Prevention : T

Joint replacement is a successful surgical procedure that provides pain relief, restores joint function and improves the quality of life of patients. A minority of patients will experience complications like aseptic failure or prosthetic joint infection (PJI; Tande and Patel 2014)

Attachment of Mouse Hepatitis Virus to O-Acetylated Sialic Acid Is Mediated by Hemagglutinin-Esterase and Not by the Spike Protein▿

The members of Betacoronavirus phylocluster A possess two types of surface projections, one comprised of the spike protein (S) and the other of hemagglutinin-esterase (HE). Purportedly, these viruses bind to O-acetylated sialic acids (O-Ac-Sias) primarily through S, with HE serving merely as receptor-destroying enzyme. Here, we show that, in apparent contrast to human and ungulate host range variants of Betacoronavirus-1, murine coronaviruses actually bind to O-Ac-Sias via HE exclusively. Apparently, expansion of group A betacoronaviruses into new hosts and niches was accompanied by changes in HE ligand and substrate preference and in the roles of HE and S in Sia receptor usage

An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection

Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials.</p

Intrawound Treatment for Prevention of Surgical Site Infections in Instrumented Spinal Surgery : A Systematic Comparative Effectiveness Review and Meta-Analysis

Study Design: Systematic review and meta-analysis. Objectives: To determine the efficacy of intrawound treatments in reducing deep surgical site infections (SSIs) in instrumented spinal surgery. Methods: The electronic databases MEDLINE, EMBASE, and Cochrane were systematically searched for intrawound treatments for the prevention of SSIs in clean instrumented spine surgery. Both randomized controlled trials and comparative cohort studies were included. The results of included studies were pooled for meta-analysis. Results: After full text- and reference screening, 20 articles were included. There were 2 randomized controlled trials and 18 observational studies. Sixteen studies investigated the use of intrawound antibiotics, and 4 studies investigated the use of intrawound antiseptics. The relative risk of deep SSI for any treatment was 0.26 (95% confidence interval [CI] 0.16-0.44, P < .0001), a significant reduction compared with controls receiving no treatment. For patients treated with local antibiotics the relative risk was 0.29 (95% CI 0.17-0.51, P < .0001), and patients treated with local antiseptics had a relative risk of 0.14 (95% CI 0.05-0.44, P = .0006). Conclusions: Both the use of antibiotic and antiseptic intrawound prophylactics was associated with a significant 3 to 7 times reduction of deep SSIs in instrumented spine surgery. No adverse events were reported in the included studies

The influence of biomechanical stability on bone healing and fracture-related infection: the legacy of Stephan Perren

Bone healing is a complicated process of tissue regeneration that is influenced by multiple biological and biomechanical processes. In a minority of cases, these physiological processes are complicated by issues such as nonunion and/or fracture-related infection (FRI). Based on a select few in vivo experimental animal studies, construct stability is considered an important factor influencing both prevention and treatment of FRI. Stephan Perren played a pivotal role in the evolution of our current understanding of the critical relationship between biomechanics, fracture healing and infection. Furthermore, his concept of strain theory and the process of fracture healing is familiar to several generations of surgeons and has influenced implant development and design for the past 50 years. In this review we describe the role of biomechanical stability on fracture healing, and provide a detailed analysis of the preclinical studies addressing this in the context of FRI. Furthermore, we demonstrate how Perren's concepts of stability are still applied to current surgical techniques to aid in the prevention and treatment of FRI. Finally, we highlight the key knowledge gaps in the underlying basic research literature that need to be addressed as we continue to optimize patient care.status: publishe

The influence of biomechanical stability on bone healing and fracture-related infection : the legacy of Stephan Perren

Bone healing is a complicated process of tissue regeneration that is influenced by multiple biological and biomechanical processes. In a minority of cases, these physiological processes are complicated by issues such as nonunion and/or fracture-related infection (FRI). Based on a select few in vivo experimental animal studies, construct stability is considered an important factor influencing both prevention and treatment of FRI. Stephan Perren played a pivotal role in the evolution of our current understanding of the critical relationship between biomechanics, fracture healing and infection. Furthermore, his concept of strain theory and the process of fracture healing is familiar to several generations of surgeons and has influenced implant development and design for the past 50 years. In this review we describe the role of biomechanical stability on fracture healing, and provide a detailed analysis of the preclinical studies addressing this in the context of FRI. Furthermore, we demonstrate how Perren's concepts of stability are still applied to current surgical techniques to aid in the prevention and treatment of FRI. Finally, we highlight the key knowledge gaps in the underlying basic research literature that need to be addressed as we continue to optimize patient care.</p

Missed low-grade infection in suspected aseptic loosening has no consequences for the survival of total hip arthroplasty

Background and purpose - Aseptic loosening and infection are 2 of the most common causes of revision of hip implants. Antibiotic prophylaxis reduces not only the rate of revision due to infection but also the rate of revision due to aseptic loosening. This suggests under-diagnosis of infections in patients with presumed aseptic loosening and indicates that current diagnostic tools are suboptimal. In a previous multicenter study on 176 patients undergoing revision of a total hip arthroplasty due to presumed aseptic loosening, optimized diagnostics revealed that 4-13% of the patients had a low-grade infection. These infections were not treated as such, and in the current follow-up study the effect on mid- to long-term implant survival was investigated. Patients and methods - Patients were sent a 2-part questionnaire. Part A requested information about possible re-revisions of their total hip arthroplasty. Part B consisted of 3 patient-related outcome measure questionnaires (EQ5D, Oxford hip score, and visual analog scale for pain). Additional information was retrieved from the medical records. The group of patients found to have a low-grade infection was compared to those with aseptic loosening. Results - 173 of 176 patients from the original study were included. In the follow-up time between the revision surgery and the current study (mean 7.5 years), 31 patients had died. No statistically significant difference in the number of re-revisions was found between the infection group (2 out of 21) and the aseptic loosening group (13 out of 152); nor was there any significant difference in the time to re-revision. Quality of life, function, and pain were similar between the groups, but only 99 (57%) of the patients returned part B. Interpretation - Under-diagnosis of low-grade infection in conjunction with presumed aseptic revision of total hip arthroplasty may not affect implant survival