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Propranolol as a potentially novel treatment of arteriovenous malformations: from bench to bedside
(2022)
Background: Propranolol is a non-selective blocker of the β-adrenergic receptor and has been used for treatment of proliferative infantile hemangiomas. The vasoconstrictive and antiangiogenic effects of propranolol led us to explore its potential application for the treatment of AVMs.
Methods: AVM tissue was cultured after surgical resection in the presence of 100μM propranolol or solvent DMSO. After incubation for 72 hours, tissue was harvested for testing. The expression levels of SDF1α, CXCR4, VEGF and HIF-1 was measured by rt-PCR. Furthermore, data of patients in 2 vascular centres harboring AVM was retrospectively interrogated for a time period of 20 years. The database included information about hemorrhage, AVM size and antihypertensive medication. Descriptive analyses were performed, focusing on the risk of hemorrhage, size of the lesion at presentation and clinical follow-up in patients on β-blocker medication versus those who were not.
Results: Among 483 patients, 73 (15%) were under β-blocker-treatment. 48% AVMs presented with hemorrhage at diagnosis. Patients under β-blocker-treatment had a lower risk of hemorrhage at the time of diagnosis in a univariate analysis (p<0,0001;OR13). Patients under β-blocker-treatment showed a significant higher chance for a lower Spetzler-Martin-grade ≤III (p<0,0001;OR6,5) and a lower risk for the presence of an associated aneurysm (p<0,0001;OR3,6).
Multivariate analysis including Spetzler-Martin-Grading, young age ≤50, presence of associated aneurysm and β-blocker-treatment showed reduced risk for hemorrhage under β-blocker-treatment (p<0,01,OR0,2).
The expression of CXCR4 was suppressed by propranolol most likely through the HIF-1-pathways. The gene-expression of vasculogenesis factors was decreased in with propranolol incubated AVMs.
Conclusion: β-Blocker medication seems to be associated with a decreased risk of AVM-related hemorrhage and AVM-size at presentation or during follow-up. Propranolol inhibits SDF1α-induced vasculogenesis by suppressing the expression of CXCR4 most likely through the HIF-1-pathways. Therefore, SDF1α/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in AVM lesions.
Due to ongoing demographic changes, the need for care is increasing in Germany. The number of outpatient care services is also rising, and with it, the number of employees in outpatient care, who are also continuously becoming older. Workplace health promotion (WHP) becomes relevant in this context, as it can reduce negative strain reactions and promote employees’ health. The aim of this study was (1) to reveal implemented WHP interventions in German outpatient care services; (2) to examine the potential challenges regarding a successful implementation of WHP measures; and (3) to illuminate further requests and needs experienced by outpatient careworkers. In qualitative field research, 30 semi-structured individual interviews were conducted with German caregivers, using the problem-centered interview method. The collected data were deductively and inductively evaluated and interpreted, using qualitative content analysis according to Mayring. Outpatient caregivers reported various WHP measures known from their workplaces, such as the provision of fruit baskets, programmes to increase physical activity, or a subsidy for a personal gym. They further reported WHP, such as back training, known from other care services. However, the respondents spoke of the challenges regarding the implementation or the use of WHP interventions in general. The most frequently named barriers were a lack of time after work and interventions that were only offered in their leisure time. In the same course, the participants still needed offers to increase physical activity, joint activities, or relaxation techniques. However, respondents highlighted that they preferred the interventions to take place during working hours. This way, they would also be more likely to take advantage of the interventions. The results of this study provide an insight into various WHP measures that already exist, or that are desirable for implementation with regard to caregivers’ needs. Subjectively perceived challenges for a successful implementation of WHP measures represent the importance of adjustments in the work organization of caregivers. It becomes clear that WHP is not yet established in the ambulant care sector, although it appears to be imperative for keeping caregivers healthy. Considering the different needs of employees, the results can provide a basis for the development of needs-based health promotion measures for caregivers.
Invasive fungal infections are associated with increased mortality in hematological patients. Despite considerable advances in antifungal therapy, the evaluation of suspected treatment failure is a common clinical challenge requiring extensive diagnostic testing to rule out potential causes, such as mixed infections. We present a 64-year-old patient with secondary AML, diabetes mellitus, febrile neutropenia, and sinusitis. While cultures from nasal tissue grew Aspergillus flavus, a microscopic examination of the tissue was suggestive of concomitant mucormycosis. However, fluorescence in situ hybridization (FISH) using specific probes targeting Aspergillus and Mucorales species ruled out mixed infection. This was confirmed by specific qPCR assays amplifying the DNA of Aspergillus, but not of Mucorales. These results provided a rational basis for step-down targeted therapy, i.e., the patient received posaconazole after seven days of calculated dual therapy with liposomal amphotericin B and posaconazole. Despite clinical response to the antifungal therapy, he died due to the progression of the underlying disease within two weeks after diagnosis of fungal infection. Molecular diagnostics applied to tissue blocks may reveal useful information on the etiology of invasive fungal infections, including challenging situations, such as with mixed infections. A thorough understanding of fungal etiology facilitates targeted therapy that may improve therapeutic success while limiting side effects.