Background: Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer, with increasing incidence each year. Although the treatment of BCC is typically surgical, a non-surgical approach is highly desirable for patients with non-aggressive BCC recurrence, multiple tumors, poor general health, or with lesions in vulnerable areas. In the last few years, advanced cancer treatment options have targeted the Hedgehog pathway, known to regulate the proliferation of cancer stem cells and increase tumor invasiveness. Itraconazole, a triazole antifungal that inhibits ergosterol synthesis in fungi, have also proven a clinically significant tumor size reduction in BCC via inhibition of this pathway. However, serious adverse effects might preclude itraconazole use in broader population where multiple medications or comorbidities might be present. Preliminary studies demonstrate posaconazole, another member of the triazole family, may present a safer clinical alternative to the currently used pharmacological methods utilised in the management of BCC. Therefore, this phase II study aims to analyze the efficacy of posaconazole as a safe therapeutic option for nodular BCC lesions. Methods: This is a study protocol designed as a single center, randomized, double-blinded, placebo-controlled trial. Patients over 18 years of age, diagnosed with at least 2 nodular BCC lesions and that are awaiting to undergo surgery are eligible to participate in this phase II study. Before undergoing surgical excision, 170 patients (1:1 allocation) will be randomized to receive 800 mg daily of posaconazole or placebo for four weeks. Discussion: The main strengths of this study are the potential to increase general understanding of the therapeutic and metabolic impact of posaconazole. The results from this trial may also provide valuable insights to guide a larger clinical trial of posaconazole for inoperable BCC. The main limitations of the study consist of the limited intervention time frame of four weeks and the sample representativeness since it is a single-center study of patients with nodular BCC.

BackgroundThe impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to investigate the safety and short-term efficacy of reperfusion therapy in this patient population.MethodsWe searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran’s Q test and I2 statistics.ResultsWe included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16–2.05, p < 0.001), while the nominally increased risk of symptomatic ICH in these patients did not reach statistical significance (RR 2.04, 95% CI 0.97–4.31; p = 0.06). COVID-19 positive stroke patients also had a significantly higher in-hospital mortality compared to COVID-19 negative stroke patients (RR 2.78, 95% CI 2.15–3.59, p < 0.001). Moreover, COVID-19 positive stroke patients were less likely to achieve a favorable functional outcome at discharge (RR 0.66, 95% CI 0.51–0.86, p < 0.001) compared to COVID-19 negative patients, but this difference was not observed at 3-month follow-up (RR 0.64, 95% CI 0.14–2.91, p = 0.56).ConclusionCOVID-19 appears to have an adverse impact on acute ischemic stroke patients who undergo reperfusion therapy, leading to an elevated risk of any ICH, higher mortality and lower likelihood of favorable functional outcome.Systematic review registrationhttps://clinicaltrials.gov/, identifier CRD42022309785.