!

Dr. Xavier Casanova Canals"ORTHOPAEDICS AND TRAUMATHOLOGY DEPARTMENT"

UPPER LIMB SURGERY UNIT"

EGARSAT!!

1.  What is there about PRP and Epycondylitis?"

2.  Our results: prospective study in workers"

INTRODUCTION

“Tennis Elbow”"•  Prevalence 1-3% (45-55y) !

" "14,5% streneous jobs"

REPETITIVE MICROTRAUMATISM: "

•  Angiofibrobastic Hyperplasia!! NO INFLAMATORY CELLS "" " " "(Nirschl 2003)!

ECRB!

Nirschl RP, Ashman ES. Elbow tendinopathy: tennis elbow. Clin Sports Med 2003;22:813-836.!

TREATMENT" RESULTS" PROBLEM"

WAIT AND SEE" 83% recovery after 8-12M (acute)" sports medicine?!work compensation?!

SPLINTS" no diferences wrist/forearm! combined with other treatments!

PHYSICAL THERAPY" satisfaction early time points! Lomg Therm outcomes?? !

ULTRASOUND" contradictory studies! combined with other treatments!

AINE’s ORAL / TOPIC" Initial treatment , Adverse effects!

ANESTHETIC + CORTICOID INJECTION"

90% symptoms improvements at 4weeks,!no differences at 1 year with naproxen or placebo!

skin problems!NO LONG THERM EFFECT"

BOTULINUM TOXIN" improvement at 6 and 18 weeks! finger paresis, extension weakness!NO LONG THERM EFFECT!

AUTOLOGOUS BLOOD"

good results 1 injection!excel.lent with 2-3 injections! NO long therm studies!

ESWT" little benefit compared with other treatments! morbidity (skin lesions, haematoma, swelling)!

ACCUPUNCTURE" short therm pain relief! NO LONG THERM EFFECT!

LASER THERAPY" no efficacy compared to placebo!

SURGERY "(open, percutaneous,

arthroscopic)"

failure conservative treatment!73% symptom resolution!

97% return to work!

agressive treatment!(5y) 9% moderate to severe pain!(5y) 28% low grade symptoms!

F. Faro, MD, J. M. Wolf, MD. Lateral Epicondylitis: Review and current concepts. J Hand Surg 2007;32A:1271-1279)!

…although the treatment of LE has evolved, the response

(and nonreponse) to the multiple nonoperative and surgical

interventions in lateral epincondylitis indicate that our

understanding of the disease process is currently

incomplete… (Faro F., et al. 2007)!

Another treatment for lateral epicondylitis…"

PLATELET "RICH "

PLASMA"(PRP)"

PRP: BASIC SCIENCE

IN VITRO + IN VIVO"(2 studies)"

2/2 ⬆ cell proliferation!⬆ GF expression!⬆ Collagen expression!⬆ Fiber organization!!

Human tenocytes!Sheep / Mice!

PRP CONFERS SEVERAL EFFECTS ON TENDON MODELS COMPARED WITH A CONTROL"(LIMITATIONS)"

379 studies database searching➯ 31 studies fit “inclusion criteria”, control group"

IN VIVO"(14 studies)"

8/13 earlier healing"8/13⬆longitudinal organization"!3/3 ⬆ [GF]0"3/3 ⬆ vascul/blood flow!4/4 ⬆ collagen deposition!3/4 ⬆ load to failure"!

Animal (white rabbit 57%)!Achilles / Patellar tendon!

IN VITRO"(15 studies)"

8/9 ⬆cell proliferation!7/8 ⬆ GF levels!4/5 ⬆collagen expression!

Tenocytes or tendon stem cells!7 animal/7 human!

PRP: RANDOMIZED CLINICAL TRIALS

Mishra"(2006)"

Peerbooms"(2010)"

Gosens"(2011)"

Thanasas"(2011)"

Krogh"(2013)"

Study"

Mishra!(2006)"

Peerbooms!(2010)"

Gosens!(2011)"

Thanasas!(2011)"

Krogh!(2013)"

Design"

Pilot trial!Level 2!

RCT!Double blind!

Level 1!

RCT!Double blind!

Level 1!

RCT!Single blind!

Level 1!

RCT!Single blind!

Level 1!

Group of patients"

CHRONIC">3m!!

VAS>6!

CHRONIC">6m!!

VAS>5!

CHRONIC">3m!!

VAS>5!

CHRONIC">3m!!!

CHRONIC">3m!!

N"

20"15 PRP!5 Bupi!

100"51 PRP!

49 CORT!

100"51 PRP!

49 CORT!

28"14 PRP!

14 Blood!

60"20 PRP!

20 CORT!20 SS!

PRP"(BIOMET GPS

SYSTEM)"

1A"NO Activ"

2-3mL"+Bupi (sc)"

1A"NO Activ"

1mL"+Bupi (mixed)"

1A"NO Activ"

1mL"+Bupi (mixed)"

1A"NO Activ"

3mL"US guidance"

2A"NaHCO3"

3mL"Lido (sc)"

RHB"(weeks)"

4w RHB!!

4w RHB!!

Progressive sustained

improvement!!

better than Cort at 2y !!

4w RHB!better than Blood

short therm!!

No RHB!

PAIN"statistical

differences"

FUNCTION statistical

differences"

⇓VAS"8w - 60%"6m - 81%"2y - 93%"

Improve Mayo Score

72% 6m"

⇓VAS"1y - 73%" (vs 49%)"

⇓DASH"1y - 73% "

(vs 51%)"

⇓VAS"2y- 76,5%)"

⇓DASH"2y -72,5%"

⇓VAS "only 6w"

NO"Liverpool

Elbow Scrore"

"PRTEE: NO DIF at 3m"postinf pain PRP > SS > Cort"

duration PRP,,SS > CORT""

“Any attempt to generalize about the value of PRP based on a

methanalysys of the literature would be difficult. There are simply too

many different application techniques and poor documentation of what

was actually given to the subjects”. !

!

Mishra et al. Platelet rich plasma and upper extremity. Hand Clin

2012;28:481-491.!

PRP: CLASSIFICATION

TYPE" WHITE BLOOD CELLS" ACTIVATION" PLATELET

CONCENTRATION"

1! INCREASED! NO!

A>5XPLATELETS!!B<5XPLATELETS!

2! INCREASED! YES!

3! NO/MINIMAL! NO!

4! NO/MINIMAL! YES!

Mishra A, Harmon K, Woodall J et al. Sports medicione applications of platelet rich plasma. Curr Pharm Biotechnol 2012;13(7):1185-95.!

Mazzoca AD et al. The positive effects of different platelet rich plasms methods on human muscle, bone, and tendon cells. Am J Sports Med 2012;40:1742-49. !

•  Varying preparations of PRP had different in vitro effects on proliferation and GF expression in tenocytes, osteoblasts and myocytes.!

Dragoo JL et al. Comparison of the acute inflammatory response of two comercial platelet rich plasma systems in healthy rabbit tendons. Am J Sport Med 2012;40:1274-81.!

•  The effect of leukocyte concentration is poorly understood. !

> 800 proteins">16 separation systems "Boswell SG, D.V.M, Cole BJ, MD, et al. Platelet Rich Plasma: A milieu of bioactive factors. Arthroscopy 2012; 28:429-439.!!Foster TE et al. Platelet-Rich Plasma from basic science to clinical applications. Am J Sport Med 2009; 37(11):2259-2272.!

2. Prospective analysis of 48 patients in workers’ compensation

environment

(EGARSAT)

HYPOTHESIS AND OBJETIVES

HYPOTHESIS"•  PRP injections reduce pain and improve functionality enough to prevent

more agressives treatments.!

GENERAL OBJECTIVE"

"

"

SPECIFIC OBJECTIVES"•  To determine after-treatment variations in PAIN, FUNCTION, LIFE

QUALITY and GRIP FORCE.!

•  To determine the proportion of patients that can prevent surgical treatment!

•  To determine the survival function !

To Determine the effectivenes of PRP injection on Chronic LE in the general clinical practice at work compensation environment"

PATIENTS AND METHODS DESIGN !

•  Prospective quasi-experimental clinical study pre-post intervention without control group.!

AMBIT AND POPULATION "•  Labor Insurance Corporation (EGARSAT) 220.000 insured workers!

INCLUSION CRITERIA" EXCLUSION CRITERIA "

Clinical diagnose of LE!>3m chronicity"

Conservative treatment failure"Informed consent!

!

Previous elbow surgery!Systemic rheumatic or Methabolic pathology!

Radiculopathy!Elbow osseous deformity!

Complet Rupture on MRI"Corticoid injection in last 3m"

*Croisier JL, Foidart-Dessalle M, Tinant F et al. An isokinetic eccentric programme for the management of chronic lateral epicondylar tendinopathy. Br J Sports Med 2007;41:269-75 !

PATIENTS AND METHODS

 ORTHOPAEDIC  SURGEON  

 

REHAB.      THERAPY*  

FIRST  ASSITANCE  WORK  

LATERAL  EPICONDYLITIS  

NEAI   STRECHING   PRP  

WORK  REST)   ECCENTRICAL  EXERCISES  

SURGICAL  PROCEDURE  

CRIOTHERAPY  

BRACE  

CORTICOID  INJECTION  

ELECTRO  THERAPY  

April 2011 – December 2012!

4 patients excluded:!･Discal haernia!･Language!

･Complete rupture on MRI!･Burocrathic reasons!

13 patients lost during sample

selection!2 pacientes reject

PRP injections!2 abandonments after 1st injection!

Flow Diagram of the study.!

PATIENTS AND METHODS

PRE injections! INJECTIONS! POST injections!

INCL/EXCL Criteria!Consetment!

Data Collecting!Blood analysis!

1st !INJ!

2nd!INJ!

3rd!INJ!

1m! Control!

3m !Control!

6-12m !Control!

EVA"QDASH"

SF12"DEXTER"

EVA"QDASH"

SF12"DEXTER"

15d! 15d!T0! 4m! 7-13m!Time"

Average follow-up: 7.2months!

2m!

Schedule of the study: PRP injections protocol"

PATIENTS AND METHODS

•  T-test for paired data: "•  Comparison of pre-post response variables"

•  Fisher exact test (qualitative) and U of Mann Whitney test (quantitative)!

•  Bivariate analysis: determination of the differences between non-operated and operated subgroups in some of the studied variables ifferences of variables!

•  Kaplan-Meyer survival function !•  considering failure surgical treatment!

•  STATA S/Evs9 statistical pack!

•  Statistical significance p<0.05"

PATIENTS AND METHODS STATISTICAL ANALYSIS"

•  Anítua* methodology!•  PRP 4B Mishra"

•  [platelets]= x 2-3 [PBlood]!

•  Laminar flux!•  24mL peripheral blood sample (sodic citrate)!

•  Centrifugation 8’- 1800rpm!

•  Activation: CaCl2!

*E. Anítua, MD, DDS. Plasma Rich in Growth Factors: Preliminary Results of Usein the Preparation of Future Sites for Implants. Int J Oral Maxilofac Implants. 1999 Jul,Aug;14(4):529,35. !

PATIENTS AND METHODS

PATIENTS AND METHODS

Platelet Rich Plasma "Platelet Poor Plasma"

Leukocyte band" Peppering Technique!

1!

4!

3!2!1!

6!

5!

3CC"Activation CaCl2!

Density gradient after centrifugation!

•  NO Anaesthesia!•  Paracetamol 1g/8h !•  48h work rest!•  NO RHB associated!

PATIENTS AND METHODS

RESULTS SAMPLE DESCRIPTION"

VARIABLE! MESURE! MEAN! SD! RANG!

AGE" years! 45,9" 6,6! 32 - 59!

WEIGHT" kg! 69,4" 11,4! 52 - 102!

HEIGHT" cm! 165,8" 10! 147 - 187!

PLATELETS RECOUNT" x103/mL! 246,6" 59,2! 92 - 415!

YEARS IN PROFESSION" years! 15,3" 12,1! 1- 40!

SICK LEAVE BEFORE PRP" days! 40,4" 53,5! 0 - 251!

LE Nº EPISODES" episodes! 1,7" 1,1! 1 - 5!

CHRONICITY" months! 23,1" 28,9! 4 - 120!

82%

18%

RIGHT LEFT

13%

43%

44%

NO LOADEDMEDIUM LOADEDHIGHT LOADED

25%

75%

SICK LEAVEWORKING

77%

23%

CORTICOID INJNO CORTICOIDS

16%

84%

DOMINANTNON-DOMINANT

60%

40%

MAN WOMEN

AVERAGE 5.2M pre-PRP!

RESULTS

0

10,25

RESONANCIA MAGNÉTICA

EDEMA (8)

PARTIALRUPTURE (9)ARTICULAREFFUSION (6)CARTILAGELESION (1) OSSEOUSLESION (1)

•  Irregularity, distortion and thickening of the common extensor insertion"

•  MRI severity signs do not correlate positively with symptoms in chronic.!

Walton MJ t al.The reliability and validity of MRI in the assessment of chronic lateral epicondylitis. J Hand Surg 2011;36A:475-79).!

RESULTS

Test"

1m Postinj!(N 29)!

3m Postinj!(N 26)!

6-12m postinj!(N 15)!

｜x｜!(sd)! p*! ｜x｜

(sd)! p*! ｜x｜!(sd)! p*!

EVA" 16,4"(32,8)! 0,0116! 27,0"

(34,9)! 0,0003! 46,7"(20,1)! 0,0000!

qDASH" 12,7"(25,8)! 0,0167! 19,1"

(23,8)! 0,0007! 32,4"(22,0)! 0,0000!

qDASH"work"

16,1"(28,9)! 0,0101! 28,4"

(31,3)! 0,0003! 43,6"(21,6)! 0,0000!

SF12"PCS"

-3,3"(6,8)! 0,0179! -7,8"

(9,4)! 0,0012! -11,1"(7,3)! 0,0000!

*p<0,05= statistical significance; ⎥X⎥ mean of differences PRE-POST; (sd) standar deviation"

DIFFERENCES PRE AND POST INTERVENTION!

RESULTS

RESULTADOS

La puntuación SF12-MCS no tiene diferencias estadísticamente significativas.!La mejoría en la Dinamometría está en el límite de la significación estadística.!

EVA!qDASH!

qDASH trab!SF12 PCS!

SF12 MCS!DEXTER!

0"

20"

40"

60"

80"

100"

120"

140"

BASAL" 1m"3m"

6.12m"

EVA"

qDASH"

qDASH"trab"

SF12"PCS"

SF12"MCS"

DEXTER"

RESULTS BIG EFFECT SIZE "

Clinical relevance of the differences !

COMPARISON   VAS PAIN   Q-DASH   SF12-PCS  0 - 1m   0,65   moderate   0,45   small   0,36   small  0 - 3m   0,96   BIG   0,83   BIG   0,85   BIG  

0 - 6/12m   2,40   BIG   1,95   BIG   1,51   BIG  

Cohen 1988 Effect Size (d value): 0.2 small; 0.5 moderate; 0.8 big!

35%

65%

IQ

NO IQ

COMPLICATIONS!1 vasovagal syndrome!

Postinjection pain(3-5d)!

RESULTS

Bivariate analysis" OP (N14) / NON-OP (N25)"

Statistical differences?" p*"

Number of previous LE episodes" no" 0,13!Sick leave days before injections" no" 0,04!

Duration of symptoms before injections" no" 0,58!Platelet count (peripheral blood)" no" 0,57!Corticoid injection before PRP" no" 0,08!

Stop working during PRP injections" no" 0,24!Job effort grade subjective classification" no" 0,72!

*p<0,05= statistical differences!

RESULTS

SURVIVAL ANALYSIS!0.

000.

250.

500.

751.

00

0 20 40 60 80analysis time

Kaplan-Meier survival estimate

71% conversions to surgical tretament were done during first 15w"(4 IQ de la 15-27)!

!60% probability of preventing surgery"

The PRP failure should be expected in 4-6 months"

RESULTS

LIMITATIONS

•  Workers’ compensation environment: low adhesion of patients to periodical testing while keep working!

•  Losts and missings"

•  Design: not controlled!•  Average Follow-up of 7,2m!

Statistical power of the comparisons pre-post between the variables of the study (VAS, quickDash, SF12 PCS) oscilates around 80-100%!

CONCLUSIONS

•  The treatment of Chronic LE with PRP (4B) injections is effective in work compensation environment improving pain and functionality with a probability of 60% of preventing surgery and a very low complicaction rate. !

•  Is necessary to universalize the method of preparation and adminstration of PRP and also specify the characteristics of the product using a common classification; this will make possible to compare its effects and results among different studies!

• More studies are needed to identify those patients who will most probably improve with this treatment and fix its indication according to some prognostic factors as the stage of tendinopathy.!

THANK YOU

!

Dr. Xavier Casanova Canals"ORTHOPAEDICS AND TRAUMATHOLOGY DEPARTMENT"

EGARSAT!!

Head of Department: Dr. Francesc Soler i Romagosa"

!

PRP is a plasma suspension that contains all components of whole blood in varying amounts (Red Cross: > 200.000/mL)*"

PRP ¿WHAT IS IT?

*Boswell SG, D.V.M, Cole BJ, MD, et al. Platelet Rich Plasma: A milieu of bioactive factors. Arthroscipy 2012; 28:429-439.!

PRP ¿HOW IT WORKS?

CITOKINES"

INTRACELLULAR SIGNALING"

NUCLEAR GENE EXPRESSION"

Tendon healing phases! 1. INFLAMMATION !2. PROLIFERATION !

3. REMODELING!

PROTEIN EXPRESSION (GF)"

cell proliferation"angiogenesis"

cell chemotaxis"cell differenciation"

extracell matrix production"

PRP Goal: positively affect gene expression and mathrix synthesis in tendon cells (enhance healing)"

BIOLOGIC TREATMENT, CELLULAR LEVEL"

Foster TE, MD, Puskas BL, MD, Mandelbaum BR, MD et al. Platelet Rich Plasma. From basic science to clinical applications. Am J Sports Med 2009;37(11):2259-2272.!Boswell SG, D.V.M, Cole BJ, MD, et al. Platelet Rich Plasma: A milieu of bioactive factors. Arthroscipy 2012; 28:429-439!

EVA"

DASH"

PRP-group sustained improvement !Cortocoid-group declination, higher recurrence and reintervention rate!

26weeks!

RESULTS RESUME

•  PRP (4B, Anítua) injections in chronic LE reduce pain and improve function and life quality with statistical and clinical significance !

•  No major complications has been registered!•  In workers’ compensation environment 65% of cases

have not received other treatments after injections, preventing the surgical procedure"

•  It has been performed without interruption of work activities in 75% of cases !

•  The Kaplan-Meier Survival function value is 0.6 (60% probability of preventing surgery)!