Intranasal Efudix reduces epistaxis in hereditary hemorrhagic telangiectasia

Jel, Dominique V.C. de; Disch, F. J. M.; Kroon, Steven; Mager, J. J.; Verdam, Froukje J.

doi:10.1007/s10456-020-09712-2

Cited by 13 publications

(14 citation statements)

References 9 publications

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“…Other anti-angiogenic agents with data published for the treatment of HHT-associated bleeding include bevacizumab [15][16][17][18], thalidomide [28], and pomalidomide [29], with the largest amount of data supporting intravenous bevacizumab. Recent studies have also highlighted the anti-angiogenic potential of the antifungal itraconazole [30] and the local hemostatic capacity of intranasal fluorouracil (Efudix) [31] in HHT. The data supporting intravenous bevacizumab were sufficient for its recommendation to manage moderate-tosevere epistaxis and/or GI bleeding in the recently published updated international HHT guidelines [32].…”

Section: Discussionmentioning

confidence: 99%

Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia

et al. 2021

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Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4. 77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial.

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Section: Discussionmentioning

confidence: 99%

Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia

et al. 2021

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“…Mfn1/2 silencing increased mitochondrial fragmentation and disrupted VEGF-mediated migration and differentiation of ECs in vitro 107 . It was also reported that reduced mitochondrial fusion contributes to oxidative stress and apoptosis in ECs 108 .…”

Section: Role Of Mqc In Coronary Microvascular Ecs Injury During MImentioning

confidence: 94%

Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

et al. 2021

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Endothelial cells (ECs) constitute the innermost layer in all blood vessels to maintain the structural integrity and microcirculation function for coronary microvasculature. Impaired endothelial function is demonstrated in various cardiovascular diseases including myocardial infarction (MI), which is featured by reduced myocardial blood flow as a result of epicardial coronary obstruction, thrombogenesis, and inflammation. In this context, understanding the cellular and molecular mechanisms governing the function of coronary ECs is essential for the early diagnosis and optimal treatment of MI. Although ECs contain relatively fewer mitochondria compared with cardiomyocytes, they function as key sensors of environmental and cellular stress, in the regulation of EC viability, structural integrity and function. Mitochondrial quality control (MQC) machineries respond to a broad array of stress stimuli to regulate fission, fusion, mitophagy and biogenesis in mitochondria. Impaired MQC is a cardinal feature of EC injury and dysfunction. Hence, medications modulating MQC mechanisms are considered as promising novel therapeutic options in MI. Here in this review, we provide updated insights into the key role of MQC mechanisms in coronary ECs and microvascular dysfunction in MI. We also discussed the option of MQC as a novel therapeutic target to delay, reverse or repair coronary microvascular damage in MI. Contemporary available MQC-targeted therapies with potential clinical benefits to alleviate coronary microvascular injury during MI are also summarized.

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“…The reactions were carried out using SYBR Premix Ex Taq™ (TaKaRa, Dalian, China). GAPDH was used as an endogenous reference [ 31 ]. The relative gene expression was evaluated by the 2 - ∆∆ CT method; each sample was measured at least three times.…”

Section: Methodsmentioning

confidence: 99%

[Retracted] LATS2 Deletion Attenuates Myocardial Ischemia‐Reperfusion Injury by Promoting Mitochondrial Biogenesis

Chen

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Reperfusion therapy is the most effective treatment for acute myocardial infarction, but it can damage cardiomyocytes through a mechanism known as myocardial ischemia/reperfusion injury (MIRI). In this study, we investigated whether the large tumor suppressor kinase 2 (LATS2) contributes to the development of myocardial MIRI by disrupting mitochondrial biogenesis. Our in vitro data demonstrate that cardiomyocyte viability was reduced and apoptosis was increased in response to hypoxia/reoxygenation (H/R) injury. However, suppression of LATS2 by shRNA sustained cardiomyocyte viability by maintaining mitochondrial function. Compared to H/R-treated control cardiomyocytes, cardiomyocytes transfected with LATS2 shRNA exhibited increased mitochondrial respiration, improved mitochondrial ATP generation, and more stable mitochondrial membrane potential. LATS2 suppression increased cardiomyocyte viability and mitochondrial biogenesis in a manner dependent on PGC1α, a key regulator of mitochondrial metabolism. These results identify LATS2 as a new inducer of mitochondrial damage and myocardial MIRI and suggest that approaches targeting LATS2 or mitochondrial biogenesis may be beneficial in the clinical management of cardiac MIRI.

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Intranasal Efudix reduces epistaxis in hereditary hemorrhagic telangiectasia

Cited by 13 publications

References 9 publications

Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia

Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia

Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control

[Retracted] LATS2 Deletion Attenuates Myocardial Ischemia‐Reperfusion Injury by Promoting Mitochondrial Biogenesis

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