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15 result(s) for "Orsini, Arianna"
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Metabolic Profiling of Distinct TP53-Mutant Esophageal Adenocarcinoma Models Reveals Different Bioenergetic Dependencies
Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. TP53, previously identified as the most frequently mutated gene in EAC in our studies, plays a central role in tumor suppression and regulation. However, the metabolic consequences of TP53 mutations in EAC remain largely uncharacterized. We metabolically profiled three TP53-mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct TP53 alterations. Our analyses revealed different metabolic phenotypes associated with TP53 status. OE33 cells predominantly use glycolytic metabolism but display limited adaptability to environmental changes, possibly due to a higher differentiation state. FLO1 cells exhibit a strong glycolytic dependence, elevated lactate production, and robust proliferation under acidic conditions, consistent with an aggressive and metastatic phenotype. OE19 cells preferentially utilize oxidative phosphorylation, demonstrated by resilience to glucose and glutamine deprivation, and ROS accumulation. These findings highlight the metabolic plasticity of EAC and suggest that TP53 mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC.
Omics Technologies Improving Breast Cancer Research and Diagnostics
Breast cancer (BC) has yielded approximately 2.26 million new cases and has caused nearly 685,000 deaths worldwide in the last two years, making it the most common diagnosed cancer type in the world. BC is an intricate ecosystem formed by both the tumor microenvironment and malignant cells, and its heterogeneity impacts the response to treatment. Biomedical research has entered the era of massive omics data thanks to the high-throughput sequencing revolution, quick progress and widespread adoption. These technologies—liquid biopsy, transcriptomics, epigenomics, proteomics, metabolomics, pharmaco-omics and artificial intelligence imaging—could help researchers and clinicians to better understand the formation and evolution of BC. This review focuses on the findings of recent multi-omics-based research that has been applied to BC research, with an introduction to every omics technique and their applications for the different BC phenotypes, biomarkers, target therapies, diagnosis, treatment and prognosis, to provide a comprehensive overview of the possibilities of BC research.
miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma
Alterations in microRNA (miRNA) expression have been reported in different cancers. We assessed the expression of 754 oncology–related miRNAs in esophageal adenocarcinoma (EAC) samples and evaluated their correlations with clinical parameters. We found that miR–221 and 483–3p were consistently upregulated in EAC patients vs. controls (Wilcoxon signed–rank test: miR–221 p < 0.0001; miR–483–3p p < 0.0001). Kaplan–Meier analysis showed worse cancer–related survival among all EAC patients expressing high miR–221 or miR–483–3p levels (log–rank p = 0.0025 and p = 0.0235, respectively). Higher miR–221 or miR–483–3p levels also correlated with advanced tumor stages (Mann–Whitney p = 0.0195 and p = 0.0085, respectively), and overexpression of miR–221 was associated with worse survival in low–risk EAC patients. Moreover, a significantly worse outcome was associated with the combined overexpression of miR–221 and miR–483–3p (log–rank p = 0.0410). To identify target genes affected by miRNA overexpression, we transfected the corresponding mimic RNA (miRVANA) for either miR–221 or miR–483–3p in a well–characterized esophageal adenocarcinoma cell line (OE19) and performed RNA–seq analysis. In the miRNA–overexpressing cells, we discovered a convergent dysregulation of genes linked to apoptosis, ATP synthesis, angiogenesis, and cancer progression, including a long non–coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, dysregulated miRNA expression, especially overexpression of miR–221 and 483–3p, was found in EAC samples. These alterations were connected with a lower cancer–specific patient survival, suggesting that these miRNAs could be useful for patient stratification and prognosis.
Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma
Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gene.
Iatrogenic Ureteropelvic Junction Disruption from Lumbar Spinal Fusion Surgery: Early Repair using The SP Robotic System
ABSTRACT Introduction: Severe iatrogenic ureteral injuries are uncommon but challenging clinical scenarios, mostly related to abdominal and gynecological surgery (1) but lately also to spinal surgery (2). Prompt management is mandatory to avoid impaired outcomes (3). Moreover, a minimally invasive approach is desirable to minimize surgical morbidity and expedite recovery (4). Single Port robotic surgery is being implemented for a variety of indications, including ureteral surgery (5, 6). Materials and Methods: We present the case of a 48-year-old, who underwent lumbar spinal fusion surgery and 3 days after discharge was readmitted presenting abdominal pain. A CT scan revealed a large abdominal fluid collection and consequently a percutaneous drain was placed. A subsequent CT-urogram revealed a right ureteral injury at level of the ureteropelvic junction (UPJ). A percutaneous nephrostomy was inserted after unsuccessful retrograde and anterograde stent placement attempts. The patient underwent SP robotic early repair of the ureter 3 weeks after spinal surgery. Results: SP robotic ureteral injury repair with transperitoneal approach was performed. The surgery was well tolerated without intraoperative complications, patient was discharged on post-operative day 2. Right percutaneous nephrostomy was removed after 2 weeks and ureteral stent after 4. At 6-months follow-up the patient was asymptomatic and CT-urogram confirmed symmetric contrast excretion without hydroureteronephrosis or contrast leakage. Conclusion: SP robotic repair of the UPJ injury is safe and feasible. This procedure provides the benefits of minimally invasive surgery, and it should be considered as a valid alternative to traditional multiport robotic approach.
Evaluation of Biocontrol Measures to Reduce Bacterial Load and Healthcare-Associated Infections
Hospital-acquired infections (HAIs) remain a major clinical and economic burden, with pathogens such as Escherichia coli contributing to high rates of morbidity and mortality. Traditional manual disinfection methods are often insufficient, particularly in high-risk hospital environments. In this study, we investigated innovative strategies to enhance surface decontamination and reduce infection risk. First, we assessed the efficacy of the SMEG BPW1260 bedpan washer-disinfector, a thermal disinfection system for human waste containers. Our results demonstrated a reduction in Clostridium difficile and Escherichia coli contamination by >99.9% (>3 log reduction), as measured by colony-forming units (CFU) before and after treatment. Molecular techniques, including spectrophotometry, cell counting, and quantitative PCR (qPCR) for DNA quantification, confirmed reduction in bacterial contamination. Specifically, Clostridium difficile showed a reduction of approximately 89% in both optical density (OD) and cell count (cells/mL). In the case of Escherichia coli, a reduction of around 82% in OD was observed, with an even more pronounced decrease in cell count, reaching approximately 99.3%. For both bacteria, DNA quantification by qPCR was below detectable limits. Furthermore, we optimized the energy efficiency of the disinfection cycle, achieving a 45% reduction in power consumption compared to standard protocols without compromising antimicrobial efficacy. Secondly, we developed a sustainable cleaning solution based on methyl ester sulfonate surfactants derived from waste cooking oil. The detergent’s antibacterial activity was tested on contaminated surfaces and further enhanced through the incorporation of nanoassemblies composed of silver, electrostatically bound either to biomimetic magnetic nanoparticles or to conventional magnetic nanoparticles. Washing with the detergent alone effectively eliminated detectable contamination, while the addition of nanoparticles inhibited bacterial regrowth. Antimicrobial testing against E. coli revealed that the nanoparticle-enriched formulations reduced the average MIC values by approximately 50%, with MIC50 values around 0.03–0.06 mg/mL and MIC90 values between 0.06 and 0.12 mg/mL, indicating improved inhibitory efficacy. Finally, recognizing the infection risks associated with intra-hospital transport, we tested the SAFE-HUG Wheelchair Cover, a disposable non-woven barrier designed to reduce patient exposure to contaminated wheelchair surfaces. Use of the cover resulted in a 3.3 log reduction in surface contamination, based on viable cell counts. Optical density and bacterial DNA were undetectable in all covered samples at both 1 and 24 h, confirming the strong barrier effect. Together, these approaches—thermal no-touch disinfection, eco-friendly detergent boosted with nanoparticles, and protective transport barriers—respond to the urgent need for effective, sustainable infection control methods in healthcare settings. Our findings demonstrate the potential of these systems to counteract microbial contamination while minimizing environmental impact, offering promising solutions for the future of infection prevention in healthcare settings.
Iatrogenic Ureteropelvic Junction Disruption from Lumbar Spinal Fusion Surgery: Early Repair using The SP Robotic System
Introduction: Severe iatrogenic ureteral injuries are uncommon but challenging clinical scenarios, mostly related to abdominal and gynecological surgery (1) but lately also to spinal surgery (2). Prompt management is mandatory to avoid impaired outcomes (3). Moreover, a minimally invasive approach is desirable to minimize surgical morbidity and expedite recovery (4). Single Port robotic surgery is being implemented for a variety of indications, including ureteral surgery (5, 6). Materials and Methods: We present the case of a 48-year-old, who underwent lumbar spinal fusion surgery and 3 days after discharge was readmitted presenting abdominal pain. A CT scan revealed a large abdominal fluid collection and consequently a percutaneous drain was placed. A subsequent CT-urogram revealed a right ureteral injury at level of the ureteropelvic junction (UPJ). A percutaneous nephrostomy was inserted after unsuccessful retrograde and anterograde stent placement attempts. The patient underwent SP robotic early repair of the ureter 3 weeks after spinal surgery. Results: SP robotic ureteral injury repair with transperitoneal approach was performed. The surgery was well tolerated without intraoperative complications, patient was discharged on post-operative day 2. Right percutaneous nephrostomy was removed after 2 weeks and ureteral stent after 4. At 6-months follow-up the patient was asymptomatic and CT-urogram confirmed symmetric contrast excretion without hydroureteronephrosis or contrast leakage. Conclusion: SP robotic repair of the UP) injury is safe and feasible. This procedure provides the benefits of minimally invasive surgery, and it should be considered as a valid alternative to traditional multiport robotic approach.
Predictors of delayed hospital discharge after robot-assisted partial nephrectomy: the impact of single-port robotic surgery
Purpose To evaluate the predictors of delayed discharge for patients undergoing robot-assisted partial nephrectomy (RAPN) at our Institution since the introduction of the single port (SP) robotic system. Methods We performed a retrospective review of our prospectively maintained database of patients undergoing RAPN from September 2020 to August 2024. Patients were categorized by the postoperative day of their discharge: POD1 (single overnight stay) or POD > 1 (more than one night stay). Multivariable logistic regression analysis was used to test the probability of prolonged hospital stay (defined as more than one night stay) adjusting for age at surgery, surgical approach, Charlson comorbidity index, baseline hemoglobin, antiplatelet or anticoagulant medications, clinical tumor stage, and intraoperative blood transfusion. Results Overall, 255 patients were identified for the analysis. Patients discharged on POD1 were younger ( p  = 0.004), reported a lower Charlson Comorbidity Index ( p  = 0.002), higher preoperative hemoglobin levels ( p  = 0.005), and smaller tumor size ( p  < 0.001). Higher rates of discharge on POD1 were recorded for both multiport transperitoneal (59.5 vs. 40.5%, p  = 0.02) and SP retroperitoneal (81.5 vs. 18.5%, p  = 0.004). Clinical tumor stage ( p  = 0.02) and intraoperative blood transfusion ( p  = 0.05) emerged as independent risk factors for POD > 1. Baseline hemoglobin emerged as a protective factor ( p  = 0.05) as well as SP approach ( p  = 0.03). Conclusion SP-RAPN holds potential to shorten hospitalization without hampering surgical outcomes. By maximizing the adoption of a RP approach and minimizing surgical invasiveness, SP robotic surgery allows to significantly expand the pool of RAPN patients that can be discharged after a single overnight stay.
Giardia duodenalis Colonization Slightly Affects Gut Microbiota and Hematological Parameters in Clinically Healthy Dogs
Giardia duodenalis (Giardia) is a worldwide cause of acute diarrheal disease both in humans and animals. The primary aim of this study was to investigate possible variations in gut microbiota in a population of asymptomatic dogs (n = 31), naturally infected or not by Giardia. Gut microbiota and the hematological, biochemical, and fecal parameters related to intestinal function were investigated. Giardia infection was associated with a significant shift of beta diversity, showing a relevant reduction of Gammaproteobacteria and an increase of Fusobacteria in male-positive dogs if compared with negatives. A significant imbalance of different bacterial taxa, with particular reference to the Erysipelotrichales, Lactobacillales, Clostridiales, and Burkholderiales orders, was observed, with the first two being higher in Giardia-positive dogs. Giardia-positive males displayed significantly higher values of cCRP than negative males as well as positive females, supporting the presence of a pro-inflammatory state. Taken together, these results indicate that the presence of Giardia does not substantially modify the microbial ecology of the intestine nor the hematological markers of disease. Thus treatments against Giardia should be considered with caution in asymptomatic subjects.
Genomic analysis of Streptococcus canis from different hosts in Italy 2004–2021: diversity, antimicrobial resistance, and virulence profiles
Streptococcus canis , a multi-host pathogen commonly isolated from dogs and cats has been occasionally reported in severe cases of human infection. This study aimed to explore the genetic diversity, antimicrobial resistance (AMR), and pathogenicity of S. canis isolates collected between 2004–2021, in Italy. Fifty-five S. canis isolates from clinical cases in domestic animals were investigated for susceptibility to antibiotics and then characterized for sequence type (ST), virulence profile, and antimicrobial-resistant genes through whole genome sequencing (WGS). All isolates were susceptible to beta-lactams, while frequently exhibiting resistance to lincosamides, chlortetracyclines, and macrolides. Six out of 55 isolates of S. canis, all collected between 2020 and 2021, were multi-drug resistant (MDR). The most common AMR gene in the dataset was lmrP conferring resistance for streptogramin, tetracycline, macrolide, streptogramin A, and lincosamide. Other determinants of AMR were the tet genes. Twenty-one distinct STs were identified, with ST9 being the most prevalent in our collection. Regarding the virulence genes, forty-three isolates were positive for the ssp-5 gene, which encodes an agglutinin receptor. Comparison with other 46 S. canis genomes available in public repositories revealed that the Italian isolates clustered by the S. canis M-like (SCM) protein gene and ST and did not group according to their host, area, or year of origin. In conclusion, our study underscores the susceptibility of Italian S. canis isolates to beta-lactam antibiotics, which remain the first line of defense in managing infections. In Italy, ST9 represents the predominant clone of this pathogen. Despite the diversity in species of origin and the various STs identified, our findings confirm that S. canis has not adapted to different ecological niches and corroborate the accidental pathogenic nature of human cases.