OxyHbMeter-a novel bedside medical device for monitoring cell-free hemoglobin in the cerebrospinal fluid-proof of principle.

Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor.

Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARS-CoV-2 Infection (COVID-19) Compared with Healthy Young Controls.

PURPOSE: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). METHODS: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l'Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant's eyes. RESULTS: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group. CONCLUSION: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02-0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues.

Persistence, prevalence, and polymorphism of sequelae after COVID-19 in unvaccinated, young adults of the Swiss Armed Forces: a longitudinal, cohort study (LoCoMo).

BACKGROUND: Persistent COVID-19 sequelae could have global, public health ramifications. We therefore aimed to describe sequelae presenting more than 180 days after COVID-19-focussing on several organ systems, general health, and laboratory parameters-in non-hospitalised, unvaccinated, young adults. METHODS: We did a longitudinal cohort study of all army bases in Switzerland. Eligible participants were personnel of the Swiss Armed Forces (SAF) who were aged 18-30 years with a positive or negative RT-PCR test for SARS-CoV-2 during their service between March 1, 2020, and Dec 31, 2020. Exclusion criteria were unwillingness to participate in testing. Females or men with a known reproductive anomaly were excluded from the optional component of male fertility testing. COVID-19 was defined as a positive diagnostic RT-PCR test result for SARS-CoV-2 with concurrent symptoms compatible with COVID-19. Participants were subdivided into four groups: control group (ie, serologically negative), asymptomatic infection group (ie, serologically positive but with no symptoms), non-recent COVID-19 group (>180 days since positive PCR test), and recent COVID-19 group (≤180 days since positive PCR test). Outcomes of interest were part of a comprehensive, intensive test battery that was administered during a single day. The test battery quantified the effect of SARS-CoV-2 infection on cardiovascular, pulmonary, neurological, renal, ophthalmological, male reproductive, psychological, general health, and laboratory parameters. This study was registered with ClinicalTrials.gov, number NCT04942249. FINDINGS: Between May 20, 2021, and Nov 26, 2021, we enrolled 501 participants. 29 (6%) of 501 were female and 464 (93%) were male, and the median age was 21 years (IQR 21-23). Eight (2%) of 501 had incomplete data and were not included into the study groups. 177 participants had previous COVID-19 that was more than 180 days (mean 340 days) since diagnosis (ie, the non-recent COVID-19 group) compared with 251 serologically negative individuals (ie, the control group). We included 19 participants in the recent COVID-19 group and 46 in the asymptomatic infection group. We found a significant trend towards metabolic disorders in participants of the non-recent COVID-19 group compared with those in the control group: higher BMI (median 24·0 kg/m2 [IQR 22·0-25·8] vs 23·2 kg/m2 [27·1-25·0]; p=0·035), lower aerobic threshold (39% [36-43] vs 41% [37-46]; p=0·012), and higher blood cholesterol (4·2 µM [3·7-4·7] vs 3·9 µM [3·5-4·5]; p<0·0001) and LDL concentrations (2·4 µM [1·9-2·9] vs 2·2 µM [1·7-2·7]; p=0·001). The only significant psychosocial difference was found in the results of the Chalder Fatigue scale with the non-recent COVID-19 group reporting higher fatigue scores than the control group (median 12 points [IQR 11-15] vs 11 [9-14]; p=0·027). No significant differences in other psychosocial questionnaire scores, ophthalmological outcomes, and sperm quality or motility were reported between the control group and non-recent COVID-19 group. INTERPRETATION: Young, previously healthy, individuals largely recover from SARS-CoV-2 infection. However, the constellation of higher BMI, dyslipidaemia, and lower physical endurance 180 days after COVID-19 is suggestive of a higher risk of developing metabolic disorders and possible cardiovascular complications. These findings will guide future investigations and follow-up management. FUNDING: Swiss Armed Forces.

Predisposing and Precipitating Risk Factors for Delirium in Elderly Patients Admitted to a Cardiology Ward: An Observational Cohort Study in 1,042 Patients.

Aim: Although the risk factors for delirium in general medicine are well-established, their significance in cardiac diseases remains to be determined. Therefore, we evaluated the predisposing and precipitating risk factors in patients hospitalized with acute and chronic heart disease. Methods and Results: In this observational cohort study, 1,042 elderly patients (≥65 years) admitted to cardiology wards, 167 with and 875 without delirium, were included. The relevant sociodemographic and cardiac- and medical-related clusters were assessed by simple and multiple regression analyses and prediction models evaluating their association with delirium. The prevalence of delirium was 16.0%. The delirious patients were older (mean 80 vs. 76 years; p < 0.001) and more often institutionalized prior to admission (3.6 vs. 1.4%, p = 0.05), hospitalized twice as long (12 ± 10 days vs. 7 ± 7 days; p < 0.001), and discharged more often to nursing homes (4.8 vs. 0.6%, p < 0.001) or deceased (OR, 2.99; 95% CI, 1.53-5.85; p = 0.003). The most relevant risk factor was dementia (OR, 18.11; 95% CI, 5.77-56.83; p < 0.001), followed by history of stroke (OR, 6.61; 95% CI 1.35-32.44; p = 0.020), and pressure ulcers (OR, 3.62; 95% CI, 1.06-12.35; p = 0.040). The predicted probability for developing delirium was highest in patients with reduced mobility and institutionalization prior to admission (PP = 31.2%, p = 0.001). Of the cardiac diseases, only valvular heart disease (OR, 1.57; 95% CI, 1.01-2.44; p = 0.044) significantly predicted delirium. The patients undergoing cardiac interventions did not have higher rates of delirium (OR, 1.39; 95% CI 0.91-2.12; p = 0.124). Conclusion: In patients admitted to a cardiology ward, age-related functional and cognitive impairment, history of stroke, and pressure ulcers were the most relevant risk factors for delirium. With regards to specific cardiological factors, only valvular heart disease was associated with risk for delirium. Knowing these factors can help cardiologists to facilitate the early detection and management of delirium.

Economic Impact of Poststroke Delirium and Associated Risk Factors: Findings From a Prospective Cohort Study.

Background and Purpose: Delirium is a common severe complication of stroke. We aimed to determine the cost-of-illness and risk factors of poststroke delirium (PSD). Methods: This prospective single-center study included n=567 patients with acute stroke from a hospital-wide delirium cohort study and the Swiss Stroke Registry in 2014. Delirium was determined by Delirium Observation Screening Scale or Intensive Care Delirium Screening Checklist 3 times daily during the first 3 days of admission. Costs reflected the case-mix index and diagnosis-related groups from 2014 and were divided into nursing, physician, and total costs. Factors associated with PSD were assessed with multiple regression analysis. Partial correlations and quantile regression were performed to assess costs and other factors associated with PSD. Results: The incidence of PSD was 39.0% (221/567). Patients with delirium were older than non-PSD (median 76 versus 70 years; P<0.001), 52% male (115/221) versus 62% non-PSD (214/346) and hospitalized longer (mean 11.5 versus 9.3 days; P<0.001). Dementia was the most relevant predisposing factor for PSD (odds ratio, 16.02 [2.83­90.69], P=0.002). Moderate to severe stroke (National Institutes of Health Stroke Scale score 16­20) was the most relevant precipitating factor (odds ratio, 36.10 [8.15­159.79], P<0.001). PSD was a strong predictor for 3-month mortality (odds ratio, 15.11 [3.33­68.53], P<0.001). Nursing and total costs were nearly twice as high in PSD (P<0.001). There was a positive correlation between total costs and admission National Institutes of Health Stroke Scale (correlation coefficient, 0.491; P<0.001) and length of stay (correlation coefficient, 0.787; P<0.001) in all patients. Quantile regression revealed rising nursing and total costs associated with PSD, higher National Institutes of Health Stroke Scale, and longer hospital stay (all P<0.05). Conclusions: PSD was associated with greater stroke severity, prolonged hospitalization, and increased nursing and total costs. In patients with severe stroke, dementia, or seizures, PSD is anticipated, and additional costs are associated with hospitalization.

Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury.

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) contributes to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. The aim of this study was to investigate the clinical and pathophysiological association between cerebrospinal fluid hemoglobin (CSF-Hb) and SAH-SBI. In a cohort of 47 patients, we collected daily CSF-samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between spectrophotometrically determined CSF-Hb and SAH-SBI. The accuracy of CSF-Hb to monitor for SAH-SBI markedly exceeded that of established methods (AUC: 0.89 [0.85-0.92]). Temporal proteome analysis revealed erythrolysis accompanied by an adaptive macrophage response as the two dominant biological processes in the CSF-space after aneurysm rupture. Ex-vivo experiments on the vasoconstrictive and oxidative potential of Hb revealed critical inflection points overlapping CSF-Hb thresholds in patients with SAH-SBI. Selective depletion and in-solution neutralization by haptoglobin or hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.

A Distinct Cytokine Profile and Stromal Vascular Fraction Metabolic Status without Significant Changes in the Lipid Composition Characterizes Lipedema.

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.

Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults.

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

Delirium is associated with an increased morbidity and in-hospital mortality in cancer patients: Results from a prospective cohort study.

OBJECTIVE: Delirium is a frequent complication in advanced cancer patients, among whom it is frequently underdiagnosed and inadequately treated. To date, evidence on risk factors and the prognostic impact of delirium on outcomes remains sparse in this patient population. METHOD: In this prospective observational cohort study at a single tertiary-care center, 1,350 cancer patients were enrolled. Simple and multiple logistic regression models were utilized to identify associations between predisposing and precipitating factors and delirium. Cox proportional-hazards models were used to estimate the effect of delirium on death rate. RESULTS: In our patient cohort, the prevalence of delirium was 34.3%. Delirium was associated inter alia with prolonged hospitalization, a doubling of care requirements, increased healthcare costs, increased need for institutionalization (OR 3.22), and increased mortality (OR 8.78). Predisposing factors for delirium were impaired activity (OR 10.82), frailty (OR 4.75); hearing (OR 2.23) and visual impairment (OR 1.89), chronic pneumonitis (OR 2.62), hypertension (OR 1.46), and renal insufficiency (OR 1.82). Precipitating factors were acute renal failure (OR 7.50), pressure sores (OR 3.78), pain (OR 2.86), and cystitis (OR 1.32). On multivariate Cox regression, delirium increased the mortality risk sixfold (HR 5.66). Age ≥ 65 years and comorbidities further doubled the mortality risk of delirious patients (HR 1.77; HR 2.05). SIGNIFICANCE OF RESULTS: Delirium is common in cancer patients and associated with increased morbidity and mortality. Systematically categorizing predisposing and precipitating factors might yield new strategies for preventing and managing delirium in cancer patients.

Social Distancing Alters the Clinical Course of COVID-19 in Young Adults: A Comparative Cohort Study.

BACKGROUND: Social distancing and stringent hygiene seem to be effective in reducing the number of transmitted virus particles, and therefore the infectivity, of coronavirus disease 2019 (COVID-19) and could alter the mode of transmission of the disease. However, it is not known if such practices can change the clinical course in infected individuals. METHODS: We prospectively studied an outbreak of COVID-19 in Switzerland among a population of 508 predominantly male soldiers with a median age of 21 years. We followed the number of infections in 2 spatially separated cohorts with almost identical baseline characteristics with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before and after implementation of stringent social distancing. RESULTS: Of the 354 soldiers infected prior to the implementation of social distancing, 30% fell ill from COVID-19, while no soldier in a group of 154, in which infections appeared after implementation of social distancing, developed COVID-19 despite the detection of viral RNA in the nasal and virus-specific antibodies within this group. CONCLUSIONS: Social distancing not only can slow the spread of SARS-CoV-2 in a cohort of young, healthy adults but it can also prevent the outbreak of COVID-19 while still inducing an immune response and colonizing nasal passages. Viral inoculum during infection or mode of transmission may be a key factor determining the clinical course of COVID-19.

The prevalence rates and adversities of delirium: Too common and disadvantageous.

OBJECTIVE: The prevalence rates and adversities of delirium have not yet been systematically evaluated and are based on selected populations, limited sample sizes, and pooled studies. Therefore, this study assesses the prevalence rates and outcome of and odds ratios for managing services for delirium. METHODS: In this prospective cohort study, based on the Diagnostic and Statistical Manual (DSM) 5, the Delirium Observation Screening (DOS) scale, and the Intensive Care Delirium Screening Checklist (ICDSC) construct, 28,118 patients from 35 managing services were included, and the prevalence rates and adverse outcomes were determined by simple logistic regressions and their corresponding odds ratios (ORs). RESULTS: Delirious patients were older, admitted from institutions (OR 3.44-5.2), admitted as emergencies (OR 1.87), hospitalized twice longer, and discharged, transferred to institutions (OR 5.47-6.6) rather than home (OR 0.1), or deceased (OR 43.88). The rate of undiagnosed delirium was 84.2%. The highest prevalence rates were recorded in the intensive care units (47.1-84.2%, pooled 67.9%); in the majority of medical services, rates ranged from 20% to 40% (pooled 26.2%), except, at both ends, palliative care (55.9%), endocrinology (8%), and rheumatology (4.4%). Conversely, in surgery and its related services, prevalence rates were lower (pooled 13.1%), except for cardio- and neurosurgical services (53.3% and 46.4%); the lowest prevalence rate was recorded in obstetrics (2%). SIGNIFICANCE OF RESULTS: Delirium remains underdiagnosed, and novel screening approaches are required. Furthermore, this study identified the impact of delirium on patients, determined the prevalence rates for 32 services, and elucidated the association between individual services and delirium.

Reduced maximal aerobic capacity after COVID-19 in young adult recruits, Switzerland, May 2020.

In March 2020, we observed an outbreak of COVID-19 among a relatively homogenous group of 199 young (median age 21 years; 87% men) Swiss recruits. By comparing physical endurance before and in median 45 days after the outbreak, we found a significant decrease in predicted maximal aerobic capacity in COVID-19 convalescent but not in asymptomatically infected and SARS-CoV-2 naive recruits. This finding might be indicative of lung injury after apparently mild COVID-19 in young adults.

Determining the Optimal Normalization Factor of Different Target Arteries for ex vivo Vascular Function Experiments: A New Standardized Procedure.

The standardization of resistance vessel preparation is crucial to compare physiologic vascular reactivity under different experimental conditions. Here, we describe a generalizable experimental setup for ex vivo vascular function experiments and their mathematical basis. Porcine basilar arteries and chicken common carotid arteries were isolated post mortem via standardized surgical approaches. The inner circumference of these vessels with a passive wall tension corresponding to 100 mm Hg (IC100) as well as the circumference at which the active force production of the vessel is maximal (IC1) were determined systematically. The IC1/IC100 ratio (also referred to as factor k), a value that is believed to be constant for a defined vessel type in one species, was calculated by a novel mathematical approach. Here, we present an easy-to-use toolbox for the systematic and computer-based calculation of factor k and simplified optimal pre-stretching of any vascular segments for wire myography experiments.

Serum lipidome analysis of healthy beagle dogs receiving different diets.

INTRODUCTION: Food and dietary ingredients have significant effects on metabolism and health. OBJECTIVE: To evaluate whether and how different diets affected the serum lipidomic profile of dogs. METHODS: Sixteen healthy beagles were fed a commercial dry diet for 3 months (control diet). After an overnight fasting period, a blood sample was taken for serum lipidomic profile analysis, and each dog was then randomly assigned to one of two groups. Group 1 was fed a commercial diet (Diet 1) and group 2 was fed a self-made, balanced diet supplemented with linseed oil and salmon oil (Diet 2) for 3 months. After an overnight fasting period, a blood sample was taken from each dog. Serum cholesterol and triacylglycerol analyses were performed and the serum lipidomic profiles were analyzed using targeted liquid chromatography-mass spectrometry. RESULTS: Dogs fed the supplemented self-made diet (Diet 2) had significantly higher omega-3 fatty acid-containing lipids species and significantly lower saturated and mono- and di-unsaturated lipid species. Concentrations of sphingosine 1-phosphate species S1P d16:1 and S1P d17:1 were significantly increased after feeding Diet 2. CONCLUSION: This study found that different diets had significant effects on the dog's serum lipidomic profile. Therefore, in studies that include lipidomic analyses, diet should be included as a confounding factor.

Predisposing and precipitating factors for delirium in neurology: a prospective cohort study of 1487 patients.

INTRODUCTION: Predisposing and precipitating factors for delirium are well known; however, their interaction and impact on delirium in neurological patients remains largely unknown. Therefore, those factors were evaluated in hospitalized patients with neurological disorders. METHODS: In this prospective cohort study, 1487 neurological patients were included, 356 patients with delirium and 1131 without delirium. Relevant neurological- and medical-related clusters were assessed with multiple regression analyses, prediction models, and cluster analysis evaluating their association with delirium. RESULTS: The 1-year incidence of delirium in this cohort was 23.9%. Delirium developed in 31% of patients with stroke, in 39.5% with epilepsy, and in 58.4% with ICH. The most relevant predisposing factors were substance-use disorders (OR 4.24, 2.28-7.78, p < 0.001), advanced age (OR 3.44, CI 2.40-4.92, p < 0.001), and neurodegenerative disorders (OR 2.58, CI 1.47-4.54, p = 0.001). The most relevant precipitating factors were meningitis (OR 21.52, CI 1.22-379.83, p = 0.036), acute renal failure (OR 10.01, CI 1.13-88.73, p = 0.039), and intracranial hemorrhage (OR 3.62, CI 2.08-6.30, p < 0.001). Delirious patients were hospitalized 6 days longer, had higher in-hospital mortality, and were discharged more often to nursing homes and rehabilitation. Best predictor for delirium was the coexistence of advanced age with epilepsy (58.3%, p < 0.001), while patients aged < 65 years without epilepsy and stroke rarely developed delirium (5.1%, p < 0.001). CONCLUSIONS: Delirium is common in elder neurological patients and associated with worse outcome. Primary cerebral conditions most frequently precipitate delirium in neurology. Neurologists are advised to monitor symptoms of delirium in the presence of risk factors to enable both timely diagnostic work-up and management of delirium.

Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm.

Delayed ischemic neurological deficit (DIND) is a major driver of adverse outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH), defining an unmet need for therapeutic development. Cell-free hemoglobin that is released from erythrocytes into the cerebrospinal fluid (CSF) is suggested to cause vasoconstriction and neuronal toxicity, and correlates with the occurrence of DIND. Cell-free hemoglobin in the CSF of patients with aSAH disrupted dilatory NO signaling ex vivo in cerebral arteries, which shifted vascular tone balance from dilation to constriction. We found that selective removal of hemoglobin from patient CSF with a haptoglobin-affinity column or its sequestration in a soluble hemoglobin-haptoglobin complex was sufficient to restore physiological vascular responses. In a sheep model, administration of haptoglobin into the CSF inhibited hemoglobin-induced cerebral vasospasm and preserved vascular NO signaling. We identified 2 pathways of hemoglobin delocalization from CSF into the brain parenchyma and into the NO-sensitive compartment of small cerebral arteries. Both pathways were critical for hemoglobin toxicity and were interrupted by the large hemoglobin-haptoglobin complex that inhibited spatial requirements for hemoglobin reactions with NO in tissues. Collectively, our data show that compartmentalization of hemoglobin by haptoglobin provides a novel framework for innovation aimed at reducing hemoglobin-driven neurological damage after subarachnoid bleeding.