Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study” Cancers 2020, 12, 3228

We read the paper by Katsarelias et al. with great interest, regarding the effect of beta-adrenergic blocking agents on cutaneous melanoma [1]. However, the study presents some methodology biases that do not allow us to support the authors’ conclusions. The paper suffers from the unification and evaluation of multiple registries, which do not provide essential data for any of the targets for research. Unlike studies in the literature [...]

Reply to Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study.” Cancers 2020, 12, 3228

We thank De Giorgi et al for their interest in our study, and for raising important and relevant questions [...]

The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study

Previous studies have demonstrated an anti-tumoral effect of beta-adrenergic blocking agents on cutaneous melanoma (CM). The aim of this study was to investigate if beta-adrenergic blocking agents have an impact on survival in Swedish patients with melanoma. A population-based retrospective registry study including all patients diagnosed with a primary invasive melanoma between 2009 and 2013 was performed. Data from the Swedish Melanoma Register were linked to the Swedish Prescribed Drug Registry and the Swedish Cause of Death Register. Cox regression analyses including competing risk assessments were performed. There were 12,738 patients included, out of which 3702 were exposed to beta-blockers vs. 9036 non-exposed patients. Age, male sex, Breslow thickness, ulceration, and nodal status were independent negative prognostic factors for melanoma-specific survival (MSS). Adding beta-blockers to the analysis did not add any prognostic value to the model (HR 1.00, p = 0.98), neither when adjusting for competing risks (HR 0.97, p = 0.61). When specifically analyzing the use of non-selective beta-blockers, the results were still without statistical significance (HR 0.76, p = 0.21). In conclusion, this population-based registry study could not verify that the use of beta-adrenergic blocking agents improve survival in patients with melanoma.

Mitochondrial Disorder Aggravated by Metoprolol

Beta-adrenergic blocking agents or beta-blockers are a class of medications used to treat cardiac arrhythmias and systemic hypertension. In therapeutic dosages, they have known adverse outcomes that can include muscular fatigue and cramping, dizziness, and dyspnea. In patients with mitochondrial disease, these effects can be amplified. Previous case reports have been published in the adult population; however, their impact in pediatric patients has not been reported. We describe a pediatric patient with a mitochondrial disorder who developed respiratory distress after metoprolol was prescribed for hypertension. As the patient improved with discontinuation of medication and no alternative etiology was found for symptoms, we surmise that administration of metoprolol aggravated his mitochondrial dysfunction, thus worsening underlying chest wall weakness.