•Apical surface heparan sulfate proteoglycans (HSPG) have unique endothelial roles.•Inflammation and shear stress derangement can alter HSPG synthesis and sulfation.•Reduced HSPG expression impacts ...mechanisms that regulate endothelial cell homeostasis.•Changes to endothelial glycocalyx HSPG sulfation are vast and contextually dependent.•Targeting endothelial HSPG biosynthesis and sulfation are promising therapeutic strategies.
The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network of proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in vascular homeostasis. Given their molecular complexity and ability to interact with the intra- and extracellular environment, heparan sulfate proteoglycans uniquely contribute to the glycocalyx’s role in regulating endothelial permeability, mechanosignaling, and ligand recognition by cognate cell surface receptors. Much attention has recently been devoted to the enzymatic shedding of heparan sulfate proteoglycans from the endothelial glycocalyx and its impact on vascular function. However, other molecular modifications to heparan sulfate proteoglycans are possible and may have equal or complementary clinical significance. In this narrative review, we focus on putative mechanisms driving non-proteolytic changes in heparan sulfate proteoglycan expression and alterations in the sulfation of heparan sulfate side chains within the endothelial glycocalyx. We then discuss how these specific changes to the endothelial glycocalyx impact endothelial cell function and highlight therapeutic strategies to target or potentially reverse these pathologic changes.
Context: The internalizing of experience of stigma among patients with substance use disorders (SUDs) can be debilitating to recovery. Individual factors such as self-regulation and abstinence ...self-efficacy can impact confidence in recovery and hope for future. Aims: The aim of the study was to explore relationship among self-stigma, self-regulation, self-efficacy, optimism, and confidence in recovery of patients with early-onset SUDs. Settings and Design: The study was carried out on a sample of 40 male patients with SUDs. The study had a single group exploratory design. Materials and Methods: The Self-Regulation Questionnaire, Drug Taking Confidence Questionnaire, Substance Abuse Self Stigma Scale, Revised Generalized Expectancy of Success (GES), and visual analog scale for craving were the measures used in the study. Statistical Analysis: Pearson and spearman's correlation coefficient were used to test associations between the variables. Multiple regression models were drawn to examine predictors of generalized expectancy of success and confidence in recovery. Results: Self-regulation, generalized expectancy of success (optimism), and confidence in recovery were found to be significantly correlated with self-stigma dimensions. The multiple regression model revealed self-regulation and self-devaluation as significant predictors of optimism (GES), whereas abstinence self-efficacy and values disengagement dimension of self-stigma predicted patients' confidence in recovery. Conclusions: Poor regulatory capacities along with internalized feelings of shame, guilt, and devaluation may lead to lower levels of optimism and poorer expectancies of success from future. Patient's self-efficacy in terms of abstaining from use behaviors and disengagement from pursuing life goals can lead to lower levels of confidence in recovery from SUDs and have implications for treatment seeking.
Abstract Background Arginine vasopressin (AVP) is a key player in maintaining the intravascular volume and pressure during hemorrhagic shock. During the past 2 decades, animal studies, case reports, ...and reviews have documented the minimized blood loss and improved perfusion pressures in those receiving pressure support with AVP. Materials and methods A PubMed search of studies was conducted with the terms: “AVP,” “arginine vasopressin,” “antidiuretic hormone,” “hemorrhagic shock,” “hemorrhage,” “circulatory shock,” “fluid resuscitation,” “trauma,” “massive transfusion protocol,” “physiology,” “cerebral,” “renal,” “cardiac,” “perfusion,” “dose,” and “hypotension.” The studies were located by a search of a combination of these terms. Also, within-PubMed citations relating to the studies gathered from the initial search were explored. Reports discussing vasopressin in hemorrhagic states were considered. No predetermined limit was used to choose or exclude articles. Results AVP is an important hormone in osmoregulation and blood pressure. During stress, such as hemorrhage, the levels have been shown to rapidly decrease. Furthermore numerous animal studies and limited human studies have shown that circulatory support with AVP is linked to improved outcomes. No large human prospective studies are available to guide its use at present, but some of its effectiveness seems to lie in its ability to increase calcium sensitivity in acidotic environs, thereby allowing for more effective maintenance of vascular tone than catecholamines. It also redirects blood from the periphery, creating a steal syndrome, and increases the oxygen supply to vital organs, minimizing blood loss, and allowing additional time for surgical repair. Conclusions With these encouraging data, there is hope that “pressure support” will be the “resuscitation” considered necessary for a patient’s optimum survival.
The endothelium is lined by a protective mesh of proteins and carbohydrates called the endothelial glycocalyx (EG). This layer creates a negatively charged gel-like barrier between the vascular ...environment and the surface of the endothelial cell. When intact the EG serves multiple functions, including mechanotransduction, cell signaling, regulation of permeability and fluid exchange across the microvasculature, and management of cell-cell interactions. In trauma and/or hemorrhagic shock, the glycocalyx is broken down, resulting in the shedding of its individual components. The shedding of the EG is associated with increased systemic inflammation, microvascular permeability, and flow-induced vasodilation, leading to further physiologic derangements. Animal and human studies have shown that the greater the severity of the injury, the greater the degree of shedding, which is associated with poor patient outcomes. Additional studies have shown that prioritizing certain resuscitation fluids, such as plasma, cryoprecipitate, and whole blood over crystalloid shows improved outcomes in hemorrhaging patients, potentially through a decrease in EG shedding impacting downstream signaling. The purpose of the following paragraphs is to briefly describe the EG, review the impact of EG shedding and hemorrhagic shock, and begin entertaining the notion of directed resuscitation. Directed resuscitation emphasizes transitioning from macroscopic 1:1 resuscitation to efforts that focus on minimizing EG shedding and maximizing its reconstitution.
The paper explores the needs of trauma patients with limited English proficiency (LEP) and the drivers bringing them in the hospital.1 When the Affordable Healthcare Act was signed, a provision was ...made for covered entities to provide “meaningful access” to language assistance services for those with LEP.2 The formidable challenge that language barriers place upon patients and healthcare system has long been cited to be responsible for worse outcomes, poor quality, and a threat to patient safety.3 Flexibility remains as to the provision of these services, and a uniform standard as to what is considered adequate and equitable access still remains uncertain. In October 2022 the United States Health and Human Services (USHHS) announced steps to improve language access and $4 million in grants to develop and test methods of informing those with LEP on how to access language services.4 This topic is important as a growing number of patients with LEP regularly access care with barriers to translational services. ...differences in discharge disposition and readmission rates between the NELP and EP groups were not recorded.
Management of hemodynamically unstable pelvic fractures remains a challenge. Hemostatic interventions are used alone or in combination. There is a paucity of data on the association between the ...pattern of hemorrhage control interventions and outcomes after a severe pelvic fracture.
To characterize clinical outcomes and study the patterns of hemorrhage control interventions in hemodynamically unstable pelvic fractures.
In this cohort study, a retrospective review was performed of data from the 2017 American College of Surgeons Trauma Quality Improvement Program database, a national multi-institutional database of trauma patients in the United States. Adult patients (aged ≥18 years) with pelvic fractures who received early transfusions (≥4 units of packed red blood cells in 4 hours) and underwent intervention for pelvic hemorrhage control were identified. Use and order of preperitoneal pelvic packing (PP), pelvic angioembolization (AE), and resuscitative endovascular balloon occlusion of the aorta (REBOA) in zone 3 were examined and compared against the primary outcome of mortality. The associations between intervention patterns and mortality, complications, and 24-hour transfusions were further examined by backward stepwise regression analyses. Data analyses were performed in September 2021.
Primary outcomes were rates of 24-hour, emergency department, and in-hospital mortality. Secondary outcomes were major in-hospital complications.
A total of 1396 patients were identified. Mean (SD) age was 47 (19) years, 975 (70%) were male, and the mean (SD) lowest systolic blood pressure was 71 (25) mm Hg. The median (IQR) Injury Severity Score was 24 (14-34), with a 24-hour mortality of 217 patients (15.5%), ED mortality of 10 patients (0.7%), in-hospital mortality of 501 patients (36%), and complication rate of 574 patients (41%). Pelvic AE was the most used intervention (774 55%), followed by preperitoneal PP (659 47%) and REBOA zone 3 (126 9%). Among the cohort, 1236 patients (89%) had 1 intervention, 157 (11%) had 2 interventions, and 3 (0.2%) had 3 interventions. On regression analyses, only pelvic AE was associated with a mortality reduction (odds ratio OR, 0.62; 95% CI, 0.47 to 0.82; P < .001). Preperitoneal PP was associated with increased odds of complications (OR, 1.39; 95% CI, 1.07 to 1.80; P = .01). Increasing number of interventions was associated with increased 24-hour transfusions (β = +5.4; 95% CI, +3.5 to +7.5; P < .001) and mortality (OR, 1.57; 95% CI, 1.05 to 2.37; P = .03), but not with complications.
This study found that among patients with pelvic fracture who received early transfusions and at least 1 invasive pelvic hemorrhage control intervention, more than 1 in 3 died, despite the availability of advanced hemorrhage control interventions. Only pelvic AE was associated with a reduction in mortality.
The morbidity associated with cervical spine injury increases in the setting of concomitant cervical spinal cord injury (CSCI). A significant proportion of these patients require placement of a ...tracheostomy. However, it remains unclear if timing to tracheostomy following traumatic CSCI can impact outcomes. The aim of our study was to characterize outcomes associated with tracheostomy timing following traumatic CSCI.
We performed a 5-year (2010-2014) analysis of the American College of Surgeons Trauma Quality Improvement Program database and included all adult (age, ≥18 years) trauma patients who had traumatic CSCI and received tracheostomy. Patients were subdivided into two groups: early tracheostomy (ET) (≤4 days from initial intubation) and late tracheostomy (LT) (>4 days). Outcome measures included respiratory complications, ventilator-free days, intensive care unit-free days and hospital length of stay, and mortality. Multivariate logistic regression analysis was performed.
A total of 5,980 patients were included in the study, of which 1,010 (17%) patients received ET, while 4,970 (83%) patients received LT. Mean age was 46 years, and 73% were men. In terms of CSCI location, 48% of the patients had high CSCI (C1-C4), while 52% had low CSCI (C5-C7). Patients in the ET group had lower rates of respiratory complications (30% vs. 46%, p = 0.01), higher ventilator-free days (13 days vs. 9 days; p = 0.02), intensive care unit-free days (11 days vs. 8 days; p = 0.01), and a shorter hospital length of stay (22 days vs. 29 days; p = 0.01) compared with those in the LT group. On regression analysis, ET was associated with lower rates of respiratory complications in patients with high CSCI (odds ratio, 0.55 0.41-0.81) and low CSCI (odds ratio, 0.93 0.72-0.95). However, no association was found between time to tracheostomy and in-hospital mortality.
Early tracheostomy regardless of CSCI level may lead to improved outcomes. Quality improvement efforts should focus on defining the optimal time to tracheostomy and considering ET as a component of SCI management bundle.
Therapeutic, level IV.
Despite the increasing number of female surgeons in general surgery programs, women are still inadequately represented in leadership positions. This study aims to investigate the magnitude of gender ...bias in university-based trauma surgery fellowship programs and leadership positions in the United States of America.
FRIEDA was used to identify trauma surgery programs. A thorough website review of each program obtained further information on faculty members, including their name, age, gender, and faculty rank. Trauma surgeons with an MD or DO qualification and a faculty rank of Professor, Associate Professor, or Assistant Professor were selected for inclusion in this study. SCOPUS was used to assess the H-index and the number of publications and citations of surgeons.
The total number of programs included was 136, consisting of 715 faculty members. Less than a quarter (n = 166; 23.2%) comprised females and less than one-fifth (n = 30; 19%) of female surgeons were Professors. The difference in the research productivity of male and female trauma surgeons was statistically significant (
< .05), with the average H-index being 10 vs 7.5, respectively, amongst the top 50 surgeons of both genders. Based on a multiple regression analysis, academic rank was significantly associated (
< .05), and gender was not significantly associated (
> .05) with H-index.
Gender disparity exists in the field of trauma surgery, as noted in senior faculty ranks and leadership positions. Female-inclusive state policies, appropriate mentorship, and supportive institutions can help to bridge this gap.
