Radiation-induced lung injury is mitigated by blockade of gastrin-releasing peptide.

Gastrin-releasing peptide (GRP), secreted by pulmonary neuroendocrine cells, mediates oxidant-induced lung injury in animal models. Considering that GRP blockade abrogates pulmonary inflammation and fibrosis in hyperoxic baboons, we hypothesized that ionizing radiation triggers GRP secretion, contributing to inflammatory and fibrotic phases of radiation-induced lung injury (RiLI). Using C57BL/6 mouse model of pulmonary fibrosis developing ≥20 weeks after high-dose thoracic radiation (15 Gy), we injected small molecule 77427 i.p. approximately 1 hour after radiation then twice weekly for up to 20 weeks. Sham controls were anesthetized and placed in the irradiator without radiation. Lung paraffin sections were immunostained and quantitative image analyses performed. Mice exposed to radiation plus PBS had increased interstitial CD68(+) macrophages 4 weeks after radiation and pulmonary neuroendocrine cells hyperplasia 6 weeks after radiation. Ten weeks later radiation plus PBS controls had significantly increased pSmad2/3(+) nuclei/cm(2). GRP blockade with 77427 treatment diminished CD68(+), GRP(+), and pSmad2/3(+) cells. Finally, interstitial fibrosis was evident 20 weeks after radiation by immunostaining for α-smooth muscle actin and collagen deposition. Treatment with 77427 abrogated interstitial α-smooth muscle actin and collagen. Sham mice given 77427 did not differ significantly from PBS controls. Our data are the first to show that GRP blockade decreases inflammatory and fibrotic responses to radiation in mice. GRP blockade is a novel radiation fibrosis mitigating agent that could be clinically useful in humans exposed to radiation therapeutically or unintentionally.

Is time to flap coverage of open tibial fractures an independent predictor of flap-related complications?

OBJECTIVES: The importance of the timing of flap coverage of open tibial shaft fractures remains controversial. Many studies have shown increased complications and infection rates associated with delay in coverage but have not controlled for risk factors that might be associated with both delay in coverage and complications. We hypothesized that the timing of flap coverage of open tibial fractures is not predictive of complications after controlling for known risk factors. DESIGN: Retrospective review. SETTING: Level I trauma center. PATIENTS: Sixty-nine patients treated for acute tibial fractures (45 tibial shaft, 17 plateau, and 12 pilon fractures) at our center from 2004 through 2009 required 74 flaps. Patients requiring flaps later for wound breakdown or infection were excluded. INTERVENTION: Electronic records and prospective trauma database were reviewed. All fractures were AO classified by a trauma fellowship-trained orthopaedic surgeon. MAIN OUTCOME MEASUREMENTS: Primary outcome was flap complication, defined as infection or other flap-related adverse outcome requiring surgical treatment. Logistic regression analysis was conducted. RESULTS: A logistic regression model that separated the first 7 days after injury from subsequent days found no increased risk for days 1 through 7. The odds of complications, and of infection in particular, increased by 11% and 16%, respectively, for each day beyond day 7 (P < 0.04). CONCLUSIONS: Even after controlling for known risk factors for complications, including injury severity, time to flap coverage was a significant predictor of complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Diagnosis of femoral neck fracture associated with femoral shaft fracture: blinded comparison of computed tomography and plain radiography.

OBJECTIVE: Femoral neck fractures that are associated with femoral shaft fractures have historically been associated with high rates of missed diagnosis. Despite the potentially serious consequences of a missed femoral neck fracture, little work has been conducted to rigorously evaluate the ability of commonly used imaging studies to detect such fractures. Our hypothesis was that axial-view computed tomography is superior to plain radiography at detecting femoral neck fractures. DESIGN: Blinded assessment of a randomized image set that included axial-view computed tomographic scans of the pelvis, anteroposterior-view radiographs of the pelvis, and anteroposterior-view radiographs of the femur. SETTING: Academic trauma center. PATIENTS: Twenty-eight patients who had femoral shaft fractures with femoral neck fractures and 60 patients who had femoral shaft fractures without femoral neck fractures. INTERVENTION: Images that were stripped of demographic data were independently viewed in random order on computer workstations by 5 trauma fellowship-trained orthopaedic surgeons who were blinded to treatment and diagnosis. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive post-test probability, and 1 minus negative post-test probability were calculated for diagnosing femoral neck fracture based on each image type. RESULTS: Interobserver reliability showed "substantial agreement" (kappa > 0.65) for all imaging modalities, indicating that the surgeons had a high level of agreement. All 3 imaging sets had high specificity (>94%) and 1 minus negative post-test probability (>95%) but had poor sensitivity (<65%) and positive post-test probability (<58%). False positives and false negatives were equally likely for all imaging modalities (P > 0.2). CONCLUSIONS: Plain radiography and computed tomography have rates of missed femoral neck fractures that are similar and substantial, with a sensitivity of only 56%-64%. Our data emphasize the importance of intraoperative and postoperative imaging in detecting nondisplaced femoral neck fractures in association with femoral shaft fractures.