Objectives: Recognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI. Methods: Consecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection !1 month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fisher's exact, Student's t and ManneWhitney U tests were used, as appropriate. Results: A total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and one elbow prostheses. The median time from last surgery until haematogenous PJI was 47 months (range, 1e417 months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (n ¼ 43), streptococci (n ¼ 32), enterococci (n ¼ 13), Gram-negative bacteria (n ¼ 9) and coagulase-negative staphylococci (n ¼ 8). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes). Conclusions: In acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.

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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.

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

Background Outcome of haematogenous periprosthetic joint infection (PJI) and reasons for failure are largely unknown. Methods Outcome of consecutive patients with haematogenous PJI treated at our institution between 2010 and 2019 was 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 Fisher's exact test. Results 132 haematogenous PJI episodes involving knee (n=76), hip (n=54), shoulder (n=1) or elbow (n=1) prostheses experienced by 110 patients were included. Median follow-up was 20.7 months (range, 0.2-89.9 months). Haematogenous PJI were caused by Staphylococcus aureus (n=49), Streptococcus spp. (n=36), Enterococcus faecalis (n=17), Enterobacterales (n=16), coagulase-negative staphylococci (n=9) and others (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 non-fatal failures, 21 were caused by a new pathogen and 8 by the same pathogen, in 7 episodes no pathogen was isolated. Of all non-fatal failures, 19 (53%) PJI were of haematogenous origin. Identification of the primary focus, causative pathogen and CRIME80-Score did not influence treatment outcome, but failure rate was higher following prosthesis retention compared to multi-stage exchange. Conclusions Persistence-/relapse-free survival after treatment of haematogenous PJI was high (84%). New haematogenous PJI due to the same or a new pathogen occurred frequently, reducing the treatment success to 62% after 4 years of follow-up, suggesting an individual predisposition to haematogenous PJI. The outcome was similar for different pathogens, but worse in episodes treated with prosthesis retention compared to multi-stage exchange.

Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high-risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study.

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