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  1. Article ; Online: Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications.

    Mucha, Simon R / Rajendram, Prabalini

    Current oncology (Toronto, Ont.)

    2023  Volume 30, Issue 5, Page(s) 5003–5023

    Abstract: Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves ... ...

    Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effects). Variations in conditioning therapies, co-stimulatory domains, CAR T-cell dose and anti-cytokine administration, pose a challenge in distinguishing cytokine mediated related toxicities from on-target, off-tumor toxicities. Timing, frequency, severity, as well as optimal management of CAR T-cell-related toxicities vary significantly between products and are likely to change as newer therapies become available. Currently the FDA approved CARs are targeted towards the B-cell malignancies however the future holds promise of expanding the target to solid tumor malignancies. Further highlighting the importance of early recognition and intervention for early and late onset CAR-T related toxicity. This contemporary review aims to describe presentation, grading and management of commonly encountered toxicities, short- and long-term complications, discuss preventive strategies and resource utilization.
    MeSH term(s) Humans ; Receptors, Chimeric Antigen/therapeutic use ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes ; Treatment Outcome ; Neoplasms/drug therapy
    Chemical Substances Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-05-15
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1236972-x
    ISSN 1718-7729 ; 1198-0052
    ISSN (online) 1718-7729
    ISSN 1198-0052
    DOI 10.3390/curroncol30050378
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cirrhotic coagulopathy: A rebalanced hemostasis.

    Singh, Achintya D / Mucha, Simon R / Lindenmeyer, Christina C

    Cleveland Clinic journal of medicine

    2022  Volume 89, Issue 9, Page(s) 523–533

    Abstract: Cirrhosis has been regarded as a hypocoagulable state associated with an increased risk of bleeding. But patients with cirrhosis also have a high incidence of thrombotic complications, challenging this dogma. We now recognize that in cirrhosis there is a ...

    Abstract Cirrhosis has been regarded as a hypocoagulable state associated with an increased risk of bleeding. But patients with cirrhosis also have a high incidence of thrombotic complications, challenging this dogma. We now recognize that in cirrhosis there is a simultaneous decrease in both clotting and anticlotting factors, leading to a new equilibrium. Conventional coagulation tests such as the platelet count and prothrombin time do not assess the reduced anticoagulation factors in cirrhosis and overestimate the bleeding risk, and any intervention based on these test results can lead to thrombotic complications. This article reviews the changes in hemostasis associated with cirrhosis, newer tests for assessing coagulation, and preprocedural minimization of coagulopathy.
    MeSH term(s) Humans ; Blood Coagulation Disorders/diagnosis ; Blood Coagulation Disorders/etiology ; Hemostasis ; Blood Coagulation ; Liver Cirrhosis/complications ; Blood Coagulation Tests ; Thrombosis
    Language English
    Publishing date 2022-09-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 639116-3
    ISSN 1939-2869 ; 0891-1150
    ISSN (online) 1939-2869
    ISSN 0891-1150
    DOI 10.3949/ccjm.89a.21018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Convalescent plasma for COVID-19: Promising, not proven.

    Mucha, Simon R / Quraishy, NurJehan

    Cleveland Clinic journal of medicine

    2020  Volume 87, Issue 11, Page(s) 664–670

    Abstract: While promising, convalescent plasma remains experimental and is not proven effective for COVID-19. In addition, many questions remain regarding the accuracy and predictive value of antibody testing of donors and patients, optimal donor selection, ... ...

    Abstract While promising, convalescent plasma remains experimental and is not proven effective for COVID-19. In addition, many questions remain regarding the accuracy and predictive value of antibody testing of donors and patients, optimal donor selection, optimal timing, and selection of patients most likely to benefit. Until these questions are answered, convalescent plasma should ideally be used in the context of well-designed clinical trials.
    MeSH term(s) Betacoronavirus/immunology ; Betacoronavirus/isolation & purification ; Clinical Laboratory Techniques/methods ; Clinical Trials as Topic ; Coronavirus Infections/diagnosis ; Coronavirus Infections/genetics ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Donor Selection ; Humans ; Immunization, Passive/adverse effects ; Immunization, Passive/methods ; Pandemics ; Patient Selection ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/genetics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; Predictive Value of Tests ; Reproducibility of Results ; Risk Assessment ; Time-to-Treatment ; Treatment Outcome
    Keywords covid19
    Language English
    Publishing date 2020-11-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639116-3
    ISSN 1939-2869 ; 0891-1150
    ISSN (online) 1939-2869
    ISSN 0891-1150
    DOI 10.3949/ccjm.87a.ccc056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Convalescent plasma for COVID-19: Promising, not proven

    Mucha, Simon R / Quraishy, NurJehan

    Cleve Clin J Med

    Abstract: While promising, convalescent plasma remains experimental and is not proven effective for COVID-19. In addition, many questions remain regarding the accuracy and predictive value of antibody testing of donors and patients, optimal donor selection, ... ...

    Abstract While promising, convalescent plasma remains experimental and is not proven effective for COVID-19. In addition, many questions remain regarding the accuracy and predictive value of antibody testing of donors and patients, optimal donor selection, optimal timing, and selection of patients most likely to benefit. Until these questions are answered, convalescent plasma should ideally be used in the context of well-designed clinical trials.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #711331
    Database COVID19

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  5. Article ; Online: Forecasting disease trajectories in critical illness: comparison of probabilistic dynamic systems to static models to predict patient status in the intensive care unit.

    Duggal, Abhijit / Scheraga, Rachel / Sacha, Gretchen L / Wang, Xiaofeng / Huang, Shuaqui / Krishnan, Sudhir / Siuba, Matthew T / Torbic, Heather / Dugar, Siddharth / Mucha, Simon / Veith, Joshua / Mireles-Cabodevila, Eduardo / Bauer, Seth R / Kethireddy, Shravan / Vachharajani, Vidula / Dalton, Jarrod E

    BMJ open

    2024  Volume 14, Issue 2, Page(s) e079243

    Abstract: Objective: Conventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk prediction ... ...

    Abstract Objective: Conventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk prediction models to dynamic probabilistic models in early critical illness.
    Design: We developed models to simulate disease trajectories of critically ill COVID-19 patients across different disease states. Eighty per cent of cases were randomly assigned to a training and 20% of the cases were used as a validation cohort. Conventional risk prediction models were developed to analyse different disease states for critically ill patients for the first 7 days of intensive care unit (ICU) stay. Daily disease state transitions were modelled using a series of multivariable, multinomial logistic regression models. A probabilistic dynamic systems modelling approach was used to predict disease trajectory over the first 7 days of an ICU admission. Forecast accuracy was assessed and simulated patient clinical trajectories were developed through our algorithm.
    Setting and participants: We retrospectively studied patients admitted to a Cleveland Clinic Healthcare System in Ohio, for the treatment of COVID-19 from March 2020 to December 2022.
    Results: 5241 patients were included in the analysis. For ICU days 2-7, the static (conventional) modelling approach, the accuracy of the models steadily decreased as a function of time, with area under the curve (AUC) for each health state below 0.8. But the dynamic forecasting approach improved its ability to predict as a function of time. AUC for the dynamic forecasting approach were all above 0.90 for ICU days 4-7 for all states.
    Conclusion: We demonstrated that modelling critical care outcomes as a dynamic system improved the forecasting accuracy of the disease state. Our model accurately identified different disease conditions and trajectories, with a <10% misclassification rate over the first week of critical illness.
    MeSH term(s) Humans ; Critical Illness/therapy ; Retrospective Studies ; Intensive Care Units ; Hospitalization ; COVID-19/epidemiology ; Critical Care
    Language English
    Publishing date 2024-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2023-079243
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Update to coagulopathy in COVID-19: Manifestations and management.

    Mucha, Simon R / Dugar, Siddharth / McCrae, Keith / Joseph, Douglas / Bartholomew, John / Sacha, Gretchen L / Militello, Michael

    Cleveland Clinic journal of medicine

    2021  

    Abstract: Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory ... ...

    Abstract Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory findings of severe COVID-19-associated coagulopathy. Prophylaxis against venous thromboembolism is paramount for all hospitalized patients with COVID-19, with more aggressive prophylaxis and screening recommended for critically ill patients with D-dimer levels above 3.0 μg/mL. Point-of-care ultrasonography is the imaging method of choice for patients at high risk, as it entails minimal risk of exposing providers to the virus.
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639116-3
    ISSN 1939-2869 ; 0891-1150
    ISSN (online) 1939-2869
    ISSN 0891-1150
    DOI 10.3949/ccjm.87a.ccc024-up
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: In Reply: COVID-19 coagulopathy.

    Mucha, Simon R / Dugar, Siddharth / McCrae, Keith / Joseph, Douglas / Bartholomew, John / Sacha, Gretchen L / Militello, Michael

    Cleveland Clinic journal of medicine

    2020  Volume 87, Issue 12, Page(s) 712

    MeSH term(s) Betacoronavirus ; Blood Coagulation Disorders ; COVID-19 ; Humans ; Pandemics
    Language English
    Publishing date 2020-11-23
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 639116-3
    ISSN 1939-2869 ; 0891-1150
    ISSN (online) 1939-2869
    ISSN 0891-1150
    DOI 10.3949/cjm.87c.12002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Coagulopathy in COVID-19: Manifestations and management.

    Mucha, Simon R / Dugar, Siddharth / McCrae, Keith / Joseph, Douglas / Bartholomew, John / Sacha, Gretchen L / Militello, Michael

    Cleveland Clinic journal of medicine

    2020  Volume 87, Issue 8, Page(s) 461–468

    Abstract: Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory ... ...

    Abstract Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory findings of severe COVID-19- associated coagulopathy. Prophylaxis against venous thromboembolism is paramount for all hospitalized patients, with more aggressive prophylaxis and screening recommended for patients with D-dimer levels above 3.0 μg/mL. Point-of-care ultrasonography is the imaging method of choice for patients at high risk, as it entails minimal risk of exposing providers to the virus.
    MeSH term(s) Anticoagulants/pharmacology ; Betacoronavirus/pathogenicity ; Betacoronavirus/physiology ; Blood Coagulation/drug effects ; Blood Coagulation/physiology ; Blood Coagulation Disorders/blood ; Blood Coagulation Disorders/etiology ; Blood Coagulation Disorders/therapy ; Blood Coagulation Tests/methods ; COVID-19 ; Chemoprevention/methods ; Coronavirus Infections/blood ; Coronavirus Infections/physiopathology ; Coronavirus Infections/therapy ; Fibrin Fibrinogen Degradation Products/analysis ; Humans ; Monitoring, Physiologic/methods ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; Thrombosis/etiology ; Thrombosis/prevention & control
    Chemical Substances Anticoagulants ; Fibrin Fibrinogen Degradation Products ; fibrin fragment D
    Keywords covid19
    Language English
    Publishing date 2020-07-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639116-3
    ISSN 1939-2869 ; 0891-1150
    ISSN (online) 1939-2869
    ISSN 0891-1150
    DOI 10.3949/ccjm.87a.ccc024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Coagulopathy in COVID-19: Manifestations and management

    Mucha, Simon R / Dugar, Siddharth / McCrae, Keith / Joseph, Douglas / Bartholomew, John / Sacha, Gretchen L / Militello, Michael

    Cleve Clin J Med

    Abstract: Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory ... ...

    Abstract Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory findings of severe COVID-19- associated coagulopathy. Prophylaxis against venous thromboembolism is paramount for all hospitalized patients, with more aggressive prophylaxis and screening recommended for patients with D-dimer levels above 3.0 µg/mL. Point-of-care ultrasonography is the imaging method of choice for patients at high risk, as it entails minimal risk of exposing providers to the virus.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #266450
    Database COVID19

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  10. Article: Coagulopathy in COVID-19

    Mucha, Simon R / Dugar, Siddharth / McCrae, Keith / Joseph, Douglas E / Bartholomew, John / Sacha, Gretchen / Militello, Michael

    Clevel. clin. j. med

    Abstract: COVID-19-associated coagulopathy is common in patients with COVID-19, causing high rates of thrombotic complications that increase the morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory ... ...

    Abstract COVID-19-associated coagulopathy is common in patients with COVID-19, causing high rates of thrombotic complications that increase the morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory findings and correlate with severity of illness and risk of thrombosis. Aggressive VTE prophylaxis is paramount for all patients with COVID-19. Patients with very high D-dimer levels (6 times the upper limit of normal, greater than 3,000 ng/mL) have the greatest risk of thrombosis and may benefit from active screening and more intensive VTE prophylaxis.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32409435
    Database COVID19

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