Investigation of the pathogen-specific antibody response in periprosthetic joint infection.

PURPOSE: Periprosthetic joint infections (PJIs) are a very demanding complication of arthroplasty. Diagnosis of PJI and pathogen identification pose considerable challenges in clinical practice. We hypothesized that the pathogen-specific immune response to PJI reflects the infection process, provides clinically relevant information on disease course, and has the potential to further optimize antimicrobial therapy. METHODS: We conducted a prospective matched cohort pilot study with 13 patients undergoing two-stage septic revision arthroplasty (PJI patients) between 06/2020 and 06/2021, as well as 11 control patients undergoing one-stage aseptic revision arthroplasty (Non-PJI patients). Pre-, intra- and postoperative serum samples were collected at standardized time points. We developed a custom Luminex®-based quantitative bead-based suspension array (Infection Array; IA), and used it for simultaneous measurement of antibody specificities against 32 pathogens commonly associated with PJI in 267 serum samples. RESULTS: The IA was able to trace the dynamics of the pathogen-specific humoral immune response in all patients against PJI-related pathogens, prominently coagulase-negative staphylococci and streptococci. Pathogen-specific serum antibody titers declined in 62% of PJI patients over the course of treatment, while no changes in antibody titers were observed in 82% of Non-PJI patients during this study. Our serological data strongly suggested that antibody signatures reflect an immune response to microbial invasion. CONCLUSION: Our results provide insights into the pathophysiology of PJI and information on the individual disease courses. The IA is therefore a promising and novel serological tool of high resolution for monitoring the immunoproteomic footprints of infectious pathogens in the course of PJI.

Cobalt and Chromium Ions Impair Macrophage Response to Staphylococcus aureus Infection.

Cobalt-chromium-molybdenum (CoCrMo) alloys are routinely used in arthroplasty. CoCrMo wear particles and ions derived from arthroplasty implants lead to macrophage-driven adverse local tissue reactions, which have been linked to an increased risk of periprosthetic joint infection after revision arthroplasty. While metal-induced cytotoxicity is well characterized in human macrophages, direct effects on their functionality have remained elusive. Synchrotron radiation X-ray microtomography and X-ray fluorescence mapping indicated that peri-implant tissues harvested during aseptic revision of different arthroplasty implants are exposed to Co and Cr in situ. Confocal laser scanning microscopy revealed that macrophage influx is predominant in patient tissue. While in vitro exposure to Cr3+ had only minor effects on monocytes/macrophage phenotype, pathologic concentrations of Co2+ significantly impaired both, monocyte/macrophage phenotype and functionality. High concentrations of Co2+ led to a shift in macrophage subsets and loss of surface markers, including CD14 and CD16. Both Co2+ and Cr3+ impaired macrophage responses to Staphylococcus aureus infection, and particularly, Co2+-exposed macrophages showed decreased phagocytic activity. These findings demonstrate the immunosuppressive effects of locally elevated metal ions on the innate immune response and support further investigations, including studies exploring whether Co2+ and Cr3+ or CoCrMo alloys per se expose the patients to a higher risk of infections post-revision arthroplasty.

Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells.

BACKGROUND: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are used in regenerative medicine and related research involving immunomodulatory, anti-inflammatory, anti-fibrotic and regenerative functions. Isolation of BM-MSCs from samples obtained during total hip arthroplasty (THA) is routinely possible. Advanced age and comorbidities of the majority of patients undergoing THA limit their applicability. Our study aimed to evaluate the potential of bone marrow obtained during periacetabular osteotomy (PAO) as a novel source of BM-MSCs from young donors by analyzing cell yield and cell characteristics. METHODS: Bone samples were obtained from the anterior Os ilium or superior Os pubis during PAO and from the femoral cavity during primary THA. Isolation of bone marrow-derived mononuclear cells (BM-MNCs) was performed by density gradient centrifugation. The samples from PAO and THA patients were compared in terms of BM-MSC yield, colony formation and the proportion of BM-MSCs within the BM-MNC population using flow cytometry analysis. The cells were characterized based on the expression of BM-MSC-specific surface markers. The functionality of the cells was compared by quantifying post-thaw viability, metabolic activity, proliferation capacity, senescence-associated beta galactosidase (SA-ß-gal) expression, trilineage differentiation potential and major secretome proteins. RESULTS: Isolation of BM-MNCs was possible in a reliable and reproducible manner when using bone from PAO containing more than 0.24 g bone marrow. PAO patients were younger than patients of the THA group. Bone obtained during PAO contained less bone marrow and led to a lower BM-MSC number after the first cell culture passage compared to BM-MSCs obtained during THA. BM-MSCs from PAO samples are characterized by a higher proliferation capacity. This results in a higher yield in cell culture passage two, when normalized to the sample weight. BM-MSCs from PAO patients showed increased secretion of TGF-ß1, TIMP2, and VEGF upon osteogenic differentiation. BM-MSCs from PAO and THA patients revealed similar results regarding the onset of SA-ß-gal expression and trilineage differentiation capacity. CONCLUSIONS: We suggest that bone obtained during PAO is a promising novel source for BM-MSCs from young donors. Limited absolute cell yield due to low sample weight must be considered in early cell culture passages and might be critical for the range of clinical applications possible for BM-MSCs from this source. The higher proliferation capacity and increased growth factor secretion of BM-MSCs from young donors may be beneficial for future regenerative cell therapies, in vitro models, and tissue engineering.

Clinical and Radiological Outcome of Disc Arthroplasty for the Treatment of Cervical Spondylotic Myelopathy.

INTRODUCTION: The aim of this study is to evaluate the clinical and radiological results of cervical disc arthroplasty (CDA) in patients with cervical spondylotic myelopathy (CSM) using the CP ESP® disc prosthesis. MATERIALS AND METHODS: Prospectively collected data of 56 patients with CSM have been analyzed. The mean age at surgery was 35.6 years (range: 25-43 years). The mean follow-up was 28.2 months (range: 13-42 months). The range of motion (ROM) of the index segments, as well as upper and lower adjacent segments, was measured before surgery and at final follow-up. The C2-C7 sagittal vertical axis (SVA), C2-C7 cervical lordosis (CL), and T1 slope minus cervical lordosis (T1s-CL) were analyzed as well. Pain intensity was measured preoperatively and during follow-up using an 11-point numeric rating scale (NRS). Modified Japanese Orthopaedic Association (mJOA) score was assessed preoperatively and during follow-up for the clinical assessment of myelopathy. Surgical and implant-associated complications were analyzed as well. RESULTS: The NRS pain score improved from a mean of 7.4 (±1.1) preoperatively to a mean of 1.5 (±0.7) at last follow-up (p < 0.001). The mJOA score improved from a mean of 13.1 (±2.8) preoperatively to a mean of 14.8 (±2.3) at last follow-up (p < 0.001). The mean ROM of the index levels increased from 5.2° (±3.0) preoperatively to 7.3° (±3.2) at last follow-up (p < 0.05). Four patients developed heterotopic ossifications during follow-up. One patient developed permanent dysphonia. CONCLUSIONS: CDA showed good clinical and radiological outcome in this cohort of young patients. The motion of index segments could be preserved. CDA may be a viable treatment option in selected patients with CSM.

Noninfectious tissue interactions at periprosthetic interfaces.

The success of hip arthroplasty is based on modern materials in addition to the continuous development of surgical techniques and clinical experience gained over six decades. The biocompatible implant materials used in hip arthroplasty can be textured or coated with biomimetic surfaces to ensure durable component ingrowth and moderate host response. Material integrity plays a critical role in the durability of the stable interface between implant components and periprosthetic tissues. Inflammation at the interfaces due to the release of degradation products from the implant materials is one of the causes of hip arthroplasty failure. This review summarizes the implant materials currently used in hip arthroplasty, their preclinical testing and the postoperative neogenesis of periprosthetic tissues, and the interactions of periprosthetic bone and the implant materials at the periprosthetic interfaces.

[Postoperative outcomes and survival rates after aseptic revision total hip arthroplasty : What can patients expect from revision surgery?] / Postoperative Ergebnisse und Überlebensraten nach aseptischem Hüft-TEP-Wechsel : Was können Patient*innen von einem Revisionseingriff erwarten?

BACKGROUND: In 2020, more than 14,000 aseptic revision procedures for total hip arthroplasty (THA) were registered in Germany. Patient expectations of revision hip arthroplasty are not substantially different from expectations of primary hip replacement. OUTCOME: However, revision surgery is associated with increased complication rates and a higher proportion of dissatisfied patients. In particular, poorer postoperative function and mobility as well as increased pain levels following revision THA have been described compared to the outcome after primary THA. Quality of life and return-to-work can also be impaired. SURVIVAL RATE: Implant survival is influenced by age, BMI, and comorbidities of the patients, but also by the size and complexity of bone defects, the extent of periprosthetic soft tissue compromise and the choice of revision implant(s). In addition, the number of previous revision surgeries inversely correlates with the survival rates. Previous revisions have been shown to be associated with increased risks of aseptic loosening, instability and periprosthetic infection.

Analytical and toxicological aspects of nanomaterials in different product groups: Challenges and opportunities.

The widespread integration of engineered nanomaterials into consumer and industrial products creates new challenges and requires innovative approaches in terms of design, testing, reliability, and safety of nanotechnology. The aim of this review article is to give an overview of different product groups in which nanomaterials are present and outline their safety aspects for consumers. Here, release of nanomaterials and related analytical challenges and solutions as well as toxicological considerations, such as dose-metrics, are discussed. Additionally, the utilization of engineered nanomaterials as pharmaceuticals or nutraceuticals to deliver and release cargo molecules is covered. Furthermore, critical pathways for human exposure to nanomaterials, namely inhalation and ingestion, are discussed in the context of risk assessment. Analysis of NMs in food, innovative medicine or food contact materials is discussed. Specific focus is on the presence and release of nanomaterials, including whether nanomaterials can migrate from polymer nanocomposites used in food contact materials. With regard to the toxicology and toxicokinetics of nanomaterials, aspects of dose metrics of inhalation toxicity as well as ingestion toxicology and comparison between in vitro and in vivo conclusions are considered. The definition of dose descriptors to be applied in toxicological testing is emphasized. In relation to potential exposure from different products, opportunities arising from the use of advanced analytical techniques in more unique scenarios such as release of nanomaterials from medical devices such as orthopedic implants are addressed. Alongside higher product performance and complexity, further challenges regarding material characterization and safety, as well as acceptance by the general public are expected.

Synchrotron-based characterization of arthroprosthetic CoCrMo particles in human bone marrow.

Particles released from cobalt-chromium-molybdenum (CoCrMo) alloys are considered common elicitors of chronic inflammatory adverse effects. There is a lack of data demonstrating particle numbers, size distribution and elemental composition of bone marrow resident particles which would allow for implementation of clinically relevant test strategies in bone marrow models at different degrees of exposure. The aim of this study was to investigate metal particle exposure in human periprosthetic bone marrow of three types of arthroplasty implants. Periprosthetic bone marrow sections from eight patients exposed to CoCrMo particles were analyzed via spatially resolved and synchrotron-based nanoscopic X-ray fluorescence imaging. These analyses revealed lognormal particle size distribution patterns predominantly towards the nanoscale. Analyses of particle numbers and normalization to bone marrow volume and bone marrow cell number indicated particle concentrations of up to 1 × 1011 particles/ml bone marrow or 2 × 104 particles/bone marrow cell, respectively. Analyses of elemental ratios of CoCrMo particles showed that particularly the particles' Co content depends on particle size. The obtained data point towards Co release from arthroprosthetic particles in the course of dealloying and degradation processes of larger particles within periprosthetic bone marrow. This is the first study providing data based on metal particle analyses to be used for future in vitro and in vivo studies of possible toxic effects in human bone marrow following exposure to arthroprosthetic CoCrMo particles of different concentration, size, and elemental composition. Graphical abstract.

[Minimally invasive periacetabular osteotomy for adult hip dysplasia]. / Minimal-invasive periazetabuläre Osteotomie zur Therapie der Hüftdysplasie des Erwachsenen.

OBJECTIVE: Performance of a periacetabular osteotomy (PAO) using a minimally invasive approach for three-dimensional correction of the acetabular position. INDICATIONS: Symptomatic developmental dysplasia of the hip in adolescents and adults. CONTRAINDICATIONS: Advanced osteoarthritis of the hip, incongruence of the hip joint surfaces. SURGICAL TECHNIQUE: A periacetabular osteotomy is performed via a minimally invasive approach. RESULTS: In total, 39 patients were followed up for 3.5 (3-4.5) years. The lateral center-edge angle of Wiberg increased significantly from 16.1° (7-24°) to 30.5° (25-37°) (p < 0.0001), the acetabular index changed from 13.2° (2-25.3°) to 2.8° (-3-13°; p < 0.0001). Mean duration of surgery was 88 (57-142) minutes. No major complications occurred.

Outcome and Failure Analysis of 132 Episodes of Hematogenous Periprosthetic Joint Infections-A Cohort Study.

Background: The outcomes of hematogenous periprosthetic joint infection (PJI) and reasons for failure are largely unknown. Methods: The outcomes of consecutive patients with hematogenous PJI treated at our institution between 2010 and 2019 were evaluated. Failure was classified as persistence or relapse of infection or new infection. Failure-free survival was assessed using Kaplan-Meier analysis. Proportions between groups were compared with the Fisher exact test. Results: One hundred thirty-two hematogenous PJI episodes involving knee (n = 76), hip (n = 54), shoulder (n = 1), or elbow (n = 1) prostheses experienced by 110 patients were included. The median follow-up (range) was 20.7 (0.2-89.9) months. Hematogenous PJIs were caused by Staphylococcus aureus (n = 49), Streptococcus spp. (n = 36), Enterococcus faecalis (n = 17), Enterobacterales (n = 16), coagulase-negative staphylococci (n = 9), and other (n = 6). Debridement and implant retention were performed in 50 (38%), prosthesis exchange or removal in 79 (60%), and no surgery in 3 episodes (2%). Treatment failed in 42 episodes (32%), including 6 infection-related deaths. Among 36 nonfatal failures, 21 were caused by a new pathogen and 8 by the same pathogen, in 7 episodes no pathogen was isolated. Of all nonfatal failures, 19 (53%) PJIs were of hematogenous origin. Identification of the primary focus, causative pathogen, and CRIME80 Score did not influence treatment outcome, but the failure rate was higher following prosthesis retention compared with multistage exchange. Conclusions: Persistence-/relapse-free survival after treatment of hematogenous PJI was high (84%). New hematogenous PJI due to the same or a new pathogen occurred frequently, reducing treatment success to 62% after 4 years of follow-up, suggesting an individual predisposition to hematogenous PJI. The outcome was similar for different pathogens but worse in episodes treated with prosthesis retention compared with multistage exchange.

The contribution of the histopathological examination to the diagnosis of adverse local tissue reactions in arthroplasty.

The histopathological examination of the periprosthetic soft tissue and bone has contributed to the identification and description of the morphological features of adverse local tissue reactions (ALTR)/adverse reactions to metallic debris (ARMD). The need of a uniform vocabulary for all disciplines involved in the diagnosis and management of ALTR/ARMD and of clarification of the parameters used in the semi-quantitative scoring systems for their classification has been considered a pre-requisite for a meaningful interdisciplinary evaluation.This review of key terms used for ALTR/ARMD has resulted in the following outcomes: (a) pseudotumor is a descriptive term for ALTR/ARMD, classifiable in two main types according to its cellular composition defining its clinical course; (b) the substitution of the term metallosis with presence of metallic wear debris, since it cannot be used as a category of implant failure or histological diagnosis; (c) the term aseptic lymphocytic-dominated vasculitis- associated lesion (ALVAL) should be replaced due to the absence of a vasculitis with ALLTR/ALRMD for lymphocytic-predominant and AMLTR/AMRMD for macrophage-predominant reaction.This review of the histopathological classifications of ALTR/ARMD has resulted in the following outcomes: (a) distinction between cell death and tissue necrosis; (b) the association of corrosion metallic debris with adverse local lymphocytic reaction and tissue necrosis; (c) the importance of cell and particle debris for the viscosity and density of the lubricating synovial fluid; (d) a consensus classification of lymphocytic infiltrate in soft tissue and bone marrow; (e) evaluation of the macrophage infiltrate in soft tissues and bone marrow; (f) classification of macrophage induced osteolysis/aseptic loosening as a delayed type of ALTR/ARMD; (g) macrophage motility and migration as possible driving factor for osteolysis; (h) usefulness of the histopathological examination for the natural history of the adverse reactions, radiological correlation, post-marketing surveillance, and implant registries.The review of key terms used for the description and histopathological classification of ALTR/ARMD has resulted in a comprehensive, new standard for all disciplines involved in their diagnosis, clinical management, and long-term clinical follow-up. Cite this article: EFORT Open Rev 2021;6:399-419. DOI: 10.1302/2058-5241.6.210013.

Metal-Specific Biomaterial Accumulation in Human Peri-Implant Bone and Bone Marrow.

Metallic implants are frequently used in medicine to support and replace degenerated tissues. Implant loosening due to particle exposure remains a major cause for revision arthroplasty. The exact role of metal debris in sterile peri-implant inflammation is controversial, as it remains unclear whether and how metals chemically alter and potentially accumulate behind an insulating peri-implant membrane, in the adjacent bone and bone marrow (BM). An intensively focused and bright synchrotron X-ray beam allows for spatially resolving the multi-elemental composition of peri-implant tissues from patients undergoing revision surgery. In peri-implant BM, particulate cobalt (Co) is exclusively co-localized with chromium (Cr), non-particulate Cr accumulates in the BM matrix. Particles consisting of Co and Cr contain less Co than bulk alloy, which indicates a pronounced dissolution capacity. Particulate titanium (Ti) is abundant in the BM and analyzed Ti nanoparticles predominantly consist of titanium dioxide in the anatase crystal phase. Co and Cr but not Ti integrate into peri-implant bone trabeculae. The characteristic of Cr to accumulate in the intertrabecular matrix and trabecular bone is reproducible in a human 3D in vitro model. This study illustrates the importance of updating the view on long-term consequences of biomaterial usage and reveals toxicokinetics within highly sensitive organs.

Systemic Effects of Metals Released from Arthroplasty Implants - a Brief Summary. / Systemische Effekte einer Metallbelastung durch Endoprothesen ­ ein Überblick.

In recent years, increasing concern has been raised regarding potential systemic toxicity of metals released from arthroplasty implants. A lack of valid metal thresholds for human (organ) toxicity and the prospect of multi-decade survival of modern hip and knee replacements pose special challenges. Indeed, evidence of systemic effects of metals released from such implants is largely missing. Systemic cobalt exposure has repeatedly been associated with cardiotoxic and neurotoxic effects, and also with thyroid dysfunction. The toxic potential of chromium is considered less pronounced. Yet, in arthroplasty there is usually a co-exposure to chromium and cobalt which complicates evaluation of element-specific effects. Toxicity of titanium dioxide nanoparticles has been subject to debate among international regulatory authorities. Their wide use in a variety of products in everyday life, such as toothpaste, cosmetics and food colorants, hampers the assessment of an arthroplasty-induced systemic titanium exposure. To date there is no clear evidence for systemic complications due to titanium dioxide released from arthroplasty implants. Release of further metals such as tantalum, niobium, nickel, vanadium and zirconium from hip and knee replacement implants has been described occasionally, but systemic effects of respective long-term exposure scenarios are unknown. Generally, the characterization of all released metals regarding their chemical and physical specifications is critical for the evaluation of potential systemic risks. Systematic studies investigating the accumulation of metals relevant in arthroplasty in different organs/organ systems and the biological consequences of such accumulations are urgently needed.

[Nerve Injuries in Hip and Knee Arthroplasty - Risk Factors, Diagnostic and Therapeutic Approaches]. / Iatrogene Nervenläsionen in der Hüft- und Knieendoprothetik.

Iatrogenic nerve injuries are rare complications of total hip and knee arthroplasty, which may cause chronic pain and loss of function, severely affecting the patient's daily activities and quality of life. Nerves "at risk" include the sciatic nerve, the femoral nerve, the lateral femoral cutaneous nerve and the superior gluteal nerve during total hip arthroplasty, and the infrapatellar branch of the saphenous nerve as well as the peroneal nerve during total knee arthroplasty. Multiple procedure-related and patient-related factors have been identified to modify the risk of nerve injury in the course of lower limb joint replacement surgery. These include the surgeon's skills, the surgical approach, the type of implant fixation, the intraoperative positioning of the patient, as well as pre-existing scars, the patient's sex, age and comorbidities. Diagnostic and therapeutic approaches should be based on the aetiology of the lesion: iatrogenic nerve lesions can result from direct (compression or transection) and/or indirect (traction, ischemia) trauma. The majority of nerve injuries encountered in hip or knee arthroplasty has been referred to as "minor" nerve lesions, which generally respond very well to non-operative treatment. "Major" nerve lesions, such as complete motor nerve transection, may result in lifelong impairment. Any perioperatively encountered neurological deficit requires a meticulous diagnostic work-up and an individually tailored treatment strategy, respecting aetiology and anatomic site of the nerve lesion as well as the individual patient's needs and comorbidities.

Diagnosis of Metal Hypersensitivity in Total Knee Arthroplasty: A Case Report.

Delayed type hypersensitivity (DTH) reactions are considered infrequent complications in arthroplasty, but have been recognized to be associated with devastating morbidity and substantial decrease in quality of life of affected patients. Chronic inflammation of artificial joints and associated loss of peri-implant bone often require revision surgery. Methods for the diagnosis of implant-related DTH are available but infrequently considered to the full extent. Sequential diagnostics based on exclusion of septic complications, local and systemic metal level determination, lymphocyte transformation testing (LTT), and local T cell subset analysis are required for an unequivocal DTH diagnosis. Here, we report on a patient with a history of chronic rheumatoid arthritis and an unfavorable outcome of unilateral knee arthroplasty. This case illustrates pitfalls and difficulties in the course of recurrent inflammation following joint replacement. In the early course, suspicion of low-grade bacterial infection led to three two-stage revisions. Afterwards, the joint was proven to be sterile. However, metal level quantification revealed release of especially cobalt and chromium from the joint, LTT indicated persisting cobalt and nickel sensitization and subset analysis of T cells from the synovium suggested DTH as a root cause for the inflammatory symptoms. This report aims to recommend the depicted diagnostic algorithm as an adequate tool for future DTH detection. Yet, systemic to local subset ratios for effector memory and regulatory T cells should be derived from sufficient patient numbers to establish it as a diagnostic marker. Moreover, future prospects regarding implant-related DTH diagnostics are discussed. Therapeutic options for the portrayed patient are proposed, considering pharmaceutical, cell-therapeutic and surgical aspects. Patients who experience peri-implant inflammation but do not have obvious mechanical or infectious problems remain a diagnostic challenge and are at high risk of being treated inadequately. Since potentially sensitizing materials are regularly used in arthroplasty, it is essential to detect cases of acute DTH-derived inflammation of an artificial joint at early postoperative stages. This would reduce the severity of inflammation-related long-term consequences for affected patients and may avoid unnecessary revision surgery.

The Allergic Bone Marrow? The Immuno-Capacity of the Human Bone Marrow in Context of Metal-Associated Hypersensitivity Reactions.

Arthroplasty ranks among the greatest achievements of surgical medicine, with total hip replacement termed "the operation of the century." Despite its wide success, arthroplasty bears risks, such as local reactions to implant derived wear and corrosion products. Prevalence of allergies across Western society increases and along the number of reported hypersensitivity reactions to orthopedic implant materials. In this context the main focus is on delayed hypersensitivity (DTH). This mechanism is mainly attributed to T cells and an overreaction of the adaptive immune system. Arthroplasty implant materials are in direct contact with bone marrow (BM), which is discussed as a secondary lymphoid organ. However, the mechanisms of sensitization toward implant wear remain elusive. Nickel and cobalt ions can form haptens with native peptides to activate immune cell receptors and are therefore common T helper allergens in cutaneous DTH. The rising prevalence of metal-related allergy in the general population and evidence for the immune-modulating function of BM allow for the assumption hypersensitivity reactions could occur in peri-implant BM. There is evidence that pro-inflammatory factors released during DTH reactions enhance osteoclast activity and inhibit osteoblast function, an imbalance characteristic for osteolysis. Even though some mechanisms are understood, hypersensitivity has remained a diagnosis of exclusion. This review aims to summarize current views on the pathomechanism of DTH in arthroplasty with emphasis on BM and discusses recent advances and future directions for basic research and clinical diagnostics.

Long-term antimicrobial suppression prevents treatment failure of streptococcal periprosthetic joint infection.

OBJECTIVES: To evaluate the effect of oral antimicrobial suppression on the outcome of streptococcal periprosthetic joint infection (PJI). METHODS: Consecutive patients with streptococcal PJI receiving antimicrobial suppression for >6 months were prospectively included and compared to a retrospective control group without suppression. Outcome was assessed with Kaplan-Meier analysis and compared by the log-rank Mantel-Cox test. Multivariate analysis was used to identify factors associated with treatment failure. RESULTS: Of 69 streptococcal PJI episodes (37 knee, 31 hip and one shoulder PJI), 43 (62%) were caused by beta-hemolytic streptococci and 26 (38%) by viridans group streptococci. Debridement and prosthesis retention was performed in 27 (39%), one-stage exchange in 5 (7%), multi-stage exchange in 31 (44%) and prosthesis removal in 6 patients (9%). 24 patients (35%) were treated with antimicrobial suppression receiving oral amoxicillin (n = 22), doxycycline (n = 1) or clindamycin (n = 1). After a median follow-up of 13 months (range, 0.5-111 months), 38 of 65 patients (58%) were infection-free. Suppressive antimicrobial treatment was associated with higher success rate compared with no suppression (93% vs. 57%, p = 0.002), representing the only significant independent factor preventing treatment failure. CONCLUSIONS: Long-term antimicrobial suppression was associated with significantly better treatment outcome and should be strongly considered in streptococcal PJI.

Multi-elemental nanoparticle exposure after tantalum component failure in hip arthroplasty: In-depth analysis of a single case.

Porous tantalum components are widely used for complex acetabular reconstructions in revision hip arthroplasty. Multiple other metal alloys such as titanium-aluminum-vanadium or cobalt-chromium-molybdenum are principally used in artificial joint setups. We report a case of tantalum component failure being both cause and effect of a multiple metal exposure. Our aims were to assess and to characterize associated particle exposure and biological consequences. Metal level quantification revealed substantial in vivo exposure to particulate and dissociated tantalum, zirconium, chromium, cobalt, molybdenum, titanium, aluminum and vanadium in periprosthetic compartments. Aside from micron-sized particles, nanoparticles of a broad size range and elemental composition were obtained. Histological exams verified a spectrum of necrotic changes in the periprosthetic tissues. In the presented case tantalum release was accompanied by concomitance of particles originating from other utilized metals. We conclude that an overall in vivo exposure assessment is mandatory for realistic appraisal of metal toxicity and associated risks.