An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodo^TM Green Zymosan Biparticles^TM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.

Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.

Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.

Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.

This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).

Precision medicine tailoring the patient pathway based on the risk, prognosis, and treatment response may bring benefits to the patients. To identify risk factors contributing to the early failure of treatment (development of events of interest) and when possible to change the prognosis via modifying these factors may improve the outcome and/or lower the risk of complications. There is an emerging goal to identify such parameters in total knee arthroplasty (TKA) thus lower the risk of revision surgery. The goal of this study was to identify factors explaining the risk for early revision of TKA using an artificial intelligence method appropriate for this task.

We applied a patient similarity network (PSN) for the identification of risk factors associated with early reoperations (n=109, 5.8%) in patients with TKA (n=1885). Next, an algorithm based on formal concept analysis was developed to support the patient decision on how to change modifying personal characteristics with respect to the estimated probability of reoperations.

The early reoperations were less frequent in women (4.4%, median time to reoperation 4.5 mo) than in men (8.2%, 10 mo), reaching the highest incidence in younger men (10.9%).

The most common reasons for total joint arthroplasty (TJA) failure are aseptic loosening (AL) and prosthetic joint infection (PJI). There is a big clinical challenge to identify the patients with high risk of AL/PJI before the TJA surgery. Although there is evidence that genetic factors contribute to the individual susceptibility to AL/PJI, a predictive model for identification of patients with a high genetic risk of TJA failure has not been developed yet.

We aimed to develop a risk evaluation tool utilising the AL/PJI-associated polymorphisms for identification of patients with high genetic risk of TJA failure based on inflammation-gene polymorphism panel.

Based on allele and genotype frequencies of twenty-five single nucleotide polymorphisms (SNPs) in TNF, IL2, IL6, IL10, IL1b, IL-1Ra, MBL2, MMP1, FTO genes and those influencing the serum levels of biomarkers of TJA outcomes (IL6, CCL2/MCP-1, CRP, ESR) in peripheral blood obtained from patients with TJA (AL, n=110; PJI, n=93; no complications, n=123), we calculated a hazard ratio and a relative entropy of alleles and genotypes associated with AL and PJI and their combinations in patient subgroups.

We conducted a risk evaluation tool based on the presence of risk alleles and genotypes in TNF (rs361525, rs1800629), DARC (rs12075), MBL2 (rs11003125) and FTO (rs9939609, rs9930506) genes associated with implant failure (AL/PJI). Of these, FTO gene variations (rs9939609, rs9930506) were associated mainly with PJI (P=0.001, OR=2.04, 95%CI=1.132–2.603; P=0.011, OR=1.72, 95%CI=1.338–3.096) and DARC (rs12075) with AL (P=0.005, OR=1.79, 95%CI=1.193–2.696). This tool calculates a hazard ratio of a combination of SNPs associated with AL and PJI for identification of patients with high and low risk of AL/PJI TJA failure.

We proposed a risk evaluation tool for stratification of patients before the TJA surgery based on the genetic risk of AL/PJI development. The effect size for each genotype combination described in the study is small. Further multiparametric data analysis and studies on an extended patient cohort and other non-genetic and genetic parameters are ongoing. Grant support: AZV MZ CR VES16-131852A, VES15-27726A, IGA LF UP_2016_011.

Aim

The diagnosis of periprosthetic joint infection (PJI) in total joint arthroplasty (TJA) remains a serious clinical challenge. Nowadays, limited biomarkers associated with PJI are available. We investigated therefore the utility of gene expression pattern of Toll-like receptors (TLR) and members of interleukin (IL)1/IL1R family, molecules critically involved in the innate immune response to invading pathogens, for detecting PJI in periprosthetic tissues around TJA.

Aim of the study: Prosthetic joint infection (PJI) is a feared complication of total joint arthroplasties. Several strategies were developed to treat it. The purpose of our study was to compare treatment strategies for PJI treatment presented in the literature.

Materials and Methods: We found more than 5000 documents in databases MEDLINE and EMBASE concerning this topic, published between January 1960 and November 2006. Using two-phase selection, 382 relevant articles were chosen, full texts were obtained for 302 of them (79%), and 77 studies was included into the analysis according to inclusion criteria (a total of 645 hips and 1145 knees). There were compared two-stage surgery, one-stage surgery, removal of prosthesis, and long-term antibiotic therapy in hip PJI, and two-stage surgery, debridement, arthrodesis, and long-term antibiotic therapy in knee PJI. The rate of PJI recurrence was a primary outcome, need for additional surgery was a secondary outcome. Capability index (c), relative risk (RR), and „number needed to treat“(NNT) were calculated for both outcomes under study.

Results:

The lowest rate of recurring PJI was reported for two-stage reimplantation (7.4 % in hip, 11 % in knee), followed by one-stage reimplantation in the case of hip PJI (9.2 %), and arthrodesis in the case of knee PJI (15.6 %);

Conclusion: Two-stage management for treatment of PJI had the smallest risk for both PJI recurrence and need for additional surgery in comparison with all other strategies. One-stage hip reimplantation is a less reliable approach, in which it is necessary to strictly respect the indication criteria. Other methods are either less reliable or are associated with high risk of following surgeries, or unacceptable functional results.

Introduction: The development of periprosthetic osteolysis (OL) in total hip arthroplasty (THA) depends on activation of distinct pathways by wear particles eventually leading to predominance of osteoclasts over osteoblasts at the bone-implant interface. These processes are orchestrated by many cytokines and chemokines. However, interindividual variability in OL was observed even in cases of comparable wear rates and identical prosthesis. To explain it, we hypothesize genetic susceptibility to OL underlined by single nucleotide polymorphisms (SNP) for genes for key signal molecules.

Patients and Methods: In this case-control association study we investigated patients with severe OL around THA (n=116). The control group included patients with the same THA and mild OL (n=89). All were Caucasian, all had a single type of cementless THA implanted at a single institution. Healthy subjects without THA (n=150) served as a genetic background. Severity of OL was determined according to the Saleh’s classification. We used the candidate gene approach and overall, 22 cytokine/cytokine receptor SNPs were genotyped by polymerase chain reaction with sequence specific primers (PCR-SSP).

Results: The results showed an association of the TNF-238*A allele with severe OL (odds ratio, OR=6.59, p=0.005, population attributable risk percentage, PAR% = 5.2), higher risk of revision (OR=infinity, p=0.017) and poorer survival of THA (p=0.022). In addition, carriers of the IL-6-174*G allele were more frequent among the patients with severe OL (OR=2.51, p=0.007, PAR%=31.5). Finally, the genetic variant IL-2-330*G was associated with lower risk for THA revision (OR=0.44, p=0.02), protection from severe OL (OR=0.55, p=0.043) and longer survival of THA (p=0.018).

Conclusions: At least in a Czech population, genetic variants of the pro-inflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL and risk of premature THA failure. Conversely, SNP in the IL-2 gene may protect from development of severe OL and risk of early revision due to OL.