The Promising Future for Complex Innovative Trial Design in Clinical Research

Description to be added.Cannot be left empt

Patterns, management options and outcome of blunt thoracic aortic injuries: a 20-year experience from a Tertiary Care Hospital

Background Blunt Thoracic aortic injury (BTAI) is the second leading cause of mortality after head injuries in blunt trauma patients. There is a paucity of information on the presentation, management and outcome of BTAIs from the Middle Eastern region. We explored the patterns, management options and outcomes of BTAIs in a level I trauma center. Methods We conducted a retrospective observational study on all adult patients who were admitted with BTAIs between 2000 and 2020. Patients were compared for the management option (conservative vs endovascular aortic repair (TEVAR) vs open surgery) and outcomes. Comparison between the respective groups was performed using one-way analysis of variance for continuous variables, and Pearson chi-square test for categorical variables. Kaplan–Meier curve and Cox regression analysis were performed for the outcome. Results Eighty-seven patients had BTAI (82% male) with mean age 37.3 ± 14.5 years. The mean injury severity score was 30 ± 10 and the aortic injury grade was III (I–IV). Grade III (41.4%) and Grade IV (33.3%) injuries were more common followed by Grade II (13.8%) and Grade I (11.5%). Forty percent of cases were treated conservatively whereas aortic interventions were performed in 60% of cases (n = 52). The TEVAR was performed in 33 patients (63.5%), and 19 (36.5%) were treated with open surgery (14 with graft interposition and 5 with clamp and direct repair). The aortic injury grade was significantly higher in the intervention groups as compared to the conservative group (p = 0.001). Patients with Grade IV injuries were more likely to be treated by open repair whereas a higher frequency of patients with grade III was managed by TEVAR (p = 0.001). All the patients with Grade I–II were treated conservatively. The overall in-hospital mortality rate was 25.3% and it was significantly higher in the conservative group (40.0%) in comparison to the open repair (31.6%) and TEVAR (6.1%) group (P = 0.004). More of the non-survivors sustained head injuries (P = 0.004), had higher ISS (P = 0.001) and greater aortic injury grades (P = 0.002), and were treated non-operatively (P = 0.001). Conclusions BTAI seems not common in trauma, however, one quarter of cases died in a level 1 trauma center, prehospital deaths were not analyzed, and postmortem examination was lacking. The associated head injury and aortic injury grade have an impact on the management option and hospital outcome. The conservative and TEVAR options were performed almost equally in 78% of cases. TEVAR and open surgery were performed only for aortic injury grade III or IV whereas the conservative treatment was offered for selected cases among the 4 injury grades. However, the mortality was higher in the conservative followed by the open surgery group and mostly due to the associated severe head injury. TEVAR should be considered for patients requiring intervention unless contraindicated due to technical difficulties. Appropriately selected patients with low-grade injuries may be managed conservatively. Long-term follow-up is needed in young adults for concerns of aortic remodeling and complications.Other Information Published in: European Journal of Trauma and Emergency Surgery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00068-022-01930-1</p

Shock index in patients with traumatic solid organ injury as a predictor of massive blood transfusion protocol activation

Purpose We aimed to assess the utility of shock index (SI) to predict the need for massive transfusion protocol (MTP) in patients with solid organ injury (SOI) in a Level 1 Trauma center. Methods We conducted a retrospective analysis for patients with SOI between 2011 and 2014. Patients were categorized according to on-admission SI into low ( Results A total of 4500 patients were admitted with trauma, of them 572 sustained SOIs (289 patients had SI ≥0.8). In comparison to low SI, patients with high SI were younger, had higher injury severity scores (ISS) and lower Trauma and Injury Severity Score (TRISS); (p  Conclusions In patients with SOI, SI is a simple bedside predictor for BT and MTP activation. Further prospective studies are needed to support our findings.Other Information Published in: Injury Epidemiology License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1186/s40621-019-0218-7</p

Underutilization of occupant restraint systems in motor vehicle injury crashes: A quantitative analysis from Qatar

<p><b>Introduction:</b> Restraint systems (seat belts and airbags) are important tools that improve vehicle occupant safety during motor vehicle crashes (MVCs). We aimed to identify the pattern and impact of the utilization of passenger restraint systems on the outcomes of MVC victims in Qatar.</p> <p><b>Methods:</b> A retrospective study was conducted for all admitted patients who sustained MVC-related injuries between March 2011 and March 2014 inclusive.</p> <p><b>Results:</b> Out of 2,730 road traffic injury cases, 1,830 (67%) sustained MVC-related injuries, of whom 88% were young males, 70% were expatriates, and 53% were drivers. The use of seat belts and airbags was documented in 26 and 2.5% of cases, respectively. Unrestrained passengers had greater injury severity scores, longer hospital stays, and higher rates of pneumonia and mortality compared to restrained passengers (<i>P</i> = .001 for all). There were 311 (17%) ejected cases. Seat belt use was significantly lower and the mortality rate was 3-fold higher in the ejected group compared to the nonejected group (<i>P</i> = .001). The overall mortality was 8.3%. On multivariate regression analysis, predictors of not using a seat belt were being a front seat passenger, driver, or Qatari national and young age. Unrestrained males had a 3-fold increase in mortality in comparison to unrestrained females. The risk of severe injury (relative risk [RR] = 1.82, 95% confidence interval [CI], 1.49–2.26, <i>P</i> = .001) and death (RR = 4.13, 95% CI, 2.31–7.38, <i>P</i> = .001) was significantly greater among unrestrained passengers.</p> <p><b>Conclusion</b>: The nonuse of seat belts is associated with worse outcomes during MVCs in Qatar. Our study highlights the lower rate of seat belt compliance in young car occupants that results in more severe injuries, longer hospital stays, and higher mortality rates. Therefore, we recommend more effective seat belt awareness and education campaigns, the enforcement of current seat belt laws, their extension to all vehicle occupants, and the adoption of proven interventions that will assure sustained behavioral changes toward improvements in seat belt use in Qatar.</p

All-terrain vehicle (ATV)-related injuries among different age groups: insights from a 9-year observational study

Purpose To describe the epidemiology, patterns, seasonality and outcome of all-terrain vehicle-related injuries (ATVRIs) among different age groups in Qatar. Methods A retrospective analysis of all patients hospitalized with ATVRI from 2010 to 2018 was conducted. Data were analyzed by age, gender, seasonality, and Injury severity Score  (ISS). Chi-square, Student t and ANOVA tests were used for analysis. Multivariate regression analysis was performed to find out predictors of head injury and severe injury among ATV users. Results Out of 15,000 trauma admissions, 521 had ATVRI (4%) with a mean age of 23.3 ± 12.3. The male-to-female ratio was 4:1 and the pediatric population represented 40%. The compliance with helmet use was 3.6%. The most injured regions were chest (29.8%), upper extremities (28.8%) and the head (25.9%). The mean ISS was 10.6 ± 7.7. Fracture fixation was the most operative intervention. Among hospitalized patients, 7.7% were transferred to rehabilitation . ATVRIs occurred more frequently between October and April and a large proportion (57.8%) occurred during weekends. The overall ATV-related hospital mortality rate was 2.1%. Young and older ATV users were more likely to suffer spine injuries than the pediatric population (p = 0.001). The mean ISS was greater in the older groups (p = 0.03). There were no statistically significant differences regarding the use of protective devices, mortality, or length of hospital stay between the different age groups. On multivariate analysis, young age and ISS were predictors of head injury among ATV users after adjusting for gender and helmet use. Conclusion This is a nationwide study looking at all age groups who sustained ATVRI in Qatar. ATVRIs were observed in all age groups following leisure and recreational use. It follows a seasonal pattern with poor protective measures compliance. There is a need to reinforce helmet use and raise public awareness.Other Information Published in: European Journal of Trauma and Emergency Surgery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00068-022-01984-1</p

Patterns and Effects of Admission Hyperglycemia and Inflammatory Response in Trauma Patients: A Prospective Clinical Study

Background The constellation of the initial hyperglycemia, proinflammatory cytokines and severity of injury among trauma patients is understudied. We aimed to evaluate the patterns and effects of on-admission hyperglycemia and inflammatory response in a level 1 trauma center. We hypothesized that higher initial readings of blood glucose and cytokines are associated with severe injuries and worse in-hospital outcomes in trauma patients. Methods A prospective, observational study was conducted for adult trauma patients who were admitted and tested for on-admission blood glucose, hemoglobin A1c, interleukin (IL)-6, IL-18 and hs-CRP. Patients were categorized into four groups [non-diabetic normoglycemic, diabetic normoglycemic, diabetic hyperglycemic (DH) and stress-induced hyperglycemic (SIH)]. The inflammatory markers were measured on three time points (admission, 24 h and 48 h). Generalized estimating equations (GEE) were used to account for the correlation for the inflammatory markers. Pearson’s correlation test and logistic regression analysis were also performed. Results During the study period, 250 adult trauma patients were enrolled. Almost 13% of patients presented with hyperglycemia (50% had SIH and 50% had DH). Patients with SIH were younger, had significantly higher Injury Severity Score (ISS), higher IL-6 readings, prolonged hospital length of stay and higher mortality. The SIH group had lower Revised Trauma Score (p = 0.005), lower Trauma Injury Severity Score (p = 0.01) and lower GCS (p = 0.001). Patients with hyperglycemia had higher in-hospital mortality than the normoglycemia group (12.5% vs 3.7%; p = 0.02). A significant correlation was identified between the initial blood glucose level and serum lactate, IL-6, ISS and hospital length of stay. Overall rate of change in slope 88.54 (95% CI:-143.39–33.68) points was found more in hyperglycemia than normoglycemia group (p = 0.002) for IL-6 values, whereas there was no statistical significant change in slopes of age, gender and their interaction. The initial IL-6 levels correlated with ISS (r = 0.40, p = 0.001). On-admission hyperglycemia had an adjusted odds ratio 2.42 (95% CI: 1.076–5.447, p = 0.03) for severe injury (ISS > 12) after adjusting for age, shock index and blood transfusion. Conclusions In trauma patients, on-admission hyperglycemia correlates well with the initial serum IL-6 level and is associated with more severe injuries. Therefore, it could be a simple marker of injury severity and useful tool for patient triage and risk assessment. Trial registration This study was registered at the ClinicalTrials.gov (Identifier: NCT02999386), retrospectively Registered on December 21, 2016. https://clinicaltrials.gov/ct2/show/NCT02999386.Other Information Published in: World Journal of Surgery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00268-021-06190-5</p

The L-Arginine Transporter Solute Carrier Family 7 Member 2 Mediates the Immunopathogenesis of Attaching and Effacing Bacteria

<div><p>Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with <i>Citrobacter rodentium</i>, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, <i>Slc7a2</i>^–/–mice infected with <i>C</i>. <i>rodentium</i> had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells. In infected <i>Slc7a2</i>^–/–mice, there were decreased levels of the proinflammatory cytokines G-CSF, TNF-α, IL-1α, IL-1β, and the chemokines CXCL1, CCL2, CCL3, CCL4, CXCL2, and CCL5. In bone marrow chimeras, the recipient genotype drove the colitis phenotype, indicative of the importance of epithelial, rather than myeloid SLC7A2. Mice lacking <i>Slc7a2</i> exhibited reduced adherence of <i>C</i>. <i>rodentium</i> to the colonic epithelium and decreased expression of Talin-1, a focal adhesion protein involved in the attachment of the bacterium. The importance of SLC7A2 and Talin-1 in the intimate attachment of <i>C</i>. <i>rodentium</i> and induction of inflammatory response was confirmed <i>in vitro</i>, using conditionally-immortalized young adult mouse colon (YAMC) cells with shRNA knockdown of <i>Slc7a2</i> or <i>Tln1</i>. Inhibition of L-Arg uptake with the competitive inhibitor, L-lysine (L-Lys), also prevented attachment of <i>C</i>. <i>rodentium</i> and chemokine expression. L-Lys and siRNA knockdown confirmed the role of L-Arg and SLC7A2 in human Caco-2 cells co-cultured with enteropathogenic <i>Escherichia coli</i>. Overexpression of <i>SLC7A2</i> in human embryonic kidney cells increased bacterial adherence and chemokine expression. Taken together, our data indicate that <i>C</i>. <i>rodentium</i> enhances its own pathogenicity by inducing the expression of SLC7A2 to favor its attachment to the epithelium and thus create its ecological niche.</p></div

Immunoprofiling of WT and <i>Slc7a2</i>^–/–mice.

<p>Animals were infected with <i>C</i>. <i>rodentium</i> (<i>C</i>. <i>rod</i>) or not (Ctrl) for 14 days. (<b>A</b>) The concentrations of the cytokines in colon lysates were determined by Luminex assay. The scale represents the concentrations of analytes in pg/mg protein in colon tissues. *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001 denote significant differences between infected WT (<i>n</i> = 14) and <i>Slc7a2</i>^–/–mice (<i>n</i> = 14). (<b>B</b>) Analysis of mRNA expression in the colon tissues. *<i>P</i> < 0.05, **<i>P</i> < 0.01; <i>n</i> = 3–5 Ctrl and <i>n</i> = 12–14 infected mice for each genotype.</p

Immunophenotyping of innate immune cells.

<p>Cells isolated from the lamina propria of <i>C</i>. <i>rodentium</i>-infected mice (<i>C</i>. <i>rod</i>) or of uninfected animals were analyzed by flow cytometry for the following markers: (<b>A</b>) F4/80, (<b>B</b>) GR1, (<b>C</b>) CD11c. For each marker, representative flow plots and combined data from <i>n</i> = 4 Ctrl and <i>n</i> = 6 infected mice are shown **<i>P</i> < 0.01, ***<i>P</i> < 0.001.</p

Analysis of focal contact proteins.

<p>WT or <i>Slc7a2</i>^–/–mice were infected with <i>C</i>. <i>rodentium</i> (<i>C</i>. <i>rod</i>) for 14 days. (<b>A</b>) ACTN1, Talin-1 and β-actin were detected in lysates of whole colonic tissues by Western blotting; each lane is from a different mouse. (<b>B</b>) Longitudinal sections of the colon were used for immunofluorescence for bacterial EspB (red), Talin-1 (green), and nuclei (blue); the merge of red and green is depicted in yellow. Representative images from 3 animals in each group are shown. Scale bar = 20 μm. (<b>C</b>) Expression of <i>Tln1</i> mRNA in whole colon tissue and CECs. **<i>P</i> < 0.01; <i>n</i> = 3 mice for Ctrl, and <i>n</i> = 5 for infected animals.</p