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      Unklare Minderung des Allgemeinzustandes bei Patientin mit Lungenkarzinom Translated title: Unexplained reduction in the general condition of a female lung cancer patient

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          Abstract

          Eine 63-jährige Patientin mit Lungenkarzinom stellte sich erstmalig in unserer Notaufnahme mit plötzlicher Reduktion des Allgemeinzustands, Erbrechen und ausgeprägter Schwäche vor. Sie gab an, aufgrund des Lungenkarzinoms eine Chemotherapie zu erhalten, und verneinte weitere, relevante Vorerkrankungen. Unsere initiale Verdachtsdiagnose waren eine zytostatikainduzierte Nausea und Emesis. Die in der Notaufnahme durchgeführte Diagnostik erbrachte entgegen dieser Verdachtsdiagnose die Befunde einer Ketoazidose auf dem Boden einer Erstmanifestation eines Diabetes mellitus mit hyperglykämischer Entgleisung sowie einer schweren, manifesten Hypothyreose. Nach Beschaffung der Vorbefunde wurde evident, dass die Patientin keine Chemotherapie, sondern eine Immuncheckpointtherapie mittels Durvalumab erhielt. Die beschriebenen Erstmanifestationen waren demzufolge als durvalumabassoziierte Immunreaktionen zu werten. Nach Einleitung einer diabetischen Rekompensationstherapie und Substitution mittels L‑Thyroxin konnte eine rasche Verbesserung des Allgemeinzustands erreicht werden. Wären für uns relevante Vorbefunde schon zu Behandlungsbeginn abrufbar gewesen, beispielsweise durch die elektronische Patientenakte, wären die korrekte Interpretation der Symptome und die korrekte Therapie früher möglich gewesen.

          Translated abstract

          A 63-year-old female patient with lung cancer presented to our emergency room for the first time with a sudden reduction in general condition, vomiting and severe weakness. She stated that she was receiving chemotherapy for the lung cancer and reported that she had no other relevant previous illnesses. Our initial suspected diagnosis was cytostatic-induced nausea and vomiting. Contrary to this suspected diagnosis, diagnostics carried out in the emergency room revealed the findings of ketoacidosis on the basis of an initial manifestation of diabetes mellitus with hyperglycemic decompensation as well as severe, manifest hypothyroidism. After obtaining the preliminary findings, it became evident that the patient was not receiving chemotherapy, but rather immune checkpoint therapy using durvalumab. The initial manifestations described were therefore to be viewed as immune reactions associated with durvalumab. After initiating diabetic recompensation therapy and substitution with L‑thyroxine, a rapid improvement in the patientʼs general condition was achieved.

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          Cancer immunotherapy using checkpoint blockade

          The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte antigen-4 (CTLA-4) or the programmed death-1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the pre-existence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long lasting disease control, yet one third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon gamma signaling pathways. New generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
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            Immune-related adverse events with immune checkpoint blockade: a comprehensive review.

            Cancer immunotherapy is coming of age; it has prompted a paradigm shift in oncology, in which therapeutic agents are used to target immune cells rather than cancer cells. The first generation of new immunotherapies corresponds to antagonistic antibodies that block specific immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. Targeting these checkpoints in patients living with cancer had led to long-lasting tumour responses. By unbalancing the immune system, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (IRAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung but can potentially affect any tissue. In view of their undisputed clinical efficacy, anti-CTLA-4 and anti-PD-1 antibodies are entering in the routine oncological practice, and the number of patients exposed to these drugs will increase dramatically in the near future. Although steroids can be used to treat these IRAEs, the associated immunosuppression may compromise the antitumour response. Oncologists must be ready to detect and manage these new types of adverse events. This review focuses on the mechanisms of IRAE generation, putative relationship between dysimmune toxicity and antitumour efficacy, as a basis for management guidelines.
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              Adaptive Immune Resistance: How Cancer Protects from Immune Attack.

              Adaptive immune resistance is a process in which the cancer changes its phenotype in response to a cytotoxic or proinflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T-cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1-blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies.
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                Author and article information

                Contributors
                Johannasibylle.braegelmann@uk-essen.de
                Journal
                Inn Med (Heidelb)
                Inn Med (Heidelb)
                Innere Medizin (Heidelberg, Germany)
                Springer Medizin (Heidelberg )
                2731-7080
                2731-7099
                19 January 2024
                19 January 2024
                2024
                : 65
                : 6
                : 612-616
                Affiliations
                [1 ]GRID grid.477805.9, ISNI 0000 0004 7470 9004, Klinik für Endokrinologie, Diabetologie und Stoffwechsel, , Universitätsmedizin Essen, ; Hufelandstraße 55, 45147 Essen, Deutschland
                [2 ]Marienhaus Klinikum Mainz, Mainz, Deutschland
                Author notes
                [Redaktion]

                H. Haller, Hannover (Schriftleitung)

                B. Salzberger, Regensburg

                C.C. Sieber, Winterthur, Schweiz

                Article
                1652
                10.1007/s00108-023-01652-5
                11136821
                38240815
                e6c06b85-84b2-49e3-9b6a-05478d3b1a97
                © The Author(s) 2024

                Open Access Dieser Artikel wird unter der Creative Commons Namensnennung 4.0 International Lizenz veröffentlicht, welche die Nutzung, Vervielfältigung, Bearbeitung, Verbreitung und Wiedergabe in jeglichem Medium und Format erlaubt, sofern Sie den/die ursprünglichen Autor(en) und die Quelle ordnungsgemäß nennen, einen Link zur Creative Commons Lizenz beifügen und angeben, ob Änderungen vorgenommen wurden.

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                History
                : 14 December 2023
                Funding
                Funded by: Universitätsklinikum Essen (8912)
                Categories
                Kasuistiken
                Custom metadata
                © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2024

                durvalumab,immunbedingte unerwünschte ereignisse (ibue),immun-checkpoint-inhibitoren-induzierter typ-1-diabetes (ici-t1d),elektronische patientenakte (epa),informationsinfrastruktur,immune-related adverse events (iraes),checkpoint inhibitor associated autoimmune diabetes mellitus (ciadm),electronic patient file (epf),information infrastructure

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