bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide landscape of mRNAs, microRNAs, lncRNAs, and circRNAs in hemorrhagic shock-induced ALI/ARDS in rats
Authors: Wang Zhiwei , Chang Panpan , Ye Jingjing , Ma Wei , Zhou Jing , Zhang Peng , Chen Xiaokun , Jia Bo , Zheng Ming , Huang Wei , Wang Tianbing 
Published: February 2021

BACKGROUND
Hemorrhagic shock (HS) can develop into multiple organ dysfunction syndrome, among which acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) usually lead to poor outcomes. The underlying molecular mechanisms of HS-induced ALI/ARDS remain unclear. This study sought to investigate gene expression profiles and predict competing endogenous RNA (ceRNA) regulatory networks in an HS-induced ALI/ARDS preclinical model.

METHODS
Sprague Dawley rats were subjected to a fixed volume of hemorrhage (HS, 40% estimated total blood volume) or not (sham) randomly. After 8 hours of observation, left lung tissue was harvested to evaluate lung injury. Right lung was collected for RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed and the long noncoding RNA (lncRNA)/circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) linkages were predicted using the ceRNA theory. Quantitative real-time polymerase chain reaction was used to validate the RNA sequencing findings.

RESULTS
Hemorrhagic shock lungs showed noticeable ALI/ARDS features, and 437 mRNAs, 31 miRNAs, 734 lncRNAs, and 29 circRNAs were differentially expressed. In Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, the differentially expressed transcripts were enriched in the following terms: the metabolic pathways, signal transduction pathways, necroptosis, DNA damage recognition and repair, inflammatory cell migration and chemotaxis, the NOD-like receptor signaling pathway, the Janus kinase/signal transducer and activator of transcription signaling pathway, the mitogen-activated protein kinase signaling pathway, the phosphatidylinositol-3-kinase/protein kinase B signaling pathway, and so on. Also, this study identified lncRNA-miRNA-mRNA linkages with 12 lncRNAs, 5 miRNAs, 15 mRNAs, and circRNA-miRNA-mRNA linkages with 10 circRNAs, 16 miRNAs, 39 mRNAs. These networks might play important regulatory roles.

CONCLUSION
This is the first high-throughput analysis of gene expression profiles in HS-induced ALI/ARDS. It shows that metabolism, cell signaling, DNA damage and repair, and necroptosis-related RNAs altered, and inflammatory response-associated RNAs and pathways have pivotal roles in HS-induced ALI/ARDS progression. It also prompts some important RNAs and regulatory networks for future research.

LEVEL OF EVIDENCE
Basic science article.
Field-Triage, Hospital-Triage and Triage-Assessment: A Literature Review of the Current Phases of Adult Trauma Triage
Authors: Morris Rachel S. , Karam Basil S. , Murphy Patrick B. , Jenkins Peter , Milia David J. , Hemmila Mark R. , Haines Krista L. , Puzio Thaddeus J. , de Moya Marc A. , Tignanelli Christopher J. 
Published: February 2021

ABSTRACT
Despite major improvements in the United States trauma system over the past two decades, prehospital trauma triage is a significant challenge. Undertriage is associated with increased mortality, and overtriage results in significant resource overuse. The American College of Surgeons Committee on Trauma benchmarks for undertriage and overtriage are not being met. Many barriers to appropriate field triage exist, including lack of a formal definition for major trauma, absence of a simple and widely applicable triage mode, and emergency medical service adherence to triage protocols. Modern trauma triage systems should ideally be based on the need for intervention rather than injury severity. Future studies should focus on identifying the ideal definition for major trauma and creating triage models that can be easily deployed. This narrative review article presents challenges and potential solutions for prehospital trauma triage.
Blunt cerebrovascular injuries: Outcomes from the American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment (PROOVIT) multicenter registry
Authors: Russo Rachel M. , Davidson Anders J. , Alam Hasan B. , DuBose Joseph J. , Galante Joseph M. , Fabian Timothy C. , Savage Stephanie , Holcomb John B. , Scalea Thomas M. ,   AAST PROOVIT Study Group, Rasmussen Todd E. 
Published: February 2021

BACKGROUND
Administering antithrombotics (AT) to the multiply injured patient with blunt cerebrovascular injury (BCVI) requires a thoughtful assessment of the risk of stroke and death associated with nontreatment. Large, multicenter analysis of outcomes stratified by injury grade and vessel injured is needed to inform future recommendations.

METHODS
Nine hundred and seventy-one BCVIs were identified from the PROspective Vascular Injury Treatment registry in this retrospective analysis. Using multivariate analysis, we identified predictors of BCVI-related stroke and death. We then stratified these risks by injury grade and vessel injured. We compared the risk of adverse outcomes in the nontreatment group with those treated with antiplatelet agents and/or anticoagulants.

RESULTS
Stroke was identified in 7% of cases. Overall mortality was 12%. Both increased with increasing BCVI grade. Treatment with ATs was associated with lower mortality and was not significantly affected by the choice of agent. Withholding ATs was associated with an increased risk of stroke and/or death across all subgroups (Grade I/II: odds ratio [OR], 4.66; 95% confidence interval [CI], 2.48–8.75; Grade III: OR, 7.0; 95% CI, 2.01–24.5; Grade IV: OR, 4.43; 95% CI, 1.76–11.1) even after controlling for covariates. Predictors of death included more severe trauma, Grade IV injury, and the occurrence of stroke. Arterial occlusion, hypotension, and endovascular intervention were significant predictors of stroke. Patients that experienced a BCVI-related stroke were at a 4.2× increased risk of death. The data set lacked the granularity necessary to evaluate AT timing or dosing regimen, which limited further analysis of stroke prevention strategies.

CONCLUSION
Stroke and death remain significant risks for all BCVI grades regardless of the vessel injured. Antithrombotics represent the only management strategy that is consistently associated with a lower incidence of stroke and death in all BCVI categories. In the multi-injured BCVI patient with a high risk of bleeding on anticoagulation, antiplatelet agents are an efficacious alternative. Given the 40% mortality rate in patients who survived their initial trauma and developed a BCVI-related stroke, nontreatment may no longer be a viable option.

LEVEL OF EVIDENCE
Epidemiological III; Therapeutic IV.
Trends in utilization of whole-body computed tomography in blunt trauma after MVC: Analysis of the Trauma Quality Improvement Program database
Authors: Bunn Corinne , Ringhouse Brendan , Patel Purvi , Baker Marshall , Gonzalez Richard , Abdelsattar Zaid M. , Luchette Fred A. 
Published: February 2021

BACKGROUND
The use of whole-body computed tomography (WBCT) in awake, clinically stable injured patients is controversial. It is associated with unnecessary radiation exposure and increased cost. We evaluate use of computed tomography (CT) imaging during the initial evaluation of injured patients at American College of Surgeons Levels I and II trauma centers (TCs) after blunt trauma.

METHODS
We identified adult blunt trauma patients after motor vehicle crash (MVC) from the American College of Surgeons Trauma Quality Improvement Program (TQIP) database between 2007 and 2016 at Level I or II TCs. We defined awake clinically stable patients as those with systolic blood pressure of 100 mm Hg or higher with a Glasgow Coma Scale score of 15. Computed tomography imaging had to have been performed within 2 hours of arrival. Whole-body computed tomography was defined as simultaneous CT of the head, chest and abdomen, and selective CT if only one to two aforementioned regions were imaged. Patients were stratified by Injury Severity Score (ISS).

RESULTS
There were 217,870 records for analysis; 131,434 (60.3%) had selective CT, and 86,436 (39.7%) had WBCT. Overall, there was an increasing trend in WBCT utilization over the study period (p < 0.001). In patients with ISS less than 10, WBCT was utilized more commonly at Level II versus Level I TCs in patients discharged from the emergency department (26.9% vs. 18.3%, p < 0.001), which had no surgical procedure(s) (81.4% vs. 80.3%, p < 0.001) and no injury of the head (53.7% vs. 52.4%, p = 0.008) or abdomen (83.8% vs. 82.1%, p = 0.001). The risk-adjusted odds of WBCT was two times higher at Level II TC vs. Level I (odds ratio, 1.88; 95% confidence interval 1.82–1.94; p < 0.001).

CONCLUSION
Whole-body computed tomography utilization is increasing relative to selective CT. This increasing utilization is highest at Level II TCs in patients with low ISSs, and in patients without associated head or abdominal injury. The findings have implications for quality improvement and cost reduction.

LEVEL OF EVIDENCE
Care management, Level IV.
Insult to injury: National analysis of return to work and financial outcomes of trauma patients
Authors: Neiman Pooja U. , Taylor Kathryn K. , Sinco Brandy , Anderson Geoffrey A. , Sangji Naveen F. , Hemmila Mark R. , Scott John W. 
Published: February 2021

BACKGROUND
While much of trauma care is rightly focused on improving inpatient survival, the ultimate goal of recovery is to help patients return to their daily lives after injury. Although the overwhelming majority of trauma patients in the United States survive to hospital discharge, little is known nationally regarding the postdischarge economic burden of injuries among trauma survivors.

METHODS
We used the National Health Interview Survey from 2008 to 2017 to identify working-age trauma patients, aged 18 to 64 years, who sustained injuries requiring hospitalization. We used propensity score matching to identify noninjured respondents. Our primary outcome measure was postinjury return to work among trauma patients. Our secondary outcomes included measures of food insecurity, medical debt, accessibility and affordability of health care, and disability.

RESULTS
A nationally weighted sample of 319,580 working-age trauma patients were identified. Of these patients, 51.7% were employed at the time of injury, and 58.9% of them had returned to work at the time of interview, at a median of 47 days postdischarge. Higher rates of returning to work were associated with shorter length of hospital stay, higher education level, and private health insurance. Injury was associated with food insecurity at an adjusted odds ratio (aOR) of 1.8 (95% confidence interval, 1.40–2.37), with difficulty affording health care at aOR of 1.6 (1.00–2.47), with medical debt at aOR of 2.6 (2.11–3.20), and with foregoing care due to cost at aOR of 2.0 (1.52–2.63). Working-age trauma patients had disability at an aOR of 17.6 (12.93–24.05).

CONCLUSION
The postdischarge burden of injury among working-age US trauma survivors is profound—patients report significant limitations in employment, financial security, disability, and functional independence. A better understanding of the long-term impact of injury is necessary to design the interventions needed to optimize postinjury recovery so that trauma survivors can lead productive and fulfilling lives after injury.

LEVEL OF EVIDENCE
Economic & Value-Based Evaluations, level II; Prognostic, level II.
Effect of injury location and severity on opioid use after trauma
Authors: Baker Rachel C. , Brown Craig S. , Montgomery John R. , Mouch Charles A. , Kenney Brooke C. , Englesbe Michael J. , Waljee Jennifer F. , Hemmila Mark R. 
Published: February 2021

OBJECTIVE
Recent data have suggested that persistent opioid use is prevalent following trauma. The effect of type of injury and total injury burden is not known. We sought to characterize the relationship between injury location and severity and risk of persistent opioid use.

METHODS
We investigated postdischarge opioid utilization among patients who were admitted for trauma between January 2010 and June 2017 using the Optum Clinformatics Database. New persistent opioid use (NPOU) was defined as one of the following scenarios: (1) two separate opioid prescription fills between 0 and 14 days postdischarge and having 1+ fills in the 91 to 180 days following discharge or (2) filling a prescription in the 15 to 90 days following discharge in addition to a filling in the 91 to 180 day postdischarge period. Multivariable logistic regression was used to assess the relationship between injury type and severity with new persistent opioid use development.

RESULTS
A total of 26,437 opioid-naive patients were included in the analysis. Overall, 2,277 patients (8.6%) met the criteria for NPOU. After adjustment for confounding, NPOU was significantly more common for patients with injury to the extremities (adjusted odds ratio [aOR], 1.75; 95% confidence interval [CI], 1.57–1.94) or abdomen (adjusted odds ratio [aOR], 1.42; 95% CI, 1.22–1.64). Importantly, patients with maximum Abbreviated Injury Scale score of ≥2 for any body region had 1.49-fold odds of NPOU compared with patients with score of 1 (95% CI, 1.28–1.73), while no difference was seen across groupings of total injury burden based on Injury Severity Score.

CONCLUSION
New persistent opioid use is common among patients suffering from trauma. In addition, patients suffering from extremity and abdominal injuries are at highest risk. Maximum individual region injury severity predicts development of new persistent use, whereas total injury severity does not.

LEVEL OF EVIDENCE
Prognostic and epidemiological, level III.
Surgical stabilization of rib fractures in octogenarians and beyond—what are the outcomes?
Authors: Pieracci Fredric M. , Leasia Kiara , Hernandez Matthew C. , Kim Brian , Cantrell Emily , Bauman Zachary , Gardner Scott , Majercik Sarah , White Thomas , Dieffenbaugher Sean , Eriksson Evert , Barns Matthew , Benjamin Christie D. , Lasso Erika Tay , Schubl Sebastian , Sauaia Angela , Doben Andrew R. 
Published: February 2021

BACKGROUND
Prospective studies of surgical stabilization of rib fractures (SSRF) have excluded elderly patients, and no study has exclusively addressed the ≥80-year-old subgroup. We hypothesized that SSRF is associated with decreased mortality in trauma patients 80 years or older.

METHODS
Multicenter retrospective cohort study involving eight centers. Patients who underwent SSRF from 2015 to 2020 were matched to controls by study center, age, injury severity score, and presence of intracranial hemorrhage. Patients with chest Abbreviated Injury Scale score less than 3, head Abbreviated Injury Scale score greater than 2, death within 24 hours, and desire for no escalation of care were excluded. A subgroup analysis compared early (0–2 days postinjury) to late (3–7 days postinjury) SSRF. Poisson regression accounting for clustered data by center calculated the relative risk (RR) of the primary outcome of mortality for SSRF versus nonoperative management.

RESULTS
Of 360 patients, 133 (36.9%) underwent SSRF. Compared with nonoperative patients, SSRF patients were more severely injured and more likely to receive locoregional analgesia. There were 31 hospital deaths among the entire sample (8.6%). Multivariable regression demonstrated a decreased risk of mortality for the SSRF group, as compared with the nonoperative group (RR, 0.41; 95% confidence interval, 0.24–0.69; p < 0.01). However, SSRF patients were more likely to develop pneumonia, and had an increased duration of both mechanical ventilation and intensive care unit stay. There were no differences in discharge destination, although the SSRF group was less likely to be discharged on narcotics (RR, 0.66; 95% confidence interval, 0.48–0.90; p = 0.01). There was no difference in adjusted mortality between the early and late SSRF subgroups.

CONCLUSION
Patients selected for SSRF were substantially more injured versus those managed nonoperatively. Despite this, SSRF was independently associated with decreased mortality. With careful patient selection, SSRF may be considered a viable treatment option in octogenarian/nonagenarians.

LEVEL OF EVIDENCE
Therapeutic, Level IV
Outcome of Liver Transplantation for Neonatal-onset Citrullinemia Type I
Authors: Liu Yuan , Luo Yi , Xia Lei , Qiu Bijun , Zhou Tao , Feng Mingxuan , Wang Chenchen , Xue Feng , Chen Xiaosong , Han Longzhi , Zhang Jianjun , Xia Qiang 
Published: February 2021

Background.
We evaluated the outcome of liver transplantation (LT) in neonatal-onset citrullinemia type I patients, especially its impact on neurological deficits and developmental retardation.

Methods.
From October 2006 to October 2019, 5 of the 2003 children who received LT at Ren Ji Hospital had been diagnosed with citrullinemia type I. The primary indication for transplantation was repeated metabolic compensation and developmental retardation in 4 patients and prophylactic transplantation in the other. Among them, 3 patients received living donor LT and 2 received orthotopic LT.

Results.
All recipients had successfully recovered within the median follow-up period of 32 months (range, 6–54 mo). Transplantation restored citrulline metabolism and liver function. Plasma ammonia and citrulline concentration decreased to normal levels with no further hyperammonemic episodes being reported, even after normal diet intake began. Meanwhile, uracil-2 and orotic acid were not detected in urinary excretion. Strikingly, patients suffered developmental retardation before LT showed improved psychomotor ability and significant catch-up growth during the follow-up period. Cognitive ability, including language skills and academic performance, also greatly improved. Three patients had sustained brain injuries and exhibited severe neurological deficits before transplantation, especially repeated generalized tonic-clonic seizures. LT halted neurological deterioration and controlled seizure episodes, which further facilitated the intellectual development and improvement of life quality.

Conclusions.
LT is an effective treatment for neonatal-onset citrullinemia type I patients, which reverses metabolism decompensation and improves quality of life. For patients who have suffered severe hyperammonemic insults, LT should be conducted at an early age to avoid further neurological or developmental deficits.
Lung Transplantation for Severe Post–coronavirus Disease 2019 Respiratory Failure
Authors: Hawkins Robert B. , Mehaffey J. Hunter , Charles Eric J. , Mannem Hannah C. , Roeser Mark 
Published: February 2021

Background.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in >72 million cases and 1.6 million deaths. End-stage lung disease from COVID-19 is a new and growing entity that may benefit from lung transplant; however, there are limited data on the patient selection, perioperative management, and expected outcomes of transplantation for this indication.

Methods.
A systematic review of the literature was performed with searches of MEDLINE and Web of Science databases as well as the gray literature. All manuscripts, editorials, commentaries, and gray literature reports of lung transplantation for COVID-related respiratory failure were included. A case from the University of Virginia is described and included in the review.

Results.
A total of 27 studies were included: 11 manuscripts, 5 commentaries, and 11 gray literature reports. The total number of transplantations for COVID-related lung disease was 21. The mean age was 55±12 years, 16 (76%) were male individuals, and the acuity was high, with 85% on extracorporeal membrane oxygenation preoperatively. There was a 95% early survival rate, with 1 additional late death. There is growing histopathologic evidence for permanent structural damage with no replicating virus at the time of transplantation.

Conclusions.
Bilateral lung transplantation is an effective treatment option with reasonable short-term outcomes for patients with end-stage lung failure secondary to COVID-19. However, specific considerations in this new population require a multidisciplinary approach. As we move into the second wave of the COVID-19 global pandemic, lung transplantation will likely have a growing role in management of these complex patients.
Uterine Transplantation Using Living Donation: A Cross-sectional Study Assessing Perceptions, Acceptability, and Suitability
Authors: Jones Benjamin P. , Rajamanoharan Abirami , Williams Nicola J. , Vali Saaliha , Saso Srdjan , Mantrali Ifigenia , Jalmbrant Maria , Thum Meen-Yau , Diaz-Garcia Cesar , Ghaem-Maghami Sadaf , Wilkinson Stephen , Quiroga Isabel , Friend Peter , Yazbek Joseph , Smith J. Richard 
Published: February 2021

Background.
A uterine transplantation is a nonvital, quality-of-life–enhancing solid organ transplant. Given improvements in donor risk profile and the anticipated shortage of suitable deceased donors, nondirected donation could facilitate sustainability as uterine transplantation moves from research into the clinical realm. The aim of this article is to determine perceptions and identify motivations of potential nondirected living uterus donors and assess acceptability and suitability.

Methods.
A cross-sectional survey using an electronic questionnaire among women who have inquired about donating their uterus for uterine transplantation.

Results.
The majority of respondents “strongly agreed” or “agreed” that the most prevalent motivations to donate their uterus include helping someone carry and give birth to their own baby (n = 150; 99%), helping others (n = 147; 97%), and because they no longer need their womb (n = 147; 97%). After considering risks of uterus donation, the majority were still keen to donate their uterus (n = 144; 95%), but following a process of exclusion using donor selection criteria, less than a third (n = 42; 29%) were found to be suitable to proceed.

Conclusions.
This study demonstrates novel insight into the motivations of women who wish to donate their uterus and displays high levels of acceptability after consideration of the risks involved. Despite the physical risk and transient impact upon ability to undertake activities of daily living, women who donate their uterus expect to gain psychological and emotional benefits from enabling another woman to gestate and give birth to their own future children. However, currently used selection criteria reduce the number of potential donors significantly.
Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management
Authors: Zanon Zotin Maria Clara , Sveikata Lukas , Viswanathan Anand , Yilmaz Pinar 
Published: February 2021

Purpose of review
We present recent developments in the field of small vessel disease (SVD)-related vascular cognitive impairment, including pathological mechanisms, updated diagnostic criteria, cognitive profile, neuroimaging markers and risk factors. We further address available management and therapeutic strategies.

Recent findings
Vascular and neurodegenerative pathologies often co-occur and share similar risk factors. The updated consensus criteria aim to standardize vascular cognitive impairment (VCI) diagnosis, relying strongly on cognitive profile and MRI findings. Aggressive blood pressure control and multidomain lifestyle interventions are associated with decreased risk of cognitive impairment, but disease-modifying treatments are still lacking. Recent research has led to a better understanding of mechanisms leading to SVD-related cognitive decline, such as blood-brain barrier dysfunction, reduced cerebrovascular reactivity and impaired perivascular clearance.

Summary
SVD is the leading cause of VCI and is associated with substantial morbidity. Tackling cardiovascular risk factors is currently the most effective approach to prevent cognitive decline in the elderly. Advanced imaging techniques provide tools for early diagnosis and may play an important role as surrogate markers for cognitive endpoints in clinical trials. Designing and testing disease-modifying interventions for VCI remains a key priority in healthcare.