Introduction: The discovery of serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9) has revolutionized pharmacological lipid-lowering treatments. The first PCSK9 antagonists (PCSK9-A), evolocumab and alirocumab, were approved in 2015. Targeting PCSK9 synthesis marked a major advancement in this field, leading to the development of inclisiran, a long-acting siRNA targeting PCSK9 mRNA. However, real-world safety data on this drug are still limited. Therefore, this study aims to provide a real-world safety evaluation of inclisiran, comparing its characteristics to those of PCSK9-As. Methods: A retrospective pharmacovigilance study was conducted using EudraVigilance (EV). Inclisiran-related individual case safety reports (I-ICSRs) from 01/01/2021 to 06/30/2023 were retrieved. ICSRs for evolocumab or alirocumab from 01/01/2015 to 06/30/2023 were collected as a reference group (RG). ADRs were classified using the MedDRA dictionary. Data were evaluated using descriptive and disproportionality analyses. Crude reporting odds ratio (ROR) with 95% confidence intervals (CI) were used as disproportionality measures. Results: Of the 15,236 ICSRs, 3.7% (n = 563) involved inclisiran, with the rest in the RG. Most I-ICSRs involved female patients (51.7%) aged 18 to 64 (52.8%). The most-reported ADRs for inclisiran were “general disorders and administration site conditions” (n = 347) and “investigations” (n = 277). Significant disproportionality was found in I-ICSRs compared to the RG for “Myalgia” (ROR: 2.43; 95% CI: 1.94–3.04), “Low-density lipoprotein increased” (ROR: 11.95; 95% CI: 9.10–15.52), and “Drug ineffective” (ROR: 6.37; 95% CI: 4.64–8.74). Conclusions: The inclisiran safety profile aligns with the existing literature and pre-commercial data. However, further studies are needed to fully understand the observed differences with PCSK9-As.

The aim of the study was to analyze glomerular filtration ratio (GFR) changes in diabetic patients assisted by General Practitioners (GPs) evaluating the risk factors related to glomerular function. patients with diabetes with at least three recorded values of creatinine were recruited in the study and GFR values were estimated. The quarterly percentage change in GFR for each patient was estimated. Nephrotoxic drugs were identified, and glucose-lowering drugs use was described. Linear regression analyses were performed to identify eGFR changes predictors. a total of 545 patients with diabetes were selected. According to the last eGFR values 64 (11.7 %) patients were classified in G1 stage, 277 (50,8 %) in G2, 175 (32.1 %) in G3a, 25 (4.6 %) in G3b and only 4 (0.7 %) in G4. Patients treated with at least one glucose-lowering drugs were 479 (87.9 %), most of them with biguanides (67.0 %). At least one nephrotoxic drug prescription was recorded in 524 (96.1 %) patients; proton pump inhibitors (74.7 %) and NSAIDs (71.6 %) were the most prescription classes. Heart failure, diabetes duration and preserved GFR values were related to reduced eGFR values. patients with diabetes should be more carefully observed regardless of kidney risk factors and GFR values in clinical practice.

Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and anti-oxidant properties. This study aims to evaluate the effects of a dietary supplement containing baicalin, bromeline and escin in CVI patients. A retrospective cohort study was performed by using the medical records of CVI affected outpatients. Patients treated with the dietary supplement were defined as “users”. A modified Venous Clinical Severity Score (VCSS) was calculated, including pain, inflammation, vessels induration and skin pigmentation. All clinical variables were evaluated at baseline (T0), after 30 (T1) and 90(T2) days in “users” and “non-users”. Out of 62 patients, 30 (48.4%) were “users”. No difference was observed between groups at baseline. A lower VCSS value was recorded in “users” than that observed in “non-users” at T2 (7.0 (4.0–9.0) vs. 9.0 (5.0–10.0); p = 0.025). Vessels’ induration and pain significantly reduced in 53.3% and 43.3% of “users” and in 18.8% and 9.4% of “non-users”. Only “users” (33.3%) showed a reduction of the inflammatory signs as well as a decrease in malleolar circumference, from 29.0 (26.5–30.0) to 27.5 (26.0–28.5) (p < 000.1). A reduction of C-reactive Protein levels was found in “users” compared to “non-users” at T2 (1.0 (0.9–1.2) vs. 1.3 (1.0–1.5); p = 0.006). These findings suggest that implementation of a dietary supplement could improve the clinical outcomes of CVI patients.

Background: Osteocalcin (OC) is a bone-derived hormone increasingly implicated in glucose and lipid metabolism. Although its metabolic role has been extensively investigated in adults, evidence in pediatric populations remains limited. This exploratory study aimed to evaluate the relationship between serum OC levels and glucose metabolism in children and adolescents with obesity. Methods: A single-center, retrospective study was conducted in a cohort of pediatric patients with essential obesity. Auxological and biochemical parameters were assessed, including fasting glucose, insulin, lipid profile, liver enzymes, thyroid function, calcium–phosphorus metabolism, vitamin D₃, parathormone (PTH), C-terminal telopeptide of type I collagen (CTX), and OC. Insulin resistance was evaluated using the HOMA-IR index (>2.5 considered positive). Correlation analyses were performed to assess the associations between serum OC levels and metabolic, biochemical, and clinical parameters. Results: Twenty-two of 33 patients (66.7%) had insulin resistance (HOMA-IR > 2.5) despite preserved glucose tolerance. Mean fasting glucose was 88.1 ± 10.83 mg/dL, fasting insulin 24.9 ± 13 μU/mL, and mean serum OC 112.1 ± 56.1 ng/mL. Serum OC levels were positively correlated with fasting insulin (r = 0.41, p = 0.023) and HOMA-IR (r = 0.46, p = 0.013). Conclusions: In children with obesity and preserved glucose tolerance, higher serum OC levels were associated with insulin resistance. Further studies in larger pediatric cohorts are needed to clarify this association and evaluate the potential role of OC as a biomarker of early metabolic dysregulation.

Medication-related osteonecrosis of the jaw (MRONJ) is a complex condition associated with the use of antiresorptive drugs, such as bisphosphonates and denosumab. The condition is characterized by the presence of exposed bone in the maxillofacial region that fails to heal. MRONJ remains highly intractable, as its pathogenic mechanisms are not yet fully understood. It is therefore essential to elucidate the molecular mechanisms underlying the disease. MiRNA expression analysis and proteomic studies were performed on a selected cohort of patients with MRONJ on jawbone tissue, using qRT-PCR and 2D electrophoresis followed by mass spectrometry. MiRNAs and proteomics data validation was carried out by Western blot analysis of differentially expressed proteins highlighted by a proteome study and predicted targets of differentially expressed miRNAs. Nineteen miRNAs were overexpressed and two downregulated in jawbone tissue from all MRONJ patients. Notably, five of these dysregulated miRNAs are involved in the regulation of angiogenesis and desmosome functions, suggesting a potential link to the molecular alterations observed at the protein level. Proteomic analysis revealed decreased concentrations of the pigment epithelium-derived factor, and of desmoglein-1, a desmosomal cadherin. Validation analysis confirmed the dysregulation of pathways involved in bone remodeling and necroptosis. The pathophysiology of MRONJ arises from a complex interplay of factors, including impaired bone remodeling, affected angiogenesis, and altered cell adhesion and differentiation mechanisms, ultimately leading to necroptosis. Through proteomic analysis and validation of miRNA expression, our study proposes specific molecular alteration in MRONJ-compromised bone tissue, involving desmosomal component imbalance and angiogenesis inhibition.