Der Internist
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Syncope is a frequent disorder, sometimes due to life-threatening causes. The uncertainty in its diagnosis requires a standardized approach. ⋯ However, some aspects require critical appraisal. The inadequate availability and reimbursement of pivotal diagnostic tests, such as tilt table testing and the implantable loop recorder is emphasized.
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The term "sickle cell disease" covers a group of genetic blood disorders caused by sickle hemoglobin (HbS) alone or in combination with other variants of the β‑globin locus. Sickle cell disease occurs frequently in sub-Saharan Africa, but is also common in Turkey, Greece, Sicily, the Middle East, India, and the Americas. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. ⋯ Complications can vary between the different genotypes and it is important to be aware of the special features of the disease. Hydroxycarbamide has been shown to reduce the morbidity and mortality of patients with sickle cell disease. New drugs and novel treatment approaches such as gene therapy are currently being tested.
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The induction of protective T cell responses requires two signals: Signal 1 is generated by activation of the T cell receptor (TCR) and signal 2 results from ligation of the CD28 molecule. Costimulation of the TCR and CD28 is necessary, as the TCR is very good at discriminating between endogenous and foreign structures (antigens), but not all foreign antigens (such as food antigens) are dangerous to the body. A strong CD28 signal, thus, indicates to the T cell that there is indeed a threat and that an immune response is urgently required. However, to avoid autoimmunity and excessive immune responses, further regulatory circuits, provided by immune checkpoints, are necessary. ⋯ Due to the clinical success of checkpoint inhibitors, the concept of cancer immunotherapy has received a massive boost and hopes are high that many more clinical advancements in cancer therapy can be achieved with novel forms of immunotherapy.