TWO STAGE ARTHROPLASTY FOR PRIMARY SEPTIC HIP JOINT ARTHRITIS

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Master thesis

Lithuanian University of Health Sciences

Faculty of Medicine

Department of Orthopedics

Kaunas, 2020

TWO STAGE ARTHROPLASTY FOR

PRIMARY SEPTIC HIP JOINT ARTHRITIS

Author:

Siawash Wejdan

Medical Student, 6th Course

Supervisor:

Linas Zeniauskas

Assistant

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1. SUMMARY

Background and purpose: Septic arthritis of native hip joint is one of the most devastating diseases of musculoskeletal system which has detrimental effects on patient function, long term outcomes and quality of life. One of the treatment options for this disease is total hip arthroplasty (THA). THA can be performed as one or two stage stages procedure in patients with current or previous history of septic arthritis of native hip joint. Although one-stage total hip arthroplasty is considered to be a safe procedure for selected septic hip arthritis patients by some authors, two stage total hip arthroplasty is still considered to be a more effective and safer treatment method of primary infectious arthritis of the hip. But some questions remain unanswered regarding this treatment method: such as time between two stages or should temporary spacers be used and what type of spacers and etc. Therefore, the purpose of this paper is to analyze available literature with two-stage THA in patients with septic arthritis of native hip joint with special focus on factors that can affect treatment outcomes.

Search strategy: The search was conducted using PubMed and Google Scholar search engine, for articles that met selection criteria. Search was performed during September 2019 and December 2019.

Selection criteria: Scientific articles and studies (unlimited time period) that analyze the treatment of native hip joint arthritis with two stage total hip arthroplasty. This review does not include publications with in vitro or animal studies.

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2. ACKNOWLEDGEMENTS

I would like to pay my special regards to my supervisor Dr. Linas Zeniauskas for being there and lending me a helping hand and making it possible for me to write this thesis.

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3. CONFLICT OF INTERESTS

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4. ABBREVIATIONS LIST

❏ THA Total Hip Arthroplasty

❏ MA Monoarticular

❏ PA Polyarticular

❏ PMN Polymorphonuclear

❏ CT Computed Tomography

❏ MRI Magnetic Resonance Imaging ❏ S. AUREUS Staphylococcus Aureus ❏ M. TUBERCULOSIS Mycobacterium Tuberculosis

❏ MSSA Methicillin Sensitive Staphylococcus Aureus ❏ MRSA Methicillin Resistant Staphylococcus Aureus ❏ HHS Harris Hip Score

❏ CRP C-Reactive Protein

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5. TERMS

❏ Arthroplasty: surgical reconstruction or replacement of a joint which restores function and relieves pain.

❏ Septic arthritis: also known as infectious arthritis or joint infection, invasion of an infectious agent to the joint which results in joint inflammation.

❏ Arthrocentesis: procedure in which synovial fluid is obtained from the joint via needle puncture.

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6. INTRODUCTION

Septic arthritis, also known as infectious arthritis, is an infection of the joint. It can be caused by variety of microorganisms such as viruses or fungi, but the most predominant causative organisms are bacteria. Septic arthritis can affect any joint, however most commonly it manifests in large joints, especially knee and hip. Infectious process can be limited to only one joint (mono-articular) or can involve multiple joints (poly-(mono-articular). Septic arthritis, although uncommon, is a very severe orthopedic emergency, which if left untreated, leads to joint damage, so early diagnosis and prompt treatment are crucial for the patient.

Pathophysiology of septic arthritis is clearly described in literature. Normally joint space is sterile and for infection to manifest, bacteria have to breach natural barriers to invade a joint.

There are three main ways of bacterial dissemination to a joint: by blood (from a distant focus), directly (threw skin and soft tissues – during injuries or interventions/surgical procedures) or per continuum (direct spread from another infectious focus – osteomyelitis, cellulitis). Bacteria invade the synovium and the joint space, afterwards the immune response leads to local and systemic inflammation which activates the release of cytokines and proteases which together with bacterial toxins, lead to the destruction and damage of the joint cartilage, surrounding soft tissues and in severe and prolonged cases – even bone destruction.

The most common and classical symptoms of septic arthritis can be divided into two main groups:

1) Local symptoms (redness, warmth, swelling, pain, loss of function).

2) Non-specific systemic symptoms (fever, fatigue, tachycardia, irritability, decreased appetite, etc.).

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Gold standard for diagnosing septic arthritis is the analysis of synovial fluid. Synovial fluid is taken from the joint by needle aspiration (with help of ultrasound or X-ray guidance). The fluid is sent to laboratory for culturing, crystal analysis, Gram stain, white blood cell count and differentiation (polymorphonuclear (PMN) percentage). Septic arthritis is diagnosed when white blood cell count in synovial fluid is >50 x 10^3 /µl and PMN consist > 75% of all cells.

Imaging studies are useful in choosing the right treatment method. Main modalities of imaging of septic arthritis are: plain radiographs, ultrasonography, CT and MRI. X-rays are helpful in revealing widened joint space, bulging of the soft tissues and bony changes. Ultrasound, is useful in identifying and quantifying joint effusion as well as aiding in needle aspiration of the joint.

CT (with or without i/v contrast) can help in distinguishing joint abnormalities from periarticular pathologies and also can aid in quantifying bone damage due to septic process. MRI is the most sensitive of the imaging modalities for early detection of joint inflammation and bone marrow abnormalities which are usually not detectable in other imaging studies, but main disadvantage – it’s not widely available (1–3).

Management of septic arthritis, is usually started with a more conservative method. So prompt treatment is the key to success. The mainstay of treatment of early septic arthritis is immediate removal of purulent material from the joint in conjunction with rational antibiotic therapy. The choice of empirical antibiotics depends from various different factors, such as local susceptibility to antibiotics, resistances, usual pathogens and so on. Most often septic arthritis is caused by gram positive organisms, so empiric treatment always should cover these organisms. The specific antibiotic treatment is always tailored to the results of synovial fluid and soft tissue cultures (3, 4). I will not go into details of specific suggested antibiotic regimens, since the focus of this analysis is the surgical management of septic arthritis, not the conservative treatment. Removal of all infected tissues from the joint space is mandatory for successful treatment of a septic native joint. This can only be achieved surgically (by open debridement or arthroscopy).

Arthroscopic debridement is usually enough in the early stages of serous synovitis. But in the later stages with already enzymatic destruction of the articular cartilage open arthrotomy, with or synovectomy is indicated.

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7. AIM & OBJECTIVES

7.1 Aim:

Analyze efficacy of two-stage THA and its specific treatment strategy factor effect on outcomes on treatment of septic arthritis of native hip joint.

7.2 Objectives:

1) Perform systematic search of literature using different databases to identify articles and publications relevant to the main thesis.

2) Evaluate treatment outcomes of two stage arthroplasty by using revision surgery or reinfection as a treatment failure.

3) Evaluate the effect of cement spacer and its type on treatment outcomes.

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8. RESEARCH METHODOLOGY & METHODS

Article eligibility: Scientific articles and studies (unlimited time period) that analyze the treatment of native hip joint arthritis with two stage total hip arthroplasty. This review does not include publications with in vitro or animal studies. Only full text articles in English language were included.

Article search strategy: The search was conducted using PubMed and Google Scholar search engine, for articles that met selection criteria. Search was performed during September 2019 and December 2019. Keywords and their combinations used: (“two stage”, arthroplasty, “septic arthritis”, “hip joint”, “native joint”, ''THA”) 435 articles were identified. After assessing eligibility only 15 full text articles were selected for final analysis.

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9. LITERATURE REVIEW

9.1 Table No.1

M – Male. F – Female. NR – not reported.

Study No. of cases (gender) Age (years) Causing microorganism (most common) Cement spacer Antibiotic therapy duration Mean interval between stages

Implant fixation at 2nd_stage

Mean follow-up Success rate

(%) Failures No spacer Static spacer Dynamic spacer Additional

antibiotics Cemented Uncemented Hybrid

Bauer et al. 2010 13 M – NR F – NR 60 (29-92) S. aureus

37.5% 0 13 (NR) - 13 weeks) 1,3 months NR NR NR 60 months 85 Infection – 2 (15.4%)

Li et al. 2016 9 M – 5 F – 4 50 (32-70) M. tuberculosis 100% 5 0 4 Streptomycin

Vancomycin 52 weeks 3 months 1 7 1

40 months (18 – 72) 100 0 Huang et al. 2008 15 M – 9 F – 6 54 (29-78) S. aureus 53.3% 0 0 15 Vancomycin

Aztreonam 1 week 3 months 0 15 0

42.5 months (25 - 72) 92.3 Infection – 1 (6.7%) Papanna et al. 2017 11 M – 11 F – 7 58 (±11) S. aureus 64% 0 11 0 Vancomycin NR 4 months (3 – 5) 7 (67%) 4 (33%) 0 70 months (13 – 120) 100 0 Fleck et al. 2011 14 M – 7 F – 7 61 (45-87) S. aureus 57% 0 0 16 Tobramycin Vancomycin 6 weeks 10 months (2 – 36) NR NR NR 50 months (13 – 107) 92.9 Infection – 1 (7.1%) Cho et al. 2017 10 M – 6 F – 4 47 (24-69) S. aureus 40% 0 0 10 Vancomycin

Cefazedone >3 weeks 3,3 months NR NR NR

44.9 months (15 – 95) ₁₀₀ 0 Chen et al. 2007 33 M – 22 F – 6 53 (27-75) S. aureus 42.4% 19 14 0 - 4 – 6 weeks 3,6 months (1 – 7) 15 8 10 77 months (30 - 151) 86 Infection – 4 (14%) Kelm et al. 2009 8 M – 4 F – 4 66 (52-77) S. aureus

62.5% 0 0 8 Vancomycin 6 weeks 3,5 months 0 0 8 13 months 100 0

Diwanji et al. 2007 9 M – 5 F – 4 52 (23-81) S. aureus

55.6% 0 0 9 Vancomycin NR 5,5 months 0 7 2 42 months 98.9

Infection – 1 (11.1%) Anagnostakos et al 2016 22 M – 11 F – 11 60 (32-78) S. aureus

73% 0 0 22 Vancomycin 6 weeks 3 months 6 2 7

44.8 months

(12 - 120) 87

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Romano et al. 2011 20 M – 9 F – 11 53 (32-77) S. aureus 50% 0 0 20 Vancomycin 5 weeks (4 – 6) 5 months 0 20 0 56.6 months (24 – 104) 95 Infection – 1 (5%) Shen et al. 2013 5 M – 2 F – 3 48 (35-62) S. aureus

40% 0 0 5 Vancomycin 6 weeks 4 months) 0 5 0

39.6 months

(30 - 59) 100 0

Regis et al. 2010 M 73 S. aureus 0 0 1 Vancomycin 6 weeks 2 months 0 1 0 24 months 100 0

Mahmud et al. 2012 18 M – 11 F – 7 54 (25-74) S. aureus 56% NR NR NR NR NR 35.4 months (3 - 120) NR NR NR NR NR NR

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9.2 OVERVIEW OF RESULTS

From all 15 articles analyzed, 4 of them are dated under 2010 and rest are all over 2010 and pretty recent. Comparing the dates of these outdated articles and the success rate of the procedure after follow up, it is visible that the older the studies, the lower the success rate, however, there exists exceptions with the new studies, for example Anagnostakos et al. (5) is a study from 2016 but the success rate of only 87%. It is also important to mention that the sample size of most of these studies are very small. Only two of the studies have a sample size of more than 20 patients. The one with the highest sample size is 33 patients, but this study is one of the old ones which is from 2007. Furthermore, comparing the patients’ gender, it is seen that almost in all studies, it is comparable and balanced, except one study from 2007 by Chen et al. (6) with 22 males and 6 females only.

The average age of patients in almost all of the studies is almost around 50 or over 50 years of age, indicating the higher risk of susceptibility of hip joint infections in older age. Moreover, it is clearly seen on the table that s. aureus is the main microorganism which is the culprit for causing the infection in mostly all the studies, except one study by Li et al. (7) 2016 in which they study patients with tuberculosis infection only. Furthermore, s. aureus being the main culprit, it is important to mention that there were two strains of this microorganism, MSSA and MRSA. MSSA was even though the most common strain, there were some studies with MRSA cases, for example a study by Romano et al. (8) in 2011, of 19 patients 4 of them were infected with MRSA. In addition, another study by Fleck et al. (9) in 2011, showed 3 patients involved with MRSA of 14 cases studied.

Additionally, reviewing the cement spacer usage, the table shows that dynamic spacers are the ones used in most of the studies. Moreover, the main antibiotic used in these spacers is Vancomycin, which is used in some cases in combination with other antibiotics regardless of the type of the microorganism involved.

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only 6 months by Piolanti et al. (11) in 2018 which shows a 100% success rate, whereas the longest mean follow up is 77 months by Chen et al. (6) in 2007 with a success rate of 86%.

Treatment outcomes of two stage arthroplasty by using revision surgery or reinfection as a treatment failure

Study by Bauer T et al. (12) showed that two stage arthroplasty was successful in 26 out of 30 cases which makes it 87%. Moreover, there were no clinical, microbiological or treatment related criteria emerged as a risk factor for septic failure.

According to the study by Cho et al. (13) there was no complication related to femoral head spacer, recurrence of infection, neurologic symptoms, notable problems related to leg length, or dislocation in any of the cases with success rate of 100%.

Furthermore, in study by Li et al. (7) with the help of antituberculosis medication and antibiotic therapy for superimposed infection patients, the two stage total hip arthroplasty procedure provides a great opportunity for eradication of infection. So there was no reactivation of tuberculosis infection or superimposed infection was found in any of the patients. No patient demonstrated postoperative dislocation or neurological complications.

The results of study by Huang et al. (10) showed that after an average follow up of 42 months there was no recurrent infection evidence and the success of the treatment was by 93% infection eradication during the first procedure and 100% after an additional debridement and a subsequent total hip arthroplasty.

The conclusion of the study by Papanna et al. (14) showed that the outcome of two-stage and single-stage total hip arthroplasty for the treatment of septic hip active and quiescent arthritis was pretty much similar to the outcome of total hip arthroplasty for primary hip osteoarthritis.

Moreover, Anagnostakos et al. (5) studied two-stage protocol and spacer implantation in the treatment of destructive septic arthritis of the hip joint in 22 patients, with a mean follow-up of 44.8 (12–120) months, the primary infection control rate (after one spacer implantation) was 87 % (13/15) and the secondary infection control rate (after two spacer implantations) 100 %.

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hip arthroplasty using preformed spacers and cementless implants for prosthetic hip joint infections of various etiologies.

To wrap it up, in analyzed studies, success rate of two-stage arthroplasty by using revision surgery or reinfection as a treatment failure, ranged from 85% to 100%. It shows a high success rate despite different treatment strategies used (such antibiotic regime, microorganism, types of cement spacers used, and also taking into consideration the mean time interval used between the two stages).

Evaluation of the effect of cement spacer and its type to treatment outcomes

Fleck et al. (9) concluded that the use of an articulating antibiotic spacer in the treatment of a degenerative hip with active or recent sepsis, well controlled and eradicated infection with improvement of pain and function in both the period after the articulating spacer as well as after conversion to a total hip arthroplasty.

Despite the limitations in this study by Cho et al. (13) it showed that unique type of antibiotic-loaded cement spacer significantly reduced pain, controlled infection and improved function. Furthermore, it works as an effective antibiotic delivery system that maintains soft-tissue tension, limb length, and function during the interval period between initial surgical intervention and later conversion to total hip arthroplasty.

In another study, by Shen et al. (15) in 2013 five consecutive patients (5 hips) with infectious arthritis of the hip were treated in a 2-stage approach using an intraoperatively made medullary-sparing hip spacer. The results showed that infection was eradicated in all 5 patients. No infection and no specific complications were associated with the use of this novel spacer. Average Harris Hip Score increased dramatically and the success rate at latest follow up was 100%.

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predictable local release of antibiotics and a mechanically tested resistance that allows early partial weight bearing and immediate joint mobilization.

In essence, to evaluate the effect of cement spacer and it’s types to treatment outcome, it is essential to mention that only two studies reported usage of static spacers, and other two – no spacer usage. While all the other studies used dynamic spacers. Functional outcome results could not be compared because in majority of the studies they were not reported. Because of the small sample of cases, effect cement spacer vs no cement spacer on treatment outcomes could not be seen.

Evaluation of the effect of time duration between two stages on treatment outcomes In study by Chen et al. (6) the time interval between these two procedures is an average of almost 4 months in order to be able to eradicate fully the bacteria from the hip joint. Even though the complication rate remains high, occurring 36% in this study, the authors still believe two-stage total hip arthroplasty remains a very important procedure in septic hip arthritis patients.

Even though, in this study by El-Ganzoury et al. (17) the time period between the two intervals is shorter, the improvement rate of these patients according to the Harris hip score are of at least 30 points.

Additionally, in the study by Kelm et al. (18) even if the duration of antibiotic-loaded spacers for some patients was only two months and for some patients 6 months with a mean of 3 months, in all cases an infection eradication could be achieved. The study concludes that antibiotic-loaded cement spacers are indicated in proximal femur infections, however, The mobility of patients between stages could be enhanced by improving the spacer's mechanical properties.

Furthermore, even though the duration between the two stages was almost 6 months in the study by Diwanji et al. (19) the outcome of the two stage arthroplasty for the treatment of primary septic arthritis provides highly satisfactory results which makes this procedure more preferred than the Girdlestone procedure described in 1926.

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removed and a preformed antibiotic loaded cement spacer was implanted. Postoperatively the patients received four months of a specific antibiotic therapy until the complete infection eradication was confirmed by the lab tests and by a scintigraphy with marked leukocytes. Once the infection was completely eradicated, the patient underwent second stage arthroplasty. Clinical performance was evaluated using the Harris Hip Score (HHS) before surgery, after spacer implantation, after prosthesis implantation and afterward at each follow-up and the success rate was 100%.

Additionally, there is one study by Mahmud et al. (20) in 2012 with longest time duration between the two stages, which is 35,5 months, but unfortunately there is not enough data revealing the outcome of the treatment and success rate of the procedure.

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9. DISCUSSION OF RESULTS

535 articles were collected for the chosen search strategy. After making the names and after reviewing the abstracts and excluding duplicates, there were 24 articles left to be downloaded and read. All articles were in full text, in English. 9 articles did not meet the selection criteria, Therefore, only 15 publications were included in the final review (selection block diagram - annex No. 1).

Two-stage arthroplasty is one of the principle procedures in order to treat primary septic arthritis currently, but unfortunately there are not adequate studies done on this procedure. During my systematic search of articles on both Pubmed and Google Scholar, after removing duplicates and half text articles, I was only able to find 15 full text articles purely related to THA for primary septic hip arthritis. Besides, of those 15 articles, 8 of them are almost a decade old. It is important to mention that these studies are lengthy and last a great amount of time, usually with a mean follow up of many years before they come up with their results and conclusion. So there might be on-going studies on this topic right now, but these 15 articles are the only ones available presently for evaluation. Of course the more studies available, the more accurate our analysis on this topic could have been.

On the other hand, another main factor worth mentioning is the sample size of these studies. The size of the sample dictates the amount of information we have and therefore, in part, determines the precision or level of confidence that we have in our sample estimates. The sample sizes of these studies are quite small, most of them are less than 20 cases. Hence smaller sample sizes undermine the internal and external validity of the study. With the exception of that, the sample sizes we have in these studies are moderately sufficient to propose a conclusion.

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indicating the higher risk of susceptibility of hip joint infections in older age. Furthermore, Methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis has emerged over the past years as an increasingly prevalent and serious infection. As it is observable and as mentioned in the results section, in two studies MRSA strain was more evident. In the study by Romano et al. (8) 4 patients who were infected with MRSA, all had post-osteosynthesis as common etiology. It was also engaging to note that most of the patients with MRSA were male gender. Although MRSA is always a tough infection to tackle, it was addressed efficiently with a combination of antibiotics which MRSA was susceptible to.

The duration of intravenous/oral antibiotic therapy post operatively is very inconsistent. There was no specific rule stating how long exactly antibiotic therapy should be continued for. I suppose the duration of antibiotic therapy was really dependent on the outcome of the surgery and condition of each patient individually.

When it comes to the outcome of treatment of two stage arthroplasty when using revision surgery or reinfection as treatment failure, the outcome of mostly all studies were more or less successful. It is vital to mention that the success of treatment was roughly dependent on the duration of the follow up. The longer the follow up, the lesser the complications. Also the reinfection or revision surgeries were not as a result of poor technique of the procedure, but more related to individual circumstances and factors of individual patients.

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10. CONCLUSION

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11. LITERATURE LIST

1. Momodu II, Savaliya V. Septic Arthritis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 [cited 2019 Oct 25]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK538176/

2. Brennan MB, Hsu JL. Septic Arthritis in the Native Joint. Curr Infect Dis Rep. 2012 Oct 1;14(5):558–65.

3. Lee J-M. The Current Concepts of Total Hip Arthroplasty. Hip Pelvis. 2016 Dec;28(4):191–200.

4. Mathews CJ, Kingsley G, Field M, Jones A, Weston VC, Phillips M, et al. Management of septic arthritis: a systematic review. Ann Rheum Dis. 2007 Apr;66(4):440–5.

5. Anagnostakos K, Duchow L, Koch K. Two-stage protocol and spacer implantation in the treatment of destructive septic arthritis of the hip joint. Arch Orthop Trauma Surg. 2016 Jul 1;136(7):899–906.

6. Chen C-E, Wang J-W, Juhn R-J. Total hip arthroplasty for primary septic arthritis of the hip in adults. Int Orthop. 2008 Oct;32(5):573–80.

7. Li L, Chou K, Deng J, Shen F, He Z, Gao S, et al. Two-stage total hip arthroplasty for patients with advanced active tuberculosis of the hip. J Orthop Surg [Internet]. 2016 Mar 30 [cited 2019 Oct 20];11. Available from:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812611/

8. Romanò CL, Romanò D, Meani E, Logoluso N, Drago L. Two-stage revision surgery with preformed spacers and cementless implants for septic hip arthritis: a prospective, non-randomized cohort study. BMC Infect Dis. 2011 May 16;11:129.

9. Fleck EE, Spangehl MJ, Rapuri VR, Beauchamp CP. An Articulating Antibiotic Spacer Controls Infection and Improves Pain and Function in a Degenerative Septic Hip. Clin Orthop. 2011 Nov;469(11):3055–64.

10. Huang T-W, Huang K-C, Lee P-C, Tai C-L, Hsieh P-H. Encouraging outcomes of staged, uncemented arthroplasty with short-term antibiotic therapy for treatment of recalcitrant septic arthritis of the native hip. J Trauma. 2010 Apr;68(4):965–9.

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case report. Int J Surg Open. 2018 Jan 1;12:1–4.

12. Bauer T, Lacoste S, Lhotellier L, Mamoudy P, Lortat-Jacob A, Hardy P. Arthroplasty following a septic arthritis history: A 53 cases series. Orthop Traumatol Surg Res. 2010 Dec 1;96(8):840–3.

13. Cho YJ, Patel D, Chun YS, Shin WJ, Rhyu KH. Novel Antibiotic-Loaded Cement Femoral Head Spacer for the Treatment of Advanced Pyogenic Arthritis in Adult Hip. J

Arthroplasty. 2018 Jun 1;33(6):1899–903.

14. Papanna MC, Chebbout R, Buckley S, Stockley I, Hamer A. Infection and failure rates following total hip arthroplasty for septic arthritis: a case-controlled study. Hip Int J Clin Exp Res Hip Pathol Ther. 2018 Jan;28(1):63–7.

15. Shen H, Wang QJ, Zhang X long, Jiang Y. Novel Articulating Medullary-sparing Spacer for the Treatment of Infectious Hip Arthritis. Orthopedics. 2013 Apr 1;36(4):e404–8. 16. Regis D, Sandri A, Rizzo A, Bartolozzi P. A preformed temporary antibiotic-loaded cement

spacer for the treatment of destructive septic hip arthritis: a case report. Int J Infect Dis. 2010 Mar 1;14(3):e259–61.

17. El-Ganzoury I, Eid AS. Two-stage arthroplasty using functional temporary prosthesis to treat infected arthroplasty and septic arthritis of the hip. J Orthop. 2014 May 28;12(Suppl 1):S86–93.

18. Kelm J, Bohrer P, Schmitt E, Anagnostakos K. Treatment of proximal femur infections with antibiotic-loaded cement spacers. Int J Med Sci. 2009 Sep 3;6(5):258–64.

19. Diwanji SR, Kong IK, Park YH, Cho SG, Song EK, Yoon TR. Two-stage reconstruction of infected hip joints. J Arthroplasty. 2008 Aug;23(5):656–61.

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