IgG4-specific responses in patients with Staphylococcus aureus bone infections are not predictive of postoperative complications.

The most prevalent pathogen in bone infections is Staphylococcus aureus; its incidence and severity are partially determined by host factors. Prior studies showed that anti-glucosaminidase (Gmd) antibodies are protective in animals, and 93.3 % of patients with culture-confirmed S. aureus osteomyelitis do not have anti-Gmd levels > 10 ng/mL in serum. Infection in patients with high anti-Gmd remains unexplained. Are anti-Gmd antibodies in osteomyelitis patients of the non-opsonising, non-complement-fixing IgG4 isotype? The relative amounts of IgG4 and total IgG against Gmd and 7 other S. aureus antigens: iron-surface determinants (Isd) IsdA, IsdB, and IsdH, amidase (Amd), α-haemolysin (Hla), chemotaxis inhibitory protein from S. aureus (CHIPS), and staphylococcal-complement inhibitor (SCIN) were determined in sera from healthy controls (Ctrl, n = 92), osteomyelitis patients whose surgical treatment resulted in infection control (IC, n = 95) or an adverse outcome (AD, n = 40), and post-mortem (PM, n = 7) blood samples from S. aureus septic-death patients. Anti-Gmd IgG4 levels were generally lower in infected patients compared to controls; however, levels among the infected were higher in AD than IC patients. Anti-IsdA, IsdB and IsdH IgG4 levels were increased in infected patients versus controls, and Jonckheere-Terpstra tests of levels revealed an increasing order of infection (Ctrl < IC < AD < PM) for anti-Isd IgG4 antibodies and a decreasing order of infection (Ctrl > IC > AD > PM) for anti-autolysin (Atl) IgG4 antibodies. Collectively, this does not support an immunosuppressive role of IgG4 in S. aureus osteomyelitis but is consistent with a paradigm of high anti-Isd and low anti-Atl responses in these patients.

Bone infection: a clinical priority for clinicians, scientists and educators.

Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection.

Deriving a dose and regimen for anti-glucosaminidase antibody passive-immunisation for patients with Staphylococcus aureus osteomyelitis.

Staphylococcus aureus (S. aureus) osteomyelitis remains a major clinical problem. Anti-glucosaminidase (Gmd) antibodies (1C11) are efficacious in prophylactic and therapeutic murine models. Feasibility, safety and pharmacokinetics of 1C11 passive immunisation in sheep and endogenous anti-Gmd levels were quantified in osteomyelitis patients. 3 sheep received a 500 mg intravenous (i.v.) bolus of 1C11 and its levels in sera were determined by enzyme-linked immunosorbent assay (ELISA) over 52 d. A humanised anti-Gmd monoclonal antibody, made by grafting the antigen-binding fragment (Fab) portion of 1C11 onto the fragment crystallisable region (Fc) of human IgG1, was used to make a standard curve of mean fluorescent intensity versus concentration of anti-Gmd. Anti-Gmd serum levels were determined in 297 patients with culture-confirmed S. aureus osteomyelitis and 40 healthy controls. No complications or adverse events were associated with the sheep 1C11 i.v. infusion and the estimated circulating half-life of 1C11 was 23.7 d. Endogenous anti-Gmd antibody levels in sera of osteomyelitis patients ranged from < 1 ng/mL to 300 µg/mL, with a mean concentration of 21.7 µg/mL. The estimated circulating half-life of endogenous anti-Gmd antibodies in sera of 12 patients with cured osteomyelitis was 120.4 d. A clinically relevant administration of anti-Gmd (500 mg i.v. = 7 mg/kg/70 kg human) was safe in sheep. This dose was 8 times more than the endogenous anti-Gmd levels observed in osteomyelitis patients and was predicted to have a half-life of > 3 weeks. Anti-Gmd passive immunisation has potential to prevent and treat S. aureus osteomyelitis. Further clinical development is warranted.

A large animal model for a failed two-stage revision of intramedullary nail-related infection by methicillin-resistant Staphylococcus aureus.

The treatment of chronic orthopaedic device-associated infection (ODRI) often requires multiple surgeries and prolonged antibiotic therapy. Despite this extensive treatment protocol, the procedure is associated with significant failure rates. Currently, no large animal model is available that recapitulates a failed revision. Therefore, our aim was to establish a large animal model for failed treatment of an ODRI in order to serve as a testbed for future interventional strategies. Adult Swiss Alpine sheep received an intramedullary nail in the tibia and a localised inoculum of either a methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA, MRSA respectively). After 8 weeks, when chronic infection had been established, the animals underwent a staged revision with debridement and temporary placement of an antibiotic-loaded cement spacer. Antibiotics were delivered systemically in a standard or pathogen-adapted manner. Debridement and implant exchange alone failed to treat the MSSA infection. Neither local therapy alone nor systemic therapy alone were effective in resolving infection with MSSA, but a combination of local and systemic therapy was effective against it. MRSA infection was not resolved by the combination of local and systemic antibiotics (standard or pathogen-adapted). A model for failed revision of MRSA infection is described despite the use of local and systemic antibiotics. Novel interventions may be assessed using this model, including antibiotic and non-antibiotic interventions.

Geriatric fracture centers-improved patient care and economic benefits : English Version.

The world's population is aging resulting in changes in the way we manage geriatric care. Furthermore, this population has a considerable risk of fragility fractures, most notably hip fractures. Hip fractures are associated with significant morbidity and mortality and have large economic consequences. It is due to these factors that the concept of an elderly trauma center was developed. These trauma centers utilize the expertise in orthopedic and geriatric disciplines to provide coordinated care to the elderly hip fracture patient. As a result, studies have demonstrated improvements in clinical outcomes within the hospital stay, a reduction in iatrogenic complications, and improvements in 1-year mortality rates compared to the usual care given at a similar facility. Furthermore, economic models have demonstrated that there is a role for regionalized hip fracture centers that can be both profitable and provide more efficient care to these patients.

[Geriatric fracture centers. Improved patient care and economic benefits]. / Geriatrische Frakturzentren. Verbesserte Patientenversorgung und ökonomische Vorteile.

The world's population is aging resulting in changes in the way we manage geriatric care. Furthermore, this population has a considerable risk of fragility fractures, most notably hip fractures. Hip fractures are associated with significant morbidity and mortality and have large economic consequences. It is due to these factors that the concept of an elderly trauma center was developed. These trauma centers utilize the expertise in orthopedic and geriatric disciplines to provide coordinated care to the elderly hip fracture patient. As a result, studies have demonstrated improvements in clinical outcomes within the hospital stay, a reduction in iatrogenic complications, and improvements in 1-year mortality rates compared to the usual care given at a similar facility. Furthermore, economic models have demonstrated that there is a role for regionalized hip fracture centers that can be both profitable and provide more efficient care to these patients.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

A systematic review of animal models for Staphylococcus aureus osteomyelitis.

Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed and Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorised by animal species and are further classified by the setting of the infection. Study methods are summarised and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model's strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting.

Literature review of outcome parameters used in studies of Geriatric Fracture Centers.

INTRODUCTION: A variety of multidisciplinary treatment models have been described to improve outcome after osteoporotic hip fractures. There is a tendency toward better outcomes after implementation of the most sophisticated model with a shared leadership for orthopedic surgeons and geriatricians; the Geriatric Fracture Center. The purpose of this review is to evaluate the use of outcome parameters in published literature on the Geriatric Fracture Center evaluation studies. MATERIALS AND METHODS: A literature search was performed using Medline and the Cochrane Library to identify Geriatric Fracture Center evaluation studies. The outcome parameters used in the included studies were evaluated. RESULTS: A total of 16 outcome parameters were used in 11 studies to evaluate patient outcome in 8 different Geriatric Fracture Centers. Two of these outcome parameters are patient-reported outcome measures and 14 outcome parameters were objective measures. CONCLUSION: In-hospital mortality, length of stay, time to surgery, place of residence and complication rate are the most frequently used outcome parameters. The patient-reported outcomes included activities of daily living and mobility scores. There is a need for generally agreed upon outcome measures to facilitate comparison of different care models.

Venous thromboembolic prophylaxis for hip fractures.

Patients with hip fractures are at very high risk for the development of venous thromboembolism (VTE). To provide an overview of cause, risk factors, current treatment strategies, and complications associated with VTE prophylaxis, we reviewed the most current, best available evidence on VTE prophylaxis for patients with hip fractures. We comprehensively reviewed the literature to assess the efficacy of VTE prophylaxis in patients with hip fractures, including the most recent published guidelines by national medical and surgical health organizations from the UK, USA, and Canada. Mechanical devices are effective in reducing the risk of VTE for hip fracture, but poor patient compliance is common and the devices are not recommended for sole VTE prophylaxis. Aspirin reduces the risk of VTE but does not provide optimal protection compared with other chemical agents; therefore, it is not recommended for sole VTE prophylaxis. Fondaparinux, warfarin, low-molecular-weight heparin, and unfractionated heparin reduce the risk of venographic deep vein thrombosis, but there is insufficient evidence that they reduce fatal pulmonary embolism or all-cause mortality. Fondaparinux is considered to be cost effective and more efficacious than low-molecular-weight heparin. At present, most major health organizations advocate at least 28 days of postoperative chemical prophylaxis. Chemical VTE prophylaxis should be administered to all patients with hip fractures unless contraindicated. Additional research is required to establish an agent that has a significant impact on fatal pulmonary embolism and all-cause mortality, without increasing bleeding complications, in this group of patients.

Co-managed care for fragility hip fractures (Rochester model).

Hip fractures in older adults are a common event with a high risk of morbidity and mortality. Patients who sustain a hip fracture often present with multiple co-morbid conditions that can benefit from co-management by orthopedic surgeons and geriatricians. This manuscript describes a co-managed model of care for patients with hip fractures. This model of care will be explained, and the benefits and results will be described. Retrospective review of the care of all native non-pathological hip fracture patients aged 60 years and older admitted between April 2005 and March 2009 to a 261-bed community teaching hospital. The outcome measures include patient characteristics, length of stay, mortality, 30-day readmission, re-operation, and costs of care. Seven hundred fifty-eight patients were identified with an average age of 84.8 (SD 8.4); 77.8% of the patients were female, 94.7% Caucasian, and 37.3% from nursing homes, and the mean Charlson score is 2.9 (SD 2.1). The length of stay was 4.3 days, 30-day readmission rate was 10.4%, 17-month re-operation rate was 1.9%, and costs of care to the system were $15,188. The 1-year mortality rate was 21.2%. This model of care resulted in improvements in all measures studied. Previous studies have shown reduction in in-hospital complications. Additional studies are needed to show if this model of care can be translated to other systems or to other surgical conditions. Wide application of this model care could substantially improve the quality of care and cost of caring for frail elders with hip fractures.

Recent aspects on outcomes in geriatric fracture patients.

As the population ages, the number of fragility fractures is expected to increase dramatically. These injuries are frequently associated with less than satisfactory outcomes. Many of the patients experience adverse events or death, and few regain their pre-injury functional status. Many also lose their independence as a result of their fracture. This manuscript will explore problems and some potential solutions to evaluate the outcomes of geriatric fracture care. Specific, system-wide, and societal concerns will be discussed. Limited suggestions will be made for future steps to improve outcomes assessments.

How to optimize patients for geriatric fracture surgery.

Low-energy fragility fractures account for >80% of fractures in elderly patients, and with aging populations, geriatric fracture surgery makes up a substantial proportion of the orthopedic workload. Elderly patients have markedly less physiologic reserve than do younger patients, and comorbidity is common. Even with optimal care, the risk of mortality and morbidity remains high. Multidisciplinary care, including early orthogeriatric input, is recommended to anticipate and treat complications. This article explores modern treatment strategies for this challenging group of patients and provides guidance for systematically preparing and optimizing elderly patients before surgery, based on best available current evidence and recommendations by relevant health organizations.

Large-scale clinical implementation of PROMIS computer adaptive testing with direct incorporation into the electronic medical record.

The objective of this research was to assess the implementation of collecting patient-reported outcomes data in the outpatient clinics of a large academic hospital and identify potential barriers and solutions to such an implementation. Three PROMIS computer adaptive test instruments, (1) physical function, (2) pain interference, and (3) depression, were administered at 23,813 patient encounters using a novel software platform on tablet computers. The average time to complete was 3.50 ± 3.12 min, with a median time of 2.60 min. Registration times for new patients did not change significantly, 6.87 ± 3.34 to 7.19 ± 2.69 min. Registration times increased for follow-up (p = .007) from 2.94 ± 1.57 (p < .01) min to 3.32 ± 1.78 min. This is an effective implementation strategy to collect patient-reported outcomes and directly import the results into the electronic medical record in real time for use during the clinical visit.

International survey among orthopaedic trauma surgeons: Lack of a definition of fracture-related infection.

INTRODUCTION: Fracture-related infection (FRI) is one of the most challenging musculoskeletal complications in orthopaedic-trauma surgery. Although the orthopaedic community has developed and adopted a consensus definition of prosthetic joint infections (PJI), it still remains unclear how the trauma surgery community defines FRI in daily clinical practice or in performing clinical research studies. The central aim of this study was to survey the opinions of a global network of trauma surgeons on the definitions and criteria they routinely use, and their opinion on the need for a unified definition of FRI. The secondary aims were to survey their opinion on the utility of currently used definitions that may be at least partially applicable for FRI, and finally their opinion on the important clinical parameters that should be considered as diagnostic criteria for FRI. METHODS: An 11-item questionnaire was developed to cover the above-mentioned aims. The questionnaire was administered by SurveyMonkey and was sent via blast email to all registered users of AO Trauma (Davos, Switzerland). RESULTS: Out of the 26'563 recipients who opened the email, 2'327 (8.8%) completed the questionnaire. Nearly 90% of respondents agreed that a consensus-derived definition for FRI is required and 66% of the surgeons also agreed that PJI and FRI are not equal with respect to diagnosis, treatment and outcome. Furthermore, "positive cultures from microbiology testing", "elevation of CRP", "purulent drainage" and "local clinical signs of infection" were voted the most important diagnostic parameters for FRI. CONCLUSION: This international survey infers the need for a consensus definition of FRI and provides insight into the clinical parameters seen by an international community of trauma surgeons as being critical for defining FRI.

Infection after fracture fixation: Current surgical and microbiological concepts.

One of the most challenging complications in trauma surgery is infection after fracture fixation (IAFF). IAFF may result in permanent functional loss or even amputation of the affected limb in patients who may otherwise be expected to achieve complete, uneventful healing. Over the past decades, the problem of implant related bone infections has garnered increasing attention both in the clinical as well as preclinical arenas; however this has primarily been focused upon prosthetic joint infection (PJI), rather than on IAFF. Although IAFF shares many similarities with PJI, there are numerous critical differences in many facets including prevention, diagnosis and treatment. Admittedly, extrapolating data from PJI research to IAFF has been of value to the trauma surgeon, but we should also be aware of the unique challenges posed by IAFF that may not be accounted for in the PJI literature. This review summarizes the clinical approaches towards the diagnosis and treatment of IAFF with an emphasis on the unique aspects of fracture care that distinguish IAFF from PJI. Finally, recent developments in anti-infective technologies that may be particularly suitable or applicable for trauma patients in the future will be briefly discussed.

Definition of infection after fracture fixation: A systematic review of randomized controlled trials to evaluate current practice.

INTRODUCTION: One of the most challenging musculoskeletal complications in modern trauma surgery is infection after fracture fixation (IAFF). Although infections are clinically obvious in many cases, a clear definition of the term IAFF is crucial, not only for the evaluation of published research data but also for the establishment of uniform treatment concepts. The aim of this systematic review was to identify the definitions used in the scientific literature to describe infectious complications after internal fixation of fractures. The hypothesis of this study was that the majority of fracture-related literature do not define IAFF. MATERIAL AND METHODS: A comprehensive search was performed in Embase, Cochrane, Google Scholar, Medline (OvidSP), PubMed publisher and Web-of-Science for randomized controlled trials (RCTs) on fracture fixation. Data were collected on the definition of infectious complications after fracture fixation used in each study. Study selection was accomplished through two phases. During the first phase, titles and abstracts were reviewed for relevance, and the full texts of relevant articles were obtained. During the second phase, full-text articles were reviewed. All definitions were literally extracted and collected in a database. Then, a classification was designed to rate the quality of the description of IAFF. RESULTS: A total of 100 RCT's were identified in the search. Of 100 studies, only two (2%) cited a validated definition to describe IAFF. In 28 (28%) RCTs, the authors used a self-designed definition. In the other 70 RCTs, (70%) there was no description of a definition in the Methods section, although all of the articles described infections as an outcome parameter in the Results section. CONCLUSION: This systematic review shows that IAFF is not defined in a large majority of the fracture-related literature. To our knowledge, this is the first study conducted with the objective to explore this important issue. The lack of a consensus definition remains a problem in current orthopedic trauma research and treatment and this void should be addressed in the near future.

Fracture-related infection: A consensus on definition from an international expert group.

Fracture-related infection (FRI) is a common and serious complication in trauma surgery. Accurately estimating the impact of this complication has been hampered by the lack of a clear definition. The absence of a working definition of FRI renders existing studies difficult to evaluate or compare. In order to address this issue, an expert group comprised of a number of scientific and medical organizations has been convened, with the support of the AO Foundation, in order to develop a consensus definition. The process that led to this proposed definition started with a systematic literature review, which revealed that the majority of randomized controlled trials in fracture care do not use a standardized definition of FRI. In response to this conclusion, an international survey on the need for and key components of a definition of FRI was distributed amongst all registered AOTrauma users. Approximately 90% of the more than 2000 surgeons who responded suggested that a definition of FRI is required. As a final step, a consensus meeting was held with an expert panel. The outcome of this process led to a consensus definition of FRI. Two levels of certainty around diagnostic features were defined. Criteria could be confirmatory (infection definitely present) or suggestive. Four confirmatory criteria were defined: Fistula, sinus or wound breakdown; Purulent drainage from the wound or presence of pus during surgery; Phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; Presence of microorganisms in deep tissue taken during an operative intervention, as confirmed by histopathological examination. Furthermore, a list of suggestive criteria was defined. These require further investigations in order to look for confirmatory criteria. In the current paper, an overview is provided of the proposed definition and a rationale for each component and decision. The intention of establishing this definition of FRI was to offer clinicians the opportunity to standardize clinical reports and improve the quality of published literature. It is important to note that the proposed definition was not designed to guide treatment of FRI and should be validated by prospective data collection in the future.

Geriatric hip fracture management: keys to providing a successful program.

BACKGROUND: Hip fractures are a common event in older adults and are associated with significant morbidity, mortality and costs. This review examines the necessary elements required to implement a successful geriatric fracture program and identifies some of the barriers faced when implementing a successful program. INTERVENTION: The Geriatric Fracture Center (GFC) is a treatment model that standardizes the approach to the geriatric fracture patient. It is based on five principles: surgical fracture management; early operative intervention; medical co-management with geriatricians; patient-centered, standard order sets to employ best practices; and early discharge planning with a focus on early functional rehabilitation. Implementing a geriatric fracture program begins with an assessment of the hospital's data on hip fractures and standard care metrics such as length of stay, complications, time to surgery, readmission rates and costs. Business planning is essential along with the medical planning process. CONCLUSION: To successfully develop and implement such a program, strong physician leadership is necessary to articulate both a short- and long-term plan for implementation. Good communication is essential-those organizing a geriatric fracture program must be able to implement standardized plans of care working with all members of the healthcare team and must also be able to foster relationships both within the hospital and with other institutions in the community. Finally, a program of continual quality improvement must be undertaken to ensure that performance outcomes are improving patient care.

Subungual bacteria of the hand: contribution to the glove juice test; efficacy of antimicrobial detergents.

Methodologies for evaluating the efficacy of antimicrobial agents in the bacterial flora of the hand involve variations of the "glove juice" or "sterile bag" procedures. In this study we demonstrate that the subungual flora contribute significantly to the recovery of bacteria in these procedures. Culturing hands that had the subungual spaces sealed with acrylic polish demonstrated a decay type of curve for the number of bacteria recovered in successive samplings with 10(6) colony forming units (CFU) bacteria recovered in the first sampling and 10(3) in the sixth while the opposite hand on which the subungual spaces were not sealed demonstrated a continuous recovery of 10(6) CFU. Serial scrubbings of three minutes with plain detergent, 10% povidone-iodine or 4% chlorhexidine demonstrated a three logarithm reduction for povidone-iodine and four logarithm reduction compared to plain detergent alone for chlorhexidine in hands that had subungual spaces sealed, while the opposite hand showed only a 0.5 to 1.0 logarithm reduction. Povidone-iodine produced a 0.6 logarithm reduction and 4% chlorhexidine or 1.4 logarithm reduction in the density of subungual bacteria.