Review Article

Antibiotic Spacers for Shoulder Periprosthetic Joint

Infection: A Review

Surena Namdari, MD, MSc

Suleiman Y. Sudah, MD
Mariano E. Menendez, MD
ABSTRACT
Patrick J. Denard, MD Periprosthetic joint infection is a rare but potentially devastating
complication of shoulder arthroplasty. The most conservative
treatment approach is a two-stage revision involving interval placement
of an antibiotic cement spacer. The purpose of this study was to
contextualize the use of antibiotic spacers in the current treatment
paradigm of shoulder periprosthetic joint infection and to review the
history of shoulder spacers, the different types (eg, stemmed versus
stemless and prefabricated versus handmade), the antibiotic
composition and dosage, and their efficacy and complications.

From the Rothman Orthopaedic Surgery,

P
Rothman Institute, Sidney Kimmel Medical eriprosthetic joint infection (PJI) is an infrequent but potentially dev-
College at Thomas Jefferson University,
Philadelphia, PA (Namdari), the Department of
astating complication of primary and revision shoulder arthroplasty
Orthopedics, Monmouth Medical Center, Long with an incidence of 1% to 4% and 4% to 15%, respectively.1 It is the
Branch, NJ (Sudah), the Midwest Orthopaedics
most common cause of revision shoulder arthroplasty within the first 2 years
at Rush, Rush University, Chicago, IL
(Menendez), and the Oregon Shoulder Institute, of the index procedure.2 Risk factors include male sex, age younger than 65
Medford, OR (Denard). years, arthroplasty for trauma, prior failed arthroplasty, previous cortico-
Namdari or an immediate family member has steroid injections, chemotherapy, and the presence of certain medical co-
received IP royalties from DJO Global and Miami
Device Solutions; serves as a paid consultant for morbidities such as diabetes, inflammatory disease, and obesity.3
DJO Global, Miami Device Solutions, and Currently, a consensus management algorithm for the treatment of
Synthes; has stock/stock options held in Flexion
Therapeutics, MD Live, Parvizi Surgical
shoulder PJI has not been reached.4 Management options include (1)
Innovations, and RubiconMD; has received débridement, antibiotics, and implant retention (DAIR); (2) one-stage revi-
research support from Arthrex, DJO Global,
sion arthroplasty; (3) two-stage revision arthroplasty; (4) antibiotic spacer
Integra LifeSciences, and Zimmer Biomet; and
serves as a paid speaker for DJO Global and retention; and (5) resection arthroplasty.5 Regardless of the procedure type,
Miami Device Solutions. Denard or an immediate all patients are treated with perioperative antibiotics.5 However, antibiotic
family member has received IP royalties from
Arthrex; serves as a paid consultant for Arthrex; therapy alone is insufficient for infection eradication, with failure rates of
has received research support from Arthrex; 60% to 75%.6,7 DAIR has been considered in patients with early shoulder
serves as an Editorial or governing board
member of Orthopedics Today; and serves as PJI within 30 days of the index procedure or less than 3 weeks from symptom
paid presenter or speaker for Arthrex and Pacira. onset, stable implants, and low-virulence organisms.4,7 However, a failure
None of the following authors or any immediate
family member has received anything of value
rate of 50% to 63% has been reported,7,8 and the long-term use of sup-
from or has stock or stock options held in a pressive antibiotic therapy may still be necessary.9 Resection arthroplasty has
commercial company or institution related
high rates of infection resolution and is often indicated in patients with
directly or indirectly to the subject of this article:
Sudah and Menendez. recalcitrant shoulder PJI.10 However, up to 50% of patients experience
J Am Acad Orthop Surg 2022;30:917-924 residual pain and poor function.6 Furthermore, failure to place an antibiotic
DOI: 10.5435/JAAOS-D-21-00984 spacer compromises the potential for future prosthesis implantation because
Copyright 2022 by the American Academy of
of rotator cuff muscle atrophy and disuse osteopenia.11 Thus, in patients
Orthopaedic Surgeons. diagnosed with shoulder PJI greater than 4 weeks postoperatively, complete

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Antibiotic Spacers for Shoulder PJI

removal of the prosthesis and treatment with one-stage possibility for staged reimplantation was adopted from
or two-stage revision arthroplasty is recommended.5 experience with infected hip and knee arthroplasties.15
The most conservative treatment approach for Ramsey and Fenlin15 were among the first to report the
shoulder PJI is a two-stage revision, involving interval use of a shoulder spacer in the revision of an infected
placement of an antibiotic cement spacer.7 Although a shoulder arthroplasty. After reimplantation of an ana-
one-stage approach may be preferred in patients with tomic shoulder arthroplasty, the patient achieved for-
low-virulence organism infections4 or contraindications ward elevation of 170º, external rotation of 30º, and
to repeated surgery,12 a two-stage approach is com- internal rotation two spinal levels below the contralateral
monly preferred in patients with clinical concern for side at the 29-month follow-up.
infection with a virulent organism.4 There are few
comparative analyses between one-stage and two-stage
revision arthroplasties for shoulder PJI.12 A recent Types of Antibiotic Cement Shoulder
systematic review and meta-analysis found that the one- Spacers: Stemmed Versus Stemless and
stage approach had a lower rate of reinfection compared Prefabricated Versus Handmade
with two-stage revision (6.3% versus 10.1%).12 How- Stemmed and stemless implants are the two main types of
ever, the difference was not notable and moderate
cement spacers used in two-stage revision shoulder ar-
heterogeneity in the data was reported. Furthermore, throplasty. Cement spacers can also be classified
inherent treatment bias was present because the one-
based on the mode of construction: prefabricated11,16-18
stage group had a higher percentage of sensitive, low- (Figure 1) or handmade intraoperatively with or without
virulence organisms (Cutibacterium acnes) (48.7%
the use of commercially designed spacer molds (Figure 2).
versus 33.6%) and acute or subacute infections (63% Handmade spacers may be fashioned using antibiotic
versus 46.1%), whereas the two-stage group had a
cement alone or antibiotic cement with the use of
higher percentage of virulent and drug-resistant bacteria Steinmann pins,17 dynamic compression plates,17 or
(methicillin-resistant Staphylococcus aureus) (10% shoulder arthroplasty implants19 (Figure 2).
versus 2.6%) and chronic infections (53.9% versus
Proposed advantages of prefabricated spacers
37%). In addition, most studies reported 12-month final include a more anatomic design to allow for improved
follow-up data, which leaves the long-term success rate
shoulder motion and function, more predictable elution
of these procedures in question.
As the use of shoulder arthroplasty continues to rise,13
Figure 1
so does the clinical and economic burden associated
with PJIs. The purpose of this study was to review the
history of antibiotic spacers for shoulder PJI, the dif-
ferent types (eg, stemmed versus stemless and pre-
fabricated versus handmade), the antibiotic composition
and dosage, and their efficacy and complications.

History of Antibiotic Cement Spacers for

Shoulder Periprosthetic Joint Infection
Few surgeons had experience with antibiotic spacers for
shoulder PJI in the 1990s. At that time, resection ar-
throplasty was commonly done for local infection con-
trol.14 Poor functional shoulder outcomes and variable
pain relief were commonplace.14 Furthermore, revision
surgery after resection arthroplasty posed many technical
challenges and was associated with poor functional
outcomes because of capsular contraction, intra-articular Radiograph showing a prefabricated shoulder spacer. AP
scar tissue, and limited soft-tissue mobilization.14 These radiograph of the left shoulder showing a prefabricated
articulating InterSpace Shoulder (Exactech) spacer
complications were minimized with the use of antibiotic comprised with gentamicin-impregnated polymethyl
cement spacers to maintain soft-tissue pliability. The methacrylate bone cement.

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 Surena Namdari, MD, MSc, et al

Review Article
Figure 2

Radiographs and photographs showing handmade shoulder spacers. AP radiographs of the left shoulder showing a stemless shoulder
spacer with antibiotic cement (A) and a surgeon-fabricated articulating hemiarthroplasty shoulder spacer made using the commercially
available StageOne (Zimmer Biomet) spacer mold (B) and intraoperative photographs depicting the creation of a stemmed shoulder
spacer with the use of antibiotic cement and a hemiarthroplasty implant (C).

of antibiotics, reduced surgical time, and less destruction vation (stemless group, 109º 6 23º versus stemmed
of the articular surface of the glenoid before revision group 94º 6 43º) were found. Rondon et al21 found
surgery.17,18 Shoulder spacers fashioned intra- that a greater percentage of stemmed implants required
operatively using commercially available spacer molds spacer exchange compared with stemless implants
afford similar advantages to prefabricated spacers with (stemless group, 12.5% versus stemmed group, 60%) in
the additional benefits of being able to adjust the anti- patients definitively treated with antibiotic shoulder
biotic content and to press-fit the stem. However, no spacers. However, this finding was not statistically
randomized studies have compared clinical outcomes significant. These data do not suggest superiority of
after the use of prefabricated and handmade antibiotic either stemmed or stemless antibiotic spacers.
spacers with or without the use of spacer molds for
shoulder PJI.
Meanwhile, the clinical outcomes among treatment
with stemmed (n = 15) and stemless (n = 22) implants for The Use of Antibiotic-Loaded Bone
periprosthetic shoulder infection have recently been Cement for the Creation of Shoulder
studied.20 All spacers were handmade with tobramycin Spacers
and vancomycin-impregnated cement. Stemless spacers A variety of antibiotic-impregnated bone cements (eg,
were created by forming a ball of cement that was placed DePuy 2 Bone Cement [DePuy, Warsaw, IN], Simplex
into the glenohumeral joint space; stemmed spacers cement [Stryker, Kalamazoo, MI], and ready-to-mix
incorporated cement into the humeral canal with or bone PALACOS cement [Heraeus Medical GmbH,
without placement of a prebent, central guidewire. No Wehrheim, Germany]) may be used for the creation
notable difference in surgical time (stemless group, of shoulder spacers and commonly contain 1 g of
127.5 6 37.1 minutes versus stemmed group, 130.5 6 gentamicin per 40-g package of polymethyl methacrylate
39.4 minutes) was found, suggesting that technical (Table 1). For the treatment of infected arthroplasty,
variables of the case, such as ease of stem excision, may effective eradication often requires the use of multiple or
be more closely linked to the overall duration of sur- different antibiotics with high-dose antibiotic-loaded
gery.20 In addition, it was noted that surgical times for bone cement (.2 g per 40-g bag of cement).24 Because
reimplantation were similar in both groups. Therefore, these spacers are not intended for definitive implant
it seems as though stemmed and stemless implants fixation, the mechanical properties of the cement are
equally maintain the joint space and are equally easy to less important and greater amounts of antibiotics are
remove on revision surgery.20 Furthermore, no notable permissible.25 Thus, surgeons often admix an additional
differences in the reimplantation rate (stemless group, 1 g of vancomycin or tobramycin per 40-g bag of
68.2% versus stemmed group, 80%) or forward ele- cement.11,18 In addition, these antimicrobials are heat-

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Antibiotic Spacers for Shoulder PJI

stable, have favorable elution characteristics, and pro- more vancomycin than a separate experimental group
vide empiric coverage against many gram-positive and with 3 g of vancomycin without tobramycin.30 In vivo
gram-negative organisms.11 Traub and Leonhard26 studies of antibiotic elution properties and bioavailability
tested the residual antimicrobial activity of 62 anti- are lacking for shoulder spacers. Meanwhile, the reported
biotics after exposure to temperatures of 56°C for amount of antibiotic elution remaining at 10 days after
30 minutes and 121°C for 15 minutes. Vancomycin and hip spacer implantation ranges from 0.05% to 0.4% for
tobramycin were among the 11 antibiotics that proved gentamicin and 0.8% to 3.3% for vancomycin.31
to be heat-stable compounds because their minimal The determination of which antibiotic-loaded bone
inhibitory concentration raised less than twofold after cement to use is surgeon-dependent and oftentimes
autoclaving.26 multifactorial. Although some rely on preoperative
The long-term elution of antibiotics from the spacer is synovial culture to differentiate the infecting organism,
dependent on the porosity of the bone cement.27 Greater others base their decision on hospital availability, the
porosity allows for more fluid uptake to dissolve anti- biologic effectiveness of the antibiotic within the cement,
biotics within the cement matrix.27 It is generally or the clinical success drawn from the hip and knee
accepted that dual-loaded antibiotic bone cement has literature.32
more favorable elution properties owing to a phenom-
enon known as passive opportunism.28 Synergistic
elution of one or both antibiotics occurs because of
increased polymethyl methacrylate porosity28 and the Eradication of Infection and Outcomes
effects of the antibiotics as soluble fillers.29 However, After Two-Stage Revision Arthroplasty
there is no consensus on the relative concentrations and Several case series have studied functional outcomes and
combinations of antibiotics used to create antibiotic reinfection rates after two-stage revision shoulder ar-
spacers for PJI.30 A recent in vitro study revealed that a throplasty in a range of 4 to 35 shoulders with a mean
combination of 3 g of tobramycin and 2 g of vanco- follow-up of 1.7 to 4.8 years.7,8,17,22,33,34 Constant
mycin had the highest cumulative drug release over a scores, forward elevation, external rotation, and rates of
28-day period.30 This combination eluted 173% more recurrent infection ranged from 35 to 57, 79º to 118º,
tobramycin than an experimental sample with 3 g of 14º to 50º, and 0% to 47%, respectively. Most of these
tobramycin without vancomycin and released 65% studies are small retrospective case series. Brown et al33

Table 1. Summary of Antibiotic Shoulder Spacers

Spacer Type Antibiotics Reference
Prefabricated — —
InterSpace (Exactech) A concentration of gentamicin by weight of 2.8% McFarland et al16
(a total of 0.8 g of gentamicin per spacer) Coffey et al17
Spacer-G A concentration of gentamicin by weight of 2.8% Magnan et al18
(a total of 0.8 g of gentamicin per spacer)
Remedy shoulder system (OsteoRemedies) A concentration of gentamicin by weight of 4.8% —
(a total of 0.9-3.2 g of gentamicin dependent on
the implant size)
Handmade — —
PROSTALAC shoulder spacer molds (DePuy) 2 g of gentamicin and 3 g of tobramycin per 40-g Strickland et al22
bag of cement; 3 total bags were used
StageOne shoulder spacer molds (Zimmer 2-4 g of various antibiotics per 40-g bag of McFarland et al16
Biomet) cement
Global Shoulder shoulder spacer molds 1 g of gentamicin per 40-g bag of cement; 1g of Stine et al11
(DePuy) vancomycin and 1.2 g of tobramycin were added
per bag
Surgeon-fabricated 0.55 g of gentamicin per 45-g cement or 0.75-g Grubhofer et al23
gentamicin per 60-g cement; 1 g of vancomycin
was added per bag

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 Surena Namdari, MD, MSc, et al

Review Article
exclusively reviewed the efficacy of two-stage revision tory function and pain relief on spacer implantation may
arthroplasty in the management of 25 patients with decline to undergo shoulder arthroplasty implant re-
shoulder PJI and reported an 80% eradication rate at a implantation.17,19,34 Stine et al11 studied 30 medically
mean follow-up of 38.3 months. fragile, low-demand patients with chronic shoulder in-
The two-stage approach generally involves removal of fections (4 primary and 26 postoperative) treated with a
all prosthetic implants and cement, débridement of infected fixed antibiotic-loaded articulating spacer. A total of 15
synovium with tissue biopsy, and insertion of an antibiotic patients retained spacers at a mean of 2.4 years and
spacer, followed by delayed reimplantation after 6 weeks experienced acceptable functional outcomes that were
of targeted intravenous antibiotic therapy.4 Several not statistically different from those who underwent
methods of confirming infection eradication before reimplantation. Similarly, Levy et al19 found that nine of
definitive reimplantation have been used, including aspi- 14 patients initially undergoing a two-stage revision
ration of joint fluid,33 open biopsy,35 and interval trending achieved notable improvements in functional outcome
of serum inflammatory markers.11,17,33 There are no scores and range of motion with retainment of a func-
consensus and notable controversy regarding ideal tests to tional hemiarthroplasty spacer at a mean follow-up of
obtain before reimplantation. Brown et al33 conducted 25 months. Cronin et al37 was the first to evaluate
fluoroscopically guided aspiration of the affected shoulder outcomes of retained antibiotic cement spacers with
joint 6 weeks after spacer implantation and initiation of greater than 5 years of average follow-up. The average
targeted IV antibiotic therapy. Those without clinical signs American Shoulder and Elbow Score was 54, Quick
of infection, normalized erythrocyte sedimentation rate Disabilities of the Arm Shoulder and Hand Score 45,
(ESR) and C-reactive protein (CRP) levels, and negative visual analog score 2.8, forward elevation 68º, and
aspirate results proceeded to the second stage of the external rotation 35º. No patients experienced
revision after 2 weeks of antibiotic cessation. Those with reinfection.
clinical signs of infection, elevated ESR and CRP, and Although definitive spacer retention seems to be a
positive aspirate results remained on IV antibiotics, and viable option in patients who refuse or are at a high
the first stage of the revision was repeated. medical risk to undergo two-stage revision arthroplasty,
On the other hand, Coffey et al17 confirmed infection the supporting studies are limited by small sample sizes.
eradication once serum IL-6 levels normalized (or were In a recent systematic review that included 368 total
down-trending) and when intraoperative tissue biopsy patients with shoulder PJI, eradication rates were not
yielded fewer than five WBCs per high-power field. markedly different among spacer retainment, one-stage
Zhang et al35 conducted open tissue biopsy before revi- or two-stage revision arthroplasty, or resection arthro-
sion arthroplasty. The decision to proceed with the sec- plasty.38 Rondon et al21 retrospectively reviewed 17
ond stage relied on negative culture results. Those with patients treated with definitive antibiotic spacer place-
persistent infection were treated with an additional course ment and reported a mortality rate of 52.9% at a mean
of irrigation and débridement and antibiotic therapy. of 1.8 years after implantation. A reinfection rate of
A new addition to the range of diagnostic tools for PJI is 29.4% was found leading to spacer exchange in affected
the alpha-defensin synovial fluid biomarker assay. This test patients. In addition, this case series reported low
has a reported sensitivity of 63% and specificity of 95% for functional scores, with a mean American Shoulder and
the diagnosis of shoulder PJI and has the added advantage Elbow Score of 33.9 and a Single Assessment Numeric
of being unaffected by previous antibiotic administra- Evaluation score of 35.6. Compared with patients who
tion.36 Although preoperative or intraoperative testing for underwent the second stage of the revision, the cohort
synovial alpha-defensin levels has been proposed as a with retained spacers had a higher comorbidity profile.
useful adjunct in the diagnosis of a painful shoulder ar- The authors concluded that definitive retention of
throplasty,36 no studies have reported its use to confirm antibiotic spacers should be considered in medically frail
infection eradication and to guide treatment decisions for patients with higher mortality risk, specifically.
the second stage of revision arthroplasty.

Complications of Antibiotic Spacers for

Outcomes of Retained Antibiotic Spacers Shoulder Periprosthetic Joint Infection
Small retrospective and prospective cohort studies have The use of antibiotic spacers for shoulder PJI is not
shown that low-demand patients who achieve satisfac- without risk. Complications may occur on spacer

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Antibiotic Spacers for Shoulder PJI

implantation, between implantation and explantation, shaft), four spacer fractures, three spacer rotations, and
during explantation, or in patients with retained im- three humeral shaft fractures. Four of the 10 patients
plants.16 Excessive amounts of distal cement during with retained antibiotic spacers experienced complica-
implantation of antibiotics spacers may result in more tions: three erosions of the humeral shaft and one
difficult spacer extraction during the second-stage pro- humeral shaft fracture; none required revision surgery
cedure. As such, for extraction purposes, it is preferred or removal. Spacer type (prefabricated versus silicone
to place the stem with only a small amount of proximal mold spacer) and the indication for spacer placement
cement placed after it has become moldable. At the time (infected nonarthroplasty versus infected arthroplasty)
of spacer implantation, fracture of the proximal were not associated with the type and pattern of spacer-
humerus may occur because of incongruity of the related complications.
implant with the humeral shaft.22 After spacer Systemic complications after antibiotic cement spacer
implantation, wear of the glenoid surface or humeral implantation are rare. Few cases of acute renal failure,
shaft, fracture of the humerus (Figure 3), fracture of the transient bone marrow suppression, and liver dysfunc-
spacer, implant instability or dislocation, and persistent tion have been reported in the hip and knee literature in
pain have been reported.11 At the time of spacer patients with measurable systemic concentrations of
explantation, greater tuberosity fracture, fracture of the vancomycin and aminoglycosides.39 Xu et al40 reported
humeral shaft, and fracture of the antibiotic spacer the first case of a widespread drug eruption (pruritic,
implant have occurred.11 maculopapular rash of torso and extremities) caused by
McFarland et al16 conducted the largest review of parenteral vancomycin in combination with a
antibiotic spacer–related complications among 53 pa- vancomycin-impregnated spacer inserted for a shoulder
tients (60 spacers) as part of a two-stage treatment PJI. Parenteral vancomycin was switched to clindamy-
plan for infection at the site of a shoulder arthroplasty cin, and the patient’s spacer was replaced with a
(n = 39), other (nonarthroplasty) shoulder surgery gentamicin spacer, resulting in symptom resolution, and
(n = 8), or primary shoulder infection without previous expected shoulder function at the final follow-up. Of
surgery (n = 6). After a mean interval of 6 months, 18 note, the patient was treated with DAIR initially and
complications were reported in 14 patients. All com- received multiple 1,000 mg injections of vancomycin by
plications occurred between spacer implantation and peripheral intravenous access for two weeks. It was
removal: eight bone erosions (6 glenoid and 2 humeral concluded that the elution properties of antibiotic
spacers are not a steady-state release and surgeons must
Figure 3 be mindful that the combination of parenteral and
intravenous vancomycin may result in unpredictable
serum concentrations.40

Authors’ Preferred Approach

We elect to conduct two-stage revision arthroplasty for
the treatment of shoulder PJI in cases where the infecting
organism is virulent or if an overt clinical sign of
infection, such as gross purulence or open sinus tract, is
present. We prefer to fabricate our shoulder spacers
intraoperatively with the use of commercially available
molds because these allow for the creation of press-fit
stems and the ability to control the antibiotic concen-
tration. After spacer implantation, patients are treated
with intravenous antibiotics for 6 weeks based on
culture-specific sensitivities. We then check ESR and
CRP levels and do a shoulder aspiration once intrave-
Radiograph showing spacer-related complication. AP nous antibiotics have been discontinued for a minimum
radiograph of the left shoulder showing a fracture of the
greater tuberosity of the proximal humerus between the time of 2 weeks. If serum markers remain elevated or if
of stemless cement ball spacer implantation and removal. cultures are positive, then repeat irrigation and

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 Surena Namdari, MD, MSc, et al

Review Article
débridement is done. If serum markers return to normal 7. Coste JS, Reig S, Trojani C, Berg M, Walch G, Boileau P: The
management of infection in arthroplasty of the shoulder. J Bone Joint Surg
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the second stage of revision at 10 to 12 weeks after the
8. Sperling JW, Kozak TK, Hanssen AD, Cofield RH: Infection after
placement of the antibiotic spacer. Five sets of intra- shoulder arthroplasty. Clin Orthop Relat Res 2001;382:206-216.
operative cultures are obtained at the time of re- 9. Dennison T, Alentorn-Geli E, Assenmacher AT, Sperling JW, Sanchez-
implantation. Patients are started on oral antibiotics Sotelo J, Cofield RH: Management of acute or late hematogenous infection
until these cultures finalize. If cultures are negative, then after shoulder arthroplasty with irrigation, debridement, and component
retention. J Shoulder Elbow Surg 2017;26:73-78.
oral antibiotics are discontinued. If positive, intravenous
10. Arenas-Miquelez A, Arbeloa-Gutierrez L, Familiari F, de Pablos J:
antibiotics are restarted for a 6-week duration followed
Salvage procedures of the shoulder: Glenohumeral arthrodesis and
by shared decision making regarding lifetime suppres- resection arthroplasty. Indian J Orthop 2021;55:27-37.
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Surg 2020;29:2476-2486.
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