Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Diagnosis, Therapeutical Management, and Prognosis

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition and these patients often have unfavorable outcomes at the long-term follow-up. Poor-grade aSAH is a severe subtype of aSAH and is defined as World Federation of Neurosurgical Surgeon (WFNS) grade IV or V. All patients should be treated by a multidisciplinary team that consists of vascular neurosurgeons, interventional neuroradiologists, neurologists, and anesthetists. Aneurysm rebleeding occurs in the poor-grade aSAH within the first 72 h after ictus. Timing of treatment for aSAH has shifted from delayed to early treatment of ruptured aneurysms, and there will be a trend toward early or ultra-early treatment for poor-grade aSAH. However, there is no consensus regarding the optimal timing of treatment for poor-grade aSAH. Endovascular coiling has provided a viable alternative to surgical clipping. An increasing number of patients have received endovascular treatment. There are limited data on high-level clinical trials focused on the treatment of poor-grade aSAH. An accurate prediction model remains challenging. Predicting long-term outcome is essential to support treatment decision-making. We reviewed the current therapeutical management and prognosis of poor-grade aSAH

Original Article Neuroprotective effect of functionalized multi-walled carbon nanotubes on spinal cord injury in rats

Abstract: Traumatic injuries to the brain and spinal cord affect a large percentage of the world's population. However, there are currently no effective treatments for these central nervous system (CNS) injuries. In our study, we evaluated the neuroprotective role of functionalized multi-walled carbon nanotubes (MWCNTs) carrying brain derived neurotrophic factor (BNDF), nogo-66 receptor (NgR) and Ras homolog gene family member A (RhoA) in spinal cord injury (SCI). Our results showed that transfection into rat cortical neurons with BDNF-DNA significantly elevated the expression of BDNF both in vitro and in vivo. Meanwhile, transfection with NgR-siRNA and RhoA-siRNA resulted in an obvious down-regulation of NgR and RhoA in neuron cells and in injured spinal cords. In addition, the functionalized MWCNTs carrying BDNF-DNA, NgR-siRNA and RhoA-siRNA exhibited remarkable therapeutic effects on injured spinal cord. Taken together, our study demonstrates that functionalized MWCNTs have a potential therapeutic application on repair and regeneration of the CNS

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

A data integration approach unveils a transcriptional signature of type 2 diabetes progression in rat and human islets.

Pancreatic islet failure is a key characteristic of type 2 diabetes besides insulin resistance. To get molecular insights into the pathology of islets in type 2 diabetes, we developed a computational approach to integrating expression profiles of Goto-Kakizaki and Wistar rat islets from a designed experiment with those of the human islets from an observational study. A principal gene-eigenvector in the expression profiles characterized by up-regulated angiogenesis and down-regulated oxidative phosphorylation was identified conserved across the two species. In the case of Goto-Kakizaki versus Wistar islets, such alteration in gene expression can be verified directly by the treatment-control tests over time, and corresponds to the alteration of α/β-cell distribution obtained by quantifying the islet micrographs. Furthermore, the correspondence between the dual sample- and gene-eigenvectors unveils more delicate structures. In the case of rats, the up- and down-trend of insulin mRNA levels before and after week 8 correspond respectively to the top two principal eigenvectors. In the case of human, the top two principal eigenvectors correspond respectively to the late and early stages of diabetes. According to the aggregated expression signature, a large portion of genes involved in the hypoxia-inducible factor signaling pathway, which activates transcription of angiogenesis, were significantly up-regulated. Furthermore, top-ranked anti-angiogenic genes THBS1 and PEDF indicate the existence of a counteractive mechanism that is in line with thickened and fragmented capillaries found in the deteriorated islets. Overall, the integrative analysis unravels the principal transcriptional alterations underlying the islet deterioration of morphology and insulin secretion along type 2 diabetes progression

Protective mechanisms of decorin and PEDF.

Pancreatic islet failure is a key characteristic of type 2 diabetes besides insulin resistance. To get molecular insights into the pathology of islets in type 2 diabetes, we developed a computational approach to integrating expression profiles of Goto-Kakizaki and Wistar rat islets from a designed experiment with those of the human islets from an observational study. A principal gene-eigenvector in the expression profiles characterized by up-regulated angiogenesis and down-regulated oxidative phosphorylation was identified conserved across the two species. In the case of Goto-Kakizaki versus Wistar islets, such alteration in gene expression can be verified directly by the treatment-control tests over time, and corresponds to the alteration of α/β-cell distribution obtained by quantifying the islet micrographs. Furthermore, the correspondence between the dual sample- and gene-eigenvectors unveils more delicate structures. In the case of rats, the up- and down-trend of insulin mRNA levels before and after week 8 correspond respectively to the top two principal eigenvectors. In the case of human, the top two principal eigenvectors correspond respectively to the late and early stages of diabetes. According to the aggregated expression signature, a large portion of genes involved in the hypoxia-inducible factor signaling pathway, which activates transcription of angiogenesis, were significantly up-regulated. Furthermore, top-ranked anti-angiogenic genes THBS1 and PEDF indicate the existence of a counteractive mechanism that is in line with thickened and fragmented capillaries found in the deteriorated islets. Overall, the integrative analysis unravels the principal transcriptional alterations underlying the islet deterioration of morphology and insulin secretion along type 2 diabetes progression.</div