i

Clinical and functional outcomes for patients following rotator cuff

repair surgery, with or without adjuvant platelet rich plasma

injections.

Jessica Anne Colliver

This thesis is presented for the degree of Master of Science of

The University of Western Australia

School of Sport Science, Exercise and Health

2015

Supervisors:

Winthrop Professor Timothy Ackland

Clinical Associate Professor Allan Wang

Doctor Brendan Joss

ii

ABSTRACT

Background: Tendon-bone healing following rotator cuff repair correlates with a

successful outcome. With the relatively high re-tear rates reported in the literature despite

multiple surgical and suture anchor techniques, there has been an increase in research into

biological adjuvant therapies that elevate local growth factor concentrations, to assist

structural tendon healing following rotator cuff surgery.

Purpose: To determine if postoperative and repeated application of platelet-rich plasma

(PRP) to the tendon repair site improves early tendon healing and enhances functional

recovery following double row arthroscopic supraspinatus repair. A secondary objective

was to determine if partial re-tears early post-surgery reveal differences in subjective

function, or objective isokinetic strength, compared to completely intact tendon repairs;

and if early tendon healing can be predicted using these measures, independent of medical

imaging.

Study Design: Randomised controlled trial; Level of evidence = 2.

Methods: 60 patients underwent arthroscopic, double row supraspinatus tendon repair.

Following post-surgery randomisation, 30 patients received two ultrasound-guided

injections of PRP to the repair site at 7 and 14 days post-surgery. Functional scores were

recorded pre-surgery and post-surgery, at 6, 12 and 16 weeks; and included the Oxford

Shoulder Score (OSS), the Quick Disability of the Arm, Shoulder and Hand

(QuickDASH), Visual Analogue Scale (VAS) for pain and the Short Form-12 (SF-12)

quality of life score. Isokinetic strength and active range of motion were also recorded at

16 weeks post-surgery. Early post surgery structural healing of the tendon was assessed

iii

with Magnetic Resonance Imaging (MRI) at 16 weeks, with cuff appearance graded

according to the Sugaya classification.

Results: PRP treatment did not improve early functional recovery, strength or range of

motion, nor influence pain scores at any time point following arthroscopic supraspinatus

repair. No difference was seen in MRI structural integrity between treatment and control

groups (p=0.35). At 16 weeks post-surgery, the PRP group had 0% full thickness tear;

23% partial tear and 77% intact, compared to the control group with 7% full-thickness

tear; 23% partial tear and 70% intact.

In the secondary study, full-thickness tears were excluded and the treatment and control

groups pooled to determine if functional and strength differences were observed between

Sugaya classified MRI groups (36% of the cohort had grade one classification; 40% grade

two; and 24% grade three). No significant differences were observed between MRI

groups for functional scores (VAS, OSS and QuickDASH) or isokinetic strength at 4

months post-surgery. Only 64% of the partial tear group, and 13% of the intact repair

group were correctly classified with five variables entered into a discriminant analysis

prediction equation.

Conclusion: Ultrasound-guided PRP injections on two occasions post-surgery does not

improve early tendon-bone healing, or functional recovery. Correct tendon healing

classification early post rotator cuff surgery must include medical imaging, and reliance

on functional scores and isokinetic strength alone to assess early tendon healing is not

supported.

iv

ACKNOWLEDGEMENTS

I would like to take the time to thank all of the people that have contributed to getting me

to this point. This thesis has taken me a lot longer than it should have, and I appreciate

the interest my family, friends and colleagues have taken in my progress.

Firstly to patients, who endured endless phone calls, appointments and paperwork, all in

the name of science and to help improve the post-surgery recovery for future patients.

This project would not have been possible without your invaluable contribution and

dedication, so thank you.

To each of my supervisors: Prof Tim Ackland, for your encouragement and patience,

especially towards the end of this project, provided me with the direction I needed. I am

grateful to have access to such a wealth of knowledge and experience. To Prof Allan

Wang, for the hours of time you dedicated to getting this project up and running, and

interest in the entire process. It is a privilege to have worked with such a well-respected

and talented surgeon. And to Dr Brendan Joss, for the years of support and

encouragement to continue to achieve in my professional and academic career. Thank

you for the hours of time you dedicated to answering endless questions.

I feel extremely grateful to have had the encouragement and support of my family and

friends, as well as my colleagues at Hollywood Functional Rehabilitation Clinic, thank

you to each and every one of you. Finally, to my wonderful fiancée Michael, I cannot

begin to thank you for your love and support over this past four years, especially in the

last six months while we have been in England. Thank you from the bottom of my heart.

vi

TABLE OF CONTENTS

CHAPTER 1: THE PROBLEM 1

Introduction 1

Statement of the Problem 2

Research Hypothesis 4

Patient Inclusion and Exclusion criteria 5

Inclusion Criteria 5

Exclusion Criteria 5

References 6

CHAPTER 2: LITERATURE REVIEW 11

Rotator Cuff Tendon Tears 11

Incidence of Rotator Cuff Tendon Tears 11

Aetiology of Rotator Cuff Tendon Tears 12

Diagnosis of Rotator Cuff Tendon Tears 14

Treatment of Rotator Cuff Tendon Tears 18

Non-surgical Treatment of Rotator Cuff Tendon Tears 18

Surgical Treatment of Rotator Cuff Tendon Tears 22

Attempts to Reduce High Rotator Cuff Tendon Re-tear Rates 30

Growth Factors Important in Tendon Healing/Regeneration 34

Platelet-rich Plasma 36

Platelet-rich Plasma and Tendon Injury 38

Platelet-rich Plasma Preparations and Rotator Cuff Tendon Repair 39

Summary 41

References 42

CHAPTER 3: PAPER 1. Do postoperative platelet-rich plasma injections

accelerate early tendon healing and functional recovery after arthroscopic

supraspinatus repair?: A randomised controlled trial. 58

Abstract 58

Introduction 60

Methods 62

Patient Selection 62

Surgical Technique 65

vii

Post-operative Protocol 66

Randomisation Protocol 66

Preparation of Platelet-rich Plasma 67

Outcome Assessments 68

Statistical Analysis 70

Results 70

Structural Evaluation 71

Functional Scores 72

Strength 73

Range of Motion 74

Discussion 75

Conclusions 79

References 79

CHAPTER FOUR: PAPER 2. Early postoperative repair status after

rotator cuff repair cannot be accurately classified using questionnaires of

patient function and isokinetic strength evaluation. 85

Preamble 85

References 86

Abstract 88

Introduction 90

Methods 91

Patients 91

Surgical Technique 93

Postoperative Management 94

Patient-reported Outcome (PRO) Measures 94

Isokinetic Strength Evaluation 95

Radiological Evaluation 97

Statistical Analysis 97

Results 98

Discussion 102

Conclusion 105

References 106

viii

CHAPTER 5: SUMMARY, CONCLUSIONS AND

RECOMMENDATIONS 111

References 116

APPENDICES 118

ix

APPENDICES

APPENDIX 1 University of Western Australia notification of research proposal

approval.

APPENDIX 2 University of Western Australia notification of ethics approval.

APPENDIX 3 South Metropolitan Area Health Service notification of ethics

approval.

APPENDIX 4 Study information sheet.

APPENDIX 5 Patient consent form.

APPENDIX 6 Visual Analogue Scale (VAS) for pain.

APPENDIX 7 Oxford shoulder score (OSS).

APPENDIX 8 Quick Deformities of the Arm, Shoulder and Hand (QuickDASH)

outcome measure.

APPENDIX 9 Short form-12 (SF-12) health survey.

APPENDIX 10 Manuscript accepted for publication in the American Journal of

Sports Medicine: Do postoperative platelet-rich plasma injections

accelerate healing and early functional recovery after arthroscopic

supraspinatus repair?: A randomized controlled trial.

APPENDIX 11 Manuscript accepted for publication in the Journal of Shoulder and

Elbow Surgery: Early postoperative repair status after rotator cuff

repair cannot be accurately classified using questionnaires of patient

function and isokinetic strength evaluation.

x

LIST OF TABLES

CHAPTER 3.

Table 1. Group demographics with concomitant complications 66

Table 2. Sugaya classification of MRI scans of treatment groups 72

Table 3. Functional scores 73

Table 4. Group mean scores (as percentage of the contralateral, un-operated

arm) and t-test results for strength measures at 6 weeks post-

surgery. 74

Table 5. Group mean scores and t-test results for range of motion for the

operated limb at 16 weeks post-surgery. 75

CHAPTER 4.

Table 1. Group demographics with detail of concomitant procedures and

complications 93

Table 2. Mean (SD) scores for the patient-reported outcome (PRO) and

isokinetic maximal strength measure (at an angular speed of 60°/)

employed, for patients with intact (grade 1) and partial (Grade 2

and 3) supraspinatus tendon re-tears. Independent sample t-test

comparisons are provided between groups (p values). 99

Table 3. Descriptive statistics (mean ± SD) for patients with intact repairs

(grade 1) and partial (grade 2 and 3 pooled) supraspinatus tendon

re-tears. 100

Table 4 Discriminant analysis for variables predicting an intact repair

(n=21, grade 1 Sugaya classification) or partial re-tears (n=37,

grade 2 and 3 Sugaya classification). 101

xi

LIST OF FIGURES

CHAPTER 2.

Figure 1. Open rotator cuff repair, landmarks and incision marked

(Ghodadra, et al., 2009).

24

Figure 2. Mini-open rotator cuff repair (Ghodadra, et al., 2009). 25

Figure 3. Arthroscopic rotator cuff repair (Ghodadra, et al., 2009). 26

CHAPTER 3.

Figure 1. CONSORT (Consolidated Standards of Reporting Trials)

flowchart.

64

Figure 2. Ultrasound image of needle placement directly at the tendon

repair site (arrow).

68

Figure 3. T1-weighted coronal magnetic resonance image displaying

Sugaya grade 1 appearance.

69

CHAPTER 4.

Figure 1. A patient performing humeral (A) internal and (B) external

rotation on the Biodex Isokinetic Dynomometer

96

1

CHAPTER 1

THE PROBLEM

INTRODUCTION

Rotator cuff tendon tear is one of the most common injuries of the shoulder joint

(Mitchell, et al., 2005), with a reported incidence rate ranging from 5 to 40% (Baydar, et

al., 2009) and over 250,000 rotator cuff repairs performed annually in the United States

alone (Yamaguchi et al., 2006). The prevalence of rotator cuff pathology increases with

age (Bokor, et al., 1993; Kinsella & Velkoff, 2001; Murrell & Walton, 2001), with

Yamaguchi, et al. (2006) also reporting an increase in the likelihood of bilateral rotator

cuff pathology among patients over the age of 60 years. As the population continues to

age, degenerative rotator cuff tears are likely to become an increasing problem.

Failure to heal and tendon re-tearing following rotator cuff surgery is not uncommon.

Re-tear rates have been reported as high as 90% in the radiology literature, and as high

57% in orthopaedic literature, depending on patient age, the size of the tendon tear and

level of degeneration, fatty infiltration, type of suture anchors, surgical technique and

compliance with post-surgery rehabilitation guidelines (Boileau, et al., 2005; Galatz, et

al., 2004; Gulotta & Rodeo, 2009; Sugaya, et al., 2007). It has been widely reported that

those over the age of 60 years have significantly poorer rates of healing following rotator

cuff repair surgery (Boileau, et al., 2005; DeFranco, et al., 2007; Oh, et al., 2010;

Thomazeau, et al., 1997). The absence of tendon healing and recurrent tears following

rotator cuff surgery lead to poor functional strength (Boileau, et al., 2005; Cho & Rhee,

2009; Galatz, et al., 2001; Harryman, et al., 1991).

2

The goal of rotator cuff surgery is to decrease pain and improve patient function. While

the majority of patients who undergo this type of surgery see this result, there are some

who continue to experience pain and loss of function and who are left unsatisfied due to

recurrent tendon tearing or failed healing. Younger, more active patients may need to

return to employment in physical roles or even to sport. Due to the lengthy nature of

post-surgical recovery, patients often require early confirmation of tendon healing so as

to tailor their rehabilitation programs accordingly.

STATEMENT OF THE PROBLEM

Despite the advances in surgical and suture anchoring techniques to improve rotator

cuff tendon-to-bone fixation, failure of the tendon repair occurs often (Boileau, et al.,

2005; Galatz, et al., 2004; Sugaya, et al., 2005; 2007). While tendon re-tears may be

due to a specific injury at the site, it may also be caused by incomplete or failed primary

healing following rotator cuff repair surgery (Boileau, et al., 2005; Carpenter, et al.,

1998).

In a bid to improve early primary tendon healing, there has been an increase in research

effort related to the use of biological adjuvant therapies that elevate local growth factor

concentrations. In particular, many studies have investigated platelet-rich plasma (PRP)

products, where a supra physiological concentration of platelets is delivered to the

tendon-bone repair site at the time of surgery. The term “PRP” remains controversial in

the literature, as this generic terminology does not differentiate between the various

commercial products available, or their respective protocols and differing platelet

concentrations (Lopez-Vidriero, et al., 2010; Sanchez, et al., 2010), with is no current

3

consensus on the actual platelet concentration required to have a clinically significant

effect (Barber, et al., 2011).

While numerous studies have been published on the topic, the success of PRP use in

improving outcomes following rotator cuff repair remains unclear. Reviewing the

related literature is complicated by variations in the tendon pathologies treated, which

range from small single tendon tears to large multi-tendon tears, concomitant use of

acromioplasty (Castricini et al., 2011; Jo et al., 2011), and the formulations of PRP

used, ranging from intra-tendon injections (Kesikburun, et al., 2013; Randelli, et al.,

2008), spray application (Randelli, et al., 2011; Ruiz-Moneo, et al., 2013) or the

incorporation of a platelet-rich fibrin matrix (PRFM) (Barber, et al., 2011; Castricini, et

al., 2010; Gumina, et al., 2012) to the tendon repair site. Another factor affecting PRP

is the timing of delivery, with the majority of studies to date using time zero delivery at

the time of surgery, with Gulotta and Rodeo (2009) stating that biological augmentation

too early in the tendon healing cascade may be ineffective.

This thesis addresses two primary questions and these have been presented as journal

manuscripts in Chapters 3 and 4. The first paper (Wang, et al., 2015) sought to

determine if injections of PRP would enhance early tendon healing and functional

recovery following double row arthroscopic supraspinatus tendon repair surgery. The

primary outcome in this study was improved early tendon healing, assessed with MRI,

and the secondary outcomes related to patient-reported shoulder function and isokinetic

shoulder strength as a measure of functional recovery.

The second paper (Colliver, et al. 2015, under review) aimed to determine if patients

with an intact repair or partial re-tear in the early stages following rotator cuff repair

4

surgery display differences in common shoulder patient reported outcome measures and

isokinetic strength tests; and if early post-surgical tendon healing could be predicted

using these common clinical shoulder evaluations.

RESEARCH HYPOTHESIS

The following hypotheses were developed and tested for study 1 (Wang, et al., 2015).

1. The use of delayed and repeated PRP ultrasound-guided injections following

supraspinatus tendon repair will improve early structural tendon healing, as

assessed by MRI, when compared to no PRP treatment.

2. The use of delayed and repeated PRP ultrasound-guided injections following

supraspinatus tendon repair will improve early patient-reported shoulder

function and isokinetic shoulder strength, compared to no PRP treatment.

In study 2 (Colliver, et al., under review), the following hypotheses were developed and

tested.

1. Following supraspinatus repair, differences in patient shoulder function and

isokinetic shoulder strength will be detected in those patients with partial tendon

re-tears or high MRI signal intensity, compared to those with intact repairs at 4

months post-surgery, regardless of their initial PRP group allocation.

2. Following supraspinatus repair, patients with partial re-tears and incomplete

healing can be predicted on the basis of patient function and strength tests alone,

without the need for post-surgery imaging.

5

PATIENT INCLUSION AND EXCLUSION CRITERIA

The methodology for each of the papers is contained in the relevant sections of the

journal manuscripts shown in Chapters 3 and 4. However, journal papers are limited by

strict word counts, which do not allow for a full description of patient selection criteria,

or data collection and analysis methods. Therefore, a complete list of patient selection

criteria is presented here.

Inclusion Criteria

1. Patients were male or female, aged between 25-80 years.

2. Full-thickness, symptomatic tear of supraspinatus tendon as identified by

preoperative imaging and confirmed by arthroscopic evaluation.

3. Patients agreed to wear a dedicated arm sling for 4-6 weeks, as directed by the

surgeon.

4. Patients needed to be in a non-dependent relationship.

Exclusion Criteria

1. Previous history of rotator cuff repair surgery.

2. Rotator cuff tears secondary to fracture.

3. Concomitant labral tear or significant degenerative glenohumeral osteoarthritis.

4. Contralateral shoulder symptoms.

5. Prior PRP injections.

6. Non-surgical rotator cuff associated treatment in the 1 month prior to surgery,

including corticosteroid injection and anti-inflammatory treatment.

6

7. Presence of rheumatalogical, neuromuscular or autoimmune disease.

8. Pre-existing conditions associated with upper extremity pain, including arthritis,

ongoing infection, carpal tunnel syndrome, cervical disc herniation, cervical

neuropathy or other nerve pathology.

9. Metabolic bone or blood disorders that could impair bone or soft tissue function.

10. Ongoing workers’ compensation claims.

11. Contraindication to postoperative MRI evaluation.

12. Likely problems with follow-up (i.e. patients with no fixed address, reported

plan to move out of town, uncooperative or patients without adequate family

support).

13. Patients who were participating in an existing ongoing trial that would interfere

with assessment of the primary or secondary outcomes.

14. Patients who did not read or speak English.

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Baydar, M., Akalin, E., El, O., Gulbahar, S., Bircan, C., Akgul, O., et al. (2009). The

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Boileau, P., Brassart, N., Watkinson, D. J., Carles, M., Hatzidakis, A. M., & Krishnan,

S. G. (2005). Arthroscopic repair of full-thickness tears of the supraspinatus:

does the tendon really heal? Journal of Bone and Joint Surgery (Am), 87(6),

1229-1240.

7

Bokor, D. J., Hawkins, R. J., Huckell, G. H., Angelo, R. L., & Schickendantz, M. S.

(1993). Results of nonoperative management of full-thickness tears of the rotator

cuff. Clin Orthop Relat Res(294), 103-110.

Carpenter, J. E., Thomopoulos, S., Flanagan, C. L., De Bano, C. M., & Soslowsky, L. J.

(1998). Rotator cuff defect healing: a biomechanic and histologic analysis in an

animal model. Journal of Shoulder and Elbow Surgery, 7(6), 599-605.

Castricini, R., Longo, U. G., De Benedetto, M., Panfoli, N., Pirani, P., Zini, R., et al.

(2010). Platelet-rich augmentation for arthroscopic rotator cuff repair: a

randomised control trial. Am J Sports Med, 39(2), 258-265.

Castricini, R., Longo, U. G., De Benedetto, M., Panfoli, N., Pirani, P., Zini, R., et al.

(2011). Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a

randomized controlled trial. Am J Sports Med, 39(2), 258-265.

Cho, N. S., & Rhee, Y. G. (2009). The factors affecting the clinical outcome and

integrity of arthroscopically repaired rotator cuff tears of the shoulder. Clin

Orthop Surg, 1(2), 96-104.

Colliver, J., Wang, A., Koh, E., Joss, B., Ebert, J., Ackland, T., et al. (2015). Early

post-operative repair status after rotator cuff repair cannot be classified

using questionnaires of patient function and isokinetic strength evalualtion.

Journal of Shoulder and Elbow Surgery (under review).

DeFranco, M. J., Bershadsky, B., Ciccone, J., Yum, J. K., & Iannotti, J. P. (2007).

Functional outcome of arthroscopic rotator cuff repairs: a correlation of

anatomic and clinical results. Journal of Shoulder and Elbow Surgery, 16(6),

759-765.

8

Galatz, L. M., Ball, C. M., Teefey, S. A., Middleton, W. D., & Yamaguchi, K. (2004).

The outcome and repair of completely arthroscopically repaired large and

massive rotator cuff tears. Journal of Bone and Joint Surgery (Am), 86(2), 219-

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Galatz, L. M., Griggs, S., Cameron, B. D., & Iannotti, J. P. (2001). Prospective

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Harryman, D. T., 2nd, Mack, L. A., Wang, K. Y., Jackins, S. E., Richardson, M. L., &

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Kesikburun, S., Tan, A. K., Yilmaz, B., Yasar, E., & Yazicioglu, K. (2013). Platelet-

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2609-2616.

Kinsella, K., & Velkoff, V. A. (2001). An ageing world: 2001.

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follow-up. J Shoulder Elbow Surg, 20(4), 518-528.

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growth factors in arthroscopic rotator cuff repair: a randomized, double-blind,

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Sugaya, H., Maeda, K., Matsuki, K., & Moriishi, J. (2007). Repair integrity and

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11

CHAPTER 2

REVIEW OF LITERATURE

ROTATOR CUFF TENDON TEARS

Full thickness rotator cuff tendon tear is one of the most common injuries affecting the

shoulder joint (Mitchell, et al., 2005; Seitz, et al., 2011), with the incidence rate ranging

from 5 to 40% of the general population (Baydar, et al., 2009; Gialanella & Prometti,

2011). Those with rotator cuff tears can experience pain and decreased functional ability

(Ainsworth & Lewis, 2007; MacDermid, et al., 2004), reduction of range of motion

(ROM) in the glenohumeral joint and muscular atrophy (Maniscalco, et al., 2008;

Mitchell, et al., 2005); having an impact on health-related quality of life (MacDermid, et

al., 2004). Reduced function may include difficulty or inability to dress independently,

attending to personal hygiene and using utensils to eat. The pain can be so severe that

the patient’s sleep is also affected (Ainsworth & Lewis, 2007).

Incidence of rotator cuff tendon tears

True prevalence of rotator cuff tears is difficult to determine in the general population, as

a tendon tear can cause significant pain, weakness and disability in some, whereas others

experience little to no pain or disability (Ainsworth & Lewis, 2007; Fehringer, et al.,

2008; Gialanella & Prometti, 2011). As a result, reported incidence of rotator cuff tendon

tears varies widely throughout the literature.

Cadaveric studies have demonstrated the incidence of rotator cuff tendon tears in subjects

aged over 60 years to be at least 30%, compared with 6% in those younger than 60 years

12

(Kinsella & Velkoff, 2001; Lehman, et al., 1995). Tempelhof, et al. (1999) investigated

the prevalence of rotator cuff tears in asymptomatic shoulders, and found that of a total

411 subjects, 96 (23.4%) had a full-thickness rotator cuff tear. Sher, Uribe, Posada,

Murphy and Zlatkin (1995) conducted a prospective study investigating the prevalence

of rotator cuff tendon tears in asymptomatic individuals of varying ages, with varying

activities. More than half (54%) of the cohort over the age of 60 years had either a partial

or full thickness rotator cuff tear, confirming age-related changes of the rotator cuff

consistent with other studies, identified with MRI.

The incidence of degenerative rotator cuff tendon tears increases with age, even in the

asymptomatic population (Boileau, et al., 2005; Bokor, et al., 1993; Cheung, et al., 2010;

Oh, et al., 2010; Tempelhof, et al., 1999). A study conducted by Murrell and Walton

(2001) found that rotator cuff tear frequency increased linearly with age from 30 years

(increasing from 33% in the 40s to 55% the in 50s). As the ageing population continues

to increase worldwide, degenerative rotator cuff tendon tears will become more prevalent

in the future.

Aetiology of rotator cuff tendon tears

A tendon is a tough band of fibrous connective tissue, usually connecting muscle to bone,

and capable of withstanding tension loads (Del Buono, et al., 2011; Nontarnicola &

Moretti, 2012). Tendons are often subjected to tendinopathies, as a result of trauma and

overuse, which may lead to inflammation and degeneration of the tendon and, in turn, to

a tendon tear or rupture (Notarnicola & Moretti, 2012). While most tendons have the

ability to heal following injury, the repair tissue is functionally inferior to that of normal

healthy tendon, and carries with it an increased risk of further injury .

13

Factors causing rotator cuff tendinopathies and tendon tears have traditionally been

described as extrinsic, intrinsic or a combination of the two (Seitz, et al., 2011). Extrinsic

factors are those causing compression of the rotator cuff tendons due to narrowing of the

subacromial space (Carpenter, et al., 1998; Mishra, et al., 2009), and can be related to

anatomical and/or biomechanical factors (Seitz, et al., 2011). Anatomical factors that can

contribute to the narrowing of the subacromial space include variations in the acromion

shape, orientation of the slope or angle of the acromion, or ossification of the inferior

aspect of the acromioclavicular joint or coracoacromial ligament (Seitz, et al., 2011).

Biomechanical factors may also contribute to extrinsic compression and can include

abnormal scapular and humeral kinematics, abnormalities in posture, muscular deficits

and soft tissue tightness (Seitz, et al., 2011). Intrinsic factors that affect the rotator cuff

tendons result in degeneration of the tendons caused by the natural ageing process,

decreased vascularity and blood flow (Mishra, et al., 2009), altered biology and

fibrocartilagenous changes (Carpenter, et al., 1998) associated with previous tendon

damage, and tensile tissue overload (Seitz, et al., 2011).

Although rotator cuff tears can occur as a result of an acute injury, most tears result from

gradual degeneration of the tendon and tendon-to-bone interface (Bokor, et al., 1993;

Cheung, et al., 2010). Chronic tendon tears are known to induce structural changes within

the tendon (fibro-vascular scar tissue forms during the healing process) (Anitua, et al.,

2005), rendering the tendon prone to re-tearing, as well as muscular atrophy (Liem,

Lichtenberg, et al., 2007).

Rotator cuff tendon tears can be caused by degeneration and overuse with repetitive

extrinsic compression, eccentric overload of the tendon, or by differential strains being

14

placed on the tendon (Millett, et al., 2006). Reilly and colleagues (2003) found that in

cadaveric shoulders, maximal differential strain was reached at approximately 120

degrees of shoulder abduction. Partial tears can also create tension overload in the

remaining tendon, which may increase the force concentration in the remainder of the

tendon tissue and over time, can lead to complete full-thickness rotator cuff tendon tear

(Millett, et al., 2006). While the rotator cuff tendons are able to tolerate huge tensile

stresses, compressive and sheer forces are poorly tolerated (Millett, et al., 2006).

Diagnosis of rotator cuff tendon tears

Rotator cuff pathologies are a major cause of shoulder pain. Ostor, et al., 2005 reported

that rotator cuff tendinopathy was present in 85% of patients presenting with shoulder

pain to a general medical practice. Rotator cuff tendon tears may account for up to 50%

of major shoulder injuries and, while clinical testing is the recommended first line

investigation (Beaudreuil, et al., 2009), an accurate diagnosis can be difficult with clinical

tests alone (Ainsworth & Lewis, 2007; Hughes, et al., 2008; Murrell & Walton, et al.,

2001). Investigative techniques such as magnetic resonance imaging (MRI) or ultrasound

(US) are commonly used to confirm or dismiss the presence of a rotator cuff tear (Bennell,

et al., 2007; Codsi, et al., 2014; Kluger, et al., 2011; Liem, Lichtenberg, et al., 2007;

Teefey, et al., 2004).

The diagnostic accuracy of common clinical tests for rotator cuff pathology has been

questioned in a number of reviews (Hughes, et al., 2008; Mitchell, et al., 2005; Murrell

& Walton, 2001). A clinical review conducted by Mitchell and colleagues (2005) of the

diagnosis and management of shoulder pain suggested that clinical investigation and

diagnosis should take into account the patient’s history (e.g. onset of pain, age, pain

15

during active and/or passive movements or at rest, patient’s occupation) as well as a

physical examination (palpation of the shoulder joints, comparison of power, stability and

ROM in both shoulders – active, passive and resisted, look for painful abduction arc and

the “drop arm test” where the patient lowers an abducted arm to the waist slowly; a

positive test result is indicated by the inability to hold the arm at 90 degrees of abduction,

or a patient’s inability to smoothly control the lowering of their arm). Patients presenting

with rotator cuff pathologies may have muscle wastage, active and resisted arm

movements are usually painful and often partially restricted (Mitchell, et al., 2005). And

while passive ROM may be full, it is usually painful, and history is a strong indicator;

young people often present following a traumatic incident, with atraumatic presentation

common among the elderly (Mitchell, et al., 2005). Mitchell and colleagues (2005) also

suggested that partial tears can be difficult to differentiate from rotator tendinopathy upon

physical examination, as weakness during resisted movement can occur with either

condition. The authors stated that the “drop arm test”, can be used to detect a large or

complete tear.

In a bid to improve the clinical diagnosis of rotator cuff tears, Murrell and Walton (2001)

conducted a prospective study to determine if any of 23 clinical tests commonly used in

assessment of the shoulder were predictive of a rotator cuff tear. They found that most

clinical tests could not distinguish between the group that had rotator cuff tears (partial

or full thickness tears and no other major shoulder pathology) and those with a shoulder

pathology not involving a rotator cuff tear. However, the researchers did find that three

clinical features were more positive in patients with tears and were predictors for this

condition. These were supraspinatus weakness, weakness in external rotation and

impingement. It was suggested that the “drop arm” test was also a predictor of a rotator

cuff tear due to its high specificity, however, it had a low sensitivity within the tear group.

16

These results show that patients presenting with these three clinical features, or with a

positive test for two of the three and who are over 60 years of age, there is a 98% chance

of having a rotator cuff tear. If only one of those three tests is positive, the result is

inconclusive and further imaging is required to confirm the diagnosis.

A systematic review conducted by Hughes, et al. (2008) of the diagnostic accuracy of

clinical tests for rotator cuff pathology suggested that most tests cannot be recommended

for clinical use. At best, suspicion may be heightened by positive palpitation, combined

Hawkins/painful arc/infraspinatus, among others; and suspicion may be reduced upon

negative palpation, empty can or Hawkins-Kennedy test. It has also been suggested that

the poor accuracy of common clinical tests for diagnosis of rotator cuff pathology and

tears may be attributed to the lack of anatomical validity of the tests, or that the complex

relationships of the shoulder structures make it difficult to identify specific pathologies

(Ainsworth & Lewis, 2007; Hughes, et al., 2008), highlighting the importance of medical

imaging in conjunction with clinical investigations.

US and MRI are non-invasive techniques used widely to identify rotator cuff tears and

tear size (Codsi, et al., 2014; Ianotti, et al., 2005; Kluger, et al., 2011; Naqvi, et al., 2009;

Seibold, et al., 1999; Teefey, et al., 2004). Assessment of the rotator cuff using US was

first published in 1979 (Seltzer, et al.) , and 1986 for MRI (Kneeland et al.). Initially,

there was a great variety of results in the detection of rotator cuff tears with US (Brandt,

et al., 1989), which was thought to be due to the limited experience of examination

procedures and use of low frequency transducers (Naqvi, et al., 2009; Teefey, et al.,

2004). As a result, MRI became the “gold standard” technique for diagnosis of partial

and full thickness rotator cuff tears, due to its high sensitivity and accuracy, despite the

relatively high cost (Iannotti, et al., 1991; Naqvi, et al., 2009). More recently though,

17

technical improvements and increased experience have led to a significant improvement

in US reliability (Teefey, et al., 2004).

A number of studies have re-evaluated the accuracy of both US and MRI in the detection

of partial and full rotator cuff tendon tears with modern equipment, standardised

techniques and imaging diagnostic criteria. Teefey, et al. (2004) found the overall

accuracy of diagnosing full thickness, partial thickness and intact rotator cuff tendons was

87%. Naqvi, et al. (2009) evaluated the accuracy of US and MRI in detection of full

thickness rotator cuff tears, with the overall accuracy of US being repeated as 89%,

compared with 80% for MRI. Codsi, et al. (2014) suggested US was comparable to MRI

when evaluating rotator cuff integrity, and that post-surgical US results should be

compared with MRI results for a period of time before relying solely on US for diagnosis.

Ardic, et al. (2006) however, reported MRI to be superior to US, while reported that US

was not a reliable tool for diagnosing full-thickness rotator cuff tears. Sonnabend, et al.

(1997) reported on the accuracy of US in diagnosing full thickness rotator cuff tears and

as a “useful adjunct” to the diagnosis of partial tears; however they also noted it was

operator-dependent.

18

TREATMENT OF ROTATOR CUFF TENDON TEARS

The optimal treatment for rotator cuff tears, particularly large tears, varies for each

patient. Decisions on how to treat patients should take into account the severity of

symptoms, patient functional requirements, and the presence of any concomitant diseases

that could complicate treatment (Gialanella & Prometti, 2011). The treatment for rotator

cuff tendon degeneration and injury ranges from conservative to surgical treatment.

Non-surgical treatment of rotator cuff tendon tears

Conservative treatments include exercise, physiotherapy (electrotherapy, ultrasound,

acupuncture and taping) and injection therapy (steroidal and non-steroidal) (Ainsworth &

Lewis, 2007; Lewis, 2010; Ruotolo & Nottage, 2002). Exercise or other conservative

treatment is often offered as the initial management approach, as satisfactory results

cannot be guaranteed with surgical intervention (Ainsworth & Lewis, 2007; Gialanella &

Prometti, 2011). The goals of non-surgical management of a rotator cuff tendon tear are

to eliminate pain and restore function (Ainsworth & Lewis, 2007; Millett, et al., 2006),

however, recommendations vary on the length of time conservative care should be

undertaken before seeking a surgical opinion (Ainsworth & Lewis, 2007; Itoi & Tabata,

1992).

Reviews of interventions for rotator cuff pathologies suggest that exercise may be an

effective treatment (Ainsworth & Lewis, 2007; Kuhn, 2009). Both Brox et al. (1999) and

Haahr et al. (2005) reported active physiotherapy to be superior to a placebo or control.

Physiotherapy aims to decrease shoulder pain and disability by improving joint

biomechanics and movement patterns, rather than treating the pathology, using a range

19

of modalities (Bennell, et al., 2007). Both exercise and physiotherapy are often used in

combination to treat rotator cuff tendon tears.

There is currently no consensus view on the ideal exercise or physiotherapy program for

patients with rotator cuff tendon pathologies. Many rehabilitation protocols in the

literature are based on empirical clinical evidence, which indicate a specific exercise or

activity progression based on tendon healing timelines (Millett, et al., 2006). An

evaluation-based protocol not only takes into account healing timelines, but also the

attainment of specific clinical goals, before progressing exercises (Millett, et al., 2006).

This makes good sense, considering patients with rotator cuff tendon tears do not all

progress through their rehabilitation phases at the same rate. Guidance as to the most

appropriate exercise treatment (including intensity, duration and frequency) remains

speculative (Ainsworth & Lewis, 2007).

Lewis (2010) suggested exercises that reduce superior migration of the humeral head may

be beneficial, as well as a graduated program of tendon reloading, including concentric,

isometric and eccentric exercises, in a pain-free manner. Millett and colleagues (2006)

discuss exercise rehabilitation of both partial and full-thickness tears of the rotator cuff.

Rehabilitation goals of both are to re-establish full range of motion, synchronise the firing

of the rotator cuff and periscapular muscles, and re-establish normal glenohumeral and

scapulothoracic kinematics. A graduated strength program was suggested by Ruotolo

and Nottage (2002); once shoulder pain has been controlled, focusing of scapular

stabilisation and removing deltoid work until pain is completely diminished. Range of

motion was observed to increase following a carefully designed exercise program,

however strength using manual testing remained unchanged (Bokor, et al., 1993; Itoi &

Tabata, 1992; Ruotolo & Nottage, 2002).

20

While physiotherapy is one of the most commonly prescribed conservative treatments of

rotator cuff pathology, there appears to be little evidence to support its effectiveness, with

many trials treating a single modality rather than multiple modalities; despite being the

most common way to treat shoulder pathologies in clinical practice (Bennell, et al., 2007).

The lack of consensus of this treatment is most likely due to the lack of good quality,

randomised controlled trials available in the literature focusing on clinical outcomes.

Corticosteroids are often prescribed for rotator cuff tears (Gialanella & Prometti, 2011),

however, evidence of the effectiveness of steroid injections for rotator cuff pathologies

is unconvincing, despite extensive research in this area (Ekeberg, et al., 2009; Gialanella

& Prometti, 2011). Therapeutic mechanisms of corticosteroid injections may include

anti-inflammatory effects, relaxation of reflex muscle spasm, influence on local tissue

metabolism, pain relief, mechanical improvements and placebo effect (Neustadt, 1991).

Research conducted by Bokor, et al. (1993) and Koubaa, et al. (2006) in patients with

rotator cuff tears showed positive results when treated with a combination of

rehabilitation, anti-inflammatories and local corticosteroid injections. Similarly,

Yamada, et al. (2000) saw improvements in pain, muscular strength and ROM in those

treated with conservative measures, including corticosteroids. Shibata, et al. (2001) also

showed pain relief in patients with rotator cuff tears. A recent study conducted by

Gialanella and Prometti (2011) demonstrated that patients receiving local corticosteroid

injections and rehabilitation had pain relief when compared to those with rehabilitation

alone. However, Darlington and Coomes (1977) found that while patients with

supraspinatus tendon tears had some relief from pain with local corticosteroids, there was

21

no improvement in ROM or the painful arc; concluding there was no objective evidence

that corticosteroids improve the condition.

Some studies reported that there is no reliable proof to suggest that corticosteroids

injected at the peritendinous level had adverse effects (Nichols, 2005; Paavola et al.,

2002); with Bhatia, et al. (2009) concluding that the use of corticosteroids should not be

considered a cause of rotator cuff tendon tears. Despite the suggestion of positive results

of steroid injections in conjunction with other therapies, subacromial and intra-articular

injections of corticosteroids remains controversial, with respect to it deleterious effects.

Tillander, et al. (1999) showed that after five corticosteroid injections into the

subacromial space of rats there was focal inflammation, necrosis and fragmentation of

collagen bundles, but no change was seen after three injections. Studies have reported

that intraarticular steroid injections had adverse effects on cartilage and tendons, and

osteoarthritic changes and tendon tears have been observed (Stannard & Bucknell, 1993;

Tillander, et al., 1999).

Mitchell (2005) suggests subacromial corticosteroids should be considered for short term

pain relief and to facilitate rehabilitation. Smidt et al. (2002) showed that in patients with

lateral epicondylitis, corticosteroid injections are merely the best treatment option in the

short term, compared to a physiotherapy and “wait-and-see” policy, however poor results

were reported after the 12 week follow-up. Similar results were found by Verhaar, et al.

(1996) and Hay, et al. (1999). It is thought that this could be due to the intratendinous

injection causing permanent adverse changes within the structure of the tendon, and that

patients may tend to overuse the arm following injection because they have experienced

pain relief (Peerbooms, et al., 2010; Smidt, et al, 2002).

22

Patient satisfaction with non-operative treatment of rotator cuff tears has been reported

widely in the literature with varied results; Itoi and Tabata (1992) reported 82%, Bokor,

et al. (1993) 56% and Bartolozzi, et al. (1994) 25% satisfaction. While partial-thickness

tears of the rotator cuff can usually be treated successfully with non-surgical

interventions, full-thickness tears treated non-surgically provide inconsistent and often

unacceptable results, with Millet and colleagues (2006) suggesting there are no reliable

methods of predicting successful treatment of these full-thickness tears. Bartolozzi, et al.

(1994) suggest that of patients with full thickness rotator cuff tears with symptoms for

more than 1 year, only 13% reported a satisfactory end result with non-surgical treatment.

A review conducted by Downie and Miller (2012) comparing non-operative and operative

treatment of rotator cuff tears in older patients (mean age of 60 years) was unable to find

sufficient evidence to recommend treatment. And while the reviewed studies reported

favourable operative outcomes, there was a lack of good quality non-operative treatment

studies in this age group for comparison; highlighting a gap in the research for this age

group.

Surgical treatment of rotator cuff tendon tears

Rotator cuff repair surgery is one of the most common orthopaedic procedures, with over

250,000 performed annually in the United States (Castricini, et al., 2010; Gulotta &

Rodeo, 2009). The procedure is generally offered for the painful rotator cuff that has

failed non-surgical treatment (Castricini, et al., 2010; Millett, et al., 2006). Surgery can

include a rotator cuff tendon repair with or without subacromial decompression

(Ainsworth & Lewis, 2007); and in more severe cases where osteoarthritis is involved,

shoulder joint replacement may be the only solution (Ainsworth & Lewis, 2007). The

goal of this type of surgery is to eliminate pain and improve shoulder function with

23

increased strength and ROM of the shoulder (Boissonault, et al., 2007; Ghodadra, et al.,

2009).

Optimal repair of the rotator cuff requires high fixation strength, minimal gap formation,

maintenance of mechanical stability under cyclic loads, and proper healing of the tendon

to the bone (Ghodadra, et al., 2009). The majority of studies reported excellent outcomes

following rotator cuff tendon repair surgery, with the integrity of repair generally being

shown to have a negative correlation with age (Boileau, et al., 2005; DeFranco, et al.,

2007; Ghodadra, et al., 2009; Oh, et al., 2010; Thomazeau, et al., 1997). However,

healing of the repair is also dependent on the number of tendons involved and the pre-

surgery tear size (Barber, et al., 2011). Cofield (1985) reviewed published results of open

rotator cuff repair, noting an average pain relief of 87%; ranging between 71% to 100%,

and a patient satisfaction rate of 77%.

In the past 15 years, the surgical treatment for rotator cuff tears has evolved from the

traditional open procedure, to a mini-open (arthroscopic-assisted) technique, to an all-

arthroscopic technique (Nho, et al., 2007). The traditional open approach was associated

with severe early post-operative pain, deltoid detachment and/or weakness, and

arthrofibrosis (Bennett, 2003a; 2003b; Bigliani, et al., 1992; Nho, et al., 2007). The mini-

open repair technique was developed with the potential advantage of less deltoid

morbidity, while demonstrating outcomes that were similar to those with the open

procedure (Levy, et al., 1990; Liu & Baker, 1994; Nho, et al., 2007; Paulos & Kody,

1994). More recently, surgeons are performing complete arthroscopic rotator cuff

repairs, with potential advantages including less pain, more rapid rehabilitation, the

ability to treat intra-articular lesions, smaller skin incisions, less soft tissue dissection and

a very low risk of deltoid detachment (Nho, et al., 2007). This technique has shown

24

promising results in both the short and long term (Bennett, 2003a; Galatz, et al., 2004;

Galatz, et al., 2001; Gartsman, 2001). Despite these advantages, the procedure is

technically demanding and requires a large amount of practice for the surgeon to be

proficient in this procedure (Nho, et al., 2007; Norberg, et al., 2000). Due to the technical

demands of the arthroscopic approach, a large number of orthopaedic surgeons favour the

mini-open procedure (Yamaguchi, et al., 2003).

The first documented rotator cuff repair was performed by Dr Codman, in 1911, using an

open technique, and further modifications to this technique were proposed by Neer in

1972 (Yamaguchi, et al., 2003). With an open rotator cuff repair approach, the patient is

placed in the “beach-chair” position, and a 3-6 cm incision is made parallel to the lateral

border of the acromion, in line with Langer’s lines (Figure 1). The deltoid is taken off

the anterior aspect of the acromion, usually beginning at the acromioclavicular joint,

extending along the anterior border of the acromion, then splitting the deltoid laterally 3-

5 cm. Following rotator cuff repair, the deltoid is reattached to the acromion, and the

longitudinal split of the deltoid repaired. Deltoid dysfunction has been a reported

complication with this surgical approach.

Figure 1. Open rotator cuff repair, landmarks and incision marked (Ghodadra, et al.,

2009).

25

Levy and colleagues (1990) described an arthroscopically assisted repair, where

arthroscopy was used to form a subacromial decompression and avoid deltoid takedown.

To perform the mini-open repair the arthroscopic portal is extended by 1-2 cm and the

deltoid fibres are split in line to obtain access to the repair site (Figure 2).

Figure 2. Mini-open rotator cuff repair (Ghodadra, et al., 2009).

An all-arthroscopic procedure requires only a small incision for insertion of several

cannulas 7-8 mm in diameter, and the only disruption to the deltoid is from insertion of

the cannula, as no tissue retraction is required. Following identification of the appropriate

anatomical landmarks, all arthroscopic portals are marked (Figure 3). Various surgical

instruments can be introduced through these portals into the shoulder to immobilise the

cuff, implant suture anchors and tie arthroscopic knots to hold the tendon to the bone.

26

Figure 3. Arthroscopic rotator cuff repair (Ghodadra, et al., 2009).

In addition to the surgical approach, much research has centred around suture anchoring

technique to establish a normal rotator cuff footprint (anatomic contact area between the

tendon and the bone of the humeral greater tuberosity) in order to optimise healing

potential and increase the mechanical strength of the primary fixation of the tendon repair

(Lo & Burkhart, 2003; Milano, et al., 2008). While excellent clinical results of

arthroscopic rotator cuff repair have been documented (Bennett, 2003a, 2003b;

DeFranco, et al., 2007; Kasten, et al., 2011; Liem, Bartl, et al., 2007), there has been

criticism of suture anchor repair techniques and repair integrity (Kim et al., 2006; Lo &

Burkhart, 2003). In the past, most arthroscopic rotator cuff repairs were done with a

single row of suture anchors, to anchor the free edge of the tendon to the bone (Milano,

et al., 2008). Imaging studies of rotator cuff integrity have shown that single row

arthroscopic repairs had a greater rate of structural failure than open rotator cuff repairs

(Galatz, et al., 2004; Liu & Baker, 1994; Thomazeau, et al., 1997). Gerber, et al. (1994,

p. 378) stated “the ideal repair should have high initial fixation strength, allow minimal

gap formation, and maintain mechanical stability until solid healing; it is clear that weak

initial fixation leads to gap formation under load, poor healing and possible complete

failure”.

27

A study conducted by Apreleva and colleagues (2002) evaluated the three-dimensional

rotator cuff footprint in the normal rotator cuff and after several methods of arthroscopic

supraspinatus tendon repair. They determined that 67% of the original rotator cuff

footprint was restored using a single row of suture anchors, while the double-row suture

repairs restored up to 85% of the surface area. The results showed that the rotator cuff

footprint is a complex three-dimensional structure, covering a large surface of the

humerus, that cannot be restored with a simple single row of sutures (Apreleva, et al.,

2002). Similarly, Kim, et al. (2006) found that the use of a double-row suture technique

created a more superior suture construct, with greater strength and stiffness, resulting in

less gap formation and less strain over the rotator cuff footprint, compared with a single-

row repair. By providing a double row of fixation, the number of fixation points doubles

compared with a single-row repair, potentially improving mechanical strength and

function by providing more complete healing across the rotator cuff footprint (Lo &

Burkhart, 2003).

Despite the many surgical repair techniques, there remains concern regarding the ability

of the rotator cuff insertion to fully heal following the repair (Castricini, et al., 2010;

Gulotta & Rodeo, 2009; Kovacevic & Rodeo, 2008), with recurrent tearing occurring

frequently (Cheung, et al., 2010). Re-tears have been reported to occur in 11-94% of

rotator cuff repair surgeries – dependent upon the size of the tear, the level of tendon

degeneration, and fatty infiltration present at the time of surgery, type of suture anchors

and suture method used during surgery, compliance with post-operative rehabilitation

guidelines and patient age (Boileau, et al., 2005; Cheung, et al., 2010; Cho & Rhee, 2009;

Galatz, et al., 2004; Gulotta & Rodeo, 2009; Sugaya, et al., 2007). The authors that

published these re-tear rates reported the predictors of re-tear included: larger tear size,

28

greater levels of tendon degeneration and fatty infiltration, and increased age at the time

of surgery, as well as non-compliance with the post-operative rehabilitation guidelines.

The large range in re-tear rates is likely due to differences in research methodology and

study follow up timeframes.

There are a variety of re-tear rates reported in the literature, with comparisons between

the open, mini-open and arthroscopic surgical approaches. Re-tear rates have been

reported as high as 80-90% in the radiology literature, and as high as 57% in orthopaedic

literature (Barber, et al., 2011; Charousset, et al., 2010; Liem, Bartl, et al., 2007; Liem,

Lichtenberg, et al., 2007).

A study conducted by Kluger, et al. (2011) reported the overall failure rate of patients

having mini-open rotator cuff repair surgery was 33% (n=107, average age=59.5 ± 9.2

years). Furthermore, they reported that 74% of the failures occurred atraumatically in the

first 3 months, 11% occurred between 3-6 months following surgery, and the remaining

failures occurred 2 to 5 years post surgery, and were related to sporting activities or direct

trauma. Miller, et al. (2011) reported 41% of their arthroscopically repaired rotator cuffs

had re-torn (n=22); with seven of the nine (78%) re-tears occurring within the first 3

months after surgery. Another study found that 100% of re-tears occurred in the first 3

months post surgery (Nho, et al., 2009).

DeFranco, et al. (2007) reported a 40% re-tear rate (n=30, average age=56.3 ±12.3 years)

in patients who underwent isolated supraspinatus repair arthroscopically, using a single-

row suture technique. They noted that patients in the no-tear group were significantly

younger than those in the re-tear group (51 ± 12 vs 64 ± 9 years, p<0.01).

29

Oh, et al. (2010) reported similar results; patients with an intact repair were significantly

younger than the failed repair group (58.4 ± 8.7 years vs 63.7 ± 7.5 years). Similarly,

Boileau, et al. (2005) reported that only 43% of the patients over the age of 65 years had

completely healed tendons (p=0.001). In this study, the rotator cuff was completely

healed in 71% of the patients, 62 of the 65 patients reported they were satisfied with the

result, and those with intact repairs had significantly greater shoulder strength.

Charousset, et al. (2010) showed that patients older than 65 (mean age 70 years, range =

65-85 years) who underwent an arthroscopic rotator cuff surgery at 6 months post-surgery

had a re-tear rate of 42%. Furthermore, the isolated supraspinatus tears showed superior

healing (28.9% failure rate), however those that had a massive tear (supraspinatus

retracted to the glenoid) had 100% failure rate. This indicated that arthroscopic tendon

repair can be considered a successful procedure for the older patient with a small or

medium tear, particularly where the tear is isolated to the supraspinatus tendon

(Charousset, et al., 2010).

There has been much debate about whether the integrity of repair of the rotator cuff

tendon affects functional outcome, with the trend being towards a better outcome with an

intact repair (DeFranco, et al., 2007; Galatz, et al., 2004; Lafosse, et al., 2007; Liem,

Bartl, et al., 2007; Oh, et al., 2010). While the radiographs may show failures at the repair

site, often the patient may still have pain relief; however, studies have shown they have

inferior function results when compared to patients with healed repairs (Boileau, et al.,

2005; Galatz, et al., 2004; Gulotta & Rodeo, 2009; Lafosse, et al., 2007). Lam and Mok

(2004), and Verma, et al. (2010) reported in older patients treated for rotator cuff repair

(open and arthrosopic respectively), that over 90% had reduced pain post-surgery. They

did not, however, consider the structural integrity of the repair sites.

30

ATTEMPTS TO REDUCE HIGH ROTATOR CUFF TENDON RE-TEAR

RATES

Though surgery is successful for many patients, the quality and speed of post-operative

healing remains problematic, with a number of studies demonstrating that native tendon-

to-bone insertions were not restored after tendon repair surgery (Carpenter, et al., 1998;

Kovacevic & Rodeo, 2008; Rodeo, et al., 2007). Tendons comprise specialised cells

including tenocytes and water (Cheung, et al., 2010; Molloy, et al., 2003; Sampson, et al.,

2008), as well as type I collagen fibres which orient towards a continuous insertion point

on the humerus (Clark & Harryman, 1992; Sampson, et al., 2008). The vasculature is

organised and dispersed through the tendon, however, the vessels decrease in number and

size closer to the bone (Cheung, et al., 2010; Clark & Harryman, 1992). There are four

distinct zones of tissue running longitudinally; tendon, non-mineralised fibrocartilage,

mineralised fibrocartilage and bone (Carpenter, et al., 1998; Clark & Harryman, 1992).

Tendons are required to transfer great forces and, as a result, can be susceptible to injury

when overloaded (Sampson, et al., 2008). With continuous overuse, micro tears can form

in the collagen fibres, which may lead to tendinosis or tendinopathy (Millett, et al., 2006;

Mishra, et al., 2009; Sampson, et al., 2008). When this occurs, the injured tendon heals

by scarring, and with its inferior biomechanical properties, affects function and increases

the risk of re-injury (Carpenter, et al., 1998; Sampson, et al., 2008). Tendons tend to heal

at a slower rate compared with other connective tissues, due to poor vascularisation

(Castricini, et al., 2010; Jo, et al., 2011; Sampson, et al., 2008).

General healing follows a pathway, beginning with inflammation, continuing with

cellular and matrix proliferation, followed by tissue formation and maturation, and finally

31

tissue remodelling (Lopez-Vidriero, et al., 2010); this can also be applied to tendon

healing. Tendon-to-bone healing is divided into three stages: the inflammatory stage, the

repair stage and the remodelling stage (Carpenter, et al., 1998; Cheung, et al., 2010;

Gulotta & Rodeo, 2009; Mishra, et al., 2009; Molloy, et al., 2003). Following a tendon

injury or surgical repair, the final bone-to-tendon insertion point bears little resemblance

to the original insertion (Kovacevic & Rodeo, 2008). The overall structure, composition

and organisation of the normal insertion site does not regenerate (Kovacevic & Rodeo,

2008). Instead of the four distinct zones following the remodelling stage of healing, the

tendon and bone become joined by a layer of fibrovascular scar tissue dominated by

poorly organised type III collagen fibres (Carpenter, et al., 1998; Cheung, et al., 2010).

Mechanically, this fibrous scar tissue is weaker than the native insertion site, and may

contribute to the high number of repair failures (Carpenter, et al., 1998; Cheung, et al.,

2010).

In an attempt to reduce the number of rotator cuff repair failures, researchers have focused

their attention on ways to minimise the scar tissue formation and at the same time,

promote the regeneration of the fibrocartilagenous insertion zones (Gulotta & Rodeo,

2009; Maniscalco, et al., 2008). Initially, studies looked at improving the biomechanical

strength of the repair site by using stronger sutures and double row repairs (Apreleva, et

al., 2002; Gulotta & Rodeo, 2009; Kim, et al., 2006; Lo & Burkhart, 2003), however,

even with these techniques, failed healing and/or re-tears still occurred in up to 12% of

cases (Lafosse, et al., 2007). Although improved biomechanics may slightly improve

tendon healing, it has been suggested that biologic augmentation of the healing process

may be required to further reduce the scar tissue formation at the repair site, and help

regenerate a normal fibrocartilagenous transition zone (Gulotta & Rodeo, 2009;

Maniscalco, et al., 2008), which may improve the strength of the repair.

32

Because of the problems faced with tendon healing following injury or surgical repair,

much of the research has been directed towards understanding the mechanisms of tendon

healing at the molecular level (Anitua, et al., 2005; Anitua, et al., 2007; Lyras, et al.,

2010; Molloy, et al., 2003; Randelli, et al., 2009). This research has been undertaken in

an effort to develop complimentary therapies to facilitate tendon healing via individual

and groups of molecules that are known to have beneficial roles in the healing process.

The more recent knowledge gained about tissue biology and the complexity of the

regulation of growth factors in normal tissue structure, as well as in reaction to tissue

damage, shows the important and effective role of an application of growth factors in the

healing of damaged tissue (Filardo, et al., 2010).

Growth factors have an essential role in the body’s healing process and tissue formation

(Anitua, et al., 2006). All stages of the repair process are controlled by a variety of

cytokines and growth factors that act as regulators of the majority of basic cell functions

(Anitua, et al., 2006). Growth factors influence many of the processes common to tissue

repair and disease, including angiogenesis, chemotaxis and cell proliferation, as well as

controlling the synthesis and degradation of extracellular matrix proteins (Anitua, et al.,

2006).

As mentioned earlier, tendon healing follows a pattern (inflammatory phase, repair phase

and remodelling phase). When tissue is damaged, blood vessels rupture which signals

the release of molecules to trigger coagulation to coordinate the formulation of a clot

around the affected area (Molloy, et al., 2003). The clot contains cells and platelets that

immediately release a variety of molecules (including growth factors), causing acute and

local inflammation (Molloy, et al., 2003). It is during the inflammatory phase that

33

extrinsic cells (neutrophils and macrophages) which are responsible for phagocytosis, and

intrinsic cells (endotenon and epitenon cells) produce another battery of cytokines which

initiates the repair phase (Molloy, et al., 2003). At this stage that we see the collagen

deposition and granular tissue formation, as well as neovascularisation, extrinsic

fibroblast migration and intrinsic fibroblast proliferation (Anitua, et al., 2005; Molloy, et

al., 2003).

Platelets are responsible for haemostasis and coagulation (Anitual, et al., 2004; Lopez-

Vidriero, et al., 2010), and also contain alpha granules with various molecules (growth

factors, endostatins, antipoietins and thrombospondin) that are secreted upon activation

during the healing process (Anitua, et al., 2004; Lopez-Vidriero, et al., 2010), assisting in

the construction of new connective tissue and revascularisation, making up approximately

6% of a blood specimen (Sampson, et al., 2008).

34

Growth factors important in tendon healing/regeneration

Growth factors have a number of crucial roles in tendon healing. Numerous studies have

revealed the complexity of the regulation of growth factors in response to tissue damage

and the important role they play in tendon healing (Anitua, et al., 2005; Anitua, et al.,

2007; Lyras, et al., 2010; Molloy, et al., 2003; Randelli, et al., 2009; Rodeo, et al., 2007).

Factors secreted from platelets such as transforming growth factor-ß (TGF- ß), platelet-

derived growth factor (PDGF), vascular endothelial growth factors (VEGF), basic

fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-1) are markedly up-

regulated throughout the tendon repair process (Anitua, et al., 2005; Molloy, et al., 2003;

Randelli, et al., 2009). They can be potentially produced by both intrinsic and extrinsic

cells, often have dose-dependent effects, require specific receptors to be active, and

usually work in synergy with other signalling molecules (Molloy, et al., 2003). Growth

factors are one of the largest groups of molecules involved in the healing process of

tendons and ligaments (Molloy, et al., 2003), with an outline provided below of some of

their functions and behaviours.

TGF- ß is active in almost all stages of tendon healing, having varied effects such as

stimulating extrinsic cell migration, regulating proteinases, fibronectin binding

interactions, termination of cell proliferation via cyclin-dependent kinase inhibitors and

stimulation of collagen production (Anitua, et al., 2005; Molloy, et al., 2003; Randelli, et

al., 2009). TGIF-ß levels have been shown to dramatically increase following tendon

injury, and it is believed to play an important role in the initial inflammatory response to

tissue damage (Molloy, et al., 2003).

35

PDGF is secreted by platelets during the early phases of inflammation and has been

identified at fracture sites (Randelli, et al., 2009). It is thought that PGDF may play a

significant role in the early stages of healing by inducing the synthesis of other growth

factors, such as IGF-1 (Molloy, et al., 2003; Randelli, et al., 2009). The role of PDGF in

tendon repairs appears to be most relevant in the remodelling phase where it has been

observed to stimulate collagen and non-collagen protein production, and DNA synthesis,

in a dose-dependent manner.

VEGF has a small role in early cellular migration and proliferation, however, has been

found to be most active after the inflammation phase during the proliferation and

remodelling phases, where it is a powerful stimulator of angiogenesis (Anitua, et al.,

2005; Molloy, et al., 2003). Increased levels of VEGF at the site of injury correlate with

a well-defined pattern of vascular ingrowth from the epi- and intra-tendinous blood

supply towards the site of repair. This increased vascularisation proceeds along the

epitenon, through a normally avascular area, providing extrinsic cells, nutrients and

growth factors to the injured site.

The bFGF promotes growth and differentiation in a range of cells, including epithelial

cells, myocytes, osteoblasts and chondocytes (Molloy, et al., 2003; Randelli, et al., 2009).

In tendons it has been shown to be a potent stimulator of angiogenesis, cellular migration

and proliferation. Kobayashi and colleagues (1997) found that bDGF provided a boost

to the initial stages of healing, and that all the subsequent steps proceeded with

significantly greater speed and efficiency.

IGF-1 is an important mediator in all phases of wound healing, particularly in the

inflammatory and proliferative phases (Molloy, et al., 2003). It is a versatile signal

36

molecule, having numerous and varied activities during tendon healing, especially when

working in synchrony with other growth factors (Molloy, et al., 2003). Its primary role

is to stimulate the proliferation and migration of fibroblasts and other cells at the repair

site, and subsequently increase the production of collagens and other extracellular matrix

structures during the remodelling phase (Anitua, et al., 2005; Molloy, et al., 2003).

It has been suggested that the concentrated addition of the above mentioned growth

factors might improve tissue healing. Recently a technique has been developed to extract

useable growth factors from autologous blood, which can be injected around an injury or

repair site, called platelet rich plasma (PRP).

Platelet rich plasma

Platelets contribute to haemostasis by preventing blood loss at sites of vascular injury,

and contain large numbers of cytokines and growth factors that play a key role in bone

regeneration and soft tissue maturation (Anitua, et al., 2006). PRP has emerged as a new

technology believed to stimulate the revascularisation of soft tissue and increase the

concentration of growth factors to improve and accelerate wound, bone, muscle and

tendon healing (Barber, et al., 2011; Peerbooms, et al., 2010). It is an autologous

concentration of platelets in a small volume of plasma, which, once activated, undergoes

degranulation to release growth factors with healing properties (Kajikawa, et al., 2008;

Lopez-Vidriero, et al., 2010). Because the PRP preparation is obtained from the patient’s

own blood, concerns regarding immunogenic reactions and disease transmission are

eliminated (Anitua, et al., 2006). Important growth factors identified in PRP include

TGF- ß, PDGF, VEGF, bFGF and IGF-1 (Lyras et al., 2010). As well as containing

platelets and concentrated growth factors, PRP also consists of plasma with fibrin, which

37

acts as a scaffold for primary cell migration and differentiation, functioning as a

biological glue (Anitua, et al., 2006; Lopez-Vidriero, et al., 2010).

The concept of using growth factors to assist healing dates back to the early 1980’s, where

it was first used to assist in wound healing (Knighton, et al., 1982). Initially it was thought

that platelets acted exclusively during clotting; however it has since been discovered that

platelets also release many bioactive proteins responsible for attracting microphages,

mesenchymal stem cells and osteoblasts, which promote the removal of necrotic tissue,

as well as enhancing tissue regeneration and healing (Sampson, et al., 2008). The early

use of PRP in the 1990’s was as a biological glue (Gibble & Ness, 1990). Because of the

high proportions of fibrin, these “glues” were used primarily in maxillofacial surgery

(Lopez-Vidriero, et al., 2010). It was during this time that PRP preparations were

discovered to have bone-forming properties, as well as anti-inflammatory and

antibacterial qualities, attributed mainly to the high concentration of platelets (Lopez-

Vidriero, et al., 2010).

Since then, research has been conducted using PRP in a variety of tissues to accelerate

and assist the healing process. Such areas include cosmetic surgery and wound healing

(Eppely, et al., 2004), as well as most orthopaedic disciplines, such as chronic patella

tendon injuries (Filardo, et al., 2010) and defects (Lyras, et al., 2010), lateral epicondylitis

(Mishra & Pavelko, 2006; Peerbooms et al., 2010), Achilles tendon injuries (Aspenberg

& Virchenko, 2004; Sanchez, et al., 2007), bone allograft integration, rotator cuff tendon

tears (Maniscalco, et al., 2008) and rotator cuff tendon repair surgery (Barber, et al., 2011;

Castricini, et al., 2010; Kovacevic, et al., 2008; Randelli, et al., 2008; Randelli, et al.,

2011).

38

Lopez-Vidriero and colleagues (2010) described the characteristics of the main PRP

commercial products currently available on the market. The term “PRP” has been

controversial in the literature, because this generic terminology doesn’t differentiate

between the various commercial products available, and their respective protocols

(Lopez-Vidriero, et al., 2010; Sanchez, et al., 2010). Concerns have been raised because

different products show varying biologic effects (Anitua, et al., 2009). The main

differences between commercial PRP systems are: speed and number of centrifugations

that lead to different platelet concentrations, the use of anticoagulant, the presence of

leukocytes in the preparation and the use of an activator (Anitua, et al., 2009; Lopez-

Vidriero, et al., 2010). The actual platelet concentration required to have a clinically

significant effect has not yet been determined, and a higher concentration may not

necessarily be superior (Barber, et al., 2011). It is important that these factors be taken

into account when analysing published results, and when surgeons are deciding on which

system to use (Anitua, et al., 2006; Castillo, et al., 2011; Lopez-Vidriero, et al., 2010).

Platelet-rich plasma and tendon injury

Aspenberg and Virchenko (2004) investigated the use of PRP to augment rat Achilles

tendon tears, finding greater maturation in tendon callus, but also reported increased force

to failure and ultimate stress in PRP treated animals (Virchenko & Aspenberg, 2006).

PRP was found by Kajikawa, et al. (2008) to enhance mobilisation of circulation-derived

cells to the injection area, and that PRP induced type I collagen production and increased

the proliferation of microphages at three and seven days.

Mishra and Pavelko (2006) reported on the use of PRP in patients with chronic severe

elbow tendinitis, who had failed a standardised, non-operative treatment protocol. They

39

found a 60% improvement in pain scores for those patients treated with PRP, compared

with a 16% improvement in the control group at 8 weeks following treatment. At final

follow-up, the PRP recipients reported over 90% reduction in pain compared to their pre-

treatment scores, and 93% of PRP patients were fully satisfied with this treatment. It

should be noted however, that this was a small sample, non-randomised study.

Anitua and colleagues (2007) reported faster recovery in athletes who underwent PRP-

enhanced Achilles tendon repair, compared to a retrospective control group of athletes

who had surgery alone. Those treated with PRP recovered their range of motion earlier,

had no wound complications and returned to training activities earlier than the control

patients.

Platelet-rich plasma preparations and rotator cuff tendon repair

Review of the literature reveals substantial rates of failure in the surgical treatment of

smaller tears. A number of studies have looked into the use of PRP constructs to

potentially enhance rotator cuff healing (Barber, et al., 2011; Castricini, et al., 2010;

Gumina, et al., 2012; Randelli, et al., 2008; Randelli, et al., 2011), but currently there are

no clear guidelines or agreement on the safest or most effective augmentation. A pilot

study conducted by Randelli and colleagues (2008) demonstrated the application of PRP

during arthroscopic rotator cuff repair is safe and effective, and results remained stable

with time.

Castricini, et al. (2010) suggest that the use of autologous platelet-rich fibrin matrix

(PRFM) for augmentation of a repair of a small or medium rotator cuff tear does not

improve shoulder function or cuff integrity, when compared to a control group at 16

40

months post-surgery. They suggested that, given the variety of PRP products on the

market, there might be another preparation that could be more effective. Barber and

colleagues (2011) also used a PRP fibrin matrix (Cascade, by Musculoskeletal Transplant

Foundation, NJ), which did not have thrombin activation, nor contain leukocytes, opting

to suture two lots of the construct into the repair. While there was no statistical difference

between the PRP and control groups in terms of functional outcomes, the MRI results

indicated that the PRP group had significantly lower re-tear rates (P= 0.03), with MRI

follow-up at 4 months post surgery.

A study by Gumina, et al. (2012) compared clinical and MRI results of arthroscopic

rotator cuff repair with and without the use of platelet-leukocyte membrane (n=80),

stating that the use of the membrane was associated with significantly better repair

integrity (p=0.04). However, this improvement in integrity was not associated with

greater improvement in functional outcomes.

Randelli, et al. (2011) published long-term results from the use of an intra-operative

application of PRP in combination with a rotator cuff repair of small to massive tears

(n=53; treatment group n=26, control group n=27) completed by a single surgeon. Pain

scores in the treatment group were significantly lower than the control group at 3, 7, 14

and 30 days post surgery (p<0.05). Functional scores (Simple Shoulder Test (SST),

University of California (UCLA and Constant) and strength in external rotation were

significantly higher in the treatment group at 3 months post surgery; however, there was

no significant difference between the groups after 6, 12 and 24 months. The 12-month

MRI analysis showed no difference in the rotator cuff healing rate between the two

groups. They concluded that the PRP application reduced pain in the first post-operative

months, and that smaller tears with less retraction would benefit from PRP.

41

More recently, Werthel and colleagues (2014) reported long term results (mean 19 month

follow-up ± 4.2) on the use of an intra-operative injection of PRP during surgical rotator

cuff repair of full thickness symptomatic supraspinatus tendon tear (retraction less than 3

in the Patte classification). No significant differences were noted functionally or

structurally between the treatment and control groups, except for a lower VAS for pain

score at final follow-up (p < 0.001). There were some limitations of this study; subjects

were not randomised, and a different surgeon operated on the subjects in each group.

There was also a significant age difference between the treatment and control groups, and

the authors suggest this may have contributed to the difference in pain reported at final

follow-up.

SUMMARY

Significant re-tear rates reported in the literature despite advancements in surgical and

suture anchor technique, along with the lengthy tendon healing timeline, has established

the need to investigate biological therapies that may improve and/or accelerate tendon

healing. Biological augmentation in conjunction with rotator cuff repair has the potential

to improve tendon healing. While research in this area has shown it to be safe, results

remain inconclusive, and have not been demonstrated sufficiently to warrant regular

clinical use.

While it has been well established that the longer-term structural and functional results

(>12 months follow-up) have not differed significantly, little research has centred on the

early tendon healing. In a primate model, Sonnabend, et al. (2010) showed that a

significant proportion of Sharpey fibres begin to reconstitute at 3 months, with maturation

42

at 4 months following surgery. It has also been well documented that the majority of re-

tears occur within the first 3 months of surgery (Kluger, et al., 2011; Miller, et al. 2011;

Nho, et al., 2009), suggesting that the early tendon healing stage is critical for long term

success.

There are a number of variables that may affect the efficacy of PRP in combination with

rotator cuff repair, including tendon tear size, formulation of PRP used and timing of

delivery; with all previous studies to our knowledge using time zero delivery at the time

of surgery. We propose that the delayed and repeated injection of PRP (Arthrex) at 7 and

14 days post-surgery will give the best opportunity to enhance early tendon healing and

functional recovery following rotator cuff repair.

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CHAPTER 3

PAPER 1

Do postoperative platelet-rich plasma injections accelerate early tendon healing

and functional recovery after arthroscopic supraspinatus repair?

A randomized controlled trial

Allan Wang,1 PhD, FRACS, Philip McCann,2 FRCS (Tr&Orth), Jessica Colliver,3 BSc,

Eamon Koh,4 FRANZCR, Timothy Ackland,3 PhD, Brendan Joss,3 PhD, Minghao

Zheng,1 PhD, and Bill Breidhal, 5 FRANZCR.

1Department of Orthopaedic Surgery, University of Western Australia, Crawley,

Australia.

2Department of Trauma and Orthopaedic Surgery, Bristol Royal Infirmary, Bristol,

United Kingdom.

3School of Sport Science, Exercise and Health, University of Western Australia,

Crawley, Australia

4Department of Radiology, Fremantle Hospital, Fremantle, Australia

5Perth Radiological Clinic, Perth, Australia

ABSTRACT

Background: Tendon bone healing after rotator cuff repair directly correlates with a

successful outcome. Biological therapies that elevate local growth factor concentrations

may potentiate healing following surgery.

Purpose: To ascertain whether postoperative and repeated application of platelet-rich

plasma (PRP) to the tendon repair site improves early tendon healing and enhances early

functional recovery following double row arthroscopic supraspinatus repair.

Study Design: Randomized controlled trial; Level of evidence, 1.

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Methods: Sixty patients underwent arthroscopic double row supraspinatus tendon repair.

Following randomization, half the patients received two ultrasound-guided injections of

PRP to the repair site at day 7 and day 14 post-surgery. Early structural healing was

assessed with Magnetic Resonance Imaging (MRI) at 16 weeks and cuff appearances

graded according to the Sugaya classification. Functional scores were recorded with the

Oxford Shoulder Score (OSS), the Quick Disability of the Arm, Shoulder and Hand

(Quick-DASH), Visual Analogue Scale (VAS) for pain and Short From-12 (SF-12)

quality of life score both pre-surgery and post-operatively at 6, 12 and 16 weeks,

isokinetic strength and active range of motion was measured at 16 weeks.

Results: PRP treatment did not improve early functional recovery, range of motion,

strength or influence pain scores at any time point after arthroscopic suprapinatus repair.

There was no difference in MRI structural integrity of the supraspinatus repair between

groups (p=0.35) (PRP group 0% full thickness re-tear; 23% partial tear; 77% intact),

compared with the control group (7% full thickness re-tear; 23% partial tear; 70% intact)

at 16 weeks post-operatively.

Conclusion: Following arthroscopic supraspinatus tendon repair, image guided PRP

treatment on two occasions does not improve early tendon bone healing or functional

recovery.

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INTRODUCTION

Despite the advent of new surgical techniques to improve rotator cuff fixation to bone,

failure of the tendon repair often occurs (Galatz, et al., 2004; Sugaya, et al., 2007).

Tendon re-tears may be due to a specific re-injury at the repair site, but also may reflect

incomplete or failed primary healing after surgery (Boileau, et al., 2005; Carpenter, et al.,

1998).

Sonnabend, et al. (2010) in a primate model of rotator cuff repair, showed that a

significant proportion of Sharpey fibres begin to reconstitute at 3 months with maturation

at 4 months after surgery. Thus the early tendon healing stage is critical for long-term

success of rotator cuff repair. Accelerated rotator cuff rehabilitation programs which

allow active exercises sooner than 3 to 4 months before early tendon bone healing occurs,

risk early failure (Parsons, et al., 2010; Zhang, et al., 2013).

Hence, there has been increasing interest in adjuvant biological therapies to improve early

primary tendon healing. In particular, many studies have investigated platelet-rich

plasma (PRP) products, where a supra physiological concentration of platelets is

delivered to the tendon-bone repair site at the time of surgery. Activated platelets

degranulate to release multiple growth factors that modulate the cascade of chemotaxis,

cell proliferation and differentiation, which assist in the tendon healing process (Bedi, et

al., 2012; Eppely, et al., 2004; Galatz, et al., 2007; Gulotta & Rodeo, 2009; Isaac, et al.,

2012; Kobayashi, et al., 2006; Manning, et al., 2011; Molloy, et al., 2003; Plate, et al.,

2013).

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Published studies reporting the use of PRP administration have met with mixed success

in improving outcomes after rotator cuff repair. Appraisal of the literature is complicated

by the range of treated pathologies, varying from small, single tendon tears to massive

multitendon tears; concomitant use of acromioplasty or not; (Castricini, et al., 2011; Jo,

et al., 2011) and the formulation of PRP used, which ranged from intra-tendon injection

(Kesikburun, et al., 2013; Randelli, et al., 2008), spray application (Randelli, et al., 2008;

Ruiz-Moneo, et al., 2013), or incorporation of a platelet-rich fibrin matrix (PRFM) into

the tendon repair site (Barber, et al., 2011; Castricini, et al., 2011; Gumina, et al., 2012;

Weber, et al., 2013).

A further variable affecting the efficacy of PRP is the timing of delivery. All previous

PRP augmented rotator cuff studies to date have used time zero delivery at the time of

surgical repair. Following activation, platelets release growth factors almost immediately

with total elution within 1 hour (Arnoczky, et al., 2011), and the half-life of growth factors

is a matter of minutes to hours (Mooren, et al., 2010), however it has been acknowledged

that biological augmentation of tendon repairs too early in the tendon healing cascade

may be ineffective (Gulotta & Rodeo, 2009). Differing classes of growth factors are

active at specific time points (Kobayashi, et al., 2006); for example, animal studies have

shown that application of platelet-derived growth factors at day-7 have a more

pronounced effect on tendon cellular maturation and biomechanical strength than earlier

application (Chan, et al., 2006). Growth factors including BMP-13, platelet-derived

growth factor-B and transforming growth factor B1 are expressed maximally at days 7

and 14 (Wurgler-Hauri, et al., 2007) and the cytokine mediated temporal expression of

collagen type I and III increases from day-7 onward (Dahlgren, et al., 2005).

62

Hence, timing for PRP delivery remains an important consideration for optimizing tendon

healing. In this study we hypothesized that delayed and repeated injection of PRP at days

7 and 14 after surgery would firstly avoid the potential dilution and washout effect of

arthroscopic administration and secondly, produce a sustained up regulation of the tendon

healing process. The purpose of this study is to determine if this PRP delivery protocol

would enhance early tendon healing and functional recovery after arthroscopic

supraspinatus tendon repair. The primary study outcome is improved early tendon

healing as assessed by MRI scanning. The secondary outcome is patient rated function

as a measure of functional recovery.

METHODS

Patient Selection

Institutional Ethics Committee approval was granted for this study. Patients with MRI or

ultrasound proven rotator cuff tears were identified over the period from November 2011

to February 2013. A power calculation was performed to determine the required number

of patients to detect a significant difference of one Sugaya grade classification between

the treatment and control groups based on previously published MRI classification scores

for post-rotator cuff repair patients (Sugaya, et al., 2007). The power analysis used an

effect size of 0.769 (moderate effect), with significance of p<0.05 and a power of 80%,

giving a minimum sample size of 56 participants (28 participants in each group). More

participants (n=60) were recruited to allow for attrition.

The inclusion criteria comprised the presence of a symptomatic full thickness tear of

supraspinatus in an active adult identified by preoperative imaging and confirmed by

63

arthroscopic evaluation. All patients also received a series of plain radiographs

(anteroposterior, outlet and axillary views) for evaluation of arthritic change. Exclusion

criteria included: patients with a history of previous rotator cuff surgery, subscapularis or

infraspinatus tear identified on preoperative imaging or arthroscopic evaluation; labral

tear; significant degenerative glenohumeral osteoarthritis; contralateral shoulder

symptoms; rheumatalogical, neuromuscular or autoimmune disease; cervical disc

herniation; ongoing workers compensation claims; or contraindication to postoperative

MRI evaluation (Figure 1).

64

Figure 1. CONSORT (Consolidated Standards of Reporting Trials) flowchart.

PASTA = partial articular supraspinatus tendon avulsion; US = ultrasound; PRP =

platelet-rich plasma

Analysed (n=30)

Excluded from analysis (n=0

Analysed (n=30)

Excluded from analysis (n= 0)

Analysis

Lost to follow-up (n=0) Discontinued intervention (n=0)

Lost to follow-up (n=0) Discontinued intervention (n=0)

Follow-Up

Allocated to arthroscopic double row rotator cuff repair without postoperative US-guided PRP injections (n=30) Received allocated intervention (n=30) Did not receive allocated intervention (n= 0)

Allocated to arthroscopic double row rotator cuff repair and postoperative US-guided PRP injections (n=30)

Received allocated intervention (n=30)

Did not receive allocated intervention (n=0)

Allocation

Randomized (n=60)

Assessed for eligibility (n=305)

Excluded (n=239) Workers Compensation = 108 PASTA repairs = 31 Greater than 2cm, not

supraspinatus alone, or involving subscapularis/infraspinatus=73

Osteoarthritis (Glenohumeral joint)=27

Declined to participate (n=6)

Enrollment

65

Surgical Technique

All surgery was performed by the senior author. All procedures were performed in the

lateral decubitus position under general anaesthesia with an interscalene nerve block. The

arm was placed in 4 kg of traction and positioned in 30 degrees of arm flexion and

abduction. Initial diagnostic glenohumeral arthroscopy was performed and the presence

of a full thickness supraspinatus tear confirmed. After debridement of the bursal tissue

and tendon margins, the tear morphology was assessed and tear size measured with a

calibrated probe with 5 mm increments. Tears over 20 mm in the anterioposterior

dimension were excluded, as were partial tears. Supraspinatus tears associated with

subscapularis or infraspinatus tears were excluded from the study. Following

acromioplasty, rotator cuff reconstruction was performed. The footprint was prepared

with a full-radius resector to decorticate the greater tuberosity. A double row suture

bridge repair (Park, et al., 2006) with bioabsorbable anchors was performed (Arthrex Bio-

Corkscrew 5.5mm FT, Biocomposite Pushloc 3.5mm, Arthrex, Naples, FL, USA). The

same reconstructive technique was utilized in each case. Concomitant shoulder

pathology was treated as clinically or radiographically indicated. Acromioclavicular joint

arthropathy was treated with arthroscopic excision of the lateral end of the clavicle and

long head of biceps tendinopathy was treated with tenotomy (Table 1).

66

Table 1. Group demographics with concomitant procedures and complications a

PRP Group (n=30) Control Group (n=30)

Sex (male/female) 11/19 17/13

Mean age (years) [range] 59.8 [28-77] 58.4 [38-76]

Acromioplasty (n) 30 30

Biceps tenotomy (n) 3 5

Acromioclavicular joint excision (n) 4 5

Complications (n) 0 0

Supraspinatus tear size (mm) 14.60 (3.78) 13.70 (3.27)

a PRP = Platelet Rich Plasma.

Post-operative Protocol

All patients were immobilized in a sling (Ultrasling III, Don Joy, Carlsbad, CA, USA)

for 6 weeks postoperatively and followed a standard rehabilitation program under the

supervision of physical therapists. This consisted of passive range of motion exercises in

the first 6 weeks, followed by active assisted range of motion exercises from 6 to 10

weeks and finally, a guided strengthening program from 10 to 16 weeks. All patients

followed this program consistently.

Randomisation Procedure

Patients were reviewed on the fifth post-operative day, and following arthroscopic

evaluation and confirmation study inclusion criteria were met, randomized to PRP or

control groups. A computer block permutation method was prepared to generate a simple

randomised computer-generated table of blocks of 10 (5 PRP; 5 Control), stratified by

the treating surgeon at the five day post-surgical follow up. Sixty consecutive patients

meeting the study inclusion criteria, and consenting to the study were randomized via the

67

above procedure, with thirty in each arm of the study. The average age was 59.1 years

(range: 28-77 years). Patient demographics along with details of concomitant surgical

procedures are illustrated in Table 1.

Preparation of Platelet–rich Plasma

The group randomized to the treatment arm of the study underwent ultrasound guided

PRP injection to the rotator cuff repair site on two separate occasions, at days 7 and 14

post-surgery. The platelet concentrate was obtained using the Arthrex Autologous

Conditioned Plasma (ACP) system (Arthrex, Naples, FL, USA). A PRP injection was

prepared from 10 ml of autologous peripheral blood. Following the addition of 1 ml of

Anticoagulant Citrate Dextrose Solution (ACD-A), the blood was spun in a centrifuge

(ROTOFIX 32 A, Andreas Hettich GmbH & Co. KG, Tuttlingen, Germany) at 1500

revolutions per minute (RPM) for 5 minutes. Following centrifugation, the PRP

supernatant (approximately 2-4 ml) was removed and stored in a separate sterile syringe

in preparation for point of care delivery.

The ACP system produces a platelet concentration of approximately 470,000

platelets/μL, (2.1 times greater than the level in whole blood) with an estimated

concentration of growth factor reported as five to 25 times that of normal physiologic

levels. It is free of both residual erythrocytes and leucocytes, which may impair local

growth factor activity by free radical activation (Jiang, et al., 2007; Scott, et al., 2004).

Immediately prior to injection, the preparation was activated with 2 ml of CaCl2

(Nikolidakis & Jansen, 2008). The injection was delivered at the tendon repair site under

direct visualisation with ultrasound by an experienced fellowship-trained musculoskeletal

68

radiologist. Needle placement was aided by the identification of the echogenic sutures at

the tendon repair site (Figure 2). The control group did not receive a placebo injection.

Figure 2. Ultrasound image of needle placement directly at the tendon repair site (arrow).

Outcome Assessments

Radiographic analysis was performed with MR imaging at 16 weeks. All scans utilized

a 1.5 Telsa unit (Sonata Maestro Class; Siemens, Erlangen, Germany) with 40 mT/m

gradient power. Multiple images were obtained in oblique coronal, oblique sagittal and

axial planes with both short-tau inversion recovery (STIR) and turbo spin echo (TSE) T1-

weighted sequence. MRI assessment was performed by an experienced fellowship

trained musculoskeletal radiologist, who had not performed the PRP injections and was

blinded to patient allocation to treatment or control group. Multiple images were

evaluated and graded as per the Sugaya classification (Figure 3) (Sugaya, et al., 2007).

69

Figure 3. T1-weighted coronal magnetic resonance image displaying Sugaya grade 1

appearance.

Outcomes were assessed clinically and radiologically. Patients were assessed using the

Oxford Shoulder Score (OSS), Quick Disability of the Arm, Shoulder and Hand (Quick

DASH), Visual Analogue Scale (VAS) for pain and Short Form-12 (SF-12); pre-surgery

and at 6, 12 and 16 weeks post-surgery. All assessors were blinded as to the identity of

he treatment and control groups, nor were they involved in any stage of the recruitment

or surgery.

Active range of motion was assessed at 16 weeks using a goniometer. Absolute values

were recorded for arm flexion, abduction and external humeral rotation in both the

operated and un-operated shoulders, using anatomical landmarks for accuracy and

consistency. Range of motion was performed within the participants’ pain tolerance to

minimise any injury risk and discomfort.

70

Isokinetic strength was also assessed at 16 weeks with the patient seated in a Biodex

Isokinetic Dynamometer (Biodex, System 4, Shirley, NY) and a series of standardized

measurements performed with the patient instructed to produce a maximum muscular

force at speeds of 60 and 90 degrees/s. External humeral rotation was performed in the

modified-neutral position, with the elbow at 90 degrees of flexion and the forearm in a

neutral position throughout. Arm flexion was performed with the elbow fully extended.

Values for both peak torque and total work performed over the range of motion were

noted. Data were recorded as both absolute values and as a percentage of the scores

obtained on the contralateral, un-operated shoulder. A difference of 10-15% in the

strength between shoulders is regarded as physiologically normal in the general

population and in those patients undergoing surgery (Bigoni, et al., 2009).

Statistical Analysis

Values are presented as means with associated standard deviations. A series of two-

factor, repeated measures ANOVA was performed to assess for difference between the

treatment and control groups over time for continuous variables. For continuous data

recorded at a single time point only, a series of independent t-tests were performed,

whereas a Mann-Whitney U test was employed for the MRI rating primary outcome

variable. Statistical analyses used SPSS software (SPSS, Chicago, IL). For all tests, a

p<0.05 was considered significant.

RESULTS

All patients complied with the study protocol, and no patient was lost to follow up. There

were no significant complications such as infection, neurological or vascular deficit for

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any patient in either arm of the study. In the control group mean tendon tear size treated

was 1.37 cm, and in the PRP group, mean tendon tear size treated was 1.46 cm. The

adjunctive procedures of acromioclavicular joint excision and biceps tenotomy are shown

in Table 1. No patient underwent a cortisone injection for pain, capsulitis or bursitis

within the study period.

Structural Evaluation

Using the Sugaya classification, the grade of supraspinatus tendon healing for the PRP

and control group is reported in Table 2. In both groups, 23% of subjects had a partial

thickness tendon repair (Sugaya grade 3). No full thickness re-tears were noted in the

PRP treatment group, two (7%) full thickness re-tears (Sugaya grades 4 and 5) occurred

in the control group. One patient in the PRP treatment group did not tolerate the

postoperative MRI scan and so underwent an ultrasound performed by an experienced

musculoskeletal radiologist. This tendon repair was intact and without any evidence of

thinning or discontinuity and so, for the purposes of the study, was included in the grade

1 group of that cohort. In the PRP treatment group, 23 subjects (77%) exhibited a healed

repair or an intact repair with high signal intensity (Sugaya grades 1 and 2), compared to

21 subjects (70%) in the control group. A Mann-Whitney U test demonstrated no

difference (p=0.351) between groups on MRI rating at 16 weeks (PRP group mean ± SD

= 1.8 ± 0.8; Control = 2.1 ± 1.0).

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Table 2. Sugaya classification of MRI scans of patient treatment groups a

Sugaya Classification b Group Number Percentage

Grade 1 (no tear)

PRP 12 40.0

Control 9 30.0

Grade 2 (sufficient tendon thickness

but with high signal change)

PRP 11 36.6

Control 12 40.0

Grade 3 (insufficient thickness but

no tendon discontinuity)

PRP 7 23.0

Control 7 23.0

Grade 4 (small full thickness re-

tear)

PRP 0 0

Control 1 3.3

Grade 5 (large full thickness re-

tear)

PRP 0 0

Control 1 3.3

a Values are reported as n (%), PRP = platelet-rich plasma.

b From Sugaya, et al., (2007). Grade 1 = no tear; grade 2 = sufficient tendon thickness but with high signal

change; grade 3 =insufficient thickness but no tendon discontinuity; grade 4 = small full-thickness re-tear;

grade 5 = large full-thickness re-tear.

Functional Scores

Outcome scores for all patients improved following surgery. At 12 and 16 weeks

postoperatively, the OSS (F=75.803; df 3; p<0.001), the QuickDASH (F=53.939; df 3;

p<0.001) and the VAS pain scores (F=75.499; df 3; p<0.001) all improved significantly

from pre-surgery. Similarly, the SF-12 quality of life indicators improved with time:

Physical Component score (F=13.967; df 3; p<0.001) and Mental Component score

(F=5.401; df 3; p=0.001). There was, however, no statistical difference (p>0.05) between

the PRP treatment and control groups for any of these functional scores at any time point

postoperatively (Table 3).

73

Table 3. Functional scores a

Variable Group

Pre-surgery 6 weeks

post-surgery

12 weeks

post-surgery

16 weeks

post-surgery

Mean SD Mean SD Mean SD Mean SD

QuickDASH

Symptoms

PRP 42.27 17.06 51.17 19.54 33.14 19.27 22.58 14.36

Control 37.16 20.38 53.48 13.27 36.33 17.40 17.23 13.56

VAS PRP 6.37 1.59 3.26 2.43 2.35 2.01 1.75 1.68

Control 5.38 2.43 1.19 2.34 2.23 1.91 1.36 1.51

OSS PRP 27.63 6.90 23.57 9.61 33.38 8.93 38.17 7.19

Control 30.68 7.76 21.48 6.61 32.53 6.92 40.37 5.12

SF-12 PCS PRP 35.17 8.43 36.31 7.40 38.73 7.06 41.78 8.34

Control 37.92 7.97 34.98 5.75 39.08 6.94 43.08 6.26

SF-12 MCS PRP 52.16 12.24 49.87 12.94 52.75 11.90 53.81 11.21

Control 50.47 12.56 49.69 13.63 53.47 10.55 55.17 7.41

a Values are reported as mean ± SD. MCS = mental component score; OSS = Oxford Shoulder Score;

PCS = physical component score; PRP = platelet-rich plasma; QuickDASH = Quick Disability of the

Arm, Shoulder and Hand; SF-12 = Short Form-12; VAS = visual analogue scale for pain.

Strength

Isokinetic strength values were obtained for active arm flexion and external rotation

movements at two speeds. Values were expressed as a percentage of the strength

recorded in the contralateral shoulder. Within the control group the relative scores for

arm flexion peak torque at 90 and 60 degrees/s were 68.7% and 75.4% respectively, and

75.6% and 74.0% respectively for external rotation peak torque. Relative scores were

similar in the PRP treatment group for arm flexion peak torque at 90 and 60 degrees/s

(74.1% and 76.3%) and external rotation peak torque (72.1% and 77.3%) respectively.

No group differences (p>0.05) for strength scores at 16 weeks post-surgery were evident

(Table 4).

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Table 4. Group mean scores (as percentage of the contralateral, un-operated arm) and t-

test results for strength measures at 16 weeks post-surgery a

Variable Group Mean (%) SD t P

Arm flexion peak torque 90°/s

PRP 74.1 10.8

-0.122 0.266

Control 68.7 24.2

Arm flexion total work 90°/s

PRP 55.5 23.2

0.107 0.915

Control 56.3 34.2

Arm flexion peak torque 60°/s

PRP 76.3 22.0

-0.190 0.85

Control 75.4 22.0

Arm flexion total work 60°/s

PRP 61.7 21.8

-0.150 0.881

Control 60. 8 27.4

External rotation peak torque 90°/s

PRP 72.2 15.7

0.470 0.640

Control 75.6 37.5

External rotation total work 90°/s

PRP 51.9 30.1

0.712 0.371

Control 55.1 35.8

External rotation peak torque 60°/s

PRP 77.3 17.8

-0.64 0.525

Control 74.0 21.3

External rotation total work 60°/s

PRP 59.8 24.3

0.277 0.783

Control 62.3 44.0

a Strength was calculated as a percentage of the contralateral, un-operated arm. Results are reported as

mean ± SD, PRP = platelet-rich plasma.

Range of Motion

The analysis revealed no significant differences (p>0.05) in any active range of motion

measure between the two groups at 16 weeks post-surgery. Complete values are

displayed in Table 5.

75

Table 5. Group mean scores and t-test results for range of motion for the operated limb

at 16 weeks post-surgery a

Range of Motion

(degrees) Group

Mean

(deg) SD t P

Arm flexion 1.274 0.208

PRP 144.8 22.8

Control 151.8 19.8

Arm abduction 0.342 0.734

PRP 134.8 28.2

Control 137.4 29.1

External rotation 0.69 0.493

PRP 41.1 10.2

Control 42.8 9.3

a PRP = platelet-rich plasma

DISCUSSION

The purpose of the study was to evaluate the efficacy of a protocol of sequential PRP

administration following arthroscopic supraspinatus repair. All previous studies have

utilized a single delivery of a PRP product at the time of surgery. The current protocol

delivered a PRP product under ultrasound guidance to the tendon repair site at 7 and 14

days after surgery to avoid a possible dilution or washout effect of PRP, which may occur

with arthroscopic fluid lavage. This protocol also allows a potentially prolonged up-

regulation of growth factors involved in the tendon-healing cascade. Our hypothesis was

that this post-surgical and sequential PRP delivery protocol would firstly improve rotator

cuff healing and secondly accelerate early functional recovery following arthroscopic

rotator cuff repair.

This study finds that at 16 weeks post-surgery, no full thickness tendon re-tears occurred

in the PRP group however, there were two (7%) full thickness re-tears in the control

76

group. Although this difference was not statistically significant, our findings are

consistent with previous reports. Castricini, et al. (2012) examined the effects of PRFM

augmentation in rotator cuff repair and reported the re-rupture rate was higher in the

control group (10.5% versus 2.5%). In contrast, Gumina, et al. (2012), using a novel

platelet rich fibrin matrix allowing slow release of growth factors on the tendon repair

site, found a 14% re-tear rate in isolated supraspinatus tears (between 2 to 4 cm) in the

PRP group compared to 50% in the control group at 13 months. However Rodeo, et al.

(2007), also using PRFM in 79 patients undergoing arthroscopic cuff repair found no

difference in tendon bone healing on ultrasound at 6 weeks and 12 weeks after surgery.

The secondary outcomes of this study were to evaluate early functional recovery in

patients receiving PRP treatment following supraspinatus repair. In a prospective RCT

of 53 patients, Randelli, et al. (2011) reported that PRP administered by spray, produced

statistically better early function scores and strength at 3 months post-surgery. No

imaging was performed at this stage, though it was concluded that PRP administration

accelerates early recovery following surgery. Zumstein, et al. (2012) also showed an early

benefit of PRP administration with improved revascularization of the tendon-bone repair

site. Doppler ultrasonography was used to assess the vascularization index of 20

shoulders at 6 and 12 weeks following surgery (Zumstein, et al., 2012). At 6 weeks, those

shoulders treated with a leucocyte rich PRP product showed significantly better

vascularization, however this was not sustained at 12 weeks.

Our study can report that early functional recovery was not improved with a sequential

post-surgical PRP delivery protocol. At 6, 12 and 16 weeks, clinical function scores were

equivalent between PRP and control group participants. Furthermore, objective testing

of shoulder function at 16 weeks showed no difference between groups in recovery of

77

active arm flexion, abduction, or external rotation range of motion. Similarly, isokinetic

peak torque and the work done through the active range of motion during each movement

was not different between groups.

PRP delivery by injection under ultrasound guidance into the supraspinatus tendon repair

site may be less accurate than injection under arthroscopic visualization. However, the

surgical technique employed in this study comprised a double row suture bridge technique

and the echogenic suture knots were readily identified on ultrasound. Moreover, the

oblique and interlocking sutures of the suture bridge potentially retains the injected PRP

at the repair site better than the single row repair site technique used in previous studies

(Randelli, et al., 2011).

As an imaging modality, ultrasound has been shown to be reliable in obtaining a precise

placement of PRP at the site of tendon injury (Wiegerinck, et al., 2011). PRP delivery by

direct injection under ultrasound guidance has been used to treat injuries of the Achilles

tendon (de Vos et al., 2010), the common extensor tendon origin (Mishra, et al., 2006;

Mishra, et al., 2014; Peerbooms, et al., 2010) and the rotator cuff. Kesikburun, et al.

(2013) demonstrated that PRP injection to non-surgically treat rotator cuff tendinopathy

and partial thickness tendon tears has no significant clinical benefit over saline injections

at 3, 6, 12 and 52 weeks. The findings of our study are consistent with this work, and

even with a second PRP injection, there was no significant clinical or functional benefit

up to 16 weeks post-surgery. Our study focus is early outcomes, however definitive

clinical outcomes require 12 to 24 month postoperative evaluation.

This study has some limitations to be acknowledged. Firstly, the follow-up was limited

to 16 weeks. It is possible that more structural tendon failures would have been seen if

78

MRI evaluation was repeated at a later time interval such as 12 months. However, it was

the primary aim of this study to assess the effects of PRP treatment on the early phases

of tendon healing. Animal models have demonstrated that a significant proportion of

Sharpey’s fibres at the tendon repair site have reconstituted and matured at the bone-

tendon repair by 3 to 4 months (Sonnabend, et al., 2010), thus supporting the validity of

assessment at the 16-week time point.

A second limitation is the non-blinding of subjects in both PRP and control groups. As

the study protocol required two separate post-surgical injections, we considered that it

would be impractical to have patients agreeing to complete two placebo injections.

Patients in the PRP treatment group may have had the benefit of a placebo as well as a

possible PRP treatment effect in their clinical and functional evaluation. Similarly, those

patients who did not receive injections may have responded differently in clinical testing.

The non-blinding of subjects could be expected to cause a positive bias in the PRP group

however, groups were equivalent in their study outcomes. MRI evaluation was performed

by an independent musculoskeletal radiologist, who had not been involved in previous

diagnostic imaging or PRP injections, and was blinded to group allocation.

A further possible study limitation was the PRP product used in this study, does not

achieve the very high concentration of platelets reported with some other PRP products

(Arnoczky, et al., 2011; Eppely, et al., 2004; Geaney, et al., 2011). Sundman, et al.

(2011), in a laboratory study suggested that markedly elevated supra physiological levels

of platelets and growth factors may be of no additional benefit due to cell-surface receptor

saturation, or may actually be detrimental to tendon healing. Optimal tendon healing

requires not only the appropriate concentration of growth factors, but those growth factors

79

be delivered at the appropriate time in the tendon healing cascade, to be maximally

effective.

CONCLUSION

This study is the first to evaluate the efficacy of a post-surgical PRP delivery protocol to

improve healing and functional outcomes after arthroscopic rotator cuff repair.

Sequential delivery of the specific injectable PRP preparation used in this study under

ultrasound guidance, at days 7 and 14 post-surgery, does not improve early rotator cuff

healing or functional recovery. Future research should include randomized controlled

trials of other PRP products with alternate delivery vehicles and dosing regimes.

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85

CHAPTER 4

PAPER 2

Early postoperative repair status after rotator cuff repair cannot be

accurately classified using questionnaires of patient function

and isokinetic strength evaluation.

PREAMBLE

Research conducted by Sonnabend and colleagues (2010), shows the reconstitution and

maturation of Sharpey fibres at 3-4 months post rotator cuff repair. Kluger, et al. (2011)

have shown that the majority of recurrent tears occurred in the first 3 months following

rotator cuff surgery, highlighting that this early tendon healing phase is critical for

longer term success. The early confirmation that tendon healing is progressing (or not),

is of benefit, and could affect post-surgery management (rehabilitation and/or revision

surgery), as well as individual structured return to work and/or sport. It is common to

introduce return-to-work strategies at 4 months post rotator cuff repair and therefore, we

believe that the prediction of tendon healing at this stage using low cost functional and

strength outcomes could prove beneficial.

The post-operative use of MRI and/or US to evaluate rotator cuff repair tendon healing

can be costly and time consuming. Studies have investigated the diagnostic accuracy of

common clinical shoulder tests for conservatively treated rotator cuff tendon tears, and

concluded that most tests are inaccurate and cannot be recommended for clinical

diagnosis (Ainsworth & Lewis, 2007; Hughes, et al., 2008; Murrell & Walton, 2001;

Hegedus, et al., 2008; 2012). This may well be the case post-operatively, and more

robust testing in this area is required (Hegedus, et al., 2008; 2012).

86

As the results of Wang, et al. (2015) showed no significant difference between the PRP

and control groups in structural tendon healing, function or strength outcomes, we saw

an opportunity to combine the original groups into one cohort, to further investigate this

gap in the research.

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of full thickness tears of the rotator cuff: a systematic review. Br J Sports Med,

41, 200-210.

Hegedus, E. J., Goode, A., Campbell, S., Morin, A., Tamaddoni, M., Moorman, C. T.,

3rd, et al. (2008). Physical examination tests of the shoulder: a systematic

review with meta-analysis of individual tests. Br J Sports Med, 42(2), 80-92;

discussion 92.

Hegedus, E. J., Goode, A. P., Cook, C. E., Michener, L., Myer, C. A., Myer, D. M., et

al. (2012). Which physical examination tests provide clinicians with the most

value when examining the shoulder? Update of a systematic review with meta-

analysis of individual tests. Br J Sports Med, 46(14), 964-978.

Hughes, P. C., Taylor, N. F., & Green, R. A. (2008). Most clinical tests cannot

accurately diagnose rotator cuff pathology: a systematic review. Aust J

Physiother, 54(3), 159-170.

Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term

survivorship of rotator cuff repairs using ultrasound and magnetic resonance

imaging analysis. Am J Sports Med, 39(10), 2071-2081.

Murrell, G. A., & Walton, J. R. (2001). Diagnosis of rotator cuff tears. Lancet,

357(9258), 769-770.

87

Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of

repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-

594.

Wang, A., McCann, P., Colliver, J., Koh, E., Ackland, T., Joss, B., et al. (2015). Do

Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing

and Functional Recovery After Arthroscopic Supraspinatus Repair? A

Randomized Controlled Trial. Am J Sports Med (in press).

88

Early post-operative repair status after rotator cuff repair cannot be accurately

classified using questionnaires of patient function and isokinetic strength

evaluation.

Jessica A. Colliver BSc1; Allan W. Wang PhD, FRACS1,2; Eamon Koh FRANZCR3;

Brendan Joss PhD1; Jay R. Ebert PhD1; Timothy R. Ackland PhD1; William Breidahl,

FRANZCR4.

1 School of Sport Science, Exercise and Health, University of Western Australia, Crawley,

Perth, Western Australia.

2 Department of Orthopaedic Surgery, The University of Western Australia, Crawley,

Perth, Western Australia.

3 Department of Radiology, Fremantle Hospital, Fremantle, Western Australia.

4 Perth Radiological Clinic, Subiaco, Perth, Western Australia.

Level of Evidence: Level IV prospective study.

ABSTRACT

Purpose: To investigate if patients with an intact repair or partial re-tear in the early

stages (16 weeks) after rotator cuff repair surgery display differences in common shoulder

patient-reported outcome (PRO) measures and isokinetic strength tests, and whether early

post-surgical tendon healing could be predicted using these clinical shoulder evaluations.

Methods: This study was undertaken in 60 patients undergoing arthroscopic double-row

supraspinatus tendon repair. All patients were assessed clinically at 16 weeks post-

89

surgery using the Oxford Shoulder Score, the Quick Disability of the Arm, Shoulder and

Hand (QuickDASH), a Visual Analogue Pain Scale and the 12-item Short Form Health

survey, as well as isokinetic strength evaluation (external humeral rotation and arm

flexion). Magnetic Resonance Imaging (MRI) was undertaken at 16 weeks post-surgery.

Independent t-tests were employed to investigate clinical differences in patients group-

stratified based on the Sugaya MRI classification for rotator cuff tears (Grades 1, 2 or 3).

Discriminant analysis was employed to determine whether intact repairs (Sugaya Grade

1) and partial re-tears (Sugaya Grades 2 and 3) could be predicted based on clinical scores.

Results: No significant differences (p<0.05) in any of the PRO or strength measures were

observed between groups at 16 weeks post-surgery. Discriminant analysis revealed the

QuickDASH alone produced a 97% true positive rate for predicting partial re-tears, but

also a 90% false positive rate. The ability to discriminate between groups was enhanced

with up to five variables entered; however, only 87% of the partial re-tear group, and 36%

of the intact repair group, were correctly classified.

Conclusion: We observed no difference in clinical scores between patient groups

stratified by the Sugaya MRI classification system at 16 weeks post-surgery, while the

presence of an intact repair or partial re-tear after surgery could not be accurately

predicted by these shoulder evaluations. Our results suggest that correct classification of

tendon healing in the early stage following surgery must involve medical imaging.

Keywords: rotator cuff repair surgery, shoulder, patient-reported outcome measures,

isokinetic strength, magnetic resonance imaging.

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INTRODUCTION

Rotator cuff surgical repair is common with in excess of 250,000 performed each year

(Gulotta & Rodeo, 2009). However, despite several proposed surgical techniques and the

increasing use of adjunct biological therapies to stimulate and/or enhance repair, the post-

operative failure rate remains relatively high (Barber, et al., 2011; Charousset, et al.,

2010; Cheung, et al., 2010). It is well documented in the literature that increased patient

age, tear size and severity of pre-operative fatty muscular degeneration contribute to an

increased incidence of post-operative rotator cuff re-tears (Boileau, et al., 2005; Cho &

Rhee, 2009; Cho, et al., 2010; Galatz, et al., 2004; Murrell & Walton, 2001; Oh, et al.,

2010). While patients with re-tears or failed healing may experience a reduction in pain,

functional outcomes including strength levels are significantly lower when compared to

patients with evidence of healed tendons (Boileau, et al., 2005; Cho & Rhee, 2009;

Galatz, et al., 2004; Harryman, et al., 1991; Sugaya, et al., 2007). These inferior

functional results may be satisfactory for an older and/or less active population, but for

patients requiring a return to sport or work, especially in roles where physical strength is

important, many are likely to be dissatisfied with the outcome.

In a primate model of rotator cuff repair, it has been shown that a significant proportion

of Sharpey fibres start to reconstitute at 3 months, with maturation seen at four months

(Sonnabend, et al., 2010). Kluger, et al. (2011) reported that the majority of recurrent

tears occurred in the first three months after rotator cuff surgery, highlighting that this

early tendon healing phase up to 3-4 months post-operatively is critical for longer term

success. Early confirmation that healing is progressing well (or not) is therefore of

benefit, and could affect post-surgery management (rehabilitation and/or re-operation),

as well as the patient’s individualised structured return to work and/or sport. For the

91

aforementioned reasons, it is commonplace to introduce return-to-work strategies at four

months post-surgery and, therefore, prediction of tendon-healing at this stage using low

cost functional and strength outcomes could prove beneficial.

The use of post-operative magnetic resonance imaging (MRI) and/or ultrasound (US) to

evaluate the outcome of rotator cuff surgery can be costly and time consuming. Several

researchers have attempted to determine whether the healing progress of a conservatively

treated rotator cuff tendon tear can be predicted using common, clinical shoulder

assessments, albeit with limited success (Ainsworth & Lewis, 2007; Hughes, et al., 2008;

Murrell & Walton, 2001). At the time of writing, the authors are unaware of any other

studies that have investigated the ability of common shoulder clinical assessments to

predict the early post-operative success of rotator cuff repair surgery, independent of

radiological assessment (MRI and/or US).

Therefore, this study aimed to: a) investigate if differences in common shoulder patient-

reported outcome (PRO) measures and isokinetic strength tests could be observed

between patients with intact repairs or partial re-tears, classified by MRI, at 16 weeks

after rotator cuff repair surgery, and; (b) determine if early post-surgical tendon healing

could be predicted using these PRO measures and strength tests alone, without the need

for radiological assessment.

METHODS

Patients

Between November 2011 and February 2013, patients with rotator cuff tears isolated to

the supraspinatus, confirmed via US or MRI, were invited to participate in this project.

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This study was part of a larger, published randomized controlled trial (RCT) that sought

to ascertain whether platelet-rich plasma (PRP) applied to the tendon repair site after

double-row arthroscopic supraspinatus repair (PRP group), improved early tendon

healing and functional recovery, compared to no adjunct post-operative treatment (control

group) (Wang, et al., 2015). Therefore, inclusion and exclusion criteria for this RCT have

been published (Wang, et al., 2015). In brief, inclusion criteria required patients to have

a symptomatic full thickness tear of supraspinatus, confirmed pre-operatively via MRI or

US and intra-operatively by arthroscopic evaluation. Patients with supraspinatus partial

tears or tears over 20 mm in the anteroposterior dimension were excluded, as were

patients with concomitant subscapularis and/or infraspinatus tears identified on pre-

operative US/MRI or intra-operative examination. Patients were excluded if they had a

history of previous rotator cuff surgery, labral tearing, significant osteoarthritis of the

glenohumeral joint, rheumatalogical, neuromuscular or autoimmune disease and/or

cervical disc herniation. Patients were further excluded if they presented with any

contralateral shoulder symptoms or had ongoing workers’ compensation claims.

Over the study recruitment period, a total of 305 patients were assessed for study

eligibility. A CONSORT (Consolidated Standards of Reporting Trials) flowchart has

been previously published (Wang, et al., 2015). As part of the primary RCT, (Wang, et

al., 2015) all patients that consented to the study and subsequently underwent

supraspinatus repair, were reviewed on the fifth post-operative day and then randomized

by a computer block permutation method into either the PRP injection group or the

control group. Therefore, a total of 60 consecutive patients (30 PRP; 30 control) meeting

the study inclusion criteria and consenting to the study were randomized via the

aforementioned procedure. Patient demographics with concomitant surgical procedures

are presented in Table 1. A priori power calculation was performed for the primary RCT

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(Wang, et al., 2015) which indicated that for an anticipated moderate effect size of 0.769

in the primary outcome variable (the Sugaya classification system of rotator cuff tear

severity (Sugaya, et al., 2007)), a total of 56 patients (28 PRP; 28 control) were required

to reveal differences at the 5% significance level, with 80% power. Therefore, a total of

60 participants were initially recruited to allow for attrition. This research was approved

by the relevant Institutional Review Board (IRB).

Table 1. Group demographics with details of concomitant procedures and complications.

PRP Group (n=30) Control Group (n=30)

Sex (male/female) 11/19 17/13

Mean age (years) [range] 59.8 [28-77] 58.4 [38-76]

Acromioplasty (n) 30 30

Biceps tenotomy (n) 3 5

Acromioclavicular joint excision (n) 4 5

Complications (n) 0 0

Supraspinatus tear size (mm) 14.6 (3.8) 13.7 (3.4)

PRP = Platelet Rich Plasma.

Surgical Technique

All surgery was performed by the senior author and has been previously published (Wang,

et al., 2015). Briefly, all procedures were performed in the lateral decubitus position

under general anesthesia with an interscalene nerve block. The arm was placed in 4 kg

of traction and positioned in 30º of arm flexion and abduction. The presence of a full

thickness supraspinatus tear was initially confirmed via diagnostic glenohumeral

arthroscopy. Tear type and size were assessed using a calibrated probe with 5 mm

increments, following debridement of bursal tissue and tendon margins. After

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acromioplasty, rotator cuff reconstruction was performed. The footprint was prepared

with a full-radius resector to decorticate the greater tuberosity. A double-row suture-

bridge repair (Park, et al., 2006) technique with bioabsorbable anchors was performed

(Arthrex Bio-Corkscrew 5.5 mm–FT, Biocomposite Pushloc 3.5 mm; Arthrex) in all

cases. Concomitant shoulder injuries were treated as clinically or radiographically

indicated. Acromioclavicular joint arthropathy was treated with arthroscopic excision of

the lateral end of the clavicle, and long head of biceps tendinopathy was treated with

tenotomy (Table 1).

Post-operative Management

All patients were immobilized in an abduction sling (Ultrasling III, Don Joy, Carlsbad,

CA, USA) for 6 weeks post-operatively and underwent a standard rehabilitation program

under the supervision of a physical therapist. Briefly, patients underwent an initial 6

weeks of passive range of motion exercises, followed by active-assisted range of motion

exercises from 6-10 weeks and a conservative strengthening program from 10-16 weeks.

All patients followed the aforementioned protocol consistently.

Patient-reported Outcome (PRO) Measures

Four PRO measures were employed pre- and post-operatively at 16 weeks, including: 1)

the Oxford Shoulder Score (OSS); 2) the Quick Disability of the Arm, Shoulder and Hand

(QuickDASH) questionnaire; 3) a Visual Analogue Pain Scale (VAS), and; 4) the 12-

item Short Form Health survey (SF-12). Firstly, the OSS is a 12-item questionnaire

evaluating pain and function, which has been validated against both general health and

clinical measures and has demonstrated good reliability in evaluating outcome after

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shoulder surgery (Dawson, et al., 1996; Dawson, et al., 2001; Olley & Carr, 2008). The

QuickDASH is an 11-item questionnaire evaluating pain, symptoms and physical

function in patients with upper limb musculoskeletal disorders, (Beaton, et al., 2005) and

has also demonstrated good reliability, validity and responsiveness (Beaton, et al., 2005;

Gummesson, et al., 2006). The VAS required patients to rate their pain intensity on a 0-

10cm sliding scale (0 = no pain, 10 = worst pain imaginable) in the preceding 24 hours.

A 1.4cm improvement on the VAS has previously been reported as the minimal clinically

important change in patients undergoing non-operative treatment for rotator cuff disease

(Tashjian, et al., 2009). Finally, the SF-12 is a generic health-related quality of life score,

(Ware, et al., 1996) that produces a physical (PCS) and mental (MCS) component

subscale.

Isokinetic Strength Evaluation

Isokinetic strength was assessed at 16 weeks post-surgery in all patients using a Biodex

Isokinetic Dynamometer (Biodex, System 4, Shirley, NY). Patients were seated with the

trunk stabilized using rigid straps, and adjustments made for humeral and forearm length,

in accordance with each patient’s stature. Patients were instructed to undertake maximal

concentric external/internal humeral rotation (Figure 1), followed by arm flexion, at an

angular velocity of 60°/s. External/internal humeral rotation was performed in the

modified-neutral position, with the elbow in 90° of flexion and the forearm in a neutral

position. Arm flexion was performed with the elbow fully extended. Each trial consisted

of three maximal repetitions. Two trials on each upper limb were undertaken, alternating

between the non-operated and operated limbs, with the first trial always undertaken on

the non-operated side. During each maximal effort, patients were asked to perform to

their maximal muscle strength, while verbal encouragement was provided, standardized

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across all patients and trials. Patients were given adequate rest in between trials to

minimize fatigue, though this was not standardized and based upon the patient’s

individual readiness to proceed. For all trials, the peak torque (Nm), time to peak torque

(secs) and total work (J) performed over the range of motion were obtained, and data were

recorded as absolute values.

Figure 1. A patient performing humeral (A) internal and (B) external rotation on the

Biodex Isokinetic Dynamometer.

97

Radiological Evaluation

Radiographic analysis was performed with MRI at 16 weeks post-surgery. All scans

utilized a 1.5T unit (Sonata Maestro Class; Siemens, Erlangen, Germany) with 40mT/m

gradient power. Multiple images were obtained in oblique coronal, oblique sagittal and

axial planes with both short-tau inversion recovery (STIR) and turbo spin echo (TSE) T1-

weighted sequence. MRI assessment was performed by an experienced radiologist, who

did not perform the PRP injections as part of the primary RCT and was therefore blinded

to patient group allocation. MR images were graded as per the Sugaya classification

(Sugaya, et al., 2007): Grade 1 = no tear; Grade 2 = sufficient tendon thickness but with

high signal change; Grade 3 = insufficient thickness but no tendon discontinuity; Grade

4 = small full-thickness re-tear; Grade 5 = large full-thickness re-tear.

Statistical Analysis

Firstly, statistical procedures were performed with both groups as part of the primary

RCT (PRP and control) pooled together (n=60). Independent sample t-tests were initially

employed to determine if partial thickness tendon re-tears led to poorer strength and

functional scores, compared to an intact repair. Participants were grouped according to

their 16-week post-operative MRI Sugaya grading (Grade 1, 2 or 3), while those with

Grade 4 or 5 were omitted from the analysis (n=2). Group means (SD) for the Sugaya

grading classifications were presented.

A series of discriminant analyses were employed to determine if the Sugaya grading

(presence and severity of a tear) could be predicted using PRO measures and/or strength

data. Linear combinations of predictor variables were formed to serve as the basis for

98

classifying cases into two groups: a partial re-tear group (Sugaya Grades 2 and 3) and an

intact repair group (Sugaya Grade 1). When using discriminant analysis, it is

recommended that the number of variables should be used so that there are data for at

least three subjects per variable, and the number of variables should not exceed the

number of subjects in the smallest group (Carter & Ackland, 1998; Tatsuoka, 1971).

These requirements were satisfied in our analysis. The discriminant analysis used the

method of Wilks’ lambda and a stepwise forward inclusion model. Analyses were

evaluated in terms of a high eigenvalue, high canonical correlation squared, low and

significant Wilks’ lambda (p<0.001), and a high percentage of correctly classified

subjects, as suggested by Carter and Ackland (1998), and successful classification would

be above 80%. We began the analysis with the variable that had the highest prediction

(QuickDASH), and then added variables to a maximum of five. Statistical analysis was

performed using SPSS software (SPSS, Version 22.0, SPSS Inc., USA), while statistical

significance was determined at P < 0.05.

RESULTS

Group means (SD) are presented for patients classified by Sugaya Grades 1 (n=21, 35%),

2 (n=23, 38%) or 3 (n=14, 23%), and these groups were compared at 16 weeks post-

surgery (Table 2). One patient did not tolerate the post-operative MRI scan due to

claustrophobia, instead undergoing an US performed by an experienced musculoskeletal

radiologist. This tendon repair was intact, with no evidence of thinning or discontinuity,

so for the purpose of this study it was included in the Grade 1 Sugaya classification. No

significant differences (p>0.05) in PRO or isokinetic strength measures were observed

between these three groups based on the Sugaya tear classification system, at 16 weeks

post-surgery.

99

Table 2. Mean (SD) scores for the patient-reported outcome (PRO) and isokinetic

maximal strength measures (at an angular velocity of 60°/s) employed, for patients with

intact (Grade 1) and partial (Grade 2 and 3) supraspinatus tendon re-tears. Independent

sample t-test comparisons are provided between groups (p values).

Variable

Sugaya Classification

Group Comparison

Grade

1

(n=21)

Grade

2

(n=23)

Grade

3

(n=14)

Grade 1 v 2

Grade 1 v 3

Grade 2 v 3

OSS 38.9

(6.4)

39.2

(5.1)

40.7

(8.0)

-0.191

(.849)

-0.723

(.475)

-0.645

(.524)

VAS 1.5

(1.4)

1.3

(1.3)

1.5

(2.0)

0.485

(.631)

0.115

(.909)

-0.235

(.815)

QuickDASH 21.9

(12.4) 17.5

(11.9) 18.3

(17.8)

1.137 (.263)

0.687 (.497)

-0.149 (.882)

SF-12 (PCS) 42.1 (8.1)

42.7 (5.8)

44.0 (9.3)

-

0.240

(.812)

-0.618 (.541)

-0.514 (.611)

SF-12 (MCS) 53.7

(11.6)

55.3

(7.7)

54.9

(9.6)

-

0.508 (.615)

-0.322

(.749)

0.109

(.914)

Arm Flexion Peak Torque

(Nm)

77.1

(22.6)

76.5

(15.4)

74.9

(18.9)

0.099

(.922)

0.297

(.768)

0.282

(.780)

Arm Flexion Total Work (J) 61.7

(26.5)

63.2

(21.3)

62.0

(26.2)

-

0.213 (.832)

-0.036

(.971)

0.153

(.879)

External Humeral Rotation

Peak Torque (Nm)

75.8

(21.2)

71.1

(16.8)

82.4

(21.8)

0.820

(.417)

-0.896

(.377)

-1.777

(.084)

External Humeral Rotation

Total Work (J)

68.2

(49.5)

53.7

(22.7)

66.2

(26.0)

1.266

(.212)

0.135

(.893)

-1.543

(.132)

OSS = Oxford Shoulder Score; VAS = Visual Analogue Pain Scale for pain; QuickDASH = Quick

Disability of the Arm, Shoulder and Hand; SF-12 = 12-item Short Form Health survey; PCS = Physical

Component Subscale; MCS = Mental Component Subscale.

Descriptive statistics for the intact (Grade 1) and partial re-tear (Grade 2 and 3 pooled)

groups are shown in Table 3. At 16 weeks post surgery, mean scores for strength and

function for the intact repair group compared to the partial re-tear group were not

100

significant. Discriminant analysis results in Table 4 revealed the QuickDASH alone

produced a 97% true positive rate for predicting partial re-tears, but also a 90% false

positive rate. The ability to discriminate between groups was enhanced with up to five

variables entered; however, only 87% of the partial re-tear group, and 36% of the intact

repair group were correctly classified.

Table 3. Descriptive statistics (mean ± SD) for patients with intact repairs (Grade 1) and

partial (Grade 2 and 3 pooled) supraspinatus tendon re-tears.

Variable Intact repair

Group (n=21)

Partial re-tear

Group (n=37) Total

OSS 38.9 ± 6.4 40.1 ± 6.3 39.6 ± 6.3

VAS 1.5 ± 1.4 1.4 ± 1.6 1.4 ± 1.5

QuickDASH 20.9 ± 12.4 18.1 ± 14.6 19.2 ± 13.7

External Humeral Rotation

Peak Torque (Nm) 76.9 ± 20.6 75.0 ± 19.9 75.7 ± 20.0

Arm Flexion Peak Torque

(Nm) 77.3 ± 22.0 76.0 ± 17.0 76.5 ± 18.9

Time to Peak Torque for

External Humeral Rotation

(s)

0.54 ± 0.45 0.60 ± 0.42 0.58 ± 0.43

OSS = Oxford Shoulder Score; VAS = Visual Analogue Pain Scale for pain; QuickDASH = Quick

Disability of the Arm, Shoulder and Hand.

101

Table 4. Discriminant analysis for variables predicting an intact repair (n=21, Grade 1 Sugaya Classification) or partial re-tears (n=37, Grade 2 and 3

Sugaya Classification).

Prediction variables entered 2

Statistic 1

Number Classified (%)

Actual Group Membership

Predicted Group Membership

EV CC WL Sig Intact repair Partial re-tear

A. QuickDASH 0.011 0.104 0.989 0.465 Intact repair 2 (10%) 19 (90%)

Partial re-tear 1 (3%) 30 (97%)

B. QuickDASH, ER Pk Tq 0.034 1.82 0.967 0.429 Intact repair 4 (18%) 18 (82%)

Partial re-tear 3 (10%) 28 (90%)

C. QuickDASH, ER Pk Tq, OSS 0.039 0.194 0.962 0.594 Intact repair 5 (23%) 17 (77%)

Partial re-tear 4 (13%) 27 (87%)

D. QuickDASH, ER Pk Tq, OSS, TPT ER 0.045 0.207 0.957 0.717 Intact repair 7 (32%) 15 (68%)

Partial re-tear 4 (13%) 26 (87%)

E. QuickDASH, ER Pk Tq, OSS, TPT ER, AF Pk Tq 0.045 0.207 0.957 0.837 Intact repair 8 (36%) 14 (64%)

Partial re-tear 4 (13%) 26 (87%)

1 EV = eigenvalue, CC = canonical correlation, WL = Wilks’ lambda, Sig = prediction significance of the discriminant function.

2 ER Pk Tq = Peak torque for humeral external rotation at 60⁰ /s; AF Pk Tq = Peak torque for arm flexion at 60⁰ /s; TPT ER = time to peak torque in humeral external rotation.

102

DISCUSSION

The use of post-operative MRI and/or US to evaluate the outcome of rotator cuff surgery

can be costly and time consuming. Several researchers have attempted to determine

whether the healing progress of a conservatively treated rotator cuff tendon tear can be

predicted using common, clinical shoulder assessments, with little success (Ainsworth &

Lewis, 2007; Hughes, et al., 2008; Murrell & Walton, 2001). This study aimed to: a)

investigate if differences in common shoulder PRO measures and isokinetic strength tests

could be observed between patients with intact or partial re-tears, classified by MRI, at

16 weeks after rotator cuff repair surgery, and; (b) determine if early post-surgical tendon

healing could be predicted using these PRO measures and strength tests alone, without

the need for radiological assessment.

This study found no significant difference in the employed shoulder PRO measures, nor

isokinetic strength evaluation, between patient groups stratified by the Sugaya MRI

classification system (Grades 1, 2 or 3) for rotator cuff tears at 16 weeks post-surgery.

Studies have investigated the diagnostic accuracy of clinical tests for rotator cuff

pathology (Hegedus, et al., 2008; Hegedus, et al., 2012; Hughes, et al., 2008), and

concluded that most tests are inaccurate and cannot be recommended for clinical

diagnosis alone. This may well be the case post-operatively, and more robust testing in

this area is required. When employing radiology to investigate rotator cuff pathology, it

has been reported in a number of studies that both US and MRI are accurate in the

detection of rotator cuff lesions (Kluger, et al., 2003; Teefey, et al., 2004). Codsi, et al.

(2014) suggested US was comparable to MRI when evaluating rotator cuff integrity, and

that post-surgical US results should be compared with MRI results for a period of time

before relying solely on US for diagnosis. However, Ardic, et al. (2006) reported MRI

103

to be superior to US, while Goldberg, et al. (2003) reported that US was not a reliable

tool for diagnosing full thickness rotator cuff tears. Sonnabend, et al. (1997) reported on

the accuracy of US in diagnosing full thickness rotator cuff tears and as a “useful adjunct”

in the diagnosis of partial tears; however, they also noted it was operator-dependent. For

these reasons, we chose to use MRI for confirmation of tendon healing.

The discriminant analysis showed the QuickDASH alone produced a 97% true positive

rate for predicting partial re-tears, but also a 90% false positive rate, revealing the test to

be sensitive but not specific. The addition of other shoulder PRO measures or isokinetic

strength evaluations did not greatly improve the predictive capability of the patient’s early

tendon repair outcome, and so we must conclude that combining such measures does not

give confidence in the diagnosis of partial re-tears. At this stage, we must conclude that

some form of radiological assessment (MRI or US) be used for this purpose. However,

it should also be noted that the concurrent use of shoulder-specific PRO measures and/or

strength evaluation remain important in guiding the rehabilitation process after rotator

cuff repair, as well as the patient’s specific return to work or sport. Furthermore, while

Nho, et al. (2009) reported that 100% of re-tears occurred in the first three months post-

surgery, Kluger, et al. (2009) reported that most early post-operative re-tears appear to be

a failure to heal, and that repair site integrity at six months was a predictor of 7-year

clinical outcome. Therefore, based on our results and pre-existing literature, if a patient

has a QuickDASH score that is greater (i.e. worse) than the mean value we report at 16

weeks post-surgery, then it may be likely they have incomplete healing or partial re-

tearing of the tendon. This would then warrant adjunct radiological assessment. While

these results suggest that PRO measures and shoulder strength in a patient with a

completely intact repair is equivalent to that of a partial re-tear, at least at 16 weeks post-

surgery, the natural history in ongoing high demand work or sport is for partial tears to

104

deteriorate. Therefore, subsequent imaging in these patients may allow for a decelerated

rehabilitation program or vocational counselling on restricted work duties and prognosis.

This study has some acknowledged inherent limitations. Firstly, the patient follow-up

was limited to 16 weeks. Research by Sonnabend, et al. (1997) has previously

demonstrated that a significant portion of Sharpey fibres have reconstituted and matured

at the tendon repair site by 3-4 months. Furthermore, accurate classification of rotator

cuff tendon healing has been suggested to be importance at this time as it affects the

rehabilitation strategy, especially for patients who intend to return to employment in

physical work or to physically demanding sports. However, if MRI evaluations were to

be repeated at a later time (such as 12 months) it is possible that more structural tearing

may be observed, contributing to more pain and diminished function. While the primary

aim of this study was to assess early post-operative tendon healing, future research may

include a longer-term follow-up.

A second limitation may result from the primary RCT, whereby half of this patient cohort

received two PRP injections post-surgery. However, as reported previously there were

no differences observed between the PRP and control groups at 16 weeks post surgery in

any of the assessments employed, including the shoulder-specific PRO measures,

shoulder range of motion, isokinetic strength evaluation and MRI-based assessment

(Wang, et al., 2015). This result created the opportunity to combine the original groups

(PRP or control) into one cohort for this analysis.

Thirdly, we employed PRO instruments used routinely through our clinical practice and

research, and we appreciate other shoulder-specific scores are available. It is possible

that differences (or an improved predictive capacity) may be observed in other clinical

105

and functional shoulder evaluations. Fourthly, strength tests also have some inherent

limitations as they are unable to differentiate between true muscular weakness and pain-

related weakness (Bigoni, et al., 2009). The results of the isokinetic strength tests also

rely upon a maximal effort being made by the patient. While clear, standardized

instructions and verbal encouragement were provided to all participants, it must be

acknowledged that this was the first time many of the patients would have maximally

stressed their operated limb since surgery, and some may have been hesitant to exert

maximal effort. Protocols for future research may require a familiarisation session prior

to the testing session. Furthermore, Bigoni, et al. (2009) has previously reported that

isokinetic strength testing is a powerful tool for evaluating strength following rotator cuff

surgery, so it may be that alternate testing protocols, incorporating shoulder abduction,

may more accurately discriminate between groups.

CONCLUSION

This study found no significant difference in the employed shoulder PRO measures, nor

isokinetic strength evaluation, between patient groups stratified by the Sugaya MRI

classification system for rotator cuff tears at 16 weeks post-surgery. Furthermore, the

presence of an intact repair or partial re-tear after rotator cuff surgery could not be

accurately predicted by these clinical and functional shoulder evaluations. Our results

suggest that correct classification of tendon healing in the early stage following rotator

cuff surgery must involve medical imaging. This will give confidence in patient

management of appropriate return-to-work and/or sport rehabilitation programs.

Reliance on PRO measures and/or functional scores alone to make an accurate assessment

is not supported by our data.

106

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Z. R. (2006). Shoulder impingement syndrome: relationships between clinical,

functional, and radiologic findings. Am J Phys Med Rehabil, 85(1), 53-60.

Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing

influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the

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G. (2005). Arthroscopic repair of full-thickness tears of the supraspinatus: does

the tendon really heal? Journal of Bone and Joint Surgery (Am), 87(6), 1229-

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Cheung, E. V., Silverio, L., & Sperling, J. W. (2010). strategies of biologic augmentation

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1(2), 96-104.

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38(4), 664-671.

Codsi, M. J., Rodeo, S. A., Scalise, J. J., Moorehead, T. M., & Ma, C. B. (2014).

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Dawson, J., Hill, G., Fitzpatrick, R., & Carr, A. (2001). The benefits of using patient-

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159-170.

Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term

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imaging analysis. Am J Sports Med, 39(10), 2071-2081.

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J. D. (2009). Prospective analysis of arthroscopic rotator cuff repair: subgroup

analysis. J Shoulder Elbow Surg, 18(5), 697-704.

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111

CHAPTER 5

SUMMARY, CONCLUSIONS AND RECOMMENDATIONS

The main purpose of this thesis was to investigate the effect of PRP injections following

rotator cuff repair surgery on early tendon healing and functional recovery. Current

research in the area of PRP augmentation following rotator cuff repair surgery remains

controversial. This is complicated by a lack of standardisation of PRP products,

differences in timing of delivery protocols, and optimal platelet concentrations. The

research investigated if delayed and repeated PRP injections would accelerate the early

structural healing following surgical repair of supraspinatus tendon as well as improving

patient function and strength (see Paper 1 in Chapter 3). In addition, the research also

aimed to determine if early post-surgery tendon healing could be predicted independently

of an MRI scan, using a combination of patient-reported functional and quality of life

questionnaires and isokinetic strength data (see Paper 2 in Chapter 4).

In Paper 1 a prospective, randomised controlled study design was used to investigate

radiological and functional assessment up to and including 16 weeks post rotator cuff

repair surgery in 60 patients (30 treatment, 30 control group). Patients randomly assigned

to the treatment group received two PRP injections under guided-US (at 7 and 14 days

post-surgery), while the control group received no placebo injection. MRI was used to

assess the structural tendon healing at 4 months, with rotator cuff appearances graded

according to the Sugaya classification. Functional assessment was undertaken pre-

surgery, and at 6, 12 and 16 weeks post-surgery. These included the OSS, QuickDASH,

VAS and SF-12 inventories. Isokinetic strength and ROM were also measured at 16

weeks post-surgery.

112

No significant difference was observed in structural healing of the tendon at 16 weeks

between the treatment and control groups, a finding that did not support our first

hypothesis. Functional outcome scores improved in all patients following surgery - at 12

and 16 weeks the OSS, VAS and SF-12 improved significantly from pre-surgery.

However, no significant difference was observed in the functional scores between the

treatment and control groups at any of the post-surgery time points. In addition, no

significant difference was observed for strength or ROM between the groups at 16 weeks.

This finding did not support the second hypothesis of Paper 1, that PRP would improve

early function and strength compared to the control group.

Participants from Paper 1 were able to be pooled for analysis in Paper 2 since no

significant differences were observed between the treatment and control groups in MRI

classification, patient reported functional scores and isokinetic strength (Wang et al.,

2015). Paper 2 aimed to determine if it were possible to predict the success of the tendon

repair at 16 weeks post-surgery without the costly and time-consuming requirement of

MRI. Previous research had shown that Sharpey fibres begin to reconstitute at 3 months,

with maturation seen at 4 months. Furthermore, it was reported that the majority of

recurrent tears occurred in the first 3-4 months (Kluger, et al., 2011; Miller, et al., 2011;

Nho, et al., 2009); highlighting this early tendon healing phase as being critical for long-

term success. Prediction of tendon healing at this early stage using low cost strength and

functional outcomes could prove useful, as this could influence early post-surgical

management as well as the patient’s individual return to work and/or sport strategy. Paper

2 sought to determine if differences in patient shoulder function and strength could be

detected for those patients with partial tendon re-tears compared to those with intact

repairs 16 weeks post surgery, regardless of their initial PRP group allocation. The second

aim of Paper 2 was to determine if patients with partial re-tears and incomplete healing

113

could be predicted based on function and strength alone, without the need for early post-

surgery imaging.

No significant differences were observed in patient shoulder function or isokinetic

strength at 16 weeks post rotator cuff repair between those with an intact repair and those

with a partial tendon re-tear; this finding did not support the first hypothesis of Paper 2.

Discriminant analysis showed that while the QuickDASH produced a 97% true positive

rate for predicting partial re-tears, it also produced a 90% false positive rate. With the

addition of up to five variables entered, the ability to discriminate between intact repairs

and partial re-tears was enhanced; only 87% of the partial re-tear group and 36% of the

intact repair group were correctly classified, thus not supporting the second hypothesis.

The results of this study suggest that correct classification of early tendon healing

following rotator cuff repair surgery must involve medical imaging.

A number of limitations should be acknowledged within these studies. Firstly, the patient

follow-up period was limited to 16 weeks. Research has previously demonstrated that a

significant proportion of Sharpey fibres have reconstituted and matured at the tendon-

repair site by 3-4 months (Sonnabend, et al., 2010). Also, accurate classification of

rotator cuff tendon healing has been suggested to be important at 16 weeks, as it affects

the rehabilitation strategy, especially for those returning to physically demanding

employment or sports. However, we acknowledge that should MRI evaluations be

repeated at a later time, more structural tearing may be observed, which would contribute

to more pain and decreased function. While this study focused on the early assessment

of tendon healing, future research should include a longer follow-up period.

114

Patients were not blinded as to their grouping in Paper 1, as it was considered impractical

to having patients complete two placebo injections. Patient knowledge of their

intervention group may cause a positive bias among members of the PRP group, however,

both groups were equivalent in terms of the study outcomes. An independent,

experienced radiologist who was blinded to the participants’ group allocation, and who

was not involved in the PRP injections, performed all MRI evaluations.

The PRP product used in Paper 1 does not achieve the high concentration of platelets that

some other commercially available PRP products report. However, it has been suggested

that markedly elevated supra physiological levels of platelets and growth factors may not

be of benefit, and could in fact be detrimental to tendon healing (Barber, et al., 2011;

Sundman, et al., 2011). Optimal tendon healing requires the appropriate concentration of

growth factors, as well as appropriate timing of delivery in the tendon-healing cascade in

order to be maximally effective. This highlights the need for a standardised protocol to

be developed for future research.

The functional scores used in both papers are used routinely in clinical practice and

research, however, we appreciate there are other shoulder-specific scores available, and

it is possible that differences, or an improved prediction capacity, may be observed with

other clinical shoulder evaluations. Strength tests also have some inherent limitations, as

they are unable to differentiate between true muscular weakness and pain-related

weakness (Bigoni, et al., 2009). The results of the isokinetic strength tests also rely on a

maximal effort being made by the patient. Whilst clear, standardised instructions and

verbal encouragement was provided, it is acknowledged that some patients may have

been hesitant to exert maximal strength. The tests undertaken at 16 weeks post-surgery

were the first time most patients would have maximally exerted their shoulder since their

115

operation. Future research protocols might require a familiarisation session prior to the

testing session. Furthermore, isokinetic strength testing has been reported to be a

powerful tool for evaluating strength following rotator cuff surgery (Bigoni, et al., 2009),

so it may be that alternate testing protocols, incorporating shoulder abduction could be

considered in future research. We did not include shoulder abduction in our protocol as

it was considered too early post-surgery to directly stress the repaired tendon.

A perceived limitation of Paper 2 may result from the primary RCT (Paper 1), where half

of the cohort received two PRP injections post-surgery. However, as previously

reported, there were no observed differences in any of the outcome measures between the

PRP and control groups at 16 weeks post-surgery (Wang, et al., 2015). This result created

the opportunity for us to combine the original groups into one cohort for this analysis.

This is the first study to our knowledge that evaluated the efficacy of a post-surgical PRP

delivery protocol to improve tendon healing and functional outcomes following rotator

cuff repair. While this research reiterated that PRP injections post rotator cuff surgery

are safe, we concluded that PRP does not accelerate early tendon healing nor improve

functional or strength outcomes. Future research might include randomised controlled

trials of other commercially available PRP products with alternative delivery vehicles and

dosing regimes, and with longer post-surgery follow-up.

116

REFERENCES

Barber, A., Hrnack, S. A., Snyder, S. J., & Hapa, O. (2011). Rotator cuff repair healing

influenced by platelet-rich Plasma construct augmentation. Arthroscopy: the

Journal of Arthroscopic and Related Surgery, 27(8), 1029-1035.

Bigoni, M., Gorla, M., Guerrasio, S., Brignoli, A., Cossio, A., Grillo, P., et al. (2009).

Shoulder evaluation with isokinetic strength testing after arthroscopic rotator cuff

repairs. Journal of Shoulder and Elbow Surgery, 18, 178.

Kluger, R., Bock, P., Mittlbock, M., Krampla, W., & Engel, A. (2011). Long-term

survivorship of rotator cuff repairs using ultrasound and magnetic resonance

imaging analysis. Am J Sports Med, 39(10), 2071-2081.

Miller, B. S., Downie, B. K., Kohen, R. B., Kijek, T., Lesniak, B., Jacobson, J. A., et al.

(2011). When do rotator cuff repairs fail? Serial ultrasound examination after

arthroscopic repair of large and massive rotator cuff tears. Am J Sports Med,

39(10), 2064-2070.

Nho, S. J., Shindle, M. K., Adler, R. S., Warren, R. F., Altchek, D. W., & MacGillivray,

J. D. (2009). Prospective analysis of arthroscopic rotator cuff repair: subgroup

analysis. J Shoulder Elbow Surg, 18(5), 697-704.

Sonnabend, D. H., Howlett, C. R., & Young, A. A. (2010). Histological evaluation of

repair of the rotator cuff in a primate model. J Bone Joint Surg Br, 92(4), 586-

594.

Sundman, E. A., Cole, B. J., & Fortier, L. A. (2011). Growth factor and catabolic cytokine

concentrations are influenced by the cellular composition of platelet-rich plasma.

Am J Sports Med, 39(10), 2135-2140.

117

Wang, A., McCann, P., Colliver, J., Koh, E., Ackland, T., Joss, B., et al. (2015). Do

Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing

and Functional Recovery After Arthroscopic Supraspinatus Repair? A

Randomized Controlled Trial. Am J Sports Med (in press).

APPENDIX 1

UNIVERSITY OF WESTERN AUSTRALIA NOTIFICATION OF RESEARCH

PROPOSAL APPROVAL

Ref 20290046

15 June 2011

Miss J Colliver132 A York StSubiaco WA 6008

Dear Miss Colliver

RESEARCH PROPOSAL - MASTER OF SCIENCE - RESEARCH

I am pleased to inform you that the Board of the Graduate Research School has considered your Research Proposal and, it is accepted without the requirement for changes or clarification.

In addition your research proposal is accepted subject to:Please note that approval is required from the appropriate UWA committee notwithstanding that the project might have been approved by an external agency (e.g hospital) or another university.

Your proposal indicates that approval from UWA Human Research Ethics Committee, iscurrently being sought in relation to your research. Until you provide us with notification that you have approval, or otherwise, from the UWA Human Research Ethics Committee, the status of your research proposal will be marked as provisory.

The supervisors for your research are recorded as being -Coordinating supervisor: Winthrop Professor T Ackland (40%)Co supervisor: Prof A Wang (40%)Co supervisor: Adj/A/Prof B Joss (20%)

On behalf of the Board please accept my best wishes for the remainder of your candidature.

Yours sincerely

Barbara TelferAdministrative Officer, Candidature

cc Professor A Gordon (Graduate Research Coordinator)Winthrop Professor T Ackland

SCHOOL OF SPORT SCIENCE, EXERCISE AND HEALTH

Students please note:* Please activate your UWA student email account and check it regularly. http://www.its.uwa.edu.au/student/email

* You can check your milestones on Student Connect http://www.studentadmin.uwa.edu.au/welcome/student_connect

Graduate Research SchoolHackett Hall - M35835 Stirling Highway,

CRAWLEY WA 6009+61 8 6488 7299 Phone

+61 8 6488 1919 Faxbarbara.telfer@uwa.edu.au Email

http://www.postgraduate.uwa.edu.auWebsiteCRICOS Provider No. 00126G

Click on the "Course and Unit" link in the list on the left side of the page, and you should see your current and previous courses displayed. For the course in which you are enrolled currently, click on the "Milestones" link under the course details. You will see your list of milestones and the current status of each. There is a description of what each milestone status means. If you believe that there is an error in the list, please contact barbara.telfer@uwa.edu.au . Please note that your re-enrolment each year is dependent on all your milestones being up to date.

APPENDIX 2

UNIVERSITY OF WESTERN AUSTRALIA NOTIFICATION OF ETHICS

APPROVAL

 

 

Winthrop Professor Timothy AcklandSport Science, Exercise & Health (School of)MBDP: M408

Dear Professor Ackland

HUMAN RESEARCH ETHICS OFFICE – RECOGNITION OF ETHICS APPROVAL FROM ANOTHER HUMAN RESEARCH ETHICS COMMITTEE

 

Research Ethics and Biosafety OfficeResearch Services

Phone:Fax:email:MBDP:  

+61 8 6488 3703+61 8 6488 8775hreo-research@uwa.edu.au M459

Our Ref: RA/4/1/4872 24 June 2011

Project:  Does autologous conditioned plasma enhance rotator cuff healing after surgery?

Thank you for your correspondence enclosing the necessary documents to facilitate recognition of the ethics approval for the above project granted by an external Human Research Ethics Committee (HREC) registered with the National Health and Medical Research Council (NHMRC).

It is noted that you have ethics approval from South Metropolitan, approval number 11/75.

The UWA students and researchers identified as working on this project are:

UWA Researchers:  

Student(s):   Jessica Anne Colliver

Although The University of Western Australia reserves the right to subject any research involving its staff and students to its own ethics review process, in this case, the Human Research Ethics Office has recognised the existing approval of the external HREC. The project is exempt from ethics review at UWA and the involvement of the above-listed researchers has been authorised. Any conditions for the recognition of the external HREC's existing approval are listed below:

Special Conditions

None specified

You are reminded that it will be the responsibility of the approving HREC to ensure compliance with all ethics requirements and to monitor and report on the project. However, should any relevant ethics issues arise during the course of the project; you should inform the Human Research Ethics Office of The University of Western Australia.

If you have any queries, please do not hesitate to contact Kate Kirk on (08) 6488 3703.

Please ensure that you quote the file reference – RA/4/1/4872  – and the associated project title in all future correspondence.

Yours sincerely

Name Faculty / School RoleWinthrop Professor Timothy Robert Ackland   Sport Science, Exercise & Health (School of)   Chief Investigator

Clinical Associate Professor Allan Wenli Wang   Sport Science, Exercise & Health (School of)   Co-Inv

Dr Brendan Keith Joss   Sport Science, Exercise & Health (School of)   Co-Inv

Peter JohnstoneManagerHuman Research Ethics Committee

 

APPENDIX 3

SOUTH METROPOLITAN AREA HEALTH SERVICE NOTIFICATION OF

ETHICS APPROVAL

APPENDIX 4

STUDY INFORMATION SHEET

Information Sheet

Does autologous conditioned plasma enhance rotator cuff healing after surgery?

TO BE USED IN CONJUNCTION WITH THE CONSENT FORM

Chief Investigator Dr Allan Wang, Consultant Orthopaedic Surgeon

and Clinical Professor, UWA awang@westnet.com.au Co Investigators Dr Eamon Koh, Consultant Radiologist, Fremantle Hospital Ms Jessica Colliver, Exercise Physiologist and Study Coordinator

Prof Timothy Ackland, Winthrop Professor, UWA Dr Brendan Joss, Clinic Director, HFRC Prof Ming Hao Zheng, Winthrop Professor, UWA

We invite you to participate in this research study, supported by Arthrex Medical Company, concerning patients who have undergone surgery for a rotator cuff tear, and comparing the efficacy of post-surgery injections of autologous conditioned plasma (ACP) versus usual care. This study has been approved by the Human Research Ethics Committees of the South Metropolitan Area Health Service and the University of Western Australia. If you decide to take part in this study, it is important that you understand the purpose of the study and the procedures you will be asked to undergo. Please read the following pages, which will provide you with information about the treatments involved and the potential benefits, discomforts and precautions of the study. If you are currently involved in a research study you will be ineligible to participate in this one. What is the purpose of this research? Your family doctor has referred you for treatment of a rotator cuff tendon tear in your shoulder, which requires surgical repair. Unfortunately, surgical repair is sometimes unsuccessful, due to retraction of the torn tendon or poor tissue quality and occasionally following surgery the tendon may fail to heal well, or re-tear and further surgery is sometimes required. To combat these problems your surgeon has been investigating other options. There is increasing evidence that tendon healing is improved by ACP injection. Plasma is the component of blood with the red blood cells removed, and containing platelets and proteins which have been shown to improve tendon healing and function with Achilles tendon injuries, tennis elbow tendon damage and shoulder rotator cuff tendon tears1,2,3. The plasma is obtained by taking 10 ml of your own blood (“autologous plasma”) and spinning it in a centrifuge for 5 minutes just prior to injection.

School of Sport Science, Exercise and Health M408, The University of Western Australia 35 Stirling Highway Crawley, Western Australia 6009 Phone +61 8 6488 2361 Fax +61 8 6488 1039 Web www.sseh.uwa.edu.au CRICOS Provider Code: 00126G Parkway (Entrance No 3) Nedlands

The purpose of this research study is to investigate the benefit of autologous plasma injections for patients following rotator cuff tendon repair surgery. Duration of study If you choose to participate in this study you will be evaluated at regular intervals by Prof. Wang and the research team for 4 months after surgery. Clinical procedure Your shoulder will be evaluated with radiological studies including ultrasound or a MRI scan to assess the extent of rotator cuff damage. The standard surgical procedure to arthroscopically decompress then repair the rotator cuff tendon will be performed. After discharge from hospital you will be reviewed one week after surgery by Prof. Wang, who will then discuss this research study and if you agree to participate, we will enter you into the program. At this time, you will choose an envelope at random containing notification regarding which arm of the study you will enter (ie. the “treatment group” or the “control group”). The study coordinator, Miss Jess Colliver will then schedule you for post-operative care and assessment sessions. Patients assigned to the treatment group will be seen by Dr Eamon Koh, consultant radiologist at Fremantle Hospital. Patients in this group will have 10 ml (approximately two teaspoons) of their own blood taken, spun down, calcium chloride is added, and then 1-2 ml of this autologous conditioned plasma (ACP) is injected under ultrasound guidance into the rotator cuff repair site. Dr Koh will repeat this injection two weeks later. Regardless of whether you are an ACP treatment patient or control patient, your post- operative care and assessments will be identical. Pre- and post-surgery tests All patients who are referred to Prof. Wang for surgical treatment of a rotator cuff repair have a standard history, examination and radiology tests performed routinely. In addition, assessments of pain and function of the shoulder musculature will have been performed. If you agree to participate in this trial, we will use these data as your “pre-surgery” baseline scores. The post-surgical management is identical between Treatment and Control groups. Post-operative questionnaires are administered at 6, 12 and 16 weeks post-surgery (in Prof. Wang’s rooms). A routine post-operative MRI scan will be performed at 16 weeks to check the tendon repair site. Questionnaires administered to both groups include the Quick Disabilities of the Arm, Shoulder and Hand (QDASH), Oxford Shoulder Score (OSS), and Short Form-12 (SF-12). These questionnaires ask you to report on your shoulder pain, symptoms and how it affects your activities of daily living. At the time of the two injections we will also ask you for information regarding the levels of pain in your shoulder. Strength and range of motion testing post-surgery (at 16 weeks) is performed under the supervision of Miss Jessica Colliver who is an accredited Exercise Physiologist, at the UWA School of Sport Science, Exercise & Health in Crawley. The strength tests are performed within your level of tolerance to minimise any risk of injury or discomfort. Post-operative strength and ROM testing will only be performed once you have been cleared by Prof. Wang at the post-surgery clinical examination.

Testing time points: Measures Pre-op 6 weeks

post-op

12 weeks

post-op

16 weeks

post-op

MRI !

Strength !

ROM !

VAS (pain) ! ! ! !

QuickDASH ! ! ! !

OSS ! ! ! !

SF-12 ! ! ! !

What happens if I choose not to participate in this study? This will not affect your medical treatment from Prof. Wang. Your routine post-surgical rehabilitation and follow up will still go ahead as planned. What are the possible benefits for me to participate in this study? In both Treatment and Control groups, patients will receive a more in depth evaluation of the shoulder, before and after surgery by the research team, compared to patients not participating in this study. If you are allocated to the ACP treatment group, your outcome following surgery may or may not be better than the control group. This study will determine if there are significant positive benefits of ACP treatment. Previous studies of this type of injection have suggested less post-surgical pain4, earlier return to function3, and possibly lower rates of infection5. What are the possible side effects and risks of participating in this study? Autologous plasma injection to potentially enhance the outcome of tendon repair surgery is relatively new technology. Recent, similar studies have shown no adverse effects from platelet rich plasma injections3,4,5. However, there are general risks of surgery and anaesthesia for both participants and non-participants in this research study. There is a possible, minor increased risk from the ACP injection, including infection and pain after surgery. In the event of any complications in either the Treatment or Control group, all necessary medical care will be provided. Your participation in this study does not prejudice the right to compensation, which you may have under Statute or Common Law. The post-surgery MRI scans, which are performed to evaluate the healing of the rotator cuff tendon, may be claustrophobic for some patients. Will my personal information be kept confidential? Yes, your personal medical details will be kept private and confidential, and accessible only by the study Investigators. However, authorisation may be given to the hospital or Human Research Ethics Committee to verify the study procedures and conduct. The results of this research may be made available to other professionals at medical meetings or publications in medical journals. However, no personal identifying data will be used. By taking part in this study, you agree to not restrict the use of this de-identified data. Voluntary participation and withdrawal from the study Participation in this study is voluntary. If you choose not to participate, Prof. Wang will continue to provide the standard treatment for your shoulder condition. You may also withdraw from this study at any time, for whatever reason. Such withdrawal will not in any

way influence decisions regarding future standard or conventional medical treatment you may require. Further information If you have any questions about the study please contact the study coordinator, Ms Jessica Colliver on 0488 367 626, or by email to jessicacolliver@gmail.com. References: 1. Kon et al. Platelet Rich Plasma: A new clinical application: A pilot study for treatment of jumpers.

Knee Injury 2009 40: 598-603 2. Mishra & Pavelko Treatment of chronic elbow tendonosis with buffered platelet rich plasma. AJSM

2006 34: 1774-1778 3. Peerbooms et al. Positive effect of an autologous platelet concentrate in lateral epicondylitis in a

double blind randomised controlled trial. AJSM 2010 38: 255-263 4. Randelli et al. Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study.

Disability and Rehabilitation 2008 30(20): 1584 5. Randelli et al. Platelet rich plasma in arthroscopic rotator cuff repair. A prospective RCT JSES (in

press)

Approval to conduct this research has been provided by the South Metropolitan Area Health Service and The University of Western Australia, in accordance with their ethics review and approval procedures. Any person considering participation in this research project, or agreeing to participate, may raise any questions or issues with the researchers at any time. If you have any complaints or concerns about the way in which the study is being conducted, you may contact the Chairman of the South Metropolitan Area Health Service Human Research Ethics Committee on 9431 2929. Alternatively, you may contact the Human Research Ethics Office at The University of Western Australia on (08) 6488 3703 or by emailing to hreo-esearch@uwa.edu.au.

Prof. Allan Wang Principal Investigator

Ms Jessica Colliver AEP & Study Coordinator

Dr Eamon Koh Consultant Radiologist

APPENDIX 5

PATIENT CONSENT FORM

Consent Form

Does autologous conditioned plasma enhance rotator cuff healing after surgery?

TO BE USED IN CONJUNCTION WITH THE INFORMATION SHEET

Participant’s Name:__________________________ Date of Birth:_________________ 1. I agree entirely voluntarily to take part in this study, supported by Arthrex Medical

Company. I am 18 years of age or over.

2. I have been given a full explanation of the purpose of this study, of the procedures involved and of what will be expected of me. The doctor has explained the possible problems that might arise as a result of my participation in this study.

3. I agree to inform the supervising doctor of any unexpected or unusual symptoms I

may experience. 4. I understand that I am entirely free to withdraw from the study at any time and that

this withdrawal will not in any way affect my future treatment or medical management. 5. I understand that the information in my medical records is essential to evaluate the

results of this study. I agree to the release of this information to the research staff and the clinical trial staff on the understanding that it will be treated confidentially.

6. I understand that I will not be referred to by name in any report concerning this study.

In turn, I cannot restrict in any way the use of the results that arise from this study. 7. I have been given and read a copy of this Consent Form and Information Sheet.

Participant Signature: _______________________________ Date _______________

Signature of Principal Investigator: _____________________ Date _______________

Approval to conduct this research has been provided by the South Metropolitan Area Health Service and The University of Western Australia, in accordance with their ethics review and approval procedures. Any person considering participation in this research project, or agreeing to participate, may raise any questions or issues with the researchers at any time. In addition, any person not satisfied with the response of researchers may raise ethics issues or concerns, and may make any complaints about this research project by contacting the Human Research Ethics Office at The University of Western Australia on (08) 6488 3703 or by emailing to hreo-esearch@uwa.edu.au

School of Sport Science, Exercise and Health M408, The University of Western Australia 35 Stirling Highway Crawley, Western Australia 6009 Phone +61 8 6488 2361 Fax +61 8 6488 1039 Web www.sseh.uwa.edu.au CRICOS Provider Code: 00126G Parkway (Entrance No 3) Nedlands

APPENDIX 6

VISUAL ANALOGUE SCALE (VAS) FOR PAIN

Visual  Analogue  Scale  (VAS)  

 

Please  rate  how  severe  the  pain  in  your  affected  shoulder  has  been  (in  the  past  7  days)  along  the  line  below.        

 

 

 

 

APPENDIX 7

OXFORD SHOULDER SCORE (OSS)

NAME:  __________________   DATE:  _________  Oxford  Shoulder  Score  

Please  circle  the  most  appropriate  answer  of  each  of  the  following  questions  for  your  affected  shoulder:  1.  How  would  you  describe  the  worst  pain  from  your  shoulder?  

Unbearable   Severe   Moderate   Mild   None    

2.  How  would  you  describe  the  pain  you  usually  get  from  your  shoulder?  

Unbearable   Severe   Moderate   Mild   None    

3.  How  much  has  the  pain  from  your  shoulder  interfered  with  your  work  (including  housework)?  

Totally   Greatly   Moderately   A  little  bit   Not  at  all    

4.  Have  you  been  troubled  by  pain  in  your  shoulder  in  bed  at  night?  

Every  night   Most  nights   Some  nights   Only  1  to  2  nights   No  nights    

5.  Have  you  had  any  trouble  dressing  yourself  because  of  your  shoulder?  

Impossible  to  do   Extreme  difficulty   Moderate  difficulty  

Very  little  difficulty  

No  difficulty  at  all  

 6. Have  you  had  any  trouble  getting  in  and  out  of  the  car  or  using  public  transport  because  of  your  

shoulder?  (Whichever  one  you  tend  to  use)  

Impossible  to  do   Extreme  difficulty   Moderate  difficulty  

Very  little  difficulty  

No  difficulty  at  all  

 7. Have  you  been  able  to  use  a  knife  and  fork  at  the  same  time?  

No.  Impossible   With  extreme  difficulty  

With  moderate  difficulty  

With  little  difficulty  

Yes,  easily  

 8. Could  you  do  the  household  shopping  on  your  own?  

No.  Impossible   With  extreme  difficulty  

With  moderate  difficulty  

With  little  difficulty  

Yes,  easily  

 9. Could  you  carry  a  tray  containing  a  plate  of  food  across  the  room?  

No.  Impossible   With  extreme  difficulty  

With  moderate  difficulty  

With  little  difficulty  

Yes,  easily  

 10. Could  you  brush/comb  your  hair  with  the  affected  arm?  

No.  Impossible   With  extreme  difficulty  

With  moderate  difficulty  

With  little  difficulty  

Yes,  easily  

 11. Could  you  hang  your  clothes  up  in  a  wardrobe  with  your  affected  arm?  

No.  Impossible   With  extreme  difficulty  

With  moderate  difficulty  

With  little  difficulty  

Yes,  easily  

 12. Have  you  been  able  to  wash  and  dry  yourself  under  both  arms?  

No.  Impossible   With  extreme  difficulty  

With  moderate  difficulty  

With  little  difficulty  

Yes,  easily  

APPENDIX 8

QUICK DEFORMITIES OF THE ARM, SHOULDER AND HAND (QUICKDASH)

OUTCOME MEASURE

NAME:  __________________   DATE:  ______  

Quick  DASH    This  questionnaire  asks  you  about  your  symptoms  as  well  as  your  ability  to  perform  certain  activities.    Please  answer  every  question,  based  on  you  condition  in  the  past  week,  by  circling  the  number  of  the  appropriate  answer.    If  you  did  not  have  the  opportunity  to  perform  a  certain  activity  in  the  past  week,  please  make  your  best  estimate  of  which  response  would  be  most  accurate.    It  doesn’t  matter  which  arm  you  use  to  perform  the  activity;  please  answer  based  on  your  ability  regardless  of  how  you  perform  the  task.       NO  DIFFICULTY   MILD  

DIFFICULTY  MODERATE  DIFFICULTY  

SEVERE  DIFFICULTY  

 UNABLE  

1. Open  a  tight  or  new  jar   1   2   3   4   5  2. Do  heavy  household  chores  (e.g.  

wash  floors)  1   2   3   4   5  

3. Carry  a  shopping  bag  or  briefcase   1   2   3   4   5  4. Wash  your  back   1   2   3   4   5  5. Use  a  knife  to  cut  food   1   2   3   4   5  6. Recreational  activities  in  which  you  

take  some  force  or  impact  through  your  arm,  shoulder  or  hand  (e.g.  golf,  hammering,  tennis  etc.)  

   1  

   2  

   3  

   4    

   5  

    NOT  AT  ALL   SLIGHTLY   MODERATELY   QUITE  A  BIT   EXTREMELY  

7. During  the  past  week,  to  what  extent  has  you  arm,  shoulder  or  hand  problem  interfered  with  your  normal  social  activities  with  friends,  family  or  groups?  

   1  

   2  

   3  

   4  

        5  

    NOT  AT  ALL  

LIMITED  SLIGHTLY  LIMITED  

MODERATELY  LIMITED  

VERY  LIMITED   UNABLE  

8. During  the  past  week,  were  you  limited  in  your  work  or  other  regular  daily  activities  as  a  result  of  you  arm,  shoulder  or  hand  problem?  

   1  

   2  

   3  

   4  

        5  

           Rate  the  severity  of  these  symptoms  in  the  past  week:    

NONE   MILD   MODERATE   SEVERE   EXTREME  

9. Arm,  shoulder  or  hand  pain   1   2   3   4   5  10.  Tingling  (pins  and  needles)in  your  

arm,  shoulder  or  hand  1   2   3   4   5  

           

  NO  DIFFICULTY   MILD  DIFFICULTY  

MODERATE  DIFFICULTY  

SEVERE  DIFFICULTY  

UNABLE  TO  SLEEP  

11.  During  the  past  week,  how  much  difficulty  have  you  had  sleeping  because  of  the  pain  in  your  arm,  shoulder  or  hand?  

 1  

 2  

 3  

 4  

 5    

     

WORK  MODULE  (optional):  The  following  questions  ask  about  the  impact  of  your  arm,  shoulder  or  hand  problem  on  your  ability  to  work  (including  homemaking  if  that  is  your  main  work  role).    Please  indicate  what  your  job  is:  _______________________________________________________       I  do  not  work.  (You  may  skip  this  section)    Please  circle  the  number  that  best  describes  your  physical  ability  in  the  past  week  at  work:    

Did  you  have  any  difficulty?   NO  DIFFICULTY  

MILD  DIFFICULTY  

MODERATE  DIFFICULTY  

SEVERE  DIFFICULTY  

 UNABLE  

1. Using  your  usual  technique  for  your  work?  

1   2   3   4   5  

2. Doing  your  usual  work  because  of  your  arm,  shoulder  or  hand  problem?  

 1  

 2  

 3  

 4  

 5  

3. Doing  your  work  as  well  as  you  would  like?  

1   2   3   4   5  

4. Spending  your  usual  amount  of  time  doing  your  work?  

1   2   3   4   5  

 SPORTS/PERFORMING  ARTS  MODULE  (optional)  The  following  questions  ask  about  the  impact  of  your  arm,  shoulder  or  hand  problem  on  playing  your  musical  instrument  or  sport  or  both.    If  you  play  more  than  one  sport  or  musical  instrument  (or  play  both),  please  answer  with  respect  to  that  activity  which  is  most  important  to  you.    Please  indicate  the  sport  or  instrument  that  is  most  important  to  you:  _________________________       I  do  not  play  a  sport  or  musical  instrument.  (You  may  skip  this  section)    Please  circle  the  number  that  best  describes  your  physical  ability  in  the  past  week  playing  sport  or  your  musical  instrument:    

Did  you  have  any  difficulty?   NO  DIFFICULTY  

MILD  DIFFICULTY  

MODERATE  DIFFICULTY  

SEVERE  DIFFICULTY  

 UNABLE  

1. Using  you  usual  technique  for  playing  sport  or  your  instrument?  

1   2   3   4   5  

2. Playing  sport  or  your  instrument  because  of  your  affected  arm,  shoulder  or  hand  problem?  

1   2   3   4   5  

3. Playing  sport  or  your  instrument  as  well  as  you  would  like?  

1   2   3   4   5  

4. Spending  your  usual  amount  of  time  practicing  or  playing  sport  or  your  musical  instrument?  

1   2   3   4   5  

APPENDIX 9

SHORT FORM-12 (SF-12) HEALTH SURVEY

NAME:  __________________   DATE:  ______      

Short  Form  –  12  (SF-­‐12)    This  questionnaire  asks  for  your  views  about  your  health.    This  information  will  help  keep  track  of  how  

you  feel  and  how  well  you  are  able  to  do  your  usual  activities.    Please  answer  every  question  by  

marking  one  box.    If  you  are  unsure  about  how  to  answer,  please  give  the  best  answer  you  can.  

1. In  general,  would  you  say  your  health  is:  

 

 

Excellent  

 

Very  good  

 

Good  

 

Fair  

 

Poor  

The  following  items  are  about  activities  you  might  do  during  a  typical  day.    Does  your  health  now  

limit  you  in  these  activities?  If  limited,  how  much?  

  Yes,  limited  a  lot   Yes,  limited  a  

little  

No,  not  

limited  at  all  

2. Moderate  activities  such  as  moving  a  

table,  pushing  a  vacuum  cleaner  ,  

bowling  or  playing  golf  

 

     

3. Climbing  several  flights  of  stairs        

 

During  the  past  month,  have  you  had  any  of  the  following  problems  with  work  or  other  regular  

activities  as  a  result  of  your  physical  health?  

  Yes,  limited  a  

lot  

Yes,  limited  a  

little  

No,  not  

limited  at  all  

4. Accomplished  less  than  you  would  like  

 

     

5. Were  limited  in  the  kind  of  work  or  other  

activities  

     

 

During  the  past  month,  have  you  had  any  of  the  following  problems  with  work  or  other  regular  

activities  as  a  result  of  any  emotional  problems  (such  as  feeling  depressed  or  anxious)?  

  Yes,  limited  a  

lot  

Yes,  limited  a  

little  

No,  not  

limited  at  all  

6. Accomplished  less  than  you  would  like  

 

     

7. Didn’t  do  work  or  other  activities  as  

carefully  as  usual  

     

 

8.  During  the  past  month,  how  much  did  pain  interfere  with  your  normal  work  (both  outside  of  

the  house  and  housework)?  

 

 

Not  at  all  

 

A  little  bit  

 

Moderately  

 

Quite  a  bit  

 

Extremely  

 

These  questions  are  about  how  you  feel  and  how  things  have  been  with  you  during  the  past  

month.    For  each  question,  please  give  one  answer  that  comes  closest  to  the  way  you  have  

been  feeling.    How  much  of  the  time  during  the  past  month:  

 

  All  of  the  

time  

Most  of  

the  

time    

A  good  bit  

of  the  time  

A  little  

bit  of  

the  

time  

None  

of  the  

time  

9. Have  you  felt  calm  and  peaceful?  

 

         

10. Did  you  have  a  lot  of  energy?  

 

         

11. Have  you  felt  downhearted  and  blue?            

   

12.  During  the  past  month,  how  much  of  the  time  has  your  physical  health  or  emotional  

problems  interfered  with  you  social  activities  (such  as  visiting  with  friends,  relatives  etc.)?  

 

 

All  of  the  time  

 

Most  of  the  time  

 

Some  of  the  time  

 

A  little  of  the  time  

 

None  of  the  time  

 

APPENDIX 10

MANUSCRIPT ACCEPTED FOR PUBLICATION IN THE AMERICAN JOURNAL

OF SPORTS MEDICINE: DO POSTOPERATIVE PLATELET-RICH PLASMA

INJECTIONS ACCELERATE HEALING AND EARLY FUNCTIONAL RECOVERY

AFTER ARTHROSCOPIC SUPRASPINATUS REPAIR?: A RANDOMIZED

CONTROLLED TRIAL

Do Postoperative Platelet-RichPlasma Injections Accelerate Early TendonHealing and Functional Recovery AfterArthroscopic Supraspinatus Repair?

A Randomized Controlled Trial

Allan Wang,*y PhD, FRACS, Philip McCann,z FRCS(Tr&Orth), Jess Colliver,§ BSc,Eamon Koh,|| FRANZCR, Timothy Ackland,§ PhD, Brendan Joss,§ PhD,Minghao Zheng,y PhD, and Bill Breidahl,{ FRANZCRInvestigation performed at St John of God Hospitaland University of Western Australia, Perth, Australia

Background: Tendon-bone healing after rotator cuff repair directly correlates with a successful outcome. Biological therapiesthat elevate local growth-factor concentrations may potentiate healing after surgery.

Purpose: To ascertain whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair siteimproves early tendon healing and enhances early functional recovery after double-row arthroscopic supraspinatus repair.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. After randomization, half thepatients received 2 ultrasound-guided injections of PRP to the repair site at postoperative days 7 and 14. Early structural healingwas assessed with MRI at 16 weeks, and cuff appearances were graded according to the Sugaya classification. Functionalscores were recorded with the Oxford Shoulder Score; Quick Disability of the Arm, Shoulder and Hand; visual analog scale forpain; and Short Form–12 quality-of-life score both preoperatively and at postoperative weeks 6, 12, and 16; isokinetic strengthand active range of motion were measured at 16 weeks.

Results: PRP treatment did not improve early functional recovery, range of motion, or strength or influence pain scores at anytime point after arthroscopic supraspinatus repair. There was no difference in structural integrity of the supraspinatus repairon MRI between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thicknessretear; 23% partial tear; 70% intact) at 16 weeks postoperatively (P = .35).

Conclusion: After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on 2 occasions does not improve earlytendon-bone healing or functional recovery.

Keywords: platelet-rich plasma; rotator cuff repair; growth factors; tendon healing; early functional recovery.

Despite the advent of new surgical techniques to improverotator cuff fixation to bone, failure of the tendon repairoften occurs.12,38 Tendon retears may be due to a specificreinjury at the repair site but also may reflect incompleteor failed primary healing after surgery.5,6

Sonnabend et al,37 in a primate model of rotator cuffrepair, showed that a significant proportion of Sharpeyfibers begin to reconstitute at 3 months with maturationat 4 months after surgery. Thus, the early tendon healingstage is critical for long-term success of rotator cuff repair.

Accelerated rotator cuff rehabilitation programs that allowactive exercises sooner than 3 to 4 months before earlytendon-bone healing occurs risk early failure.29,43

Hence, there has been increasing interest in adjuvantbiological therapies to improve early primary tendon heal-ing. In particular, many studies have investigated platelet-rich plasma (PRP) products, where a supra physiologicalconcentration of platelets is delivered to the tendon-bonerepair site at the time of surgery. Activated plateletsdegranulate to release multiple growth factors that modu-late the cascade of chemotaxis, cell proliferation, and dif-ferentiation, which assist in the tendon healing process.#

The American Journal of Sports Medicine, Vol. XX, No. XDOI: 10.1177/0363546515572602� 2015 The Author(s) #References 3, 11, 13, 15, 17, 21, 22, 25, 31.

1

AJSM PreView, published on March 19, 2015 as doi:10.1177/0363546515572602

Published studies reporting the use of PRP administra-tion have met with mixed success in improving outcomesafter rotator cuff repair. Appraisal of the literature is com-plicated by the range of treated injuries, varying from small,single-tendon tears to massive multitendon tears; concomi-tant use of acromioplasty or not7,19; and the formulation ofPRP used, which ranged from intratendon injection,20,32

spray application,33,35 or incorporation of a platelet-richfibrin matrix into the tendon repair site.2,7,16,40

A further variable affecting the efficacy of PRP is the tim-ing of delivery. All previous PRP augmented rotator cuffstudies to date have used time zero delivery at the time ofsurgical repair. After activation, platelets release growthfactors almost immediately with total elution within1 hour,1 and the half-life of growth factors is a matter ofminutes to hours.26 However, it has been acknowledgedthat biological augmentation of tendon repairs too early inthe tendon healing cascade may be ineffective.15 Differingclasses of growth factors are active at specific time points21;for example, animal studies have shown that application ofplatelet-derived growth factors at day 7 have a more pro-nounced effect on tendon cellular maturation and biome-chanical strength than earlier application.8 Growthfactors, including bone morphogenetic protein–13 (BMP-13), platelet-derived growth factor–B, and transforminggrowth factor–B1, are expressed maximally at days 7 and14,42 and the cytokine-mediated temporal expression of col-lagen types I and III increases from day 7 onward.9

Hence, timing for PRP delivery remains an importantconsideration for optimizing tendon healing. In this study,we hypothesized that delayed and repeated injection ofPRP at days 7 and 14 after surgery would first avoid thepotential dilution and washout effect of arthroscopic admin-istration and second, produce a sustained up-regulation ofthe tendon healing process. The purpose of this study wasto determine if this PRP delivery protocol would enhanceearly tendon healing and functional recovery after arthro-scopic supraspinatus tendon repair. The primary study out-come was improved early tendon healing as assessed bymagnetic resonance imaging (MRI). The secondary outcomewas patient-rated function as a measure of functionalrecovery.

METHODS

Patient Selection

Institutional ethics committee approval was granted forthis study. Patients with rotator cuff tears verified byMRI or ultrasound were identified over the period from

November 2011 to February 2013. A power calculationwas performed to determine the required number ofpatients to detect a significant difference of 1 Sugaya gradeclassification between the treatment and control groupsbased on previously published MRI classification scoresfor post–rotator cuff repair patients.38 The power analysisused an effect size of 0.769 (moderate effect), with signifi-cance of P \ .05, and a power of 80%, giving a minimumsample size of 56 participants (n = 28 participants ineach group). More participants (n = 60) were recruited toallow for attrition.

The inclusion criteria comprised the presence of a symp-tomatic full-thickness tear of supraspinatus in an activeadult identified by preoperative imaging and confirmed byarthroscopic evaluation. All patients also received a seriesof plain radiographs (anteroposterior, outlet, and axillaryviews) for evaluation of arthritic changes. Exclusion criteriaincluded patients with a history of previous rotator cuff sur-gery, subscapularis or infraspinatus tear identified on

*Address correspondence to Allan Wang, PhD, FRACS, Department of Orthopaedic Surgery, University of Western Australia, 35 Stirling Hwy, CrawleyWA 6009, Australia (email: allanwang@aapt.net.au).

yDepartment of Orthopaedic Surgery, University of Western Australia, Crawley, Australia.zDepartment of Trauma and Orthopaedic Surgery, King Edward Building, Bristol Royal Infirmary, Bristol, UK.§School of Sport Science, Exercise and Health, University of Western Australia, Crawley, Australia.||Department of Radiology, Fremantle Hospital, Fremantle, Australia.{Perth Radiological Clinic, Perth, Australia.

One or more of the authors has declared the following potential conflict of interest or source of funding: Arthrex provided a stipend for J.C., exercisephysiologist, to undertake the Biodex evaluations. Arthrex donated disposable syringes used in study protocol. M.Z. is a scientific consultant to OrthoCell,a biotech company, and holds a patent in tendon cell culture technique; A.W., M.Z., and T.A. have shares in OrthoCell.

Assessed for eligibility (N = 305)

Excluded (n = 239)● Workers’ compensation = 108● PASTA repairs = 31● >2 cm, not supraspinatus alone, or involving subscapularis/ infraspinatus = 73● OA (glenohumeral joint) = 27

Declined to participate (n = 6)

Lost to follow-up (n = 0)

Discontinued intervention (n = 0)

Allocated to arthroscopic double-row rotator cuff repair and postoperative US-guided PRP injections (n = 30)

Received allocated intervention (n = 30)

Did not receive allocated intervention (n = 0)

Analyzed (n = 30)

Excluded from analysis (n = 0)

Allocation

Analysis

Follow-up

Enrollment

Lost to follow-up (n = 0)

Discontinued intervention (n = 0)

Analyzed (n = 30)

Excluded from analysis (n = 0)

Allocated to arthroscopic double-row rotator cuff repair without postoperative US-guided PRP injections (n = 30)

Received allocated intervention (n = 30)Did not receive allocated intervention (n = 0)

Randomized (n = 60)

Figure 1. CONSORT (Consolidated Standards of ReportingTrials) flowchart. OA, osteoarthritis; PASTA, partial articularsupraspinatus tendon avulsion; PRP, platelet-rich plasma;US, ultrasound.

2 Wang et al The American Journal of Sports Medicine

preoperative imaging or arthroscopic evaluation; labraltear; significant degenerative glenohumeral osteoarthritis;contralateral shoulder symptoms; rheumatalogical, neuro-muscular, or autoimmune disease; cervical disc herniation;ongoing workers’ compensation claims; or contraindicationto postoperative MRI evaluation (Figure 1).

Surgical Technique

All surgery was performed by the senior author. All proce-dures were performed in the lateral decubitus positionunder general anesthesia with an interscalene nerve block.The arm was placed in 4 kg of traction and positioned in 30�of arm flexion and abduction. Initial diagnostic glenohum-eral arthroscopy was performed and the presence of a full-thickness supraspinatus tear confirmed. After debridementof the bursal tissue and tendon margins, the tear type wasassessed and tear size measured with a calibrated probewith 5 mm increments. Tears over 20 mm in the anteropos-terior dimension were excluded, as were partial tears.Supraspinatus tears associated with subscapularis or infra-spinatus tears were excluded from the study. After acromio-plasty, rotator cuff reconstruction was performed. Thefootprint was prepared with a full-radius resector to decor-ticate the greater tuberosity. A double-row suture-bridgerepair28 with bioabsorbable anchors was performed(Arthrex Bio-Corkscrew 5.5 mm–FT, Biocomposite Pushloc3.5 mm; Arthrex). The same reconstructive technique wasutilized in each case. Concomitant shoulder injuries weretreated as clinically or radiographically indicated. Acromio-clavicular joint arthropathy was treated with arthroscopicexcision of the lateral end of the clavicle, and long head ofbiceps tendinopathy was treated with tenotomy (Table 1).

Postoperative Protocol

All patients were immobilized in a sling (Ultrasling III;Don Joy) for 6 weeks postoperatively and followed a stan-dard rehabilitation program under the supervision of phys-ical therapists. This consisted of passive range of motionexercises in the first 6 weeks, followed by active assistedrange of motion exercises from 6 to 10 weeks, and finally,a guided strengthening program from 10 to 16 weeks. Allpatients followed this program consistently.

Randomization Procedure

Patients were reviewed on postoperative day 5 and, afterarthroscopic evaluation and confirmation study inclusioncriteria were met, randomized to PRP or control groups. Acomputer block permutation method was prepared to gener-ate a simple randomized computer-generated table of blocksof 10 (5 PRP; 5 control) stratified by the treating surgeon atthe 5-day postsurgical follow-up. Sixty consecutive patientsmeeting the study inclusion criteria and consenting to thestudy were randomized via the aforementioned procedure,with 30 in each arm of the study. The average age was59.1 years (range, 28-77 years). Patient demographics alongwith details of concomitant surgical procedures are illus-trated in Table 1.

Preparation of PRP

The group randomized to the treatment arm of the studyunderwent ultrasound-guided PRP injection to the rotatorcuff repair site on 2 separate occasions, at days 7 and 14after surgery. The platelet concentrate was obtained usingthe Arthrex Autologous Conditioned Plasma (ACP) system.A PRP injection was prepared from 10 mL of autologousperipheral blood. After the addition of 1 mL of Anticoagu-lant Citrate Dextrose Solution (ACD-A), the blood wasspun in a centrifuge (ROTOFIX 32 A; Andreas HettichGmbH & Co KG) at 1500 RPM for 5 minutes. After centri-fugation, the PRP supernatant (approximately 2-4 mL)was removed and stored in a separate sterile syringe inpreparation for point-of-care delivery.

The ACP system produces a platelet concentration ofapproximately 470,000 platelets/mL (2.13 greater thanthe level in whole blood), with an estimated concentrationof growth factor reported as 5 to 25 times that of normalphysiologic levels. It is free of both residual erythrocytesand leucocytes, which may impair local growth factoractivity by free radical activation.18,36 Immediately beforeinjection, the preparation was activated with 2 mL ofCaCl2.27 The injection was delivered at the tendon repairsite under direct visualization with ultrasound by anexperienced fellowship-trained musculoskeletal radiolo-gist. Needle placement was aided by the identification ofthe echogenic sutures at the tendon repair site (Figure2). The control group did not receive a placebo injection.

TABLE 1Group Demographics With Concomitant Procedures and Complicationsa

Tear Size, mm

Sex, Male/Female, n

Age, y,Mean (Range)

Acromioplasty,n

BicepsTenotomy, n

AcromioclavicularJoint Excision, n

Complications,n

Median(range)

Mean 6 SD

PRP group (n = 30) 11/19 59.8 (28-77) 30 3 4 0 15 (10-20) 14.60 6 3.78Control group (n = 30) 17/13 58.4 (38-76) 30 5 5 0 15 (10-20) 13.70 6 3.27

aPRP, platelet-rich plasma.

Vol. XX, No. X, XXXX Postoperative PRP Injections After Supraspinatus Repair 3

Outcome Assessments

Radiographic analysis was performed with MRI at 16weeks. All scans utilized a 1.5-T unit (Sonata MaestroClass; Siemens) with 40 mT/m gradient power. Multipleimages were obtained in oblique coronal, oblique sagittal,and axial planes with both short-tau inversion recovery(STIR) and turbo spin echo (TSE) T1-weighted sequence.MRI assessment was performed by an experiencedfellowship-trained musculoskeletal radiologist who hadnot performed the PRP injections and was blinded topatient allocation to treatment or control group. Multipleimages were evaluated and graded as per the Sugaya clas-sification (Figure 3).38

Outcomes were assessed clinically and radiologically.Patients were assessed using the Oxford Shoulder Score(OSS); Quick Disability of the Arm, Shoulder and Hand(QuickDASH); visual analog scale (VAS) for pain (notingmaximum pain in the prior 7-day period); and ShortForm–12 (SF-12) preoperatively and at 6, 12, and 16 weekspostoperatively. All assessors were blinded as to the

identity of the treatment and control groups, nor werethey involved in any stage of the recruitment or surgery.

Active range of motion was assessed at 16 weeks usinga goniometer. Absolute values were recorded for arm flex-ion, abduction, and external humeral rotation in both theoperated and unoperated shoulders, using anatomic land-marks for accuracy and consistency. Range of motion wasperformed within the participants’ pain tolerance to mini-mize any injury risk and discomfort.

Isokinetic strength was also assessed at 16 weeks withthe patient seated in a Biodex isokinetic dynamometer,and a series of standardized measurements were per-formed with the patient instructed to produce a maximummuscular force at speeds of 60 and 90 deg/s. Externalhumeral rotation was performed in the modified-neutralposition, with the elbow at 90� of flexion and the forearmin a neutral position throughout. Arm flexion was per-formed with the elbow fully extended. Values for bothpeak torque and total work performed over the range ofmotion were noted. Data were recorded as both absolutevalues and as a percentage of the scores obtained on thecontralateral, unoperated shoulder. A difference of 10%to 15% in the strength between shoulders is regarded asphysiologically normal in the general population and inthose patients undergoing surgery.4

Statistical Analysis

Values are presented as means with associated standarddeviations. A series of 2-factor, repeated-measures ANOVAswere performed to assess for difference between the treat-ment and control groups over time for continuous variables.For continuous data recorded at a single time point only,a series of independent t tests were performed, whereasa Mann-Whitney U test was employed for the MRI ratingprimary outcome variable. Statistical analyses used SPSSsoftware (IBM Corp). For all tests, P \ .05 was consideredsignificant.

RESULTS

All patients complied with the study protocol, and nopatient was lost to follow-up. There were no significantcomplications such as infection or neurological or vasculardeficit for any patient in either arm of the study. In thecontrol group, mean tendon tear size treated was1.37 cm, and in the PRP group, mean tendon tear size trea-ted was 1.46 cm. The adjunctive procedures of acromiocla-vicular joint excision and biceps tenotomy are shown inTable 1. No patient underwent a cortisone injection forpain, capsulitis, or bursitis within the study period.

Structural Evaluation

With use of the Sugaya classification, the grade of supra-spinatus tendon healing for the PRP and control group isreported in Table 2. In both groups, 23% of subjects hada partial-thickness tendon repair (Sugaya grade 3). No

Figure 2. Ultrasound image of needle placement directly atthe tendon repair site (arrow).

Figure 3. T1-weighted coronal magnetic resonance imagedisplaying Sugaya grade 1 appearance.

4 Wang et al The American Journal of Sports Medicine

full-thickness retears were noted in the PRP treatmentgroup; 2 (7%) full-thickness retears (Sugaya grades 4 and5) occurred in the control group.

One patient in the PRP treatment group did not toleratethe postoperative MRI scan and so underwent an ultra-sound performed by an experienced musculoskeletal radi-ologist. This tendon repair was intact and without anyevidence of thinning or discontinuity and so, for the purpo-ses of the study, was included in the grade 1 group of thatcohort. In the PRP treatment group, 23 subjects (77%)exhibited a healed repair or an intact repair with high sig-nal intensity (Sugaya grades 1 and 2), compared with 21subjects (70%) in the control group. A Mann-Whitney Utest demonstrated no difference (P = .351) between groupson MRI rating at 16 weeks (PRP group mean, 1.8 6 0.8;control group mean, 2.1 6 1.0).

Functional Scores

Outcome scores for all patients improved after surgery. At12 and 16 weeks postoperatively, the Oxford ShoulderScore (F = 75.803; df = 3; P \ .001), the QuickDASH (F= 53.939; df = 3; P \ .001), and the VAS pain scores (F= 75.499; df = 3; P \ .001) all improved significantlyfrom before surgery. Similarly, the SF-12 quality-of-lifeindicators (physical component score: F = 13.967; df = 3;P \ .001; mental component score: F = 5.401; df = 3; P =

.001) improved with time. There was, however, no statis-tical difference (P . .05) between the PRP treatment andcontrol groups for any of these functional scores at anytime point postoperatively (Table 3).

Strength

Isokinetic strength values were obtained for active armflexion and external rotation movements at 2 speeds. Val-ues were expressed as a percentage of the strengthrecorded in the contralateral shoulder. Within the controlgroup, the relative scores for arm flexion peak torque at90 and 60 deg/s were 68.7% and 75.4%, respectively, and75.6% and 74.0%, respectively, for external rotation peaktorque. Relative scores were similar in the PRP treatmentgroup for arm flexion peak torque at 90 and 60 deg/s (74.1%and 76.3%, respectively) and external rotation peak torque(72.1% and 77.3%, respectively). No group differences (P .

.05) for strength scores at 16 weeks after surgery were evi-dent (Table 4).

Range of Motion

The analysis revealed no significant differences (P . .05)in any active range of motion measure between the 2

TABLE 2Sugaya Classification of MRI Scans of Patient Treatment Groupsa

Sugaya Classificationb

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

PRP group (n = 30) 12 (40.0) 11 (36.6) 7 (23.0) 0 (0) 0 (0)Control group (n = 30) 9 (30.0) 12 (40.0) 7 (23.0) 1 (3.3) 1 (3.3)

aValues are reported as n (%). PRP, platelet-rich plasma.bFrom Sugaya et al.38 Grade 1 = no tear; grade 2 = sufficient tendon thickness but with high signal change; grade 3 = insufficient thickness

but no tendon discontinuity; grade 4 = small full-thickness retear; grade 5 = large full-thickness retear.

TABLE 3Functional Scoresa

Postoperative

Variable Group Preoperative 6 wk 12 wk 16 wk

QuickDASH symptoms (transformed) PRP 42.27 6 17.06 51.17 6 19.54 33.14 6 19.27 22.58 6 14.36Control 37.16 6 20.38 53.48 6 13.27 36.33 6 17.40 17.23 6 13.56

VAS PRP 6.37 6 1.59 3.26 6 2.43 2.35 6 2.01 1.75 6 1.68Control 5.38 6 2.43 1.19 6 2.34 2.23 6 1.91 1.36 6 1.51

OSS PRP 27.63 6 6.90 23.57 6 9.61 33.38 6 8.93 38.17 6 7.19Control 30.68 6 7.76 21.48 6 6.61 32.53 6 6.92 40.37 6 5.12

SF-12PCS PRP 35.17 6 8.43 36.31 6 7.40 38.73 6 7.06 41.78 6 8.34

Control 37.92 6 7.97 34.98 6 5.75 39.08 6 6.94 43.08 6 6.26MCS PRP 52.16 6 12.24 49.87 6 12.94 52.75 6 11.90 53.81 6 11.21

Control 50.47 6 12.56 49.69 6 13.63 53.47 6 10.55 55.17 6 7.41

aValues are reported as mean 6 SD. MCS, mental component score; OSS, Oxford Shoulder Score; PCS, physical component score; PRP,platelet-rich plasma; QuickDASH, Quick Disability of the Arm, Shoulder and Hand; SF-12, Short Form–12; VAS, visual analog scale for pain.

Vol. XX, No. X, XXXX Postoperative PRP Injections After Supraspinatus Repair 5

groups at 16 weeks after surgery. Complete values are dis-played in Table 5.

DISCUSSION

The purpose of the study was to evaluate the efficacy ofa protocol of sequential PRP administration after arthro-scopic supraspinatus repair. All previous studies have uti-lized a single delivery of a PRP product at the time ofsurgery. The current protocol delivered a PRP productunder ultrasound guidance to the tendon repair site at 7and 14 days after surgery to avoid a possible dilution orwashout effect of PRP, which may occur with arthroscopicfluid lavage. This protocol also allows a potentiallyprolonged up-regulation of growth factors involved inthe tendon healing cascade. Our hypothesis was thatthis postsurgical and sequential PRP delivery protocolwould (1) improve rotator cuff healing and (2) accelerateearly functional recovery after arthroscopic rotator cuffrepair.

This study finds that at 16 weeks after surgery, no full-thickness tendon retears occurred in the PRP group; how-ever, there were 2 (7%) full-thickness retears in the controlgroup. Although this difference was not statistically

significant, our findings are consistent with previousreports. Castricini et al7 examined the effects of platelet-rich fibrin matrix augmentation in rotator cuff repair andreported the re-rupture rate was higher in the control group(10.5% vs 2.5%). In contrast, Gumina et al,16 using a novelplatelet-rich fibrin matrix allowing slow release of growthfactors on the tendon repair site, found a 14% retear ratein isolated posterosuperior cuff tears in the PRP group com-pared with 50% in the control group at 13 months. HoweverRodeo et al,34 also using platelet-rich fibrin matrix in 79patients undergoing arthroscopic cuff repair, found no dif-ference in tendon bone healing on ultrasound at 6 weeksand 12 weeks after surgery.

The secondary outcomes of this study were to evaluateearly functional recovery in patients receiving PRP treat-ment after supraspinatus repair. In a prospective random-ized controlled trial of 53 patients, Randelli et al33 reportedthat PRP administered by spray produced statistically bet-ter early function scores and strength at 3 months aftersurgery. No imaging was performed at this stage, althoughit was concluded that PRP administration accelerates earlyrecovery after surgery. Zumstein et al44 also showed anearly benefit of PRP administration with improved revas-cularization of the tendon-bone repair site. Doppler ultra-sonography was used to assess the vascularization indexof 20 shoulders at 6 and 12 weeks after surgery.44 At 6weeks, those shoulders treated with a leucocyte-rich PRPproduct showed significantly better vascularization; how-ever, this was not sustained at 12 weeks.

Our study can report that early functional recovery wasnot improved with a sequential postsurgical PRP deliveryprotocol. At 6, 12, and 16 weeks, clinical function scoreswere equivalent between PRP and control group partici-pants. Furthermore, objective testing of shoulder functionat 16 weeks showed no difference between groups in recov-ery of active arm flexion, abduction, or external rotationrange of motion. Similarly, isokinetic peak torque andthe work done through the active range of motion duringeach movement was not different between groups.

PRP delivery by injection under ultrasound guidanceinto the supraspinatus tendon repair site may be less

TABLE 4Group Mean Scores and t Test Results

for Strength Measures at 16 Weeks Postoperativelya

Variable GroupIsokinetic

Strength, % t P Value

Arm flexionPeak torque 90 deg/s –.122 .266

PRP 74.1 6 10.8Control 68.7 6 24.2

Total work 90 deg/s .107 .915PRP 55.5 6 23.2Control 56.3 6 34.2

Peak torque 60 deg/s –.190 .85PRP 76.3 6 22.0Control 75.4 6 22.0

Total work 60 deg/s –.150 .881PRP 61.7 6 21.8Control 60.8 6 27.4

External rotationPeak torque 90 deg/s .470 .640

PRP 72.2 6 15.7Control 75.6 6 37.5

Total work 90 deg/s .712 .371PRP 51.9 6 30.1Control 55.1 6 35.8

Peak torque 60 deg/s –.64 .525PRP 77.3 6 17.8Control 74.0 6 21.3

Total work 60 deg/s .277 .783PRP 59.8 6 24.3Control 62.3 6 44.0

aStrength was calculated as a percentage of the contralateral,unoperated arm. Results are reported as mean 6 SD. PRP,platelet-rich plasma.

TABLE 5Group Mean Scores and t Test Results

for Range of Motion for the Operated Limbat 16 Weeks Postoperativelya

Variable GroupRange of

Motion, deg t P Value

Arm flexion 1.274 .208PRP 144.8 6 22.8Control 151.8 6 19.8

Arm abduction 0.342 .734PRP 134.8 6 28.2Control 137.4 6 29.1

External rotation 0.69 .493PRP 41.1 6 10.2Control 42.8 6 9.3

aPRP, platelet-rich plasma.

6 Wang et al The American Journal of Sports Medicine

accurate than injection under arthroscopic visualization.However, the surgical technique employed in this studycomprised a double-row suture bridge technique, and theechogenic suture knots were readily identified on ultra-sound. Moreover, the oblique and interlocking sutures ofthe suture bridge potentially retain the injected PRP atthe repair site better than the single-row repair site tech-nique used in previous studies.33

As an imaging modality, ultrasound has been shown tobe reliable in obtaining a precise placement of PRP at thesite of tendon injury.41 PRP delivery by direct injectionunder ultrasound guidance has been used to treat injuriesof the Achilles tendon,10 the common extensor tendon ori-gin,23,24,30 and the rotator cuff. Kesikburun et al20 demon-strated that PRP injection to nonsurgically treat rotatorcuff tendinopathy and partial-thickness tendon tears hasno significant clinical benefit over saline injections at 3,6, 12, and 52 weeks. The findings of our study are consis-tent with this work, and even with a second PRP injection,there was no significant clinical or functional benefit up to16 weeks after surgery. Our study focus is early outcomes,however; definitive clinical outcomes require 12- to 24-month postoperative evaluation.

This study has some limitations to be acknowledged.First, the follow-up was limited to 16 weeks. It is possiblethat more structural tendon failures would have beenseen if MRI evaluation was repeated at a later time inter-val such as 12 months. However, it was the primary aim ofthis study to assess the effects of PRP treatment on theearly phases of tendon healing. Animal models have dem-onstrated that a significant proportion of Sharpey fibersat the tendon repair site have reconstituted and maturedat the bone-tendon repair by 3 to 4 months,37 thus support-ing the validity of assessment at the 16-week time point.

A second limitation is the nonblinding of subjects in bothPRP and control groups. As the study protocol required 2separate postsurgical injections, we considered that it wouldbe impractical to have patients agreeing to complete 2 pla-cebo injections. Patients in the PRP treatment group mayhave had the benefit of a placebo as well as a possiblePRP treatment effect in their clinical and functional evalu-ation. Similarly, those patients who did not receive injec-tions may have responded differently in clinical testing.The nonblinding of subjects could be expected to cause apositive bias in the PRP group; however, groups were equiv-alent in their study outcomes. MRI evaluation was per-formed by an independent musculoskeletal radiologist whohad not been involved in previous diagnostic imaging orPRP injections and was blinded to group allocation.

A further possible study limitation was the PRP productused in this study does not achieve the very high concentra-tion of platelets reported with some other PRP products.1,11,14

Sundman et al,39 in a laboratory study, suggested that mark-edly elevated supra physiological levels of platelets andgrowth factors may be of no additional benefit due to cell-surface receptor saturation or may actually be detrimentalto tendon healing.39 Optimal tendon healing requires notonly the appropriate concentration of growth factors butthat those growth factors be delivered at the appropriatetime in the tendon healing cascade to be maximally effective.

CONCLUSION

This study is the first to evaluate the efficacy of a postsur-gical PRP delivery protocol to improve healing and func-tional outcomes after arthroscopic rotator cuff repair.Sequential delivery of the specific injectable PRP prepara-tion used in this study under ultrasound guidance, at days7 and 14 after surgery, does not improve early rotator cuffhealing or functional recovery. Future research shouldinclude randomized controlled trials of other PRP productswith alternative delivery vehicles and dosing regimes.

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8 Wang et al The American Journal of Sports Medicine

APPENDIX 11

MANUSCRIPT ACCEPTED FOR PUBLICATION IN THE JOURNAL OF

SHOULDER AND ELBOW SURGERY: EARLY POSTOPERATIVE REPAIR

STATUS AFTER ROTATOR CUFF REPAIR EVALUATION.CANNOT BE

ACCURATELY CLASSIFIED USING QUESTIONNAIRES OF PATIENT

FUNCTION AND ISOKINETIC STRENGTH EVALUATION

The University

Ethics Committ

J Shoulder Elbow Surg (2016) 25, 536-542

1058-2746/$ - s

http://dx.doi.org

www.elsevier.com/locate/ymse

BASIC SCIENCE

Early postoperative repair status after rotatorcuff repair cannot be accurately classified usingquestionnaires of patient function andisokinetic strength evaluation

Jessica Colliver, BSca, Allan Wang, PhD, FRACSa,b,c,Brendan Joss, PhDa, Jay Ebert, PhDa,*, Eamon Koh, FRANZCRd,William Breidahl, FRANZCRe, Timothy Ackland, PhDa

aSchool of Sport Science, Exercise and Health, University of Western Australia, Crawley, Perth, WA, AustraliabDepartment of Orthopaedic Surgery, University of Western Australia, Crawley, Perth, WA, AustraliacSt John of God Hospital, Subiaco, Perth, WA, AustraliadDepartment of Radiology, Fremantle Hospital, Fremantle, WA, AustraliaePerth Radiological Clinic, Subiaco, Perth, WA, Australia

Background: This study investigated if patients with an intact tendon repair or partial-thickness retearearly after rotator cuff repair display differences in clinical evaluations and whether early tendon healingcan be predicted using these assessments.Methods: We prospectively evaluated 60 patients at 16 weeks after arthroscopic supraspinatus repair. Eval-uation included theOxford Shoulder Score, 11-itemversion of theDisabilities of theArm, Shoulder andHand,visual analog scale for pain, 12-item Short Form Health Survey, isokinetic strength, and magnetic resonanceimaging (MRI). Independent t tests investigated clinical differences in patients based on the Sugaya MRI ro-tator cuff classification system (grades 1, 2, or 3). Discriminant analysis determined whether intact repairs(Sugaya grade 1) and partial-thickness retears (Sugaya grades 2 and 3) could be predicted.Results: No differences (P < .05) existed in the clinical or strength measures. Although discriminant anal-ysis revealed the 11-item version of the Disabilities of the Arm, Shoulder and Hand produced a 97% true-positive rate for predicting partial thickness retears, it also produced a 90% false-positive rate whereby itincorrectly predicted a retear in 90% of patients whose repair was intact. The ability to discriminate be-tween groups was enhanced with up to 5 variables entered; however, only 87% of the partial-reteargroup and 36% of the intact-repair group were correctly classified.Conclusions: No differences in clinical scores existed between patients stratified by the Sugaya MRI clas-sification system at 16 weeks. An intact repair or partial-thickness retear could not be accurately predicted.Our results suggest that correct classification of healing in the early postoperative stages should involveimaging.

of Western Australia (RA/4/1/4872) Human Research

ee (HREC) approved this research.

*Reprint requests: Jay R. Ebert, PhD, School of Sport Science, Exer-

cise and Health, University of Western Australia, 35 Stirling Hwy,

Crawley, 6009, WA, Australia.

E-mail address: jay.ebert@uwa.edu.au (J. Ebert).

ee front matter � 2016 Journal of Shoulder and Elbow Surgery Board of Trustees.

/10.1016/j.jse.2015.09.019

Clinical scores cannot classify cuff status 537

Level of evidence: Basic Science Study, Validation of Patient Reported Outcome Instruments.� 2016 Journal of Shoulder and Elbow Surgery Board of Trustees.

Keywords: Rotator cuff repair surgery; shoulder; patient-reported outcome measures; isokinetic strength;

magnetic resonance imaging

Rotator cuff surgical repair is common, with in excess of250,000 performed each year.18 Despite advances in sur-gical techniques and the increasing use of adjunct biologictherapies to stimulate or enhance repair, or both, the post-operative failure rate remains a concern.3,8,9 Although pa-tients with retears or failed healing may experience areduction in pain, functional outcomes, including strengthlevels, are significantly lower compared with patients withevidence of completely healed tendons.6,10,16,20,32 Theseinferior functional results may be satisfactory for an olderor less active population, or both, but patients who require areturn to sport or work where physical strength is importantmay be dissatisfied with the outcome.

A primate model of rotator cuff repair showed that asignificant proportion of Sharpey fibers start to reconstituteat 3 months, with maturation seen at 4 months.29 Klugeret al24 reported that most recurrent tears occur in the first 3months after rotator cuff surgery, highlighting that thisearly phase of tendon healing up to 3 to 4 months post-operatively is critical for longer-term success. Earlyconfirmation of tendon healing is reassuring for the patientin the early postoperative stages. Likewise, identification ofimpaired healing or partial disruption of the tendon repaircould affect management after surgery. This may includemodifying the patient’s ongoing rehabilitation program,more focused patient education on potentially provocativeor damaging movements and activities, recommending re-strictions in future work and sport practices, ongoing sur-veillance of future patient symptoms and imaging, and evenconsideration for further surgery. Therefore, identifying thepresence of incomplete tendon healing at an early stageafter surgery using clinical and strength evaluation couldprove beneficial.

The routine use of postoperative imaging studies toevaluate the outcome of rotator cuff surgery can be costly.Ultrasound (US), although readily available and cost-effective, is operator dependent for accuracy.17,30 Mag-netic resonance imaging (MRI) is generally considered tobe superior to US2,11 but remains an expensive imagingmodality. Several researchers have attempted to determinewhether the clinical progress of a nonoperatively treatedrotator cuff tendon tear can be predicted using commonclinical shoulder assessments, albeit with limited suc-cess.1,23,25 At the time of writing, we are unaware of anyother studies that have investigated whether commonshoulder clinical assessments can predict the early post-operative success of rotator cuff repair surgery.

Therefore, this study aimed to (1) investigate if differ-ences in common shoulder patient-reported outcome (PRO)measures and isokinetic strength tests could be observedbetween patients with completely intact repairs or partial-thickness tendon retears, classified by MRI, at 16 weeksafter rotator cuff repair surgery; and (2) determine if thesePRO measures and strength tests could predict the early(16 weeks) postoperative success of rotator cuff repair.

Materials and methods

Patients

This prospective comparative study recruited 60 consecutive pa-tients with rotator cuff tears isolated to the supraspinatus (Table I).Patients were recruited between November 2011 and February2013 and were included if they presented with a symptomatic full-thickness tear of the supraspinatus, confirmed preoperatively byMRI or US and intraoperatively by arthroscopic evaluation. Pa-tients with supraspinatus partial tears or tears exceeding 20 mm inthe anteroposterior dimension were excluded, as were patientswith concomitant subscapularis or infraspinatus tears, or both,identified on preoperative US or MRI or intraoperative examina-tion. Patients were excluded if they had any or all of a history ofprevious rotator cuff surgery, labral tearing, significant osteoar-thritis of the glenohumeral joint, rheumatologic, neuromuscular,or autoimmune disease, or cervical disc herniation. Patients werefurther excluded if they presented with any contralateral shouldersymptoms or had ongoing workers’ compensation claims.

A priori power calculation based on our first study goal wasdetermined from the recommendations of Cohen.12 The minimalclinically important difference reported for the 11-item version ofthe Disability of the Arm, Shoulder and Hand (QuickDASH)questionnaire varies, ranging from 14.0 to 17.1 for patients withshoulder pathology,15,31,35 equating to an effect size of 0.75 to0.98. Therefore, to detect this degree of difference (effect size of0.85) with 80% power at a ¼ 0.05, we estimated that 18 patientsin each of the intact-repair (Sugaya grade 1) and partial-retear(Sugaya grade 2 and 3 pooled) groups would be required forthis study.

Surgical technique

All surgery was performed by the senior author (A.W.). Briefly, allprocedures were performed with the patient in the lateral decu-bitus position under general anaesthesia with an interscalene nerveblock. The arm was placed in 4 kg of traction and positioned in30� of arm flexion and abduction. The presence of a full-thicknesssupraspinatus tear was initially confirmed by diagnostic

Table I Group demographics with details of concomitantprocedures and complications

Variable Result (n ¼ 60)

SexMale 28Female 32

Age, mean (range) years 58.8 (28-77)Acromioplasty, No. 60Biceps tenotomy, No. 8Acromioclavicular joint excision, No. 9Complications, No. 0Supraspinatus tear size, mean (SD) mm 14 (4)

SD, standard deviation.

538 J. Colliver et al.

glenohumeral arthroscopy. Tear type and size were assessed usinga calibrated probe with 5-mm increments after d�ebridement ofbursal tissue and tendon margins.

After acromioplasty, rotator cuff reconstruction was per-formed. The footprint was prepared with a full-radius resector todecorticate the greater tuberosity. A double-row suture-bridgerepair28 technique with bioabsorbable anchors was performed(Arthrex Bio-Corkscrew 5.5 mm–FT, BioComposite PushLock3.5 mm; Arthrex, Naples, FL, USA) in all cases. Concomitantshoulder injuries were treated as clinically or radiographicallyindicated. Acromioclavicular joint arthropathy was treated witharthroscopic excision of the lateral end of the clavicle, and longhead of biceps tendinopathy was treated with tenotomy (Table I).

Postoperative management

All patients were immobilized in an abduction sling (UltraSlingIII; DonJoy, Carlsbad, CA, USA) for 6 weeks postoperatively andunderwent a standard rehabilitation program under the supervisionof a physical therapist. Briefly, patients undertook an initial6 weeks of passive range of motion exercises, followed by active-assisted range of motion exercises from 6 to 10 weeks, and aconservative strengthening program from 10 to 16 weeks. Allpatients followed the protocol consistently.

PRO measures

Four PRO measures were used at 16 weeks after surgery: (1) theOxford Shoulder Score (OSS); (2) the QuickDASH questionnaire;(3) a visual analog scale (VAS) for rating pain, and (4) the 12-item Short Form Health Survey (SF-12). The OSS is a 12-itemquestionnaire evaluating pain and function that has been validatedagainst general health and clinical measures and has demonstratedgood reliability in evaluating outcome after shoulder sur-gery.13,14,27 The QuickDASH is an 11-item questionnaire evalu-ating pain, symptoms, and physical function in patients withupper limb musculoskeletal disorders4 and has also demonstratedgood reliability, validity, and responsiveness.4,19 The VASrequired patients to rate their pain intensity on a 0- to 10-cmsliding scale (0 ¼ no pain, 10 ¼ worst pain imaginable) in thepreceding 24 hours. A 1.4-cm improvement on the VAS has beenreported as the minimal clinically important change in patientsundergoing nonoperative treatment for rotator cuff disease.33

Finally, the SF-12 is a generic health-related quality of lifescore36 that produces a physical (PCS) and mental (MCS)component subscale.

Isokinetic strength evaluation

Isokinetic strength was assessed at 16 weeks after surgery in allpatients using a Biodex Isokinetic Dynamometer (Biodex, Sys-tem 4, Shirley, NY, USA). Patients were seated with the trunkstabilized using rigid straps, and adjustments were made forhumeral and forearm length in accordance with each patient’sstature. Patients were instructed to undertake maximal concentricexternal/internal humeral rotation, followed by arm flexion, at anangular velocity of 60�/s. External/internal humeral rotation wasperformed in the modified-neutral position with the elbow in 90�

of flexion and the forearm in a neutral position. Arm flexion wasperformed with the elbow fully extended. Each trial consisted of3 maximal repetitions. Two trials on each upper limb were un-dertaken, alternating between the nonoperated and operatedlimbs, with the first trial always undertaken on the nonoperatedside. During each effort, patients were asked to perform to theirmaximal muscle strength, although without exerting themselvesto excessive pain. Verbal encouragement was provided, stan-dardized across all patients and trials. Patients were givenadequate rest between trials to minimize fatigue, although thiswas not standardized and was determined by the patient’s indi-vidual readiness to proceed. The peak torque (Nm) and time topeak torque (seconds) were obtained for all trials.

Radiologic evaluation

Radiographic analysis was performed using MRI at 16 weeks aftersurgery. A Sonata Maestro Class 1.5-T unit (Siemens, Erlangen,Germany) with 40 mT/m gradient power was used for all scans.Multiple images were obtained in oblique coronal, oblique sagittal,and axial planes with short-tau inversion recovery and turbo spinecho T1-weighted sequence. MRI assessment was performed by afellowship-trained musculoskeletal radiologist with more than20 years of experience. MRIs were graded according to the Sugayaclassification32: grade 1 ¼ no tear (sufficient tendon thickness withhomogeneously low intensity); grade 2 ¼ sufficient tendon thick-ness but with partial high intensity; grade 3¼ insufficient thicknessbut no tendon discontinuity; grade 4 ¼ small full-thickness retear(the presence of a minor discontinuity); grade 5 ¼ large full-thickness retear (the presence of a major discontinuity).

Statistical analysis

To address the first goal of this study, independent-sample t testswere used to determine if residual tendinopathy or partial-thickness tendon retears (Sugaya grade 2 or 3) led to poorerstrength and functional scores compared with an intact repair(Sugaya grade 1). Participants were grouped according to their 16-week postoperative MRI Sugaya grading (grade 1, 2, or 3), andthose with grade 4 or 5 were omitted from the analysis (n ¼ 2).Group means (standard deviation) for the Sugaya grading classi-fications are presented.

To address the second study goal, discriminant analysis wasused to determine if the Sugaya grading (presence and severity of

Table II Scores for the patient-reported outcome and isokinetic strength measures used for patients with intact (Sugaya grade 1) andpartial-thickness (Sugaya grade 2 and 3) supraspinatus tendon retears)

Variable Sugaya classification Group comparison

Grade 1(n ¼ 21)

Grade 2(n ¼ 23)

Grade 3(n ¼ 14)

Grade

1 vs 2 1 vs 3 2 vs 3

OSS 39.2 (6.4) 39.2 (5.1) 40.7 (8.0) 0.849 0.475 0.524VAS for pain 1.5 (1.4) 1.3 (1.3) 1.4 (2.0) 0.631 0.909 0.815QuickDASH 21.7 (12.4) 17.5 (11.9) 18.3 (17.8) 0.263 0.497 0.882SF-12

PCS 42.1 (8.1) 42.7 (5.8) 44.0 (9.3) 0.812 0.541 0.611MCS 53.7 (11.6) 55.3 (7.7) 54.9 (9.6) 0.615 0.749 0.914

Arm flexionPeak torque, Nm 77.1 (22.6) 76.5 (15.4) 74.9 (18.9) 0.922 0.768 0.780Time to peak torque, sec 0.53 (0.36) 0.56 (0.45) 0.52 (0.46) 0.393 0.312 0.387

External humeral rotationPeak torque, Nm 75.8 (21.2) 71.1 (16.8) 82.4 (21.8) 0.417 0.377 0.084Time to peak torque, sec 0.54 (0.45) 0.61 (0.42) 0.54 (0.42) 0.411 0.300 0.150

MCS, Mental Component Subscale; OSS, Oxford Shoulder Score; PCS, Physical Component Subscale; QuickDASH, 11-question Disability of the Arm, Shoulder

and Hand; SF-12, 12-item Short Form Health Survey; VAS, visual analog scale.) Data are presented as mean (standard deviation). Independent-sample t-test comparisons are provided between groups (P values).

Clinical scores cannot classify cuff status 539

tendinopathy or a partial-thickness retear) could be predictedusing PRO measures or strength data, or both. Linear combina-tions of predictor variables were formed to serve as the basis forclassifying patients into 2 groups: a partial-retear group (Sugayagrades 2 and 3) and an intact-repair group (Sugaya grade 1). Whendiscriminant analysis is used, it is recommended that the numberof variables should be used so that there are data for at least 3subjects per variable and that the number of variables should notexceed the number of individuals in the smallest group.7,34 Theserequirements were satisfied in our analysis. The discriminantanalysis used the method of Wilks lambda and a stepwise forwardinclusion model. Analyses were evaluated in terms of a higheigenvalue, high canonical correlation squared, low and significantWilks lambda (P < .001), and a high percentage of correctlyclassified participants, as suggested by Carter and Ackland,7 withsuccessful classification exceeding 80%. We began the analysiswith the variable that had the highest prediction (QuickDASH),and then added variables to a maximum of 5. Statistical analysiswas performed using SPSS 22.0 software (IBM Corp, Armonk,NY, USA). Statistical significance was determined at P < .05.

Results

Group means (standard deviations) are presented for pa-tients classified by Sugaya grades 1 (21 [36%]), 2 (23[40%]), or 3 (14 [24%]), and these groups were comparedat 16 weeks after surgery (Table II). One patient did nottolerate the postoperative MRI scan due to claustrophobiaand instead underwent an US performed by an experiencedmusculoskeletal radiologist. This tendon repair was intact,with no evidence of thinning or discontinuity, so for thepurpose of this study, it was included in the grade 1 Sugaya

classification. No significant differences (P > .05) in PROor isokinetic strength measures were observed among these3 groups by the Sugaya tear classification system at16 weeks after surgery (Table II).

Descriptive variables for the groups with intact (Sugayagrade 1) and residual tendinopathy and partial retear (Sugayagrade 2 and 3 pooled) are reported in Table III, with no dif-ferences (P > .05) observed at 16 weeks after surgery.Discriminant analysis results in Table IV revealed theQuickDASH produced a 97% true-positive rate for predictingpartial retears but also a 90% false-positive rate. The ability todiscriminate between groups was enhanced with up to 5 var-iables entered; however, only 87% of the partial-retear groupand 36% of the intact-repair group were correctly classified.

Discussion

This study evaluated the early clinical, functional, and MRIstatus of the supraspinatus tendon after arthroscopic sur-gical repair. Firstly, we investigated whether differences incommon shoulder PRO measures and isokinetic strengthtests could be observed between patients with intact repairsor partial-thickness tendon retears, classified by MRI, at16 weeks after rotator cuff repair surgery. Secondly, wedetermined whether early postsurgical tendon healing couldbe predicted using these PRO measures and strength tests.

This study found no significant difference in shoulderPRO and strength measures between patients stratified bythe Sugaya MRI classification system (grades 1, 2, or 3) forrotator cuff tears at 16 weeks after surgery. Studies haveinvestigated the diagnostic accuracy of clinical examination

Table III Mean scores for all patients classified with aSugaya grade 1, 2, or 3 outcome and for patients with intactrepairs (Sugaya grade 1) or with partial-thickness (Sugayagrade 2 and 3 pooled) supraspinatus tendon retears

Variable Intactrepair(n ¼ 21)

Partialretear(n ¼ 37)

Total(n ¼ 58)

Mean (SD) Mean (SD) Mean (SD)

Oxford Shoulder Score 39.2 (6.4) 40.1 (6.3) 39.6 (6.3)Visual analogscale for pain

1.5 (1.4) 1.4 (1.6) 1.4 (1.5)

QuickDASH 21.7 (12.4) 18.1 (14.6) 19.2 (13.7)SF-12 (PCS) 42.1 (8.1) 43.2 (7.5) 42.6 (7.6)SF-12 (MCS) 53.7 (11.6) 55.1 (8.1) 54.5 (9.6)Arm flexionPeak torque, Nm 77.1 (22.6) 76.0 (17.0) 76.5 (18.9)Time to peaktorque, sec

0.53 (0.36) 0.52 (0.44) 0.52 (0.41)

External humeralrotationPeak torque, Nm 75.8 (21.2) 75.0 (19.9) 75.7 (20.0)Time to peaktorque, sec

0.54 (0.45) 0.60 (0.42) 0.58 (0.43)

MCS, Mental Component Subscale; PCS, Physical Component Subscale;

QuickDASH, 11-item version of the Disabilities of the Arm, Shoulder and

Hand; SD, standard deviation; SF-12, 12-item Short Form Health

Survey.

540 J. Colliver et al.

for rotator cuff pathology21-23 and concluded that mostclinical tests are inaccurate. This study showed that clinicalevaluation is also inaccurate after surgery in differentiatinga completely intact supraspinatus tendon repair from arepair with residual tendinopathy or partial-thickness retearat 16 weeks after surgery. In this study, all concomitantpathology (lesions of the long head of biceps, acromialspurs and acromioclavicular arthropathy) that might haveaffected the outcome evaluations had been treated at thetime of surgery.

Although discriminant analysis revealed that theQuickDASH produced a 97% true-positive rate for pre-dicting partial retears, it also produced a 90% false-positiverate whereby it incorrectly predicted a retear in 90% ofpatients whose repaired tendons were in fact intact. Theaddition of other shoulder PRO measures or isokineticstrength evaluations did not greatly improve the capabilityof predicting the patient’s early tendon repair outcome.This study concludes that combining such measures doesnot give confidence in the diagnosis of partial-thicknesstendon retears. Some form of imaging assessment (MRI orUS) should be used if necessary for the purpose of diag-nosing residual tendinopathy or partial-thickness tendonretearing after arthroscopic supraspinatus repair.

However, the early use of shoulder-specific PRO mea-sures or strength evaluations remain important in guidingthe rehabilitation process after rotator cuff repair as well as

the patient’s specific return to work or sport. Although notspecific, these measures appear sensitive for identifyingincomplete tendon tearing at 16 weeks after surgical repair.Nho et al26 reported that 100% of retears occurred in thefirst 3 months after surgery. Kluger et al24 reported thatmost early postoperative retears appear to be a failure toheal and that repair site integrity at 6 months was a pre-dictor of 7-year clinical outcome. On the basis of our re-sults, if a patient has a QuickDASH score that is greaterthan the mean value we report at 16 weeks after surgery,then incomplete healing or partial-thickness retearing of thetendon requires exclusion by an imaging assessment.Although these results suggest that PRO measures andshoulder strength in a patient with a completely intactrepair is equivalent to that of a partial-thickness tendonretear at 16 weeks after surgery, the natural history inongoing high-demand work or sport is for partial tears todeteriorate. Therefore, early diagnosis of a failing cuffrepair by subsequent imaging in these patients may allowfor a decelerated rehabilitation program or vocationalcounselling on restricted work duties and prognosis.

This study has some acknowledged inherent limitations.Firstly, the patient follow-up was limited to 16 weeks. In aprimate model of rotator cuff repair, Sonnabend et al29

reported that a significant proportion of Sharpey fibersstart to reconstitute at 3 months, with maturation seen at 4months. However, if clinical, functional and MRI evalua-tions were to be repeated at a later time (such as12 months), it is possible that more structural tearing mightbe observed, contributing to more pain, diminished func-tion, and improved diagnostic accuracy of the combinedtesting protocol. Although the primary aim of this studywas to assess early postoperative tendon healing, futureresearch may include a longer-term follow-up.

A second limitation is that the PRO instruments we usedare used routinely through our clinical practice andresearch, and we appreciate other shoulder-specific scoresare available. It is possible that differences (or an improvedpredictive capacity) may be observed in other clinical andfunctional shoulder evaluations.

Thirdly, strength tests also have some inherent limita-tions because they are unable to differentiate between truemuscular weakness, muscular inhibition, and pain-relatedweakness.5 The results of the isokinetic strength tests alsorely on the patient making a maximal effort. Clear, stan-dardized instructions and verbal encouragement were pro-vided to all participants, but we acknowledged that this wasthe first time many of the patients would have maximallystressed their operated-on limb since surgery and that somemay have been hesitant to exert maximal effort. However,Bigoni et al5 reported that isokinetic strength testing is apowerful tool for evaluating strength after rotator cuffsurgery, so it may be that alternate testing protocols,incorporating shoulder abduction, may more accuratelydiscriminate between groups. Although maximal loading ofthe supraspinatus during shoulder abduction may be more

Table IV Discriminant analysis for variables predicting an intact repair (grade 1 Sugaya classification) or partial-thickness tendonretear (grade 2 and 3 Sugaya classification)

Prediction variables enteredy Statistic) Number classified (%)

Actual groupmembership

Predicted group membership

EV CC WL SigIntact repair(n ¼ 21)

Partial retear(n ¼ 37)

A. QuickDASH 0.011 0.104 0.989 0.465 Intact repair 2 (10) 19 (90)Partial retear 1 (3) 30 (97)

B. QuickDASH, ER Pk Tq 0.034 1.82 0.967 0.429 Intact repair 4 (18) 18 (82)Partial retear 3 (10) 28 (90)

C. QuickDASH, ER Pk Tq, OSS 0.039 0.194 0.962 0.594 Intact repair 5 (23) 17 (77)Partial retear 4 (13) 27 (87)

D. QuickDASH, ER Pk Tq, OSS, TPT ER 0.045 0.207 0.957 0.717 Intact repair 7 (32) 15 (68)Partial retear 4 (13) 26 (87)

E. QuickDASH, ER Pk Tq, OSS,TPT ER, AF Pk Tq

0.045 0.207 0.957 0.837 Intact repair 8 (36) 14 (64)Partial retear 4 (13) 26 (87)

OSS, Oxford Shoulder Score; QuickDASH, 11-item version of the Disabilities of Arm, Shoulder and Hand.) EV, eigenvalue; CC, canonical correlation; WL, Wilks lambda; Sig, prediction significance of the discriminant function.y ER Pk Tq, peak torque for humeral external rotation at 60�/s; AF Pk Tq, peak torque for arm flexion at 60�/s; TPT ER, time to peak torque in humeral

external rotation.

Clinical scores cannot classify cuff status 541

specific for eliciting pain and weakness, the aim of thisstudy was to evaluate whether these tests could predictearly (16-week) outcome, which we consider too early tomaximally stress the supraspinatus. Again, this also high-lights the need for longer-term evaluation.

Finally, our sample size had 80% power to detect only alarge effect size of 0.85 as estimated from prior studies, andtherefore, we can be confident that our data provide evi-dence that such large differences in outcome betweengroups do not exist. We may have failed to detect smallergroup differences with the available sample size.

Conclusion

This study found no significant difference in the shoul-der PRO measures used or in the isokinetic strengthevaluation between patient groups stratified by theSugaya MRI rotator cuff classification system at16 weeks after surgery. Furthermore, the presence of anintact repair or partial-thickness tendon retear after ro-tator cuff surgery could not be accurately predicted bythese clinical and functional shoulder evaluations at16 weeks. Our results suggest that if accurate classifi-cation of tendon healing is required in the early stageafter rotator cuff surgery, then medical imaging shouldbe used. This will give confidence in patient manage-ment of appropriate return to work or sport rehabilitationprograms. Reliance on PRO measures and functionalscores alone to make an accurate assessment is notsupported by our data.

Acknowledgments

We thank Arthrex for their financial support in under-taking the clinical evaluations for this study.

Disclaimer

Financial support was provided by Arthrex to assist inthe clinical evaluations for this study. The authors, theirimmediate families, and any research foundations withwhich they are affiliated have not received any financialpayments or other benefits from any commercial entityrelated to the subject of this article.

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