Clinical experiences, current approaches, opinions and awareness of healthcare professionals regarding the audio-vestibular consequences of individuals with traumatic brain injury: a cross-sectional online survey study.

OBJECTIVE: To explore the experiences, current approaches, opinions and awareness of healthcare professionals (HCPs) caring for adults with traumatic brain injury (TBI) regarding the audio-vestibular consequences. DESIGN/SETTING: Cross-sectional online survey study. PARTICIPANTS: HCPs with experience of caring for adults with TBI, who were not ENT (ear nose throat) specialists or audiologists. METHODS: The study was conducted from May 2022 to December 2022. The online survey consisted of 16 closed and open-text questions in English and Turkish about clinical experience, current approaches and awareness of audio-vestibular consequences following TBI. Frequencies of responses to closed questions and associations between variables were analysed using SPSS V.28. Open-text responses were summarised in Microsoft Excel. RESULTS: Seventy HCPs participated from 17 professions and 14 countries, with the majority from the UK (42.9%). HCPs stated that 'some' to 'all' of their patients had auditory problems such as 'inability to understand speech-in-noise' (66%), 'tinnitus' (64%), 'hyperacusis' (57%) and balance problems such as 'dizziness' (79%) and 'vertigo' (67%). Usually, HCPs asked about the balance status of patients at appointments and when they observed dizziness and/or balance disorder they used screening tests, most commonly finger-to-nose (53%). For auditory impairments, HCPs preferred referring patients with TBI to audiology/ENT services. However, 6% of HCPs felt that audio-vestibular conditions could be ignored on referral because patients with TBI struggled with many impairments. Additionally, 44% would suggest hearing aids to patients with TBI with hearing loss 'if they would like to use' rather than 'definitely'. CONCLUSIONS: Many audio-vestibular impairments are observed by HCPs caring for patients with TBI. The assessment and intervention opinions and awareness of HCPs for these impairments vary. However, non-expert HCPs may not be aware of negative consequences of untreated audio-vestibular impairments following TBI. Therefore, developing a simple framework for screening and indications of audio-vestibular impairments for referral may be helpful for non-audiological specialists regularly seeing these patients.

Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion (GET FAB): protocol for a multisite Canadian randomised controlled trial.

INTRODUCTION: Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments. METHODS AND ANALYSIS: We will conduct a multisite randomised controlled trial with three arms. Participants (n=220) will be recruited from concussion clinics and emergency departments in three Canadian provinces and randomly assigned (1:2:2 ratio) to receive enhanced usual care, GET or prescribed aerobic exercise. The outcome assessment will occur remotely 14-18 weeks following baseline assessment, after completing the 12-week treatment phase. The primary outcome will be symptom severity (Rivermead Post-concussion Symptoms Questionnaire). ETHICS AND DISSEMINATION: Informed consent will be obtained from all participants. All study procedures were approved by the local research ethics boards (University of British Columbia Clinical Research Ethics Board, University of Calgary Conjoint Health Research Ethics Board, University Health Network Research Ethics Board-Panel D). Operational approvals were obtained for Vancouver Coastal Health Research Institute and Provincial Health Services Authority. If GET proves effective, we will disseminate the GET treatment manual and present instructional workshops for clinicians. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT05365776.

Microrna Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study.

BACKGROUND: After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery. OBJECTIVE: The aim of this study was to investigate the variances in plasma microRNAs on the day of injury between individuals with mTBI who report post-concussive symptoms at the 28- day mark and those who do not. METHODS: Patients who presented to an adult, tertiary referral hospital emergency department on the day of the injury and were diagnosed with isolated mTBI (n=35) were followed up for 28 days. Venous blood samples were collected and symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 28 days. Patients who reported ongoing symptoms of total RPQ score ≥10 or at least one symptom severity ≥2, were compared to those with lesser symptom severity or symptom resolution. RESULTS: There were 9 (25.7%; 95%CI: 12.5-43.3) patients who reported persistent symptoms. Day of injury plasma miR-223-3p levels were significantly higher in individuals with ongoing symptoms compared to those without, however, no such differences were observed for miRs 142- 3p, 423-3p, 32-5p, 144-3p, and let-7f-5p. CONCLUSION: Acute plasma miR-223-3p levels appear to detect patients who later have persistent symptoms after mTBI. The results demonstrate the potential utility for such biomarkers to assist in decisions towards early referral for therapy after mTBI.

Experiences of patients, parents, and healthcare professionals in the process of transitioning from hospital to community after inpatient pediatric rehabilitation among children with special health care needs.

PURPOSE: Children with Special Health Care Needs (CSHCN) may experience disruptions in education due to extended hospitalizations. The purpose of this study was to describe how CSHCN experience educational supports during inpatient rehabilitation and identify the ongoing challenges when planning to return to school. MATERIALS AND METHODS: Semi-structured focus groups were conducted with parents (n = 12), former patients (n = 20), and rehabilitation professionals (n = 8). RESULTS: Through qualitative thematic analysis based on descriptive phenomenology, we developed three themes: 1) Inpatient educational support such as instruction and schoolwork helped reduce the learning loss during hospitalization. However, these supports were sometimes complicated by lags in school approvals and challenges in coordination between systems. 2) Transition planning involved establishing necessary services to support CSHCN's educational and healthcare needs at school re-entry. However, families reported limited information and guidance as key barriers. 3) Dynamic courses of school re-entry required continued support after discharge. The participants recommended that reassessment and adjustment of transition plans were often necessary to account for evolving developmental and educational needs but were not always received. CONCLUSIONS: There is an ongoing need to improve communication between clinicians and educators, information for families, and long-term follow-up on the changing educational needs for CSHCN after rehabilitation.

School re-entry after extended hospitalization is challenging for children with special health care needs (CSHCN) due to school disruption, social disconnection, and change in functional abilities.The hospital-to-school transition processes include inpatient educational programs during hospitalization, pre-discharge transition planning, and the subsequent implementation and adjustment of transition plans to facilitate individualized school re-entry.Key areas in need of improving school re-entry include coordination between the hospital and school about rehabilitation and educational goals and information provided to families about transition processes, particularly for newly acquired health conditions.A common need expressed by parents and CSHCN is to simplify and accelerate the process to establish services that support children's educational and healthcare needs.

Early Intravenous Beta-Blockade with Esmolol in Adults with Severe Traumatic Brain Injury: A Phase 2a Intervention Design Study.

BACKGROUND: Targeted beta-blockade after severe traumatic brain injury may reduce secondary brain injury by attenuating the sympathoadrenal response. The potential role and optimal dosage for esmolol, a selective, short-acting, titratable beta-1 beta-blocker, as a safe, putative early therapy after major traumatic brain injury has not been assessed. METHODS: We conducted a single-center, open-label dose-finding study using an adaptive model-based design. Adults (18 years or older) with severe traumatic brain injury and intracranial pressure monitoring received esmolol within 24 h of injury to reduce their heart rate by 15% from baseline of the preceding 4 h while ensuring cerebral perfusion pressure was maintained above 60 mm Hg. In cohorts of three, the starting dosage and dosage increments were escalated according to a prespecified plan in the absence of dose-limiting toxicity. Dose-limiting toxicity was defined as failure to maintain cerebral perfusion pressure, triggering cessation of esmolol infusion. The primary outcome was the maximum tolerated dosage schedule of esmolol, defined as that associated with less than 10% probability of dose-limiting toxicity. Secondary outcomes include 6-month mortality and 6-month extended Glasgow Outcome Scale score. RESULTS: Sixteen patients (6 [37.5%] female patients; mean age 36 years [standard deviation 13 years]) with a median Glasgow Coma Scale score of 6.5 (interquartile range 5-7) received esmolol. The optimal starting dosage of esmolol was 10 µg/kg/min, with increments every 30 min of 5 µg/kg/min, as it was the highest dosage with less than 10% estimated probability of dose-limiting toxicity (7%). All-cause mortality was 12.5% at 6 months (corresponding to a standardized mortality ratio of 0.63). One dose-limiting toxicity event and no serious adverse hemodynamic effects were seen. CONCLUSIONS: Esmolol administration, titrated to a heart rate reduction of 15%, is feasible within 24 h of severe traumatic brain injury. The probability of dose-limiting toxicity requiring withdrawal of esmolol when using the optimized schedule is low. Trial registrationI SRCTN, ISRCTN11038397, registered retrospectively January 7, 2021 ( https://www.isrctn.com/ISRCTN11038397 ).

Impact of English proficiency on use of Glasgow Coma Scale in geriatric patients with traumatic brain injury.

Background: The relationship between English proficiency (EP), Glasgow Coma Scale (GCS) and traumatic brain injury (TBI) is not well characterized. We aimed to understand the impact of limited English proficiency (LEP) on the evaluation and outcomes of TBI. Methods: Retrospective comparative study in a single institution of patients aged ⪰65 who presented to the emergency department after a fall with head strike between January 2018 and December 2021. TBI was defined as documented loss of consciousness or intracranial hemorrhage (ICH). Relationships between EP, GCS, and TBI were analyzed with multivariable and propensity score-matched models. Results: Of the 2905 included, 1233 (42%) had LEP. Most LEP patients were Asian (60%) while the majority of EP patients were non-Hispanic Caucasians (72%). In a univariate analysis, LEP had higher incidence of decreased GCS and was strongly correlated with risk of TBI (OR 1.47, CI 1.26 to 1.71). After adjusting for multiple covariates including race, LEP did not have a significantly increased risk for GCS score <13 (OR 1.66, CI 0.99 to 2.76) or increased risk of TBI. In the matched analysis, LEP had a small but significantly higher risk of GCS score <13 (OR 1.03, CI 1.02 to 1.05) without an increased risk in TBI. Decreased GCS remained strongly correlated with presence of ICH in LEP patients in the adjusted model (OR 1.39, CI 1.30 to 1.50). Conclusions: LEP correlated with lower GCS in geriatric patients with TBI. This association weakened after adjusting for factors like race, suggesting racial disparities may have more influence than language differences. Moreover, GCS remained effective for predicting ICH in LEP individuals, highlighting its value with suitable translation resources. Level of evidence: This is a Level III evidence restrospective comparative study.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Long-Term Effects of Intensive Rehabilitation on Memory Functions in Acquired Brain-Damaged Patients.

OBJECTIVE: Memory difficulties after brain injury are a frequent and concerning outcome, affecting a wide range of daily activities, employment, and social reintegration. Despite the importance of functional memory capacities throughout life, most studies examined the short-term effects of memory interventions in brain-damaged patients who underwent a rehabilitation program. In the present study, we investigated the long-term outcomes and intensity of memory interventions in acquired (traumatic brain injury [TBI] and non-TBI) brain-damaged patients who participated in an intensive cognitive rehabilitation program and either suffered or did not suffer from memory impairments. METHOD: We measured pre-post-treatment memory performance of patiients (N = 24) suffering from memory deficits in four common and validated memory tasks (e.g. ROCFT). We compared them to other acquired brain injury patients treated at the same rehabilitation facility who did not suffer from memory impairments (N = 16). RESULTS: Patients with memory deficits showed long-term improvements in three out of four tasks, while patients without memory deficits showed memory enhancements in only one task. In addition, rehabilitation intensity and type of brain damage predicted the extent of the memory change over time. DISCUSSION: Long-term improvements in objective memory measures can be observed in patients suffering from brain injury. These improvements can be enhanced by intensifying the treatment program. Findings also suggest that these memory improvements are more pronounced in non-TBI than TBI patients. We discuss the implications of these results in designing optimal memory rehabilitation interventions.

Drugs, Delirium, and Trauma: Substance Use and Incidence of Delirium After Traumatic Brain Injury.

INTRODUCTION: There is a paucity of data on the effect of preinjury substance (alcohol, drugs) abuse on the risk of delirium in patients with traumatic brain injury (TBI). This study aimed to assess the incidence of delirium among patients with blunt TBI in association with different substances. METHODS: We analyzed the 2020 American College of Surgeons-Trauma Quality Improvement Program. We included all adult (≥18 y) patients with blunt TBI who had a recorded substance (drugs and alcohol) screening. Our primary outcome was the incidence of delirium. RESULTS: A total of 72,901 blunt TBI patients were identified. The mean (standard deviation) age was 56 (20) years and 68.0% were males. The median (interquartile range) injury severity score was 17 (10-25). Among the study population, 23.1% tested positive for drugs (Stimulants: 3.0%; Depressants: 2.9%, hallucinogens: 5.1%, Cannabinoids: 13.4%, TCAs: 0.1%), and 22.8% tested positive for Alcohol. Overall, 1856 (2.5%) experienced delirium. On univariate analysis, patients who developed delirium were more likely to have positive drug screening results. On multivariable regression analyses, positive screen tests for isolated stimulants (adjusted odds ratio [aOR]: 1.340, P = 0.018), tricyclic antidepressants (aOR: 3.107, P = 0.019), and cannabinoids (aOR: 1.326, P ≤ 0.001) were independently associated with higher odds of developing delirium. CONCLUSIONS: Nearly one-fourth of adult patients with blunt TBI had an initial positive substance screening test. Patients with positive results for isolated stimulants, tricyclic antidepressants, and cannabinoids were at a higher risk of developing delirium, whereas this association was not evident with other drugs and alcohol-positive tests. These findings emphasize the need for early drug screening in TBI patients and close monitoring of patients with positive screening tests.

Nutritional interventions and related efforts addressing undernutrition during rehabilitation after acquired brain injury: a scoping review protocol.

INTRODUCTION: Patients with an acquired brain injury (ABI) are at an increased risk of undernutrition due to the disease-related inflammation and other numerous symptoms that impact their nutrition. Unfortunately, recommendations related to nutritional interventions and related efforts vary. The objective of this scoping review is to map the body of literature on nutritional interventions and related efforts provided by health professionals, such as screening or assessments, addressing undernutrition in adults with a moderate to severe ABI during the subacute rehabilitation pathway. METHODS AND ANALYSIS: The review follows the Joanna Briggs Institute methodology for scoping reviews. The librarian-assisted search strategy will be conducted in the bibliographical databases: MEDLINE (PubMed), Embase, CINAHL, Web of Science and OpenGrey. Indexed and grey literature in English, German or Scandinavian languages from January 2010 will be considered for inclusion. Two independent reviewers will conduct the iterative process of screening the identified literature, paper selection and data extraction. Disagreements will be resolved by discussion until a consensus is reached. A template will be used to guide the data extraction. This scoping review will include research articles, methodological papers and clinical guidelines reporting on nutritional interventions or related efforts to prevent or address undernutrition in adult patients (≥18 years) with moderate to severe ABI within the first year after admission to rehabilitation hospital. We will map all kinds of nutritional efforts provided by professionals in different settings within high-income countries, including interventions targeting relatives. ETHICS AND DISSEMINATION: This review will involve the collection and analysis of secondary sources that have been published and/or are publicly available. Therefore, ethics approval is not required. The results will be published in an international peer-reviewed journal, presented at scientific conferences and disseminated through digital science communication platforms. STUDY REGISTRATION: Open Science Framework: https://doi.org/10.17605/OSF.IO/H5GJX.

Cost-effectiveness of craniotomy versus decompressive craniectomy for UK patients with traumatic acute subdural haematoma.

OBJECTIVE: To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH). DESIGN: Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial. SETTING: UK secondary care. PARTICIPANTS: 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122). INTERVENTIONS: Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery). MAIN OUTCOME MEASURES: In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists. RESULTS: In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be -£5520 (95% CI -£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be -£4536 (95% CI -£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE. CONCLUSIONS: In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant). ETHICS: Ethical approval for the trial was obtained from the North West-Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076). TRIAL REGISTRATION NUMBER: ISRCTN87370545.

Cardiorespiratory fitness assessment and training in the early sub-acute phase of recovery following traumatic brain injury: a systematic review.

OBJECTIVES: To examine the safety of cardiorespiratory fitness (CRF) assessment and training in the early sub-acute phase of recovery (≤3 months) following moderate-to-extremely severe traumatic brain injury (TBI). METHODS: A systematic review was completed in accordance with the PRISMA guidelines. Studies investigating adults and adolescents ≥15 years with moderate-to-extremely severe TBI were considered for inclusion. The methodological quality of the included studies was evaluated according to the McMaster Guidelines for Critical Review Form - Quantitative Studies. RESULTS: Eleven studies with a total of 380 participants were included in the review. Adverse events (AEs) and symptom monitoring were poorly reported. Only four studies reported on the occurrence of AEs, with a total of eight AEs reported. Three of the reported AEs were concussion-like symptoms with no further exercise-induced symptom exacerbation reported. No serious AEs were reported. CONCLUSION: There is no evidence to suggest that CRF assessment and training is unsafe in the early sub-acute phase of recovery following moderate-to-extremely severe TBI. However, despite the low AE and symptom exacerbation rates identified, a timeframe for safe commencement was unable to be established due to poor reporting and/or monitoring of exercise-induced symptoms and AEs in the current literature.

Work-support techniques used by occupational therapists to facilitate support after acquired brain injuries: A qualitative study.

Background: Ensuring effective return to work following acquired brain injuries is crucial from the perspectives of both quality of life and the economy. However, techniques of occupational therapy support for return to work remain relatively unelucidated. Aims/Objectives: To clarify the specific contents of occupational therapy required for work and work support for clients with acquired brain injuries. Material and Methods: An interview-based survey was conducted with participants who had >10 years of occupational therapy experience and had provided work support. We selected participants via snowball sampling. Data were analyzed using thematic analysis. Results: A total of 20 participants (15 women and 5 men; 6, 12, 1, and 1 in their 30s, 40s, 50s, and 60s, respectively) were included. Six concepts were generated on reviewing the support for work items considered important by the occupational therapist as follows: "Support for vocational life," "Support for interpersonal skills," "Support for work," "Support for illness, disability, and awareness," "Support for utilization of compensation measures," and "Support for goal setting." Conclusions: We clarified the specific contents of work support, including support for vocational life and support for work, that is administered by occupational therapists who provide work support for clients with acquired brain injury. The insights from the study improve understanding of OTs' roles and contributions in supporting clients with acquired brain injuries in returning to work.

Comparison of the efficacy of 0.9% normal saline with balanced crystalloid (Plasmalyte) in maintaining the metabolic profile in head injury patients undergoing evacuation of acute subdural haematoma - A randomised controlled trial.

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups' metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann-Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

EXPRESS: Astragaloside IV ameliorated neuroinflammation and improved neurological functions in mice exposed to traumatic brain injury by modulating the PERK-eIF2α-ATF4 signaling pathway.

Increasing evidence suggests that endoplasmic reticulum stress (ER stress) and neuroinflammation are involved in the complex pathological process of traumatic brain injury (TBI). However, the pathological mechanisms of their interactions in TBI remain incompletely elucidated. Therefore, investigating and ameliorating neuroinflammation and ER stress post-TBI may represent effective strategies for treating secondary brain injury. Astragaloside IV (AS-IV) has been reported as a potential neuroprotective and anti-inflammatory agent in neurological diseases. This study utilized a mouse TBI model to investigate the pathological mechanisms and crosstalk of ER stress, neuroinflammation, and microglial cell morphology in TBI, as well as the mechanisms and potential of AS-IV in improving TBI. The research revealed that post-TBI, inflammatory factors IL-6, IL-1ß, and TNF-α increased, microglial cells were activated, and the specific inhibitor of PERK phosphorylation, GSK2656157, intervened to alleviate neuroinflammation and inhibit microglial cell activation. Post-TBI, levels of ER stress-related proteins (p-PERK, p-eIF2a, ATF4, ATF6, and p-IRE1a) increased. Following AS-IV treatment, neurological dysfunction in TBI mice improved. Levels of p-PERK, p-eIF2a, and ATF4 decreased, along with reductions in inflammatory factors IL-6, IL-1ß, and TNF-α. Changes in microglial/macrophage M1/M2 polarization were observed. Additionally, the PERK activator CCT020312 intervention eliminated the impact of AS-IV on post-TBI inflammation and ER stress-related proteins p-PERK, p-eIF2a, and ATF4. These results indicate that AS-IV alleviates neuroinflammation and brain damage post-TBI through the PERK pathway, offering new directions and theoretical insights for TBI treatment.

Distinct profiles of cerebral oxygenation in focal vs. secondarily generalized EEG seizures in children undergoing cardiac surgery.

Objectives: Seizures are common in children undergoing cardiopulmonary bypass (CPB). Cerebral oxygen saturation (ScO2) by near-infrared spectroscopy is routinely monitored in many centers, but the relations between the levels and changes of ScO2 and brain injuries remain incompletely understood. We aimed to analyze the postoperative profiles of ScO2 and cerebral blood flow velocity in different types of EEG seizures in relation to brain injuries on MRI. Methods: We monitored continuous EEG and ScO2 in 337 children during the first 48 h after CPB, which were analyzed in 3 h periods. Cerebral blood flow peak systolic velocity (PSV) in the middle cerebral artery was measured daily by transcranial Doppler. Postoperative cerebral MRI was performed before hospital discharge. Results: Based on the occurrence and spreading types of seizures, patients were divided into three groups as patients without seizures (Group N; n = 309), those with focal seizures (Group F; n = 13), or with secondarily generalized seizures (Group G; n = 15). There were no significant differences in the onset time and duration of seizures and incidence of status epilepticus between the two seizures groups (Ps ≥ 0.27). ScO2 increased significantly faster across Group N, Group G, and Group F during the 48 h (p < 0.0001) but its overall levels were not significantly different among the three groups (p = 0.30). PSV was significantly lower (p = 0.003) but increased significantly faster (p = 0.0003) across Group N, Group G, and Group F. Group F had the most severe brain injuries and the highest incidence of white matter injuries on MRI among the three groups (Ps ≤ 0.002). Conclusion: Postoperative cerebral oxygenation showed distinct profiles in secondarily generalized and particularly focal types of EEG seizures in children after CPB. A state of 'overshooting' ScO2 with persistently low PSV was more frequently seen in those with focal seizures and more severe brain injury. Information from this study may have important clinical implications in detecting brain injuries when monitoring cerebral oxygenation in this vulnerable group of children after CPB.

Paroxysmal sympathetic hyperactivity during neurorehabilitation for severe acquired brain injury: current Scandinavian practice and Delphi consensus recommendations.

OBJECTIVES: To document current practice and develop consensus recommendations for the assessment and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation after severe acquired brain injury. DESIGN: Delphi consensus process with three rounds, based on the Guidance on Conducting and REporting DElphi Studies (CREDES) guidelines, led by three convenors (the authors) with an expert panel. Round 1 was exploratory, with consensus defined before round 2 as agreement of at least 75% of the panel. SETTING: A working group within the Nordic Network for Neurorehabilitation. PANEL PARTICIPANTS: Twenty specialist physicians, from Sweden (9 participants), Norway (7) and Denmark (4), all working clinically with patients with severe acquired brain injury and with current involvement in clinical decisions regarding PSH. RESULTS: Consensus was reached for 21 statements on terminology, assessment and principles for pharmacological and non-pharmacological treatment, including some guidance on specific drugs. From these, an algorithm to support clinical decisions at all stages of inpatient rehabilitation was created. CONCLUSIONS: Considerable consensus exists in the Nordic countries regarding principles for PSH assessment and treatment. An interdisciplinary approach is needed. Improved documentation and collation of data on treatment given during routine clinical practice are needed as a basis for improving care until sufficiently robust research exists to guide treatment choices.