A novel animal model of primary blast lung injury and its pathological changes in mice

alexandrossfakianakis shared this article with you from Inoreader A novel animal model of primary blast lung injury and its pathological changes in mice via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study. METHODS The animal model of PBLI was established using a self-made mini shock tube simulation device. In brief, mice were randomly divided into two groups: the control group and the model group, the model group were suffered 0.5 bar shock pressures. Mice were sacrificed at 2 hours, 4 hours, 6 hours, 12 hours, and 24 hours after injury. Lung tissue gross observation, hematoxylin and eosin staining and lung pathology scoring were performed to evaluated lung tissue damage. Evans blue dye leakage and bronchoalveolar lavage fluid examination were performed to evaluated pulmonary edema. The relative expression levels of inflammation factors were measured by real-time quantitative polymerase chain reaction and Western blotting analysis. The release of neutrophil extracellular traps was observed by immunofluorescence stain. RESULTS In the model group, the gross observation and hematoxylin and eosin staining assay showed the inflammatory cell infiltration, intra-alveolar hemorrhage, and damaged lung tissue structure. The Evans blue dye and bronchoalveolar lavage fluid examination revealed that the lung tissue permeability and edema was significantly increased after injury. Real-time quantitative polymerase chain reaction and Western blotting assays showed that IL-1β, IL-6, TNF-α were upregulated in the model group. Immunofluorescence assay showed that the level of neutrophil extracellular traps in the lung tissue increased significantly in the model group. CONCLUSION The self-made mini shock tube simulation device can be used to establish the animal model of PBLI successfully. Pathological changes of PBLI mice were characterized by mechanical damage and inflammatory response in lung tissue. View on Web

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Ventilator-associated pneumonia and intubation location in adults with traumatic injuries: Systematic review and meta-analysis

alexandrossfakianakis shared this article with you from Inoreader Ventilator-associated pneumonia and intubation location in adults with traumatic injuries: Systematic review and meta-analysis via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality among critically ill patients, particularly those who present with traumatic injuries. This review aims to determine whether patients with traumatic injuries who are intubated in the prehospital setting are at higher risk of developing VAP compared with those intubated in the hospital. METHODS A systematic review of Medline, Scopus, and Cochrane electronic databases was conducted from inception to January 2021. Inclusion criteria were patients with traumatic injuries who were intubated in the prehospital or hospital settings with VAP as an outcome. Using a random-effects model, the risk of VAP across study arms was compared by calculating a summary relative risk with 95% confidence intervals. The results of individual studies were also summarized qualitatively. RESULTS The search identified 754 articles of which 6 studies (N = 2,990) met the inclusion criteria. All studies were good quality based on assessment with the Newcastle Ottawa scale. Prehospital intubation demonstrated an increased risk of VAP development in two of the six studies. Among the six studies, the overall quality weighted risk ratio was 1.09 (95% confidence interval, 0.90–1.31). CONCLUSION Traumatically injured patients who are intubated in the prehospital setting have a similar risk of developing VAP compared with those that are intubated in the hospital setting. LEVEL OF EVIDENCE Systematic review and meta-analysis; Level IV. View on Web

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Youth violence prevention can be enhanced by geospatial analysis of trauma registry data

alexandrossfakianakis shared this article with you from Inoreader Youth violence prevention can be enhanced by geospatial analysis of trauma registry data via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Geographic information systems (GIS) have been used to understand relationships between trauma mechanisms, locations, and social determinants for injury prevention. We hypothesized that GIS analysis of trauma center registry data for assault patients aged 14 years to 29 years with census tract data would identify geospatial and structural determinants of youth violence. METHODS Admissions to a Level I trauma center from 2010 to 2019 were retrospectively reviewed to identify assaults in those 14 years to 29 years. Prisoners were excluded. Home and injury scene addresses were geocoded. Cluster analysis was performed with the Moran I test for spatial autocorrelation. Census tract comparisons were done using American Communities Survey (ACS) data by t-test and linear regression. RESULTS There were 1,608 admissions, 1,517 (92.4%) had complete addresses and were included in the analysis. Mean age was 23 ± 3.8 years, mean ISS was 7.5 ± 6.2, there were 11 (0.7%) in-hospital deaths. Clusters in six areas of the trauma catchment were identified with a Moran I value of 0.24 (Z score = 17.4, p View on Web

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Scalable deep learning algorithm to compute percent pulmonary contusion among patients with rib fractures

alexandrossfakianakis shared this article with you from Inoreader Scalable deep learning algorithm to compute percent pulmonary contusion among patients with rib fractures via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Pulmonary contusion exists along a spectrum of severity, yet is commonly binarily classified as present or absent. We aimed to develop a deep learning algorithm to automate percent pulmonary contusion computation and exemplify how transfer learning could facilitate large-scale validation. We hypothesized that our deep learning algorithm could automate percent pulmonary contusion computation and that greater percent contusion would be associated with higher odds of adverse inpatient outcomes among patients with rib fractures. METHODS We evaluated admission-day chest computed tomography scans of adults 18 years or older admitted to our institution with multiple rib fractures and pulmonary contusions (2010–2020). We adapted a pretrained convolutional neural network that segments three-dimensional lung volumes and segmented contused lung parenchyma, pulmonary blood vessels, and computed percent pulmonary contusion. Exploratory analysis evaluated associations between percent pulmonary contusion (quartiles) and odds of mechanical ventilation, mortality, and prolonged hospital length of stay using multivariable logistic regression. Sensitivity analysis included pulmonary blood vessel volumes during percent contusion computation. RESULTS A total of 332 patients met inclusion criteria (median, 5 rib fractures), among whom 28% underwent mechanical ventilation and 6% died. The study population's median (interquartile range) percent pulmonary contusion was 4% (2%–8%). Compared to the lowest quartile of percent pulmonary contusion, each increasing quartile was associated with higher adjusted odds of undergoing mechanical ventilation (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.1–2.1) and prolonged hospitalization (OR, 1.6; 95% CI, 1.1–2.2), but not with mortality (OR, 1.1; 95% CI, 0.6–2.0). Findings were similar on sensitivity analysis. CONCLUSION We developed a scalable deep learning algorithm to automate percent pulmonary contusion calculating using chest computed tomography scans of adults admitted with rib fractures. Open code sharing and collaborative research are needed to validate our algorithm and exploratory analysis at a large scale. Transfer learning can help harness the full potential of big data and high-performing algorithms to bring precision medicine to the bedside. LEVEL OF EVIDENCE Prognostic and epidemiological, Level III. View on Web

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Burnout reduction in acute care surgeons: Impact of faculty schedule change at a level 1 trauma and tertiary care center

alexandrossfakianakis shared this article with you from Inoreader Burnout reduction in acute care surgeons: Impact of faculty schedule change at a level 1 trauma and tertiary care center via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Acute care surgeons are prone to burnout because of heavy workload, concurrent clinical responsibilities, and busy in-house call. Modifiable burnout factors have been identified, but few studies have looked for longitudinal effects after change is implemented. We hypothesized that optimizing faculty workflow could decrease burnout without compromising productivity. METHODS We streamlined the faculty schedule at our institution to eliminate 24-hour call by creating weekly blocks of 12-hour day and night call, free from other clinical obligations. Protected academic time was added. The Maslach Burnout Inventory and Areas of Worklife Survey for health care providers were given to faculty, as well as close friends or family, at baseline, 6 months, and 12 months. Maslach Burnout Inventory and Areas of Worklife Survey proprietary formulas were used to assess change in factors contributing to burnout. Our primary outcome measure was the presence of factors contributing to burnout. Chart delinquency, relative value units, and academic projects were secondary outcome measures assessing clinical productivity change. RESULTS Survey completion rates were 92% for faculty and 80% for family. All burnout risk factors improved at 6 and 12 months. In surgeon and family groups, the following improvements were noted in the mean scores of risk factors at 1 year: workload (74%, 68%), control (38%, 16%), reward (14%, 24%), fairness (69%, 22%), emotional exhaustion (27.5%, 24%), depersonalization (37.5%, 14%), personal accomplishment (12.5%, 2%), community (3%, 5%), values (10%, 15%), and over-all burnout (12.5%, 23.3%). There was a reduction in charts reaching delinquent status. Relative value unit production did not decrease. CONCLUSION This study demonstrates that implementing a weekly, 12-hour call schedule can improve factors leading to burnout. Improvements were noted in surgeon and family groups alike, signifying both subjective improvements and observed change in the surgeons' behavior, without compromising clinical productivity. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III. View on Web

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Cellular microRNAs correlate with clinical parameters in multiple injury patients

alexandrossfakianakis shared this article with you from Inoreader Cellular microRNAs correlate with clinical parameters in multiple injury patients via Journal of Trauma and Acute Care Surgery - Current Issue INTRODUCTION The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs). METHODS Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization. RESULTS Polytrauma patients (n = 180) had high Injury Severity Score (26 [20–34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78. CONCLUSION Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation. LEVEL OF EVIDENCE Diagnostic Tests/Criteria; Level II. View on Web

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Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial

alexandrossfakianakis shared this article with you from Inoreader Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial via Clinical Infectious Diseases Advance Access Abstract BackgroundThis study aimed to determine whether paromomycin plus miltefosine (PM/MF) is noninferior to sodium stibogluconate plus paromomycin (SSG/PM) for treatment of primary visceral leishmaniasis in eastern Africa. Methods An open-label, phase 3, randomized, controlled trial was conducted in adult and pediatric patients at 7 sites in eastern Africa. Patients were randomly assigned to either 20 mg/kg paromomycin plus allometric dose of miltefosine (14 days), or 20 mg/kg sodium stibogluconate plus 15 mg/kg paromomycin (17 days). The primary endpoint was definitive cure after 6 months. Results Of 439 randomized patients, 424 completed the trial. Definitive cure at 6 months was 91.2% (155 of 170) and 91.8% (156 of 170) in the PM/MF and SSG/PM arms in primary efficacy modified intention-to-treat analysis (difference, 0.6%; 97.5% confidence interval [CI], −6.2 to 7.4), narrowly missing the noninferiority margin of 7%. In the per-protocol analysis, efficacy was 92% (149 of 162) and 91.7% (155 of 169) in the PM/MF and SSG/PM arms (difference, −0.3%; 97.5% CI, –7.0 to 6.5), demonstrating noninferiority. Treatments were well tolerated. Four of 18 serious adverse events were study drug–related, and 1 death was SSG-related. Allometric dosing ensured similar MF exposure in children (<12 years) and adults. Conclusions PM/MF and SSG/PM efficacies were similar, and adverse drug reactions were as expected given the drugs safety profiles. With 1 less injection each day, reduced treatment duration, and no risk of SSG-associated life-threatening cardiotoxicity, PM/MF is a more patient-friendly alternative for children and adults with primary visceral leishmaniasis in eastern Africa.Clinical Trials Registration. NCT03129646. View on Web

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Hydrogen sulfide inhibits human T‐cell leukemia virus type‐1 (HTLV‐1) protein expression via regulation of ATG4B

alexandrossfakianakis shared this article with you from Inoreader Hydrogen sulfide inhibits human T‐cell leukemia virus type‐1 (HTLV‐1) protein expression via regulation of ATG4B via Journal of Medical Virology Abstract Hydrogen sulfide（H2S）is a redox gasotransmitter. It has been shown that H2S has a key role in host antiviral defense by inhibiting interleukin (IL)-6 production and S-sulfhydrating Keap1 lead to Nrf2/ARE pathway activation. However, it is yet unclear whether H2S can play an antiviral role by regulating autophagy. In this research, we found that exogenous H2S decreased the expression of HTLV-1 protein and HTLV-1 induced autophagosomes accumulation. Transmission electron microscope assays indicated that autophagosomes accumulation decreased after H2S administration. HTLV-1-transformed T-cell lines had a high level of CSE (H2S endogenous enzyme) which could be induced in Hela by HTLV-1 infection. Immunoblot demonstrated that overexpression of CSE inhibited HTLV-1 protein expression and autophagy. And we got the opposite after CSE knockdown. Meanwhile, H2S could not restrain the aut ophagy when ATG4B had a mutant at its site of 89. In a word, these results suggested that H2S modulated HTLV-1 protein expression via ATG4B. Therefore, our findings suggested a new mechanism by which H2S defended against virus infection. This article is protected by copyright. All rights reserved. View on Web

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A novel variant in the transmembrane 4 domain of ANO3 identified in a two-year-old girl with developmental delay and tremor

alexandrossfakianakis shared this article with you from Inoreader A novel variant in the transmembrane 4 domain of <i>ANO3</i> identified in a two-year-old girl with developmental delay and tremor via Journal of Human Genetics - Issue - nature.com science feeds Journal of Human Genetics, Published online: 27 September 2022; doi:10.1038/s10038-022-01082-5 A novel variant in the transmembrane 4 domain of ANO3 identified in a two-year-old girl with developmental delay and tremor View on Web

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Description of Opioid Involved Hospital Deaths that Do Not Have a Subsequent Autopsy

alexandrossfakianakis shared this article with you from Inoreader Description of Opioid Involved Hospital Deaths that Do Not Have a Subsequent Autopsy via Epidemiology - Published Ahead-of-Print Background: Surveillance systems rely on death records to monitor the most severe outcome of the opioid epidemic. However, few studies have linked data from hospital systems with death records to determine potential undercount of opioid involved deaths occurring in hospitals. This study describes characteristics of decedents less likely to have an autopsy following an opioid-involved death in hospitals and estimates the resulting undercount. Methods: A probabilistic data linkage of hospital and medical examiner data involving 4,936 opioid involved deaths among residents of Cook County, Illinois, US from 2016 to 2019. We included only hospital deaths that met a national case definition and presented with clinical signs of opioid overdose. Results: Decedents had higher odds of not having an autopsy if they were 50+ years, admitted to the hospital (aOR=3.7: 2.1, 6.5), hospitalized for 4+ days (aOR=2.2: 1.5, 3.1), and had a comorbid diagnosis of malignant cancer (aOR=4.3: 1.8, 10.1). However, decedents exposed to heroin and synthetic opioids (aOR=0.39: 0.28, 0.55), and concurrent exposure to stimulants (aOR=0.44: 0.31, 0.64) were more likely to have an autopsy). Compared to estimates from the US Centers for Disease Control and Prevention (CDC), we observed undercounts of opioid overdose deaths ranging from 6%-15%. Conclusions: Surveillance systems may undercount decedents that do not meet the typical profile of those more likely to have an autopsy, particularly older patients with chronic health conditions. Our undercount estimate likely exists in addition to the estimated 20-40% undercount reported elsewhere. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. View on Web

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