[Recurrent, severe epistaxis in COVID-19 patients]. / Rezidivierende, schwere Epistaxis bei COVID-19-Patienten.

A 12-year-old female patient presented in the emergency room due to spontaneous, recurrent, fulminant epistaxis. As an additional finding a COVID-19-infection was noticed. Persisting hemorrhage led to increasing symptoms of shock. The current literature indicates a clear correlation of a SARS-CoV­2-infection to spontaneous fulminant epistaxis, most likely due to a mucosal inflammation; however, other typical causes must be ruled out.

Correction: Role of growth arrest-specific gene 6-mer axis in multiple myeloma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effects of p38α/ß inhibition on acute lymphoblastic leukemia proliferation and survival in vivo.

P38α/ß has been described as a tumor-suppressor controlling cell cycle checkpoints and senescence in epithelial malignancies. However, p38α/ß also regulates other cellular processes. Here, we describe a role of p38α/ß as a regulator of acute lymphoblastic leukemia (ALL) proliferation and survival in experimental ALL models. We also report first evidence that p38α/ß phosphorylation is associated with the occurrence of relapses in TEL-AML1-positive leukemia. First, in vitro experiments show that p38α/ß signaling is induced in a cyclical manner upon initiation of proliferation and remains activated during log-phase of cell growth. Next, we provide evidence that growth-permissive signals in the bone marrow activate p38α/ß in a novel avian ALL model, in which therapeutic targeting can be tested. We further demonstrate that p38α/ß inhibition by small molecules can suppress leukemic expansion and prolong survival of mice bearing ALL cell lines and primary cells. Knockdown of p38α strongly delays leukemogenesis in mice xenografted with cell lines. Finally, we show that in xenografted TEL-AML1 patients, ex vivo p38α/ß phosphorylation is associated with an inferior long-term relapse-free survival. We propose p38α/ß as a mediator of proliferation and survival in ALL and show first preclinical evidence for p38α/ß inhibition as an adjunct approach to conventional therapies.

Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma.

Multiple myeloma is a mostly incurable malignancy characterized by the expansion of a malignant plasma cell (PC) clone in the human bone marrow (BM). Myeloma cells closely interact with the BM stroma, which secretes soluble factors that foster myeloma progression and therapy resistance. Growth arrest-specific gene 6 (Gas6) is produced by BM-derived stroma cells and can promote malignancy. However, the role of Gas6 and its receptors Axl, Tyro3 and Mer (TAM receptors) in myeloma is unknown. We therefore investigated their expression in myeloma cell lines and in the BM of myeloma patients and healthy donors. Gas6 showed increased expression in sorted BMPCs of myeloma patients compared with healthy controls. The fraction of Mer(+) BMPCs was increased in myeloma patients in comparison with healthy controls whereas Axl and Tyro3 were not expressed by BMPCs in the majority of patients. Downregulation of Gas6 and Mer inhibited the proliferation of different myeloma cell lines, whereas knocking down Axl or Tyro3 had no effect. Inhibition of the Gas6 receptor Mer or therapeutic targeting of Gas6 by warfarin reduced myeloma burden and improved survival in a systemic model of myeloma. Thus, the Gas6-Mer axis represents a novel candidate for therapeutic intervention in this incurable malignancy.

Instructions for infection control in outpatient care of patients with cystic fibrosis.

RATIONALE AND GOALS: Infections of the respiratory tract with multiresistant bacteria and other pathogens lead to a poor prognosis in patients with cystic fibrosis. The patient-to-patient transmission of infectious agents during the clinic visit and the transmission via the hands of healthcare workers has gained increased attention in the cystic fibrosis community. For this reason practical and possibly evidence-based instructions for infection control measures are needed that are feasible in every day outpatient management of patients with cystic fibrosis. - METHODS: For generating these instructions, a committee consisting of medical doctors and nursing staff providing care to cystic fibrosis patients, infectious diseases specialists and members of the department of infection control analyzed the patients' route through our cystic fibrosis unit during a routine clinic visit. First, the expert committee defined instructions concerning important infection control measures for each step. Next, each instruction was compared with the published literature and categorized as to its grade of evidence (I, II, 0). Instructions with grades of evidence I and II and instructions without demonstrated evidence (0) but theoretically reasonable and practically feasible, were accepted and outlined in a flow diagram. All other instructions were rejected. - RESULTS: The expert committee defined 45 instructions for infection control measures during an outpatient visit of a cystic fibrosis patient. 43 instructions within the categories "principles", "measures before entering the clinic", "measures in the examination room" and "measures when leaving the clinic" matched the criteria mentioned above and were accepted. 2 instructions were rejected. - CONCLUSIONS: Here we report evidence-based instructions for infection control in the setting of outpatient care for cystic fibrosis patients which are feasible in every day care. Since some instructions could only be assigned low evidence grade levels, i. e. II or 0, a further clarification of these issues by scientific investigations is warranted. Unresolved issues are primarily the recommendation for or against wearing a face mask for patients with certain pathogens and the issues of colonization with Stenotrophomonas maltophilia and Alcaligines xylosidans, but also with Aspergillus spp.. Continuous education of patients and healthcare workers as well as the validation of these practical instructions by a close monitoring and documentation of pathogens are of great importance.