Tracking dendritic cells: use of an in situ method to label all blood leukocytes

Here we describe an in situ procedure with a labeling index (percent of labeled blood leukocytes) >98%, which is high enough to permit the direct tracking of dendritic cell (DC) precursors from blood into lymphoid tissues, while circumventing the pitfalls associated with in vitro labeling. DC and lymphocytes have similar blood to afferent lymph migratory capabilities. This method has additional applications in tracking other rare cell populations in both normal and pathological state

Risk Factors Associated With Infection in Open Fractures of the Upper and Lower Extremities

Introduction: Open fractures are associated with a high risk of infection. The prevention of infection is the single most important goal, influencing perioperative care of patients with open fractures. Using data from 2,500 participants with open fracture wounds enrolled in the Fluid Lavage of Open Wounds trial, we conducted a multivariable analysis to determine the factors that are associated with infections 12 months postfracture. Methods: Eighteen predictor variables were identified for infection a priori from baseline data, fracture characteristics, and surgical data from the Fluid Lavage of Open Wounds trial. Twelve predictor variables were identified for deep infection, which included both surgically and nonoperatively managed infections.We used multivariable Cox proportional hazards regression analyses to identify the factors associated with infection. Irrigation solution and pressure were included as variables in the analysis. The results were reported as adjusted hazard ratios (HRs), 95% confidence intervals (CIs), and associated P values. All tests were two tailed with alpha = 0.05. Results: Factors associated with any infection were fracture location (tibia: HR 5.13 versus upper extremity, 95% CI 3.28 to 8.02; other lower extremity: HR 3.63 versus upper extremity, 95% CI 2.38 to 5.55; overall P\u3c 0.001), low energy injury (HR 1.64, 95% CI 1.08 to 2.46; P = 0.019), degree of wound contamination (severe: HR 2.12 versus mild, 95% CI 1.35 to 3.32; moderate: HR 1.08 versus mild, 95% CI 0.78 to 1.49; overall P = 0.004), and need for flap coverage (HR 1.82, 95% CI 1.11 to 2.99; P = 0.017). Discussion: The results of this study provide a better understanding of which factors are associated with a greater risk of infection in open fractures. In addition, it can allow for surgeons to better counsel patients regarding prognosis, helping patients to understand their individual risk of infection

Risk Factors Associated With Infection in Open Fractures of the Upper and Lower Extremities

Introduction: Open fractures are associated with a high risk of infection. The prevention of infection is the single most important goal, influencing perioperative care of patients with open fractures. Using data from 2,500 participants with open fracture wounds enrolled in the Fluid Lavage of Open Wounds trial, we conducted a multivariable analysis to determine the factors that are associated with infections 12 months postfracture. Methods: Eighteen predictor variables were identified for infection a priori from baseline data, fracture characteristics, and surgical data from the Fluid Lavage of Open Wounds trial. Twelve predictor variables were identified for deep infection, which included both surgically and nonoperatively managed infections.We used multivariable Cox proportional hazards regression analyses to identify the factors associated with infection. Irrigation solution and pressure were included as variables in the analysis. The results were reported as adjusted hazard ratios (HRs), 95% confidence intervals (CIs), and associated P values. All tests were two tailed with alpha = 0.05. Results: Factors associated with any infection were fracture location (tibia: HR 5.13 versus upper extremity, 95% CI 3.28 to 8.02; other lower extremity: HR 3.63 versus upper extremity, 95% CI 2.38 to 5.55; overall P\u3c 0.001), low energy injury (HR 1.64, 95% CI 1.08 to 2.46; P = 0.019), degree of wound contamination (severe: HR 2.12 versus mild, 95% CI 1.35 to 3.32; moderate: HR 1.08 versus mild, 95% CI 0.78 to 1.49; overall P = 0.004), and need for flap coverage (HR 1.82, 95% CI 1.11 to 2.99; P = 0.017). Discussion: The results of this study provide a better understanding of which factors are associated with a greater risk of infection in open fractures. In addition, it can allow for surgeons to better counsel patients regarding prognosis, helping patients to understand their individual risk of infection

Are large clinical trials in orthopaedic trauma justified?

© 2018 The Author(s). Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Direct labelling presents new opportunities to study blood leukocyte migration

grantor: University of TorontoLeukocyte traffic in the blood compartment is a dynamic and complex process. There is a constant influx of leukocytes from primary lymphoid organs and recirculating lymphocytes via the lymphatic system, which is counterbalanced by monocyte and lymphocyte emigration from the blood and leukocyte death. These ongoing processes working in coordination to maintain blood leukocyte homeostasis produce characteristic half-times of leukocytes within the blood compartment. The half-times of fluorescently labelled monocytes, neutrophils, and lymphocytes were investigated in the blood of sheep. The results obtained represent the most detailed and technically advanced halftimes to date. In addition a methodology was established to directly label the entire blood leukocyte pool in situ, and the functional ability of lymphocytes to recirculate was assessed post labelling. This method establishes the framework for many novel experiments to be performed investigating low frequency blood leukocyte populations that were not previously possible.M.Sc

Long-term outcomes of total elbow arthroplasty for distal humeral fracture: results from a prior randomized clinical trial

© 2019 Journal of Shoulder and Elbow Surgery Board of Trustees Background: Total elbow arthroplasty (TEA) is a reliable treatment for elderly patients with comminuted intra-articular distal humeral fractures. However, the longevity and long-term complications associated with this procedure are unknown. The objectives of this study were to examine long-term outcomes and implant survival in elderly patients undergoing TEA for fracture. Methods: Patients from a previously published randomized controlled trial of 42 patients in which TEA was compared with open reduction–internal fixation (ORIF) were followed up long term. Patients were aged 65 years or older with comminuted intra-articular distal humeral fractures. Outcomes included patient-reported grading of function and pain, revision surgical procedures, and implant survival. Results: Data were obtained for 40 patients, 15 treated with ORIF and 25 treated with TEA, with a mean follow-up period of 12.5 years for surviving patients and 7.7 years for deceased patients. The reoperation rate was 3 of 25 in the TEA group and 4 of 15 in the ORIF group (P = .39). Of the 25 patients with TEAs, only 1 required (early) revision arthroplasty; 7 were living with their original arthroplasty, and 15 died with a well-functioning implant in situ. Three were lost to follow-up. Conclusions: TEA is an effective and reliable procedure for the treatment of comminuted distal humeral fractures in the elderly patient. Our study reveals reliable implant long-term survival, with no patient requiring a late revision. For the majority of these patients, a well-performed TEA will give them a well-functioning elbow for life and will be the last elbow procedure required

Are Volar Locking Plates Superior to Percutaneous K-wires for Distal Radius Fractures? A Meta-analysis

Distal radius fractures are common, costly, and increasing in incidence. Percutaneous K-wire fixation and volar locking plates are two of the most commonly used surgical treatments for unstable dorsally displaced distal radius fractures. However, there is uncertainty regarding which of these treatments is superior. We performed a meta-analysis of randomized controlled trials to determine whether patients treated with volar locking plates (1) achieved better function (2) attained better wrist motion, (3) had better radiographic outcomes, and (4) had fewer complications develop than did patients treated with K-wires for dorsally displaced distal radius fractures. We performed a comprehensive search of MEDLINE (inception to 2014, October Week 2), EMBASE (inception to 2014, Week 42), and the Cochrane Central Register of Controlled Trials to identify relevant randomized controlled trials; we supplemented these searches with manual searches. We included studies of extraarticular and intraarticular distal radius fractures. Adjunctive external fixation was acceptable as long as the intent was to use only K-wires where possible and external fixation was used in less than 25% of the procedures. We considered a difference in the DASH scores of 10 as the minimal clinically important difference. We performed quality assessment with the Cochrane Risk of Bias tool and evaluated the strength of recommendations using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Seven randomized trials with a total of 875 participants were included in the meta-analysis. Patients treated with volar locking plates had slightly better function than did patients treated with K-wires as measured by their DASH scores at 3 months (mean difference [MD], 7.5; 95% CI, 4.4-10.6; p < 0.001) and 12 months (MD, 3.8; 95% CI, 1.2-6.3; p = 0.004). Neither of these differences exceeded the a priori-determined threshold for clinical importance (10 points). There was a small early advantage in flexion and supination in the volar locking plate group (3.7° [95% CI, 0.3°-7.1°; p = 0.04] and 4.1° [95% CI, 0.6°-7.6°; p = 0.02] greater, respectively) at 3 months, but not at later followups (6 or 12 months). There were no differences in radiographic outcomes (volar tilt, radial inclination, and radial height) between the two interventions. Superficial wound infection was more common in patients treated with K-wires (8.2% versus 3.2%; RR = 2.6; p = 0.001), but otherwise no difference in complication rates was found. Despite the small number of studies and the limitations inherent in a meta-analysis, we found that volar locking plates show better DASH scores at 3- and 12-month followups compared with K-wires for displaced distal radius fractures in adults; however, these differences were small and unlikely to be clinically important. Further research is required to better delineate if there are specific radiographic, injury, or patient characteristics that may benefit from volar locking plates in the short term and whether there are any differences in long-term outcomes and complications. Level I, therapeutic stud