Did COVID-19 lockdown delay actually worsen melanoma prognosis?

BACKGROUND: The COVID-19 lockdown possibly meant a delay in the diagnosis and treatment of melanoma and therefore, worsening its prognosis. This unique situation of diagnosis deferral is an exceptional opportunity to investigate melanoma biology. OBJECTIVES: To evaluate the immediate and mid-term impact of diagnosis delay on melanoma. METHODS: A retrospective observational study of melanoma diagnosed between March 14th 2019 and March 13th 2021. We compared the characteristics of melanomas diagnosed during the first 6-month period after the lockdown instauration and a second period after recovery of normal activity with the same periods of the previous year, respectively. RESULTS: A total of 119 melanomas were diagnosed. There were no differences in age, sex, incidence, location, presence of ulceration or mitoses, and in situ/invasive melanoma rate (p>0.05). After the recovery of the normal activity, Breslow thickness increased in comparison with the previous year (2.4 vs 1.9mm, p<0.05) resulting in a significant upstaging according to the AJCC 8th ed. (p<0.05). STUDY LIMITATIONS: The main limitation is that this is a single-center study. CONCLUSIONS: The COVID-19 lockdown implied a diagnosis delay leading to a mid-term increase in Breslow thickness and an upstaging of invasive melanomas. However, the detection deferral did not result in a higher progression of in situ to invasive melanoma, in our sample.

MSIMEP: Predicting microsatellite instability from microarray DNA methylation tumor profiles.

Deficiency in DNA MMR activity results in tumors with a hypermutator phenotype, termed microsatellite instability (MSI). Beyond its utility in Lynch syndrome screening algorithms, today MSI has gained importance as predictive biomarker for various anti-PD-1 therapies across many different tumor types. Over the past years, many computational methods have emerged to infer MSI using either DNA- or RNA-based approaches. Considering this together with the fact that MSI-high tumors frequently exhibit a hypermethylated phenotype, herein we developed and validated MSIMEP, a computational tool for predicting MSI status from microarray DNA methylation tumor profiles of colorectal cancer samples. We demonstrated that MSIMEP optimized and reduced models have high performance in predicting MSI in different colorectal cancer cohorts. Moreover, we tested its consistency in other tumor types with high prevalence of MSI such as gastric and endometrial cancers. Finally, we demonstrated better performance of both MSIMEP models vis-à-vis a MLH1 promoter methylation-based one in colorectal cancer.

Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA.

BACKGROUND: Current noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions. METHODS: We evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR. RESULTS: LINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients. CONCLUSIONS: Hypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions.

Did COVID-19 lockdown delay actually worsen melanoma prognosis?

Abstract Background: The COVID-19 lockdown possibly meant a delay in the diagnosis and treatment of melanoma and therefore, worsening its prognosis. This unique situation of diagnosis deferral is an exceptional opportunity to investigate melanoma biology. Objectives: To evaluate the immediate and mid-term impact of diagnosis delay on melanoma. Methods: A retrospective observational study of melanoma diagnosed between March 14th 2019 and March 13th 2021. We compared the characteristics of melanomas diagnosed during the first 6-month period after the lockdown instauration and a second period after recovery of normal activity with the same periods of the previous year, respectively. Results: A total of 119 melanomas were diagnosed. There were no differences in age, sex, incidence, location, presence of ulceration or mitoses, and in situ/invasive melanoma rate (p > 0.05). After the recovery of the normal activity, Breslow thickness increased in comparison with the previous year (2.4 vs 1.9 mm, p < 0.05) resulting in a significant upstaging according to the AJCC 8th ed. (p < 0.05). Study limitations: The main limitation is that this is a single-center study. Conclusions: The COVID-19 lockdown implied a diagnosis delay leading to a mid-term increase in Breslow thickness and an upstaging of invasive melanomas. However, the detection deferral did not result in a higher progression of in situ to invasive melanoma, in our sample.

Tuberculosis miliar durante el tratamiento con adalimumab en enfermedad de Crohn / Miliary tuberculosis during adalimumab therapy in Crohn's disease

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