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  1. Article ; Online: Role of bridging therapy during chimeric antigen receptor T cell therapy.

    Bhaskar, Shakthi T / Dholaria, Bhagirathbhai R / Sengsayadeth, Salyka M / Savani, Bipin N / Oluwole, Olalekan O

    EJHaem

    2021  Volume 3, Issue Suppl 1, Page(s) 39–45

    Abstract: Chimeric antigen receptor (CAR) T-cell therapy has been approved for use in several relapsed/refractory hematologic malignancies and has significantly improved outcomes for these diseases. A number of different CAR T products are now being used in ... ...

    Abstract Chimeric antigen receptor (CAR) T-cell therapy has been approved for use in several relapsed/refractory hematologic malignancies and has significantly improved outcomes for these diseases. A number of different CAR T products are now being used in clinical practice and have demonstrated excellent outcomes to those in clinical trials. However, increased real-world use of CAR T therapy has uncovered a number of barriers that can lead to significant delays in treatment. As a result, bridging therapy has become a widely used tool to stabilize or debulk disease between leukapheresis and CAR T cell administration. Here we review the available data regarding bridging therapy, with a focus on patient selection, choice of therapy, timing of therapy, and potential pitfalls.
    Language English
    Publishing date 2021-11-19
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.335
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients.

    Al-Droubi, Samer S / Jahangir, Eiman / Kochendorfer, Karl M / Krive, Marianna / Laufer-Perl, Michal / Gilon, Dan / Okwuosa, Tochukwu M / Gans, Christopher P / Arnold, Joshua H / Bhaskar, Shakthi T / Yasin, Hesham A / Krive, Jacob

    European heart journal. Digital health

    2023  Volume 4, Issue 4, Page(s) 302–315

    Abstract: Aims: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for ... ...

    Abstract Aims: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care.
    Methods and results: De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals.
    Conclusion: Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.
    Language English
    Publishing date 2023-05-08
    Publishing country England
    Document type Journal Article
    ISSN 2634-3916
    ISSN (online) 2634-3916
    DOI 10.1093/ehjdh/ztad031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Chimeric Antigen Receptor T-Cell Therapy in the Outpatient Setting: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

    Oluwole, Olalekan O / Dholaria, Bhagirathbhai / Knight, Tristan E / Jain, Tania / Locke, Frederick L / Ramsdell, Linda / Nikiforow, Sarah / Hashmi, Hamza / Mooney, Kathy / Bhaskar, Shakthi T / Morris, Katrina / Gatwood, Katie / Baer, Brittney / Anderson, Larry D / Hamadani, Mehdi

    Transplantation and cellular therapy

    2023  Volume 30, Issue 2, Page(s) 131–142

    Abstract: The first series of chimeric antigen receptor T (CAR-T) cell therapy products were approved in 2017 to 2019 and have shown remarkable efficacy in both clinical trials and the real-world setting, but at the cost of prolonged patient hospitalization. As ... ...

    Abstract The first series of chimeric antigen receptor T (CAR-T) cell therapy products were approved in 2017 to 2019 and have shown remarkable efficacy in both clinical trials and the real-world setting, but at the cost of prolonged patient hospitalization. As the toxicity management protocols were refined, the concept of cellular therapy administered in the outpatient setting gained steam, and single institutions began to perform certain aspects of CAR-T monitoring in the outpatient setting for select patients. However, there are many considerations for a successful outpatient program. In anticipation of increasing use of CAR-T-cell therapy in the outpatient setting as a mechanism to overcome frequent hospital bed shortages and high cost of inpatient care, the American Society for Transplantation and Cellular Therapy convened a group of experts in hematology, oncology, and cellular therapy to provide a comprehensive review of the existing publications on outpatient CAR-T cell therapy, discuss selected ongoing clinical trials of outpatient CAR-T, and describe strategies to optimize safety without compromising efficacy for patients treated and monitored in the outpatient setting.
    MeSH term(s) Humans ; United States ; Receptors, Chimeric Antigen/therapeutic use ; Outpatients ; Immunotherapy, Adoptive/adverse effects ; Societies ; Cell- and Tissue-Based Therapy
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2023-11-10
    Publishing country United States
    Document type Review ; Practice Guideline
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2023.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5082: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome.

    Bhaskar, Shakthi T / Patel, Vivek G / Porter, David L / Schuster, Stephen J / Nastoupil, Loretta J / Perales, Miguel-Angel / Tomas, Ana Alarcon / Bishop, Michael R / McGuirk, Joseph P / Maziarz, Richard T / Chen, Andy I / Bachanova, Veronika / Maakaron, Joseph E / Riedell, Peter A / Oluwole, Olalekan O

    Blood advances

    2022  Volume 7, Issue 17, Page(s) 4765–4772

    Abstract: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), ... ...

    Abstract Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening. Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown whether patients who did not develop CRS had reduced CAR-T cell activity and were therefore likely to have worse outcomes. We conducted a multicenter retrospective analysis of 352 adult patients treated at 8 academic medical centers in the United States who received axicabtagene ciloleucel or tisagenlecleucel for the treatment of LBCL. The outcomes of interest included progression-free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74.4%) developed CRS. There was no significant difference in progression-free survival (P = .99) or overall survival (P = .16) between patients who developed CRS and those who did not develop CRS. Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase levels greater than the institutional upper limit of normal before lymphodepleting chemotherapy were associated with significantly worse progression-free and overall survival in the multivariate analysis. There was no significant difference in the complete response or overall response rates between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have clinical outcomes similar to those of patients without CRS treated with commercial anti-CD19 CAR-T cells.
    MeSH term(s) Adult ; Humans ; United States ; Receptors, Chimeric Antigen/therapeutic use ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/therapy ; Retrospective Studies ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Antigens, CD19 ; Cell- and Tissue-Based Therapy
    Chemical Substances Receptors, Chimeric Antigen ; Antigens, CD19
    Language English
    Publishing date 2022-11-24
    Publishing country United States
    Document type Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2022008937
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7153: Show issues Location:
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  5. Article ; Online: Efficacy of CD19 directed therapies in patients with relapsed or refractory large b-cell lymphoma relapsing after CD19 directed chimeric antigen receptor T-cell therapy.

    Iqbal, Madiha / Jagadeesh, Deepa / Chavez, Julio / Khurana, Arushi / Rosenthal, Allison / Craver, Emily / Epperla, Narendranath / Li, Zhuo / Isufi, Iris / Awan, Farrukh T / Dholaria, Bhagirathbhai R / Maakaron, Joseph E / Sandoval-Sus, Jose D / Mishra, Rahul / Saha, Aditi / Annunzio, Kaitlin / Bhaskar, Shakthi T / Sumransub, Nuttavut / Fijalka, Andrew /
    Ivanov, Stanislav A / Lin, Yi / Kharfan-Dabaja, Mohamed A

    Bone marrow transplantation

    2023  Volume 59, Issue 2, Page(s) 211–216

    Abstract: Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab ... ...

    Abstract Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1-199) weeks from CAR-T infusion. Median number of systemic therapies pre-CAR-T therapy was 3 (range: 1-6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2-38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0-5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1-56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.
    MeSH term(s) Humans ; Antigens, CD19 ; Cell- and Tissue-Based Therapy ; Immunotherapy, Adoptive ; Lymphoma, Large B-Cell, Diffuse/therapy ; Lymphoma, Large B-Cell, Diffuse/pathology ; Neoplasm Recurrence, Local/drug therapy ; Receptors, Chimeric Antigen/therapeutic use
    Chemical Substances Antigens, CD19 ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2023-11-16
    Publishing country England
    Document type Multicenter Study ; Journal Article
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/s41409-023-02148-4
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    Zs.A 2168: Show issues Location:
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  6. Article ; Online: Driving opposing behaviors with ensembles of piriform neurons.

    Choi, Gloria B / Stettler, Dan D / Kallman, Benjamin R / Bhaskar, Shakthi T / Fleischmann, Alexander / Axel, Richard

    Cell

    2011  Volume 146, Issue 6, Page(s) 1004–1015

    Abstract: Anatomic and physiologic studies have suggested a model in which neurons of the piriform cortex receive convergent input from random collections of glomeruli. In this model, odor representations can only be afforded behavioral significance upon ... ...

    Abstract Anatomic and physiologic studies have suggested a model in which neurons of the piriform cortex receive convergent input from random collections of glomeruli. In this model, odor representations can only be afforded behavioral significance upon experience. We have devised an experimental strategy that permits us to ask whether the activation of an arbitrarily chosen subpopulation of neurons in piriform cortex can elicit different behavioral responses dependent upon learning. Activation of a small subpopulation of piriform neurons expressing channelrhodopsin at multiple loci in the piriform cortex, when paired with reward or shock, elicits either appetitive or aversive behavior. Moreover, we demonstrate that different subpopulations of piriform neurons expressing ChR2 can be discriminated and independently entrained to elicit distinct behaviors. These observations demonstrate that the piriform cortex is sufficient to elicit learned behavioral outputs in the absence of sensory input. These data imply that the piriform does not use spatial order to map odorant identity or behavioral output.
    MeSH term(s) Animals ; Appetitive Behavior ; Behavior, Animal ; Channelrhodopsins ; Conditioning, Psychological ; Mice ; Neurons/cytology ; Neurons/physiology ; Odorants ; Olfactory Pathways/cytology ; Olfactory Pathways/physiology ; Smell
    Chemical Substances Channelrhodopsins
    Language English
    Publishing date 2011-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2011.07.041
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    Zs.MG 58: Show issues

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  7. Article: Driving Opposing Behaviors with Ensembles of Piriform Neurons

    Choi, Gloria B. / Stettler, Dan D. / Kallman, Benjamin R. / Bhaskar, Shakthi T. / Fleischmann, Alexander / Axel, Richard

    Cell

    Volume v. 146,, Issue no. 6

    Abstract: Anatomic and physiologic studies have suggested a model in which neurons of the piriform cortex receive convergent input from random collections of glomeruli. In this model, odor representations can only be afforded behavioral significance upon ... ...

    Abstract Anatomic and physiologic studies have suggested a model in which neurons of the piriform cortex receive convergent input from random collections of glomeruli. In this model, odor representations can only be afforded behavioral significance upon experience. We have devised an experimental strategy that permits us to ask whether the activation of an arbitrarily chosen subpopulation of neurons in piriform cortex can elicit different behavioral responses dependent upon learning. Activation of a small subpopulation of piriform neurons expressing channelrhodopsin at multiple loci in the piriform cortex, when paired with reward or shock, elicits either appetitive or aversive behavior. Moreover, we demonstrate that different subpopulations of piriform neurons expressing ChR2 can be discriminated and independently entrained to elicit distinct behaviors. These observations demonstrate that the piriform cortex is sufficient to elicit learned behavioral outputs in the absence of sensory input. These data imply that the piriform does not use spatial order to map odorant identity or behavioral output.
    Keywords models ; cortex ; odor compounds ; odors ; loci ; learning ; neurons
    Language English
    Document type Article
    ISSN 0092-8674
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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