1. Ultrasound-guided Regenerative Medicine Procedures: Pandora or Panacea Ken Mautner, MD Director, Primary Care Sports Medicine Emory Sports Medicine

2. Goal of talk ““I would like you to talk about stem cells and PRP, the evidence for them in tendons and joints, and why ultrasound guidance is important” JJon Finnoff, DO DDo it less than 20 minutes !

3. Outline  Ultrasound guidance for regenerative medicine procedures  Dangers of steroids in treating tendinopathy  Regenerative injections for recalcitrant tendons  Needle Tenotomy  PRP  Stem cells  Regenerative Medicine for Cartilage/OA (knee)  1-2:30 pm today!

4. Is ultrasound guidance needed for regenerative medicine procedures ?  Accuracy  Efficacy  Cost-effectiveness

5. Reactive vs Degenerative Tendon

6. What is ideal way to treat tendinopathy?  “Old School” Treatments  Rest  Ice  Immobilization  NSAIDS  Physical Therapy/ biomechanics  Possible corticosteroid Injection (CSI)  RTP when pain free/ functional  But is tissue healed?  If symptoms persist  Surgery  LACK OF EVIDENCE FOR TRADITIONAL TREATMENTS

7. Lancet, 2010

9. JAMA, 2013

10. What is ideal way to treat tendinopathy?  Evolving algorithm -- “New School”  Pathology specific conservative treatments  NSAIDS If inflammatory  Mechanotransduction for tendinosis  Eccentrics exercises  IASTM/ CFM/ART  Nitric Oxide  ESWT  Regenerative intervention  Percutaneous needle tenotomy (PNT)  High Volume Injection (HVIGI)  Scraping  PRP  TENEX (FAST)  ADSC +/- PRP  BMAC  TIMING OF INTERVENTION AND TYPE OF INTERVENTION HAS NOT BEEN FIGURED OUT

11. Percutaneous Needle Tenotomy (PNT) and Platelet Rich Plasma (PRP)

12. PNT (needle tenotomy) for lateral epicondylosis  McShane et al, Journal of Ultrasound Med. 2006  Ultrasound guided PNT with steroid for chronic lat. epicondylitis  Failed conservative tx  58 pts-- avg f/u 28 mo.  80 % Good or Excellent Outcome  85% would refer friend or family for procedure  McShane et al, Journal of Ultrasound Med 2008  Ultrasound guided PNT without steroid for chronic lat. Epicondylitis  Failed conservative tx  57 pts --avg f/u 22 mo.  92% Good or Excellent Outcome  90% would refer friend or close relative for procedure

13. PRP for chronic lateral epicondylosis  140 pts evaluated for lateral epicondylosis  20 had refractory pain an avg. of 15 months later  15 in treatment group, 5 in bupivicaine control group  Intervention – Injection w/ autologous PRP once into common extensor tendon followed by gradual increase in rehab program through 4 weeks after which full activity allowed  Outcome – A 46%, 60% and 81% improvement in VAS pain scores at 1, 2 and 6 months respectively in tx group – 3/5 in bupivicaine group withdrew/ sought other tx – At final F/U (12-38 months) 93% pain free (<10/100 VAS) – No complications, no one got worse AJSM, 2006

14.  Pts age 16-70 (avg 48 yrs)  Greater than 6 months of pain (avg 36 months)  Diagnosed by clinical exam plus MRI or diagnostic US  Failed conventional treatments  Medications  Bracing  Stretching  Strengthening  CFM  Modalities  PRP done under US guidance PMR journal, 2013

15. Data of PRP procedures  325 patients with isolated tendinopathy sent questionnaire  Eliminated all non tendons and regional PRP treatments  180 responded (55%)  All retrospective data analyzed with following questions:  Overall improvement  Not at all, slightly, moderately, mostly, completely  VAS score –pre and post  Overall satisfaction  Nirchl phase scale

16. Distribution of Tendons  Lateral Epicondyle30  Patella Tendon27  Achilles27  Rotator Cuff21  Hamstring17  Gluteus Medius16  Medial Epicondyle11  Plantar Fascia9  13 other tendons<5 each

17. Improvement 82% reported moderate to complete improvement – 50%- 100% relief of symptoms 70 % reported mostly to complete improvement -- 75-100% relief of symptoms

18. Pain Score pre and post PRP ➤ 74 % Reduction in VAS 7.3 2.1

19. Why are we still debating if orthobiologics works?  Need to define what we are injecting ?  Platelet counts  MSC counts  Leukocyte +/ -  Differential  RBC +/ RBC –  Autologous/ Allogenic  Need to define the procedure  US guidance  Needle tenotomy?  Rehabilitation methods  Immobilization ?  Timing of eccentrics  Do different body regions require different formulas ? Slide from 2011

20. ____________________________ 1 If WBC are present (+) the % of neutrophils should also be reported. 2 The method of exogenous activation should be reported. April, 2015

21. 80 patients randomized PRP vs Placebo ACP vs saline 2 injections 5 days apart 5 days after injury End point was RTP No difference Average 42 days 2014, Reurink

22. Rehabilitation L+ PRP 42 days vs 26 days

23. Why the difference ? MY TAKE: L+ PRP may reduce recovery from acute hamstring muscle injury

24. Is it the Needle? AJSM, 2013

27. PRP vs PNT for RTC pathology  DBRCT comparing 2 PNT vs 2 PRP injections under US guidance for RTC tendinosis or small, partial tear  Measured results using Shoulder Pain and Disability Index Clinical Rehabiliation, 2012

28.  60 patients randomized to US- guided injection of PRP vs no injection on POD 7, 14  Outcomes tracked through 16 wks  MRI done at 16 wks  RESULTS:  PRP did NOT improve early fxnl recovery, ROM, or strength  NO difference in structural integrity at 16 wks.  Did not look at long term outcomes…. AJSM, 2015

29. Stem cells for Tendinopathy April, 2015

30. Stem Cells for soft tissue  Surprisingly few clinical studies examining stem cells use for soft tissue injuries  Many more studies looking at cartilage  Soft tissue studies predominantly involve PRP  Early clinical studies promising but much more work needed in the area.

31.  46 pts, 60 patellar tendons  Dermal fibroblasts  Cultured for 4 wks  Injected in autologous plasma  US guidance used  Compared to autologous plasma only AJSM, 2011

32. Is it worth it? High cost Lag time (4 wks) Regulatory issues

33.  45 patients in received BMC during single-row arthroscopic RTC repair  51,000 MSC +/- 25,000  45 age matched controls  Up to 10 years follow up with MRI imaging  RESULTS:  6 mo  100% of MSC group healed  67% of control group healed  10 years  87% of MSC group with intact RTC  44% of control group  Results most correlated with MSC concentration

34. Conclusions  Needle tenotomy is effective for tendinosis  US guidance will improve accuracy  Tenotomy helpful no matter the injectate  Saline, WB, ACP, PRP, Stem Cells  PRP may have better results than needling alone  Unsure if related to pathology (tendinosis vs tear)  Stem cells may have better results than PRP/ needling  No head to head studies  Is it worth the cost and increased risk to perform this procedure for tendons ?  I rarely utilize stem cells as a first line treatment for recalcitrant tendinopathy

35. Ken.mautner@emory.org