The Journal Club

Synovial Fluid Biomarkers for

Periprosthetic Joint Infections

Abdulaziz F. Ahmed, MBBS

PGY-2

HGI-02-PHY-P139
No Conflict of Interest
Lee et al. The Journal of Bone & Joint Surgery
Volume 99; Number 24; December 20, 2017
Introduction
• Periprosthetic joint infections (PJI) after total joint
arthroplasty is catastrophic.

• The diagnosis relies on

• Clinical judgement
• Serologic testing
• Synovial fluid aspiration
• Radiographic assessment
• Microbiology and histopathology
Introduction
• Thus far, analysis limited to:
• Synovial fluid WBC
• WBC differential
• Culture

• NO SINGLE REFERENCE HAS BEEN

DEVELOPED!
Introduction
Characteristics of an ideal biomarker:

1. Accurate

2. Easy to identify

3. Quick to analyze

4. Cost effective to detect

Aims
In periprosthetic joint infections, to:

1. Evaluate the diagnostic accuracy of synovial fluid

biomarkers.

2. Evaluate which biomarker has the highest diagnostic

odds ratio (DOR).
Materials and Methods (Search Strategy)
• Adhered to the PRISMA guidelines.

• Databases:
• Medline; Embase; Cochrane database.

• Keywords:
• Total Joint Arthroplasty, total knee arthroplasty, total hip
arthroplasty,
• Periprosthetic infection
• Diagnostic test
 Materials and Methods (Eligibility)
• Inclusion
• Studies that evaluated synovial fluid biomarkers in knee
and/or hip PJI.
• Provided sensitivity and specificity values for biomarkers
• Only studies in English
• Studies after the year 2000.
• Studies evaluating diagnostic modalities
 Materials and Methods (Eligibility)
• Exclusion:
• Studies investigating non-synovial fluid biomarkers.

• Specimens obtained at reimplantation, serum markers, and

• intraoperative cultures were excluded.

• Studies that lacked sensitivity and specificity values

 Materials and Methods (Data Extraction)
• For a biomarker to be included:

1. Data on biomarker reported in >= 2 articles.

2. Biomarkers reported in 1 article were excluded.

Materials and Methods (Quality Assessment)
Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool
1. Domain 1: Patient Selection

2. Domain 2: Index Test

3. Domain 3: Reference Standard

4. Domain 4: Flow and Timing

Materials and Methods (Statistics)
• Meta-analyses for the diagnostic tests were performed using the MADA
package.

• MADA was used to generate forest plots for

• sensitivity
• specificity
• the log of the DOR

• The log DOR was used to compare the performances of the various tests.
Diagnostic odds ratio rapid review
What is diagnostic odds ratio (DOR)?

It’s a single indicator of a diagnostic test performance.

Used for comparison of diagnostic accuracies between two or more

diagnostic tests.

DOR depends significantly on the sensitivity and specificity of a test.

DOR does NOT depend on prevalence

Materials and Methods
In PJI, synovial fluid biomarkers included:

Leukocyte count PMN% CRP a-defensin

Leukocyte Culture IL-10 IL-8

esterase
IL-10 IL-1b VEGF G-CSF

PCR analysis
Results of the search
• Included 33 articles

• All were diagnostic studies.

• Level I (3), Level II (9), Level III (14), Level IV (7)

• 16 articles = TKA & THA

• 6 articles = THA & 11 articles = TKA

Results of the search
• More than 50 biomarkers were evaluates; 13 included.

• Out of the 13 biomarkers:

• 5 reported only in two articles
• 8 reported in more than two articles.

• Pooling and analysis was appropraite only for the 8 biomarkers.

• For a biomarker to be included, must be reported on 2 or more articles.

Forest plot rapid review
Area under the curve (AUC) rapid review
• The shape of a ROC curve and the area under the
curve (AUC) helps us estimate how high is the
discriminative power of a test.

• The closer the curve is located to upper-left hand

corner and the larger the area under the curve.

• The better the test is at discriminating between

diseased and non-diseased.

• A perfect diagnostic test has an AUC 1.0. whereas

a nondiscriminating test has an area 0.5.
Results
Results (Quality Assessment)

1. Domain 1: Patient Selection: Low bias; unclear bias

2. Domain 2: Index Test: Low bias; unclear bias

3. Domain 3: Reference Standard: Low bias; High bias

4. Domain 4: Flow and Timing: Low bias; unclear bias

 Conclusion
• a-defensin was the best synovial fluid marker for diagnosing PJI
based on the highest log DOR.

• Culture had the most inferior diagnostic performance.

• Except for culture, each test had a sensitivity of

• > 0.8. The specificity of each test was > 0.9.

• Therefore, all synovial fluid biomarkers in our meta-analysis

appeared useful for the diagnosis of PJI.
Critical appraisal
1. Was the research question clear?

• 2. Is it likely that all relevant studies (published and unpublished)

were identified?

• 3. Were the criteria used to select articles for inclusion

predetermined, clearly stated, and appropriate?

• 4. Were the included studies sufficiently valid?

Critical appraisal (cont.)

5- Were studies selected and data extracted by 2 or more

individuals.

6- Were the results similar from study to study?

7- Conflict of Interest.
Critical appraisal (cont.)
8- Clinical Importance?

9- How are the results presented?

 Thank you
A Friendly Reminder
Suspected septic arthritis of any joint
(Monoarthritis; Native Joint; age>= 18)

Please call me or Motasem