Differential time series analysis shows deceleration in melanoma mortality prior to the widespread use of highly effective therapies.

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.

Analyses and Correlation of Pathologic and Ocular Cutaneous Changes in Murine Graft versus Host Disease.

Graft versus host disease (GVHD) is initiated by donor allo-reactive T cells activated against recipient antigens. Chronic GVHD (cGVHD) is characterized by immune responses that may resemble autoimmune features present in the scleroderma and Sjogren's syndrome. Unfortunately, ocular involvement occurs in approximately 60-90% of patients with cGVHD following allo-hematopoietic stem cell transplants (aHSCT). Ocular GVHD (oGVHD) may affect vision due to ocular adnexa damage leading to dry eye and keratopathy. Several other compartments including the skin are major targets of GVHD effector pathways. Using mouse aHSCT models, the objective was to characterize cGVHD associated alterations in the eye and skin to assess for correlations between these two organs. The examination of multiple models of MHC-matched and MHC-mismatched aHSCT identified a correlation between ocular and cutaneous involvement accompanying cGVHD. Studies detected a "positive" correlation, i.e., when cGVHD-induced ocular alterations were observed, cutaneous compartment alterations were also observed. When no or minimal ocular signs were detected, no or minimal skin changes were observed. In total, these findings suggest underlying cGVHD-inducing pathological immune mechanisms may be shared between the eye and skin. Based on the present observations, we posit that when skin involvement is present in aHSCT patients with cGVHD, the evaluation of the ocular surface by an ophthalmologist could potentially be of value.

Update on the Pathogenesis of Keloid Formation.

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.

Geotemporal Analysis of Melanoma Incidence and Mortality Identifies Distinct Clusters of Trends within the United States Between 2001 and 2019.

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.

Melanoma maligno en Puerto Rico / Malignant melanoma in Puerto Rico

Se efectuó un estudio epidemiológico de melanoma maligno mediante la revisión de todos los casos de melanomas reportados al Registro de Cáncer de Puerto Rico entre los años 1981 al 1987. Se documentaron un total de 367 casos nuevos con una incidencia anual que fluctuó entre 1.20 y 2.12 por 100,000 habitantes y un promedio de 1.59. La mayoría de los pacientes tenín entre los 40 y 80 años de edad, con una mayoría en los 60. Casi la mitad de los tumores ocurrieron en las extremidades, sobre todo en los pies, compartiendo esta tendencia con otras razas como los negros y japoneses. El tipo clínico-histológico más frecuente lo fue el melanoma superficial expansivo seguido del acral lentiginoso , el nodular y el melanoma lentigo maligna. Cerca de un tercio del total de casos no fue clasificado de acuerdo al tipo histológico, mientras que los niveles de Clark y el grosor de Breslow no fueron reportados en 44 y 84% de los casos respectivamente. Cuando comparamos nuestra data a la de un estudio previo en Puerto Rico entre los años de 1977 al 1980, la incidencia anual promedio de casos nuevos aumentó de 0.92 a 1.59 por 100,000 habitantes, documentándose un aumento de incidencia en nuestra población, pero no tan significativo como el aumento registrado en los Estados Unidos

Phaeohyphomycosis: first case in Puerto Rico

A 24 year-old woman with systemic lupus erythematosus developed a subcutaneous nodule on the back wich upon histopathological examination was found to be a case of phaeohyphomycosis. To our knowledge, this is the first case of the condition to be reported in Puerto Rico