Antonio Pellegrini

Osteomyelitis (OM) is a major challenge in orthopedic surgery. The diagnosis of OM is based on imaging and laboratory tests, but it still presents some limitations. Therefore, a deeper comprehension of the pathogenetic mechanisms could enhance diagnostic and treatment approaches. OM pathogenesis is based on an inflammatory response to pathogen infection, leading to bone loss. The present study aims to investigate the potential diagnostic role of a panel of osteoimmunological serum biomarkers in the clinical approach to OM. The focus is on the emerging infection biomarker sCD14-ST, along with osteoimmunological and inflammatory serum biomarkers, to define a comprehensive biomarker panel for a multifaced approach to OM. The results, to our knowledge, demonstrate for the first time the diagnostic and early prognostic role of sCD14-ST in OM patients, suggesting that this biomarker could address the limitations of current laboratory tests, such as traditional inflammatory markers, in diagnosing OM. In addition, the study highlights a relevant diagnostic role of SuPAR, the chemokine CCL2, the anti-inflammatory cytokine IL-10, the Wnt inhibitors DKK-1 and Sclerostin, and the RANKL/OPG ratio. Moreover, CCL2 and SuPAR also exhibited early prognostic value.

The most frequent cause of periprosthetic infections (PJIs) is intraoperative contamination; hence, antibiotic prophylaxis plays a crucial role in prevention. Modifications to standard prophylaxis can be considered if there is a high incidence of microorganisms resistant to current protocols. To date, very few studies regarding microbial etiology have been published in Italy. In this single-center, retrospective study conducted at IRCCS Ospedale Galeazzi-Sant’Ambrogio in Milan, we analyzed hip, knee, and shoulder PJIs in patients undergoing first implantation between 1 January 17 and 31 December 2021. The primary aim was to derive a local microbiological case history. The secondary aim was to evaluate the adequacy of preoperative antibiotic prophylaxis in relation to the identified bacteria. A total of 57 PJIs and 65 pathogens were identified: 16 S. aureus, 15 S. epidermidis, and 10 other coagulase-negative staphylococci (CoNS), which accounted for 63% of the isolations. A total of 86.7% of S. epidermidis were methicillin-resistant (MRSE). In line with other case reports, we found a predominance of staphylococcal infections, with a lower percentage of MRSA than the Italian average, while we found a high percentage of MRSE. We estimated that 44.6% of the bacteria isolated were resistant to cefazolin, our standard prophylaxis. These PJIs could be prevented by using glycopeptide alone or in combination with cefazolin, but the literature reports conflicting results regarding the adequacy of such prophylaxis. In conclusion, our study showed that in our local hospital, our standard antibiotic prophylaxis is ineffective for almost half of the cases, highlighting the importance of defining specific antibiotic guidelines based on the local bacterial prevalence of each institution.

Periprosthetic joint infections (PJIs) in arthroplasty and osteosynthesis-associated infections (OAIs) in reconstructive surgery still represent a challenging complication in orthopaedics and traumatology causing a burden worsening the patient’s quality of life, for caregiver and treating physicians, and for healthcare systems. PJIs and OAIs are the result of bacterial adhesion over an implant surface with subsequent biofilm formation. Therefore, the clinical pathological outcome is a difficult-to-eradicate persistent infection. Strategies to treat PJIs and OAIs involve debridement, the replacement of internal fixators or articular prostheses, and intravenous antibiotics. However, long treatments and surgical revision cause discomfort for patients; hence, the prevention of PJIs and OAIs represents a higher priority than treatment. Local antibiotic treatments through coating-release systems are becoming a smart approach to prevent this complication. Hydrophilic coatings, loaded with antibiotics, simultaneously provide a barrier effect against bacterial adhesion and allow for the local delivery of an antibiotic. The intraoperative use of a hyaluronan (HY)-derivative coating in the form of a gel, loaded with antibiotics to prevent PJI, has recently raised interest in orthopaedics. Current evidence supports the use of this coating in the prophylaxis of PJI and IRIs in terms of clinical outcomes and infection reduction. Thus, the purpose of this narrative review is to assess the use of a commercially available HY derivative in the form of a gel, highlighting the characteristics of this biomaterial, which makes it attractive for the management of PJIs and IRIs in orthopaedics and traumatology.

The analysis of synovial fluid is a crucial step in the diagnosis of prosthetic joint infections (PJIs). Recently several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI. In this study, synovial calprotectin was analyzed by a commercial stool test to explore whether it might accurately predict PJIs. The synovial fluids of 55 patients were analyzed and calprotectin levels were compared to other synovial biomarkers of PJI. Of the 55 synovial flu-ids, 12 patients were diagnosed with PJI and 43 with an aseptic failure of the implant. Specificity, sensitivity, and AUC of calprotectin resulted in 0.944, 0.80, and 0.852 (95%CI: 0.971–1.00), respectively, with a set threshold of 529.5 µg/g. Calprotectin had a statistically relevant correlation with the synovial leucocyte counts (rs = 0.69, p < 0.001) and the percentage of synovial neutrophils (rs = 0.61, p < 0.001). From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicators of local infection, and the use of a commercial lateral flow stool test could be a cost-effective strategy delivering rapid and reliable results and supporting the diagnostic process of PJI.

Periprosthetic joint infection (PJI) is among the most feared orthopedic complications. Critical questions are whether the infection is completely resolved before reimplantation and what the clinical significance of positive culture is at reimplantation. The aim of this study was to determine whether a correlation exits between culture results at reimplantation after spacer insertion for hip and knee PJI and treatment failure rate. The data of 84 patients who underwent two-stage exchange arthroplasty for hip or knee PJI were reviewed and the results of intraoperative culture at reimplantation were analyzed quantitatively and qualitatively. Correlations were sought between these patterns and treatment outcome. Our data indicate no evidence for a correlation between positive culture at reimplantation and greater risk of treatment failure. Nonetheless, we noted a higher, albeit statistically not significant rate of treatment failure in patients with at least two samples testing positive. The role of microbiology at reimplantation remains unclear, but a positive culture might signal increased risk for subsequent implant failure. Further studies are needed to elucidate the implications of this finding.

Bone is a very dynamic tissue, subject to continuous renewal to maintain homeostasis through bone remodeling, a process promoted by two cell types: osteoblasts, of mesenchymal derivation, are responsible for the deposition of new material, and osteoclasts, which are hematopoietic cells, responsible for bone resorption. Osteomyelitis (OM) is an invasive infectious process, with several etiological agents, the most common being Staphylococcus aureus, affecting bone or bone marrow, and severely impairing bone homeostasis, resulting in osteolysis. One of the characteristic features of OM is a strong state of oxidative stress (OS) with severe consequences on the delicate balance between osteoblastogenesis and osteoclastogenesis. Here we describe this, analyzing the effects of OS in bone remodeling and discussing the need for new, easy-to-measure and widely available OS biomarkers that will provide valid support in the management of the disease.

Classification and management options for prosthetic joint infection Antonio Pellegrini, Virginia Suardi, Claudio Legnani