A Novel Protocol for Nasal Decolonization Using Prolonged Application of an Alcohol-Based Nasal Antiseptic Reduces Surgical Site Infections in Total Joint Arthroplasty Patients: A Retrospective Cohort Study.

Background: Current nasal decolonization strategies utilize pre-operative agents without consideration for short-term re-colonization or de novo colonization. Many strategies utilize an antibiotic-based agent, raising concerns of limited gram-negative antimicrobial coverage and the emergence of resistant bacterial strains. This study evaluated the clinical utility of a non-antibiotic, alcohol-based nasal decolonization agent in decreasing surgical site infection (SSI) rates after total joint arthroplasty. Patients and Methods: We retrospectively compared an 18-month cohort of elective primary total joint arthroplasty patients treated peri-operatively with an alcohol-based sanitizer to historical controls. The alcohol-based agent was administered pre-operatively the day of surgery and for two weeks after surgery. Patients were followed for 90 days and assessed for signs or symptoms of SSI. Patient and caregiver compliance was recorded. There were 779 patients included in the experimental group and 647 included in the historical control group. Results: Patients receiving alcohol-based nasal decolonization had a lower rate of SSI compared with controls not receiving nasal decolonization (0.64% [5/779] vs. 1.55% [10/647]; p = 0.048; odds ratio, 2.43). Utilization of an alcohol-based nasal sanitizer in the pre-operative and prolonged post-operative setting decreased infection rates by 41.3% in our elective total joint arthroplasty setting. Conclusions: When used pre- and post-operatively, alcohol-based nasal decolonization of bacteria in patients undergoing total joint arthroplasty led to a substantial decrease in SSIs.

Thromboelastography is predictive of mortality, blood transfusions, and blood loss in patients with traumatic pelvic fractures: a retrospective cohort study.

PURPOSE: In patients with traumatic pelvic fractures, thromboelastography (TEG) is a useful tool to rapidly evaluate and identify coagulation disturbances. The purpose of this study was to examine the coagulation kinetics of patients with traumatic pelvic fractures (pelvic ring and/or acetabulum) by analyzing the TEG results at initial presentation and its relationship with mortality and blood loss. METHODS: A retrospective review at our Level-1 trauma center was conducted to identify Full Trauma Team activations (FTTa) with traumatic pelvic and/or acetabular fractures who were evaluated with a TEG on initial presentation between 2012 and 2016. In-hospital mortality, product transfusion, and hemoglobin changes were analyzed. Subgroup analysis was performed based on pelvic fracture type. RESULTS: 141 patients with a mean age of 49.0 ± 20.8 years and mean Injury Severity Score (ISS) of 25.18 ± 12.8 met inclusion criteria. PRBC transfusion occurred in 78.0% of patients; a total of 1486 blood products were transfused. A total of 65 patients (46.1%) underwent operative treatment for the pelvic injuries, and 18 patients (12.7%) required embolization. The overall in-hospital mortality rate was 14.9%. The degree of clot lysis at 30 min (LY30) was significantly associated with blood loss (p < 0.0001), units of packed red blood cells (PRBCs) transfused (p < 0.0001), and mortality rate (p = 0.0002). CONCLUSION: Increased fibrinolysis evidenced by an elevated LY30 on initial TEG in patients with traumatic pelvic fractures is associated with increased blood loss, blood product transfusions, and mortality. Future studies should evaluate the clinical utility of reversing hyperfibrinolysis on initial TEG. LEVEL OF EVIDENCE: Prognostic level III.

Complex Primary Total Hip Arthroplasty: Small Stems for Big Challenges.

Total hip arthroplasty is one of the most successful operations in all of medicine. Femoral deformities from malunion, prior osteotomy, and retained surgical implants all present unique challenges. Corrective osteotomy and hardware removal add significant morbidity to an operation that typically has a fast recovery. Short stems can be used in these cases to spare patients' increased morbidity. We present a case-based illustration and surgical technique for the use of short stems in complex primary total hip arthroplasty with femoral deformity and retained hardware. We discuss how these implants can spare significant morbidity, show radiographic examples of their use, and present short-term outcomes.

Rate of surface contamination in the operating suite during revision total joint arthroplasty.

BACKGROUND: This study estimated operating room surface contamination rates during aseptic vs septic total joint arthroplasty and evaluated the similarity between clinically infecting organisms and those isolated from contaminated surfaces. METHODS: Patients undergoing total hip and knee revision arthroplasties were identified, and surface and tissue samples were collected. Cases were classified aseptic or septic based on Musculoskeletal Infection Society criteria for prosthetic joint infection. Positive surface cultures were compared with intraoperative tissue cultures. Positive cultures were speciated and tested for antimicrobial sensitivity. RESULTS: Samples were collected from 31 aseptic and 18 septic cases. Patients had similar demographics and time to explantation. Surface contamination rates for septic revisions were greater than those for aseptic revisions (77% vs 13%). During septic revisions, when intraoperative tissue cultures were positive, the surgical field was contaminated in 14 of 15 cases. The kappa correlation statistic for positive surgical cultures matching the surface sample was 0.9 (95% confidence interval: 0.78-1). CONCLUSIONS: Septic revisions had a significantly higher rate of surgical field contamination than aseptic revisions. Cultures suggest that bacteria contaminating the septic revision surgical field likely originated from the infected joint. Although this observation seems obvious, it is an important piece of information when discussing best practices during a single-stage exchange revision. Further clinical studies will demonstrate the use of a preparation and reset period during a single-stage revision to remove contaminated surfaces.

Highly metastatic K7M2 cell line: A novel murine model capable of in vivo imaging via luciferase vector transfection.

Osteosarcoma is rare and little improvement in survival rates has occurred in the last 25 years despite modern chemotherapeutic treatment. Bioluminescent cell lines for the modeling of osteosarcoma have shown success in tracking metastases in vivo, but commonly use adenoviral vectors to transfect the native cell line with bioluminescent reporters. The purpose of this study was to develop an orthotopic model for metastatic osteosarcoma capable of in vivo monitoring of metastatic and primary tumor burden in an immunocompetent mouse and compare that model to its wild type pathogenesis. K7M2 cells were transfected using a plasmid vector and were stable after 12 weeks. Thirty-four female BALB/c mice aged 4-5 weeks underwent orthotopic implantation of either wild type (n = 12) or transfected (n = 22) K7M2 cells in the proximal tibia. Mice were monitored for tumor growth and weekly In Vivo Imaging System (IVIS) imaging was performed to monitor for pulmonary metastasis. Although tumors developed sooner in the wild type group, no significant differences were seen compared to Transfected Group 1 in rate of inoculation, growth rates after first detection, metastatic rate, and time between inoculation and death. This study establishes a new murine model for metastatic osteosarcoma using the K7M2-wt cell line transfected with a non-viral plasmid luciferase vector. The benefits of this preclinical model include an intact immune system and orthotopically driven metastatic disease; this model appears comparable to its wild type counterpart. In the future, the model may be used to examine promising immunomodulatory therapies using bioluminescence in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Novel rat tail discitis model using bioluminescent Staphylococcus aureus.

Management of spondylodiscitis is a challenging clinical problem requiring medical and surgical treatment strategies. The purpose of this study was to establish a rat model of spondylodiscitis that utilizes bioluminescent Staphylococcus aureus (S. aureus), thus permitting in vivo surveillance of infection intensity. Inocula of the bioluminescent S. aureus strain XEN36 were created in concentrations of 102 CFU/0.1 ml, 104 CFU/0.1 ml, and 106 CFU/0.1 ml. Three groups of rats were injected with the bacteria in the most proximal intervertebral tail segment. The third most proximal tail segment was injected with saline as a control. Bioluminescence was measured at baseline, 3 days, and weekly for a total of 6 weeks. Detected bioluminescence for each group peaked at day 3 and returned to baseline in 21 days. The average intensity was highest for the experimental group injected with the most concentrated bacterial solution (106 CFU/0.1 ml). Radiographic analysis revealed loss of intervertebral disc space and evidence of osseous bridging. Saline-injected spaces exhibited no decrease in intervertebral spacing as compared to distal sites. Histologic analysis revealed neutrophilic infiltrates, destruction of the annulus fibrosus and nucleus pulposus, destruction of vertebral endplates, and osseous bridging. Saline-injected discs exhibited preserved annulus fibrosus and nucleus pulposus on histology. This study demonstrates that injection of bioluminescent S. aureus into the intervertebral disc of a rat tail is a viable animal model for spondylodiscitis research. This model allows for real-time, in vivo quantification of infection intensity, which may decrease the number of animals required for infection studies of the intervertebral disc. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2075-2081, 2017.

Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide.

BACKGROUND: Manifestations of reperfusion injury include myocyte death leading to infarction, contractile dysfunction, and vascular injury characterized by the "no-reflow" phenomenon. Mitochondria-produced reactive oxygen species are believed to be centrally involved in each of these aspects of reperfusion injury, although currently no therapies reduce reperfusion injury by targeting mitochondria specifically. METHODS AND RESULTS: We investigated the cardioprotective effects of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a spectrum of experimental cardiac ischemia/reperfusion models. Postischemic administration of Bendavia reduced infarct size in an in vivo sheep model by 15% (P=0.02) and in an ex vivo guinea pig model by 38% to 42% (P<0.05). In an in vivo rabbit model, the extent of coronary no-reflow was assessed with Thioflavin S staining and was significantly smaller in the Bendavia group for any given ischemic risk area than in the control group (P=0.0085). Myocardial uptake of Bendavia was ≈25% per minute, and uptake remained consistent throughout reperfusion. Postischemic recovery of cardiac hemodynamics was not influenced by Bendavia in any of the models studied. Isolated myocytes exposed to hypoxia/reoxygenation showed improved survival when treated with Bendavia. This protection appeared to be mediated by lowered reactive oxygen species-mediated cell death during reoxygenation, associated with sustainment of mitochondrial membrane potential in Bendavia-treated myocytes. CONCLUSIONS: Postischemic administration of Bendavia protected against reperfusion injury in several distinct models of injury. These data suggest that Bendavia is a mitochondria-targeted therapy that reduces reperfusion injury by maintaining mitochondrial energetics and suppressing cellular reactive oxygen species levels. (J Am Heart Assoc. 2012;1:e001644 doi: 10.1161/JAHA.112.001644.).

Mitochondrial permeability transition in the diabetic heart: contributions of thiol redox state and mitochondrial calcium to augmented reperfusion injury.

Mitochondria from diabetic hearts are sensitized to mitochondrial permeability transition pore (PTP) opening, which may be responsible for the increased propensity for cardiac injury in diabetic hearts. The purpose of this study was to determine if redox-dependent PTP opening contributes to augmented injury in diabetic hearts, and if compounds targeted at mitochondrial PTP, ROS, and calcium influx protected diabetic hearts from injury. Hearts from control or streptozotocin-induced diabetic rats were excised for either whole-heart or isolated mitochondria experiments. Myocardial glutathione content was oxidized in diabetic hearts when compared to control, and this translated to increased oxidation of the adenine nucleotide translocase in diabetic hearts. Diabetic mitochondria displayed significantly greater sensitivity to PTP opening than non-diabetic counterparts, which was reversed with the thiol-reducing agent dithiothreitol. The thiol-oxidant diamide increased calcium sensitivity in control, but not diabetic mitochondria. Diabetic animals treated with the mitochondria-targeted ROS suppressing peptide MTP-131 also showed improved resistance to PTP opening. In separate experiments hearts underwent ex vivo ischemia/reperfusion (IR). Diabetic hearts were more susceptible to IR injury, with infarct sizes of 60 ± 4% of the area-at-risk (vs. 46 ± 2% in non-diabetics; P<0.05). Administration of the PTP blocker NIM811 (5 µM), MTP-131 (1 nM) or the mitochondrial calcium uniporter blocker minocycline (1 µM) at the onset of reperfusion reduced infarct sizes in both control and diabetic hearts. These findings suggest that augmented susceptibility to injury in the diabetic heart is mediated by redox-dependent shifts in PTP opening, and that three novel mitochondria-targeted agents administered at reperfusion may be suitable adjuvant reperfusion therapies to attenuate injury in diabetic patients.

Short-term exercise preserves myocardial glutathione and decreases arrhythmias after thiol oxidation and ischemia in isolated rat hearts.

The purpose of this study was to determine if exercise (Ex) protects hearts from arrhythmias induced by glutathione oxidation or ischemia-reperfusion (I/R). Female Sprague-Dawley rats were divided into two experimental groups: sedentary controls (Sed) or short-term Ex (10 days of treadmill running). Twenty-four hours after the last session, hearts were excised and exposed to either perfusion with the thiol oxidant diamide (200 µM) or global I/R. Ex significantly delayed the time to the onset of ventricular arrhythmia after irreversible diamide perfusion. During a shorter diamide perfusion protocol with washout, Ex significantly decreased the incidence of arrhythmia, as evidenced by a delayed time to the first observed arrhythmia, lower arrhythmia scores, and lower incidence of ventricular fibrillation. Ex hearts exposed to I/R (30-min ischemia/30-min reperfusion) also showed lower arrhythmia scores and incidence of ventricular fibrillation compared with Sed counterparts. Our finding that Ex protected intact hearts from thiol oxidation was corroborated in isolated ventricular myocytes. In myocytes from Ex animals, both the increase in H(2)O(2) fluorescence and incidence of cell death were delayed after diamide. Although there were no baseline differences in reduced-to-oxidized glutathione ratios (GSH/GSSG) between the Sed and Ex groups, GSH/GSSG was better preserved in Ex groups after diamide perfusion and I/R. Myocardial glutathione reductase activity was significantly enhanced after Ex, and this was preserved in the Ex group after diamide perfusion. Our results show that Ex protects the heart from arrhythmias after two different oxidative stressors and support the hypothesis that sustaining the GSH/GSSG pool stabilizes cardiac electrical function during conditions of oxidative stress.