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Perioperative Testing for Joint Infection in Patients Undergoing Revision Total Hip Arthroplasty
Mark F. Schinsky, MD1; Craig J. Della Valle, MD2; Scott M. Sporer, MD2; Wayne G. Paprosky, MD2
1 Castle Orthopaedics and Sports Medicine, S.C., 2111 Ogden Avenue, Aurora, IL 60504., E-mail address: mfs@castleortho.com
2 Midwest Orthopaedics at Rush, Rush University Medical Center, 1725 West Harrison Street, Suite 1063, Chicago, IL 60612
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from Zimmer in the form of statistical analysis. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits or a commitment or agreement to provide such benefits from commercial entities in excess of $10,000 (Zimmer) and less than $10,000 (Stryker, Smith and Nephew). Also, a commercial entity (Zimmer) paid or directed in any one year, or agreed to pay or direct, benefits in excess of $10,000 to a research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which one or more of the authors, or a member of his or her immediate family, is affiliated or associated.
Investigation performed at Midwest Orthopaedics at Rush, Rush University Medical Center, and Central DuPage Hospital, Chicago, Illinois

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2008 Sep 01;90(9):1869-1875. doi: 10.2106/JBJS.G.01255
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Abstract

Background: While multiple tests are used to determine the presence of infection at the site of a total hip arthroplasty, few studies have applied a consistent algorithm to determine the utility of the various tests that are available. The purpose of the present study was to evaluate the utility of commonly available tests for determining the presence of periprosthetic infection in patients undergoing revision total hip arthroplasty.

Methods: Two hundred and thirty-five consecutive total hip arthroplasties in 220 patients were evaluated by one of two surgeons using a consistent algorithm to identify infection and were treated with reoperation. Receiver-operating-characteristic curve analysis was used to determine the optimal cut-point values for the white blood-cell count and the percentage of polymorphonuclear cells of intraoperatively aspirated hip synovial fluid. Sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were determined. Patients were considered to have an infection if two of three criteria were met; the three criteria were a positive intraoperative culture, gross purulence at the time of reoperation, and positive histopathological findings.

Results: Thirty-four arthroplasties were excluded because of the presence of a draining sinus, incomplete data, or a preoperative diagnosis of inflammatory arthritis, leaving 201 total hip arthroplasties available for evaluation. Fifty-five hips were judged to be infected. No hip in a patient with a preoperative erythrocyte sedimentation rate of <30 mm/hr and a C-reactive protein level of <10 mg/dL was determined to be infected. Receiver-operating-characteristic curve analysis of the synovial fluid illustrated optimal cut-points to be >4200 white blood cells/mL for the white blood-cell count and >80% polymorphonuclear cells for the differential count. However, when combined with an elevated erythrocyte sedimentation rate and C-reactive protein level, the optimal cut-point for the synovial fluid cell count was >3000 white blood cells/mL, which yielded the highest combined sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the tests studied.

Discussion: A synovial fluid cell count of >3000 white blood cells/mL was the most predictive perioperative testing modality in our study for determining the presence of periprosthetic infection when combined with an elevated preoperative erythrocyte sedimentation rate and C-reactive protein level in patients undergoing revision total hip arthroplasty.

Level of Evidence: Diagnostic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    References

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Mark F. Schinsky, MD
    Posted on January 06, 2010
    Dr. Schinsky and colleagues respond to Drs. Liao and Lin
    Castle Orthopaedics & Sports Medicine, S.C., Aurora, Illinois

    We appreciate the insight shared on our recent publication, "Perioperative Testing for Joint Infection in Patients Undergoing Revision Total Hip Arthroplasty" (1). We regret any confusion in the review of Tables IV and V related to the set of statistical parameters (i.e., sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) we presented. In Table IV, the parameters of concern corresponded to the dichotomy of synovial fluid white blood cell (WBC) counts at a cut-point of >4200, the value which maximized the magnitudes of statistical parameters when cross-classified erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) information was ignored. Similarly, in Table V the parameters of concern corresponded to dichotomies of synovial fluid WBC counts at cut-points of >3000 and >9000, values which corresponded to maxima in statistical parameters for the respective groups:

    1. All patients (N=79) who had both an elevated erythrocyte sedimentation rate (ESR; >30 millimeters per hour) and an elevated C-reactive protein level (CRP; >10 milligrams per liter).

    2. All patients (n=60) who had an elevated ESR (>30 millimeters per hour) who did not have an elevated CRP level (10 milligrams per liter) who did not have an elevated ESR (

    We defined our analysis subgroups summarized in Table V on page 1873 of our paper. Results from a third group of patients, those with ESR and CRP levels at or below elevation (i.e., ESR

    We reported that a synovial fluid WBC cut-point of >3,000 maximized the statistical parameters for the group with elevations in both ESR and CRP. This cut-point was lower than the "marginal" synovial fluid WBC cut-point of >4,200. For the group with elevations in ESR or CRP (but not both) we reported that a synovial fluid WBC cut-point of >9,000 maximized the statistical parameters. Thus, the synovial fluid WBC cut-point decreased going from an elevation of ESR or CRP to an elevation of both ESR and CRP (e.g., going from "or" to "and"). As there was no benefit in considering WBC in patients without ESR and CRP elevations, differential dependencies between ESR, CRP, and WBC support the need for sequential preoperative testing: ESR and CRP level followed by synovial fluid WBC count.

    We viewed the infection rates at synovial fluid WBC >3000 and synovial fluid WBC >9000 in the absence of ESR and CRP unnecessary, holding a view similar to that expressed by McCullough and Nelder (2) on "nuisance parameters". We felt these parameters were largely irrelevant to the conclusions. When the synovial fluid WBC was examined independently of ESR, CRP, and other clinical parameters we chose to report the parameters at a cut-point of >4200, the cut-point at which statistical parameters were at maxima (Table IV).

    We provide the summaries of statistical parameters at synovial fluid WBC cut-points of >3,000 and >9,000 in Table 1.

    TABLE 1 Diagnostic Test Characteristics for All Patients
    Test Sensitivity Specificity PPV NPV Accuracy
    Synovial Fluid WBC Count >3,000 89%
    (81%,97%)
    88%
    (83%,94%)
    75%
    (64%,85%)
    96%
    (92%,99%)
    89%
    (84%,93%)
    Synovial Fluid WBC Count >9,000 73%
    (62%,85%)
    97%
    (95%,100%)
    89%
    (83%,99%)
    90%
    (86%,95%)
    91%
    (87%,95%)
    () = Values given in parentheses are the 95% confidence intervals.

    Given the group definitions provided, the marginal statistical parameters provided above can not be compared against the statistical parameters we presented in Table V. This is because the summaries we present above have included patients both without elevated ESR and without elevated CRP levels. The addition of these patients has increased misclassification and led to lower statistical parameters. This explains why a seemingly "paradoxical" increase in statistical parameters was obtained in stratified analyses.

    We appreciate Dr. Liao's concern regarding the statistical parameters we presented in Table VI. This table contained errors missed during review. We provide the correction for the table representing "Synovial fluid WBC differential >80% PMN" in Table 2.

    TABLE 2 Diagnostic Test Characteristics for Hip Aspirate WBC Count Differential Greater Than 80% PMNs as Related to Elevated Erythrocyte Sedimentation Rate and C-Reactive Protein
    ESR and CRP Status Sensitivity Specificity PPV NPV Accuracy
    All Patients 84%
    (74%,93%)
    82%
    (76%,89%)
    65%
    (54%,76>%)
    93%
    (88%,97%)
    83%
    (77%,88%)
    Elevated ESR and CRP 71%
    (52%,91%)
    92%
    (82%,100%)
    88%
    (73%,100%)
    80%
    (66%,94%)
    83%
    (72%,94%)
    () = Values given in parentheses are the 95% confidence intervals.

    During our further review of this manuscript, two additional areas for clarification were identified. First, the units reported for the synovial fluid white blood cell count were reported as being measured per mL (milliliter) when in fact, the accurate label is per uL (microliter). The second correction is regarding the units reported for the C-reactive protein level; these were reported in our manuscript as mg/dL when in fact, the appropriate label is mg/L. We apologize for these oversights.

    The additional information provided in Table 1 of this response and the corrections to Table VI (Table 2 of this response) do not affect our original conclusions. We maintain that a synovial fluid cell count of >3,000 white blood cells/uL was the most predictive perioperative testing modality for determining the presence of periprosthetic infection when combined with an elevated preoperative ESR and CRP level in patients undergoing revision total hip arthroplasty.

    References

    1. Schinsky MF, Della Valle CJ, Sporer SM, Paprosky WG. Perioperative testing for joint infection in patients undergoing revision total hip arthroplasty. J Bone Joint Surg Am. 2008;90:1869-75.

    2. McCullagh P, Nelder JA. Generalized linear models. 2nd ed. New York: Chapman and Hall; 1989.

    Yuan-Ya Liao
    Posted on November 29, 2009
    OR and AND Rules for Parallel Multiple Tests
    Chung Shan Medical University Hospital, Taichung, Taiwan

    To the Editor:

    We read with great interest the well-written article entitled, "Perioperative Testing for Joint Infection in Patients Undergoing Revision Total Hip Arthroplasty" by Schinsky et al (1). We were confused while reading the results of Tables V and VI. According to the laws of probability and set theory, the union is greater than or equal to the intersection. We noticed that the authors reported the numbers of patients with both elevated ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) levels (n = 79) are greater than the numbers of patients with either elevated ESR or CRP levels (n = 60). Besides, the authors did not provide the sensitivities and specificities of synovial fluid white blood cells (WBC) count > 3000 WBC/mL and > 9000 WBC/mL, respectively, which makes utilization, recalculation, and confirmation of their diagnostic test results difficult. Furthermore, on Tables V and VI, we observe strange results contrary to the general principles while utilizing multiple tests. Given two parallel tests, A and B, assuming the sensitivity and specificity of one test are independent of the results of the other test. There are two methods in which the tests can be combined in parallel (2): The OR rule, in which the diagnosis is positive if either A or B is positive. Both A and B must be negative for the diagnosis to be negative. The AND rule, in which the diagnosis is positive if both A and B are positive. Either A or B can be negative for the diagnosis to be negative. With the OR rule, the sensitivity of the combined result is higher than either test individually, but the specificity is lower than either test individually. With the AND rule, specificity is higher than either test individually, but the sensitivity is lower than either test individually. However, the authors reported otherwise on Tables V and VI. Between Tables IV and VI, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy are different for all patients (n = 201) concerning WBC differential of > 80% polymorphonuclear cells. We hope the authors can clarify and correct the proofreading errors.

    The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

    References

    1. Schinsky MF, Della Valle CJ, Sporer SM, Paprosky WG. Perioperative testing for joint infection in patients undergoing revision total hip arthroplasty. J Bone Joint Surg Am. 2008;90:1869-75.

    2. Zhou XH, Obuchowski NA, McClish DK. Statistical methods in diagnostic medicine. New York: Wiley-Interscience; 2002. p 15-56.

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