CLINICAL OUTCOME PAPERS

Stone, K.R., Walgenbach, A.W., Slatter, S., Turek, T.J., Ferguson-Dryden, C., Dicker, M., Miltenberger, E., Cowles, H., Liu, V., Wu, S., Vessal, M. 2024. "Meniscus Allograft Transplantation in Conjunction with Biologic Knee Restoration Delays Arthroplasty in Patients Older Than 50 Years." Arthroscopy.

Objective: To evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years previously advised joint arthroplasty.

Design: A total of 108 meniscus allograft transplants using the arthroscopic 3-tunnel technique between 1997 and 2019 in patients older than 50 years were retrospectively reviewed with a 2-year minimum follow-up period. Inclusion criteria were patients recommended for knee arthroplasty with pain and preservation of some joint space by standing flexion radiographs. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol, and failure to complete research questionnaires. International Knee Documentation Committee composite and isolated pain scale were evaluated longitudinally. Time from meniscus allograft transplant to arthroplasty was measured, with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain.

Results: Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (P < .001) in pain and function as assessed by International Knee Documentation Committee Score. These improvements were sustained 10 years postoperatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference through 10 years postoperatively.

Conclusions: Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates older than 50 years. Influences of concomitant procedures cannot be defined.

Stone, K.R., Walgenbach, A.W., Turek, T.J. et al. 2023. "Xenograft bone-patellar tendon-bone ACL reconstruction: a case series at 20-year follow-up as proof of principle." Journal of Experimental Orthopaedics.

Purpose: ACL reconstruction has a significant failure rate. To address the need for inexpensive strong tissue, a treatment process to “humanize” porcine tissue was developed and tested in primates and humans. This report describes the long-term outcomes from the first human clinical trial using a porcine xenograft ACL reconstruction device.
Methods: The study was performed with Z-Lig™ xenograft ACL device in 2003 as a pilot clinical feasibility study. This device was processed to slow its immune-mediated destruction by enzymatic elimination of α-gal epitopes and by partial crosslinking to slow the infiltration of macrophages into the biotransplant.

Results: Ten patients underwent reconstruction with the Z-Lig™ device. Five of 10 patients failed due to subsequent trauma (n = 3), arthrofibrosis (n = 1), and surgical technical error (n = 1). One patient was lost to follow-up after the 12-year evaluation. Each remaining patient reported a stable fully athletic knee. Physical exams are consistent with a score of less than one on the ACL stability tests. MRIs demonstrate mature remodeling of the device. There is no significant degradation in patient-reported outcome scores, physical exams, or MRI appearance from 12 to 20-year follow-ups.

Conclusions: The studies in a small group of patients have demonstrated that implantation of porcine ligament bioprosthesis into patients with torn ACLs can result in the reconstruction of the bioprosthesis into autologous ACL that remains successful over 20 years. The possibility of humanizing porcine tissue opens the door to unlimited clinical material for tissue reconstructions if supported by additional clinical trials.

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Daniel Grande, Todd Goldstein, Thomas J. Turek, Susan Hennessy, Ann W. Walgenbach, Le Hanh Dung Do, David Greene, and Kevin R. Stone. May, 12 2020. "Osteochondral Autograft Plugs versus Paste Graft: Ex Vivo Morselization Increases Chondral Matrix Production" SAGE Journal.

Objective: Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs.

Design: This institutional review board–approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology.

Results: Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post-processing, respectively (P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant (P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae.

Conclusions: Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.

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Stone KR, Pelsis JR, Na K, Walgenbach AW, Turek TJ. 2016. "Articular cartilage paste graft for severe osteochondral lesions of the knee: a 10- to 23-year follow-up study."Knee Surgery, Sports Traumatology, Arthroscopy.

Purpose: The purpose of this study is to evaluate the clinical outcomes of the articular cartilage paste graft procedure at a minimum of 10 years from surgery. It is hypothesized that articular cartilage paste grafting can provide patients with a durable repair of severe full-thickness osteochondral injuries, measured by persistence of procedure-induced benefit and subjective outcome scores at 10 or more years.

Methods: Seventy-four patients undergoing paste grafting at a mean age of 45.3 ± 10.8 years (range 13-69 years) were followed up at a mean of 16.8 ± 2.4 years (range 10.6-23.2 years) post-operatively using validated subjective outcome measures; Kaplan-Meier survival analysis was performed to estimate expected population benefit time.

Results: Kaplan-Meier estimated median benefit time of 19.1 years (mean: 16.6 ± 0.9 years) for all patients undergoing paste grafting. Thirty-one (41.9 %) patients had progressed to arthroplasty at a mean of 9.8 ± 5.6 years (range 0.4-20.6 years). Ninety percent of patients reported that the procedure provided good to excellent pain relief. Median IKDC subjective score increased significantly at most recent follow-up (70.1) compared to preoperative (55.7, p = 0.013). Median WOMAC scores decreased significantly from 26 to 14 (p = 0.001). Median Tegner score increase from 4 to 6 was not found to be significant (ns). VAS pain averaged 23/100 at most recent follow-up. CONCLUSIONS: Patients who underwent the paste grafting reported improved pain, function, and activity levels for an expected mean of 16.6 years, and for those who ultimately progressed to knee replacement, surgical treatment including the paste graft was able to delay arthroplasty until a mean age of 60.2 years, an age at which the procedure is commonly performed. Full-thickness articular cartilage loss can be successfully treated, reducing pain, and improving function, using this single-step, inexpensive arthroscopic procedure. LEVEL OF EVIDENCE: IV.

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Feuerstein JD, Pelsis JR, Lloyd S, Cheifetz AS,Stone KR. 2016. "Systematic analysis of the quality of the scientific evidence and conflicts of interest in osteoarthritis of the hip and knee practice guidelines." Seminars in Arthritis and Rheumatism. 45(4), 379–385.

Objective: To determine the validity of the hip and knee osteoarthritis guidelines.

Methods: A systematic search of PubMed using a combination of Mesh and text terms with limitations to guidelines was performed to identify hip and knee osteoarthritis guidelines. The study was performed from April 17, 2014 to October 1, 2014. Guidelines were reviewed for graded levels of evidence, methods used to grade the evidence, and disclosures of conflicts of interest. Additionally, guidelines were also assessed for key quality measures using the AGREE II system for assessing the quality of guidelines.

Results: A total of 13 guidelines relevant to the diagnosis and/or treatment of hip/knee osteoarthritis was identified. The 180 recommendations reviewed were supported by 231 pieces of evidence. In total, 35% (n = 80; range: 0-26) were supported by level A evidence, 15% (n = 35; range: 0-10) were by level B, and 50% (n = 116; range: 0-62) were by level C. Median age of the guidelines was 4 years (±4.8; range: 0-16) with no comments on planned updates. In total, 31% of the guidelines included patients in the development process. Only one guideline incorporated cost consideration, and only 15% of the guidelines addressed the surgical management of osteoarthritis. Additionally, 46% of guidelines did not comment on conflicts of interest (COI). When present, there was an average 29.8 COI. Notably, 82% of the COI were monetary support/consulting. Conclusions: In total, 50% of the hip/knee osteoarthritis guideline recommendations are based on lower quality evidence. Nearly half the guidelines fail to disclose relevant COI and when disclosed, multiple potential COI are present. Future hip/knee osteoarthritis guideline development committees should strive to improve the transparency and quality of evidence used to formulate practice guidelines.

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Stone K.R., Adelson W.S., Pelsis J.R., Walgenbach A.W., Turek T.J. 2010. "Long-term survival of concurrentmeniscus allograft transplantation and articular cartilage repair: A PROSPECTIVE TWO- TO 12-YEAR FOLLOW-UP REPORT." J Bone Joint Surg Br 92-B(7): 941-948.

We describe 119 meniscal allograft transplantations performed concurrently with articular cartilage repair in 115 patients with severe articular cartilage damage. In all, 53 (46.1%) of the patients were over the age of 50 at the time of surgery. The mean follow-up was for 5.8 years (2 months to 12.3 years), with 25 procedures (20.1%) failing at a mean of 4.6 years (2 months to 10.4 years). Of these, 18 progressed to knee replacement at a mean of 5.1 years (1.3 to 10.4). The Kaplan-Meier estimated mean survival time for the whole series was 9.9 years (sd 0.4). Cox's proportional hazards model was used to assess the effect of covariates on survival, with age at the time of surgery (p = 0.026) and number of previous operations (p = 0.006) found to be significant. The survival of the transplant was not affected by gender, the severity of cartilage damage, axial alignment, the degree of narrowing of the joint space or medial versus lateral allograft transplantation. Patients experienced significant improvements at all periods of follow-up in subjective outcome measures of pain, activity and function (all p-values < 0.05), with the exception of the seven-year Tegner index score (p = 0.076).

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Stone K.R., A.W. Walgenbach, A. Freyer. 2008. "Lessons Learned From Our First 100 Meniscus Allograft Transplants in Arthritic Knees." Musculoskeletal tissue regeneration : biological materials and methods. Totowa, NJ: Humana Press.

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Stone, K.R., A.W. Walgenbach, T.J. Turek, A. Freyer, and M.D. Hill. 2006. "Meniscus allograft survival in patients with moderate to severe unicompartmental arthritis: a 2- to 7-year follow-up." Arthroscopy 22 (5): 469-478.

Purpose: We present meniscus allograft survival data at least 2 years from surgery for 45 patients (47 allografts) with significant arthrosis to determine if the meniscus can survive in an arthritic joint. Type of Study: Prospective, longitudinal survival study.

Methods: Data were collected for 31 men and 14 women, mean age 48 years (range, 14 to 69 years), with preoperative evidence of significant arthrosis and an Outerbridge classification greater than II. Failure is established by previous studies as allograft removal. No patient was lost to follow-up.

Results: The success rate was 42 of 47 allografts (89.4%) with a mean failure time of 4.4 years as assessed by Kaplan-Meier survival analysis. Statistical power is greater than 0.9, with alpha = 0.05 and N = 47. There was significant mean improvement in preoperative versus postoperative self-reported measures of pain, activity, and functioning, with P = .001, P = .004, and P = .001, respectively, as assessed by a Wilcoxon rank-sum test with P = .05.

Conclusions: Meniscus allografts can survive in a joint with arthrosis, challenging the contraindications of age and arthrosis severity. These results compare favorably with those in previous reports of meniscus allograft survival in patients without arthrosis.

Level of Evidence: Level IV.

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Stone, K.R., A.W. Walgenbach, A. Freyer, T.J. Turek, and D.P. Speer. 2006. "Articular cartilage paste grafting to full-thickness articular cartilage knee joint lesions: a 2- to 12-year follow-up." Arthroscopy 22 (3): 291-299.

Purpose: To prospectively assess clinical outcomes and regeneration of osteoarthritic cartilage lesions treated with an articular cartilage paste grafting technique.

Type of Study: Prospective, longitudinal case series.

Methods: We treated 125 patients (136 procedures; 34% female, 66% male; mean age, 46 years; range, 17 to 73 years) with an Outerbridge classification of grade IV lesions with an articular cartilage paste graft. Clinical data were recorded 2 to 12 years from surgery, with 20 of 145 patients lost to follow-up over 12 years (13.7%). Clinical outcomes were captured annually with validated Western Ontario and McMaster Universities Arthritis Index (WOMAC), International Knee Documentation Committee (IKDC), and Tegner subjective questionnaires. Regenerated cartilage biopsy specimens were obtained at second-look arthroscopy from 66 patients and evaluated as to quality and quantity of defect fill by a blinded, independent histopathology reviewer.

Results: Preoperative versus postoperative validated pain, functioning, and activity measures improved significantly (P < .001). Clinically, 18 of the 125 patients were considered failures (14.4%), with 10 patients undergoing subsequent joint arthroplasty and 8 who reported worse pain after surgery. Regional histologic variation occurred. Forty-two of 66 biopsy specimens (63.6%) showed strong and consistent evidence of replacement of their articular surface, and 18 of 66 biopsy specimens (27.3%) showed development of areas of cartilage.

Conclusions: Paste grafting is a low-cost, 1-stage arthroscopic treatment for patients with Outerbridge classification grade IV arthritic chondral lesions. The procedure offers excellent, long-lasting, pain relief, restored functioning, and the possibility of tissue regeneration for patients with painful chondral lesions in both arthritic and traumatically injured knees.

Level of Evidence: Level IV, case series.

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TECHNIQUE PAPERS

Stone, K.R. 2024. "Anterior Cruciate Ligament Reconstruction: 3-Incision Technique With Allograft Quad Tendon ACL Reconstruction." Video Journal of Sports Medicine 4 (2).

The 3-incision outside-in technique utilizes the donor quadriceps tendon, an extraordinarily strong graft, without damage from autogenous harvesting of patellar tendon or hamstrings. While some data suggest higher re-rupture risk with donor tissue, this is counterbalanced by avoiding secondary surgical site damage. The 3-incision technique with allograft quadriceps tendon for ACL reconstruction is a reproducible surgical technique that avoids harvest from the patient's own body.

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Stone, K.R., Pelsis J.R., Adelson W.S., Walgenbach, A.W. 2010. "Meniscus Reconstruction: the new field of rebuilding meniscus cartilage." Knee Surgery, Arthroscopy, Sport Traumatology 7 (3): 9-18.

The collagen meniscus implant serves as a regeneration template for tissue repair and may expand the range of meniscus injuries that can be saved rather than resected. The objective of this monograph is to describe a new field of meniscus reconstruction in which regeneration templates are used to re-build missing segments of the meniscus and to expand the indications for meniscus repairs.

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Stone, K.R., A. Freyer, T. Turek, A.W. Walgenbach, S. Wadhwa, and J. Crues. 2007. "Meniscal sizing based on gender, height, and weight." Arthroscopy 23 (5): 503-508.

PURPOSE: Successful meniscus transplantation may depend on accurate sizing. Meniscal sizing is currently determined by measuring a combination of bony landmarks and soft-tissue insertion points through images obtained radiographically or by magnetic resonance imaging (MRI). The literature widely reports inaccuracy in sizing resulting from radiographic errors in magnification, erroneous identification of bony landmarks, and difficulty in differentiating between the soft-tissue and bone interface. In our meniscus transplantations we have observed that when the height and weight of the recipient matched those of the donor, the meniscal size appeared to be a match at surgical implantation; we designed this study to confirm this observation.

METHODS: The MRI-based meniscal sizing of 111 patients (63 male and 38 female patients; mean age, 44 years [range, 15 to 76 years]), totaling 147 menisci (87 lateral and 60 medial), was compared with the height, weight, gender, and body mass index (BMI) of each patient. MRI scans were obtained with a 1.0-Tesla MRI system (ONI Medical Systems, Wilmington, MA). Sizing was performed by an independent musculoskeletal MRI radiologist as established by the literature. Statistical methods include nonparametric Pearson correlation (r) between MRI-based lateral meniscal width, lateral meniscal length, medial meniscal width, medial meniscal length, total tibial plateau width, and patient height, weight, gender, and BMI. Significance at the P = .05 level was used.

RESULTS: Height was found to have a linear relationship to total tibial plateau, which has a good predictive correlation with meniscal dimensions of r > 0.7. Female patients generally present with smaller dimensions than male patients. High-BMI groups present with significantly larger meniscal dimensions than low-BMI groups at any given height.

CONCLUSIONS: Height, weight, and gender are easily obtained variables and are proportional to meniscal tissue dimensions. These exploratory statistics establish correlations between height, weight, gender, total tibial plateau width, and meniscal size.

CLINICAL RELEVANCE: Height, weight, and gender should be considered by both tissue banks and surgeons as fast and cost-effective variables by which to predict meniscal dimensions.

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Stone K.R., A.W. Walgenbach. 2003. "Meniscal allografting: the three-tunnel technique." Arthroscopy 19 (4): 426-30.

This technical note describes an improved arthroscopic technique of meniscal transplan- tation that simplifies the surgical procedure and secures the allograft to the tibia at 3 sites. The technique is useful for both medial and lateral meniscal transplantation and has been used in our clinic for over 60 meniscal transplantation procedures.

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Stone K.R., A.W. Walgenbach. 1997. "Surgical technique for articular cartilage transplantation to full thickness cartilage defects in the knee joint." Oper Tech Orthop (7):305-311.

Focal arthritic defects in the knee lead to pain, swelling, and dysfunction. Treatment of the defects has includeddrilling, abrasion, and grafting. This report describes our surgical technique of autogenous articular cartilage grafting of arthritic and traumatic articular cartilage lesions. Articular cartilage grafting can be performed as a single arthroscopic outpatient procedure. The mixture of articular cartilage and cancellous bone appears to provide a supportive matrix for cartilage formation. Pain relief is excellent if careful surgical technique and a defined rehabilitation program is followed. Further collagen typing data and additional biopsies will reveal more about the durability of the newly formed cartilage.

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2006 Meniscus Survival