Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration

Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish

Pediatric Emergency Care Applied Research Network (PECARN) prediction rules in identifying high risk children with mild traumatic brain injury

Purpose: Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) prognostic rules is a scoring system for prediction of the need for computed tomography (CT) scanning in children with mild TBI. However, its validation has not been assessed in developing countries. Therefore, the present study was designed to assess the value of PECARN rule in identification of children with clinically important TBI (ciTBI). Method: In this prospective cross-sectional study, 594 children (mean age: 7.9 ± 5.3 years; 79.3 boys) with mild TBI brought to emergency ward of two healthcare centers in Tehran, Iran were assessed. PECARN checklist was filled for all patients and children were divided to three groups of low, intermediate and high risks. Patients were followed for 2 weeks by phone to assess their ciTBI status. At the end, discrimination power, calibration and overall performance of PECARN rule were assessed. Results: PECARN had a sensitivity and specificity of 92.3 and 40.6, respectively, in predicting ciTBI in children under 2 years and 100.0 and 57.8, respectively, in individuals between the ages of 2 and 18. PECARN rule had a proper calibration in prediction of ciTBI and CT scan findings. Brier score (overall performance) of PECARN rule in predicting ciTBI in children under 2 and 2�18 years were 1.5 and 1.2, respectively. Conclusion: PECARN prediction rule has a proper validity in the prediction of ciTBI. Therefor it can be used for screening and identification of high risk children with mild TBI. © 2017, Springer-Verlag GmbH Germany

Diagnostic value of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) in detection of pediatric acute kidney injury; a systematic review and meta-analysis

Background: Two questions about diagnostic value of urinary neutrophil gelatin associated lipocalin (uNGAL) in detection of acute kidney injury (AKI) in children have remained unanswered; first, which cut-off point of uNGAL has the highest value in detection of AKI; and second when is the best time for measuring this biomarker in a patient? Accordingly, the present study aimed to conduct a systematic review and meta-analysis to provide evidence on the diagnostic and prognostic value of uNGAL in detection of AKI in children. Materials and Methods: An extensive search in the electronic databases up to the end of August 2016 was performed. Data were summarized and then the diagnostic performance characteristics of uNGAl in AKI were evaluated. Results: Data from 37 articles were summarized. Analyses based on area under the curve, sensitivity, specificity and diagnostic odds ratio revealed that uNGAL provides the optimum prognostic and diagnostic value in detection of AKI in children when measured during 0 to 6 hours after admission or surgery with a cut-off point of 50 mg/dL. In this setting, area under the curve, sensitivity, specificity and diagnostic odds ratio of uNGAL are 0.97 (95 CI: 0.95 to 0.98), 0.92 (95 CI: 0.84 to 0.97), 0.92 (95 CI: 0.83 to 0.97) and 148.14 (95 CI: 32.13 to 683.10), respectively. Conclusion: Based on these results, measuring uNGAL during the first 6 hours after admission or surgery with a cut-off point of 50 mg/dL, provides the optimum diagnostic value in detection of AKI in children

Value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury; a systematic review and meta-analysis

Background: Major attention has been drawn to the prognostic value of plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) in detection of acute kidney injury (AKI) in children, but still no consensus has been reached. Accordingly, the present study aimed to assess the diagnostic value of this biomarker in detection of acute kidney injury in children through a systematic review and meta-analysis. Materials and Methods: Two independent reviewers carried out a comprehensive search in electronic databases up to the end of August, 2016. After summarization of studies, screening performance characteristics of plasma/serum NGAL were evaluated in detection of AKI. The area under the curve of receiver operating characteristics curve, sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio of NGAL were calculated using a mixed-effects binary regression model. A p-value less than 0.05 was considered as significance threshold in all analyses. Results: Data from 22 studies (2,213 non-AKI children and 1,109 AKI patients) were pooled and analyzed. Analyses revealed that the performance of plasma/seum NGAL is maximal when the level of this biomarker is measured in the first 12 hours after admission or surgery, considering a cut-off level of 100 mg/dL. In this setting the area under the curve, sensitivity, specificity and diagnostic odds ratio of plasma/serum NGAL were 0.94 (95 CI: 0.91-0.95), 0.87 (95 CI: 0.67-0.96), 0.88 (95 CI: 0.65-0.96) and 48.05 (95 CI: 9.20-251.04), respectively. Conclusion: The high diagnostic value in the first few hours is one of the advantages of plasma/serum NGAL, emphasizing its usefulness in clinical evaluations

Performance of physiology scoring systems in prediction of in-hospital mortality of traumatic children: A prospective observational study

Background: This study is designed to compare the value of four physiologic scoring systems of rapid acute physiology score (RAPS), rapid emergency medicine score (REMS), Worthing physiology scoring system (WPSS) and revised trauma score (RTS) in predicting the in-hospital mortality of traumatic children brought to the emergency department. Method: We used the data gathered from six healthcare centers across Iran between the April-October 2016. Included patients were all children with trauma. Patients were assessed and followed until discharge. Moreover, patients were divided to two groups of died and alive, and discriminatory power and general calibration of models in prediction of in-hospital mortality were compared. Results: Data was gathered from 814 children (average age of 11.65 +/- 5.36 years, 74.32 boys). Highest measured area under the curve was for RAPS and REMS with 0.986 and 0.986, respectively. Areas under the curve of WPSS and RTS were 0.920 and 0.949, respectively (p = 0.02). Sensitivity and specificity of RAPS were 100.0 and 95.05, respectively. These amounts for REMS were 100.0 and 94.04, respectively. Two models of RTS and WPSS had the same sensitivity of 84.62. Specificity of these two was 98.22 and 96.95, respectively. Three models of RAPS, REMS and RTS had proper calibrations in predicting mortality; however, it seems that WPSS overestimates the mortality in high risk patients. Conclusion: As calculations of RAPS is easier than REMS and their proper calibrations, it seems that RAPS is the best physiologic model in predicting in-hospital mortality and classifying in traumatic children based on severity of injury. However, further validation of the recommended score is essential before implementing them into routine clinical practice

Worthing physiological score vs revised trauma score in outcome prediction of trauma patients; a comparative study

Introduction: Awareness about the outcome of trauma patients in the emergency department (ED) has become a topic of interest. Accordingly, the present study aimed to compare the rapid trauma score (RTS) and worthing physiological scoring system (WPSS) in predicting in-hospital mortality and poor outcome of trauma patients. Methods: In this comparative study trauma patients brought to five EDs in different cities of Iran during the year 2016were included. After data collection, discriminatory power and calibration of the modelswere assessed and compared using STATA 11. Results: 2148 patientswith themean age of 39.50±17.27 yearswere included (75.56 males). The AUC of RTS and WPSS models for prediction ofmortalitywere 0.86 (95 CI: 0.82-0.90) and 0.91 (95 CI: 0.87-0.94), respectively (p=0.006). RTS had a sensitivity of 71.54 (95CI: 62.59-79.13) and a specificity of 97.38 (95 CI: 96.56-98.01) in prediction of mortality. These measures for the WPSS were 87.80 (95 CI: 80.38-92.78) and 83.45 (95 CI: 81.75-85.04), respectively. The AUC of RTS and WPSS in predicting poor outcome were 0.81 (95 CI: 0.77-0.85) and 0.89 (95 CI: 0.85-0.92), respectively (p < 0.0001). Conclusion: The findings showed a higher prognostic value for the WPSS model in predicting mortality and severe disabilities in trauma patients compared to the RTS model. Both models had good overall performance in prediction of mortality and poor outcome. © (2016) Shahid Beheshti University ofMedical Sciences

Worthing Physiological score vs revised trauma score in outcome prediction of trauma patients; a comparative study

Introduction: Awareness about the outcome of trauma patients in the emergency department (ED) has become a topic of interest. Accordingly, the present study aimed to compare the rapid trauma score (RTS) and worthing physiological scoring system (WPSS) in predicting in-hospital mortality and poor outcome of trauma patients. Methods: In this comparative study trauma patients brought to five EDs in different cities of Iran during the year 2016 were included. After data collection, discriminatory power and calibration of the modelswere assessed and compared using STATA 11. Results: 2148 patients with the mean age of 39.50±17.27 years were included (75.56 males). The AUC of RTS and WPSS models for prediction of mortality were 0.86 (95 CI: 0.82-0.90) and 0.91 (95 CI: 0.87-0.94), respectively (p=0.006). RTS had a sensitivity of 71.54 (95CI: 62.59-79.13) and a specificity of 97.38 (95 CI: 96.56-98.01) in prediction of mortality. These measures for the WPSS were 87.80 (95 CI: 80.38-92.78) and 83.45 (95 CI: 81.75-85.04), respectively. The AUC of RTS and WPSS in predicting poor outcome were 0.81 (95 CI: 0.77-0.85) and 0.89 (95 CI: 0.85-0.92), respectively (p<0.0001). Conclusion: The findings showed a higher prognostic value for the WPSS model in predicting mortality and severe disabilities in trauma patients compared to the RTS model. Both models had good overall performance in prediction of mortality and poor outcome. © (2017) Shahid Beheshti University of Medical Sciences

Transplantation of olfactory ensheathing cells on functional recovery and neuropathic pain after spinal cord injury; systematic review and meta-analysis

There are considerable disagreements on the application of olfactory ensheathing cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta-analysis was designed to investigate the efficacy of OEC transplantation on motor function recovery and neuropathic pain alleviation in SCI animal models. Accordingly, all related studies were identified and included. Two independent researchers assessed the quality of the articles and summarized them by calculating standardized mean differences (SMD). OEC transplantation was shown to significantly improve functional recovery (SMD = 1.36; 95% confidence interval: 1.05-1.68; p < 0.001). The efficacy of this method was higher in thoracic injuries (SMD = 1.41; 95% confidence interval: 1.08-1.74; p < 0.001) and allogeneic transplants (SMD = 1.53; 95% confidence interval: 1.15-1.90; p < 0.001). OEC transplantation had no considerable effects on the improvement of hyperalgesia (SMD = -0.095; 95% confidence interval: -0.42-0.23; p = 0.57) but when the analyses were limited to studies with follow-up = 8 weeks, it was associated with increased hyperalgesia (SMD = -0.66; 95% confidence interval: -1.28-0.04; p = 0.04). OEC transplantation did not affect SCI-induced allodynia (SMD = 0.54; 95% confidence interval: -0.80-1.87; p = 0.43). Our findings showed that OEC transplantation can significantly improve motor function post-SCI, but it has no effect on allodynia and might lead to relative aggravation of hyperalgesia