Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

Colorectal cancer detection and treatment with engineered probiotics.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool. We also demonstrate specific colonization of EcN to solitary neoplastic lesions in an orthotopic murine model of CRC. We then exploit this neoplasia-homing property of EcN to develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate, and demonstrate that oral delivery of this strain results in significantly increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. We also assess EcN engineered to locally release immunotherapeutics at the neoplastic site. Oral delivery to mice bearing adenomas, reduced adenoma burden by ∻50%, with notable differences in the spatial distribution of T cell populations within diseased and healthy intestinal tissue, suggesting local induction of robust anti-tumor immunity. Together, these results support the use of EcN as an orally-delivered platform to detect disease and treat CRC through its production of screening and therapeutic molecules.

Smith-Petersen Versus Watson-Jones Approach Does Not Affect Quality of Open Reduction of Femoral Neck Fracture.

OBJECTIVE: To compare immediate quality of open reduction of femoral neck fractures by alternative surgical approaches. DESIGN: Retrospective cohort study. SETTING: Twelve Level 1 North American trauma centers. PATIENTS: Eighty adults 18-65 years of age with isolated, displaced, OTA/AO type 31-B2 or -B3 femoral neck fractures treated with internal fixation. INTERVENTION: Thirty-two modified Smith-Petersen anterior approaches versus 48 Watson-Jones anterolateral approaches for open reduction performed by fellowship-trained orthopaedic trauma surgeons. MAIN OUTCOME: Reduction quality as assessed by 3 senior orthopaedic traumatologists as "acceptable" or "unacceptable" on AP and lateral postoperative radiographs. RESULTS: No difference was observed in the rate of acceptable reduction by modified Smith-Petersen (81%) versus Watson-Jones (81%) approach (risk difference null, 95% confidence interval -17.4% to 17.4%, P = 1.00) with 90.4% panel agreement (Fleiss' weighted κ = 0.63, P < 0.01). Stratified analyses did not identify a significant difference in the rate of acceptable reduction between approaches when stratified by Pauwels angle, basicervical or transcervical fracture location, or posterior comminution. The Smith-Petersen approach afforded a better reduction when preoperative skeletal traction was not applied (RR = 1.67 [95% CI 1.10-2.52] vs. RR = 0.87 [95% CI 0.70-1.08], P = 0.006). CONCLUSIONS: No difference was observed in the quality of open reduction of displaced femoral neck fractures in young adults when a Watson-Jones anterolateral approach versus a modified Smith-Petersen anterior approach was performed by orthopaedic trauma surgeons. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Open Reduction Is Associated With Greater Hazard of Early Reoperation After Internal Fixation of Displaced Femoral Neck Fractures in Adults 18-65 Years.

OBJECTIVES: To determine (1) which factors are associated with the choice to perform an open reduction and (2) by adjusting for these factors, if the choice of reduction method is associated with reoperation. DESIGN: Retrospective cohort study with radiograph and chart review. SETTING: Twelve Level 1 North American trauma centers. PATIENTS: Two hundred thirty-four adults 18-65 years of age with an isolated, displaced, OTA/AO type 31-B2 or type 31-B3 femoral neck fracture treated with internal fixation with minimum of 6-month follow-up or reoperation. Exclusion criteria were pathologic fractures, associated femoral head or shaft fractures, and primary arthroplasty. INTERVENTION: Open or closed reduction technique during internal fixation. MAIN OUTCOME: Cox proportional hazard of reoperation adjusting for propensity score for open reduction based on injury, demographic, and medical factors. Reduction quality was assessed by 3 senior orthopaedic traumatologists as "acceptable" or "unacceptable" on AP and lateral postoperative radiographs. RESULTS: Median follow-up was 1.5 years. One hundred six (45%) patients underwent open reduction. Reduction quality was not significantly affected by open versus closed approach (71% vs. 69% acceptable, P = 0.378). The propensity to receive an open reduction was associated with study center; younger age; male sex; no history of injection drug use, osteoporosis, or cerebrovascular disease; transcervical fracture location; posterior fracture comminution; and surgery within 12 hours. A total of 35 (33%) versus 28 (22%) reoperations occurred after open versus closed reduction (P = 0.056). Open reduction was associated with a 2.4-fold greater propensity-adjusted hazard of reoperation (95% confidence interval 1.3-4.4, P = 0.004). A total of 35 (15%) patients underwent subsequent total hip arthroplasty or hemiarthroplasty. CONCLUSIONS: Open reduction of displaced femoral neck fractures in nonelderly adults is associated with a greater hazard of reoperation without significantly improving reduction. Prospective randomized trials are indicated to confirm a causative effect of open versus closed reduction on outcomes after femoral neck fracture. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Quality of Diagnostic Studies in Periprosthetic Joint Infections: Can We Do Better?

BACKGROUND: The diagnosis of periprosthetic joint infections (PJIs) continues to be a subject of extensive debate. This is in part due to the lack of a single "gold standard" test, and the marked heterogeneity in the design of studies evaluating the accuracy of different diagnostic modalities. The goal of this review is to critically analyze the evidence cited by the proceedings of the 2013 International Consensus Meeting (ICM) on PJI with regards to the diagnosis of PJI. METHODS: References from the Proceedings of the ICM on PJI related to PJI minor criteria were retrieved and manually reviewed. A total of 25 studies were analyzed using a Validated Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: A large number of studies were determined to have a high risk of bias for flow and timing domains due to the large numbers of exclusions. Studies of synovial white blood cells count and polymorphonuclear neutrophils percentage suffered from threshold optimization and lack of internal validity. Furthermore, due to the lack of homogeneity across studies, index test and reference standard domains showed high risk of bias for white blood cell/polymorphonuclear neutrophil percentage and the utility histological analysis, respectively. Leukocyte esterase testing lacked standardization with regard to the strip reagent used, and the exclusion of bloody samples limited sample sizes. CONCLUSION: The 2013 ICM minor criteria were based on studies with a low quality of evidence. As the committee continues to adjust these guidelines, they should encourage future studies with sound clinical design, patient selection, and testing procedures.

Emergency Department Visits Within Thirty Days of Discharge After Primary Total Hip Arthroplasty: A Hidden Quality Measure.

BACKGROUND: Thirty-day hospital readmissions following total hip arthroplasty (THA) have received increasing scrutiny by policy makers and hospitals. Emergency department (ED) visits may not necessarily result in an inpatient readmission but can be a measure of performance and can incur costs to the health system. The purpose of this study is to describe the following: (1) the frequency and subsequent disposition; (2) patient characteristics; (3) reasons; and (4) potential risk factors for ED visits that did not result in a readmission within 30 days of discharge after THA. METHODS: All primary THAs performed at a large healthcare system between 2013 and 2015 were identified. Patients who received unplanned hospital services for complications within 30 days following surgery were identified and analyzed. A multiple regression analysis was utilized to identify risk factors predisposing for returning to the ED without readmission. RESULTS: From a total of 6270 primary THAs, 440 patients (7%) had an unplanned return to the hospital within 30 days. Of those, 227 (3.6%) patients presented to the ED and were not readmitted. Higher percentage of African Americans was noted among patients who returned to the ED versus those who did not (20.2% vs 9.8%, P < .01). The most common medical diagnoses were nonspecific medical symptoms (24.8%) followed by minor gastrointestinal problems (10.5%). The most common surgery-related diagnoses were pain and swelling (35%), followed by wound complications (12%) and hip dislocations (7.3%). Nearly 50% of wound complications and 40% of hip dislocations were managed and discharged from the ED without a readmission. Both African Americans (odds ratio 2.28, 95% confidence interval 1.55-3.36) and home discharge (odds ratio 1.90, 95% confidence interval 1.28-2.82) were independent risk factors for return to the ED without readmission. CONCLUSION: ED visits that do not result in hospital readmissions, many of which may be due to serious complications, are more frequent than inpatient readmission. This is extremely relevant to policy makers and quality metrics, especially as comprehensive and bundled payment initiatives become more prevalent.

The Diagnostic Utility of Synovial Fluid Markers in Periprosthetic Joint Infection: A Systematic Review and Meta-analysis.

INTRODUCTION: This study is a systematic review of all reported synovial fluid markers for the diagnosis of periprosthetic joint infection and a meta-analysis of the most frequently reported markers to identify those of greatest diagnostic utility. METHODS: A search of six databases was conducted to identify all studies evaluating the utility of synovial fluid markers in the diagnosis of periprosthetic joint infection. Two observers assessed methodologic quality and extracted data independently. A meta-analysis of the most frequently reported markers was performed. RESULTS: Twenty-three studies were included in the meta-analysis. The most common markers (and their respective area under the curve) were interleukin-17 (0.974), leukocyte esterase (0.968), α-defensin (0.958), interleukin-6 (0.956), interleukin-1ß (0.948), and C-reactive protein (0.927). Among these markers, α-defensin had the highest diagnostic odds ratio but did not achieve statistically significant superiority. CONCLUSION: The most frequently studied synovial fluid markers for the diagnosis of periprosthetic joint infection are C-reactive protein, leukocyte esterase, interleukin-6, interleukin-1ß, α-defensin, and interleukin-17, all of which have high diagnostic utility. LEVEL OF EVIDENCE: Level II.

The Use of Transcutaneous Electrical Nerve Stimulation After Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

INTRODUCTION: Multimodal pain management is used after total knee arthroplasty (TKA) to reduce opioid intake. Transcutaneous electrical nerve stimulation (TENS) has generated much interest as a non-pharmacologic, patient-controlled therapy. The aims of this study were to evaluate the efficacy of TENS in reducing opioid intake and improving recovery after TKA. MATERIALS AND METHODS: This was a prospective, parallel-group, double-blinded, randomized trial of patients receiving femoral nerve catheter block with allocation to either active or placebo TENS device groups. All participants were 18-85 years and underwent unilateral, primary TKA at two academic hospitals. Device usage was monitored during inpatient and outpatient phases. Participants were requested to return at second, fourth, and sixth postoperative weeks for follow-up. The primary endpoint was opioid usage, as indicated by medication intake in equianalgesic equivalents to morphine. Secondary measures included: visual analogue scale (VAS) pain scores; functional assessments as measured from knee joint range of motion (ROM) and Timed Up and Go (TUG) test; and clinical outcomes as defined by modified Knee injury and Osteoarthritis Outcome Scores (KOOS) and the 12-item Short Form Survey Instrument (SF-12). RESULTS: Among 116 participants, overall withdrawal was 37.9% (44 patients) at similar rates in both study arms. After excluding for non-femoral nerve catheter (FNC) blocks (i.e., protocol deviations), there were 35 patients in the active group and 31 patients in the placebo group whose complete records were analyzed. There were no significant differences between groups in any of the clinical endpoints.

Neer Award 2015: Analysis of cytokine profiles in the diagnosis of periprosthetic joint infections of the shoulder.

BACKGROUND: Periprosthetic joint infection (PJI) after shoulder arthroplasty can present a diagnostic and therapeutic challenge. This study evaluated the diagnostic utility of broader synovial fluid cytokine analysis for identifying PJI in patients undergoing revision shoulder arthroplasty. METHODS: Synovial fluid levels of 9 cytokines (interleukin [IL] 6, granulocyte-macrophage colony-stimulating factor, IL-1ß, IL-12, IL-2, IL-8, interferon-γ, IL-10, and tumor necrosis factor-α) were measured in 75 cases of revision shoulder arthroplasty with a multiplex immunoassay. Cases were classified into infection categories and groups based on objective perioperative findings. Differences in cytokine levels among infection groups were evaluated. Receiver operating characteristic curves were used to assess the diagnostic utility of the individual synovial fluid cytokines and combinations of cytokines in determining infection status. RESULTS: Synovial IL-6, granulocyte-macrophage colony-stimulating factor, interferon-γ, IL-1ß, IL-2, IL-8, and IL-10 were significantly elevated in cases of revision shoulder arthroplasty classified as infected. Individually, IL-6, IL-1ß, IL-8, and IL-10 showed the best combination of sensitivity and specificity for predicting infection, and a combined cytokine model consisting of IL-6, tumor necrosis factor-α, and IL-2 showed better diagnostic test characteristics than any cytokine alone, with sensitivity of 0.80, specificity of 0.93,, positive and negative predictive values of 0.87 and 0.89, and positive and negative likelihood ratios of 12.0 and 0.21. CONCLUSIONS: Individual and combined synovial fluid cytokine analysis were both more effective than routine perioperative testing, such as serum erythrocyte sedimentation rate and C-reactive protein, in the diagnosis of PJI of the shoulder. Once validated, combined synovial fluid cytokine analysis could be used as a predictive tool to determine the probability of PJI in patients undergoing revision shoulder arthroplasty and better guide treatment.

The Reamer-Irrigator-Aspirator System: A Review.

The reamer-irrigator-aspirator (RIA) system has been recently developed to decrease the incidence of osseous thermal necrosis and fat embolism associated with intramedullary reaming of long bones in trauma cases. This is achieved by continuous irrigation and suction. Recently, the use of RIA has been expanded to harvest bone graft and debride the medullary canal of long bones in cases of osteomyelitis and intramedullary tumors. Additionally, the collection system of this device has been utilized for its ability to capture bone graft and marrow aspirate. The purpose of this study is to report a comprehensive literature review on the: 1) use of RIA for canal reaming prior to intramedullary nailing; 2) use of RIA for the treatment of intramedullary osteomyelitis of long bones; 3) use of RIA for bone graft harvesting; 4) osteogenic potential of the RIA aspirate; and 5) future applications of the RIA system.

Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation.

BACKGROUND: Diagnosing periprosthetic joint infection (PJI) requires a combination of clinical and laboratory parameters, which may be expensive and difficult to interpret. Synovial fluid cytokines have been shown to accurately differentiate septic from aseptic failed total knee (TKA) and hip (THA) arthroplasties. However, after first-stage explantation, there is still no reliable test to rule out PJI before a second-stage reimplantation procedure. QUESTIONS/PURPOSES: (1) Which synovial fluid cytokines have the highest diagnostic accuracy for PJI? (2) Which cytokine shows the greatest decrease associated with the resolution of infection in the same patient between explantation and subsequent reimplantation of an infected arthroplasty? (3) What is the accuracy of synovial fluid cytokines and the Musculoskeletal Infection Society (MSIS) criteria to rule out PJI after first-stage explantation? (4) What are the most studied synovial fluid cytokines for diagnosing PJI as reported in the literature and what are their cumulative diagnostic accuracy? METHODS: Between May 2013 and March 2014, 104 patients with painful THA and TKA evaluated for possible PJI were included in our study. Of these, 90 (87%) had cytokine levels measured from synovial fluid samples collected as part of this prospective study (n = 33 hips, n = 57 knees). A second group of 35 patients (n = 36 samples) who presented during the same time period with an antibiotic spacer also had synovial cytokines measured before second-stage reimplantation. For the first group of 90 patients, the MSIS definition classified each joint at the time of surgery as infected (n = 31) or not infected (n = 59) and was used as the standard to test the accuracy in diagnosing PJI. Of the 35 patients with synovial marker data before second-stage surgery, 15 patients had cytokine measurements both at explantation and reimplantation and were used to quantify the change between stages. The reimplantation group had a minimum 1-year followup (with four [11%] patients lost to followup) and was classified into successful or failed treatment based on Delphi-based consensus data and was used to test the accuracy in detecting infection resolution at reimplantation. RESULTS: Interleukin (IL)-1ß and interferon-γ demonstrated the highest diagnostic utility (area under the curve 0.92, 0.91, respectively); IL-1ß and IL-6 had the highest sensitivities (0.90 [95% confidence interval {CI}, 0.74-0.98] and 0.81 [0.63-0.93]). As a measure of infection resolution, IL-1ß had the greatest decrease (12.4-fold; level at explantation: 232.4 [range, 23.1-1545.7]; level at reimplantation: 18.8 (range 1.2-298.9); mean difference: 325.5 [95% CI, 65.0-596.0]; p = 0.0001), and IL-6 had a nearly similar decrease (11.2-fold; level at explantation: 228.1 [range, 10,158.4-182,725.0]; level at reimplantation: 2518.2 [range, 10.4-41,319.3]; mean difference: 33,176.0 [95% CI, 7543.6-58,808.3]; p < 0.0001). Cytokines and MSIS criteria had low sensitivity to rule out infection in a joint treated for PJI. CONCLUSIONS: IL-6 and IL-1ß demonstrated high sensitivities to diagnose PJI and showed the greatest decrease between first and second stages, which may potentially be used to monitor treatment response to PJI. However, cytokines and MSIS criteria had low sensitivity to rule out infection before reimplantation. LEVEL OF EVIDENCE: Level III, diagnostic study.

α-Defensin Accuracy to Diagnose Periprosthetic Joint Infection-Best Available Test?

BACKGROUND: The purpose of this study was to test the accuracy of a single synovial fluid biomarker, α-defensin, in diagnosing periprosthetic joint infection in revision total hip and revision total knee arthroplasty. METHODS: A total of 102 patients comprising 116 revision total hip arthroplasty and revision total knee arthroplasty procedures performed between May 2013 and March 2014 were prospectively evaluated. Cases were categorized as infected or notinfected using Musculoskeletal Infection Society criteria. Synovial fluid was obtained and tested for α-defensin using a commercially available kit (Synovasure [CD Diagnostics, Baltimore, Maryland]). RESULTS: For first-stage and single-stage revisions, the α-defensin test had a sensitivity of 100% (95% confidence interval [CI], 86%-100%) and a specificity of 98% (95% CI, 90%-100%) with a positive predictive value of 96% (95% CI, 80%-99%) and negative predictive value of 100% (95% CI, 93%-100%). CONCLUSION: A positive α-defensin test result was significantly more sensitive and specific for predicting infection than current diagnostic testing and should be considered when managing periprosthetic joint infection. LEVEL OF EVIDENCE: Level III, Study of Diagnostic Test.

Chronic Suppression of Periprosthetic Joint Infections with Oral Antibiotics Increases Infection-Free Survivorship.

BACKGROUND: The clinical benefit of chronic suppression with oral antibiotics as a salvage treatment for periprosthetic joint infection is unclear. The purpose of this study was to compare infection-free prosthetic survival rates between patients who received chronic oral antibiotics and those who did not following irrigation and debridement with polyethylene exchange or two-stage revision for periprosthetic joint infection. METHODS: We reviewed the records on all irrigation and debridement procedures with polyethylene exchange and two-stage revisions performed at our institution from 1996 to 2010 for hip or knee periprosthetic joint infection. Of 625 patients treated with a total of 655 eligible revisions, ninety-two received chronic oral antibiotics for a minimum of six months and were eligible for inclusion in our study. These patients were compared with a matched cohort (ratio of 1:3) who did not receive chronic oral antibiotics. RESULTS: The five-year infection-free prosthetic survival rate was 68.5% (95% confidence interval [CI] = 59.2% to 79.3%) for the antibiotic-suppression group and 41.1% (95% CI = 34.9% to 48.5%) for the non-suppression group (hazard ratio [HR] = 0.63, p = 0.008). Stratification by the type of surgery and the infecting organism showed a higher five-year survival rate for the patients in the suppression group who underwent irrigation and debridement with polyethylene exchange (64.7%) compared with those in the non-suppression group who underwent irrigation and debridement with polyethylene exchange (30.4%, p < 0.0001) and a higher five-year survival rate for the patients in the suppression group who had a Staphylococcus aureus infection (57.4%) compared with those in the non-suppression group who had a Staphylococcus aureus infection (40.1%, p = 0.047). CONCLUSIONS: Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit.

Bone Mesenchymal Stem Cells with Growth Factors Successfully Treat Nonunions and Delayed Unions.

BACKGROUND: While the gold standard of treatment of nonunion is open autologous bone grafting, studies have shown that injecting bone marrow aspirate concentrates (BMAC) is effective in treating tibial nonunions with fracture gaps less than 5 mm. QUESTIONS/PURPOSES: We aim to demonstrate that combining BMAC with osteoinductive agents can effectively treat delayed or nonunion regardless of fracture gap size, nonunion site, or osteoinductive agent used. METHODS: In this non-randomized retrospective-prospective cohort study, 49 patients with tibial nonunion met the inclusion criteria and underwent BMAC injection with demineralized bone matrix (DBM) and/or recombinant human bone morphogenic protein-2 (rhBMP-2). Radiologic healing of the fracture was the primary outcome. Patients were followed until radiographic union was achieved or another procedure was performed. Radiographic healing was defined as bridging of three out of four cortices on anteroposterior and lateral films. RESULTS: There was no difference in the healing rate (p = 0.81) between patients with fracture gaps less than and greater than 5 mm. On multivariate analysis, the use of rhBMP-2 was associated with a lower healing rate compared to DBM (p = 0.036). Patients who underwent early intervention (within 6 months of fixation) had higher union rates (p = 0.04). CONCLUSION: This study shows that percutaneous BMAC injection combined with either DBM and/or rhBMP-2 is a safe and effective treatment for delayed or nonunion regardless of the fracture gap size or fracture site. DBM may be superior to rhBMP-2 in this procedure.

Early Versus Late Culture Growth of Propionibacterium acnes in Revision Shoulder Arthroplasty.

BACKGROUND: Propionibacterium acnes is recognized as a pathogenic organism associated with periprosthetic joint infection following shoulder arthroplasty. The goal of our study was to determine the relationship between the time to P. acnes growth in culture and the likelihood of a culture result being a true positive versus a false positive based on the proportion of positive cultures and other perioperative findings in cases of revision shoulder arthroplasty. METHODS: We retrospectively reviewed forty-six cases with P. acnes-positive cultures among patients who underwent revision shoulder arthroplasty between May 2010 and October 2014. Tissue and fluid was cultured anaerobically for a mean (and standard deviation) of 13.1 ± 3 days. Cases were categorized into one of two groups for analysis: probable true positive or probable contaminant (false-positive) on the basis of culture results and perioperative findings. RESULTS: The time to P. acnes culture growth was significantly shorter (p = 0.002) in the probable true-positive culture group compared with the probable contaminant group (median of five days [interquartile range, four to seven days]) compared with nine days [interquartile range, six to twelve days]). Among the thirty-seven cases in the probable true-positive group, no culture result turned positive after eleven days, whereas in the probable contaminant group, cultures turned positive after this time point in 44% (four of nine) of the cases. There were also significantly fewer days to P. acnes culture growth among cases with a higher number of positive cultures (p = 0.001) and a higher proportion of positive cultures (p < 0.001), regardless of group classification. CONCLUSIONS: P. acnes is the most commonly identified organism following revision shoulder arthroplasty. The proportion of positive cultures and the timing of culture growth may help to distinguish a true-positive from a false-positive culture result. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

α-Defensin as a predictor of periprosthetic shoulder infection.

BACKGROUND: Diagnosis of periprosthetic joint infection (PJI) in revision shoulder arthroplasty can be challenging because of the indolent nature of the common offending organisms. The purpose of this study was to evaluate the diagnostic utility of synovial fluid α-defensin levels in identifying PJI of the shoulder. METHODS: Thirty patients evaluated for painful shoulder arthroplasty were prospectively enrolled and underwent revision surgery (n = 33 cases). Cases were categorized into infection (n = 11) and no-infection (n = 22) groups on the basis of preoperative and intraoperative findings. Synovial fluid was obtained from preoperative aspirations or intraoperative aspiration before arthrotomy. α-Defensin was tested by the Synovasure (CD Diagnostics, Wynnewood, PA, USA) test for joint infection. Synovial fluid was also obtained intraoperatively from a control group undergoing arthroscopic rotator cuff repair (n = 16) for baseline data on normal α-defensin levels in the shoulder. A receiver operating characteristic curve was used to determine the diagnostic utility of synovial fluid α-defensin. RESULTS: Synovial α-defensin had an area under the curve, sensitivity, specificity, and positive and negative likelihood ratios of 0.78, 63%, 95%, 12.1, and 0.38, respectively. There was a significant difference in α-defensin levels between the infection (median, 3.2 S/CO [signal to cutoff ratio]) and no-infection groups (median, 0.21 S/CO; P = .006). Synovial α-defensin was elevated in the presence of a culture positive for Propionibacterium acnes (median, 1.33 S/CO; P = .03) and showed moderate correlation with the number of positive cultures. CONCLUSION: Synovial fluid α-defensin was more effective than current diagnostic testing in predicting positive cultures and may be an effective adjunct in the workup of shoulder PJI.

Synovial fluid interleukin-6 as a predictor of periprosthetic shoulder infection.

BACKGROUND: Diagnosis of periprosthetic joint infection (PJI) in patients undergoing revision shoulder arthroplasty is challenging because of the low virulence of the most common infecting organisms. The goal of this study was to evaluate the diagnostic utility of measuring synovial fluid interleukin-6 (IL-6) levels for identifying PJI of the shoulder. METHODS: Thirty-two consecutive patients evaluated for pain at the site of a shoulder arthroplasty were prospectively enrolled from November 2012 to September 2013 and underwent revision surgery (thirty-five procedures during which samples were obtained for synovial fluid IL-6 analysis). Cases were categorized into infection (n = 15) and no-infection (n = 20) groups on the basis of objective preoperative and intraoperative findings. Twenty patients treated with arthroscopic rotator cuff repair were also enrolled to serve as a non-infected control group. Synovial fluid was obtained through aspiration intraoperatively for all patients, as well as preoperatively for some. Synovial fluid IL-6 levels were measured with use of a cytokine immunoassay that utilizes electrochemiluminescent detection. A receiver operating characteristic curve was used to determine the diagnostic utility of synovial fluid IL-6 analysis. RESULTS: Based on receiver operating characteristic curve analysis, synovial fluid IL-6 measurement had an area under the curve of 0.891 with an ideal cutoff value of 359.3 pg/mL. The sensitivity, specificity, and positive and negative likelihood ratios were 87%, 90%, 8.45, and 0.15, respectively. Seven patients who underwent a single-stage revision had negative results on standard perioperative testing, including the erythrocyte sedimentation rate and C-reactive protein levels, but multiple positive intraoperative tissue cultures. The level of synovial fluid IL-6 was elevated in five of these seven patients, with a median value of 1400 pg/mL. Intraoperative synovial fluid IL-6 values correlated well with preoperative IL-6 synovial fluid values (correlation = 0.61; p = 0.025) and frozen-section histologic findings (p < 0.001). Synovial fluid IL-6 levels were also significantly elevated in patients with Propionibacterium acnes infection (p = 0.01). CONCLUSIONS: Measurement of synovial fluid IL-6 levels is more sensitive and specific than current preoperative testing for predicting positive cultures for patients undergoing revision shoulder arthroplasty. This diagnostic accuracy can lead to improved decision-making in the management of PJI.

Glycopeptides versus ß-lactams for the prevention of surgical site infections in cardiovascular and orthopedic surgery: a meta-analysis.

OBJECTIVE: To compare the efficacy of glycopeptides and ß-lactams in preventing surgical site infections (SSIs) in cardiac, vascular, and orthopedic surgery. BACKGROUND: The cost-effectiveness of switching from ß-lactams to glycopeptides for preoperative antibiotic prophylaxis has been controversial. ß-Lactams are generally recommended in clean surgical procedures, but they are ineffective against resistant gram-positive bacteria. METHODS: PubMed, International Pharmaceuticals Abstracts, Scopus, and Cochrane were searched for randomized clinical trials comparing glycopeptides and ß-lactams for prophylaxis in adults undergoing cardiac, vascular, or orthopedic surgery. Abstracts and conference proceedings were included. Two independent reviewers performed study selection, data extraction, and assessment of risk of bias. RESULTS: Fourteen studies with a total of 8952 patients were analyzed. No difference was detected in overall SSIs between antibiotic types. However, compared with ß-lactams, glycopeptides reduced the risk of resistant staphylococcal SSIs by 48% (relative risk, 0.52; 95% confidence interval, 0.29-0.93; P = 0.03) and enterococcal SSIs by 64% (relative risk, 0.36; 95% confidence interval, 0.16-0.80; P = 0.01), but increased respiratory tract infections by 54% (relative risk, 1.54; 95% confidence interval, 1.19-2.01; P ≤ 0.01). Subgroup analysis of cardiac procedures showed superiority of ß-lactams in preventing superficial and deep chest SSIs, susceptible staphylococcal SSIs, and respiratory tract infections. CONCLUSIONS: Glycopeptides reduce the risk of resistant staphylococcal SSIs and enterococcal SSIs, but increase the risk of respiratory tract infections. Additional high-quality randomized clinical trials are needed as these results are limited by high risk of bias.