PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Osimertinib­induced erythromelalgia: A case report.

The present study reports a case of osimertinib-induced erythromelalgia in a patient with metastatic lung adenocarcinoma. Osimertinib is an antineoplastic drug that irreversibly inhibits the epidermal growth factor receptor (EGFR) pathway by binding to the intracellular receptor tyrosine kinase site, thus preventing EGFR signal transduction. A 77-year-old female with a lung adenocarcinoma recurrence with secondary metastases was prescribed osimertinib therapy. The patient presented with painful erythema and warmth in the distal phalanges of all fingers on both hands, which worsened with heat and relieved with cold. Based on clinical data, erythromelalgia was diagnosed. Considering the age of onset, a primary erythromelalgia was ruled out. Further investigations excluded other secondary causes of erythromelalgia, therefore osimertinib was suspected as the cause. Although no cases of EGFR inhibitor-induced erythromelalgia have been reported, cutaneous adverse events induced by EGFR inhibitors have been documented. The present case may be the first evidence of osimertinib-induced erythromelalgia and may help clinicians to properly support patients who develop this EGFR inhibitor adverse event.

The Importance of Reading the Skin: Cutaneous Metastases of Pancreatic Cancer, a Systematic Review.

BACKGROUND: Pancreatic cancer is notorious for its aggressive nature and low survival rate, with less than 10% of patients surviving beyond five years. Early detection is difficult, but skin metastases can be a rare but significant indicator. This systematic review focuses on the epidemiology, clinical features, and histology of skin metastases from pancreatic cancer to determine their importance in early diagnosis and overall management of the disease. MATERIALS AND METHODS: Following PRISMA guidelines, we conducted an exhaustive search of MEDLINE/PubMed, EMBASE, and SCOPUS databases up to June 2023, using specific keywords. Four independent investigators screened the studies using predefined criteria, and two investigators checked the accuracy and consistency of the data extraction. We assessed the quality of the trials using adapted criteria from the Joanna Briggs Institute. A narrative synthesis rather than a meta-analysis was chosen because of the different study designs. RESULTS: The final analysis included 57 patients with skin metastases from pancreatic cancer. Cutaneous metastases, although rare, presented with approximately equal gender distribution and a mean age of 63.4 years. Predominantly non-umbilical (77%), these metastases showed clinical diversity, ranging from asymptomatic nodules to painful or ulcerated lesions. Notably, skin metastases often preceded the diagnosis of primary pancreatic cancer (58%). Primary tumor characteristics revealed different localizations, with adenocarcinoma being the most prevalent histological type (77%). A significant association (p = 0.008) was observed between pancreatic tumor location and the timing of presentation of skin metastases. Tumors located in the body and tail of the pancreas were more likely to manifest skin metastases as an initial clinical manifestation (62.2%) than those in the head of the pancreas (20.8%). CONCLUSIONS: In conclusion, although skin metastases are rare, they are important indicators of pancreatic cancer, highlighting the need for multidisciplinary healthcare collaboration and thorough skin examination. Recognizing them could lead to earlier diagnosis, which is crucial in a cancer with limited treatment options.

Measuring Caloric Intake at the Population Level (NOTION): Protocol for an Experimental Study.

BACKGROUND: The monitoring of caloric intake is an important challenge for the maintenance of individual and public health. The instruments used so far for dietary monitoring (eg, food frequency questionnaires, food diaries, and telephone interviews) are inexpensive and easy to implement but show important inaccuracies. Alternative methods based on wearable devices and wrist accelerometers have been proposed, yet they have limited accuracy in predicting caloric intake because analytics are usually not well suited to manage the massive sets of data generated from these types of devices. OBJECTIVE: This study aims to develop an algorithm using recent advances in machine learning methodology, which provides a precise and stable estimate of caloric intake. METHODS: The study will capture four individual eating activities outside the home over 2 months. Twenty healthy Italian adults will be recruited from the University of Padova in Padova, Italy, with email, flyers, and website announcements. The eligibility requirements include age 18 to 66 years and no eating disorder history. Each participant will be randomized to one of two menus to be eaten on weekdays in a predefined cafeteria in Padova (northeastern Italy). Flows of raw data will be accessed and downloaded from the wearable devices given to study participants and associated with anthropometric and demographic characteristics of the user (with their written permission). These massive data flows will provide a detailed picture of real-life conditions and will be analyzed through an up-to-date machine learning approach with the aim to accurately predict the caloric contribution of individual eating activities. Gold standard evaluation of the energy content of eaten foods will be obtained using calorimetric assessments made at the Laboratory of Dietetics and Nutraceutical Research of the University of Padova. RESULTS: The study will last 14 months from July 2017 with a final report by November 2018. Data collection will occur from October to December 2017. From this study, we expect to obtain a series of relevant data that, opportunely filtered, could allow the construction of a prototype algorithm able to estimate caloric intake through the recognition of food type and the number of bites. The algorithm should work in real time, be embedded in a wearable device, and able to match bite-related movements and the corresponding caloric intake with high accuracy. CONCLUSIONS: Building an automatic calculation method for caloric intake, independent on the black-box processing of the wearable devices marketed so far, has great potential both for clinical nutrition (eg, for assessing cardiovascular compliance or for the prevention of coronary heart disease through proper dietary control) and public health nutrition as a low-cost monitoring tool for eating habits of different segments of the population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12116.

(Ab)use of Health Claims in Websites: The Case of Italian Bottled Waters.

The massive use of web marketing makes the monitoring of nutrition and health claims used in advertising campaigns much more difficult. The present study aimed at reviewing the website content for bottled waters produced in Italy to assess (i) if nutrition and health claims are reported, (ii) what types of nutrition and health claims are reported most frequently, and (iii) if the nutrition and health claims could be considered appropriate according to the current regulation in the field. A review of the website content of the 253 bottled waters produced in Italy and reported in the annual report of Bevitalia 2016-2017 was conducted. For each brand, indications related to the preventive, curative or therapeutic properties of the water reported were examined. Bottled waters that included potentially misleading information apparently not consistent with the European Directive on the exploitation and marketing of natural mineral waters were identified. Forty bottled waters with uncertain website content were identified. The information reported in the websites referred most often to beneficial effects for urinary tract and cardiovascular systems. Present results highlight, using the bottled water case study, that website content sometimes happens to deliver misleading information to consumers, also thanks to uncertain regulation in this sensitive field.