William Breidahl

Autologous Tenocyte Injection for the Treatment of Severe, Chronic Resistant Lateral Epicondylitis A Pilot Study

Background: Severe chronic lateral epicondylitis (LE) is associated with degenerative tendon changes, extracellular matrix breakdown, and tendon cell loss. On the basis of positive outcomes from preclinical studies, this study is the first clinical trial of autologous tenocyte injection (ATI) on severe tendinopathy associated with chronic LE. Hypothesis: Autologous tenocyte injection is a safe and effective procedure that enables a reduction in pain and improvement in function in resistant LE. Study Design: Case series; Level of evidence, 4. Methods: Patients with severe refractory LE underwent clinical evaluation and magnetic resonance imaging (MRI) before intervention. A patellar tendon needle biopsy was performed under local anesthetic, and tendon cells were expanded by in vitro culture. Tenocytes used for the injection were characterized by flow cytometry and real-time polymerase chain reaction. Autologous tenocytes were injected into the site of tendinopathy identified at the origin of the extensor carpi radialis brevis tendon under ultrasound guidance on a single occasion. Patients underwent serial clinical evaluations and repeat MRI at 12 months after intervention. Results: A total of 20 consecutive patients were included in the study. Three patients withdrew consent after enrollment and before ATI. No adverse event was reported at either biopsy or injection sites. Furthermore, no infection or excessive fibroblastic reaction was found in any patient at the injection site. Clinical evaluation revealed an improvement in mean visual analog scale scores, for a maximum pain score from 5.94 at the initial assessment to 0.76 at 12 months (P < .001). Mean quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and grip strength scores also significantly improved over the 12-month follow-up (QuickDASH score, 45.88 [baseline] to 3.84; grip strength, 20.17 kg [baseline] to 37.38 kg; P < .001). With use of a validated MRI scoring system, the grade of tendinopathy at the common extensor origin improved significantly by 12 months (P < .001). One patient elected to proceed to surgery 3 months after ATI following a reinjury at work. Conclusion: In this study, patients with chronic LE who had previously undergone an unsuccessful full course of nonoperative treatment showed significantly improved clinical function and structural repair at the origin of the common extensor tendon after ATI. This novel treatment is encouraging for the treatment of tendinopathy and warrants further evaluation.

The Reliability and Validity of Magnetic Resonance Imaging in the Assessment of Chronic Lateral Epicondylitis

PURPOSE Lateral epicondylitis is a painful condition affecting the proximal enthesis of the extensor carpi radialis brevis tendon. Although magnetic resonance imaging (MRI) has been highlighted as an important diagnostic tool, to our knowledge no previous study has established the observer reliability of MRI for lateral epicondylitis or the relationship between MRI abnormalities of the common extensor origin and the patients clinical assessment. METHODS Twenty-one consecutive subjects with a clinical diagnosis of chronic lateral epicondylitis were assessed. An MRI scoring system was used to grade the degree of tendinosis and length of tendon separation of the common extensor origin from the lateral epicondyle. Three independent musculoskeletal radiologists, who were blinded to patient clinical severity, scored images separately. Each scored the images on 3 separate occasions. Clinical symptoms were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Upper Extremity Functional Scale clinical measures. Maximum pain levels were scored on a visual analog scale, and objective assessment was made with grip strength. RESULTS Moderate or severe signal changes consistent with tendinosis were observed in 18 of 21 patients. Significant inter-observer reliability and intra-observer agreement were demonstrated for MRI interpretation of grade of tendinosis and length of tendon separation. Significant negative correlation was found between the length of tendon separation and both the QuickDASH and maximum pain levels. CONCLUSIONS Magnetic resonance imaging is a reliable tool in determining radiological severity of lateral epicondylitis. However, the severity of MRI signal changes does not positively correlate with symptoms. These findings question the validity of MRI in the assessment of lateral epicondylitis.

Autologous tenocyte implantation, a novel treatment for partial-thickness rotator cuff tear and tendinopathy in an elite athlete

Tendinopathy and small partial-thickness tears of the rotator cuff tendon are common presentations in sports medicine. No promising treatment has yet been established. Corticosteroid injections may improve symptoms in the short term but do not primarily treat the tendon pathology. Ultrasound-guided autologous tenocyte implantation (ATI) is a novel bioengineered treatment approach for treating tendinopathy. We report the first clinical case of ATI in a 20-year-old elite gymnast with a rotator cuff tendon injury. The patient presented with 12 months of increasing pain during gymnastics being unable to perform most skills. At 1 year after ATI the patient reported substantial improvement of clinical symptoms. Pretreatment and follow-up MRIs were reported and scored independently by two experienced musculoskeletal radiologists. Tendinopathy was improved and the partial-thickness tear healed on 3 T MRI. The patient was able to return to national-level competition.

Evidence for the Durability of Autologous Tenocyte Injection for Treatment of Chronic Resistant Lateral Epicondylitis Mean 4.5-Year Clinical Follow-up

Background: Chronic lateral epicondylitis (LE) induces cell apoptosis and autophagy, which lead to the reduction of tendon-derived cells in the torn tendon. Our previous study has shown that ultrasound-guided autologous tenocyte injection (ATI) to the torn tendon in patients with chronic resistant LE significantly improves pain, function, and structural repair at 1 year. This report is the continued assessment of the clinical outcomes of these patients at mean 4.5-year follow-up. Hypothesis: Improvements in LE clinical function and structural repair after ATI will be maintained at mean 4.5-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with severe refractory LE underwent clinical evaluation and MRI before intervention. A patellar tendon needle biopsy was performed under local anesthetic, and tendon cells were expanded by in vitro culture. Autologous tenocytes were injected into the central tendinopathy identified at the common extensor tendon origin under ultrasound guidance on a single occasion. Patients underwent serial clinical evaluations for up to 5 years after ATI, including the visual analog scale (VAS) for pain, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), Upper Extremity Functional Scale (UEFS), and grip strength. Post-ATI MRI scanning was performed at 1 year and final follow-up. Results: A total of 16 patients (9 male, 7 female), aged between 37 and 63 years, were included in the study. The mean duration of symptoms before study recruitment was 29.24 months (range, 6-240 months). One patient elected to proceed to surgery 3 months after ATI due to reinjury at work, and 1 patient died of prostate cancer with metastases during the follow-up period. The mean final follow-up time for the remaining 15 patients was 4.51 years (range, 3.08-5.17 years). No complications were observed at the patellar tendon biopsy site for any patient. No adverse events, infection, or excessive fibroblastic reactions were observed in any patient at the injection site. Clinical evaluation revealed significant (P < .001) improvement in mean VAS pain score from 5.73 at initial assessment to 1.21 (78% improvement) at final follow-up. Mean QuickDASH, UEFS, and grip strength scores also significantly (P < .001) improved from initial assessment to final follow-up (from 45.88 to 6.61 [84%], from 31.73 to 9.20 [64%], and from 19.85 to 46.60 [208%], respectively). There was no difference in mean QuickDASH and UEFS scores at 1 year and final follow-up (P > .05); however, grip strength continued to improve (P < .001). A validated MRI scoring system indicated that the mean grade of tendinopathy at the common extensor origin improved significantly (P < .001) from initial assessment (4.31) to 1 year (2.88) and was maintained (P > .05) at final follow-up (2.87). At final follow-up, 93% of patients were either highly satisfied or satisfied with their ATI treatment. Conclusion: ATI significantly improved clinical function and MRI tendinopathy scores for up to 5 years in patients with chronic resistant LE who had previously undergone unsuccessful nonsurgical treatment. This study provides evidence for the midterm durability of ATI for treatment of LE tendinopathy.

Incidence, Degree, and Development of Graft Hypertrophy 24 Months After Matrix-Induced Autologous Chondrocyte Implantation Association With Clinical Outcomes

Background: Graft hypertrophy is a common occurrence after periosteal, collagen-covered and matrix-induced autologous chondrocyte implantation (MACI). Purpose/Hypothesis: The purpose of this study was to investigate the incidence, development, and degree of graft hypertrophy at 24 months after MACI. The hypothesis was that graft hypertrophy would not be associated with clinical outcome at 24 months. Study Design: Case series, Level of evidence, 4. Methods: This study was undertaken in 180 consecutive patients (113 male, 67 female) after MACI in the knee. All patients were assessed clinically using the Knee injury and Osteoarthritis Outcome Score (KOOS) and underwent magnetic resonance imaging (MRI) at 3, 12, and 24 months after surgery. The incidence of hypertrophy relevant to anatomic graft site was investigated, as was the progressive change in hypertrophic studies postoperatively. The degree of tissue overgrowth in hypertrophic cases was investigated, as was its association with patient clinical outcome at 24 months after surgery. Results: Of the 180 patients, 50 demonstrated a hypertrophic graft at 1 or more postoperative time points. This included 9 grafts (5.0%) at 3 months and 32 grafts (18.7%) at 12 months. At 24 months, 47 grafts (26.1%)—43 (32.1%) tibiofemoral and 4 (8.7%) patellofemoral—were hypertrophic. Patients with hypertrophic grafts at 24 months (n = 47) were younger (P = .051), they had a lower body mass index (BMI; P = .069), and significantly fewer of them had patellofemoral grafts (P = .007) compared with patients who had grafts with full (100%) tissue infill (n = 61). There were no significant differences in any of the KOOS subscales between patients with graft hypertrophy or full (100%) tissue infill at 24 months after surgery, while the severity of graft hypertrophy was not associated with KOOS subscales at 24 months. Conclusion: Hypertrophic grafts after MACI were common and continued to develop through to 24 months after surgery. Hypertrophic growth was associated with being younger and having a lower BMI, was more common on the femoral condyles, and overall was not associated with clinical outcome at 24 months after surgery. However, further research with longer term follow-up is required to evaluate the effect of persistent hypertrophy on graft stability and to assess the use of early surgical intervention to prevent such failure.

Autologous Tenocyte Injection for the Treatment of Chronic Recalcitrant Gluteal Tendinopathy: A Prospective Pilot Study

Background: Gluteal tendinopathy is a common cause of lateral hip pain, and existing conservative treatment modalities demonstrate high symptom recurrence rates. Autologous tenocyte injection (ATI) is a promising cell therapy that may be useful for the treatment of gluteal tendinopathy. Purpose: To investigate the safety and effectiveness of ATI, specifically in patients with chronic recalcitrant gluteal tendinopathy. Study Design: Case series; Level of evidence, 4. Methods: Twelve female patients with a clinical and radiological diagnosis of gluteal tendinopathy were recruited. Patients demonstrated a mean duration of symptoms of 33 months (range, 6-144 months), had undergone a mean 3.2 prior corticosteroid injections (range, 2-5), and had failed to respond to existing conservative treatments including physiotherapy and injections. In an initial procedure, tendon cells were harvested from a needle biopsy of the patella tendon and propagated in a certified Good Manufacturing Practice (GMP) laboratory. In a secondary procedure, a single injection of 2 mL autologous tenocytes (2-5 × 106 cells/mL) suspended in patient serum was injected into the site of the pathological gluteal tendons under ultrasound guidance. Patients were assessed pre- and postinjection (3, 6, 12, and 24 months) using the Oxford Hip Score (OHS), a visual analog pain scale (VAS), the Short Form–36 (SF-36), and a satisfaction scale. Magnetic resonance imaging (MRI) was undertaken at 8.7 months (range, 6-12 months) postinjection. Results: Molecular characterization of autologous tendon cells showed a profile of growth factor production in all cases, including platelet-derived growth factor α, fibroblast growth factor β, and transforming growth factor β. The OHS (mean, 24.0 preinjection to 38.9 at 12 months [14.9-point improvement]; 95% CI, 10.6-19.2; P < .001), VAS (mean, 7.2 preinjection to 3.1 at 12 months [4.1-point improvement]; 95% CI, 2.6-5.6; P < .001), and SF-36 (mean, 28.1 preinjection to 43.3 at 12 months [15.2-point improvement]; 95% CI, 9.8-20.5; P < .001) significantly improved to 12 months postinjection, sustained to 24 months. Eight patients were satisfied with their outcomes. Significant MRI-based improvement could not be demonstrated in the majority of cases. Conclusion: ATI for gluteal tendinopathy is safe, with improved and sustained clinical outcomes to 24 months.

A Midterm Evaluation of Postoperative Platelet-Rich Plasma Injections on Arthroscopic Supraspinatus Repair: A Randomized Controlled Trial

Background: Platelet-rich plasma (PRP) has been applied as an adjunct to rotator cuff repair to improve tendon-bone healing and potentially reduce the incidence of subsequent tendon retears. Purpose: To investigate whether the midterm clinical and radiographic outcomes of arthroscopic supraspinatus repair are enhanced after repeated postoperative applications of PRP. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 60 patients (30 control; 30 PRP) were initially randomized to receive 2 ultrasound-guided injections of PRP to the tendon repair site at 7 and 14 days after double-row arthroscopic supraspinatus repair or not. A total of 55 patients (91.7%) underwent a clinical review and magnetic resonance imaging (MRI) at a mean of 3.5 years after surgery (range, 36-51 months). Patient-reported outcome measures (PROMs) included the Constant score, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, Oxford Shoulder Score (OSS), and visual analog scale (VAS) for pain. Global rating of change (GRC) scale and patient satisfaction scores were evaluated. Structural integrity of the surgical repair was assessed via MRI using the Sugaya classification system. Results: At the midterm review, there was no difference between the groups for any of the PROMs. No differences between the groups were demonstrated for the subjective and range of motion subscales of the Constant score, although a significantly higher Constant strength subscale score was observed in the PRP group (3.3 points; 95% CI, 1.0-5.7; P = .006). There was no evidence for any group differences in MRI scores or retear rates, with 66.7% of PRP patients and 64.3% of control patients rated as Sugaya grade 1. Two control patients had symptomatic retears (both full thickness) within the first 16 weeks after surgery compared with 2 PRP patients, who suffered symptomatic retears (both partial thickness) between 16 weeks and a mean 3.5-year follow-up. Conclusion: Significant postoperative clinical improvements and high levels of patient satisfaction were observed in patients at the midterm review after supraspinatus repair. While pain-free, maximal abduction strength was greater in the midterm after PRP treatment, repeated applications of PRP delivered at 7 and 14 days after surgery provided no additional benefit to tendon integrity.

Ultrasonography Detects Deep Tissue Injuries in the Subcutaneous Layers of the Buttocks Following Spinal Cord Injury

Background: Ultrasonography may have potential as an effective diagnostic tool for deep tissue injury (DTI) in tissues overlying bony prominences that are vulnerable when under sustained loading in sitting. Methods: Three cases of DTI in the fat and muscle layers overlying the ischial tuberosity of the pelvis in 3 persons with spinal cord injury (SCI) with different medical histories and abnormal tissue signs are described. Conclusion: There is a need for prospective studies using a reliable standardized ultrasonography protocol to diagnose DTI and to follow its natural history to determine its association with the development of pressure injuries.

Cortical desmoid of the humerus: radiographic and MRI correlation

Cortical desmoids are self-limiting fibro-osseous lesions commonly occurring at the medial supracondylar femur in active adolescents, at either the origin of the medial head of the gastrocnemius or at the insertion of the adductor magnus aponeurosis. Less commonly, in a similar demographic, cortical desmoids may occur in the proximal humerus medially at the insertion of the pectoralis major muscle or laterally at the insertion of the deltoid. The radiographic appearance of the proximal humerus cortical desmoid has been described previously, but not the MRI appearance. We present the radiographic and MRI appearances of a proximal humerus cortical desmoid in a young adolescent who presented for investigation of right shoulder pain.

Evidence of long term durability of autologous tenocyte injection for treatment of chronic lateral epicondylitis

Introduction: Initiated oral contraceptive (OC) use reduces peak aerobic capacity (VO2peak) in active women. However, whether training adaptations are influenced by OC use is yet to be explored. This study investigated whether OC use influenced VO2peak and peak power output (PPO) adaptations to 12 highintensity interval training (HIIT) sessions in recreationally-active women. Methods: Women taking an oral contraceptive (OC; n=25; age 25.2±5.2 years, BMI 22.6±2.1 kg/m2, VO2peak 36.1±5.6mL/kg/min; mean± SD) or experiencing natural menstrual cycles (MC; n=22; age 26.2±5.0 years, BMI 22.7±2.2 kg/m2, VO2peak 35.0±5.0mL/kg/min; mean± SD) completed a VO2peak familiarisation and hormone cycle mapping prior to beginning the study. Under stringently controlled test conditions, participants completed an incremental exercise test to volitional exhaustion to determine VO2peak and PPO prior to and following 12 sessions of HIIT (completed over four weeks). HIIT sessions consisted of 10 one-minute cycling intervals in a 1:2 work:rest ratio at 100–120% PPO. Paired t-tests were used to determine change from baseline. A two-way repeated measures ANOVA (with a main effect for training time×group) was used to determine whether an interaction occurred between training and group. The statistical significance level set at p 0.05). Following training, PPO increased in both groups (MC, 13.1%; p<0.001, and OC, 13.3%; p<0.001) with nodifferencebetweengroups (p=0.945). VO2peak increased followingHIIT (MC, 11.9%;p<0.001,OC, 7.6%;p<0.001),withMCshowing significantly greater improvement (p=0.028). Discussion: HIIT increased both PPO and VO2peak in recreationally active women; however OC users showed reduced improvements in VO2peak compared with MC women. OC use therefore appears to reduce physiological (VO2peak) adaptation to HIIT, however does not appear to detriment performance (PPO) outcomes. In conclusion, the data from this study provide a strong case for inclusion of ovarian hormone status control measures in female-specific research. Additionally, results encourage careful interpretation of VO2peak outcomes in female populations especially when investigating clinical relevance of VO2peak and associated health outcomes with training interventions. Practically, findings encourage careful consideration by active women regarding whether OC use may influence individual exercise goals. Further research should investigate potentialmechanisms responsible for this effect and whether performance and health benefits gained through HIIT are negatively impacted by OC use.