Contusion Progression Following Traumatic Brain Injury: A Review of Clinical and Radiological Predictors, and Influence on Outcome

Abstract: Secondary injuries remain an important cause of the morbidity and mortality associated with traumatic brain injury (TBI). Progression of cerebral contusions occurs in up to 75% of patients with TBI, and this contributes to subsequent clinical deterioration and requirement for surgical intervention. Despite this, the role of early clinical and radiological factors in predicting contusion progression remains relatively poorly defined due to studies investigating progression of all types of hemorrhagic injuries as a combined cohort. In this review, we summarize data from recent studies on factors which predict contusion progression, and the effect of contusion progression on clinical outcomes

Multiclass semantic segmentation and quantification of traumatic brain injury lesions on head CT using deep learning: an algorithm development and multicentre validation study

Background: Computed tomography (CT) is the most common imaging modality in traumatic brain injury (TBI). However, its conventional use requires expert clinical interpretation and does not provide detailed quantitative outputs, which may have prognostic importance. Deep learning could reliably and efficiently detect, distinguish, and quantify different lesion types, providing opportunities for personalised treatment strategies and clinical research. Methods: An initial convolutional neural network (CNN) was trained and validated on expert manual segmentations (97 scans). This CNN was then used to automatically segment a new set of 839 scans, which were then manually corrected by experts. From these, a subset of 184 scans was used to train a final CNN for multi-class, voxel-wise segmentation of lesion types. The performance of this CNN was evaluated on a held-out test set with 655 scans. External validation was performed on a large, independent set of 500 patients from a different continent. Findings: When compared to manual reference, CNN-derived lesion volumes showed a mean error of 0·86mL (95% CI -5·23 to 6·94) for intraparenchymal haemorrhage (IPH), 1·83mL (-12·01 to 15·66) for extra-axial haemorrhage (EAH), 2·09mL (-9·38 to 13·56) for perilesional oedema and 0·07mL (-1·00 to 1·13) for intraventricular haemorrhage (IVH). Further, the CNN detected lesions with AUCs of 0·90 (0·86-0·94) for IPH, 0·80 (0·75-0·85) for EAH, 0·95 (0·89-1·00) for IVH on the external, independent patient dataset. Interpretation: We demonstrate the ability of a CNN to separately segment, detect and quantify multi-class haemorrhagic lesions and importantly, perilesional oedema. These volumetric lesion estimates allow clinically relevant quantification of lesion burden and progression, with potential applications in clinical care and research in TBI. Funding: European Union 7th Framework Programme, Hannelore Kohl Stiftung; OneMind; Integra Neurosciences; European Research Council Horizon 2020; Engineering and Physical Sciences Research Council (UK); Academy of Medical Sciences/Health Foundation (UK); National Institute for Health Research (UK).CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150). Additional funding sources: Hannelore Kohl Stiftung; NeuroTrauma Sciences; Integra Neurosciences; European Research Council (ERC) Horizon 2020 (EC grant 757173); Engineering and Physical Sciences Research Council (EPSRC) (EP/R511547/1); Academy of Medical Sciences/The Health Foundation (UK); National Institute for Health Research (UK)

Relationship of platelet reactivity and inflammatory markers to recurrent adverse events in patients with ST-elevation myocardial infarction

© 2019 Thieme Publishing Group. This is an accepted manuscript of an article accepted for publication in Thrombosis and Haemostasis: https://dx.doi.org/10.1055/s-0039-1695007Background Patients with ST-elevation myocardial infarction (STEMI) exhibit pro-thrombotic and pro-inflammatory states. Markers of enhanced platelet reactivity and inflammation are predictive of adverse outcome. However, the relationship between these biomarkers, and their combined usefulness for risk stratification, is not clear. Methods ?In a prospective study of 541 patients presenting with STEMI, blood samples were taken on arrival to measure high-sensitivity C-reactive protein (hs-CRP), neutrophil/lymphocyte ratio (NLR) and platelet reactivity using the point-of-care Global Thrombosis Test. These biomarkers, alone and in combination, were related to the occurrence of major adverse cardiovascular events (MACE, defined as composite of cardiovascular death, myocardial infarction and cerebrovascular accident) at 30 days and 12 months. Results ?Platelet reactivity and hs-CRP, but not NLR, were weakly predictive of MACE at 30 days and 12 months. The combination of enhanced platelet reactivity and raised hs-CRP was strongly predictive of MACE at 30 days (hazard ratio [HR] 3.46 [95% confidence interval [CI] 1.81-6.62], p < 0.001) and 12 months (HR 3.46 [95% CI 1.81-6.63], p < 0.001). Combination of all three biomarkers (NLR, hs-CRP and platelet reactivity) provided the best prediction of MACE at 30 days (HR 3.73 [95% CI 1.69-8.27], p < 0.001) and 12 months (HR 3.85 [95% CI 1.72-8.60], p < 0.001), and improved the prediction of MACE when added to Thrombolysis In Myocardial Infarction score (net reclassification index 0.296, p < 0.001). Conclusion ?A combination of three easy to measure biomarkers on arrival, namely hs-CRP, NLR and platelet reactivity, can help identify STEMI patients at high risk of recurrent adverse events over the subsequent year.Peer reviewedFinal Accepted Versio

Out-of-hospital cardiac arrest : A systematic review of current risk scores to predict survival

Funding Information: Funding: None. Publisher Copyright: © 2020 Elsevier Inc.Importance: The arrest and the post-arrest period are an incredibly emotionally traumatic time for family and friends of the affected individual. There is a need to assess prognosis early in the patient pathway to offer objective, realistic and non-emotive information to the next-of-kin regarding the likelihood of survival. Objective: To present a systematic review of the clinical risk scores available to assess patients on admission following out-of-hospital cardiac arrest (OHCA) which can predict in-hospital mortality. Evidence review: A systematic search of online databases Embase, MEDLINE and Cochrane Central Register of Controlled Trials was conducted up until 20th November 2020. Findings: Out of 1,817 initial articles, we identified a total of 28 scoring systems, with 11 of the scores predicting mortality following OHCA included in this review. The majority of the scores included arrest characteristics (initial rhythm and time to return of spontaneous circulation) as prognostic indicators. Out of these, the 3 most clinically-useful scores, namely those which are easy-to-use, comprise of commonly available parameters and measurements, and which have high predictive value are the OHCA, NULL-PLEASE, and rCAST scores, which appear to perform similarly. Of these, the NULL-PLEASE score is the easiest to calculate and has also been externally validated. Conclusions: Clinicians should be aware of these risk scores, which can be used to provide objective, nonemotive and reproducible information to the next-of-kin on the likely prognosis following OHCA. However, in isolation, these scores should not form the basis for clinical decision-making.Peer reviewe

Usefulness of the NULL-PLEASE Score to predict 1 survival in out-of hospital cardiac arrest

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.Purpose: Out-of-hospital cardiac arrest (OHCA) carries a very high mortality even after successful cardiopulmonary resuscitation. Currently, information given to relatives regarding prognosis following resuscitation is often emotive and subjective, and varies with clinician experience. We aimed to validate the NULL-PLEASE score to predict survival following OHCA. Methods: A multicentre cohort study was conducted, with retrospective and prospective validation in consecutive unselected patients presenting with OHCA. The NULL-PLEASE score was calculated by attributing points to the following variables: Non-shockable initial rhythm, Unwitnessed arrest, Long low-flow period, Long no-flow period, pH7.0 mmol/l, End-stage renal failure, Age ≥85 years, Still resuscitation and Extra cardiac cause. The primary outcome was in-hospital death. Results: We assessed 700 patients admitted with OHCA, of whom 47% survived to discharge. In 300 patients we performed a retrospective validation, followed by prospective validation in 400 patients. The NULL-PLEASE score was lower in patients who survived compared to those who died (0 [IQR 0-1] vs. 4 [IQR 2-4], p<0.0005) and strongly predictive of in-hospital death (c-statistic 0.874, 95% confidence interval [CI] 0.848-0.899). Patients with a score ≥3 had a 24-fold increased risk of death (OR 23.6; 95%CI 14.840-37.5, p<0.0005) compared to those with lower scores. A score ≥3 has a 91% positive predictive value for in-hospital death, whilst a score <3 predicts a 71% chance of survival. Conclusion: The easy-to-use NULL-PLEASE score predicts in-hospital mortality with high specificity and can help clinicians explain the prognosis to relatives in an easy-to-understand, objective fashion, to realistically prepare them for the future.Peer reviewe

Blood Biomarkers and Structural Imaging Correlations Post-Traumatic Brain Injury: A Systematic Review.

BACKGROUND: Blood biomarkers are of increasing importance in the diagnosis and assessment of traumatic brain injury (TBI). However, the relationship between them and lesions seen on imaging remains unclear. OBJECTIVE: To perform a systematic review of the relationship between blood biomarkers and intracranial lesion types, intracranial lesion injury patterns, volume/number of intracranial lesions, and imaging classification systems. METHODS: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, and Cumulative Index to Nursing and Allied Health Literature from inception to May 2021, and the references of included studies were also screened. Heterogeneity in study design, biomarker types, imaging modalities, and analyses inhibited quantitative analysis, with a qualitative synthesis presented. RESULTS: Fifty-nine papers were included assessing one or more biomarker to imaging comparisons per paper: 30 assessed imaging classifications or injury patterns, 28 assessed lesion type, and 11 assessed lesion volume or number. Biomarker concentrations were associated with the burden of brain injury, as assessed by increasing intracranial lesion volume, increasing numbers of traumatic intracranial lesions, and positive correlations with imaging classification scores. There were inconsistent findings associating different biomarkers with specific imaging phenotypes including diffuse axonal injury, cerebral edema, and intracranial hemorrhage. CONCLUSION: Blood-based biomarker concentrations after TBI are consistently demonstrated to correlate burden of intracranial disease. The relation with specific injury types is unclear suggesting a lack of diagnostic specificity and/or is the result of the complex and heterogeneous nature of TBI.No funding was sort for the production of this article. DM reports grants from National Institute for Health Research (NIHR; UK), during the conduct of the study; grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from Neurotrauma Sciences, personal fees from Lantmaanen AB, personal fees from Pressura, personal fees from Pfizer, outside the submitted work. AM declares consulting fees from PresSura Neuro, Integra Life Sciences and NeuroTrauma Sciences. EC, KA (Amrein) and AB report grants Higher Education Institutional Excellence Programme – Grant No. 20765-3/2018/FEKUTSTRAT , FIKP II/S , EFOP- 3.6.2.-16-2017-00008 , GINOP-2.3.2-15-2016-00048 , and GINOP-2.3.3-15-2016- 00032 and the Hungarian Brain Research Program 2.0 Grant No. 2017-1.2.1-NKP- 2017-00002. VFJN is supported by an Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship and holds a grant funded by Roche pharmaceuticals

Challenges and patient outcomes in chronic subdural haematoma at the level of a regional care system: A multi-centre, mixed-methods study from the East of England

Background: Chronic subdural haematoma (cSDH) is a common neurosurgical pathology affecting older patients with other health conditions. A significant proportion (up-to 90%) of referrals for surgery in neurosciences units (NSU) come from secondary care. However, the organisation of this care and the experience of patients repatriated to non-specialist centres are currently unclear. Objectives: This study aimed to clarify patient outcome in non-specialist centres following NSU discharge for cSDH surgery and to understand key system challenges. The study was set within a representative neurosurgical care system in the east of England. Design and methods: We performed a retrospective cohort analysis of patients referred for cSDH surgery. Alongside case record review, patient and staff experience were explored using surveys as well as an interactive c-design workshop. Challenges were identified from thematic analysis of survey responses and triangulated by focussed workshop discussions. Results: Data on 381 patients referred for cSDH surgery from six centres was reviewed. One hundred and fifty-six (41%) patients were repatriated following surgery. Sixty-one (39%) of those repatriated suffered an inpatient complication (new infection, troponin rise or renal injury) following NSU discharge, with 58 requiring institutional discharge or new care. Surveys for staff (n = 42) and patients (n = 209) identified that resourcing, communication, and inter-hospital distance posed care challenges. This was corroborated through workshop discussions with stakeholders from two institutions. Conclusions: A significant amount of perioperative care for cSDH is delivered outside of specialist centres. Future improvement initiatives must recognise the system-wide nature of delivery and the challenges such an arrangement presents

Challenges and patient outcomes in chronic subdural haematoma at the level of a regional care system A multi-centre, mixed-methods study from the East of England.

BACKGROUND: Chronic subdural haematoma (cSDH) is a common neurosurgical pathology affecting older patients with other health conditions. A significant proportion (up-to 90%) of referrals for surgery in neurosciences units (NSU) come from secondary care. However, the organisation of this care and the experience of patients repatriated to non-specialist centres are currently unclear. OBJECTIVES: This study aimed to clarify patient outcome in non-specialist centres following NSU discharge for cSDH surgery and to understand key system challenges. The study was set within a representative neurosurgical care system in the east of England. DESIGN AND METHODS: We performed a retrospective cohort analysis of patients referred for cSDH surgery. Alongside case record review, patient and staff experience were explored using surveys as well as an interactive c-design workshop. Challenges were identified from thematic analysis of survey responses and triangulated by focussed workshop discussions. RESULTS: Data on 381 patients referred for cSDH surgery from six centres was reviewed. One hundred and fifty-six (41%) patients were repatriated following surgery. Sixty-one (39%) of those repatriated suffered an inpatient complication (new infection, troponin rise or renal injury) following NSU discharge, with 58 requiring institutional discharge or new care. Surveys for staff (n = 42) and patients (n = 209) identified that resourcing, communication, and inter-hospital distance posed care challenges. This was corroborated through workshop discussions with stakeholders from two institutions. CONCLUSIONS: A significant amount of perioperative care for cSDH is delivered outside of specialist centres. Future improvement initiatives must recognise the system-wide nature of delivery and the challenges such an arrangement presents.Wellcome Trust PhD Fellowship Addenbrooke's Charitable Trus