The Impact of In Vivo Reflectance Confocal Microscopy for the Diagnostic Accuracy of Melanoma and Equivocal Melanocytic Lesions

In vivo confocal reflectance microscopy recently showed promising results for melanoma (MM) diagnosis on a limited series. The aim of the study was to evaluate the sensitivity and specificity of confocal features for the diagnosis of MM 351 equivocal melanocytic lesions (136 MMs and 215 nevi) were evaluated for 37 confocal features by two blinded expert observers. χ2 test, multivariate discriminant analysis and binary logistic regression were performed for the identification of the significant features and for testing newly created diagnostic models. Melanomas were mostly characterized by epidermal disarray and pagetoid cells in the epidermis, non-edged papillae, and cellular atypia at the junction, and atypical nests and bright nucleated cells in the upper dermis. On the other hand, regular dermal–epidermal architecture, and absence of pagetoid infiltration and atypical cells were suggestive of benign lesions. Five out of 136 melanomas, with mildly atypical melanocytes and occasional pagetoid cells at histopathology, were not diagnosed by confocal microscopy. Nevertheless, new diagnostic models showed no significant improvement compared with the previously proposed confocal microscopy algorithm. Owing to the visualization of cellular aspects, confocal microscopy seems useful for second level examination of clinically and dermoscopically equivocal lesions

Dermoscopic evaluation of nodular melanoma

Importance: Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Time to diagnosis, of melanoma: same trend in different continents

Background: Patients and physicians both play an important role in the diagnosis of malignant melanoma. Objective: The purpose of this study was to assess important factors of delay in diagnosis at different centers and on three continents. Methods: Between October 2001 and October 2002, patients with histologically confirmed invasive melanoma were included in the study and given an established questionnaire. Recorded patients and tumor characteristics included age, sex, anatomic location, Breslow thickness, patients' awareness of the lesion and time with suspicion, and physicians' time (delay) before the operation. Results: The study included 985 patients (486 males, 499 females): 253 from Germany, 464 from Sweden, 58 from Brazil, and 210 from Australia. More females detected their lesions by themselves. The change to a darker color (21%) and enlargement of the area of the lesion (19%) were the major signs. The highest knowledge among patients that early detection may improve the outcome was found in Sweden and Australia. At each center, the media (newspaper, magazine, radio, and television) provided the best sources of information about melanoma. Twenty to 33% of all physicians initially consulted missed the melanoma diagnosis, independent of their specialty. Conclusions: There are still factors for the delay in melanoma diagnosis in different countries and continents, but the differences are rather small. The results should be included in planning prevention campaigns in this specific field and in the education of medical students, physicians of all specialties, and other health professionals