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.

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.

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

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.

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

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: 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. We aimed to use deep learning to reliably and efficiently quantify and detect different lesion types. METHODS: Patients were recruited between Dec 9, 2014, and Dec 17, 2017, in 60 centres across Europe. We trained and validated an initial convolutional neural network (CNN) on expert manual segmentations (dataset 1). This CNN was used to automatically segment a new dataset of scans, which we then corrected manually (dataset 2). From this dataset, we used a subset of scans to train a final CNN for multiclass, voxel-wise segmentation of lesion types. The performance of this CNN was evaluated on a test subset. Performance was measured for lesion volume quantification, lesion progression, and lesion detection and lesion volume classification. For lesion detection, external validation was done on an independent set of 500 patients from India. FINDINGS: 98 scans from one centre were included in dataset 1. Dataset 2 comprised 839 scans from 38 centres: 184 scans were used in the training subset and 655 in the test subset. Compared with manual reference, CNN-derived lesion volumes showed a mean difference of 0·86 mL (95% CI -5·23 to 6·94) for intraparenchymal haemorrhage, 1·83 mL (-12·01 to 15·66) for extra-axial haemorrhage, 2·09 mL (-9·38 to 13·56) for perilesional oedema, and 0·07 mL (-1·00 to 1·13) for intraventricular haemorrhage. INTERPRETATION: We show the ability of a CNN to separately segment, quantify, and detect multiclass haemorrhagic lesions and perilesional oedema. These volumetric lesion estimates allow clinically relevant quantification of lesion burden and progression, with potential applications for personalised treatment strategies and clinical research in TBI. FUNDING: European Union 7th Framework Programme, Hannelore Kohl Stiftung, OneMind, NeuroTrauma Sciences, Integra Neurosciences, European Research Council Horizon 2020.

Usefulness of the NULL-PLEASE Score to Predict Survival in Out-of-Hospital Cardiac Arrest.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) carries a very high mortality rate even after successful cardiopulmonary resuscitation. Currently, information given to relatives about 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 multicenter 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: Nonshockable initial rhythm, Unwitnessed arrest, Long low-flow period, Long no-flow period, pH <7.2, Lactate >7.0 mmol/L, End-stage renal failure, Age ≥85 years, Still resuscitation, and Extracardiac 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 with those who died (0 [interquartile range 0-1] vs 4 [interquartile range 2-4], P < .0005) and strongly predictive of in-hospital death (C-statistic 0.874; 95% confidence interval, 0.848-0.899). Patients with a score ≥3 had a 24-fold increased risk of death (odds ratio 23.6; 95% confidence interval, 14.840-37.5; P < .0005) compared with those with lower scores. A score ≥3 has a 91% positive predictive value for in-hospital death, while 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.

Lateral Brain Displacement and Cerebral Autoregulation in Acutely Comatose Patients.

OBJECTIVES: Lateral displacement and impaired cerebral autoregulation are associated with worse outcomes following acute brain injury, but their effect on long-term clinical outcomes remains unclear. We assessed the relationship between lateral displacement, disturbances to cerebral autoregulation, and clinical outcomes in acutely comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Acutely comatose patients (Glasgow Coma Score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebral oximetry index, derived from near-infrared spectroscopy multimodal monitoring, was used to evaluate cerebral autoregulation. Associations between lateral brain displacement, global cerebral autoregulation, and interhemispheric cerebral autoregulation asymmetry were assessed using mixed random effects models with random intercept. Patients were grouped by functional outcome, determined by the modified Rankin Scale. Associations between outcome group, lateral displacement, and cerebral oximetry index were assessed using multivariate linear regression. Increasing lateral brain displacement was associated with worsening global cerebral autoregulation (p = 0.01 septum; p = 0.05 pineal) and cerebral autoregulation asymmetry (both p < 0.001). Maximum lateral displacement during the first 3 days of coma was significantly different between functional outcome groups at hospital discharge (p = 0.019 pineal; p = 0.008 septum), 3 months (p = 0.026; p = 0.007), 6 months (p = 0.018; p = 0.010), and 12 months (p = 0.022; p = 0.012). Global cerebral oximetry index was associated with functional outcomes at 3 months (p = 0.019) and 6 months (p = 0.013). CONCLUSIONS: During the first 3 days of acute coma, increasing lateral brain displacement is associated with worsening global cerebral autoregulation and cerebral autoregulation asymmetry, and poor long-term clinical outcomes in acutely comatose patients. The impact of acute interventions on outcome needs to be explored.

Relationship of Platelet Reactivity and Inflammatory Markers to Recurrent Adverse Events in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND: 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.

Effect of Body Temperature on Cerebral Autoregulation in Acutely Comatose Neurocritically Ill Patients.

OBJECTIVES: Impaired cerebral autoregulation following neurologic injury is a predictor of poor clinical outcome. We aimed to assess the relationship between body temperature and cerebral autoregulation in comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Eighty-five acutely comatose patients (Glasgow Coma Scale score of ≤ 8) admitted between 2013 and 2017. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Cerebral autoregulation was monitored using multimodal monitoring with near-infrared spectroscopy-derived cerebral oximetry index. Cerebral oximetry index was calculated as a Pearson correlation coefficient between low-frequency changes in regional cerebral oxygenation saturation and mean arterial pressure. Patients were initially analyzed together, then stratified by temperature pattern over the monitoring period: no change (< 1°C difference between highest and lowest temperatures; n = 11), increasing (≥ 1°C; n = 9), decreasing (≥ 1°C; n = 9), and fluctuating (≥ 1°C difference but no sustained direction of change; n = 56). Mixed random effects models with random intercept and multivariable logistic regression analysis were used to assess the association between hourly temperature and cerebral oximetry index, as well as between temperature and clinical outcomes. Cerebral oximetry index showed a positive linear relationship with temperature (ß = 0.04 ± 0.10; p = 0.29). In patients where a continual increase or decrease in temperature was seen during the monitoring period, every 1°C change in temperature resulted in a cerebral oximetry index change in the same direction by 0.04 ± 0.01 (p < 0.001) and 0.02 ± 0.01 (p = 0.12), respectively, after adjusting for PaCO2, hemoglobin, mean arterial pressure, vasopressor and sedation use, and temperature probe location. There was no significant difference in mortality or poor outcome (modified Rankin Scale score of 4-6) between temperature pattern groups at discharge, 3, or 6 months. CONCLUSIONS: In acute coma patients, increasing body temperature is associated with worsening cerebral autoregulation as measured by cerebral oximetry index. More studies are needed to clarify the impact of increasing temperature on cerebral autoregulation in patients with acute brain injury.

Anti-NMDA-Receptor Encephalitis: From Bench to Clinic.

NMDAR encephalitis is a common cause of autoimmune encephalitis, predominantly affecting young adults. Current data supports the idea that autoantibodies targeting NMDARs are responsible for disease pathogenesis. While these autoantibodies occur in the setting of underlying malignancy in approximately half of all patients, initiating factors for the autoimmune response in the remainder of patients are unclear. While there is increasing evidence supporting viral triggers such as herpes simplex encephalitis, this association and the mechanism of action have not yet been fully described. Although the majority of patients achieve good outcomes, those without an underlying tumor consistently show worse outcomes, prolonged recovery, and more frequent relapses. The cloning of patient-specific autoantibodies from affected individuals has raised important questions as to disease pathophysiology and clinical heterogeneity. Further advances in our understanding of this disease and underlying triggers are necessary to develop treatments which improve outcomes in patients presenting in the absence of tumors.