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Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment.To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma.This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in CSDH thickness, and midline shift.Fifty-seven patients met inclusion criteria. The median age was 66 years (IQR 58-76) with 21.1% females. Sixty-six embolizations were performed. The median length to follow-up was 20 days (IQR 14-44). Nineteen patients (33.3%) had rapid reinitiation of antithrombotics (5 antiplatelet, 11 anticoagulation, and 3 both). Baseline characteristics between the no antithrombotic (no-AT) and the AT groups were similar. The recurrence rate was higher in the AT group (no-AT vs AT, 9.3 vs 30.4%, P = .03). Mean absolute reduction in CSDH thickness and midline shift was similar between groups. Rate of reoperation did not differ (4.7 vs 8.7%, P = .61).Rapid reinitiation of AT after MMA embolization for CSDH leads to higher rates of recurrence with similar rates of reoperation. Care must be taken when initiating antithrombotics after treatment of CSDH with MMA embolization.

Translational symmetry breaking is antagonistic to static fluidity but can be realized in superconductors, which host a quantum-mechanical coherent fluid formed by electron pairs. A peculiar example of such a state is the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state, induced by a time-reversal symmetry–breaking magnetic field applied to spin-singlet superconductors. This state is intrinsically accompanied by the superconducting spin smecticity, spin density–modulated fluidity with spontaneous translational-symmetry breaking. Detection of such spin smecticity provides unambiguous evidence for the FFLO state, but its observation has been challenging. Here, we report the characteristic “double-horn” nuclear magnetic resonance spectrum in the layered superconductor Sr 2 RuO 4 near its upper critical field, indicating the spatial sinusoidal modulation of spin density that is consistent with superconducting spin smecticity. Our work reveals that Sr 2 RuO 4 provides a versatile platform for studying FFLO physics.

UTe2 is a recently discovered spin-triplet superconductor. One of the characteristic features of UTe2 is a magnetic field (H)-boosted superconductivity above 16 T when H is applied exactly parallel to the b axis. To date, this superconducting (SC) state has not been thoroughly investigated, and the SC properties as well as the spin state of this high-H SC (HHSC) phase are not well understood. In this study, we performed AC magnetic susceptibility and nuclear magnetic resonance (NMR) measurements and found that, up to 24.8 T, the HHSC state is intrinsic to UTe2 and quite sensitive to the H angle, and that its SC character is different from that in the low-H SC (LHSC) state. The dominant spin component of the spin-triplet pair is along the a axis in the LHSC state but is changed in the HHSC state along the b axis. Our results indicate that H-induced multiple SC states originate from the remaining spin degrees of freedom., 6 pages, 3 figures, 2 tables

In 2016, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan. The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. Given the public health burden of injuries to the central nervous system, neurotrauma was one of 11 panels formed to address this recommendation with a gap analysis and generation of high-priority research questions.We recruited interdisciplinary experts to identify gaps in the neurotrauma literature, generate research questions, and prioritize those questions using a consensus-driven Delphi survey approach. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the importance of the questions on a 9-point Likert scale. Consensus was defined as 60% or greater of panelists agreeing on the priority category. We then coded research questions using an National Trauma Research Action Plan taxonomy of 118 research concepts, which were consistent across all 11 panels.Twenty-eight neurotrauma experts generated 675 research questions. Of these, 364 (53.9%) reached consensus, and 56 were determined to be high priority (15.4%), 303 were deemed to be medium priority (83.2%), and 5 were low priority (1.4%). The research topics were stratified into three groups-severe traumatic brain injury (TBI), mild TBI (mTBI), and spinal cord injury. The number of high-priority questions for each subtopic was 46 for severe TBI (19.7%), 3 for mTBI (4.3%) and 7 for SCI (11.7%).This Delphi gap analysis of neurotrauma research identified 56 high-priority research questions. There are clear areas of focus for severe TBI, mTBI, and spinal cord injury that will help guide investigators in future neurotrauma research. Funding agencies should consider these gaps when they prioritize future research.Diagnostic Test or Criteria, Level IV.

Ischemic stroke is a serious cerebrovascular event that results in cell death, blood-brain barrier dysfunction, tissue degradation, and inflammation, often leading to permanent disability or death. As the incidence of ischemic stroke continues to rise globally, it is crucial to examine the mechanisms of the various proteins and molecules contributing to worsened patient outcome and recovery. Cathepsin L, a cysteine protease known for degrading tissues in lysosomes and elsewhere, may play a role in brain tissue loss and inflammation after stroke. Studies have suggested that cathepsin L appears in the ischemic core shortly after stroke is induced. Using immunohistochemical staining, mass spectrometry, and other assays, the increase of cathepsin L in the brain was correlated with extracellular matrix and perlecan degradation after ischemic stroke. Additionally, injection of a cathepsin L inhibitor significantly reduced brain infarct size and improved functional scores. More research is needed to elucidate cathepsin L's role in post-stroke inflammation and brain damage, in order to further explore the factors contributing to worsened patient outcome after ischemic stroke and work toward finding better therapeutic interventions.

The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime. Our results showed that these compounds displayed comparable in vitro reactivation also pointed by the in silico studies, suggesting that they are promising compounds to tackle organophosphorus poisoning.

ObjectiveTo determine whether machine learning (ML) algorithms can improve the prediction of delayed cerebral ischemia (DCI) and functional outcomes after subarachnoid hemorrhage (SAH).MethodsML models and standard models (SMs) were trained to predict DCI and functional outcomes with data collected within 3 days of admission. Functional outcomes at discharge and at 3 months were quantified using the modified Rankin Scale (mRS) for neurologic disability (dichotomized as good [mRS ≤ 3] vs poor [mRS ≥ 4] outcomes). Concurrently, clinicians prospectively prognosticated 3-month outcomes of patients. The performance of ML, SMs, and clinicians were retrospectively compared.ResultsDCI status, discharge, and 3-month outcomes were available for 399, 393, and 240 participants, respectively. Prospective clinician (an attending, a fellow, and a nurse) prognostication of 3-month outcomes was available for 90 participants. ML models yielded predictions with the following area under the receiver operating characteristic curve (AUC) scores: 0.75 ± 0.07 (95% confidence interval [CI] 0.64–0.84) for DCI, 0.85 ± 0.05 (95% CI 0.75–0.92) for discharge outcome, and 0.89 ± 0.03 (95% CI 0.81–0.94) for 3-month outcome. ML outperformed SMs, improving AUC by 0.20 (95% CI −0.02 to 0.4) for DCI, by 0.07 ± 0.03 (95% CI −0.0018 to 0.14) for discharge outcomes, and by 0.14 (95% CI 0.03–0.24) for 3-month outcomes and matched physician's performance in predicting 3-month outcomes.ConclusionML models significantly outperform SMs in predicting DCI and functional outcomes and has the potential to improve SAH management.

In search of a novel class of compounds against Alzheimer's disease (AD), a new series of 7-chloro-aminoquinoline derivatives containing methylene spacers of different sizes between the 7-chloro-4-aminoquinoline nucleus and imino methyl substituted phenolic rings, and also their reduced analogues, were designed, synthesized and evaluated as neuroprotective agents for AD

Background Epidural hematomas (EDHs) involving the venous sinuses are uncommon and carry the risk of hemorrhage or venous infarction. We report the largest case series for superior sagittal sinus− and transverse sinus−related EDHs including surgical and nonsurgical management. We compare our findings to the relevant literature. Methods A retrospective review of the EDH cases at our center was performed from 2013–2018. Patients were analyzed by surgical versus conservative management, outcomes, and complications. Results Of the 268 EDH patients identified, 32 involved the venous sinuses (23 supratentorial and 9 infratentorial). Ten of the patients had surgery, and 22 were managed conservatively. No surgical complications occurred, and all had a Glasgow Outcome Scale score of 5 at follow-up. All of the nonsurgical patients had a Glasgow Outcome Scale score of 4 or 5 at follow-up except for 1 patient with prior disability. The literature search resulted in 39 infratentorial and 47 supratentorial EDHs involving venous sinuses. Conclusions Surgical and nonsurgical management of EDHs involving the venous sinuses are both viable options with good outcomes. Surgical intervention is based on location, size, neurologic examination, expansion on serial imaging, and vascular imaging findings. Surgery has the potential for significant complications, but all surgical patients in our series had good outcomes at follow-up. Similarly, nonsurgically managed patients had good outcomes and our overall series demonstrates better outcomes with fewer complications than other similar series in the literature.

Background Modern science and healthcare generate vast amounts of data, and, coupled with the increasingly inexpensive and accessible computing, a tremendous opportunity exists to use these data to improve care. A better understanding of data science and its relationship to neurosurgical practice will be increasingly important as we transition into this modern “big data” era. Methods A review of the literature was performed for key articles referencing big data for neurosurgical care or related topics. Results In the present report, we first defined the nature and scope of data science from a technical perspective. We then discussed its relationship to the modern neurosurgical practice, highlighting key references, which might form a useful introductory reading list. Conclusions Numerous challenges exist going forward; however, organized neurosurgery has an important role in fostering and facilitating these efforts to merge data science with neurosurgical practice.

The inflammatory processes following traumatic brain injury (TBI) have not been fully characterized. We hypothesize that differences in systemic cytokine/chemokine (CC) levels are associated with TBI clinical outcomes. To test this hypothesis, we examined systemic levels of CCs and their relationship with patient outcomes. Plasma from acute TBI subjects was collected at 24–48 h, and the CC levels were measured using a multiplex 41-plex-kit. Clinical outcomes were assessed using the modified Rankin scale (mRS) with good outcomes defined as mRS ≤ 3 and poor outcome as mRS ≥ 4. The differences in CC concentrations between groups were then compared using the Mann-Whitney U test. Seventy-six acute TBI subjects were included in this study. In the mRS ≥ 4 group, interleukin-6 (IL-6) and interleukin-10 (IL-10) were elevated, indicating early activation of immune reaction and modulation. Simultaneously, PDGFAA and RANTES were lower in the mRS ≥ 4 group. Poor outcomes after TBI were associated with elevated levels of IL-6 and IL-10 and lower levels of PDGFAA and RANTES within 24–48 h after injury.

Coagulopathy may be defined as the loss of balance between hemostatic and fibrinolytic processes resulting in excessive bleeding, intravascular thrombosis or abnormalities in coagulation testing. It is frequently encountered across a wide range of conditions seen in the neurocritical care unit and can contribute to poor outcomes. Early recognition and appropriate management are key, with traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage presenting unique challenges to the neurointensivist. We will discuss techniques to assess coagulopathies as well as treatment strategies for the brain injured patient.

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Objective Anticoagulant therapy (ACT) after traumatic intracranial hemorrhage may lead to progression of hemorrhage, but in the presence of thromboembolic events, the clinician must decide if the benefits outweigh the risks. Currently, no data exist to guide therapy in the acute setting. Methods We retrospectively identified all patients admitted to our institution with traumatic intracranial hemorrhage that received intravenous heparin, full-dose enoxaparin, or warfarin during their initial hospitalization over a 3-year period. We reviewed their demographics, hospital course, clinical indication and timing for initiation of ACT, and complications. Results A total of 112 patients were identified. The median age and Glasgow Coma Scale score of these patients was 50.5 years and 9.5, respectively. Twenty-two patients required neurosurgical procedures for their presenting injury, including intracranial pressure monitors and/or open surgeries. Fifty-four patients had deep vein thrombosis or pulmonary embolism prior to initiation, and the remaining 20 patients had preexisting conditions or other indications for initiating ACT. The median time from injury to starting ACT was 8 days. Immediate complications occurred in 6 patients; however, none of these patients required a neurosurgical intervention. Delayed complications included progression of acute to chronic subdural hematoma that required intervention in 2 patients. One patient died from delayed hemorrhage. Conclusions For this patient population, the risk of immediate and delayed intracranial hemorrhages from initiating ACT therapy in intracranial injury must be weighed against the morbidity of delaying treatment. Although further studies are needed, our review provides the first rates of complications for this patient population.

BACKGROUND: Early diagnosis of Alzheimer’s disease (AD) remains challenging. It is speculated that structural atrophy in white matter tracts commences prior to the onset of AD symptoms. OBJECTIVE: We hypothesize that disruptions in white matter tract connectivity precedes the onset of AD symptoms and these disruptions could be leveraged for early prediction of AD. METHODS: Diffusion tensor images (DTI) from 52 subjects with mild cognitive impairment (MCI) were selected. Subjects were dichotomized into two age and gender matched groups; the MCI-AD group (22 subjects who progressed to develop AD) and the MCI-control group (who did not develop AD). DTI images were anatomically parcellated into 90 distinct regions ROIs followed by tractography methods to obtain different biophysical networks. Features extracted from these networks were used to train predictive algorithms with the objective of discriminating the MCI-AD and MCI-control groups. Model performance and best features are reported. RESULTS: Up to 80% prediction accuracy was achieved using a combination of features from the ‘right anterior cingulum’ and ‘right frontal superior medial’. Additionally, local network features were more useful than global in improving the model’s performance. CONCLUSION: Connectivity-based characterization of white matter tracts offers potential for early detection of MCI-AD and in the discovery of novel imaging biomarkers.

This study aims to introduce an approach of scour detection for an in-service railway bridge in terms of a remote microtremor monitoring. Japanese railway companies make decisions on occurrence of scour by investigating changes in a target frequency, and it is very common to conduct the impact test on the railway bridge pier as a promising scour detection method to identify changes in frequencies. However, the impact test is a laborious and time-consuming method, and has difficulties in real time monitoring to make a proper decision on the train operation control during flood. This study investigates feasibility of scour detection from microtremor monitoring as an alternative method for the conventional impact test. A railway bridge has been being monitored utilizing a sensing unit including functions of vibration measurement, data processing and remote control. Observations from the microtremor data before and after a flood event showed that target frequency was slightly decreased under increase of water surface during flood. However, the slightly decreased frequency recovered once water surface level decreased after flood. Scour assessment following a Japanese guideline showed an extremely low probability of scour of the target bridge due to the flood.

Background Hypothermia is neuroprotective in some ischemia–reperfusion injuries. Ischemia–reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia–reperfusion injury and improve global neurologic outcome. Methods This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. Results Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. Conclusions This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.

Background Quantitative flow ratio (QFR) is an image-based virtual fractional flow reserve (FFR) computed by three dimensional quantitative coronary angiography (3D-QCA) and estimated flow velocity. Several studies have reported that QFR had a good diagnostic performance as compared with wire-based FFR or instantaneous wave-free ratio (iFR). Purpose We compared the diagnostic reliability of QFR for detection of myocardial ischemia with other angiographic and visual predicted indices. Methods In 301 coronary lesions (263 patients) from our QFR database for previously-reported two studies, the diagnostic reliability of QFR, several angiographic and visual predicted indices were investigated using ROC analysis as reference of FFR≤0.8 or iFR≤0.89. Visual predicted FFR were estimated by 3 physicians (25-year experienced expert, 10-year experienced senior physician and 3-year experienced trainee) blinded to other indices. Results Area under the curve (AUC) of each index in ROC analysis is shown in Table. Conclusion QFR was reliable index detecting myocardial ischemia compared with other angiographic and experience-dependent visual predicted indices. Funding Acknowledgement Type of funding source: None

Background Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place. Methods Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting. Results We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms. Conclusions These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference. Electronic supplementary material The online version of this article (10.1007/s00134-019-05900-x) contains supplementary material, which is available to authorized users.

Background: Acute subdural hematoma (aSDH) in the elderly is an increasingly important public health issue. Mortality rate in this population can be as high as 90% (Copper et al., 1976; Cagetti et al., 1992; Taussky et al., 2012; Hanif, 2009; Raj et al., 2016; Luerssen et al., 1988). Objective: The goal of this study is to examine outcomes for patients 70 years and older who underwent craniotomy for aSDH. Methods: This is a retrospective study of patients 70 years and older who underwent craniotomy for evacuation of aSDH between 2006 and 2016. Patients with subacute, chronic, acute-on-chronic SDH and those considered too neurologically devastated to benefit from surgery were excluded. A multivariable logistic regression was performed to identify independent clinical factors associated with mortality. Results: A total of 1953 elderly patients with SDH were seen between 2006 and 2016. 1325 patients had non-surgical SDH, 307 were too neurologically devastated to benefit from surgery, and 321 elderly patients had surgery. 112 patients had a craniotomy for aSDH. The overall mortality rate was 42%. 24% of patients were discharged to home or a rehabilitation facility. Multivariable logistic regression analysis showed that age, Glasgow Coma Scale (GCS) score, and surgery type had a significant impact on mortality. Conclusion: Elderly patients with aSDH requiring surgery have a high likelihood of mortality. 24% of surgical patients were functional enough to go home or to a rehabilitation facility from the hospital. Age over 80 years old, GCS

Growth of large area single crystal CdTe layers was studied on $25 \times 25$ mm2 (211) Si substrates using metalorganic vapor phase epitaxy. High crystalline quality thick crystals with very good material uniformity were obtained. A 2-D monolithic detector array comprising ( $20 \times 20$ ) pixels was developed and evaluated. Each pixel is $1.12 \times 1.12$ mm2 size in a 1.17-mm pitch and consists of a p-CdTe/n-CdTe/n+-Si heterojunction diode structure, which is isolated from the surrounding pixels by making deep vertical cuts. The detector array exhibited highly uniform and low dark current, typically less than 0.5- $\mu \text{A}$ /cm2 per pixel at an applied reverse bias of 50 V. The spectroscopic performance was separately confirmed by dicing out a small portion from the array which clearly resolved energy peaks from 241Am gamma isotopes at room temperature. On the other hand, a significant improvement in the detection property was observed by cooling it to −30 °C.

Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with worse outcomes. PHI pathophysiology remains poorly understood and difficult to predict. We performed an exploratory analysis aimed at identifying markers in need of further investigation to establish their predictive value in PHI following TBI.We performed a retrospective chart review of prospectively collected data from 424 highest-level activation trauma patients from January 2012 through December 2013. Patients with severe TBI, defined as head acute injury scale (AIS) score ≥3 and intracranial hemorrhage (ICH) on initial CT, were included. Stable hemorrhage (SH) and PHI was determined by measuring ICH expansion on repeat CT within 6 h. Of 424 patients evaluated, 72 met inclusion criteria. Twenty-five patients had repeated samples available and were dichotomized into SH (n = 6, 24%) and PHI (n = 19, 76%). Levels of plasminogen, urokinase and tissue plasminogen activators (uPA, tPA), plasminogen activator inhibitor-1, α2-antiplasmin (α2AP), and D-Dimers (DD) were measured upon admission and 2, 4, and 6 h later.Longitudinal models identified tPA and DD as positively associated and α2AP inversely associated with PHI. High DD levels are strongly associated with developing PHI over time. Using the full TBI cohort of N = 72, receiver operating curve analysis provided a cutoff of 3.04 μg/mL admission DD to distinguish SH from PHI patients.Our findings support a relationship between markers of fibrinolysis in polytrauma patients with severe TBI and PHI, warranting further investigation into the potential for novel, predictive biomarkers.

Single-crystal (211) and (100) CdTe layers have been grown by metalorganic vapor-phase epitaxy using the same condition on (211) and (100) Si substrates, respectively. Prior to the growth, substrates of both orientations were pretreated using the same pretreatment procedure. The crystal qualities of the grown layers were evaluated by full-width at half-maximum values of double-crystal x-ray rocking curves, and photoluminescence spectra at 4.2 K. (211) CdTe layers showed better crystallinity than (100) layers. The crystal quality of the (100) CdTe layers was also compared with that of layers grown on an epitaxial (100) GaAs layer on Si substrate. The results suggest that (100) CdTe layers with improved crystal quality could be obtained by optimizing the procedure of the Si substrates.

Permethylation is a common derivatization method for MS-based glycomic analyses. Permethylation enhances glycan ionization efficiency in positive MS analysis and improves glycan structural stability. Recent biological glycomic studies have added to the growing body of knowledge and suggest the need for complete structural analysis of glycans. However, reverse phase LC analysis of permethylated glycans usually results in poor isomeric separation. To achieve isomeric separation of permethylated glycans, a porous graphitic carbon (PGC) column was used. PGC columns are well known for their isomeric separation capability for hydrophilic analyses. In this study, we have optimized temperature conditions to overcome the issues encountered while separating permethylated glycans on a PGC column and found that the highest temperature examined, 75°C, was optimal. Additionally, we utilized tandem MS to elucidate detailed structural information for the isomers separated. Glycan standards were also utilized to facilitate structural identifications through MS/MS spectra and retention time comparison. The result is an efficient and sensitive method capable of the isomeric separation of permethylated glycans. This method was successfully applied for the isomeric characterization of N-glycans released from the breast cancer cell lines MDA-MB-231 and MDA-MB-231BR (brain seeking). A total of 127 unique glycan structures were identified with 39 isobaric structures, represented as 106 isomers, with 21 non-isomeric glycans. Thirty seven structures exhibited significant differences in isomeric distribution (P < 0.05). Additionally, alterations in the distribution of isomeric sialylated glycans, structures known to be involved in cell attachment to the blood-brain barrier during brain metastasis, were observed.

Background Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. Methods We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. “Early plasma” was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Results Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71–1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20–9.35). Conclusion Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage.

This study aims to assess outcomes of pediatric patients with blunt traumatic brain injury (TBI) with a presenting Glasgow Coma Score (GCS) of 3.After local institutional review board approval, we identified patients ages 0 to15 years with blunt TBI and a reported GCS of 3 between 2007 and 2017 from a pediatric level 1 trauma center prospective registry. Exclusion criteria were cardiac death on arrival and penetrating injury. We recorded clinical variables from patients with a non-pharmacologic GCS of 3 and pupillary exam documented by a neurosurgical attending or resident. The original Glasgow Outcome Scale (GOS) was used to compare with other studies. Importance of variables to survival was calculated.A total of 88 patients (mean age 6.9 years) were included with a mortality rate of 68%. Twelve percent had a poor long-term outcome (GOS 2 or 3) while 20% had a good long-term outcome (GOS 4 or 5). Median follow-up was 1.8 years. Initial group comparison revealed patients in group 1 (survivors) had less hypotension on arrival (14% SBP 90 mmHg vs. 66%, p 0.0001), higher temperatures on arrival (36.3 °C vs 34.9 °C, p = 0.0002), lower ISS (29.7 vs 39.5, p = 0.003), less serious injury to other major organs (34% vs 61%, p = 0.02), more epidural hematomas (24% vs 7%, p = 0.04), and less evidence of brain ischemia on CT (7% vs 39%, p = 0.002) or brainstem infarct, hemorrhage, or herniation (0% vs 27%, p = 0.002). Differences between the 2 groups in age, sex, race, MOI, AIS score, presence of midline shift 5 mm, or time from injury to hospital arrival or time to surgery were not statistically significant. Classification tree analysis showed that the most important variable for survival was pupillary exam; mortality was 92% in presence of bilateral, fixed dilated pupils. The relative importance of initial temperature, MOI, and hypotension to survivability was 0.79, 0.75, and 0.47, respectively.Twenty percent of our pediatric non-pharmacologic GCS 3 cohort had a good functional outcome. Lack of bilaterally fixed and dilated pupils was the most important factor for survival. Temperature, MOI, and hypotension also correlated with survival. The data support selective aggressive management for these patients.

Background Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions. Methods Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods ( Results Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes. Conclusions Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.

Diffuse axonal injury (DAI) is a type of traumatic brain injury (TBI) that results from a blunt head injury. In this particular subtype, accelerating-decelerating motions cause white matter tract damage and preferentially impact regions including the corpus callosum and brainstem. The neurological compromise therefore relates to the severity of the axonal insult. The most common mechanism for DAI is high-speed motor vehicle accidents, and the clinical presentation is typically out of proportion to the CT findings. As a result, MRI is the modality of choice. Currently, there are limited therapeutic options, and management is identical to other forms of TBI including intracranial pressure and cerebral perfusion pressure management. As this disease is heterogeneous, survivors have a wide range of functional outcomes.

Brain injury; Head trauma; Algorithm Daño cerebral; Trauma en la cabeza; Algoritmo Lesió cerebral; Trauma al cap; Algoritme Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management. We thank our financial supporters who include Adler/Geirsch Attorney at Law, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care, Bard, the Brain Trauma Foundation, DePuy, Hemedex, Integra, the Neurointensive Care Section of the European Society of Intensive Care Medicine, Neurosurgical Society of Australasia, Medtronic, Moberg Research, Natus, Neuroptics, Raumedic, Sophysa, Stryker, and Zoll.

Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.

Background Intracranial hemorrhage carries significant morbidity and mortality, particularly if associated with hydrocephalus. Management of hydrocephalus includes temporary external ventricular drainage, with or without shunting. Thalamic location is an independent predictor of mortality and increases the likelihood of shunt dependence. Objective To determine whether endoscopic third ventriculostomy (ETV) can avoid the need for shunt placement and expedite recovery. Methods We prospectively identified thalamic intracranial hemorrhage patients who developed acute hydrocephalus requiring cerebrospinal fluid diversion by extraventricular drain placement from November 2017 to February 2019. Patients who failed an extraventricular drain clamping trial were then evaluated for eligibility for an ETV procedure. Patients who underwent ETV were then followed up for the development of hydrocephalus, need for shunting, and length of stay in the intensive care unit. Results Eight patients (7 males, 1 female) were prospectively enrolled. All patients underwent an ETV successfully. None of the patients required shunting. ETV was performed despite the presence of other factors that would have prevented shunt placement, including fever, leukocytosis, and gastrostomy tube placement. Seven patients who underwent ETV were evaluated at 3-mo follow-up and did not require shunting. Conclusion ETV is a safe and effective technique for the management of hydrocephalus resulting from an extraventricular obstruction in thalamic hemorrhage. It can avoid the need for permanent shunting in this patient population. Larger studies should be conducted to validate and further analyze this intervention.

Object: Although contact sport-related head injuries are frequently reported, golf cart accidents may have significant consequences including severe traumatic brain injury (TBI) or head injury. As no standardized regulations exist, this mechanism may be underreported. Methods: A retrospective review of TBI or cranial trauma after a golf cart accident at a level I trauma center over 5 years were performed. Data regarding age, sex, race, initial Glasgow Coma Scale score, alcohol status, type and location of the injury, and outcomes were analyzed and reported in terms of Modified Rankin Scale (MRS). Results: A total of 23 patients with TBI or cranial trauma following golf cart accident were identified. The mean age was 36 years old with the most common injury being skull fracture followed by acute subdural hematoma. Most patients had good outcomes, MRS 0-3, at discharge, but like most forms of TBI, surgical interventions, intracranial pressure monitoring, post-traumatic seizures, hydrocephalus, and death did occur. Conclusions: Head injuries sustained by golf cart accidents are not insignificant and may be underreported. More awareness of these injuries and safety guidelines are needed.

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.

Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood–brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5–8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×106 cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065–1079

H2/Ar electron cyclotron resonance plasma processing of the high-resistivity (111) CdTe crystals was studied to find its effect on the leakage current and the gamma ray detection properties of the detectors. All the crystals were chemically etched in a bromine–methanol (BM) solution prior to the plasma processing to obtain a smooth surface. A remarkable reduction in both the surface and the bulk leakage current was observed in the plasma processed detectors when compared with the unprocessed one. The gamma detection property of the detectors, both the spectral resolution and the peak shape, was also significantly improved. X-ray photoelectron spectroscopy confirmed that an excess Te-rich surface layer was present on the BM etched crystal, however, such layer was removed, and the surface atomic ratio was modified after the plasma processing. The improvement in the detector performance could be related to the change in the surface chemical states of the crystals. Hence, this could be a promising process for improving the detectors performance and their stabilities.