Search Results (301)

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

The ongoing exploration of planets such as Mars is producing a wealth of data to define habitable environments beyond the Earth. The inferred presence of neutral to alkaline aqueous fluids on Mars in its early history suggests that many potentially habitable environments existed on the planet. Terrestrial analogues with similar chemical and physical properties are being explored and characterized in order to assess their suitability for triggering the Origin of Life on Mars. Recently, a novel Mars analogue site has been identified in the Bagno dell’Acqua Lake, which is located in the island of Pantelleria in Sicily (Italy). We report here that microbialite from the Bagno dell’Acqua Lake acts as an efficient catalyst for prebiotic processes, starting from a ternary mixture of well-recognized chemical precursors, including ammonium formate, diaminomalonitrile, and alpha-amino acids. Under thermal conditions, significant amounts of building blocks of both RNA and PNA were obtained. Furthermore, samples of the water from the Bagno dell’Acqua Lake have been found to promote the polymerization of the H-form of 3′,5′-cyclic GMP, resulting in the generation of RNA oligomers of up to 15 units in length. Full article

Background: Rectal cancer management involves surgery, chemotherapy (CT), radiotherapy (RT), and patient care strategies, all of which significantly affect health-related quality of life (HRQoL). Understanding these effects is critical for optimizing treatment protocols. This review aimed to systematically analyze the impact of rectal cancer treatment on HRQoL. Methods: Four databases, Scopus, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials, were searched for randomized controlled trials (RCTs) published between January 2013 and December 2023. RCTs specifically focusing on rectal cancer treatments (surgical interventions, pre- and/or post-CT and/or RT, and patient care strategies) were included. An abstract review, data extraction, and a risk-of-bias assessment were independently conducted by two reviewers. Results: The 41 included studies comprised 9240 patients: 16 evaluated surgical interventions (3507 patients), 15 evaluated pre- and/or post-CT and/or RT protocols (5114 patients), and 10 focused on patient-care strategies (619 patients). Sphincter-sparing procedures were associated with better HRQoL than abdominoperineal resection, and rectal-sparing techniques were associated with better overall HRQoL than rectal resection. RT was associated with a poorer HRQoL. Continuity-of-care interventions improved HRQoL in ostomy patients, whereas transanal irrigation improved HRQoL after ostomy closure. Conclusions: This systematic review of RCTs underscores the importance of organ-sparing strategies, such as rectum-sparing approaches and continuity-of-care packages, in improving HRQoL in patients with rectal cancer. Although RT negatively affects HRQoL, treatment regimens should be individualized. Tailored organ-preservation approaches and structured follow-up care are essential for optimizing HRQoL in patients with rectal cancer. Full article

Thyroid nodules are a common clinical finding, with their prevalence influenced by multiple environmental and occupational factors, including exposure to ionizing radiation. Healthcare workers, particularly those operating in radiology, nuclear medicine, interventional cardiology, and radiation oncology, are potentially at increased risk due to chronic low-dose radiation exposure. This review aims to evaluate the current evidence regarding the association between occupational radiation exposure and the development of thyroid nodules among healthcare professionals. The findings suggest a higher prevalence of thyroid nodules in radiation-exposed workers compared to the general population, although data heterogeneity and methodological limitations exist. Factors such as the duration of exposure, radiation protection practices, and frequency of monitoring play critical roles in modulating the individual risk. While some studies report no significant difference in malignancy rates, the increased detection of nodules underlines the need for regular thyroid surveillance in at-risk populations. Further longitudinal and multicentric studies are warranted to clarify the causality and guide preventive strategies. This review highlights the importance of occupational health protocols, including radiation shielding and periodic thyroid evaluation, in safeguarding the long-term endocrine health of healthcare workers. Full article

Leukoplakia is a condition marked by white patches on the inner surfaces of the oral cavity. Its potential to progress to oral squamous cell carcinoma underscores the need for effective screening and early diagnosis procedures. We employed NMR-based salivary and tissue metabolomics to identify potential biomarkers for leukoplakia and dysplastic leukoplakia. Univariate and multivariate methods were used to evaluate the NMR-derived metabolite concentrations. The salivary metabolite profile of leukoplakia exhibited specific alterations compared to healthy controls. These metabolic changes were more pronounced in cases of dysplastic lesions. Multivariate ROC curve analysis, based on a selection of salivary metabolites, ascribed high diagnostic accuracy to the models that discriminate between dysplastic and healthy cases. However, NMR analysis of tissue biopsies was ineffective in extracting metabolic signatures to differentiate between lesional, peri-lesional, and healthy tissues. Our pilot study employing a metabolomics-based approach led to the development of salivary models that represent a complementary strategy for clinically detecting leukoplakia. However, larger-scale validation is required to fully evaluate their diagnostic potential and to effectively stratify leukoplakia patients according to dysplasia status. Full article

Mass customization (MC) has become a pivotal manufacturing strategy for addressing the growing demand for personalized products without compromising cost efficiency and scalability. The emergence of Industry 4.0 (I4.0) has further expanded the potential of MC by enabling intelligent, flexible, and interconnected production systems. This paper presents a systematic literature review covering the period from 2011 to 2024, aimed at examining how I4.0 technologies influenced the conceptual evolution, technological enablers, and supply chain implications of MC. A total of 3441 publications were retrieved from Scopus and analyzed using a combination of bibliometric mapping and qualitative synthesis. The review identifies three primary research streams: (1) MC conceptual frameworks and performance metrics, (2) enabling technologies and methods across the product lifecycle, and (3) supply chain strategies tailored to MC environments. Key enablers such as product modularity, customer co-design platforms, additive manufacturing, and reconfigurable production systems are discussed, along with barriers related to complexity, integration challenges, and sustainability trade-offs. The study highlights a gradual convergence toward mass personalization, supported by real-time data, artificial intelligence, and predictive analytics. The findings offer a structured understanding of MC in the I4.0 context and point toward future research opportunities involving digital twin integration, cross-disciplinary implementation models, and sustainability-driven customization frameworks. Full article

Background: The blood–brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) but also limits drug delivery. Insufficient knowledge of how the CNS promotes the onset and maintenance of peripheral neuropathic pain limits therapeutic methods for the treatment of persistent neuropathic pain. Thus, this study aimed to evaluate the ability of a novel combination of Palmitoylethanolamide (PEA) and Equisetum arvense L. (Equisetum A.L.) to cross the BBB and modulate nociceptive pathways. Methods: Using a humanised in vitro BBB tri-culture model, the permeability, cytotoxicity, and integrity of the barrier were assessed after exposure to two different PEA forms, PEA ultramicronized (PEA-um) and PEA80mesh, Equisetum A.L., and a combination of the last two samples. The samples exhibited no cytotoxicity, maintained tight junction integrity, and efficiently crossed the blood–brain barrier (BBB), with the combination displaying the highest permeability. The eluate from the BBB model was then used to stimulate the co-culture of CCF-STTG1 astrocytes and SH-SY5Y neurons pre-treated with H₂O₂ 200 µM. Results: Treatment with the combination significantly increased cell viability (1.8-fold, p < 0.05), reduced oxidative stress (2.5-fold, p < 0.05), and decreased pro-inflammatory cytokines (TNFα, IL-1β) compared to single agents. Mechanistic analysis revealed modulation of key targets involved in pain pathways, including decreased FAAH and NAAA activity, increased levels of endocannabinoids (AEA and 2-AG), upregulation of CB2 receptor expression, enhanced PPARα activity, and reduced phosphorylation of PKA and TRPV1. Conclusions: These findings suggest that the combination of PEA and Equisetum A.L. effectively crosses the BBB and exerts combined anti-inflammatory and analgesic effects at the CNS level, suggesting a possible role in modulating neuroinflammatory and nociception responses. Full article

A major challenge in developing new functional foods is effectively protecting and releasing bioactive compounds in specific body areas. The Multiform Administration Timed Release Ingredients System (M.A.T.R.I.S.) is an innovative method that coats active ingredient particles with a permeable membrane, allowing for diffusion without the presence of inactive materials. This study aimed to test how M. A. T. R. I. S. modulated the absorption and effects of two molecules: α-lipoic acid and acetyl-L-carnitine. This study examined the structures of these molecules with or without M.A.T.R.I.S. and investigated their intestinal absorption. Peripheral nervous system analyses were also conducted to confirm the ability of substances to maintain their functions in the presence of M.A.T.R.I.S. Results showed that M.A.T.R.I.S. modulated the absorption of both molecules compared to granular raw material forms (p < 0.05). Additionally, the M.A.T.R.I.S. molecules better supported peripheral nerve well-being than their granular raw material forms (p < 0.05). In conclusion, this study demonstrates that M.A.T.R.I.S. technology can be used to create innovative, safe treatments by enhancing absorption mechanisms to improve the effectiveness of substances in reaching their specific targets. Full article

Pleural carcinomatosis (PC) and malignant pleural effusion (MPE) affect up to 20% of patients with non-small cell lung cancer (NSCLC) and are usually synonymous with poor prognosis. Pressurized Intra-Thoracic Aerosol Chemotherapy (PITAC) is a novel and promising technique to control MPE in PC-NSCLC. This pilot study aimed to assess the feasibility, safety, and efficacy of PITAC in terms of palliative pleurodesis and evaluate the local antineoplastic control by analyzing patient-derived primary cell cultures. From January to December 2023, seven patients underwent PITAC with tailored doses of cisplatin and doxorubicin. There were four males and three females, with a median age of 65 (IQR:19) years. No operating room contamination by aerosolized chemotherapeutics was observed. No intraoperative complications occurred, and 30-day mortality was nil. One patient developed a postoperative prolonged air leak. The median chest tube stay was 2 (IQR:2) days, and the median hospital stay was 4 (IQR:2) days. No systemic toxicity nor hypersensitivity to chemotherapeutics were observed. All patients developed effective pleurodesis in 30 days. Cell cultures obtained from biopsy of PC-NSCLC sampled before PITAC formed confluent and monolayer sheets of attached tumor cells, while after 30 min from PITAC, cultures exhibited a significant reduction in the cancer cells’ growth. Effective pleurodesis was observed three and six months after surgery in all patients. PITAC is a safe and effective technique to control MPE recurrence and might revolutionize loco-regional therapy for PC-NSCLC. Further research should assess its oncological role. Full article

Together with Granulicatella spp., A. defectiva was formerly classified within the group of nutritionally variant streptococci (NVS). NVS-related endocarditis has been associated with higher rates of complications, bacteriological failure, and mortality compared to other streptococci, partially due to challenges related to timely and accurate identification. PJI caused by A. defectiva are rarely reported, and standardized management strategies have not yet been established. We describe a case of a 68-year-old man with concomitant A. defectiva PJI and native mitral valve endocarditis. The patient was managed conservatively for endocarditis and subsequently underwent a two-stage arthroplasty of the infected prosthetic knee. A. defectiva was identified using MALDI-TOF mass spectrometry on both synovial fluid and blood cultures. As penicillin susceptibility data were not available, the patient was treated with vancomycin at a dose of 2 g/day, resulting in a favorable clinical response. In addition, we performed a literature review on A. defectiva and Granulicatella PJI. Despite the limited number of reported cases in the literature, the findings suggest a potential correlation between clinical outcomes and antimicrobial treatment duration. Further comprehensive studies are needed to establish standardized management strategies for A. defectiva and Granulicatella PJI. Full article

Background: Thoracic ultrasound (TUS) has emerged as a viable alternative of computed tomography (CT) for pneumothorax diagnosis. Ultrasound elastography (USE), a technique assessing tissue elasticity, has recently been proposed as a novel tool for pneumothorax evaluation. Methods: This prospective, monocentric, observational study aimed to compare the diagnostic accuracy of static and dynamic USE with TUS in detecting iatrogenic pneumothorax after CT-guided transthoracic needle aspiration (TTNA). Results: Thirty-two patients were enrolled, with pneumothorax confirmed via CT in 40.63% of cases. The results showed that elastographic-mode images had significantly higher sensitivity (76.9% vs. 21.2%, p < 0.001) and improved positive and negative predictive values (67.8% vs. 52.4%, p-value 0.01, 82.6% vs. 61.7%, p-value < 0.001, respectively), compared to B-mode images. Concordance between expert and non-expert evaluators was also higher for elastographic images, suggesting improved interpretability. However, dynamic USE did not demonstrate a statistically significant advantage over B-mode videos. Conclusions: These findings suggest that USE may enhance static ultrasound-based pneumothorax detection and provide an objective imaging marker for reports. Further multicenter studies are needed to confirm these findings and explore the potential role of USE in other settings. Full article

Tricuspid regurgitation is a common valvular disease associated with high morbidity and mortality if left untreated. While surgery has been the standard intervention, transcatheter tricuspid edge-to-edge repair (T-TEER) has emerged as an alternative for high-risk surgical candidates. Transesophageal echocardiography (TEE) is the gold-standard imaging modality for guiding T-TEER due to its high spatial and temporal resolution. However, it requires general anesthesia and esophageal intubation, limiting its use in certain patients. Additionally, TEE image quality may be compromised by anterior structure shadowing, which is common in T-TEER. The development of 4D intracardiac echocardiography (ICE) offers real-time, three-dimensional imaging, potentially overcoming these limitations. This study compared TEE and Acuson AcuNav 4D-ICE in guiding T-TEER in ten high-risk patients across eight crucial procedural steps. ICE showed optimal feasibility in key procedural steps, including valve steering and leaflet grasping, due to its proximity to target structures, minimizing shadowing artifacts. Both modalities performed equally in lesion identification and residual regurgitation assessment and achieved non-statistically different results in most quantitative measurements. This study supports the integration of 4D-ICE into T-TEER procedures, particularly for patients unsuited for TEE or with complex TEE windows. Its real-time imaging, reduced invasiveness, and feasibility in critical steps highlight its potential as a viable alternative or complement to TEE. Further multicenter studies are needed to validate its role, optimize protocols, and evaluate long-term outcomes in 4D-ICE-guided T-TEER. Full article

Background/Objectives: Anemia and renal impairment are key predictors of adverse outcomes in acute coronary syndromes (ACSs). The hemoglobin-to-creatinine (Hb/Cr) ratio combines these parameters into a simple index. This study aimed to evaluate its prognostic value at discharge in patients with ST-elevation myocardial infarction (STEMI). Methods: The primary endpoint was one-year all-cause mortality; secondary endpoints included major bleeding and the composite of all-cause mortality or reinfarction. Optimal Hb/Cr cut-off values were identified using Liu’s method. Multivariable logistic regression and propensity score matching were used to assess associations with outcomes. Results: We analyzed 11,236 STEMI patients from the PRAISE registry with available hemoglobin and creatinine values at discharge. The optimal cut-points were 13.68 for mortality and 14.42 for secondary endpoints. Patients were stratified into low (<13.68; 26.5%) and high (≥13.68; 73.5%) Hb/Cr groups. The low Hb/Cr group was older, had more comorbidities, and received less intensive therapy. At one year, low Hb/Cr patients had significantly higher rates of all-cause mortality (8.7% vs. 2.4%), major bleeding (5.0% vs. 2.4%), and the composite outcome (11.5% vs. 4.9%). In the multivariate logistic regression, the Hb/Cr ratio was inversely associated with all outcomes, namely all-cause mortality (odds ratio [OR] 0.94; 95% confidence interval [CI]: 0.92–0.96), major bleeding (OR 0.96; 95% CI: 0.94–0.97), and the composite endpoint (OR 0.93; 95% CI: 0.91–0.96). The Hb/Cr ratio outperformed hemoglobin and creatinine alone in predicting mortality (AUC 0.684 vs. 0.649 and 0.645; p < 0.001). Conclusions: The Hb/Cr ratio is independently associated with one-year adverse outcomes in STEMI and may serve as a simple marker of increased vulnerability. Prospective studies are needed to validate its clinical utility. Full article

Background: Hereditary colorectal cancer syndromes, including familial adenomatous polyposis (FAP), Lynch syndrome (LS), and Peutz–Jeghers syndrome (PJS), are associated with an increased risk of small bowel cancer (SBC). Due to the low incidence and non-specific presentation of SBC, effective surveillance strategies are essential for early detection and management. This review aims to evaluate and compare current endoscopic techniques for small bowel surveillance in these patients. Methods: A comprehensive review was conducted using peer-reviewed studies sourced from PubMed. Various endoscopic modalities, including capsule endoscopy (CE), device-assisted enteroscopy (DAE), and intraoperative enteroscopy (IOE), were assessed for their diagnostic yield, safety, and clinical utility. Surveillance recommendations of the different syndromes were also examined. Results: CE offers high sensitivity but lacks histological sampling capability. DAE, including double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE), enables direct visualization, biopsy, and therapeutic interventions, albeit with greater procedural complexity. In FAP, duodenal surveillance follows the Spigelman classification to stratify cancer risk, while jejunal and ileal polyps remain less studied. LS patients have an increased SBC risk, warranting tailored endoscopic approaches. In PJS, surveillance aims to mitigate intussusception risks and allow early malignancy detection. Conclusions: Optimized surveillance strategies in hereditary colorectal cancer syndromes require a multimodal approach, integrating advanced endoscopic techniques with genetic risk stratification. Centralized care in tertiary centers improves outcomes by ensuring standardized surveillance protocols and enhancing early cancer detection. Artificial intelligence (AI) applied to CE and DAE is shaping promising prospects for the future surveillance of small bowel polyps by enhancing diagnostic accuracy and reducing the duration of the diagnostic process. Further research should investigate AI-assisted imaging and molecular biomarkers to optimize screening strategies. Full article

Background/Objectives: The indirect impact of the pandemic on the diagnosis and treatment of new primary melanoma has been carefully evaluated in recent years. The aim of the present study was to investigate if the indirect impact of the pandemic in Italy could be detectable also in the second year of the pandemic, as suggested by the characteristics of melanoma at diagnosis. Methods: Retrospective analysis of 1640 diagnoses of cutaneous melanoma in pre-pandemic period and 1292 diagnoses in the pandemic period from 10 centers (from 1 March 2019 to 28 February 2022). Results: Our findings confirmed an indirect impact of the pandemic on characteristics of incident melanoma, also in the second year of the pandemic in Italy (Breslow thickness p < 0.0001, tumor stage p = 0.002, ulceration p = 0.04, SNLB p = 0.03), without statistically significant differences between centers. A statistically significant reduction in the time interval from diagnosis to surgical treatment was observed, but only in centers that had to modify their case mix to address the needs of treating COVID-19 patients (p = 0.0002). Conclusions: Our study confirmed the indirect impact of the pandemic on melanoma characteristics at the diagnosis in the second year of the pandemic in Italy. We also found no differences in melanoma characteristics between hospitals with different organization. Diagnostic delays may be related to a delayed access of the patient to the entire diagnostic pathway, and therefore, especially in the case of a pandemic, policies to support early diagnosis are crucial. Full article