The inappropriate use of antibiotics in man is driving to insurgence of pathogenic bacteria resistant to multiple drugs (MDR) representing a challenge in critical illness. The interaction of MDR bacteria with host cells can guide molecular perturbations of host transcriptional programmes involving epigenetic-sensitive mechanisms, mainly DNA methylation, histone modifications, and non-coding RNAs leading to pathogen survival. Clinical evidence of epigenetic manipulation from MDR bacteria mainly arises from Mycobacterium tuberculosis as well as Helicobacter pylori, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Legionella pneumophila infection suggesting possible biomarkers of disease. For example, DNA hypermethylation of E-cadherin (CDH1), upstream transcription factor 1/2 (USF1/2), WW domain containing oxidoreductase (WWOX), and mutL homolog 1 (MLH1) genes in gastric mucosa is correlated with malignancy suggesting useful biomarkers of early disease state. Moreover, upregulated circulating miR-361-5p, miR-889, miR-576-3p may be useful biomarkers to discriminate tuberculosis patients. Moreover, Listeria monocytogenes can indirectly induce H3 hyperacetylation leading to inflammation in human endothelial cells whereas Pseudomonas aeruginosa excretes QS 2-AA to directly induce H3 deacetylation leading to bacterial persistence in human monocytes. Remarkably, epigenetic-sensitive drugs may aid to counteract MDR in clinical setting. Trichostatin A, a histone deacetyltransferase inhibitor (HDACi), leads to AMP β-defensin 2 (HBD2) gene up-regulation in human epithelial cells suggesting a useful ‘epi-therapy’ for Escherichia coli-induced intestinal diseases. We update on the most current clinical studies focusing on epigenetic changes involved in bacterial-host interactions and their putative role as biomarkers or drug targets to improve precision medicine and personalized therapy in critical illness and transplantation setting.
Introduction: Metastases represent one of the most outstanding characteristics of malignant neoplasms and are relatively rare in the skin, in spite of the great extension of the cutaneous organs. Development of cutaneous metastases from colon cancer is a rare event, usually occurring in widely disseminated disease and commonly leading to a poor prognosis. As to location, cutaneous metastases often favor areas close to the primary malignancy, such as lung cancer and skin metastases on the trunk. However, remote sites as the scalp may be also involved. Case presentation: We present the case of a 92-year-old female patient with a massive single nodular skin lesion on her left supraclavicular area, that came back positive for cutaneous metastasis of colon adenocarcinoma. Discussion: Cutaneous metastasis of colorectal cancer a rare event (2.3%-6%) that usually occur two years after the detection or resection of the primary tumor. It seldom occurs before the identification of the primary tumor and involvement of secondary organs, such as the liver. There are few cases reported with only cutaneous metastases. Conclusion: In conclusion, dermatological evaluation of patients who are undergoing screening or who have already been diagnosed with cancer is extremely important. Highlights:
Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx