Development and challenges in setting up an international bone infection registry.

INTRODUCTION: Osteomyelitis is an increasing burden on the society especially due to the emergence of multiple drug-resistant organisms. The lack of a central registry that prospectively collects data on patient risk factors, laboratory test results, treatment modalities, serological analysis results, and outcomes has hampered the research effort that could have improved and provided guidelines for treatments of bone infections. The current manuscript describes the lessons learned in setting up a multi-continent registry. MATERIALS AND METHODS: This multicenter, international registry was conducted to prospectively collect essential patient, clinical, and surgical data with a 1-year follow-up period. Patients 18 years or older with confirmed S. aureus long bone infection through fracture fixation or arthroplasty who consented to participate in the study were included. The outcomes using the Short Form 36 Health Survey Questionnaire (version 2), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at baseline and at 1 month, 6 months, and 12 months. Serological samples were collected at follow-ups. RESULTS: Contract negotiation with a large number of study sites was difficult; obtaining ethics approvals were time-consuming but straightforward. The initial patient recruitment was slow, leading to a reduction of target patient number from 400 to 300 and extension of enrollment period. Finally, 292 eligible patients were recruited by 18 study sites (in 10 countries of 4 continents, Asia, North and South America, and Central Europe). Logistical and language barriers were overcome by employing courier service and local monitoring personnel. CONCLUSIONS: Multicenter registry is useful for collecting a large number of cases for analysis. A well-defined data collection practice is important for data quality but challenging to coordinate with the large number of study sites.

Axial sesamoiditis in the horse: A review.

Axial sesamoiditis or osteitis of the proximal sesamoid bones (PSBs) in the horse is described as a rare condition. The cause remains unknown and speculative, with vascular, infectious, and traumatic aetiologies implicated. It is specifically associated with injury of the palmar or plantar ligament (PL), also known as the intersesamoidean ligament. Imaging findings are generally rewarding and radiological changes are typical, if not pathognomonic, for the condition. Lesions consist of bone lysis at the apical to mid-body axial margins of the PSBs, with variable degrees of joint effusion. Radiographic technique warrants careful attention to make a diagnosis, and exposure factors may need to be adjusted. Perineural, intra-articular and intra-thecal anaesthesia does not seem to provide consistent improvement of lameness in these cases, with literature reporting inconsistent findings. Ultrasonographic findings include digital flexor sheath effusion, loss of the normal fibre structure of the PL at its attachment to the PSBs, abnormal echogenicity or change in thickness of the PL, and irregular hyperechoic cortical margins of the axial margins of the PSBs. Scintigraphy, computed tomography and magnetic resonance imaging, although not necessary to make a diagnosis, may add valuable information regarding the location and extent of lesions. The prognosis remains guarded to poor for return to athletic function. The focus of this paper is a comprehensive review of the proposed aetiopathogenesis of the condition, the prognosis, and a summary of the literature findings with focus on the notable diagnostic imaging features, including radiography, ultrasonography, scintigraphy, computed tomography and magnetic resonance imaging.

Bone and joint infection.

Bone and joint infections include septic arthritis, prosthetic joint infections, osteomyelitis, spinal infections (discitis, vertebral osteomyelitis and epidural abscess) and diabetic foot osteomyelitis. All of these may present through the acute medical take. This article discusses the pathogenesis of infection and highlights the importance of taking a careful history and fully examining the patient. It also emphasises the importance of early surgical intervention in many cases. Consideration of alternative diagnoses, appropriate imaging and high-quality microbiological sampling is important to allow appropriate and targeted antimicrobial therapy. This article makes some suggestions as to empiric antibiotic choice; however, therapy should be guided by local antimicrobial policies and infection specialists. Involvement of a multidisciplinary team is essential for optimal outcomes.

Osteoarticular complications of brucellosis: The diagnostic value and importance of detection matrix metalloproteinases.

OBJECTIVES: Matrix metalloproteinases (MMPs) has been implicated in the pathogenesis of infective, cancer and autoimmune diseases. In this study, we investigated the serum level of MMPs and its clinical importance in human brucellosis. PATIENTS AND METHODS: This study included 60 brucellosis patients treated at the Clinic for Infectious Diseases, Clinical Centre, University of Sarajevo. Matrix metalloproteinases serum levels were quantified by ELISA. RESULTS: The investigation involved three groups: 30 patients with complications, 30 patients without complications of brucellosis and 30 healthy control examinees. The complications of human brucellosis varied but osteoarticular involvement dominated (n=21/30; 70%). Matrix metalloproteinases serum levels in the patients with complications were highest. The serum level of MMP-1 in patients with complications was the highest at 9.45; in patients without complications it was 3.78 and in the control examinees it was lowest at 3.62 (p=0.001). The serum level of MMP-9 in patients with complications was the highest at 105.66; in patients without complications 64.67, and in the control examinees it was lowest at 37.32 (p=0.001). The serum level of MMP-13 in patients with complications was highest at 138.86; in patients without complications at 64.85; and in the control examinees it was the lowest at 29.55 (p=0.001). Pearson's coefficient showed a statistically significant positive correlation between levels of tested matrix metalloproteinases and development complications in human brucellosis (p=0.001). CONCLUSION: This study showed the diagnostic value and importance of detection of matrix metalloproteinases in human brucellosis. MMPs are a useful serum biomarker for assessment of disease activity.

Two-stage approach to primary TKA in infected arthritic knees using intraoperatively molded articulating cement spacers.

BACKGROUND: The treatment of knee arthritis with coexistent bone or joint sepsis is challenging. Despite the condition causing considerable morbidity, there is no generally agreed-upon approach to its treatment. DESCRIPTION OF TECHNIQUE: We used aggressive débridement of the knee and implantation of intraoperatively molded articulating antibiotic cement spacers with 4 g vancomycin and 2 g streptomycin per bag of cement for patients with unknown organisms as a first stage. When the infecting organism was known, organism-specific antibiotics were used. For fungal infections, 400 mg amphotericin B was added per bag of cement. This was followed by TKA as a second stage once soft tissues had healed 2 to 29 months later, (mean, 6 months) and return of laboratory parameters to within a normal range. One patient underwent two débridement and spacer procedures for suspected persistent infection. METHODS: To determine whether this approach resulted in adequate control of infection and satisfactory scores for pain and function, we retrospectively reviewed 15 patients who presented with infected arthritic knees between 2001 and 2009; all patients with infected arthritic knees were treated with this same technique during this period. We assessed knee ROM, Knee Society scores, WOMAC scores, and VAS scores preoperatively and during followup. Followup was at a mean of 4 years (range, 2-7 years); No patient was lost to followup before 2 years. RESULTS: Two of the 15 patients were comfortable with the spacers and declined a more definitive reconstruction, and no patient had a recurrent infection after TKA. Before spacer placement, the mean ROM was 103.° (range, 60°-150°), with the spacers in place it decreased to a mean 87° (range, 60°-135°), and after TKA it improved to a mean of 115° (range, 75°-150°). The mean Knee Society Knee and Function scores progressed from 41 and 43 preoperatively to 85 and 83 at latest followup, respectively. The WOMAC scores improved from 51 initially to 18 after TKA. The mean VAS scores improved from 66 preoperatively to 18 after the TKA. CONCLUSIONS: In this small proof-of-concept series, we found that joint débridement and use of intraoperatively molded articulating antibiotic cement spacers as part of a staged approach to treat the infected arthritic knee before TKA resulted in infection control in all patients at a minimum of 2 years' followup, reduction of knee pain, and restoration of knee function. We suggest that larger, comparative series be performed to further validate these results.

Pediatric bone scintigraphy update.

Bone scintigraphy is a sensitive tool to evaluate the musculoskeletal system in children. Hybrid imaging using computed tomography (CT) in combination with conventional bone scan and single photon emission computed tomography improves specificity and diagnostic accuracy. It also improves laboratory efficiency and may save the patient an additional visit to the hospital for a separate cross-sectional imaging study. We have found this technique to be particularly helpful in localizing a cause for pain in children who are nonverbal and to better delineate small bone and soft-tissue lesions that can occur with diagnoses of trauma, infection, and tumor. Special attention to technique of positioning the patient for potential CT examination is an adaptation that must be made by the technologist. Because of radiation concerns of the additional CT, obviously these examinations should be tailored to the individual child and be performed for limited sites directed to the abnormality observed on the associated single photon emission computed tomography examination or directed by the appropriate history.

Gradenigo syndrome without acute otitis media.

Acute otitis media complications are less and less common, thanks to the more widespread availability and use of adequate antibiotics. Nevertheless, when they occur, they may be inconspicuous or silent but with dangerous evolution. Described here is the case of a 5-year-old child suffering from incomplete Gradenigo syndrome without acute otitis media, which was managed medically with favorable outcome.

rhBMP-2 modulation of gene expression in infected segmental bone defects.

The osteoinductive capability of BMPs appears diminished in the setting of acute infection. We applied rhBMP-2 to a segmental defect in a rat femur and measured the expression of key bone formation genes in the presence of acute infection. Types I and II collagen, osteocalcin, and BMP Type II receptor mRNA expression were characterized in 72 Sprague-Dawley rats, which received either bovine collagen carrier with 200 mug rhBMP-2 plus Staphylococcus aureus, carrier with bacteria only, carrier with rhBMP-2 only, or carrier alone. Six animals from each group were euthanized at 1, 2, and 4 weeks. Total RNA was isolated and extracted, and mRNA was determined by real-time comparative quantitative PCR. Infected defects had little expression of collagen I and II and osteocalcin mRNAs, while BMP receptor II expression with infection was greater than carrier-only controls at weeks 2 and 4. Notably, all four genes were upregulated in infected defects in the presence of rhBMP-2. Thus, in a clinical setting with a high risk of infection and nonunion, such as a compound fracture with bone loss, rhBMP-2 may increase the rate and extent of bone formation. Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time.

An alternative method for the treatment of nonunion of the tibia with bone loss.

In this retrospective study we evaluated the method of acute shortening and distraction osteogenesis for the treatment of tibial nonunion with bone loss in 17 patients with a mean age of 36 years (10 to 58). The mean bone loss was 5.6 cm (3 to 10). In infected cases, we performed the treatment in two stages. The mean follow-up time was 43.5 months (24 to 96). The mean time in external fixation was 8.0 months (4 to 13) and the mean external fixator index was 1.4 months/cm (1.1 to 1.8). There was no recurrence of infection. The bone evaluation results were excellent in 16 patients and good in one, while functional results were excellent in 15 and good in two. The complication rate was 1.2 per patient. We conclude that acute shortening and distraction osteogenesis is a safe, reliable and successful method for the treatment of tibial nonunion with bone loss, with a shorter period of treatment and lower rate of complication.

Disseminated Mycobacterium kansasii infection in an HIV-negative patient presenting with mimicking multiple bone metastases.

We report a patient with disseminated Mycobacterium kansasii infection, but with no underlying disease, presenting with mimicking multiple bone metastases with cancer of unknown primary site. Disseminated M. kansasii infection is rare in HIV-negative patients without underlying diseases. This patient had disseminated M. kansasii infection manifested with vertebral osteomyelitis, sacroiliitis, psoas abscess, bone marrow granuloma, liver granuloma, and possible spleen abscesses. The clinical manifestations are described and discussed in details.

[Is bone infection of endogenous or exogenous origin? A pathophysiological approach]. / Origine de l'infection osseuse: endogène ou exogène? Eléments de physiopathologie.

Osteomyelitis is a bacterial implant in bone matrix. Infection occurs as a result of a bacteremia, an inoculation during aseptic or orthopedic surgery, or a contiguous infectious focus. Persistent and relapsing infection may be due to three situations: underlying conditions such as diabetes mellitus or rheumatoid arthritis, presence of foreign surgical implant, and a causative bacterial strain. The pathogenesis of osteomyelitis has been explored through various experimental models, involving mostly Staphylococcus (S. aureus, S. epidermidis) and has given new insights. Bacterial adherence to implanted devices or bone matrix via surface proteins is critical for bacterial survival. Further bacterial growth depends on various mechanisms: the capacity to exhibit matrix-embedded lifestyle known as biofilm and the ability for bacterial subpopulations to switch to a dormant metabolic state known as small colony variants. In addition to bacterial factors, the presence of foreign material induces a defect in local inflammatory response partly responsible for the high susceptibility to infection.

Hard labour: bacterial infection of the skeleton.

The skeleton is the largest mammalian organ system, containing a myriad of blood vessels, tissue surfaces and bone cells for bacterial colonization. Although rock-like, the skeleton is a dynamic structure that is undergoing constant remodelling. This is the result of the opposing actions of two key cells: the osteoblast, which produces bone, and the osteoclast, a multinucleate cell that 'eats' bone. It is not generally realized that the most prevalent chronic bacterial diseases of Homo sapiens afflict the skeleton. Several pathogens, and members of the normal microbiota, have evolved specific cellular and molecular mechanisms for invading bone, including its cellular constituents. The host cellular pathways that are activated and lead to destruction or loss of the bone matrix will be described.

Spinal infections.

Spinal infections can occur in a variety of clinical situations. Their presentation ranges from the infant with diskitis who is unwilling to crawl or walk to the adult who develops an infection after a spinal procedure. The most common types of spinal infections are hematogenous bacterial or fungal infections, pediatric diskitis, epidural abscess, and postoperative infections. Prompt and accurate diagnosis of spinal infections, the cornerstone of treatment, requires a high index of suspicion in at-risk patients and the appropriate evaluation to identify the organism and determine the extent of infection. Neurologic function and spinal stability also should be carefully evaluated. The goals of therapy should include eradicating the infection, relieving pain, preserving or restoring neurologic function, improving nutrition, and maintaining spinal stability.

Cintigrafía ósea trifásica con Tc-99mMDP en el diagnóstico y manejo de infecciones osteoarticulares agudas en niños / Three-phase bone cintigraphy with Tc-99mMDP in the diagnosis and management of acute osteoarticular infections in children

One of the most important causes of residual damage in skeleton is incompletely treated osteoarticular infections (OAI). Goal: to assess the value of emergency three-phase bone scan (3FBS) in the evaluation of OAI. Methods: Thirty-eight children were studied with 54 3FBS. Results: Global analysis: 76% of the cases were principally articular; staphylococcus germs and hip's affection were the common. Nine patients with preoperative scan were positive with 16 foci, 86% confirmed by surgery cultivate. Seven children had negative 3FBS without posterior clinical symptomatology; in 5 of them it was demonstrated soft tissue involvement with normal osteoblastic phase. In 14/17 cases evaluated after surgical intervention, there was a relation between the scan and the clinical course. In two of those cases, in the 3FBS a new location was found. Conclusion: 3FBS is a helpful tool in the diagnosis and assessment of acute OAI in pediatric population. A positive 3FBS is highly accurate for OAI and a negative one rules it out securely.

La principal causa de daño esquelético residual son las infecciones osteoarticulares (IOA) con un tratamiento inadecuado. Objetivo: Determinar el valor del cintigrama óseo trifásico (CO3F) de urgencia en la evaluación de IOA. Material y método: Se estudiaron 38 niños en quienes se efectuaron 54 CO3F. Resultados: Análisis Global: 76% de los casos fueron principalmente articulares; el germen más frecuente fue Staphylococcus y la articulación más afectada la cadera. Nueve pacientes con CO3F preoperatorio fueron positivos con 16 focos, 86% confirmados con cultivo quirúrgico. Siete niños tuvieron CO3F negativo sin sintomatología clínica posterior. En cinco casos el estudio fue negativo para compromiso osteoarticular, pero se demostró compromiso de partes blandas con fase osteoblástica normal. En 14 de 17 casos evaluados post-cirugía, hubo relación entre el CO3F y la evolución clínica, en dos de esos casos en el CO3F se encontró una nueva localización. Conclusión: El CO3F es una herramienta útil en el diagnóstico y evaluación de las IOA agudas en población pediátrica. Un CO3F positivo es altamente seguro de IOA y uno negativo lo descarta con certeza.