The role of external fixation in the management of infected avascular necrosis after traumatic talus fractures.

PURPOSE: Avascular necrosis (AVN) after fractures of the talus is a distinct and challenging clinical entity that is associated with poor outcomes. Although several articles are published on the management of posttraumatic AVN of the talus, very little is known about the management of infected AVN after talus fractures. Therefore, three cases of infected AVN were treated successfully by extensive debridement, external fixation and arthrodesis. METHODS: Three cases of infected AVN of the talus were encountered after a mean of 3 months (range 2-6 months) after initial reconstructive surgery. Suspected infection was confirmed by positron emission tomography scan (PET-CT). Management involved extensive debridement, PMMA cement if necessary and final fusion using medial external fixator, accompanied by culture guided antibiotics. Functional outcome was assessed using the Foot Function Index (FFI) and the American Orthopaedic Foot and Ankle Society hindfoot score (AOFAS). Quality of life (QOL) was measured by the EuroQol-5D (EQ-5D). RESULTS: After a mean follow up of 24 months (range 13-29), FFI index scores ranged from poor to good (23, 50, 56) with similar AOFAS scores indicating poor to fair functional outcome (38, 41, 71). The EQ-5D score was 0.78. Overall patient satisfaction was high with a mean VAS of 8.3 (range 8-9). CONCLUSION: Infected talar AVN is a rare condition associated with severe long-term morbidity in term of joint function. The authors recommend extensive debridement and arthrodesis by means of external fixation, followed by post-operative culture-guided antibiotics for the treatment of infected avascular necrosis of traumatic talar fractures. Shared decision-making and expectation management are of crucial importance and may lead to high patient satisfaction despite low functional outcomes. LEVEL OF EVIDENCE: IV, Retrospective case series.

Chronic myelogenous leukemia presenting with osteonecrosis of the jaw as a rare but debilitating toxicity of dasatinib: a case report and literature review.

This report describes a case of osteonecrosis of the jaw developing after a routine dental extraction in a patient being treated with dasatinib, a tyrosine kinase inhibitor, for chronic myelogenous leukemia. As the role of tyrosine kinase inhibitors in cancer treatment expands, patterns of debilitating complications involving the osseous structures of the oral cavity have begun to emerge, and many long-term side effects of this promising therapy remain unknown. To limit the occurrence of known complications, health care providers and patients must be aware of the potential for serious complications of dasatinib, and appropriate protocols should be in place before administration of this medication.

The association of medication-related osteonecrosis of the jaw with Actinomyces spp. infection.

Medication-related osteonecrosis of the jaw (MRONJ) represents a complication of bisphosphonate treatment that responds poorly to standard treatment. In a retrospective cohort study we investigated a possible role of Actinomyces spp. in the pathogenesis of MRONJ. Deep biopsies of necrotic bone were collected during surgical treatment of MRONJ and evaluated by histology and microbiology for the presence of Actinomyces spp. Microbiological, demographic and clinicpathological data were analyzed for risk of Actinomyces-associated MRONJ. Between 2005 and 2014, 111 patients suffering from histologically-confirmed MRONJ were identified. Actinomyces spp. were detected in 99 cases (89%) by histology and in six further patients by microbiological culture. A diverse microbial flora was found in all specimens without association with Actinomyces spp. Demographic and clinicopathological characteristics did not separate significantly Actinomyces-positive from Actinomyces-negative cases. Our observations confirm previous reports of a high prevalence of Actinomyces spp. in MRONJ in the single largest cohort available up to now. The high prevalence of Actinomyces spp. and the lack of clinicopathological risk factors underline the prominent role of Actinomyces spp. in MRONJ and may change the current understanding of MRONJ. Established prolonged antimicrobial treatment regimens against Actinomyces spp. infection could therefore be a mainstay of future MRONJ management.

Meningococcemia in Adults: A Review of the Literature.

We mainly refer to the acute setting of meningococcemia. Meningococcemia is an infection caused by Neisseria meningitidis, which has 13 clinically significant serogroups that are distinguishable by the structure of their capsular polysaccharides. N. meningitidis, also called meningococcus, is a Gram-negative, aerobic, diplococcus bacterium. The various consequences of severe meningococcal sepsis include hypotension, disseminated intravascular coagulation (DIC), multiple organ failure, and osteonecrosis due to DIC. The gold standard for the identification of meningococcal infection is the bacteriologic isolation of N. meningitidis from body fluids such as blood, cerebrospinal fluid (CSF), synovial fluid, and pleural fluid. Blood, CSF, and skin biopsy cultures are used for diagnosis. Meningococcal infection is a medical emergency that requires antibiotic therapy and intensive supportive care. Management of the systemic circulation, respiration, and intracranial pressure is vital for improving the prognosis, which has dramatically improved since the wide availability of antibiotics. This review of the literature provides an overview of current concepts on meningococcemia due to N. meningitidis infection.

SURGICAL TREATMENT FOR INFECTED LONG BONE DEFECTS AFTER LIMB-THREATENING TRAUMA: APPLICATION OF LOCKED PLATE AND AUTOGENOUS CANCELLOUS BONE GRAFT.

BACKGROUND: Treatment strategies for bone defects include free bone grafting, distraction osteogenesis, and vascularized bone grafting. Because bone defect morphology is often irregular, selecting treatment strategies may be difficult. With the Masquelet technique, a fracture site is bridged and fixed with a locking plate after treating deep infection with antibiotic-containing cement, and a free cancellous bone-graft is concomitantly placed into the defects. This procedure avoids excessive bone resection. METHODS: We studied 6 patients who underwent surgical treatment for deep infection occurring after extremity trauma (2004 through 2009). Ages at surgery ranged from 29 to 59 years (largest age group: 30 s). Mean follow-up was 50.7 months (minimum/maximum: 36/72 months). One patient had complete amputation of the upper extremity, 3 open forearm fractures, 1 closed supracondylar femur fracture, and 1 open tibia fracture. In all patients, bone defects were filled with antibiotic-containing cement beads after infected site debridement. If bacterial culture of infected sites during curettage was positive, surgery was repeated to refill bone defects with antibiotic-containing cement beads. After confirmation of negative bacterial culture, osteosynthesis was performed, in which bone defects were bridged and fixed with locking plates. Concomitantly, crushed cancellous bone grafts harvested from the autogenous ilium was placed in the bone defects. RESULTS: Time from bone grafting and plate fixation to bone union was at least 3 and at most 6 months, 4 months on average. Infection relapsed in one patient with methicillin-resistant Staphylococcus aureus, necessitating vascularized fibular grafting which achieved bone union. No patients showed implant loosening or breakage or infection relapse after the last surgery during follow-up. CONCLUSION: The advantage of cancellous bone grafting include applicability to relatively large bone defects, simple surgical procedure, bone graft adjustability to bone defect morphology, rapid bone graft revascularization resulting in high resistance to infection, and excellent osteogenesis.

Outcome of reactive arthritis after an extensive Finnish waterborne gastroenteritis outbreak: a 1-year prospective follow-up study.

The purpose of the study was to assess the 1-year outcome of definitive reactive arthritis (ReA) after a waterborne outbreak. A cohort of 21 patients (15 females and 6 males, median age 54 years) with ReA related to an extensive waterborne outbreak in Finland was clinically followed-up by rheumatologists with visits at baseline, at 1 month and 3, 6 and 12 months. Although the outcome was in general favourable, 1/3 of the patients had chronic course; 7 (33 %) of the 21 patients needed disease-modifying anti-rheumatic drugs (DMARDs) and even 8 (38 %) of them used glucocorticoids at 12 months. Four (19 %) were using non-steroidal anti-inflammatory drugs and nine (43 %) other analgesics. Many patients had articular pain and impaired physical function still at 12 months, even though inflammatory parameters and the number of swollen joints were low. Only one patient (5 %) was human leucocyte antigen-B27-positive. She had the most severe ReA and also additional infectious arthritis caused by Salmonella serotype enteritidis leading to osteonecrosis of her hip joint with subsequent need for arthroplasty. ReA as observed in our study was overall fairly mild, but in many individuals, postinfectious arthralgia and DMARD use continued at least up to 1 year.

Sunitinib related osteonecrosis of jaw: a case report.

A 58-year-old woman presented to the Oral and Maxillofacial Surgery Clinic experiencing severe limited mouth opening and exposed bone in the socket of the right mandibular third molar 8 months following the extraction of the tooth. The patient had been treated during the year before her presentation with sunitinib, an antiangiogenic drug, for renal cell carcinoma. The clinical, radiographic, and histologic picture of a chronic nonhealing extraction socket was consistent with osteonecrosis of the jaw (ONJ), although she had never been treated with bisphosphonates or corticosteroids. The treatment with sunitinib was discontinued and the patient was treated with antibiotics and physiotherapy for 12 weeks with complete recovery. Sunitinib may cause osteonecrosis of the jaw after oral surgical interventions with no previous exposure to bisphosphonates. The pathogenesis may be related to its antiangiogenic mechanism and impaired wound healing. Full recovery may require long-term cessation of the insulting drug combined with prolonged antibiotic treatment.

A role of oral bacteria in bisphosphonate-induced osteonecrosis of the jaw.

No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.

Clinical comparison of patients with osteonecrosis of the jaws, with and without a history of bisphosphonates administration.

This retrospective study aimed to evaluate the role of bisphosphonates in jaw osteomyelitis. 29 patients were included: 18 had been treated with bisphosphonates (12 with multiple myelomas, 3 with breast carcinomas, 2 with prostate carcinomas, and 1 with osteoporosis). Of 11 control patients, 2 had breast carcinomas, 2 had bronchial carcinomas, and 7 had no cancer. Descriptive and statistical evaluations were conducted to investigate the influence of chemotherapy, corticosteroids, stem cell transplantation, and bisphosphonates on the development and clinical picture of osteomyelitis. Both groups had similar disease histories, clinical pictures, treatment methods, and outcome. Wound dehiscence frequencies were also similar (Mann-Whitney rank sum test 1.66±1.5 vs. 1.45±2.0 p=0.393). Chemotherapy, steroid therapy, stem cell transplantation, or bisphosphonate administration did not correlate with the clinical picture. Neither the duration of therapy nor the type of bisphosphonate influenced the clinical picture (negative Fisher's tests). The bisphosphonate group showed a characteristic settlement of Actinomyces in the exposed bone (positive Fisher's test, p=0.021). These results suggested that osteomyelitis developed as a consequence of the simultaneous, cumulative action of many factors. Bisphosphonates played a role comparable to other predisposing features. Coating the jaws with bisphosphonates could promote the settlement of Actinomyces.

Evaluation of the oral flora in 150 patients suffering from chronic craniofacial pain: a retrospective study.

This study was conducted to determine if microbial infection was a significant factor in patients with undiagnosed craniofacial pain. Of the 150 patients from whom intra-bony cultures were obtained, 23 different groups of isolates were obtained. There were 49 (32.67%) patients whose cultures exhibited growth of microbes other than routine oral flora, mixed skin flora or routine respiratory flora. The most common was of the Streptococcus species (11 or 22.91%) of the 49. Sixty-seven (67) (44.67%) of the total cultures demonstrated the growth of mixed skin flora, nineteen (12.67%) demonstrated the growth of routine respiratory flora and sixteen (10.67%) demonstrated the growth of routine oral flora. No bacterial isolates were found in 16 (10.67%) cultures. The most common histological diagnoses of those who exhibited pathogenic microbial growth were, in order: 1. focal osteoporotic marrow defect; 2. ischemic osteonecrosis; and 3. chronic nonsuppurative osteomyelitis.

The role of microbial biofilms in osteonecrosis of the jaw associated with bisphosphonate therapy.

Microbial biofilms have been observed and described in bone specimens of patients with bisphosphonate (BP)-associated osteonecrosis of the jaw (BONJ) and investigators are more recently suggesting that this condition essentially represents an osteomyelitis of the jaw clinically, with greater susceptibility in some patients on BP therapy. This article explains the role of microbial biofilms in BONJ and also discusses associated factors in the disease pathogenesis, which include BP effects on bone remodeling, anti-angiogenesis, matrix necrosis, microcracks, soft tissue toxicity, and inflammation and wound healing. Recent findings suggest a key role for microbial biofilms in the pathogenesis of BONJ; this has important therapeutic implications because biofilm organisms represent a clinical target for prevention and treatment efforts aimed at reducing the significant morbidity and costs associated with this condition.

Resolution of oral bisphosphonate and steroid-related osteonecrosis of the jaw--a serial case analysis.

PURPOSE: To offer recommendations of risk factors, prevention, and treatment of oral bisphosphonate and steroid-related osteonecrosis of the jaw (BSRONJ) in Taiwan. MATERIALS AND METHODS: Twelve patients were clinicopathologically proved to have bisphosphonate-related osteonecrosis of the jaw (BRONJ). All of the patients were taking oral bisphosphonates and were concurrently administered long-term steroids. Of the 12 patients, 3 patients were assigned to the first stage of BRONJ; 5 patients were assigned to the second stage, and 4 patients were assigned to the third stage. The patients' symptoms, localization of necrosis, presence of a fistula, and association with possible triggering factors for onset of the lesion were recorded. RESULTS: The radiologic investigations revealed osteolytic areas and scintigraphy demonstrated increased bone metabolism. Microbiologic analysis showed pathogenic actinomycosis organisms in a majority of patients (91.6%). Antibiotic therapy, minor debridement surgery, and combined hyperbaric oxygen therapy were useful in obtaining short-term symptomatic relief. CONCLUSIONS: Comorbidities of steroid use along with bisphosphonates may cause osteonecrosis of the jaw to occur sooner, be more severe, and respond more slowly to a drug discontinuation. The clinical disease of BSRONJ is more severe and more unpredictable to treat than BRONJ. From the data gained from other published studies of BRONJ and our clinical experience with the series of cases of BSRONJ, we offer recommendations of risk factors, prevention, and treatment of BSRONJ in southern Taiwan.

Invasive infections of Aggregatibacter (Actinobacillus) actinomycetemcomitans.

BACKGROUND/PURPOSE: Aggregatibacter (Actinobacillus) actinomycetemcomitans, part of the normal flora of the mouth, is frequently found in human periodontal cultures and is an important pathogen causing various invasive infections, particularly infective endocarditis. In this study, we describe the clinical course and outcome of patients with A. actinomycetemcomitans infection. METHODS: All patients suffering invasive A. actinomycetemcomitans infections at the National Taiwan University Hospital from January 1985 to December 2004 were included in this study. Relevant data regarding clinical presentation, antimicrobial treatment and outcome of these patients were analyzed. RESULTS: During the study period, there were 11 patients with invasive A. actinomycetemcomitans infections, including eight patients with infective endocarditis, one with osteonecrosis and two with pneumonia and chest wall lesions. Among the patients with infective endocarditis, four had prosthetic valve replacement, four suffered from rheumatic heart disease and one had undergone surgical repair of ventricular septal defect. Lesions in the oral cavity were the probable portals of entry of the microorganism, and included carious teeth, periodontitis or radiotherapy of the ear-nose-throat field, and were noted in nine patients. Transthoracic echocardiography and/or transesophageal echocardiography were performed on the patients with probable infective endocarditis but growth was demonstrated in only four of these patients. Blood culture yielded A. actinomycetemcomitans after prolonged incubation. Three isolates were resistant to penicillin and two of these were also resistant to ampicillin. CONCLUSION: The diagnosis of invasive A. actinomycetemcomitans infection was delayed due to the indolent clinical course, non-specific presentation and slow growth of the organism. Antibiotic therapy using amoxicillin/clavulanic acid, ampicillin, ampicillin/sulbactam, ceftriaxone, clindamycin, cefotaxime, or levofloxacin was successful in all patients. None of the patients demonstrated recurrence of infection 2-36 months following treatment.

Septic arthritis in adults with sickle cell disease often is associated with osteomyelitis or osteonecrosis.

BACKGROUND: Septic arthritis is a known complication of sickle cell disease (SCD) in children, and the association with osteomyelitis and osteonecrosis has been described. However, it is unclear whether this association applies to adults. QUESTIONS/PURPOSES: We therefore asked whether septic arthritis is a frequent complication in adults with SCD and whether it also is associated with osteomyelitis or osteonecrosis. METHODS: We retrospectively reviewed the charts of 2000 consecutive adult patients diagnosed with SCD and recorded symptoms, select findings during physical examination, laboratory data, and select radiographic CT, and MRI observations. RESULTS: Fifty-nine of the 2000 patients (3%) had septic arthritis, 56 of the 59 patients had hemoglobin SS. Thirty-six of the 59 infections (61%) were in the hip. The most frequent findings were pain, swelling, fever greater than 38.2 degrees C (71% of cases), a leukocyte count exceeding 15,000/mm(3) (range, 7900-32,300/mm(3)), a Westergren sedimentation rate greater than 24 mm/hour, and C-reactive protein exceeding 20 mg/L. Cultures were positive in 96% of the joint aspirates. Staphylococcus and Gram-negative infection predominated; no patients had Salmonella joint infections. Preexisting factors of bacterial arthritis included osteonecrosis (29 patients) and osteomyelitis (37 cases) in childhood. Diabetes, rheumatoid arthritis, glucocorticoids, and immunoparesis related to medical treatment by hydroxyurea were associated comorbidities. CT and MRI confirmed the diagnosis of associated osteonecrosis or osteomyelitis and allowed joint aspiration and detection of soft tissue abscess. CONCLUSIONS: The incidence of septic arthritis in adults with SCD is low, but often is associated with osteomyelitis or osteonecrosis. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Bisphosphonate-related osteonecrosis of the jaw: the role of actinomyces.

The etiology of bisphosphonate-related osteonecrosis of the jaw is unknown but was initially postulated to be mediated by bisphosphonate accumulation within the jaws, resulting in avascular necrosis. Bisphosphonates may not be the primary cause. Actinomyces are an underrecognized agent in pathogenesis, and timely actinomycosis-specific treatment may improve outcome.

Microbial biofilms in osteomyelitis of the jaw and osteonecrosis of the jaw secondary to bisphosphonate therapy.

BACKGROUND: The authors report their observations with respect to microbial biofilms in osteomyelitis of the jaw (OMJ), compare these findings with those for osteonecrosis of the jaw (ONJ) secondary to bisphosphonate therapy and discuss recent findings that the pathogenesis of ONJ may represent a biofilm-mediated infectious disease in the context of bisphosphonate therapy. METHODS: In 2004, a program was established at the University of Southern California, Los Angeles, to evaluate, treat and monitor patients who have OMJ and ONJ. Twenty people from this cohort of study patients who were scheduled to undergo surgical debridement or sequestrectomy and who met the authors' inclusion criteria gave informed consent for the study. The authors examined bone samples histopathologically and via scanning electron microscopy, a technique applicable to biofilm characterization. RESULTS: Specimens from all patients with OMJ and ONJ exhibited large surface areas of bone occluded with well-developed biofilms comprising microbial organisms embedded in an extracellular polymeric substance. Actinomyces predominated in OMJ cases, whereas ONJ cases represented more diverse bacterial organisms in addition to fungal organisms not seen in OMJ. The authors observed resorption pits, septic clots, putative nanowires and host inflammatory cells in all specimens. CONCLUSIONS: The findings of this study support a role for microbial biofilms in both disease processes. CLINICAL IMPLICATIONS: Microbial biofilms are a potential target for therapy that includes antibiofilm modalities in the treatment and prevention of OMJ and ONJ.

The clinical spectrum of Actinomyces-associated lesions of the oral mucosa and jawbones: correlations with histomorphometric analysis.

OBJECTIVES: To characterize the clinical manifestations of Actinomyces-associated lesions of the oral mucosa and jawbones, and to correlate the clinical course and treatment requirements with the findings of histomorphometric analysis. STUDY DESIGN: The study was a 10-year retrospective analysis of archived cases with microscopic identification of Actinomyces infection. Actinomyces colonies were identified, using hematoxylin-eosin, Gram, and periodic acid-Schiff stains, exhibiting filamentous morphology with color variation between center and periphery. Only colonies with adjacent tissue reaction (inflammation, fibrosis) were analyzed. Actinomyces density (AD) was calculated by dividing total number of colonies by tissue surface, Actinomyces relative surface (ARS) was calculated by dividing total bacterial surface by tissue surface. RESULTS: The study included 106 cases (48 male, 58 female; aged 13-84 years, mean 50.5 years). Cases presented a wide clinical spectrum, involving jawbone and/or oral soft tissues. Cases included osteomyelitis associated with bisphosphonates, osteoradionecrosis, osteomyelitis unrelated to radiation or bisphosphonates, periapical lesions, odontogenic cysts, periimplantitis, and lesion mimicking periodontal disease. The AD correlated with median length of antibiotic treatment (R = 0.284; P = .028). CONCLUSIONS: Because we were able to identify 106 such cases, the results indicate that Actinomyces-associated lesions may not be as rare as would be expected from the relatively low number of cases in the literature. Actinomyces-associated lesions presented in a wide spectrum of clinical settings and a variety of contributing factors. Quantitative analysis of the number of bacterial colonies (representing bacterial load) could help in evaluating the aggressive potential of the lesion and help in treatment planning.