Differential expression of microRNAs during melanoma progression:miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors

BACKGROUND: The incidence of malignant melanoma is increasing faster than that for any other cancer. Histological examination of skin excision biopsies remains the standard method for melanoma diagnosis and prognosis. Significant morphological overlap between benign and malignant lesions complicates diagnosis, and tumour thickness is not always an accurate predictor of prognosis. METHODS: To identify improved molecular markers to support histological examination, we used microarray analysis of formalin-fixed and paraffin-embedded samples from different stages of melanomagenesis to identify differentially expressed microRNAs (miRNAs). Differential expression was validated by qRT–PCR, and functional studies were carried out after transfection of miRNA precursors or inhibitors into melanoma cells to modulate miRNA expression. RESULTS: In all, 20 miRNAs showed highly significant differential expression between benign naevi and either primary or metastatic melanomas, the majority being downregulated in melanoma, whereas only 2 miRNAs, namely miR-203 and miR-205, were differentially expressed between primary and metastatic melanomas. In functional in vitro assays, overexpression of miR-200c and miR-205 inhibited anchorage-independent colony formation and overexpression of miR-211 inhibited both anchorage-independent colony formation and invasion. CONCLUSION: We have identified a series of differentially expressed miRNAs that could be useful as diagnostic or prognostic markers for melanoma and have shown that three miRNAs (namely miR-200c, miR-205 and miR-211) act as tumour suppressors

The good, the bad, and the ugly of medication coverage: Is altering a diagnosis to ensure medication coverage ethical?

Recently, a patient presented to the dermatology clinic suffering from disabling, recurrent palmoplantar vesicles and pustules. Biopsy demonstrated nondiagnostic histologic findings without unequivocal evidence for psoriasis. The localized rash was recalcitrant to a host of standard therapies. An anti-tumor necrosis factor biologic was considered, and experience suggested that this expensive medication would only be approved for coverage if a diagnosis was submitted for a Food and Drug Administration–approved indication as psoriasis. All health-care providers face similar dilemmas in caring for their own patients. To whom is the physician’s primary responsibility when what is best for the patient may not align with the realities of our health-care system? Should a physician alter or exaggerate a medical diagnosis to obtain insurance coverage for a needed medication? What are the ethical implications of this action? If the physician’s fiduciary duty to the patient had no limits, there would be multiple potential consequences including compromise of the health-care provider’s integrity and relationships with patients, other providers, and third-party payers as well as the risk to an individual patient’s health and creation of injustices within the health-care system

Letter to the editor: Delayed presentation of non-COVID-19 patients during the covid-19 pandemic is not limited to children

We read with interest the report about four minors who were diagnosed late with non-COVID-19 diseases during the COVID-19 pandemic. We would like to emphasize that, firstly, such delays are not limited to minors, and secondly, that also in minors should we distinguish the administrative and the physiological meanings of the term “child” and hence distinguish administratively defined “children” who bodily are already mature from those young patients who bodily are indeed still children. The 16-year-old patient that was presented to the emergency room with endocarditis was bodily no longer a child, although administratively and probably also psychologically, due to his Down syndrome, he was still a child. Two of the other patients, one with hemolytic anemia (2.5 years old) and one with Ewing sarcoma (4 years old), were still pre-pubertal children, while the 13-year-old minor with a septic hip was already adolescent. The author of the cited paper works in a pediatric department and reports those patients that he has seen during his work. However, in our view there is nothing specifically pediatric in his observations. Several recent papers discuss delays of diagnosis and treatment of non-COVID-19 diseases during the pandemic, including head and neck cancer, appendicitis, heart failure and septicemia, pulmonary thromboembolism, pyelonephritis, and cancer in general. Some patients in these papers are administratively still “children,” some are adults, and appendicitis is discussed in both. The delay the COVID-19 pandemic has caused in the timely diagnosis of various diseases is not a “pediatric” challenge, but a challenge for medicine in general

COVID-19 and Treatment and Immunization of Children the Time to Redefine Pediatric Age Groups is Here

Children are infected with coronavirus disease 2019 (COVID-19) as often as adults, but with fewer symptoms. During the first wave of the COVID-19 pandemic, multisystem inflammatory syndrome (MIS) in children (MIS-C), with symptoms similar to Kawasaki syndrome, was described in young minors testing positive for COVID-19. The United States (US) Centers for Disease Control and Prevention (CDC) defined MIS-C as occurring in <21-year-olds, triggering hundreds of PubMed-listed papers. However, postpubertal adolescents are no longer children biologically; the term MIS-C is misleading. Furthermore, MIS also occurs in adults, termed MIS-A by the CDC. Acute and delayed inflammations can be triggered by COVID-19. The 18th birthday is an administrative not a biological age limit, whereas the body matures slowly during puberty. This blur in defining children leads to confusion regarding MIS-C/MIS-A. United States and European Union (EU) drug approval is handled separately for children, defined as 18-year-olds, ascribing non-existent physical characteristics up to the 18th birthday. This blur between the administrative and the physiological meanings for the term child is causing flawed demands for pediatric studies in all drugs and vaccines, including those against COVID-19. Effective treatment of all conditions, including COVID-19, should be based on actual physiological need. Now, the flawed definition for children in the development of drugs and vaccines and their approval is negatively impacting prevention and treatment of COVID-19 in minors. This review reveals the necessity for redefining pediatric age groups to rapidly establish recommendations for optimal prevention and treatment in minors

Basal cell carcinoma: an emerging epidemic in women in Iceland.

To access publisher's full text version of this article click on the hyperlink belowBackground: An epidemic of basal cell carcinoma (BCC) has led to a significant healthcare burden in white populations. Objectives: To provide an update on incidence rates and tumour burden in an unselected, geographically isolated population that is exposed to a low level of ultraviolet radiation. Methods: This was a whole-population study using a cancer registry containing records of all cases of BCC in 1981-2017. We assessed BCC incidence according to age, residence and multiplicity and assessed trends using join-point analysis. Age-standardized and age-specific incidence rates were calculated along with cumulative and lifetime risks. Results: During the study period, the age-standardized incidence rates increased from 25·7 to 59·9 for men, and from 22·2 to 83·1 for women (per 100 000). Compared with the single-tumour burden, the total tumour burden in the population was 1·72 times higher when accounting for multiplicity. At the beginning of the study period, the world-standardized rates in men and women were similar, but by the end of the study period the rates were 39% higher in women (83·1 per 100 000, 95% confidence interval 77·9-88·3) than in men (59·9 per 100 000, 95% confidence interval 55·6-64·2). This increase was most prominent in women on sites that are normally not exposed to ultraviolet radiation in Iceland: the trunk and legs. Conclusions: This is the only reported population in which the incidence of BCC is significantly higher in women than in men. The period of notable increase in BCC lesions correlates with the period of an increase in tanning beds and travel popularity. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought