Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.

BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI. METHODS: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events. RESULTS: Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events). CONCLUSIONS: Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.

Detection of Acute Brain Injury in Intensive Care Unit Patients on ECMO Support Using Ultra-Low-Field Portable MRI: A Retrospective Analysis Compared to Head CT.

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program.

Clinical Use of Bedside Portable Low-field Brain Magnetic Resonance Imaging in Patients on ECMO: The Results from Multicenter SAFE MRI ECMO Study.

Purpose: Early detection of acute brain injury (ABI) is critical for improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to evaluate the safety of ultra-low-field portable MRI (ULF-pMRI) and the frequency and types of ABI observed during ECMO support. Methods: We conducted a multicenter prospective observational study (NCT05469139) at two academic tertiary centers (August 2022-November 2023). Primary outcomes were safety and validation of ULF-pMRI in ECMO, defined as exam completion without adverse events (AEs); secondary outcomes were ABI frequency and type. Results: ULF-pMRI was performed in 50 patients with 34 (68%) on venoarterial (VA)-ECMO (11 central; 23 peripheral) and 16 (32%) with venovenous (VV)-ECMO (9 single lumen; 7 double lumen). All patients were imaged successfully with ULF-pMRI, demonstrating discernible intracranial pathologies with good quality. AEs occurred in 3 (6%) patients (2 minor; 1 serious) without causing significant clinical issues.ABI was observed in ULF-pMRI scans for 22 patients (44%): ischemic stroke (36%), intracranial hemorrhage (6%), and hypoxic-ischemic brain injury (4%). Of 18 patients with both ULF-pMRI and head CT (HCT) within 24 hours, ABI was observed in 9 patients with 10 events: 8 ischemic (8 observed on ULF-oMRI, 4 on HCT) and 2 hemorrhagic (1 observed on ULF-pMRI, 2 on HCT). Conclusions: ULF-pMRI was shown to be safe and valid in ECMO patients across different ECMO cannulation strategies. The incidence of ABI was high, and ULF-pMRI may more sensitive to ischemic ABI than HCT. ULF-pMRI may benefit both clinical care and future studies of ECMO-associated ABI.

Lysophospholipids Are Associated With Outcomes in Hospitalized Patients With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) accounts for 70-90% of all TBI cases. Lipid metabolites have important roles in plasma membrane biogenesis, function, and cell signaling. As TBI can compromise plasma membrane integrity and alter brain cell function, we sought to identify circulating phospholipid alterations after mTBI, and determine if these changes were associated with clinical outcomes. Patients with mTBI (Glasgow Coma Score [GCS] ≥13 and loss of consciousness <30 min) were recruited. A total of 84 mTBI subjects were enrolled after admission to a level I trauma center, with the majority having evidence of traumatic intracranial hemorrhage on brain computed tomography (CT). Plasma samples were collected within 24 h of injury with 32 mTBI subjects returning at 3 months after injury for a second plasma sample to be collected. Thirty-five healthy volunteers were enrolled as controls and had a one-time blood draw. Lipid metabolomics was performed on plasma samples from each subject. Fold change of selected lipid metabolites was determined. Multivariable regression models were created to test associations between lipid metabolites and discharge and 6-month Glasgow Outcomes Scale-Extended (GOSE) outcomes (dichotomized between "good" [GOSE ≥7] and "bad" [GOSE ≤6] functional outcomes). Plasma levels of 31 lipid metabolites were significantly associated with discharge GOSE using univariate models; three of these metabolites were significantly increased, while 14 were significantly decreased in subjects with good outcomes compared with subjects with poor outcomes. In multivariable logistic regression models, higher circulating levels of the lysophospholipids (LPL) 1-linoleoyl-glycerophosphocholine (GPC) (18:2), 1-linoleoyl-GPE (18:2), and 1-linolenoyl-GPC (18:3) were associated with both good discharge GOSE (odds ratio [OR] 12.2 [95% CI 3.35, 58.3], p = 5.23 × 10-4; OR 9.43 [95% CI 2.87, 39.6], p = 7.26 × 10-4; and OR 5.26 [95% CI 1.99, 16.7], p = 2.04 × 10-3, respectively) and 6-month (OR 4.67 [95% CI 1.49, 17.7], p = 0.013; OR 2.93 [95% CI 1.11, 8.87], p = 0.039; and OR 2.57 [95% CI 1.08, 7.11], p = 0.046, respectively). Compared with healthy volunteers, circulating levels of these three LPLs were decreased early after injury and had normalized by 3 months after injury. Logistic regression models to predict functional outcomes were created by adding each of the described three LPLs to a baseline model that included age and sex. Including 1-linoleoyl-GPC (18:2) (8.20% improvement, p = 0.009), 1-linoleoyl-GPE (18:2) (8.85% improvement, p = 0.021), or 1-linolenoyl-GPC (18:3) (7.68% improvement, p = 0.012), significantly improved the area under the curve (AUC) for predicting discharge outcomes compared with the baseline model. Models including 1-linoleoyl-GPC (18:2) significantly improved AUC for predicting 6-month outcomes (9.35% improvement, p = 0.034). Models including principal components derived from 25 LPLs significantly improved AUC for prediction of 6-month outcomes (16.0% improvement, p = 0.020). Our results demonstrate that higher plasma levels of LPLs (1-linoleoyl-GPC, 1-linoleoyl-GPE, and 1-linolenoyl-GPC) after mTBI are associated with better functional outcomes at discharge and 6 months after injury. This class of phospholipids may represent a potential therapeutic target.

Assessing HIV Care Outcomes Among Persons Who Use Drugs in Puerto Rico Before and After Hurricane Maria.

OBJECTIVES: To explore the health impacts of Hurricane Maria (HM) on HIV care outcomes among people living with HIV who use drugs. METHODS: Using data from an ongoing cohort study in San Juan, Puerto Rico (Proyecto PACTo), we measured differences in HIV care outcomes (viral load, viral suppression, and CD4 counts) before and after HM using assessments conducted at 6-month intervals. Generalized estimating equations were used to assess factors associated with HIV care outcomes. RESULTS: All HIV care outcomes showed a deterioration from pre-HM values to post-HM values (mean viral load increased, CD4 counts decreased, and rate of viral suppression decreased) after controlling for pre-HM sociodemographic and health characteristics. In addition to HM, age (aIRR = 1·01), being homeless (aIRR = 0·78) and having health insurance (aIRR = 1·6) were independently associated with viral suppression. PARTICIPANTS: 219 participants completed follow-up visits between April 2017 and January 2018, before and after HM. CONCLUSIONS: People living with HIV who use drugs in Puerto Rico experienced poorer HIV outcomes following HM. Socio-environmental factors contributing to these outcomes is discussed in the context of disaster response, recovery, and program planning.

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients.

OBJECTIVES: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU. DESIGN: Observational cohort study and separate in vitro laboratory study. SETTING: Multicenter tertiary referral ICUs. PATIENTS: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: -0.52, p = 0.002; TEG r: -0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings. CONCLUSIONS: Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient's hemoglobin concentration.

The Spot Sign and Intraventricular Hemorrhage are Associated with Baseline Coagulopathy and Outcome in Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is the second most prevalent subtype of stroke and has high mortality and morbidity. The utility of radiographic features to predict secondary brain injury related to hematoma expansion (HE) or increased intracranial pressure has been highlighted in patients with ICH, including the computed tomographic angiography (CTA) spot sign and intraventricular hemorrhage (IVH). Understanding the pathophysiology of spot sign and IVH may help identify optimal therapeutic strategies. We examined factors related to the spot sign and IVH, including coagulation status, hematoma size, and location, and evaluated their prognostic value in patients with ICH. METHODS: Prospectively collected data from a single center between 2012 and 2015 were analyzed. Patients who underwent thromboelastography within 24 h of symptom onset and completed follow-up brain imaging and CTA within 48 h after onset were included for analysis. Multivariate logistic regression analyses were performed to identify determinants of the spot sign and IVH and their predictive value for HE, early neurological deterioration (END), in-hospital mortality, and functional outcome at discharge. RESULTS: Of 161 patients, 50 (31.1%) had a spot sign and 93 (57.8%) had IVH. In multivariable analysis, the spot sign was associated with greater hematoma volume (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.00-1.03), decreased white blood cell count (OR 0.88; 95% CI 0.79-0.98), and prolonged activated partial thromboplastin time (OR 1.14; 95% CI 1.06-1.23). IVH was associated with greater hematoma volume (OR 1.02; 95% CI 1.01-1.04) and nonlobar location of hematoma (OR 0.23; 95% CI 0.09-0.61). The spot sign was associated with greater risk of all adverse outcomes. IVH was associated with an increased risk of END and reduced HE, without significant impact on mortality or functional outcome. CONCLUSIONS: The spot sign and IVH are associated with specific hematoma characteristics, such as size and location, but are related differently to coagulation status and clinical course. A combined analysis of the spot sign and IVH can improve the understanding of pathophysiology and risk stratification after ICH.

Sex differences in global metabolomic profiles of COVID-19 patients.

Coronavirus disease (COVID-19), caused by SARS-CoV-2, leads to symptoms ranging from asymptomatic disease to death. Although males are more susceptible to severe symptoms and higher mortality due to COVID-19, patient sex has rarely been examined. Sex-associated metabolic changes may implicate novel biomarkers and therapeutic targets to treat COVID-19. Here, using serum samples, we performed global metabolomic analyses of uninfected and SARS-CoV-2-positive male and female patients with severe COVID-19. Key metabolic pathways that demonstrated robust sex differences in COVID-19 groups, but not in controls, involved lipid metabolism, pentose pathway, bile acid metabolism, and microbiome-related metabolism of aromatic amino acids, including tryptophan and tyrosine. Unsupervised statistical analysis showed a profound sexual dimorphism in correlations between patient-specific clinical parameters and their global metabolic profiles. Identification of sex-specific metabolic changes in severe COVID-19 patients is an important knowledge source for researchers striving for development of potential sex-associated biomarkers and druggable targets for COVID-19 patients.

Reducing acetylated tau is neuroprotective in brain injury.

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.