Glioma grade and post-neurosurgical meningitis risk.

BACKGROUND: Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas. METHODS: We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 106/L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4 mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84). RESULTS: Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12 days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association. CONCLUSIONS: The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries.

Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial.

BACKGROUND: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. METHODS: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. FINDINGS: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). INTERPRETATION: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. FUNDING: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.

Effect of Rural Trauma Team Development on the Outcomes of Motorcycle Accident-Related Injuries (Motor Registry Project): Protocol for a Multicenter Cluster Randomized Controlled Trial.

BACKGROUND: Injury is a global health concern, and injury-related mortality disproportionately impacts low- and middle-income countries (LMICs). Compelling evidence from observational studies in high-income countries shows that trauma education programs, such as the Rural Trauma Team Development Course (RTTDC), increase clinician knowledge of injury care. There is a dearth of such evidence from controlled clinical trials to demonstrate the effect of the RTTDC on process and patient outcomes in LMICs. OBJECTIVE: This multicenter cluster randomized controlled clinical trial aims to examine the impact of the RTTDC on process and patient outcomes associated with motorcycle accident-related injuries in an African low-resource setting. METHODS: This is a 2-arm, parallel, multi-period, cluster randomized, controlled, clinical trial in Uganda, where rural trauma team development training is not routinely conducted. We will recruit regional referral hospitals and include patients with motorcycle accident-related injuries, interns, medical trainees, and road traffic law enforcement professionals. The intervention group (RTTDC) and control group (standard care) will include 3 hospitals each. The primary outcomes will be the interval from the accident to hospital admission and the interval from the referral decision to hospital discharge. The secondary outcomes will be all-cause mortality and morbidity associated with neurological and orthopedic injuries at 90 days after injury. All outcomes will be measured as final values. We will compare baseline characteristics and outcomes at both individual and cluster levels between the intervention and control groups. We will use mixed effects regression models to report any absolute or relative differences along with 95% CIs. We will perform subgroup analyses to evaluate and control confounding due to injury mechanisms and injury severity. We will establish a motorcycle trauma outcome (MOTOR) registry in consultation with community traffic police. RESULTS: The trial was approved on August 27, 2019. The actual recruitment of the first patient participant began on September 01, 2019. The last follow-up was on August 27, 2023. Posttrial care, including linkage to clinical, social support, and referral services, is to be completed by November 27, 2023. Data analyses will be performed in Spring 2024, and the results are expected to be published in Autumn 2024. CONCLUSIONS: This trial will unveil how a locally contextualized rural trauma team development program impacts organizational efficiency in a continent challenged with limited infrastructure and human resources. Moreover, this trial will uncover how rural trauma team coordination impacts clinical outcomes, such as mortality and morbidity associated with neurological and orthopedic injuries, which are the key targets for strengthening trauma systems in LMICs where prehospital care is in the early stage. Our results could inform the design, implementation, and scalability of future rural trauma teams and trauma education programs in LMICs. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR202308851460352); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25763. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55297.

Early versus delayed cranioplasty after decompressive craniectomy in traumatic brain injury: a multicenter observational study within CENTER-TBI and Net-QuRe.

OBJECTIVE: The aim of this study was to compare the outcomes of early (≤ 90 days) and delayed (> 90 days) cranioplasty following decompressive craniectomy (DC) in patients with traumatic brain injury (TBI). METHODS: The authors analyzed participants enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Neurotraumatology Quality Registry (Net-QuRe) studies who were diagnosed with TBI and underwent DC and subsequent cranioplasty. These prospective, multicenter, observational cohort studies included 5091 patients enrolled from 2014 to 2020. The effect of cranioplasty timing on functional outcome was evaluated with multivariable ordinal regression and with propensity score matching (PSM) in a sensitivity analysis of functional outcome (Glasgow Outcome Scale-Extended [GOSE] score) and quality of life (Quality of Life After Brain Injury [QOLIBRI] instrument) at 12 months following DC. RESULTS: Among 173 eligible patients, 73 (42%) underwent early cranioplasty and 100 (58%) underwent delayed cranioplasty. In the ordinal logistic regression and PSM, similar 12-month GOSE scores were found between the two groups (adjusted odds ratio [aOR] 0.87, 95% CI 0.61-1.21 and 0.88, 95% CI 0.48-1.65, respectively). In the ordinal logistic regression, early cranioplasty was associated with a higher risk for hydrocephalus than that with delayed cranioplasty (aOR 4.0, 95% CI 1.2-16). Postdischarge seizure rates (early cranioplasty: aOR 1.73, 95% CI 0.7-4.7) and QOLIBRI scores (ß -1.9, 95% CI -9.1 to 9.6) were similar between the two groups. CONCLUSIONS: Functional outcome and quality of life were similar between early and delayed cranioplasty in patients who had undergone DC for TBI. Neurosurgeons may consider performing cranioplasty during the index admission (early) to simplify the patient's chain of care and prevent readmission for cranioplasty but should be vigilant for an increased possibility of hydrocephalus. Clinical trial registration nos.: CENTER-TBI, NCT02210221 (clinicaltrials.gov); Net-QuRe, NTR6003 (trialsearch.who.int) and NL5761 (onderzoekmetmensen.nl).

Rural trauma team development training amongst medical trainees and traffic law enforcement professionals in a low-income country: a protocol for a prospective multicenter interrupted time series.

Background: Road traffic injuries and their resulting mortality disproportionately affect rural communities in low-middle-income countries (LMICs) due to limited human and infrastructural resources for postcrash care. Evidence from high-income countries show that trauma team development training could improve the efficiency, care, and outcome of injuries. A paucity of studies have evaluated the feasibility and applicability of this concept in resource constrained settings. The aim of this study protocol is to establish the feasibility of rural trauma team development and training in a cohort of medical trainees and traffic law enforcement professionals in Uganda. Methods: Muticenter interrupted time series of prospective interventional trainings, using the rural trauma team development course (RTTDC) model of the American College of Surgeons. A team of surgeon consultants will execute the training. A prospective cohort of participants will complete a before and after training validated trauma related multiple choice questionnaire during September 2019-November 2023. The difference in mean prepost training percentage multiple choice questionnaire scores will be compared using ANOVA-test at 95% CI. Time series regression models will be used to test for autocorrelations in performance. Acceptability and relevance of the training will be assessed using 3 and 5-point-Likert scales. All analyses will be performed using Stata 15.0. Ethical approval was obtained from Research and Ethics Committee of Mbarara University of Science and Technology (Ref: MUREC 1/7, 05/05-19) and Uganda National Council for Science and Technology (Ref: SS 5082). Retrospective registration was accomplished with Research Registry (UIN: researchregistry9490).

Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction." Results: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain." Discussion and conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries-A Prospective Cohort Study.

Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients' outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53-89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83-65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.

Preliminary Evaluation of the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries with Glial Fibrillary Acidic Protein.

Glial fibrillary acidic protein (GFAP) has become the most promising biomarker for detecting traumatic abnormalities on head computed tomography (CT) in patients with traumatic brain injury (TBI), but most studies have not addressed the potential added value of combining the biomarker with clinical variables that confer risk for intracranial injuries. The Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults were the first clinical decision rules in the field with an incorporated biomarker, the S100 astroglial calcium-binding protein B (S100B), which is used in the Mild (Low Risk) group defined by the guidelines. Our aim was to evaluate the performance of the guidelines when S100B was substituted with GFAP. The sample (N = 296) was recruited from the Tampere University Hospital's emergency department between November 2015 and November 2016, and there were 49 patients with available GFAP results who were stratified in the Mild (Low Risk) group (thus patients undergoing biomarker triaging). A previously reported cutoff of plasma GFAP ≥140 pg/mL was used. Within the Mild (Low Risk) group (n = 49), GFAP sensitivity (with 95% confidence intervals in parentheses) for detecting traumatic CT abnormalities was 1.0 (0.40-1.00), specificity 0.34 (0.19-0.53), the negative predictive value (NPV) 1.0 (0.68-1.00), and the positive predictive value (PPV) 0.16 (0.05-0.37). The sensitivity and specificity of the modified guidelines with GFAP, when applied to all imaged patients (n = 197) in the whole sample, were 0.94 (0.77-0.99) and 0.20 (0.15-0.28), respectively. NPV was 0.94 (0.80-0.99) and PPV 0.18 (0.13-0.25). In the Mild (Low Risk) group, none of the patients with GFAP results below 140 pg/mL had traumatic abnormalities on their head CT. These findings were derived from a small patient subgroup. Future researchers should replicate these findings in larger samples and assess whether GFAP has added or comparable value to S100B in acute TBI management.

Late Blood Levels of Neurofilament Light Correlate With Outcome in Patients With Traumatic Brain Injury.

Neurofilament light (NF-L) is an axonal protein that has shown promise as a traumatic brain injury (TBI) biomarker. Serum NF-L shows a rather slow rise after injury, peaking after 1-2 weeks, although some studies suggest that it may remain elevated for months after TBI. The aim of this study was to examine if plasma NF-L levels several months after the injury correlate with functional outcome in patients who have sustained TBIs of variable initial severity. In this prospective study of 178 patients with TBI and 40 orthopedic injury controls, we measured plasma NF-L levels in blood samples taken at the follow-up appointment on average 9 months after injury. Patients with TBI were divided into two groups (mild [mTBI] vs. moderate-to-severe [mo/sTBI]) according to the severity of injury assessed with the Glasgow Coma Scale upon admission. Recovery and functional outcome were assessed using the Extended Glasgow Outcome Scale (GOSE). Higher levels of NF-L at the follow-up correlated with worse outcome in patients with moderate-to-severe TBI (Spearman's rho = -0.18; p < 0.001). In addition, in computed tomography-positive mTBI group, the levels of NF-L were significantly lower in patients with GOSE 7-8 (median 18.14; interquartile range [IQR] 9.82, 32.15) when compared with patients with GOSE <7 (median 73.87; IQR 32.17, 110.54; p = 0.002). In patients with mTBI, late NF-L levels do not seem to provide clinical benefit for late-stage assessment, but in patients with initially mo/sTBI, persistently elevated NF-L levels are associated with worse outcome after TBI and may reflect ongoing brain injury.

Association of Central Nervous System-Affecting Medications With Occurrence and Short-Term Mortality of Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: The use of medications commonly prescribed after traumatic brain injury (TBI) has been little studied before TBI. This study examined the association between the use of medications that affect the central nervous system (CNS) and the occurrence and short-term mortality of TBI. METHODS: Mandatory Finnish registries were used to identify TBI admissions, fatal TBIs, and drug purchases during 2005-2018. Patients with TBI were 1:1 matched to nontrauma control patients to investigate the association between medications and the occurrence of TBI and 30-day mortality after TBI. Number needed to harm (NNH) was calculated for all medications. RESULTS: The cohort included 59 606 patients with TBI and a similar number of control patients. CNS-affecting drugs were more common in patients with TBI than in controls [odds ratio = 2.07 (2.02-2.13), P < .001)]. Benzodiazepines were the most common type of medications in patients with TBI (17%) and in controls (11%). The lowest NNH for the occurrence of TBI was associated with benzodiazepines (15.4), selective serotonin uptake inhibitors (18.5), and second-generation antipsychotics (25.8). Eight percent of the patients with TBI died within 30 days. The highest hazard ratios (HR) and lowest NNHs associated with short-term mortality were observed with strong opioids [HR = 1.41 (1.26-1.59), NNH = 33.1], second-generation antipsychotics [HR = 1.36 (1.23-1.50), NNH = 37.1], and atypical antidepressants [HR = 1.17 (1.04-1.31), NNH = 77.7]. CONCLUSION: Thirty-seven percent of patients with TBI used at least 1 CNS-affecting drug. This proportion was significantly higher than in the control population (24%). The highest risk and lowest NNH for short-term mortality were observed with strong opioids, second-generation antipsychotics, and atypical antidepressants. The current risks underscore the importance of weighing the benefits and risks before prescribing CNS-affecting drugs in patients at risk of head injury.

Outlier Analysis for Acute Blood Biomarkers of Moderate and Severe Traumatic Brain Injury.

Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo/sTBI (n = 85) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-tau), amyloid ß40 (Aß40) and amyloid ß42 (Aß42), within 24 h of admission. Similar analyses were conducted for controls (n = 40) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal (n = 9/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5-8) versus unfavorable (GOSE <5) (n = 38/42, 5 missing) outcome. Outliers were sought individually from all subgroups from and the whole TBI patient population. Biomarker levels outside Q1 - 1.5 interquartile range (IQR) or Q3 + 1.5 IQR were considered as outliers. The medical records of each outlier patient were reviewed in a team meeting to determine possible reasons for outlier values. A total of 29 patients (34%) combined from all subgroups and 12 patients (30%) among the controls showed outlier values for one or more of the eight biomarkers. Nine patients with TBI and five control patients had outlier values in more than one biomarker (up to 4). All outlier values were > Q3 + 1.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B).

Outcome and survival of surgically treated acute subdural hematomas and postcraniotomy hematomas - A retrospective cohort study.

Background: The morbidity and mortality of acute subdural hematoma (aSDH) remains high. Several factors have been reported to affect the outcome and survival of these patients. In this study, we explored factors potentially associated with the outcome and survival of surgically treated acute subdural hematoma (aSDH), including postcraniotomy hematomas (PCHs). Methods: This retrospective cohort study was conducted in a single tertiary university hospital between 2008 and 2012 and all aSDH patients that underwent surgical intervention were included. A total of 132 cases were identified for collection of demographics, clinical, laboratory, and imaging data. Univariate and multivariable analyses were performed to assess factors associated with three-month Glasgow Outcome Scale (GOS) and survival at one- and five-year. Results: In this study, PCH (n = 14, 10.6%) was not associated with a worse outcome according to the 3- month GOS (p = 0.37) or one (p = 0.34) and five-year (p = 0.37) survival. The multivariable analysis showed that the volume of initial hematoma (p = 0.009) and Abbreviated Injury Scale score (p = 0.016) were independent predictors of the three-month GOS. Glasgow Coma Scale (GCS) score (p < 0.001 and p = 0.037) and age (p = 0.048 and p = 0.003) were predictors for one and five-year survival, while use of antiplatelet drug (p = 0.030), neuroworsening (p = 0.005) and smoking (p = 0.026) were significant factors impacting one year survival. In addition, blood alcohol level on admission was a predictor for five-year survival (p = 0.025). Conclusions: These elucidations underscore that, although PCHs are pertinent, a comprehensive appreciation of multifarious variables is indispensable in aSDH prognosis. These findings are observational, not causal. Expanded research endeavors are advocated to corroborate these insights.

Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury.

BACKGROUND: It is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI. METHODS: Ninety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups. RESULTS: The levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001-p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found. CONCLUSION: In patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. METHODS: The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. DISCUSSION: Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Venous thromboembolism risk among pediatric patients with traumatic brain injury: a nationwide study of 44,128 patients.

OBJECTIVE: Venous thromboembolism (VTE) chemoprophylaxis in pediatric patients with traumatic brain injury (TBI) requires balancing the risk of progression of intracranial bleeding versus the risk of VTE. The identification of VTE risk factors requires analysis of a very large data set. This case-control study aimed to identify VTE risk factors in pediatric patients with TBI in order to develop a TBI-specific association model that can be used for VTE risk stratification in this population. METHODS: The study included patients (aged 1-17 years) from the 2013-2019 US National Trauma Data Bank who were admitted for TBI in order to identify risk factors for VTE. Stepwise logistic regression was used to develop an association model. RESULTS: Of 44,128 study participants, 257 (0.58%) developed VTE. Risk factors associated with VTE included age (OR 1.045, 95% CI 1.010-1.080), body mass index (OR 1.034, 95% CI 1.013-1.055), Injury Severity Score (OR 1.049, 95% CI 1.039-1.059), blood product administration (OR 1.436, 95% CI 1.008-2.046), presence of a central venous catheter (OR 3.333, 95% CI 2.431-4.571), and development of ventilator-associated pneumonia (OR 3.650, 95% CI 2.469-5.396). Based on this model, the predicted VTE risk in pediatric patients with TBI ranged from 0% to 16.8%. CONCLUSIONS: A model that includes age, body mass index, Injury Severity Score, blood transfusion, use of a central venous catheter, and ventilator-associated pneumonia can help to risk stratify pediatric patients with TBI from the standpoint of implementation of VTE chemoprophylaxis.

Causes of fatal traumatic brain injury in Finland.

OBJECTIVE: The phenotype of patients who suffer fatal traumatic brain injury (TBI) is poorly characterized. The authors examined the external causes, contributing diseases, and preinjury medication in adult patients with fatal TBI in a nationwide Finnish cohort. METHODS: Deaths caused by TBIs in Finland were examined among decedents aged ≥ 16 years during 2005-2020 from the national Cause of Death Registry. Usage of prescription medications prior to TBI was studied using medication purchase data from the Social Insurance Institution of Finland. RESULTS: The cohort consisted of 71,488,347 person-years, 821,259 total deaths, and 14,630 TBI-related deaths during 2005-2020, of which 67% (n = 9792) occurred in men. Women were older than men among those who suffered TBI-related death (mean age 77.2 ± 17.1 vs 64.5 ± 19.5 years, p < 0.0001). The overall crude incidence rate of fatal TBIs was 20.5/100,000 person-years (28.1/100,000 in men and 13.2/100,000 in women). TBI was the cause of death in 1.8% of all deaths in the Finnish population during the study years, but in patients aged 16-19 years, TBIs caused more than 17% of all deaths. The most common external cause of fatal TBI was a fall (70%), followed by poisoning or toxic effects (20%) and violence or self-harm (15%) overall. In men, the order of the most common causes of fatal TBI was similar to overall results (64%, 25%, and 19%, respectively), while in women, the most common cause was a fall (82%), followed by complications in healthcare (10%) and poisoning or toxic effects (9%). Cardiovascular diseases, psychiatric diseases, and infections were the most common diseases contributing to death. Blood pressure (lowering) medications were the most common type of medications used before fatal TBI. CNS medications were the second most common medication group. In the context of fatal TBI in Europe, Finland remains at the upper end of fatal TBI incidence. CONCLUSIONS: TBI is a common cause of death in young adults, whereas the incidence of fatal TBI becomes increasingly higher with age in Finland. Cardiovascular diseases and psychiatric conditions were the most common diseases related to death, with opposite age trends. Healthcare facility complications were an alarmingly common cause of death in women with fatal TBI.

Trajectories of interleukin 10 and heart fatty acid-binding protein levels in traumatic brain injury patients with or without extracranial injuries.

Background: Interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have gained interest as diagnostic biomarkers of traumatic brain injury (TBI), but factors affecting their blood levels in patients with moderate-to-severe TBI are largely unknown. Objective: To investigate the trajectories of IL-10 and H-FABP between TBI patients with and without extracranial injuries (ECI); to investigate if there is a correlation between the levels of IL-10 and H-FABP with the levels of inflammation/infection markers C-reactive protein (CRP) and leukocytes; and to investigate if there is a correlation between the admission level of H-FABP with admission levels of cardiac injury markers, troponin (TnT), creatine kinase (CK), and creatine kinase MB isoenzyme mass (CK-MBm). Materials and methods: The admission levels of IL-10, H-FABP, CRP, and leukocytes were measured within 24 h post-TBI and on days 1, 2, 3, and 7 after TBI. The admission levels of TnT, CK, and CK-MBm were measured within 24 h post-TBI. Results: There was a significant difference in the concentration of H-FABP between TBI patients with and without ECI on day 0 (48.2 ± 20.5 and 12.4 ± 14.7 ng/ml, p = 0.02, respectively). There was no significant difference in the levels of IL-10 between these groups at any timepoints. There was a statistically significant positive correlation between IL-10 and CRP on days 2 (R = 0.43, p < 0.01) and 7 (R = 0.46, p = 0.03) after injury, and a negative correlation between H-FABP and CRP on day 0 (R = -0.45, p = 0.01). The levels of IL-10 or H-FABP did not correlate with leukocyte counts at any timepoint. The admission levels of H-FABP correlated with CK (R = 0.70, p < 0.001) and CK-MBm (R = 0.61, p < 0.001), but not with TnT. Conclusion: Inflammatory reactions during the early days after a TBI do not significantly confound the use of IL-10 and H-FABP as TBI biomarkers. Extracranial injuries and cardiac sources may influence the levels of H-FABP in patients with moderate-to-severe TBI.

Use of Support Vector Machines Approach via ComBat Harmonized Diffusion Tensor Imaging for the Diagnosis and Prognosis of Mild Traumatic Brain Injury: A CENTER-TBI Study.

The prediction of functional outcome after mild traumatic brain injury (mTBI) is challenging. Conventional magnetic resonance imaging (MRI) does not do a good job of explaining the variance in outcome, as many patients with incomplete recovery will have normal-appearing clinical neuroimaging. More advanced quantitative techniques such as diffusion MRI (dMRI), can detect microstructural changes not otherwise visible, and so may offer a way to improve outcome prediction. In this study, we explore the potential of linear support vector classifiers (linearSVCs) to identify dMRI biomarkers that can predict recovery after mTBI. Simultaneously, the harmonization of fractional anisotropy (FA) and mean diffusivity (MD) via ComBat was evaluated and compared for the classification performances of the linearSVCs. We included dMRI scans of 179 mTBI patients and 85 controls from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a multi-center prospective cohort study, up to 21 days post-injury. Patients were dichotomized according to their Extended Glasgow Outcome Scale (GOSE) scores at 6 months into complete (n = 92; GOSE = 8) and incomplete (n = 87; GOSE <8) recovery. FA and MD maps were registered to a common space and harmonized via the ComBat algorithm. LinearSVCs were applied to distinguish: (1) mTBI patients from controls and (2) mTBI patients with complete from those with incomplete recovery. The linearSVCs were trained on (1) age and sex only, (2) non-harmonized, (3) two-category-harmonized ComBat, and (4) three-category-harmonized ComBat FA and MD images combined with age and sex. White matter FA and MD voxels and regions of interest (ROIs) within the John Hopkins University (JHU) atlas were examined. Recursive feature elimination was used to identify the 10% most discriminative voxels or the 10 most discriminative ROIs for each implementation. mTBI patients displayed significantly higher MD and lower FA values than controls for the discriminative voxels and ROIs. For the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD voxel-wise linearSVC provided significantly higher classification scores (81.4% accuracy, 93.3% sensitivity, 80.3% F1-score, and 0.88 area under the curve [AUC], p < 0.05) compared with the classification based on age and sex only and the ROI approaches (accuracies: 59.8% and 64.8%, respectively). Similar to the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD maps voxelwise approach yields statistically significant prediction scores between mTBI patients with complete and those with incomplete recovery (71.8% specificity, 66.2% F1-score and 0.71 AUC, p < 0.05), which provided a modest increase in the classification score (accuracy: 66.4%) compared with the classification based on age and sex only and ROI-wise approaches (accuracy: 61.4% and 64.7%, respectively). This study showed that ComBat harmonized FA and MD may provide additional information for diagnosis and prognosis of mTBI in a multi-modal machine learning approach. These findings demonstrate that dMRI may assist in the early detection of patients at risk of incomplete recovery from mTBI.

Adult-onset epilepsy and risk of traumatic brain injury: a nationwide cohort study.

BACKGROUND: A knowledge gap exists regarding the risk of traumatic brain injury (TBI) in patients with epilepsy. METHODS: Patients with adult-onset epilepsy during 2005-2018 in Finland were studied using retrospective longitudinal national registry-linkage design. Patients with epilepsy (n=35 686; 51% men; mean age 56.6 years) were 1:1 matched to non-epileptic controls by age, sex, comorbidity burden and cohort entry year. The primary outcome was TBI leading to admission or death, secondary outcomes were TBI admission, fatal TBI, acute neurosurgical operations (ANOs) for TBI and TBI recurrence. RESULTS: The cumulative rate of the primary endpoint was 1.2% at 1 year, 5.6% at 10 years and 7.3% at 14 years in the epilepsy group versus 2.9% at 14 years in the matched controls (HR=3.77; p<0.0001). Epilepsy was associated with increased risk of TBI admission (6.9% vs 2.7%; HR=3.96; p<0.0001), ANOs (1.3% vs 0.4%; HR=7.00; p<0.0001) and fatal TBI (1.3% vs 0.5%; HR=3.82; p<0.0001), during follow-up. Competing risk analyses confirmed the association of epilepsy with all outcomes (p<0.0001). Epilepsy was associated with TBI recurrence during follow-up (HR 1.72; p=0.002). CONCLUSION: Patients with adult-onset epilepsy have a significantly increased risk of severe and fatal TBI. The results underline the importance of TBI prevention in epilepsy.