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  1. AU="Hancock, Brandon"
  2. AU="Gatesy, Samuel W M"
  3. AU="Chénard, Caroline"
  4. AU="Krishna Chinthapalli"
  5. AU="Eneyda Secada Cárdenas"
  6. AU="Talbot, Nick"
  7. AU="Perez-Shibayama, Christian"
  8. AU="Melissa M. Mills"
  9. AU="Goli, Haneesha"
  10. AU="Viviana Falcón-Cama"
  11. AU="Januschek, Friederike"
  12. AU="Bonilla-Aldana, D. Katterine"
  13. AU="Stix, Michael S"
  14. AU="Xiao, Bing"
  15. AU="Algattas, Hanna N"
  16. AU="Ihm, M"
  17. AU="Nivelo, Luis A"
  18. AU="Nirja Kaka"
  19. AU="Bahnă, Adriana Florina"
  20. AU="Wen, Changchun"
  21. AU="Nizami, Sarea Islam Nuha"
  22. AU="Douglas J Kelly"
  23. AU=Kingston Elizabeth V
  24. AU="Jyoti Nepal"
  25. AU="González, Ana M Martín"

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  1. Artikel ; Online: Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells.

    Ng, Julie / Marneth, Anna E / Griffith, Alec / Younger, Daniel / Ghanta, Sailaja / Jiao, Alan / Willis, Gareth / Han, Junwen / Imani, Jewel / Niu, Bailin / Keegan, Joshua W / Hancock, Brandon / Guo, Fei / Shi, Yang / Perrella, Mark A / Lederer, James A

    Journal of innate immunity

    2023  Band 15, Heft 1, Seite(n) 765–781

    Abstract: Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We ... ...

    Abstract Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis. Here, we used a chimeric mouse model to demonstrate that MSCs secrete paracrine factors that act on lineage-negative c-kit+ hematopoietic stem cells (HSCs), leaving them "poised" to enhance emergency granulopoiesis months after transplantation. Chimeric mice developed from HSCs exposed to conditioned media from MSCs and CpG-ODN-preconditioned MSCs showed significantly higher bacterial clearance and increased neutrophil granulopoiesis following lung infection than control mice. By Cleavage Under Targets and Release Using Nuclease (CUT&RUN) chromatin sequencing, we identified that MSC-conditioned media leaves H3K4me3 histone marks in HSCs at genes involved in myelopoiesis and in signaling persistence by the mTOR pathway. Both soluble factors and extracellular vesicles from MSCs mediated these effects on HSCs and proteomic analysis by mass spectrometry revealed soluble calreticulin as a potential mediator. In summary, this study demonstrates that trained immunity can be mediated by paracrine factors from MSCs to induce neutrophil-trained immunity by reprogramming HSCs for long-lasting functional changes in neutrophil-mediated antimicrobial immunity.
    Mesh-Begriff(e) Mice ; Animals ; Mesenchymal Stem Cell Transplantation ; Neutrophils ; Culture Media, Conditioned/metabolism ; Proteomics ; Trained Immunity ; Hematopoietic Stem Cells ; Mesenchymal Stem Cells/metabolism
    Chemische Substanzen Culture Media, Conditioned
    Sprache Englisch
    Erscheinungsdatum 2023-10-05
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2454158-8
    ISSN 1662-8128 ; 1662-811X
    ISSN (online) 1662-8128
    ISSN 1662-811X
    DOI 10.1159/000533732
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping.

    Guo, Fei / Hancock, Brandon / Griffith, Alec / Lin, Hui / Howard, Kaitlyn / Keegan, Joshua / Zhang, Fan / Chicoine, Adam / Cahill, Laura / Ng, Julie / Lederer, James

    Frontiers in immunology

    2022  Band 13, Seite(n) 833100

    Abstract: ... ...

    Abstract CD4
    Mesh-Begriff(e) Animals ; Cell Proliferation ; Mice ; Receptors, Antigen, T-Cell, alpha-beta ; T-Lymphocytes, Regulatory
    Chemische Substanzen Receptors, Antigen, T-Cell, alpha-beta
    Sprache Englisch
    Erscheinungsdatum 2022-05-12
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.833100
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  3. Artikel ; Online: Severe cerebral edema in substance-related cardiac arrest patients.

    Kulpanowski, Annelise M / Copen, William A / Hancock, Brandon L / Rosenthal, Eric S / Schoenfeld, David A / Dodelson, Jacob A / Edlow, Brian L / Kimberly, W Taylor / Amorim, Edilberto / Westover, M Brandon / Ning, Ming Ming / Schaefer, Pamela W / Malhotra, Rajeev / Giacino, Joseph T / Greer, David M / Wu, Ona

    Resuscitation

    2022  Band 173, Seite(n) 103–111

    Abstract: Background: Studies of neurologic outcomes have found conflicting results regarding differences between patients with substance-related cardiac arrests (SRCA) and non-SRCA. We investigate the effects of SRCA on severe cerebral edema development, a ... ...

    Abstract Background: Studies of neurologic outcomes have found conflicting results regarding differences between patients with substance-related cardiac arrests (SRCA) and non-SRCA. We investigate the effects of SRCA on severe cerebral edema development, a neuroimaging intermediate endpoint for neurologic injury.
    Methods: 327 out-of-hospital comatose cardiac arrest patients were retrospectively analyzed. Demographics and baseline clinical characteristics were examined. SRCA categorization was based on admission toxicology screens. Severe cerebral edema classification was based on radiology reports. Poor clinical outcomes were defined as discharge Cerebral Performance Category scores > 3.
    Results: SRCA patients (N = 86) were younger (P < 0.001), and more likely to have non-shockable rhythms (P < 0.001), be unwitnessed (P < 0.001), lower Glasgow Coma Scale scores (P < 0.001), absent brainstem reflexes (P < 0.05) and develop severe cerebral edema (P < 0.001) than non-SRCA patients (N = 241). Multivariable analyses found younger age (P < 0.001), female sex (P = 0.008), non-shockable rhythm (P = 0.01) and SRCA (P = 0.05) to be predictors of severe cerebral edema development. Older age (P < 0.001), non-shockable rhythm (P = 0.02), severe cerebral edema (P < 0.001), and absent pupillary light reflexes (P = 0.004) were predictors of poor outcomes. SRCA patients had higher proportion of brain deaths (P < 0.001) compared to non-SRCA patients.
    Conclusions: SRCA results in higher rates of severe cerebral edema development and brain death. The absence of statistically significant differences in discharge outcomes or survival between SRCA and non-SRCA patients may be related to the higher rate of withdrawal of life-sustaining treatment (WLST) in the non-SRCA group. Future neuroprognostic studies may opt to include neuroimaging markers as intermediate measures of neurologic injury which are not influenced by WLST decisions.
    Mesh-Begriff(e) Brain Edema/diagnostic imaging ; Brain Edema/etiology ; Cardiopulmonary Resuscitation/methods ; Coma ; Female ; Glasgow Coma Scale ; Humans ; Out-of-Hospital Cardiac Arrest/etiology ; Out-of-Hospital Cardiac Arrest/therapy ; Retrospective Studies
    Sprache Englisch
    Erscheinungsdatum 2022-02-08
    Erscheinungsland Ireland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 189901-6
    ISSN 1873-1570 ; 0300-9572
    ISSN (online) 1873-1570
    ISSN 0300-9572
    DOI 10.1016/j.resuscitation.2022.01.033
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.

    Horisberger, Alice / Griffith, Alec / Keegan, Joshua / Arazi, Arnon / Pulford, John / Murzin, Ekaterina / Howard, Kaitlyn / Hancock, Brandon / Fava, Andrea / Sasaki, Takanori / Ghosh, Tusharkanti / Inamo, Jun / Beuschel, Rebecca / Cao, Ye / Preisinger, Katie / Gutierrez-Arcelus, Maria / Eisenhaure, Thomas M / Guthridge, Joel / Hoover, Paul J /
    Dall'Era, Maria / Wofsy, David / Kamen, Diane L / Kalunian, Kenneth C / Furie, Richard / Belmont, Michael / Izmirly, Peter / Clancy, Robert / Hildeman, David / Woodle, E Steve / Apruzzese, William / McMahon, Maureen A / Grossman, Jennifer / Barnas, Jennifer L / Payan-Schober, Fernanda / Ishimori, Mariko / Weisman, Michael / Kretzler, Matthias / Berthier, Celine C / Hodgin, Jeffrey B / Demeke, Dawit S / Putterman, Chaim / Brenner, Michael B / Anolik, Jennifer H / Raychaudhuri, Soumya / Hacohen, Nir / James, Judith A / Davidson, Anne / Petri, Michelle A / Buyon, Jill P / Diamond, Betty / Zhang, Fan / Lederer, James A / Rao, Deepak A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations ... ...

    Abstract Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation in patients with LN and to identify correlates of renal parameters and treatment response. Unbiased analysis identified 3 immunologically distinct groups of patients with LN that were associated with different patterns of histopathology, renal cell infiltrates, urine proteomic profiles, and treatment response at one year. Patients with enriched circulating granzyme B+ T cells at baseline showed more severe disease and increased numbers of activated CD8 T cells in the kidney, yet they had the highest likelihood of treatment response. A second group characterized primarily by a high type I interferon signature had a lower likelihood of response to therapy, while a third group appeared immunologically inactive by immunophenotyping at enrollment but with chronic renal injuries. Main immune profiles could be distilled down to 5 simple cytometric parameters that recapitulate several of the associations, highlighting the potential for blood immune profiling to translate to clinically useful non-invasive metrics to assess immune-mediated disease in LN.
    Sprache Englisch
    Erscheinungsdatum 2024-03-09
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.01.14.575609
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.

    Inamo, Jun / Keegan, Joshua / Griffith, Alec / Ghosh, Tusharkanti / Horisberger, Alice / Howard, Kaitlyn / Pulford, John / Murzin, Ekaterina / Hancock, Brandon / Jonsson, Anna Helena / Seifert, Jennifer / Feser, Marie L / Norris, Jill M / Cao, Ye / Apruzzese, William / Louis Bridges, S / Bykerk, Vivian / Goodman, Susan / Donlin, Laura /
    Firestein, Gary S / Perlman, Harris / Bathon, Joan M / Hughes, Laura B / Tabechian, Darren / Filer, Andrew / Pitzalis, Costantino / Anolik, Jennifer H / Moreland, Larry / Guthridge, Joel M / James, Judith A / Brenner, Michael B / Raychaudhuri, Soumya / Sparks, Jeffrey A / Michael Holers, V / Deane, Kevin D / Lederer, James A / Rao, Deepak A / Zhang, Fan

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in 'At-Risk' populations prior to clinical disease onset is crucial to establishing ... ...

    Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in 'At-Risk' populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48). We identified significant cell expansions in At-Risk individuals compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5
    Sprache Englisch
    Erscheinungsdatum 2023-07-04
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.07.03.547507
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Imaging cellulose synthase motility during primary cell wall synthesis in the grass Brachypodium distachyon.

    Liu, Derui / Zehfroosh, Nina / Hancock, Brandon L / Hines, Kevin / Fang, Wenjuan / Kilfoil, Maria / Learned-Miller, Erik / Sanguinet, Karen A / Goldner, Lori S / Baskin, Tobias I

    Scientific reports

    2017  Band 7, Heft 1, Seite(n) 15111

    Abstract: The mechanism of cellulose synthesis has been studied by characterizing the motility of cellulose synthase complexes tagged with a fluorescent protein; however, this approach has been used exclusively on the hypocotyl of Arabidopsis thaliana. Here we ... ...

    Abstract The mechanism of cellulose synthesis has been studied by characterizing the motility of cellulose synthase complexes tagged with a fluorescent protein; however, this approach has been used exclusively on the hypocotyl of Arabidopsis thaliana. Here we characterize cellulose synthase motility in the model grass, Brachypodium distachyon. We generated lines in which mEGFP is fused N-terminal to BdCESA3 or BdCESA6 and which grew indistinguishably from the wild type (Bd21-3) and had dense fluorescent puncta at or near the plasma membrane. Measured with a particle tracking algorithm, the average speed of GFP-BdCESA3 particles in the mesocotyl was 164 ± 78 nm min
    Mesh-Begriff(e) Arabidopsis/genetics ; Arabidopsis/metabolism ; Brachypodium/genetics ; Brachypodium/metabolism ; Cell Membrane/metabolism ; Cell Wall/genetics ; Cell Wall/metabolism ; Cellulose/metabolism ; Glucosyltransferases/genetics ; Glucosyltransferases/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Microscopy, Fluorescence ; Plant Proteins/genetics ; Plant Proteins/metabolism ; Plants, Genetically Modified ; Protein Transport ; Seedlings/genetics ; Seedlings/metabolism
    Chemische Substanzen Plant Proteins ; Green Fluorescent Proteins (147336-22-9) ; Cellulose (9004-34-6) ; Glucosyltransferases (EC 2.4.1.-) ; cellulose synthase (EC 2.4.1.-)
    Sprache Englisch
    Erscheinungsdatum 2017-11-08
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-14988-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics.

    Bonkhoff, Anna K / Ullberg, Teresa / Bretzner, Martin / Hong, Sungmin / Schirmer, Markus D / Regenhardt, Robert W / Donahue, Kathleen L / Nardin, Marco J / Dalca, Adrian V / Giese, Anne-Katrin / Etherton, Mark R / Hancock, Brandon L / Mocking, Steven J T / McIntosh, Elissa C / Attia, John / Cole, John W / Donatti, Amanda / Griessenauer, Christoph J / Heitsch, Laura /
    Holmegaard, Lukas / Jood, Katarina / Jimenez-Conde, Jordi / Kittner, Steven J / Lemmens, Robin / Levi, Christopher R / McDonough, Caitrin W / Meschia, James F / Phuah, Chia-Ling / Ropele, Stefan / Rosand, Jonathan / Roquer, Jaume / Rundek, Tatjana / Sacco, Ralph L / Schmidt, Reinhold / Sharma, Pankaj / Slowik, Agnieszka / Sousa, Alessandro / Stanne, Tara M / Strbian, Daniel / Tatlisumak, Turgut / Thijs, Vincent / Vagal, Achala / Woo, Daniel / Zand, Ramin / McArdle, Patrick F / Worrall, Bradford B / Jern, Christina / Lindgren, Arne G / Maguire, Jane / Wu, Ona / Frid, Petrea / Rost, Natalia S / Wasselius, Johan

    Frontiers in neuroscience

    2022  Band 16, Seite(n) 994458

    Abstract: Background purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.: Materials and methods: Analyses relied ... ...

    Abstract Background purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.
    Materials and methods: Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome.
    Results: We analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3,
    Conclusion: Multiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.
    Sprache Englisch
    Erscheinungsdatum 2022-08-25
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.994458
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

    Bonkhoff, Anna K / Schirmer, Markus D / Bretzner, Martin / Hong, Sungmin / Regenhardt, Robert W / Donahue, Kathleen L / Nardin, Marco J / Dalca, Adrian V / Giese, Anne-Katrin / Etherton, Mark R / Hancock, Brandon L / Mocking, Steven J T / McIntosh, Elissa C / Attia, John / Cole, John W / Donatti, Amanda / Griessenauer, Christoph J / Heitsch, Laura / Holmegaard, Lukas /
    Jood, Katarina / Jimenez-Conde, Jordi / Kittner, Steven J / Lemmens, Robin / Levi, Christopher R / McDonough, Caitrin W / Meschia, James F / Phuah, Chia-Ling / Ropele, Stefan / Rosand, Jonathan / Roquer, Jaume / Rundek, Tatjana / Sacco, Ralph L / Schmidt, Reinhold / Sharma, Pankaj / Slowik, Agnieszka / Sousa, Alessandro / Stanne, Tara M / Strbian, Daniel / Tatlisumak, Turgut / Thijs, Vincent / Vagal, Achala / Wasselius, Johan / Woo, Daniel / Zand, Ramin / McArdle, Patrick F / Worrall, Bradford B / Jern, Christina / Lindgren, Arne G / Maguire, Jane / Wu, Ona / Rost, Natalia S

    Human brain mapping

    2022  Band 44, Heft 4, Seite(n) 1579–1592

    Abstract: This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their ... ...

    Abstract This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.
    Mesh-Begriff(e) Female ; Humans ; Male ; Middle Aged ; Bayes Theorem ; Brain ; Ischemic Stroke/diagnostic imaging ; Ischemic Stroke/pathology ; Models, Neurological ; Stroke
    Sprache Englisch
    Erscheinungsdatum 2022-11-28
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1197207-5
    ISSN 1097-0193 ; 1065-9471
    ISSN (online) 1097-0193
    ISSN 1065-9471
    DOI 10.1002/hbm.26159
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome.

    Bonkhoff, Anna K / Hong, Sungmin / Bretzner, Martin / Schirmer, Markus D / Regenhardt, Robert W / Arsava, E Murat / Donahue, Kathleen / Nardin, Marco / Dalca, Adrian / Giese, Anne-Katrin / Etherton, Mark R / Hancock, Brandon L / Mocking, Steven J T / McIntosh, Elissa / Attia, John / Benavente, Oscar / Cole, John W / Donatti, Amanda / Griessenauer, Christoph /
    Heitsch, Laura / Holmegaard, Lukas / Jood, Katarina / Jimenez-Conde, Jordi / Kittner, Steven / Lemmens, Robin / Levi, Christopher / McDonough, Caitrin W / Meschia, James / Phuah, Chia-Ling / Rolfs, Arndt / Ropele, Stefan / Rosand, Jonathan / Roquer, Jaume / Rundek, Tatjana / Sacco, Ralph L / Schmidt, Reinhold / Sharma, Pankaj / Slowik, Agnieszka / Soederholm, Martin / Sousa, Alessandro / Stanne, Tara M / Strbian, Daniel / Tatlisumak, Turgut / Thijs, Vincent / Vagal, Achala / Wasselius, Johan / Woo, Daniel / Zand, Ramin / McArdle, Patrick / Worrall, Bradford B / Jern, Christina / Lindgren, Arne G / Maguire, Jane / Golland, Polina / Bzdok, Danilo / Wu, Ona / Rost, Natalia S

    Neurology

    2022  Band 99, Heft 13, Seite(n) e1364–e1379

    Abstract: Background and objectives: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways.: Methods: MR neuroimaging and NIH Stroke Scale data ... ...

    Abstract Background and objectives: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways.
    Methods: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age
    Results: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location.
    Discussion: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.
    Mesh-Begriff(e) Aged ; Bayes Theorem ; Brain Ischemia ; Female ; Humans ; Ischemic Stroke ; Leukoaraiosis/pathology ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Stroke ; White Matter/pathology
    Sprache Englisch
    Erscheinungsdatum 2022-07-08
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000200926
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Sex-specific lesion pattern of functional outcomes after stroke.

    Bonkhoff, Anna K / Bretzner, Martin / Hong, Sungmin / Schirmer, Markus D / Cohen, Alexander / Regenhardt, Robert W / Donahue, Kathleen L / Nardin, Marco J / Dalca, Adrian V / Giese, Anne-Katrin / Etherton, Mark R / Hancock, Brandon L / Mocking, Steven J T / McIntosh, Elissa C / Attia, John / Benavente, Oscar R / Bevan, Stephen / Cole, John W / Donatti, Amanda /
    Griessenauer, Christoph J / Heitsch, Laura / Holmegaard, Lukas / Jood, Katarina / Jimenez-Conde, Jordi / Kittner, Steven J / Lemmens, Robin / Levi, Christopher R / McDonough, Caitrin W / Meschia, James F / Phuah, Chia-Ling / Rolfs, Arndt / Ropele, Stefan / Rosand, Jonathan / Roquer, Jaume / Rundek, Tatjana / Sacco, Ralph L / Schmidt, Reinhold / Sharma, Pankaj / Slowik, Agnieszka / Söderholm, Martin / Sousa, Alessandro / Stanne, Tara M / Strbian, Daniel / Tatlisumak, Turgut / Thijs, Vincent / Vagal, Achala / Wasselius, Johan / Woo, Daniel / Zand, Ramin / McArdle, Patrick F / Worrall, Bradford B / Jern, Christina / Lindgren, Arne G / Maguire, Jane / Fox, Michael D / Bzdok, Danilo / Wu, Ona / Rost, Natalia S

    Brain communications

    2022  Band 4, Heft 2, Seite(n) fcac020

    Abstract: Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent ... ...

    Abstract Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
    Sprache Englisch
    Erscheinungsdatum 2022-02-02
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcac020
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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