OBJECTIVE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends.
METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices.
RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted.
CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.

OBJECTIVE: To develop an ensemble multi-task deep learning (DL) framework for automatic and simultaneous detection, segmentation, and classification of primary bone tumors (PBTs) and bone infections based on multi-parametric MRI from multi-center.
METHODS: This retrospective study divided 749 patients with PBTs or bone infections from two hospitals into a training set (N = 557), an internal validation set (N = 139), and an external validation set (N = 53). The ensemble framework was constructed using T1-weighted image (T1WI), T2-weighted image (T2WI), and clinical characteristics for binary (PBTs/bone infections) and three-category (benign/intermediate/malignant PBTs) classification. The detection and segmentation performances were evaluated using Intersection over Union (IoU) and Dice score. The classification performance was evaluated using the receiver operating characteristic (ROC) curve and compared with radiologist interpretations.
RESULTS: On the external validation set, the single T1WI-based and T2WI-based multi-task models obtained IoUs of 0.71 ± 0.25/0.65 ± 0.30 for detection and Dice scores of 0.75 ± 0.26/0.70 ± 0.33 for segmentation. The framework achieved AUCs of 0.959 (95%CI, 0.955-1.000)/0.900 (95%CI, 0.773-0.100) and accuracies of 90.6% (95%CI, 79.7-95.9%)/78.3% (95%CI, 58.1-90.3%) for the binary/three-category classification. Meanwhile, for the three-category classification, the performance of the framework was superior to that of three junior radiologists (accuracy: 65.2%, 69.6%, and 69.6%, respectively) and comparable to that of two senior radiologists (accuracy: 78.3% and 78.3%).
CONCLUSIONS: The MRI-based ensemble multi-task framework shows promising performance in automatically and simultaneously detecting, segmenting, and classifying PBTs and bone infections, which was preferable to junior radiologists.
CONCLUSIONS: Compared with junior radiologists, the ensemble multi-task deep learning framework effectively improves differential diagnosis for patients with primary bone tumors or bone infections. This finding may help physicians make treatment decisions and enable timely treatment of patients.
CONCLUSIONS: • The ensemble framework fusing multi-parametric MRI and clinical characteristics effectively improves the classification ability of single-modality models. • The ensemble multi-task deep learning framework performed well in detecting, segmenting, and classifying primary bone tumors and bone infections. • The ensemble framework achieves an optimal classification performance superior to junior radiologists\' interpretations, assisting the clinical differential diagnosis of primary bone tumors and bone infections.

暂无摘要。

BACKGROUND: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails.
METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients\' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates.
RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036).
CONCLUSIONS: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement.
METHODS: III comparative, observational, non-randomized.

BACKGROUND: Septic nonunion is one of the major complications in fracture healing. The challenge is to identify the infection as the cause of nonunion first and then to achieve healing of the infection and the bone.
OBJECTIVE: Because of the more heterogeneous appearance of an infected nonunion, the prevalence of germ detection in surgical nonunion revision is often underestimated.
METHODS: In a retrospective study between 2010 and 2017, 86 patients with radiologically confirmed femoral shaft nonunion without clinical evidence and unremarkable medical history of a florid infection as the cause of nonunion, who had undergone primary single-stage surgical nonunion revision were analyzed. At least four intraoperatively obtained samples were evaluated for microbiological diagnosis. A distinction was made between tissue samples with subsequent 48‑h short-term incubation and tissue samples with 14-day long-term cultivation. The finding \"germ detection\" was made if at least two of the samples demonstrated bacterial growth.
RESULTS: In 18 of 86 patients with a nonunion preoperatively judged to be aseptic, positive bacterial evidence was obtained after short-term incubation. After long-term cultivation, positive bacterial detection was possible in 38 of 86 patients with a femoral shaft nonunion initially classified as aseptic. Regarding potential risk factors, the two groups demonstrated no relevant differences. In 29 patients, 1 pathogen was isolated from the obtained samples, whereas in the remaining 9 patients, a mixed culture with an average of 2.9 ± 0.5 different bacteria was detected. Identification revealed mainly low-virulence bacteria, most commonly Staphylococcus epidermidis.
CONCLUSIONS: If the preoperative diagnostics including clinical, laboratory and radiological examination as well as a careful anamnesis reveal indications of a possible infectious event, the surgical nonunion revision should be performed in two stages with specimen collection before definitive nonunion revision. For microbiological diagnosis, several representative tissue samples should independently be obtained from the nonunion site and incubated for 14 days. Only in the absence of evidence of septic nonunion is a single-stage procedure suggested.
UNASSIGNED: HINTERGRUND: Die infizierte Pseudarthrose stellt eine der schwerwiegendsten Komplikationen bei der Frakturheilung dar. Die Herausforderung besteht darin, die Infektion zuerst als Ursache einer Pseudarthrose zu erkennen und dann die Heilung der Infektion und des Knochens zu erreichen.
UNASSIGNED: Aufgrund des heterogeneren Erscheinungsbildes infizierter Pseudarthrosen wird die Prävalenz eines Keimnachweises bei der operativen Pseudarthrosenrevision häufig unterschätzt.
UNASSIGNED: In einer retrospektiven Untersuchung zwischen 2010 und 2017 wurden 86 Patienten, die aufgrund einer radiologisch gesicherten Femurschaftpseudarthrose primär revidiert wurden und die ohne klinische Hinweise auf einen floriden Infekt als Ursache der Pseudarthrose waren, analysiert. Es wurden mindestens 4 intraoperativ gewonnene Proben mikrobiologisch ausgewertet. Dabei wurde zwischen Gewebeproben mit anschließender 48-stündiger Kurzzeitbebrütung und Gewebeproben mit 14-tägiger Langzeitkultivierung unterschieden. Der Befund „Keimnachweis“ wurde gestellt, wenn mindestens 2 der Proben ein Keimwachstum zeigten.
UNASSIGNED: Bei 18 der 86 präoperativ als aseptisch eingeschätzten Pseudarthrosen konnte nach Kurzzeitbebrütung ein positiver Keimnachweis erhoben werden. Nach Langzeitbebrütung war bei 38 von 86 Patienten ein positiver Keimnachweis möglich. Hinsichtlich potenzieller Risikofaktoren zeigten die beiden Gruppen keine relevanten Unterschiede. Bei 29 Patienten wurde ein einzelner Erregertyp aus den gewonnenen Proben isoliert, während bei den übrigen 9 Patienten eine Mischkultur mit durchschnittlich 2,9 ± 0,5 verschiedenen Bakterien nachgewiesen wurde. Bei der Keimidentifizierung fanden sich mit Staphylococcus epidermidis am häufigsten niedrigvirulente Bakterien.
UNASSIGNED: Ergibt die präoperative Diagnostik unter Einbeziehung der klinischen, laborchemischen und radiologischen Untersuchung sowie der Anamnese Hinweise auf ein mögliches Infektgeschehen, sollte die operative Revision zweizeitig mit Probengewinnung vor der definitiven Pseudarthrosenrevision erfolgen. Zur mikrobiologischen Diagnostik sollten mehrere repräsentative Gewebeproben unabhängig voneinander aus der Pseudarthrosenzone gewonnen und für 14 Tage bebrütet werden. Nur bei fehlenden Hinweisen auf eine infizierte Pseudarthrose wird das einzeitige Vorgehen vorgeschlagen.

We investigate dalbavancin efficiency and tolerance among elderly in Grenoble-Alpes 32 university hospital. Among the 65 patients who received dalbavancin, 51% (33) were considered as old. Patients presented mainly bones and joint infections (52%), surgical site infection 34 (31%), and infective endocarditis (IE) (8%). Clinical cure was confirmed for 79% of old 35 patients at 1, 3, and 6 months. Six adverse events (9%) were reported after 36 dalbavancin\'s administration, but each time in combination with other antibiotics. 37 Dalbavancin had a significant effectiveness and safety profile and represents a real 38 therapeutic option in the management of deep and complex infections of elderly patients.

OBJECTIVE: We aimed to estimate the prevalence of Staphylococcus aureus producing Panton-Valentine leucocidin (PVL) isolated from children diagnosed with osteoarticular infections (OAIs), and to examine risk factors and clinical features.
METHODS: This prospective study was conducted from January 2017 to December 2018. All hospitalised children diagnosed with S. aureus OAI are included. Blood cultures, articular fluids, synovial tissues and/or bone fragments were collected for bacteriological culture. Antimicrobial susceptibility tests were determined by disk diffusion method. Genes encoding methicillin resistance (mecA) and PVL virulence factors (luk-S-PV and luk-F-PV) were detected by multiplex polymerase chain reaction. The demographic, clinical, laboratory, radiographic and clinical features were reviewed prospectively from medical records.
RESULTS: A total of 37 children with S. aureus OAIs were included, 46% of them have PVL-positive infection and 70.6% were male. The mean age was 8.12 years (±4.57), and almost were from rural settings (76.5%). Children with Staphylococcus aureus producing Panton-Valentine leucocidin (SA-PVL) were significantly associated with type of infection (P = 0.005), location of infection (P = 0.037) and abnormal X-ray (P = 0.029). All strains SA-PVL+ are sensitive to methicillin, but one strain SA-PVL negative was methicillin-resistant S. aureus, confirmed by gene mecA positive.
CONCLUSIONS: The prevalence of S. aureus infections producing PVL toxin was high in OAIs amongst Moroccan children, mainly due to methicillin-susceptible S. aureus. Type and location of infections and abnormal X-ray were significantly associated with SA-PVL. Routine diagnostic testing of PVL-SA, continuous epidemiological surveillance and multidisciplinary management of OAI is essential to prevent serious complications.

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being \"GMP-like\") targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally \"phage therapy 2.0\" has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial-academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against Staphylococcus aureus growth and biofilm formation in vitro. We successfully established an infected calvarial defect rat model. Bacterial colony numbers were significantly lower in tissues surrounding the bone in rats of the GG/nHA/CHX group after debride surgery and hydrogel implantation in the defect regions than in rats of the blank group. Rats in the GG/nHA/CHX group exhibited significantly increased new bone formation compared to those in the blank group at 4 and 8 weeks. These findings indicate that gellan gum-based hydrogel with nHA/CHX can accelerate the repair of infected bone defects.

An internal fixation composite structure of antibiotic cement plates was created. The aim of this study was to analyse the infection control effect of this structure when applied to treat a bone infection. We retrospectively analysed patients with bone infection admitted to our hospital between January 2013 and June 2019. After debridement, an antibiotic cement plate composite structure was used to fill and stabilize the defects. The treatment effect was evaluated at six months after surgery, and the infection control rate, factors associated with the recurrence of infection, and complications were analysed. If the patients had bone defects, the defect was repaired after infection control, and the infection control rate of all of the patients was re-evaluated at 12 months after surgery. A total of 548 patients were treated with this technique, including 418 men and 130 women. The infection sites included 309 tibias, 207 femurs, 16 radii and ulnae, 13 humeri, and 3 clavicles. After at least 6 months of follow-up, 92 patients (16.79%) had an infection recurrence and needed further treatment. The recurrence rate of the tibia was higher than that of the femur (P = 0.025). Eighty-nine out of 92 patients who relapsed underwent a second debridement with the same method, and the infection control rate after the second debridement was 94.71%. Complications included 8 cases of epidermal necrosis around the incision, 6 cases of internal fixation failure, and 30 cases of lower limb swelling. By the follow-up time of 12 months, another 6 patients had experienced recurrence of infection, and 4 cases were controlled after debridement. Finally, among all 548 cases, 7 patients remained persistently infected, and 6 underwent amputation. The infection control rate was 97.6% at the 1-year follow-up. The clinical efficacy of this new antibiotic cement plate composite structure for internal fixation after debridement of bone infection is stable and reliable.