Abstract WMP97: Haptoglobin is Associated With Increased Early Perihematoma Edema Progression in Spontaneous Intracranial Hemorrhage

Introduction: Perihematomal edema in intracranial hemorrhage (ICH) is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting clearance as well as free radical production, resulting in inflammation. Of the three phenotypes of Haptoglobin, Hp 1-1 has the greatest effect on free hemoglobin clearance. We hypothesized that individuals with the Hp 1-1 phenotype have different rates of early perihematomal edema formation as compared to those with Hp 2-1 and Hp 2-2. Methods: We determined Hp phenotype, ICH volume, and rate of early change in perihematomal volume (ePHE) in participants from three prospectively collected ICH cohorts; Johns Hopkins University hospital (JHH), Massachusetts General Hospital (MGH), and the MISTIE III trial. The association of Hp phenotypes 1-1, 2-1, 2-2, with ePHE, while controlling for key clinical characteristics was analyzed using a multivariate model. Findings: 166 participants, 57 from JHH, 30 from MGH, and 79 from the MISTIE III trial were included: 73 (44%) female, 41(25%) African Americans, 34 (20%) diabetics, 133 (80%) with hypertension, and 75 (45%) active smokers. There were 15 subjects with Hp phenotype 1-1, 86 with 2-1 and 65 with 2-2. In the adjusted analysis, controlling for race, diabetes, hypertension, smoking status, and change in intracranial hemorrhage volume over time (cc/hr), Hp 1-1 had a significantly increased estimated mean rate of ePHE at 1·15, (95% CI 0·58-1·71) as compared to all other Hp 2-1 or Hp 2-2 containing phenotypes (0·30, 95% CI 0·06-0·54; 0.29 95% CI 0·02-0·56). Neither mortality nor discharge mRS differed between Hp phenotypes. Interpretation: Haptoglobin phenotype is associated with ePHE. Hp 1-1 significantly increased mean rate of ePHE suggests that haptoglobin phenotype may be a key player in understanding the multiphasic progression of PHE in sICH, which may help identify windows for targeted interventions to improve clinical outcomes. Conclusion: In our adjusted models, patients with the Haptoglobin 1-1 phenotype had an increased rate of ePHE formation within the first 96 hours. The Hp 1-1 phenotype may increase perihematomal progression in sICH. A larger prospective observational study is warranted.

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Haptoglobin is associated with increased early perihematoma edema progression in spontaneous intracranial hemorrhage

International Journal of Stroke ◽

10.1177/1747493020912602 ◽

2020 ◽

Vol 15 (8) ◽

pp. 899-908

Author(s):

Michael R Halstead ◽

W Andrew Mould ◽

Kevin N Sheth ◽

Jonathan Rosand ◽

Richard Thompson ◽

...

Keyword(s):

Confidence Interval ◽

Intracranial Hemorrhage ◽

Free Hemoglobin ◽

Edema Formation ◽

Early Change ◽

Serum Haptoglobin ◽

Haptoglobin Phenotype ◽

Spontaneous Intracranial Hemorrhage ◽

Hemorrhage Volume ◽

Perihematomal Edema

Introduction Perihematomal edema in intracranial hemorrhage is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting heme clearance and free radical production. Of the three Hp phenotypes, Hp 1-1 has the greatest effect on free hemoglobin clearance. Aim To determine if individuals with Hp 1-1 phenotype have different rates of early perihematomal edema formation as compared to those with Hp 2-1 and Hp 2-2. Methods We determined Hp phenotype, intracranial hemorrhage volume, and rate of early change in perihematomal volume in participants from three prospectively collected intracranial hemorrhage cohorts. The association of Hp phenotypes 1-1, 2-1, 2-2, with early change in perihematomal volume, while controlling for key clinical characteristics was analyzed using a multivariate model. Findings One-hundred and sixty-six participants were included: 73 (44%) female, 41 ( 25%) African Americans, 34 (20%) diabetics, 133 (80%) with hypertension, and 75 (45%) active smokers. There were 15 subjects with Hp phenotype 1-1, 86 with 2-1, and 65 with 2-2. In fully adjusted analysis, Hp 1-1 had a significantly increased estimated mean rate of early change in perihematomal volume at 1.15 (95% confidence interval 0.58–1.71) as compared to all other Hp 2-1 or Hp 2-2 containing phenotypes (0.30, 95% confidence interval 0.06–0.54; 0.29 95% CI 0.02–0.56). Neither mortality nor discharge mRS differed between Hp phenotypes. Conclusion Haptoglobin phenotype is associated with early change in perihematomal volume. Hp 1-1 phenotype had significantly increased mean rate of early change in perihematomal volume within the first 96 h, suggesting that haptoglobin phenotype may be a key player in understanding the multiphasic progression of perihematomal volume in spontaneous intracerebral hemorrhage. A larger prospective observational study is warranted.

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Abstract TP343: The 1-1 Haptoglobin Phenotype is Associated With Perihematoma Edema Progression in Acute Intracranial Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.tp343 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Michael R Halstead ◽

William A Mould ◽

Kevin N Sheth ◽

Jonathon Rosand ◽

Richard Thompson ◽

...

Keyword(s):

Intracranial Hemorrhage ◽

Ldl Cholesterol ◽

Massachusetts General Hospital ◽

University Hospital ◽

Edema Formation ◽

Change Rate ◽

Haptoglobin Phenotype ◽

Johns Hopkins University ◽

Haptoglobin Genotype ◽

Baseline Characteristics

Introduction: Haptoglobin phenotype affects inflammation and may change rate of perihematoma edema formation (PHE) affecting outcomes. We reported better functional recovery in patients with intracranial hemorrhage (ICH) and the Haptoglobin 1-1 phenotype. This may be mediated through Haptoglobin 1-1 effects on PHE. Hypothesis: The Haptoglobin 1-1 phenotype has a different rate of PHE compared to 2-1 and 2-2. Different PHE related to Haptoglobin phenotype affects clinical outcomes. Methods: We determined Haptoglobin phenotype, ICH volume, and PHE in individuals identified prospectively from ICH cohorts, at Johns Hopkins University hospital (JHU) and the Massachusetts General Hospital (MGH) using established CT methodology. PHE were measured as differences in CT ICH edema volume divided by hours between scans. Associations of Haptoglobin phenotype (1-1 compared to 2-1, 2-2) and rate of PHE (cc/hr) using multivariate analysis adjusting for age, sex, race, diabetes (DM), hypertension (HTN), LDL cholesterol > 130 mm/dl (HDL), smoking, prior ICH, and use of antiplatelet or systemic anticoagulation were determined. Results: 87 patients were included with the following characteristics: Mean age 61.6 (15), 44 (50%) females, 28 (32%) AA, 64 (74%) HTN, 17 (20%) HDL, 22 (25%) active smokers, 29 (33%) on some form of anticoagulation/antiplatelet and 9 (10%) with prior ICH. We included 57 JHU and 30 MGH participants with different baseline characteristics. There were 9 subjects with Haptoglobin genotype 1-1, 45 with 2-1 and 33 with 2-2, Mean PHE varied within each group. Fully adjusted estimated mean PHE for 1-1 haplotype was 1.84cc/hr (95%CI 0.87-2.28 cc/hr), which was significantly greater than Haplotype 2-1 at 0.29 cc/hr (-0.15-0.72 cc/hr) and Haplotype 2-2, at 0.44 cc/hr (-0.07-0.96 cc/hr). Conclusion: In adjusted models, Haptoglobin 1-1 phenotype on average had a significantly increased rate of PHE in the early stages of ICH onset, opposite that predicted by our biological model. Our study suggests Haptoglobin haplotype is associated with PHE and may account for variability in disability and mortality in ICH. Our study is limited by insufficient power to determine haplotype effect on disability and mortality and larger prospective studies are warranted.

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Coagulopathy and its effect on treatment and mortality in patients with traumatic intracranial hemorrhage

Acta Neurochirurgica ◽

10.1007/s00701-021-04808-0 ◽

2021 ◽

Author(s):

Janne Kinnunen ◽

Jarno Satopää ◽

Mika Niemelä ◽

Jukka Putaala

Keyword(s):

Intracranial Hemorrhage ◽

Multivariable Analysis ◽

International Normalized Ratio ◽

University Hospital ◽

Lower Mortality ◽

Traumatic Intracranial Hemorrhage ◽

Hemorrhage Volume ◽

Anticoagulant Medication ◽

Admission Glasgow Coma Scale

Abstract Background The role of coagulopathy in patients with traumatic brain injury has remained elusive. In the present study, we aim to assess the prevalence of coagulopathy in patients with traumatic intracranial hemorrhage, their clinical features, and the effect of coagulopathy on treatment and mortality. Methods An observational, retrospective single-center cohort of consecutive patients with traumatic intracranial hemorrhage treated at Helsinki University Hospital between 01 January and 31 December 2010. We compared clinical and radiological parameters in patients with and without coagulopathy defined as drug- or disease-induced, i.e., antiplatelet or anticoagulant medication at a therapeutic dose, thrombocytopenia (platelet count < 100 E9/L), international normalized ratio > 1.2, or thromboplastin time < 60%. Primary outcome was 30-day all-cause mortality. Logistic regression analysis allowed to assess for factors associated with coagulopathy and mortality. Results Of our 505 patients (median age 61 years, 65.5% male), 206 (40.8%) had coagulopathy. Compared to non-coagulopathy patients, coagulopathy patients had larger hemorrhage volumes (mean 140.0 mL vs. 98.4 mL, p < 0.001) and higher 30-day mortality (18.9% vs. 9.7%, p = 0.003). In multivariable analysis, older age, lower admission Glasgow Coma Scale score, larger hemorrhage volume, and conservative treatment were independently associated with mortality. Surgical treatment was associated with lower mortality in both patients with and without coagulopathy. Conclusions Coagulopathy was more frequent in patients with traumatic intracranial hemorrhage presenting larger hemorrhage volumes compared to non-coagulopathy patients but was not independently associated with higher 30-day mortality. Hematoma evacuation, in turn, was associated with lower mortality irrespective of coagulopathy.

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Footstrike is the major cause of hemolysis during running

Journal of Applied Physiology ◽

10.1152/japplphysiol.00631.2001 ◽

2003 ◽

Vol 94 (1) ◽

pp. 38-42 ◽

Cited By ~ 127

Author(s):

R. D. Telford ◽

G. J. Sly ◽

A. G. Hahn ◽

R. B. Cunningham ◽

C. Bryant ◽

...

Keyword(s):

Oxygen Uptake ◽

Blood Cell ◽

Red Blood Cell ◽

Random Order ◽

Peak Oxygen Uptake ◽

Red Cell ◽

Free Hemoglobin ◽

Serum Haptoglobin ◽

Total Hemoglobin ◽

Exercise Induced

There is a wide body of literature reporting red cell hemolysis as occurring after various forms of exercise. Whereas the trauma associated with footstrike is thought to be the major cause of hemolysis after running, its significance compared with hemolysis that results from other circulatory stresses on the red blood cell has not been thoroughly addressed. To investigate the significance of footstrike, we measured the degree of hemolysis after 1 h of running. To control for the potential effects of oxidative and circulatory stresses on the red blood cell, the same subjects cycled for 1 h at equivalent oxygen uptake. Our subjects were 10 male triathletes, who each completed two separate 1-h sessions of running and cycling at 75% peak oxygen uptake, which were performed in random order 1 wk apart. Plasma free hemoglobin and serum haptoglobin concentrations were measured as indicators of hemolysis. We also measured methemoglobin as a percentage of total hemoglobin immediately postexercise as an indicator of red cell oxidative stress. Plasma free hemoglobin increased after both running ( P < 0.01) and cycling ( P < 0.01), but the increase was fourfold greater after running ( P < 0.01). This was reflected by a significant fall in haptoglobin 1 h after the running trials, whereas no significant changes occurred after cycling at any sample point. Methemoglobin increased twofold after both running and cycling ( P < 0.01), with no significant differences between modes of exercise. The present data indicate that, whereas general circulatory trauma to the red blood cells associated with 1 h of exercise at 75% maximal oxygen uptake may result in some exercise-induced hemolysis, footstrike is the major contributor to hemolysis during running.

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Factors Related to Self-care in Patients with Type 2 Diabetes

The Open Nursing Journal ◽

10.2174/1874434602014010064 ◽

2020 ◽

Vol 14 (1) ◽

pp. 64-73

Author(s):

Seung-Yeon Kong ◽

Mi-Kyoung Cho

Keyword(s):

Type 2 Diabetes ◽

Self Efficacy ◽

Smoking Status ◽

Explanatory Power ◽

Fasting Blood Glucose ◽

Self Care ◽

Self Report ◽

University Hospital ◽

Diabetes Patients

Purpose: The prevalence of diabetes and the personal and national burden from diabetes, a serious health issue around the globe, continues to increase. The purpose of this study was to identify factors influencing self-care among patients with type 2 diabetes. Methods: We conducted a cross-sectional descriptive survey of 118 outpatients with type 2 diabetes in national university hospital C in Korea. Data were collected from self-report questionnaires covering information on demographics, self-care, and self-efficacy. Additional data were collected from medical records including information on HbA1c, fasting blood glucose levels, and cholesterol levels. Collected data were analyzed using descriptive statistics, Pearson’s correlation coefficient, and multiple regression using SPSS/WIN version 22.0 software. Results: Factors affecting self-care were the following four: self-efficacy, HbA1c, occupation status, and smoking status. Higher engagement in self-care was associated with higher self-efficacy (β = .53, p < .001), lower HbA1c (β = -0.33, p < .001), unemployment (β = -0.20, p < .001), and non-smoking status (β = -0.15, p = .011). The regression model of self-care among the type 2 diabetes patients was statistically significant (F = 67.15, p < .001), and the explanatory power of the adjusted R2 was 69%. Conclusion: Type 2 diabetes patients with high self-efficacy and self-care scores showed good glycemic control. Therefore, this finding suggests that nursing interventions should be developed to enhance self-efficacy, which is the greatest influencing factor for self-care.

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Neonatal Neurosonographic Correlates of Cerebral Palsy in Preterm Infants

PEDIATRICS ◽

10.1542/peds.78.1.88 ◽

1986 ◽

Vol 78 (1) ◽

pp. 88-95

Author(s):

Leonard J. Graziani ◽

Matthew Pasto ◽

Christian Stanley ◽

Frank Pidcock ◽

Hemant Desai ◽

...

Keyword(s):

Cerebral Palsy ◽

Preterm Infants ◽

Intracranial Hemorrhage ◽

Motor Development ◽

Periventricular Leukomalacia ◽

Cyst Formation ◽

University Hospital ◽

Lateral Ventricles ◽

Minimum Age ◽

Grade Iii

Serial neurosonographic examinations are routinely performed at frequent intervals during the nursery course of all preterm infants of 33 weeks or less gestation who are admitted to the intensive care nursery of Thomas Jefferson University Hospital. After discharge, the following survivors during the past 5 years had repeated ultrasound examinations until the anterior fontanel closed and clinical assessments until the presence or absence of cerebral palsy at a minimum age of 12 months was established: (1) all infants with grade III/IV intracranial hemorrhage, periventricular echodensity and periventricular cyst formation, (2) selected infants with either normal ultrasound findings or grade I/II intracranial hemorrhage. Fifteen survivors were found to have cerebral palsy, and all had at least one of the following ultrasound abnormalities: (a) diffuse, bilateral, and multiple periventricular cysts 3 mm or more in diameter that persisted beyond term age, (b) bilateral asymmetrical dilation of the lateral ventricles following grade III intracranial hemorrhage with small periventricular cysts, and (c) ventricular porencephaly following an ipsilateral grade IV intracranial hemorrhage. The periventricular cysts were usually preceded by extensive echodensities of the white matter surrounding the lateral ventricles; these findings were suggestive of periventricular leukomalacia and were the most common abnormal findings on ultrasound in the infants with cerebral palsy. Of 124 infants without cerebral palsy, 121 had no or less severe abnormal findings on ultrasound; the exceptions were three infants with bilateral persistent large periventricular cysts who had normal motor development in late infancy.

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Abstract WMP106: Soluble CD163 as a Prognostic Marker for Perihematomal Edema Formation and Functional Outcomes in Intracerebral Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.wmp106 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Meaghan Roy-O’Reilly ◽

Davis So ◽

Glenda Torres ◽

Liang Zhu ◽

Jaroslaw Aronowski ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Functional Outcomes ◽

Mixed Model ◽

Linear Mixed Model ◽

Tissue Injury ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Edema Formation ◽

Soluble Cd163 ◽

Perihematomal Edema

Introduction: Macrophages are the predominant cell capable of removing toxic hemoglobin at sites of tissue injury, and CD163 has been recognized as the hemoglobin scavenger receptor present on the macrophage cell surface. In this study, we explored the levels of soluble CD163 (sCD163) in patients with intracerebral hemorrhage (ICH) to ascertain whether sCD163 was associated with clinicoradiologic features and long-term functional outcomes. Methods: Our ICH cohort was comprised of 50 patients with moderate-sized basal ganglia hematomas. We collected serial serum and cerebrospinal fluid (CSF) at pre-specified timepoints (24 hours, 48 hours, 3-5 days, 6-8 days, and greater than 10 days post-ictus). We also obtained samples from 10 healthy controls. Levels of sCD163 were measured by enzyme-linked immunosorbent assay. A linear mixed model was used to compare sCD163 values among various groups, using a Bonferroni correction for multiple test adjustment. The method of generalized estimating equations was used to determine associations with dichotomized outcomes (modified Rankin Scale score 0-3 versus 4-6). Results: Compared to healthy controls, serum sCD163 was higher in the ICH patients (40.6 versus 128.4 ng/mL). Within the ICH cohort, early values (24 hours to 5 days post-ictus) of serum sCD163 were significantly higher in patients who elaborated minimal perihematomal edema (PHE) (200.3 in patients with less than 10 mL PHE versus 71.8; p = 0.046). 6 to greater than 10 days post-ictus, sCD163 levels tailed off for patients with less PHE whereas levels rose in patients with greater PHE. Continued subacute elevation of sCD163, particularly in the CSF, was highly associated with poorer outcomes, both at discharge and at 90 days (p < 0.001). These associations were independent of age, gender, peak hematoma volume, and ICH score; there was a statistically significant association of CSF sCD163 values with degree of intraventricular hemorrhage (p = 0.04). Conclusions: sCD163 may be a dynamic marker in ICH, with acute levels distinguishing edema patterns and subacute levels predicting functional outcome. Further studies are needed to confirm these findings and explore the pathophysiology behind these observations.

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Toward robust mammography-based models for breast cancer risk

Science Translational Medicine ◽

10.1126/scitranslmed.aba4373 ◽

2021 ◽

Vol 13 (578) ◽

pp. eaba4373 ◽

Cited By ~ 1

Author(s):

Adam Yala ◽

Peter G. Mikhael ◽

Fredrik Strand ◽

Gigin Lin ◽

Kevin Smith ◽

...

Keyword(s):

Breast Cancer ◽

Deep Learning ◽

High Risk ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Massachusetts General Hospital ◽

The United States ◽

University Hospital ◽

Chang Gung Memorial Hospital ◽

Risk Models

Improved breast cancer risk models enable targeted screening strategies that achieve earlier detection and less screening harm than existing guidelines. To bring deep learning risk models to clinical practice, we need to further refine their accuracy, validate them across diverse populations, and demonstrate their potential to improve clinical workflows. We developed Mirai, a mammography-based deep learning model designed to predict risk at multiple timepoints, leverage potentially missing risk factor information, and produce predictions that are consistent across mammography machines. Mirai was trained on a large dataset from Massachusetts General Hospital (MGH) in the United States and tested on held-out test sets from MGH, Karolinska University Hospital in Sweden, and Chang Gung Memorial Hospital (CGMH) in Taiwan, obtaining C-indices of 0.76 (95% confidence interval, 0.74 to 0.80), 0.81 (0.79 to 0.82), and 0.79 (0.79 to 0.83), respectively. Mirai obtained significantly higher 5-year ROC AUCs than the Tyrer-Cuzick model (P < 0.001) and prior deep learning models Hybrid DL (P < 0.001) and Image-Only DL (P < 0.001), trained on the same dataset. Mirai more accurately identified high-risk patients than prior methods across all datasets. On the MGH test set, 41.5% (34.4 to 48.5) of patients who would develop cancer within 5 years were identified as high risk, compared with 36.1% (29.1 to 42.9) by Hybrid DL (P = 0.02) and 22.9% (15.9 to 29.6) by the Tyrer-Cuzick model (P < 0.001).

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