Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes-an analysis of CENTER-TBI data.

PURPOSE: We analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI). METHODS: From patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)]. RESULTS: Among 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001). CONCLUSION: Though less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.

Intracranial Pressure Monitoring and Management in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage is a medical condition that can lead to intracranial hypertension, negatively impacting patients' outcomes. This review article explores the underlying pathophysiology that causes increased intracranial pressure (ICP) during hospitalization. Hydrocephalus, brain swelling, and intracranial hematoma could produce an ICP rise. Although cerebrospinal fluid withdrawal via an external ventricular drain is commonly used, ICP monitoring is not always consistently practiced. Indications for ICP monitoring include neurological deterioration, hydrocephalus, brain swelling, intracranial masses, and the need for cerebrospinal fluid drainage. This review emphasizes the importance of ICP monitoring and presents findings from the Synapse-ICU study, which supports a correlation between ICP monitoring and treatment with better patient outcomes. The review also discusses various therapeutic strategies for managing increased ICP and identifies potential areas for future research.

Individualized blood pressure targets in the postoperative care of patients with intracerebral hemorrhage.

OBJECTIVE: Recent guidelines recommend targeting a systolic blood pressure (SBP) < 140 mm Hg in the early management of patients with spontaneous intracerebral hemorrhage (ICH). The optimal SBP targets for ICH patients after hematoma evacuation (HE) remain unclear. Here, the authors aimed to define the optimal SBP range based on multimodal neuromonitoring data. METHODS: Forty poor-grade ICH patients who had undergone HE and then monitoring of intracerebral pressure, brain tissue oxygen tension (PbtO2), and cerebral metabolism (via cerebral microdialysis [CMD]) were prospectively included. Episodes of brain tissue hypoxia (BTH) (1-hour averaged PbtO2 < 20 mm Hg) and metabolic distress (CMD-lactate/pyruvate ratio [LPR] ≥ 40) were identified and linked to corresponding parameters of hemodynamic monitoring (SBP and cerebral perfusion pressure [CPP]). Multivariable regression analysis was performed using generalized estimating equations to identify associations between SBP levels, PbtO2, and brain metabolism. RESULTS: The mean patient age was 60 (range 51-66) years and the median [IQR] initial ICH volume was 47 [29-60] ml. In multivariable models adjusted for Glasgow Coma Scale score, probe location, ICH volume, and age, lower SBP was independently associated with a higher risk of BTH (≤ 120 mm Hg: adjusted OR 2.9, p = 0.007; 120-130 mm Hg: adj OR 2.4, p = 0.002; 130-140 mm Hg: adj OR 1.6, p = 0.017) compared to a reference range of 140-150 mm Hg at the level of the foramen interventriculare Monroi, which corresponded to a CPP of 70-80 mm Hg and SBP levels between 150 and 160 mm Hg at the heart level. After exclusion of episodes with mitochondrial dysfunction, SBP targets < 140 mm Hg were associated with higher odds of cerebral metabolic distress (≤ 130 mm Hg: OR 2.5, p = 0.041; 130-140 mm Hg: OR 2.3, p = 0.033). Patients with a modified Rankin Scale score ≥ 5 at neurological ICU discharge more often exhibited BTH than patients with better outcomes (51% vs 10%, p = 0.003). CONCLUSIONS: These data suggest that lower SPB and CPP levels are associated with a higher risk for BTH. Further studies are needed to evaluate whether a higher SPB target may prevent BTH and improve outcomes.

The influence of fish farm activity on the social structure of the common bottlenose dolphin in Sardinia (Italy).

In a wide variety of habitats, including some heavily urbanised areas, the adaptability of populations of common bottlenose dolphin (Tursiops truncatus) may depend on the social structure dynamics. Nonetheless, the way in which these adaptations take place is still poorly understood. In the present study we applied photo-identification techniques to investigate the social structure of the common bottlenose dolphin population inhabiting the Gulf of Alghero (Sardinia, Italy), analysing data recorded from 2008 to 2019. The social structure analysis showed a division of the entire population into five different communities and the presence of non-random associations, while there was no evidence of segregation between sexes. Furthermore, results highlighted an important change in social structure through time, likely due to a reduction in fish farm activity since 2015. The division of the population into different communities, the presence of segregation based on the foraging strategy (inside or outside the fish farm area) and the social network measures were evaluated by analysing independently the two datasets: the intense and low farm activity periods: 2008-2014 and 2015-2020, respectively. Segregation among individuals belonging to the same foraging strategy class was found only in the earlier period, and the composition of the four communities was consistent with this result. Our study improves the knowledge about bottlenose dolphin adaptation, as a lower complexity in social structure was linked to a reduction in anthropogenic food availability.

Brain temperature regulation in poor-grade subarachnoid hemorrhage patients - A multimodal neuromonitoring study.

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (Tdelta +0.18°C, IQR -0.01 - 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate (p = 0.003) and CMD-lactate (p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, Tdelta was significantly lower (0°C, IQR -0.2 - 0.1; p < 0.001). A higher Tdelta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH.

Delayed Resolution of Cerebral Edema Is Associated With Poor Outcome After Nontraumatic Subarachnoid Hemorrhage.

Background and Purpose- Global cerebral edema occurs in up to 57% of patients with subarachnoid hemorrhage (SAH) and is associated with prolonged hospital stay and poor outcome. Recently, admission brain edema was successfully graded using a simplified computed tomography-based semiquantitative score (subarachnoid hemorrhage early brain edema score [SEBES]). Longitudinal evaluation of the SEBES grade may discriminate patients with rapid and delayed edema resolution after SAH. Here, we aimed to describe the resolution of brain edema and to study the relationship between this radiographic biomarker and hospital course and outcome after SAH. Methods- For the current observational cohort study, computed tomography scans of 283 consecutive nontraumatic SAH patients admitted to the neurological intensive care unit of a tertiary hospital were graded based on the absence of visible sulci at 2 predefined brain tissue levels in each hemisphere (SEBES ranging from 0 to 4). A score of ≥3 was defined as high-grade SEBES. Multivariable regression models using generalized linear models were used to identify associated factors with delayed edema resolution based on the median time to resolution (SEBES ≤2) in SAH survivors. Results- Patients were 57 years old (interquartile range, 48-68) and presented with a median admission Hunt and Hess grade of 3 (interquartile range, 1-5). High-grade SEBES was common (106/283, 37%) and resolved within a median of 8 days (interquartile range, 4-15) in survivors (N=80). Factors associated with delayed edema resolution were early (<72 hours) hypernatremia (>150 mmol/L; adjusted odds ratio [adjOR], 4.88; 95% CI, 1.68-14.18), leukocytosis (>15 G/L; adjOR, 3.14; 95% CI, 1.24-8.77), hyperchloremia (>121 mmol/L; adjOR, 5.24; 95% CI, 1.64-16.76), and female sex (adjOR, 3.71; 95% CI, 1.01-13.64) after adjusting for admission Hunt and Hess grade and age. Delayed brain edema resolution was an independent predictor of worse functional 3-month outcome (adjOR, 2.52; 95% CI, 1.07-5.92). Conclusions- Our data suggest that repeated quantification of the SEBES can identify SAH patients with delayed edema resolution. Based on its' prognostic value as radiographic biomarker, the SEBES may be integrated in future trials aiming to improve edema resolution after SAH.

Late presentation of NMOSD as rapidly progressive leukoencephalopathy with atypical clinical and radiological findings.

Brain abnormalities in neuromyelitis optica spectrum disorder (NMOSD) are highly heterogeneous and often non-specific. Extensive white matter involvement has been described and frequently manifests with encephalopathy requiring prompt intervention. Rarely, this may represent the only manifestation at onset without concurrent suggestive features of the disease, thus making diagnosis challenging. NMOSD may potentially occur at any age, but it seems that this disorder has distinctive clinical features in the elderly. We describe a case of NMOSD presenting as rapidly progressive leukoencephalopathy with atypical clinical and magnetic resonance imaging (MRI) findings in a 69-year-old woman.

First insights on the mitochondrial genetic variability of Lightiella magdalenina (Crustacea), the sole Mediterranean cephalocarid species.

BACKGROUND: Here we report the first insight into the mitochondrial (Cytochrome c Oxidase subunit I - COI and Cytochrome b - Cyt b) genetic variation of the only Mediterranean cephalocarid Lightiella magdalenina. FINDINGS: COI sequences provide a scenario of low intraspecific variability, while significant genetic divergence occurs between L. magdalenina and L. incisa. Interestingly, Cyt b sequences reveal a higher degree of intraspecific variability, with no shared haplotypes between the sites considered. CONCLUSIONS: In the future, COI and Cyt b molecular markers could be used as valuable tools to shed new light into the extant species within the genus Lightiella thus providing molecular support to the taxonomical identifications carried out on a morphological basis.