1.4 ± 1.4 surgeries for ACL-intact patients (P = .014). Grafts used for the last ACLR included bone-patellar tendon-bone autograft, hamstring autograft, Achilles tendon allograft, and tibialis allograft (data available for only 11 of 25 patients). At final follow-up, 22% of ACL-intact and 32% of ACL-reconstructed patients had undergone reoperation. OCA survivorship was 90% and 96% at 2 years and 79% and 85% at 5 years in ACL-intact and ACL-reconstructed patients, respectively (P = .774). ACLR was not independently associated with failure. Both groups demonstrated clinically significant improvements in the Short Form-36 pain and physical functioning, International Knee Documentation Committee subjective, and Knee Outcome Survey-Activities of Daily Living scores at final follow-up (P < .001), with no significant differences in preoperative, postoperative, and change scores between groups.

Conclusions: OCA in the setting of prior or concomitant ACLR does not portend higher failure rates or compromise clinical outcomes.

Level Of Evidence: Level III, retrospective comparative study.
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http://dx.doi.org/10.1016/j.arthro.2017.06.034DOI Listing
December 2017

Perivascular Stem Cells Diminish Muscle Atrophy Following Massive Rotator Cuff Tears in a Small Animal Model.

J Bone Joint Surg Am 2017 Feb;99(4):331-341

1Hospital for Special Surgery, New York, NY 2University of California, Los Angeles, Los Angeles, California 3University of Edinburgh, Edinburgh, United Kingdom 4University of California, Davis, Davis, California 5Washington University, St. Louis, Missouri 6University of Southern California, Los Angeles, California 7University of California, San Francisco, San Francisco, California.

Background: Rotator cuff tears are a common cause of shoulder pain and often necessitate operative repair. Muscle atrophy, fibrosis, and fatty infiltration can develop after rotator cuff tears, which may compromise surgical outcomes. This study investigated the regenerative potential of 2 human adipose-derived progenitor cell lineages in a murine model of massive rotator cuff tears.

Methods: Ninety immunodeficient mice were used (15 groups of 6 mice). Mice were assigned to 1 of 3 surgical procedures: sham, supraspinatus and infraspinatus tendon transection (TT), or TT and denervation via suprascapular nerve transection (TT + DN). Perivascular stem cells (PSCs) were harvested from human lipoaspirate and sorted using fluorescence-activated cell sorting into pericytes (CD146 CD34 CD45 CD31) and adventitial cells (CD146 CD34 CD45 CD31). Mice received no injection, injection with saline solution, or injection with pericytes or adventitial cells either at the time of the index procedure ("prophylactic") or at 2 weeks following the index surgery ("therapeutic"). Muscles were harvested 6 weeks following the index procedure. Wet muscle weight, muscle fiber cross-sectional area, fibrosis, and fatty infiltration were analyzed.

Results: PSC treatment after TT (prophylactic or therapeutic injections) and after TT + DN (therapeutic injections) resulted in less muscle weight loss and greater muscle fiber cross-sectional area than was demonstrated for controls (p < 0.05). The TT + DN groups treated with pericytes at either time point or with adventitial cells at 2 weeks postoperatively had less fibrosis than the TT + DN controls. There was less fatty infiltration in the TT groups treated with pericytes at either time point or with adventitial cells at the time of surgery compared with controls.

Conclusions: Our findings demonstrated significantly less muscle atrophy in the groups treated with PSCs compared with controls. This suggests that the use of PSCs may have a role in the prevention of muscle atrophy without leading to increased fibrosis or fatty infiltration.

Clinical Relevance: Improved muscle quality in the setting of rotator cuff tears may increase the success rates of surgical repair and lead to superior clinical outcomes.
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http://dx.doi.org/10.2106/JBJS.16.00645DOI Listing
February 2017

Kappa opioid receptor signaling protects cartilage tissue against posttraumatic degeneration.

JCI Insight 2017 01 12;2(1):e88553. Epub 2017 Jan 12.

Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Osteoarthritis is the most common form of arthritis, and pain relief with opioid-like drugs is a commonly used therapeutic for osteoarthritic patients. Recent studies published by our group showed that the kappa opioid receptor (KOR) is highly expressed during human development in joint-forming cells. However, the precise role of this receptor in the skeletal system remains elusive. The main aim of the current study was to investigate the role of KOR signaling in synovial and cartilaginous tissues in pathological conditions. Our data demonstrate that KOR null mice exhibit accelerated cartilage degeneration after injury when compared with WT mice. Activation of KOR signaling increased the expression of anabolic enzymes and inhibited cartilage catabolism and degeneration in response to proinflammatory cytokines such as TNF-α. In addition, selective KOR agonists increased joint lubrication via the activation of cAMP/CREB signaling in chondrocytes and synovial cells. Taken together, these results demonstrate direct effects of KOR agonists on cartilage and synovial cells and reveals a protective effect of KOR signaling against cartilage degeneration after injury. In addition to pain control, local administration of dynorphin or other KOR agonist represents an attractive therapeutic approach in patients with early stages of osteoarthritis.
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http://dx.doi.org/10.1172/jci.insight.88553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214705PMC
January 2017

Complications and Rates of Subsequent Lumbar Surgery Following Lumbar Total Disc Arthroplasty and Lumbar Fusion.

Spine (Phila Pa 1976) 2016 Jan;41(2):173-81

*Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, CA †Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO ‡Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, CA §Department of Orthopaedic Surgery, University of California at Los AngelesLos Angeles, CA.

Study Design: Retrospective analysis.

Objective: To examine complications and rates of subsequent surgery following lumbar spinal fusion (LF) and lumbar total disc arthroplasty (TDA) at up to 5-year follow-up.

Summary Of Background Data: LF is commonly used in the management of degenerative disc disease causing pain refractory to nonoperative management. Lumbar TDA was developed as an alternative to fusion with the theoretical advantage of reducing rates of adjacent segment pathology and reoperation. Most prior reports comparing these 2 interventions have come from industry-sponsored investigational device exemption trials and no large-scale administrative database comparisons exist.

Methods: The California Office of Statewide Health Planning and Development discharge database was queried for patients aged 18 to 65 years undergoing lumbar TDA and LF for degenerative disc disease from 2004 to 2010. Patient characteristics were collected, and rates of complications and readmission were identified. Rates of repeat lumbar surgery were calculated at 90-day and 1-, 3-, and 5-year follow-up intervals.

Results: A total of 52,877 patients met the inclusion criteria (LF = 50,462, TDA = 2415). Wound infections were more common following LF than TDA (1.03% vs. 0.25%, P < 0.001). Rates of subsequent lumbar surgery at 90-day and 1-year follow-up were lower with lumbar TDA than LF (90-day-TDA: 2.94% vs. LF: 4.01%, P = 0.007; 1-yr-TDA: 3.46% vs. LF: 4.78%, P = 0.009). However, there were no differences in rates of subsequent lumbar surgery between the 2 groups at 3-year and 5-year follow-up.

Conclusion: Lumbar TDA was associated with fewer early reoperations, though beyond 1 year, rates of reoperation were similar. Lumbar TDA may be associated with fewer acute infections, though this may be approach related and unrelated to the device itself.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000001180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710859PMC
January 2016

Hypoxic culture conditions induce increased metabolic rate and collagen gene expression in ACL-derived cells.

J Orthop Res 2016 06 16;34(6):985-94. Epub 2015 Dec 16.

Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, 90095, California.

There has been substantial effort directed toward the application of bone marrow and adipose-derived mesenchymal stromal cells (MSCs) in the regeneration of musculoskeletal tissue. Recently, resident tissue-specific stem cells have been described in a variety of mesenchymal structures including ligament, tendon, muscle, cartilage, and bone. In the current study, we systematically characterize three novel anterior cruciate ligament (ACL)-derived cell populations with the potential for ligament regeneration: ligament-forming fibroblasts (LFF: CD146(neg) , CD34(neg) CD44(pos) , CD31(neg) , CD45(neg) ), ligament perivascular cells (LPC: CD146(pos) CD34(neg) CD44(pos) , CD31(neg) , CD45(neg) ) and ligament interstitial cells (LIC: CD34(pos) CD146(neg) , CD44(pos) , CD31(neg) , CD45(neg) )-and describe their proliferative and differentiation potential, collagen gene expression and metabolism in both normoxic and hypoxic environments, and their trophic potential in vitro. All three groups of cells (LIC, LPC, and LFF) isolated from adult human ACL exhibited progenitor cell characteristics with regard to proliferation and differentiation potential in vitro. Culture in low oxygen tension enhanced the collagen I and III gene expression in LICs (by 2.8- and 3.3-fold, respectively) and LFFs (by 3- and 3.5-fold, respectively) and increased oxygen consumption rate and extracellular acidification rate in LICs (by 4- and 3.5-fold, respectively), LFFs (by 5.5- and 3-fold, respectively), LPCs (by 10- and 4.5-fold, respectively) as compared to normal oxygen concentration. In summary, this study demonstrates for the first time the presence of three novel progenitor cell populations in the adult ACL that demonstrate robust proliferative and matrix synthetic capacity; these cells may play a role in local ligament regeneration, and consequently represent a potential cell source for ligament engineering applications. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:985-994, 2016.
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http://dx.doi.org/10.1002/jor.23116DOI Listing
June 2016