Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty.

PURPOSE: Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications. METHODS: The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3. RESULTS: For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738. CONCLUSION: It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Oligopeptide Sortase Inhibitor Modulates Staphylococcus aureus Cell Adhesion and Biofilm Formation.

Prevention of bacterial adhesion is one of the most important antivirulence strategies for meeting the global challenge posed by antimicrobial resistance. We aimed to investigate the influence of a peptidic S. aureus sortase A inhibitor on bacterial adhesion to eukaryotic cells and biofilm formation as a potential method for reducing S. aureus virulence. The pentapeptide LPRDA was synthesized and characterized as a pure individual organic compound. Incubation of MSSA and MRSA strains with LPRDA induced a subsequent reduction in staphylococcal adhesion to Vero cells and biofilm formation, as visualized by microscopic and spectrophotometric methods, respectively. LPRDA did not have a cytotoxic effect on eukaryotic or bacterial cells. The pentapeptide LPRDA deserves further investigation using in vitro and in vivo models of Gram-positive bacteriemia as a potential antibacterial agent with an antiadhesive mechanism of action.

Human bone graft cytocompatibility with mesenchymal stromal cells is comparable after thermal sterilization and washing followed by γ-irradiation: an in vitro study.

Human bone allografts present a better alternative to autografts in terms of minimization of the harvesting procedure complications. Prior to the use in clinical applications, they require sterilization which aims to reduce bioburden. This often comes at the expense of their biological properties as carriers of cells. In this study, we evaluated the cytocompatibility of human bone allografts processed and sterilized by three different methods with mesenchymal stromal cells. Bone morphology, biological and biochemical properties of the extracted bone-conditioned medium and viability of cells were assessed. We found that chemical sterilization had a strong negative effect on cell viability, whereas thermal sterilization and washing with subsequent γ-irradiation both resulted in a bone graft compatible with the progenitor cells. Moreover, washing of the bone prior to sterilization allowed solid removal of cell debris and other bone marrow components. Taken together, our findings demonstrate the importance of a proper choice of the bone graft processing method for the production of the biomaterial suitable for tissue engineering.

Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip.

BACKGROUND: The unsuccessful treatment of prosthetic joint infection (PJI) with two-stage revision leads to infection recurrence. The objectives of the study were to assess the clinical and demographic characteristics of patients with polymicrobial PJI, and to evaluate the role of the microbial profile involved in PJI in the risk of infection recurrence after the first step of two-stage revision surgery. MATERIALS AND METHODS: A retrospective analysis of 189 cases of culture-positive PJI following total hip replacement over a 5-year period was performed. The demographic characteristics of patients, clinical symptoms, microbiology cultures of intraoperative biopsies, laboratory values of C-reactive protein (CRP), white blood cell count and erythrocyte sedimentation rate were analyzed. Patients were divided into two groups-135 with monomicrobial and 54 with polymicrobial infection. RESULTS: Of all patients, 68.9 % in the monomicrobial and 83.3 % in the polymicrobial group had a body mass index >25 kg/m2 (p = 0.05). The median CRP values were 5.7 mg/L (IQR 4.0-10.0 mg/L) in the monomicrobial compared to 8.8 mg/L (IQR 5.0-27 mg/L) in the polymicrobial group (p = 0.01). The percentage of successful outcomes was 27.8 % in patients with microbial associations (p < 0.0001). Gram-negative pathogens caused polymicrobial PJI in 61.5 % of cases with infection recurrence (OR 4.4; 95 % CI 1.18-16.37; p = 0.03). CONCLUSIONS: Overweight and obese patients or those with elevated CRP had a greater risk of polymicrobial PJI. They were predisposed to recurrence of infection after the first step of two-stage revision. An unsuccessful outcome was more likely in cases with polymicrobial infection compared to those with monomicrobial infection. In addition, the presence of multidrug-resistant strains of Gram-negative bacteria substantially increased the risk of PJI treatment being unsuccessful. LEVEL OF EVIDENCE: Level III, therapeutic study.

Risk factors and a prognostic model of hip periprosthetic infection recurrence after surgical treatment using articulating and non-articulating spacers.

PURPOSE: The purpose of this study was evaluation of the efficacy of the first step of a two-stage procedure for treatment of hip prosthetic joint infection (PJI) using articulating and non-articulating spacers as well as development of a prediction model and prognostic score for infection recurrence. METHODS: In a cohort of 217 patients treated for PJI of the hip, demographic characteristics, clinical symptoms, body temperature, body mass index (BMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBC), microbiological cultures and the type of the spacer used were retrospectively analyzed for association with the recurrence of PJI. RESULTS: Patients with infection recurrence had increased levels of ESR and CRP (P < 0.001) together with higher BMI and shorter infection manifestation period after previous surgery (P < 0.05). Among these patients, there was no significant difference of clinical characteristics between subjects with articulating and non-articulating spacers. Microbial associations were more often identified in patients with recurrent infection (50 %, P < 0.01) where Gram-negative bacteria were predominant (61.5 %, P < 0.01). These patients had higher percentage of Acinetobacter sp. and P. aeruginosa isolates (28.2 %, P < 0.01). CONCLUSIONS: Efficacy of the first step of two-stage revision was 64.1 %. Placement of either articulating or non-articulating spacers did not influence recovery from PJI. Laboratory values of ESR, CRP, BMI and the type of previous surgery were identified as main factors that affect outcomes of the two-stage procedure. A prognostic model with the calculation of a total risk score for PJI recurrence was developed.