Federica Colapietra

Background: Cold atmospheric plasma (CAP) has emerged as a promising experimental anticancer strategy, yet its influence on oral squamous cell carcinoma (OSCC) migration and viability remains moderately understood. The aim of this workpaper was to examine how CAP exposure influences wound closure, WST-1 metabolic signal, and key proteins involved in epithelial adhesion and cell-cycle regulation in OSCC models. Methods: HSC-3 and CAL27 head and neck squamous cell carcinoma (HNSCC) cells were exposed to CAP generated via Piezoelectric Direct Discharge (PDD) technology for 20 s under standardized conditions. Wound closure was assessed by wound-healing assay under proliferation-restricted conditions (50 μM Ara-C), while relative cellular metabolic activity was measured using WST-1. E-cadherin, N-cadherin, and Cyclin A were evaluated by Western blot. Publicly available baseline transcriptomic data were additionally analyzed to characterize migration- and cytoskeleton-related expression patterns in the two HNSCC models. These transcriptomic data were independent of CAP treatment. Results: A 20 s CAP exposure significantly delayed wound closure in both HNSCC cell lines under proliferation-restricted conditions and reduced the WST-1 signal. Cyclin A levels also decreased, supporting an effect on cell growth and cell-cycle regulation, although the available data do not establish cell-cycle arrest. E-cadherin increased after CAP treatment, whereas N-cadherin remained low without a statistically significant change. Baseline transcriptomic mapping further showed differences between HSC-3 and CAL27 in genes related to actin-cytoskeleton organization, focal adhesion, and migration. These data were used to contextualize the experimental phenotype and were not interpreted as CAP-induced transcriptional changes. Conclusions: In these in vitro OSCC models, CAP exposure was associated with slower wound closure, lower WST-1 signal, increased E-cadherin, and reduced Cyclin A expression. These findings suggest further investigation of CAP as a potential modulator of OSCC cellular metabolic activity, adhesion-related markers, and cell-cycle-associated proteins.

Background: Ultrasound-guided radiofrequency ablation (RFA) has become an established minimally invasive treatment for selected benign and autonomously functioning thyroid nodules. Although clinical outcomes are well documented, the biological mechanisms underlying tissue remodeling after ablation remain incompletely characterized. The integration of imaging, molecular, and histopathological data may provide a more comprehensive understanding of treatment response. Methods: We conducted a prospective monocentric observational translational cohort study including 60 patients undergoing ultrasound-guided RFA for benign or autonomously functioning thyroid nodules between November 2024 and December 2025. Patients underwent standardized pre-procedural assessment including high-resolution ultrasound with volumetric evaluation, three-dimensional reconstruction, and collection of peripheral blood samples for exploratory extracellular vesicle (EV)-derived microRNA (miRNA) profiling. Clinical outcomes, volumetric changes, vascular remodeling, and procedural complications were assessed during scheduled follow-up visits (mean follow-up duration: 11 months; range: 5–17 months). A subgroup of patients who subsequently required surgery because of insufficient volumetric response underwent thyroidectomy, allowing histopathological evaluation of post-ablation tissue changes. Clinical, imaging, molecular, and pathological data were integrated within a multimodal translational framework. Results: RFA resulted in a mean nodule volume reduction of 56% at early follow-up, with progressive volumetric reduction observed during longitudinal ultrasound evaluation. A clinically relevant improvement in compressive symptoms was observed, with a 44% reduction in symptom burden. Doppler ultrasound demonstrated progressive changes in vascular patterns consistent with post-ablation devascularization and tissue remodeling. Ten patients underwent thyroidectomy after RFA because of insufficient volumetric response, providing histological validation of treatment-induced tissue alterations, including coagulative necrosis, fibrosis, inflammatory changes, and architectural remodeling. Exploratory EV-derived miRNA profiling was incorporated into the translational workflow to investigate potential molecular correlates of treatment response; however, molecular findings require further validation in larger cohorts. Conclusions: This study provides a multimodal translational characterization of tissue response after thyroid RFA by integrating clinical outcomes, ultrasound imaging, histopathology, and exploratory EV-derived miRNA analysis. The proposed framework may contribute to a deeper understanding of biological changes following thermal ablation and support future investigations aimed at identifying reliable biomarkers of treatment response.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy and is generally associated with a favorable prognosis. However, a subset of these tumors exhibits more aggressive behavior, underscoring the need for refined molecular and immunohistochemical characterization to improve diagnostic precision and prognostic stratification. Given the shared embryologic origin of the thyroid gland and gastrointestinal tract from the endoderm, intestinal differentiation markers (CDX2 and SATB2) and alterations in DNA mismatch repair (MMR) pathways, including MLH1 promoter methylation, may represent biologically relevant features in thyroid tumors. This study performed MLH1 promoter methylation analysis by pyrosequencing and protein expression of MLH1, PMS2, MSH2, MSH6, SATB2 and CDX2 by immunohistochemistry in 63 PTCs. Clinicopathological and molecular data were also collected for comparative analyses and correlation with progression-free survival (PFS). All PTCs retained expression of MMR proteins (MLH1, PMS2, MSH2, and MSH6), including the three tumors with MLH1 promoter hypermethylation. CDX2 positivity was detected in only two (3.2%) PTCs (classic and follicular subtypes), and SATB2 expression was absent in all cases. No significant association was identified between MLH1 promoter methylation, MMR protein expression, CDX2 or SATB2 expression, and PFS. In contrast, venous invasion was confirmed as a significant predictor of worse PFS (HR = 3.34; 95% CI 1.27–8.76; p = 0.014) in univariate analysis. MLH1 promoter methylation, MMR deficiency, and CDX2 are rare events in PTC and do not appear to influence PFS. Although infrequent, the expression of CDX2 is not exclusive to any PTC subtype.

Autoimmune thyroid diseases (AITDs) represent T cell-mediated, organ-specific autoimmune disorders caused by immune dysregulation, culminating in an immune-mediated attack on thyroid tissue. AITD etiopathogenesis is the result of the interplay between a genetic susceptibility and environmental factors; hypothyroidism and thyrotoxicosis are the respective clinical hallmarks of autoimmune thyroiditis and Graves’disease, the two main forms of AITD. The application of nanomedicine in the context of thyroid disorders ranges from nanodiagnosis and nanotherapy to nanotheranostics. Nanomedicine has been used to develop new sensitive methods for the determination of the TSH, iodine and TSAb. Furthermore, other studies have used nanomedicine to explore new treatments of autoimmune thyroiditis, Graves’disease and also thyroid eye disease. In the future, the application of nanomedicine will be personalized in accordance with individual genetic profiles, thus improving the therapeutic effectiveness and reducing the undesirable side effects with improved patient outcomes.

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring.

Thyroid nodule evaluation relies heavily on ultrasound imaging, yet it suffers from significant inter-operator variability. To address this, we present a preliminary validation of the Synergy-Net platform, an AI-driven Computer-Aided Diagnosis (CAD) system designed to standardize acquisition and improve diagnostic accuracy. The system integrates a U-Net architecture for anatomical segmentation and a ResNet-50 classifier for lesion characterization within a Human-in-the-Loop (HITL) workflow. The study enrolled 110 patients (71 benign, 39 malignant) undergoing surgery. Performance was evaluated against histopathological ground truth. The system achieved an Accuracy of 90.35% (95% CI: 88.2–92.5%), Sensitivity of 90.64% (95% CI: 87.9–93.4%), and an AUC of 0.90. Furthermore, the framework introduces a multimodal approach, performing late fusion of imaging features with genomic profiles (TruSight One panel). While current results validate the 2D diagnostic pipeline, the discussion outlines the transition to the ANTHEM framework, incorporating future 3D volumetric analysis and digital pathology integration. These findings suggest that AI-assisted standardization can significantly enhance diagnostic precision, though multi-center validation remains necessary.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous tumor group arising from neuroendocrine cells, commonly originating in the gastroenteropancreatic tract and bronchopulmonary system. Their incidence has risen significantly, owing to improved diagnostic techniques and increased clinical recognition. While previous reviews have explored the molecular and genetic basis of NENs, limited attention has been given to the role of epigenetic modifications, particularly DNA methylation, in tumorigenesis and disease progression. This review focuses on lung, pancreas, and thyroid well-differentiated neuroendocrine tumors (NETs), highlighting epigenetic mechanisms, particularly DNA methylation, as promising biomarkers for early diagnosis and risk stratification. Aberrant DNA methylation can silence key tumor suppressor genes, including RASSF1A and CDKN2A, thereby promoting tumorigenesis. Integrating DNA methylation profiles with conventional biomarkers such as chromogranin A (CgA) may enhance diagnostic accuracy and inform therapeutic strategies. Emerging epigenetic therapies offer potential avenues for personalized treatment based on molecular profiling. Unlike prior reviews that broadly cover genetic and epigenetic changes in NENs, this review uniquely emphasizes the translational potential of epigenetic biomarkers in clinical practice. By synthesizing recent findings and evaluating their clinical implications, we aim to bridge the gap between molecular research and practical applications in diagnosis, prognosis, and therapy.

The progress of artificial intelligence (AI), particularly its core algorithms—machine learning (ML) and deep learning (DL)—has been significant in the medical field, impacting both scientific research and clinical practice. These algorithms are now capable of analyzing ultrasound images, processing them, and providing outcomes, such as determining the benignity or malignancy of thyroid nodules. This integration into ultrasound machines is referred to as computer-aided diagnosis (CAD). The use of such software extends beyond ultrasound to include cytopathological and molecular assessments, enhancing the estimation of malignancy risk. AI’s considerable potential in cancer diagnosis and prevention is evident. This article provides an overview of AI models based on ML and DL algorithms used in thyroid diagnostics. Recent studies demonstrate their effectiveness and diagnostic role in ultrasound, pathology, and molecular fields. Notable advancements include content-based image retrieval (CBIR), enhanced saliency CBIR (SE-CBIR), Restore-Generative Adversarial Networks (GANs), and Vision Transformers (ViTs). These new algorithms show remarkable results, indicating their potential as diagnostic and prognostic tools for thyroid pathology. The future trend points to these AI systems becoming the preferred choice for thyroid diagnostics.

While the frequency of papillary thyroid carcinoma (PTC) has increased in recent decades, both due to improvements in diagnostic procedures and a real, effective percentage increase in cases, the frequency of medullary thyroid carcinoma (MTC), however, has remained almost unchanged, representing 3–5% of thyroid cancer cases. Our experience relates to the observation of cases with the synchronous presence of PTC and MTC, also in chronic autoimmune thyroiditis, and this led us to carry out a brief review of the literature on the subject, with the aim above all of identifying the most correct postoperative therapeutic process.

Dexmedetomidine, a selective α2-adrenergic agonist, is favoured in intensive care for its minimal respiratory depression. This study evaluated the reporting frequency of rhabdomyolysis with dexmedetomidine compared to midazolam and propofol using the European pharmacovigilance database Eudravigilance. We conducted an observational, retrospective analysis of Individual Case Safety Reports (ICSRs) from 1 January 2013, to 31 December 2023. Primary and secondary outcomes included the reporting frequencies of rhabdomyolysis and its indicative signs and symptoms, respectively. We retrieved 19,268 ICSRs, of which 364 reported rhabdomyolysis associated with dexmedetomidine (3.8%), midazolam (10.2%), propofol (76.9%), or combinations thereof (9.1%). Dexmedetomidine showed a significantly lower reporting frequency of rhabdomyolysis compared to propofol (ROR, 0.32; 95% CI, 0.19–0.55) but no significant difference compared to midazolam. Subgroup analyses revealed higher frequencies in males, especially with propofol. Despite limitations such as underreporting, our findings suggest dexmedetomidine poses a lower rhabdomyolysis risk than propofol, supporting its safe use for sedation in high-risk patients. It is important to note that due to the retrospective design of this study our findings are indicative of correlations rather than causation. Continuous monitoring and further studies are recommended to validate these results.