Machine learning driven prediction of cerebrospinal fluid rhinorrhoea following endonasal skull base surgery: A multicentre prospective observational study

Background. Cerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis. Methods. A dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score. Results. CSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches. Conclusion. Neural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling

The pathophysiology of chronic subdural haematoma and the role of the dexamethasone

Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid overlying the surface of the brain, which is often treated with surgical drainage to prevent cerebral compression. Despite treatment it can recur, requiring further surgery and causing significant morbidity. Historically CSDH formation was considered to occur due to the ageing and expansion of acute bleeding following head trauma. However, within this thesis the natural progression of CSDH was assessed with serial imaging following trauma and highlighted the novel process of CSDH formation from a normal CT. This was hypothesised to occur through injury initiating inflammation within the subdural space which drives formation of a hypervascular membrane responsible for fluid and blood accumulation over time. This theory was investigated by examining 68 CSDH samples for the presence of selected inflammatory markers and haemoglobin concentration. All pro-inflammatory markers were significantly elevated in CSDH fluid compared to venous blood, particularly vascular endothelial growth factor (VEGF). Haemoglobin degradation products were quantified with UV-Vis spectroscopy and more recent haemorrhage indicated an increased CSDH recurrence risk. This work was performed alongside the Dex-CSDH trial, a randomised, placebo-controlled trial of the potent anti-inflammatory dexamethasone. Blinded interim results of the trial are discussed, but the main focus are the scientific, mechanistic sub-studies. A method for detecting dexamethasone in CSDH and blood was developed using high performance liquid chromatography (HPLC), and suggested there is no accumulation of the drug within the CSDH space. However, many of the inflammatory markers were reduced post-operatively following dexamethasone treatment. Volumetric and density analysis of pre-operative and post-operative imaging was also performed and may aid prediction of which patients are more likely to have a poor outcome or recurrence. This could help identify patients in the future who would benefit most from adjuvant therapies such as dexamethasone.Royal college of Surgeons of England research fellowship, Rosetrees Trust funding and National Institute of Health Research (NIHR)- Health Technology Assessment (HTA) funding for the Dex-CSDH trial

Balancing risks and benefits when recommencing oral anticoagulants after major bleeding

No Abstrac

Integrated care pathways in neurosurgery: A systematic review.

IntroductionIntegrated care pathways (ICPs) are a pre-defined framework of evidence based, multidisciplinary practice for specific patients. They have the potential to enhance continuity of care, patient safety, patient satisfaction, efficiency gains, teamwork and staff education. In order to inform the development of neurosurgical ICPs in the future, we performed a systematic review to aggregate examples of neurosurgical ICP, to consider their impact and design features that may be associated with their success.MethodsElectronic databases MEDLINE, EMBASE, and CENTRAL were searched for relevant literature published from date of inception to July 2020. Primary studies reporting details of neurosurgical ICPs, across all pathologies and age groups were eligible for inclusion. Patient outcomes in each case were also recorded.ResultsTwenty-four studies were included in our final dataset, from the United States, United Kingdom, Italy, China, Korea, France, Netherlands and Switzerland, and a number of sub-specialties. 3 for cerebrospinal fluid diversion, 1 functional, 2 neurovascular, 1 neuro-oncology, 2 paediatric, 2 skull base, 10 spine, 1 for trauma, 2 miscellaneous (other craniotomies). All were single centre studies with no regional or national examples. Thirteen were cohort studies while 11 were case series which lacked a control group. Effectiveness was typically evaluated using hospital or professional performance metrics, such as length of stay (n = 11, 45.8%) or adverse events (n = 17, 70.8%) including readmission, surgical complications and mortality. Patient reported outcomes, including satisfaction, were evaluated infrequently (n = 3, 12.5%). All studies reported a positive impact. No study reported how the design of the ICP was informed by published literature or other methods.ConclusionsICPs have been successfully developed across numerous neurosurgical sub-specialities. However, there is often a lack of clarity over their design and weaknesses in their evaluation, including an underrepresentation of the patient's perspective

Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy.

Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid on the surface of the brain. Historically considered a result of head trauma, recent evidence suggests there are more complex processes involved. Trauma may be absent or very minor and does not explain the progressive, chronic course of the condition. This review focuses on several key processes involved in CSDH development: angiogenesis, fibrinolysis and inflammation. The characteristic membrane surrounding the CSDH has been identified as a source of fluid exudation and haemorrhage. Angiogenic stimuli lead to the creation of fragile blood vessels within membrane walls, whilst fibrinolytic processes prevent clot formation resulting in continued haemorrhage. An abundance of inflammatory cells and markers have been identified within the membranes and subdural fluid and are likely to contribute to propagating an inflammatory response which stimulates ongoing membrane growth and fluid accumulation. Currently, the mainstay of treatment for CSDH is surgical drainage, which has associated risks of recurrence requiring repeat surgery. Understanding of the underlying pathophysiological processes has been applied to developing potential drug treatments. Ongoing research is needed to identify if these therapies are successful in controlling the inflammatory and angiogenic disease processes leading to control and resolution of CSDH.EE was supported by a Royal College of Surgeons of England Fellowship, funded by the Rosetrees Trust. PJH is supported by a Research Professorship from the National Institute for Health Research (NIHR) and by the NIHR Biomedical Research Centre, Cambridge. KLHC is supported by the NIHR Biomedical Research Centre, Cambridge

Is information provided within chronic subdural haematoma education resources adequate? A scoping review

Background Chronic subdural haematoma (CSDH) is becoming increasingly prevalent, due to an aging population with increasing risk factors. Due to its variable disease course and high morbidity, patient centred care and shared decision making are essential. However, its occurrence in frail populations, remote from specialist neurosurgeons who currently triage treatment decisions, challenges this. Education is an important component of enabling shared decisions. This should be targeted to avoid information overload. However, it is unknown what this should be. Objectives Our objectives were to conduct analysis of the content of existing CSDH educational materials, to inform the development of patient and relative educational resources to facilitate shared decision making. Methods A literature search was conducted (July 2021) of MEDLINE, Embase and grey literature, for all self-specified resources on CSDH education, and narrative reviews. Resources were classified into a hierarchical framework using inductive thematic analysis into 8 core domains: Aetiology, epidemiology and pathophysiology; natural history and risk factors; symptoms; diagnosis; surgical management; nonsurgical management; complications and recurrence; and outcomes. Domain provision was summarised using descriptive statistics and Chi-squared tests. Results 56 information resources were identified. 30 (54%) were resources designed for healthcare professionals (HCPs), and 26 (46%) were patient-orientated resources. 45 (80%) were specific to CSDH, 11 (20%) covered head injury, and 10 (18%) referenced both acute and chronic SDH. Of 8 core domains, the most reported were aetiology, epidemiology and pathophysiology (80%, n = 45) and surgical management (77%, n = 43). Patient orientated resources were more likely to provide information on symptoms (73% vs 13%, p\u3c0.001); and diagnosis (62% vs 10%, p\u3c0.001) when compared to HCP resources. Healthcare professional orientated resources were more likely to provide information on nonsurgical management (63% vs 35%, p = 0.032), and complications/recurrence (83% vs 42%, p = 0.001). Conclusion The content of educational resources is varied, even amongst those intended for the same audience. These discrepancies indicate an uncertain educational need, that will need to be resolved in order to better support effective shared decision making. The taxonomy created can inform future qualitative studies

Statistical analysis plan for the Dex-CSDH trial: a randomised, double-blind, placebo-controlled trial of a 2-week course of dexamethasone for adult patients with a symptomatic chronic subdural haematoma

Abstract: Background: The incidence of chronic subdural haematoma (CSDH) is increasing. Although surgery remains the mainstay of management for symptomatic patients, uncertainty remains regarding the role of steroids. Hence, the Dex-CSDH trial was launched in the UK in 2015 aiming to determine whether, compared to placebo, dexamethasone can improve the 6-month functional outcome of patients with symptomatic CSDH by reducing the rate of surgical intervention and recurrence rate. Methods and design: Dex-CSDH is a multi-centre, pragmatic, parallel group, double-blind, randomised trial assessing the clinical utility of a 2-week course of dexamethasone following a CSDH. Seven hundred fifty patients were randomised to either dexamethasone or placebo. The primary outcome is the modified Rankin Scale at 6 months which is dichotomised to favourable (a score of 0–3) versus unfavourable (a score of 4–6). Conclusions: This paper and the accompanying additional material describe the statistical analysis plan for the trial. Trial registration: ISRCTN, ISRCTN80782810. Registered on 7 November 2014. http://www.isrctn.com/ISRCTN80782810. EudraCT, 2014-004948-35. Registered on 20 March 2015

A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial)

BACKGROUND: Chronic subdural haematoma is a collection of ‘old blood’ and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. OBJECTIVE: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. DESIGN: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. SETTING: Neurosurgical units in the UK. PARTICIPANTS: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. INTERVENTIONS: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. MAIN OUTCOMES MEASURES: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0–3) or an unfavourable (score of 4–6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. RESULTS: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (−8.2%, 95% confidence interval −13.3% to −3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be –£97.19. CONCLUSIONS: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group