We are hereby investigating for the first time the effect of the association ethinylestradiol30μg-drospirenone 3mg (DRP/EE30μg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS).

Obesity is a systemic disease and represents one of the leading causes of death worldwide by constitutingthe main risk factor for a series of non-communicable diseases such as type 2 diabetes mellitus (T2DM),cardiovascular diseases and dyslipidemia. Lifestyle interventions have been attempting to prevent T2DM andobesity but are difficult to maintain by most patients. However, the recent focus on the intestinal microbiotaand its important role in the host’s metabolism provides a new key for improving metabolic health. Modulatingthe composition of the gut microbiota was proposed as a method to manage these metabolic diseases andmost frequently this is undertaken by using probiotics, prebiotics or synbiotics. Furthermore, the action ofmetformin, the most commonly prescribed drug for treating T2DM, is mediated in part by the gut microbiota,although this interplay may also be responsible for the frequent gastrointestinal adverse effects of metformin.Thus, adding a gut microbiota modulator (GMM), such as probiotics or prebiotics, to metformin therapy couldamplify its anti-diabetic effects, while decreasing its adverse reactions. This review summarizes the varioustherapies that are used to shift the composition of the microbiome and their efficacy in alleviating metabolicparameters, it assesses the interaction between metformin and the gut microbiota, and it evaluates the existingclinical and preclinical studies that analyze the potential synergy of a combined metformin-GMM therapy.

The worldwide prevalence and incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and of NENs, in general, have been increasing recently. While valuing the considerable progress made in the treatment strategies for GEP-NEN in recent years, patients with advanced, metastasized disease still have a poor prognosis, which calls for urgent novel therapies. The immune system plays a dual role: both host-protecting and “tumor-promoting.” Hence, immunotherapy is potentially a powerful weapon to help NEN patients. However, although recent successes with checkpoint inhibitors have shown that enhancing antitumor immunity can be effective, the dynamic nature of the immunosuppressive tumor microenvironment presents significant hurdles to the broader application of these therapies. Studies led to their approval in NEN of the lung and Merkel cell carcinoma, whereas results in other settings have not been so encouraging. Oncolytic viruses can selectively infect and destroy cancer cells, acting as an in situ cancer vaccine. Moreover, they can remodel the tumor microenvironment toward a T cell-inflamed phenotype. Oncolytic virotherapy has been proposed as an ablative and immunostimulatory treatment strategy for solid tumors that are resistant to checkpoint inhibitors alone. Future efforts should focus on finding the best way to include immunotherapy in the GEP-NEN treatment scenario. In this context, this study aims at providing a comprehensive generalized review of the immune checkpoint blockade and the oncolytic virotherapy use in GEP-NENs that might improve GEP-NEN treatment strategies.

Background/Objectives: Pasireotide (PAS) is a somatostatin receptor ligand (SRL) used to treat acromegaly, a chronic condition caused by excess growth hormone. While it offers significant benefits as a second-line treatment for uncontrolled acromegaly, its use raises major concerns due to hyperglycemic side effects and gastrointestinal issues, the latter being similar to those seen with first-generation SRLs. The aim of this study is to evaluate the real-world evidence on adverse drug reactions (ADRs) reported for PAS in the EudraVigilance database, in comparison to other established drug-based therapies for acromegaly. Methods: A descriptive analysis and a disproportionality analysis were conducted. Results: The fewest individual case safety reports (ICSRs) and adverse drug reactions (ADRs) were reported for PAS, with 698 (4%) ICSRs and 1,647 (4%) ADRs, which is even lower than for pegvisomant (PEG), which had 1765 (11%) ICSRs and 4842 (10%) ADRs. Both PAS and lanreotide (LAN) exhibited the lowest proportion of cases classified as serious. Among the total reported ADRs, those categorized as “Metabolic and nutrition disorders” were most frequent and severe for PAS (PAS—17.5% vs. OCT—4.6%, LAN—4.5%, and PEG—2.7%). Additionally, PAS demonstrated a higher likelihood of reporting endocrine disorders, which were frequently classified as serious, as well as stones affecting the hepatobiliary system compared to other drugs. Conclusions: Although PAS had the fewest ICSRs and ADRs, and less frequent serious ADRs, it had more reports frequently classified as serious in the “Metabolism and Nutrition Disorders” category (including events such as elevated blood glucose levels or diabetes) and “Endocrine Disorders” category compared to other SRLs and PEG. Furthermore, there was a higher likelihood of reporting hepatobiliary stones with PAS compared to OCT and PEG. This highlights the importance of adequately monitoring glycemic control and the biliary tract through ultrasound at the initiation and during follow-up of PAS therapy. Improved monitoring and reporting of these ADRs could enhance care for patients with acromegaly.