A pilot study of mitochondrial response to an in vivo prosthetic joint Staphylococcus aureus infection model.

Prosthetic joint infections (PJI) are associated with orthopaedic morbidity and mortality. Mitochondria, the "cell's powerhouses," are thought to play crucial roles in infection response and in increased risk of sepsis mortality. No current research discusses PJI's effect on mitochondrial function and a lack of understanding of immune-infection interactions potentially hinders patient care. The purpose of this pilot study was to evaluate the impact of simulated PJI on local tissue mitochondrial function. Using an established prosthetic implant-associated in vivo model, tissues were harvested from the surgical limb of a methicillin-sensitive Staphylococcus aureus implant-associated infection group (n = 6) and compared to a noninfected group (n = 6) at postoperative day (POD) 21. Using mitochondrial coupling assays, oxygen consumption rate and extracellular acidification rate were assessed in each group. Electron flow through mitochondrial complexes reflected group activity. Electron Paramagnetic Resonance (EPR) spectrometry measured the oxidizing potential of serum samples from infected versus noninfected groups. On POD21, colony-forming units per gram of tissue showed 5 × 109 in the infected group and 101 in the noninfected group (p < 0.0001). Maximal respiration and oxygen consumption due to adenosine triphosphate synthesis were significantly lower in isolated mitochondria from infected limbs (p = 0.04). Both groups had similar complex I, III, IV, and V activity (p > 0.1). Infected group EPR signal intensity reflecting reactive oxygen species levels was 1.31 ± 0.30 compared to 1.16 ± 0.28 (p = 0.73) in the noninfected group. This study highlights PJI's role in mammalian cell mitochondrial dysfunction and oxidative tissue damage, which can help develop interventions to combat PJI.

Program Barriers and Facilitators in Virtual Cancer Exercise Implementation: A Qualitative Analysis.

Introduction/Purpose: Due to the coronavirus disease 2019 (COVID-19) pandemic, many in-person cancer exercise and rehabilitation programs necessarily transitioned to virtual formats to meet the needs of individuals living with and beyond cancer. The purpose of this study was to qualitatively assess program-level facilitators and barriers to virtual exercise program implementation and to identify preferred strategies to overcome implementation barriers. Methods: US-based virtual cancer exercise and rehabilitation programs were recruited from professional networks via an emailed screening questionnaire. Eligible programs identified a point of contact for a 1:1 semi-structured interview to discuss program-level barriers and facilitators to implementing virtual exercise programs. Interview transcript analysis was conducted via inductive coding techniques using NVivo software. Barriers were categorized according to the Consolidated Framework for Implementation Research and a prioritized list of strategies to support implementation was created by mapping barriers to a list of Expert Recommendations for Implementing Change. Results: Of the 41 unique responses received, 24 program representatives completed semi-structured interviews. Interviewees represented individual programs, community-based programs, and hospital-based cancer exercise/rehabilitation programs. Analysis showed high correlation between facilitators and barriers by program type, with both program- and individual-level strategies used to implement exercise programs virtually. Strategies that ranked highest to support implementation include promoting program adaptability, building a coalition of stakeholders and identifying program champions, developing an implementation blueprint, altering organizational incentives and allowances, providing education across stakeholder groups, and accessing funding. Conclusions: Learning from the transition of cancer exercise and rehabilitation programs to virtual formats due to the COVID-19 pandemic, we identify program-level barriers and facilitators encountered in the implementation of virtual programs and highlight implementation strategies that are most relevant to overcome common barriers. We present a roadmap for programs to use these strategies for future work in virtual exercise and rehabilitation program implementation.

The role of adipose-derived mesenchymal stem cells in knee osteoarthritis: a meta-analysis of randomized controlled trials.

Background: Adipose-derived mesenchymal stem cells (ADMSCs) have recently been studied for the treatment of knee osteoarthritis. The goal is pain reduction and improvement of joint function leading to superior health-related quality of life. Objectives: The aim of this study was to provide a comprehensive meta-analysis assessing the evidence on the use of ADMSCs in knee osteoarthritis. Design: This is a Meta-analysis of randomised controlled trials. Data Sources and Methods: PubMed/MEDLINE, Embase, and Cochrane Databases were searched for randomized controlled trials using ADMSCs to treat patients with knee osteoarthritis. Only trials comparing ADMSCs to placebo or conservative treatment were included. The outcomes studied were improvement in functional, pain, and quality of life scores along with radiographic findings. Results: A total of four trials were included, representing 138 patients with knee osteoarthritis. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores favored ADMSCs with a statistically and clinically significant difference over controls at 6- and 12-month follow-ups (p value < 0.0001). Pain, functional, and quality of life scores also favored ADMSCs at 12-month follow-up (p value < 0.0001). Conclusion: ADMSCs are effective in treating knee osteoarthritis symptoms as observed by functional and pain improvements. Furthermore, ADMSCs injection showed improvement of cartilage integrity, which indicates the potential for regenerating the knee cartilage. Future trials with larger number of patients and longer follow-up periods would help to elaborate further the therapeutic potential of ADMSCs. Plain Language Summary: Adipose-derived mesenchymal stem cells use in knee osteoarthritis Knee osteoarthritis is an extremely common disease that causes damage of the lining of the knee joint.This will lead to pain and limited range of motion of the knee hence limited functionality.Multiple treatments are used currently for knee osteoarthritis which all aim at slowing down the progression and limiting the need for knee replacement surgery.Adipose-derived mesenchymal stem cells (ADMSCs) are stem cells harvested from the fat around the belly. These stem cells have the potential to be converted into cells of a certain origin (cartilage, muscle, fat).Many studies are being performed to see whether these cells can transform to cartilage and repair the damaged knee joint.In this study, we tried to find how the results of different studies comparing the usual treatments for knee osteoarthritis with that of ADMSCs compared.We were mostly interested in the pain, functional, stiffness, and quality of life scores.We also reviewed the MRI findings to find out whether the lining of the knee joint improved.Four studies were included with 138 patients having knee osteoarthritis.WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score which is a self-administered questionnaire evaluating hip and knee osteoarthritis, showed better results in patients receiving ADMSC injections compared with other usual treatments at 12-month follow-up.Pain, functional, stiffness, and quality of life scores also showed better results in ADMSCs at 12-month follow-up.MRI images also showed better cartilage lining in the patients treated with ADMSCs.We concluded that ADMSCs are both effective and safe to be used in treating knee osteoarthritis symptoms. However, studies with longer follow-up periods are needed to better assess the regenerative potential of ADMSCs.