Significant Intracranial Hemorrhage Research Articles

Expanded Brain CT Dataset for the Development of AI Systems for Intracranial Hemorrhage Detection and Classification

Intracranial hemorrhage (ICH) is a dangerous life-threatening condition leading to disability. Timely and high-quality diagnosis plays a huge role in the course and outcome of this disease. The gold standard in determining ICH is computed tomography. This method requires a prompt involvement of highly qualified personnel, which is not always possible, for example, in case of a staff shortage or increased workload. In such a situation, every minute counts, and time can be lost. The solution to this problem seems to be a set of diagnostic decisions, including the use of artificial intelligence, which will help to identify patients with ICH in a timely manner and provide prompt and quality medical care. However, the main obstacle to the development of artificial intelligence is a lack of high-quality datasets for training and testing. In this paper, we present a dataset including 800 brain CT scans consisting of multiple series of DICOM images with and without signs of ICH, enriched with clinical and technical parameters, as well as the methodology of its generation utilizing natural language processing tools. The dataset is publicly available, which contributes to increased competition in the development of artificial intelligence systems and their advancement and quality improvement.

Traverse: A Phase 2, Open-Label, Randomized Study of Acalabrutinib in Combination with Venetoclax and Rituximab in Patients with Treatment-Naive Mantle Cell Lymphoma

Background and Significance: Despite advances in treatment for mantle cell lymphoma (MCL), no curative option exists. Currently, the majority of patients with treatment-naive (TN) MCL receive chemoimmunotherapy, which can result in prolonged remissions, but is associated with significant toxicity. Almost all patients inevitably relapse, and therefore, frontline chemotherapy-free options are being increasingly explored. Acalabrutinib is a highly selective, second-generation Bruton tyrosine kinase inhibitor (BTKi) approved for the treatment of adult patients with relapsed/refractory (R/R) MCL. In a phase 1b study in patients with TN MCL, acalabrutinib in combination with venetoclax and rituximab (AVR) demonstrated high rates of clinical and molecular response with an acceptable toxicity profile, supporting its continued development as a chemotherapy-free treatment option (Wang et al. Blood. 2021; Wang et al. Blood. 2022). Furthermore, the occurrence of complete responses (CRs) with clearance of minimal residual disease (MRD) in MCL clinical trials suggests that treatment may be stopped in these patients, as observed in patients with chronic lymphocytic leukemia who received combination therapy with venetoclax and rituximab. Study Design and Methods: TrAVeRse (NCT#05951959) is a phase 2, open-label, randomized, multicenter, international study of AVR in patients with TN MCL. Patients aged ≥18 years with an Eastern Cooperative Oncology Group performance status of 0-2 (3 if due to lymphoma), and Ann Arbor stage II, III, or IV disease are eligible. Key exclusion criteria are active central nervous system involvement by lymphoma or leptomeningeal disease, severe/life-threatening illness or medical condition, clinically significant cardiovascular disease, stroke, or intracranial hemorrhage within 6 months of enrollment, and any active uncontrolled infection. Approximately 125 patients will be screened to achieve a study population of 100 patients. During the induction phase, patients will receive oral acalabrutinib 100 mg twice daily (BID) in 28-day cycles for 13 cycles, starting at cycle 1; oral venetoclax once daily, starting at cycle 2 at a dose of 20 mg daily, with ramp-up to a maximum of 400 mg daily over 5 weeks for a total of 12 cycles; and intravenous rituximab 375 mg/m 2 on day 1 of every cycle for 12 cycles, starting at cycle 1. Patients who complete 13 cycles of AVR induction will be centrally tested for MRD status and continue to receive acalabrutinib 100 mg BID for 1 additional cycle (cycle 14) while awaiting disease response assessment and MRD results. Patients who achieve an MRD-negative CR (in peripheral blood at a threshold of 10 -5) at the end of induction will be randomly assigned in a 1:1 ratio to either continue to receive acalabrutinib 100 mg BID or to observation from cycle 15. Randomization will be stratified according to the simplified MCL International Prognostic Index [sMIPI] score (low [score, 0-3] and intermediate risk [4-5] vs high risk [6-11]), histologic features (blastoid or pleomorphic vs classical histology), and TP53 status (mutated vs unmutated). Those with an MRD-positive CR, partial response (PR), or stable disease (SD) at end of induction will continue to receive acalabrutinib 100 mg BID until disease progression, death, or unacceptable toxicity. Patients who progress during observation may be retreated with acalabrutinib 100 mg BID at relapse. The primary endpoint of this study is the MRD-negative CR rate at the end of AVR induction (ie, end of cycle 13). Secondary endpoints include MRD-negative CR rate at any point during the study, objective response rate and CR rate, duration of response, time to next treatment, progression-free survival, event-free survival, overall survival, safety, and tolerability. The study will also assess the feasibility of response-adapted treatment cessation for those who achieve MRD-negative CR after AVR induction and the efficacy of acalabrutinib retreatment in the subgroup of patients randomized to observation who subsequently relapse. Patients will be followed for 36 months post last patient randomized. Enrollment is planned to begin Q3 of 2023 including sites in North America, Australia, and Europe. Summary: This study will evaluate the efficacy of AVR, a chemotherapy-free triplet combination therapy, in patients with TN MCL.

BRUIN MCL-321: A phase 3, open-label, randomized study of pirtobrutinib versus investigator choice of BTK inhibitor in patients with previously treated, BTK inhibitor naïve mantle cell lymphoma.

TPS7587 Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKi) have transformed the management of MCL, but these agents are not curative. cBTKi share pharmacologic liabilities (e.g., low oral bioavailability, short half-life), which collectively may lead to suboptimal BTK target coverage especially in rapidly proliferating tumors with high BTK protein turnover such as MCL, which can manifest as acquired resistance to BTKi. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. In the phase 1/2 BRUIN study, pirtobrutinib demonstrated promising durable overall response rates and was well tolerated in patients (pts) with MCL regardless of prior therapy (including cBTKi), number of prior lines of therapy, or reason for prior cBTKi discontinuation. Pirtobrutinib was approved by the FDA in January 2023 for R/R MCL after 2 prior lines of therapy including a BTKi. The objective of this study is to establish whether pirtobrutinib is superior to investigator’s choice of cBTKi in pts with previously treated, BTKi naïve MCL. Methods: BRUIN MCL-321 (NCT04662255) is a randomized, open-label, global phase 3 study comparing pirtobrutinib monotherapy versus investigator’s choice of cBTKi monotherapy (ibrutinib, acalabrutinib, or zanubrutinib) in pts with previously treated, BTKi naïve MCL. Approximately 500 pts will be randomized 1:1 and stratified by sMIPI risk (low/intermediate vs high), comparator BTKi (ibrutinib vs acalabrutinib/zanubrutinib), and number of prior lines of therapy (1 vs ≥ 2). Enrollment for this study is ongoing. Adults with a diagnosis of MCL who have received ≥ 1 prior line of systemic therapy for MCL and are BTKi naïve are eligible. Pts must have measurable disease by imaging per Lugano criteria and have progressed on or relapsed following the most recent line of therapy. A history of current or prior CNS involvement, significant cardiovascular disease, stroke or intracranial hemorrhage within 6 months of randomization, and autologous stem cell transplant (SCT), allogeneic SCT or chimeric antigen receptor (CAR) T-cell therapy within 60 days of randomization are key exclusion criteria. Progression-free survival (PFS) per Lugano criteria assessed by an independent review committee is the primary endpoint. Overall response rate, duration of response, investigator-assessed PFS per Lugano criteria, overall survival, event-free survival, time to treatment failure, time to next treatment, PFS2 (time from randomization to disease progression on next line of treatment or death from any cause), safety and tolerability, and pt reported outcomes are secondary endpoints. Clinical trial information: NCT04662255 .

Surgical Resection of Deep-Seated Arteriovenous Malformations Through Stereotactically Guided Tubular Retractor Systems: A Case Series.

Arteriovenous malformations (AVMs) in the subcortical and/or periventricular regions can cause significant intraventricular and intracranial hemorrhage. These AVMs can pose a unique surgical challenge because traditional, open approaches to the periventricular region require significant cortical/white matter retraction to establish sufficient operative corridors, which may result in risk of neurological injury. Minimally invasive tubular retractor systems represent a novel, feasible surgical option for treating deep-seated AVMs. To explore 5 cases of NICO BrainPath-assisted resection of subcortical/periventricular AVMs. Five patients from a single institution were operated on for deep-seated AVMs using tubular retractor systems. Collected data included demographics, AVM specifications, preoperative neurological status, postoperative neurological status, and postoperative/intraoperative angiogram results. Five patients, ranging from age 10 to 45 years, underwent mini-craniotomy for stereotactically guided tubular retractor-assisted AVM resection using neuronavigation for selecting a safe operative corridor. No preoperative embolization was necessary. Mean maximum AVM nidal diameter was 8.2 mm. All deep-seated AVMs were completely resected without complications. All AVMs demonstrated complete obliteration on intraoperative angiogram and on 6-month follow-up angiogram. Minimally invasive tubular retractors are safe and present a promising surgical option for well-selected deep-seated AVMs. Furthermore, study may elucidate whether tubular retractors improve outcomes after microsurgical AVM resection secondary to mitigation of iatrogenic retraction injury risk.

Effect of tracheostomy timing in pediatric patients with traumatic brain injury.

Traumatic brain injury (TBI) is a prevalent cause of disability and death in the pediatric population, often requiring prolonged mechanical ventilation. Patients with significant TBI or intracranial hemorrhage require advanced airway management to protect against aspiration, hypoxia, and hypercarbia, eventually necessitating tracheostomy. While tracheostomy is much less common in children compared to adults, its prevalence among pediatric populations has been steadily increasing. Although early tracheostomy has demonstrated improved outcomes in adult patients, optimal tracheostomy timing in the pediatric population with TBI remains to be definitively established. This retrospective cohort analysis aims to evaluate pediatric TBI patients who undergo tracheostomy and to investigate the impact of tracheostomy timing on outcomes. The Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), collected between in 2016 and 2019, was queried using International Classification of Disease 10th edition (ICD10) codes for patients with traumatic brain injury who had received a tracheostomy. Baseline demographics, insurance status, and procedural day data were analyzed with univariate and multivariate regression analyses. Propensity score matching was performed to estimate the incidence of medical complications and mortality related to early versus late tracheostomy timing (as defined by median=9 days). Of the 68,793 patients (mean age=14, IQR 4-18) who suffered a TBI, 1,956 (2.8%) received a tracheostomy during their hospital stay. TBI patients who were tracheostomized were older (mean age=16.5 vs 11.4 years), more likely to have injuries classified as severe TBIs and more likely to have accumulated more than one indicator of parenchymal injury as measured by the Composite Stroke Severity Scale (CSSS >1) than non-tracheostomized TBI patients. TBI patients with a tracheostomy were more likely to encounter serious complications such as sepsis, acute kidney injury (AKI), meningitis, or acute respiratory distress syndrome (ARDS). They were also more likely to necessitate an external ventricular drain (EVD) or decompressive hemicraniectomy (DHC) than TBI patients without a tracheostomy. Tracheostomy was also negatively associated with routine discharge. Procedural timing was assessed in 1,867 patients; older children (age >15 years) were more likely to undergo earlier placements (p<0.001). Propensity score matching (PSM) comparing early versus late placement was completed by controlling for age, gender, and TBI severity. Those who were subjected to late tracheostomy (>9 days) were more likely to face complications such as AKI or deep vein thrombosis (DVT) as well as a host of respiratory conditions such as pulmonary embolism, aspiration pneumonitis, pneumonia, or ARDS. While the timing did not significantly impact mortality across the PSM cohorts, late tracheostomy was associated with increased length of stay (LOS) and ventilator dependence. Tracheostomy, while necessary for some patients who have sustained a TBI, is itself associated with several risks that should be assessed in context of each individual patient's overall condition. Additionally, the timing of the intervention may significantly impact the trajectory of the patient's recovery. Early intervention may reduce the incidence of serious complications as well as length of stay and dependence on a ventilator and facilitate a timelier recovery.

Text Analysis of Radiology Reports with Signs of Intracranial Hemorrhage on Brain CT Scans Using the Decision Tree Algorithm.

The initial data is a download from the Unified Radiological Information Service of the Unified Medical Information and Analytical System (URIS UMIAS) containing 34,188 studies obtained by a non-contrast CT of the brain in 56 inpatient medical settings. Data analysis and preprocessing were carried out using NLTK (Natural Language Toolkit, version 3.6.5), a library for symbolic and statistical processing of natural language, and scikit-learn, a machine learning library containing tools for classification tasks. According to 14 selected ICH-related key words, as well as 33 stop-phrases with key words denoting absence of ICH, an automatic selection of the CT investigations and their subsequent expert verification were carried out. Two classes of investigations were formed based on the sample from 3980 protocol descriptions: containing descriptions of ICH and without them. The problem of binary classification was solved using the decision tree algorithm as a model. To evaluate the performance of the model, the CT investigations were divided randomly into samples in the ratio of 7:3. Of 3980 protocols, 2786 were assigned to the training data set, 1194 - to the test one. According to the test results, the designed and trained algorithm in the binary classification of the CT reports "with signs of ICH" and "without signs of ICH" has shown sensitivity of 0.94, specificity of 0.88, F-score of 0.83. The developed and trained algorithm for the analysis of radiology reports has demonstrated high accuracy in relation to brain CT with signs of intracranial hemorrhage and can be used to solve binary classification problems and create appropriate data sets. However, it is limited by the need for manual revision of CT studies to ensure quality control.

Centromedian thalamic deep brain stimulation for drug-resistant epilepsy: single-center experience.

Neuromodulation of the centromedian nucleus of the thalamus (CM) has unclear effectiveness in the treatment of drug-resistant epilepsy. Prior reports suggest that it may be more effective in the generalized epilepsies such as Lennox-Gastaut syndrome (LGS). The objective of this study was to determine the outcome of CM deep brain stimulation (DBS) at the authors' institution. Retrospective chart review was performed for all patients who underwent CM DBS at Emory University, which occurred between December 2018 and May 2021. CM DBS electrodes were implanted using three different surgical methods, including frame-based, robot-assisted, and direct MRI-guided. Seizure frequency, stimulation parameters, and adverse events were recorded from subsequent clinical follow-up visits. Fourteen patients underwent CM DBS: 9 had symptomatic generalized epilepsy (including 5 with LGS), 3 had primary or idiopathic generalized epilepsy, and 2 had bifrontal focal epilepsy. At last follow-up (mean [± SEM] 19 ± 5 months, range 4.1-33 months, ≥ 6 months in 11 patients), the median seizure frequency reduction was 91%. Twelve patients (86%) were considered responders (≥ 50% decrease in seizure frequency), including 10 of 12 with generalized epilepsy and both patients with bifrontal epilepsy. Surgical adverse events were rare and included 1 patient with hardware breakage, 1 with a postoperative aspiration event, and 1 with a nonclinically significant intracranial hemorrhage. CM DBS was an effective treatment for drug-resistant generalized and bifrontal epilepsies. Additional studies and analyses may investigate whether CM DBS is best suited for specific epilepsy types, and the relationship of lead location to outcome in different epilepsies.

BRUIN MCL-321: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib Versus Investigator Choice of BTK Inhibitor in Patients with Previously Treated, BTK Inhibitor Naïve Mantle Cell Lymphoma (Trial in Progress)

BRUIN MCL-321: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib Versus Investigator Choice of BTK Inhibitor in Patients with Previously Treated, BTK Inhibitor Naïve Mantle Cell Lymphoma (Trial in Progress)

29 Comparison of Risk Factors and Outcomes for Blunt Trauma Patients on Anticoagulants or Antiplatelet Agents Evaluated in Urban and Suburban Settings

In the United States, there has been an increase in anticoagulation or anti-platelet agents in the geriatric population. This demographic is also at risk for falls or other blunt trauma, resulting in significant post-injury bleeding. The best management strategy for anti-platelet-related bleeding is still under debate. Preliminary data suggest that the incidence of clinically significant intracranial hemorrhage is significantly lower with NOAC/DOACs than with anti-Vitamin K anticoagulants. Nonetheless, the risk of bleeding is still present.

Comparison of the Safety of Prophylactic Anticoagulants After Intracranial Surgery.

Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited. To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery. We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature. In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n=27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7%vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4%vs 0.5%, P=.008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P=.005). We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH.

P133 Types and timing Of venous thromboembolism Prophylaxis for Traumatic Brain Injury (TOP TBI) Study

BackgroundPatients with traumatic brain injury are at significant risk for both developing venous thromboembolisms and haemorrhagic progression. Pharmacological thromboprophylaxis and mechanical thromboprophylaxis may be able to minimise the incidence of venous thromboembolisms. Problematically, pharmacological thromboprophylaxis also has the potential to augment clinically significant intracranial haemorrhage expansion. Compounding this issue is that the evidence for mechanical thromboprophylaxis is not based on neurotrauma populations, and there is insufficient evidence to guide clinicians on the optimum agent, dose, and timing of pharmacological thromboprophylaxis. Based on the need for high quality evidence, we propose the Types and timing Of venous thromboembolism Prophylaxis for Traumatic Brain Injury (TOP TBI) Study.AimTo collect high quality and relevant data regarding thromboprophylaxis practice and associated outcomes - including rates of venous thromboembolisms, intracranial haemorrhage expansion and mortality – for TBI patients in the UK and Ireland in order to optimise management for these patients.MethodsWe will adopt a multicentre, prospective, observational cohort design. All neurosurgical units: in the UK and Ireland will be eligible to participate. Patient eligibility will be determined according to pre-specified criteria. Eligible cases will be prospectively recruited over two months and followed-up in 6 months. Based on epidemiological investigations and data from the Trauma Audit and Research Network, we expect to recruit between 1000 to 2000 patients. Anonymised data will be collected locally and submitted to a secure web-based central database.Outcome measuresThese include all-cause mortality, venous thromboembolism events, haemorrhagic progression, re-admission, surgical intervention, length of stay in admitting unit, neurological status, and Extended Glasgow Outcome Scale during follow-up.ConclusionTOP TBI is an important step in the ongoing efforts to optimise the outcomes of patients who have suffered a traumatic brain injury. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and inform future studies.

Evaluation of the single stage treatment of intracranial or extracranial artery stenosis combined with intracranial aneurysm:experience from a single center

Objective: To investigate the strategy and the clinical effect of single stage treatment for intracranial or extracranial artery stenosis with intracranial aneurysm. Methods: The clinical data of 15 patients with intracranial aneurysms and extracranial or intracranial artery stenosis treated by one-stage endovascular therapy at Department of Neurosurgery of Peking University First Hospital from April 2013 to September 2018 were analyzed,respectively.There were 6 males and 9 females,aged (63.9±9.1)years (range:43 to 79 years).Fifteen arterial stenosis were found, including 8 in anterior circulatiion and 7 in posterior circulation, and the stenosis rates ranged from 75% to 95%. There were 17 aneurysms, among which 11 in the anterior circulation and 6 in the posterior.The maximal diameter was (5.3±1.2)mm (range:3 to 7 mm).All patients were treated with stenting and embolization at one stage. The operation choices, perioperative and postoperative symptoms,imaging data and complications were recorded. Results: Stents were successfully implanted into arterial stenosis of 15 cases, reducing the stenosis rates to less than 30%.Among the 17 aneurysms,10 cases were treated by coil embolization alone,7 cases by stenting and coil embolization. Eventually all the 17 aneurysms reached complete embolization.One patient had mild symptoms of the cerebral infarction during the perioperative period,and the rest had not shown surgical complications.The follow-up time was (43.8±8.2)months (range:24 to 85 months). All the patients underwent digital subtraction angiography 6 to 12 months after operation.Among them,2 cases had asymptomatic in-stent restenosis,and no recurrence was found in aneurysms.Up to the last follow-up,no patients had showed new symptoms or signs of intracranial hemorrhage or ischemic stroke. Conclusions: For patients suffered from both stenosis and aneurysms,individualized treatment should be made based on the location and severity of the vascular stenosis and aneurysms.With careful preoperative evaluation and surgical planning,the single stage endovascular treatment for intracranial or extracranial artery stenosis combined with intracranial aneurysm is safe,feasible and effective for selected patients.

S100B protein level for the detection of clinically significant intracranial haemorrhage in patients with mild traumatic brain injury: a subanalysis of a prospective cohort study

BackgroundClinical assessment of patients with mild traumatic brain injury (mTBI) is challenging and overuse of head CT in the ED is a major problem. Several studies have attempted to reduce...

Delayed Intracranial Hemorrhage After Blunt Head Injury With Direct Oral Anticoagulants

IntroductionPatients presenting to the Emergency Department (ED) following head injury are frequently evaluated with an initial computed tomography scan (CT) of the brain. Imaging is particularly important in patients who are receiving medications that alter normal blood hemostasis. As an imaging modality, CT has a high negative predictive value when used to rule out clinically significant acute intracranial hemorrhage. Patients receiving anticoagulant or antiplatelet therapy have both an increased risk of initial hemorrhage, as well as an increased risk of mortality above nonanticoagulated patients, should they suffer hemorrhage. Multiple studies of delayed intracranial hemorrhage have placed the risk among the patients taking warfarin at the time of head injury in the range of 0.6-6.0%. However, data regarding the risk of delayed intracranial hemorrhage in patients taking the class of agents referred to as Direct-Acting Oral Anticoagulants (DOACs) remains limited. This study aims to estimate this risk. MethodsA retrospective chart review was performed to identify patients on DOACs who presented to our Level I trauma center following blunt head injury between January 2017 and August 2018. Patients with a negative initial head CT were selected. From this subset, data regarding demographics, injury characteristics, anticoagulant use, and antiplatelet use were collected. ResultsOverall, 314 patients were included; 129 patients taking rivaroxaban, 182 patients taking apixaban, and four patients taking dabigatran. In approximately 29% of the patients, the sole indication for admission was close monitoring following head injury while taking an anticoagulant agent. The mechanism of injury for the majority of the patients was fall. Of the 314 patients, three were found to have delayed intracranial hemorrhage on the repeated head CT (0.95%). Two of these three patients were on concomitant antiplatelet medication. None of the three individuals required neurosurgical intervention. Conclusionsat the time of submission, this is the largest study estimating the risk of delayed intracranial hemorrhage among patients on DOACs. Based on the results of this study, patients who sustain a blunt head injury while taking only DOACs; that is, without concurrent antiplatelet medication, admission, and repeat head CT may not be necessary after confirming a negative initial CT scan.

Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma.

Pediatric low-grade gliomas (pLGGs) are the most common CNS tumor of childhood and comprise a heterogenous group of tumors. Children with progressive pLGG often require numerous treatment modalities including surgery, chemotherapy, rarely radiation therapy and, more recently, molecularly targeted therapy. We describe our institutional experience using the MEK inhibitor, trametinib, for recurrent/progressive pLGGs. We performed a retrospective, IRB-approved, chart review of all pediatric patients treated with trametinib for recurrent/progressive pLGGs at Dana-Farber/Boston Children's Cancer and Blood Disorder Center between 2016 and 2018. Eleven patients were identified, of which 10 were evaluable for response. Median age at commencement of trametinib treatment was 14.7years (range 7.3-25.9years). Tumor molecular status included KIAA1549-BRAF fusion(n = 4), NF1 mutation(n = 4), FGFR mutation(n = 1) and CDKN2A loss (n = 1). Median number of prior treatment regimens was 5 (range 1-12). Median duration of treatment with trametinib was 19.2months (range 3.8-29.8months). Based on modified RANO criteria, best responses included partial (n = 2), minor response (n = 2) and stable disease (n = 6). Two patients remain on therapy (29.8 and 25.9months, respectively). The most common toxicities attributable to trametinib were rash, fatigue and gastrointestinal disturbance. Five patients required dose reduction for toxicities. Two patients experienced significant intracranial hemorrhage (ICH) while on trametinib. While it is unclear whether ICH was directly attributable to trametinib, therapy was discontinued. Trametinib appears to be an effective treatment for patients with recurrent/progressive pLGG. The toxicities of this therapy warrant further investigation, with particular attention to the potential risk for intracranial hemorrhage. Early phase multi-institutional clinical trials are underway.

Safety of immediate use of nonsteroidal antiinflammatory drugs after pediatric craniotomy for tumor.

Postoperative pain can limit the recovery of children undergoing craniotomy for tumor resection, and pain management is highly variable between institutions and practitioners. Nonsteroidal antiinflammatory drugs (NSAIDs) are effective in treating postoperative pain following craniotomy, but their use has been limited by concerns about postoperative hemorrhage. The risk of postoperative hemorrhage is not insignificant in patients undergoing craniotomy for tumor resection. No study has specifically addressed the safety of NSAIDs in the immediate postoperative setting following craniotomy for tumor resection in pediatric patients. The authors performed a retrospective cohort study in patients younger than 18 years of age who underwent craniotomy for tumor resection at a single tertiary referral center between 2009 and 2019. The study outcomes were 1) postoperative hemorrhage requiring return to the operating room for decompression, evacuation, or CSF diversion for hemorrhage-associated hydrocephalus; and 2) more-than-minimal hemorrhage on routine postoperative imaging. Patients receiving any NSAID in the hospital formulary on the same day as surgery (postoperative day zero [POD0]) were designated as such. Two hundred seventy-six children underwent 308 craniotomies for tumor resection over the study period. One hundred fifty-four patients (50.0%) received at least one dose of an NSAID on POD0. Six patients (1.9%) required a return to the operating room for a hemorrhagic complication, including 3 who received an NSAID on POD0 (OR 1.00, 95% CI 0.20-5.03). Seventeen patients (6.3% of patients imaged) had more-than-minimal hemorrhage on routine postoperative imaging, 9 of whom received an NSAID on POD0 (OR 1.08, 95% CI 0.40-2.89). Use of NSAIDs on POD0 was not associated with either an increased risk of hemorrhage requiring a return to the operating room or asymptomatic hemorrhage on routine postoperative imaging. The overall incidence of clinically significant postoperative intracranial hemorrhage is low. These data support the use of NSAIDs as a safe measure for pain control in the postoperative setting for children undergoing craniotomy for tumor resection.

MP46: Clinically significant traumatic intracranial haemorrhage following minor head trauma in older adults: a retrospective cohort study

Introduction: The primary objective of this study was to determine the incidence of clinically significant traumatic intracranial haemorrhage (T-ICH) following minor head trauma in older adults. Secondary objective was to investigate the impact of anticoagulant and antiplatelet therapies on T-ICH incidence. Methods: This retrospective cohort study extracted data from electronic patient records. The cohort consisted of patients presenting after a fall and/or head injury and presented to one of five ED between 1st March 2010 and 31st July 2017. Inclusion criteria were age ≥ 65 years old and a minor head trauma defined as an impact to the head without fulfilling criteria for traumatic brain injury. Results: From the 1,000 electronic medical records evaluated, 311 cases were included. The mean age was 80.1 (SD 7.9) years. One hundred and eighty-nine (189) patients (60.8%) were on an anticoagulant (n = 69), antiplatelet (n = 130) or both (n = 16). Twenty patients (6.4%) developed a clinically significant T-ICH. Anticoagulation and/or antiplatelets therapies were not associated with an increased risk of clinically significant T-ICH in this cohort (Odds ratio (OR) 2.7, 95% CI 0.9-8.3). Conclusion: In this cohort of older adults presenting to the ED following minor head trauma, the incidence of clinically significant T-ICH was 6.4%.

LO88: S100B serum protein level for the detection of clinically significant intracranial hemorrhage in patients with mild traumatic brain injury: a prospective cohort study

Introduction: Clinical assessment of patients with mTBI is challenging and overuse of head CT in the emergency department (ED) is a major problem. During the last decades, studies have attempted to reduce unnecessary head CTs following a mTBI by identifying new tools aiming to predict intracranial bleeding. S100B serum protein level might be helpful reducing those imaging since a higher level of S-100B protein has been associated with intracranial hemorrhage following a mTBI in previous literature. The main objective of this study was to assess whether the S100B serum protein level is associated with clinically important brain injury and could be used to reduce the number of head CT following a mTBI. Methods: This prospective multicenter cohort study was conducted in five Canadian ED. MTBI patients with a Glasgow Coma Scale (GCS) score of 13-15 in the ED and a blood sample drawn within 24-hours after the injury were included. S-100B protein was analyzed using enzyme-linked immunosorbent assay (ELISA). All types of intracranial bleedings were reviewed by a radiologist who was blinded to the biomarker results. The main outcome was the presence of clinically important brain injury. Results: A total of 476 patients were included. Mean age was 41 ± 18 years old and 150 (31.5%) were female. Twenty-four (5.0%) patients had a clinically significant intracranial hemorrhage while 37 (7.8%) had any type of intracranial bleeding. S100B median value (Q1-Q3) of was: 0.043 ug/L (0.008-0.080) for patients with clinically important brain injury versus 0.039 μg/L (0.023-0.059) for patients without clinically important brain injury. Sensitivity and specificity of the S100B protein level, if used alone to detect clinically important brain injury, were 16.7% (95% CI 4.7-37.4) and 88.5% (95% CI 85.2-91.3), respectively. Conclusion: S100B serum protein level was not associated with clinically significant intracranial hemorrhage in mTBI patients. This protein did not appear to be useful to reduce the number of CT prescribed in the ED and would have missed many clinically important brain injuries. Future research should focus on different ways to assess mTBI patient and ultimately reduce unnecessary head CT.

Clinically significant traumatic intracranial hemorrhage following minor head trauma in older adults: a retrospective cohort study

ABSTRACT Objectives The primary objective of this study was to determine the incidence of clinically significant traumatic intracranial hemorrhage (T-ICH) following minor head trauma in older adults. Secondary objective was to investigate the impact of anticoagulant and antiplatelet therapies on T-ICH incidence. Methods This retrospective cohort study extracted data from electronic patient records. The cohort consisted of patients presenting after a fall and/or head injury and presented to one of five ED between 1st March 2010 and 31st July 2017. Inclusion criteria were age ≥ 65 years old and a minor head trauma defined as an impact to the head without fulfilling criteria for traumatic brain injury. Results From the 1,000 electronic medical records evaluated, 311 cases were included. The mean age was 80.1 (SD 7.9) years. One hundred and eighty-nine (189) patients (60.8%) were on an anticoagulant (n = 69), antiplatelet (n = 130) or both (n = 16). Twenty patients (6.4%) developed a clinically significant T-ICH. Anticoagulation and/or antiplatelets therapies were not associated with an increased risk of clinically significant T-ICH in this cohort (Odds ratio (OR) 2.7, 95% CI 0.9–8.3). Conclusions In this cohort of older adults presenting to the ED following minor head trauma, the incidence of clinically significant T-ICH was 6.4%.

A descriptive study on acute gastroenteritis with convulsion: 1-year analysis

Introduction Several etiologies explain the occurrence of seizures with acute gastroenteritis, such as electrolyte abnormalities and dehydration, a high fever, infectious fragments of pathogens crossing blood-brain barrier and causing significant central nervous system damage, septicemia, intracranial hemorrhage, and hypoglycemia. The aim of this study was to detect the frequency and etiology of convulsion in children with acute gastroenteritis admitted to Assiut University Children Hospital during 1 year from January 2017 to the end of December 2017. Patients and methods This is a one-year descriptive study that was carried out on 130 patients having acute gastroenteritis with convulsion, aged from 1 month to 5 years. Patients were divided according to the age into two groups: group 1, from 1 to 12 months of age, and group 2, from more than 1 to 5 years. All cases were subjected to full history, complete physical examination, and investigations, which included complete blood count, serum electrolytes, renal function tests, arterial blood gases, random blood sugar, and blood culture, which was done only when sepsis is suspected. Results The results show that the frequency of convulsion was 4.6%. The most common cause was electrolyte disturbance, which was noticed in 106 (81.5%) cases, followed by central nervous system infection, which was noticed in 39 (30%) cases, then septicemia and hypoglycemia, which were noticed in 13 (10%) cases each, then febrile convulsion, which was noticed in 11 (8.5%) cases [regarding febrile convulsions, there was a statistically significant difference between the two age groups (P = 0.027)], and lastly, intracranial hemorrhage, which was noticed in five (3.8%) cases. Conclusion Convulsion is one of the most serious complications associated with acute gastroenteritis. A younger age group (1–12 months) is more susceptible to complications than the older age group. Electrolyte disturbance is still a major cause of convulsion with acute gastroenteritis.