Δευτέρα 1 Φεβρουαρίου 2021

Distinct immunologic endotypes are associated with clinical trajectory after severe blunt trauma and hemorrhagic shock

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imageBACKGROUND The genomic/cytokine "storm" after severe trauma is well described. However, the differing composition, magnitude and resolution of this response, and its relationship to clinical outcomes remain unclear. METHODS This is a secondary analysis of a prospective longitudinal cohort study of severely injured trauma patients in hemorrhagic shock. Peripheral blood sampling was performed at 0.5, 1, 4, 7, 14, and 28 days after injury for measurement of circulating immune biomarkers. K-means clustering using overall mean and trajectory slope of selected immunologic biomarkers were used to identify distinct temporal immunologic endotypes. Endotypes were compared with known clinical trajectories defined as early death (
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Freeze-dried platelets promote clot formation, attenuate endothelial cell permeability, and decrease pulmonary vascular leak in a murine model of hemorrhagic shock

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imageBACKGROUND Hemorrhagic shock (HS) and trauma induce endothelial barrier compromise, inflammation, and aberrant clotting. We have shown that fresh human platelets (Plts) and Plt extracellular vesicles mitigate vascular leak in murine models of injury. Here, we investigate the potential of freeze-dried platelets (FDPlts) to attenuate pulmonary vascular permeability, decrease inflammation, and promote clotting in a murine model of HS. METHODS Human FDPlts were characterized using in vitro assays of Plt marker expression, aggregation, coagulation, and endothelial cell permeability. An intravital model of vascular injury in the mouse cremaster muscle was used to assess the ability of FDPlts to incorporate into clots. Mouse groups subjected to controlled hemorrhage for 90 minutes were (1) lactated Ringer solution (LR), (2) FDPlts, (3) fresh human Plts, (4) murine whole blood (WB), and (5) shams (only instrumented). Hemorrhagic shock mouse endpoints included coagulation, pulmonary vascular permeability, and lung injury. RESULTS Freeze-dried Plts expressed Plt-specific markers and retained functionality similar to fresh Plts. In in vitro assays of Plt aggregation, differences were noted. In vivo, FDPlts and Plts were found to incorporate into clots in postcapillary venules in the mouse cremaster muscle. Hemorrhagic shock mice resuscitated with LR displayed increased pulmonary vascular permeability compared with sham (sham, 686.6 ± 359.7; shock-LR, 2,637 ± 954.7; p = 0.001), and treatment with FDPlts or WB attenuated permeability compared with shock: shock-FDPlts, 1,328 ± 462.6 (p = 0.05), and shock-WB, 1,024 ± 370.5 (p = 0.0108). However, human Plts (Days 1–3) did not attenuate vascular leak in HS mice compared with shock-LR (shock-Plts, 3,601 ± 1,581; p = 0.33). CONCLUSION FDPlts contribute to clot formation similar to fresh human Plts. FDPlts also attenuated vascular permeability in vitro and in vivo. Mouse WB resuscitation but not fresh human Plts attenuated vascular permeability after HS. These data suggest that the effect of FDPlts may be a suitable alternative to fresh Plts in modulating hemostasis and the endotheliopathy associated with injury.
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External validation of a nomogram predicting risk of bleeding control interventions after high-grade renal trauma: The Multi-institutional Genito-Urinary Trauma Study

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imageBACKGROUND Renal trauma grading has a limited ability to distinguish patients who will need intervention after high-grade renal trauma (HGRT). A nomogram incorporating both clinical and radiologic factors has been previously developed to predict bleeding control interventions after HGRT. We aimed to externally validate this nomogram using multicenter data from level 1 trauma centers. METHODS We gathered data from seven level 1 trauma centers. Patients with available initial computed tomography (CT) scans were included. Each CT scan was reviewed by two radiologists blinded to the intervention data. Nomogram variables included trauma mechanism, hypotension/shock, concomitant injuries, vascular contrast extravasation (VCE), pararenal hematoma extension, and hematoma rim distance (HRD). Mixed-effect logistic regression was used to assess the associations between the predictors and bleeding intervention. The prediction accuracy of the nomogram was assessed using the area under the receiver operating characteristic curve and its 95% confidence interval (CI). RESULTS Overall, 569 HGRT patients were included for external validation. Injury mechanism was blunt in 89%. Using initial CT scans, 14% had VCE and median HRD was 1.7 (0.9–2.6) cm. Overall, 12% underwent bleeding control interventions including 34 angioembolizations and 24 nephrectomies. In the multivariable analysis, presence of VCE was associated with a threefold increase in the odds of bleeding interventions (odds ratio, 3.06; 95% CI, 1.44–6.50). Every centimeter increase in HRD was associated with 66% increase in odds of bleeding interventions. External validation of the model provided excellent discrimination in predicting bleeding interventions with an area under the curve of 0.88 (95% CI, 0.84–0.92). CONCLUSION Our results reinforce the importance of radiologic findings such as VCE and hematoma characteristics in predicting bleeding control interventions after renal trauma. The prediction accuracy of the proposed nomogram remains high using external data. These variables can help to better risk stratify high-grade renal injuries. LEVEL OF EVIDENCE Prognostic and epidemiological study, level III.
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Bile duct clearance and cholecystectomy for choledocholithiasis: Definitive single-stage laparoscopic cholecystectomy with intraoperative endoscopic retrograde cholangiopancreatography versus staged procedures

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imageBACKGROUND Clinical equipoise exists regarding optimal sequencing in the definitive management of choledocholithiasis. Our current study compares sequential biliary ductal clearance and cholecystectomy at an interval to simultaneous laparoendoscopic management on index admission in a pragmatic retrospective manner. METHODS Records were reviewed for all patients admitted between January 2015 and December 2018 to a Swedish and an Irish university hospital. Both hospitals differ in their practice patterns for definitive management of choledocholithiasis. At the Swedish hospital, patients with choledocholithiasis underwent laparoscopic cholecystectomy with intraoperative rendezvous endoscopic retrograde cholangiopancreatography (ERCP) at index admission (one stage). In contrast, interval day-case laparoscopic cholecystectomy followed index admission ERCP (two stages) at the Irish hospital. Clinical characteristics, postprocedural complications, and inpatient duration were compared between cohorts. RESULTS Three hundred fifty-seven patients underwent treatment for choledocholithiasis during the study period, of whom 222 (62.2%) underwent a one-stage procedure in Sweden, while 135 (37.8%) underwent treatment in two stages in Ireland. Patients in both cohorts were closely matched in terms of age, sex, and preoperative serum total bilirubin. Patients in the one-stage group exhibited a greater inflammatory reaction on index admission (peak C-reactive protein, 136 ± 137 vs. 95 ± 102 mg/L; p = 0.024), had higher incidence of comorbidities (age-adjusted Charlson Comorbidity Index, ≥3; 37.8% vs. 20.0%; p = 0.003), and overall were less fit for surgery (American Society of Anesthesiologists, ≥3; 11.7% vs. 3.7%; p
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Hybrid emergency room shows maximum effect on trauma resuscitation when used in patients with higher severity

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imageBACKGROUND The hybrid emergency room (ER) system is a novel trauma workflow that uses angio–computed tomography equipment in a trauma resuscitation room. Although the hybrid ER system decreases time to start surgery and endovascular treatments and improves mortality, the optimal target benefitting from this system remained unclear. We aimed to identify a subset of trauma patients likely to receive the greatest benefits from the hybrid ER. METHODS This retrospective cohort study was conducted in a tertiary hospital in Japan from August 2007 to January 2020. We consecutively included severe adult blunt trauma patients (Injury Severity Score [ISS], ≥16) and divided them into two groups: conventional group (August 2007 to July 2011) and hybrid ER (August 2011 to January 2020) group. We evaluated the association between the hybrid ER group and 28-day mortality using multivariable logistic regression analysis. The 28-day mortality trend during the study period was evaluated with restricted cubic spline analysis. To evaluate heterogeneity of effects within various patient severities, we evaluated whether the patients' ISS modified the effect of the hybrid ER on survival. RESULTS Among 1,050 trauma patients, the conventional group comprised 360 patients and the hybrid ER group comprised 690 patients. Injury Severity Score and probability of survival (Ps) were not significantly different between the groups. Twenty-eight-day mortality was significantly lower in the hybrid ER group (Ps-adjusted odds ratio, 0.48; 95% confidence interval, 0.32–0.71; p 25, survival probabilities in the hybrid ER group were higher compared with those in the conventional group. CONCLUSION The hybrid ER may improve posttraumatic mortality, especially in patients with higher baseline severity. LEVEL OF EVIDENCE Therapeutic/care management, level IV.
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Universal screening for blunt cerebrovascular injury

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imageBACKGROUND Blunt cerebrovascular injury (BCVI) can result in thromboembolic stroke. Many trauma centers selectively screen patients with cervical computed tomographic angiography (CTA) based on clinical criteria. In 2016, our institution adopted universal screening for BCVI for all blunt trauma patients. The aim of this study was to accurately determine the incidence of BCVI and to evaluate the diagnostic performance of the Denver criteria (DC), expanded Denver criteria (eDC), and Memphis criteria (MC) in selecting patients for screening. METHODS Retrospective cohort study of adult (≥16 years) blunt trauma patients who presented to the Level I trauma center at University of Alabama at Birmingham. We reviewed all CTA reports and selected CTA images to obtain the true incidence rate of BCVI. We then evaluated the diagnostic performance of the DC, eDC, and MC. RESULTS A total of 6,800 patients who had suffered blunt trauma were evaluated, of whom 6,287 (92.5%) had a neck CTA. Of these, 480 (7.6%) patients had CTA evidence of BCVI. The eDC identified the most BCVI cases (sensitivity 74.7%) but had the lowest positive predictive value (14.6%). The DC and MC had slightly greater positive predictive values (19.6% and 20.6%, respectively) and had the highest diagnostic ability in terms of likelihood ratio (2.8 and 2.9) but had low sensitivity (57.5% and 47.3%). Consequently, if relying on the traditional screening criteria, the DC, eDC, and MC would have respectively resulted in 42.5%, 25.3%, and 52.7% of patients with BCVI identified by universal screening not receiving a neck CTA to screen for BCVI. CONCLUSION Blunt cerebrovascular injury is even more common than previously thought. The diagnostic performance of selective clinical screening criteria is poor. Consideration should be given to the implementation of universal screening for BCVI using neck CTA in all blunt trauma patients. LEVEL OF EVIDENCE Diagnostic, level III.
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Do patients with minimal blunt thoracic aortic injury require thoracic endovascular repair?

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imageINTRODUCTION The optimal management of minimal blunt thoracic aortic injuries (BTAIs) remains controversial, with experienced centers using therapy ranging from medical management (MM) to thoracic endovascular aortic repair (TEVAR). METHODS The Aortic Trauma Foundation registry was used to examine demographics, injury characteristics, management, and outcomes of patients with BTAI. RESULTS Two hundred ninety-six patients from 28 international centers were analyzed (mean age, 44.5 years [SD, 18 years]; 76% [225/296] male; mean Injury Severity Score, 34 [SD, 14]). Blunt thoracic aortic injury was classified as Grade I, 22.6% (67/296); Grade II, 17.6% (52/296); Grade III, 47.3% (140/296); and Grade IV, 12.5% (37/296). Overall aortic-related mortality (ARM) was 4.7% (14/296). Among all deaths, 33% (14/42) were ARM. Open repair was required for only 2%, with most undergoing TEVAR (58.4%) or MM (28.0%). Thoracic endovascular repair complications occurred in 3.4% (6/173), most commonly Type 1 endoleak (2.3%; 4/173). Among patients with minimal aortic injury (Grades I and II), 59.7% (71/119) received MM, while 40.3% (48/119) underwent TEVAR. Two patients initially managed with MM required subsequent TEVAR for injury progression during initial hospital stay. No significant difference in ARM between MM and TEVAR was noted for Grades I and II injuries. CONCLUSION A third of the trauma victims with BTAI succumb to ARM. Thoracic endovascular repair has replaced open repair but remains equivalent in outcomes to MM for minimal injuries. These data support MM of patients with minimal aortic injury. LEVEL OF EVIDENCE Therapeutic study, level IV.
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Antiplatelet and anticoagulant agents have minimal impact on traumatic brain injury incidence, surgery, and mortality in geriatric ground level falls: A multi-institutional analysis of 33,710 patients

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imageBACKGROUND Falls are the leading cause of traumatic brain injury (TBI) and TBI-related deaths for older persons (age, ≥65 years). Antiplatelet and/or anticoagulant therapy (antithrombotics [ATs]) is generally felt to increase this risk, but the literature is inconsistent. The purpose of this study was to determine the impact of AT use on the rate, severity, and outcomes of TBI in older patients following ground level falls. METHODS Ground level fall patients from 90 hospitals' trauma registries were selected. Patients were excluded if younger than 65 years or had an Abbreviated Injury Scale score of >2 in a region other than head. Electronic medical record data for preinjury AT therapy were obtained. Patients were grouped by regimen for no AT, single, or multiple agents. Groups were compared on rates of diagnosed TBI, TBI surgery, and mortality. RESULTS There were 33,710 patients (35% male; mean age, 80.5 years; mean Glasgow Coma Scale, 14.6), with 47.6% on single or combination AT therapy. The proportion of patients with TBI diagnoses did not differ between those on no AT (21.25%) versus AT (21.61%; p = 0.418). Apixaban (15.7%; p
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Increased Incidence of Inflammatory Bowel Disease after Hirschsprung Disease: A Population-based Cohort Study

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Supported by a Foundation Grant from the Canadian Institutes of Health Research (CIHR) and a CIHR Operating Grant Reference Number PJT 162393. C.B. is supported in part by the Bingham Chair in Gastroenterology. E.B. was supported by a New Investigator Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology and Crohn's and Colitis Canada and by the Career Enhancement Program of the Canadian Child Health Clinician Scientist Program. M.K. was supported by a Mitacs Elevate Post-Doctoral Fellowship.
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Connectome-Based Predictive Modeling of Individual Anxiety

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Abstract
Anxiety-related illnesses are highly prevalent in human society. Being able to identify neurobiological markers signaling high trait anxiety could aid the assessment of individuals with high risk for mental illness. Here, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity (rsFC) data to predict the degree of trait anxiety in 76 healthy participants. Using a computational "lesion" approach in CPM, we then examined the weights of the identified main brain areas as well as their connectivity. Results showed that the CPM successfully predicted individual anxiety based on whole-brain rsFC, especially the rsFC between limbic areas and prefrontal cortex. The prediction power of the model significantly decreased from simulated lesions of limbic areas, lesions of the connectivity within limbic areas, and lesions of the connectivity between limbic areas and prefrontal cortex. Importantly, this neu ral model generalized to an independent large sample (n = 501). These findings highlight important roles of the limbic system and prefrontal cortex in anxiety prediction. Our work provides evidence for the usefulness of connectome-based modeling in predicting individual personality differences and indicates its potential for identifying personality factors at risk for psychopathology.
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Chandelier Cartridge Density Is Reduced in the Prefrontal Cortex in Autism

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Abstract
An alteration in the balance of excitation-inhibition has been proposed as a common characteristic of the cerebral cortex in autism, which may be due to an alteration in the number and/or function of the excitatory and/or inhibitory cells that form the cortical circuitry. We previously found a decreased number of the parvalbumin (PV)+ interneuron known as Chandelier (Ch) cell in the prefrontal cortex in autism. This decrease could result from a decreased number of Ch cells, but also from decreased PV protein expression by Ch cells. To further determine if Ch cell number is altered in autism, we quantified the number of Ch cells following a different approach and different patient cohort than in our previous studies. We quantified the number of Ch cell cartridges—rather than Ch cell somata—that expressed GAT1—rather than PV. Specifically, we quantified GAT1+ cartridges in prefrontal areas BA9, BA46, and BA47 of 11 cases with autism and 11 co ntrol cases. We found that the density of GAT1+ cartridges was decreased in autism in all areas and layers. Whether this alteration is cause or effect remains unclear but could result from alterations that take place during cortical prenatal and/or postnatal development.
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