Clinical characteristics of patients hospitalised with traumatic brain injury in an Australian tertiary hospital.

INTRODUCTION: Hepatocellular carcinoma (HCC) incidence rates are increasing among older adults in the U.S. Age-related disparities in prognosis and treatment receipt have been described in other cancers; however, there are limited data examining outcomes in older adults with HCC. Our study's aim was to evaluate age-related differences in HCC treatment receipt and prognosis. METHODS: We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at 2 U.S. hospital systems. Older and younger adults were defined as ≥65 and <65 years old, respectively. Curative therapy was defined as liver transplantation, surgical resection, or local ablation. We used multivariable logistic regression to identify factors associated with curative treatment receipt and Cox proportional hazard models to identify factors associated with overall survival (OS). RESULTS: Of 1110 patients with HCC, 261 (23.5%) were ≥65 and 849 (76.5%) were <65 years old; the cohort was racially/ethnically diverse (33.3% white, 32.4% black, 27.5% Hispanic). A higher proportion of older adults had non-viral cirrhosis compared to younger adults (46.1% vs 21.8%, P < 0.001). A similar proportion of HCC were detected by surveillance in both groups (41.0% vs 40.0%, P = 0.80), but a higher proportion of older adults presented with early stage HCC (BCLC 0/A; 44.8% vs 40.6%, P < 0.001) compared to younger adults; further, a higher proportion of older adults had Child A cirrhosis (61.1% vs 43.4%, P < 0.001) compared to younger adults. Among treated patients (n = 750), older adults were more likely to receive curative therapy (OR 1.71, 95% CI 1.06–2.77) even after adjusting for sex, race, Child Pugh score, BCLC stage and ECOG performance status; there was no significant difference in complete response rates (31.0% vs 28.9%, P = 0.58) between older and younger adults. Among those who received curative therapy, median OS was significantly lower among older compared to younger adults (37.9 vs 57.5 months, P = 0.04) while survival was similar among older and younger adults receiving palliative HCC therapy (12.6 vs 12.2 months, P = 0.46) and best supportive care (1.6 vs 2.4 months, P = 0.05). Older adults had higher mortality than younger adults (HR 1.28, 95%CI 1.05–1.56) after adjusting for sex, race, Child Pugh score, BCLC stage and ECOG performance status. CONCLUSION: Despite being more likely than younger adults to receive curative treatment, older adults with HCC had worse overall survival, independent of BCLC stage or cirrhosis severity.

To investigate associations of lifetime history of traumatic brain injury (TBI) with prescription opioid use and misuse among noninstitutionalized adults. Ohio Behavioral Risk Factor Surveillance System (BRFSS) participants in the 2018 cohort who completed the prescription opioid and lifetime history of TBI modules (n = 3448). Secondary analyses of a statewide population-based cross-sectional survey. Self-report of a lifetime history of TBI using an adaptation of the Ohio State University TBI-Identification Method. Self-report of past year: (1) prescription pain medication use (ie, prescription opioid use); and (2) prescription opioid misuse, defined as using opioids more frequently or in higher doses than prescribed and/or using a prescription opioid not prescribed to the respondent. In total, 22.8% of adults in the sample screened positive for a lifetime history of TBI. A quarter (25.5%) reported past year prescription opioid use, and 3.1% met criteria for prescription opioid misuse. A lifetime history of TBI was associated with increased odds of both past year prescription opioid use (adjusted odds ratio [AOR] = 1.52; 95% CI, 1.27-1.83; P < .01) and prescription opioid misuse (AOR = 1.65; 95% CI, 1.08-2.52; P < .05), controlling for sex, age, race/ethnicity, and marital status. Results from this study support the "perfect storm" hypothesis-that persons with a history of TBI are at an increased risk for exposure to prescription opioids and advancing to prescription opioid misuse compared with those without a history of TBI. Routine screening for a lifetime history of TBI may help target efforts to prevent opioid misuse among adults.

Although traumatic brain injury (TBI) has a disproportionate impact on older adults, there has been limited inclusion of these individuals in post-TBI cognitive-communication research. This study was undertaken to compare demographic and injury characteristics, speech-language pathology input, and broad outcomes for younger and older adults admitted to inpatient rehabilitation following TBI. A retrospective audit of first occasion adult TBI admissions in 2019 to inpatient rehabilitation in an Australian metropolitan subacute hospital was conducted via medical record data. Admissions were located using International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) coding that aligned with TBI. Comparisons were made for younger (18-54 years) and older (≥ 55 years) adults. A total of 114 admissions (51.75% older adults) were included. Patient age ranged between 18 and 90 years. Falls caused TBI in the majority of older adults, whereas transport-related accidents were the most common cause for younger adults. Age-based trends for intracranial injury were observed. Cognitive-communication difficulties were the most common speech-language pathology diagnosis with no significant difference in prevalence between younger and older adults. Age group was not significantly associated with length of stay or discharge home. The implications of injury-related trends for older adults on post-TBI cognitive-communication are poorly understood. This lack of information is problematic given the frequency of cognitive-communication difficulties in this population. Research into cognitive-communication following new onset TBI in older adults is crucial to support rehabilitation service provision and improve outcomes for older adults.

Background and importance Older adults are at higher risk of undertriage and mortality following a traumatic brain injury (TBI). Early identification and accurate triage of severe cases is therefore critical. However, the Glasgow Coma Scale (GCS) might lack sensitivity in older patients. Objective This study investigated the effect of age on the association between the GCS and TBI severity. Design, settings, and participants This multicentre retrospective cohort study (2003-2017) included TBI patients aged ≥16 years with an Abbreviated Injury Scale (AIS of 3, 4 or 5). Older adults were defined as aged 65 and over. Outcomes measure and analysis Median GCS score were compared between older and younger adults, within subgroups of similar AIS. Multivariable logistic regressions were computed to assess the association between age and mortality. The primary analysis comprised patients with isolated TBI, and secondary analysis included patients with multiple trauma. Main results A total of 12 562 patients were included, of which 9485 (76%) were isolated TBIs. Among those, older adults represented 52% ( n = 4931). There were 22, 27 and 51% of older patients with an AIS-head of 3, 4 and 5 respectively compared to 32, 25 and 43% among younger adults. Within the different subgroups of patients, median GCS scores were higher in older adults: 15 (14-15) vs. 15 (13-15), 15 (14-15) vs. 14 (13-15), 15 (14-15) vs. 14 (8-15), for AIS-head 3, 4 and 5 respectively (all P < 0.0001). Older adults had increased odds of mortality compared to their younger counterparts at all AIS-head levels: AIS-head = 3 [odds ratio (OR) = 2.9, 95% confidence interval (CI) 1.6-5.5], AIS-head = 4, (OR = 2.7, 95% CI 1.6-4.7) and AIS-head = 5 (OR = 2.6, 95% CI 1.9-3.6) TBI (all P < 0.001). Similar results were found among patients with multiple trauma. Conclusions In this study, among TBI patients with similar AIS-head score, there was a significant higher median GCS in older patients compared to younger patients.

There is a lack of evidence relating to cognitive-communication difficulties following traumatic brain injury (TBI) sustained in older adulthood. A prominent area in which post-TBI cognitive-communication difficulties manifest is at the level of social communication. An investigation of social communication focusing on comparison of those injured in older and younger adulthood is a practical starting point for age-related cognitive-communication outcome comparison. The overall objective of this study was to explore the social communication of individuals who sustained severe TBI in an early period of older adulthood (50-70 years) compared to younger adulthood (18-40 years), as informed by self and close other reports. This exploratory controlled group comparison study involved analysis of self-reported and close other reported La Trobe Communication Questionnaire data for 22 adults with severe TBI (11 older at injury; 11 younger at injury) and 22 control participants (11 older; 11 younger). TBI participants were matched for injury variables and participant groups were matched for sex, age and education. The close others of the older and younger adults with TBI reported them to have significantly more frequent difficulty with social communication than the close others of age-matched control groups. Older adults with TBI reported significantly more frequent difficulty with social communication than uninjured older adults. In contrast, younger adults with TBI and uninjured younger adults reported a similar frequency of difficulty with social communication. No age-based difference in the frequency of social communication difficulty was evident when comparing the self or close other reports of older and younger adults with TBI. Awareness of social communication difficulty, as indexed by comparing self and close other perceptions, showed a different pattern across the TBI groups. The older TBI group rated themselves as having significantly less frequent social communication difficulty than was perceived by their close others. In contrast, no statistically significant difference was evident between the self and close other social communication ratings of the younger TBI group. Where possible clinicians need to work with close communication partners to understand the nature and degree of social communication difficulty following severe TBI. This may be especially important when working with people who sustain TBI in older adulthood if future research shows that this population have greater difficulty with self-awareness of social communication difficulty. What is already known on the subject Cognitive-communication difficulties are a common consequence of traumatic brain injury (TBI) that can have long-term impact on everyday functioning. These challenges have primarily been investigated in individuals who sustained TBI in younger adulthood. What this paper adds to existing knowledge Individuals who sustain severe TBI in early older adulthood have a higher frequency of reported social communication difficulty to non-injured adults of a similar age, albeit they may underreport such difficulties potentially in the context of reduced self-awareness. What are the potential or actual clinical implications of this work? Social communication difficulty is an issue for people who sustain severe TBI in early older adulthood. However, a poorer overall social communication outcome in comparison to those injured in younger adulthood should not be assumed. Clinical service delivery for these challenges is most optimally delivered in a collaborative manner with the individual and their close others. Future research is required to investigate the identified trends from this study.

Aim: To study the discrepency between disability and reported well-being after traumatic brain injury. Study design: Prospective study. Place and duration of study: Ghulam Muhammad Mahar Medical College Sukkur and S. M. Benazir Bhutto Medical University Larkana from 7th July 2021 to 15th Jun 2022. Methodology: Two hundred and sixty patients suffering from brain injury were enrolled. The patient’s of traumatic brain injury which was represent able through brain computed tomography scan and was reported within 24 hours of the injury and age 10-55 years were included. Scoring tests as Glasgow outcome scale extended and Short Form as well as quality of life scoring was performed in all cases. Functional outcomes were also observed with a follow up of 6 month post traumatic brain injury. There were mild cases of traumatic brain injury as well as moderate to severe cases which for interpretation purposes were divided into two groups. Results: The mean age of these two groups was 36±3.5 and 29±9.7 years and there was more males than females. The satisfaction level for support from hospitalization was seen significantly higher in all cases with no significant variance while it was poorly reported from rehabilitation centers outpatient support to moderate to severe traumatic brain injury cases. The cases with severe disability of upper and lower regions have a very poor functional outcome in cases with moderate to severe traumatic brain injury. The score for quality of life and mental physical well-being was not in normal ranges for moderate to severe cases of traumatic brain injury. Conclusion: There are discrepancies in patients reporting of well-being and disability outcomes in traumatic brain injury cases. Keywords: Discrepancy; Disability; Traumatic Brain Injury

Diaschisis is a phenomenon in which damage to one brain region leads to dysfunction in remote, yet functionally connected, areas. Although it has been well characterized in stroke, the complex, multifocal nature of traumatic brain injury (TBI) suggests that similar network-level disruptions could occur, yet the presence and impact of diaschisis in TBI remain underexplored. This gap may stem from a historical focus on cerebrovascular events, underrecognition of diaschisis in TBI, and methodological challenges related to TBI's heterogeneous nature. This review maps diaschisis in TBI by examining models, mechanisms, neuroimaging, clinical features, and therapeutic interventions. A PRISMA-ScR guided search of PubMed, Embase, and Cochrane included studies explicitly addressing diaschisis in TBI from inception up to January 2025. Two independent reviewers screened titles, abstracts, and full texts, with discrepancies resolved by consensus. Twenty-three studies were included, encompassing 110 human participants, 497 animals, and one in vitro model. Among these, 57% used neuroimaging, 39% assessed functional outcomes, and 22% examined potential interventions. The predominant experimental model was rodent-controlled cortical impact, typically simulating moderate TBI. Contrarily, human studies were fewer and focused on severe TBI cases. Crossed cerebellar diaschisis was the most common neuroimaging finding (36%), with MRI used most frequently, followed by PET and SPECT. Across both clinical studies and preclinical models, key mechanisms of diaschisis included deafferentation, reduced metabolism, altered glutamate signaling, hypoperfusion, and distant apoptotic cell death. Motor deficits were more common with better recovery than cognitive impairments. Interventions such as MK-801 and Ifenprodil showed potential to reverse diaschisis, but others had limited effects. This review underscores the limited but growing understanding of diaschisis in TBI. Targeted research on mild-to-moderate TBI, interventions, and imaging-validation trials is needed to improve diagnosis and treatment.

Introduction: Acute Respiratory Distress Syndrome (ARDS) develops in about 20-30% of patients with Traumatic Brain Injury (TBI), and is a predictor of poor outcome. 1 TBI has been considered as a formal contraindication for Extra Corporeal Membrane Oxygenation (ECMO) as systemic anticoagulation is necessary. 2There is limited literature on feasibility of ECMO for the treatment of severe ARDS in TBI patients. 3,4 Here, we present a case of a severe traumatic brain injury with aspiration pneumonia and severe ARDS salvaged by VV ECMO.Clinical presentation: A 51 years male suffered from road traffic accident with severe traumatic brain injury, and aspiration pneumonia.He was intubated in outside hospital in view of low GCS (E1V1M4).Though he was planned for craniotomy and intracranial hematoma drainage, it was postponed in view of worsening respiratory status and was referred to our centre.At presentation to our ICU: he was sedated and paralyzed, pupil: left-4mm (nonreactive to light), right -2mm (sluggishly reactive), on high ventilatory support.As he had features of raised intracranial pressure, routine ARDS ventilatory management like high PEEP/PEEP titration, prone ventilation etc. was not feasible.He continued to have severe hypoxia (PF ratio of 55), respiratory acidosis; and Murray score of 3.3.Intervention/ Management: He was put on VV ECMO: Femoro-Jugular, (25F right femoral venous drainage cannula, 19F right IJV return cannula).During cannulation, heparin was not given, and ECMO was run for initial 48 hours without heparin anticoagulation.After 48 hours of ECMO run, heparin was started with a lower ACT target of 140-160.Outcome: His sensorium improved over the days, and became fully conscious by day 8. Gradually his lungs improved, and he was weaned off from ECMO on day 14.He was weaned off from ventilator by day 24, and shifted out of ICU on day 31 in a stable condition.Conclusion: This case suggests that ECMO can be run safely in severe TBI cases though with a modified anticoagulation protocol.With appropriate protocol implementation and close monitoring, VV ECMO can be considered in severe TBI cases with refractory hypoxia for better clinical outcome.

Comparative analysis of plasma and salivary S100B as predictors of traumatic brain injury severity according to GCS and MAIS/head.

Traumatic brain injury (TBI) is a huge public health challenge worldwide. Epidemiological monitoring is important to inform healthcare policy. We aimed at determining the prevalence, outcome, and causes of TBI in Cameroon by conducting a 5-year retrospective study in three referral trauma centers. Data on demographics, causes, injury mechanisms, clinical aspects, and discharge status were recorded. Comparisons between two categorical variables were done using Pearson's chi-square test or Fisher's exact test. A total of 6248 cases of TBI were identified of 18,151 trauma cases, yielding a prevalence of 34%. The number of TBI cases increased across the years (915 in 2016, 1406 in 2020). Demographic data and causes of TBI were available for 6248 subjects and detailed data on clinical characteristics on 2178 subjects. Median age was 30.0 (24.0, 41.0) years. Males were more affected (80%). Road traffic incidents (RTIs; 75%) was the main cause of TBI, with professional bike riders being more affected (17%). Computed tomography (CT) imaging was performed in 67.7% of cases. Of the 597 (27.4%) cases who did not undergo neuroimaging, 311 (52.1%) did not have neuroimaging performed because of financial constraints, among which 7% were severe TBI cases. A total of 341 (19.6%) patients were discharged against medical advice, of which 83% had financial limitations. Mortality was 10.3% (225 of 2178) in the overall population, but disproportionately high in patients with severe TBI (55%) compared to those in high-income settings (27%). TBI occurrence is high in Cameroon, and RTIs are the main causes. Disparities in care provision were identified as attributable to financial constraints regarding CT scanning and continuation of care. The data presented can inform preventive interventions to improve care provision and transport policies. Implementation of a universal health insurance may be expected to improve hospital care and reduce the adverse effects of TBI among Cameroonians.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury Research In this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition of the Guidelines for the Management of Pediatric Severe Traumatic Brain Injury (TBI). This body of work updates the Second Edition of the guidelines that was published in 2012 (1). It represents a substantial effort by a multidisciplinary group of individuals assembled to reflect the team approach to the treatment of these complex, critically ill patients that is essential to optimizing critical care and improving outcomes. This work also represents the strong and always-evolving partnership between investigators from the medical and research communities, forged in Chicago in 2000, from which the first pediatric TBI guidelines were developed. The mutual trust and respect we share have been the foundation of our commitment to bringing evidence-based care to children with TBI. Updating these guidelines was particularly exciting to the individuals who have participated in the previous two editions because several new studies have been published which begin to address a number of major gaps in the pediatric TBI literature—gaps that were specifically identified as targets for future research in earlier editions. For example, we are now able to include reports on the effects of commonly used sedatives and analgesics on intracranial pressure (ICP). Similarly, initial head-to-head comparisons of the influence of agents in routine "real world" use such as hypertonic saline (HTS), fentanyl, and others now inform these guidelines (2,3). A total of 48 new studies were included in this Third Edition. Although some progress has been made and should be celebrated, overall the level of evidence informing these guidelines remains low. High-quality randomized studies that could support level I recommendations remain absent; the available evidence produced only three level II recommendations, whereas most recommendations are level III, supported by low-quality evidence. Based in part on a number of requests from the readership to individual clinical investigators, we have included a companion article in the regular pages of Pediatric Critical Care Medicine that presents a "Critical Pathway" algorithm of care for both first-tier and second-tier (refractory intracranial hypertension) approaches. The algorithm reflects both the evidence-based recommendations from these guidelines and consensus-based expert opinion, vetted by the clinical investigators, where evidence was not available. An algorithm was provided in the First but not Second Editions of the guidelines, and we believe that given the new reports available, along with the existing gaps in evidence, a combination of evidence-based and consensus-based recommendations provides additional and much-needed guidance for clinicians at the bedside. The algorithm also addresses a number of issues that are important but were not previously covered in the guidelines, given the lack of research and the focus on evidence-based recommendations. This includes addressing issues such as a stepwise approach to elevated ICP, differences in tempo of therapy in different types of patients, scenarios with a rapidly escalating need for ICP-directed therapy in the setting of impending herniation, integration of multiple monitoring targets, and other complex issues such as minimal versus optimal therapeutic targets and approaches to weaning therapies. We hope that the readership finds the algorithm document helpful, recognizing that it represents a challenging albeit important step. Designing and developing this pediatric TBI evidence-based guidelines document required an expert administrative management team, and to that end, we are extremely grateful to the staff of the Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, for their vital contribution to this work. We are also grateful to the Brain Trauma Foundation and the Department of Defense for supporting the development and publication of these guidelines documents. We are grateful to the endorsing societies for recognizing the importance of this work and for the considerable work of the clinical investigators in constructing the final document. We are also pleased to have collaborated with the Congress of Neurological Surgeons and the journal Neurosurgery that is copublishing the Executive Summary document of these guidelines for its readership. We are also grateful to Hector Wong for serving as Guest Editor, along with the external reviewers of this final document. Finally, we thank each of the clinical investigators and coauthors on this project. We believe that the considerable uncompensated time and effort devoted to this important project will help to educate clinicians worldwide and enhance the outcomes of children with severe TBI. Clinical investigators provided Conflict of Interest Disclosures at the beginning of the process, which were re-reviewed at the time of publication. No clinical investigator made inclusion decisions or provided assessments on publications for which they were an author. Looking forward, it is important to recognize that these guidelines were written as the Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT) (4–6), one of the most important in the field of pediatric TBI, was coming to a close. The ADAPT completed enrollment of 1,000 cases of severe pediatric TBI and is one example of the recent heightened general interest in TBI as a disease. This new interest in the importance of TBI has emerged in part from the recognition of the high prevalence of TBI across the injury severity spectrum, particularly concussion, and from the need for new classification systems and new trial design for TBI in both children and adults (7,8). In addition, the emerging links between TBI and a number of neurodegenerative diseases have broadened the interest in TBI, have led to additional support of TBI research, and have produced an unprecedented level of research in TBI and a quest for new therapies (9–11). We expect that the results of ADAPT, along with those of other ongoing and recently completed research in the field, will help provide new insight and clarity into the acute medical management (MM) of infants, children, and adolescents with severe TBI, and mandate further refinement of the recommendations in these documents. We know that we speak for the entire team of clinical investigators in welcoming the opportunity to incorporate additional high-level evidence into future updates of these guidelines. METHODS The methods for developing these guidelines were organized in two phases: a systematic review, assessment, and synthesis of the literature; and use of that product as the foundation for evidence-based recommendations. These guidelines are the product of the two-phased, evidence-based process. Based on almost 2 decades of collaboration, the team of clinical investigators and methodologists (Appendix A, Supplemental Digital Content 1, https://links.lww.com/PCC/A774) is grounded in and adheres to the fundamental principles of evidence-based medicine to derive recommendations, and is committed to maintaining the distinction between evidence and consensus. It is important that this distinction is clear to promote transparency and inspire innovative future research that will expand the evidence base for TBI care. Because these guidelines only provide recommendations based on available evidence, most often they do not provide direction for all phases of clinical care. Ideally, clinically useful protocols begin with evidence-based guidelines, and then use clinical experience and consensus to fill the gaps where evidence is insufficient. The goal is to use the evidence and the evidence-based recommendations as the backbone to which expertise and consensus can be added to produce protocols appropriate to specific clinical environments (Fig. 1, "Future Research section"). In a process independent from developing this Third Edition of the guidelines, the team engaged in a consensus process and produced the algorithm for treatment of severe TBI in pediatric patients.Figure 1.: Dynamic process for guidelines, protocols, and future research. The diagram shows the flow of information from available evidence to a guideline. The guideline leads to gaps that identify future research and consensus-based clinical protocols that fill gaps, both of which lead to a generation of new research.The following "Methods section" describes the process we used to produce the systematic review and evidence-based recommendations. The methods used to develop the algorithm are described in that document (12). Phase I: Systematic Evidence Review and Synthesis Scope of the Systematic Review Criteria for Including Publications Appendix B (Supplemental Digital Content 1, https://links.lww.com/PCC/A774) lists the criteria for including studies for review using the categories of population, interventions, comparators, outcomes, timing, settings, study designs, and publication types. The criteria for population are as follows: Age 18 years old or younger TBI Glasgow Coma Scale (GCS) score less than 9 Included Topics. The team chose to carry forward topics from the Second Edition of these guidelines. No new topics were added. The topics are organized in three categories that are specific to severe TBI in children: monitoring, thresholds, and treatments. Monitoring 1. ICP 2. Advanced neuromonitoring 3. Neuroimaging Thresholds 4. ICP 5. Cerebral perfusion pressure (CPP) Treatments 6. Hyperosmolar therapy 7. Analgesics, sedatives, and neuromuscular blockade (NMB) 8. Cerebrospinal fluid (CSF) drainage 9. Seizure prophylaxis 10. Ventilation therapies 11. Temperature control 12. Barbiturates 13. Decompressive craniectomy 14. Nutrition 15. Corticosteroids Major Changes for This Edition. Major changes for this edition are summarized here, and details are provided in Appendix C (Supplemental Digital Content 1, https://links.lww.com/PCC/A774). The clinical investigators and methods team identified three primary endpoints considered important health outcomes for pediatric patients with TBI: To improve overall outcomes (mortality, morbidity, function) To control ICP To prevent posttraumatic seizures (PTSs) Two new meta-analyses were added to the evidence base for temperature control. The title of "Hyperventilation" was changed to "Ventilation Therapies." Recommendations are provided as level I, II, or III. In some cases, publications from the second edition were not included in this 3rd Edition. Our rationale for excluding previously included studies was based on identification of current material that superseded our earlier work (See Appendix E, Supplemental Digital Content 1, https://links.lww.com/PCC/A774). Similarly, we removed or changed recommendations from the 2nd Edition when the current literature provided new and/or more accurate information (see Appendix A, Supplemental Digital Content 1, https://links.lww.com/PCC/A774). Study Selection and Compilation of Evidence Literature Search Strategies. The research librarian who worked on the Second Edition reviewed and updated the search strategies for that edition and executed the searches for this Third Edition. Ovid/MEDLINE was searched from 2010 to May of 2015, and an update was performed to include articles published and indexed through June of 2017. Publications recommended by peers that were not captured in the search were reviewed, and those meeting inclusion criteria were included in the final library. The search strategy is in Appendix D (Supplemental Digital Content 1, https://links.lww.com/PCC/A774). Abstract and Full-Text Review. Abstracts for publications captured in the search were reviewed independently by two members of the methods team. Articles were retained for full-text review if at least one person considered them relevant based on the abstract. Two methods team members read each full-text article and determined whether it met the inclusion criteria (Appendix B, Supplemental Digital Content 1, https://links.lww.com/PCC/A774). The included and excluded full-text articles for each topic were also reviewed by one or more clinical investigators who took the lead on each topic, and full-text articles were available for review by all authors. The key criteria for inclusion were as follows: the study population was pediatric patients (age, ≤ 18 yr old) with severe TBI (defined as GCS score of 3–8) and the study assessed an included outcome. Publications with samples that included adults, moderate or mild severities, or pathologies other than TBI (indirect evidence) were considered when direct evidence was limited or not available. Discrepancies between reviewers were resolved via consensus or by a third reviewer. A list of studies excluded after full-text review is in Appendix E (Supplemental Digital Content 1, https://links.lww.com/PCC/A774). Use of Indirect Evidence and Intermediate Outcomes Direct evidence comes from studies that compare important health outcomes (e.g., mortality, morbidity, function) between two or more intervention groups or between an intervention group and a control group that represent the population of interest, in this case pediatric patients with severe TBI. When direct evidence was limited or not available, indirect evidence was used to support a recommendation. Indirect evidence has been defined in previous work by this methods team (1,13,14) and other evidence-based methods groups (15,16). In this edition, we included two types of indirect evidence. 1. Evidence That Improvement in an Intermediate Outcome Is Associated With Important Health Outcomes In some cases, there is a lack of direct evidence that utilization of a specific treatment option results in improved patient outcomes such as mortality or morbidity, but there is evidence about changes in an intermediate outcome, which is then associated with improved mortality or morbidity. The most notable intermediate outcome for the treatment of TBI is management of ICP. Multiple studies (cited in the ICP Monitoring topic of this guideline) consistently demonstrate that patients whose ICP is successfully maintained at or under a maximum threshold have reduced mortality and improved function. As a consequence, the clinical investigators elected to identify "Control of ICP" as an important intermediate outcome, and use the available indirect evidence to support the recommendations about monitoring ICP and for treatments designed to lower ICP. Intermediate outcomes and indirect evidence of this nature were used in three topics for this edition of the guidelines: ICP Monitoring, Ventilation Therapies, and Temperature Control. In each of these topics, an intermediate outcome was used as the endpoint because, although direct evidence was lacking that intervening improves mortality or function, indirect evidence was available associating management of the intermediate outcome with improved mortality or function. For ICP monitoring, the intermediate outcome was managed ICP; indirect evidence that patients with managed ICP had better outcomes was used to support the recommendation. For ventilation therapies, the intermediate outcomes were prevention of severe hypocarbia (SH). There were no pediatric studies that directly related hyperventilation to poor outcomes. However, there was evidence of an association between SH and mortality; thus, studies that demonstrated this association were used as indirect evidence. For temperature control, the intermediate outcomes were mean and peak CSF myelin basic protein concentrations and phenytoin levels. 2. Evidence From Samples With Mixed Ages, Severities, or Pathologies In some cases, when direct evidence was lacking, we considered studies that included patients with mixed severities (mild, moderate, and severe TBI), mixed ages, or mixed pathologies (traumatic and non-TBI) using the following criteria: How relevant to (or different from) our target population is the population in the indirect study? To what extent does the relevant physiology of the population in the indirect study approximate the relevant physiology of the population of interest? To what extent are differences in physiology expected to influence the outcome? In what direction would these differences influence the observed effect? In this edition, indirect evidence from studies with mixed severities, ages, or pathologies was included in the topics about analgesics, sedatives, and NMB; CSF drainage; and seizure prophylaxis. When indirect evidence was included, it is noted in the table describing the quality of the body of evidence. Quality Assessment of Individual Studies All included studies were assessed for potential for bias, which is an approach to assessing the internal validity or quality of an individual study. This assessment is a core component of systematic review methods. It is an approach to considering and rating studies in terms of how the study design and conduct addressed issues such as selection bias, confounding, and attrition. The criteria used for this edition are described in Appendix F (Supplemental Digital Content 1, https://links.lww.com/PCC/A774). Two reviewers independently evaluated each study using the criteria appropriate for the study design (i.e., randomized controlled trials [RCTs], observational studies, studies of thresholds) and rated the study as class 1, 2, or 3 evidence based on the combination of study design and conduct. Class 1 is the highest class and is limited to good-quality RCTs. Class 2 includes moderate-quality RCTs and good-quality cohort or case-control studies. Class 3 is the lowest class and is given to low-quality RCTs, moderate- to low-quality cohort or case-control studies, and treatment series and other noncomparative designs. Differences in ratings were reconciled via consensus or the inclusion of a third reviewer as needed. Data Abstraction Data were abstracted from studies by a member of the methods team and checked for accuracy by a second member. Information was recorded about the study population, design, and results. Key elements of each included study are presented in the Summary of Evidence tables for each topic. Complete abstraction tables are available upon request. Synthesis The final phase of the evidence review is the synthesis of individual studies into information that the clinical investigators and the methods team use to develop recommendations. This synthesis is described for each topic in the section titled "Evaluation of the Evidence," following the Recommendations and preceding the Evidence Summary. Identification of Subtopics and Synthesis For each monitoring, thresholds, or treatment topic, the clinical investigators identified important subtopics or clinical questions. The studies in each topic were reviewed to determine if quantitative synthesis—meta-analysis—was feasible. This involved determining if the patient populations, specifics of the intervention, and the outcomes were similar enough across several studies that the study results could be combined. The result of this assessment is included in the Quality of the Body of Evidence table for each subtopic. For this edition, we did not identify any topics for which quantitative synthesis was appropriate according to current standards. For this reason, the evidence was synthesized qualitatively. Quality of the Body of Evidence Assessing the quality of the body of evidence involves four domains: the aggregate quality of the included individual studies, the consistency of the results across studies, whether the evidence provided is direct or indirect, and the precision of the estimates of the outcomes. The criteria and ratings are outlined below, and more detailed definitions are given in Appendix G (Supplemental Digital Content 1, https://links.lww.com/PCC/A774). In addition, the number of studies and number of included subjects are considered. Based on these, an overall assessment is made as to whether the quality of the body of evidence is high, moderate, low, or insufficient. The assessment of the body of evidence for each subtopic is included in a summary table in each section following the recommendations. Criteria Quality of Individual Studies: This identifies the quality of the individual studies. It details how many studies are class 1, class 2, and class 3. Consistency: is the extent to which the results and are similar across studies. It is rated high are moderate are or one is more It is not when the body of evidence of a study. We as whether the study population is the as the population of interest and whether the outcomes are clinical than intermediate outcomes. Evidence is as indirect, or is the of the for a given outcome. is rated high, moderate, or low. How this is determined on the of used in a specific study but include of the of other of or the of used to determine These criteria are then considered when a rating to the body of evidence. The ratings are defined as follows: that the evidence reflects the research is to the in the of that the evidence reflects the research the in the of and the that the evidence reflects the research is to the in the of and is to the Evidence is or does not a A of quality of the body of evidence a about the importance of the and these across topics and The following general are provided to the that are but are not as two or more class 1 studies demonstrate for a topic, the overall quality of the body of evidence be assessed as because there is about the Similarly, class 1 or 2 studies that provide indirect evidence only low-quality evidence In some cases, the body of evidence be a but the rating A study a body of evidence if it is a class 1 a moderate-quality body of evidence if it is a class 2 study with a and moderate or evidence if the is and the precision of the of is low. is the extent to which research are useful for informing recommendations for a population the population that is the target of the is important to when assessing will on the topic, and the assessment is there is no rating for focus on the of the patient population (e.g., to which patients are the results and the for care (e.g., where could a similar result be if the patient population the inclusion criteria for the review, there be specific that The of the setting in which a study was also be important to For example, a study in a or not be to other settings, on how similar the are to the population of interest or how similar the of the is to the care setting of to be considered include the (e.g., or and the of (e.g., level of The and of are considered because it is that the patients, and available are different across In this edition, we the of individual studies in the of the Body of Evidence and section" following the recommendations. Phase of Recommendations of Recommendations Class 1, 2, or 3 studies the evidence on which the recommendations are our current identification of evidence is but not for the development of recommendations. No recommendations were made a in evidence. evidence was whether it could be used to inform recommendations was based on the quality of the body of evidence and of there were cases in which evidence was but the quality was and our to the evidence into recommendations. if a was not the evidence was included for future because in the new studies be in changes in the assessment of the quality of the body of evidence. of Recommendations in this edition are as level I, level II, or level III. The level of is determined by the assessment of the quality of the body of evidence, than the class of the included studies. The were based on the quality of the body of evidence as follows: I recommendations were based on a body of evidence. II recommendations were based on a moderate-quality body of evidence. recommendations were based on a low-quality body of evidence. could result in a level (e.g., a body of with In this edition, was not used to a recommendation. However, given the lack of and methods in this we issues that were identified and by the clinical was used in cases where there were no studies identified or because the body of evidence had major quality the evidence was no recommendations were Review and of the literature review, identification of new studies, quality assessment, and the methods team for each topic to two clinical The clinical investigators read the included studies and the recommendations, provided and additional studies for team members the and reviewed new studies, and provided the clinical investigators with new publications and a summary of the evidence for each topic. Clinical Review In a meeting in each topic was presented and by the Based on these the methods team the guidelines. Review of Complete The of all topics and the other of the guidelines (e.g., Supplemental Digital Content 1, https://links.lww.com/PCC/A774) was to all clinical investigators for review and and through to the and the document. Review. were made based on from the clinical investigators, the Third Edition and an Executive Summary were to the journal Pediatric Critical Care Medicine for A review was also by members of the of Neurological of Neurological Surgeons Guidelines Review in with the clinical investigators and methods team, to publication in the journal ICP Monitoring Recommendations of I and II There was evidence to support a level I or II for this topic. To Use of ICP monitoring is Changes From Edition. There are no changes from the Second Edition to the recommendations. new class 3 observational studies were added to the evidence base for this topic injury to the after severe TBI is a result of a of that perfusion of and and of and Brain from and or the of the leads to intracranial further and of ICP represents a key in the of injury phase following TBI the in both and outcome after severe TBI have been using

Traumatic brain injury (TBI) is a leading cause of long-term disability, often accompanied by mental health issues such as depression and anxiety. Digital mental health interventions (DMHIs) present promising opportunities for improving the management of these issues, offering solutions such as remote monitoring and outcome tracking through ecological momentary assessment. This scoping review aims to explore the current landscape of DMHIs and the use of patient-reported outcome measures (PROMs) in post-TBI populations. A systematic search across six databases identified 23 relevant studies, predominantly from high-income countries. Almost half of retrieved studies focused on mild TBI populations, with limited evidence reporting DMHI use exclusively in moderate or severe cases. The findings highlight the benefits of DMHIs, including real-time data collection, enhanced patient engagement, and the potential to improve care accessibility. However, challenges such as technology literacy, low response rates, and inconsistent measures of clinical efficacy were noted. Most interventions utilised asynchronous methods of communication, such as smartphone applications and SMS, with PROMs used to track emotional, behavioural, and psychological outcomes. A number of gaps were identified, including the need for more research in moderate and severe TBI cases, better integration into existing healthcare infrastructure, and standardisation of outcome measures. This review underscores the potential of DMHIs to enhance mental health care in TBI patients, while calling for more robust, user-centred designs and longer-term studies to ensure sustainability and effectiveness. Further, this review advocates for more interdisciplinary collaboration in the design and deployment of DMHIs, and the application of a systems-based approach to better integrate digital mental health technologies into TBI care pathways, with full consideration of people, systems, design, and risk. Future research should address these gaps to optimise post-injury care and outcomes for TBI patients when digital mental health solutions are implemented.

Highlights: 1. The main focus of this study was to underscore the importance of exploring the characteristics of traumatic brain injury (TBI) patients, which have not been extensively investigated, to help establish effective clinical procedures and decisions.2. Three out of every four trauma patients in the emergency unit had mild TBIs, and those who did not survive showed a significant trend of rapid deterioration.3. It is crucial to consistently conduct a thorough and comprehensive head-to-toe examination for all trauma patients. Abstract Traumatic brain injury (TBI) is a prevalent neurological condition in emergency units. TBI cases are frequently diagnosed with severe conditions. Underdiagnosis is common in mild TBI cases. As a result, physicians have an uncomprehensive understanding of the patients' characteristics in their daily practice. This study aimed to discuss the characteristics of trauma patients who were diagnosed with TBIs in an emergency unit. We conducted a retrospective cohort observational study to examine the adult population of TBI patients from April 2022 to March 2023. This study collected several data points, including demographics, clinical characteristics, surgical procedures, and disposition distribution. All variables were compiled and summarized using descriptive statistics and analyzed by calculating frequencies and percentages. During the period of this study, 483 trauma patients were admitted to the emergency unit. A total of 361 (74.7%) of these cases were identified as TBIs. Most of the traumatic brain injuries occurred in men (75.6%), with the predominant age range being 18–22 years (22.4%). Mild TBI cases (74.5%) were the most prevalent, followed by moderate (20.2%) and severe (5.3%) TBI cases. The average score from the Glasgow Coma Scale assessment was 15. Most patients (80.9%) had no hypotension, while a greater number of patients (98.1%) did not exhibit hypoxia as a comorbidity. The Injury Severity Score revealed that the highest percentage of TBIs was categorized as minor (62.3%). It was found that 53.5% of the patients were discharged, while 36% of the patients were hospitalized. However, 7 patients (1.9%) passed in the emergency unit, and 30 patients (8.3%) opted to be discharged against medical advice. Only 21 patients (5.8%) received neurosurgical management. As the most prevalent trauma, TBI necessitates careful management to handle the implications of clinical decision-making. It is crucial to investigate the underlying risk of mortality in TBI cases because the majority of patients do not require neurosurgical intervention.

Introduction: Acute respiratory distress syndrome (ARDS) develops in about 20-30% of patients with traumatic brain injury (TBI) and is a predictor of poor outcome.Traumatic brain injury has been considered as a formal contraindication for extracorporeal membrane oxygenation (ECMO) as systemic anticoagulation is necessary.There is limited literature on the feasibility of ECMO for the treatment of severe ARDS in TBI patients.Here, we present a case of a severe TBI with aspiration pneumonia and severe ARDS salvaged by venovenous (VV) ECMO.Clinical presentation: A 51-year-old male suffered a road traffic accident with severe TBI and aspiration pneumonia.He was intubated at an outside hospital due to low a Glasgow Coma Scale (E1V1M4).Though he was planned for craniotomy and intracranial hematoma drainage, it was postponed in view of worsening respiratory status and was referred to our center.At presentation to our intensive care unit (ICU), he was sedated and paralyzed.Pupil: left -4 mm (nonreactive to light), right -2 mm (sluggishly reactive).He was on high ventilatory support.Due to features of raised intracranial pressure, routine ARDS ventilatory management like high positive end-expiratory pressure (PEEP)/PEEP titration, prone ventilation, etc. was not feasible.He continued to have severe hypoxia (PF ratio of 55), respiratory acidosis, and a Murray score of 3.3.Intervention/management: He was placed on VV ECMO using a femorojugular (25F right femoral venous drainage cannula, 19F right internal jugular vein (IJV) return cannula).During cannulation, heparin was not given, and ECMO was run for initial 48 h without heparin anticoagulation.After 48 h of ECMO run, heparin was started with a lower activated clotting time (ACT) target of 140-160.Outcome: His sensorium improved over the days, and became fully conscious by day 8. Gradually his lungs improved, and he was weaned off from ECMO on day 14.He was weaned off from ventilator by day 24, and shifted out of ICU on day 31 in a stable condition.Conclusion: This case suggests that ECMO can be run safely in severe TBI cases though with a modified anticoagulation protocol.With appropriate protocol implementation and close monitoring, VV ECMO can be considered in severe TBI cases with refractory hypoxia for better clinical outcome.

Objective:History of traumatic brain injury (TBI) is associated with increased risk of dementia, but few studies have evaluated whether TBI history alters the course of neurocognitive decline, and existing literature on this topic is limited to short follow-up and smaller samples. The primary aim of this study was to evaluate whether a history of TBI (TBI+) influences neurocognitive decline later-in-life among older adults with or without cognitive impairment [i.e., normally aging, Mild Cognitive Impairment (MCI), or dementia].Participants and Methods:Participants included individuals from the National Alzheimer’s Coordinating Center (NACC) who were at least 50 years old and with 3 to 6 visits (M number of visits = 4.43). Participants with any self-reported history of TBI (n = 1,467) were matched 1:1 to individuals with no reported history of TBI (TBI-) from a sample of approximately 45,000 participants using case-control matching based on age (+/- 2 years), sex, education, race, ethnicity, cognitive diagnosis [cognitively normal (CN), MCI, or all-cause dementia], etiology of cognitive impairment, functional decline (Clinical Dementia Rating Scale, CDR), number of Apolipoprotein E4 (APOE ε4) alleles, and number of annual visits (3 to 6). Mixed linear models were used to assess longitudinal neuropsychological test composites (using NACC normative data) of executive functioning/attention/speed (EFAS), language, and memory in TBI+ and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined.Results:Following matching procedures, TBI+ (n=1467) and TBI- (n=1467) groups were nearly identical in age (TBI+ M = 71.59, SD = 8.49; TBI- M = 71.63, SD = 8.44), education (TBI+ M = 16.12, SD = 2.59; TBI- M = 16.10, SD = 2.52), sex (both 55% male), race (both 90% White), ethnicity (both 98% non-Hispanic), APOE ε4 alleles (both 0 = 62%, 1 = 33%, 2 = 5%), baseline cognitive diagnoses (both CN = 60%, MCI = 18%, dementia = 12%), and global CDR (TBI+ M = 0.30, SD = 0.38, TBI- M = 0.30, SD = 0.38). At baseline, groups had similar Z-scores of in EFAS (TBI+ Mefas = -0.02, SD = 1.21; TBI- Mefas = -0.04, SD = 1.27), language (TBI+ MLanguage = -0.48, SD = 0.98; TBI- MLanguage = -0.55, SD = 1.05), and memory (TBI+ MMemory = -0.45, SD = 1.28; TBI- MMemory = -0.45, SD =1.28). The course of change in neuropsychological functioning worsened longitudinally, but did not differ between TBI groups (p’s &gt; .110). There were no significant interactions between TBI history and age, sex, education, race/ethnicity, number of APOE ε4 status, or cognitive diagnosis (all p’s &gt; .027).Conclusions:In this matched case-control design, our findings suggest that a history of TBI, regardless of demographic factors, APOE ε4 status, and cognitive diagnosis, does not significantly alter the course of neurocognitive functioning later-in-life in older adults with and without cognitive impairment. Future clinicopathological longitudinal studies with well characterized TBI histories and the associated clinical course are needed to help clarify the mechanism by which TBI may increase dementia risk for some individuals, without affecting course of decline.