The combined evaluation of fibrinogen and D‐dimer levels are a helpful tool to exclude periprosthetic knee infection

Balato, Giovanni; Ascione, Tiziana; Festa, Enrico; Vecchi, Elena De; Pagliano, Pasquale; Pellegrini, Antonio; Pandolfo, Giuseppe; Siciliano, Roberta; Logoluso, Nicola

doi:10.1002/jor.25515

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…Based on previous investigations, serum D-dimer levels are considered helpful in differentiating aseptic failure from PJI in patients without thrombosis or hypercoagulation disorders 5,9,[39][40][41] . In such patients, D-dimer levels have a diagnostic value comparable with those of CRP and ESR levels.…”

Section: Discussionmentioning

confidence: 99%

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange

Ascione,

Balato,

Festa

et al. 2024

Journal of Bone and Joint Surgery

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Background: This study evaluated appropriate thresholds for serum biomarkers, synovial fluid white blood cell (SF-WBC) count, and synovial fluid neutrophil (polymorphonuclear leukocyte [PMN]) percentage to predict infection in a patient group who underwent definitive reimplantation after receiving a continuous course of antibiotic therapy for chronic knee periprosthetic joint infection (PJI). These thresholds were then used to generate a scoring system to predict recurrence (or persistence) of infection. Methods: The study included 153 patients with a median age of 73 years (range, 46 to 91 years) who underwent 2-stage revision for chronic knee PJI. Staphylococci were identified at baseline in 107 (70%) of the patients. After the 96-week follow-up period, 12% (19) of the 153 patients had recurrence of the PJI. A receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of common serum biomarkers and SF aspiration before reimplantation, and the area under the curve (AUC) was evaluated. Variables that were significantly different between patients with and without infection recurrence were evaluated using a multivariable logistic regression model. A half-integer-point scoring system was created based on the final beta coefficients. Results: Regarding the prediction of recurrent infection, a D-dimer level of >1110 ng/mL yielded a sensitivity of 74%, specificity of 61%, and AUC of 0.69; an SF-WBC count of >934 cells/µL showed a sensitivity of 68%, specificity of 90%, and AUC of 0.79; and an SF-PMN percentage of >52% showed a sensitivity of 73%, specificity of 90%, and AUC of 0.82. The beta coefficients were approximated to 1.5 for the D-dimer level and to 2 for the SF-WBC count and SF-PMN percentage. A total score of >2 was used to classify patients with a high risk of infection recurrence. The ability to discriminate infection recurrence was demonstrated by an AUC of 0.90 (95% confidence interval: 0.82 to 0.99). Conclusions: Patients with a score of >2 on our proposed scoring system based on serum biomarkers, SF-WBC count, and SF-PMN percentage should not undergo reimplantation, as they are at a high risk for recurrent PJI. Patients with a score of ≤2 can undergo definitive reimplantation with the lowest risk of recurrence. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Section: Discussionmentioning

confidence: 99%

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange

Ascione,

Balato,

Festa

et al. 2024

Journal of Bone and Joint Surgery

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“…The use of serum biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer in distinguishing PJI from aseptic prosthetic implant loosening is well-established by MSIS-18 criteria. However, their role in guiding reimplantation remains a topic of debate [ 24 ]. Several studies report that CRP and ESR are not unequivocal biomarkers for assessing microbiologic eradication after implant removal in individuals undergoing a two-stage exchange procedure.…”

Section: Serum and Plasma Biomarkers At The Time Of Reimplantationmentioning

confidence: 99%

“…Moreover, further investigations have validated the role of serum D-dimer in ruling out a prosthetic infection, adopting a cutoff value higher than proposed by Shahi et al. [ 24 , 27 – 29 ]. In a study involving 125 patients with aseptic loosening or PJI of a knee implant, D-dimer dosage at a different cutoff was found to be more accurate than ESR and CRP in diagnosing PJI [ 24 ].…”

Section: Serum and Plasma Biomarkers At The Time Of Reimplantationmentioning

confidence: 99%

“…[ 24 , 27 – 29 ]. In a study involving 125 patients with aseptic loosening or PJI of a knee implant, D-dimer dosage at a different cutoff was found to be more accurate than ESR and CRP in diagnosing PJI [ 24 ]. Additionally, there is limited research exploring the predictive value of serum D-dimer in identifying the patients at the highest risk of recurrence during the two-stage exchange procedure [ 30 ].…”

Section: Serum and Plasma Biomarkers At The Time Of Reimplantationmentioning

confidence: 99%

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Upcoming evidence in clinical practice of two-stage revision arthroplasty for prosthetic joint infection

Ascione,

Balato,

Pagliano

2024

J Orthop Traumatol

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Total joint arthroplasty is the recommended treatment for patients with end-stage osteoarthritis, as it reduces disability and pain and restores joint function. However, prosthetic joint infection is a serious complication of this procedure, with the two-stage exchange being the most common treatment method. While there is consensus on diagnosing prosthetic joint infection, there is a lack of agreement on the parameters that can guide the surgeon in performing definitive reimplantation in a two-stage procedure. One approach that has been suggested to improve the accuracy of microbiologic investigations before definitive reimplantation is to observe a holiday period from antibiotic therapy to improve the accuracy of cultures from periprosthetic tissues, but these cultures report some degree of aspecificity. Therefore, several pieces of evidence highlight that performing reimplantation using continuous antibiotic therapy should be considered a safe and effective approach, leading to higher cure rates and a shorter period of disability. Dosage of C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer are helpful in diagnosing prosthetic joint infection, but only D-dimer has shown sufficient accuracy in predicting the risk of infection recurrence after a two-stage procedure. Synovial fluid analysis before reimplantation has been shown to be the most accurate in predicting recurrence, and new cutoff values for leukocyte count and neutrophil percentage have shown a useful predictive rule to identify patients at risk of unfavourable outcome. A new scoring system based on a numerical score calculated from the beta coefficient derived through multivariate analysis of D-dimer levels, synovial fluid leukocytes and relative neutrophils percentage has demonstrated high accuracy when it comes to guiding the second step of two-stage procedure. In conclusion, reimplantation may be a suitable option for patients who are on continuous therapy without local symptoms, and with CRP and ERS within the normal range, with low synovial fluid leukocytes (< 952/mL) and a low relative neutrophil percentage (< 52%) and D-dimer below 1100 µg/mL. A numerical score derived from analysing these three parameters can serve as a valuable tool in determining the feasibility of reimplantation in these patients.

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Synovial calprotectin in prosthetic joint infection. A systematic review and meta-analysis of the literature

Festa,

Ascione,

Di Gennaro

et al. 2024

Arch Orthop Trauma Surg

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Introduction Calprotectin is a protein endowed with antimicrobial properties, rendering it a distinctive marker for infection. Two methods are currently available for the assay of calprotectin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test (LFT). We aimed to assess the diagnostic accuracy of synovial fluid calprotectin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. Materials and methods We searched (from inception to November 2023) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on calprotectin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed. The receiver-operating curve for each method was calculated. Results We included 14 articles in our meta-analysis, including 902 patients who underwent total hip and knee arthroplasties revision; 331 (37%) had a joint infection according to MSIS, MSIS-modified criteria, ICM 2018 and EBJIS 2021. Considering the false-positive result rate of 6% and false-negative result rate of 7%, pooled sensitivity and specificity were 0.92 (95% CI 0.89–0.94) and 0.93 (0.91–0.95), respectively. The area under the curve (AUC) was 0.93 (95% CI 0.91–0.94). No statistical differences in terms of sensitivity and specificity were found between ELISA and LFT. The pooled sensitivity and specificity of the two calprotectin assessment methods were: LFT 0.90 (95% CI 0.869–0.935) and 0.92 (95% CI 0.894–0.941), respectively; ELISA 0.96 (95% CI 0.914–0.986) and 0.97 (95% CI 0.934–0.988), respectively. The diagnostic odds ratio of the ELISA was superior to that of the LFT (906.6667, 95% CI 271.2686–3030.3712 versus 113.8886, 95% CI 70.4001-184.2414; p < 0.001). The AUC for ELISA and LFT was 0.968 (95% CI 0.944–0.984) and 0.915 (95% CI 0.895–0.933), respectively. Conclusions Detection of synovial calprotectin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two calprotectin assessment methods is almost comparable. The LFT is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

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The combined evaluation of fibrinogen and D‐dimer levels are a helpful tool to exclude periprosthetic knee infection

Cited by 4 publications

References 36 publications

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange

Upcoming evidence in clinical practice of two-stage revision arthroplasty for prosthetic joint infection

Synovial calprotectin in prosthetic joint infection. A systematic review and meta-analysis of the literature

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