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Bone & Joint Research
Vol. 7, Issue 1 | Pages 12 - 19
1 Jan 2018
Janz V Schoon J Morgenstern C Preininger B Reinke S Duda G Breitbach A Perka CF Geissler S

Objectives. The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). Methods. The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus. Results. The 16s rDNA test proved to be very robust and was able to provide a result in 97% of all samples within 25 minutes. The 16s rDNA test was able to diagnose PJI with a sensitivity of 87.5% and 82%, and a specificity of 100% and 89%, in the proof-of-principle and validation cohorts, respectively. The microbiological culture of synovial fluid achieved a sensitivity of 80% and a specificity of 93% in the validation cohort. Conclusion. The 16s rDNA test offers reliable intraoperative detection of all bacterial species within 25 minutes with a sensitivity and specificity comparable with those of conventional microbiological culture of synovial fluid for the detection of PJI. The 16s rDNA test performance is independent of possible blood contamination, culture time and bacterial species. Cite this article: V. Janz, J. Schoon, C. Morgenstern, B. Preininger, S. Reinke, G. Duda, A. Breitbach, C. F. Perka, S. Geissler. Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study. Bone Joint Res 2018;7:12–19. DOI: 10.1302/2046-3758.71.BJR-2017-0103.R2


Bone & Joint Research
Vol. 10, Issue 10 | Pages 693 - 703
1 Oct 2021
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X

Aims. To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ). Methods. In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB). Results. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II, and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMD. SV. significantly increased aggrecan, collagen II, PPARγ, and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, and control groups. Conclusion. UTMDSV promotes cartilage extracellular matrix synthesis by modulating the PPARγ-mediated cholesterol efflux pathway in OA rabbits. Cite this article: Bone Joint Res 2021;10(10):693–703


Bone & Joint Research
Vol. 7, Issue 6 | Pages 388 - 396
1 Jun 2018
Langton DJ Sidaginamale RP Joyce TJ Bowsher JG Holland JP Deehan D Nargol AVF Natu S

Objectives. We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). Patients and Methods. We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties. Results. In the resurfacing cohort (n = 76), the statistical modelling indicated that the presence of severe ALVAL and a large fluid collection were associated with greater joint fluid Co concentrations after adjustment for volumetric wear rates (p = 0.005). These findings were replicated in the mixed implant group (n = 178), where the presence of severe ALVAL and a large fluid collection were significantly associated with greater fluid Co concentrations (p < 0.001). Conclusion. The development of severe ALVAL is associated with elevations in metal ion concentrations far beyond those expected from the volumetric loss from the prosthetic surfaces. This finding may aid the understanding of the sequence of events leading to soft-tissue reactions following MoM hip arthroplasties. Cite this article: D. J. Langton, R. P. Sidaginamale, T. J. Joyce, J. G. Bowsher, J. P. Holland, D. Deehan, A. V. F. Nargol, S. Natu. Aseptic lymphocyte-dominated vasculitis-associated lesions are related to changes in metal ion handling in the joint capsules of metal-on-metal hip arthroplasties. Bone Joint Res 2018;7:388–396. DOI: 10.1302/2046-3758.76.BJR-2018-0037


The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 177 - 184
1 Jun 2021
Uvodich ME Dugdale EM Osmon DR Pagnano MW Berry DJ Abdel MP

Aims. It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs. Methods. We retrospectively identified 27,066 primary TKAs performed between 2000 and 2019. Within 12 weeks, 169 patients (170 TKAs) had an aspiration. The patients were divided into two groups: those evaluated ≤ six weeks, or between six and 12 weeks postoperatively. The 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI diagnosis in 22 TKAs. The mean follow-up was five years (two months to 17 years). The results were compared using medians and Mann-Whitney U tests and thresholds were analyzed using receiver operator characteristic curves. Results. Within six weeks, the median CRP (101 mg/l vs 35 mg/l; p = 0.011), synovial WBCs (58,295 cells/μl vs 2,121 cells/μl; p ≤ 0.001), percentage of synovial neutrophils (91% vs 71% (p < 0.001), and absolute synovial neutrophil count (ANC) (50,748 cells/μl vs 1,386 cells/μl (p < 0.001) were significantly higher in infected TKAs. Between six and 12 weeks, the median CRP (85 mg/l vs 5 mg/l (p < 0.001)), ESR (33 mm/hr vs 14 mm/hr (p = 0.015)), synovial WBCs (62,247 cells/μl vs 620 cells/μl (p < 0.001)), percentage of synovial neutrophils (93% vs 54% (p < 0.001)), and ANC (55,911 cells/μl vs 326 cells/μl (p < 0.001)) were also significantly higher in infected TKAs. Optimal thresholds at ≤ six weeks were: CRP ≥ 82 mg/l (sensitivity 70%, specificity 77%), synovial WBCs ≥ 8,676 cells/μl (83%, 90%), percentage of synovial neutrophils ≥ 88% (67%, 78%), and ANC ≥ 8,346 cells/μl (83%, 91%). Between six and 12 weeks, thresholds were: CRP ≥ 34 mg/l (90%, 93%), synovial WBCs ≥ 1,983 cells/μl (80%, 85%), percentage of synovial neutrophils ≥ 76% (80%, 81%), and ANC ≥ 1,684 cells/μl (80%, 87%). Conclusion. Early PJI after TKA should be suspected within six weeks if the CRP is ≥ 82 mg/l, synovial WBCs are ≥ 8,676 cells/μl, the percentage of synovial neutrophils is ≥ 88%, and/or the ANC is ≥ 8,346 cells/μl. Between six and 12 weeks, thresholds include a CRP of ≥ 34 mg/l, synovial WBC of ≥ 1,983 cells/μl, a percentage of synovial neutrophils of ≥ 76%, and/or an ANC of ≥ 1,684 cells/μl. Cite this article: Bone Joint J 2021;103-B(6 Supple A):177–184


Bone & Joint Research
Vol. 9, Issue 12 | Pages 857 - 869
1 Dec 2020
Slullitel PA Coutu D Buttaro MA Beaule PE Grammatopoulos G

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article: Bone Joint Res 2020;9(12):857–869


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 39 - 45
1 Jan 2021
Fang X Cai Y Mei J Huang Z Zhang C Yang B Li W Zhang W

Aims. Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples. Methods. Between July 2014 and October 2019, patients with suspected joint infection (JI) from whom synovial fluid (SF) was obtained preoperatively were enrolled. Preoperative aspirated SF was analyzed by conventional microbial culture and mNGS. In addition to samples taken for conventional microbial culture, some samples were taken for intraoperative culture to optimize the culture method according to the preoperative mNGS results. The demographic characteristics, medical history, laboratory examination, mNGS, and culture results of the patients were recorded, and the possibility of the optimized culture methods improving diagnostic efficiency was evaluated. Results. A total of 56 cases were included in this study. There were 35 cases of JI and 21 cases of non-joint infection (NJI). The sensitivity, specificity, and accuracy of intraoperative microbial culture after optimization of the culture method were 94.29%, 76.19%, and 87.5%, respectively, while those of the conventional microbial culture method were 60%, 80.95%, and 67.86%, respectively. Conclusion. Preoperative aspirated SF detected via mNGS can provide more aetiological information than preoperative culture, which can guide the optimization and improve the sensitivity of intraoperative culture. Cite this article: Bone Joint J 2021;103-B(1):39–45


Bone & Joint Research
Vol. 9, Issue 5 | Pages 236 - 241
1 May 2020
Li R Wang C Ji X Zheng Q Li X Ni M Zhang G Chen J

Aims. The purpose of this study was to validate our hypothesis that centrifugation may eliminate false-positive leucocyte esterase (LE) strip test results caused by autoimmune diseases in the diagnosis of knee infection. Methods. Between January 2016 and May 2019, 83 cases, including 33 cases of septic arthritis and 50 cases of aseptic arthritis, were enrolled in this study. To further validate our hypothesis, another 34 cases of inflammatory arthritis from the Department of Rheumatology of our institution were also included. After aspiration, one drop of synovial fluid was applied to LE strips before and after centrifugation. The results were recorded after approximately three minutes according to the different colour grades on the colour chart. The differences of LE results between each cohort were analyzed. Results. Before centrifugation, 46% (23/50) of the LE strip tests in the aseptic arthritis group were false-positives. Most of the false-positive results were due to inflammatory arthritis; after centrifugation, 78.3% (18/23) of the tests yielded negative results. Similar results were observed in cases from the Department of Rheumatology. The sensitivity of the centrifuged LE strip test was 0.818 (0.639 to 0.924), which is still an acceptable level compared with the uncentrifuged results, which yielded a sensitivity of 0.909 (0.745 to 0.976). However, the specificity was increased from 0.540 (0.395 to 0.679) to 0.900 (0.774 to 0.963) after centrifugation. Conclusion. Although inflammatory arthritis can yield a false-positive LE strip test result in the diagnosis of knee infection, centrifugation may eliminate these false-positive results. Cite this article: Bone Joint Res. 2020;9(5):236–241


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 925 - 933
1 Jul 2016
Sidaginamale RP Joyce TJ Bowsher JG Lord JK Avery PJ Natu S Nargol AVF Langton DJ

Aims. We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. . Patients and Methods. We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. . Results. The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. Conclusion. The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925–33


The Bone & Joint Journal
Vol. 102-B, Issue 5 | Pages 593 - 599
1 May 2020
Amanatullah DF Cheng RZ Huddleston III JI Maloney WJ Finlay AK Kappagoda S Suh GA Goodman SB

Aims. To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). Methods. A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). Results. Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. Conclusion. The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593–599



The Bone & Joint Journal
Vol. 97-B, Issue 2 | Pages 173 - 176
1 Feb 2015
Omar M Ettinger M Reichling M Petri M Guenther D Gehrke T Krettek C Mommsen P

The aim of this study was to assess the role of synovial C-reactive protein (CRP) in the diagnosis of chronic periprosthetic hip infection. We prospectively collected synovial fluid from 89 patients undergoing revision hip arthroplasty and measured synovial CRP, serum CRP, erythrocyte sedimentation rate (ESR), synovial white blood cell (WBC) count and synovial percentages of polymorphonuclear neutrophils (PMN). Patients were classified as septic or aseptic by means of clinical, microbiological, serum and synovial fluid findings. The high viscosity of the synovial fluid precluded the analyses in nine patients permitting the results in 80 patients to be studied. There was a significant difference in synovial CRP levels between the septic (n = 21) and the aseptic (n = 59) cohort. According to the receiver operating characteristic curve, a synovial CRP threshold of 2.5 mg/l had a sensitivity of 95.5% and specificity of 93.3%. The area under the curve was 0.96. Compared with serum CRP and ESR, synovial CRP showed a high diagnostic value. According to these preliminary results, synovial CRP may be a useful parameter in diagnosing chronic periprosthetic hip infection. Cite this article: Bone Joint J 2015; 97-B:173–6


Objectives. Previously, we reported the improved transfection efficiency of a plasmid DNA-chitosan (pDNA-CS) complex using a phosphorylatable nuclear localization signal-linked nucleic kinase substrate short peptide (pNNS) conjugated to chitosan (pNNS-CS). This study investigated the effects of pNNS-CS-mediated miR-140 and interleukin-1 receptor antagonist protein (IL-1Ra) gene transfection both in rabbit chondrocytes and a cartilage defect model. Methods. The pBudCE4.1-miR-140, pBudCE4.1-IL-1Ra, and negative control pBudCE4.1 plasmids were constructed and combined with pNNS-CS to form pDNA/pNNS-CS complexes. These complexes were transfected into chondrocytes or injected into the knee joint cavity. Results. High IL-1Ra and miR-140 expression levels were detected both in vitro and in vivo. In vitro, compared with the pBudCE4.1 group, the transgenic group presented with significantly increased chondrocyte proliferation and glycosaminoglycan (GAG) synthesis, as well as increased collagen type II alpha 1 chain (COL2A1), aggrecan (ACAN), and TIMP metallopeptidase inhibitor 1 (TIMP-1) levels. Nitric oxide (NO) synthesis was reduced, as were a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS-5) and matrix metalloproteinase (MMP)-13 levels. In vivo, the exogenous genes reduced the synovial fluid GAG and NO concentrations and the ADAMTS-5 and MMP-13 levels in cartilage. In contrast, COL2A1, ACAN, and TIMP-1 levels were increased, and the cartilage Mankin score was decreased in the transgenic group compared with the pBudCE4.1 group. Double gene combination produced greater efficacies than each single gene, both in vitro and in vivo. Conclusion. This study suggests that pNNS-CS is a good candidate for treating cartilage defects via gene therapy, and that IL-1Ra in combination with miR-140 produces promising biological effects on cartilage defects. Cite this article: R. Zhao, S. Wang, L. Jia, Q. Li, J. Qiao, X. Peng. Interleukin-1 receptor antagonist protein (IL-1Ra) and miR-140 overexpression via pNNS-conjugated chitosan-mediated gene transfer enhances the repair of full-thickness cartilage defects in a rabbit model. Bone Joint Res 2019;8:165–178. DOI: 10.1302/2046-3758.83.BJR-2018-0222.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 126 - 130
1 Jan 2011
Bruins MJ Zwiers JH Verheyen CCPM Wolfhagen MJHM

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive. We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples


The Bone & Joint Journal
Vol. 105-B, Issue 3 | Pages 284 - 293
1 Mar 2023
Li Y Zhang X Ji B Wulamu W Yushan N Guo X Cao L

Aims

Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity.

Methods

We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure.


The Bone & Joint Journal
Vol. 99-B, Issue 1 | Pages 66 - 72
1 Jan 2017
Sigmund IK Holinka J Gamper J Staats K Böhler C Kubista B Windhager R

Aims. The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, α-defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of α-defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. Patients and Methods. We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of α-defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. Results. The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p-values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). Conclusion. With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI. Cite this article: Bone Joint J 2017;99-B:66–72


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1021 - 1030
1 Sep 2024
Oto J Herranz R Fuertes M Plana E Verger P Baixauli F Amaya JV Medina P

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Methods

We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.


The Bone & Joint Journal
Vol. 99-B, Issue 5 | Pages 660 - 665
1 May 2017
Wouthuyzen-Bakker M Ploegmakers JJW Kampinga GA Wagenmakers-Huizenga L Jutte PC Muller Kobold AC

Aims . Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. Patients and Methods. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. . Results. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI. . Conclusion . Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. . Cite this article: Bone Joint J 2017;99-B:660–5


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 373 - 381
15 Mar 2023
Jandl NM Kleiss S Mussawy H Beil FT Hubert J Rolvien T

Aims

The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA).

Methods

In this retrospective cohort study, 147 consecutive patients with acute or chronic complaints following THA and TKA were included. Diagnosis of PJI was established based on the 2018 International Consensus Meeting criteria. A total of 39 patients diagnosed with PJI (32 chronic and seven acute) and 108 patients with aseptic complications were surgically revised.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 372 - 382
1 Aug 2024
Luger M Böhler C Puchner SE Apprich S Staats K Windhager R Sigmund IK

Aims

Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP.

Methods

From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).