paper 29 brian j. cole, md, mba · paper 29 prospective randomized trial of biologic augmentation...
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Paper 29 Prospective Randomized Trial Of Biologic Augmentation With Mesenchymal Stem Cells In Patients undergoing Arthroscopic Rotator Cuff Repair
Brian J. Cole, MD, MBA1, Nikhil N. Verma, MD1, Adam Blair Yanke, MD, PhD2, Bernard R. Bach, MD1, Robert Stephen Otte3, Susan Chubinskaya, PhD4, Anthony A. Romeo, MD1, Taylor Marie Southworth5, Neal Bhojraj Naveen5. 1Midwest Orthopaedics at Rush, Chicago, IL, 2Rush University, Chicago, IL, 3Rush, Midwest Orthopedics at Rush, IL, 4Rush University Medical Center, Chicago, IL, 5Midwest Orthopedics at Rush, Chicago, IL
Objectives: To compare the clinical outcome of arthroscopic rotator cuff repair with and without augmentation with MSCs and to identify the incidence of persistent structural defects in the tendon following surgery.
Methods: Patients aged 18-70 undergoing repair of a full-thickness supraspinatus tear or partial thickness converted to full thickness tear determined by MRI were identified and prospectively enrolled. Exclusion criteria included involvement of the subscapularis tendon, revision surgery or irreparable tear. In the injection group, 60 cc of bone marrow aspirate was drawn from the iliac crest and processed to bone marrow aspirate concentrate (BMAC) using the Arthrex Angel System (Arthrex, Naples, FL). After completion of the rotator cuff repair, half of the BMAC was injected into the tendon at the junction of the bone and tendon while the other half was injected at the site of the footprint. The control group received a small 0.5 cm incision on the hip to maintain blinding. All patients underwent a shoulder exam pre-operatively as well as at 3 months, 6 months, 1 year and 2 years post-operatively. All patients completed the Standardized Shoulder Test (SST), ASES, Constant, SANE, and VR/SF-12 questionnaires preoperatively as well as 3 months, 6 months, 12 months, 18 months and 24 months postoperatively. Baseline questionnaire scores were subtracted from scores at each timepoint to find the improvement and unpaired T-tests were performed between the two groups. Additionally, all patients underwent an MRI at 12 months postoperatively to evaluate the rotator cuff. MRIs were read by a board-certified orthopaedic surgeon and graded using the Sugaya classification system.
Results: 34 patients were randomized to the control group and 28 were randomized to the receive the injection. Average BMA MSC concentration (#/uL) was 2.63 compared to 14.95 for the BMAC MSC concentration. As a result, the BMAC was on average 5.68 times as concentrated with respect to MSC per ul when compared to the BMA.
Patients received an average BMAC volume of 2.7 mL, equating to 50410.79 +/- 25375.45 mesenchymal stem cells. There were no differences across improvement in patient reported outcomes from baseline between the control group and the group randomized to receive the injection, except for the Standardized Shoulder Test at 6 months. The mean SST score at 12 months was 87.50 in the BMAC group compared with 85.32 in the control (p=0.18). The mean ASES score at 12 months was 87.38 in the BMAC group and 89.96 in the control group (0.67). Mean Sugaya score for the control group was
3.25±1.12 (range 2-5). Mean Sugaya score for the injection group was 2.60±0.91 (range 2-5). Sugaya scores showed statistical significance with Chi-squared test at 1 year postoperative MRI (p=0.0012), and approached statistical significance with independent t test (p=0.067). Conclusion: MSCs injected into the shoulder at the time of rotator cuff repair show improved tendon quality on post-operative MRI at 1-year post-op, based on the Sugaya scoring system, with the difference in mean Sugaya score approaching significance. Further investigation is needed into this new and evolving treatment; however, it shows promise for improving the rate of rotator cuff repair healing and overall functional outcome.
Paper 30 Pre-Operative Quantitative MRI-Based Rotator Cuff Muscle Fat Fractions Are Associated with Patient-Reported Outcomes Following Rotator Cuff Repair Drew A. Lansdown, MD, Cyrus Morrison, Musa Zaid, MD, Rina Patel, MD, Alan L. Zhang, MD, Christina R. Allen, MD, Brian T. Feeley, MD, Chunbong Benjamin Ma, MD. University of California, San Francisco, San Francisco, CA, . Objectives: Advanced fatty infiltration is correlated with poor outcomes after rotator cuff repair, and high-grade fatty infiltration is considered a contraindication for repair. The influence of lower levels of fatty infiltration on outcomes after rotator cuff repair remains unclear. Quantitative magnetic resonance (MR) imaging sequences, specifically IDEAL imaging (iterative decomposition of water and fat with echo asymmetry and least-squares estimation), has been recently applied to measuring fatty infiltration of the rotator cuff muscles. Our purpose was to evaluate the relationship between rotator cuff intramuscular fat and patient-reported outcome measures after rotator cuff repair. We hypothesized that higher pre-operative fat content would be negatively correlated with post-operative outcomes. Methods: We retrospectively identified patients who underwent arthroscopic rotator cuff repair with pre-operative MRI scan with sagittal-oblique IDEAL imaging. All procedures were approved by our Institutional Review Board. Pre-operative tear size, tendon involvement, and tendon retraction were measured by a musculoskeletal radiologist. Image segmentation was performed manually on four consecutive slices with perimuscular fat excluded. Patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity computer adapted survey at a minimum of two years after repair. Correlations between intramuscular fat measurements and PROMIS scores were determined with Spearman’s rank correlation coefficient. Patients were grouped by PROMIS scores above and below 50, as 50 represents population mean. Mann-Whitney U tests were used to compare fat fractions between patients with high PROMIS scores (at or above 50) or low PROMIS scores (less than 50). Multivariate linear regression was performed with PROMIS score as the dependent variable, and individual muscle fat fractions, age, BMI, sex, and total tear size as independent predictors. Significance was defined as p<0.05. Results: A total of 80 patients were included (Table 1). Mean follow-up was 42.5 ±10.7 months. Post-operative PROMIS scores were significantly correlated with the infraspinatus fat fraction (rho = -0.25, p = 0.02) and subscapularis fat fraction (rho = -0.29, p = 0.009). The infraspinatus fat fraction for patients with a low PROMIS score (N=31) was significantly higher relative to those with a PROMIS score above 50 (N=49) (7.2±4.9% vs. 5.2 ±3.0%; p=0.046) (Figure 1). The subscapularis fat fraction was significantly higher for patients with a low PROMIS score relative to those with a PROMIS score above 50 (10.4 ±5.1% vs. 8.2 ±5.0%; p=0.001). In controlling for age, BMI, sex, and total tear size, multivariate regression modeling identified infraspinatus fat fraction (beta = -0.68, p = 0.029) as the only significant independent predictor of post-operative PROMIS score.
Conclusion: We observed significant relationships between infraspinatus and subscapularis muscle quality and post-operative patient-reported outcomes after rotator cuff repair. Infraspinatus fat fraction was the only significant predictor when accounting for demographics and rotator cuff tear size. Importantly, these patients were selected for rotator cuff repair and therefore excluded patients with advanced fatty infiltration. Even in patients with lower degrees of muscle degeneration, small differences in muscle quality may impact outcomes after tendon repair.
Paper 31 The Effect of Time Interval from MRI to Rotator Cuff Repair on Tear Size: Imaged vs. Actual Tear Size Amanda J. Naylor, MA1, Michael D. Charles, MD1, Allison Jamie Rao, MD1, Gregory Louis Cvetanovich, MD2, Michael C. O'Brien, MA1, Gregory P. Nicholson, MD1. 1Rush University Medical Center, Chicago, IL, 2Ohio State University Hospital Program, Columbus, OH Objectives: Magnetic resonance imaging (MRI) is the advanced imaging modality of choice for the evaluation and diagnosis of full thickness rotator cuff tears (RCT). Tear size progression has been correlated with increasing pain. However, there is little data on tear size progression in symptomatic RCT with regard to time from MRI to actual rotator cuff repair (RCR). The purpose of the study was to evaluate the effect of time (from date of MRI measured tear dimensions to date of RCR measured intraoperative tear dimensions) on tear size progression. Methods: In the course of a study on physical examination manual muscle tests in patients with known full thickness RCT requiring repair, MRI was obtained for each patient undergoing RCR. Tears were measured intraoperatively in the Anterior-Posterior (A-P) and Medial-Lateral (M-L) dimensions with a graduated probe. Location (anterior, central, posterior in the supraspinatus tendon), area of the tear, and anterior band of supraspinatus status (intact/ not intact) were recorded.The preoperative MRI was evaluated by the same examiner blinded to the operative results at least 4 weeks after the RCR and the same parameters measured.There were 64 consecutive shoulders with 40 male, 24 female at an average age of 58 yrs (40-76) that had MRI and underwent RCR. The mean MRI dimensions were: A-P tear:16.53mm (SD 9.70); M-L tear: 17.3mm (SD 9.75); Tear area: 366.7 square mm. The average time from preoperative MRI to RCR was 107.3 days (range 12-399 days). Operative mean RCT dimensions were: A-P tear: 18.38mm (SD 10.0); M-L tear: 14.06mm (SD 8.15); Tear area: 307.7 square mm.Descriptive statistical analysis with two-sample T-test was performed to determine the temporal effect on tear size from date of MRI to the date of surgery, and whether there was a change.Patients were grouped in the following time cohorts based on the length of time elapsed between the preoperative MRI and date of RCR: ≤1 month, 1 month to 2 months, 2 months to 3 months, 3 months to 9 months, and ≥9 months. The delta, or difference between intraoperative measurements and preoperative MRI measurements, was calculated for each cohort. Results: The t-test revealed a significant time effect with regard to tear size between the MRI and the intraoperative measured tear requiring repair. This was significant for the A-P dimension (p<0.001), the Medial-Lateral dimension (p<0.001), and the total area of the tear (p=0.009). In an attempt to determine a “watershed” or critical time interval where MRI and RCT size correlated, an additional analysis was performed. The change in A-P tear dimension between MRI and RCR findings showed increasing delta with increasing time. Positive mean delta in A-P dimension was seen in the 2-3 month group (2.64), with larger differences seen in the 3 month to 9 month (5.89) and ≥9 month (7.3) groups. A similar trend was seen for mean delta values in the M-L dimension among the cohorts.
Conclusion: In a consecutive series of RCTs undergoing repair, the measured MRI dimensions and the intraoperative dimensions were recorded and analyzed. A surgeon can have a level of confidence that the RCT size will correlate with MRI tear size within a certain time frame. There is a significant effect of time on tear size progression from MRI dimensions to actual RCT dimensions at time of repair.
Paper 32 Superior Capsular Reconstruction Patients Have High Rates of Return to Sports and Similar Functional Outcomes Compared to a Reverse Shoulder Arthroplasty Matched Cohort. Brandon C. Cabarcas1, Grant Hoerig Garcia, MD1, Joseph Liu, MD2, Gregory Louis Cvetanovich, MD3, Anirudh K. Gowd1, Brandon J. Manderle, MD1, Nikhil N. Verma, MD1, Anthony A. Romeo, MD1. 1Midwest Orthopaedics at Rush, Chicago, IL, 2Loma Linda University Medical Center, Chicago, IL, 3Ohio State University Hospital Program, Columbus, OH Objectives: Superior capsular reconstruction (SCR) is a relatively new procedure to address irreparable rotator cuff tears and rotator cuff arthropathy. Biomechanical studies have produced favorable results on cadaveric models, but few studies have evaluated clinical outcomes, and none have addressed return to sport (RTS). The purpose of this study was to evaluate rates of RTS and functional outcomes after SCR compared to a reverse total shoulder arthroplasty (rTSA) matched cohort. Methods: A prospectively collected registry was queried retrospectively for consecutive patients who underwent SCR from 2015 to 2016. Inclusion criteria were ≥2 tendon irreparable rotator cuff tear by
arthroscopic evaluation and minimum one-year follow up. All eligible SCR patients were matched by gender, age, handedness, and follow up time to patients that underwent rTSA with a similar preoperative diagnosis. All surgeries were performed by a single surgeon at one institution with consistent operative techniques. Patients were evaluated with the ASES questionnaire, VAS Pain Scale, as well as VR/SF-12 and VR6D. Patients were also administered a detailed outcomes survey regarding surgical history and return to sport and work activities. Results: Overall 75.0% of 32 eligible patients were available at follow up. Average age at surgery and follow up did not significantly differ between cohorts (p>0.500 both). Postoperative
outcome scores for ASES, VAS, VR/SF-12, and VR6D did not differ (p>0.310 for all) between cohorts. Overall RTS rate was 77.8% for SCR and 87.5% for rTSA (p > 0.610). Average months to return to sports
was significantly greater after SCR (7.3 ± 3.0) compared to rTSA (3.5 ± 2.2; p = 0.032). Patients in both cohorts participated in golf, weight-lifting, gym activity, basketball and cycling postoperatively. Direct RTS for these sports are displayed in Fig. 1. Return to work rate was 71.4% (10/14) SCR and 50.0% (4/8) rTSA (p = 0.326) at average 2.7 ± 2.8 and 1.9 ± 1.9 months, respectively (p = 0.591). Stratified by duty status, rates of return to work were sedentary (100% both SCR and rTSA), light (100% both SCR and rTSA), moderate (0% SCR and 66.67% rTSA), and heavy (0% both SCR and rTSA). Overall, 85.71% SCR patients and 90.0% rTSA patients were satisfied or very satisfied with their general postoperative outcome. Conclusion: At short-term follow-up, SCR patients had RTS rates comparable to rTSA patients with irreparable rotator cuff tears. However, time to RTS was more prolonged after SCR. Outcome scores did not significantly differ between the two cohorts, suggesting that SCR may achieve postoperative function and pain reduction similar to rTSA at one year. Return to work was also similar, although rates were not as high as return to sport. When stratified by duty status, return to more intense physical work demands was not consistent in either cohort. Despite this, over 85% of SCR and rTSA patients were satisfied postoperatively. The findings of this study demonstrate that SCR patients have high RTS levels, as well as similar functional outcomes and satisfaction compared to rTSA for irreparable rotator cuff tears. Clinicians can utilize this information for preoperative counseling, particularly with younger more athletic patients, considering SCR or rTSA for an irreparable rotator cuff tear.
Paper 33 The Subacromial Bursa is a Viable Source of Autologous Mesenchymal Stem Cells for Rotator Cuff Repair Ryan J. Warth, Polina Matre, PhD, Adam Kozemchak, MS, Dylan N. Supak, BS, Johnny Huard, PhD, Christopher D. Harner, MD, James M. Gregory, MD. University of Texas Health Science Center at Houston, Houston, TX Objectives: Chronic rotator cuff tears still represent a significant source of morbidity and functional decline in the general population. The purpose of this study was to establish protocols for isolation and expansion of bursa-derived mesenchymal stem cells (BDSCs) and to evaluate their differentiation capacity, including tenogenesis. We hypothesized that BDSCs would be capable of multilineage differentiation (including tenogenesis) and represent an important source for autologous stem cells for patients undergoing rotator cuff repair. Methods: After IRB approval, 10 patients (ages 43-65 years) scheduled to undergo arthroscopic repair for chronic rotator cuff tears were enrolled. During diagnostic arthroscopy, subacromial bursa tissue was harvested using an arthroscopic shaver and collected by attaching the outflow tubing to a specialized specimen cup. Tissue specimens were transported to our laboratory for analysis. BDSCs were isolated via adherent culture and plated in Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% Fetal Bovine Serum (FBS). Chondrogenic, adipogenic, and osteogenic induction media were used to induce differentiation. Tenogenic induction was performed using DMEM supplemented with varying concentrations of BMP-12, ascorbic acid, and human tenocyte-conditioned media. Alcian Blue staining was used to evaluate chondrogenesis, Oil Red O staining for adipogenesis, and Alkaline Phosphatase staining for osteogenesis. Gene expression markers for adipogenesis (ADIPOQ, FABP4, PPARγ), chondrogenesis (COL2A1 and SOX5), and osteogenesis (osteocalcin, osterix), along with primary antibodies to tenogenic markers (scleraxis, tenomodulin), were used to verify each cell lineage. Results: BDSCs isolated by adherent culture without collagen exhibited a spindle-shaped morphology characteristic of mesenchymal stem cells (MSCs), formed colonies, and demonstrated great expandability for six to eight passages without morphology changes (Figure 1A). After 3 weeks of culture, 95% (p<0.0001) of the BDSCs expressed the MSC surface marker CD90 and were negative for non-MSC cell markers (CD45, CD146, CD31, and CD34) (Figure 1B and C). These BDSCs demonstrated a capacity for adipogenesis (positive Oil Red O staining, ADIPOQ, FABP4, PPARγ expression), osteogenesis (positive alkaline phosphatase staining, positive osteocalcin and scleraxis expression), chondrogenesis (positive Alcian Blue staining, positive COL2A1 and SOX5 expression), and tenogenesis (scleraxis and tenomodulin expression) (Figure 2). The results indicate that BDSCs are multipotent as evidenced by their differentiation into fat, bone, cartilage, and tendon cells. For tenogenesis, we found that 7-day incubation in DMEM supplemented with 100 ng/mL of BMP-12 and 50 μg/mL of ascorbic acid produced superior tenogenic induction. These BDSCs adapted an elongated morphology combined with the expression of both scleraxis and tenomodulin - a unique characteristic of native tenocytes.
Conclusion: Our results demonstrate that subacromial bursa represents a viable source of mesenchymal stem cells. We developed a reliable protocol for isolation of BDSCs from patient bursa samples. We show that BDSCs in the presence of BMP-12 and ascorbic acid can differentiate toward a tenogenic lineage. Our work provides strong evidence that BDSCs may be a potent tool for cellular therapy and may benefit future patients who undergo surgical repair of chronic rotator cuff tears.
