High frequency of BCP, but less CPP crystal-mediated calcification in cartilage and synovial membrane of osteoarthritis patients.

OBJECTIVE: Ectopic articular calcification is a common phenomenon of osteoarthritic joints, and closely related to disease progression. Identification of the involved calcium crystal types represents an important topic in research and clinical practice. Difficulties in accurate detection and crystal type identification have led to inconsistent data on the prevalence and spatial distribution of Basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) deposition. METHOD: Combining multiple imaging methods including conventional radiography, histology and Raman spectroscopy, this study provides a comprehensive analysis of BCP and CPP-based calcification, its frequency and distribution in cartilage and synovial membrane samples of 92 osteoarthritis patients undergoing knee replacement surgery. RESULTS: Conventional radiography showed calcifications in 35% of patients. Von Kossa staining detected calcified deposits in 88% and 57% of cartilage and synovial samples, respectively. BCP crystals presented as brittle deposits on top of the cartilage surface or embedded in synovial tissue. CPP deposits appeared as larger granular needle-shaped clusters or dense circular pockets below the cartilage surface or within synovial tissue. Spectroscopic analysis detected BCP crystals in 75% of cartilage and 43% of synovial samples. CPP deposition was only detected in 18% of cartilage and 15% of synovial samples, often coinciding with BCP deposits. CONCLUSION: BCP is the predominant crystal type in calcified cartilage and synovium while CPP deposition is rare, often coinciding with BCP. Distinct and qualitative information on BCP and CPP deposits in joint tissues gives rise to the speculation that different disease entities are involved that might need different treatment strategies.

Collagen 1 gel may improve the regenerative capacity of minced adult and preosteoarthritic cartilage.

PURPOSE: Minced cartilage implantation (MCI) is an evolving technique for the treatment of osteochondral lesions. It was hypothesised that mincing of cartilage may affect chondrocyte viability and phenotype and that embedding in collagen 1 gel results in an improved outcome. The objective of this study was to evaluate the impact of cartilage mincing and whether collagen 1 gel mediates beneficial effects on the chondrocyte phenotype and viability. METHODS: Human cartilage samples from 11 patients undergoing total knee arthroplasty were collected and minced according to the MCI protocol. Minced cartilage was cultured for 1 week with and without embedding in collagen 1 gel and was compared with unminced cartilage flakes as control. Quantitative reverse transcription-PCR and immunohistochemical staining for the chondrocyte marker genes SOX9, COL2, ACAN, COL10 and MMP13 were used to examine the chondrocyte phenotype. Cell death was assessed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. RESULTS: Increased chondrocyte cell death of cultured cartilage after mincing was observed. Chondrocytes from minced cartilage exhibited significantly decreased expression and protein levels of homeostatic and hypertrophic chondrocyte markers. Embedding in collagen 1 gel showed no positive effect on viability. However, remarkable is the increased expression of ACAN and the preserved protein level of SOX9 in the collagen 1-embedded minced cartilage. CONCLUSIONS: This study shows that the mincing of cartilage leads to increased chondrocyte death and decreased expression of chondrocyte phenotypic marker genes after 7 days. The use of collagen 1 gel may improve the stability of the phenotype, which needs to be further elucidated. LEVEL OF EVIDENCE: Level III (therapeutic).

Influence of humeral position of the Affinis Short stemless shoulder arthroplasty system on long-term survival and clinical outcome.

BACKGROUND: The purpose of this study was to evaluate the influence of humeral position of the Affinis Short implant in stemless anatomic total shoulder arthroplasties (STSAs) on clinical and radiologic results and mid- to long-term survival in the treatment of primary osteoarthritis (OA) of the shoulder. METHODS: Eighty patients treated with a stemless shoulder arthroplasty for OA of the shoulder were evaluated with a mean follow-up of 92 ± 14 months (range 69-116 months) by the Constant Score (CS), Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH), and active range of motion (ROM). Radiographic assessment for bone adaptations and humeral implant position was performed by plain radiographs. Comparison of the pre- and postoperative centers of rotation (CORs) was used to assess the restoration of the geometry of the humeral head. The appraisal of proper humeral component positioning was correlated with the functional outcomes. A Kaplan-Meier analysis was performed to investigate the influence of humeral implant position compared to survival time. Complications were noted. RESULTS: The ROM (P < .001), CS (P < .001), and DASH scores (P < .001) showed significant improvements after surgery for the entire series. The COR restoration was anatomic in 75% (n = 60) of all implants and in 25% (n = 20) nonanatomic implants (pre- and postoperative COR deviation of 2.7 ± 1.8 mm vs. 5.1 ± 3.2 mm, P = .0380). The humeral component position did not affect the functional outcome whereas the 10-year unadjusted cumulative survival rate for the anatomic group was significantly higher in comparison with the nonanatomic group (96.7% vs. 75%, P = .002). The radiologic evaluation revealed minor periprosthetic bone adaptions in various forms without clinical significance or further intervention. No revision was necessary because of a failed fixation of the stemless humeral component. CONCLUSIONS: Regarding the treatment of primary OA of the shoulder, STSA shows excellent long-term survival and clinical outcomes. In particular, STSA implants are able to restore the geometry of the humeral head. Nonanatomic reconstruction may influence the survival over the long term in different pathways. Further studies are necessary to elucidate the effect of humeral component position in STSA on function, pain, and implant survival rates.

Vibro-Acoustic Sensing of Instrument Interactions as a Potential Source of Texture-Related Information in Robotic Palpation.

The direct tactile assessment of surface textures during palpation is an essential component of open surgery that is impeded in minimally invasive and robot-assisted surgery. When indirectly palpating with a surgical instrument, the structural vibrations from this interaction contain tactile information that can be extracted and analysed. This study investigates the influence of the parameters contact angle α and velocity v→ on the vibro-acoustic signals from this indirect palpation. A 7-DOF robotic arm, a standard surgical instrument, and a vibration measurement system were used to palpate three different materials with varying α and v→. The signals were processed based on continuous wavelet transformation. They showed material-specific signatures in the time-frequency domain that retained their general characteristic for varying α and v→. Energy-related and statistical features were extracted, and supervised classification was performed, where the testing data comprised only signals acquired with different palpation parameters than for training data. The classifiers support vector machine and k-nearest neighbours provided 99.67% and 96.00% accuracy for the differentiation of the materials. The results indicate the robustness of the features against variations in the palpation parameters. This is a prerequisite for an application in minimally invasive surgery but needs to be confirmed in realistic experiments with biological tissues.

Sortilin Is Upregulated in Osteoarthritis-Dependent Cartilage Calcification and Associated with Cellular Senescence.

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage calcification, loss of articular cartilage, bone changes, pain, and disability. Cartilage calcification is one hallmark of OA and is predominantly caused by basic calcium crystals formed due to an imbalance of the pyrophosphate pathway. Sortilin is a transmembrane protein that contributes to vascular calcification in atherosclerosis by externalizing alkaline phosphatase (ALP)-containing vesicles. Calcification in atherosclerosis and osteoarthritis has been associated with cellular senescence. The aim of this study was to investigate the potential role of sortilin and senescence in osteoarthritis-dependent cartilage calcification. Osteoarthritic cartilage from human knee joints was collected after joint replacement, and samples were analyzed by immunohistochemistry and quantitative RT-PCR analysis. Human chondrocytes were treated with osteogenic medium for up to 21 days to induce calcification. Western blots for sortilin and ALP, as well as an ALP activity assay, were performed. Human chondrocytes were treated with mitomycin C to induce senescence, and sortilin expression was quantified at the protein and gene levels. Sections of knee joints from a murine model of osteoarthritis were stained for sortilin and p16 and analyzed by immunohistochemistry. Treatment of wild-type chondrocytes using an osteogenic medium similar to human chondrocytes was performed. Osteoarthritic cartilage from mouse and human knee joints showed an increased number of sortilin and p16-positive chondrocytes compared to healthy cartilage. This observation was corroborated by increased gene expression of sortilin and p16 in mild and moderate osteoarthritic cartilage samples. To investigate the mechanism of sortilin regulation, human chondrocytes were treated with osteogenic medium to induce calcification. Sortilin protein levels and expression were increased after 7 days of stimulation, whereas ALP levels and activity were upregulated after 21 days of stimulation. Similar observations were made in a murine osteoarthritis model. Mechanistically, senescent chondrocytes induced by mitomycin C showed an upregulation of sortilin and ALP gene expression compared to non-senescent chondrocytes. Our data indicate that sortilin and ALP are upregulated during cartilage calcification, which is associated with chondrocyte senescence and thus might contribute to the pathogenesis of osteoarthritis. Cellular senescence seems to induce sortilin expression.

CoNiCrMo Particles, but Not TiAlV Particles, Activate the NLRP3 Inflammasome in Periprosthetic Cells.

Aseptic loosening is the main reason for arthroplasty failure. The wear particles generated at the tribological bearings are thought to induce an inflammatory tissue response, leading to bone loss and the subsequent loosening of the implant. Different wear particles have been shown to activate the inflammasome, thereby contributing to an inflammatory milieu in the direct vicinity of the implant. The aim of this study was to investigate whether the NLRP3 inflammasome is activated by different metal particles in vitro and in vivo. Three different cell lines representing periprosthetic cell subsets (MM6, MG63 and Jurkat) were incubated with different amounts of TiAlV or CoNiCrMo particles. The activation of the NLRP3 inflammasome was determined through the detection of the caspase 1 cleavage product p20 in a Western blot. The formation of the inflammasome was also investigated in vivo using immunohistological staining for ASC in primary synovial tissues as well as tissues containing TiAlV and CoCrMo particles and in vitro after the stimulation of the cells. The results show that the CoCrMo particles induced ASC more markedly, as a readout for inflammasome formation in vivo, compared to TiAlV particular wear. The CoNiCrMo particles also induced ASC-speck formation in all the tested cell lines, which was not induced by the TiAlV particles. The Western blot shows that NRLP3 inflammasome activation, measured through caspase 1 cleavage, was increased only by the CoNiCrMo particles in the MG63 cells. We conclude from our data that the activation of the inflammasome is mainly driven by CoNiCrMo particles and less by TiAlV particles, indicating that different inflammatory pathways are activated by the different alloys.

Injection of autologous conditioned plasma combined with a collagen scaffold may improve the clinical outcome in shoulder impingement syndrome: a prospective study.

BACKGROUND: Shoulder impingement syndrome (SIS) is one of the most common diseases of the shoulder and can be addressed with various therapeutic concepts. Orthobiological agents such as platelet rich plasma with a low side effect rate gain importance in the conservative treatment of SIS. Currently, the knowledge about success rate influencing factors, such as the growth factors (GF) concentration or acromion type, is limited. The aim of this study was to analyze the clinical outcome in the therapy of external SIS using autologous conditioned plasma combined with recombinant human collagen scaffold (ACP/STR) injection in comparison with a corticosteroid-local anesthetic (CSA) injection. Additionally, the influence of potential limiting factors such as GF concentration, age and acromial morphology was proved. MATERIALS AND METHODS: This prospective pseudo-randomized trial recruited 58 patients with external SIS who received an ultrasound-guided subacromial injection either an ACP/STR or a CSA followed by physical therapy. Follow-up (FU) was performed at 6 weeks, 3 and 6 months. The outcome was assessed with Constant-Murley score, disability of arm, shoulder and hand score and simple shoulder test. The concentration of GF was measured using ELISA. RESULTS: During the FU, the improvement of outcome measures was observed with no differences between both groups. Shoulder force was significantly increased in the ACP/STR group (p < 0.01). We found no correlation between the amount of GF and age or gender in the ACP/STR patients. An acromion Bigliani type III predisposes for therapy failure (p < 0.001, OR = 56) in both treatment groups. CONCLUSIONS: Patients with SIS benefit regarding to PROMs after both ACP/STR and CSA injection and physical therapy. Patients who received ACP/STR obtained superior improvement in force. The quantity of GF did not vary depending on the age, so that ACP/STR can be a treatment option for SIS in elderly patients with multimorbidity. The presence of an acromion type III seems to be a predictive factor for limited effectivity of injections in the clinical management of SIS.

The use of antibiotic-loaded bone cement does not increase antibiotic resistance after primary total joint arthroplasty.

PURPOSE: One of the preventive strategies for periprosthetic joint infection (PJI) is the use of antibiotic-loaded bone cement (ALBC) in primary total joint arthroplasty (TJA). Even though it is widely used, there are concerns about the development of antibacterial resistance. The aim of the study was to investigate whether using ALBC in primary TJA increases the antibiotic-resistant PJI. The hypothesis was that the regular use of ALBC does not increase the rate of resistant PJI. METHODS: Patients with confirmed PJI who had revision surgery from year 2010 to 2019 were included in this international multicenter study. The ALBC group was compared to the non-ALBC TJA group from the same time period. Medical records were used to collect clinical (age, gender, body mass index, comorbidities), TJA-related (type of operation, implant type and survival) and PJI-related (cultured microorganism, antibiogram) data. Resistance to gentamicin, clindamycin and vancomycin were recorded from the antibiograms. Multiple logistic regression model was used to identify risk factors and account for the potential confounders. RESULTS: 218 patients with PJI were included in the study: 142 with gentamicin-loaded bone cement and 76 in the non-ALBC group. The average age in the ALBC group was 71 ± 10 years and 62 ± 12 years in the comparison group (p < 0.001). Coagulase negative Staphylococci (CONS) were the most common (49%) isolated pathogens. The use of ALBC did not increase the rate of any resistant bacteria significantly (OR = 0.79 (0.42-1.48), p = 0.469). The presence of CONS was associated with higher risk of antibiotic resistance. CONCLUSIONS: The current study demonstrates no increase in antibiotic resistance due to ALBC after primary TJA. Thus, the use of ALBC during primary TJA should not be feared in the context of antimicrobial resistance. LEVEL OF EVIDENCE: III.

Evaluation of the standard procedure for treatment of periprosthetic joint infections of total knee and hip arthroplasty: a comparison of the 2015 and 2020 census in total joint replacement centres in Germany.

BACKGROUND: There are different procedures for both, the diagnosis and the therapy of a periprosthetic joint infection (PJI), however, national or international guidelines for a standardised treatment regime are still lacking. The present paper evaluates the use of the predominant treatment protocols for PJI in certified total joint replacement centres (EPZ) in Germany based on an EndoCert questionnaire. MATERIALS AND METHODS: The questionnaire was developed in cooperation with the EndoCert Certification Commission to survey the treatment protocols for septic revision arthroplasties in EPZ. Questions targeted the various treatment options including prosthesis preserving procedures (DAIR - Debridement, antibiotics, irrigation, and retention of the prosthesis), one-stage revision, two-stage revision, removal of the endoprosthesis and diagnostic sampling prior to re-implantation. All certified EPZ participated (n = 504) and the results from the current survey in 2020 were compared to data from a previous analysis in 2015. RESULTS: The number of centres that performed DAIR up to a maximum of 4 weeks and more than 10 weeks after index surgery decreased since 2015, while the number of centres that provided a one-stage revision as a treatment option increased (hip: + 6.3%; knee: + 6.6%). The majority of the centres (73.2%) indicated a 4-8 week period as the preferred interval between prosthesis removal and re-implantation in two-stage revision in hip as well as knee revisions. Centres with a higher number of revision surgeries (> 200 revisions/year), opted even more often for the 4-8 week period (92.3%). In two-stage revision the use of metal-based spacers with/without reinforcement with antibiotic-containing cement as an interim placeholder was significantly reduced in 2020 compared to 2015. There was also a clear preference for cemented anchoring in two-stage revision arthroplasty in the knee in 2020, whereas the majority of hip replacements was cementless. Additionally, in 2020 the number of samples for microbiological testing during the removal of the infected endoprosthesis increased and 72% of the centres took five or more samples. Overall, the number of EPZ with a standardised protocol for the procedure expanded from 2015 to 2020. CONCLUSION: While there was a trend towards standardised therapeutic algorithms for PJI with more uniform choices among the centres in 2020 compared to 2015, the treatment often remains an individual decision. However, since a consistent treatment regime is of vital importance with an expected rise of total numbers of revision arthroplasties, uniform definitions with regard to comparability and standardisation are necessary for the further development of the EndoCert system.

BCP crystals promote chondrocyte hypertrophic differentiation in OA cartilage by sequestering Wnt3a.

OBJECTIVE: Calcification of cartilage with basic calcium phosphate (BCP) crystals is a common phenomenon during osteoarthritis (OA). It is directly linked to the severity of the disease and known to be associated to hypertrophic differentiation of chondrocytes. One morphogen regulating hypertrophic chondrocyte differentiation is Wnt3a. METHODS: Calcification and sulfation of extracellular matrix of the cartilage was analysed over a time course from 6 to 22 weeks in mice and different OA grades of human cartilage. Wnt3a and ß-catenin was stained in human and murine cartilage. Expression of sulfation modulating enzymes (HS2St1, HS6St1) was analysed using quantitative reverse transcription PCR (RT-PCR). The influence of BCP crystals on the chondrocyte phenotype was investigated using quantitative RT-PCR for the marker genes Axin2, Sox9, Col2, MMP13, ColX and Aggrecan. Using western blot for ß-catenin and pLRP6 we investigated the activation of Wnt signalling. The binding capacity of BCP for Wnt3a was analysed using immunohistochemical staining and western blot. RESULTS: Here, we report that pericellular matrix sulfation is increased in human and murine OA. Wnt3a co-localised with heparan sulfate proteoglycans in the pericellular matrix of chondrocytes in OA cartilage, in which canonical Wnt signalling was activated. In vitro, BCP crystals physically bound to Wnt3a. Interestingly, BCP crystals were sufficient to induce canonical Wnt signalling as assessed by phosphorylation of LRP6 and stabilisation of ß-catenin, and to induce a hypertrophic shift of the chondrocyte phenotype. CONCLUSION: Consequently, our data identify BCP crystals as a concentrating factor for Wnt3a in the pericellular matrix and an inducer of chondrocyte hypertrophy.

Evaluation of the standard procedure for the treatment of periprosthetic joint infections (PJI) in Germany - results of a survey within the EndoCert initiative.

BACKGROUND: The periprosthetic joint infection (PJI) is a severe complication in the field of arthroplasty. Despite the rising number of primary joint replacements, no unified therapeutic standard has been established for the treatment of PJI yet. METHODS: A survey on the principles of treatment of PJI in Germany was conducted. A total of 515 EndoProthetikZentren (EPZ) were included, resulting in a response rate of 100%. RESULTS: For early infections 97.6% of the centers use prosthesis-preserving procedures (DAIR). A one-stage exchange was implemented by less than 50% of the centers. If implemented, this treatment entails a prior selection of patients for a successful treatment. The two-stage exchange is performed in all centers, and most centers proceed with the implantation of a cemented spacer between stages. 75% of the centers proceed with a center-based concept for the treatment of PJI. CONCLUSION: The aim of a uniform PJI standard at the centers has not yet been fully achieved. Further improvements within the certification were initiated. The most relevant treatment options in Germany are displayed. The two-stage revision with a cemented spacer is the most widely implemented treatment. This exposition of principles could help for the further development of standardized treatment guidelines and definitions.

The Genetic Variations Associated With Time to Aseptic Loosening After Total Joint Arthroplasty.

BACKGROUND: Total joint arthroplasty (TJA) is one of the most frequent surgical procedures performed in modern hospitals, and aseptic loosening is the most common indication for revision surgeries. We conducted a systemic exploration of potential genetic determinants for early aseptic loosening. METHODS: Data from 423 patients undergoing TJA were collected and analyzed. Three analytical groups were formed based on joint arthroplasty status. Group 1 were TJA patients without symptoms of aseptic loosening of at least 1 year, group 2 were patients with primary TJA, and group 3 were patients receiving revision surgery because of aseptic loosening. Genome-wide genotyping comparing genotype frequencies between patients with and without aseptic loosening (group 3 vs groups 1 and 2) was conducted. A case-control association analysis and linear modeling were applied to identify the impact of the identified genes on implant survival with time to the revision as an outcome measure. RESULTS: We identified 52 single-nucleotide polymorphisms (SNPs) with a genome-wide suggestive P value less than 10-5 to be associated with the implant loosening. The most remarkable odds ratios (OR) were found with the variations in the IFIT2/IFIT3 (OR, 21.6), CERK (OR, 12.6), and PAPPA (OR, 14.0) genes. Variations in the genotypes of 4 SNPs-rs115871127, rs16823835, rs13275667, and rs2514486-predicted variability in the time to aseptic loosening. The time to aseptic loosening varied from 8 to 16 years depending on the genotype, indicating a substantial effect of genetic variance. CONCLUSION: Development of the aseptic loosening is associated with several genetic variations and we identified at least 4 SNPs with a significant effect on the time for loosening. These data could help to develop a personalized approach for TJA and loosening management.

Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease in which synovial fibroblasts (SF) play a key role. Baricitinib and Tofacitinib both act intracellularly, blocking the ATP-binding side of JAK proteins and thereby the downstream signalling pathway via STAT-3. Therefore, we investigated the role of organic cation transporters (OCTs) in Baricitinib and Tofacitinib cellular transport. METHODS: OCT expression was analysed in SF isolated from RA and osteoarthritis (OA) patients, as well as peripheral blood mononuclear cells. The interaction of Baricitinib and Tofacitinib with OCTs was investigated using quenching experiments. The intracellular accumulation of both drugs was quantified using LC/MS. Target inhibition for both drugs was tested using Western blot for phosphorylated JAK1 and STAT3 upon stimulation with IL-6. RESULTS: MATE-1 expression increased in OASF compared to RASF. The other OCTs were not differentially expressed. The transport of Baricitinib was not OCT dependent. Tofacitinib; however, was exported from RASF in a MATE-1 dependent way. Tofacitinib and Baricitinib showed comparable inhibition of downstream signalling pathways. CONCLUSION: We observed different cellular uptake strategies for Baricitinib and Tofacitinib. Tofacitinib was exported out of healthy cells due to the increased expression of MATE1. This might make Tofacitinib the favourable drug.

Screw Track Osteolysis in the Cementless Total Knee Replacement Design.

BACKGROUND: There is a paucity of reports on osteolysis associated with tibial screw fixation in cementless total knee arthroplasty (TKA), and the pathophysiology is not clear. This study aimed to describe the pathology related to screw track osteolysis around the tibia in cementless TKA. METHODS: The study cohort comprised 100 revised cementless TKAs with tibial screw fixation. Screw track osteolysis and various screw angles were analyzed radiologically. Tissue samples from the joint capsule and the osteolytic cavity were investigated for metal/polyethylene wear. The type of tissue response was determined using immunohistochemistry. Retrieved tibial polyethylene inserts were analyzed for screw hole impression and mode of wear. Tissue metal content was measured by inductively coupled plasma optical emission spectrometry. Electrochemical reactions between the tibial tray and the cancellous screws were investigated. RESULTS: Radiological analysis showed screw track osteolysis predominantly at the medial aspect of the tibial component, and the severity of osteolysis positively correlated with smaller medial proximal tibial screw angles. Osteolysis was associated with high titanium concentrations but not with polyethylene particles. An open circuit potential between the screw and the tibial base plate was measured. Necrosis, osteolytic cyst formation and macrophages, T and B cells, and dendritic cells were present. CONCLUSION: The present study highlights the risk for screw track osteolysis in cementless TKA with screw fixation. Our data collectively suggest that titanium wear may contribute to screw track osteolysis in the cementless TKA design. The contribution of screw angles is difficult to prove.

The terminal complement pathway is activated in septic but not in aseptic shoulder revision arthroplasties.

BACKGROUND: The early diagnosis of suspected periprosthetic low-grade infections in shoulder arthroplasties is important for the outcome of the revision surgical procedures. The aim of this study was to investigate new biomarkers of infection in revision shoulder arthroplasties, taking into account the implant design, patient age, and comorbidities. METHODS: The study included 33 patients with shoulder arthroplasties undergoing revision surgical procedures. Microbiological diagnostic testing was performed in all cases. C-reactive protein serum levels and white blood cell counts were evaluated, and the periprosthetic tissue was stained immunohistologically for the terminal complement pathway components (C3, C5, and C9) and for CD68 and α-defensin. RESULTS: Microbiological diagnostic testing detected a periprosthetic infection in 10 reverse shoulder arthroplasties and in 4 anatomic shoulder arthroplasties, while the remaining 19 shoulder arthroplasties were classified as aseptic. We observed more Staphylococcus epidermidis infections in reverse shoulder arthroplasties and more Staphylococcus aureus infections in anatomic shoulder arthroplasties. The revision rate correlated with pre-existing comorbidities and number of previous surgical procedures. The C-reactive protein values and the incidence of specific periprosthetic radiolucent lines were significantly increased in septic revision cases. We found increased staining for all tested complement factors (C3, C5, and C9) but not for α-defensin and CD68 in septic tissue. The most interesting finding was that C9 separated septic from aseptic tissue with a predictive specificity of 100% and a sensitivity of 88.89%. CONCLUSION: We observed a strong correlation between C9 expressions in septic revision tissue. We propose that the terminal complement pathway, especially C9 deposition, may be a potential biomarker to identify septic complications using tissue biopsy specimens.

What Is the Role of Diagnostic and Therapeutic Sonication in Periprosthetic Joint Infections?

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most dreaded complications in joint replacement surgery. Diagnosis and treatment can be difficult and biofilms are of major concern due to their low susceptibility toward antibiotics. METHODS: This review focuses on the use of sonication as an evolving diagnostic and adjunct treatment modality in the context of PJI. Therapeutic application of sonication is discussed separately for its (i) direct action on bacteria, (ii) synergistic effects with antibiotics, and (iii) effects on release of antibiotics from bone cement. RESULTS: Used as a diagnostic tool, sonication shows promising results with respect to sensitivity and specificity when compared to conventional methods, notably after previous administration of antibiotics. As an adjunct treatment modality, the chemical, physical, and mechanical effects of sonication are primarily driven by cavitation and recognized as the main cause for bactericidal effects but the exact underlying mechanisms have not been identified yet. Sonication alone does not have the ability to completely eradicate biofilms but synergistic effects when used in conjunction with antibiotics have been reported. There is also evidence for enhanced antibiotic release from bone cement. CONCLUSION: Sonication is as an evolving modality in the context of PJIs. As a diagnostic tool, it has not been introduced in routine clinical practice and sonication as a treatment modality in PJIs is still in an experimental stage. Factors such as frequency, pressure, chemical activity, intensity, and exposure time need to be evaluated for optimal application of sonication and may also improve study comparison.

Effects of low-frequency ultrasound treatment of titanium surface roughness on osteoblast phenotype and maturation.

OBJECTIVE: Low-frequency ultrasound is widely used in the treatment of chronically infected wounds. To investigate its feasibility as a method for in situ restoration of metal implant surfaces in cases of peri-implantitis, we evaluated how low-frequency ultrasound affected surface properties of and response of human osteoblast-like MG63 cells to titanium (Ti). MATERIAL AND METHODS: Three Ti surfaces [hydrophobic/smooth (pretreatment, PT); hydrophobic/rough (sandblasted/acid-etched, SLA); and hydrophilic/rough (SLA processed and stored hydrophilicity, mSLA)] were subjected to 25 kHz ultrasound for 10 min/cm2 . Substrate roughness, chemical composition, and wettability were analyzed before and after ultrasound application. Osteoblastic maturation of cells on sonicated disks was compared to cells on untreated disks. RESULTS: Ultrasound treatment altered the topography of all surfaces. Contact angles were reduced, and chemical compositions were altered by ultrasound on PT and SLA surfaces. Cell response to sonicated PT was comparable to untreated PT. Alkaline phosphatase was increased on sonicated SLA compared to untreated SLA, whereas DNA, osteocalcin, BMP2, osteoprotegerin, and VEGF-A were unchanged. Cells produced less osteocalcin and BMP2 on sonicated mSLA than on untreated mSLA, but no other parameters were affected. CONCLUSIONS: These results show that low-frequency ultrasound altered Ti surface properties. Osteoblasts were sensitive to the changes induced by ultrasound treatment. The data suggest that the effect is to delay differentiation, but it is unclear whether this delay will prevent osseointegration. These results suggest that low-frequency ultrasound may be useful for treating implant surfaces in situ leading to successful re-osseointegration of implants affected by peri-implantitis.

[A review on psychosomatic factors affecting the outcome after total knee-arthroplasty (TKA)]. / Übersicht zu psychosomatischen Aspekten des Kniegelenksersatzes (TKA).

A review on psychosomatic factors affecting the outcome after total knee-arthroplasty (TKA) Objectives: In today's ageing Western societies, arthroplasty is a common treatment for endstage osteoarthritis. Despite highly developed implants and surgery, however, this treatment does not always succeed in relieving pain and restoring joint function, i.e., in restoring satisfactory algofunction. Clinicians partly blame psychological factors for this discrepancy, especially in the absence of objective medical complications. METHODS: The present review summarizes previous studies on the role of psychosomatic interactions affecting the course after total knee arthroplasty (TKA). RESULTS: During the perioperative period, patients with TKA suffer from marked psychic distress that is also linked to the postoperative algofunction. CONCLUSIONS: We discuss the theoretical and clinical implications of the findings reviewed.

Interference screw fixation of free tendon grafts: significant time-dependent decrease of the initial contact forces.

PURPOSE: Interference screw fixation of tendon grafts is a common practice in ACL surgery. Tissues like tendons and bone show a complex viscoelastic behaviour, which could affect the contact forces in interference screw fixation. These effects are not well investigated, especially over prolonged periods of time. The time-dependent behaviour of tendons was thus the subject of the study. It was our hypothesis that a substantial decrease of the contact forces will be observed. METHODS: Using an artificial bone surrogate and pig tendons, the time-dependent behaviour of the contact force in a simulated interference screw fixation was investigated over a 12-h period. As the screwing in can have deleterious effects on tendons, two scenarios, screwing in (A) and pressing the screw against the tendon (B), were investigated. RESULTS: The initial contact forces showed a magnitude of 1,299 N (A) and 2,156 N (B), respectively. A significant decrease to 530 N (A) and 461 N (B) after 12 h was observed (p < 0.001). However, more than 80 % of the relaxation occurred during the first hour. CONCLUSION: Significant relaxation of the contact force in interference screw fixation of ACL grafts occurs, which has implications for research and clinical practice. The strength of ACL fixation methods should not be assessed immediately after assembly of the specimens and comparisons should be done only when the same time intervals from assembly to testing were used. Also, in clinical practice, the initial fixation strength will probably not be maintained. Therefore, a backup fixation might be advisable.

SPECT/CT demonstrates the osseointegrative response of a stemless shoulder prosthesis.

BACKGROUND: This study evaluates bone remodeling processes in the proximal humerus induced by the implantation of a stemless shoulder prosthesis with regard to time of response and type and extent of bone turnover. METHODS: Twenty-eight patients with primary osteoarthritis of the shoulder undergoing a stemless shoulder arthroplasty were prospectively evaluated. The local metabolic bone activity in 5 regions of interest (ROIs 1-5) around the implant and in 1 reference region (ROI ref.) in the humeral diaphysis was analyzed after the application of technetium Tc 99m DPD using single-photon emission computed tomography integrated with multidetector computed tomography (SPECT/CT). The study cohort was divided into 4 groups according to the timing of the most recent follow-up appointment to evaluate the primary osseointegrative response after surgery. The bone uptake values were expressed in target (ROIs 1-5) to nontarget (ROI ref.) ratios. RESULTS: No difference within the 4 subgroups with respect to the time of local metabolic bone activity in the ROIs was found at 90 days after surgery. The highest initial metabolic activity and most temporal modifications were found in ROI 1, which was localized in the superior segment of the stem. CONCLUSIONS: SPECT/CT data suggest that the primary osseointegration of a stemless shoulder prosthesis is almost completed 3 months after implantation. Variations in metabolic activity pattern in the ROIs during follow-up may be caused by different loading conditions of the bone.