Αρχειοθήκη ιστολογίου

Κυριακή 19 Δεκεμβρίου 2021

Asthmatic Patients Have an Increased Risk of Hyperthyroidism

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Clinical Thyroidology, Volume 33, Issue 12, Page 523-525, December 2021.
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Obesity Is Associated with Increased Adipocyte Infiltration in the Thyroid Tissue: A New Perspective?

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Clinical Thyroidology, Volume 33, Issue 12, Page 516-519, December 2021.
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Impact of modern personalized treatment of breast cancer on surgical attitude and outcomes

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Exp Ther Med. 2022 Jan;23(1):57. doi: 10.3892/etm.2021.10979. Epub 2021 Nov 17.

ABSTRACT

Multimodal treatment of breast cancer has made steady progress in recent years. The involvement of modern oncology, diagnostic imaging techniques and surgical treatment, have brought a definite benefit to patients, defining the multidisciplinary treatment of breast cancer. The introduction of immunohistochemical testing and genetic screening has led to the prioritization of therapy according to their results and a correct approach to initiating treatment. The main aim of the present study was to conduct a comparative analysis through a retrospective study of the therapeutic means used in breast cancer with the statistical evaluation of the obtained results. To carry out the study, a group of 125 patients hospitalized during the period January 2015 to December 2020, were included, and the parameters were selected from the observation sheets. The res ults of the study demonstrated the superiority of multimodal treatment of breast cancer over surgical treatment as the only therapeutic management. The introduction of ultrasound-guided biopsies and conservative surgical options has led to increased diagnostic accuracy and a significant improvement in aesthetic outcome. The multidisciplinary approach to breast cancer allows an individualized treatment by performing immunohistochemical testing and through the use of neoadjuvant and adjuvant treatment combined with conservative surgical techniques with a more favorable cosmetic and oncological result, with reduced postoperative complications.

PMID:34917183 | PMC:PMC8630438 | DOI:10.3892/etm.2021.10979

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ASA Physical Status Classification and Complications Following Facial Fracture Repair

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Ann Otol Rhinol Laryngol. 2021 Dec 17:34894211059599. doi: 10.1177/00034894211059599. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate the association between American Society of Anesthesiologists (ASA) physical status classification and rates of postoperative complications in patients undergoing facial fracture repair.

METHODS: Patients were divided into 2 cohorts based on the ASA classification system: Class I/II and Class III/IV. Chi-square and Fisher's ex act tests were used for univariate analyses. Multivariate logistic regressions were used to assess the independent associations of covariates on postoperative complication rates.

RESULTS: A total of 3575 patients who underwent facial fracture repair with known ASA classification were identified. Class III/IV patients had higher rates of deep surgical site infection (P = .012) as well as bleeding, readmission, reoperation, surgical, medical, and overall postoperative complications (P < .001). Multivariate regression analysis found that Class III/IV was significantly associated with increased length of stay (P < .001) and risk of overall complications (P = .032). Specifically, ASA Class III/IV was associated with increased rates of deep surgical site infection (P = .049), postoperative bleeding (P = .036), and failure to wean off ventilator (P = .027).

CONCLUSIONS: Higher ASA class is associated with increased length o f hospital stay and odds of deep surgical site infection, bleeding, and failure to wean off of ventilator following facial fracture repair. Surgeons should be aware of the increased risk for postoperative complications when performing facial fracture repair in patients with high ASA classification.

PMID:34918565 | DOI:10.1177/00034894211059599

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Impact of the Mutational Landscape of the Sodium/Iodide Symporter in Congenital Hypothyroidism

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Thyroid, Volume 31, Issue 12, Page 1776-1785, December 2021.
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Bispecific antibodies in onco-hematology: Applications and perspectives

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Bull Cancer. 2021 Oct;108(10S):S195-S204. doi: 10.1016/j.bulcan.2021.10.002.

ABSTRACT

Bispecific antibodies are novel approaches of immunotherapy engaging immune cells to destroy tumor cells. Their structure is variable and underlies their pharmacocinetic properties. These coumpounds are now being evaluated across multiple hematological malignancies. The anti-CD3/CD19 antibody blinatumomab is the first in class and have been approved for the treatment of patients with Ph-negative B-cell acute lymphoblastic leukemia. Other emerging applications are lymphoma, multiple myeloma and acute myeloid leukemia. The safety profile of bispecific antibodies is acceptable while limited by neurotoxicity and cytokine-release syndrome. The present review aims to depict the landscape of emerging bispecific antibodies currently in development for hematological malignancies.

PMID:34920803 | DOI:10.1016/j.bulcan.2021.10.002

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CAR-T cells in lymphomas: Current and evolving role

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Bull Cancer. 2021 Oct;108(10S):S28-S39. doi: 10.1016/j.bulcan.2021.04.022.

ABSTRACT

Three CD19 CAR-T cells (Yescarta®, Kymriah® and Breyanzi®), have been approved in relapsed or refractory diffuse large B cell lymphomas (DLBCL) after at least two previous lines of therapy. These immunotherapies have transformed the prognosis of these lymphomas, which can't be cured by conventional treatments. Long-term updates of registration studies as well as the first real-life data allow a better knowledge of the efficacy of these emerging therapies, their toxicity and their resistance mechanisms. These advances have also led to consider the earlier use of CAR-T cells in the therapeutic strategy and to extend it to other B lymphomas such as mantle cell and indolent lymphomas. Indeed, Yescarta® and Tecartus® have been recently approved in those malignancies, Furthermore, other strategies are being investigated to develop new CAR-T cells to targ et Hodgkin's lymphomas and T-cell lymphomas, although data in these settings still have to be completed. In this article, we review the latest data on the use of CAR-T cells in lymphomas.

PMID:34920805 | DOI:10.1016/j.bulcan.2021.04.022

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CAR-T cells, from principle to clinical applications

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Bull Cancer. 2021 Oct;108(10S):S4-S17. doi: 10.1016/j.bulcan.2021.02.017.

ABSTRACT

Chimeric antigen receptors (CAR)-T cells are genetically engineered T-lymphocytes redirected with a predefined specificity to any target antigen, in a non-HLA restricted manner, therefore combining antibody-type specificity with effector T-cell function. This strategy was developed some thirty years ago, after extensive work established the key role of the immune system against cancer. The first-engineered T-cell with chimeric molecule was designed in 1993 by Israeli immunologist Zelig Eshhar. Since then, several modifications took place, including the addition of co-stimulatory domain, to further improve CAR-T cell anti-tumor potency. The first clinical application of CAR-T cell was done in Rotterdam in 2005 for metastatic renal cell carcinoma and simultaneously at the National Cancer Institute (NCI) for metastatic ovarian cancer. These pioneered studie s failed to demonstrate a therapeutic benefit, but warning emerged concerning their safety of use. The real clinical success came with anti-CD19 CAR-T cells, used since 2009 by Steven Rosenberg at the NCI in a patient with refractory follicular lymphoma and in 2011 by Carl June and David Porter from the University of Pennsylvania in patients with chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia. From that time, large centers in North America have embarked in several early phase and pivotal trials that have demonstrated unprecedent response rate in heavily pretreated chemo refractory patient with B-cell malignancies. Theses clinical success have led to the approval of three anti-CD19 CAR-T cells products for the management of B-cell malignancies in the United States and in Europe as of December 2020.

PMID:34920806 | DOI:10.1016/j.bulcan.2021.02.017

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CAR T-cells in acute lymphoblastic leukemia: Current results

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Bull Cancer. 2021 Oct;108(10S):S40-S54. doi: 10.1016/j.bulcan.2021.08.001.

ABSTRACT

The marketing authorization of tisagenlecleucel, a 2nd generation of CD19-directed CAR T-cells, containing the 4-1 BB co-stimulatory domain, in 2017 in USA and in 2018 in EU, has revolutionized the therapeutic strategy in advanced B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents and young adults (AYAs) with relapsed or refractory disease. This innovative treatment, based on a "living drug", has shown very impressive short-term responses. However, safety profile and complex logistics require high expertise centers and tight collaborations between addressing and treating centers. Current research is exploring the possibility to move to first line ALL with high-risk features and/or first high-risk relapse. More efficient CAR T-cells products, are still lacking to counteract the escape mechanisms already described. Moreover, to define th e bridge-to-CAR time for each patient remains a challenge to obtain optimal disease burden allowing expansion and persistence of CAR T-cells. Also difficult is to identify patients who will benefit from further therapy after infusion, such as allogeneic HSCT or may be immuno-modulatory treatment. Finally, CAR T-cells directed against T-ALL are only in their beginning but require more complex engineering process to avoid T- cell immune-deficiency or fratricide.

PMID:34920807 | DOI:10.1016/j.bulcan.2021.08.001

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CARTi: The French-speaking group for the harmonization of immune monitoring in patients treated with CAR-T cells

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Bull Cancer. 2021 Oct;108(10S):S141-S142. doi: 10.1016/j.bulcan.2021.06.006.

NO ABSTRACT

PMID:34920796 | DOI:10.1016/j.bulcan.2021.06.006

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Bispecific antibodies: An old story with a bright future… with CAR-T cells!

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Bull Cancer. 2021 Oct;108(10S):S168-S180. doi: 10.1016/j.bulcan.2021.02.016.

ABSTRACT

CAR-T cells originate from two different approaches, cellular immunotherapy based on tumor immunosurveillance by T lymphocytes, combined with molecular engineering of bispecific antibodies and antibody fragments. The latter makes it possible to retarget immune effector cytotoxic cells (such as NK cells and T lymphocytes) to tumor cells through the binding to tumor-associated antigens. We present herein the history of bispecific antibodies, highlighting how such antibodies played a major role in CAR-T cell development. We will first evoke how antibody engineering led to the construction of various bispecific formats, in particular using the single chain Fv fragment (scFv) which has been used as the initial building block to generate chimeric bi-, tri- or multifunctional molecules. We will also describe how bispecific antibodies, either full IgG or as s cFv or F(ab')2 format, directed against Fcγ receptors or CD3ɛ and against tumor-associated antigens, induce a potent anti-tumor cytotoxicity following the recruitment and activation of immune effector cells, including CD3+ T lymphocytes. These anti-tumor effects have been translated into the clinics, especially to treat malignant hemopathies. At last, recently generated bispecific CAR-T cells suggest that the embrace between cell therapy and bispecific antibodies is not over and that we are yet to witness further discoveries enabling these cells to be even more efficient.

PMID:34920800 | DOI:10.1016/j.bulcan.2021.02.016

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CAR-T cell: Toxicities issues: Mechanisms and clinical management

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Bull Cancer. 2021 Oct;108(10S):S117-S127. doi: 10.1016/j.bulcan.2021.05.003.

ABSTRACT

CAR-T cells are modified T cells expressing a chimeric antigen receptor targeting a specific antigen. They have revolutionized the treatment of B cell malignancies (aggressive lymphomas, B-ALL), and this has raised hopes for application in many other pathologies (myeloma, AML, solid tumors, etc.). However, these therapies are associated with novel and specific toxicities (cytokine release syndrome and neurotoxicity). These complications, although mostly managed in a conventional hospitalization unit, can sometimes be life threatening, leading to admission of patients to the intensive care unit. Management relies mainly on anti-IL6R (tocilizumab) and corticosteroids. However, the optimal treatment regimen is still a matter of debate, and the management of the most severe forms is even less well codified. In addition to CRS and ICANS, infections, cytope nia and hypogammaglobulinemia are other frequent complications. This article reviews the mechanisms, risk factors, clinical presentation, and management of these toxicities.

PMID:34920794 | DOI:10.1016/j.bulcan.2021.05.003

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