Total blood loss and early clinical outcomes under different tranexamic acid regimes in total knee arthroplasty.

BACKGROUND: Many different regimes of intravenous and local tranexamic acid (TXA) reduce total blood loss (TBL) in patients undergoing total knee arthroplasty (TKA). However, the most effective TXA regime in reducing blood loss might not be most beneficial for the patient. The aim of the present study was to investigate the effect of commonly used TXA regimes on blood loss and on early clinical outcomes. METHODS: We performed this monocentric retrospective study in patients undergoing primary TKA. Primary outcome was the estimated TBL. Secondary outcomes were the rates of adverse events (AE) as well as the range of motion (ROM), mobility and pain intensity during the first three physiotherapy sessions (PTS). RESULTS: We analysed the data of 1250 TKAs. 5 different TXA regimes were applied. TBL (mean ± SE) was 953 ± 64 ml (2xiv), 999 ± 19 ml (2xiv + 1xlocal), 1075 ± 19 ml (1xiv + 1xlocal), 1191 ± 39 ml (1xlocal) and 1241 ± 48 ml (1xiv) (p < 0.01). In the linear regression model for TBL a lower number of TXA applications was a predictor for increased blood loss (p < 0.01). AE rates were lowest under 2xiv (0%) and 2xiv + 1xlocal (4.8%). Highest mobility and lowest pain intensity were observed under 1x iv and 2x iv. The largest portions of fully mobile patients on day three were observed under 1xiv (100%), 2xiv (100%) and 2xiv + 1local TXA (86.9%). CONCLUSION: Our results suggest that multiple applications of TXA are more effective in decreasing blood loss than excessive dosing of TXA. Interestingly, local use of TXA might be associated with higher pain intensity and decreased mobility on the first days after surgery.

[Individualized surgical treatment of sarcomas of the extremities]. / Chirurgische Therapieindividualisierung bei Sarkomen der Extremitäten.

Sarcomas of the extremities are rare entities, the treatment of which requires special expertise. Even if the treatment of patients is always interdisciplinary, the surgical R0 resection is the key point of each curatively intended treatment. In addition to resection in sano, the aim is to preserve the extremities and function, so that defect reconstruction after resection plays a decisive role. Due to the heterogeneity of tumors as well as their localization and extent, reconstruction is always an individually adapted treatment. Modular tumor endoprostheses are often used in this context, which can be constructed according to the size of the defect. The transplantation of autologous or allogeneic bone is also frequently used alone or as an additive procedure. Patient-specific (mega)prostheses are used particularly for pelvic tumors. Defect reconstruction using scaffold-based procedures from the field of tissue engineering is being tested as a promising procedure for the future. This article provides an overview of the treatment principles for sarcomas of the extremities and their individual reconstruction options.

Does Body Mass Index (BMI) Affect the Reconstruction of Biomechanical Parameters in Patients Undergoing Total Hip Replacement (THR) through the Direct Anterior Approach (DAA)?

OBJECTIVE: Direct anterior approach total hip replacement (DAA-THR) is gaining increased interest due to its tissue-sparing nature and rapid recovery. Obesity has been shown to be a significant parameter influencing cup positioning in DAA-THR. It was the intention of this retrospective study to examine how obesity would influence the restoration of native hip biomechanical parameters during DAA-THR. MATERIALS AND METHODS: A total of 74 patients from a high-volume university orthopedic center after unilateral DAA-THA were included. Patients were retrospectively allocated to a study group (BMI > 30 kg/m2) and a control group (BMI < 30 kg/m2). Furthermore, propensity-score matching for baseline parameters was performed, leaving 30 patients in each group. Biomechanical parameters of the hip (i.e., femoral offset (FO), abductor lever arm (ABL), acetabular offset (AO), center of rotation (COR), stem alignment (SA), body weight lever arm (BWL), cup inclination (CI), and leg length discrepancy (LLD) were evaluated on standardized plain radiographs, and parameters were compared to the native contralateral hip. RESULTS: Mean BMI in the study group was 35.07 ± 5.13 kg/m2 and 25.43 ± 2.64 kg/m2 in the control group. There was a significant decrease of the ABL only in the study cohort (p = 0.01). CI and SA did not differ between both cohorts. FO was slightly increased compared to the native hip in both groups. There was a marginally higher but non-significant proportion of improper FO restoration in the study group (19 vs. 16 patients, p = 0.60). CONCLUSIONS: Obesity, as quantified by BMI, only has a limited impact on the adequate reconstruction of native biomechanical parameters of the hip during DAA-THR. ABL was the only parameter to be significantly decreased in the overweight patients after DAA-THR. Therefore, special care should be taken on proper acetabular reaming and consequent seating of the cup in the obese patient to avoid excessive lateral positioning.

Development of an Effective Functional Lipid Anchor for Membranes (FLAME) for the Bioorthogonal Modification of the Lipid Bilayer of Mesenchymal Stromal Cells.

The glycosylation of cellular membranes is crucial for the survival and communication of cells. As our target is the engineering of the glycocalyx, we designed a functionalized lipid anchor for the introduction into cellular membranes called Functional Lipid Anchor for MEmbranes (FLAME). Since cholesterol incorporates very effectively into membranes, we developed a twice cholesterol-substituted anchor in a total synthesis by applying protecting group chemistry. We labeled the compound with a fluorescent dye, which allows cell visualization. FLAME was successfully incorporated in the membranes of living human mesenchymal stromal cells (hMSC), acting as a temporary, nontoxic marker. The availability of an azido function─a bioorthogonal reacting group within the compound─enables the convenient coupling of alkyne-functionalized molecules, such as fluorophores or saccharides. After the incorporation of FLAME into the plasma membrane of living hMSC, we were able to successfully couple our molecule with an alkyne-tagged fluorophore via click reaction. This suggests that FLAME is useful for the modification of the membrane surface. Coupling FLAME with a galactosamine derivative yielded FLAME-GalNAc, which was incorporated into U2OS cells as well as in giant unilamellar vesicles (GUVs) and cell-derived giant plasma membrane vesicles (GPMVs). With this, we have shown that FLAME-GalNAc is a useful tool for studying the partitioning in the liquid-ordered (Lo) and the liquid-disordered (Ld) phases. The molecular tool can also be used to analyze the diffusion behavior in the model and the cell membranes by fluorescence correlation spectroscopy (FCS).

Handmade articulating spacer for two-stage exchange at the knee.

OBJECTIVE: Two-stage exchange with implantation of a temporary spacer is considered gold standard treatment for chronic periprosthetic joint infection of the knee. This article describes a simple and safe technique for handmade articulating spacers at the knee. INDICATION: Chronic or relapsing periprosthetic joint infection of the knee. RELATIVE CONTRAINDICATIONS: Known allergy against components of polymethylmethacrylate (PMMA) bone cements or admixed antibiotics. Inadequate compliance for two-stage exchange. Patient not able to undergo two-stage exchange. Bony defect situation at the tibia or femur leading to collateral ligament insufficiency. Soft tissue damage with need for plastic temporary vacuum-assisted wound closure (VAC) therapy. SURGICAL TECHNIQUE: Removal of the prosthesis, thorough debridement of necrotic and granulation tissue, tailoring bone cement with antibiotics. Preparation of a tibial and femoral stem. Customizing the tibial and femoral articulating spacer components to bony anatomy and soft tissue tension. Confirmation of correct position by intraoperative radiography. POSTOPERATIVE MANAGEMENT: Protection of the spacer with an external brace. Restricted weight-bearing. Passive range of motion as possible. Intravenous-followed by oral antibiotics. Reimplantation after successful treatment of infection.

Periprosthetic joint infection: Comparison of automated multiplex-PCR Unyvero i60 ITI cartridge system with bacterial culture and real-time PCR.

BACKGROUND: In the past, various efforts have been made to investigate diagnostic tools for periprosthetic-joint-infection (PJI). It is little-known about the diagnostic utility of polymerase-chain-reaction (PCR) in this context, especially concerning the role of multiplex-PCR assays comparing with conventional tissue culture. OBJECTIVE: Evaluation of an automated-multiplex-PCR cartridge system for patients with suspicion of PJI in comparison with conventional microbiological culture and 16S-rDNA-PCR. METHODS: On suspicion of PJI synovial fluid specimen were taken preoperatively or periprosthetic tissue was collected intraoperatively. Microbiological analysis included conventional culture, 16S-rDNA-PCR and automated-multiplex-PCR (Unyvero-i60-ITI®). The European-Bone-and-Joint-Infection-Society (EBJIS) criteria were used for PJI diagnosis. Positive and negative percent agreement was calculated. Total percentage agreement and Cohen's kappa coefficient were calculated. Sensitivity, specificity and positive predictive value of conventional culture, 16S-rDNA-PCR and multiplex-PCR were calculated. Ten specimens of proved PJI were used as control group. RESULTS: Fifty specimen were suitable for culture. 14 (28%) were classified as PJI, 36 (72%) were aseptic. Coagulase-negative staphylococci was the most frequent detected pathogen. Concordance-rate between mPCR and culture results was 75.6% with a Cohen's kappa of 0.28. Concordance-rate between mPCR and 16S-rDNA was 82.9%, Cohen's kappa was 0.13. Concordance analysis between culture results and 16S-rDNA lead to a concordance-rate of 88.9%. Cohen's kappa was calculated with 0.6. With regard to the microbiological culture as reference, sensitivity of the mPCR was 0.33 and specificity was 0.91. Sensitivity and specificity of the 16S-rDNA-PCR was 0.55 and 0.97. The positive predictive value was 0.57 for the mPCR and 0.83 for the 16S-rDNA-PCR. CONCLUSIONS: Due to fair agreement between mPCR and conventional microbiological culture, the tested multiplex-PCR could be an additional instrument for the detection of PJI but is not superior over the conventional culture.

Influence of Tranexamic Acid on Elution Characteristics and Compressive Strength of Antibiotic-Loaded PMMA-Bone Cement with Gentamicin.

PURPOSE: The topical application of tranexamic acid (TXA) into the joint space during total joint arthroplasty (TJA) with no increase of complications, has been widely reported. We investigated the influence of TXA on antibiotic release, activity of the released antibiotic against a clinical isolate of S. aureus, and compressive strength of a widely used commercially prepared gentamicin-loaded cement brand (PALACOS R + G). METHOD: 12 bone cement cylinders (diameter and height = 6 and 12 mm, respectively) were molded. After curing in air for at least 1 h, six of the cylinders were completely immersed in 5 mL of fetal calf serum (FCS) and the other six were completely immersed in a solution consisting of 4.9 mL of FCS and 0.1 mL (10 mg) of TXA. Gentamicin elution tests were performed over 7 d. Four hundred µL of the gentamicin eluate were taken every 24 h for the first 7 d without renewing the immersion fluid. The gentamicin concentration was determined in a clinical analyzer using a homogeny enzyme immuno-assay. The antimicrobial activity of the eluate, obtained after day 7, was tested. An agar diffusion test regime was used with Staphylococcus aureus. Bacteria were grown in a LB medium and plated on LB agar plates to get a bacterial lawn. Fifty µL of each eluate were pipetted on 12-mm diameter filter discs, which were placed in the middle of the agar gel. After 24 h of cultivation at 37 °C, the zone of inhibition (ZOI) for each specimen was measured. The compressive strength of the cements was determined per ISO 5833. RESULTS: At each time point in the gentamicin release test, the difference in gentamicin concentration, obtained from specimens immersed in the FCS solution only and those immersed in the FCS + TXA solution was not significant (p = 0.055-0.522). The same trend was seen in each of the following parameters, after 7 d of immersion: (1) Cumulative gentamicin concentration (p < 0.297); (2) gentamicin activity against S. aureus (strongly visible); (3) ZOI size (mostly > 20 mm) (p = 0.631); and (4) compressive strength (p = 0.262). CONCLUSIONS: For the PALACOS R + G specimens, the addition of TXA to FCS does not produce significant decreases in gentamicin concentration, in the activity of the gentamicin eluate against a clinical isolate of S. aureus, the zone of inhibition of S. aureus, and in the compressive strength of the cement, after 7 d of immersion in the test solution.

NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells.

Skeletal development and remodeling of adult bone are critically controlled by activated NOTCH signaling in genetically modified mice. It is yet unclear whether NOTCH signaling is activated by mechanical strain sensed by bone cells. We found that expression of specific NOTCH target genes is induced after in vivo tibial mechanical loading in wild-type mice. We further applied mechanical strain through cyclic stretching in human bone marrow-derived mesenchymal stromal cells (BMSCs) in vitro by using a bioreactor system and detected upregulation of NOTCH target gene expression. Inhibition of the NOTCH pathway in primary BMSCs as well as telomerase-immortalized human BMSCs (hMSC-TERT) through the gamma-secretase inhibitor GSI XII blocked mechanotransduction and modulated actin cytoskeleton organization. Short-hairpin RNA gene silencing identified NOTCH2 as the key receptor mediating NOTCH effects on hMSC-TERT cells. Our data indicate a functional link between NOTCH activation and mechanotransduction in human BMSCs. We suggest that NOTCH signaling is an important contributor to molecular mechanisms that mediate the bone formation response to mechanical strain.

The Effect of Antiseptics in the Prophylaxis of Infection in Orthopaedic Surgery.

INTRODUCTION: Over the past decade, the incidence of revision arthroplasty has increased substantially. One of the main reasons for revision arthroplasty is periprosthetic joint infection, often resulting in multiple surgical interventions with variable success and poor clinical outcome. Intraoperative wound irrigation has been proposed to reduce bacterial contamination and thus the risk of periprosthetic infection. However, there is currently no widely accepted recommendation for the use of topical antiseptics within the operative setting for primary implantation. We performed a systematic review of studies pertaining to the use of intraoperative topical antiseptics and their effectiveness in preventing infection of orthopaedic implants. MATERIALS AND METHODS: A comprehensive literature search including MEDLINE (PubMed), Cochrane Library, and Current Contents Medicine (CCMED-Medpilot) was performed according to a standardised protocol. RESULTS: Overall, 1905 articles were initially assessed. Four studies met the inclusion criteria and remained for further analysis, comprising two prospective cohort studies using retrospective control groups (evidence level II - III) and two randomised controlled trials (evidence level I). 0.35% Povidone-iodine (PVP-I) was used in three of these studies and a solution of 6.25% PVP-I and 6.25%-hydrogen peroxide (H2O2) in one study for intraoperative wound irrigation. There was a clear trend in all studies suggesting that intraoperative topical antiseptics are effective in preventing periprosthetic infection. CONCLUSION: Although no clear regimen can be recommended, the available literature indicates that the use of intraoperative topical antiseptics is of clinical relevance in preventing infection of orthopaedic implants. Further randomised controlled trials are recommended.

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling.

Controlling the adipo-osteogenic lineage decision of trabecular human bone marrow stromal cells (hBMSCs) in favor of osteogenesis represents a promising approach for osteoporosis therapy and prevention. Previously, Fibroblast Growth Factor 1 (FGF1) and its subfamily member FGF2 were scored as leading candidates to exercise control over skeletal precursor commitment and lineage decision albeit literature results are highly inconsistent. We show here that FGF1 and 2 strongly prevent the osteogenic commitment and differentiation of hBMSCs. Mineralization of extracellular matrix (ECM) and mRNA expression of osteogenic marker genes Alkaline Phosphatase (ALP), Collagen 1A1 (COL1A1), and Integrin-Binding Sialoprotein (IBSP) were significantly reduced. Furthermore, master regulators of osteogenic commitment like Runt-Related Transcription Factor 2 (RUNX2) and Bone Morphogenetic Protein 4 (BMP4) were downregulated. When administered under adipogenic culture conditions, canonical FGFs did not support osteogenic marker expression. Moreover despite the presence of osteogenic differentiation factors, FGFs even disabled the pro-osteogenic lineage decision of pre-differentiated adipocytic cells. In contrast to FGF Receptor 2 (FGFR2), FGFR1 was stably expressed throughout osteogenic and adipogenic differentiation and FGF addition. Moreover, FGFR1 and Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2) were found to be responsible for underlying signal transduction using respective inhibitors. Taken together, we present new findings indicating that canonical FGFR-ERK1/2 signaling entrapped hBMSCs in a pre-committed state and arrested further maturation of committed precursors. Our results might aid in unraveling and controlling check points relevant for ageing-associated aberrant adipogenesis with consequences for the treatment of degenerative diseases such as osteoporosis and for skeletal tissue engineering strategies. J. Cell. Biochem. 118: 263-275, 2017. © 2016 Wiley Periodicals, Inc.

Comparative retrospective study of the direct anterior and transgluteal approaches for primary total hip arthroplasty.

PURPOSE: The presented retrospective study compares clinical outcomes five years after total hip arthroplasty performed through a minimally invasive direct anterior approach and a direct transgluteal lateral approach. METHODS: A total of 171 arthroplasties in 167 patients were evaluated utilizing the Harris hip score (HHS), the SF-36, a daily activity questionnaire, and the UCLA activity score. RESULTS: The average HHS showed no significant difference equalling 91.4 points in the anterior group and 92.4 in the lateral group (p = 0.952). The SF-36 physical component scores were 50.7 (anterior) and 50.0 (lateral) while the psychometric properties added up to 48.6 (anterior) and 50.3 (lateral) with no significant differences evident (p = 0.782, p = 0.071). Daily activity was found to result in 4,855 (anterior) and 5,016 (lateral) cycles, respectively (p = 0.364). No difference regarding pain sensation was determined (p = 0.859). A significant difference was found for the UCLA score, which was calculated to be 5.9 in the anterior and 6.4 in the lateral approach group (p = 0.008). CONCLUSION: In summary, our mid-term results show comparable outcomes for both approaches regarding functionality, pain, quality of life and daily activity.

Fibula and tibia fusion with cancellous allograft vitalised with autologous bone marrow: first results for infected tibial non-union.

BACKGROUND AND AIMS: Autogenous bone grafting has been used in reconstructing bone defects and in stimulating fracture healing, producing high healing rates in the treatment of infected tibial non-unions. A novel therapeutic alternative is now available known as "vitalised allograft", a cancellous bone graft procured from femoral heads from living human donors and "vitalised" through the injection of autologous bone marrow. The aim of this study is to summarise the initial results of the fibula and tibia fusion using vitalised cancellous allograft in the treatment of infected tibial non-unions. PATIENTS AND METHODS: We initiated a follow-up of 15 prospective non-randomized patients who received a vitalised allograft in the treatment of infected tibial non-unions in order to produce bony union. The patients included 13 men and 2 women with an average age of 48 years. All patients received a multi-stage surgical approach. After establishing an infection-free environment, allogenic cancellous bone grafting was performed, intended as the final surgical procedure in fibula and tibia fusion. Our follow-up included a clinical and radiographic investigation of the calf in four planes. We analysed union-rate and time required for bony consolidation, as well as recurrent infections, re-fractures, potential graft-resorption, and time needed for graft and bone remodelling. RESULTS: With an average follow-up of 17.1 months, infection control was obtained in 14 of 15 patients, producing an infection arrest rate of 93.3%. Radiographs indicated consolidation in 11 out of 15 cases, with a union rate of 73.3%. Bone union was achieved on average in 17.1 weeks. CONCLUSIONS: Fibula and tibia fusion with allogenic cancellous bone grafting, vitalised through autogenic bone marrow, could well become an innovative treatment option for infected tibial non-unions. We need, however, to analyse a higher number of cases over a longer follow-up period in order to assess more accurately recurrent infections and re-fractures.