PURPOSE: To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival. MATERIALS AND METHODS: A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas. RESULTS: Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma. CONCLUSIONS: There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.
Gene Expression ; Genome ; Guanosine Monophosphate ; Humans ; Melanoma ; Phosphodiesterase 5 Inhibitors ; Sequence Analysis, RNA ; Sildenafil Citrate ; Statistics as Topic ; Tadalafil ; Vardenafil Dihydrochloride

Hospitalization ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Reproductive Techniques, Assisted ; Retrospective Studies

INTRODUCTION: Hospital-based resuscitation interventions, such as therapeutic temperature management (TTM), emergency percutaneous coronary intervention (PCI) and extracorporeal membrane oxygenation (ECMO) can improve outcomes in out-of-hospital cardiac arrest (OHCA). We investigated post-resuscitation interventions and hospital characteristics on OHCA outcomes across public hospitals in Singapore over a 9-year period. METHODS: This was a prospective cohort study of all OHCA cases that presented to 6 hospitals in Singapore from 2010 to 2018. Data were extracted from the Pan-Asian Resuscitation Outcomes Study Clinical Research Network (PAROS CRN) registry. We excluded patients younger than 18 years or were dead on arrival at the emergency department. The outcomes were 30-day survival post-arrest, survival to admission, and neurological outcome. RESULTS: The study analysed 17,735 cases. There was an increasing rate of provision of TTM, emergency PCI and ECMO (P<0.001) in hospitals, and a positive trend of survival outcomes (P<0.001). Relative to hospital F, hospitals B and C had lower provision rates of TTM (≤5.2%). ECMO rate was consistently <1% in all hospitals except hospital F. Hospitals A, B, C, E had <6.5% rates of provision of emergency PCI. Relative to hospital F, OHCA cases from hospitals A, B and C had lower odds of 30-day survival (adjusted odds ratio [aOR]<1; P<0.05 for hospitals A-C) and lower odds of good neurological outcomes (aOR<1; P<0.05 for hospitals A-C). OHCA cases from academic hospitals had higher odds ratio (OR) of 30-day survival (OR 1.3, 95% CI 1.1-1.5) than cases from hospitals without an academic status. CONCLUSION Post-resuscitation interventions for OHCA increased across all hospitals in Singapore from 2010 to 2018, correlating with survival rates. The academic status of hospitals was associated with improved survival.
Hospitals, Public ; Humans ; Out-of-Hospital Cardiac Arrest/therapy* ; Percutaneous Coronary Intervention ; Prospective Studies ; Singapore/epidemiology*

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.