44 results on '"Pasquale Vitale"'
Search Results
2. TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities
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Morena Fasano, Mario Pirozzi, Chiara Carmen Miceli, Mariateresa Cocule, Michele Caraglia, Mariarosaria Boccellino, Pasquale Vitale, Vincenzo De Falco, Stefano Farese, Alessia Zotta, Fortunato Ciardiello, and Raffaele Addeo
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angiogenesis ,colorectal cancer ,EMT ,microenvironment ,TGF-β ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-β signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-β signals through SMAD proteins, which are intracellular molecules that transmit TGF-β signals from the cell membrane to the nucleus. Alterations in the TGF-β pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-β signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-β influences metastasis development. TGF-β promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-β affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-β in mCRC patients, aiming to identify new therapeutic options.
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- 2024
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3. A Resilient Approach to a Test Rig Setup in the Qualification of a Tilt Rotor Carbon Fiber-Reinforced Polymer (CFRP) Wing
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Pasquale Vitale, Gianluca Diodati, Salvatore Orlando, Francesco Timbrato, Mario Miano, Antonio Chiariello, and Marika Belardo
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tiltrotor ,wing ,carbon fiber-reinforced polymer ,shear force and bending moment ,cross plot ,static test ,Motor vehicles. Aeronautics. Astronautics ,TL1-4050 - Abstract
The evolution of aircraft wing development has seen significant progress since the early days of aviation, with static testing emerging as a crucial aspect for ensuring safety and reliability. This study focused specifically on the engineering phase of static testing for the Clean Sky 2 T-WING project, which is dedicated to testing the innovative composite wing of the Next-Generation Civil Tiltrotor Technology Demonstrator. During the design phase, critical load cases were identified through shear force/bending moment (SFBM) and failure mode analyses. To qualify the wing, an engineering team designed a dedicated test rig equipped with hydraulic jacks to mirror the SFBM diagrams. Adhering to specifications and geometric constraints due to several factors, the jacks aimed to minimize the errors (within 5%) in replicating the diagrams. An effective algorithm, spanning five phases, was employed to pinpoint the optimal configuration. This involved analyzing significant components, conducting least square linear optimizations, selecting solutions that met the directional constraints, analyzing the Pareto front solutions, and evaluating the external jack forces. The outcome was a test rig setup with a viable set of hydraulic jack forces, achieving precise SFBM replication on the wing with minimal jacks and overall applied forces.
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- 2024
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4. Virtual Full Scale Static Test of a Civil Tilt Rotor Composite Wing in Non-Linear Regime
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Antonio Chiariello, Gaetano Perillo, Mauro Linari, Raffaele Russo, Salvatore Orlando, Pasquale Vitale, and Marika Belardo
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full scale static ,tiltrotor ,wing ,non-linear analysis ,Motor vehicles. Aeronautics. Astronautics ,TL1-4050 - Abstract
This study addresses the crucial role of post-buckling behavior analysis in the structural design of composite aeronautical structures. Traditional engineering practices tend to result in oversized composite components, increasing structural weight. EASA AMC 20-29’s Building Block Approach suggests phased testing, but its time and cost challenges necessitate a shift to high-fidelity post-buckling analyses, exemplified by MSC NASTRAN SOL 400. This approach, showcased in the analysis of the Next Generation Civil Tilt Rotor Technology Demonstrator’s wing (NGTCTR-TD), effectively de-risks static tests, contributing to a more efficient certification process. The study demonstrates how advanced simulations provide detailed insights into local buckling phenomena, allowing precise stress distribution analysis. These analyses eliminate the risk of structural failure, paving the way for safer, more efficient, and cost-effective airframe structures. Future developments aim to validate numerical analyses with experimental data, further emphasizing the reliability and benefits of high-fidelity simulations.
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- 2024
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5. Prognostic value of diabetes and metformin use in a real-life population of head and neck cancer patients
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Vincenzo De Falco, Pasquale Vitale, Christian Brancati, Giuseppe Cicero, Annunziata Auriemma, and Raffaele Addeo
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diabetes ,head and neck cancer ,oral cancer ,metformin ,HNC ,HNSCC ,Medicine (General) ,R5-920 - Abstract
IntroductionHead and neck carcinoma (HNC) is a disease with a poor prognosis despite currently available treatments. The management of patients with this tumor is often complicated by several comorbidities. Among these, diabetes is the second most frequent and its influence on the prognosis is not known.MethodsIn this work, we collected data on progression free survival (PFS) and overall survival (OS) of one hundred twenty-three patients with HNC who received biweekly cetuximab maintenance treatment after first-line chemotherapy. We then compared the survival of nondiabetic patients versus diabetics’ one.ResultsSurprisingly, both PFS (4 vs. 5 months, HR 2.297, p
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- 2023
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6. The Art of Counseling in the Treatment of Head and Neck Cancer: Exploratory Investigation among Perceptions of Health Professionals in Southern Italy
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Raffaele Addeo, Luca Pompella, Pasquale Vitale, Silvia Ileana Sara Fattoruso, Ilaria Di Giovanni, Francesco Perri, Michele Caraglia, Morena Fasano, and Raffaele Arigliani
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metastatic squamous cell carcinoma of the head and neck ,counseling ,open communication ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
(1) Background: Recurrent and/or metastatic patients with head and neck squamous cell carcinoma show a poor prognosis, which has not changed significantly in 30 years. Preserving quality of life is a primary goal for this subset of patients; (2) Methods: A group of 19 physicians working in South Italy and daily involved in head and neck cancer care took an anonymous online survey aimed at revealing the level of knowledge and the application of communication techniques in daily patient care; (3) Results: Several specialists, 18 out 19 (95%), considered that patient participation in therapeutic choices is mandatory. The main obstacles to complete and reciprocate communication still consist of lack of time and staff, but also in the need for greater organization, which goes beyond the multidisciplinary strategy already used; (4) Conclusions: A greater impulse to training and updating on issues related to counseling can improve communication between the different clinicians involved in the treatment plan.
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- 2022
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7. Non-Linear Analysis in Post-Buckling Regime of a Tilt Rotor Composite Wing Structure Using Detailed Model and Robust Loading Approach
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Antonio Chiariello, Pasquale Vitale, Marika Belardo, Francesco Di Caprio, Mauro Linari, Claudio Pezzella, Jacopo Beretta, and Luigi Di Palma
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post-buckling ,composite ,tilt-rotor ,wing ,inertia relief ,DFEM ,Technology ,Science - Abstract
The design and development of a wing for a completely brand-new aircraft represents, in aeronautics, one of the highest challenges from an engineering point of view. The present work describes a novel methodology devoted to execute numeric simulation in a non-linear post-buckling regime to verify the composite wing compliance under the design load conditions. The procedure was developed as part of a wing design and research activity and was motivated by the need to have more realistic results, without standard conservatisms like the no-buckling up to ultimate load, to be of use for achieving further weight savings. To carry this out, it was obviously necessary to ensure that the structural integrity was also guaranteed in the post-buckling regime, above the limit load, and therefore in a highly non-linear regime. The present work illustrates a numerical approach based on non-linear finite element analysis which uses the inertia relief option in order to have a more realistic representation of the structural response of the wing in its real context. All that represents a novelty since, at present, the commercial FE codes allow us to use the inertia relief option exclusively for linear analysis. Obviously, the approach can be applied to any other structural component with similar needs. The obtained results show that the differences between linear and non-linear regime are not negligible and, above all, that it is possible to design a wing (or other structural components) considering, at the same time, the large deformation due to the post-buckling regime, the material non-linearities due to the failures and any other non-linearities in order to achieve the challenging weight requirement of the new aircraft generation.
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- 2023
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8. Primary versus secondary antiemetic prophylaxis with NK1 receptor antagonists in patients affected by gastrointestinal malignancies and treated with a doublet or triplet combination regimen including oxaliplatin and/or irinotecan plus fluoropyrimidines: A propensity score matched analysis
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Alessandro Parisi, Riccardo Giampieri, Alex Mammarella, Cristiano Felicetti, Lisa Salvatore, Maria Bensi, Maria Grazia Maratta, Antonia Strippoli, Roberto Filippi, Maria Antonietta Satolli, Angelica Petrillo, Bruno Daniele, Michele De Tursi, Pietro Di Marino, Guido Giordano, Matteo Landriscina, Pasquale Vitale, Ina Valeria Zurlo, Emanuela Dell’Aquila, Silverio Tomao, Ilaria Depetris, Francesca Romana Di Pietro, Federica Zoratto, Davide Ciardiello, Maria Vittoria Pensieri, Ornella Garrone, Barbara Galassi, Claudio Ferri, Rossana Berardi, and Michele Ghidini
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gastrointestinal cancers ,FOLFOX ,FOLFIRI ,FOLFOXIRI ,FLOT ,netupitant/palonosetron ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
AimThe aim of the current study is to investigate the impact of primary compared to secondary chemotherapy-induced nausea and vomiting (CINV) prophylaxis with NK1 receptor antagonists (NK1-RA) in patients affected by gastrointestinal malignancies and treated with oxaliplatin- and/or irinotecan-based doublet or triplet regimens.Study design and methodsClinical data of patients affected by gastrointestinal malignancies, treated with an oxaliplatin and/or irinotecan-based doublet or triplet regimen as neo/adjuvant or advanced-line treatment, and who received NK1-RA as primary (from the first cycle of treatment) or secondary (after the onset of CINV with a previous regimen with 5HT3-RA and dexamethasone) prophylaxis for CINV, were retrospectively collected in an observational study involving 16 Italian centers. A propensity score matching was performed by taking into account the following stratification factors: sex (male vs. female), age (< vs. ≥70 years old), overweight (body mass index, BMI < vs. ≥25), underweight (BMI < vs. ≥19), disease spread (early vs. advanced/metastatic), tumor type (esophagogastric cancer vs. the rest, hepatobiliary tumor vs. the rest, colorectal cancer vs. the rest), type of NK1-RA used as primary/secondary prophylaxis (netupitant-palonosetron vs. fosaprepitant/aprepitant), concomitant use of opioids (yes vs. no), concomitant use of antidepressant/antipsychotic drugs (yes vs. no), Eastern Cooperative Oncology Group (ECOG) performance status at the start of NK1-RA treatment (0 vs. 1–2), and intensity of chemotherapy regimen (doublet vs. triplet).ResultsAmong 409 patients included from January 2015 to January 2022 and eligible for analysis, 284 (69%) and 125 (31%) were treated with NK1-RA as primary and secondary antiemetic prophylaxis, respectively. After matching, primary NK1-RA use was not associated with higher rates of protection from emesis regardless the emesis phase (acute phase, p = 0.34; delayed phase, p = 0.14; overall phase, p = 0.80). On the other hand, a lower rate of relevant nausea (p = 0.02) and need for rescue antiemetic therapy (p = 0.000007) in the overall phase was found in primary NK1-RA users. Furthermore, a higher rate of both complete antiemetic response (p = 0.00001) and complete antiemetic protection (p = 0.00007) in the overall phase was more frequently observed in primary NK1-RA users. Finally, chemotherapy delays (p = 0.000009) and chemotherapy dose reductions (p = 0.0000006) were less frequently observed in primary NK1-RA users.ConclusionIn patients affected by gastrointestinal malignancies, a primary CINV prophylaxis with NK1-RA, 5HT3-RA, and dexamethasone might be appropriate, particularly in those situations at higher risk of emesis and in which it is important to avoid dose delays and/or dose reductions, keeping a proper dose intensity of chemotherapy drugs.
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- 2022
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9. Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer
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Valeria Merz, Domenico Mangiameli, Camilla Zecchetto, Alberto Quinzii, Silvia Pietrobono, Carlo Messina, Simona Casalino, Marina Gaule, Camilla Pesoni, Pasquale Vitale, Chiara Trentin, Michela Frisinghelli, Orazio Caffo, and Davide Melisi
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resectable pancreatic cancer ,predictive factors ,neoadjuvant therapy ,preoperative treatment ,target therapy ,molecular profiling ,Surgery ,RD1-811 - Abstract
The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences disease relapse, even when a combination adjuvant therapy is offered. Therefore, aiming at improving disease free survival and overall survival of these patients, there is an increasing interest in evaluating the activity and efficacy of neoadjuvant and perioperative treatments. In this view, it is of utmost importance to find biomarkers able to select patients who may benefit from a preoperative therapy rather than upfront surgical resection. Defined genomic alterations and a dynamic inflammatory microenvironment are the major culprits for disease recurrence and resistance to chemotherapeutic treatments in pancreatic cancer patients. Signal transduction pathways or tumor immune microenvironment could predict early recurrence and response to chemotherapy. In the last decade, distinct molecular subtypes of pancreatic cancer have been described, laying the bases to a tailored therapeutic approach, started firstly in the treatment of advanced disease. Patients with homologous repair deficiency, in particular with mutant germline BRCA genes, represent the first subgroup demonstrating to benefit from specific therapies. A fraction of patients with pancreatic cancer could take advantage of genome sequencing with the aim of identifying possible targetable mutations. These genomic driven strategies could be even more relevant in a potentially curative setting. In this review, we outline putative predictive markers that could help in the next future in tailoring the best therapeutic strategy for pancreatic cancer patients with a potentially curable disease.
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- 2022
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10. Post-Induction Management in Patients With Left-Sided RAS and BRAF Wild-Type Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR-Based Doublet Regimens: A Multicentre Study
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Alessandro Parisi, Alessio Cortellini, Olga Venditti, Roberto Filippi, Lisa Salvatore, Giampaolo Tortora, Michele Ghidini, Olga Nigro, Fabio Gelsomino, Ina Valeria Zurlo, Claudia Fulgenzi, Pasquale Lombardi, Susana Roselló Keränen, Ilaria Depetris, Riccardo Giampieri, Cristina Morelli, Pietro Di Marino, Francesca Romana Di Pietro, Nicoletta Zanaletti, Pasquale Vitale, Ingrid Garajova, Gian Paolo Spinelli, Federica Zoratto, Michela Roberto, Angelica Petrillo, Giacomo Aimar, Leonardo Patruno, Carla D’Orazio, Corrado Ficorella, Claudio Ferri, and Giampiero Porzio
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MCRC ,FOLFOX ,FOLFIRI ,cetuximab ,panitumumab ,maintenance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundFew data regarding post-induction management following first-line anti-epidermal growth factor receptor (EGFR)-based doublet regimens in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available.MethodsThis multicenter, retrospective study aimed at evaluating clinicians’ attitude, and the safety and effectiveness of post-induction strategies in consecutive patients affected by left-sided RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR as first-line regimen, who did not experience disease progression within 6 months from induction initiation, at 21 Italian and 1 Spanish Institutions. The measured clinical outcomes were: progression-free survival (PFS), overall survival (OS), adverse events, and objective response rate (ORR).ResultsAt the data cutoff, among 686 consecutive patients with left-sided RAS/BRAF wild-type mCRC treated with doublet plus anti-EGFR as first-line regimen from March 2012 to October 2020, 355 eligible patients have been included in the present analysis. Among these, 118 (33.2%), 66 (18.6%), and 11 (3.1%) received a maintenance with 5-fluorouracil/leucovorin (5FU/LV)+anti-EGFR, anti-EGFR, and 5FU/LV, respectively, while 160 (45.1%) patients continued induction treatment (non-maintenance) until disease progression, unacceptable toxicity, patient decision, or completion of planned treatment. The median period of follow-up for the overall population was 33.7 months (95%CI = 28.9–35.6). The median PFS values of the 5FU/LV+anti-EGFR, anti-EGFR, 5FU/LV, and non-maintenance cohorts were 16.0 (95%CI = 14.3–17.7, 86 events), 13.0 (95%CI = 11.4–14.5, 56 events), 14.0 (95%CI = 8.1–20.0, 8 events), and 10.1 months (95%CI = 9.0–11.2, 136 events), respectively (p < 0.001). The median OS values were 39.6 (95%CI = 31.5–47.7, 43 events), 36.1 (95%CI = 31.6–40.7, 36 events), 39.5 (95%CI = 28.2–50.8, 4 events), and 25.1 months (95%CI = 22.6–27.6, 99 events), respectively (p < 0.001). After adjusting for key covariates, a statistically significant improvement in PFS in favor of 5FU/LV+anti-EGFR (HR = 0.59, 95%CI = 0.44–0.77, p < 0.001) and anti-EGFR (HR = 0.71, 95%CI = 0.51–0.98, p = 0.039) compared to the non-maintenance cohort was found. Compared to the non-maintenance cohort, OS was improved by 5FU/LV+anti-EGFR (HR = 0.55, 95%CI = 0.38–0.81, p = 0.002) and, with marginal significance, by anti-EGFR (HR = 0.67, 95%CI = 0.51–0.98, p = 0.051). No difference was found in ORR. Any grade non-hematological and hematological events were generally higher in the non-maintenance compared to the maintenance cohorts.ConclusionAmong the treatment strategies following an anti-EGFR-based doublet first-line induction regimen in patients affected by left-sided RAS/BRAF wild-type mCRC treated in a “real-life” setting, 5FU/LV+anti-EGFR resulted the most adopted, effective, and relatively safe regimen.
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- 2021
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11. DNA fragmentation in two cytometric sperm populations: relationship with clinical and ultrasound characteristics of the male genital tract
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Francesco Lotti, Lara Tamburrino, Sara Marchiani, Elisa Maseroli, Pasquale Vitale, Gianni Forti, Monica Muratori, Mario Maggi, and Elisabetta Baldi
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color-Doppler ultrasonography ,DNA fragmentation ,male infertility ,male sex organs ,spermatozoa ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
We investigated whether DNA fragmentation in two cytometric sperm populations (PIdimmer and PIbrighter) with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound (CDUS) parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms (with the National Institutes of Health-Chronic Prostatitis Symptom Index) and sperm DNA fragmentation (sDF) in PIdimmer and PIbrighter populations (using TUNEL/PI method coupled with flow cytometry). Data were adjusted for age (Model 1) along with waistline, testosterone levels, smoking habit, and sexual abstinence (Model 2). According to the statistical Model 2, PIdimmer sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume (r = −0.21 and r = −0.20, respectively; P < 0.05), higher FSH levels (r = 0.34, P < 0.0001) and occurrence of testicular inhomogeneity (P < 0.05) and hypoechogenicity (P < 0.05). PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia (all P < 0.05), and higher arterial peak systolic velocity (r = 0.25, P < 0.05). Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.
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- 2017
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12. Atypical haemolytic-uraemic syndrome in patient with metastatic colorectal cancer treated with fluorouracil and oxaliplatin: a case report and a review of literature
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Fortunato Ciardiello, Erika Martinelli, Teresa Troiani, Morena Fasano, Nicoletta Zanaletti, Maria Giovanna Ferrara, Antonello Sica, Umberto Falcone, Salvatore Guastafierro, Umberto Bracale, Dario Ribero, Stefania Napolitano, Pasquale Vitale, Vincenzo De Falco, Emilio Francesco Giunta, and Davide Ciardiello
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background. Thrombotic microangiopathies (TMA) are relatively rare but severe disorders characterised by non-immune haemolytic anaemia, thrombocytopaenia and organ failure. In patients with metastatic cancer, sporadic forms of TMA can be triggered by chemotherapeutic agents or can occur as complication of malignancy itself or of infections.Case report. Hereby, we report a case of a patient diagnosed with metastatic colorectal cancer who experienced an atypical haemolytic-uraemic syndrome (aHUS) during chemotherapy treatment with FOLFOX6 scheme. The use of eculizumab led to prompt recovery of laboratory parameters that was maintained despite treatment discontinuation due to appearance of pneumonia infectious. Additionally, genetic analyses revealed the presence in heterozygosis of CFH gene polymorphisms associated with aHUS.Conclusion. This case emphasises the importance of considering TMA as a possible diagnosis in patients with cancer presenting with haemolytic non-immune mediate anaemia and thrombocytopaenia associated with worsening of renal function. Prompt diagnosis is crucial for the requirement of its specific treatment that can impact on long-term outcome and prognosis.
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- 2019
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13. Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas
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Stefania Crisci, Raffaele Di Francia, Sara Mele, Pasquale Vitale, Giuseppina Ronga, Rosaria De Filippi, Massimiliano Berretta, Paola Rossi, and Antonio Pinto
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anticancer mAbs ,tyrosine kinase inhibitors ,tailored therapy ,personalized medicine ,NHL ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.
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- 2019
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14. Development of a Morphing Landing Gear Composite Door for High Speed Compound Rotorcraft
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Antonio Chiariello, Salvatore Orlando, Pasquale Vitale, Mauro Linari, Raffaele Longobardi, and Luigi Di Palma
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landing gear door ,morphing surface ,flushness ,composite ,Motor vehicles. Aeronautics. Astronautics ,TL1-4050 - Abstract
In the framework of fast rotorcraft, smoothness and flushness of external aerodynamic surfaces present challenges for high-speed conditions, where aerodynamics is the driver of helicopter performance. For AIRBUS-RACER helicopter the main landing gear trap doors are parts of the lower wing skins (in retracted configuration) affecting helicopter performance by minimizing the drag. Flushness requirements must not be in contrast with the functionally of the Landing gear system that must open and close the doors during the landing gear retraction-extension phases at moderately low velocity. To manage these goals, a novel design logic has been identified to support the trap doors development phase. The identified way to proceed needs of relevant numerical method and tool as well. This method is aimed at identifying the main landing gear composite compartment doors in pre-shaped configuration to match the smoothness and door-stopper engagements over each aerodynamic conditions. The authors propose a detailed non-linear Finite Element method, based on MSC Nastran (MSC Software, Newport Beach, US) SOL-400 solver in which the structure is modelled with deformable contact bodies in a multiple load step sequence, open door condition and pre-shaped, deformed under actuator pre-load, under flight load conditions. The method includes the entire pre-stressed field due to the preload and the actual door stiffness, considering the achieved large displacement to verify the most representative strain field during loads application. The paper defines a robust methodology to predict the deformation and ensure the most appropriate door “pre-bow” and pre-load, in order to achieve the desiderated structural shape that matches aerodynamic requirements. The main result is the identification of a pre-shaped doors configuration for the Airbus RACER Fast Rotorcraft.
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- 2020
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15. Evaluation of Second-Line Anti-VEGF after First-Line Anti-EGFR Based Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter 'SLAVE' Study
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Alessandro Parisi, Alessio Cortellini, Katia Cannita, Olga Venditti, Floriana Camarda, Maria Alessandra Calegari, Lisa Salvatore, Giampaolo Tortora, Daniele Rossini, Marco Maria Germani, Alessandra Boccaccino, Emanuela Dell’Aquila, Claudia Fulgenzi, Daniele Santini, Michele De Tursi, Nicola Tinari, Pietro Di Marino, Pasquale Lombardi, Susana Roselló Keränen, Marisol Huerta Álvaro, Ina Valeria Zurlo, Domenico Cristiano Corsi, Alessandra Emiliani, Nicoletta Zanaletti, Teresa Troiani, Pasquale Vitale, Riccardo Giampieri, Filippo Merloni, Mario Alberto Occhipinti, Paolo Marchetti, Michela Roberto, Federica Mazzuca, Michele Ghidini, Alice Indini, Ingrid Garajova, Federica Zoratto, Simona Delle Monache, Giampiero Porzio, and Corrado Ficorella
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RAS wild-type mCRC ,anti-angiogenics ,second-line treatment ,Aflibercept ,Bevacizumab ,Panitumumab ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. Methods: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. Results: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7–34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95–1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3–18.1) and 12.7 (95%CI: 8.8–17.5) months, respectively (HR= 1.31 (95%CI: 0.89–1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02–2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99–2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). Conclusion: Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.
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- 2020
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16. Clinical Practice Use of Liquid Biopsy to Identify RAS/BRAF Mutations in Patients with Metastatic Colorectal Cancer (mCRC): A Single Institution Experience
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Pietro Paolo Vitiello, Vincenzo De Falco, Emilio Francesco Giunta, Davide Ciardiello, Claudia Cardone, Pasquale Vitale, Nicoletta Zanaletti, Carola Borrelli, Luca Poliero, Marinella Terminiello, Gianluca Arrichiello, Vincenza Caputo, Vincenzo Famiglietti, Valentina Mattera Iacono, Francesca Marrone, Alessandra Di Liello, Giulia Martini, Stefania Napolitano, Michele Caraglia, Angela Lombardi, Renato Franco, Ferdinando De Vita, Floriana Morgillo, Teresa Troiani, Fortunato Ciardiello, and Erika Martinelli
- Subjects
colorectal cancer ,liquid biopsy ,ras testing ,anti-egfr ,acquired resistance ,clonal evolution ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla™ Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-naïve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-naïve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla™ Biocartis platform is feasible and reliable in mCRC patients in clinical practice.
- Published
- 2019
- Full Text
- View/download PDF
17. Overview of Current Targeted Anti-Cancer Drugs for Therapy in Onco-Hematology
- Author
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Stefania Crisci, Filomena Amitrano, Mariangela Saggese, Tommaso Muto, Sabrina Sarno, Sara Mele, Pasquale Vitale, Giuseppina Ronga, Massimiliano Berretta, and Raffaele Di Francia
- Subjects
anticancer mAbs ,Tyrosine kinase inhibitors ,tailored therapy ,personalized medicine ,pharmacogenomics ,Medicine (General) ,R5-920 - Abstract
The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells’ inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.
- Published
- 2019
- Full Text
- View/download PDF
18. The coagulopathy in sepsis: significance and implications for treatment
- Author
-
Berardino Pollio, Mauro Pagliarino, Carlo Scolfaro, Paola Saracco, Fabio Timeus, and Pasquale Vitale
- Subjects
Sepsis, disseminated activated coagulation, coagulopathy, treatment ,Medicine ,Pediatrics ,RJ1-570 - Abstract
Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC). There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.
- Published
- 2011
- Full Text
- View/download PDF
19. Development of a Morphing Landing Gear Composite Door for High Speed Compound Rotorcraft
- Author
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Mauro Linari, Raffaele Longobardi, Luigi Di Palma, Salvatore Orlando, A. Chiariello, and Pasquale Vitale
- Subjects
020301 aerospace & aeronautics ,Computer science ,lcsh:Motor vehicles. Aeronautics. Astronautics ,Aerospace Engineering ,Mechanical engineering ,flushness ,02 engineering and technology ,Aerodynamics ,Solver ,01 natural sciences ,Finite element method ,landing gear door ,010305 fluids & plasmas ,Morphing ,0203 mechanical engineering ,Drag ,0103 physical sciences ,11. Sustainability ,Doors ,morphing surface ,composite ,lcsh:TL1-4050 ,Actuator ,Landing gear - Abstract
In the framework of fast rotorcraft, smoothness and flushness of external aerodynamic surfaces present challenges for high-speed conditions, where aerodynamics is the driver of helicopter performance. For AIRBUS-RACER helicopter the main landing gear trap doors are parts of the lower wing skins (in retracted configuration) affecting helicopter performance by minimizing the drag. Flushness requirements must not be in contrast with the functionally of the Landing gear system that must open and close the doors during the landing gear retraction-extension phases at moderately low velocity. To manage these goals, a novel design logic has been identified to support the trap doors development phase. The identified way to proceed needs of relevant numerical method and tool as well. This method is aimed at identifying the main landing gear composite compartment doors in pre-shaped configuration to match the smoothness and door-stopper engagements over each aerodynamic conditions. The authors propose a detailed non-linear Finite Element method, based on MSC Nastran (MSC Software, Newport Beach, US) SOL-400 solver in which the structure is modelled with deformable contact bodies in a multiple load step sequence, open door condition and pre-shaped, deformed under actuator pre-load, under flight load conditions. The method includes the entire pre-stressed field due to the preload and the actual door stiffness, considering the achieved large displacement to verify the most representative strain field during loads application. The paper defines a robust methodology to predict the deformation and ensure the most appropriate door &ldquo, pre-bow&rdquo, and pre-load, in order to achieve the desiderated structural shape that matches aerodynamic requirements. The main result is the identification of a pre-shaped doors configuration for the Airbus RACER Fast Rotorcraft.
- Published
- 2020
20. Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas
- Author
-
Pasquale Vitale, Sara Mele, Raffaele Di Francia, Antonio Pinto, Giuseppina Ronga, Stefania Crisci, Paola Rossi, Massimiliano Berretta, Rosaria De Filippi, Crisci, S., Francia, R. D., Mele, S., Vitale, P., Ronga, G., De Filippi, R., Berretta, M., Rossi, P., and Pinto, A.
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Mini Review ,medicine.medical_treatment ,Monoclonal antibody ,lcsh:RC254-282 ,NHL ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Anticancer mAb ,Internal medicine ,tyrosine kinase inhibitors ,medicine ,Tumor microenvironment ,Hematology ,Anticancer mAbs ,Personalized medicine ,Tailored therapy ,Tyrosine kinase inhibitors ,business.industry ,anticancer mAbs ,personalized medicine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Chimeric antigen receptor ,Lymphoma ,Clinical trial ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,tailored therapy ,business - Abstract
The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.
- Published
- 2019
21. Overview of current targeted anti-cancer drugs for therapy in onco-hematology
- Author
-
Raffaele Di Francia, Pasquale Vitale, Sabrina Sarno, Massimiliano Berretta, Sara Mele, Tommaso Muto, Mariangela Saggese, Stefania Crisci, Giuseppina Ronga, and Filomena Amitrano
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Review ,Bioinformatics ,Targeted therapy ,Therapeutic approach ,Antineoplastic Agents, Immunological ,Internal medicine ,medicine ,Humans ,Tailored therapy ,RNA, Small Interfering ,Tyrosine kinase inhibitors ,lcsh:R5-920 ,Hematology ,business.industry ,Cancer ,General Medicine ,medicine.disease ,Personalized medicine ,Clinical trial ,MicroRNAs ,Oncolytic Viruses ,Review Literature as Topic ,Pharmacogenomics ,Anticancer mAbs ,lcsh:Medicine (General) ,business ,Pharmacogenetics ,Targeted Gene Repair - Abstract
The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells’ inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.
- Published
- 2019
22. DNA fragmentation in two cytometric sperm populations: relationship with clinical and ultrasound characteristics of the male genital tract
- Author
-
Mario Maggi, Lara Tamburrino, Sara Marchiani, Gianni Forti, Monica Muratori, Francesco Lotti, Elisa Maseroli, Pasquale Vitale, and Elisabetta Baldi
- Subjects
0301 basic medicine ,Adult ,Male ,Aging ,Urology ,Prostatitis ,DNA fragmentation ,color-Doppler ultrasonography ,Biology ,Genitalia, Male ,lcsh:RC870-923 ,male sex organs ,male infertility ,Male infertility ,Andrology ,03 medical and health sciences ,Semen quality ,Young Adult ,0302 clinical medicine ,Semen ,medicine ,Humans ,spermatozoa ,Clinical significance ,Sex organ ,Testosterone ,Ultrasonography, Doppler, Color ,Infertility, Male ,Sexual Abstinence ,spermatozoa, Sperm DNA fragmentation, Male genital tract, ultrasound ,030219 obstetrics & reproductive medicine ,Smoking ,General Medicine ,Middle Aged ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Sperm ,Spermatozoa ,030104 developmental biology ,Original Article ,Follicle Stimulating Hormone - Abstract
We investigated whether DNA fragmentation in two cytometric sperm populations (PIdimmer and PIbrighter) with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound (CDUS) parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms (with the National Institutes of Health-Chronic Prostatitis Symptom Index) and sperm DNA fragmentation (sDF) in PIdimmer and PIbrighter populations (using TUNEL/PI method coupled with flow cytometry). Data were adjusted for age (Model 1) along with waistline, testosterone levels, smoking habit, and sexual abstinence (Model 2). According to the statistical Model 2, PIdimmer sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume (r = −0.21 and r = −0.20, respectively; P < 0.05), higher FSH levels (r = 0.34, P < 0.0001) and occurrence of testicular inhomogeneity (P < 0.05) and hypoechogenicity (P < 0.05). PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia (all P < 0.05), and higher arterial peak systolic velocity (r = 0.25, P < 0.05). Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.
- Published
- 2016
23. Drug importation into Italy by body packing: An analysis of the UNODC Individual Drug Seizures Database
- Author
-
Simone Cappelletti, Francesco Lombardo, Giuseppe Vallone, Pasquale Vitale, Costantino Ciallella, and Alessandro Iaria
- Subjects
Drug ,Databases, Factual ,media_common.quotation_subject ,education ,030508 substance abuse ,Poison control ,Body Packers ,body packing ,body packers ,cocaine traffic ,drug traffic ,drug trafficking ,heroin traffic ,Suicide prevention ,Occupational safety and health ,03 medical and health sciences ,0302 clinical medicine ,Injury prevention ,medicine ,Humans ,030212 general & internal medicine ,Drug Trafficking ,media_common ,Body Packing ,business.industry ,Illicit Drugs ,Human factors and ergonomics ,General Medicine ,medicine.disease ,Italy ,Medical emergency ,0305 other medical science ,business ,human activities - Abstract
Internal concealment and transportation of illegal substances by body packing is a major business with very high profits, attracting criminals all over the world. As body packers are rarely arrested, it is difficult to quantify their proportion in the general population and, consequently, identify the countries involved in this kind of drug traffic; as a consequence, the percentage of undetected cases is undoubtedly high. The aim of this study is to provide useful information concerning the country of origin of body packers travelling to Italy through the analysis of the United Nations Office on Drugs and Crime Individual Drug Seizures Report database in the period 2010–2015. Results of our study highlighted a total of 85 cases, producing a total of 52.4 kg of drugs transported through body packing towards Italy. Data obtained from our analysis could represent an useful starting point to: (a) enhance police controls on people coming from targeted countries and improve collaborations between Italian Police Forces and those of other countries; (b) understand the reason why some cities/airports are so frequently used in drug trafficking through body packing and, as a consequence, enhance police controls in these places; and (c) train airport security staffs in international airports recognized as important departure points for body packers travelling to Italy.
- Published
- 2018
24. Heroin-piracetam mixture: Suggested mechanisms of action and risks of misinterpretation for drug users
- Author
-
Francesco Lombardo, Simone Cappelletti, Pasquale Vitale, Giuseppe Vallone, and Costantino Ciallella
- Subjects
0301 basic medicine ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Drug trafficking ,Heroin ,Toxicology ,Drug Users ,03 medical and health sciences ,0302 clinical medicine ,piracetam ,heroin ,withdrawal ,body packer ,body packing ,forensic toxicology ,medicine ,Humans ,Heroin adulterant ,Psychiatry ,media_common ,Adulterant ,business.industry ,Forensic toxicology ,Piracetam ,General Medicine ,Drug Combinations ,030104 developmental biology ,Action (philosophy) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Piracetam is a positive allosteric modulator of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor that has been frequently used in the treatment of cognitive disorders. Press and internet reports indicate that the use of piracetam, as a heroin adulterant, has spread rapidly in some countries, especially in Asia and Europe. Its use, as adulterant, is believed to produce more profound desirable effects, while decreasing hangover. Recent surveys demonstrated that piracetam protects neurons from heroin-induced apoptosis. The protective role of this adulterating substance may be related to restoration of beta-endorphin levels and to its neuroprotective effects. The aim of this paper is to review the relevant literature and suggest the main hypothetical mechanisms that justify its use as a heroin adulterant, try to understand if its use could help people who want to come off heroin by reducing withdrawal symptoms and, finally, give useful information that permit us to understand why drug trafficking organisations started to use piracetam as heroin adulterant.
- Published
- 2017
25. ENETS Newsletter Winter 2014
- Author
-
Ylenia Perone, Elizabeth K. Nousen, Gabriella Deli, Sámuel Komoly, Pasquale Vitale, Werner Druck Medien Ag, Alain Caraty, Clive W. Coen, Claudia Pivonello, Renata S. Auriemma, Volker Fendrich, Carla Giordano, Luciana Granieri, Zsolt Liposits, Zsuzsanna Bardóczi, Edit Bosnyák, Erik Hrabovszky, Anett Szilvásy-Szabó, Maurizio Gasperi, Peter H. Kann, Fruzsina Rabi, Asli Silahtaroglu, Imre Kalló, Mariano Galdiero, Juliana G. Franco, Gergely Feher, Jens D. Mikkelsen, Barbara Vida, Chiara Simeoli, Annamaria Colao, Max B. Albers, Mariarosaria Negri, Jens Waldmann, Silke Herzer, Richard Knoop, Imre Farkas, Gabriella Pusch, Björn Meister, Satz Mengensatzproduktion, Detlef K. Bartsch, Rosario Pivonello, Elinor L. Sullivan, Tamas F. Molnar, and Teresa Mannarino
- Subjects
Gerontology ,Cellular and Molecular Neuroscience ,medicine.medical_specialty ,Endocrinology ,Endocrine and Autonomic Systems ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,medicine ,Psychology - Published
- 2013
26. Daily practice of mechanical ventilation in Italian pediatric intensive care units: A prospective survey*
- Author
-
Andrea Wolfler, Md, Edoardo Calderoni, Md, Giancarlo Ottonello, Md, Giorgio Conti, Md, Simonetta Baroncini, Md, Pierantonio Santuz, Md, Pasquale Vitale, Md, Ida Salvo, Md, on behalf of the SISPE Study Group, Papoff, Paola, and Moretti, Corrado
- Subjects
Mechanical ventilation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,MEDLINE ,Critical Care and Intensive Care Medicine ,Intensive care ,Daily practice ,Critical care nursing ,Pediatrics, Perinatology and Child Health ,Emergency medicine ,medicine ,Intubation ,Observational study ,Intensive care medicine ,Prospective cohort study ,business - Abstract
Objectives:To assess how children requiring endotracheal intubation are mechanically ventilated in Italian pediatric intensive care units (PICUs).Design:A prospective, national, observational, multicenter, 6-month study.Setting:Eighteen medical-surgical PICUs.Patients:A total of 1943 consecutive chi
- Published
- 2011
27. Surveillance Study of Healthcare-Associated Infections in a Pediatric Neurosurgery Unit in Italy
- Author
-
Pier Paolo Gaglini, Paola Ragazzi, Carmelina Calitri, Paola Dalmasso, Alessandra Conio, Michele Pinon, Pier-Angelo Tovo, Pier Federico Pretti, Paola Peretta, Irene Raffaldi, Carlo Scolfaro, Pasquale Vitale, and Silvia Garazzino
- Subjects
Male ,Healthcare associated infections ,medicine.medical_specialty ,animal structures ,Surveillance study ,Adolescent ,Pediatric neurosurgery ,Neurosurgery ,MEDLINE ,Healthcare-associated infections ,Pediatrics ,Unit (housing) ,Children ,Devices ,Surveillance ,Risk Factors ,Gram-Negative Bacteria ,medicine ,Humans ,Prospective Studies ,Child ,Prospective cohort study ,Intensive care medicine ,Cross Infection ,business.industry ,Incidence ,Incidence (epidemiology) ,Infant, Newborn ,Infant ,virus diseases ,General Medicine ,Length of Stay ,Hospitals ,Italy ,Catheter-Related Infections ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Surgery ,Neurology (clinical) ,Gram-Negative Bacterial Infections ,business - Abstract
Background: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit. Methods: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0–18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs. Results: The study included 260 patients, with a mean age of 4.3 ± 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs. Conclusion: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management.
- Published
- 2011
28. Complete disappearance of a GH-secreting pituitary macroadenoma in a patient with acromegaly: effect of treatment with lanreotide Autogel and consequence of treatment withdrawal
- Author
-
Alessia Cozzolino, Mariano Galdiero, Rosario Pivonello, Ludovica F S Grasso, Annamaria Colao, Renata S. Auriemma, Gaetano Lombardi, Pasquale Vitale, Auriemma, RENATA SIMONA, Galdiero, Mariano, Grasso, LUDOVICA FRANCESCA STELLA, Vitale, Pasquale, Cozzolino, Alessia, Lombardi, Gaetano, Colao, Annamaria, and Pivonello, Rosario
- Subjects
Adenoma ,medicine.medical_specialty ,Pituitary macroadenoma ,Endocrinology, Diabetes and Metabolism ,Treatment withdrawal ,Lanreotide ,Peptides, Cyclic ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Acromegaly ,Humans ,Medicine ,Pituitary Neoplasms ,acromegaly ,lanreotide autogel ,business.industry ,Remission Induction ,Pituitary tumors ,General Medicine ,Middle Aged ,medicine.disease ,Discontinuation ,Somatostatin ,chemistry ,Female ,GH-secerning pituitary macroadenoma ,business ,Hormone - Abstract
BackgroundSomatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumor in patients treated with SA as long-acting formulations have been reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1 at least in a small subset of patients well responsive to SA, although it is generally followed by disease recurrence after several months.Case reportA 61-year-old female patient bearing a very large GH-secreting pituitary macroadenoma was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120 mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong the administration interval from 28 to 56 days. After 6 months of treatment, a significant tumor shrinkage (90% of baseline size) was observed, whereas GH and IGF1 excess was still well controlled. After 12-month therapy, a complete disappearance of the pituitary tumor was observed, and the hormonal evaluation confirmed the complete biochemical remission of acromegaly. Lanreotide ATG treatment was withdrawn. The clinical, biochemical, and radiological remission of acromegaly was maintained 24 months after lanreotide ATG treatment discontinuation, without evidence of disease recurrence.ConclusionsThis report represents an exemplary case of the potentiality of treatment with lanreotide ATG in inducing a complete remission of acromegalic disease, persistent after a long period of time from treatment withdrawal.
- Published
- 2010
29. Pathophysiology of Diabetes Mellitus in Cushing’s Syndrome
- Author
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Annamaria Colao, Gaetano Lombardi, Maria Cristina De Martino, Alessia Cozzolino, Monica De Leo, Pasquale Vitale, Rosario Pivonello, Chiara Simeoli, Pivonello, Rosario, DE LEO, Monica, Vitale, Pasquale, Cozzolino, Alessia, Simeoli, C., DE MARTINO, MARIA CRISTINA, Lombardi, Gaetano, and Colao, Annamaria
- Subjects
Diabetes mellitu ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Impaired glucose tolerance ,Cellular and Molecular Neuroscience ,Cushing syndrome ,Cushing's disease ,diabetes mellitus ,glucose intolerance ,Endocrinology ,Insulin resistance ,Insulin-Secreting Cells ,Diabetes mellitus ,Internal medicine ,Insulin Secretion ,Diabetes Mellitus ,medicine ,Humans ,Insulin ,Cushing Syndrome ,Endocrine and Autonomic Systems ,Insulin receptor signaling pathway ,business.industry ,medicine.disease ,Glucose ,Insulin Resistance ,Metabolic syndrome ,business ,Cushing - Abstract
Cushing’s syndrome is commonly complicated with an impairment of glucose metabolism, which is often clinically manifested as diabetes mellitus. The development of diabetes mellitus in Cushing’s syndrome is both a direct and indirect consequence of glucocorticoid excess. Indeed, glucocorticoid excess induces a stimulation of gluconeogenesis in the liver as well as an inhibition of insulin sensitivity both in the liver and in the skeletal muscles, which represent the most important sites responsible for glucose metabolism. In particular, glucocorticoid excess stimulates the expression of several key enzymes involved in the process of gluconeogenesis, with a consequent increase of glucose production, and induces an impairment of insulin sensitivity either directly by interfering with the insulin receptor signaling pathway or indirectly, through the stimulation of lipolysis and proteolysis and the consequent increase of fatty acids and amino acids, which contribute to the development of insulin resistance. Moreover, the peculiar distribution of adipose tissue throughout the body, with the predominance of visceral adipose tissue, significantly contributes to the worsening of insulin resistance and the development of a metabolic syndrome, which participates in the occurrence and maintenance of the impairment of glucose tolerance. Finally, glucocorticoid excess is able to impair insulin secretion as well as act at the level of the pancreatic beta cells, where it inhibits different steps of the insulin secretion process. This phenomenon is probably responsible for the passage from an impairment of glucose tolerance to an overt diabetes mellitus in susceptible patients with Cushing’s syndrome.
- Published
- 2010
30. A long-term continuous infusion via a sciatic catheter in a 3-year-old boy
- Author
-
Giorgio Ivani, Ferdinando Gagliardi, Valeria Mossetti, Pasquale Vitale, Luigi Codipietro, and Franca Rosso
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Analgesic ,Clonidine ,law.invention ,Catheters, Indwelling ,law ,medicine ,Humans ,Ropivacaine ,Anesthetics, Local ,Infusion Pumps ,Pain Measurement ,Analgesics ,Pain, Postoperative ,Foot ,business.industry ,Local anesthetic ,Nerve Block ,Amides ,Long-Term Care ,Sciatic Nerve ,Intensive care unit ,Surgery ,Catheter ,Anesthesiology and Pain Medicine ,Amputation ,Child, Preschool ,Anesthesia ,Pediatrics, Perinatology and Child Health ,Sciatic nerve ,business ,medicine.drug - Abstract
Summary We describe the case of a 3-year-old boy with a subtotal amputation of the right foot who received treatment for pain via a peripheral catheter positioned at the level of the sciatic nerve (lateral approach).We administered a continuous infusion of 0.2% ropivacaine, 0.4 mg·kg−1·h−1 plus clonidine 0.12 μg·kg−1·h−1 for 21 days. Pain relief was complete and the patient did not require any further rescue analgesia throughout the period even during medications and surgical treatment in our intensive care unit. We discuss the safety and efficacy of the use of a peripheral continuous infusion in children compared with other techniques of analgesia.
- Published
- 2003
31. Comparison of Racemic Bupivacaine, Ropivacaine, And Levo-Bupivacaine for Pediatric Caudal Anesthesia
- Author
-
Alessandra Conio, Giorgio Ivani, Pasquale Vitale, Ferdinando Gagliardi, Claudia Vercellino, Per-Arne Lönnqvist, Pasquale DeNegri, Staffan Eksborg, and Roberto Grossetti
- Subjects
Male ,medicine.medical_specialty ,Analgesic ,Sevoflurane ,law.invention ,Motor block ,Racemic bupivacaine ,Randomized controlled trial ,law ,medicine ,Humans ,Ropivacaine ,Prospective Studies ,Anesthetics, Local ,Prospective cohort study ,Bupivacaine ,Pain, Postoperative ,business.industry ,Infant ,Stereoisomerism ,General Medicine ,Amides ,Surgery ,Anesthesiology and Pain Medicine ,Child, Preschool ,Anesthesia ,Female ,business ,Anesthesia, Caudal ,medicine.drug - Abstract
Background and Objectives To compare ropivacaine, levo-bupivacaine, and racemic bupivacaine for caudal blockade in children. Methods Using a prospective observer blinded design, 60 sevoflurane anesthetized children (1 to 7 years) undergoing minor subumbilical surgery, were randomized to receive a caudal block (1 mL/kg) with either ropivacaine 0.2%, racemic bupivacaine 0.25%, or levo-bupivacaine 0.25%. Postoperative analgesia (number of patients needing supplemental analgesia as defined by an objective pain score [OPS] score of ≥ 5; time to first analgesic demand) during the first 24 postoperative hours was chosen as the primary end-point. Early postoperative motor block (3-point scale) was assessed as a secondary end-point. Results All blocks were judged to be clinically successful based on the presence of adequate intraoperative and early postoperative analgesia. An OPS score ≥ 5 was found in 5/20 patients in each study group. No difference regarding the time to first analgesic demand was found between the study groups. The use of ropivacaine (P = .02), but not levo-bupivacaine (P = .18), was found to be associated with less motor block during the first postoperative hour compared with racemic bupivacaine. Conclusion All 3 investigated local anesthetics were found to be clinically comparable despite the slight reduction of early postoperative motor block associated with the use of ropivacaine.
- Published
- 2002
32. Effect of chronic cabergoline treatment and testosterone replacement on metabolism in male patients with prolactinomas
- Author
-
Ciro Salzano, Mariano Galdiero, Rosario Pivonello, Claudia Pivonello, Renata S. Auriemma, Cristina de Angelis, Luciana Granieri, Federica Cariati, Lucia Ferreri, Annamaria Colao, Pasquale Vitale, Fabio Lo Calzo, and Giorgio Coppola
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cabergoline ,Hormone Replacement Therapy ,Endocrinology, Diabetes and Metabolism ,Cellular and Molecular Neuroscience ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,Hormone replacement therapy (male-to-female) ,Humans ,Pituitary Neoplasms ,Prolactinoma ,Testosterone ,Testosterone replacement ,Ergolines ,Endocrine and Autonomic Systems ,business.industry ,Pituitary tumors ,Metabolism ,Middle Aged ,medicine.disease ,Prolactin ,Hyperprolactinemia ,Dopamine Agonists ,Metabolome ,Metabolic syndrome ,business ,medicine.drug - Abstract
Introduction: Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients. Patients and Methods: Thirty-two men with prolactinomas, including 22 with total testosterone (TT) 8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment. Results: Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI₀), homeostatic model assessment of insulin secretion (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-β. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI₀, HOMA-β and HOMA-IR significantly improved compared to baseline, with FI, ISI₀, HOMA-β and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC. Conclusions: In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB.
- Published
- 2014
33. Contents Vol. 98, 2013
- Author
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Sámuel Komoly, Ylenia Perone, Jens Waldmann, Satz Mengensatzproduktion, Elizabeth K. Nousen, Pasquale Vitale, Barbara Vida, Alain Caraty, Mariarosaria Negri, Chiara Simeoli, Maurizio Gasperi, Tamas F. Molnar, Carla Giordano, Asli Silahtaroglu, Mariano Galdiero, Max B. Albers, Detlef K. Bartsch, Rosario Pivonello, Claudia Pivonello, Renata S. Auriemma, Imre Kalló, Juliana G. Franco, Teresa Mannarino, Zsuzsanna Bardóczi, Erik Hrabovszky, Clive W. Coen, Gabriella Deli, Fruzsina Rabi, Imre Farkas, Björn Meister, Anett Szilvásy-Szabó, Werner Druck Medien Ag, Annamaria Colao, Volker Fendrich, Zsolt Liposits, Gergely Feher, Peter H. Kann, Jens D. Mikkelsen, Edit Bosnyák, Silke Herzer, Richard Knoop, Elinor L. Sullivan, Gabriella Pusch, and Luciana Granieri
- Subjects
Cellular and Molecular Neuroscience ,medicine.medical_specialty ,Endocrinology ,Traditional medicine ,Endocrine and Autonomic Systems ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,medicine ,business - Published
- 2014
34. Effect of Cabergoline on Metabolism in Prolactinomas
- Author
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Rosario Pivonello, Maurizio Gasperi, Mariarosaria Negri, Pasquale Vitale, Carla Giordano, Ylenia Perone, Teresa Mannarino, Claudia Pivonello, Renata S. Auriemma, Annamaria Colao, Luciana Granieri, Chiara Simeoli, Mariano Galdiero, Auriemma, RENATA SIMONA, Granieri, Luciana, Galdiero, Mariano, Simeoli, Chiara, Perone, Y, Vitale, Pasquale, Pivonello, Claudia, Negri, M, Mannarino, T, Giordano, C, Gasperi, M, Colao, Annamaria, Pivonello, Rosario, Auriemma, RS, Granieri, L, Galdiero, M, Simeoli, C, Vitale, P, Pivonello, C, Colao, A, and Pivonello, R
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Treatment outcome ,prolactinomas ,Antineoplastic Agents ,Settore MED/13 - Endocrinologia ,Pathogenesis ,Cellular and Molecular Neuroscience ,Endocrinology ,Insulin resistance ,Metabolic Diseases ,Cabergoline ,Internal medicine ,Prevalence ,Medicine ,Humans ,Insulin ,Pituitary Neoplasms ,Prospective Studies ,Ergolines ,Adiposity ,Metabolic Syndrome ,Dose-Response Relationship, Drug ,Endocrine and Autonomic Systems ,business.industry ,Pituitary tumors ,Metabolism ,Fasting ,medicine.disease ,Prognosis ,Prolactin ,Hyperprolactinemia ,Treatment Outcome ,prolactinoma ,cabergoline ,Female ,Metabolic syndrome ,Insulin Resistance ,business ,metabolism ,medicine.drug - Abstract
Introduction: Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. Patients and Methods: 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Results: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). Conclusions: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.
- Published
- 2014
35. Role of reversal of hypogonadism on the improvement of metabolic syndrome in male patients with hyperprolactinemia during chronic treatment with cabergoline
- Author
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Ciro Salzano, Annamaria Colao, Rosario Pivonello, Federica Cariati, Pasquale Vitale, Mariano Galdiero, Ylenia Perone, Fabio Lo Calzo, Claudia Pivonello, and Renata S. Auriemma
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Male patient ,Internal medicine ,Cabergoline ,Medicine ,Metabolic syndrome ,business ,medicine.disease ,medicine.drug - Published
- 2013
36. Effect of short- and long-term treatment with pasireotide on hemochrome in patients with Cushing's disease
- Author
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Davide Iacuaniello, Annamaria Colao, Laura Trementino, Giorgio Arnaldi, Chiara Simeoli, Alessia Cozzolino, Leo Monica De, Marco Boscaro, Aurora Albano, Rosario Pivonello, and Pasquale Vitale
- Subjects
Pediatrics ,medicine.medical_specialty ,chemistry.chemical_compound ,Long term treatment ,chemistry ,business.industry ,medicine ,In patient ,Cushing's disease ,medicine.disease ,business ,Pasireotide - Published
- 2013
37. The coagulopathy in sepsis: significance and implications for treatment
- Author
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Pasquale Vitale, Fabio Timeus, Paola Saracco, Carlo Scolfaro, Mauro Pagliarino, and Berardino Pollio
- Subjects
medicine.medical_specialty ,Pathology ,lcsh:Medicine ,Review ,Pediatrics ,Gastroenterology ,Fibrin ,treatment ,Sepsis, disseminated activated coagulation, coagulopathy, treatment ,coagulopathy ,Sepsis ,sepsis ,Tissue factor ,Internal medicine ,medicine ,Coagulopathy ,Disseminated intravascular coagulation ,biology ,business.industry ,lcsh:R ,Antithrombin ,lcsh:RJ1-570 ,lcsh:Pediatrics ,medicine.disease ,Coagulation ,biology.protein ,business ,Protein C ,medicine.drug ,disseminated activated coagulation - Abstract
Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC). There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.
- Published
- 2011
38. Diabetes and Cancer
- Author
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Annamaria Colao, Pasquale Vitale, Antongiulio Faggiano, Colao, Annamaria, Vitale, Pasquale, and Faggiano, Antongiulio
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Endocrinology, Diabetes and Metabolism ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Metastasis ,Insulin resistance ,Endocrinology ,Diabetes mellitus ,Pancreatic cancer ,Internal medicine ,medicine ,Hyperinsulinemia ,Diabetes Mellitus ,Insulin ,Neoplastic transformation ,Cancer ,endocrinology ,diabetes ,metabolism ,cancer ,lcsh:RC648-665 ,business.industry ,General Commentary ,medicine.disease ,Hyperglycemia ,Insulin Resistance ,business - Abstract
The hypothesis that diabetes mellitus (DM) is associated with an increased risk of cancer is a deep-rooted suggestion, formulated probably during nineteenth century, surely very far away from knowledge of the pathogenic mechanisms of both diseases. Nowadays, numerous meta-analysis demonstrate the strong positive correlation existing between DM and site-specific cancer. In addition, patients developing cancer with pre-existing DM are reported to experience higher short- and long-term mortality. Anyway, the increased risk of cancer development in subjects with an alteration of glucose metabolism is not yet explained: this lack could be addressed to the overlapping risk factors of both diseases like physical inactivity and overalimentation or to the confounding factor represented by anti-diabetic treatments. The strongest association between DM and site-specific cancer regards liver and pancreatic cancer. Liver cells are exposed to high levels of insulin and, consequently, to its mitogenic effect due to portal circulation. However, this event occurs both in diabetic and non-diabetic subjects, so limiting the relevance of this mechanism to explain the high frequency of liver cancer in DM. On the other hand, diabetic patients are more prone to develop cirrhosis, steatosis, and non-alcoholic fatty liver disease (NAFLD) and these conditions are surely correlated to liver cancer. The relationship between DM and pancreatic cancer is very difficult to prove because it is arduous to establish which condition begins firstly between cancer or hyperglycemia (like the question of the chicken and the egg). However, lots of reported findings give support to consider DM as risk factor for pancreatic cancer; actually, deeper researches are necessary to clarify the mechanism and the implication of this intriguing connection. Another of the main site-specific cancer frequently associated with DM is breast cancer (BC), the most common cause of death due to cancer in European women. Around one in five women with BC is affected also by DM and probably their coexistence could be explained by similar risk factors like obesity, dyslipidemia, and hyperinsulinemia, although the mechanism underlying this articulated relation needs to be clarify. Several longitudinal and retrospective cohort studies demonstrate that the frequency of BC is significantly increased in postmenopausal women with DM; furthermore, they reveal that the prognosis of women with BC and DM is worse and overall mortality is higher in comparison with non-diabetic patients. An increase of the development of other organ cancers in correlation with DM is reported, although in some cases studies are not so numerous or well built. They include endometrial, colorectal, and bladder cancer in which the most recent evidence underline not only a raise in the prevalence in the cohort of patients with DM but also an increased mortality. As all the rules that must be respected, the positive correlation between DM and cancer has an exception represented by prostate cancer. In contrast with the other evidences, in fact, recent meta-analysis report a reduced frequency of prostate cancer in men affected by DM. Even though insulin can play a role also in the progression and the prognosis of this specific cancer, especially during the androgen deprivation therapy, diabetes-related hypogonadism seems to represent the pivotal determining of the decreased risk of developing this neoplasm. Focusing on the possible pathogenic mechanism that sustained this linkage, the metabolic disequilibrium that characterize a diabetic person contains various elements of interest able to explain several aspects of the increased risk of neoplasm or tumoral progression in these patients. These are represented by hyperglycemia, hyperinsulinemia and insulin resistance, obesity and chronic inflammation which are singularly or contemporary present in DM. By definition, cancer cells have a very sustained proliferation and need more glucose than other cells; DM and correlated hyperglycemia are optimal conditions for sustaining this metabolic change occurring in cancer cells, that, opportunely, increase the expression of glucose membrane transporters. This abnormal activation of glucose catabolism leads to an increased production of lactate that reduced ph of extracellular matrix, causing the death of non-tumoral cells and promoting the activation of matrix collagenases which make easier the development of metastasis. In addition, hyperglycemia cause the accumulation of advanced glycation end-products (AGEs) which are responsible for oncogenic DNA damaging through the production of reactive oxygen species (ROS). In non-type I DM, insulin levels are almost always elevated upon the upper range limit and it is associated with the intensification of its pro-proliferative effect. Several studies in literature confirm the mitogenic effect of insulin that could be considered as a peculiar growth factor; this peculiarity became stronger if we consider that insulin can activate non-only its proper receptor (IR), which results in anti-apoptotic activities, but also insulin-like growth factor 1 receptor (IGF-1R) whose pathway play an essential role in cell multiplication and immortalization. The importance of the function of insulin in the development of cancer in diabetic patients is confirmed by the significantly increased expression of IR and IGF-1R in tumoral cells. A significant percentage of patients affected by DM has a BMI compatible with the diagnosis of obesity. Apart from the induced hyperinsulinemia and insulin resistance, typical in these patients, peptide hormones secreted by adipose tissue can represent the keystones to explain the mechanism by which obesity favors cancer in diabetic patients. Adiponectin and leptin are in fact probably involved in regulating carcinogenesis; the first has an anti-inflammatory activity and stimulate the glucose metabolism, increasing the insulin sensitivity. Leptin, on the other hand, is been demonstrated having a pro-inflammatory effect which finally results in the stimulation of neoplastic transformation, cell proliferation, and neo-angiogenesis. The multiform relation between DM and cancer is far away to be definitively understood and all the studies of the next years will have to reckon with the complexity of both DM and neoplasms and consider the heterogeneity of the population involved. But, in the third millenium medicine, all the scientist are called to make an effort in order to give a solution to the emerging health questions of our society. This is the mission they are expected to accomplish. I am hopeful.
- Published
- 2011
39. The kidney in acromegaly: renal structure and function in patients with acromegaly during active disease and 1 year after disease remission
- Author
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Ludovica F S Grasso, Renata S. Auriemma, Annamaria Colao, Mariano Galdiero, Monica De Leo, Gaetano Lombardi, Rosario Pivonello, Alessia Cozzolino, Maria Cristina De Martino, Pasquale Vitale, Auriemma, RENATA SIMONA, Galdiero, Mariano, DE MARTINO, MARIA CRISTINA, DE LEO, Monica, Grasso, LUDOVICA FRANCESCA STELLA, Vitale, Pasquale, Cozzolino, Alessia, Lombardi, Gaetano, Colao, Annamaria, and Pivonello, Rosario
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Urinary system ,Renal function ,Endocrinology ,diabetes and metabolism ,endocrinology ,Kidney ,Citric Acid ,Internal medicine ,Acromegaly ,medicine ,Humans ,active disease ,Aged ,Body surface area ,business.industry ,Remission Induction ,Kidney metabolism ,General Medicine ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Cross-Sectional Studies ,Creatinine ,Microalbuminuria ,Female ,business ,Somatostatin ,Kidney disease - Abstract
BackgroundThe GH/insulin-like growth factor 1 axis is physiologically involved in the regulation of electrolytes and water homeostasis by kidneys, and influences glomerular filtration and tubular re-absorption processes. The aim of the study was to investigate renal structure and function in acromegalic patients during active disease and disease remission.PatientsThirty acromegalic patients (15 males and 15 females), aged 32–70 years, were enrolled for the study. Tende novopatients had active disease, whereas 20 patients showed disease remission 1 year after medical treatment with somatostatin analogs (SA) (ten patients) or surgery (ten patients). Thirty healthy subjects matched for age, gender, and body surface area were enrolled as controls.ResultsIn both active (A) and controlled (C) patients, creatinine clearance (PPPPPPPPPPPPr=0.871,Pr=0.639,PConclusionsThe results of the current study demonstrated that acromegaly affects both renal structure and function. The observed changes are not completely reversible after disease remission.
- Published
- 2010
40. Cardiovascular disease in Cushing's syndrome: heart versus vasculature
- Author
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Annamaria Colao, Chiara Simeoli, Monica De Leo, Maria Cristina De Martino, Rosario Pivonello, Pasquale Vitale, Gaetano Lombardi, Alessia Cozzolino, Renata S. Auriemma, DE LEO, Monica, Pivonello, Rosario, Auriemma, RENATA SIMONA, Cozzolino, Alessia, Vitale, Pasquale, Simeoli, C., DE MARTINO, MARIA CRISTINA, Lombardi, Gaetano, and Colao, Annamaria
- Subjects
Risk ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Cushing's syndrome ,Coronary artery disease ,Cellular and Molecular Neuroscience ,Endocrinology ,cardiovascular disease ,Internal medicine ,atherosclerosis ,medicine ,Humans ,Endothelial dysfunction ,Cushing Syndrome ,Framingham Risk Score ,Endocrine and Autonomic Systems ,business.industry ,Vascular disease ,Heart ,Cushing's disease ,medicine.disease ,vasculature ,Cushing ,Cardiovascular Diseases ,Heart failure ,Metabolic syndrome ,business ,Dyslipidemia - Abstract
Cushing’s syndrome (CS) causes metabolic abnormalities that determine an increased cardiovascular risk not only during the active phase of the disease but also for a long time after cure. Cardiovascular complications, such as premature atherosclerosis, coronary artery disease, heart failure, and stroke, in patients with CS cause a mortality rate higher than that observed in a normal population. The increased cardiovascular risk is mainly due to metabolic complications, such as metabolic syndrome, but also to vascular and cardiac alterations such as atherosclerosis and cardiac structural and functional changes. In the clinical management of patients with CS the focus should be on identifying the global cardiovascular risk and the aim should be to control not only hypertension but also other correlated risk factors, such as obesity, glucose intolerance, insulin resistance, dyslipidemia, endothelial dysfunction and the prothrombotic state. Considering that remission from hypercortisolism is often difficult to achieve and that the cardiovascular risk can persist even during disease remission, care and control of all cardiovascular risk factors should be one of the primary goals during the follow-up of these patients.
- Published
- 2010
41. Associazione tra varicocele, eiaculazione precoce e sintomi di prostatite: possibili meccanismi
- Author
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Francesco Lotti, S. Degli Innocenti, Annamaria Colao, Alessandra Sforza, Mario Maggi, Pasquale Vitale, Giuseppe Corona, Carlo Biagini, Gianni Forti, Csilla Krausz, Giovanni M. Colpi, M. Mancini, Mauro Gacci, Edoardo Mannucci, and E. Filimberti
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business - Published
- 2011
42. 1,000 consecutive blocks in a children's hospital: How to manage them safely
- Author
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Giuseppe Papurel, Alessandra Conio, Flavio Ciliberto, Giorgio Ivani, and Pasquale Vitale
- Subjects
business.industry ,Infant, Newborn ,Infant ,Nerve Block ,General Medicine ,medicine.disease ,Hospitals, Pediatric ,Pediatrics ,Anesthesiology and Pain Medicine ,Anesthesiology ,Child, Preschool ,Medicine ,Humans ,Medical emergency ,business ,Child - Published
- 2001
43. I livelli di prolattina predicono indipendentemente gli eventi cardiovascolari maggiori nei pazienti con disfunzione erettile
- Author
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Cecilia Melani, V. Boddi, Matteo Monami, Pasquale Vitale, Gianni Forti, E Mannucci, Rosario Pivonello, Daniela Balzi, Gaetano Lombardi, Giulia Rastrelli, Mario Maggi, Mariano Galdiero, Alessandra Sforza, and Giuseppe Corona
- Subjects
business.industry ,Medicine ,business ,Humanities - Abstract
Il ruolo fisiologico della prolattina (PRL) nell’uomo non e ancora completamente chiaro. Il gruppo di Autori del presente articolo ha gia dimostrato in passato che, nei soggetti ch e si sottopongon o a controlli per disfunzioni sessuali, bassi livelli di PRL sono associati ad alterati profili glicemici e lipidici, cosi come a piu alta prevalenza di sindrome metabolica e disfunzione erettile (DE) di origine vascolare. L’obiettivo di questo studio e quello di verificare la possibile associazione tra i livelli di PRL e l’incidenza degli eventi cardiovascolari maggiori (ECAM) nei soggetti con DE. A tale scopo sono stati arruolati 1.687 pazienti afferiti all’Unita Andrologica del Dipartimento di Fisiopatologia Clinica dell’Universita di Firenze per DE; ciascuno di essi e stato sottoposto a una valutazione ormonale completa basale e alla somministrazione dell’intervista strutturata sulla DE (SIEDY) costituita da 13 item (suddivisi in tre categorie: Scale 1, 2, 3 corrispondenti rispettivamente ai disordini organici, ai disturbi nella relazione con la partner primaria e alla descrizione del tratto psicologico del paziente) che individuano e quantificano le componenti che concorrono al le determinazione della DE. In aggiunta, ai pazienti e stato somministrato il Middlesex Hospital Questionnaire (MHQ) per valutare l’eventuale presenza di tratti di psicopatologia ansiosa; inoltre, e stata valutata l’interferenza sui livelli di PRL dei medicamenti eventualmente assunti.
- Published
- 2010
44. Subject Index Vol. 92, 2010
- Author
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Manuela Albertelli, Gloria Appolloni, Satz Mengensatzproduktion, Maria Grazia Redaelli, Valentina Piccini, Alberto Rebora, Alia Munir, Bernard Conte-Devolx, Wouter W. de Herder, Andrea Laurenzi, Miryam Talco, Anne-Sophie Thonnard, Maria Cristina De Martino, Leo J. Hofland, Elisa Borgogni, Gabriella Nesi, Piero Picozzi, Steven W. J. Lamberts, Philippe Chanson, Carla Scaroni, Viviana Daidone, Monica Mangoni, Michaela Luconi, Jens Otto Lunde Jørgensen, Yona Greenman, Renata S. Auriemma, Thierry Brue, Patrick Petrossians, Ann Mosegaard Bak, L.J. Hofland, Elena Nazzari, M.C. De Martino, Annamaria Colao, Elena Rapizzi, Richard A Feelders, Umberto Goglia, Diego Ferone, Daniela Esposito, Kristine Zøylner Rubeck, Pasquale Vitale, Marco Boscaro, Alberto M. Pereira, R.N. Clayton, Silvia Vandeva, Sabina Zacharieva, Ashley B. Grossman, Sven Schlaffer, Charlotte Steffensen, Alessia Cozzolino, Alberto M Pedroncelli, Tonino Ercolino, Chiara Simeoli, Adrian F. Daly, Giada Poli, Mara Boschetti, Krystallenia I Alexandraki, Marco Losa, Gregory Kaltsas, Sylvie Salenave, Marina Cardinaletti, P. M. van Koetsveld, Giorgio Arnaldi, Johannes A. Romijn, Federico Gatto, Alessandra Casonato, Massimo Mannelli, Gaetano Lombardi, Druck Reinhardt Druck Basel, Polyzois Makras, Letizia Canu, Franco Mantero, Maria Verena Cicala, John Newell-Price, Jitske Tiemensma, Marica Arvigo, Albert Beckers, Laura Trementino, Monica De Leo, Pietro Mortini, Valerio Mattia Scandali, Maria Yaneva, Frederic Castinetti, Giulia Cantini, R. Pivonello, Francesco Minuto, Michael Buchfelder, and Rosario Pivonello
- Subjects
Gerontology ,Cellular and Molecular Neuroscience ,Endocrinology ,Index (economics) ,Endocrine and Autonomic Systems ,Endocrinology, Diabetes and Metabolism ,Subject (documents) ,Psychology - Published
- 2010
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