Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations

Intracranial pressure; Brain injury; ConsensusPresión intracraneal; Lesión cerebral; ConsensoPressió intracranial; Lesió cerebral; ConsensBACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)

Brain injury; Head trauma; AlgorithmDaño cerebral; Trauma en la cabeza; AlgoritmoLesió cerebral; Trauma al cap; AlgoritmeBackground: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.We thank our financial supporters who include Adler/Geirsch Attorney at Law, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care, Bard, the Brain Trauma Foundation, DePuy, Hemedex, Integra, the Neurointensive Care Section of the European Society of Intensive Care Medicine, Neurosurgical Society of Australasia, Medtronic, Moberg Research, Natus, Neuroptics, Raumedic, Sophysa, Stryker, and Zoll

The impact of conjunctival flap method and drainage cannula diameter on bleb survival in the rabbit model

Purpose To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS). Methods Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based con- junctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26-gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. Filtration blebs were evaluated every three days by a masked observer. Bleb failure was defined as the primary endpoint in this study and was recorded after two consecutive flat bleb evaluations. Results Group 1 (LBCF, 22- gauge cannula) had a mean bleb survival time (Mean ± SD) of 18.7 ± 2.9 days. Group 2 (LBCF, 26-gauge cannula) also had a mean bleb survival time of 18.7 ± 2.9 days. Group 3 (FBCF, 22-gauge cannula) had a mean bleb survival time of 19.2 ± 3.8 days. Group 4 (FBCF, 26-gauge cannula) had a mean bleb survival time of 19.7 ± 4.1 days. A 2-way analysis of variance showed that neither surgical approach nor cannula gauge made a statistically significant difference in bleb survival time (P = 0.634 and P = 0.874). Additionally, there was no significant interaction between cannula gauge and conjunctival flap approach (P = 0.874), suggesting that there was not a combination of drainage gauge and conjunctival flap method that produced superior bleb survival. Conclusion Limbus and fornix-based conjunctival flaps are equally effective in promoting bleb survival using both 22 and 26-gauge cannulas in the rabbit model. The 26-gauge drainage tube may be preferred because its smaller size facilitates the implantation process, reducing the risk of corneal contact

A hybrid digital parenting programme delivered within the Malaysian preschool system: protocol for a feasibility study of a small scale cluster randomised factorial trial

Background: Achieving Sustainable Development Goal 4, and in particular target 4.2, to ensure that all children have access to quality early childhood development, care and preprimary education so that they are ready for primary education, is far from being attained. COVID-19 further compromised progress by disrupting early education, reducing access to wellbeing resources, and increasing family violence. Evidence from low- and middle-income countries suggests in-person parenting interventions are effective at improving child learning and preventing violence. Scaling-up these programmes, however, is challenged because of resource constraints. Integrating digital and human-delivered intervention components is one potential solution to addressing these challenges. There is a need to understand the feasibility and the effectiveness of such interventions in low resource settings including Malaysia. Objectives: This study aims to determine the feasibility and the effectiveness of a digital parenting programme (Naungan Kasih) delivered with varying combinations of two components included to encourage engagement in Malaysia. The study is framed around the following objectives 1) to determine the recruitment, retention, and engagement rates in each intervention conditions; 2) to document implementation fidelity; 3) to explore programme acceptability among key stakeholders; 4) to estimate the costs of the intervention; and 5) to provide preliminary indications of the effectiveness of the different components. Methods: This ten week factorial cluster randomised trial compares ParentText, a chatbotled intervention that delivers parenting and violence prevention content to caregivers of preschool aged children, in combination with two engagement components 1) a WhatsApp support group, and 2) either one or two in-person sessions. The trial aims to recruit 160 primary and 160 secondary caregivers of children (aged between four and six years) from eight schools split equally across two states in Malaysia: Kuala Lumpur and Negeri Sembilan. Primary outcomes relate to the feasibility and acceptability of the intervention and its components, including recruitment, retention and engagement. Effectiveness outcomes include caregiver parenting practices, mental health and relationship quality, and child developmental and behavioural outcomes. The evaluation involves mixed methods research utilising quantitative surveys among caregivers, digitally tracked engagement data of caregivers’ usage of the digital intervention components, direct assessments of children, and focus group discussions with caregivers and key stakeholders of the preschool system. Results: Recruitment took place in December 2023. 208 parents were recruited at baseline: 151 primary caregivers, and 57 secondary caregivers. In January 2024, 168 parents enrolled in the programme. Results will be reported in the second half of 2024. Conclusions: This is the first factorial randomised trial to assess the feasibility of a hybrid human-digital playful parenting programme in Southeast Asia. The results of this study will inform a large-scale optimisation trial to establish the most effective, cost-effective, and scalable version of the intervention in Malaysia. Trial Registration: The trial was registered on the Open Science Framework on 5 December 2023 (https://doi.org/10.17605/OSF.IO/F32KY)

Recipient mucosal-associated invariant T cells control GVHD within the colon

Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I–like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT. Allogeneic BMT recipients deficient in IL-17A also develop accelerated GVHD, suggesting MAIT cells likely regulate GVHD, at least in part, by the generation of this cytokine. Indeed, analysis of stool microbiota and colon tissue from IL-17A–/– and MR1–/– mice identified analogous shifts in microbiome operational taxonomic units (OTU) and mediators of barrier integrity that appear to represent pathways controlled by similar, IL-17A–dependent mechanisms. Thus, MAIT cells act to control barrier function to attenuate pathogenic T cell responses in the colon and, given their very high frequency in humans, likely represent an important population in clinical BMT

Variability in Serum Sodium Concentration and Prognostic Significance in Severe Traumatic Brain Injury: A Multicenter Observational Study.

BACKGROUND/OBJECTIVE: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. METHODS: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. RESULTS: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048). CONCLUSIONS: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients

Early Osmotherapy in Severe Traumatic Brain Injury : An International Multicenter Study

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone (n = 46) with those who received HTS alone (n = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.Peer reviewe

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian 4 Birth Cohort 1936

Cognitive decline is among the most feared aspects of ageing. We have generated induced pluripotent stem cells (iPSCs) from 24 people from the Lothian Birth Cohort 1936, whose cognitive ability was tested in childhood and in older age. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT). All lines demonstrated STR matched karyotype and pluripotency was validated by multiple methods. These iPSC lines are a valuable resource to study molecular mechanisms underlying individual differences in cognitive ageing and resilience to age-related neurodegenerative diseases

A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

BACKGROUND: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based. METHODS: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations. RESULTS: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. CONCLUSIONS: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management