Stephen Honeybul

Objectives: Blood-based and diffusion MRI (dMRI) biomarkers of white matter injury after acute mild traumatic brain injury (mTBI) were examined to: (1) distinguish mTBI from healthy controls (HC); (2) quantify inter-modality relationships; (3) identify associations between acute biomarker changes and recovery; (4) evaluate moderating influences of resilience and coping style. Methods: 36 adults with mTBI (37.6±13.7 years; 37.1% female) and 35 HC participants (34.2 ± 11.9; 47.1% female) underwent baseline testing (≤ 9 days post-mTBI) including: blood-sampling (neurofilament light-chain [NfL], brain-derived tau, glial fibrillary acidic protein, ubiquitin carboxyl terminal hydroxylase-L1, four-repeat tau [4R-tau]), dMRI analysis of 48 white matter tracts, symptom (Post-Concussion Symptom Scale [PCSS]) and psychological questionnaires (Brief Resilience Scale, Utrecht Coping List). Recovery was determined at 3-, 6- and 12-month follow-ups using PCSS scores. Associations were evaluated using correlations, logistic regression, and exploratory moderation analyses. Trial registration Number: ACTRN12619001226190. Results: 37.1% of participants reported persistent symptoms at 3 months, 42.9% and 28.6% at 6 and 12 months, respectively. NfL and 4R-tau were acutely elevated post-mTBI, alongside widespread increases in radial, mean, and axial diffusivity. Divergent recovery trajectories were defined by distinct baseline biomarker profiles: elevated NfL and mean diffusivity characterized recovered participants, while elevated 4R-tau and radial diffusivity characterized those who remained symptomatic. NfL was associated with recovery at 3 months and 4R-tau with symptomatic status at 12 months. Coping style, not resilience, moderated blood biomarker–outcome relationships. Conclusion: Divergent acute profiles of blood biomarkers, white matter diffusivity, and coping style distinguish mTBI recovery trajectories, providing hypothesis-generating support for biologically informed molecular, microstructural, and psychological mTBI phenotypes. Trial registration number: ACTRN12619001226190 approved March 2023.

Introduction Pre-treatment re-bleeding is a devastating complication following aneurysmal subarachnoid haemorrhage (aSAH) with reported mortality up to 73% and a reported rate of poor neurological outcome in up to 84% of patients. Even with ultra-early treatment within 24 hours of ictus it affects up to 7.2% of patients. Three scoring systems have been described incorporating accepted clinical and radiological re-bleed predictors in various combinations. In this study we compared the predictive utility of each scoring system and individual established clinical and radiological predictors. Methods Retrospective analysis of our single centre 9-year cohort of 642 consecutive aSAH patients treated within an ultra-early timeframe, 36 had pre-treatment re-bleeding (5.6%). Thirty suitable cases who had a single culprit saccular aneurysm and pre-treatment non-invasive cerebrovascular imaging were matched based on size and parent vessel location to 90 controls who did not re-bleed on a 1:3 basis. Demographic, clinical and radiological data were extracted and predictive scores calculated. Univariate, multivariate and area under the receiver operator characteristic curve (AUROCC) analyses were performed. Results The majority of all patients (95%) were treated using endovascular techniques at a median time 15.25 hours post-ictus. Both of these metrics did not differ in a statistically significant manner between cases and control on univariate analysis. Median World Federation of Neurological Surgeons (WFNS) grade at presentation for cases was 4 compared to 2 for controls (p=0.021) whilst the median Fisher grade at presentation was 4 for cases and 3 for controls (p=0.001). At presentation 60% of cases had an ICH compared to 26% of controls (p=0.001). Symptomatic hydrocephalus requiring the placement of an external ventricular drain prior to aneurysm treatment was present for 60% of cases compared to 38% of controls (p=0.033). On AUROCC analysis the score of Liu et al. displayed minimal predictive utility (AUROCC 0.526, 95%CI 0.416 - 0.636) whilst the score of Oppong et al. (AUROCC 0.648 95% CI 0.541 - 0.754) and the ARISE-extended score (AUROCC 0.652 95% CI 0.529 - 0.775) displayed moderate utility. On multivariate modelling WFNS grade at presentation alone was the most parsimonious predictive model for re-bleed prediction (AUROCC 0.787, 95% CI 0.0.687 - 0.887) with superiority over all other potential factors in single, two or three factor combinations and each of the three described predictive scores. Conclusion In aSAH patients treated within an ultra-early timeframe, WFNS grade at presentation displayed optimal utility for re-bleed prediction compared to three published scoring systems incorporating varying combinations of multiple re-bleed predictors. Future re-bleed prediction models should incorporate the WFNS. Furthermore, earlier aneurysm occlusion should not be withheld from high grade aSAH patients with favourable prognostic factors as these patients may stand to benefit most from re-bleed prevention. Disclosures A. Dissanayake: None. E. Burrows: None. K. Ho: None. T. Phillips: None. S. Honeybul: None. G. Hankey: None.

Background: Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage (aSAH) affects up to 7.2% of patients even with ultra-early treatment within 24 hours. We retrospectively compared the utility of three published re-bleed prediction models and individual predictors between cases who re-bled matched to controls using size and parent vessel location from a cohort of patients treated in an ultra-early, ‘endovascular first’ manner.Methods: On retrospective analysis of our 9-year cohort of 707 patients suffering 710 episodes of aSAH, there were 53 episodes of pre-treatment re-bleeding (7.5%). Forty-seven cases who had a single culprit aneurysm were matched to 141 controls. Demographic, clinical and radiological data were extracted and predictive scores calculated. Univariate, multivariate, area under the receiver operator characteristic curve (AUROCC) and Kaplan–Meier (KM) survival curve analyses were performed.Results: The majority of patients (84%) were treated using endovascular techniques at a median 14.5 hours post-diagnosis. On AUROCC analysis the score of Liuet al.had minimal utility (C-statistic 0.553, 95% confidence interval (CI) 0.463 to 0.643) while the risk score of Opponget al.(C-statistic 0.645 95% CI 0.558 to 0.732) and the ARISE-extended score of van Lieshoutet al.(C-statistic 0.53 95% CI 0.562 to 0.744) had moderate utility. On multivariate modeling, the World Federation of Neurosurgical Societies (WFNS) grade was the most parsimonious predictor of re-bleeding (C-statistic 0.740, 95% CI 0.664 to 0.816).Conclusions: For aSAH patients treated in an ultra-early timeframe matched on size and parent vessel location, WFNS grade was superior to three published models for re-bleed prediction. Future re-bleed prediction models should incorporate the WFNS grade.

Background: Core outcome sets (COSs) are important and necessary as they help standardize reporting in research studies. Cranioplasty following traumatic brain injury (TBI) or stroke is becoming increasingly common, leading to an ever-growing clinical and research interest, especially regarding the optimal material, cost-effectiveness, and timing of cranioplasty concerning neurological recovery and complications. Consequently, heterogeneous reporting of outcomes from such diverse studies has led to limited meta-analysis ability and an ongoing risk of outcome reporting bias. This study aims to define a standardized COS for reporting in all future TBI and stroke cranioplasty studies. Objective: This study has four aims: (1) undertake a systematic review to collate the most current outcome measures used within the cranioplasty literature; (2) undertake a qualitative study to understand better the views of clinicians, patients' relatives, and allied health professionals regarding clinical outcomes following cranioplasty; (3) undertake a Delphi survey as part of the process of gaining consensus for the COS; and (4) finalize consensus through a consensus meeting resulting in the COS. Methods: An international steering committee has been formed to guide the development of the COS. In addition, recommendations from other clinical initiatives such as COMET (Core Outcomes and Effectiveness Trials) and OMERACT (Outcome Measures in Rheumatology) have been adhered to. Phase 1 is data collection through a systematic review and qualitative study. Phase 2 is the COS development through a Delphi survey and consensus meetings with consensus definitions decided and agreed upon before the Delphi survey begins to avoid bias. Results: Phase 1 started at the end of 2019, following ethical approval in December 2019, and the project completion date is planned for the end of 2022 or beginning of 2023. Conclusions: This study should result in a consensus on a COS for cranioplasty, following TBI or stroke, to help standardize outcome reporting for future studies, which can be applied to future research and clinical services, help align future studies, build an increased understanding of cranioplasty and its impact on a patient’s function and recovery, and help standardize the evidence base. International Registered Report Identifier (IRRID): DERR1-10.2196/37442

A new hypervirulent variant of Klebsiella pneumoniae has emerged. In contrast to classic Klebsiella pneumoniae, it can cause serious and life-threatening infection. It has the ability of spreading ...