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The potent oral inhibitor of BCL2, venetoclax (VEN), used to treat adults with chronic lymphocytic leukaemia, has been approved in US for the treatment of naïve patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy and recently in Europe, too. However, the drug has been used for years in combination with hypomethylating agents (HMAs) in patients not eligible to other treatment option, according to the so-called off-label use. We collected real-world data about patients treated with VEN + HMAs in the context of a pharmacovigilance project focused on the evaluation of the safety and effectiveness of drugs used for unapproved indication in Italian hospitals. From March to December 2020, 24 patients started treatment with VEN combined with HMAs. 21 patients have been assessed for response. Eleven (52%) patients reached complete remission (CR), and three patients (14%) CR with partial hematological recovery (CRh), with a median duration of response of 4.5 months (range 0.5–12.5). 19 patients experienced at least 1 adverse drug reaction (ADR), mostly serious, including 3 deaths (9% of ADRs; 12.5% of patients) in febrile neutropenia. Hematological toxicities and infections (cytopenia, neutropenia, febrile neutropenia, sepsis), were the most reported ADRs (84.4%). In general, neutropenic fever occurred more frequently in patients treated with decitabine (7 out of 9, 78%) compared to azacitidine (5 out of 15, 33%; p = 0.03), whereas response assessment did not differ based on used HMA (p = 0.1). These results confirm the benefit-risk profile of VEN in a real-world setting of patients with no adequate therapeutic options. [ABSTRACT FROM AUTHOR]

Background: With the "Artemis"-mission mankind will return to the Moon by 2024. Prolonged periods in space will not only present physical and psychological challenges to the astronauts, but also pose risks concerning the medical treatment capabilities of the crew. So far, no guideline exists for the treatment of severe medical emergencies in microgravity. We, as a international group of researchers related to the field of aerospace medicine and critical care, took on the challenge and developed a an evidence-based guideline for the arguably most severe medical emergency - cardiac arrest., Methods: After the creation of said international group, PICO questions regarding the topic cardiopulmonary resuscitation in microgravity were developed to guide the systematic literature research. Afterwards a precise search strategy was compiled which was then applied to "MEDLINE". Four thousand one hundred sixty-five findings were retrieved and consecutively screened by at least 2 reviewers. This led to 88 original publications that were acquired in full-text version and then critically appraised using the GRADE methodology. Those studies formed to basis for the guideline recommendations that were designed by at least 2 experts on the given field. Afterwards those recommendations were subject to a consensus finding process according to the DELPHI-methodology., Results: We recommend a differentiated approach to CPR in microgravity with a division into basic life support (BLS) and advanced life support (ALS) similar to the Earth-based guidelines. In immediate BLS, the chest compression method of choice is the Evetts-Russomano method (ER), whereas in an ALS scenario, with the patient being restrained on the Crew Medical Restraint System, the handstand method (HS) should be applied. Airway management should only be performed if at least two rescuers are present and the patient has been restrained. A supraglottic airway device should be used for airway management where crew members untrained in tracheal intubation (TI) are involved., Discussion: CPR in microgravity is feasible and should be applied according to the Earth-based guidelines of the AHA/ERC in relation to fundamental statements, like urgent recognition and action, focus on high-quality chest compressions, compression depth and compression-ventilation ratio. However, the special circumstances presented by microgravity and spaceflight must be considered concerning central points such as rescuer position and methods for the performance of chest compressions, airway management and defibrillation.