Objectives We describe rates of success for two-stage revision of prosthetic joint infection (PJI), including data on reimplantation microbiology. Methods We retrospectively collected data from all ...the cases of PJI that were managed with two-stage revision over a 4 year period. Patients were managed with an antibiotic-free period before reimplantation, in order to confirm, clinically and microbiologically, that infection was successfully treated. Results One hundred and fifty-two cases were identified. The overall success rate (i.e. retention of the prosthesis over 5.75 years of follow-up) was 83%, but was 89% for first revisions and 73% for re-revisions hazard ratio = 2.9, 95% confidence interval (CI) 1.2–7.4, P = 0.023. Reimplantation microbiology was frequently positive (14%), but did not predict outcome (hazard ratio = 1.3, 95% CI 0.4–3.7, P = 0.6). Furthermore, most unplanned debridements following the first stage were carried out before antibiotics were stopped (25 versus 2 debridements). Conclusions We did not identify evidence supporting the use of an antibiotic-free period before reimplantation and routine reimplantation microbiology. Re-revision was associated with a significantly worse outcome.
The recent consensus definition for the diagnosis of fracture-related infection (FRI) includes the identification of indistinguishable microorganisms in at least 2 surgical deep-tissue specimens as a ...confirmatory criterion. However, this cut-off, and the total number of specimens from a patient with suspected FRI that should be sent for microbiological testing, have not been validated. We endeavored to estimate the accuracy of different numbers of specimens and diagnostic cut-offs for microbiological testing of deep-tissue specimens in patients undergoing surgical treatment for possible FRI.
A total of 513 surgical procedures in 385 patients with suspected FRI were included. A minimum of 2 surgical deep-tissue specimens were submitted for microbiological testing; 5 or more specimens were analyzed in 345 procedures (67%). FRI was defined by the presence of any confirmatory criteria other than microbiology. Resampling was utilized to model the sensitivity and specificity of diagnostic cut-offs for the number of surgical specimens yielding indistinguishable microorganisms and for the total number of specimens. The likelihood of detecting all clinically relevant microorganisms was also assessed.
A diagnostic cut-off of at least 2 of 5 specimens with indistinguishable microorganisms identified by culture was 68% sensitive (95% confidence interval CI, 62% to 74%) and 87% specific (95% CI, 81% to 94%) for the diagnosis of FRI. Two out of 3 specimens were 60% sensitive (95% CI, 55% to 66%) and 92% specific (95% CI, 88% to 96%). Submitting only 3 deep-tissue specimens risked missing clinically relevant microorganisms in at least 1 in 10 cases.
The present study was the first to validate microbiological criteria for the diagnosis of FRI, supporting the current confirmatory diagnostic criteria for FRI. Analysis of at least 5 deep-tissue specimens in patients with possible FRI is recommended.
Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Objectives We describe treatment failure rates by antibiotic duration for prosthetic joint infection (PJI) managed with debridement, antibiotics and implant retention (DAIR). Methods We ...retrospectively collected data from all the cases of PJI that were managed with DAIR over a 5 year period. Surgical debridement, microbiological sampling, early intravenous antibiotics and prolonged oral follow-on antibiotics were used. Results One hundred and twelve cases of PJI were identified. Twenty infections (18%) recurred during a mean follow-up of 2.3 years. The mean duration of antibiotic use was 1.5 years. Failure was more common after arthroscopic debridement, for previously revised joints and for Staphylococcus aureus infection. There were 12 failures after stopping antibiotics and 8 while on antibiotics hazard ratio (HR) = 4.3, 95% confidence interval (CI) 1.4–12.8, P = 0.01. However, during the first 3 months of follow-up, there were eight failures after stopping antibiotics and two while on antibiotics (HR = 7.0, 95% CI 1.5–33, P = 0.015). The duration of antibiotic therapy prior to stopping did not predict outcome. Conclusions PJI may be managed by DAIR. The risk of failure with this strategy rises after stopping oral antibiotics, but lengthening antibiotic therapy may simply postpone, rather than prevent, failure.
Sex-specific niche differentiation is common in marine vertebrates, but how this varies long-term is poorly understood. Here we investigated interannual variation in sexual segregation among breeding ...northern gannets
Morus bassanus
, wide-ranging central-place foragers with slight sexual dimorphism. Over 11 breeding seasons, we used GPS tracking and/or stable isotopes to test for sex differences in foraging trip characteristics (range, duration and timing); spatial distribution; habitat selection; and carbon and nitrogen isotopes in blood. When combining data from all years, females foraged further and for longer than males, yet despite this, the foraging areas of the sexes almost completely overlapped. Males and females selected foraging habitats that differed in terms of oceanography but not fishing vessel density. We also detected temporal segregation: females were more likely to be at sea during the day than at night, while males were more likely to be at sea during the night. However, foraging behaviour quantified by all GPS analyses varied interannually, with sex differences detected in some years but not others. Finally, males had consistently higher red blood cell δ
13
C and δ
15
N than females across all years, which was not driven by size dimorphism, instead likely by prey choice or very fine-scale habitat selection. We conclude that environmental variation influenced short-term sex differences in movement, but sex differences in stable isotopes that integrate behaviour over longer periods reveal more consistent differences. Our results suggest that inferences drawn from single-year studies may not relate to general patterns, highlighting the importance of long-term studies and combining methods.
A host of technical and operative improvements have seen the rates of infection associated with joint replacement reach historic lows. However, the increasing number of operations being performed ...means that the absolute number of such infections remains significant. Diagnosis may be challenging and delaying appropriate treatment can lead to reduced joint function and the need for more complex, perhaps multiple, procedures. Individual centres tend to see small numbers of such cases, and in the absence of large clinical trials management varies. Early diagnosis, selection of an appropriate surgical strategy, accurate identification of the responsible microorganisms and construction of an appropriate antibiotic regimen are essential elements of any management strategy. Such packages of care are best delivered by a multidisciplinary team composed of orthopaedic and plastic surgeons, microbiologists, infectious disease physicians, specialist nurses, physiotherapists and occupational therapists. Each treatment plan must be developed in consultation with the patient, taking into account their aims and realistic goals. This review provides an overview of current understanding regarding diagnosis and treatment of prosthetic joint infections and suggests a treatment algorithm.
This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).
The clinical features, microbiology culture results, and ...histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis.
Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%).
Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966-72.
Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and ...evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects.
We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure.
Patients were followed up for a mean of 19.5 months (12 to 34). Infection was eradicated in 96 patients with a single procedure and all four recurrences were successfully managed with repeat surgery. Adverse events were uncommon, with three fractures, six wound leaks and three unrelated deaths. Outcome was not dependant on C-M host class, microbial culture, wound leakage or presence of nonunion.
This single-stage protocol, facilitated by the absorbable local antibiotic, is effective in the treatment of chronic osteomyelitis. It offers a more patient-friendly treatment compared with other published treatment options. Cite this article: Bone Joint J 2016;98-B:1289-96.
Advocates of debridement, antibiotics and implant retention (DAIR) in hip periprosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to ...lead to better survival and functional outcome compared with revision. This case-control study aims were to compare outcome of DAIRs for infected primary total hip arthroplasty (THA) with outcomes following primary THA and two-stage revision of infected primary THAs.
We retrospectively reviewed all DAIRs, performed for confirmed infected primary hip arthropasty (n = 82) at out institution, between 1997 and 2013. Data recorded included full patient information and type of surgery. Outcome measures included complications, mortality, implant survivorship and functional outcome. Outcome was compared with two control groups matched for gender and age; a cohort of primary THAs (n = 120) and a cohort of two-stage revisions for infection (n = 66).
Mean age at DAIR was 69 years (33 to 87) and mean follow-up was eight years (2 to 17; standard deviation (sd) 5). A total of 52 (63%) of DAIRs were for early PJI (less than six weeks). Greater success in the eradication of infection with DAIR was identified with early PJI, comprising an interval less than a week between onset of symptoms and exchange of modular components with the DAIR procedure. Eradication of infection, complications and re-operation rates were similar in the DAIR and two-stage revision groups. For hips with successful eradication of infection with DAIR, the five-year survival (98%; 95% confidence interval (CI) 94 to 100) was similar to the primary THA group (98%; 95% CI 95 to 100) (n = 43; p = 0.3). The DAIR group had inferior mean Oxford Hip Scores (OHS) (38; 12 to 48) compared with the primary THA group (42; 15 to 48) (p = 0.02) but a significantly better mean OHS compared with the two-stage revision group (31; 0 to 48) (p = 0.008). Patients who required only one DAIR for eradication of infection had a similar mean OHS (41; 20 to 48) to the primary THA group (p = 0.2).
The DAIR procedure is associated with a similar complication rate and ability to eradicate infection as two-stage revision. This study emphasises the need for exchange of modular components for improved chances of eradication of infection. This is the first study showing that DAIR is better than a two-stage revision regarding functional outcome. Cite this article:
2017;99-B:614-22.
We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed ...to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny-Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation. We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.
Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We ...hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin. We verified that high fat diet lipid accumulation is also capable of inducing Wnt/β-catenin. Caloric restriction inhibits hepatosteatosis, reduces Wnt/β-catenin activation and blocks the expansion of TICs leading to complete inhibition of tumorigenesis without affecting the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) loss regulated protein kinase B (AKT) activation. Pharmacological inhibition or loss of the Wnt/β-catenin signal represses TIC growth in vitro, and decreases the accumulation of TICs in vivo. In human liver cancers, ontology analysis of gene set enrichment analysis (GSEA)-defined Wnt signature genes indicates that Wnt signaling is significantly induced in tumor samples compared with healthy livers. Indeed, Wnt signature genes predict 90% of tumors in a cohort of 558 patient samples. Selective depletion of macrophages leads to reduction of Wnt and suppresses tumor development, suggesting infiltrating macrophages as a key source for steatosis-induced Wnt expression. These data established Wnt/β-catenin as a novel signal produced by infiltrating macrophages induced by steatosis that promotes growth of tumor progenitor cells, underlying the increased risk of liver tumor development in obese individuals.
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