Der Internist
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Following the first demonstration of efficacy of anti-CD19-directed chimeric antigen receptor (CAR) T cells in a patient with relapsed chronic lymphocytic leukemia (CLL) in 2011, pivotal studies for this innovative therapy were initially conducted in multiple relapsed or refractory (r/r) childhood and young adult acute B‑cell leukemia and in aggressive adult B‑cell lymphoma. The studies demonstrated efficacy even in chemotherapy-refractory disease, resulting in the first approval of autologous and genetically engineered T cells for the treatment of r/r B‑cell acute lymphoblastic leukemia (B-ALL) in the US for the product tisagenlecleucel (Kymriah®, Novartis) back in 2018. Approval for the treatment of r/r aggressive B‑cell lymphoma followed shortly thereafter for tisagenlecleucel and axicabtagene ciloleucel (Yescarta, Kite/Gilead). This review focuses on the treatment of aggressive B‑cell lymphoma and other CD19 positive B‑cell lymphomas by summarizing the study results of clinically tested CAR T cells, discussing possible resistance mechanisms, and providing an outlook on ongoing studies with new target antigens for the treatment of B‑cell lymphomas.
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Case Reports
[Confusion, tachypnea, and tachycardia in a 71-year-old man with type 2 diabetes mellitus].
Patients with type 2 diabetes who present with confusion and/or abdominal pains should be screened for sodium-glucose cotransporter 2 (SGLT-2)-induced diabetic ketoacidosis. Severe acidosis was diagnosed despite only moderately increased blood sugar levels. If so, immediate ICU treatment is essential.
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The incidence of type 1 diabetes (T1D) has been rising steadily over the last 30 years, especially among children and adolescents, with the result that the number of cases in this age group doubles every 20 years. The development of T1D goes through three stages, which can vary in duration from individual to individual. Late diagnosis or incorrect interpretation of the symptoms leads to the life-threatening diabetic ketoacidosis, from which every third child in Germany suffers at the manifestation of T1D. ⋯ There are no fundamental differences in the insulin therapy of T1D in children, adolescents and adults. The use of insulin pump therapy and continuous glucose monitoring is steadily increasing with the aim of reducing the number and duration of hypo- and hyperglycemic episodes, increasing the time in range between 70-180 mg/dl (3,9-10 mmol/l) and reaching the treatment goal of an HbA1c below 7% (53 mmol/mol). In addition to the prevention of diabetes-related long-term microvascular complications, the timely detection and treatment of cardiovascular risk factors is of extraordinary importance also for young people with T1D.