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Background: Decompressive craniectomy (DC) is performed for the management of the patients with acutely elevated intracranial pressure (ICP). Considering the paucity of the evidence regarding the outcome predictors in patients with non-traumatic raised ICP, we aimed to assess short- and long-term outcome related factors in DC subjects. Methods: In this cross-sectional study, health records of the patients who underwent DC for non-traumatic etiologies over the five years were interrogated and demographic data, clinical features, operative findings, and follow-up notes were collected. The primary short- and long-term outcomes were in-hospital mortality and functional status, respectively. Functional status was evaluated using Glasgow Outcome Scale (GOS) at 6-month follow-up. Results: Of the 223 eligible patients, 113 (50.7 %) were male and the mean age was 48.68 ± 13.97 years. In-hospital mortality rate was 48.4 % (n = 108). Of the survivors, 28 (30.4 %) had favorable outcomes (GOS 4–5). The most common post-operative complications were infection with respiratory source (n = 52, 23 %) and external cerebral herniation (n = 61, 27.4 %). Presence of diabetes mellitus (DM) (OR = 6.09; 95 % CI = 2.0–18.51; P = 0.001), subarachnoid hemorrhage (SAH) (OR = 5.61; 95 % CI = 1.47––21.3; P = 0.01), and prolonged duration of ICU-stay (OR = 1.37; 95 % CI: 1.03, 1.24; P = 0.006) were associated with in-hospital mortality. Also, preexisting DM was two times more prevalent among the subjects deceased in the hospital than those who survived. Conclusions: Concomitant SAH, DM, and prolonged ICU stay were associated with increased in-hospital mortality. In addition, preexisting DM may increase mortality rates, likely irrespective of age factor.

Langerhans cell histiocytosis is a rare disease with diverse clinical presentations. We report a 4-year-old boy with progressive weakness in lower extremities, a large head lump, and inability to walk. On physical examination, bulged scalp, ulcerative skin lesions, engorged veins over the abdomen and chest, and decreased muscle strength were evident. The computed tomography and magnetic resonance imaging revealed lytic lesions on vertebral bodies (T5-T8), resulting in the destruction of T7 vertebra and compression of the spinal cord, along with abnormal meningeal enhancement and multiple enhanced cerebral lesions, mainly at the junction of white and gray matter. Biopsy of T7 vertebra revealed Langerhans cell histiocytosis, confirmed by S-100 and CD1a expression in immunohistochemistry. The clinical team should be vigilant for the insidious development of central nervous system (CNS) symptoms and seek the required neurosurgical interventions to have a timely and definitive diagnosis and tackle the CNS lesions before resulting in permanent deficits.

Abstract Biomedical ontologies are widely used to harmonize heterogeneous data and integrate large volumes of clinical data from multiple sources. This study analyzed the utility of ontologies beyond their traditional roles, that is, in addressing a challenging and currently underserved field of feature engineering in machine learning workflows. Machine learning workflows are being increasingly used to analyze medical records with heterogeneous phenotypic, genotypic, and related medical terms to improve patient care. We performed a retrospective study using neuropathology reports from the German Neuropathology Reference Center for Epilepsy Surgery at Erlangen, Germany. This cohort included 312 patients who underwent epilepsy surgery and were labeled with one or more diagnoses, including dual pathology, hippocampal sclerosis, malformation of cortical dysplasia, tumor, encephalitis, and gliosis. We modeled the diagnosis terms together with their microscopy, immunohistochemistry, anatomy, etiologies, and imaging findings using the description logic-based Web Ontology Language (OWL) in the Epilepsy and Seizure Ontology (EpSO). Three tree-based machine learning models were used to classify the neuropathology reports into one or more diagnosis classes with and without ontology-based feature engineering. We used five-fold cross validation to avoid overfitting with a fixed number of repetitions while leaving out one subset of data for testing, and we used recall, balanced accuracy, and hamming loss as performance metrics for the multi-label classification task. The epilepsy ontology-based feature engineering approach improved the performance of all the three learning models with an improvement of 35.7%, 54.5%, and 33.3% in logistics regression, random forest, and gradient tree boosting models respectively. The run time performance of all three models improved significantly with ontology-based feature engineering with gradient tree boosting model showing a 93.8% reduction in the time required for training and testing of the model. Although, all three models showed an overall improved performance across the three-performance metrics using ontology-based feature engineering, the rate of improvement was not consistent across all input features. To analyze this variation in performance, we computed feature importance scores and found that microscopy had the highest importance score across the three models, followed by imaging, immunohistochemistry, and anatomy in a decreasing order of importance scores. This study showed that ontologies have an important role in feature engineering to make heterogeneous clinical data accessible to machine learning models and also improve the performance of machine learning models in multilabel multiclass classification tasks.

Introduction Cerebral vasospasm (CVS) is the leading cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (aSAH). One of the recently implicated underlying mechanisms of CVS is inflammatory cascades. Specific feasibility objectives include determining the ability to recruit 30 participants over 24 months while at least 75% of them comply with at least 75% of the study protocol and being able to follow 85% of them for 3 months after discharge.Methods and analysis This is a feasibility study for a randomised controlled trial. Eligible participants are adult patients who are 18 years of age and older with an aSAH confirmed by a brain CT scan, and CT angiography, or magnetic resonance angiography, or digital subtraction angiography who admitted to the emergency department within 12 hours of the ictus. Eligible subjects will be randomised 1:1 for the administration of either ibuprofen or a placebo, while both groups will concomitantly be treated by the standard of care for 2 weeks. Care givers, patients, outcome assessors and data analysts will be blinded. This will be the first study to investigate the preventive effects of a short-acting non-steroidal anti-inflammatory drug on CVS and the key expected outcome of this pilot study is the feasibility and safety assessment of the administration of ibuprofen in patients with aSAH. The objectives of the definitive trial would be to assess the effect of ibuprofen relative to placebo on mortality, CVS, delayed cerebral ischaemia, and level of disability at 3-month follow-up.Ethics and dissemination This study is approved by Mashhad University of Medical Sciences ethical committee (IR.MUMS.MEDICAL.REC.1398.225). Results from the study will be submitted for publication regardless of whether or not there are significant findings.Trial registration number ISRCTN14611625.

Gliomas, the most common form of brain cancer, can range from relatively slow-growing low-grade to highly aggressive glioblastoma that has a median overall survival of only 15 months despite multimodal standard therapy. Although immunotherapy with checkpoint inhibitors has significantly improved patient survival for some cancers, to date, these agents have not shown consistent efficacy against malignant gliomas. Therefore, there is a pressing need to better understand the impact of host inflammatory responses on the efficacy of emerging immunotherapy approaches for these resistant tumors. RAGE is a multi-ligand pattern recognition receptor that is activated in various inflammatory states such as diabetes, Alzheimer’s disease, cystic fibrosis, and cancer. Low levels of RAGE can be found under normal physiological conditions in neurons, immune cells, activated endothelial, and vascular smooth muscle cells, but it is over-expressed under chronic inflammation due to the accumulation of its ligands. RAGE binds to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA which mediate downstream cellular responses that promote tumor growth, angiogenesis, and invasion. Both in vitro and in vivo studies have shown that inhibition of RAGE signaling can disrupt inflammation and cancer progression and metastasis. Here, we will review our current understanding of the role of RAGE pathway on glioma progression and how it could be exploited to improve the efficacy of immunotherapy approaches.

Abstract Background Healthcare-associated infections (HAIs) challenge modern medicine. Considering their high prevalence in Iran, we aimed to provide knowledge on the subject, and to teach about the importance of infection prevention and control (IPC) to a broad audience of pre-graduate healthcare professionals, focusing on education as the cornerstone of IPC. Main body We invited Iranian medical students to present ideas on “how to reduce HAIs.” Projects were eligible if being original and addressing the call. Accepted projects were quality assessed using a scoring system. Forty-nine projects were submitted, of which 37 met the inclusion criteria. They had a mean score of 69.4 ± 18.3 out of the maximum possible score of 115. Four reviewers assessed the 37 projects for clinical applicability, impact on patient safety, and innovation, and selected the best 12 to compete at the 2nd International Congress on Prevention Strategies for Healthcare-associated Infections, Mashhad, Iran, 2018. The competition took place in three rounds. The selected teams presented their projects in the first round and debated one by one in a knockout manner, while the jury reviewed their scientific content and presentation skills. In the second round, the top 5 projects competed for reaching the final stage, in which the teams presented their ideas in front of a panel of international IPC experts to determine the first three ranks. At the end of the contest, the participants gained valuable criticisms on how to improve their ideas. Moreover, by its motivating atmosphere, the contest created an excellent opportunity to promote IPC in medical schools. Conclusions Using innovation contests in pre-graduates is an innovative education strategy. It sensitizes medical students to the challenges of IPC and antimicrobial resistance and drives them to think about solutions. By presenting and defending their innovations, they deepen their understanding on the topic and generate knowledge transfer in both ways, from students to teachers and vice versa.

Background: The Woven EndoBridge (WEB) aneurysm embolization device is a relatively recent developed intrasaccular flow disruptor committed to intracranial wide-neck and complex aneurysm occlusion. In this study, we aimed to assess hemodynamic profiles of an AcomA aneurysm treated with WEB Single Layer (WEB-SL) to shed light on the understanding of hemodynamic alterations in the context of a recanalized aneurysm. Methods: Image-Based computational fluid dynamics (CFD) was used to simulate pre and post-treatment blood flow of an anterior communicating aneurysm treated with WEB-SL. The simulated velocity field was used to visualize and quantify velocity, wall shear stress (WSS), and pressure distributions. Results: Following WEB deployment, infiltration of flow and mean velocity magnitude were decreased considerably within the aneurysm sac. WSS was the only measured index that demonstrated a dual hemodynamic pattern; it reduced along the superior half of the aneurysm sac while slightly increased in the neck region. At one-year follow-up, angiography showed recanalization of the aneurysm, and the WEB had been pushed to the dome. Conclusions: All assessed hemodynamic parameters reduced significantly from pre to post-WEB placement in the sac of AcomA aneurysm; however, recanalization may happen secondary to filling the proximal portion of the WEB-SL and increased WSS in the neck of the aneurysm. Conduction of larger studies is warranted to elaborately investigate the potential role of CFD techniques for correlating the hemodynamics indices with clinical outcomes.

Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk.Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05.Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2–137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up.Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold.

Objective: Electrical stimulation (ES) potentially delineates epileptogenic cortex through induction of typical seizures. Although frequently employed, its value for epilepsy surgery remains controversial. Similarly, ES is used to identify symptomatogenic zones, but with greater success and a long-standing evidence base. Recent work points to new seizure symptoms such as ictal central apnea (ICA) that may enhance presurgical hypotheses. The aims of this review are 2-fold: to determine the value of ES-induced seizures (ESIS) in epilepsy surgery and to analyze current evidence on ICA as a new surrogate of symptomatogenic cortex.Methods: Three databases were searched for ESIS. Investigators independently selected studies according to pre-specified criteria. Studies reporting postoperative outcome in patients with ESIS were included in a meta-analysis. For ES-induced apnea, a thorough search was performed and reference list searching was employed.Results: Of 6,314 articles identified for ESIS, 25 were considered eligible to be reviewed in full text. Fourteen studies were included in the qualitative synthesis (1,069 patients); six studies were included in the meta-analysis (530 patients). The meta-analysis showed that favorable outcome is associated with ESIS prior to surgery (OR: 2.02; 95% CI: 1.332–3.08). In addition, the overall estimation of the occurrence of favorable outcome among cases with ESIS is 68.13% (95% CI: 56.62–78.7). On the other hand, recent studies have shown that stimulation of exclusively mesial temporal lobe structures elicits central apnea and represents symptomatogenic anatomic substrates of ICA. This is in variance with traditional teaching that mesial temporal ES is non-symptomatogenic.Conclusions: ES is a tool highly likely to aid in the delineation of the epileptogenic zone, since ESIS is associated with favorable postoperative outcomes (Engel I). There is an urgent need for prospective evaluation of this technique, including effective stimulation parameters and surgical outcomes, that will provide knowledge base for practice. In addition, ES-induced apnea studies suggest that ICA, especially when it is the first or only clinical sign, is an important semiological feature in localizing the symptomatogenic zone to mesial temporal lobe structures, which must be considered in SEEG explorations where this is planned, and in surgical resection strategies.