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  1. Article ; Online: Immunopathology of Hyperinflammation in COVID-19.

    Gustine, Joshua N / Jones, Dennis

    The American journal of pathology

    2020  Volume 191, Issue 1, Page(s) 4–17

    Abstract: The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome ... ...

    Abstract The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.
    MeSH term(s) Adrenal Cortex Hormones/therapeutic use ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/therapy ; Cytokine Release Syndrome ; Extracellular Traps ; Humans ; Immune System ; Immunity, Innate ; Inflammation ; Killer Cells, Natural/immunology ; Macrophage Activation ; Macrophages/immunology ; Monocytes/immunology ; Neutrophils/immunology ; Phagocytosis ; SARS-CoV-2/physiology ; Systemic Inflammatory Response Syndrome/epidemiology ; T-Lymphocytes/immunology ; Virus Replication
    Chemical Substances Adrenal Cortex Hormones
    Keywords covid19
    Language English
    Publishing date 2020-09-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2020.08.009
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  2. Article ; Online: Immunopathology of Hyperinflammation in COVID-19

    Gustine, Joshua N. / Jones, Dennis

    The American Journal of Pathology ; ISSN 0002-9440

    2020  

    Keywords Pathology and Forensic Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.1016/j.ajpath.2020.08.009
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Dose reductions in patients with Waldenström macroglobulinaemia treated with ibrutinib.

    Sarosiek, Shayna / Gustine, Joshua N / Flynn, Catherine A / Leventoff, Carly / Little, Megan / White, Timothy / Meid, Kirsten / Treon, Steven P / Castillo, Jorge J

    British journal of haematology

    2023  Volume 201, Issue 5, Page(s) 897–904

    Abstract: Waldenström macroglobulinaemia (WM) is characterized by the presence of a ... ...

    Abstract Waldenström macroglobulinaemia (WM) is characterized by the presence of a MYD88
    MeSH term(s) Male ; Female ; Humans ; Waldenstrom Macroglobulinemia/drug therapy ; Waldenstrom Macroglobulinemia/genetics ; Waldenstrom Macroglobulinemia/pathology ; Drug Tapering ; Retrospective Studies ; Mutation
    Chemical Substances ibrutinib (1X70OSD4VX)
    Language English
    Publishing date 2023-01-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18643
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  4. Article ; Online: Light chain amyloidosis associated with Waldenström macroglobulinemia: treatment and survival outcomes.

    Gustine, Joshua N / Szalat, Raphael E / Staron, Andrew / Joshi, Tracy / Mendelson, Lisa / Sloan, J Mark / Sanchorawala, Vaishali

    Haematologica

    2023  Volume 108, Issue 6, Page(s) 1680–1684

    MeSH term(s) Humans ; Waldenstrom Macroglobulinemia/complications ; Waldenstrom Macroglobulinemia/diagnosis ; Waldenstrom Macroglobulinemia/drug therapy ; Amyloidosis ; Immunoglobulin Light Chains
    Chemical Substances Immunoglobulin Light Chains
    Language English
    Publishing date 2023-06-01
    Publishing country Italy
    Document type Letter
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2022.282264
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  5. Article: Immunopathology of Hyperinflammation in COVID-19

    Gustine, Joshua N / Jones, Dennis

    Am. j. pathol

    Abstract: The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome ... ...

    Abstract The rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented public health crisis worldwide. Recent studies indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to disease severity and mortality in COVID-19. In this review, an overview of the pathophysiology underlying the hyperinflammatory syndrome in severe COVID-19 is provided. The current evidence suggests that the hyperinflammatory syndrome results from a dysregulated host innate immune response. The gross and microscopic pathologic findings as well as the alterations in the cytokine milieu, macrophages/monocytes, natural killer cells, T cells, and neutrophils in severe COVID-19 are summarized. The data highlighted include the potential therapeutic approaches undergoing investigation to modulate the immune response and abrogate lung injury in severe COVID-19.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #754006
    Database COVID19

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  6. Article ; Online: Predictors of treatment response and survival outcomes in patients with advanced cardiac AL amyloidosis.

    Gustine, Joshua N / Staron, Andrew / Mendelson, Lisa / Joshi, Tracy / Gopal, Deepa M / Siddiqi, Omar K / Ruberg, Frederick L / Sanchorawala, Vaishali

    Blood advances

    2023  Volume 7, Issue 20, Page(s) 6080–6091

    Abstract: Patients with advanced cardiac immunoglobulin light chain (AL) amyloidosis have a poor prognosis. Early hematologic and cardiac responses can prolong survival, but predictors of these outcomes have yet to be clarified. We report on 142 patients with ... ...

    Abstract Patients with advanced cardiac immunoglobulin light chain (AL) amyloidosis have a poor prognosis. Early hematologic and cardiac responses can prolong survival, but predictors of these outcomes have yet to be clarified. We report on 142 patients with newly diagnosed stage IIIb AL amyloidosis. After a median follow-up of 60 months, the median overall survival (OS) was 9 months. Independent baseline factors associated with shorter OS were symptom onset to diagnosis >6 months (hazard ratio [HR], 1.94; P = .003); bone marrow plasmacytosis ≥ 10% (HR, 1.98; P = .01); troponin I > 0.635 ng/mL (HR, 1.62; P = .04); New York Heart Association class III or IV (HR, 1.67; P = .04); and 6-minute walk test distance < 200 m (HR, 1.85; P = .01). Early hematologic (within 1 month) and cardiac (within 3 months) responses were significantly associated with longer survival. In a 1-month landmark analysis, patients with a hematologic very good partial response, partial response, and no response had a median OS of 47, 25, and 5 months, respectively (P < .0001). Patients with cardiac response at 3 months had significantly longer OS (47 vs 11 months; P < .0001). On multivariable modeling, bortezomib use was associated with early hematologic and cardiac responses and longer OS. Symptom onset to diagnosis duration of >6 months and difference between the involved and uninvolved free light chain > 350 mg/L were independently associated with lower odds of an early cardiac response. This study identified factors predictive of treatment outcomes and survival in advanced cardiac AL amyloidosis.
    MeSH term(s) Humans ; Immunoglobulin Light-chain Amyloidosis/diagnosis ; Immunoglobulin Light-chain Amyloidosis/therapy ; Retrospective Studies ; Immunoglobulin Light Chains ; Treatment Outcome ; Proportional Hazards Models
    Chemical Substances Immunoglobulin Light Chains
    Language English
    Publishing date 2023-08-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023010324
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  7. Article ; Online: Fitting mSMART Into the Current Clinical Management of Waldenström Macroglobulinemia.

    Castillo, Jorge J / Gustine, Joshua N / Treon, Steven P

    JAMA oncology

    2018  Volume 4, Issue 5, Page(s) 744–745

    MeSH term(s) Humans ; Waldenstrom Macroglobulinemia
    Language English
    Publishing date 2018-01-30
    Publishing country United States
    Document type Letter ; Comment
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2017.0734
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  8. Article ; Online: Ibrutinib withdrawal symptoms in patients with Waldenström macroglobulinemia.

    Castillo, Jorge J / Gustine, Joshua N / Meid, Kirsten / Dubeau, Toni / Severns, Patricia / Treon, Steven P

    Haematologica

    2018  Volume 103, Issue 7, Page(s) e307–e310

    MeSH term(s) Adenine/analogs & derivatives ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Biomarkers ; Humans ; Piperidines ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/therapeutic use ; Pyrazoles/administration & dosage ; Pyrazoles/therapeutic use ; Pyrimidines/administration & dosage ; Pyrimidines/therapeutic use ; Substance Withdrawal Syndrome/diagnosis ; Substance Withdrawal Syndrome/etiology ; Waldenstrom Macroglobulinemia/complications ; Waldenstrom Macroglobulinemia/diagnosis ; Waldenstrom Macroglobulinemia/drug therapy ; Withholding Treatment
    Chemical Substances Antineoplastic Agents ; Biomarkers ; Piperidines ; Protein Kinase Inhibitors ; Pyrazoles ; Pyrimidines ; ibrutinib (1X70OSD4VX) ; Adenine (JAC85A2161)
    Language English
    Publishing date 2018-02-22
    Publishing country Italy
    Document type Letter
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2017.186908
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  9. Article ; Online: Comparing apples to oranges: A commentary on the Mayo study of MYD88 significance in Waldenstrom's macroglobulinemia.

    Castillo, Jorge J / Gustine, Joshua N / Meid, Kirsten / Xu, Lian / Hunter, Zachary R / Treon, Steven P

    American journal of hematology

    2017  Volume 93, Issue 3, Page(s) E69–E71

    MeSH term(s) Adaptor Proteins, Signal Transducing ; Humans ; Immunoglobulin M ; Mutation ; Myeloid Differentiation Factor 88/genetics ; Waldenstrom Macroglobulinemia
    Chemical Substances Adaptor Proteins, Signal Transducing ; Immunoglobulin M ; Myeloid Differentiation Factor 88
    Language English
    Publishing date 2017-12-23
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.24997
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  10. Article ; Online: Predictors of hematologic response and survival with stem cell transplantation in AL amyloidosis: A 25-year longitudinal study.

    Gustine, Joshua N / Staron, Andrew / Szalat, Raphael E / Mendelson, Lisa M / Joshi, Tracy / Ruberg, Frederick L / Siddiqi, Omar / Gopal, Deepa M / Edwards, Camille V / Havasi, Andrea / Kaku, Michelle / Lau, K H Vincent / Berk, John L / Sloan, J Mark / Sanchorawala, Vaishali

    American journal of hematology

    2022  Volume 97, Issue 9, Page(s) 1189–1199

    Abstract: High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was ... ...

    Abstract High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow-up interval of 8 years, the median event-free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1 ng/mL, and serum creatinine >2.0 mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low-risk (0 factors), intermediate-risk (1 factor), and high-risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p < .001). The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.
    MeSH term(s) Amyloidosis/complications ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Longitudinal Studies ; Melphalan/therapeutic use ; Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome
    Chemical Substances Melphalan (Q41OR9510P)
    Language English
    Publishing date 2022-07-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26641
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