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BACKGROUND: Although the recent drop in melanoma mortality has been attributed to the introduction of newer therapies, the impact of ongoing public efforts remains unknown. OBJECTIVE: Characterize and model melanoma mortality trends before the era of molecular and immune therapies (1969-2014) in the U.S. and Australia. METHODS: Differential time series analysis based on population-ascertained melanoma mortality rates from the U.S. and Australia. Mortality rates were modeled and compared to the trajectories of ten other cancers. RESULTS: Melanoma mortality rates have been significantly decelerating since the 1970s in both the U.S. (P < .0001) and Australia (P = .0021). Zero acceleration occurred around 2001 (95% CI: 1996, 2008) for the U.S. and 2004 (95% CI: 1999, 2011) for Australia. Male mortality rates decelerated 3x-4x faster than females in both countries. Melanoma mortality followed a similar quadratic function (R2 > 0.9) to 10 other cancers, albeit with a later inflection point (1986 vs 2001) and broader focal width. LIMITATIONS: Absolute mortality data used without further stratification or considering cancer incidence or covariates. CONCLUSION: Melanoma deaths have been decelerating for the past 5 decades, reaching an inflection point around 2001, suggesting that mitigating campaigns were already afoot in both the U.S. and Australia before the advent of modern therapies.
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Keloids are abnormal skin growths occurring in a significant portion of the global population. Despite their pervasiveness, the underlying pathophysiology of this scarring process is yet to be fully understood. In this review article, we delve into the current literature on the pathophysiological mechanisms of keloids. We take a top-down approach, first looking at host factors such as genetics and endocrine factors and then taking a more granular approach describing specific control factors such as germline keloid predisposition variants, epigenetics and transcriptomics, inflammatory and immune dysregulation, and the role of profibrotic and angiogenic cell signaling pathways. We then discuss current knowledge gaps, propose further research avenues, and explore potential future treatment options considering our increased understanding of keloid pathogenesis.
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The extent to which the geographic diversity of the US plays a significant role in melanoma incidence and mortality over time has not been precisely characterized. We obtained age-adjusted melanoma data for the 50 states between 2001 and 2019 from the Surveillance, Epidemiology, and End Results registry and performed hierarchical clustering (complete linkage, Euclidean space) to uncover geo-temporal trend groups over 2 decades. While there was a global increase in incidence during this time (b1 = +0.41, P < .0001), there were 6 distinct clusters (by absolute and Z-score) with significantly different temporal trends (analysis of covariance P < .0001). Cluster 2 states had the sharpest increase in incidence with b1 = +0.66, P < .0001. For mortality, the global rate decreased (b1 = -0.03, P = .0003) with 3 and 6 clusters by absolute and Z-scores, respectively (analysis of covariance P < .05). Cluster 1 states exhibited the smallest decline in mortality (b1 = -0.017, P = .008). Mortality to incidence ratios declined (b1 = -0.0037, P < .0001) and harbored 4 and 6 clusters by absolute and Z-score analysis, respectively (analysis of covariance P < .0001). Cluster 4 states had the lowest rate of mortality to incidence ratios decline (b1 = -0.003, P < .0001). These results provide an unprecedented higher dimensional view of melanoma behavior over space and time. With more refined analyses, geospatial studies can uncover local trends which can inform public health agencies to more properly allocate resources.