Progression Of Hemorrhage Research Articles

Obesity as a Risk Factor for Severe COVID-19 and Complications: A Review.

Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.

Pre-injury antithrombotic agents predict intracranial hemorrhagic progression, but not worse clinical outcome in severe traumatic brain injury

BackgroundThe incidence of traumatic brain injury (TBI) patients of older age with comorbidities, who are pre-injury treated with antithrombotic agents (antiplatelets and/or anticoagulants), has increased. In this study, our aim was to investigate if pre-injury antithrombotic treatment was associated with worse intracranial hemorrhagic/injury progression and clinical outcome in patients with severe TBI.MethodsIn this retrospective study, including 844 TBI patients treated at our neurointensive care at Uppsala University Hospital, Sweden, 2008–2018, 159 (19%) were pre-injury treated with antithrombotic agents. Demography, admission status, radiology, treatment, and outcome variables were evaluated. Significant intracranial hemorrhagic/injury evolution was defined as hemorrhagic progression seen on the second computed tomography (CT), emergency neurosurgery after the initial CT, or death following the initial CT.ResultsPatients with pre-injury antithrombotics were significantly older and with a higher Charlson comorbidity index. They were more often injured by falls and more frequently developed acute subdural hematomas. Sixty-eight (8%) patients were pre-injury treated with monotherapy of antiplatelets, 67 (8%) patients with anticoagulants, and 24 (3%) patients with a combination of antithrombotics. Pre-injury anticoagulants, but not antiplatelets, were independently associated with significant intracranial hemorrhagic/injury evolution in a multiple regression analysis. However, neither anticoagulants nor antiplatelets were associated with mortality and unfavorable outcome in multiple regression analyses.ConclusionsOnly anticoagulants were associated with intracranial hemorrhagic/injury progression, but no antithrombotic agent correlated with worse clinical outcome. Management, including early anticoagulant reversal, availability of emergency neurosurgery, and neurointensive care, may be important aspects for reducing the adverse effects of pre-injury antithrombotics.

The progression of intracerebral hemorrhage (ICH) is related to the expression of integrin \u03921 (ITGB1)

BackgroundIntracerebral hemorrhage (ICH) is fatal and detrimental to quality of life. Clinically, options for monitoring are often limited, potentially missing subtle neurological changes. Integrin β 1 (ITGB1) and β 3 (ITGB3) are the main components of integrin family receptors, which regulate the formation and stability of blood vessels. This study explored the relationship between the expression of ITGB1 and ITGB3 in intracerebral hemorrhage (ICH) to analyze their functional and clinical relevance.MethodsThe expression of ITGB1 and ITGB3 in ICH was accomplished by immunohistochemical (IHC) staining and western blotting (WB) analysis, respectively.ResultsFurthermore, the results demonstrated that ITGB1 was expressed in ICH tissues, but ITGB3 was not expressed in ICH tissues.ConclusionsIn summary, the clinical progression of ICH was related to the expression of ITGB1. ITGB1 may be a potential biomarker and contribute to the treatment of ICH.

Incorporating Immunoproteins in the Development of Classification Models of Progression of Intracranial Hemorrhage After Traumatic Brain Injury.

To define clinical, radiographic, and blood-based biomarker features to be incorporated into a classification model of progression of intracranial hemorrhage (PICH), and to provide a pilot assessment of those models. Patients with hemorrhage on admission head computed tomography were identified from a prospectively enrolled cohort of subjects with traumatic brain injury. Initial and follow-up images were interpreted both by 2 independent readers, and disagreements adjudicated. Admission plasma samples were analyzed and principal components (PCs) composed of the immune proteins (IPs) significantly associated with the outcome of interest were selected for further evaluation. A series of logistic regression models were constructed based on (1) clinical variables (CV) and (2) clinical variables + immune proteins (CV+IP). Error rates of these models for correct classification of PICH were estimated; significance was set at P < .05. We identified 106 patients, 36% had PICH. Dichotomized admission Glasgow Coma Scale (P = .004), Marshall score (P = .004), and 3 PCs were significantly associated with PICH. For the CV only model, sensitivity was 1.0 and specificity was 0.29 (95% CI, 0.07-0.67). The CV+IP model performed significantly better, with a sensitivity of 0.93 (95% CI, 0.64-0.99) and a specificity of 1.0 (P = .008). Adjustments to refine the definition of PICH and better define radiographic predictors of PICH did not significantly improve the models' performance. In this pilot investigation, we observed that composites of IPs may improve PICH classification models when combined with CVs. However, overall model performance must be further optimized; results will inform feature inclusion included in follow-up models.

Complications Following Decompressive Craniectomy.

Decompressive craniectomy (DC) has become the definitive surgical procedure to manage a medically intractable rise in intracranial pressure. DC is a life-saving procedure resulting in lower mortality but also higher rates of severe disability. Although technically straightforward, DC is accompanied by many complications. It has been reported that complications are associated with worse outcome. We reviewed a series of patients who underwent DC at our department to establish the incidence and types of complications. We retrospectively evaluated the incidence of complications after DC performed in 135 patients during the time period from January 2013 to December 2018. Postoperative complications were evaluated using clinical status and CT during 6 months of follow-up. In addition, the impact of potential risk factors on the incidence of complications and the impact of complications on outcome were assessed. DC was performed in 135 patients, 93 of these for trauma, 22 for subarachnoid hemorrhage, 13 for malignant middle cerebral artery infarction, and 7 for intracerebral hemorrhage. Primary DC was performed in 120 patients and secondary DC in 15 patients. At least 1 complication occurred in each of 100 patients (74%), of which 22 patients (22%) were treated surgically. The following complications were found: edema or hematoma of the temporal muscle (34 times), extracerebral hematoma (33 times), extra-axial fluid collection (31 times), hemorrhagic progression of contusions (19 times), hydrocephalus (12 times), intraoperative malignant brain edema (10 times), temporal muscle atrophy (7 times), significant intraoperative blood loss (6 times), epileptic seizures (5 times), and skin necrosis (4 times). Trauma (p = 0.0006), coagulopathy (p = 0.0099), and primary DC (p = 0.0252) were identified as risk factors for complications. There was no significant impact of complications on outcome. The incidence of complications following DC is high. However, we did not confirm a significant impact of complications on outcome. We emphasize that some phenomena are so frequent that they can be considered a consequence of primary injury or natural sequelae of the DC rather than its direct complication.

Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24hours of admission, or progression of bleed on 6hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24hours) and late (>24hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17hours and 47hours in the early and late groups, respectively (P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7hours following injury.

Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis.

Intracerebral haemorrhage (ICH) is a devastating subtype of stroke with high morbidity and mortality. It has been reported that paeonol (PAN) inhibits the progression of ICH. However, the mechanism by which paeonol mediates the progression of ICH remains unclear. To mimic ICH in vitro, neuronal cells were treated with hemin. An in vivo model of ICH was established to detect the effect of paeonol on ferroptosis in neurons during ICH. Cell viability was tested by MTT assay. Furthermore, cell injury was detected by GSH, MDA and ROS assays. Ferroptosis was examined by iron assay. RT-qPCR and western blotting were used to detect gene and protein expression, respectively. The correlation among HOTAIR, UPF1 and ACSL4 was explored by FISH, RNA pull-down and RIP assays. Paeonol significantly inhibited the ferroptosis of neurons in ICH mice. In addition, paeonol significantly reversed hemin-induced injury and ferroptosis in neurons, while this phenomenon was notably reversed by HOTAIR overexpression. Moreover, paeonol notably inhibited ferroptosis in hemin-treated neuronal cells via inhibition of ACSL4. Additionally, HOTAIR bound to UPF1, and UPF1 promoted the degradation of ACSL4 by binding to ACSL4. Furthermore, HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis by mediating the UPF1/ACSL4 axis. Paeonol inhibits the progression of ICH by mediating the HOTAIR/UPF1/ACSL4 axis. Therefore, paeonol might serve as a new agent for the treatment of ICH.

Lack of Progression of Intraventricular Hemorrhage in Premature Infants: Implications for Head Ultrasound Screening.

Very preterm infants are at risk for germinal matrix hemorrhage- intraventricular hemorrhage (GH-IVH). Severe GH-IVH may cause death or severe neurodevelopmental disability while mild GH-IVH is considered a static, non-progressive disease. This retrospective study aimed to determine if infants with no GH-IVH or mild GH-IVH on initial screening head ultrasound (HUS) advanced to severe GH-IVH. A total of 353 eligible infants with birth gestational age ≤32 0/7 weeks who received a HUS during hospitalization were identified. Of the 343 (97%) infants who had mild GH-IVH (grade II or less) on initial screening, only 4 (1.2%) progressed to severe (grade III or IV). Each of these infants required mechanical ventilation for at least 40 days. Therefore, premature infants who have no GH-IVH or mild GH-IVH on initial routine screening HUS without other risk factors may not require follow-up HUSs. Infants with prolonged mechanical ventilation may require further screening despite reassuring initial HUS findings.

Activation of Nurr1 with Amodiaquine Protected Neuron and Alleviated Neuroinflammation after Subarachnoid Hemorrhage in Rats

Background. Nurr1, a member of the nuclear receptor 4A family (NR4A), played a role in neuron protection, anti‐inflammation, and antioxidative stress in multidiseases. We explored the role of Nurr1 on subarachnoid hemorrhage (SAH) progression and investigated the feasibility of its agonist (amodiaquine, AQ) as a treatment for SAH. Methods. SAH rat models were constructed by the endovascular perforation technique. AQ was administered intraperitoneally at 2 hours after SAH induction. SAH grade, mortality, weight loss, neurological performance tests, brain water content, western blot, immunofluorescence, Nissl staining, and qPCR were assessed post‐SAH. In vitro, hemin was introduced into HT22 cells to develop a model of SAH. Results. Stimulation of Nurr1 with AQ improved the outcomes and attenuated brain edema. Nurr1 was mainly expressed in neuron, and administration of AQ alleviated neuron injury in vivo and enhanced the neuron viability and inhibited neuron apoptosis and necrosis in vitro. Besides, AQ reduced the amount of IL‐1β+Iba‐1+ cells and inhibited the mRNA level of proinflammatory cytokines (IL‐1β and TNF‐α) and the M1‐like phenotype markers (CD68 and CD86). AQ inhibited the expression of MMP9 in HT22 cells. Furthermore, AQ reduced the expression of nuclear NF‐κB and Nurr1 while increased cytoplasmic Nurr1 in vivo and in vitro. Conclusion. Pharmacological activation of Nurr1 with AQ alleviated the neuron injury and neuroinflammation. The mechanism of antineuroinflammation may be associated with the Nurr1/NF‐κB/MMP9 pathway in the neuron. The data supported that AQ might be a promising treatment strategy for SAH.

Single Center Experience With Veno-Venous Extracorporeal Membrane Oxygenation in Patients With Traumatic Brain Injury.

We retrospectively reviewed TBI patients ≥ 18years of age treated with VV-ECMO. The primary outcome was survival to discharge. Secondary outcomes included progression of intracranial hemorrhage, bleeding complications, and episodes of oxygenator thrombosis requiring exchange. Medians and interquartile ranges were reported where appropriate. 13 TBI patients received VV-ECMO support during the study period. The median age was 28years (Interquartile range (IQR) 25-37.5) and 85% were men. Median admission Glasgow coma scale was 5 (IQR 3-13.5). Median injury severity score (ISS) was 48 (IQR 33.5-66). Median pre-ECMO PaO2:FiO2 ratio was 58 (IQR 47-74.5). Five (38.4%) patients survived to discharge. Six patients (46%) received systemic A/C while on ECMO. No patient had worsening of intracranial hemorrhage on computed tomography imaging. There were two bleeding complications in patients on A/C, neither was related to TBI. Four patients required an oxygenator change; 2 in patients on A/C. VV-ECMO appears safe with TBI. We have demonstrated that A/C can be withheld without increased complications. Traumatic brain injury should not be considered an absolute contraindication to the use of VV-ECMO for severe respiratory failure and should be decided on a case by case basis. Additional research is needed to confirm these preliminary findings.

Evaluation of the relationship between glaucomatous disc subtypes and occurrence of disc hemorrhage and glaucoma progression in open angle glaucoma

To compare the occurrence of disc hemorrhages (DH) and glaucoma progression in open-angle glaucoma (OAG) patients with different glaucomatous disc types. Prospective, hospital-based, observational cohort study. OAG patients examined between 2000 and 2005, whose discs were classified as typical myopic glaucomatous (MG), generalized enlargement of cup (GE), or focal glaucomatous (FG) disc type were included and followed for 5 years. The first occurrence of DH during follow-up was analyzed using Kaplan–Meier analysis and difference in DH occurrence based on glaucomatous disc type using the Cox proportional-hazards model to adjust for effects of confounding factors. For inter-group comparison of glaucoma progression, the change rate of the mean deviation, Collaborative Initial Glaucoma Treatment Study scores, and fundus photographs were used. Thirty-nine patients with MG-, 18 with FG-, and 17 with GE-disc types were included. No significant inter-group difference was seen in the rate of glaucoma progression. The five-year probability of DH occurrence was much lower with MG- than with FG- or GE-disc types (P < 0.0220). The central corneal thickness (P = 0.0024) and mean intraocular pressure and its variations (P = 0.0450, 0.0219) contributed to DH occurrence. The MG-disc type demonstrated a much lower DH occurrence during follow-up than other disc types.

A Stitch in Time Saves Clots: Venous Thromboembolism Chemoprophylaxis in Traumatic Brain Injury

BackgroundVenous thromboembolism chemoprophylaxis (VTE-CHEMO) is often delayed in patients with traumatic brain injury because of the concern for intracranial hemorrhage (ICH) progression. We hypothesize that (1) late time to VTE-CHEMO (≥48 h) is associated with higher incidence of VTE, and (2) VTE-CHEMO use does not correlate with ICH progression. Materials and methodsThis is a multiinstitutional retrospective study of patients with traumatic brain injury admitted between 2014 and 2016. Inclusion criteria were head Abbreviated Injury Code ≥2, ICH present on initial head computed tomography, and two or more head computed tomography scans after admission. The primary outcome was VTE, and the secondary outcome was ICH progression. Patients were classified as receiving VTE-CHEMO early (<48 h) or late (≥48 h). Multivariable analysis with Cox proportional hazards regression was performed. ResultsOverall, 1803 patients were included. Patients with VTE (n = 137) were more likely to have spinal cord injury, blunt cerebrovascular injury, pelvic or femur fractures, and missed VTE-CHEMO doses. After multivariable regression, body mass index >30 (hazard ratio [HR], 1.05; P = 0.002), Injury Severity Score (HR, 1.004; P < 0.001), pelvic or femur fractures (HR, 1.05; P < 0.0001), spinal cord injury (HR, 1.28; P = 0.02), and missed VTE-CHEMO doses (HR, 1.08; P = 0.01) were significant predictors of VTE. In those who required neurosurgery, late VTE-CHEMO predicted VTE (HR, 1.21; P = 0.0001). Overall, 32% patients experienced ICH progression, which did not correlate with VTE-CHEMO use or timing. ConclusionsThis multicenter study highlights benefits from early VTE-CHEMO and identifies high-risk groups who may benefit from more aggressive prophylaxis. These data also emphasize risk to patients by withholding VTE-CHEMO.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. ClinicalTrials.gov Identifier: NCT01990768.

Preinjury Antiplatelet Use Does Not Increase the Risk of Progression of Small Intracranial Hemorrhage.

The modified brain injury guidelines (mBIG) provide an algorithm for surgeons to manage some mild traumatic brain injury (TBI) with intracranial hemorrhage (ICH) without neurosurgical consultation or repeat imaging. Currently, antiplatelet use among patients with any ICH classifies a patient at the highest level, mBIG 3. This study assesses the risk of clinical progression among patients taking antiplatelet medications with mild TBI with ICH. A retrospective analysis of patients with traumatic ICH over a 5-year period was conducted. Demographics, injury severity, and outcome data were collected for each patient. Patients taking antiplatelet agents were reclassified as if they were not taking these medications. Patients who would have met criteria for a lower classification (mBIG 1 or 2) without antiplatelet agents were designated mBIG 3 Antiplatelet and compared with all other mBIG 1 and 2 patients. 736 patients met the inclusion criteria. 158 patients were taking antiplatelet medications and 53 were reclassified as mBIG 3 Antiplatelet. When comparing mBIG 3 Antiplatelet to the 226 patients originally classified as mBIG 1 and 2, mBIG 3 Antiplatelet patients were more likely to undergo repeat head computed tomography (98.1% vs 76.6%; P < .001) and neurosurgical consultation (94.2% vs 76.5%; P < .001) but had no significant differences in outcomes. No mBIG 3 Antiplatelet patients had a worsening examination or needed operative intervention. This data suggests that antiplatelet medication use should not automatically classify a patient as mBIG 3. Adoption of this strategy would better utilize resources and avoid unnecessary costs without sacrificing care.

Low Risk of Traumatic Intracranial Hematoma Expansion with Factor Xa Inhibitors without Andexanet Reversal

Andexanet alfa, a novel anticoagulation reversal agent for factor Xa inhibitors, was recently approved. Traumatic intracranial hemorrhage presents a prime target for this drug. The Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors study established the efficacy of andexanet alfa in reversing factor Xa inhibitors. However, the association between anticoagulation reversal and traumatic intracranial hemorrhage progression is not well understood. The objective of this study was to determine progression rates of patients with traumatic intracranial hemorrhage on factor Xa inhibitors prior to hospitalization who were managed without the use of andexanet alfa. A retrospective cohort study was performed between 2016 and 2019 at a single institution. An institutional traumatic brain injury (TBI) registry was queried. Patients with recorded use of apixaban or rivaroxaban <18 hours before injury were included. The primary study outcome was <35% increase in hemorrhage volume or thickness on repeated head computed tomography (CT) scans. We identified 25 patients meeting the inclusion criteria. Two patients were excluded because of a lack of necessary CT data. Twelve patients (52%) were receiving apixaban, and 11 were (48%) on rivaroxaban. On admission CT scan, 14 patients had subdural hematoma, 6 had traumatic intraparenchymal hemorrhage, and 3 had subarachnoid hemorrhage. Anticoagulation reversal was attempted in 17 patients (74%), primarily using 4-factor prothrombin complex concentrate. Twenty patients (87%) were adjudicated as having excellent or good hemostasis on repeat imaging. Our results indicate that patients on factor Xa inhibitors with complicated mild TBI have a similar intracranial hemorrhage progression rate to patients who are not anticoagulated or anticoagulated with a reversible agent. The hemostatic outcomes in our cohort were similar to those reported after andexanetalfa administration.

Emergency department observation of mild traumatic brain injury with minor radiographic findings: shorter stays, less expensive, and no increased risk compared to hospital admission.

ObjectiveThe management of mild traumatic brain injury (mTBI) with minor radiographic findings traditionally involves hospital admission for monitoring, although this practice is expensive with unclear benefit. We implemented a protocol to manage these patients in our emergency department observation unit (EDOU), hypothesizing that this pathway was cost effective and not associated with any difference in clinical outcome.MethodsmTBI patients with minor radiographic findings were managed under the EDOU protocol over a 3‐year period from May 1, 2015 to April 30, 2018 (inclusions: ≥19 years old, isolated acute head trauma, normal neurological exam [except transient alteration in consciousness], and a computed tomography [CT] scan of the head with at least 1 of the following: cerebral contusions <1 cm in maximum extent, convexity subarachnoid hemorrhage, or closed, non‐displaced skull fractures). These patients were retrospectively analyzed; clinical outcomes and charges were compared to a control cohort of matched mTBI hospital admissions over the preceding 3 years.ResultsSixty patients were observed in the EDOU over the 3‐year period, and 85 patients were identified for the control cohort. There were no differences in rate of radiographic progression, neurological exam change, or surgical intervention, and the overall incidence of hemorrhagic expansion was low in both groups. The EDOU group had a significantly faster time to interval CT scan (Mean Difference (MD) 3.92 hours, [95%CI 1.65, 6.19]), P = 0.001), shorter length of stay (MD 0.59 days [95% CI 0.29, 0.89], P = 0.001), and lower encounter charges (MD $3428.51 [95%CI 925.60, 5931.42], P = 0.008). There were no differences in 30‐day re‐admission, 30‐day mortality, or delayed chronic subdural formation, although there was a high rate of loss to follow‐up in both groups.ConclusionsCompared to hospital admission, observing mTBI patients with minor radiographic findings in the EDOU was associated with significantly shorter time to interval scanning, shorter length of stay, and lower encounter charges, but no difference in observed clinical outcome. The overall risk of hemorrhagic progression in this subset of mTBI was very low. Using this approach can reduce unnecessary admissions while potentially yielding patient care and economic benefits. When designing a protocol, close attention should be given to clear inclusion criteria and a formal mechanism for patient follow‐up.

Bloodletting Puncture at Hand Twelve Jing-Well Points Improves Neurological Recovery by Ameliorating Acute Traumatic Brain Injury-Induced Coagulopathy in Mice.

Traumatic brain injury (TBI) contributes to hypocoagulopathy associated with prolonged bleeding and hemorrhagic progression. Bloodletting puncture therapy at hand twelve Jing-well points (BL-HTWP) has been applied as a first aid measure in various emergent neurological diseases, but the detailed mechanisms of the modulation between the central nervous system and systemic circulation after acute TBI in rodents remain unclear. To investigate whether BL-HTWP stimulation modulates hypocoagulable state and exerts neuroprotective effect, experimental TBI model of mice was produced by the controlled cortical impactor (CCI), and treatment with BL-HTWP was immediately made after CCI. Then, the effects of BL-HTWP on the neurological function, cerebral perfusion state, coagulable state, and cerebrovascular histopathology post-acute TBI were determined, respectively. Results showed that BL-HTWP treatment attenuated cerebral hypoperfusion and improve neurological recovery post-acute TBI. Furthermore, BL-HTWP stimulation reversed acute TBI-induced hypocoagulable state, reduced vasogenic edema and cytotoxic edema by regulating multiple hallmarks of coagulopathy in TBI. Therefore, we conclude for the first time that hypocoagulopathic state occurs after acute experimental TBI, and the neuroprotective effect of BL-HTWP relies on, at least in part, the modulation of hypocoagulable state. BL-HTWP therapy may be a promising strategy for acute severe TBI in the future.

Impact of Antithrombotic Agents on Radiological Lesion Progression in Acute Traumatic Brain Injury: A CENTER-TBI Propensity-Matched Cohort Analysis.

An increasing number of elderly patients are being affected by traumatic brain injury (TBI) and a significant proportion are on pre-hospital antithrombotic therapy for cardio- or cerebrovascular indications. We have quantified the impact of antiplatelet/anticoagulant (APAC) agents on radiological lesion progression in acute TBI, using a novel, semi-automated approach to volumetric lesion measurement, and explored the impact of use on clinical outcomes in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We used a 1:1 propensity-matched cohort design, matching controls to APAC users based on demographics, baseline clinical status, pre-injury comorbidities, and injury severity. Subjects were selected from a pool of patients enrolled in CENTER-TBI with computed tomography (CT) scan at admission and repeated within 7 days of injury. We calculated absolute changes in volume of intraparenchymal, extra-axial, intraventricular, and total intracranial hemorrhage (ICH) between scans, and compared volume of hemorrhagic progression, proportion of patients with significant degree of progression (>25% of initial volume), proportion with new ICH on follow-up CT, as well as clinical course and outcomes. A total of 316 patients were included (158 APAC users; 158 controls). The mean volume of progression was significantly higher in the APAC group for extra-axial (3.1 vs. 1.3 mL, p = 0.01), but not intraparenchymal (3.8 vs. 4.6 mL, p = 0.65), intraventricular (0.2 vs. 0.0 mL, p = 0.79), or total intracranial hemorrhage (ICH; 7.0 vs. 6.0 mL, p = 0.08). More patients had significant hemorrhage growth (54.1 vs. 37.0%, p = 0.003) and delayed ICH (4 of 18 vs. none; p = 0.04) in the APAC group compared with controls, but this was not associated with differences in length of stay (LOS), rates of neurosurgical intervention, mortality or Glasgow Outcome Scale Extended (GOS-E) score at 6 months. Pre-injury use of antithrombotic agents was associated with greater expansion of extra-axial lesions, higher rates of significant hemorrhagic progression, and higher risk of delayed traumatic ICH, but this was not associated with worse clinical course or functional outcomes.

Aggravated pulmonary injury after subarachnoid hemorrhage in PDGF-Bret/ret mice

BackgroundRecent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage (SAH). However, pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes. Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks, we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH.MethodsIn our experiments, platelet-derived growth factor B (PDGF-B) retention motif knockout (PDGF-Bret/ret) mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression. Neurological score, SAH grade, hematoxylin-eosin staining, and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery, as well as western blotting and immunofluorescence staining for underlying molecular expressions.ResultsWe found that neonatal PDGF-Bret/ret mice exhibited pulmonary atelectasis 12 h after birth. Further investigation showed a decrease in PaO2/FiO2 and lung-specific surfactant proteins in adult PDGF-Bret/ret mice. These dysfunctions were much worse than those in wild-type mice at 24 h after SAH. PDGF-B overexpression alleviated pulmonary dysfunction after SAH.ConclusionsThese results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH. Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.

HEMORRHAGIC PROGRESSION OF CONTUSION IN PATIENTS WITH MILD TRAUMATIC BRAIN INJURY ON THE ROUTINE REPEAT HEAD COMPUTED TOMOGRAPHY

Computed tomography (CT) scan is a standard for the diagnosis of intracranial pathology after traumatic brain injury (TBI). Hemorrhagic progression of contusion (HPC) is frequently seen on repeat CT, but its clinical and radiological significance in case of mild TBI is not well define. The aim of the study: to evaluate the result of routine repeat head CT in patients with mild TBI and brain contusions. Materials and methods: retrospective analysis of management of patients with mild TBI (Glasgow Coma Scale (GCS) score – 13 to 15) and cerebral contusion. All patients were treated at the Kyiv City Clinical Emergency Hospital between 2016 and 2017. Results: within 202 patients with mild TBI, 87 (43.1 %) met the inclusion criteria and were selected for detailed analysis. There were 69 (79.3 %) men and 18 (20.7 %) women. The mean age of the patients was 43.8±12.7 years (17–82 years). The average time between trauma and CT was 3.3 hours. The average volume of contusion on the initial CT was 1.9±0.6 cm3 (0.2–9.6 cm3). The average time of routine CT was 6.8 hours (range 4–24 hours) after the initial scans. HPC was found in 24 (30.7 %) of 87 cases. The average volume of brain contusion on the repeat CT was 2.3±0.5 cm3 (0.2-17.1 cm3). In 3 (3.4 %) patients the size of the hematoma increased. Clinical deterioration occurred in 10 (11.5 %) patients. Six (6.9 %) patients were operated after a CT scan due to HPC with midline shift in 4 cases and increasing of subdural hematoma – 2 cases. Four of these patients had clinical deterioration, and 2 patients were neurological stable. Patients with HPC at admission had lower points of GCS, fractures of the skull (both p &lt;0.001), subdural blood collection (p=0.002), a higher average duration of treatment 8.1±4.2 vs 14.3±5.2 days (p=0.0001), and mortality rate 0 vs. 3 (12.5 %) (p=0.02). Conclusions: Routine repeat CT in patients with mild TBI with brain contusions is aimed to find a patients with s high risk for clinical deterioration. One third of patients with mild TBI and brain contusion experienced HPC. Patients with HPC often have unfavorable clinical course with higher average duration of treatment, delay surgical treatment and mortality rate.