The effect of prebiotic fibre on the gut microbiome and surgical outcomes in patients with prosthetic joint infection (PENGUIN) - study protocol for a randomised, double-blind, placebo-controlled trial (ACTRN12623001273673).

Background: Prosthetic Joint Infection (PJI) is the most devastating complication of arthroplasty surgery and affects 1-5% of patients. Despite strict adherence to aseptic protocols and preventive measures, infection is the most common reason for revision arthroplasty, and the incidence is increasing. Treatment of PJI is challenging and often requires repeated major surgeries with sequentially poor results.

Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular infections in osteocytes.

Osteomyelitis caused by can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12 strains, at pH 5.

The mouse epididymal amyloid matrix is a mammalian counterpart of a bacterial biofilm.

The mouse epididymis is a long tubule connecting the testis to the vas deferens. Its primary functions are to mature spermatozoa into motile and fertile cells and to protect them from pathogens that ascend the male tract. We previously demonstrated that a functional extracellular amyloid matrix surrounds spermatozoa in the epididymal lumen and has host defense functions, properties not unlike that of an extracellular biofilm that encloses and protects a bacterial community.

Rapid bacterial evaluation beyond the colony forming unit in osteomyelitis.

Examination of bacteria/host cell interactions is important for understanding the aetiology of many infectious diseases. The colony forming unit (CFU) has been the standard for quantifying bacterial burden for the past century, however, this suffers from low sensitivity and is dependent on bacterial culturability in vitro. Our data demonstrate the discrepancy between the CFU and bacterial genome copy number in an osteomyelitis-relevant co-culture system and we confirm diagnosis and quantify bacterial load in clinical bone specimens.

Patient-Related Predictors of Treatment Failure After Two-Stage Total Hip Arthroplasty Revision for Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis.

Background: Periprosthetic joint infection (PJI) treatment has high failure rates even after 2-stage revision. Risk factors for treatment failure (TF) after staged revision for PJI are not well defined, nor is it well established how they correlate with the risks of developing an index PJI. Identifying modifiable risk factors may allow preoperative optimization, while identifying nonmodifiable risk factors can influence surgical options or advise against further surgery.

Is RANKL a potential molecular target in osteoarthritis?

Objective: Osteoarthritis (OA) is a disease of joints, in which the bone under the articular cartilage undergoes increased remodelling activity. The question is whether a better understanding of the causes and mechanisms of bone remodelling can predict disease-modifying treatments.

Design: This review summarises the current understanding of the aetiology of OA, with an emphasis on events in the subchondral bone (SCB), and the cells and cytokines involved, to seek an answer to this question.

The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section.

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates.

The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section.

Musculoskeletal infections (MSKI), which are a major problem in orthopedics, occur when the pathogen eludes or overwhelms the host immune system. While effective vaccines and immunotherapies to prevent and treat MSKI should be possible, fundamental knowledge gaps in our understanding of protective, nonprotective, and pathogenic host immunity are prohibitive. We also lack critical knowledge of how host immunity is affected by the microbiome, implants, prior infection, nutrition, antibiotics, and concomitant therapies, autoimmunity, and other comorbidities.

Saos-2 cells cultured under hypoxia rapidly differentiate to an osteocyte-like stage and support intracellular infection by Staphylococcus aureus.

The intracellular infection of osteocytes represents a clinically important aspect of osteomyelitis. However, few human osteocyte in vitro models exist and the differentiation of immature osteoblasts to an osteocyte stage typically takes at least 4-weeks of culture, making the study of this process challenging and time consuming. The osteosarcoma cell line Saos-2 has proved to be a useful model of human osteoblast to mature osteocyte differentiation.

Unbiased gene expression analysis of the delayed fracture healing observed in Zucker diabetic fatty rats.

Aims: Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Microstructural and cellular characterisation of the subchondral trabecular bone in human knee and hip osteoarthritis using synchrotron tomography.

Objective: It is unclear if different factors influence osteoarthritis (OA) progression and degenerative changes characterising OA disease in hip and knee. We investigated the difference between hip OA and knee OA at the subchondral bone (SCB) tissue and cellular level, relative to the degree of cartilage degeneration.

Design: Bone samples were collected from 11 patients (aged 70.

Hemodialysis Access Type and Access Patency Loss: An Observational Cohort Study.

Rationale & Objective: Access patency outcomes for arteriovenous fistulas (AVFs) as compared with arteriovenous grafts (AVGs) in patients receiving hemodialysis (HD) who have achieved a functioning permanent access are not fully explored.

Study Design: Observational cohort study.

Setting & Population: Fee-for-service Medicare beneficiaries aged ≥18 years with kidney failure who were newly using a permanent access for maintenance HD from the United States Renal Data System (2010-2015).

Ex vivo assessment of surgically repaired tibial plateau fracture displacement under axial load using large-volume micro-CT.

Postoperative weight bearing has the potential to generate fragmental motion of surgically repaired tibial plateau fractures (TPFs), which may contribute to loss of fracture reduction. The effect of loading on the internal distribution of fragmentary displacements is currently unknown. The aim of this study was to determine the internal displacements of surgically repaired split TPFs due to a three-bodyweight load, using large-volume micro-CT imaging and image correlation.

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis.

Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S.

Assigning trabecular bone material properties in finite element models simulating the pelvis before and after the development of peri-prosthetic osteolytic lesions.

Estimating strain distribution in the acetabulum before and after the development of peri-prosthetic osteolytic lesions secondary to total hip arthroplasty may assist with understanding the pathogenesis of this condition. This could be achieved by performing patient-specific finite element analysis of (1) total hip arthroplasty recipients with developed acetabular osteolytic lesions, and (2) models simulating the patient's pelvis and implant immediately after primary surgery. State of the art patient-specific total hip arthroplasty finite element analysis simulations obtain trabecular bone material properties from Hounsfield units within computed tomography (CT) scans of patients.

Hemodialysis Vascular Access and Risk of Major Bleeding, Thrombosis, and Cardiovascular Events: A Cohort Study.

Rationale & Objective: The risks of major bleeding, thrombosis, and cardiovascular events are elevated in patients receiving maintenance hemodialysis (HD). Our objective was to compare the risk of these outcomes in HD according to the permanent vascular access type.

Study Design: Observational cohort study.

Stressors and Acceptability of Services Among Black Caregivers of Persons With Memory Problems.

The purpose of the current study was to identify stressors of Black family caregivers (FCGs) of persons with memory problems (PWMPs), services of interest, and barriers to use of these services. Black FCGs were recruited from the Alzheimer's family program at the University of Alabama at Birmingham and affiliated geriatric clinics, media sources, and word-of-mouth referrals. Of 38 Black FCGs interviewed, 26 (68%) were female, 18 (47%) were employed, and 21 (55%) were adult children.

Elevated levels of active Transforming Growth Factor β1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis.

Objective: The association between the spatially distributed level of active TGFβ1 in human subchondral bone, and the characteristic structural and cellular parameters of human knee OA, was assessed.

Design: Paired subchondral bone samples from 35 OA arthroplasty patients, (15 men and 20 women, aged 69 ± 9 years) were obtained from beneath macroscopically present (CA+) or denuded cartilage (CA-) to determine the concentration of active TGFβ1 (ELISA) and its relationship to bone quality (synchrotron micro-CT), cellularity, and vascularization (histology).

Results: Bone samples beneath (CA-) regions had significantly increased concentrations of active TGFβ1 protein (mean difference: 26.

Erratum: Generation and analysis of innovative genomically humanized knockin , (TDP-43), and mouse models.

[This corrects the article DOI: 10.1016/j.isci.