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  1. Article ; Online: A Host of Host Assays: The Clinical Accuracy of Two Host Gene Expression Assays in Acute Infection.

    Vlasschaert, Caitlyn / Rauh, Michael J

    Critical care medicine

    2021  Volume 49, Issue 10, Page(s) 1812–1814

    MeSH term(s) Gene Expression ; Humans ; Influenza, Human
    Language English
    Publishing date 2021-09-16
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 197890-1
    ISSN 1530-0293 ; 0090-3493
    ISSN (online) 1530-0293
    ISSN 0090-3493
    DOI 10.1097/CCM.0000000000005220
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    Zs.A 1261: Show issues Location:
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  2. Article ; Online: Microscopic hematuria.

    Vlasschaert, Caitlyn / Lanktree, Matthew B

    CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne

    2020  Volume 192, Issue 14, Page(s) E370

    MeSH term(s) Cystoscopy ; Hematuria/diagnosis ; Hematuria/etiology ; Humans ; Kidney Diseases/complications ; Kidney Diseases/genetics ; Urinalysis
    Language English
    Publishing date 2020-04-05
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 215506-0
    ISSN 1488-2329 ; 0008-4409 ; 0820-3946
    ISSN (online) 1488-2329
    ISSN 0008-4409 ; 0820-3946
    DOI 10.1503/cmaj.191615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A DNA methylation based measure outperforms circulating CRP as a marker of chronic inflammation and partly reflects the monocytic response to long-term inflammatory exposure: A Canadian Longitudinal Study on Aging analysis.

    Verschoor, Chris P / Vlasschaert, Caitlyn / Rauh, Michael J / Paré, Guillaume

    Aging cell

    2023  Volume 22, Issue 7, Page(s) e13863

    Abstract: A key hallmark in the age-related dysfunction of physiological systems is disruption related to the regulation of inflammation, often resulting in a chronic, low-grade inflammatory state (i.e., inflammaging). In order to understand the causes of overall ... ...

    Abstract A key hallmark in the age-related dysfunction of physiological systems is disruption related to the regulation of inflammation, often resulting in a chronic, low-grade inflammatory state (i.e., inflammaging). In order to understand the causes of overall system decline, methods to quantify the life-long exposure or damage related to chronic inflammation are critical. Here, we characterize a comprehensive epigenetic inflammation score (EIS) based on DNA methylation loci (CpGs) that are associated with circulating levels of C-reactive protein (CRP). In a cohort of 1446 older adults, we show that associations to age and health-related traits such as smoking history, chronic conditions, and established measures of accelerated aging were stronger for EIS than CRP, while the risk of longitudinal outcomes such as outpatient or inpatient visits and increased frailty were relatively similar. To determine whether variation in EIS actually reflects the cellular response to chronic inflammation we exposed THP1 myelo-monocytic cells to low levels of inflammatory mediators for 14 days, finding that EIS increased in response to both CRP (p = 0.011) and TNF (p = 0.068). Interestingly, a refined version of EIS based only on those CpGs that changed in vitro was more strongly associated with many of the aforementioned traits as compared to EIS. In conclusion, our study demonstrates that EIS outperforms circulating CRP with regard to its association to health-traits that are synonymous with chronic inflammation and accelerated aging, and substantiates its potential role as a clinically relevant tool for stratifying patient risk of adverse outcomes prior to treatment or following illness.
    MeSH term(s) Humans ; Aged ; C-Reactive Protein/metabolism ; DNA Methylation/genetics ; Longitudinal Studies ; Canada ; Inflammation/genetics ; Aging/genetics
    Chemical Substances C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2023-05-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13863
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  4. Article: Clonal hematopoiesis of indeterminate potential-associated non-small cell lung cancer risk is potentiated by small particulate matter air pollution among non-smokers: a novel somatic variant-environment interaction.

    Vlasschaert, Caitlyn / Buttigieg, Marco / Pershad, Yash / Lanktree, Matthew / Aldrich, Melinda C / Rauh, Michael J / Bick, Alexander G

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Small particulate matter air pollution ( ... ...

    Abstract Small particulate matter air pollution (PM
    Language English
    Publishing date 2024-01-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.17.24301439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Interleukin-6 Receptor Polymorphism Attenuates Clonal Hematopoiesis-Mediated Coronary Artery Disease Risk Among 451 180 Individuals in the UK Biobank.

    Vlasschaert, Caitlyn / Heimlich, J Brett / Rauh, Michael J / Natarajan, Pradeep / Bick, Alexander G

    Circulation

    2023  Volume 147, Issue 4, Page(s) 358–360

    MeSH term(s) Humans ; Coronary Artery Disease ; Clonal Hematopoiesis ; Biological Specimen Banks ; Receptors, Interleukin-6/genetics ; United Kingdom ; Mutation
    Chemical Substances Receptors, Interleukin-6
    Language English
    Publishing date 2023-01-23
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.122.062126
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Solid organ transplant recipients exhibit more TET2-mutant clonal hematopoiesis of indeterminate potential not driven by increased transplantation risk.

    Silver, Alexander J / Vlasschaert, Caitlyn / Mack, Taralynn / Sharber, Brian / Xu, Yaomin / Bick, Alexander G / Pinson, C Wright / Savona, Michael R

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2024  

    Abstract: Purpose: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk ... ...

    Abstract Purpose: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants.
    Experimental design: We use two national biobank cohorts comprised of >650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts.
    Results: We find individuals with an allograft prior to their biobank enrollment had an increased prevalence of TET2 mutations (OR 1.90; p = 4.0e-4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. Additionally, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR 1.02; p = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure.
    Conclusions: These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.
    Language English
    Publishing date 2024-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-3840
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    Zs.A 4223: Show issues Location:
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  7. Article ; Online: Clonal haematopoiesis, ageing and kidney disease.

    Vlasschaert, Caitlyn / Lanktree, Matthew B / Rauh, Michael J / Kelly, Tanika N / Natarajan, Pradeep

    Nature reviews. Nephrology

    2023  Volume 20, Issue 3, Page(s) 161–174

    Abstract: Clonal haematopoiesis of indeterminate potential (CHIP) is a preclinical condition wherein a sizeable proportion of an individual's circulating blood cells are derived from a single mutated haematopoietic stem cell. CHIP occurs frequently with ageing - ... ...

    Abstract Clonal haematopoiesis of indeterminate potential (CHIP) is a preclinical condition wherein a sizeable proportion of an individual's circulating blood cells are derived from a single mutated haematopoietic stem cell. CHIP occurs frequently with ageing - more than 10% of individuals over 65 years of age are affected - and is associated with an increased risk of disease across several organ systems and premature death. Emerging evidence suggests that CHIP has a role in kidney health, including associations with predisposition to acute kidney injury, impaired recovery from acute kidney injury and kidney function decline, both in the general population and among those with chronic kidney disease. Beyond its direct effect on the kidney, CHIP elevates the susceptibility of individuals to various conditions that can detrimentally affect the kidneys, including cardiovascular disease, obesity and insulin resistance, liver disease, gout, osteoporosis and certain autoimmune diseases. Aberrant pro-inflammatory signalling, telomere attrition and epigenetic ageing are potential causal pathophysiological pathways and mediators that underlie CHIP-related disease risk. Experimental animal models have shown that inhibition of inflammatory cytokine signalling can ameliorate many of the pathological effects of CHIP, and assessment of the efficacy and safety of this class of medications for human CHIP-associated pathology is ongoing.
    MeSH term(s) Animals ; Humans ; Clonal Hematopoiesis ; Hematopoiesis/physiology ; Aging ; Hematopoietic Stem Cells/metabolism ; Acute Kidney Injury/metabolism ; Mutation
    Language English
    Publishing date 2023-10-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2490366-8
    ISSN 1759-507X ; 1759-5061
    ISSN (online) 1759-507X
    ISSN 1759-5061
    DOI 10.1038/s41581-023-00778-x
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    Zs.A 6334: Show issues Location:
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    Zs.MG 107: Show issues

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  8. Article ; Online: The Myeloid-Kidney Interface in Health and Disease.

    Vlasschaert, Caitlyn / Moran, Sarah M / Rauh, Michael J

    Clinical journal of the American Society of Nephrology : CJASN

    2021  Volume 17, Issue 2, Page(s) 323–331

    Abstract: Kidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident ... ...

    Abstract Kidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident proinflammatory and profibrotic macrophages leads to kidney structural damage and scarring after kidney injury. Fibrosis throughout the kidney parenchyma contributes to the progressive functional decline observed in CKD, independent of the etiology. Circulating myeloid cells bearing intrinsic defects also affect the kidney substructures, such as neutrophils activated by autoantibodies that cause GN in ANCA-associated vasculitis. The kidney can also be affected by disorders of myelopoiesis, including myeloid leukemias (acute and chronic myeloid leukemias) and myelodysplastic syndromes. Clonal hematopoiesis of indeterminate potential is a common, newly recognized premalignant clinical entity characterized by clonal expansion of hyperinflammatory myeloid lineage cells that may have significant kidney sequelae. A number of existing therapies in CKD target myeloid cells and inflammation, including glucocorticoid receptor agonists and mineralocorticoid receptor antagonists. The therapeutic indications for these and other myeloid cell-targeted treatments is poised to expand as our understanding of the myeloid-kidney interface evolves.
    MeSH term(s) Humans ; Kidney/physiology ; Kidney Diseases/etiology ; Myeloid Cells/physiology
    Language English
    Publishing date 2021-09-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2226665-3
    ISSN 1555-905X ; 1555-9041
    ISSN (online) 1555-905X
    ISSN 1555-9041
    DOI 10.2215/CJN.04120321
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  9. Article ; Online: Sodium/glucose cotransporter 2 inhibitors in chronic kidney disease and heart failure: ready for prime time in patients without diabetes.

    Vlasschaert, Caitlyn / Sidhu, Bikrampal / Silver, Samuel A

    Current opinion in nephrology and hypertension

    2021  Volume 30, Issue 3, Page(s) 361–368

    Abstract: Purpose of review: The benefits of sodium/glucose cotransporter 2 (SGLT2) inhibitors seem to extend beyond glycemic control. We review recent randomized trial evidence evaluating SGLT2 inhibition in nondiabetic settings, including in patients with ... ...

    Abstract Purpose of review: The benefits of sodium/glucose cotransporter 2 (SGLT2) inhibitors seem to extend beyond glycemic control. We review recent randomized trial evidence evaluating SGLT2 inhibition in nondiabetic settings, including in patients with chronic kidney disease (CKD) and heart failure (HF).
    Recent findings: DAPA-CKD, DAPA-HF and EMPEROR-Reduced compared SGLT2 inhibitors to placebo, enrolling 5868 patients without diabetes. In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73 m2 and macroalbuminuria irrespective of kidney disease aetiology had improved cardiovascular and kidney outcomes if randomized to receive SGLT2 inhibitors (primary composite endpoint: hazard ratio [HR] 0.61, 95% CI 0.51-0.72; absolute risk reduction [ARR] 5.3%). In DAPA-HF and EMPEROR-Reduced, participants with reduced ejection fraction (HFrEF) had improved cardiovascular outcomes when an SGLT2 inhibitor was added to guideline-directed medical therapy, mainly through a reduction in HF hospitalizations (HR 0.70, 95% CI 0.59-0.83; ARR 3.7% and HR 0.69, 95% CI 0.59-0.81; ARR 5.1% with dapagliflozin and empagliflozin, respectively). In all 3 trials, the benefits were not modified by diabetes, baseline eGFR or proteinuria.
    Summary: SGLT2 inhibitors improve kidney and HF outcomes in patients with high-risk CKD and HFrEF, irrespective of diabetes. Clinicians should become more comfortable prescribing these medications as we await studies that may further broaden their indications.
    MeSH term(s) Diabetes Mellitus/drug therapy ; Heart Failure/drug therapy ; Humans ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic/drug therapy ; Sodium-Glucose Transport Proteins/antagonists & inhibitors ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Stroke Volume
    Chemical Substances Sodium-Glucose Transport Proteins ; Sodium-Glucose Transporter 2 Inhibitors
    Language English
    Publishing date 2021-10-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1151092-4
    ISSN 1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
    ISSN (online) 1473-6543 ; 1535-3842
    ISSN 1062-4813 ; 1062-4821
    DOI 10.1097/MNH.0000000000000703
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    Zs.A 3686: Show issues Location:
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  10. Article ; Online: Infection risk associated with clonal hematopoiesis of indeterminate potential is partly mediated by hematologic cancer transformation in the UK Biobank.

    Vlasschaert, Caitlyn / Akwo, Elvis / Robinson-Cohen, Cassianne / Cook, Elina K / Lanktree, Matthew B / Rauh, Michael J / Bick, Alexander G

    Leukemia

    2023  Volume 37, Issue 11, Page(s) 2306–2308

    MeSH term(s) Humans ; Clonal Hematopoiesis ; Biological Specimen Banks ; Hematologic Neoplasms/genetics ; Hematopoiesis/genetics ; Disease Susceptibility ; United Kingdom/epidemiology ; Mutation
    Language English
    Publishing date 2023-09-09
    Publishing country England
    Document type Letter
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-023-02023-7
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