STRYKER EXHIBIT 1011, pg. 1
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`STRYKER CORPORATION v. ORTHOPHOENIX, LLC
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`IPR2014-01433
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`

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`personaluseonly.
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`ScandJRheumatolDownloadedfrominforrnahealthcarecombyChrisWodarskion06/18/14For
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`380
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`WAP Hayward et al
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`Table 1. Hand-generated maximal pressures of different sizes of syringe.
`
`Size of
`mechanical
`syringe (mL)
`
`Experimental
`maximum pressure,
`mean : SD (psi)
`
`Significance from
`next smaller
`syringe size,
`p-value
`
`Calculated
`maximum
`pressure,
`mean 2 SD (psi)
`
`Significance from
`experimental
`maximum pressure,
`p-value
`
`Maximum
`pressure
`relative to the
`10 mL syringe
`
`Maximum
`pressure
`relative to the
`3 mL syringe
`
`1
`3
`5
`10
`20
`60
`
`
`
`363 :I: 197
`177 :: 96
`73 :I: 40
`53 :: 29
`32 :I: 18
`19 : 12
`
`Not applicable
`0.001
`0.001
`0.08
`0.005
`0.01
`
`
`
`472 :I: 256
`195 :: 106
`77 :I: 42
`55 :: 30
`33 :I: 18
`19 :12
`
`0.14
`0.58
`0.76
`0.83
`0.86
`No difference
`
`6.89
`3.36
`1.39
`1.00
`0.61
`0.34
`
`2.05
`1.00
`0.41
`0.30
`0.18
`0.11
`
`Pressure generation
`
`Pressure was measured in pounds per square inch (psi) with
`a digital pressure meter (DPM-2000 Digital Pressure Meter,
`BC Group, Chicago, IL, USA). The operator generated
`maximum pressure with one hand with each syringe size
`(from 1 mL to 60 mL). The order of syringe size was
`randomized to prevent a consistent or
`training bias.
`Theoretical pressures were calculated from the experimental
`results of the 60 mL syringe and adjusted for syringe size.
`
`Injection of dense connective tissue lesions
`
`For injection of rheumatoid nodules and Dupuytren’s
`contracture, the target was the centre of the nodule. The
`target for trigger finger was the tendon sheath overlying
`the palmar protuberance of the metacarpal head just
`proximal to the A1 pulley and the digital-palmar skin
`crease (5). After antisepsis with 2% chlorhexidine
`(ChloraPrep®, Cardinal Health, Inc., Dublin, OH, USA),
`a 25-gauge 1-inch needle (305761, 25 g 1.0” BD
`EclipseTM Needle, Becton Dickinson,
`Inc, Franklin
`
`600
`
`I» .. _
`
`100%
`
`
`
`Pressure(psi) §5
`
`(%)
`
`Injectionsuccess
`
`
`
`Lakes, NJ, USA) mounted on a 1, 3, or 10 mL mechanical
`syringe with 1.5 mL of 2% lidocaine (Xylocaine® 2%,
`AstraZeneca Pharmaceuticals LP, Wilmington, DE,
`USA) was advanced until the target tissue was hydrodis-
`sected and intralesionally injected with lidocaine.
`Successful hydrodissection was defined as: (i) rupture or
`deformation of the rheumatoid nodule from the internal
`
`pressure, (ii) the deformation of the fibrotic nodule of
`Dupuytren’s contracture, and (iii) dilation of the tendon
`sheath of the trigger finger target, respectively. If the
`lesion could not be injected with the 3 mL or the 10 mL
`syringe because of inadequate pressure, the needle was
`left in place, the syringe was removed, a 1 mL syringe
`with lidocaine was attached, and the hydrodissection pro-
`cedure completed. In this way all of the hydrodissection
`procedures were successfully completed prior to corticos-
`teroid injection. After hydrodissection, the needle was left
`in position, the first syringe removed, and a syringe with
`triamcinolone acetonide attached. Small
`rheumatoid
`
`nodules were injected with 0.25 mL (10 mg) and large
`rheumatoid nodules, Dupuytren’s
`contracture,
`and
`trigger fingers with 0.5 mL (20 mg)
`triamcinolone
`acetonide suspension (Kenalog® 40, Westwood-Squibb
`Pharmaceuticals, Inc (Bristol-Myers Squibb), New York,
`NY, USA).
`
`outcome measures
`
`Procedural pain was assessed with the 0—10 cm visual
`analogue pain scale (VAS)
`(11, 12). Response was
`defined at 2 weeks as (i) a 50% or more reduction in the
`diameter of the rheumatoid nodule or Dupuytren’s lesion,
`or (ii) complete resolution of the trigger finger (1—5).
`
`linl
`
`Sin]
`
`10'ml
`Sinl
`SyringeVolume
`
`20'ml
`
`60ml
`
`Statistical analysis
`
`Figure 1. Effect of syringe size on manual pressure generation and
`injection success. The solid line represents pressure generation for each
`syringe in pounds per square inch (psi) and the dashed line the percen-
`tage initial injection success with each size mechanical syringe. As can
`be seen, the smaller 1 mL and 3 mL syringes have both high levels of
`pressure generation and high levels of injection success of dense con-
`nective tissue lesions compared to the 10 mL syringe.
`
`Data were entered into Excel (Version 5, Microsoft, Seattle,
`WA, USA) and analysed in SAS (SAS/STAT Software,
`Release 6.11, Cary, NC, USA). Differences in categorical
`data were determined with Fisher’s exact test and differ-
`
`ences in parametric data with the t-test, while differences
`between multiple parametric data sets were determined with
`Fisher’s least significant difference method.
`
`www.scandjrheumatol.dk
`
`STRYKER EXHIBIT 1011, pg. 2
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`STRYKER EXHIBIT 1011, pg. 2
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`ScandJRheumatolDownloadedfrominformahealthcarecombyChrisWodarskion06/18/14For
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`High-pressure injections
`
`381
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`
`
`Initialsuccesswith1rnLsyringe
`
`
`
`Initialsuccesswith3mLsyringe
`
`
`
`Initialsuccesswith10mLsyringeProceduralpain,VAS(cm)Percentage
`
`clinicalresponse
`
`Complications
`
`Results
`The calculated pressures were slightly greater than the
`measured pressures, but did not reach statistical signifi-
`cance (Table 1). Smaller syringes generated higher pres-
`sures up to 600 psi for a 1 rnL syringe, while larger
`syringes generated proportionately lower pressures
`(Figure 1). The 3 mL syringe generated four times greater
`pressure than the 10 mL syrmge; the 1 mL generated
`seven times greater pressure than the 10 rnL syringe
`(Table 1). Thus, the 1 rnL and 3 mL syringes consistently
`
`generated high levels of pressure (300—600 psi) while the
`5, 10, 20, and 60 mL syringes generated markedly lower
`.
`levels of pressure (9—150 ps1).
`The injection success of dense connective tissue
`lesions paralleled the ability to generate high pressure
`(Figure 1, Table 2). The 1 mL and 3 rnL mechanical
`syringes provided an initial success rate of 100% and
`93%, respectively, in hydrodissection and intralesional
`injection. However, the 10 rnL mechanical syringe had a
`fail
`f76‘7Predal'
`h'h
`f
`ure rateo
`0.
`oc ur
`pam was
`1g est or
`trigger finger, intermediate for Dupuytren’s contracture,
`and the least for rheumatoid nodules (Table 2). The clin-
`ical results of failed hydrodissection could not be assessed
`because when initial injection failed, the procedure was
`completed with a 1 mL syringe. The clinical results for
`.
`.
`.
`.
`.
`.
`.
`hydrodlssectlon and mjectlon of dense connectlve les1ons
`were generally excellent, with significant reduction in
`-
`.
`.
`.
`s1ze of the nodules or resolutlon of trigger finger w1th
`low levels of dermal atrophy consistent with rates
`reported in the literature (Table 2) (1—9).
`
`Discussion
`
`that hydrodissection and
`report demonstrates
`This
`intralesional injection of dense connective tissue lesions
`can be predictably achieved with smaller syringe sizes
`(S 3 mL) (Figure 1, Tables 1 and 2). With syringes S 3
`mL, levels of pressure up to 600 psi for hydrodissection
`and corresponding levels of injection success are possible
`(Tables 1 and 2). By contrast, larger syringe sizes 2 5 mL
`are associated with lower levels of pressure and reduced
`rates of injection success (Figure 1, Tables 1 and 2).
`Syringe size has been a concern to proceduralists, espe-
`.
`.
`.
`.
`c1ally 1n relatlon to needle control and vacuum generatlon
`(13—15). Smaller syringes provide consistently better nee-
`dle control than do larger syringes (13). By contrast, larger
`syringes, including the 10, 20, and even 60 mL, generate
`higher levels of vacuum and are recommended for suction
`biopsy procedures (15). The present study demonstrates
`that smaller syringes predictably generate greater pressure
`and correspondingly improved intralesional injection suc-
`cess. The pressure in a syringe is determined by the force
`generated by the hand and applied to the plunger divided
`by the cross-sectional surface area of the barrel. The hand
`force to generate maximum pressure is limited by the
`operator’s native hand and arm musculature. As the
`cross-sectional surface area of the syringe barrel increases
`
`www.scandjrheumatol.dk
`STRYKER EXHIBIT 1011, pg. 3
`
`
`
`
`
`Table2.Effectofsyringesizeoninjectionsuccessandoutcome.
`
`STRYKER EXHIBIT 1011, pg. 3
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`ScandJRheumatolDownloadedfrominfom'rahealthcarecombyChrisWodarskion06/18/14For
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`382
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`WAP Hayward et al
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`progressively from the 1 mL to the 60 mL syringe, the
`maximum possible pressure generated by hand force
`decreases as the syringe size increases (Table 1, Figure 1).
`These findings are also consistent with prior reports
`that demonstrate that corticosteroid injection is effec-
`tive for dense connective tissue lesions,
`including
`rheumatoid nodules, Dupuytren’s contracture,
`and
`trigger finger (1, 3—5). Although there was a low
`incidence of dermal atrophy with high-pressure intra-
`lesional injections in this study, it is anticipated that
`low-pressure extralesional injection outside of dense
`connective tissue lesions would result in higher levels
`of complications (6—8). Furthermore, the precise intra-
`lesional injection of collagenase into the dense con-
`nective tissue lesions of Dupuytren’s contracture and
`Peyronie’s disease also requires high pressures for
`success, and the present study provides guidance as
`to appropriate syringe selection to achieve these high
`levels of pressure (2). Furthermore, as hydrodissection
`and high-pressure injections become increasingly used
`in minimally invasive therapies, the selection of the
`appropriate syringe devices is important
`to achieve
`predictable levels of pressure and injection success
`while avoiding complications, device failure, and a
`failed procedure (2, 9—12).
`In summary, the present study demonstrates that smal-
`ler syringes (S 3 mL) permit more robust pressure
`generation than do larger syringes, and thus facilitate
`predictably successful intralesional hydrodissection and
`injection of dense connective tissue lesions.
`
`References
`
`1. Ketchum LD, Donahue TK. The injection of nodules of Dupuytren‘s
`disease with triamcinolone
`acetonide.
`J Hand Surg (Am)
`2000;25:1157—62.
`
`Gilpin D, Coleman S, Hall S, Houston A, Karrasch J, Jones N.
`Injectable
`collagenase Clostridium histalyticum:
`a
`new
`nonsurgical treatment for Dupuytren’s disease. J Hand Surg Am
`2010;35:2027—38.
`.Baan H, Haagsma CJ, van de Laar MA. Corticosteroid
`injections reduce size of rheumatoid nodules. Clin Rheumatol
`2006;25:21—3.
`Peters-Veluthamaningal C, Winters JC, Groenier Kl-I, Meyboom—de
`Jong B. Corticosteroid injections effective for trigger finger in
`adults in general practice: a double-blinded randomized placebo
`controlled trial. Ann Rheum Dis 2008;67:1262—6.
`Sibbitt WL Jr, Eaton RP. Corticosteroid responsive tenosynovitis is
`a common pathway for limited joint mobility in the diabetic hand. J
`Rheumatol 1997;24:931—6.
`Gottlieb NL, Riskin WG. Complications of local corticosteroid
`injections. J Am Med Assoc 1980;243:1547—8.
`Amin N, Brancaccio R, Cohen D. Cutaneous reactions to injectable
`corticosteroids. Dermatitis 2006;17:143—6.
`. Taras JS, Iiams GJ, Gibbons M, Culp RW. Flexor pollicis longus rupture
`in a trigger thumb: a case report J Hand Surg (Am) 1995;20:276—7.
`. Gimbel HV. Hydrodissection and hydrodelineation. Int Ophthalmol
`Clin 1994;34:73—90.
`Mejia R, Saxena P, Tam RK. Hydrodissection in redo stemotornies.
`Ann Thorac Surg 2005;79:363—4.
`Sibbitt WL Jr, Peisajovich A, Michael AA, Park KS, Sibbitt RR,
`Band PA, et al. Does sonographic guidance influence the outcome
`of intraarticular injections? J Rheumatol. 2009;36:1892—902.
`Sibbitt WL Jr, Band PA, Chavez-Chiang NR, Delea SL, Norton HE,
`Bankhurst AD. A randomized controlled trial of the cost-effectiveness
`ofultrasound-guided intraarticular injection ofinflammatory arthritis. J
`Rheumato12011;38:252—63.
`Michael AA, Park KS, Moorjani GR, Peisjovich A, Sibbitt WL Jr,
`Bankhurst AD. Syringe size: does it matter in physician performed
`procedures? J Clin Rheumatol 2009;15:56—60.
`Sibbitt RR, Sibbitt WL Jr, Nunez SE, Kettwich LG, Kettwich SC,
`Bankhurst AD. Control and performance characteristics of
`eight different suction biopsy devices. J Vasc Interv Radiol
`2006;17:1657—69.
`Haseler LJ, Sibbitt RR, Sibbitt WL Jr, Michael AA, Gasparovic
`CM, Bankhurst AD. Syringe and needle size, syringe type, vacuum
`generation, and needle control in aspiration procedures. Cardiovasc
`Interth Radiol 2010 Nov. 6 [Epub ahead of print], doi:10.1007/
`500270-010-001 1—z.
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`10.
`
`11.
`
`12.
`
`13.
`
`14.
`
`15.
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`www.scandjrheumatol.dk
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`STRYKER EXHIBIT 1011, pg. 4
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`STRYKER EXHIBIT 1011, pg. 4
`
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