Early identification of patients with pelvic fractures at risk of severe bleeding requiring intervention is critical. We performed a multi-institutional study to test our hypothesis that pelvic ...fracture patterns predict the need for a pelvic hemorrhage control intervention.
This prospective, observational, multicenter study enrolled patients with pelvic fracture due to blunt trauma. Inclusion criteria included shock on admission (systolic blood pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the ability to review pelvic imaging). Demographic data, open pelvic fracture, blood transfusion, pelvic hemorrhage control intervention (angioembolization, external fixator, pelvic packing, and/or REBOA resuscitative balloon occlusion of the aorta), and mortality were recorded. Pelvic fracture pattern was classified according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage control intervention and mortality were analyzed by univariate and multivariate regression analyses.
A total of 163 patients presenting in shock were enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern was lateral compression I, followed by lateral compression I, and vertical shear. Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%) required a pelvic hemorrhage control intervention. Factors associated with the need for pelvic fracture hemorrhage control intervention on univariate analysis included vertical shear pelvic fracture pattern, increasing age, and transfusion of blood products. Anterior-posterior compression III fracture patterns and open pelvic fracture predicted the need for pelvic hemorrhage control intervention on multivariate analysis. Overall in-hospital mortality for patients admitted in shock with pelvic fracture was 30% and did not differ based on pelvic fracture pattern on multivariate analysis.
Blunt trauma patients admitted in shock with anterior-posterior compression III fracture patterns or patients with open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage control intervention.
Prognostic/epidemiologic study, level III.
The human genome contains a unique, distinct, and human-specific alpha 7-nicotinic acetylcholine receptor ( alpha 7nAChR) gene CHRNA7 (gene-encoding alpha 7-nicotinic acetylcholine receptor) called ...CHRFAM7A (gene-encoding dup- alpha 7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5' upstream from the "wild-type" CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000-fold between different gut epithelial cells. A 3-hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000-fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human-specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild-type alpha 7nAChR ligand-gated pentameric ion channel, the findings point to the existence of a species-specific alpha 7nAChR response that might regulate gut epithelial function in a human-specific fashion.-Dang, X., Eliceiri, B. P., Baird, A., Costantini, T. W. CHRFAM7A: a human-specific alpha 7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS.
Over the last two decades, landmark studies have improved the efficacy of prophylaxis by identifying the utility of anti-Xa guidance for enoxaparin dose adjustment1 and individualized enoxaparin ...dosing2; sped the initiation of safe prophylaxis in patients with traumatic brain injury3 or blunt solid organ injury4; demonstrated the increased VTE risk that occurs when medication doses are missed5; and enlisted patients and nurses in multidisciplinary educational efforts to improve medication adherence.6 Despite these efforts, morbidity and mortality from VTE remain unacceptably high, and additional improvements are needed. After reviewing more than >2000 patients, they confirmed that any delay in prophylaxis administration increases the incidence of VTE, even when controlled for traditional risk factors; on average each hour delay increased the likelihood of VTE by 1.5%. J Trauma Acute Care Surg 2013; 74: 128–33; doi:10.1097/TA.0b013e3182788fa7 2 Berndtson AE, Costantini TW, Lane J, Box K, Coimbra R. If some is good, more is better: an Enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis.
The US-Mexico border is the busiest land crossing in the world and faces continuously increasing numbers of undocumented border crossers. Significant barriers to crossing are present in many regions ...of the border, including walls, bridges, rivers, canals, and the desert, each with unique features that can cause traumatic injury. The number of patients injured attempting to cross the border is also increasing, but significant knowledge gaps regarding these injuries and their impacts remain. The purpose of this scoping literature review is to describe the current state of trauma related to the US-Mexico border to draw attention to the problem, identify knowledge gaps in the existing literature, and introduce the creation of a consortium made up of representatives from border trauma centers in the Southwestern United States, the Border Region Doing Research on Trauma Consortium. Consortium members will collaborate to produce multicenter up-to-date data on the medical impact of the US-Mexico border, helping to elucidate the true magnitude of the problem and shed light on the impact cross-border trauma has on migrants, their families, and the US health care system. Only once the problem is fully described can meaningful solutions be provided.
Review on the human‐specific α7‐nicotinic acetylcholine receptor in leukocytes and human‐specialized mechanisms to regulate inflammatory response to injury.
Conventional wisdom presumes that the ...α7nAChR product of CHRNA7 expression mediates the ability of the vagus nerve to regulate the inflammatory response to injury and infection. Yet, 15 years ago, a 2nd structurally distinct and human‐specific α7nAChR gene was discovered that has largely escaped attention of the inflammation research community. The gene, originally called dupα7nAChR but now known as CHRFAM7A, has been studied exhaustively in psychiatric research because of its association with mental illness. However, dupα7nAChR/CHRFAM7A expression is relatively low in human brain but elevated in human leukocytes. Furthermore, α7nAChR research in human tissues has been confounded by cross‐reacting antibodies and nonspecific oligonucleotide primers that crossreact in immunoblotting, immunohistochemistry, and RT‐PCR. Yet, 3 independent reports show the human‐specific CHRFAM7A changes cell responsiveness to the canonical α7nAChR/CHRNA7 ion‐gated channel. Because of its potential for the injury research community, its possible significance to human leukocyte biology, and its relevance to human inflammation, we review the discovery and structure of the dupα7nAChR/CHRFAM7A gene, the distribution of its mRNA, and its biologic activities and then discuss its possible role(s) in specifying human inflammation and injury. In light of emerging concepts that point to a role for human‐specific genes in complex human disease, the existence of a human‐specific α7nAChR regulating inflammatory responses in injury underscores the need for caution in extrapolating findings in the α7nAChR literature to man. To this end, we discuss the translational implications of a uniquely human α7nAChR‐like gene on new drug target discovery and therapeutics development for injury, infection, and inflammation.
This cohort study examines the incidence, severity, and mortality of fall-related injuries among migrants at the US-Mexico border in San Diego, California.
ABSTRACT
The human genome contains a unique, distinct, and human‐specific αT‐nicotinic acetylcholine receptor (α7nAChR) gene CHRNA7 (gene‐encoding α7‐nicotinic acetylcholine receptor) called CHRFAM7A ...(gene‐encoding dup‐α7‐nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5′ upstream from the “wild‐type” CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000‐fold between different gut epithelial cells. A 3‐hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000‐fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human‐specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild‐type α7nAChR ligand‐gated pentameric ion channel, the findings point to the existence of a species‐specific α7nAChR response that might regulate gut epithelial function in a human‐specific fashion.— Dang, X., Eliceiri, B. P., Baird, A., Costantini, T. W. CHRFAM7A: a human‐specific α7‐nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS. FASEB J. 29, 2292‐2302 (2015). www.fasebj.org
Abstract
Conventional wisdom presumes that the α7nAChR product of CHRNA7 expression mediates the ability of the vagus nerve to regulate the inflammatory response to injury and infection. Yet, 15 ...years ago, a 2nd structurally distinct and human-specific α7nAChR gene was discovered that has largely escaped attention of the inflammation research community. The gene, originally called dupα7nAChR but now known as CHRFAM7A, has been studied exhaustively in psychiatric research because of its association with mental illness. However, dupα7nAChR/CHRFAM7A expression is relatively low in human brain but elevated in human leukocytes. Furthermore, α7nAChR research in human tissues has been confounded by cross-reacting antibodies and nonspecific oligonucleotide primers that crossreact in immunoblotting, immunohistochemistry, and RT-PCR. Yet, 3 independent reports show the human-specific CHRFAM7A changes cell responsiveness to the canonical α7nAChR/CHRNA7 ion-gated channel. Because of its potential for the injury research community, its possible significance to human leukocyte biology, and its relevance to human inflammation, we review the discovery and structure of the dupα7nAChR/CHRFAM7A gene, the distribution of its mRNA, and its biologic activities and then discuss its possible role(s) in specifying human inflammation and injury. In light of emerging concepts that point to a role for human-specific genes in complex human disease, the existence of a human-specific α7nAChR regulating inflammatory responses in injury underscores the need for caution in extrapolating findings in the α7nAChR literature to man. To this end, we discuss the translational implications of a uniquely human α7nAChR-like gene on new drug target discovery and therapeutics development for injury, infection, and inflammation.
Patients with spinal cord injury (SCI) are at high risk of venous thromboembolism (VTE). Pharmacologic VTE prophylaxis (VTEppx) is frequently delayed in patients with SCI because of concerns for ...bleeding risk. Here, we hypothesized that delaying VTEppx until >48 hours would be associated with increased risk of thrombotic events.
This is a secondary analysis of the 2018 to 2020 prospective, observational, cohort Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study of patients aged 18 to 40 years, at 17 US level 1 trauma centers. Patients admitted for >48 hours with documented SCI were evaluated. Timing of initiation of VTEppx, rates of thrombotic events (deep vein thrombosis DVT and pulmonary embolism PE), and missed VTEppx doses were analyzed. The primary outcome was VTE (DVT + PE).
There were 343 patients with SCI. The mean ± SD age was 29.0 ± 6.6 years, 77.3% were male, and 78.7% sustained blunt mechanism. Thrombotic events occurred in 33 patients (9.6%): 30 DVTs (8.7%) and 3 PEs (0.9%). Venous thromboembolism prophylaxis started at ≤24 hours in 21.3% of patients and 49.3% at ≤48 hours. The rate of VTE for patients started on VTEppx ≤48 hours was 7.1% versus 12.1% if started after 48 hours ( p = 0.119). After adjusting for differences in risk factors between cohorts, starting ≤48 hours was independently associated with fewer VTEs (odds ratio, 0.45; 95% confidence interval, 0.101-0.978; p = 0.044). Unfractionated heparin was associated with a VTE rate of 21.0% versus 7.5% in those receiving enoxaparin as prophylaxis ( p = 0.003). Missed doses of VTEppx were common (29.7%) and associated with increased thrombotic events, although this was not significant on multivariate analysis.
Rates of thrombotic events in patients with SCI are high. Prompt initiation of VTEppx with enoxaparin and efforts aimed at avoiding missed doses are critical to limit thrombotic events in these high-risk patients.
Prognostic and Epidemiological; Level IV.
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