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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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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Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1740622

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Distinct Cytokine Signatures in Thyroiditis Induced by PD-1 or CTLA-4 Blockade: Insights from a New Mouse Model

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Thyroid, Volume 31, Issue 12, Page 1839-1849, December 2021.
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Bispecific antibodies targeting CD3 in oncology and hematology

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Bull Cancer. 2021 Oct;108(10S):S181-S194. doi: 10.1016/j.bulcan.2021.06.003.

ABSTRACT

Bispecific therapies targeting CD3, so-called T-cell engagers (TCE), belong to the new spectrum of anti-tumor immunotherapies stimulating T-lymphocytes. TCE are unique constructs targeting the MHC-independent CD3 epsilon subunit (CD3e) and a tumor antigen. To date, only blinatumomab have reached market agreements in lymphoid malignancies with constructs targeting CD3exCD19. Other TCE are in advances development, with promising results targeting CD20 and BSMA in lymphoma and myeloma. These successes have relaunched the development of TCE in solid tumors, bringing mixed results so far (notably in terms of tolerance). Still, TCE pave the way to new immunotherapy in tumors considered to be refractory to inhibitors of immune checkpoints such as prostate cancer or colorectal cancer.

PMID:34920802 | DOI:10.1016/j.bulcan.2021.06.003

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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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Chimeric antigen receptor T cells

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Bull Cancer. 2021 Oct;108(10S):S55-S64. doi: 10.1016/j.bulcan.2021.08.003.

ABSTRACT

Chimeric antigen receptor T-cell (CAR T-cells) therapies which are genetically modified T lymphocyte targeting tumor antigens have modified therapeutic landscape in hematology. Aggressive B cells lymphoma are currently treated in daily practice with anti-CD19 CAR T. In indolent B cell lymphomas, their efficacy has been established by recent clinical trials. Longer follow-up evaluation is needed to determine their added value in a field where approved strategies already provide high long-term survival rates. They will also be challenged by another immunotherapy with bispecific antibodies. In chronic lymphoid leukemia, early phase trials have identified several limitations related to the immune context of this disease, but associations with targeted therapy like ibrutinib are very promising. In this moving therapeutic landscape, molecular and cellular eng ineering progress will increase the capacities of these new cellular-based therapies.

PMID:34920808 | DOI:10.1016/j.bulcan.2021.08.003

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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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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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T cell-based immunotherapies in solid tumors

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Bull Cancer. 2021 Oct;108(10S):S96-S108. doi: 10.1016/j.bulcan.2021.06.004.

ABSTRACT

In solid tumors, adoptive T cell therapies based on ex vivo amplification of antitumor T cell are represented by three main complementary approaches : (i) tumor infiltrating lymphocytes (TILs) which are amplified in vitro before reinjection to the patient, (ii) chimeric antigen receptor (CAR) engineered T cells and (iii) T cell receptor (TCR) engineered T cells. Despite encouraging results, some obstacles remain, such as optimal target selection and tumor microenvironment. In this Review, we discuss pros and cons of these different therapeutic strategies that may open new perspectives in the treatment of solid tumors.

PMID:34920813 | DOI:10.1016/j.bulcan.2021.06.004

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CAR-T CELLS: How does the EBMT registry monitor European activities, identify hurdles and prepare for changes in regulations

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Bull Cancer. 2021 Oct;108(10S):S155-S161. doi: 10.1016/j.bulcan.2021.08.004.

ABSTRACT

CAR-T Cells are gene therapy medicinal products, a subcategory of Advanced Therapy Medicinal Products as defined in the EC Regulation 1394/2007. They may represent the first example of such medicinal products that are industry-manufactured and commercialized on a large scale. Their very nature, their manufacturing processes, pricing and conditions upon which they were approved by regulatory agencies, all lead the latter to require long-term follow-up after marketing approval with a view for a better definition of CAR-T Cells safety profile and efficacy profile in real world conditions. Collection and analysis of data over a 15-year period of time represents a technical and political challenge. So does the a priori definition of data to be collected for a wealth of forthcoming analyses that focus on the interests of a variety of stakeholders. EBMT has been collecting and analyzing data on hematopoietic cell transplants for decades. EBMT currently works with many interested parties to collect data on patients treated with CAR-T Cells.

PMID:34920798 | DOI:10.1016/j.bulcan.2021.08.004

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