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Background and ObjectivesThere is significant heterogeneity in the reporting of outcome measures in aneurysmal subarachnoid hemorrhage (aSAH) research. The modified Rankin scale (mRS) is the most commonly reported functional outcome measure. The mRS focuses on physical disability; however, many aSAH survivors experience sequalae in other domains, and the mRS may therefore not capture outcomes important to aSAH survivors. The objective of this study was to assess the clinical relevance of the mRS as a research outcome measure to people with lived aSAH experience.MethodsWe conducted an international cross-sectional survey of 355 aSAH survivors, family members, and caregivers to evaluate patient-perceived outcomes in relation to the mRS. The mRS was assessed using a previously validated web-based tool.ResultsResponse rate was 60%; respondents from 7 continents were composed of 86% aSAH survivors and 14% family members/caregivers. Agreement between self-assessed outcome and the mRS was poor (Kappa 0.26 [CI 0.14–0.39]). Of the 172 respondents who self-assessed as having had a good aSAH outcome, 122 (71%) had a score of 0–2 on the mRS. Approximately 19% of respondents with a good outcome, based on a measured mRS score of 0–2, self-assessed as having had a poor aSAH outcome. When the mRS score was dichotomized as 0–3 corresponding to a good outcome, agreement between the score and self-assessed outcome remained poor with a Kappa score of 0.40 (CI 0.20–0.60). Approximately 30% of respondents believed that the mRS should not be used as an outcome measure in future aSAH trials.DiscussionThe findings suggest that there is poor agreement between aSAH survivors' self-assessed outcome, their actual mRS score, and the dichotomization of the mRS score into good/poor outcomes. Patient-centered and patient-informed outcome measurement tools are needed to guide the aSAH research agenda.

Background: Neurofilament light chain protein (NfL) and tau are plasma biomarkers of neuronal injury which can be elevated in patients with neurodegenerative diseases. N-terminal pro-brain natriuretic peptide (NT-proBNP) is an established marker of volume status in patients with heart failure (HF) and plasma cBIN1 score (CS) is an emerging biomarker of cardiac muscle health. It is not known if, in HF patients, there is a correlation between cardiac markers and brain injury markers.Methods: We studied ambulatory HF patients with either preserved and reduced ejection fraction (N = 50 with 25 HFrEF and 25 HFpEF) and age and sex matched healthy controls (N = 50). Plasma NT-proBNP and CS were determined using commercial kits. A bead-based ELISA assay was used to quantify femtomolar concentrations of plasma neuronal markers NfL and total tau.Results: Plasma levels of NT-proBNP and CS in heart failure patients were significantly higher than those from healthy controls. In both patients with HFrEF and HFpEF, we found independent and direct correlations between the volume status marker NT-proBNP, but not the cardiomyocyte origin muscle health marker CS, with NfL (r = 0.461, p = 0.0007) and tau (r = 0.333, p = 0.0183).Conclusion: In patients with HF with or without preserved ejection fraction, plasma levels of NfL and tau correlate with volume status rather than muscle health, indicating volume overload-associated neuronal injury.

Additional file 1: Figure S1. The plasma level of endotoxin was significantlyelevated in the UTI mice compared to non-UTI controls. The endotoxin level was quantifiedusing a chromogenic endotoxin quantification kit. Quantitative data areexpressed in mean �� SD. ****p < 0.0001. Figure S2. UTI causes an increase in plasma IL-6 levels by 36 hourspost-inoculation that is sustained at 72 hours. Blood was collected at baseline, 36-, and 72-hours post-inoculation andplasma IL-6 levels were quantified via ELISA. The data show that there is anapproximate, and significant 8-fold increase in plasma IL-6 acutely followingtransurethral inoculation that persists at 72 hours, which is the final timepoint for all other cohorts. Quantitative data are expressed in mean �� SD. *p< 0.05, **p < 0.01. Figure S3. ��-IL-6 treatment to non-UTI micecauses no change in either brain histology or behavior. Non-inoculated,wild-type mice were given the same ��-IL6 antibody treatments as the UTI cohort,i.e., once daily doses for 3 days. A-B: IHC analysis of CC3 levels within thefrontal cortex and hippocampus showed no difference in animals treated with theantibody compared to those treated with saline (vehicle). C-M: The miceunderwent behavioral testing (i.e., open field and Y-Maze) and treated miceshowed no difference in behavior compared to controls. Quantitative data areexpressed in mean �� SD. Figure S4. There is no significant difference in overalllocomotor activity in UTI compared to control or UTI+��-IL-6 groups. A-E: Quantitative dataof open field behavioral test show no significant difference in total distancetraveled, average speed, maximum speed, total mobile time, or total immobiletime between the groups. F-G: Quantitative dataof Y-maze behavioral test showing no significant change in the total number ofentries in different arms between the experimental groups. Each dot representsone animal (n=9 in control, n=10 in UTI, n=12 in UTI+��-IL-6). Figure S5. A: Quantitativedata via ELISA corroborate immunohistochemistry findings by showing significantmitigation of frontal IL-6 in UTI mice treated with systemic anti-IL-6antibody compared to UTI mice. B: Quantitative data via RT-PCR show nosignificant differences in cortical IL-6 mRNA across the three experimentalgroups. Quantitative data are expressed in mean �� SD. *p < 0.05, ****p

Introduction. Mild hypotension is a well-recognized complication of intravenous pentobarbital; however fulminant cardiopulmonary failure has not been previously reported. Case Report. A 28-year-old woman developed pentobarbital-induced cardiopulmonary failure that was successfully treated with maximal medical management including arteriovenous extracorporeal membrane oxygenation. She made an excellent cardiopulmonary and neurological recovery. Discussion and Conclusion. Pentobarbital is underrecognized as a potential cause of myocardial stunning. The mechanism involves direct myocardial depression and inhibition of autonomic neuroanatomical structures including the medulla and hypothalamus. Early recognition and implementation of aggressive cardiopulmonary support are essential to optimize the likelihood of a favorable outcome.