ORCID Profile
0000-0002-5374-3161
Current Organisation
Università degli Studi di Milano-Bicocca
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Publisher: Springer Science and Business Media LLC
Date: 13-04-2018
Publisher: Mary Ann Liebert Inc
Date: 06-2020
Abstract: The aim of this study is to investigate the prognostic value of using the National Institute of Neurological Disorders and Stroke (NINDS) standardized imaging-based pathoanatomic descriptors for the evaluation and reporting of acute traumatic brain injury (TBI) lesions. For a total of 3392 patients (2244 males and 1148 females, median age = 51 years) enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we extracted 96 Common Data Elements (CDEs) from the structured reports, spanning all three levels of pathoanatomic information (i.e., 20 "basic," 60 "descriptive," and 16 "advanced" CDE variables per patient). Six-month clinical outcome scores were dichotomized into favorable (Glasgow Outcome Scale Extended [GOS-E] = 5-8) versus unfavorable (GOS-E = 1-4). Regularized logistic regression models were constructed and compared using the optimism-corrected area under the curve (AUC). An abnormality was reported for the majority of patients (64.51%). In 79.11% of those patients, there was at least one coexisting pathoanatomic lesion or associated finding. An increase in lesion severity, laterality, and volume was associated with more unfavorable outcomes. Compared with the full set of pathoanatomic descriptors (i.e., all three categories of information), reporting "basic" CDE information provides at least equal discrimination between patients with favorable versus unfavorable outcome (AUC = 0.8121 vs. 0.8155, respectively). Addition of a selected subset of "descriptive" detail to the basic CDEs could improve outcome prediction (AUC = 0.8248). Addition of "advanced" or "emerging/exploratory" information had minimal prognostic value. Our results show that the NINDS standardized-imaging based pathoanatomic descriptors can be used in large-scale studies and provide important insights into acute TBI lesion patterns. When used in clinical predictive models, they can provide excellent discrimination between patients with favorable and unfavorable 6-month outcomes. If further validated, our findings could support the development of structured and itemized templates in routine clinical radiology.
Publisher: BMJ
Date: 10-05-2022
Abstract: Following traumatic brain injury (TBI), the clinical focus is often on disability. However, patients’ perceptions of well-being can be discordant with their disability level, referred to as the ‘disability paradox’. We aimed to examine the relationship between disability and health-related quality of life (HRQoL) following TBI, while taking variation in personal, injury-related and environment factors into account. We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. Disability was assessed 6 months post-injury by the Glasgow Outcome Scale-Extended (GOSE). HRQoL was assessed by the SF-12v2 physical and mental component summary scores and the Quality of Life after Traumatic Brain Injury overall scale. We examined mean total and domain HRQoL scores by GOSE. We quantified variance in HRQoL explained by GOSE, personal, injury-related and environment factors with multivariable regression. Six-month outcome assessments were completed in 2075 patients, of whom 78% had mild TBI (Glasgow Coma Scale 13–15). Patients with severe disability had higher HRQoL than expected on the basis of GOSE alone, particularly after mild TBI. Up to 50% of patients with severe disability reported HRQoL scores within the normative range. GOSE, personal, injury-related and environment factors explained a limited amount of variance in HRQoL (up to 29%). Contrary to the idea that discrepancies are unusual, many patients with poor functional outcomes reported well-being that was at or above the boundary considered satisfactory for the normative s le. These findings challenge the idea that satisfactory HRQoL in patients with disability should be described as ‘paradoxical’ and question common views of what constitutes ‘unfavourable’ outcome.
Publisher: Mary Ann Liebert Inc
Date: 15-07-2020
Publisher: Springer Vienna
Date: 2012
DOI: 10.1007/978-3-7091-0956-4_9
Abstract: Hypotension is a recognized -secondary insult after traumatic brain injury (TBI). There are many definitions of hypotension, an often cited ex le being the Brain Trauma Foundation's current (2007) "Guidelines for the Management of Severe Traumatic Brain Injury," which defines hypotension as systolic pressure <90 mmHg. However, this same document declares "The importance of mean arterial pressure, as opposed to systolic pressure should also be stressed, …." Our work shows that when using the Edinburgh University Secondary Insult Grades (EUSIG) definitions, which require monitoring of both systolic and mean arterial pressures, that most hypotensive events are in fact triggered by a breach of the mean arterial level of 70 mmHg. We suggest that close monitoring of mean arterial pressure would enable clinical teams to avoid more potentially damaging hypotensive events. An analysis of 100 patients from the Brain-IT database was performed. Using the EUSIG definitions, 2,081 events can be obtained by analyzing the systolic and mean blood pressures on a minute by minute basis. A software program was written to identify and classify the trigger pattern for each event. A categorical analysis of these triggering patterns has been carried out. Our analysis shows that most events are triggered by a drop in mean arterial pressure. In fact a large number of events (91%) occur where the mean arterial pressure is below the threshold limits whereas the systolic pressure does not cross the 90 mmHg limit at all. We suggest that more emphasis should be placed on closely monitoring mean arterial pressure as well as systolic pressure when trying to guard against hypotensive problems in traumatically brain injured patients. In future work we will study the underlying physiological mechanisms and attempt to further classify concomitant conditions that may be contributing to the onset of a hypotensive event.
Publisher: Mary Ann Liebert Inc
Date: 24-02-2023
Publisher: Springer Science and Business Media LLC
Date: 05-09-2019
Publisher: Springer Science and Business Media LLC
Date: 16-12-2021
DOI: 10.1007/S12028-021-01400-3
Abstract: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury. Results from blood s les (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) ( n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR 1.2 and (2) INR ≥ 1.2. An INR 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick’s value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers. Patients with iTBI with INR ≥ 1.2 ( n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR 1.2 ( n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15–20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR 1.2 to 1,301 mg/L in patients with INR ≥ 1.2. This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
Publisher: Mary Ann Liebert Inc
Date: 2020
Abstract: The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone (
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-10-2020
Abstract: The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). In iduals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system d ens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified in iduals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy in iduals. Together, these studies identify a means by which in iduals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 see also p. 404
Publisher: Springer Science and Business Media LLC
Date: 06-09-2023
Publisher: Elsevier BV
Date: 08-2021
Publisher: Springer Science and Business Media LLC
Date: 29-07-2017
DOI: 10.1007/S00134-017-4895-9
Abstract: In this research agenda on the acute and critical care management of trauma patients, we concentrate on the major factors leading to death, namely haemorrhage and traumatic brain injury (TBI). In haemostasis biology, the results of randomised controlled trials have led to the therapeutic focus moving away from the augmentation of coagulation factors (such as recombinant factor VIIa) and towards fibrinogen supplementation and administration of antifibrinolytics such as tranexamic acid. Novel diagnostic techniques need to be evaluated to determine whether an in idualised precision approach is superior to current empirical practice. The timing and efficacy of platelet transfusions remain in question, while new blood products need to be developed and evaluated, including whole blood variants, lyophilised products and novel red cell storage modalities. The current cornerstones of TBI management are intracranial pressure control, maintenance of cerebral perfusion pressure and avoidance of secondary insults (such as hypotension, hypoxaemia, hyperglycaemia and pyrexia). Therapeutic hypothermia and decompressive craniectomy are controversial therapies. Further research into these strategies should focus on identifying which subgroups of patients may benefit from these interventions. Prediction of the long-term outcome early after TBI remains challenging. Early magnetic resonance imaging has recently been evaluated for predicting the long-term outcome in mild and severe TBI. Novel biomarkers may also help in outcome prediction and may predict chronic neurological symptoms. For trauma in general, rehabilitation is complex and multidimensional, and the optimal timing for commencement of rehabilitation needs investigation. We propose priority areas for clinical trials in the next 10 years.
Publisher: Wiley
Date: 15-08-2019
DOI: 10.1111/AAS.13453
Abstract: Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID-ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU-acquired delirium. AID-ICU is an investigator-initiated, pragmatic, international, randomised, blinded, parallel-group, trial allocating adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. Trial participants will receive intravenous 2.5 mg haloperidol three times daily or matching placebo (isotonic saline 0.9%) if they are delirious. If needed, a maximum of 20 mg/daily haloperidol lacebo is given. An escape protocol, not including haloperidol, is part of the trial protocol. The primary outcome is days alive out of the hospital within 90 days post-randomisation. Secondary outcomes are number of days without delirium or coma, serious adverse reactions to haloperidol, usage of escape medication, number of days alive without mechanical ventilation mortality, health-related quality-of-life and cognitive function at 1-year follow-up. A s le size of 1000 patients is required to detect a 7-day improvement or worsening of the mean days alive out of the hospital, type 1 error risk of 5% and power 90%. The AID-ICU trial is based on gold standard methodology applied to a large s le of clinically representative patients and will provide pivotal high-quality data on the benefits and harms of haloperidol for the treatment ICU-acquired delirium.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
DOI: 10.1186/S13054-020-2791-0
Abstract: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant ( p 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high five out of seven had less than 10 events per centre. Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators. The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 22-02-2021
Publisher: American Medical Association (AMA)
Date: 11-11-2021
Publisher: Springer Science and Business Media LLC
Date: 25-02-2015
Publisher: The Royal Society
Date: 13-07-2009
Abstract: The ability to predict adverse hypotensive events, where a patient's arterial blood pressure drops to abnormally low (and dangerous) levels, would be of major benefit to the fields of primary and secondary health care, and especially to the traumatic brain injury domain. A wealth of data exist in health care systems providing information on the major health indicators of patients in hospitals (blood pressure, temperature, heart rate, etc.). It is believed that if enough of these data could be drawn together and analysed in a systematic way, then a system could be built that will trigger an alarm predicting the onset of a hypotensive event over a useful time scale, e.g. half an hour in advance. In such circumstances, avoidance measures can be taken to prevent such events arising. This is the basis for the Avert-IT project ( www.avert-it.org ), a collaborative EU-funded project involving the construction of a hypotension alarm system exploiting Bayesian neural networks using techniques of data federation to bring together the relevant information for study and system development.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1186/S12910-020-00480-8
Abstract: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally ( N = 11, 61%) or locally ( N = 7, 39%) and primary IRB approval was obtained after one ( N = 8, 44%), two ( N = 6, 33%) or three ( N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.
Publisher: Informa UK Limited
Date: 17-10-2020
DOI: 10.1080/09638288.2020.1832589
Abstract: There is conflicting literature on the effect of post- utation pain on quality of life (QOL) and no available literature on the relationship of pain medications to QOL of utees in pain. The aims of the study were to compare QOL in lower limb utees with significant pain to those with minimal pain and compare QOL in utees on multiple pain medications (≥3 and/or ≥ 40 mg morphine equivalent/day) to those on minimal. Cross-sectional study of utees ( Post- utation pain was common (69%), but only 13% of the participants were using more pain medications. High-pain interference and poor self-efficacy were associated with poorer QOL after adjusting for age, gender and cause of utation. High medication use was associated with high-pain interference and poor self-efficacy, but there was minimal correlation between pain scores and medication usage ( Post- utation pain continues to be a major determinant of QOL in lower limb utees, but the role of pain medications on an utee's QOL remains unclear.IMPLICATIONS FOR REHABILITATIONAn utee's QOL is affected by the severity of their post- utation pain even beyond six months post their utation.An utee with more pain may not necessarily take more pain medications to manage their pain. The amount of pain medications taken may not influence their self-reported QOL.Pain and QOL assessment should be integrated into routine clinical evaluation of adult utees. Standardized screening tools and/or formative assessment can be utilized for assessing QOL.
Publisher: Springer Science and Business Media LLC
Date: 16-12-2022
DOI: 10.1186/S12913-022-08908-0
Abstract: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Patients ( n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. ClinicalTrials.gov NCT02210221.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 02-03-2018
DOI: 10.1007/S00134-018-5086-Z
Abstract: To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions-using a sequential approach to avoid biases and misinterpretations-was used to generate the final consensus statement. The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.
Publisher: Springer Vienna
Date: 2012
DOI: 10.1007/978-3-7091-0956-4_8
Abstract: Hypotension is recognized as a potentially damaging secondary insult after traumatic brain injury. Systems to give clinical teams some early warning of likely hypotensive instability could be added to the range of existing techniques used in the management of this group of patients. By using the Edinburgh University Secondary Insult Grades (EUSIG) definitions for -hypotension (systolic arterial pressure <90 mmHg OR mean arterial -pressure <70 mmHg) we collected a group of ∼2,000 events by analyzing the Brain-IT database. We then constructed a Bayesian Artificial Neural Network (an advanced statistical modeling technique) that is able to provide some early warning when trained on this previously collected demographic and physiological data. Using EUSIG defined event data from the Brain-IT database, we identified a Bayesian artificial neural network (BANN) topology and constructed a series of datasets using a group of clinically guided input variables. This allowed us to train a BANN, which was then tested on an unseen set of patients from the Brain-IT database. The initial tests used a particularly harsh assessment criterion whereby a true positive prediction was only allowed if the BANN predicted an upcoming event to the exact minute. We have now developed the system to the point where it is about to be used in a two-stage Phase II clinical trial and we are also researching a more realistic assessment technique. We have constructed a BANN that is able to provide early warning to the clinicians based on a model that uses information from the physiological inputs systolic and mean arterial pressure and heart rate and demographic variables age and gender. We use 15-min SubWindows starting at 15 and 30 min before an event and process mean, slope and standard deviations. Based on 10 simulation runs, our current sensitivity is 36.25% (SE 1.31) with a specificity of 90.82% (SE 0.85). Initial results from a Phase I clinical study shows a model sensitivity of 40.95% (SE 6%) and specificity of 86.46% (SE 3%) Although this figure is low it is considered clinically useful for this dangerous condition, provided the false positive rate can be kept sufficiently low as to be practical in an intensive care environment. We have shown that using advanced statistical modeling techniques can provide clinical teams with useful information that will assist clinical care.
Publisher: Elsevier BV
Date: 2022
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 05-2021
Abstract: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13–15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p 0.001). Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.
Publisher: Mary Ann Liebert Inc
Date: 15-01-2018
Abstract: Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (
Publisher: Springer Science and Business Media LLC
Date: 19-12-2018
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S13613-019-0610-Z
Abstract: Following publication of the original article [1], we were notified that the collaborators’ names part of the “The TBI Collaborative” group has not been indexed in Pubmed. Below the collaborators names full list:
Publisher: Springer Science and Business Media LLC
Date: 26-10-2020
Publisher: Frontiers Media SA
Date: 18-08-2022
DOI: 10.3389/FNEUR.2022.861688
Abstract: Spine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI). Data from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended GOSe & 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up. A total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI. Rates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.
Publisher: Mary Ann Liebert Inc
Date: 07-2020
Publisher: IEEE
Date: 12-2010
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
Publisher: Springer Science and Business Media LLC
Date: 05-04-2023
DOI: 10.1186/S13073-023-01173-8
Abstract: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected in iduals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10 −4 ) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10 −4 ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10 −3 ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10 −8 ). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years P = 1.68 × 10 −5 ). Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1998
DOI: 10.1097/00003246-199801000-00031
Abstract: To determine the degree of regional and systemic coagulation activation soon after isolated severe head injury. Prospective, controlled clinical study. The emergency room and intensive care unit (ICU) of a trauma center in a university hospital serving a population of 5 million people. Twenty-four trauma victims: 20 patients with isolated severe head injury (head trauma group, Glasgow Coma Score of < or =8) and four patients with isolated bone fracture (control group). Insertion of central venous, i.e. superior caval vein, jugular bulb, and arterial catheters for blood s ling. Central venous (i.e., superior caval vein) global coagulation variables (i.e., prothrombin time, activated partial thromboplastin time, fibrinogen concentration, antithrombin III activity, and platelet count) and central venous and jugular bulb activation coagulation and fibrinolysis variables (i.e., prothrombin fragment F1+2, thrombin-antithrombin III complex, soluble fibrin, and D-dimer concentration) were measured soon after trauma (<6 hrs) and 3 hrs later. When compared with the control group patients, upon ICU admission, fibrinogen concentration (p < .005) and platelet count (p < .025) were significantly decreased in the head trauma group. Thrombin-antithrombin III complex (p < .025), prothrombin fragment F1+2 (p < .025), and D-dimer (p < .005) concentrations measured at the time of ICU admission were significantly higher in the head trauma group than in the control group. Only in the head trauma group were soluble fibrin concentrations increased above the normal range thrombin-antithrombin III complex and the prothrombin fragment F1+2 were found to be significantly higher in cerebrovenous blood than in central venous blood (p < .025). There was no cerebrocentral venous difference in the concentrations of soluble fibrin or D-dimer in either group. Within 6 hrs after severe isolated head trauma, systemic procoagulant overflow from the traumatized cerebral microvasculature proceeds to the thrombin level and is then inhibited by antithrombin III. Regional and systemic hypercoagulability and increased D-dimer concentrations appear to be common among head trauma patients. Increased procoagulant and consecutive fibrinolytic turnover may, therefore, spark disseminated intravascular coagulation in this patient group.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2022
Publisher: Oxford University Press (OUP)
Date: 22-02-2023
Abstract: Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13–15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of in idual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.
Publisher: Springer Science and Business Media LLC
Date: 06-08-2016
Publisher: Wiley
Date: 13-09-2019
DOI: 10.1111/ANAE.14838
Publisher: Springer Science and Business Media LLC
Date: 24-05-2018
DOI: 10.1007/S10877-018-0139-Y
Abstract: Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.
Publisher: Mary Ann Liebert Inc
Date: 15-05-2021
Abstract: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS ≤12, age ≥14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS ≤14, age ≥16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (
Publisher: Springer Science and Business Media LLC
Date: 10-05-2022
DOI: 10.1038/S41467-022-30227-5
Abstract: Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.
Publisher: Springer Science and Business Media LLC
Date: 02-10-2020
Publisher: Elsevier BV
Date: 08-2022
Publisher: Elsevier BV
Date: 07-2022
Publisher: Springer Science and Business Media LLC
Date: 13-03-2017
DOI: 10.1007/S00134-017-4757-5
Abstract: We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, lifying the effects of each in idual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.
Publisher: Springer Science and Business Media LLC
Date: 23-02-2021
DOI: 10.1186/S13054-020-03370-Y
Abstract: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). We studied high TIL treatments (metabolic suppression, hypothermia ( 35 °C), intensive hyperventilation (PaCO 2 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP. 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0–2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome. Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies. Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments. The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, t2/show/NCT02210221?id=NCT02210221& draw=1& rank=1 and with Resource Identification Portal (RRID: SCR_015582).
Publisher: Elsevier BV
Date: 10-2020
Publisher: Mary Ann Liebert Inc
Date: 15-09-2021
Publisher: Springer Science and Business Media LLC
Date: 29-11-2019
DOI: 10.1186/S13017-019-0270-1
Abstract: The acute phase management of patients with severe traumatic brain injury (TBI) and polytrauma represents a major challenge. Guidelines for the care of these complex patients are lacking, and worldwide variability in clinical practice has been documented in recent studies. Consequently, the World Society of Emergency Surgery (WSES) decided to organize an international consensus conference regarding the monitoring and management of severe adult TBI polytrauma patients during the first 24 hours after injury. A modified Delphi approach was adopted, with an agreement cut-off of 70%. Forty experts in this field (emergency surgeons, neurosurgeons, and intensivists) participated in the online consensus process. Sixteen recommendations were generated, with the aim of promoting rational care in this difficult setting.
Publisher: BMJ
Date: 02-12-2020
Abstract: Cognitive impairment is a key cause of disability after traumatic brain injury (TBI) but relationships with overall functioning in daily life are often modest. The aim is to examine cognition at different levels of function and identify domains associated with disability. 1554 patients with mild-to-severe TBI were assessed at 6 months post injury on the Glasgow Outcome Scale—Extended (GOSE), the Short Form-12v2 and a battery of cognitive tests. Outcomes across GOSE categories were compared using analysis of covariance adjusting for age, sex and education. Overall effect sizes were small to medium, and greatest for tests involving processing speed ( η p 2 0.057–0.067) and learning and memory ( η p 2 0.048–0.052). Deficits in cognitive performance were particularly evident in patients who were dependent (GOSE 3 or 4) or who were unable to participate in one or more major life activities (GOSE 5). At higher levels of function (GOSE 6–8), cognitive performance was surprisingly similar across categories. There were decreases in performance even in patients reporting complete recovery without significant symptoms. Medium to large effect sizes were present for summary measures of cognition ( η p 2 0.111), mental health ( η p 2 0.131) and physical health ( η p 2 0.252). This large-scale study provides novel insights into cognitive performance at different levels of disability and highlights the importance of processing speed in function in daily life. At upper levels of outcome, any influence of cognition on overall function is markedly attenuated and differences in mental health are salient.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2022
DOI: 10.1007/S00134-022-06660-X
Abstract: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.
Publisher: Springer Science and Business Media LLC
Date: 02-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-10-2020
DOI: 10.1097/CCM.0000000000004673
Abstract: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study. Sixty-five ICUs across Europe. For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay. We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5–1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours acute kidney injury stage 2 equals to serum creatinine × 2–2.9 times baseline acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% ( n = 100), acute kidney injury stage 2 equals to 1% ( n = 14), and acute kidney injury stage 3 equals to 3% ( n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1–4 d). Renal history (hazard ratio = 2.48 95% CI, 1.39–4.43 p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52 95% CI, 1.22–5.197 p = 0.012), hypernatremia (hazard ratio = 1.88 95% CI, 1.31–2.71 p = 0.001), and osmotic therapy administration (hazard ratio = 2.08 95% CI, 1.45–2.99 p 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality. Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.
Publisher: Massachusetts Medical Society
Date: 29-12-2022
Publisher: Elsevier BV
Date: 03-2022
Publisher: Mary Ann Liebert Inc
Date: 10-2020
Publisher: Mary Ann Liebert Inc
Date: 15-11-2015
Abstract: Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein in idual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups 3) strongly calls for further research on ICP interpretation and use 4) should be applied cautiously to regions with much different treatment milieu 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension 6) should not change the practice of those currently monitoring ICP and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.
Publisher: Springer Science and Business Media LLC
Date: 20-10-2022
Publisher: Mary Ann Liebert Inc
Date: 10-2022
Abstract: There is increasing emphasis on assessing multi-dimensional outcomes in traumatic brain injury (TBI), but achieving this aim is h ered by a plethora of overlapping assessment tools. There is a clear need for advice on the choice of outcomes and we examined level of functional recovery as a framework to guide selection of assessments. In this cohort study we analysed cross-sectional data from 2604 patients enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project. Patients were followed up 6 months after injury and assessed on the Glasgow Outcome Scale-Extended (GOSE), cognitive tests, and patient-reported outcomes. We describe assessment completeness and prevalence of impairment. Relationships between outcomes were visualized using UpSet plots and hierarchical cluster analysis. GOSE categories varied markedly for both completion rates, 34-91% for patient-reported outcomes and 9-81% for cognitive tests, and prevalence of impairment, 3-82% for patient-reported outcomes and 9-59% for cognitive tests. In complete case s les, the GOSE identified impairment in 59-61%, whereas the most impaired patient-reported outcome was the Short Form-12 version 2 (SF-12v2) Physical Component Summary (28% overall), and the most impaired cognitive test was Trail Making Test (TMT) Part A (19% overall). The findings show that degree of disability is a key context of use for cognitive tests and patient-reported outcomes. Level of functional recovery provides a guide to the feasibility of different types of assessment and the likelihood of impairment, and can help tailor suitable assessment approaches in clinical practice and research studies.
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2021
DOI: 10.1101/2021.07.21.21260624
Abstract: Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5 th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA , a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Springer Science and Business Media LLC
Date: 28-03-2020
Publisher: Springer Science and Business Media LLC
Date: 20-05-2022
DOI: 10.1007/S00134-022-06702-4
Abstract: Traumatic brain injury (TBI) remains one of the most fatal and debilitating conditions in the world. Current clinical management in severe TBI patients is mainly concerned with reducing secondary insults and optimizing the balance between substrate delivery and consumption. Over the past decades, multimodality monitoring has become more widely available, and clinical management protocols have been published that recommend potential interventions to correct pathophysiological derangements. Even while evidence from randomized clinical trials is still lacking for many of the recommended interventions, these protocols and algorithms can be useful to define a clear standard of therapy where novel interventions can be added or be compared to. Over the past decade, more attention has been paid to holistic management, in which hemodynamic, respiratory, inflammatory or coagulation disturbances are detected and treated accordingly. Considerable variability with regards to the trajectories of recovery exists. Even while most of the recovery occurs in the first months after TBI, substantial changes may still occur in a later phase. Neuroprognostication is challenging in these patients, where a risk of self-fulfilling prophecies is a matter of concern. The present article provides a comprehensive and practical review of the current best practice in clinical management and long-term outcomes of moderate to severe TBI in adult patients admitted to the intensive care unit.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2022
DOI: 10.1186/S13054-022-04079-W
Abstract: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights. We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation ( 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset ( N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation. Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p 0.001). Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
Publisher: Springer Science and Business Media LLC
Date: 07-2010
DOI: 10.1007/S00701-010-0719-1
Abstract: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain-injured patients and to facilitate a more efficient infrastructure for assessing new health care technology with the primary objective of improving patient care. European Community (EC) funding supported meetings over a year to discuss and define a core dataset to be collected from patients with traumatic brain injury using IT-based methods. We now present the results of a subsequent EC-funded study with the aim of testing the feasibility of collecting this core dataset across a number of European sites and discuss the future direction of this research network. Over a 3-year period, data collection client- and web-server-based tools were developed and core data (grouped into nine categories) were collected from 200 head-injured patients by local nursing staff in 22 European neuro-intensive care centres. Data were uploaded through the BrainIT website and random s les of received data were selected automatically by computer for validation by data validation staff against primary sources held in each local centre. Validated data were compared with originally transmitted data and percentage error rates calculated by data category. Feasibility was assessed in terms of the proportion of missing data, accuracy of data collected and limitations reported by users of the IT methods. Thirteen percent of data files required cleaning. Thirty "one-off" demographic and clinical data elements had significant amounts of missing data (>15%). Validation staff conducted 19,461 comparisons between uploaded database data with local data sources and error rates were commonly less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found. Nearly 10,000 therapies were successfully recorded with start-times but approximately a third had inaccurate or missing "end-times" which limits the analysis of duration of therapy. Over 40,000 events and procedures were recorded but events with long durations (such as transfers) were more likely to have end-times missed. The BrainIT core dataset is a rich dataset for hypothesis generation and post hoc analyses, provided that studies avoid known limitations in the dataset. Limitations in the current IT-based data collection tools have been identified and have been addressed. In order for multi-centre data collection projects to be viable, the resource intensive validation procedures will require a more automated process and this may include direct electronic access to hospital-based clinical data sources for both validation purposes and for minimising the duplication of data entry. This type of infrastructure may foster and facilitate the remote monitoring of patient management and protocol adherence in future trials of patient management and monitoring.
Publisher: Oxford University Press (OUP)
Date: 15-07-2022
DOI: 10.1093/HMG/DDAC158
Abstract: Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian in iduals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Publisher: Mary Ann Liebert Inc
Date: 15-08-2020
Publisher: American Medical Association (AMA)
Date: 09-2021
Publisher: Elsevier BV
Date: 02-2022
Publisher: Springer Science and Business Media LLC
Date: 10-11-2015
DOI: 10.1007/S00134-015-4105-6
Abstract: To evaluate the feasibility and efficacy of an apnea test (AT) technique that combines the application of positive end expiratory pressure (PEEP) with subsequent pulmonary recruitment in a large cohort of brain-dead patients. This study was a retrospective analysis of prospectively collected data on brain-dead patients admitted to our institution (Hospital San Gerardo, Monza, Italy) between January 2010 and December 2014. The rate of aborted apnea tests (ATs), occurrence of complications (i.e., pneumothorax, cardiac arrhythmias, cardiac arrest, and severe hypoxia, defined as PaO2 < 40 mmHg), ventilator settings, hemodynamics, and blood gas analyses were evaluated. Subgroup analysis was performed, with patients classified into veno-arterial extracorporeal membrane oxygenation (ECMO) or non-ECMO groups, and into hypoxic (i.e., baseline PaO2/FiO2 200 mmHg) groups. In total, 169 consecutive patients including 25 on ECMO were included in the study. No AT abortion nor severe complications were detected. The AT was completed in all patients. Fluid boluses and increases or initiation of vasoactive drugs were required in less than 10 and 3% of the AT procedures, respectively. No clinically meaningful alteration in hemodynamics was recorded. Severe hypoxia occurred during 7 (2.4%) and 4 (8%) of the ATs performed in non-ECMO and ECMO patients, respectively (p = 0.063), and it occurred more frequently in hypoxic patients than in non-hypoxic patients (11.1 vs. 4.8%, respectively p = 0.002). In a large cohort of consecutive patients, including the largest patient population on ECMO reported to date, our AT technique that combines the application of PEEP with subsequent pulmonary recruitment proved to be feasible and safe.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2019
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
Publisher: Springer Science and Business Media LLC
Date: 24-07-2021
Publisher: Mary Ann Liebert Inc
Date: 12-2021
Abstract: Men and women differ in outcomes following mild traumatic brain injury (TBI). In the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we previously found that women had worse 6-month functional outcome (Glasgow Outcome Score Extended [GOSE]), health-related quality of life (HRQoL), and mental health following mild TBI. The aim of this study was to investigate whether those differences were mediated by psychiatric history, gender-related sociodemographic variables, or by care pathways. We analyzed sex/gender differences in 6-month GOSE, generic and TBI-specific HRQoL, and post-concussion and mental health symptoms using three sets of mediators: psychiatric history, sociodemographic variables (living alone, living with children, education and employment status/job category), and care-pathways (referral to study hospital and discharge destination after emergency department) while controlling for a substantial number of potential confounders (pre-injury health and injury-related characteristics). We included 1842 men and 1022 women (16+) with a Glasgow Coma Score 13-15, among whom 83% had GOSE available and about 60% other 6-month outcomes. We used natural effects models to decompose the total effect of sex/gender on the outcomes into indirect effects that passed through the specified mediators and the remaining direct effects. In our study population, women had worse outcomes and these were only partly explained by psychiatric history, and not considerably explained by sociodemographic variables nor by care pathways. Factors other than differences in specified variables seem to underlie observed differences between men and women in outcomes after mild TBI. Future studies should explore more aspects of gender roles and identity and biological factors underpinning sex and gender differences in TBI outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-01-2021
DOI: 10.1097/CCM.0000000000004899
Abstract: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. The Surviving Sepsis C aign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization’s definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. The Surviving Sepsis C aign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis C aign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. The Surviving Sepsis C aign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
Publisher: Springer Science and Business Media LLC
Date: 20-06-2022
Publisher: Wiley
Date: 13-07-2020
DOI: 10.1111/AAS.13661
Publisher: Elsevier BV
Date: 11-2022
Publisher: Mary Ann Liebert Inc
Date: 07-2021
Abstract: In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns 2) choose a method of imputation 3) perform imputation 4) assess diagnostics of the imputation and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.
Publisher: The Royal Society
Date: 28-08-2009
Publisher: Springer Science and Business Media LLC
Date: 17-06-2017
Publisher: Springer Science and Business Media LLC
Date: 26-03-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-08-2021
DOI: 10.1126/SCIIMMUNOL.ABL4340
Abstract: Autoantibodies neutralizing type I IFNs increase in prevalence over 60 years of age and underlie about 20% of all fatal COVID-19 cases.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2022
DOI: 10.1038/S41598-022-20170-2
Abstract: Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in in iduals after TBI with differential severity. Data for six language groups ( n ≥ 200 Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in in iduals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of in iduals suffering from PTSD symptoms after TBI.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
DOI: 10.1186/S13054-020-02858-X
Abstract: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 0.5 ml/kg/h) in acutely ill patients and its association with the need for renal replacement therapy (RRT) and outcome. International observational study. All adult ( 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay ( n = 1349) were ided into three groups: transient—oliguria resolved within 48 h after the admission day ( n = 390 [28.9%]), prolonged—oliguria resolved 48 h after the admission day ( n = 141 [10.5%]), and permanent—oliguria persisting for the whole ICU stay or again present at the end of the ICU stay ( n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19–1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97–1.34], p = 0.103). Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.
Publisher: Springer Science and Business Media LLC
Date: 15-07-2020
DOI: 10.1007/S11136-020-02583-6
Abstract: The Quality of Life after Brain Injury overall scale (QOLIBRI-OS) measures health-related quality of life (HRQoL) after traumatic brain injury (TBI). The aim of this study was to derive value sets for the QOLIBRI-OS in three European countries, which will allow calculation of utility scores for TBI health states. A QOLIBRI-OS value set was derived by using discrete choice experiments (DCEs) and visual analogue scales (VAS) in general population s les from the Netherlands, United Kingdom and Italy. A three-stage procedure was used: (1) A selection of health states, covering the entire spectrum of severity, was defined (2) General population s les performed the health state valuation task using a web-based survey with three VAS questions and an at random selection of sixteen DCEs (3) DCEs were analysed using a conditional logistic regression and were then anchored on the VAS data. Utility scores for QOLIBRI-OS health states were generated resulting in estimates for all potential health states. The questionnaire was completed by 13,623 respondents. The biggest weight increase for all attributes is seen from “slightly” to “not at all satisfied”, resulting in the largest impact on HRQoL. “Not at all satisfied with how brain is working” should receive the greatest weight in utility calculations in all three countries. By transforming the QOLIBRI-OS into utility scores, we enabled the application in economic evaluations and in summary measures of population health, which may be used to inform decision-makers on the best interventions and strategies for TBI patients.
Publisher: Wiley
Date: 16-08-2020
DOI: 10.1111/AAS.13679
Publisher: Springer Science and Business Media LLC
Date: 06-12-2021
DOI: 10.1007/S12028-021-01386-Y
Abstract: In traumatic brain injury (TBI), large between-center differences in treatment and outcome for patients managed in the intensive care unit (ICU) have been shown. The aim of this study is to explore if European neurotrauma centers can be clustered, based on their treatment preference in different domains of TBI care in the ICU. Provider profiles of centers participating in the Collaborative European Neurotrauma Effectiveness Research in TBI study were used to assess correlations within and between the predefined domains: intracranial pressure monitoring, coagulation and transfusion, surgery, prophylactic antibiotics, and more general ICU treatment policies. Hierarchical clustering using Ward’s minimum variance method was applied to group data with the highest similarity. Heat maps were used to visualize whether hospitals could be grouped to uncover types of hospitals adhering to certain treatment strategies. Provider profiles were available from 66 centers in 20 different countries in Europe and Israel. Correlations within most of the predefined domains varied from low to high correlations (mean correlation coefficients 0.2–0.7). Correlations between domains were lower, with mean correlation coefficients of 0.2. Cluster analysis showed that policies could be grouped, but hospitals could not be grouped based on their preference. Although correlations between treatment policies within domains were found, the failure to cluster hospitals indicates that a specific treatment choice within a domain is not a proxy for other treatment choices within or outside the domain. These results imply that studying the effects of specific TBI interventions on outcome can be based on between-center variation without being substantially confounded by other treatments. We do not report the results of a health care intervention.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-03-2020
DOI: 10.1097/CCM.0000000000004363
Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. The Surviving Sepsis C aign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. The Surviving Sepsis C aign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2023
Publisher: Springer Science and Business Media LLC
Date: 29-11-2022
DOI: 10.1186/S13054-022-04250-3
Abstract: Magnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings. Data were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS) 13 or patient intubated with unrecorded pre-intubation GCS, CT with Marshall score 3, serum biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1) s led ≤ 24 h of injury, MRI 30 days of injury. The degree of axonal injury on MRI was graded using the Adams-Gentry classification. The association between serum concentrations of biomarkers and Adams-Gentry stage was assessed and the optimum threshold concentration identified, assuming different minimum sensitivities for the detection of brainstem injury (Adams-Gentry stage 3). A cost–benefit analysis for the USA and UK health care settings was also performed. Among 65 included patients (30 moderate-severe, 35 unrecorded) axonal injury was detected in 54 (83%) and brainstem involvement in 33 (51%). In patients with moderate-severe TBI, brainstem injury was associated with higher concentrations of NSE, Tau, UCH-L1 and GFAP. If the clinician did not want to miss any brainstem injury, NSE could have avoided MRI transfers in up to 20% of patients. If a 94% sensitivity was accepted considering potential transfer-related complications, GFAP could have avoided 30% of transfers. There was no added net cost, with savings up to £99 (UK) or $612 (US). No associations between proteins and axonal injury were found in intubated patients without a recorded pre-intubation GCS. Serum protein biomarkers show potential to safely reduce the number of transfers to MRI in critically ill patients with moderate-severe TBI at no added cost.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2018
Publisher: Springer Science and Business Media LLC
Date: 21-03-2014
DOI: 10.1186/S13049-021-00930-1
Abstract: Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients. Patients with moderate and severe TBI (Glasgow Coma Scale 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively. A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78–1.69), nor with survival at discharge (1.05, 0.58–1.90). Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2020
DOI: 10.1007/S00415-020-10174-1
Abstract: The original version of this article unfortunately contained a mistake.
Publisher: IEEE
Date: 06-2012
Publisher: Mary Ann Liebert Inc
Date: 19-10-2020
Publisher: Springer Science and Business Media LLC
Date: 06-09-2017
Publisher: Mary Ann Liebert Inc
Date: 04-2019
Abstract: Observer variability in local radiological reading is a major concern in large-scale multi-center traumatic brain injury (TBI) studies. A central review process has been advocated to minimize this variability. The aim of this study is to compare central with local reading of TBI imaging datasets and to investigate the added value of central review. A total of 2050 admission computed tomography (CT) scans from subjects enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were analyzed for seven main CT characteristics. Kappa statistics were used to calculate agreement between central and local evaluations and a center-specific analysis was performed. The McNemar test was used to detect whether discordances were significant. Central interobserver and intra-observer agreement was calculated in a subset of patients. Good agreement was found between central and local assessment for the presence or absence of structural pathology (CT+, CT-, κ = 0.73) and most CT characteristics (κ = 0.62 to 0.71), except for traumatic axonal injury lesions (κ = 0.37). Despite good kappa values, discordances were significant in four of seven CT characteristics (i.e., midline shift, contusion, traumatic subarachnoid hemorrhage, and cisternal compression p = 0.0005). Central reviewers showed substantial to excellent interobserver and intra-observer agreement (κ = 0.73 to κ = 0.96), contrasted by considerable variability in local radiological reading. Compared with local evaluation, a central review process offers a more consistent radiological reading of acute CT characteristics in TBI. It generates reliable, reproducible data and should be recommended for use in multi-center TBI studies.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 12-08-2021
DOI: 10.1126/SCIIMMUNOL.ABL4348
Abstract: TLR7 and plasmacytoid dendritic cells are essential for type I IFN–dependent immunity to SARS-CoV-2 in the lungs.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 25-02-2020
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1007/S00701-022-05257-Z
Abstract: To compare outcomes between patients with primary external ventricular device (EVD)–driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)–driven treatment. The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with “center” as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36–1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34–2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor–guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).
Publisher: Wiley
Date: 31-05-2022
DOI: 10.1111/AAS.14091
Abstract: Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID‐ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. This protocol describes the secondary, pre‐planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID‐ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile‐based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. The results of this secondary, pre‐planned Bayesian analysis will complement the primary frequentist analysis of the AID‐ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
DOI: 10.1007/S00415-020-10022-2
Abstract: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities. Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported. Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and in iduals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue. A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-10-2020
Abstract: The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). In iduals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system d ens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified in iduals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy in iduals. Together, these studies identify a means by which in iduals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 see also p. 404
Publisher: Mary Ann Liebert Inc
Date: 19-10-2020
Publisher: SAGE Publications
Date: 07-08-2020
Abstract: Although rehabilitation is beneficial for in iduals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care. Therefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI. Data from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge. In the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62 reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47 reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24). Based on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.
Publisher: Elsevier BV
Date: 09-2023
No related grants have been discovered for Giuseppe Citerio.