Genomic Insights into Host Susceptibility to Periprosthetic Joint Infections: A Comprehensive Literature Review.

Periprosthetic joint infection (PJI) is a multifactorial disease, and the risk of contracting infection is determined by the complex interplays between environmental and host-related factors. While research has shown that certain individuals may have a genetic predisposition for PJI, the existing literature is scarce, and the heterogeneity in the assessed genes limits its clinical applicability. Our review on genetic susceptibility for PJI has the following two objectives: (1) Explore the potential risk of developing PJI based on specific genetic polymorphisms or allelic variations; and (2) Characterize the regulatory cascades involved in the risk of developing PJI.

SARS-CoV-2 ORF8 drives osteoclastogenesis in preexisting immune-mediated inflammatory diseases.

Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure.

Diamond-like carbon (DLC) surface treatment decreases biofilm burden by S. aureus on titanium alloy in vitro- a pilot study.

Purpose: Periprosthetic joint infection is a complication of total joint arthroplasty with treatment costs over $1.6 billion dollars per year in the US with high failure rates. Therefore, generation of coatings that can prevent infection is paramount.

The Mark Coventry Award: PhotothermAA Gel Combined With Debridement, Antibiotics, and Implant Retention Significantly Decreases Implant Biofilm Burden and Soft-Tissue Infection in a Rabbit Model of Knee Periprosthetic Joint Infection.

Background: Chronic periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. The underlying pathogenesis often involves the formation of bacterial biofilm that protects the pathogen from both host immune responses and antibiotics. The gold standard treatment requires implant removal, a procedure that carries associated morbidity and mortality risks.

Mechanistic insights into bone remodelling dysregulation by human viral pathogens.

Bone-related diseases (osteopathologies) associated with human virus infections have increased around the globe. Recent findings have highlighted the intricate interplay between viral infection, the host immune system and the bone remodelling process. Viral infections can disrupt bone homeostasis, contributing to conditions such as arthritis and soft tissue calcifications.

Periprosthetic joint infection and immunity: Current understanding of host-microbe interplay.

Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. Even with current treatments, failure rates are unacceptably high with a 5-year mortality rate of 26%. Majority of the literature in the field has focused on development of better biomarkers for diagnostics and treatment strategies including innovate antibiotic delivery systems, antibiofilm agents, and bacteriophages.

The Use of Oral Antibiotics After Total Joint Arthroplasty: A Critical Analysis Review.

» There is conflicting and insufficient evidence that extended oral antibiotic (EOA) therapy prevents infection in high-risk patients undergoing primary total joint arthroplasty (TJA), limiting recommendation for or against the practice.» In the case of aseptic revision TJA, the evidence is also conflicting and limited by underlying confounders, preventing recommendation for use of EOA.» There is fair evidence that use of EOA after debridement antibiotic therapy and implant retention of the prosthesis prolongs infection-free survival, but randomized controlled trials are needed.

Exploring Differences in Screening and Enrollment Metrics in Orthopaedic Clinical Trials.

The success of any clinical trial relies heavily on patient recruitment and retention. The purpose of this study was to review screening and enrollment metrics for orthopaedic clinical trials, comparing different patient populations to determine common challenges to recruitment and differences in rates of enrollment. Screening logs and study trackers were manually reviewed for four clinical trials at a single academic institution and included randomized controlled trials (RCTs) and an observational study.

Combination d-Amino Acid and Photothermal Hydrogel for the Treatment of Prosthetic Joint Infections.

Prosthetic joint infection (PJI) is a devastating complication requiring surgical intervention and prolonged antimicrobial treatment. The prevalence of PJI is on the rise, with an average incidence of 60,000 cases per year and a projected annual cost of $1.85 billion in the US.

Standardized quantification of biofilm in a novel rabbit model of periprosthetic joint infection.

Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. The underlying pathogenesis involves the formation of bacterial biofilm that protects the pathogen from the host immune response and antibiotics, making eradication difficult. The aim of this study was to develop a rabbit model of knee PJI that would allow reliable biofilm quantification and permit the study of treatments for PJI.

Current treatments for biofilm-associated periprosthetic joint infection and new potential strategies.

Periprosthetic joint infection (PJI) remains a devastating complication after total joint arthroplasty. Bacteria involved in these infections are notorious for adhering to foreign implanted surfaces and generating a biofilm matrix. These biofilms protect the bacteria from antibiotic treatment and the immune system making eradication difficult.

A Web-Based Interactive Patient-Provider Software Platform Does Not Increase Patient Satisfaction or Decrease Hospital Resource Utilization in Total Knee and Hip Arthroplasty Patients in a Single Large Hospital System.

Background: Web-based platforms used to enhance patient-provider communication are being explored to improve patient satisfaction and care delivery, and decrease cost. This study tested a web-based interactive patient-provider software platform (IPSP), JointCOACH, which enabled patient communication with their care team and preparatory/recovery guidance. The aims of this study are to compare (1) patient satisfaction and (2) healthcare resource utilization by patients who underwent total knee and hip replacements and added IPSP to standard of care (SOC).

Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?

Regulatory T cells (Tregs) are critical regulators of peripheral immune tolerance. Treg insufficiency can lead to autoimmune disorders, including type 1 diabetes (T1D). Increasing evidence in mouse models of T1D, as well as other autoimmune disorders, suggests that there are defects in Treg-mediated suppression.

γδ T cells support gut Ag-reactive colitogenic effector T-cell generation by enhancing Ag presentation by CD11b(+) DCs in the mesenteric LN.

T cells expressing the γδ TCR are dominant T-cell subsets in the intestinal immune system. We previously demonstrated that γδ T cells play important roles in augmenting Th17-type colitogenic immune responses in a T-cell-induced colitic inflammation model. However, its underlying mechanism remains poorly understood.

Cellular factors targeting APCs to modulate adaptive T cell immunity.

The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves.

γδ T cells restrain extrathymic development of Foxp3+-inducible regulatory T cells via IFN-γ.

Inducible Treg (iTreg) cells generated from Ag-stimulated naïve CD4(+) T cells in the periphery play an important role in regulating immune responses. TGF-β is a key cytokine that promotes this conversion process; however, how this process is regulated in vivo remains unclear. Here, we report that γδ T cells play a crucial role in controlling iTreg generation and suppressor function.

Colitogenic effector T cells: roles of gut-homing integrin, gut antigen specificity and γδ T cells.

Disturbance of T-cell homeostasis could lead to intestinal inflammation. Naive CD4 T cells undergoing spontaneous proliferation, a robust proliferative response that occurs under severe lymphopenic conditions, differentiate into effector cells producing Th1- and/or Th17-type cytokines and induce a chronic inflammation in the intestine that resembles human inflammatory bowel disease. In this study, we investigated the key properties of CD4 T cells necessary to induce experimental colitis.

Memory CD4 T cells induce selective expression of IL-27 in CD8+ dendritic cells and regulate homeostatic naive T cell proliferation.

Naive T cells undergo robust proliferation in lymphopenic conditions, whereas they remain quiescent in steady-state conditions. However, a mechanism by which naive T cells are kept from proliferating under steady-state conditions remains unclear. In this study, we report that memory CD4 T cells are able to limit naive T cell proliferation within lymphopenic hosts by modulating stimulatory functions of dendritic cells (DC).

CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals.

A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)β1-dependent mechanism, thus considered 'innate' IL-17-producing cells.

Cutting edge: Generation of colitogenic Th17 CD4 T cells is enhanced by IL-17+ γδ T cells.

Th 17 cells have been implicated in the pathogenesis of colitis; however, a cellular mechanism by which colitogenic Th17 immunity arises in vivo remains unclear. In this study, we report that a subset of IL-17(+) γδ T cells plays a crucial role in enhancing in vivo Th17 differentiation and T cell-mediated colitis. TCRβ(-/-) mice were highly susceptible to T cell-mediated colitis, whereas TCRβδ(-/-) mice were resistant to the disease.

Pyriform spidroin 1, a novel member of the silk gene family that anchors dragline silk fibers in attachment discs of the black widow spider, Latrodectus hesperus.

Spiders spin high performance threads that have diverse mechanical properties for specific biological applications. To better understand the molecular mechanism by which spiders anchor their threads to a solid support, we solubilized the attachment discs from black widow spiders and performed in-solution tryptic digests followed by MS/MS analysis to identify novel peptides derived from glue silks. Combining matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry and cDNA library screening, we isolated a novel member of the silk gene family called pysp1 and demonstrate that its protein product is assembled into the attachment disc silks.