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Dipole-bound states in anions exist when a polar neutral core binds an electron in a diffuse orbital through charge–dipole interaction. Electronically excited polar neutral cores can also bind an electron in a diffuse orbital to form Core-Excited Dipole-Bound States (CE-DBSs), which are difficult to observe because they usually lie above the electron detachment threshold, leading to very short lifetimes and, thus, unstructured transitions. We report here the photodetachment spectroscopy of cryogenically cooled acetylacetonate anion (C5H7O2−) recorded by detecting the neutral radical produced upon photodetachment and the infrared spectroscopy in He-nanodroplets. Two DBSs were identified in this anion. One of them lies close to the electron detachment threshold (∼2.74 eV) and is associated with the ground state of the radical (D0-DBS). Surprisingly, the other DBS appears as resonant transitions at 3.69 eV and is assigned to the CE-DBS associated with the first excited state of the radical (D1-DBS). It is proposed that the resonant transitions of the D1-DBS are observed ∼1 eV above the detachment threshold because its lifetime is determined by the internal conversion to the D0-DBS, after which the fast electron detachment takes place. [ABSTRACT FROM AUTHOR]

Background: Approximately one-third of trauma-related deaths are due to traumatic brain injury (TBI), particularly among young adults and elderly patients. Management strategies may vary across different age groups, potentially influencing short-term neurological outcomes. This study aims to investigate age-related disparities in treatment approaches and 3-month neurological outcomes among TBI patients. Methods: We conducted a retrospective study on TBI patients requiring Intensive Care Unit (ICU) admission from January 1, 2015, to January 1, 2024, in a tertiary University hospital. Patient demographics, major comorbidities, ICU admission parameters, interventions and ICU complications were collected. An unfavorable neurological outcome at 3 months (UO) was defined as a Glasgow Outcome Scale (GOS) score of 1–3. A high therapy intensity level (TIL) was defined as a TIL basic of 3–4. A multivariable logistic regression model and a Cox proportional Hazard Regression model were used to assess the association of age and TIL with neurological outcome and mortality. A sensitivity analysis on low TIL (0–2) and high TIL subgroups was also conducted. Results: We enrolled 604 TBI patients, of which 240 (40%) had UO. The highest prevalence of UO was found in patients aged ≥80 years (53/94, 56%), followed by patients aged 50–79 years (104/255, 41%). The age group 35–49 years had the lowest rate of UO (38/127, 30%). Older patients (age ≥ 80 years) received less frequently high TIL than others (p = 0.03). In the multivariable analysis, age ≥ 80 years [OR: 3.42 (95% CI 1.72–6.81)] was independently associated with UO, while age ≥ 80 years [HR 5.42 (95% CI 3.00–9.79)] and age 50–79 years [HR 2.03, (95% CI 1.19–3.48)] were independently associated with mortality. Although there was no interaction between age groups and TIL on outcome, an exploratory analysis showed that in the high TIL subgroup of patients, age had no independent impact on the outcome, whereas, in the low TIL group, age ≥ 80 years was independently associated with UO [OR: 3.65 (95% CI: 1.64–8.14)]. Conclusion: Older age, especially in the setting of low intensity treatment, may impact short-term neurological outcome of traumatic brain-injured patients. [ABSTRACT FROM AUTHOR]

Background: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. Methods: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. Results: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18–22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. Conclusions: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management. [ABSTRACT FROM AUTHOR]

Neurocritical patients frequently exhibit abnormalities in cerebral hemodynamics (CH) and/or intracranial compliance (ICC), all of which significantly impact their clinical outcomes. Transcranial Doppler (TCD) and the cranial micro-deformation sensor (B4C) are valuable techniques for assessing CH and ICC, respectively. However, there is a scarcity of data regarding the predictive value of these techniques in determining patient outcomes. We prospectively included neurocritical patients undergoing intracranial pressure (ICP) monitoring within the first 5 days of hospital admission for TCD and B4C assessments. Comprehensive clinical data were collected alongside parameters obtained from TCD (including the estimated ICP [eICP] and estimated cerebral perfusion pressure [eCPP]) and B4C (measured as the P2/P1 ratio). These parameters were evaluated individually as well as in combination. The short-term outcomes (STO) of interest were the therapy intensity levels (TIL) for ICP management recommended by the Seattle International Brain Injury Consensus Conference, as TIL 0 (STO 1), TIL 1–3 (STO 2) and death (STO 3), at the seventh day after last data collection. The dataset was randomly separated in test and training samples, area under the curve (AUC) was used to represent the noninvasive techniques ability on the STO prediction and association with ICP. A total of 98 patients were included, with 67% having experienced severe traumatic brain injury and 15% subarachnoid hemorrhage, whilst the remaining patients had ischemic or hemorrhagic stroke. ICP, P2/P1, and eCPP demonstrated the highest ability to predict early mortality (p = 0.02, p = 0.02, and p = 0.006, respectively). P2/P1 was the only parameter significant for the prediction of STO 1 (p = 0.03). Combining B4C and TCD parameters, the highest AUC was 0.85 to predict death (STO 3), using P2/P1 + eCPP, whereas AUC was 0.72 to identify ICP > 20 mmHg using P2/P1 + eICP. The combined noninvasive neuromonitoring approach using eCPP and P2/P1 ratio demonstrated improved performance in predicting outcomes during the early phase after acute brain injury. The correlation with intracranial hypertension was moderate, by means of eICP and P2/P1 ratio. These results support the need for interpretation of this information in the ICU and warrant further investigations for the definition of therapy strategies using ancillary tests. Trial registration: NCT03144219, Registered 01 May 2017, https://www.clinicaltrials.gov/ct2/show/NCT03144219. Highlights: Noninvasive methods as transcranial Doppler and a cranial pulsation sensor provided pathophysiological parameters which may be associated with poorer outcomes in acute brain injury. P2/P1 ratio, eICP and eCPP demonstrated high negative predictive values for ruling out either intracranial hypertension or imminence of death. The combination of these techniques was important to improve their predictive value, rather than using them separately. The strong correlation of these parameters with outcomes but only moderate correlation with intracranial pressure values seems to reinforce the need for a physiological and dynamic reasoning when dealing with neurocritical patients and monitoring ICP. [ABSTRACT FROM AUTHOR]

Key Points: Question: How does use of a liberal or restrictive strategy of blood transfusion influence neurological outcome among patients with acute brain injury? Findings: In this randomized clinical trial that included 850 patients with acute brain injury and a hemoglobin level below 9 g/dL, those who were treated with a liberal transfusion strategy triggered by hemoglobin below 9 g/dL had a lower probability of unfavorable neurological outcome at 180 days than those treated with a restrictive strategy triggered by hemoglobin below 7 g/dL (62.6% vs 72.6%, respectively; adjusted relative risk, 0.86). Meaning: A liberal transfusion strategy compared with a restrictive strategy resulted in a lower rate of unfavorable neurological outcome among patients with acute brain injury. Importance: Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population. Objective: To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. Design, Setting, and Participants: Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023. Interventions: Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period. Main Outcomes and Measures: The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization. Results: Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, −10.0% [95% CI, −16.5% to −3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P =.002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]). Conclusions and Relevance: Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02968654 This randomized clinical trial assesses the effect of a liberal vs a restrictive hemoglobin threshold for red blood cell transfusion on unfavorable neurological outcome in patients with acute brain injury. [ABSTRACT FROM AUTHOR]

Background We determined the relationships between cytokine expression in sputum and clinical data to characterize and understand chronic obstructive pulmonary disease (COPD) exacerbations in people with COPD. Methods We measured 30 cytokines in 936 sputum samples, collected at stable state and exacerbation visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (ClinicalTrials.gov NCT01360398). We determined their longitudinal expression and examined differential expression based on disease status or exacerbation type. Results Of the cytokines, 17 were suitable for analysis. As for disease states, in exacerbation sputum samples, interleukin (IL) 17A, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 were significantly increased compared to stable state sputum samples, but a logistic mixed model could not predict disease state. As for exacerbation types, bacteria-associated exacerbations showed higher expression of IL-17A, TNF-α, IL-1β, and IL-1α. IL-1α, IL-1β, and TNF-α were identified as suitable biomarkers for bacteria-associated exacerbation. Bacteria-associated exacerbations also formed a cluster separate from other exacerbation types in principal component analysis. Conclusions Measurement of cytokines in sputum from COPD patients could help identify bacteria-associated exacerbations based on increased concentrations of IL-1α, IL-1β, or TNF-α. This finding may provide a point-of-care assessment to distinguish a bacterial exacerbation of COPD from other exacerbation types. [ABSTRACT FROM AUTHOR]

Background: Fever is a common condition in intensive care unit (ICU) patients, with an incidence between 30 and 50% in non-neurological ICU patients and up to 70–90% in neurological ICU patients. We aim to perform systematic review and meta-analysis of current literature to assess impact of fever on neurological outcomes and mortality of acute brain injury patients. Methods: We searched PubMed/Medline, Scopus and Embase databases following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and we included both retrospective and prospective observational studies, interventional studies, and randomized clinical trials that had data on body temperature and fever during ICU admission. The primary endpoints were neurological outcome and mortality at any time. Secondary outcomes included: early neurological deterioration, delayed cerebral ischemia (DCI, only for patients with subarachnoid hemorrhage), large infarct or hemorrhage size, hemorrhagic transformation (only for patients with ischemic stroke). This study was registered in PROSPERO (CRD42020155903). Results: 180 studies from 14692 records identified after the initial search were included in the final analysis, for a total of 460,825 patients. Fever was associated with an increased probability of unfavorable neurological outcome (pooled OR 2.37 [95% CI 2.08–2.71], I2:92%), death (pooled OR 1.31 [95% CI 1.28–1.34], I2:93%), neurological deterioration (pooled OR 1.10 [95% CI 1.05–1.15]), risk of DCI (pooled OR 1.96 [95% CI 1.73–2.22]), large infarct size (pooled OR 2.94 [95% CI 2.90–2.98]) and hemorrhagic transformation (pooled OR 1.63 [95% CI 1.34–1.97]) and large hemorrhagic volume (pooled OR 2.38 [95% CI 1.94–2.93]). Conclusion: Fever was associated with poor neurological outcomes and mortality in patients with acute brain injury. Whether normothermia should be targeted in the management of all neuro critically ill patients warrants specific research. [ABSTRACT FROM AUTHOR]

Objective: To investigate the accuracy of information provided by ChatGPT-4o to patients about tracheotomy. Methods: Twenty common questions of patients about tracheotomy were presented to ChatGPT-4o twice (7-day intervals). The accuracy, clarity, relevance, completeness, referencing, and usefulness of responses were assessed by a board-certified otolaryngologist and a board-certified intensive care unit practitioner with the Quality Analysis of Medical Artificial Intelligence (QAMAI) tool. The interrater reliability and the stability of the ChatGPT-4o responses were evaluated with intraclass correlation coefficient (ICC) and Pearson correlation analysis. Results: The total scores of QAMAI were 22.85 ± 4.75 for the intensive care practitioner and 21.45 ± 3.95 for the otolaryngologist, which consists of moderate-to-high accuracy. The otolaryngologist and the ICU practitioner reported high ICC (0.807; 95%CI: 0.655–0.911). The highest QAMAI scores have been found for clarity and completeness of explanations. The QAMAI scores for the accuracy of the information and the referencing were the lowest. The information related to the post-laryngectomy tracheostomy remains incomplete or erroneous. ChatGPT-4o did not provide references for their responses. The stability analysis reported high stability in regenerated questions. Conclusion: The accuracy of ChatGPT-4o is moderate-to-high in providing information related to the tracheotomy. However, patients using ChatGPT-4o need to be cautious about the information related to tracheotomy care, steps, and the differences between temporary and permanent tracheotomies. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia. Methods: Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0–3. Time-to-death and the occurrence of adverse events were also reported. Results: From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%—OR 1.49, 95% CI 1.05–2.14; p = 0.026). Conclusions: In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies. [ABSTRACT FROM AUTHOR]

Introduction: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Methods: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. Ethics and dissemination: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration: Trial registration number:NCT05833607. https://clinicaltrials.gov/study/NCT05833607. [ABSTRACT FROM AUTHOR]

Background: The objective of this animal study was to evaluate the hemodynamic performance of a new centrifugal pump for extra-corporeal membrane oxygenation (ECMO) support in neonates. Methods: Six healthy swines were supported with veno-venous ECMO with the New Born ECMOLife centrifugal pump (Eurosets, Medolla, Italy) at different flow rates: 0.25, 0.5, 0.6, and 0.8 L/min; three animals were evaluated at low-flows (0.25 and 0.5 L/min) and three at high-flows (0.6 and 0.8 L/min). Each flow was maintained for 4 hours. Blood samples were collected at different time-points. Hematological and biochemical parameters and ECMO parameters [flow, revolutions per minute (RPM), drainage pressure, and the oxygenator pressure drop] were evaluated. Results: The increase of the pump flow from 0.25 to 0.5 L/min or from 0.6 to 0.8 L/min required significantly higher RPM and produced significantly higher pump pressures [from 0.25 to 0.5 L/min: 1470 (1253–1569) versus 2652 (2589–2750) RPM and 40 (26–57) versus 125 (113–139) mmHg, respectively; p <.0001 for both - from 0.60 to 0.8 L/min: 1950 (1901–2271) versus 2428 (2400–2518) RPM and 66 (62–86) versus 106 (101–113) mmHg, respectively; p <.0001 for both]. Median drainage pressure significantly decreased from −18 (−22; −16) mmHg to −55 (−63; −48) mmHg when the pump flow was increased from 0.25 to 0.5 L/min (p <.0001). When pump flow increased from 0.6 to 0.8 L/min, drainage pressure decreased from −32 (−39; −24) mmHg to −50 (−52; −43) mmHg, (p <.0001). Compared to pre-ECMO values, the median levels of lactate dehydrogenase, d-dimer, hematocrit, and platelet count decreased after ECMO start at all flow rates, probably due to hemodilution. Plasma-free hemoglobin, instead, showed a modest increase compared to pre-ECMO values during all experiments at different pump flow rates. However, these changes were not clinically relevant. Conclusions: In this animal study, the "New Born ECMOLife" centrifugal pump showed good hemodynamic performance. Long-term studies are needed to evaluate biocompatibility of this new ECMO pump. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine glioma (DIPG) remains a significant therapeutic challenge due to the lack of effective and safe treatment options. This study explores the potential of combining histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors in treating DIPG. Analysis of RNA sequencing data and tumor tissue from patient samples for the expression of the carbonic anhydrase family and hypoxia signaling pathway activity revealed clinical relevance for targeting CA9 in DIPG. A synergy screen was conducted using CA9 inhibitor SLC-0111 and HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. The combination of SLC-0111 and pyroxamide demonstrated the highest synergy and was selected for further analysis. Combining SLC-0111 and pyroxamide effectively inhibited DIPG cell proliferation, reduced cell migration and invasion potential, and enhanced histone acetylation, leading to decreased cell population in S Phase. Additionally, the combination therapy induced a greater reduction in intracellular pH than either agent alone. Data from this study suggest that the combination of SLC-0111 and pyroxamide holds promise for treating experimental DIPG, and further investigation of this combination therapy in preclinical models is warranted to evaluate its potential as a viable treatment for DIPG. [ABSTRACT FROM AUTHOR]

Aims: Cerebral complications after cardiac arrest (CA) remain a major problem worldwide. The aim was to test the effects of sodium-ß-hydroxybutyrate (SBHB) infusion on brain injury in a clinically relevant swine model of CA. Results: CA was electrically induced in 20 adult swine. After 10 min, cardiopulmonary resuscitation was performed for 5 min. After return of spontaneous circulation (ROSC), the animals were randomly assigned to receive an infusion of balanced crystalloid (controls, n = 11) or SBHB (theoretical osmolarity 1189 mOsm/l, n = 8) for 12 h. Multimodal neurological and cardiovascular monitoring were implemented in all animals. Nineteen of the 20 animals achieved ROSC. Blood sodium concentrations, osmolarity and circulating KBs were higher in the treated animals than in the controls. SBHB infusion was associated with significantly lower plasma biomarkers of brain injury at 6 (glial fibrillary acid protein, GFAP and neuron specific enolase, NSE) and 12 h (neurofilament light chain, NFL, GFAP and NSE) compared to controls. The amplitude of the stereoelectroencephalograph (sEEG) increased in treated animals after ROSC compared to controls. Cerebral glucose uptake was lower in treated animals. Conclusions: In this experimental model, SBHB infusion after resuscitated CA was associated with reduced circulating markers of cerebral injury and increased sEEG amplitude. [ABSTRACT FROM AUTHOR]

Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury. We performed a search in Pubmed/Medline and Embase databases for randomized controlled trials and cohort studies involving humans or experimental settings with various causes of ABI. We formulated the search using the PICO method, considering ABI patients or animal models as population (P), comparing pharmacological and non-pharmacological therapy targeting the nucleosome as Intervention (I) to standard of care or no treatment as Control (C). The outcome (O) was mortality or functional outcome in experimental animals and patients affected by ABI undergoing anti-NET treatments. We identified 28 studies from 1246 articles, of which 7 were experimental studies and 21 were human clinical studies. Among these studies, only four assessed the effect of anti-NET therapy on circulating markers. Three of them were preclinical and reported better outcome in the interventional arm compared to the control arm. All the studies observed a significant reduction in circulating NET-derived products. NETosis could be a target for new treatments. Monitoring NET markers in blood and cerebrospinal fluid might predict mortality and long-term outcomes. However, longitudinal studies and randomized controlled trials are warranted to fully evaluate their potential, as current evidence is limited. [ABSTRACT FROM AUTHOR]

Background: In patients requiring extracorporeal cardiopulmonary resuscitation (ECPR), there is a need for studies to assess the potential benefits of therapeutic interventions to improve survival and reduce hypoxic-ischemic brain injuries. However, conducting human studies may be challenging. This study aimed to describe two experimental models developed in our laboratory and to conduct a systematic review of existing animal models of ECPR reported in the literature. Results: In our experiments, pigs were subjected to 12 min (model 1) or 5 min (model 2) of untreated ventricular fibrillation, followed by 18 min (model 1) or 25 min (model 2) of conventional cardiopulmonary resuscitation. Results showed severe distributive shock, decreased brain oxygen pressure and increased intracranial pressure, with model 1 displaying more pronounced brain perfusion impairment. A systematic review of 52 studies, mostly conducted on pigs, revealed heterogeneity in cardiac arrest induction methods, cardiopulmonary resuscitation strategies, and evaluated outcomes. Conclusions: This review emphasizes the significant impact of no-flow and low-flow durations on brain injury severity following ECPR. However, the diversity in experimental models hinders direct comparisons, urging the standardization of ECPR models to enhance consistency and comparability across studies. [ABSTRACT FROM AUTHOR]

Natural Language Processing (NLP) is a subset of artificial intelligence that enables machines to understand and respond to human language through Large Language Models (LLMs)‥ These models have diverse applications in fields such as medical research, scientific writing, and publishing, but concerns such as hallucination, ethical issues, bias, and cybersecurity need to be addressed. To understand the scientific community's understanding and perspective on the role of Artificial Intelligence (AI) in research and authorship, a survey was designed for corresponding authors in top medical journals. An online survey was conducted from July 13th, 2023, to September 1st, 2023, using the SurveyMonkey web instrument, and the population of interest were corresponding authors who published in 2022 in the 15 highest-impact medical journals, as ranked by the Journal Citation Report. The survey link has been sent to all the identified corresponding authors by mail. A total of 266 authors answered, and 236 entered the final analysis. Most of the researchers (40.6%) reported having moderate familiarity with artificial intelligence, while a minority (4.4%) had no associated knowledge. Furthermore, the vast majority (79.0%) believe that artificial intelligence will play a major role in the future of research. Of note, no correlation between academic metrics and artificial intelligence knowledge or confidence was found. The results indicate that although researchers have varying degrees of familiarity with artificial intelligence, its use in scientific research is still in its early phases. Despite lacking formal AI training, many scholars publishing in high-impact journals have started integrating such technologies into their projects, including rephrasing, translation, and proofreading tasks. Efforts should focus on providing training for their effective use, establishing guidelines by journal editors, and creating software applications that bundle multiple integrated tools into a single platform. [ABSTRACT FROM AUTHOR]

Purpose: This pilot study aimed to determine the capacity of automated infrared pupillometry (AIP) alone and in combination with transcranial doppler (TCD) on admission to rule out need for intense neuroAQ2 critical care (INCC) in severe traumatic brain injury (TBI). Methods: In this observational pilot study clinicians performed AIP and TCD measurements on admission in blunt TBI patients with a Glasgow Coma Score (GCS) < 9 and/or motor score < 6. A Neurological Pupil index (NPi) < 3, Pulsatility Index (PI) > 1,4 or diastolic blood flow velocity (dV) of < 20 cm/s were used to rule out the need for INCC (exceeding the tier 0 Seattle Consensus Conference). The primary outcome was the negative likelihood ratio (nLR) of NPi < 3 alone or in combination with TCD to detect need for INCC. Results: A total of 69 TBI patients were included from May 2019 to September 2020. Of those, 52/69 (75%) median age was 45 [28–67], median prehospital GCS of 7 [5–8], median Injury Severity Scale of 13.0 [6.5–25.5], median Marshall Score of 4 [3–5], the median Glasgow Outcome Scale at discharge was 3 [1–5]. NPi < 3 was an independent predictor of INCC. NPi demonstrated a nLR of 0,6 (95%CI 0.4–0.9; AUROC, 0.65, 95% CI 0.51–0.79), a combination of NPi and TCD showed a nLR of 0.6 (95% CI 0.4–1.0; AUROC 0.67 95% CI 0.52–0.83) to predict INCC. Conclusion: This pilot study suggests a possible useful contribution of NPi to determine the need for INCC in severe blunt TBI patients on admission. [ABSTRACT FROM AUTHOR]

Transpulmonary pressure (PL) calculation requires esophageal pressure (PES) as a surrogate of pleural pressure (Ppl), but its calibration is a cumbersome technique. Central venous pressure (CVP) swings may reflect tidal variations in Ppl and could be used instead of PES, but the interpretation of CVP waveforms could be difficult due to superposition of heartbeat-induced pressure changes. Thus, we developed a digital filter able to remove the cardiac noise to obtain a filtered CVP (f-CVP). The aim of the study was to evaluate the accuracy of CVP and filtered CVP swings (ΔCVP and Δf-CVP, respectively) in estimating esophageal respiratory swings (ΔPES) and compare PL calculated with CVP, f-CVP and PES; then we tested the diagnostic accuracy of the f-CVP method to identify unsafe high PL levels, defined as PL>10 cmH2O. Twenty patients with acute respiratory failure (defined as PaO2/FiO2 ratio below 200 mmHg) treated with invasive mechanical ventilation and monitored with an esophageal balloon and central venous catheter were enrolled prospectively. For each patient a recording session at baseline was performed, repeated if a modification in ventilatory settings occurred. PES, CVP and airway pressure during an end-inspiratory and -expiratory pause were simultaneously recorded; CVP, f-CVP and PES waveforms were analyzed off-line and used to calculate transpulmonary pressure (PLCVP, PLf-CVP, PLPES, respectively). Δf-CVP correlated better than ΔCVP with ΔPES (r = 0.8, p = 0.001 vs. r = 0.08, p = 0.73), with a lower bias in Bland Altman analysis in favor of PLf-CVP (mean bias − 0.16, Limits of Agreement (LoA) -1.31, 0.98 cmH2O vs. mean bias − 0.79, LoA − 3.14, 1.55 cmH2O). Both PLf-CVP and PLCVP correlated well with PLPES (r = 0.98, p < 0.001 vs. r = 0.94, p < 0.001), again with a lower bias in Bland Altman analysis in favor of PLf-CVP (0.15, LoA − 0.95, 1.26 cmH2O vs. 0.80, LoA − 1.51, 3.12, cmH2O). PLf-CVP discriminated high PL value with an area under the receiver operating characteristic curve 0.99 (standard deviation, SD, 0.02) (AUC difference = 0.01 [-0.024; 0.05], p = 0.48). In mechanically ventilated patients with acute respiratory failure, the digital filtered CVP estimated ΔPES and PL obtained from digital filtered CVP represented a reliable value of standard PL measured with the esophageal method and could identify patients with non-protective ventilation settings. [ABSTRACT FROM AUTHOR]

Knowing the location, the extent and the characteristics of any earthquake-induced environmental phenomenon is becoming an increasingly pressing need for civil protection agencies and local administrations. In particular, earthquake-triggered landslides are known for being among the most important sources of secondary hazard, as they may cause significant losses and may delay rescue operations across large areas. The combination of the relatively frequent seismic release with a very high landslide susceptibility makes the Italian territory especially prone to the occurrence of earthquake-induced landslides. The CFTIlandslides dataset features over 1,000 landslides triggered by historical Italian earthquakes (up to 1997). The landslides effects are subdivided into classes based on location accuracy and type of movement. Knowing the distribution of the past earthquake-induced landslides provides the input information for assessing the related hazard. This dataset is addressed to a large audience of potential users, including researchers and scholars, administrators and technicians belonging to local institutions, and civil protection authorities. [ABSTRACT FROM AUTHOR]

Background: The importance of perfusion-guided resuscitation in septic shock has recently emerged. We explored whether the use of hemoadsorption led to a potential beneficial role in microvascular alterations in this clinical setting. Methods: A pre-planned secondary analysis of a Phase-II interventional single-arm pilot study (NCT05658588) was carried out, where 17 consecutive septic shock children admitted into PICU were treated with continuous renal replacement therapy (CRRT) and CytoSorb. Thirteen patients were eligible to be investigated with sublingual microcirculation at baseline, 24, 48, 72 and 96 h from the onset of blood purification. Patients achieving a microvascular flow index (MFI) ≥ 2.5 and/or proportion of perfused vessels (PPV) exceeding 90% by 96 h were defined as responders. Results: In 10/13 (77%), there was a significant improvement in MFIs (p = 0.01) and PPVs% (p = 0.04) between baseline and 24 h from the end of treatment. Eight patients displayed a high heterogenicity index (HI > 0.5) during blood purification and among these, five showed an improvement by the end of treatment (HI < 0.5). Conclusions: In this pilot study, we have found a potential association between CytoSorb hemoadsorption and a microcirculation improvement in pediatric patients with septic shock, particularly when this observation has been associated with hemodynamic improvement. [ABSTRACT FROM AUTHOR]

Circulating nucleosome levels are commonly elevated in physiological and pathological conditions. Their potential as biomarkers for diagnosing and prognosticating sepsis remains uncertain due, in part, to technical limitations in existing detection methods. This scoping review explores the possible role of nucleosome concentrations in the diagnosis, prognosis, and therapeutic management of sepsis. A comprehensive literature search of the Cochrane and Medline libraries from 1996 to 1 February 2024 identified 110 potentially eligible studies, of which 19 met the inclusion criteria, encompassing a total of 39 SIRS patients, 893 sepsis patients, 280 septic shock patients, 117 other ICU control patients, and 345 healthy volunteers. The enzyme-linked immunosorbent assay [ELISA] was the primary method of nucleosome measurement. Studies consistently reported significant correlations between nucleosome levels and other NET biomarkers. Nucleosome levels were higher in patients with sepsis than in healthy volunteers and associated with disease severity, as indicated by SOFA and APACHE II scores. Non-survivors had higher nucleosome levels than survivors. Circulating nucleosome levels, therefore, show promise as early markers of NETosis in sepsis, with moderate diagnostic accuracy and strong correlations with disease severity and prognosis. However, the available evidence is drawn mainly from single-center, observational studies with small sample sizes and varied detection methods, warranting further investigation. [ABSTRACT FROM AUTHOR]

Background Vasospasm and delayed cerebral ischemia (DCI) are the leading causes of morbidity and mortality after intracranial aneurysmal subarachnoid hemorrhage (aSAH). Vasospasm detection, prevention and management, especially endovascular management varies from center to center and lacks standardization. We aimed to evaluate this variability via an international survey of how neurointerventionalists approach vasospasm diagnosis and endovascular management. Methods We designed an anonymous online survey with 100 questions to evaluate practice patterns between December 2021 and September 2022. We contacted endovascular neurosurgeons, neuroradiologists and neurologists via email and via two professional societies -- the Society of NeuroInterventional Surgery (SNIS) and the European Society of Minimally Invasive Neurological Therapy (ESMINT). We recorded the physicians' responses to the survey questions. Results A total of 201 physicians (25% [50/201] USA and 75% non-USA) completed the survey over 10 months, 42% had >7 years of experience, 92% were male, median age was 40 (IQR 35-46). Both high-volume and low- volume centers were represented. Daily transcranial Doppler was the most common screening method (75%) for vasospasm. In cases of symptomatic vasospasm despite optimal medical management, endovascular treatment was directly considered by 58% of physicians. The most common reason to initiate endovascular treatment was clinical deficits associated with proven vasospasm/DCI in 89%. The choice of endovascular treatment and its efficacy was highly variable. Nimodipine was the most common first- line intra-arterial therapy (40%). Mechanical angioplasty was considered the most effective endovascular treatment by 65% of neurointerventionalists. Conclusion Our study highlights the considerable heterogeneity among the neurointerventional community regarding vasospasm diagnosis and endovascular management. Randomized trials and guidelines are needed to improve standard of care, determine optimal management approaches and track outcomes. [ABSTRACT FROM AUTHOR]

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5–9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5–9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7–8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70–0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15–3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07–2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76–1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59–6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients. Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022–11–07. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. Methods: In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. Results: PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. Conclusions: In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU). Methods: We selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases. Results: A total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92–0.95) in the US external validation cohort and 0.85 (95% CI 0.83–0.88) in the Italian external validation cohort. Conclusions: A machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice. [ABSTRACT FROM AUTHOR]

Intracranial multimodal monitoring (iMMM) is increasingly used for neurocritical care. However, concerns arise regarding iMMM invasiveness considering limited evidence in its clinical significance and safety profile. We conducted a synthesis of evidence regarding complications associated with iMMM to delineate its safety profile. We performed a systematic review and meta-analysis (PROSPERO Registration Number: CRD42021225951) according to the Preferred Reporting Items for Systematic Review and Meta-Analysis and Peer Review of Electronic Search Strategies guidelines to retrieve evidence from studies reporting iMMM use in humans that mention related complications. We assessed risk of bias using the Newcastle–Ottawa Scale and funnel plots. The primary outcomes were iMMM complications. The secondary outcomes were putative risk factors. Of the 366 screened articles, 60 met the initial criteria and were further assessed by full-text reading. We included 22 studies involving 1206 patients and 1434 iMMM placements. Most investigators used a bolt system (85.9%) and a three-lumen device (68.8%), mainly inserting iMMM into the most injured hemisphere (77.9%). A total of 54 postoperative intracranial hemorrhages (pooled rate of 4%; 95% confidence interval [CI] 0–10%; I2 86%, p < 0.01 [random-effects model]) was reported, along with 46 misplacements (pooled rate of 6%; 95% CI 1–12%; I2 78%, p < 0.01) and 16 central nervous system infections (pooled rate of 0.43%; 95% CI 0–2%; I2 64%, p < 0.01). We found 6 system breakings, 18 intracranial bone fragments, and 5 cases of pneumocephalus. Currently, iMMM systems present a similar safety profile as intracranial devices commonly used in neurocritical care. Long-term outcomes of prospective studies will complete the benefit-risk assessment of iMMM in neurocritical care. Consensus-based reporting guidelines on iMMM use are needed to bolster future collaborative efforts. [ABSTRACT FROM AUTHOR]

Introduction: Neuromonitoring represents a cornerstone in the comprehensive management of patients with traumatic brain injury (TBI), allowing for early detection of complications such as increased intracranial pressure (ICP) [1]. This has led to a search for noninvasive modalities that are reliable and deployable at bedside. Among these, ultrasonographic optic nerve sheath diameter (ONSD) measurement is a strong contender, estimating ICP by quantifying the distension of the optic nerve at higher ICP values. Thus, this scoping review seeks to describe the existing evidence for the use of ONSD in estimating ICP in adult TBI patients as compared to gold-standard invasive methods. Materials and Methods: This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Sixteen studies were included for analysis, with all studies conducted in high-income countries. Results: All of the studies reviewed measured ONSD using the same probe frequency. In most studies, the marker position for ONSD measurement was initially 3 mm behind the globe, retina, or papilla. A few studies utilized additional parameters such as the ONSD/ETD (eyeball transverse diameter) ratio or ODE (optic disc elevation), which also exhibit high sensitivity and reliability. Conclusion: Overall, ONSD exhibits great test accuracy and has a strong, almost linear correlation with invasive methods. Thus, ONSD should be considered one of the most effective noninvasive techniques for ICP estimation in TBI patients. [ABSTRACT FROM AUTHOR]

Alterations in skin blood flow (SBF) may help to detect occult hypoperfusion in critically ill patients after fluid resuscitation. In this study, SBF is globally unaltered by red blood cell transfusion (RBCT) in non-bleeding critically ill patients after initial resuscitation; however, 37.5% of patients showed a significant increase in SBF. No correlation between relative changes in SBF and systemic variables after RBCT was observed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) may lead to morbidity and mortality. Endovascular mechanical angioplasty may be performed if symptomatic CV is refractory to noninvasive medical management. Off-label compliant remodelling balloons tend to conform to the course of the vessel, contrary to noncompliant or semi-compliant balloons. Our objective is to describe our initial experience with the semi-compliant Neurospeed balloon (approved for intracranial stenosis) in cerebral vasospasm treatment following aSAH. Methods: All patients included in the prospective observational SAVEBRAIN PWI (NCT05276934 on clinicaltrial.gov) study who underwent cerebral angioplasty using the Neurospeed balloon for the treatment of medically refractory and symptomatic CV after aSAH were identified. Patient demographic information, procedural details and outcomes were obtained from electronic medical records. Results: Between February 2022 and June 2023, 8 consecutive patients underwent CV treatment with the Neurospeed balloon. Angioplasty of 48 arterial segments (supraclinoid internal carotid artery, A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery) was attempted and 44/48 (92%) were performed. The vessel diameter significantly improved following angioplasty (+81%), while brain hypoperfusion decreased (−81% of the mean TMax). There was no long-term clinical complication, 4% periprocedural complications occurred. Conclusion: The semi-compliant Neurospeed balloon is effective in the treatment of cerebral vasospasm following aSAH, bringing a new device into the armamentarium of the neurointerventionalist to perform intracranial angioplasty. [ABSTRACT FROM AUTHOR]

Aims and scope: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. Methods: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. Results: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0–37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. Conclusions: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting. [ABSTRACT FROM AUTHOR]

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts. [ABSTRACT FROM AUTHOR]

In patients with septic shock, compensatory tachycardia initially serves to maintain adequate cardiac output and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation. This sustained elevation in heart rate and altered heart rate variability, indicative of autonomic dysfunction, is a well-established independent predictor of adverse outcomes in critical illness. Elevated heart rate exacerbates myocardial oxygen demand, reduces ventricular filling time, compromises coronary perfusion during diastole, and impairs the isovolumetric relaxation phase of the cardiac cycle, contributing to ventricular-arterial decoupling. This also leads to increased ventricular and atrial filling pressures, with a heightened risk of arrhythmias. Ivabradine, a highly selective inhibitor of the sinoatrial node's pacemaker current (If or "funny" current), mitigates heart rate by modulating diastolic depolarization slope without affecting contractility. By exerting a selective chronotropic effect devoid of negative inotropic properties, ivabradine shows potential for improving hemodynamics in septic shock patients with cardiac dysfunction. This review evaluates the plausible mechanisms and existing evidence regarding the utility of ivabradine in managing patients with septic shock. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the prevalence of delayed deterioration of electroencephalogram (EEG) in patients with cardiac arrest (CA) without early highly malignant patterns and to determine their associations with clinical findings. Methods: This was a retrospective study of adult patients with CA admitted to the intensive care unit (ICU) of a university hospital. We included all patients with CA who had a normal voltage EEG, no more than 10% discontinuity, and absence of sporadic epileptic discharges, periodic discharges, or electrographic seizures. Delayed deterioration was classified as the following: (1) epileptic deterioration, defined as the appearance, at least 24 h after CA, of sporadic epileptic discharges, periodic discharges, and status epilepticus; or (2) background deterioration, defined as increasing discontinuity or progressive attenuation of the background at least 24 h after CA. The end points were the incidence of EEG deteriorations and their association with clinical features and ICU mortality. Results: We enrolled 188 patients in the analysis. The ICU mortality was 46%. Overall, 30 (16%) patients presented with epileptic deterioration and 9 (5%) patients presented with background deterioration; of those, two patients presented both deteriorations. Patients with epileptic deterioration more frequently had an out-of-hospital CA, and higher time to return of spontaneous circulation and less frequently had bystander resuscitation than others. Patients with background deterioration showed a predominantly noncardiac cause, more frequently developed shock, and had multiple organ failure compared with others. Patients with epileptic deterioration presented with a higher ICU mortality (77% vs. 41%; p < 0.01) than others, whereas all patients with background deterioration died in the ICU. Conclusions: Delayed EEG deterioration was associated with high mortality rate. Epileptic deterioration was associated with worse characteristics of CA, whereas background deterioration was associated with shock and multiple organ failure. [ABSTRACT FROM AUTHOR]

Background: Cerebral hypoxia is a frequent cause of secondary brain damage in patients with acute brain injury. Although hypercapnia can increase intracranial pressure, it may have beneficial effects on tissue oxygenation. We aimed to assess the effects of hypercapnia on brain tissue oxygenation (PbtO2). Methods: This single-center retrospective study (November 2014 to June 2022) included all patients admitted to the intensive care unit after acute brain injury who required multimodal monitoring, including PbtO2 monitoring, and who underwent induced moderate hypoventilation and hypercapnia according to the decision of the treating physician. Patients with imminent brain death were excluded. Responders to hypercapnia were defined as those with an increase of at least 20% in PbtO2 values when compared to their baseline levels. Results: On a total of 163 eligible patients, we identified 23 (14%) patients who underwent moderate hypoventilation (arterial partial pressure of carbon dioxide [PaCO2] from 44 [42–45] to 50 [49–53] mm Hg; p < 0.001) during the study period at a median of 6 (4–10) days following intensive care unit admission; six patients had traumatic brain injury, and 17 had subarachnoid hemorrhage. A significant overall increase in median PbtO2 values from baseline (21 [19–26] to 24 [22–26] mm Hg; p = 0.02) was observed. Eight (35%) patients were considered as responders, with a median increase of 7 (from 4 to 11) mm Hg of PbtO2, whereas nonresponders showed no changes (from − 1 to 2 mm Hg of PbtO2). Because of the small sample size, no variable independently associated with PbtO2 response was identified. No correlation between changes in PaCO2 and in PbtO2 was observed. Conclusions: In this study, a heterogeneous response of PbtO2 to induced hypercapnia was observed but without any deleterious elevations of intracranial pressure. [ABSTRACT FROM AUTHOR]

Background: In acute brain injury (ABI), the effects of hypoxemia as a potential cause of secondary brain damage and poor outcome are well documented, whereas the impact of hyperoxemia is unclear. The primary aim of this study was to assess the episodes of hypoxemia and hyperoxemia in patients with ABI during the intensive care unit (ICU) stay and to determine their association with in-hospital mortality. The secondary aim was to identify the optimal thresholds of arterial partial pressure of oxygen (PaO2) predicting in-hospital mortality. Methods: We conducted a secondary analysis of a prospective multicenter observational cohort study. Adult patients with ABI (traumatic brain injury, subarachnoid aneurysmal hemorrhage, intracranial hemorrhage, ischemic stroke) with available data on PaO2 during the ICU stay were included. Hypoxemia was defined as PaO2 < 80 mm Hg, normoxemia was defined as PaO2 between 80 and 120 mm Hg, mild/moderate hyperoxemia was defined as PaO2 between 121 and 299 mm Hg, and severe hyperoxemia was defined as PaO2 levels ≥ 300 mm Hg. Results: A total of 1,407 patients were included in this study. The mean age was 52 (±18) years, and 929 (66%) were male. Over the ICU stay, the fractions of patients in the study cohort who had at least one episode of hypoxemia, mild/moderate hyperoxemia, and severe hyperoxemia were 31.3%, 53.0%, and 1.7%, respectively. PaO2 values below 92 mm Hg and above 156 mm Hg were associated with an increased probability of in-hospital mortality. Differences were observed among subgroups of patients with ABI, with consistent effects only seen in patients without traumatic brain injury. Conclusions: In patients with ABI, hypoxemia and mild/moderate hyperoxemia were relatively frequent. Hypoxemia and hyperoxemia during ICU stay may influence in-hospital mortality. However, the small number of oxygen values collected represents a major limitation of the study. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated brain dysfunction (SABD) is frequent and is associated with poor outcome. Changes in brain hemodynamics remain poorly described in this setting. The aim of this study was to investigate the alterations of cerebral perfusion pressure and intracranial pressure in a cohort of septic patients. Methods: We conducted a retrospective analysis of prospectively collected data in septic adults admitted to our intensive care unit (ICU). We included patients in whom transcranial Doppler recording performed within 48 h from diagnosis of sepsis was available. Exclusion criteria were intracranial disease, known vascular stenosis, cardiac arrhythmias, pacemaker, mechanical cardiac support, severe hypotension, and severe hypocapnia or hypercapnia. SABD was clinically diagnosed by the attending physician, anytime during the ICU stay. Estimated cerebral perfusion pressure (eCPP) and estimated intracranial pressure (eICP) were calculated from the blood flow velocity of the middle cerebral artery and invasive arterial pressure using a previously validated formula. Normal eCPP was defined as eCPP ≥ 60 mm Hg, low eCPP was defined as eCPP < 60 mm Hg; normal eICP was defined as eICP ≤ 20 mm Hg, and high eICP was defined as eICP > 20 mm Hg. Results: A total of 132 patients were included in the final analysis (71% male, median [interquartile range (IQR)] age was 64 [52–71] years, median [IQR] Acute Physiology and Chronic Health Evaluation II score on admission was 21 [15–28]). Sixty-nine (49%) patients developed SABD during the ICU stay, and 38 (29%) were dead at hospital discharge. Transcranial Doppler recording lasted 9 (IQR 7–12) min. Median (IQR) eCPP was 63 (58–71) mm Hg in the cohort; 44 of 132 (33%) patients had low eCPP. Median (IQR) eICP was 8 (4–13) mm Hg; five (4%) patients had high eICP. SABD occurrence and in-hospital mortality did not differ between patients with normal eCPP and patients with low eCPP or between patients with normal eICP and patients with high eICP. Eighty-six (65%) patients had normal eCPP and normal eICP, 41 (31%) patients had low eCPP and normal eICP, three (2%) patients had low eCPP and high eICP, and two (2%) patients had normal eCPP and high eICP; however, SABD occurrence and in-hospital mortality were not significantly different among these subgroups. Conclusions: Brain hemodynamics, in particular CPP, were altered in one third of critically ill septic patients at a steady state of monitoring performed early during the course of sepsis. However, these alterations were equally common in patients who developed or did not develop SABD during the ICU stay and in patients with favorable or unfavorable outcome. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a significant public health issue because of its increasing incidence and the substantial short-term and long-term burden it imposes. This burden includes high mortality rates, morbidity, and a significant impact on productivity and quality of life for survivors. During the management of TBI, extracranial complications commonly arise during the patient's stay in the intensive care unit. These complications can have an impact on both mortality and the neurological outcome of patients with TBI. Among these extracranial complications, cardiac injury is a relatively frequent occurrence, affecting approximately 25–35% of patients with TBI. The pathophysiology underlying cardiac injury in TBI involves the intricate interplay between the brain and the heart. Acute brain injury triggers a systemic inflammatory response and a surge of catecholamines, leading to the release of neurotransmitters and cytokines. These substances have detrimental effects on the brain and peripheral organs, creating a vicious cycle that exacerbates brain damage and cellular dysfunction. The most common manifestation of cardiac injury in TBI is corrected QT (QTc) prolongation and supraventricular arrhythmias, with a prevalence up to 5 to 10 times higher than in the general adult population. Other forms of cardiac injury, such as regional wall motion alteration, troponin elevation, myocardial stunning, or Takotsubo cardiomyopathy, have also been described. In this context, the use of β-blockers has shown potential benefits by intervening in this maladaptive process. β-blockers can limit the pathological effects on cardiac rhythm, blood circulation, and cerebral metabolism. They may also mitigate metabolic acidosis and potentially contribute to improved cerebral perfusion. However, further clinical studies are needed to elucidate the role of new therapeutic strategies in limiting cardiac dysfunction in patients with severe TBI. [ABSTRACT FROM AUTHOR]

Background and purpose: Depth electroencephalography (dEEG) is an emerging neuromonitoring technology in acute brain injury (ABI). We aimed to explore the concordances between electrophysiological activities on dEEG and on scalp EEG (scEEG) in ABI patients. Methods: Consecutive ABI patients who received dEEG monitoring between 2018 and 2022 were included. Background, sporadic epileptiform discharges, rhythmic and periodic patterns (RPPs), electrographic seizures, brief potentially ictal rhythmic discharges, ictal–interictal continuum (IIC) patterns, and hourly RPP burden on dEEG and scEEG were compared. Results: Sixty‐one ABI patients with a median dEEG monitoring duration of 114 h were included. dEEG significantly showed less continuous background (75% vs. 90%, p = 0.03), higher background amplitude (p < 0.001), more frequent rhythmic spike‐and‐waves (16% vs. 3%, p = 0.03), more IIC patterns (39% vs. 21%, p = 0.03), and greater hourly RPP burden (2430 vs. 1090 s/h, p = 0.01), when compared to scEEG. Among five patients with seizures on scEEG, one patient had concomitant seizures on dEEG, one had periodic discharges (not concomitant) on dEEG, and three had no RPPs on dEEG. Features and temporal occurrence of electrophysiological activities observed on dEEG and scEEG are not strongly associated. Patients with seizures and IIC patterns on dEEG seemed to have a higher rate of poor outcomes at discharge than patients without these patterns on dEEG (42% vs. 25%, p = 0.37). Conclusions: dEEG can detect abnormal electrophysiological activities that may not be seen on scEEG and can be used as a complement in the neuromonitoring of ABI patients. [ABSTRACT FROM AUTHOR]

Severe acute brain injuries, stemming from trauma, ischemia or hemorrhage, remain a significant global healthcare concern due to their association with high morbidity and mortality rates. Accurate assessment of secondary brain injuries severity is pivotal for tailor adequate therapies in such patients. Together with neurological examination and brain imaging, monitoring of systemic secondary brain injuries is relatively straightforward and should be implemented in all patients, according to local resources. Cerebral secondary injuries involve factors like brain compliance loss, tissue hypoxia, seizures, metabolic disturbances and neuroinflammation. In this viewpoint, we have considered the combination of specific noninvasive and invasive monitoring tools to better understand the mechanisms behind the occurrence of these events and enhance treatment customization, such as intracranial pressure monitoring, brain oxygenation assessment and metabolic monitoring. These tools enable precise intervention, contributing to improved care quality for severe brain injury patients. The future entails more sophisticated technologies, necessitating knowledge, interdisciplinary collaboration and resource allocation, with a focus on patient-centered care and rigorous validation through clinical trials. [ABSTRACT FROM AUTHOR]

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We investigated independent factors predicting neurological outcome and death, comparing in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) patients. The study was conducted in the mixed 34-bed Intensive Care Department at the Hôpital Universitaire de Bruxelles (HUB), Belgium. All adult consecutive cardiac arrest (CA) survivors were included between 2004 and 2022. For all patients, demographic data, medical comorbidities, CA baseline characteristics, treatments received during Intensive Care Unit stay, in-hospital major complications, and neurological outcome at three months after CA, using the Cerebral Performance Category (CPC) scale, were collected. In the multivariable analysis, in the IHCA group (n = 540), time to return of spontaneous circulation (ROSC), older age, unwitnessed CA, higher lactate on admission, asystole as initial rhythm, a non-cardiac cause of CA, the occurrence of shock, the occurrence of acute kidney injury (AKI), and the presence of previous neurological disease and of liver cirrhosis were independent predictors of an unfavorable neurological outcome. Among patients with OHCA (n = 567), time to ROSC, older age, higher lactate level on admission, unwitnessed CA, asystole or pulseless electrical activity (PEA) as initial rhythm, the occurrence of shock, a non-cardiac cause of CA, and a previous neurological disease were independent predictors of an unfavorable neurological outcome. To conclude, in our large cohort of mixed IHCA and OHCA patients, we observed numerous factors independently associated with a poor neurological outcome, with minimal differences between the two groups, reflecting the greater vulnerability of hospitalized patients. [ABSTRACT FROM AUTHOR]