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- Edlmann, E, et al.
(författare)
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Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 5885-
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Tidskriftsartikel (refereegranskat)abstract
- The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.
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- Edlmann, E, et al.
(författare)
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Dexamethasone reduces vascular endothelial growth factor in comparison to placebo in post-operative chronic subdural hematoma samples: A target for future drug therapy?
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13, s. 952308-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic subdural hematoma (CSDH) is a collection of blood and fluid that arises on the brain surface due to a combination of trauma and/or inflammation. The mainstay of treatment is surgical drainage, but CSDH can recur. Dexamethasone has been shown to reduce CSDH recurrence, but its mechanism of action has not been fully elucidated. Understanding the inflammatory mediators driving CSDH formation and recurrence and how dexamethasone alters this can help develop new therapeutic strategies.MethodsA subgroup of adult patients recruited to the Dex-CSDH trial, randomized to dexamethasone or placebo, who had surgery for their CSDH, were included. CSDH fluid and peripheral blood were collected intraoperatively, from post-operative drains and operated recurrences. Samples were analyzed using a 12-plex panel of inflammatory mediators. Clinical patient data were also reviewed.ResultsA total of 52 patients, with a mean age of 76 years, were included. Five recurrent CSDHs occurred. Vascular endothelial growth factor (VEGF) had the highest concentration across all CSDHs, and only matrix metalloproteinase (MMP)-9 had lower concentrations in CSDH compared to plasma but was increased in recurrent CSDHs. The interleukin (IL)-10 concentration was significantly lower in primary CSDHs that recurred. Most inflammatory mediators increased post-operatively, and dexamethasone significantly reduced the post-operative peak in VEGF on day 2, compared to placebo.ConclusionIt is evident that VEGF plays a critical role in the inflammatory response in CSDH. The post-operative reduction with dexamethasone could signal the mechanism by which it reduces recurrence. Novel therapies with a better side-effect profile than dexamethasone should be targeted at VEGF or potential alternatives such as IL-10 supplementation.
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- Fletcher-Sandersjoo, A, et al.
(författare)
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Clinical Significance of Vascular Occlusive Events following Moderate-to-Severe Traumatic Brain Injury: An Observational Cohort Study
- 2022
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Ingår i: Seminars in thrombosis and hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 48:033, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Preventing hemorrhage progression is a potential therapeutic opportunity in traumatic brain injury (TBI) management, but its use has been limited by fear of provoking vascular occlusive events (VOEs). However, it is currently unclear whether VOE actually affects outcome in these patients. The aim of this study was to determine incidence, risk factors, and clinical significance of VOE in patients with moderate-to-severe TBI. A retrospective observational cohort study of adults (≥15 years) with moderate-to-severe TBI was performed. The presence of a VOE during hospitalization was noted from hospital charts and radiological reports. Functional outcome, using the Glasgow Outcome Scale (GOS), was assessed at 12 months posttrauma. Univariate and multivariate logistic regressions were used for endpoint assessment. In total, 848 patients were included, with a median admission Glasgow Coma Scale of 7. A VOE was detected in 54 (6.4%) patients, of which cerebral venous thrombosis was the most common (3.2%), followed by pulmonary embolism (1.7%) and deep vein thrombosis (1.3%). Length of ICU stay (p < 0.001), body weight (p = 0.002), and skull fracture (p = 0.004) were independent predictors of VOE. VOE development did not significantly impact 12-month GOS, even after adjusting for potential confounders using propensity score matching. In conclusion, VOE in moderate-to-severe TBI patients was relatively uncommon, and did not affect 12-month GOS. This suggests that the potential benefit of treating bleeding progression might outweigh the risks of VOE.
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- Fletcher-Sandersjoo, A, et al.
(författare)
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Time Course of Hemostatic Disruptions After Traumatic Brain Injury: A Systematic Review of the Literature
- 2021
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Ingår i: Neurocritical care. - : Springer Science and Business Media LLC. - 1556-0961 .- 1541-6933. ; 34:2, s. 635-656
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Tidskriftsartikel (refereegranskat)abstract
- Almost two-thirds of patients with severe traumatic brain injury (TBI) develop some form of hemostatic disturbance, which contributes to poor outcome. While the initial head injury often leads to impaired clot formation, TBI is also associated with an increased risk of thrombosis. Most likely there is a progression from early bleeding to a later prothrombotic state. In this paper, we systematically review the literature on the time course of hemostatic disruptions following TBI. A MEDLINE search was performed for TBI studies reporting the trajectory of hemostatic assays over time. The search yielded 5,049 articles, of which 4,910 were excluded following duplicate removal as well as title and abstract review. Full-text assessment of the remaining articles yielded 33 studies that were included in the final review. We found that the first hours after TBI are characterized by coagulation cascade dysfunction and hyperfibrinolysis, both of which likely contribute to lesion progression. This is then followed by platelet dysfunction and decreased platelet count, the clinical implication of which remains unclear. Later, a poorly defined prothrombotic state emerges, partly due to fibrinolysis shutdown and hyperactive platelets. In the clinical setting, early administration of the antifibrinolytic agent tranexamic acid has proved effective in reducing head-injury-related mortality in a subgroup of TBI patients. Further studies evaluating the time course of hemostatic disruptions after TBI are warranted in order to identify windows of opportunity for potential treatment options.
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- Grevfors, N, et al.
(författare)
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Delayed Neurosurgical Intervention in Traumatic Brain Injury Patients Referred From Primary Hospitals Is Not Associated With an Unfavorable Outcome
- 2021
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 11, s. 610192-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Secondary transports of patients suffering from traumatic brain injury (TBI) may result in a delayed management and neurosurgical intervention, which is potentially detrimental. The aim of this study was to study the effect of triaging and delayed transfers on outcome, specifically studying time to diagnostics and neurosurgical management.Methods: This was a retrospective observational cohort study of TBI patients in need of neurosurgical care, 15 years and older, in the Stockholm Region, Sweden, from 2008 throughout 2014. Data were collected from pre-hospital and in-hospital charts. Known TBI outcome predictors, including the protein biomarker of brain injury S100B, were used to assess injury severity. Characteristics and outcomes of direct trauma center (TC) and those of secondary transfers were evaluated and compared. Functional outcome, using the Glasgow Outcome Scale, was assessed in survivors at 6–12 months after trauma. Regression models, including propensity score balanced models, were used for endpoint assessment.Results: A total of n = 457 TBI patients were included; n = 320 (70%) patients were direct TC transfers, whereas n = 137 (30%) were secondary referrals. In all, n = 295 required neurosurgery for the first 24 h after trauma (about 75% of each subgroup). Direct TC transfers were more severely injured (median Glasgow Coma Scale 8 vs. 13) and more often suffered a high energy trauma (31 vs. 2.9%) than secondary referrals. Admission S100B was higher in the TC transfer group, though S100B levels 12–36 h after trauma were similar between cohorts. Direct or indirect TC transfer could be predicted using propensity scoring. The secondary referrals had a shorter distance to the primary hospital, but had later radiology and surgery than the TC group (all p < 0.001). In adjusted multivariable analyses with and without propensity matching, direct or secondary transfers were not found to be significantly related to outcome. Time from trauma to surgery did not affect outcome.Conclusions: TBI patients secondary transported to a TC had surgical intervention performed hours later, though this did not affect outcome, presumably demonstrating that accurate pre-hospital triaging was performed. This indicates that for selected patients, a wait-and-see approach with delayed neurosurgical intervention is not necessarily detrimental, but warrants further research.
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- Iacobelli, R, et al.
(författare)
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Predictors of brain infarction in adult patients on extracorporeal membrane oxygenation: an observational cohort study
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 3809-
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Tidskriftsartikel (refereegranskat)abstract
- Non-hemorrhagic brain infarction (BI) is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and associated with increased mortality. However, predictors of BI in these patients are poorly understood. The aim of this study was to identify predictors of BI in ECMO-treated adult patients. We conducted an observational cohort study of all adult patients treated with venovenous or venoarterial (VA) ECMO at our center between 2010 and 2018. The primary endpoint was a computed tomography (CT) verified BI. Logistic regression models were employed to identify BI predictors. In total, 275 patients were included, of whom 41 (15%) developed a BI. Pre-ECMO Simplified Acute Physiology Score III, pre-ECMO cardiac arrest, VA ECMO and conversion between ECMO modes were identified as predictors of BI. In the multivariable analysis, VA ECMO demonstrated independent risk association. VA ECMO also remained the independent BI predictor in a sub-group analysis excluding patients who did not undergo a head CT scan during ECMO treatment. The incidence of BI in adult ECMO patients may be higher than previously believed and is independently associated with VA ECMO mode. Larger prospective trials are warranted to validate these findings and ascertain their clinical significance.
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- Kopfer, S, et al.
(författare)
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Incidence and predictors of brain infarction in neonatal patients on extracorporeal membrane oxygenation: an observational cohort study
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 17932-
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Tidskriftsartikel (refereegranskat)abstract
- To determine the incidence and identify predictors of brain infarctions (BI) in neonatal patients treated with extracorporeal membrane oxygenation (ECMO). We performed a retrospective cohort study at ECMO Centre Karolinska, Stockholm, Sweden. Logistic regression models were used to identify BI predictors. Neonates (age 0–28 days) treated with veno-arterial (VA) or veno-venous (VV) ECMO between 2010 and 2018. The primary outcome was a computed tomography (CT) verified BI diagnosed during ECMO treatment. In total, 223 patients were included, 102 patients (46%) underwent at least one brain CT and 27 patients (12%) were diagnosed with a BI. BI diagnosis was associated with increased 30-day mortality (48% vs. 18%). High pre-ECMO Pediatric Index of Mortality score, sepsis as the indication for ECMO treatment, VA ECMO, conversion between ECMO modes, use of continuous renal replacement therapy, and extracranial thrombosis were identified as independent predictors of BI development. The incidence of BI in neonatal ECMO patients may be higher than previously understood. Risk factor identification may help initiate steps to lower the risk or facilitate earlier diagnosis of BI in neonates undergoing ECMO treatment.
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