Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1β, TNFα, IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.

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The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.

Biofilm refers to the complex, sessile communities of microbes found either attached to a surface or buried firmly in an extracellular matrix as aggregates. The biofilm matrix surrounding bacteria makes them tolerant to harsh conditions and resistant to antibacterial treatments. Moreover, the biofilms are responsible for causing a broad range of chronic diseases and due to the emergence of antibiotic resistance in bacteria it has really become difficult to treat them with efficacy. Furthermore, the antibiotics available till date are ineffective for treating these biofilm related infections due to their higher values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), which may result in in-vivo toxicity. Hence, it is critically important to design or screen anti-biofilm molecules that can effectively minimize and eradicate biofilm related infections. In the present article, we have highlighted the mechanism of biofilm formation with reference to different models and various methods used for biofilm detection. A major focus has been put on various anti-biofilm molecules discovered or tested till date which may include herbal active compounds, chelating agents, peptide antibiotics, lantibiotics and synthetic chemical compounds along with their structures, mechanism of action and their respective MICs, MBCs, minimum biofilm inhibitory concentrations (MBICs) as well as the half maximal inhibitory concentration (IC50) values available in the literature so far. Different mode of action of anti biofilm molecules addressed here are inhibition via interference in the quorum sensing pathways, adhesion mechanism, disruption of extracellular DNA, protein, lipopolysaccharides, exopolysaccharides and secondary messengers involved in various signaling pathways. From this study, we conclude that the molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host. It should also be ensured that minimum effective concentration of these molecules must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.

https://www.tandfonline.com/doi/pdf/10.1080/21505594.2017.1313372

Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action

Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.

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Strategies for combating bacterial biofilm infections

ESCMID∗ guideline for the diagnosis and treatment of biofilm infections 2014

Background
Enhanced recovery programmes (ERPs) have been developed over the past 10 years to improve patient outcomes and to accelerate recovery after surgery. The existing literature focuses on specific specialties, mainly colorectal surgery. The aim of this review was to investigate whether the effect of ERPs on patient outcomes varies across surgical specialties or with the design of individual programmes.

Methods
MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched from inception to January 2013 for randomized or quasi-randomized trials comparing ERPs with standard care in adult elective surgical patients.

Results
Thirty-eight trials were included in the review, with a total of 5099 participants. Study design and quality was poor. Meta-analyses showed that ERPs reduced the primary length of stay (standardized mean difference −1·14 (95 per cent confidence interval −1·45 to −0·85)) and reduced the risk of all complications within 30 days (risk ratio (RR) 0·71, 95 per cent c.i. 0·60 to 0·86). There was no evidence of a reduction in mortality (RR 0·69, 95 per cent c.i. 0·34 to 1·39), major complications (RR 0·95, 0·69 to 1·31) or readmission rates (RR 0·96, 0·59 to 1·58). The impact of ERPs was similar across specialties and there was no consistent evidence that elements included within ERPs affected patient outcomes.

Conclusion
ERPs are effective in reducing length of hospital stay and overall complication rates across surgical specialties. It was not possible to identify individual components that improved outcome. Qualitative synthesis may be more appropriate to investigate the determinants of success.

Systematic review and meta-analysis of enhanced recovery programmes in surgical patients.

Prosthesis-related infection is a serious complication for patients after orthopedic joint replacement, which is currently difficult to treat with antibiotic therapy. Consequently, in most cases, removal of the infected prosthesis is the only solution to cure the infection. It is, therefore, important to understand the comprehensive interaction between the microbiological situation and the host immune responses that lead to prosthesis infections. Evidence indicates that prosthesis infections are actually biofilm-correlated infections that are highly resistant to antibiotic treatment and the host immune responses. The authors reviewed the related literature in the context of their clinical experience, and discussed the possible etiology and mechanism leading to the infections, especially problems related to bacterial biofilm, and prophylaxis and treatment of infection, including both microbiological and surgical measures. Recent progress in research into bacterial biofilm and possible future treatment options of prosthesis-related infections are discussed.

Prosthesis infections after orthopedic joint replacement: the possible role of bacterial biofilms.

This study aimed at determining if synovial cell cultures from rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls (HC) differ and are suitable disease models in pharmacological studies, and tested their response to some anti-inflammatory drugs. Synovial cells were isolated from synovial membrane or joint fluid. Cells were cultivated and exposed to no or TNF-α stimulation without, or in the presence of, betamethasone, ibuprofen, or a standardized ginger extract. Concentrations of a panel of cytokines, growth factors, and chemokines were mapped for each culture and condition. Our cells secreted an increased amount of the cytokines IL-1β, IL-6, and IL-8 in response to TNF-α stimulation in all conditions. OA cells showed a higher IL-6 and IL-8 and a lower IL-1β production, when not stimulated, than RA and HC cells, which were similar. TNF-α stimulation caused similar IL-1β, IL-6, and IL-8 release in all groups. Ibuprofen showed no effect on cytokine production, while ginger extract was similar to betamethasone. Ginger extract was as effective an anti-inflammatory agent as betamethasone in this in vitro model. Cultured fibroblast-like synoviocytes from OA and RA subjects promise to be a useful pharmacological disease model, but further studies, to support results from such a model are needed.

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A synoviocyte model for osteoarthritis and rheumatoid arthritis: response to Ibuprofen, betamethasone, and ginger extract-a cross-sectional in vitro study.

Objectives: To determine bone mineral density [BMD] of the calcaneus in premenopausal women with fibromyalgia [FMS] as compared to age matched controls.Methods: We measured BMD of the calcaneus in 116 premenopausal women with FMS and made comparisons with 141 age matched controls. Additionally, muscle strength of the thigh was measured in patients with FMS.Results: Patients with FMS and controls were comparable regarding BMD and age, but the controls were slightly taller and had a lower body mass than the patients with FMS. Calcaneus BMD per kg body mass was lower in patients with FMS compared to controls [P < 0.004]. There was no demonstrable correlation between muscle strength of the thigh and BMD of the calcaneus.Conclusions: Patients with FMS maintain normal levels of bone mass in the calcaneus despite a self-reported low level of physical activity. The patients with FMS were obese compared to the controls. This obesity increases the loading on the calcaneus and may preserve bone mass.

Bone Mass in the Calcaneus in Patients with Fibromyalgia

Background and purpose Over the last 5 years, there has been increasing interest in reducing length of hospitalization (LOS) through accelerated programs. We examined the clinical outcome of patients undergoing a unicompartmental knee replacement (UKR) in an accelerated care program (A group) compared to a conventional care program (C group).Methods 40 patients randomized into 2 groups were included (A group: 17 patients; C group: 23 patients). Nausea, micturition problems, lower limb dysfunction, pain (VAS), opiate consumption, Knee Society score (KSS), day of discharge, rehospitalization within 3 months, contact with a general physician or nurse, and level of satisfaction were registered. Patients in the A group attended an information meeting. An intraarticular infiltration with Marcaine and adrenaline was used peroperatively. Patients in the C group had an epidural pump for 2 or 3 days. Patients in the A program were treated with NSAID and paracetamol postoperatively. Opiates were used in both groups ...

Similar Clinical Outcome After Unicompartmental Knee Arthroplasty Using a Conventional or Accelerated Care Program: A Randomized, Controlled Study of 40 Patients

We perform a non-randomized, consecutive pilot study on the ASR and ReCap resurfacing hip implants and have completed 7 years follow-up. Forty-six non-osteoporotic patients with hip osteoarthritis and anatomical conditions suitable for resurfacing were divided into 2 equal groups and operated sequentially, starting with the ASR implants. Sixteen patients operated with ASR and 19 patients with ReCap have been followed-up. There were no significant differences between the two groups preoperatively as to physical function, pain, or femoral BMD. The serum concentrations of cobalt and chromium were higher in the ASR group from 1/2 to 7 years postoperatively. Five of 16 ASR implants have been revised, and none of the ReCap implants. BMD below the femoral component increased in both groups.

Arne Borgwardt

Papers

Prosthesis infections after orthopedic joint replacement: the possible role of bacterial biofilms.

A synoviocyte model for osteoarthritis and rheumatoid arthritis: response to Ibuprofen, betamethasone, and ginger extract-a cross-sectional in vitro study.

Bone Mass in the Calcaneus in Patients with Fibromyalgia

Similar Clinical Outcome After Unicompartmental Knee Arthroplasty Using a Conventional or Accelerated Care Program: A Randomized, Controlled Study of 40 Patients

Clinical Performance of the ASR and ReCap Resurfacing Implants—7 Years Follow-Up