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  • 1
    In: American Journal of Kidney Diseases, Elsevier BV, Vol. 82, No. 4 ( 2023-10), p. 443-453.e1
    Type of Medium: Online Resource
    ISSN: 0272-6386
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 2
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    Online Resource
    Elsevier BV ; 2020
    In:  Journal of the American College of Cardiology Vol. 75, No. 11 ( 2020-03), p. 896-
    In: Journal of the American College of Cardiology, Elsevier BV, Vol. 75, No. 11 ( 2020-03), p. 896-
    Type of Medium: Online Resource
    ISSN: 0735-1097
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1468327-1
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  • 3
    Online Resource
    Online Resource
    Mary Ann Liebert Inc ; 2021
    In:  Journal of Palliative Medicine Vol. 24, No. 4 ( 2021-04-01), p. 632-634
    In: Journal of Palliative Medicine, Mary Ann Liebert Inc, Vol. 24, No. 4 ( 2021-04-01), p. 632-634
    Type of Medium: Online Resource
    ISSN: 1096-6218 , 1557-7740
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2021
    detail.hit.zdb_id: 2030890-5
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of the American Society of Nephrology Vol. 31, No. 4 ( 2020-4), p. 855-864
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 4 ( 2020-4), p. 855-864
    Abstract: Cognitive impairment is common among individuals receiving maintenance hemodialysis, but few data exist regarding how well screening tests for cognitive function perform in this population. The authors assessed the ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test to predict severe cognitive impairment in a cohort of 150 patients on dialysis whose cognitive status had been first defined with a battery of neurocognitive tests. The Montreal Cognitive Assessment was the best-performing overall screening test, and the authors recommend it as the preferred test to screen for severe cognitive impairment in patients receiving maintenance hemodialysis. Identification of such impairment may then facilitate optimal medical management and discussion of relevant issues with patients and family members. Background Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management. Methods From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment. Using area-under-the-curve (AUC) analysis, we then examined the predictive ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test, determining each test’s performance for identifying severe cognitive impairment. Results Mean age was 64 years; 61% were men, 39% were black, and 94% had at least a high-school education. Of the 150 participants, 21% had normal cognitive function, 17% had mild cognitive impairment, 33% had moderate impairment, and 29% had severe impairment. The Montreal Cognitive Assessment had the highest overall predictive ability for severe cognitive impairment (AUC, 0.81); a score of ≤21 had a sensitivity of 86% and specificity of 55% for severe impairment, with a negative predictive value of 91%. The Trails B and Digit Symbol tests also performed reasonably well (AUCs, 0.73 and 0.78, respectively). The other tests had lower predictive performances. Conclusions The Montreal Cognitive Assessment, a widely available and brief cognitive screening tool, showed high sensitivity and moderate specificity in detecting severe cognitive impairment in patients on maintenance hemodialysis.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2029124-3
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  • 5
    In: ATS Scholar, American Thoracic Society
    Type of Medium: Online Resource
    ISSN: 2690-7097
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2023
    detail.hit.zdb_id: 3041845-8
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  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1401-1401
    Abstract: Neutrophils and macrophages are critical mediators of innate immunity that share multiple features, including differentiation from common myeloid progenitors that exhibit similar changes in protein expression profiles as they mature into each lineage. Proteins common to both lineages include those critical to phagocyte functions, such as antimicrobial enzymes, cell surface receptors and adhesion proteins. These cells also exhibit similar changes to their nuclear structure, at least during the early stages of differentiation when their nuclei become indented or kidney-shaped. While regulators that control myeloid cell protein expression are well characterized, very little is known about why changes occur to their nuclear shape or how this process is regulated. We previously reported that murine neutrophils with homozygous mutations in the lamin B receptor (Lbr) gene exhibited loss of nuclear lobulation, similar to Pelger-Huët anomaly found in humans with deficient LBR expression. These Lbr-/- neutrophils also exhibited deficient chemotaxis, oxidative bursts and proliferation at the promyelocyte stage, indicating that this inner nuclear envelope (NE) protein influences both nuclear morphology and functional maturation. Based on these results, we have studied possible roles of additional NE components in either neutrophil or macrophage differentiation. We focused on three NE-associated proteins that we found were differentially expressed during the maturation of each lineage, the two isoforms of A-type lamins (lamins A and C) that form intermediate filaments within the nuclear lamina, and a component of the linker of nucleoskeleton and cytoskeleton complex termed Sun2. We show that as mouse neutrophil progenitors mature, they exhibit increased Lbr and Sun2 expression but decreased amounts of lamin A or C, consistent with previous results generated from human myeloblastic HL-60 cells. By comparison, differentiating monocytes exhibit dramatically increased levels of lamin A/C expression but decreased levels of Lbr and Sun2 as they mature into macrophages. We hypothesize that these changes indicate that expression levels of each NE protein must be precisely regulated during normal neutrophil and macrophage differentiation, and therefore aberrant expression of these proteins will impact the maturation of either lineage. Moreover, changes in NE protein expression levels in maturing macrophages may affect functional responses in addition to those that mediate innate immunity, including those that support inflammation. To test this hypothesis, we have manipulated myeloid cell line models of mouse neutrophil or macrophage differentiation to overexpress lamin A, lamin C or Sun2, and have examined how overexpression of each protein affects their morphologic and functional maturation. Our studies demonstrate that overexpression of either lamin A or C causes a severe loss of nuclear lobulation in maturing neutrophils, while they accelerate nuclear maturation in differentiating macrophages. Neutrophils overexpressing each A-type lamin also exhibit deficient chemotaxis and phagocytosis, suggesting that these two responses depend on precise levels of each lamina protein. By comparison, mature macrophages overexpressing either lamin A or C exhibit deficient phagocytosis but increased Mac-1 expression that may lead to enhanced cellular adhesion. We also have preliminary evidence that indicate oxidative bursts produced by either lineage are enhanced by ectopic lamin A or C expression. Our preliminary studies of neutrophils with ectopic Sun2 expression indicate a disruption to GM-CSF-dependent growth at the promyelocyte stage similar to that observed in Lbr-/- promyelocytes, while those that do survive and differentiate exhibit normal nuclear morphology but decreased oxidative bursts. Our continued analyses of these different manipulated models will provide unique knowledge of the influence that NE proteins have on not only myeloid cell nuclear structure but also important functional features not previously known to depend on specific levels of NE protein expression. We predict that these studies will provide a new appreciation for the complexity of NE protein expression patterns in maturing myeloid lineages, and for the important roles that NE proteins perform in orchestrating both nuclear morphologic maturation and key phagocyte functions. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e24051-e24051
    Abstract: e24051 Background: CVD is the leading cause of non-cancer mortality for BC survivors. Clinical practice guidelines support the assessment and management of ASCVD risk factors among BC pts, including lipid-lowering therapy when indicated. We performed a single-institution, retrospective, longitudinal study of ASCVD risk factors and statin use for primary and secondary ASCVD prevention among BC pts. Methods: Pts diagnosed with BC from 2009-2015 were identified from the institutional cancer registry. Pts with non-metastatic BC or ductal carcinoma in situ and at least 2 years of follow up were included. Records were reviewed at 12-month intervals from BC diagnosis until last follow up or the study end date of 12/31/19. BC characteristics and treatment, prevalent and incident CV risk factors, CV diagnoses, CV medications, and CV events were manually abstracted and confirmed by a second reviewer. 10-year estimated ASCVD risk, based on non-laboratory predictors, was calculated for each pt. Chi-square tests were performed to assess the relationship between race/ethnicity, age category, and statin exposure. Results: 326 pts were included (median age at diagnosis 60.7 yrs; 67% White, 16% Asian (Chinese), 10% Black; 54% with stage I disease). At baseline, 53% had hypertension, 40% had hyperlipidemia, 37% were former or current smokers, 32% had a BMI ≥30, 7% had a history of ASCVD, and 5% had a family history of premature coronary artery disease. 52% received radiation therapy. 114 pts had radiation dosimetry available; 59 (18%) received a mean heart dose ≥1 Gy. Median follow up was 6.5 yrs. At the time of BC diagnosis, 64% of pts had an established indication for lipid-lowering therapy: history of ASCVD, diabetes, or estimated 10-year ASCVD risk ≥7.5% (Table). Of these pts with an indication for statin, 35% were prescribed a statin at baseline and 57% were prescribed a statin at any time during the study period. No association between baseline statin exposure and pt age category (X 2 = 3.75, p = 0.290) or race/ethnicity (X 2 = 2.64, p = 0.562) was observed. Among 11% of pts with ASCVD at any time, 83% were prescribed a statin but only 40% received a guideline-recommended high-intensity statin. Conclusions: A majority of pts in our study were candidates for statin therapy for primary or secondary ASCVD prevention at the time of BC diagnosis. 43% were never prescribed a statin, predominantly pts whose indication was primary prevention. There is opportunity for improvement in ASCVD prevention during BC treatment and follow up. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: American Journal of Nephrology, S. Karger AG
    Abstract: Introduction: In 2017, the Centers for Medicare and Medicaid Services allowed survivors of hospitalized acute kidney injury requiring dialysis (AKI-D) who were ambulatory and still dependent on hemodialysis (HD) to receive treatment in outpatient dialysis facilities. This policy change generated the ongoing need to improve AKI-D care in the outpatient setting. Methods: Quality improvement study in adult patients admitted to an outpatient HD unit with the diagnosis of AKI-D. We developed a protocol to manage these patients that included: a) multidisciplinary evaluations; b) personalized 3-tier HD prescription for dose/ultrafiltration rate and frequency; c) weekly assessment of kidney recovery; and d) patient empowerment. Patient- and protocol-specific characteristics were described. We analyzed hourly HD data and protocol adherence, and relevant hemodynamic data were compared according to HD-free survival at 90 days. Results: A total of 457.3 hours of HD from nine patients under the AKI-D protocol were interrogated. Three out of nine patients were alive and liberated from HD within the first 90 days of outpatient HD. Overall protocol adherence was 53.8% and did not differ by HD-free survival (54.5% vs. 53.7% in those that recovered vs. not). Protocol adherence was associated with fewer intradialytic hypotension events (peak to nadir BP, p 〈 0.01), while intradialytic hypotension (pre to post BP) occurred more frequently in patients who did not recover kidney function (p=0.009). Conclusion: We demonstrated the feasibility of implementing a management protocol for AKI-D patients in an outpatient dialysis facility. We found that fewer episodes of intradialytic hypotension occurred when the outpatient HD management was adherent to the protocol. The feasibility of this protocol should be confirmed in other facilities, and importantly, efficacy testing to evaluate its impact on AKI-D outpatient care is necessary.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1468523-1
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  • 9
    In: ImmunoHorizons, The American Association of Immunologists, Vol. 6, No. 1 ( 2022-01-01), p. 16-35
    Abstract: Neutrophils mediate critical innate immune responses by migrating to sites of infection or inflammation, phagocytosing microorganisms, and releasing an arsenal of antimicrobial agents, including reactive oxygen species. These functions are shared by other innate immune cell types, but an interesting feature of neutrophils is their hallmark lobulated nuclei. Although why this bizarre nuclear shape forms is still being elucidated, studies of two intermediate filament proteins that associate with the nuclear envelope, lamin A and C, indicate that expression levels of these proteins govern nuclear maturation. These A-type lamins also modulate nuclear stiffness, the loss of which may be critical to the migration of not only neutrophils but also cancer cells that become prone to metastasis. We investigated whether increased expression of either lamin A or C affects neutrophil nuclear morphologic maturation, but more importantly we tested whether overexpression of either lamin also affects neutrophil functional responses, using two mouse myeloid progenitor models that can be induced toward functionally responsive neutrophil-like cells. Collectively, our results demonstrate that overexpression of either lamin A or C not only disrupts nuclear lobulation but also causes aberrant functional responses critical to innate immunity, including chemotaxis, phagocytosis, and reactive oxygen species production. Moreover, the lamin A–overexpressing cells exhibit decreased expression of a critical NADPH oxidase complex factor, gp91phox, and transcriptomic profiling demonstrated differential expression of a number of myeloid differentiation and functional pathway components. Taken together, these data demonstrate that A-type lamin expression levels modulate not only nuclear morphologic features but also gene expression changes as neutrophils mature.
    Type of Medium: Online Resource
    ISSN: 2573-7732
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2022
    detail.hit.zdb_id: 2882729-6
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