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189 results on '"LAFFI"'

1. Coronavirus disease 2019 in patients with neuroendocrine neoplasms

Author

Mohamad Bassam Sonbol, Simona Grozinsky-Glasberg, Anna La Salvia, Manila Rubino, Rocio Garcia-Carbonero, Anna Koumarianou, Maura Rossi, D. Tamayo, Alice Laffi, S. Boselli, Francesca Spada, Gregory Kaltsas, J. Hernando, Wouter W. de Herder, Vincenzo Bagnardi, Nicola Fazio, Johannes Hofland, Jaume Capdevila, Kira Oleinikov, Lorenzo Gervaso, Thorvardur R. Halfdanarson, Internal Medicine, Fazio, N, Gervaso, L, Halfdanarson, T, La Salvia, A, Hofland, J, Hernando, J, Sonbol, M, Garcia-Carbonero, R, Capdevila, J, de Herder, W, Koumarianou, A, Kaltsas, G, Rossi, M, Grozinsky-Glasberg, S, Oleinikov, K, Boselli, S, Tamayo, D, Bagnardi, V, Laffi, A, Rubino, M, and Spada, F

Subjects
0301 basic medicine, Male, Cancer Research, Time Factors, coronavirus, Comorbidity, Global Health, 0302 clinical medicine, Risk Factors, Neuroendocrine tumour, Prospective Studies, Young adult, Prospective cohort study, Original Research, education.field_of_study, Middle Aged, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Corrigendum, Preliminary Data, Adult, medicine.medical_specialty, Coronaviru, Population, 03 medical and health sciences, Young Adult, SDG 3 - Good Health and Well-being, Internal medicine, Intensive care, Carcinoma, medicine, Humans, education, Aged, Retrospective Studies, neuroendocrine neoplasms, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, medicine.disease, Discontinuation, Carcinoma, Neuroendocrine, Neuroendocrine neoplasm, 030104 developmental biology, neuroendocrine tumors, business
Abstract

Background Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Material and methods This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. Results Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. Conclusions Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

Published
2021

2. Effectiveness of MicroShunt in Patients with Primary Open-Angle and Pseudoexfoliative Glaucoma

Author

Leon Au, Antonio Maria Fea, E. Martini, Matteo Sacchi, Gian Luca Laffi, Mario A. Economou, and Paolo Caselgrandi

Subjects
Intraocular pressure, medicine.medical_specialty, genetic structures, Minimally invasive glaucoma surgery, Open angle glaucoma, business.industry, medicine.medical_treatment, Glaucoma, Retrospective cohort study, General Medicine, medicine.disease, eye diseases, Ophthalmology, medicine, Glaucoma surgery, Trabeculectomy, sense organs, business, Hyphema
Abstract

PURPOSE To evaluate the effectiveness and safety of the Preserflo MicroShunt implant (Santen) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). DESIGN Retrospective, open-label, multicenter study. PARTICIPANTS Patients with insufficiently controlled primary POAG or PXG who underwent a standalone MicroShunt implantation procedure. METHODS Consecutive patients with POAG and PXG who underwent surgery with the ab externo minimally invasive glaucoma surgery device Preserflo MicroShunt with mitomycin C. MAIN OUTCOME MEASURES Primary end points were mean change in intraocular pressure (IOP) and number of hypotensive medications from baseline through month 12. Success was defined as an IOP of 18 mmHg or less and an IOP reduction of 20% or more, with (qualified) or without (complete) any hypotensive medication. RESULTS Among the 130 patients who underwent MicroShunt implantation, 104 fulfilled the inclusion and exclusion criteria and were included in the analysis. Eighty-one eyes (77.9%) were diagnosed with POAG and 23 eyes (22.1%) were diagnosed with PXG. The mean age was 71.4 ± 12.6 years, and 45 patients (43.3%) were women. Mean IOP was lowered significantly from 25.1 ± 6.5 mmHg at baseline to 14.1 ± 3.4 mmHg at month 12 (P < 0.0001). At month 12, 27 eyes (26.0%) were categorized as complete successes and 61 eyes (58.7%) were categorized as qualified successes. The mean number of hypotensive medications was reduced significantly from 3.0 ± 1.0 medications at the preoperative visit to 0.77 ± 0.95 medication at month 12 (P < 0.001). Throughout the study, 19 eyes (18.3%) required needling and 14 eyes (13.5%) underwent surgical revision. Eight eyes (7.7%) showed hyphema and 5 eyes (4.8%) showed choroidal detachment. These were resolved with medical therapy without sequelae. Four patients underwent subsequent surgeries, and 2 patients underwent trabeculectomy (at months 3 and 6): One patient underwent transscleral cyclophotocoagulation at month 3 and 1 patient underwent MicroPulse cyclophotocoagulation at month 4. CONCLUSIONS In this retrospective study, the MicroShunt effectively lowered IOP and the need for IOP-lowering medications.

Published
2022

3. Ten years-experience of sunitinib in the treatment of advanced pan-NETs: an update on safety profile

Author

Francesca Spada, G Vivanet, Nicola Fazio, Manila Rubino, Alice Laffi, and Lorenzo Gervaso

Subjects
Pediatrics, medicine.medical_specialty, Sunitinib, business.industry, Receptor Protein-Tyrosine Kinases, Antineoplastic Agents, General Medicine, Neutropenia, medicine.disease, Kidney Neoplasms, Well differentiated, Discontinuation, Clinical trial, Safety profile, Tolerability, Expert opinion, Quality of Life, medicine, Humans, Pharmacology (medical), business, Carcinoma, Renal Cell, medicine.drug
Abstract

Introduction Sunitinib still represents a milestone in the treatment for progressive, well-differentiated, advanced panNETs. Areas covered We performed an evidence reappraisal to critically discuss its safety profile. We included nine studies, five clinical trials and four real-world (RW) studies. Within non-real-world (NRW) studies, diarrhea was the most frequent clinical AE. With regard to G3-4 AEs, fatigue and hypertension were the two most frequent, while neutropenia was the most recurrent hematological one. Considering four real-world trials, hand-foot-syndrome (HFS) was the most frequent clinical any-grade AE of any grade and neutropenia was the most common G3-4. Alongside to the AEs rate, the discontinuation rate of sunitinib due to TRAEs was variable among all the nine selected studies, ranging from 10% to 35% in the NRW setting and from 7% to 31% in the RW setting. Conversely, temporary interruption is an accepted strategy to reduce toxicity, even though not specifically tested in pan-NET. Expert opinion Till now, sunitinib continues to be one of the main therapeutic options for patients with well differentiated advanced panNETs, potentially covering any line of treatment. Therefore, tolerability plays a crucial role to increase adherence to therapy and maximize QoL.

Published
2021

4. Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis

Author

Vincenzo Bagnardi, Francesca Spada, Massimo Barberis, Manila Rubino, Eleonora Pisa, Nicola Fazio, S. Frassoni, Alice Laffi, Laffi, A, Spada, F, Bagnardi, V, Frassoni, S, Pisa, E, Rubino, M, Barberis, M, and Fazio, N

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Neuroendocrine tumors, G3, Endocrinology, Single entity, Fluorodeoxyglucose F18, Stomach Neoplasms, Positron Emission Tomography Computed Tomography, Intestinal Neoplasms, medicine, Retrospective analysis, Organometallic Compounds, Humans, Prospective cohort study, Early Detection of Cancer, Retrospective Studies, Response rate (survey), Heterogeneous group, medicine.diagnostic_test, business.industry, Patient Selection, NEN, Middle Aged, medicine.disease, Prognosis, Occult, Immunohistochemistry, Survival Analysis, Pancreatic Neoplasms, NET, Neuroendocrine Tumors, Ki-67 Antigen, Neuroendocrine, Italy, Positron emission tomography, Female, Radiology, Neoplasm Grading, Radiopharmaceuticals, business
Abstract

Purpose: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. Patients and methods: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. Results: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048). Conclusion: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

Published
2022

5. Causes of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: Findings from the SYNCOPACED registry

Author

Gabriele Dell'Era, Natale Daniele Brunetti, Enrico Boggio, Pier Luigi Pellegrino, Antonio Dello Russo, Germano Gaggioli, Alessandro Guido, Mauro Biffi, Gerardo Nigro, Ernesto Ammendola, Giuseppe Patti, Mattia Laffi, Matteo Ziacchi, Federico Guerra, Pietro Palmisano, Vittorio Aspromonte, Lorenzo Pimpini, Cardiac Pacing, Michele Accogli, and Francesco Santoro

Subjects
Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Syncope, Bifascicular block, 03 medical and health sciences, Orthostatic vital signs, 0302 clinical medicine, Heart Rate, Recurrence, Physiology (medical), Internal medicine, medicine, Humans, In patient, Prospective Studies, Registries, 030212 general & internal medicine, Vasovagal syncope, Collapse (medical), Aged, biology, business.industry, Incidence, Cardiac Pacing, Artificial, Syncope (genus), Atrial fibrillation, medicine.disease, biology.organism_classification, Italy, Chronic Disease, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Atrioventricular block, Follow-Up Studies
Abstract

Background Few studies have examined the causes of syncope/collapse recurrences in patients with a previously implanted pacemaker for bradyarrhythmic syncope. Objective The purpose of this study was to assess the causes of syncope/collapse recurrences after pacemaker implantation for bradyarrhythmic syncope in a large patient population. Methods The SYNCOpal recurrences in patients treated with permanent PACing for bradyarrhythmic syncope (SYNCOPACED) registry was a prospective multicenter observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for bradyarrhythmic syncope. During follow-up, the time to the first syncope/collapse recurrence was recorded. Patients with syncope/collapse recurrences underwent a predefined diagnostic workup aimed at establishing the mechanism of syncope/collapse. Results During a median follow-up of 50 months, 213 patients (15.6%) reported at least 1 syncope/collapse recurrence. The risk of syncope/collapse recurrence was highest in patients who underwent implantation for cardioinhibitory vasovagal syncope (26.4%), followed by unexplained syncope and chronic bifascicular block (21.5%), cardioinhibitory carotid sinus syndrome (17.2%), atrial fibrillation needing pacing (15.5%), atrioventricular block (13.6%), and sinus node disease (12.5%) (P = .017). The most frequent cause of syncope/collapse recurrence was reflex syncope (27.7%), followed by orthostatic hypotension (26.3%), pacemaker or lead malfunction (5.6%), structural cardiac disease (5.2%), and atrial and ventricular tachyarrhythmias (4.7% and 3.8%, respectively). In 26.8% of cases, the mechanism of syncope/collapse remained unexplained. Conclusion In patients receiving a pacemaker for bradyarrhythmic syncope, reflex syncope and orthostatic hypotension are the most frequent mechanisms of syncope/collapse recurrence after implantation. Pacing system malfunction, structural cardiac diseases, and tachyarrhythmias are rare mechanisms. The mechanism remains unexplained in >25% of patients.

Published
2021

6. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Author

Francesco Giuseppe Foschi, Gianpaolo Vidili, Andrea Mega, Antonio Gasbarrini, Marco Zoli, Edoardo G. Giannini, Rodolfo Sacco, Alessandro Vitale, Francesco Tovoli, Giacomo Laffi, Maria Di Marco, Giovanni Raimondo, Gianluca Svegliati-Baroni, Claudia Campani, Francesco Azzaroli, Fabio Farinati, Umberto Arena, Fabio Marra, Gabriele Dragoni, Alberto Masotto, Franco Trevisani, Maurizia Rossana Brunetto, Giuseppe Cabibbo, Elisabetta Biasini, Gian Ludovico Rapaccini, Eugenio Caturelli, Gerardo Nardone, Maria Guarino, Umberto Cillo, Campani, C., Vitale, A., Dragoni, G., Arena, U., Laffi, G., Cillo, U., Giannini, E. G., Tovoli, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Sacco, R., Cabibbo, G., Mega, A., Guarino, M., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Nardone, G., Raimondo, G., Azzaroli, F., Vidili, G., Brunetto, M. R., Farinati, F., Trevisani, F., Marra, F., Campani C., Vitale A., Dragoni G., Arena U., Laffi G., Cillo U., Giannini E.G., Tovoli F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Sacco R., Cabibbo G., Mega A., Guarino M., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Biasini E., Masotto A., Nardone G., Raimondo G., Azzaroli F., Vidili G., Brunetto M.R., Farinati F., Trevisani F., and Marra F.

Subjects
ALBI grade, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, ITALICA staging system, MESIAH, medicine.medical_specialty, lcsh:RC254-282, Gastroenterology, Internal medicine, Medicine, In patient, Radiologic Response, Settore MED/12 - Gastroenterologia, Original Paper, Hepatology, business.industry, Proportional hazards model, Confounding, Hazard ratio, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Oncology, Hepatocellular carcinoma, Akaike information criterion, business, Liver cancer
Abstract

Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10–1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.

Published
2021

7. Second-order grey-scale texture analysis of pleural ultrasound images to differentiate acute respiratory distress syndrome and cardiogenic pulmonary edema

Author

Brusasco, C., Santori, G., Tavazzi, G., Via, G., Robba, C., Gargani, L., Mojoli, F., Mongodi, S., Bruzzo, E., Tro, R., Boccacci, P., Isirdi, A., Forfori, F., Corradi, F., Biagini, R., Calvaruso, A., Costanzo, D., Cundari, F., Della Rocca, A., Laffi, A., Marchi, E., Marino, F., Monfroni, M., Mongiovi, N., Narteni, S., Piagnani, C., Prizio, S., Protsyak, L., Romani, M., Soldati, I., Taddei, E., Tecchi, L., Trunfio, D., University of Zurich, and Corradi, Francesco

Subjects
Artificial intelligence, medicine.medical_specialty, ARDS, Critical Illness, Lung ultrasonography, Pulmonary Edema, Heart failure, 610 Medicine & health, Health Informatics, Acute respiratory failure, Critical Care and Intensive Care Medicine, 11171 Cardiocentro Ticino, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Statistical significance, Anesthesiology, Computer aided diagnosis, Quantitative lung ultrasonography, Humans, Medicine, Lung, 2718 Health Informatics, Respiratory Distress Syndrome, business.industry, Ultrasound, 030208 emergency & critical care medicine, medicine.disease, Intensive care unit, Anesthesiology and Pain Medicine, 030228 respiratory system, Computer-aided diagnosis, Extravascular Lung Water, 2703 Anesthesiology and Pain Medicine, Radiology, Differential diagnosis, 2706 Critical Care and Intensive Care Medicine, business
Abstract

Discriminating acute respiratory distress syndrome (ARDS) from acute cardiogenic pulmonary edema (CPE) may be challenging in critically ill patients. Aim of this study was to investigate if gray-level co-occurrence matrix (GLCM) analysis of lung ultrasound (LUS) images can differentiate ARDS from CPE. The study population consisted of critically ill patients admitted to intensive care unit (ICU) with acute respiratory failure and submitted to LUS and extravascular lung water monitoring, and of a healthy control group (HCG). A digital analysis of pleural line and subpleural space, based on the GLCM with second order statistical texture analysis, was tested. We prospectively evaluated 47 subjects: 16 with a clinical diagnosis of CPE, 8 of ARDS, and 23 healthy subjects. By comparing ARDS and CPE patients’ subgroups with HCG, the one-way ANOVA models found a statistical significance in 9 out of 11 GLCM textural features. Post-hoc pairwise comparisons found statistical significance within each matrix feature for ARDS vs. CPE and CPE vs. HCG (P ≤ 0.001 for all). For ARDS vs. HCG a statistical significance occurred only in two matrix features (correlation: P = 0.005; homogeneity: P = 0.048). The quantitative method proposed has shown high diagnostic accuracy in differentiating normal lung from ARDS or CPE, and good diagnostic accuracy in differentiating CPE and ARDS. Gray-level co-occurrence matrix analysis of LUS images has the potential to aid pulmonary edemas differential diagnosis.

Published
2020

8. Brain Cystic Metastases in a Patient with Advanced Atypical Lung Carcinoid

Author

Nicola Fazio, Alice Laffi, Francesca Spada, Manila Rubino, Dario Zerini, Francesco Di Meco, Cecilia Casali, Guido Bonomo, Chiara Maria Grana, Luigi Funicelli, Eleonora Pisa, Emilio Bertani, and Davide Ravizza

Subjects
medicine.medical_specialty, Lung, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Cancer, Neuroendocrine tumors, medicine.disease, Lesion, medicine.anatomical_structure, Biopsy, medicine, Cyst, Radiology, medicine.symptom, business, Craniotomy, Rare disease
Abstract

Introduction: Cystic brain lesions represented a rare finding in cancer patients, even more uncommon in rare disease as neuroendocrine neoplasms. Patient Presentation: We presented a case of a patient with neurologic symptoms as first and only presentation of a neuroendocrine tumor of the lung. Management and Outcome: First of all, the patient underwent neuroradiologic assessment with the finding of cystic brain lesions. A chest and abdomen CT scan detected a pulmonary lesion; a biopsy of this mass revealed an atypical carcinoid of the lung. Considering the absence of other symptoms, in order to clarify the nature of the cystic brain lesions, a right frontal craniotomy was performed, and a cyst was completely excised. Pathology confirmed the metastatic nature of the brain lesions. Unfortunately, the conditions of the patient quickly worsened, and he passed away before the start of the treatment. Conclusion: Due to the low awareness about neuroendocrine tumors and their clinical and radiological presentations, multidisciplinary approach can represent the cornerstone to provide an accurate and timely diagnosis.

Published
2020

9. On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Author

Alessandro Federico, M. Colpani, Paolo Caraceni, Marco Domenicali, Manuel Tufoni, L. Simone, A Alberti, Giovanni Raimondo, A. Risso, Antonietta Sticca, Salvatore Piano, Anna Visani, Francesco Salerno, Giacomo Laffi, Piera Rossi, Paolo Angeli, F. Fidone, Pierluigi Toniutto, Vincenza Calvaruso, Silvia Nardelli, Aldo Airoldi, Sara Massironi, Stefania Gioia, A. Roncadori, Marco Marzioni, Nicola Caporaso, N.M. Castellaneta, Stefano Fagiuoli, Francesco Giuseppe Foschi, Raffaele Cozzolongo, Maria Rendina, Irene Cacciola, Oliviero Riggio, Sergio Neri, Raffaella Viganò, Ferdinando Giannone, Chiara Mazzarelli, Maria Marsico, Giovanni Parrella, Riccardo Guarisco, Chiara Elia, F. Levantesi, M. Cavallin, Alida Andrealli, A. Pecchioli, Loredana Prestianni, Rosanna De Marco, T Gabbani, Elga Neri, S. Boccia, Arianna Lanzi, Giacomo Zaccherini, Marcello Dallio, Giovanni Perricone, Giorgio Ballardini Natascia Celli, Francesco Auriemma, Federica Mirici Cappa, Agnese Antognoli, Annalisa Tortora, Gianfranco Elia, R. Bringiotti, Francesco De Leonardis, Marcello Vangeli, Agostino Rizzotto, Dario Conte, Manuela Merli, Francesca Capretti, Mauro Bernardi, Chiara Pasquale, Pietro Leo, D. Maiorca, M. Zappimbulso, Filomena Morisco, Vincenzo Sangiovanni, Maurizio Baldassarre, Lucia Cesarini, Gianluca Svegliati-Baroni, Maria Guarino, Carmelina Loguercio, Alessandra Galioto, Antonio Mastroianni, Giorgio Maria Saracco, Antonio Gasbarrini, G. Magini, Alba Kostandini, Carlo Alessandria, Josè Petruzzi, Vito Di Marco, Silvano Fasolato, Elisa Negri, Fabio Pugliese, Mario Angelico, Daniela Campion, Caraceni P., Tufoni M., Zaccherini G., Riggio O., Angeli P., Alessandria C., Neri S., Foschi F.G., Levantesi F., Airoldi A., Simone L., Svegliati-Baroni G., Fagiuoli S., Laffi G., Cozzolongo R., Di Marco V., Sangiovanni V., Morisco F., Toniutto P., Gasbarrini A., De Marco R., Piano S., Nardelli S., Elia C., Roncadori A., Baldassarre M., Bernardi M., Domenicali M., Giannone F.A., Antognoli A., Merli M., Pasquale C., Gioia S., Fasolato S., Sticca A., Campion D., Risso A., Saracco G.M., Prestianni L., Fidone F., Maiorca D., Rizzotto A., Cappa F.M., Lanzi A., Neri E., Visani A., Mastroianni A., Perricone G., Alberti A.B., Cesarini L., Mazzarelli C., Vangeli M., Vigano R., Marzioni M., Capretti F., Kostandini A., Magini G., Colpani M., Gabbani T., Marsico M., Zappimbulso M., Petruzzi J., Calvaruso V., Parrella G., Caporaso N., Auriemma F., Guarino M., Pugliese F., Tortora A., Leo P., Angelico M., De Leonardis F., Pecchioli A., Rossi P., Raimondo G., Cacciola I., Elia G., Negri E., Dallio M., Loguercio C., Federico A., Conte D., Massironi S., Natascia Celli G.B., Rendina M., Bringiotti R., Castellaneta N.M., Salerno F., Boccia S., Guarisco R., Galioto A., Cavallin M., Andrealli A., Caraceni, P., Tufoni, M., Zaccherini, G., Riggio, O., Angeli, P., Alessandria, C., Neri, S., Foschi, F. G., Levantesi, F., Airoldi, A., Simone, L., Svegliati-Baroni, G., Fagiuoli, S., Laffi, G., Cozzolongo, R., Di Marco, V., Sangiovanni, V., Morisco, F., Toniutto, P., Gasbarrini, A., De Marco, R., Piano, S., Nardelli, S., Elia, C., Roncadori, A., Baldassarre, M., Bernardi, M., Domenicali, M., Giannone, F. A., Antognoli, A., Merli, M., Pasquale, C., Gioia, S., Fasolato, S., Sticca, A., Campion, D., Risso, A., Saracco, G. M., Prestianni, L., Fidone, F., Maiorca, D., Rizzotto, A., Cappa, F. M., Lanzi, A., Neri, E., Visani, A., Mastroianni, A., Perricone, G., Alberti, A. B., Cesarini, L., Mazzarelli, C., Vangeli, M., Vigano, R., Marzioni, M., Capretti, F., Kostandini, A., Magini, G., Colpani, M., Gabbani, T., Marsico, M., Zappimbulso, M., Petruzzi, J., Calvaruso, V., Parrella, G., Caporaso, N., Auriemma, F., Guarino, M., Pugliese, F., Tortora, A., Leo, P., Angelico, M., De Leonardis, F., Pecchioli, A., Rossi, P., Raimondo, G., Cacciola, I., Elia, G., Negri, E., Dallio, M., Loguercio, C., Federico, A., Conte, D., Massironi, S., Natascia Celli, G. B., Rendina, M., Bringiotti, R., Castellaneta, N. M., Salerno, F., Boccia, S., Guarisco, R., Galioto, A., Cavallin, M., Andrealli, A., Caraceni, P, Tufoni, M, Zaccherini, G, Riggio, O, Angeli, P, Alessandria, C, Neri, S, Foschi, F, Levantesi, F, Airoldi, A, Simone, L, Svegliati-Baroni, G, Fagiuoli, S, Laffi, G, Cozzolongo, R, Di Marco, V, Sangiovanni, V, Morisco, F, Toniutto, P, Gasbarrini, A, De Marco, R, Piano, S, Nardelli, S, Elia, C, Roncadori, A, Baldassarre, M, Bernardi, M, Domenicali, M, Giannone, F, Antognoli, A, Merli, M, Pasquale, C, Gioia, S, Fasolato, S, Sticca, A, Campion, D, Risso, A, Saracco, G, Prestianni, L, Fidone, F, Maiorca, D, Rizzotto, A, Cappa, F, Lanzi, A, Neri, E, Visani, A, Mastroianni, A, Perricone, G, Alberti, A, Cesarini, L, Mazzarelli, C, Vangeli, M, Vigano, R, Marzioni, M, Capretti, F, Kostandini, A, Magini, G, Colpani, M, Gabbani, T, Marsico, M, Zappimbulso, M, Petruzzi, J, Calvaruso, V, Parrella, G, Caporaso, N, Auriemma, F, Guarino, M, Pugliese, F, Tortora, A, Leo, P, Angelico, M, De Leonardis, F, Pecchioli, A, Rossi, P, Raimondo, G, Cacciola, I, Elia, G, Negri, E, Dallio, M, Loguercio, C, Federico, A, Conte, D, Massironi, S, Natascia Celli, G, Rendina, M, Bringiotti, R, Castellaneta, N, Salerno, F, Boccia, S, Guarisco, R, Galioto, A, Cavallin, M, and Andrealli, A

Subjects
Male, 0301 basic medicine, Cirrhosis, ascites, complications, liver cirrhosis, serum albumin, survival, Serum albumin, Survival, Logistic regression, Gastroenterology, Biomarkers, Pharmacological, Ascites, Complications, 0302 clinical medicine, Medicine, biology, Middle Aged, Intention to Treat Analysis, Treatment Outcome, Ascite, Female, 030211 gastroenterology & hepatology, Drug Monitoring, medicine.symptom, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, Serum Albumin, Human, 03 medical and health sciences, Serum albumin level, Predictive Value of Tests, Internal medicine, Post-hoc analysis, Humans, In patient, Biological Products, Cirrhosi, Hepatology, business.industry, Albumin, medicine.disease, Long-Term Care, Survival Analysis, 030104 developmental biology, biology.protein, business, Complication
Abstract

Background & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. Results: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. Conclusion: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. Lay summary: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.

Published
2020

10. Transjugular Intrahepatic Portosystemic Shunt does not affect the efficacy and safety of direct-acting antivirals in patients with advanced cirrhosis: A real-life, case-control study

Author

Pietro Andreone, Silvia Aspite, Claudia Campani, Francesco Vizzutti, Fabio Marra, Pasquale Apolito, Sinan Sadalla, Filippo Schepis, A. Scuteri, Laura Turco, Stefano Gitto, Fabio Conti, Giacomo Laffi, Federica Lombardo, Umberto Arena, Giovanni Vitale, Erica Villa, Fabrizio Fanelli, W. Debernardi-Venon, Gitto S., Vizzutti F., Schepis F., Turco L., Aspite S., Vitale G., Arena U., Villa E., Laffi G., Debernardi-Venon W., Fanelli F., Andreone P., Marra F., Apolito P., Campani C., Sadalla S., Lombardo F., Conti F., and Scuteri A.

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis complication, medicine.medical_treatment, Kaplan-Meier Estimate, Antiviral therapy, Advanced liver disease, Cirrhosis complications, Portal hypertension, Hepatology, Gastroenterology, Logistic regression, Antiviral Agents, Severity of Illness Index, End Stage Liver Disease, 03 medical and health sciences, Liver disease, Postoperative Complications, 0302 clinical medicine, Internal medicine, Hypertension, Portal, medicine, Humans, Adverse effect, Aged, Univariate analysis, business.industry, Case-control study, Middle Aged, medicine.disease, Hepatitis C, Logistic Models, Treatment Outcome, Italy, Case-Control Studies, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Portasystemic Shunt, Transjugular Intrahepatic, business, Transjugular intrahepatic portosystemic shunt
Abstract

Background Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a well-established treatment for complications of portal hypertension. Aims To analyze the impact of TIPS on virologic response and safety profile in patients treated with direct-acting antivirals (DAAs). Methods We analyzed data from HCV-positive cirrhotic patients treated with DAAs. Twenty-one patients with previous TIPS placement were compared with 42 matched subjects without TIPS. Logistic regression was used to identify predictors of hepatic function worsening and adverse events. Results No differences were found between the two groups in particular regarding sustained virologic response (92.5 and 97.6% in TIPS vs no-TIPS, p = 0.559). Model for End-stage Liver Disease (MELD) of both TIPS and no-TIPS groups declined from baseline to week 24 of follow-up (from 12.5 ± 3.5 to 10.8 ± 3.4 and from 11.1 ± 3.5 to 10.3 ± 3.4, p = 0.044 and 0.025). There were no differences in adverse event rates. At univariate analysis, age was associated with MELD increase from baseline to week 24 (OR 1.111, 95% CI 1.019-1.211, p = 0.017), and patients with higher baseline MELD developed serious adverse events more frequently (OR 0.815, 95% CI 0.658–1.010, p = 0.062). Patients with or without TIPS did not show differences in transplant-free survival. Conclusion TIPS placement does not affect virologic response and clinical outcome of patients receiving DAAs.

Published
2019

11. Transjugular intrahepatic portosystemic shunt (TIPS): current indications and strategies to improve the outcomes

Author

Fabrizio Fanelli, Giacomo Laffi, Silvia Aspite, Francesco Vizzutti, Gabriele Dragoni, Fabio Marra, Stefano Gitto, Filippo Schepis, Umberto Arena, and Laura Turco

Subjects
medicine.medical_specialty, medicine.medical_treatment, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Hepatorenal syndrome, Hypertension, Portal, Outcome Assessment, Health Care, Ascites, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Hepatic encephalopathy, Vascular disease, business.industry, Heart failure, Variceal bleeding, Portasystemic Shunt, Transjugular Intrahepatic, Treatment Outcome, medicine.disease, Portal vein thrombosis, Surgery, Emergency Medicine, Portal hypertension, medicine.symptom, business, Transjugular intrahepatic portosystemic shunt, Abdominal surgery
Abstract

Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of complications of portal hypertension. Established indications to TIPS in cirrhotic patients include portal hypertensive bleeding and refractory ascites. Over the years additional indications have been proposed, such as the treatment of vascular disease of the liver, hepatic hydrothorax, hepatorenal syndrome and bleeding from ectopic varices. Indications under evaluation include treatment of portal hypertension prior to major abdominal surgery and treatment of portal vein thrombosis. In spite of these advances, there are still uncertainties regarding the appropriate workup for patients to be scheduled for TIPS. Moreover, prevention and management of post-TIPS complications including hepatic encephalopathy and heart failure are still suboptimal. These issues are particularly relevant considering aging in TIPS candidates in Western countries. Correct selection of patients is mandatory to prevent complications which may eventually frustrate the good hemodynamic results and worsen the patient's quality of life or even life expectancy. The possible role of small diameter TIPS to prevent post-procedural complications is discussed.

Published
2020

12. Association between alterations of corneal sub-basal nerve plexus analyzed with in vivo confocal microscopy and long-term glycemic variability

Author

Gilberto Laffi, Piera Versura, Marco Pellegrini, Stefano Sebastiani, Giuseppe Giannaccare, Simona Moscatiello, Guido Di Dalmazi, Uberto Pagotto, Lorenzo Tucci, and Marco Pellegrini, Stefano Sebastiani, Lorenzo Tucci, Giuseppe Giannaccare, Simona Moscatiello, Gilberto Laffi, Uberto Pagotto, Guido Di Dalmazi, Piera Versura

Subjects
Pathology, medicine.medical_specialty, Diabetic neuropathy, type 1 diabetes, In vivo confocal microscopy, Ophthalmic Nerve, 030209 endocrinology & metabolism, NO, Cornea, 03 medical and health sciences, Basal (phylogenetics), Nerve Fibers, 0302 clinical medicine, Diabetic Neuropathies, Humans, Medicine, Glycemic variability, Glycemic, Type 1 diabetes, Corneal nerves, in vivo confocal microscopy, diabetic neuropathy, HbA1C, type 1 diabetes, Glycemic variability, Microscopy, Confocal, HbA1C, business.industry, Nerve plexus, General Medicine, medicine.disease, diabetic neuropathy, Ophthalmology, medicine.anatomical_structure, 030221 ophthalmology & optometry, business, Corneal nerves, in vivo confocal microscopy
Abstract

Purpose: The effect of long-term glycemic variability upon corneal sub-basal nerve plexus (CSNP) morphology analyzed by in vivo confocal microscopy (IVCM) has been poorly investigated in the setting of type 1 diabetes mellitus (T1DM). Our purpose was to analyze the association between morphometric parameters of CSNP and new markers of glycemic variability in a population of patients with T1DM. Methods: Forty patients with T1DM underwent: assessment of diabetic neuropathy (DN); analysis of subcutaneous advanced glycated end-products; IVCM scans of CSNP. The fully automated software ACCMetrics was employed to analyze IVCM images and calculate seven corneal nerve parameters. Data of diabetes duration, mean and standard deviation (SD) of either last-year and all-time glycated hemoglobin (HbA1C) were retrieved. Results: Diabetes duration and all-time SD of HbA1C were independently associated with CNFD (R = –0.26, p = 0.01; R = –0.27, p = 0.047 respectively), CNFL (R = –0.12; p = 0.01; R = –0.17, p = 0.01 respectively) and CNFrD (R = –0.001, p = 0.009; R = –0.002, p = 0.007 respectively). The analysis of the association among IVCM parameters and specific subtypes of DN showed that altered cold sensitivity was independently associated with CNFD (B = –0.24, p = 0.01), CNFL (B = –0.46, p = 0.01) and CNFrD (B = –28.65, p = 0.03). Conclusions: All-time SD of HbA1C and disease duration were found to be independent predictors of damage to CSNP in patients with T1DM.

Published
2021

13. Carcinoid Syndrome and Hyperinsulinemic Hypoglycemia Associated with Neuroendocrine Neoplasms: A Critical Review on Clinical and Pharmacological Management

Author

Manila Rubino, Franco Grimaldi, Francesca Spada, Alice Laffi, Elda Kara, Sara Massironi, Roberta Elisa Rossi, Nicola Fazio, and Sherrie Bhoori

Subjects
Pancreatic Insulinoma, Oncology, medicine.medical_specialty, medicine.medical_treatment, Pharmaceutical Science, carcinoid syndrome, 030209 endocrinology & metabolism, Review, Neuroendocrine tumors, insulinoma, medicine.disease_cause, Serotonin secretion, 03 medical and health sciences, Pharmacy and materia medica, 0302 clinical medicine, Quality of life, NENs, Internal medicine, Drug Discovery, medicine, Hyperinsulinemic hypoglycemia, Insulinoma, business.industry, Insulin, medicine.disease, RS1-441, 030220 oncology & carcinogenesis, Medicine, Molecular Medicine, neuroendocrine tumors, business, Carcinoid syndrome
Abstract

The carcinoid syndrome (CS) and hyperinsulinemic hypoglycemia (HH) represent two of the most common clinical syndromes associated with neuroendocrine neoplasms (NENs). The former is mainly related to the serotonin secretion by a small bowel NEN, whereas the latter depends on an insulin hypersecretion by a pancreatic insulinoma. Both syndromes/conditions can affect prognosis and quality of life of patients with NENs. They are often diagnosed late when patients become strongly symptomatic. Therefore, their early detection and management are a critical step in the clinical management of NEN patients. A dedicated and experienced multidisciplinary team with appropriate therapeutic strategies is needed and should be encouraged to optimize clinical outcomes. This review aims to critically analyze clinical features, evidence and treatment options of CS and HH and therefore to improve their management.

Published
2021

14. Corrigendum to ‘Coronavirus disease 2019 in patients with neuroendocrine neoplasms: Preliminary results of the INTENSIVE study’ [European Journal of Cancer 154 (2021) 246-252]

Author

Rocio Garcia-Carbonero, Alice Laffi, Wouter W. de Herder, Manila Rubino, Gregory Kaltsas, Thorvardur R. Halfdanarson, Simona Grozinsky-Glasberg, Johannes Hofland, Kira Oleinikov, Jaume Capdevila, J. Hernando, S. Boselli, D. Tamayo, Lorenzo Gervaso, Mohamad Bassam Sonbol, Francesca Spada, Vincenzo Bagnardi, Anna La Salvia, Anna Koumarianou, Nicola Fazio, and Maura Rossi

Subjects
Cancer Research, 2019-20 coronavirus outbreak, Oncology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, Cancer, In patient, business, medicine.disease, Virology
Published
2022

15. Optimization of coronary sinus lead placement targeted to right-to-left delay in patients undergoing cardiac resynchronization therapy

Author

Fabio Di Lorenzo, Marzia Giaccardi, Romina Carpi, Diana Solari, Mattia Laffi, Roberto Mureddu, Davide Giorgi, Daniele Oddone, Gaetano Senatore, Eliana Cipolla, Nicola Bottoni, Nadir Sitta, Michele Brignole, Massimo Giammaria, Giuseppe Arena, René Nangah, and Elena Marras

Subjects
Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Cardiac resynchronization therapy, 030204 cardiovascular system & hematology, Risk Assessment, Cardiac Resynchronization Therapy, 03 medical and health sciences, QRS complex, Basal (phylogenetics), Patient Admission, 0302 clinical medicine, Risk Factors, Physiology (medical), Internal medicine, Humans, Medicine, Cardiac Resynchronization Therapy Devices, Prospective Studies, 030212 general & internal medicine, Lead (electronics), Coronary sinus, Aged, Aged, 80 and over, Heart Failure, business.industry, Coronary Sinus, Arrhythmias, Cardiac, Recovery of Function, Middle Aged, medicine.disease, Clinical trial, Treatment Outcome, Italy, Heart failure, Disease Progression, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Lead Placement
Abstract

AIMS Anatomical placement of the coronary sinus (CS) lead in basal or mid-ventricular positions of the posterior and lateral walls is associated with a better clinical outcome of cardiac resynchronization therapy (CRT). We hypothesized that optimization of CS lead placement targeted the right-to-left electrical delay (RLD) predicts an additional clinical benefit. METHODS AND RESULTS The CS lead was placed according to current standards in 90 patients (Conventional group) and at the site of the longest RLD in 121 patients (RLD group). Non-responders were defined as those who died or underwent hospitalization for heart failure or did not improve in their Clinical Composite Score within 6 months. There were 67 (32%) non-responders. Compared with Conventional group, the final CS pacing site was more frequently in the basal segments in the RLD group (40% vs. 23%, P = 0.007); moreover, the RLD ratio (%RLD) of the total QRS width was longer (77 ± 13 vs. 73 ± 15, P = 0.05) and biventricular QRS shortened more from the baseline (-31 ± 21 ms vs. -21 ± 26 ms, P = 0.004). Nevertheless, the rate of non-responders was similar in the RLD and Conventional groups (35% vs. 28%, P = 0.30), as was %RLD (76 ± 16 vs. 75 ± 13, P = 0.66). QRS width during right ventricular (RV) pacing was an independent predictors of adverse outcome, with a 2% increase in the risk of failure for each 1 ms increase in QRS (P = 0.006). CONCLUSION Optimization of CS lead placement targeted to latest electrical activation does not provide additional clinical benefit to anatomical placement in basal or mid-ventricular positions of the posterior and lateral walls. QRS width during RV pacing was a strong predictor of CRT failure. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT03204864.

Published
2018

16. Should temozolomide be used on the basis of O6-methylguanine DNA methyltransferase status in patients with advanced neuroendocrine tumors? A systematic review and meta-analysis

Author

Vincenzo Bagnardi, E. Guerini Rocco, Nicola Fazio, Giulia Peveri, Lorenzo Gervaso, Caterina Fumagalli, Alice Laffi, Francesca Spada, Giuseppe Curigliano, P. Trillo Aliaga, Eleonora Pisa, Manila Rubino, Trillo Aliaga, P, Spada, F, Peveri, G, Bagnardi, V, Fumagalli, C, Laffi, A, Rubino, M, Gervaso, L, Guerini Rocco, E, Pisa, E, Curigliano, G, and Fazio, N

Subjects
Oncology, medicine.medical_specialty, Cochrane Library, Neuroendocrine tumors, Neuroendocrine tumor, Internal medicine, Temozolomide, medicine, Radiology, Nuclear Medicine and imaging, Prospective cohort study, neoplasms, business.industry, Absolute risk reduction, O-6-methylguanine-DNA methyltransferase, General Medicine, medicine.disease, Confidence interval, NET, methylguanine DNA methyltransferase, Meta-analysis, TEM, MGMT, TMZ, business, medicine.drug
Abstract

Background: Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O6-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated. Methods: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021. Results: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13–0.50; p < 0.001; I2: 73%) and risk ratio of 2.29 (95% CI: 1.34–3.91; p < 0.001; I2: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43–0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20–0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs. Conclusions: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.

Published
2021

17. Low diaphragm muscle mass predicts adverse outcome in patients hospitalized for COVID-19 pneumonia: An exploratory pilot study

Author

Corradi, F., Isirdi, A., Malacarne, P., Santori, G., Barbieri, G., Romei, C., Bove, T., Vetrugno, L., Falcone, M., Bertini, P., Guarracino, F., Landoni, G., Forfori, F., UCARE (Ultrasound in Critical care and Anesthesia Research Group): Claudia BRUSASCO, Nicoletta, Carpenè, Carrozzi, Laura, Celi, Alessandro, Virginia, Chirici, Diego, Costanzo, Francesco, Cundari, Salvatore DE MARCO, Alessandra DELLA ROCCA, Massimo, Desideri, Gargani, Luna, Lorenzo, Ghiadoni, Alberto, Laffi, Francesco, Menichetti, Marco, Monfroni, Fabio, Monzani, Chiara, Piagnani, Massimo, Santini, Ludovica, Tecchi, Giusy, Tiseo, Virdis, Agostino, Corradi, F., Isirdi, A., Malacarne, P., Santori, G., Barbieri, G., Romei, C., Bove, T., Vetrugno, L., Falcone, M., Bertini, P., Guarracino, F., Landoni, G., and Forfori, F.

Subjects
Male, medicine.medical_specialty, Diaphragm, Respiratory insufficiency, Ultrasonography, Aged, Aged, 80 and over, COVID-19, Cohort Studies, Female, Hospital Mortality, Humans, Italy, Kaplan-Meier Estimate, Middle Aged, Pilot Projects, Pneumonia, Viral, Predictive Value of Tests, Respiration, Artificial, Respiratory Insufficiency, Respiratory Muscles, Treatment Outcome, medicine.medical_treatment, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, medicine, 80 and over, Viral, Mechanical ventilation, business.industry, Respiration, 030208 emergency & critical care medicine, Pneumonia, medicine.disease, Diaphragm (structural system), Anesthesiology and Pain Medicine, Respiratory failure, Predictive value of tests, Emergency medicine, Artificial, Abnormality, business, Cohort study
Abstract

BACKGROUND: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. METHODS: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P

Published
2021

18. Irinotecan-based chemotherapy in extrapulmonary neuroendocrine carcinomas: survival and safety data from a multicentric Italian experience

Author

Lorenzo Antonuzzo, Alice Laffi, Marco Ferrari, Federica Bertolini, Daniele Lavacchi, Riccardo Marconcini, Krisida Cerma, Chiara Santini, Gabriele Luppi, Massimo Dominici, Fabio Gelsomino, Margherita Rimini, Annalisa Fontana, C. Bardasi, Stefania Benatti, Kalliopi Andrikou, Andrea Spallanzani, Massimiliano Salati, Francesco Caputo, Francesca Spada, and Andrea Casadei-Gardini

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Neutropenia, Irinotecan, Gastroenterology, Chemotherapy, NEC, Neuroendocrine carcinoma, Second-line treatment, Survival, Endocrinology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Etoposide, Aged, XELIRI, business.industry, Standard treatment, Middle Aged, medicine.disease, Carcinoma, Neuroendocrine, Neuroendocrine Tumors, Regimen, Italy, FOLFIRI, Female, business, medicine.drug
Abstract

Neuroendocrine carcinomas (NECs) are a rare subgroup of neuroendocrine neoplasms that occasionally originate from gastro-entero-pancreatic (GEP) tract. Evidence of the effectiveness of chemotherapy is scarce. Platinum plus Etoposide regimens are currently the standard treatment in first-line, while little data are available on second-line treatments. The aim of this study is to evaluate the efficacy and safety of irinotecan (IRI)-based chemotherapy in a series of extrapulmonary NECs. Patients with NEC diagnosis treated at University Hospitals of Modena, Florence, Pisa, and European Institute of Oncology of Milan with an IRI-based regimen (FOLFIRI or XELIRI) after progression to a first-line platinum-based therapy were enrolled. Objective responses were assessed according to RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. Thirty-four patients, 16 males, and 18 females, median age of 59 years (range 32–77), with metastatic NEC were included. Twenty-seven patients had Ki-67 ≥ 55% and four patients Ki-67 of

Published
2021

19. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

Author

Caraceni, Paolo, Riggio, Oliviero, Angeli, Paolo, Alessandria, Carlo, Neri, Sergio, Foschi, Francesco G, Levantesi, Fabio, Airoldi, Aldo, Boccia, Sergio, Svegliati-Baroni, Gianluca, Fagiuoli, Stefano, Romanelli, Roberto G, Cozzolongo, Raffaele, Di Marco, Vito, Sangiovanni, Vincenzo, Morisco, Filomena, Toniutto, Pierluigi, Tortora, Annalisa, De Marco, Rosanna, Angelico, Mario, Cacciola, Irene, Elia, Gianfranco, Federico, Alessandro, Massironi, Sara, Guarisco, Riccardo, Galioto, Alessandra, Ballardini, Giorgio, Rendina, Maria, Nardelli, Silvia, Piano, Salvatore, Elia, Chiara, Prestianni, Loredana, Cappa, Federica Mirici, Cesarini, Lucia, Simone, Loredana, Pasquale, Chiara, Cavallin, Marta, Andrealli, Alida, Fidone, Federica, Ruggeri, Matteo, Roncadori, Andrea, Baldassarre, Maurizio, Tufoni, Manuel, Zaccherini, Giacomo, Bernardi, Mauro, Domenicali, Marco, Giannone, Ferdinando A, Merli, Manuela, Gioia, Stefania, Fasolato, Silvano, Sticca, Antonietta, Campion, Daniela, Risso, Alessandro, Saracco, Giorgio M, Maiorca, Daniela, Rizzotto, Agostino, Lanzi, Arianna, Neri, Elga, Visani, Anna, Mastroianni, Antonio, Alberti, Alberto B, Mazzarelli, Chiara, Vangeli, Marcello, Marzioni, Marco, Capretti, Francesca, Kostandini, Alba, Magini, Giulia, Colpani, Maria, Laffi, Giacomo, Gabbani, Tommaso, Marsico, Maria, Zappimbulso, Marianna, Petruzzi, Josè, Calvaruso, Vincenza, Parrella, Giovanni, Caporaso, Nicola, Auriemma, Francesco, Guarino, Maria, Pugliese, Fabio, Gasbarrini, Antonio, Leo, Pietro, De Leonardis, Francesco, Pecchioli, Alessandra, Rossi, Piera, Raimondo, Giovanni, Negri, Elisa, Dallio, Marcello, Loguercio, Carmelina, Conte, Dario, Celli, Natascia, Bringiotti, Roberto, Castellaneta, Nicola M, Salerno, Francesco, ANSWER Study Investigators, Caraceni, Paolo, Riggio, Oliviero, Angeli, Paolo, Alessandria, Carlo, Neri, Sergio, Foschi, Francesco G, Levantesi, Fabio, Airoldi, Aldo, Boccia, Sergio, Svegliati-Baroni, Gianluca, Fagiuoli, Stefano, Romanelli, Roberto G, Cozzolongo, Raffaele, Di Marco, Vito, Sangiovanni, Vincenzo, Morisco, Filomena, Toniutto, Pierluigi, Tortora, Annalisa, De Marco, Rosanna, Angelico, Mario, Cacciola, Irene, Elia, Gianfranco, Federico, Alessandro, Massironi, Sara, Guarisco, Riccardo, Galioto, Alessandra, Ballardini, Giorgio, Rendina, Maria, Nardelli, Silvia, Piano, Salvatore, Elia, Chiara, Prestianni, Loredana, Cappa, Federica Mirici, Cesarini, Lucia, Simone, Loredana, Pasquale, Chiara, Cavallin, Marta, Andrealli, Alida, Fidone, Federica, Ruggeri, Matteo, Roncadori, Andrea, Baldassarre, Maurizio, Tufoni, Manuel, Zaccherini, Giacomo, Bernardi, Mauro, Domenicali, Marco, Giannone, Ferdinando A, Merli, Manuela, Gioia, Stefania, Fasolato, Silvano, Sticca, Antonietta, Campion, Daniela, Risso, Alessandro, Saracco, Giorgio M, Maiorca, Daniela, Rizzotto, Agostino, Lanzi, Arianna, Neri, Elga, Visani, Anna, Mastroianni, Antonio, Alberti, Alberto B, Mazzarelli, Chiara, Vangeli, Marcello, Marzioni, Marco, Capretti, Francesca, Kostandini, Alba, Magini, Giulia, Colpani, Maria, Laffi, Giacomo, Gabbani, Tommaso, Marsico, Maria, Zappimbulso, Marianna, Petruzzi, Josè, Calvaruso, Vincenza, Parrella, Giovanni, Caporaso, Nicola, Auriemma, Francesco, Guarino, Maria, Pugliese, Fabio, Gasbarrini, Antonio, Leo, Pietro, De Leonardis, Francesco, Pecchioli, Alessandra, Rossi, Piera, Raimondo, Giovanni, Negri, Elisa, Dallio, Marcello, Loguercio, Carmelina, Conte, Dario, Celli, Natascia, Bringiotti, Roberto, Castellaneta, Nicola M, Salerno, Francesco, Caraceni P1, Riggio O2, Angeli P3, Alessandria C4, Neri S5, Foschi FG6, Levantesi F7, Airoldi A8, Boccia S9, Svegliati-Baroni G10, Fagiuoli S11, Romanelli RG12, Cozzolongo R13, Di Marco Vito, Sangiovanni V15, Morisco F16, Toniutto P17, Tortora A18, De Marco R19, Angelico M20, Cacciola I21, Elia G22, Federico A23, Massironi S24, Guarisco R25, Galioto A26, Ballardini G27, Rendina M28, Nardelli S2, Piano S3, Elia C4, Prestianni L5, Cappa FM6, Cesarini L8, Simone L9, Pasquale C2, Cavallin M3, Andrealli A4, Fidone F5, Ruggeri M29, Roncadori A30, Baldassarre M1, Tufoni M1, Zaccherini G1, Bernardi M31, Domenicali M, Giannone FA, Merli M, Gioia S, Fasolato S, Sticca A, Campion D, Risso A, Saracco GM, Maiorca D, Rizzotto A, Lanzi A, Neri E, Visani A, Mastroianni A, Alberti AB, Mazzarelli C, Vangeli M, Marzioni M, Capretti F, Kostandini A, Magini G, Colpani M, Laffi G, Gabbani T, Marsico M, Zappimbulso M, Petruzzi J, Calvaruso Vincenza, Parrella G, Caporaso N, Auriemma F, Guarino M, Pugliese F, Gasbarrini A, Leo P, De Leonardis F, Pecchioli A, Rossi P, Raimondo G, Negri E, Dallio M, Loguercio C, Conte D, Celli N, Bringiotti R, Castellaneta NM, Salerno F., Caraceni P, Riggio O, Angeli P, Alessandria C, Neri S, Foschi FG, Levantesi F, Airoldi A, Boccia S, Svegliati-Baroni G, Fagiuoli S, Romanelli RG, Cozzolongo R, Di Marco V, Sangiovanni V, Morisco F, Toniutto P, Tortora A, De Marco R, Angelico M, Cacciola I, Elia G, Federico A, Massironi S, Guarisco R, Galioto A, Ballardini G, Rendina M, Nardelli S, Piano S, Elia C, Prestianni L, Cappa FM, Cesarini L, Simone L, Pasquale C, Cavallin M, Andrealli A, Fidone F, Ruggeri M, Roncadori A, Baldassarre M, Tufoni M, Zaccherini G, Bernardi M, Domenicali M, Giannone FA, Merli M, Gioia S, Fasolato S, Sticca A, Campion D, Risso A, Saracco GM, Maiorca D, Rizzotto A, Lanzi A, Neri E, Visani A, Mastroianni A, Alberti AB, Mazzarelli C, Vangeli M, Marzioni M, Capretti F, Kostandini A, Magini G, Colpani M, Laffi G, Gabbani T, Marsico M, Zappimbulso M, Petruzzi J, Calvaruso V, Parrella G, Caporaso N, Auriemma F, Guarino M, Pugliese F, Gasbarrini A, Leo P, De Leonardis F, Pecchioli A, Rossi P, Raimondo G, Negri E, Dallio M, Loguercio C, Conte D, Celli N, Bringiotti R, Castellaneta NM, Salerno F., Caraceni, P, Riggio, O, Angeli, P, Alessandria, C, Neri, S, Foschi, F, Levantesi, F, Airoldi, A, Boccia, S, Svegliati-Baroni, G, Fagiuoli, S, Romanelli, R, Cozzolongo, R, Di Marco, V, Sangiovanni, V, Morisco, F, Toniutto, P, Tortora, A, De Marco, R, Angelico, M, Cacciola, I, Elia, G, Federico, A, Massironi, S, Guarisco, R, Galioto, A, Ballardini, G, Rendina, M, Nardelli, S, Piano, S, Elia, C, Prestianni, L, Cappa, F, Cesarini, L, Simone, L, Pasquale, C, Cavallin, M, Andrealli, A, Fidone, F, Ruggeri, M, Roncadori, A, Baldassarre, M, Tufoni, M, Zaccherini, G, Bernardi, M, Domenicali, M, Giannone, F, Merli, M, Gioia, S, Fasolato, S, Sticca, A, Campion, D, Risso, A, Saracco, G, Maiorca, D, Rizzotto, A, Lanzi, A, Neri, E, Visani, A, Mastroianni, A, Alberti, A, Mazzarelli, C, Vangeli, M, Marzioni, M, Capretti, F, Kostandini, A, Magini, G, Colpani, M, Laffi, G, Gabbani, T, Marsico, M, Zappimbulso, M, Petruzzi, J, Calvaruso, V, Parrella, G, Caporaso, N, Auriemma, F, Guarino, M, Pugliese, F, Gasbarrini, A, Leo, P, De Leonardis, F, Pecchioli, A, Rossi, P, Raimondo, G, Negri, E, Dallio, M, Loguercio, C, Conte, D, Celli, N, Bringiotti, R, Castellaneta, N, and Salerno, F

Subjects
Liver Cirrhosis, Male, Time Factors, Cirrhosis, Kaplan-Meier Estimate, law.invention, ascites, 0302 clinical medicine, Hepatorenal syndrome, Randomized controlled trial, Furosemide, law, Ascites, Clinical endpoint, Paracentesis, Diuretics, albumin, decompensated cirrhosi, Mineralocorticoid Receptor Antagonists, Settore MED/12 - Gastroenterologia, Medicine (all), Hazard ratio, General Medicine, Middle Aged, Survival Rate, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Quality-Adjusted Life Years, medicine.symptom, Hyponatremia, medicine.medical_specialty, 03 medical and health sciences, Albumins, Internal medicine, medicine, Humans, Survival rate, albumin, Aged, business.industry, cirrhosis, medicine.disease, Clinical trial, albumin, cirrhosis, ascites, liver decompensation, Quality of Life, Hyperkalemia, business, Esophagus Varices, Portal Hypertension, Varicosis
Abstract

Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Funding Italian Medicine Agency. Copyright © 2018 Elsevier Ltd. All rights reserved.

Published
2018

20. Super-Resolution Microscopy Reveals an Altered Fibrin Network in Cirrhosis: The Key Role of Oxidative Stress in Fibrinogen Structural Modifications

Author

Matteo Becatti, Niccolò Taddei, Giacomo Laffi, Amanda Mannucci, Stefano Gitto, Francesco Vizzutti, Claudia Fiorillo, Fabio Marra, and Flavia Rita Argento

Subjects
Pore size, medicine.medical_specialty, Cirrhosis, Physiology, fibrinogen oxidation, Clinical Biochemistry, Oxidative phosphorylation, 030204 cardiovascular system & hematology, Fibrinogen, medicine.disease_cause, Biochemistry, Article, Fibrin, 03 medical and health sciences, stimulated emission depletion (STED) microscopy, 0302 clinical medicine, Internal medicine, medicine, Thrombus, Molecular Biology, biology, business.industry, cirrhosis, lcsh:RM1-950, Cell Biology, medicine.disease, Redox status, Endocrinology, lcsh:Therapeutics. Pharmacology, fibrin structure, thrombus, biology.protein, 030211 gastroenterology & hepatology, business, Oxidative stress, medicine.drug
Abstract

Cirrhotic patients show a reduced synthesis of both pro- and anti-coagulant factors. Recent reports indicate that they are characterized by a higher risk of thrombotic rather than hemorrhagic complications, but the mechanisms conferring this risk are not fully elucidated. Oxidative-mediated fibrinogen modifications may explain, at least in part, a prothrombotic profile. The aim of the present pilot study was to investigate the alterations in fibrinogen structure and function in patients with cirrhosis of various severity and to correlate these findings with the mechanisms of thrombus formation. We assessed in plasma specific oxidative stress markers and measured oxidative modifications, functional and structural parameters in purified fibrinogen fractions obtained from cirrhotic patients and control subjects. We enrolled 15 cirrhotic patients (5 patients belonging to each of the three Child&ndash, Turcotte&ndash, Pugh classes) and 20 age- and sex-matched healthy controls. Plasma redox status, fibrinogen oxidative modifications, thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in cirrhotic patients and were associated to disease severity. Importantly, clot structure obtained by stimulated emission depletion (STED) super-resolution microscopy indicated modifications in fiber diameter and in clot porosity in cirrhotic patients. Fibrin fiber diameter significantly decreased in cirrhotic patients when compared to controls, and this difference became more marked with disease progression. In parallel, fibrin pore size progressively decreased along with disease severity. In cirrhotic patients, fibrinogen clot analysis and oxidative-dependent changes reveal novel structural and functional fibrinogen modifications which may favor thrombotic complications in cirrhosis.

Published
2020

21. SARS-CoV-2-related pneumonia can be successfully managed in patients with metastatic neuroendocrine tumors: a critical point of view

Author

Luigi Funicelli, Manila Rubino, Rocio Garcia-Carbonero, Giulia Zampino, S. Pellicori, Francesca Spada, Alice Laffi, Lorenzo Gervaso, and Nicola Fazio

Subjects
Male, Axitinib, Endocrinology, Diabetes and Metabolism, Disease, Comorbidity, Neuroendocrine tumors, Azithromycin, medicine.disease_cause, Tyrosine-kinase inhibitor, 0302 clinical medicine, Endocrinology, Viral, Tomography, Coronavirus, Randomized Controlled Trials as Topic, Protein-Tyrosine Kinases, X-Ray Computed, Thymus, Neuroendocrine Tumors, Treatment Outcome, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Italy, 030220 oncology & carcinogenesis, Coronavirus Infections, medicine.drug, Hydroxychloroquine, medicine.medical_specialty, medicine.drug_class, Pneumonia, Viral, 030209 endocrinology & metabolism, Carcinoid Tumor, 03 medical and health sciences, Betacoronavirus, Viewpoint, medicine, Humans, Intensive care medicine, Pandemics, Aged, business.industry, SARS-CoV-2, Cancer, COVID-19, Pneumonia, Thymus Neoplasms, medicine.disease, NET, business, Tomography, X-Ray Computed
Abstract

Primary neuroendocrine tumors of the thymus are extremely rare. In patients with advanced disease, tumor growth control, and sometimes also syndrome control are the main goals of systemic therapy. Unfortunately, no standard therapies are available in clinical practice; therefore, clinical studies are strongly recommended. Axitinib (AXI) is a tyrosine kinase inhibitor, currently under investigation in an international phase II/III trial including thymic neuroendocrine tumors. Over the past 5 months, the entire world has been facing a devastating medical emergency brought about by a pandemic due to a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, in late 2019. Since then, health professionals have been expending all their efforts on trying to provide the best available treatments for patients involved. Patients with cancer, especially those with thoracic involvement, are at higher risk of coronavirus disease 19 (COVID-19) and its complications because of their immunosuppressive status caused by the cancer and the anticancer therapies. As it remains unclear how to optimally manage such patients, we wished to report our experience with a patient with a metastatic neuroendocrine tumor of the thymus infected with SARS-CoV-2 in the hope that it may provide some insights and reflections on the management of cancer patients during this challenging time in our history.

Published
2020

22. Altered clot formation and lysis are associated with increased fibrinolytic activity in ascites in patients with advanced cirrhosis

Author

Francesco Vizzutti, Donatella Lami, Mario Del Rosso, Rosanna Abbate, Anna Paola Cellai, Gabriella Fibbi, Stefano Gitto, Roberto Giulio Romanelli, Giacomo Laffi, and Francesca Margheri

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, 030204 cardiovascular system & hematology, Tissue plasminogen activator, Fibrin, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fibrinolysis, Ascites, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Blood Coagulation, Aged, biology, business.industry, medicine.disease, Prognosis, Endocrinology, Coagulation, Hemostasis, Emergency Medicine, biology.protein, Female, Blood Coagulation Tests, medicine.symptom, business, Plasminogen activator, Biomarkers, medicine.drug
Abstract

Analysis of coagulation disorders and assessment of rebalanced hemostasis with the use of traditional coagulation assays is challenging in cirrhotic patients. Therefore, alternative tests are under investigation for the evaluation of coagulopathy in this specific setting. Aim of this study was to analyze the modifications of clot structure and function in cirrhotic patients with different degrees of severity. Cirrhotic patients referred to our Unit were consecutively enrolled. Global test measurements, including clot and lysis assays, clot lysis time, and determination of other fibrinolytic parameters, were performed. Analyses of clot formation, morphology, and lysis were performed with a turbidimetric clotting and lysis assay (EuroCLOT). Lysis of a tissue factor-induced clot by exogenous tissue plasminogen activator was analyzed by studying the modifications of turbidity during clot formation and the following lysis. We evaluated coagulative and fibrinolytic parameters in both plasma and ascites. Urokinase plasminogen activator (uPA) and gelatinase activity in ascites were also measured. We analyzed data from 33 cirrhotic patients (11 in Child–Pugh class A; 22 in class B or C and with ascites) and 21 healthy subjects (HS). In class B/C patients prolonged latency time, a decline in clotting absorbance, and decreased fibrin formation were observed in comparison with class A and HS. Generated curves and Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) progressively declined from HS to class C patients, whereas levels of plasminogen activator inhibitor-1 and tissue plasminogen activator increased. D-dimer levels were markedly increased in ascites, together with significantly smaller levels of TAFI, αlfa2-antiplasmin, and plasminogen. Caseinolytic activity was also present. Class C patients showed smaller amount of uPA and significantly lower levels of matrix metallopeptidases (MMP)2 in ascites in comparison with Class B subjects. Clot formation and lysis are altered in cirrhosis and fibrinolysis is activated in ascites. Ascitic levels of uPA and MMP2 are reduced and inversely related to the severity of liver disease.

Published
2020

23. Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study

Author

Tiziana Olivieri, Nicola De Maria, Gian Piero Guerrini, Andrea Mega, Heinz Zoller, Paolo Magistri, Giovanna Valente, Paolo De Simone, Laura Turco, Erica Villa, Stefano Gitto, Guido Piai, Paolo Forte, Stefano Di Sandro, Fabio Marra, Valentina Serra, Giuseppe Tarantino, Giacomo Laffi, Paola Carrai, Margherita Falcini, Francesco Vizzutti, Edoardo Borelli, Stefania Petruccelli, Roberto Ballarin, Margherita Marocchi, Giovanni Vitale, Rachele Puntili, Fabrizio Di Benedetto, L. Marzi, Filippo Schepis, and Pietro Andreone

Subjects
medicine.medical_specialty, Multivariate analysis, Cardiovascular risk factors, Diabetes mellitus, Metabolic syndrome, Follow-Up Studies, Humans, Retrospective Studies, Risk Factors, Cardiovascular Diseases, Diabetes Mellitus, Liver Transplantation, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, Medicine, 030212 general & internal medicine, Risk factor, Survival analysis, Proportional hazards model, business.industry, medicine.disease, medicine.symptom, business, Weight gain
Abstract

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Published
2020

25. Pharmacodynamics, clinical findings and approval status of current and emerging tyrosine-kinase inhibitors for pancreatic neuroendocrine tumors

Author

Paola Zagami, Alice Laffi, Francesca Spada, Nicola Fazio, Chiara Alessandra Cella, Marzia Del Re, and Manila Rubino

Subjects
Oncology, medicine.medical_specialty, Cabozantinib, sunitinib, Context (language use), panNET, Angiogenesis Inhibitors, Antineoplastic Agents, Neuroendocrine tumors, Toxicology, 030226 pharmacology & pharmacy, Pazopanib, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Development, Internal medicine, tyrosine kinase inhibitors, medicine, Animals, Humans, Protein Kinase Inhibitors, Pharmacology, Everolimus, business.industry, Sunitinib, Clinical study design, General Medicine, medicine.disease, respiratory tract diseases, Pancreatic Neoplasms, Neuroendocrine Tumors, chemistry, 030220 oncology & carcinogenesis, business, Lenvatinib, medicine.drug
Abstract

Introduction: Pancreatic neuroendocrine tumors (panNETs) represent a rare group of malignancies. For decades, chemotherapy, somatostatin analogs and interferon represented the only systemic therapies; however, over the latest years, new options were registered, including Everolimus, Sunitinib (SUN), and Peptide Receptor Radionuclide Therapy.Areas covered: This review discusses the role of tyrosine kinase inhibitors (TKIs) in advanced panNETs.Expert opinion: TKIs showed an antiangiogenic and antiproliferative impact on advanced panNETs. Sunitinib is the only TKI currently available in clinical practice, having been approved on the basis of relevant results of a specific panNET phase III trial. New TKIs, such as Cabozantinib, Lenvatinib, Pazopanib, Surufatinib are still on investigation in panNETs. Although some phase II studies with the new TKIs yielded better PFS and RR compared with SUN, different study designs and tumor populations may have induced selection biases. However, it was reported that panNETs resistant to SUN could respond to a new TKI, indicating a possible further therapeutic line in this context. The global investigation plan of TKIs in panNETs is not homogeneous and it is difficult to understand what kind of development this can have in the near future for clinical practice.

Published
2019

26. Epidemiological, demographic and clinical data on chronic viral hepatitis C in Tuscany

Author

Alessandro Nerli, Roberto Berni, Andrea Galli, Santino Marchi, Massimo Giusti, Maurizia Rossana Brunetto, Caterina Silvestri, Paola Carrai, Rodolfo Sacco, Silvia Chigiotti, Pierluigi Blanc, Giampaolo Bresci, Paolo Forte, Piero Colombatto, Andrea Cozzi, Alessandro Bartoloni, Cesira Nencioni, Cristina Orsini, Sauro Luchi, Giampaolo Corti, Franco Filipponi, Silvia Carloppi, P. Almi, Ricciardi L, Giacomo Laffi, Anna Linda Zignego, Stefano Milani, Fabio Voller, Cristina Stasi, Andrea De Luca, D. Aquilini, Francesco Cipriani, and Angelo Ricchiuti

Subjects
Adult, Male, medicine.medical_specialty, Hepatitis C virus, Comorbidity, Hepacivirus, 030204 cardiovascular system & hematology, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, 030212 general & internal medicine, Chronic viral hepatitis C, Antiviral treatment, Aged, Hepatitis, business.industry, Public health, General Medicine, Hepatitis C, Chronic, Middle Aged, medicine.disease, Virology, Italy, Female, sense organs, business
Abstract

Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries' economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy.We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress.Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin's lymphoma in 10.5%).Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

Published
2018

27. QT Adaptation during Exercise in Cirrhosis

Author

Giacomo Laffi, Giuseppe Barletta, Fabio Marra, Maria Riccarda Del Bene, Francesco Venditti, and Roberto Giulio Romanelli

Subjects
medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, medicine.drug_class, Long QT syndrome, Gastroenterology, Diastole, Physical exercise, medicine.disease, QT interval, Cirrhotic cardiomyopathy, Internal medicine, Cardiology, Natriuretic peptide, Medicine, Repolarization, business
Abstract

AIM: QT-interval prolongation is frequently seen in cirrhosis; whether it is simply a marker of disease severity is debated. Analysis of QT-interval behavior during physical exercise may disclose more specific abnormalities of cardiac repolarization of cirrhotic cardiomyopathy. MATERIALS AND METHODS: Thirty-eight out-patients with non-alcoholic liver cirrhosis and portal hypertension (32 males, aged 62 ± 9 years) and 36 sex- and age-matched healthy volunteers (32 males; aged 59 ± 7 years) underwent bicycle exercise test with QT-interval measurement, echocardiographic and Doppler analysis of systolic and diastolic left ventricular function, determinations of systemic hemodynamic and pro-brain natriuretic peptide concentration. RESULTS: Patients had longer Fridericia-corrected QT-interval than healthy subjects at baseline and peak-exercise, and reduced chronotropic index, despite similar predicted workload. Corrected-QT shortening extent at peak-exercise was the same; however, in early-exercise, corrected-QT increased in 6 healthy subjects versus 25 patients, and in patients the increase was greater and significantly delayed. QT hysteresis was greater in patients. Abnormal repolarization during exercise and recovery in patients with normal baseline corrected-QT did not correlate to Child-Pugh class and hemodynamic alterations, whereas patients with > 440 ms corrected-QT (n = 16) showed diastolic dysfunction and increased pro-brain natriuretic peptide. CONCLUSIONS: QT behavior during physical exercise supports the hypothesis of anomalous modulation of potassium currents in cirrhosis; only long rest corrected-QT correlates to clinical signs of cirrhotic cardiomyopathy.

Published
2018

28. 1104P Functional imaging and clinical outcomes in grade 3 neuroendocrine tumors (NETs G3): A single-center retrospective analysis

Author

Massimo Barberis, Eleonora Pisa, Vincenzo Bagnardi, G. Buonsanti, Manila Rubino, Francesca Spada, M.C. Grana, Marzia Colandrea, Samuele Frassoni, Alice Laffi, and Nicola Fazio

Subjects
Functional imaging, medicine.medical_specialty, Oncology, business.industry, medicine, Retrospective analysis, Hematology, Radiology, Neuroendocrine tumors, Single Center, medicine.disease, business
Published
2021

29. Comparison of the effects of lockdown due to COVID-19 on glucose patterns among children, adolescents, and adults with type 1 diabetes: CGM study

Author

Andrea Pession, Uberto Pagotto, Simona Moscatiello, Gilberto Laffi, Lorenzo Tucci, Giulio Maltoni, Claudio Bongiorno, Guido Di Dalmazi, Valeria Di Natale, Stefano Zucchini, DI Dalmazi G., Maltoni G., Bongiorno C., Tucci L., DI Natale V., Moscatiello S., Laffi G., Pession A., Zucchini S., and Pagotto U.

Subjects
Blood Glucose, Male, Research design, Pediatrics, Activities of daily living, Endocrinology, Diabetes and Metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Insulin, Child, diabetes mellitu, Middle Aged, type 1, Italy, diabetes mellitus, Female, Coronavirus Infections, Human, Adult, Insulin pump, medicine.medical_specialty, Adolescent, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Monitoring, Ambulatory, Betacoronavirus, Diabetes mellitus, Blood Glucose Self-Monitoring, medicine, Humans, Hypoglycemic Agents, Pandemics, Exercise, Type 1 diabetes, lcsh:RC648-665, Betacoronaviru, Hypoglycemic Agent, Pandemic, SARS-CoV-2, Coronavirus Infection, business.industry, COVID-19, Emerging Technologies, Pharmacology and Therapeutics, medicine.disease, Diabetes Mellitus, Type 1, Metabolic control analysis, Communicable Disease Control, business, Stress, Psychological
Abstract

IntroductionThe COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 (‘lockdown’), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors.Research design and methodsWe enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13–17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires.ResultsIn children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)ConclusionIn patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.

Published
2020

30. Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

Author

Anna Lisa Iorio, Giacomo Laffi, Maurizio de Martino, Francesco Cardile, Lorenzo Genitori, Claudio Pisano, Martina Da Ros, Maurizio Lucchesi, Fabiana Colelli, Iacopo Sardi, and Giacomo Signorino

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, Animal model, Blood-brain barrier, Glioblastoma, Morphine, Temozolomide, temozolomide, Pharmacology, Blood–brain barrier, 03 medical and health sciences, 0302 clinical medicine, In vivo, Internal medicine, medicine, Chemotherapy, business.industry, animal model, glioblastoma, morphine, blood-brain barrier, medicine.disease, Radiation therapy, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Toxicity, business, Research Paper, medicine.drug
Abstract

// Anna Lisa Iorio 1 , Martina da Ros 1 , Lorenzo Genitori 1 , Maurizio Lucchesi 1 , Fabiana Colelli 2 , Giacomo Signorino 2 , Francesco Cardile 2 , Giacomo Laffi 3 , Maurizio de Martino 1 , Claudio Pisano 2 and Iacopo Sardi 1 1 Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, Florence, Italy 2 BIOGEM Research Institute, Ariano Irpino, Italy 3 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy Correspondence to: Iacopo Sardi, email: iacopo.sardi@meyer.it Keywords: temozolomide, glioblastoma, morphine, blood-brain barrier, animal model Received: November 15, 2016 Accepted: July 13, 2017 Published: August 03, 2017 ABSTRACT Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months. Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ. The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy. The effect of morphine, on tumor cell growth and P-glycoprothein (P-gp) activity, was investigate in in vitro models. The results demonstrated that GBM cells growth is not influenced by morphine treatment and, for the first time, we show that morphine is an inhibitor of the activity of P-gp efflux transporter who is markedly expressed on BBB. In vivo , response to the treatments TMZ plus morphine was investigated in an orthotopic nude mice model of GBM. Animals treated with TMZ metronomic doses showed a significant tumor growth inhibition compared to untreated mice and association with morphine appears to improve TMZ efficacy. Moreover, the combination of morphine with lower dose of TMZ result in a cytostatic effect on tumor growth over the period of the pharmacological treatments. In conclusion this novel approach could be a successful strategy to overcome chemoresistance and side effects TMZ mediated, reducing drug dosage and improving long term response, in GBM therapy.

Published
2017

31. Neuroendocrine tumors of the cervix: an urgent call for joining forces

Author

Giovanni Aletti and Alice Laffi

Subjects
Gynecology, Female circumcision, Oncologists, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, Uterine Cervical Neoplasms, Enteroendocrine cell, Reproductive age, Neuroendocrine tumors, medicine.disease, female genital diseases and pregnancy complications, 03 medical and health sciences, Neuroendocrine Tumors, 0302 clinical medicine, medicine.anatomical_structure, Uterine cervix, Oncology, 030220 oncology & carcinogenesis, medicine, Humans, Female, business, Cervix
Abstract

Neuroendocrine tumors are aggressive and develop from endocrine cells in various organs, including the female genital tract, and specifically the uterine cervix. They account for 0.9%–1.5% of all tumors of the uterine cervix and generally affect women of reproductive age. Given the rarity of the

Published
2019

32. Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

Author

Basili, Stefania, Carnevale, Roberto, Nocella, Cristina, Bartimoccia, Simona, Raparelli, Valeria, Talerico, Giovanni, Stefanini, Lucia, Romiti, Giulio F, Perticone, Francesco, Corazza, Gino R, Piscaglia, Fabio, Pietrangelo, Antonello, Violi, Francesco, and PRO-LIVER collaborators, : Ainora Maria Elena, Andreozzi, Paola, Andriulli, Angelo, Angelico, Francesco, Angelico, Mario, Figliomeni, Antonio, Anzaldi, Massimiliano, Arena, Umberto, Averna, Maurizio, Barone, Milena, Bazzini, Cristina, Bergamaschi, Gaetano, Bertoni, Michele, Bianchi Giovanni Battista, Bianchi Paola Ilaria, Boari, Benedetta, Bombonato, Giancarlo, Bracco, Christian, Brocco, Silvia, Buonauro, Agostino, Buttà, Carmelo, Buzzetti, Elena, Cacciola, Irene, Calabria, Stefano, Cangemi, Roberto, Capeci, William, Caradio, Federica, Carderi, Isabella, Carleo, Pietro, Caroleo, Benedetto, Carrabba Maria Domenica, Castorani, Luigi, Cavallo, Maurizio, Cecchetto, Lara, Cesaro, Flavio, Cicco, Sebastiano, Cimini, Claudia, Colombo Barbara Maria, Corradini, Elena, Corrao, Salvatore, Costantino, Giorgio, Costanzo, Filippo, Croce, Giuseppe, Cuoghi, Chiara, Curigliano, Valentina, D’Alitto, Felicia, D’Amico, Gennaro, De Franchis Roberto, De Giorgi Alfredo, De Vuono Stefano, Debernardi Venon Wilma, Del Ben Maria, Del Corso Lisette, Delitala, Giuseppe, Denegri, Andrea, Di Cesare Valentina, Di Giosia Paolo, Di Michele Dario, Di Minno Giovanni, Donnarumma, Emilia, Drenaggi, Davide, Durante-Mangoni, Emanuele, Falsetti, Lorenzo, Farcomeni, Alessio, Farinaro, Vincenza, Fasolato, Silvano, Ferrari, Giovanni, Fierro, Tiziana, Forgione, Alessandra, Frugiuele, Pierluigi, Galati, Giovanni, Gallo, Paolo, Garcovich, Matteo, Gargano, Ruggiero, Gasbarrini, Antonio, Gatta, Angelo, Giammanco, Antonina, Giannelli, Gianluigi, Giorgini, Paolo, Gobbi, Paolo, Granito, Alessandro, Grassi, Davide, Greco, Antonio, Grembiale, Alessandro, Gresele, Paolo, Hijazi, Daniel, Iacobellis, Angelo, Iamele, Luigi, Invernizzi, Pietro, Ippolito, Antonio, Laffi, Giacomo, Licata, Anna, Liguori Maria Livia, Lorusso, Giusi, Maimone, Sergio, Manfredini, Roberto, Marcacci, Matteo, Marchese, Alessandra, Marinelli, Sara, Marra Alberto Maria, Martino Giuseppe Pio, Masala, Maristella, Masotti, Michela, Merla, Antonio, Miceli, Giuseppe, Montebianco Abenavoli Ludovico, Morana, Ignazio, Morelli, Olivia, Murgia, Giuseppe, Naccarato, Paola, Neri, Sergio, Niro, Grazia, Nobili, Lorenzo, Padula, Donatella, Palasciano, Giuseppe, Palmieri Vincenzo Ostilio, Pastori, Daniele, Pattoneri, Paolo, Perego, Francesca, Perticone, Maria, Pesce, Paola, Petramala, Luigi, Pettinari, Irene, Piano, Salvatore, Picardi, Antonio, Pignataro Francesca Serena, Pignataro, Pietro, Pignatelli, Pasquale, Pinna, Miriam, Pinto, Antonio, Pinto, Daniela, Polimeni, Licia, Pretti, Vincenzo, Privitera, Graziella, Proietti, Marco, Pucci, Giacomo, Purrello, Francesco, Ragone, Enrico, Raimondo, Giovanni, Restuccia, Tea, Riccardi, Laura, Rizzetto, Mario, Rodríguez-Castro Kryssia Isabel, Romanelli Roberto Giulio, Ruscio, Eleonora, Sacerdoti, David, Salinaro, Francesco, Salvi, Aldo, Salzano, Andrea, Santangelo, Giuseppe, Santarossa, Claudia, Santilli, Francesca, Santovito, Daniela, Scarpini, Francesca, Schiavone, Cosima, Scicali, Roberto, Senzolo, Marco, Serra, Carla, Serviddio, Gaetano, Sirico, Domenico, Soresi, Maurizio, Sperduti, Nicolò, Staffolani, Silvia, Staltari, Orietta, Stasi, Cristina, Suppressa, Patrizia, Svegliati Baroni Gianluca, Talia, Michela, Tana, Claudio, Tassone Eliezer Joseph, Todisco, Tommaso, Toriello, Filippo, Torres, Daniele, Traversa, Matteo, Tripepi, Giovanni, Tufano, Antonella, Tuttolomondo, Antonino, Varvara, Doriana, Vazzana, Natale, Vecchio Claudia Rita, Vendemiale, Gianluigi, Ventura, Paolo, Vespasiani-Gentilucci, Umberto, Vettore, Elia, Vidili, Gianpaolo, Villani, Rosanna, Vincenzo, Ronca, Visioli, Giacomo, Vitale, Francesco, Zocco Maria, Assunta., and Stefania Basili, Roberto Carnevale, Cristina Nocella, Simona Bartimoccia, Valeria Raparelli, Giovanni Talerico, Lucia Stefanini, Giulio F. Romiti, Francesco Perticone, Gino R. Corazza, Fabio Piscaglia, Antonello Pietrangelo, Francesco Violi, PRO-LIVER Collaborators, Alessandro Granito

Subjects
medicine.medical_specialty, Cirrhosis, Isoprostane, Urinary system, serum albumin, Serum albumin, Gastroenterology, NO, chemistry.chemical_compound, Internal medicine, Medicine, Platelet, portal vein thrombosis, Platelet activation, Portal vein thrombosis, Albumin, risk, protein, albumin, risk, Hepatology, biology, business.industry, cirrhosis, Albumin, Original Articles, medicine.disease, Portal vein thrombosis, chemistry, biology.protein, Original Article, protein, albumin, portal vein thrombosis, cirrhosis, business
Abstract

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound‐detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross‐sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, −0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40‐ligand (P = 0.0238), soluble Nox2‐derived peptide (sNox2‐dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD40L (Spearman’s rank correlation coefficient [rs], −0.33; P < 0.001), sNox2‐dp (rs, −0.57; P < 0.0001), and urinary excretion of isoprostanes (rs, −0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2‐dp, and urinary 8‐iso prostaglandin F2α‐III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2‐dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation.

Published
2019

33. Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis

Author

Chiara Alessandra Cella, Marta Pozzari, Nicola Fazio, Maicon Falavigna, Alice Laffi, S. Pellicori, Francesca Spada, and Taiane F. Rebelatto

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Organoplatinum Compounds, medicine.medical_treatment, Genes, BRCA2, Genes, BRCA1, Cochrane Library, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Pancreatic cancer, Internal medicine, Germline BRCA mutation, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Radiology, Nuclear Medicine and imaging, Stage (cooking), Germ-Line Mutation, Platinum-based chemotherapy, Randomized Controlled Trials as Topic, BRCA2 Protein, Chemotherapy, business.industry, BRCA1 Protein, Carcinoma, General Medicine, medicine.disease, BRCA1, BRCA2, Pancreatic Neoplasms, 030104 developmental biology, Genes, Pancreatic Ductal, 030220 oncology & carcinogenesis, Meta-analysis, Cohort, Carcinoma, Pancreatic Ductal, business
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Recent studies have shown that 4-20% of patients with PDAC have a germline BReast CAncer (gBRCA) genes 1 and 2 mutation (m). Because homologous recombination is impaired in patients with gBRCAm, some reports suggested that these tumors may be more sensitive to platinum compounds. Therefore, this systematic review and meta-analysis focused on benefit of patients with gBRCAm receiving a platinum-based chemotherapy (PtCh) compared with those treated with a non-platinum-based chemotherapy (NPtCh).The following electronic databases were searched from inception to May 12, 2018: PubMed (MEDLINE), EMBASE, and Cochrane Library. Abstracts from conferences were also reviewed for inclusion. Cohort, case-control and randomized studies of patients with PDAC and gBRCAm were eligible for inclusion if they provided data to compare patients receiving PtCh vs NPtCh. The primary endpoint was overall survival (OS) in the PtCh group vs the NPtCh group in patients with clinical stage III (locally advanced) or IV (metastatic) (CS III-IV) PDAC.Of 112 studies identified, 6 were included (total of 108 patients); of these, 4 provided sufficient data for meta-analysis. Half of the patients were males, with a mean age ranging from 58 to 63 years. The OS in the 85 patients with CS III-IV PDAC was higher in the PtCh group (23.7 vs 12.2 months; mean difference of 10.21 months, 95% confidence interval [CI] 5.05-15.37; P 0.001; very low quality of evidence). PtCh was associated with a lower mortality (62.3 vs 87.5%; relative risk of 0.80, 95%CI 0.66-0.97; P = 0.021; very low quality of evidence).Our study confirmed the hypothesis that patients with CS III-IV gBRCAm preferably benefit from a PtCh compared with NPtCh. However the very low quality of evidence should induce to be careful about the risk of potential biases. The generated hypothesis should be prospectively investigated in homogenous clinical settings.

Published
2019

34. A Machine Learning Decision Support System (DSS) for Neuroendocrine Tumor Patients Treated with Somatostatin Analog (SSA) Therapy

Author

Virginia Rossi, Serena Pillozzi, Rachele Fabbri, Jasminka Hasic Telalovic, Amedeo Amedei, Lorenzo Dreoni, Ernesto Iadanza, Daniele Lavacchi, Alice Laffi, Nicola Fazio, Lorenzo Antonuzzo, and Francesca Spada

Subjects
Medicine (General), Decision support system, Clinical Biochemistry, random forest classifier, Neuroendocrine tumors, Machine learning, computer.software_genre, Article, predictive biomarkers, 03 medical and health sciences, R5-920, 0302 clinical medicine, medicine, Stage (cooking), Adverse effect, 030304 developmental biology, Predictive biomarker, 0303 health sciences, business.industry, machine learning, neuroendocrine tumors, prognostic factors, somatostatin analogs, medicine.disease, Random forest, 030220 oncology & carcinogenesis, Artificial intelligence, business, Somatostatin analog, computer, Progressive disease
Abstract

The application of machine learning (ML) techniques could facilitate the identification of predictive biomarkers of somatostatin analog (SSA) efficacy in patients with neuroendocrine tumors (NETs). We collected data from 74 patients with a pancreatic or gastrointestinal NET who received SSA as first-line therapy. We developed three classification models to predict whether the patient would experience a progressive disease (PD) after 12 or 18 months based on clinic-pathological factors at the baseline. The dataset included 70 samples and 15 features. We initially developed three classification models with accuracy ranging from 55% to 70%. We then compared ten different ML algorithms. In all but one case, the performance of the Multinomial Naïve Bayes algorithm (80%) was the highest. The support vector machine classifier (SVC) had a higher performance for the recall metric of the progression-free outcome (97% vs. 94%). Overall, for the first time, we documented that the factors that mainly influenced progression-free survival (PFS) included age, the number of metastatic sites and the primary site. In addition, the following factors were also isolated as important: adverse events G3–G4, sex, Ki67, metastatic site (liver), functioning NET, the primary site and the stage. In patients with advanced NETs, ML provides a predictive model that could potentially be used to differentiate prognostic groups and to identify patients for whom SSA therapy as a single agent may not be sufficient to achieve a long-lasting PFS.

Published
2021

35. Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF‐TIMI 48 Trial

Author

Senior, R., Paul, J., McKnight, T., Formoso, I., Saravia Toledo, S., Codutti, O., Sanjurjo, M., Bowen, L., Sanchez, A., Alvarez, M., Rodriguez, M., Navarrete, S., Ramos, H., Venturini, C., Prado, A., Fernandez, E., Pozzer, D., Casares, E., Povedano, G., Tommasi, A., Piskorz, D., Verdini, E., Nul, D., Gandur, H., Muntaner, J., Funes, I., Marino, J., Calderon, M., Manuale, O., Carne, M., Mackinnon, I., Raimondi, G., Lotti, J., Shatsky, K., Rodkey, K., Lorente, C., Vignau, S., Llanos, J., Nigro, A., Litvak, B., Iglesias, M., Liniado, G., Belcuore, M., Lanternier, G., Monaco, F., Kevorkian, R., Jure, D., Jure, H., Bianchini, M., Avery, D., Hominal, M., von Wulffen, M., McKenzie, M., Miranda, J., Wright, L., Pye, M., Flint, L., Newby, D., Andrews, A., Goicoechea, R., Huerta, M., Giannaula, R., Eden, M., Giacomi, G., Ceirano, C., Garrido, M., Perlo, D., Garcia Duran, R., Meiller, F., Gant Lopez, J., Zanotti, A., Fuselli, J., Arrieta, M., Femenia, F., Falu, E., Facello, M., Facello, A., Murdoch, D., Helliwell, L., More, R., Isted, C., Maxwell, T., Jones, D., Marazzi, P., McGhee, C., MacLeod, M., Ebano, P., MacCallum, P., Davolos, M., Estol, C., Moreno, V., Dran, R., Cendali, G., D'Amico, A., Bocanera, M., Cuneo, C., Rosell, M., Cuello, J., Morandini, M., Colombo, H., Brown, R., Saa Zarandon, R., Caruso, O., Novas, V., Cartasegna, L., Fracaro, V., Caccavo, A., Saravia, M., Bustamante Labarta, G., Valle, M., Budassi, N., Lip, G., Finlayson, M., Linker, N., McGuire, K., Atkinson, C., Lindsay, S., Ramasamy, V., Lie, F., Dickinson, D., Douglas, H., D'Costa, D., Wilmott, R., Cohen, A., Duff, J., Choy, A., Davies, D., Chapman, O., Dougal, K., Camm, J., Price, R., Blagden, M., Schwarz, L., McGarvey, J., Stubbs, L., McCartney, M., Hicks, T., Massin, E., Bedenko, E., Marenberg, M., Rabadi-Marar, D., Dunn, S., Beeton, I., Smith, S., Aggarwal, R., Marar, I., Hernandez, S., Berli, M., Petrucci, J., Beloscar, J., Caceres, M., Amuchastegui, M., Ameriso, P., Ameriso, S., Garcia, M., Alvarez, C., Reguero, M., Allall, O., Rosales, E., Albisu, J., Ahuad Guerrero, R., Gonzalez, C., Vogelmann, O., Magnuson, Elizabeth A., Cohen, David J., Giugliano, Robert P., Mandviwala, M., Casas, R., Makam, S., Lisiecki, B., Mainigi, S., Doctor, A., Magee, A., Bush, D., Macomber, J., Edelstein, J., Lurie, M., Wright, H., Lui, H., Ault, S., Looby, R., Davids, M., Lone, B., Shah, D., Lomnitz, D., Wofford, E., Littlefield, R., Murphy, R., Ling, L., Miller, D., Lillestol, M., Bonds, C., Lewis, D., Hartley, L., Lesser, M., Smith, D., Lentz, M., Royse, H., Ledbetter, L., Faucett, S., Langevin, E., Simmons, T., Lang, J., Ferguson, D., Landau, C., Coyle, G. Stagi, Lambert, C., Jauregui, V., Laliotis, A., Marquez, D., Krichmar, P., Watts, S., Kozlowski, J., Sanchez, E., Kotha, P., Godfrey, C., Korpas, D., Averett, P., Kindman, L., Khan, G., Khan, M., Binns, M., Khan, B., DiCorcia, L., Kesselbrenner, M., Buhler, A., Kersh, R., Bartholomaus, D., Kerkering, M., Keller, J., Keller, R., Davis, C., Kastelic, R., Behm, K., Karunaratne, H., Ruggiero, M., Kapoor, A., Cook, S., Kaplan, K., Kostedt, G., Kandath, D., Dugal, J., Kai, W., Coombs, V., Kahn, B., Royes, A., Judson, P., Nichols, M., Jovin, I., Hughett, G., Jones, R., Phillips, T., Johnson, F., Andresen, T., Jardula, M., Butcher, S., Ison, R., Tambawala, M., Hussain, M., Garza, M., Hurst, P., Battistelli, E., Hunter, J., Truva, C., Huang, P., Craft, D., Howard, L., Hays, D., Howard, V., Adams, K., Houchin, V., Turner, N., Hotchkiss, D., Sloss, D., Horton, K., Homayouni, A., Homan, J., Young, C., Hoekstra, J., Dutter, S., Hippert, R., Vieira, P., Hinchman, D., Carey, G., Herson, S., Miranda, D., Herrod, J., Batchell, K., Hermany, P., Harkins, V., Henry, S., Millard, D., Henderson, D., Dandekar, U., Heiman, M., Krater, C., Hearne, S., Bobade, M., Harris, J., Cavanna, L., Han, M., Bentivenga, L., Hamroff, G., Morelli, L., Hack, T., McLean, R., Gvora, T., Felsman, D., Guthrie, R., Foster, B., Guerrero, Guerrero, Fisher, M., Guarnieri, T., Gabela, W., Guarino, J., Mabe, K., Grove, D., Davis, A., Grossman, C., Goodman, V., Griffin, J., Aull, L., Griffin, S., Bonora, M., Graham, S., Rafala, E., Gowda, S., Goldstein, M., Latteri, J., Goldscher, D., Ewing, B., Gogia, H., Keane-Richmond, P., Gillespie, E., Hinchion, N., Gerber, J., Valentine, H., George, F., Garb, J., Jones, J., Gaffney, M., Smith, K., Friedlander, I., Morales, C., French, W., Gentry, P., Franco, M., Thrope, C., Frais, M., Solis, A., Forman, S., Slayton, C., Flores, E., Donahue, S., Fishbein, G., Drew, B., Fischell, T., Lim, G., Finkelstein, S., Shriver, D., Finkel, M., Calvo, M., Fialkow, J., Prior, J., Felten, W., Tang, N., Feldman, J., Tameron, A., Feld, L., Watkins, D., Fahmy, R., DeSalle, D., Everhart, B., Shipp, A., Ettinger, N., O'Brien, J., Johnson, C., Erenrich, N., Cristaldi, J., Ellis, J., Quick, R., Eldadah, Z., Dunn, K., Eade, J., Cullen, T., D'Souza, A., Habibi, S., Drozdiak, R., Olson, A., Dotani, I., Rodriguez, L., Donovan, D., Tisdale, L., DiGiovanna, M., Ucik, S., Dhar, S., Briscoe, C., Devenport, S., Waters, L., Desire, A., Steward, A., Desai, A., Carey, J., DeGarmo, R., Warmack, D., Dean, J., Debes, C., De Lemos, J., Ebreo, N., Davuluri, A., Dave, B., Dave, K., Wulf, A., Datta, S., Leka, G., Daniels, S., Morgan, T., Dang, N., Sarpola, N., Curtis, B., Nelson, L., Cowan, L., Masson, E., Cottiero, R., Mullinax, K., Cossu, S., Svadbik, L., Corbett, B., Martinez, E., Concha, M., Cole, J., Salpas, S., Colan, D., Bossaers, J., Cohen, R., Dutka, C., McClelland, M., Clay, A., Clapp, T., Bagby, J., Ciaramita, J., Sawaya, K., Chaturvedi, S., Tamayo, M., Charlat, M., Hatfield, G., Chang, M., Phan, D., Carr, K., Jameson, L., Caplan, J., Hartranft, E., Canosa, R., Canaday, D., Morton, S., Cader, C., Al-Maliky, T., Bybee, K., Triano, A., Brown, H., Frey, W., Brilakis, E., Terry, P., Bradley, A., Ziegler, K., Bowden, W., Wade, W., Bouchard, A., Hickenbotham, D., Borsheim, M., Vernon, M., Blue, B., Bloomberg, K., Bloomberg, R., Ensminger, E., Blonder, R., Talbot-Lawson, C., Block, T., Antonino, M., Bingham, S., Langone, L., Bilazarian, S., Preston, S., Bilal, B., Eldred, R., Bernard, J., Ibarra, M., Berk, M., Garman, V., Bensimhon, D., Swaim, D., Beinart, S., Craig, M., Bedwell, N., Luis-Valdes, M., Bedoya, R., Hoffman, T., Beasley, R., Benton, J., Bartkowiak, A., Gordon, L., Barrington, P., Faircloth, C., Barker, T., Altonen, D., Barber, M., Campbell, G., Baman, R., Batista, M., Baine, S., Thompson, B., Ayesu, K., Baldwin, E., Awasty, V., Cobos, D., Aude, Y., Strickland, S., Attanti, S., Rasmussen, L., Arouni, A., Shoaf, R., Arnold, T., York, T., Anderson, J., 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H., Iriarte, M., Morissette, A., Wang, Kaijun, Li, Haiyan, and Yalcin, R.

Subjects
Male, medicine.medical_specialty, Complications, Time Factors, Pyridines, Health Status, Embolism, Hemorrhage, Arrhythmias, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Risk Factors, Surveys and Questionnaires, Internal medicine, Atrial Fibrillation, Humans, Medicine, In patient, Prospective Studies, 030212 general & internal medicine, anticoagulation, Blood Coagulation, Original Research, Aged, Aged, 80 and over, Quality and Outcomes, business.industry, Anticoagulants, Atrial fibrillation, Middle Aged, bleeding, medicine.disease, Stroke, Thiazoles, Treatment Outcome, quality of life, utility, Physical therapy, Cardiology, Female, Warfarin, Gastrointestinal Hemorrhage, Cardiology and Cardiovascular Medicine, business, TIMI, Health Services and Outcomes Research, Factor Xa Inhibitors
Abstract

Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood. Methods and Results The ENGAGE AF ‐ TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol‐5D ( EQ ‐5D‐3L) questionnaire, prospectively collected at 3‐month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health‐state utility over 12 months following the event. Longitudinal mixed‐effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (−0.029 [−0.044 to −0.014; P P =0.001], respectively). These effects decreased in magnitude over time, and were no longer significant for major nongastrointestinal bleeds at 9 months, but remained borderline significant for major gastrointestinal bleeds at 12 months. Clinically relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility (−0.010 [−0.016 to −0.005] and −0.016 [−0.024 to −0.008]; P Conclusions All categories of bleeding events were associated with negative impacts on health‐state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT00781391.

Published
2017

36. Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a Prospective, Non-randomized Study of Patients With Cirrhosis

Author

Tommaso Di Maira, Stefano Fagiuoli, Rita Golfieri, Umberto Arena, Fabio Marra, Stefano Gitto, Stefano Colopi, Alessandro Cannavale, Filippo Schepis, Pietro Torricelli, Luca S. Belli, Pietro Quaretti, Giacomo Laffi, Angelo Luca, Cristian Caporali, Roberto Agazzi, Roberto Miraglia, Federico Banchelli, Nicola De Maria, Guido Marzocchi, Ilaria Fiorina, Roberto Nani, Antonio Rampoldi, Erica Villa, Mario De Santis, Raffaele Bruno, Lorenzo Paolo Moramarco, Guadalupe Garcia-Tsao, Aldo Airoldi, Francesco Vizzutti, Fabrizio Fanelli, L. Rega, Matteo Renzulli, Cristina Mosconi, Fabrizio Di Benedetto, Schepis, F, Vizzutti, F, Garcia-Tsao, G, Marzocchi, G, Rega, L, De Maria, N, Di Maira, T, Gitto, S, Caporali, C, Colopi, S, De Santis, M, Arena, U, Rampoldi, A, Airoldi, A, Cannavale, A, Fanelli, F, Mosconi, C, Renzulli, M, Agazzi, R, Nani, R, Quaretti, P, Fiorina, I, Moramarco, L, Miraglia, R, Luca, A, Bruno, R, Fagiuoli, S, Golfieri, R, Torricelli, P, Di Benedetto, F, Belli, L, Banchelli, F, Laffi, G, Marra, F, Villa, E, Schepis, Filippo, Vizzutti, Francesco, Garcia-Tsao, Guadalupe, Marzocchi, Guido, Rega, Luigi, De Maria, Nicola, Di Maira, Tommaso, Gitto, Stefano, Caporali, Cristian, Colopi, Stefano, De Santis, Mario, Arena, Umberto, Rampoldi, Antonio, Airoldi, Aldo, Cannavale, Alessandro, Fanelli, Fabrizio, Mosconi, Cristina, Renzulli, Matteo, Agazzi, Roberto, Nani, Roberto, Quaretti, Pietro, Fiorina, Ilaria, Moramarco, Lorenzo, Miraglia, Roberto, Luca, Angelo, Bruno, Raffaele, Fagiuoli, Stefano, Golfieri, Rita, Torricelli, Pietro, Di Benedetto, Fabrizio, Belli, Luca Saverio, Banchelli, Federico, Laffi, Giacomo, Marra, Fabio, and Villa, Erica

Subjects
Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Liver, liver, portal hypertensive bleeding, portal hypertensive complications, treatment, vascular disease, Hemodynamics, Inferior vena cava, 03 medical and health sciences, 0302 clinical medicine, Model for End-Stage Liver Disease, Vascular Disease, Ascites, medicine, Humans, Prospective Studies, Aged, Hepatology, Vascular disease, business.industry, Incidence, Gastroenterology, Stent, Middle Aged, medicine.disease, Fibrosis, Surgery, Treatment, Treatment Outcome, Italy, Portal Hypertensive Bleeding, medicine.vein, Hepatic Encephalopathy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Portasystemic Shunt, Transjugular Intrahepatic, medicine.symptom, business, Transjugular intrahepatic portosystemic shunt
Abstract

Background & Aims: Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time. Methods: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient. Results: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P =.015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls). Conclusions: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective.

Published
2018

37. Assessment of liver fibrosis in primary biliary cholangitis: Comparison between indirect serum markers and fibrosis morphometry

Author

Luisa Leoncini, Maria Rosa Biagini, Umberto Arena, Cristina Stasi, Stefano Milani, Giacomo Laffi, Fabio Marra, and S. Madiai

Subjects
Male, medicine.medical_specialty, Pathology, Biopsy, Gastroenterology, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Primary biliary cirrhosis, Fibrosis, Internal medicine, Image Processing, Computer-Assisted, medicine, Humans, Aspartate Aminotransferases, Stage (cooking), Sirius Red, Aged, Retrospective Studies, Hepatology, medicine.diagnostic_test, biology, Liver Cirrhosis, Biliary, business.industry, Biopsy, Needle, Alanine Transaminase, Retrospective cohort study, gamma-Glutamyltransferase, Middle Aged, Alkaline Phosphatase, medicine.disease, Liver, chemistry, Alanine transaminase, 030220 oncology & carcinogenesis, Disease Progression, biology.protein, Female, 030211 gastroenterology & hepatology, business, Biomarkers
Abstract

The accuracy of non-invasive methods for the quantification of liver fibrosis in primary biliary cholangitis (PBC) is still debated.To determine the histo-morphometric measurement of fibrotic tissue and to explore the possible association between indirect markers (APRI, FORNS, FIB-4, and Lok) and morphometry.Retrospective analysis of medical data from patients with PBC, on whom needle liver biopsy was performed as part of the diagnostic assessment. One section of each biopsy stained with Sirius red was used for calculating the percentage of collagen. Quantitative measure of fibrotic tissue (fibrosis morphometry) was calculated as a percentage of collagen content by digital image analysis. Morphometry results were divided into four groups reflecting Ludwig's staging and compared with values for indirect serum markers.50 PBC patients were enrolled (86% females, mean age 57 ± 12.30 years), 19 were Ludwig's stage I (38%), 14 stage II (28%), 12 stage III (24%), and five stage IV (10%). Morphometry results were significantly different among Ludwig stages (p0.05). No significant differences were found for indirect serum markers. A significant correlation was found between morphometry results and indirect serum markers tested (p0.05).In our cohort, the histo-morphometric values of fibrotic tissue increased progressively with Ludwig's stages of PBC, while non-invasive markers did not.

Published
2016

38. Characterization of lymphocyte subsets in ascitic fluid and peripheral blood of decompensated cirrhotic patients with chronic hepatitis C and alcoholic liver disease: A pivotal study

Author

Alessia Carraresi, Giacomo Laffi, Roberta Biagiotti, Roberto Giulio Romanelli, Stefano Gitto, Francesco Vizzutti, Gianfranco Vitiello, Fabio Almerigogna, and Maria Grazia Giudizi

Subjects
Liver Cirrhosis, Male, 0301 basic medicine, Alcoholic liver disease, medicine.medical_specialty, Hepatitis C virus, Immunology, lymphocyte immunophenotyping, medicine.disease_cause, Gastroenterology, ascites, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, Liver Cirrhosis, Alcoholic, Internal medicine, Ascites, medicine, Ascitic Fluid, Humans, Immunology and Allergy, Original Research Article, Aged, Aged, 80 and over, Pharmacology, Ascitic fluid, business.industry, Antibodies, Monoclonal, inflammatory response, Middle Aged, medicine.disease, Natural killer T cell, Hepatitis C, Lymphocyte Subsets, Peripheral blood, natural killer T cells, Killer Cells, Natural, 030104 developmental biology, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, decompensated cirrhosis, Lymphocyte subsets
Abstract

Hepatitis C virus and alcoholic liver disease are major causes of chronic liver diseases worldwide. Little is known about differences between chronic hepatitis C and alcoholic liver disease in terms of lymphocytes’ sub-population. Aim of the present study was to compare the sub-populations of lymphocytes in both ascitic compartment and peripheral blood in patients with decompensated liver cirrhosis due to chronic hepatitis C and alcoholic liver disease. Patients with decompensated liver cirrhosis due to hepatitis C virus or alcoholic liver disease evaluated from April 2014 to October 2016 were enrolled. Whole blood and ascitic fluid samples were stained with monoclonal antibodies specific for human TCRɑβ, TCRɣδ, CD3, CD4, CD8, CD19, CCR6, CD16, CD56, CD25, HLA-DR, Vɑ24. Sixteen patients with decompensated liver cirrhosis were recruited (9 with hepatitis C virus and 7 with alcoholic liver disease). In ascitic fluid, the percentage of both CD3+CD56− and CD3+CD56+iNKT cells resulted higher in hepatitis C virus patients than in alcoholic liver disease patients (1.82 ± 0.35% vs 0.70 ± 0.42% (p +CD56− and CD3+CD56+iNKT cells resulted significantly higher in alcoholic liver disease than in hepatitis C virus patients (4.70 ± 2.69% vs 1.50 ± 1.21% (p +CD4+ cells and a higher percentage of CD3−CD16+, Vα24+CD3+CD56− and Vα24+CD3+CD56+iNKT cells in ascitic fluid than hepatitis C virus positive subjects. Further studies might analyze the role of immune cells in the vulnerability toward infections and detect potential targets for new treatments especially for alcoholic liver disease patients.

Published
2020

39. 3293Healthcare resources utilization due to complications of cardiac implantable electronic devices: preliminary results from the IMPACT registry

Author

G. De Luca, M Laffi, Eraldo Occhetta, Germano Gaggioli, Matteo Ziacchi, Federico Guerra, Michele Accogli, Gabriele Dell'Era, Mauro Biffi, Giovanni Nigro, Francesca Troiano, Ernesto Ammendola, Aiac, Pietro Palmisano, Alessandro Capucci, and G Boriani

Subjects
business.industry, Medicine, Electronics, Medical emergency, Cardiology and Cardiovascular Medicine, business, medicine.disease
Published
2018

40. Interferon-free therapy in hepatitis C virus mixed cryoglobulinaemia: a prospective, controlled, clinical and quality of life analysis

Author

Andrea Giovannelli, Antonella Simone, Luisa Petraccia, Anna Linda Zignego, P. Caini, A. Xheka, Marco Matucci-Cerinic, Carolina Steidl, Guia Cerretelli, Serena Lorini, Umberto Arena, Sinan Sadalla, T. Urraro, Monica Monti, Giacomo Laffi, Laura Gragnani, and Diego Vergani

Subjects
0301 basic medicine, Mixed cryoglobulinaemia, medicine.medical_specialty, Hepatology, business.industry, Interferon free, Hepatitis C virus, medicine.medical_treatment, Gastroenterology, Hepatitis C, Immunotherapy, medicine.disease, medicine.disease_cause, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Quality of life, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Pharmacology (medical), Clinical efficacy, business, Vasculitis
Abstract

BACKGROUND Cryoglobulinaemic vasculitis (CV) is a lymphoproliferative disorder related to hepatitis C virus (HCV) infection; anti-viral therapy is the first therapeutic option. CV can be incapacitating, compromising the patients' quality of life (QoL). In a controlled study, interferon-based therapy was associated with a lower virological response in vasculitic patients than in patients without vasculitis. Limited, uncontrolled data on direct-acting anti-virals are available. AIM To evaluate safety, clinical efficacy, virological response and the impact of interferon-free treatment on QoL in HCV patients with and without mixed cryoglobulinaemia (MC). METHODS We prospectively studied HCV patients with cryoglobulinaemia (with vasculitis-CV- and without vasculitis-MC-) and without cryoglobulinaemia (controls), treated with direct-acting anti-virals. Hepato-virological parameters, CV clinical response and impact on QoL were assessed. RESULTS One hundred and eighty-two HCV patients were recruited (85 with CV, 54 with MC and 43 controls). A sustained virological response at 12 weeks (SVR12) was achieved in 166 (91.2%) patients (77/85 CV, 48/54 MC, 41/43 controls). In CV SVR patients, cryocrit levels progressively decreased and clinical response progressively improved, reaching 96.7%, 24 weeks after treatment. QoL, baseline physical and mental component summaries were lower in the CV group compared to the other groups (P < 0.05). Scores improved in all groups, and significantly in CV patients after SVR. CONCLUSIONS No significant differences in SVR rates were recorded between cryoglobulinaemic patients and controls and a high clinical and immunological efficacy was confirmed in CV, supporting the role of interferon-free therapy as the first therapeutic option. Interestingly, CV patients had worse baseline QoL than other HCV-positive groups and interferon-free therapy was effective in significantly increasing QoL, suggesting the important role of direct-acting anti-viral-based therapy in improving CV's individual and social burden.

Published
2018

41. Systemic therapies in patients with advanced well-differentiated pancreatic neuroendocrine tumors (PanNETs): When cytoreduction is the aim. A critical review with meta-analysis

Author

Vito Amoroso, Alfredo Berruti, Marta Pozzari, Emilio Bertani, S. Pellicori, Francesca Spada, Alice Laffi, Nicola Fazio, Chiara Alessandra Cella, and Patrick Maisonneuve

Subjects
Vascular Endothelial Growth Factor A, 0301 basic medicine, Oncology, medicine.medical_specialty, Proliferation index, Well-differentiated pancreatic neuroendocrine tumors, Population, Neuroendocrine tumors, Tumor response rate, Cytoreduction, Cytoreductive treatments, Pancreatic NET, Tumor shrinkage, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Sunitinib, Temozolomide, medicine, Humans, Radiology, Nuclear Medicine and imaging, Molecular Targeted Therapy, education, education.field_of_study, business.industry, Cytoreduction Surgical Procedures, General Medicine, medicine.disease, Pancreatic Neoplasms, Clinical trial, Neuroendocrine Tumors, Regimen, 030104 developmental biology, 030220 oncology & carcinogenesis, Radionuclide therapy, Radiopharmaceuticals, business, medicine.drug
Abstract

Introduction Cytoreduction is sometimes an important aim of systemic anti-tumor therapies in well-differentiated pancreatic neuroendocrine tumors (PanNETs). As there is not a gold standard treatment for these tumors in this field, we conducted a literature review in order to identify objective criteria for treatment choice. Materials and methods We critically reviewed and performed a meta-analysis of all published clinical studies of systemic therapies in patients with well-differentiated unresectable PanNETs, selecting only those articles which reported tumor shrinkage (TS) with a waterfall plot (WP). Tumor downsizing of ≥10% was considered as objective response. Results We selected 17 out of 2758 studies, comprising 1118 patients with tumor response reported as WP. Proliferation index, tumor burden and anti-tumor therapies were heterogeneous. Chemotherapy alone (mainly, capecitabine/temozolomide) or in combination showed the best results, with ≥10% TS ranging from 65% to 93%. Peptide receptor radionuclide therapy combined with chemotherapy (Chemo-PRRT) and sunitinib appeared promising by inducing objective response in a significant proportion of patients (93% and 60%, respectively). Time to tumor response was reported in only two trials. No clear clinical and/or biological predictive factors emerged. Conclusion Based on response criteria used in our retrospective analysis, systemic chemotherapy alone or in combination appeared to have the main cytoreductive impact. However no conclusions regarding either a specific regimen or combination can be drawn. Furthermore, tumor population selection and/or choice of regimen may have a significant influence. Further analysis should be also conducted to identify potential predictive biomarkers of responses, in order to design future prospective interventional clinical trials enrolling more homogenous populations of advanced well-differentiated PanNETs.

Published
2018

42. Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-word large-scale cohort study

Author

Piero Colombatto, Cristina Stasi, Giampaolo Bresci, Alessandro Nerli, Anna Linda Zignego, D. Aquilini, Paolo Forte, Andrea Cozzi, Cristina Orsini, Silvia Chigiotti, Rodolfo Sacco, Sauro Luchi, Giampaolo Corti, Cesira Nencioni, Stefano Milani, Santino Marchi, Massimo Giusti, Angelo Ricchiuti, Caterina Silvestri, Silvia Carloppi, Roberto Berni, Andrea Galli, P. Almi, Paola Carrai, Francesco Cipriani, Ricciardi L, Franco Filipponi, Alessandro Bartoloni, Maurizia Rossana Brunetto, Pierluigi Blanc, Fabio Voller, Giacomo Laffi, and Andrea De Luca

Subjects
medicine.medical_specialty, Pediatrics, Cirrhosis, Epidemiology, Liver fibrosis, Clinical epidemiology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Hepatitis B virus infection, Retrospective Cohort Study, Chronic viral hepatitis B, Public health, Hepatology, business.industry, medicine.disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Real word, business, Cohort study
Abstract

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system. METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Published
2018

43. Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Author

Mirijello, Antonio, Viazzi, Francesca, Fioretto, Paola, Giorda, Carlo, Ceriello, Antonio, Russo, Giuspina T., Guida, Pietro, Pontremoli, Roberto, De Cosmo, Salvatore, Cimino, Antonino, Fava, Danila, Giorda, Carlo Bruno, Meloncelli, Illidio, Nicolucci, Antonio, Pellegrini, Fabio, Rossi, Maria Chiara, Turco, Salvatore, Vespasiani, Giacomo, Pellegrini, F., Graziano, G., Lucisano, G., Memmo, R., Pellicciotta, E., Paciotti, V., Pupillo, M., Armentano, G., Giovannini, C., Armentano, V., Laudato, M., Turco, S., Acquati, S., Ciardullo, A. V., Laffi, G., Felace, G., Taboga, C., Tortul, C., Santantonio, G., Suraci, C., Ghisoni, G., Raffa, M., Genovese, S., Lovagnini-Scher, C. A., Rampini, P., Rocca, A., Ruggeri, P., Tortato, E., Cotti, L., Cristofaro, M. R., Tagliaferri, M., Comoglio, M., Fornengo, R., De Cosmo, S., Gentile, F. M., Gigante, A., Mastinu, F., Di Benedetto, A., Pata, P., Arcangeli, A., Orsini, P., Acler, P., De Blasi, G., Cicioni, G., Pocciati, S., Marangoni, A., Nogara, A., Lanero, M., Bertero, M. G., Damassino, R., Bergonzini, C., Schumtz, L., Seksich, L., Pipitone, A., Boaretto, M., Manfroi, I., Parmesan, L., Conte, B., Soccol, F., Pagano, A., Papini, E., Rinaldi, R., Petrucci, L., Graziano, F., Chianelli, M., Silvagni, S., Rosco, M., Ansaldi, E., Malvicino, F., Battezzati, M., Maresca, P., Palenzona, C., Boemi, M., Rabini, R. A., Brandoni, G., Lanari, L., Gatti, C., Testa, I., Cherubini, V., Doveri, G., Pecorelli, L., Ciccarelli, A., Gallardini, M. B., Courthoud, R., Sara Bredy, S., Ricciardi, G. P., Vitalone, G., Setti, D., Contrini, P., Corsi, A., Ghigliotti, V., Oddone, G., Ponzani, P., Valbonesi, G., Mazzini, V., Di Berardino, P., Colleluori, P., Montani, V., Trosini, V., Velussi, M., Alfidi, P., Verdecchia, B., Baliva, L., Di Pietro, A., Franchi, G., Luce, R. P., Pianta, A., Ferrari, M., Balzano, S., Beltranello, G., Dal Fabbro, S., Aricò, C. N., Cervo, L., Zanon, R., Rossa, S., Di Pace, M. C., Ciavarella, A., Giangiulio, S., Grimaldi, M., Mustacchio, A., Santacroce, G., Fattor, B., Monauni, T., Cristini, M., Orion, G., Crazzolara, D., Amor, F., Eisath, J. E., Lintner, S., Garavelli, S., Calari, T., Marini, P., Sandri, O., Scala, M., Stroppa, C., Trentin, A., Carlin, R., Carli, B., Sandonà, M., Zortea, C., Bonet, L., Pradel, L., Reato, S., Buschini, M., Bonfiglioli, D., Mones, D., Beldì, F., Morea, A., Bondesan, L., Perbellini, S., Cimino, A., Valentini, U., Agosti, B., Corsini, R., Girelli, A., Zarra, E., Rocca, L., Bergmann, M., Pradi, I., Unterkircher, S., Piok, M., Pichler, M., Trinchera, A., Palamà, G., Palma, P., Carboni, L., Murtas, M. G., Mudadu, T., Turco, M. P., Floris, M., Delogu, A., Farris, L., Songini, M., Piras, G., Seguro, R., Floris, R., Corona, G., Lai, M., Piras, E., Contini, P. P., Cocco, S., Pilosu, R. M., Sannia, M. C., Spanu, F., Busciantella Ricci, N., Cartechini, M. G., Agostinelli, G., Fiorelli, C., Nuzzi, A., Ballauri, C., Giorda, C. B., Lesina, A., Romeo, F., Giudici, G., Maciejewska, E. G., Deroma, A., Paduano, M., Rossi, L., Vagnini, C., Dolci, M., Mori, M., Baccetti, F., Gregori, G., Straface, E., Pozzuoli, G., Barone, M., Stasio, G. B., Tondini, S., Borgoni, F., Grosso, J., Scarsellato, C., Sciulli, A., De Marco, F., Confortin, L., Marin, N., Lamonica, M., Gialdino, S., Borzì, V., Gatta, C., Rapisard, R., Strano, S., Calabrò, M., Puccio, L., Zolli, M., Coracina, A., Starnone, V., Del Buono, A., Terracciano, A. M., Monda, M. V., Castro, F., Guaglianone, A., Maccari, V., Corsi, L., Versari, G., Falivene, M. R., Boletto, N., Corsi, S., Marafetti, L., Vitacolonna, E., Capani, F., Caputo, L., Di Nisio, L., Simonetti, F., Boscolo Bariga, A., Ballarin, G., De Boni, S., Di Benedetto, S., Chiambretti, A. M., Di Vito, L., Pascuzzo, M. D., Urli, P., Rumi, P., Balzarini, B., Galli, P., Castellan, M., Giannetti, A., Russotti, C., De Blasi, A., Perna, A., Campanelli, C., Ranchelli, A., Biccheri, D., Dadi, G., Massa, L., Baldi, G. P., Sciacca, F., Costanzo, E., Spada, M., Paolini, G., Ziller, P., Portolan, F., Pasolini, G., Ghilardi, G., Fiorina, P., Grata, M. L., Capretti, L., Speroni, G., Fugazza, L., Massafra, C., Lovagnini Scher, A., Cimicchi, M. C., Percudani, C., Risolo, T., Saccò, P., Gidoni Guarnieri, G. L., Piccolo, D., Bravin, C., De Noni, E., Scarpel, M., Marcon, M., Giacon, F., Panebianco, G., Tadiotto, F., Da Tos, V., D'Ambrosio, M., Pellizzola, D., Zampini, M. A., Frezzati, E., Mari, E., Raminelli, E., Gaiti, D., Bosi, E. A., Chierici, G., Pilla, S., Copelli, M., Zanichelli, P., Bertelli, L., Caretta, P., Vezzani, V., Bodecchi, S., Longobucco, A., Di Lembo, S., Spotti, E., Carrai, E., Degli Innocenti, A., Manini, L., Persico, R., Rossi, C., Magro, G., Marelli, G., Vilei, V., Andrioli, M., Bellato, L., Fedeli, M., Merlini, A., Pinelli, G., Marin, G., Contin, M. L., Gallo, A., Parlato, P., Pecchielan, W., Jacovacci, J., Placentino, G., Richini, D., Molinari, S., Strazzeri, R., Fabbri, T., Di Bartolo, P., Garrapa, G., D'Incau, F., Lagomanzini, P., Conte, P., Todesco, F., Foglini, P., Pantanetti, P., Bedetta, C., Maricotti, R., Tomasi, F., Monesi, M., Graziani, R., Beretta, F., Penna, L., Guberti, A., Dazzi, D., Forte, E., Gasbarrone, A., Marrocco, T., Moschetta, R., Tuccinardi, F., De Meo, F., Coppola, A., Pirolozzi, P., Placitelli, E., Vallefuoco, R., Catone, B., Ceschia, S., Urban, M., Fabbri, F., Torresani, M., Crovetto, R., Battistini, M., Carosia, P., Viviani, G. L., Durante, A., Pais, F., Lilliu, V., Quieto, C., D'Ugo, E., Squadrone, M., Amenduni, T., Iovannisci, M. M., Della Penna, L., Potente, F., Delle Donne, T., Massa, C., Ulisse, M. A., De Berardinis, S., Guarnieri, I., Pace, S., Splendiani, M., Di Giuseppe, R., Brunato, B., Assaloni, R., Muraro, R., Loro, R., Bucciol, S., Lavacca, C., Rossi, M., Sabbatini, G., Quadri, F., Sambuco, L., Santacroce, C., Paola Caretta, D., Marino, C., Micheletti, A., Petrelli, A., Corda, A., Pisano, L., Guaita, G., Deias, C., Trevisan, G., Coletti, I., Iannarelli, R., De Luca, A., Minnucci, A., Antenucci, D., Di Florio, C., Angelicola, G., Bosco, A., Fresco, R., Di Marco, G., Ugolotti, D., Cadossi, T., Di Caro, P., Mazzocchetti, M., Buzzetti, R., Leto, G., Gnessi, C., Cipolloni, L., Foffi, C., Moretti, C., Venditti, C., Meniconi, R., Bertoli, S., Cosimi, S., Di Cianni, G., Turco, A., Richini, A., Marconi, S., Sannino, C., Lemmi, P., Giuntoli, S., Manfrè, N., Giannini, F., Di Carlo, A., Casadidio, I., Melandri, P., Maolo, G., Polenta, B., Piccinini, N., Vincenti, C., Pastore, N., Mega, P., Magurano, E., Cananiello, A., Francescutto, C. A., Brussa Toi, E., Gaspardo, G., Angeli, L., Ronchese, L., Sciangula, L., Ciucci, A., Contartese, A., Banfi, E., Castelli, E., Tatti, P., Bloise, D., Di Mauro, P., Masselli, L., Lo Presti, A., Scarpitta, A. M., Gambina, F., Venezia, A., Morea, R., Lagonigro, G., Copeta, G., Iannucci, V., Milano, V., Trupo, M., Lochmann, A., Marchetto, P. E., Incelli, G., De Paola, G., Steiger, M. M., Gamper, M. A., Breitenberger, S., Holzner, M., Frischmann, J., Lambiase, C., Di Vece, T., D'Aniello, M., Fezza, M., Giordano, C., Leo, F., Saitta, G., Cucinotta, D., Di Vieste, G., Pintaudi, B., Mancuso, T., Musacchio, N., Giancaterini, A., Pessina, L., Salis, G., Schivalocchi, F., Testori, G., Rampini, P. A., Cerutti, N., Morpugo, P. S., Cavaletto, M. L., Bonino, G., Morreale, F., Mariani, G., Ragonesi, P. D., Bollati, P., Colapinto, P., Bosi, E., Falqui, L., Bortolato, L., Cosma, A., Pistolato, P., Centenaro, B., Ceccato, A., Campobasso, G., Zaurino, F., Mazzotta, G., Manti, R., Da Ros, R., Carlucci, S., Narduzzi, L., Bortolotto, D., D'Acunto, L., Stanic, L., Volpi, A., Cospite, A. M., Manicardi, V., Michelini, M., Finardi, L., Borghi, F., Manicardi, E., Lombardi, S., Tommasi, C., Iaccarino, M., Cozza, S., Binotto, M., Marini, F., Mecenero, I., Massignani, S., Stecco, P., Urbani, E., Massariol, W., Parolin, R., Gatti, A., Bonavita, M., Creso, E., Giannettino, R., Gobbo, M., Iovine, C., Turco, A. A., Riccardi, G., Iazzetta, N., Giannattasio, C., Egione, O., Galdieri, S., Velotti, A., Azzolina, A., Annicelli, G., Sorrentino, T., Gaeta, I., Zenari, L., Bertolini, L., Sorgato, C., Grippaldi, F., Stroppiana, M., Popolizio, R., Carbone, N., Grasso, S., Abate, S., Gaggero, G. C., Strazzabosco, M., Brun, E., Carlesi, G. P., Garrone, S., Cicalò, A. 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Subjects
Adult, Male, Nephrology, medicine.medical_specialty, endocrine system diseases, Renal function, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, lcsh:RC870-923, Kidney, urologic and male genital diseases, GFR, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, Albuminuria, Diabetic kidney disease, Type 1 diabetes, urogenital system, business.industry, Incidence (epidemiology), Middle Aged, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, female genital diseases and pregnancy complications, Albuminuria, Diabetic kidney disease, GFR, Nephrology, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Italy, Disease Progression, Female, medicine.symptom, business, Research Article, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease
Abstract

Background Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR 30% from baseline was evaluated. Results The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening. Electronic supplementary material The online version of this article (10.1186/s12882-018-1136-6) contains supplementary material, which is available to authorized users.

Published
2018

44. Dysregulated Intrahepatic CD4+ T-Cell Activation Drives Liver Inflammation in Ileitis-Prone SAMP1/YitFc Mice

Author

Theresa T. Pizarro, Alex Yee-Chen Huang, Saada Eid, Wendy A. Goodman, Sara Omenetti, Marco Brogi, Fabio Cominelli, Colleen M. Croniger, Massimo Pinzani, Giacomo Laffi, and Tania Roskams

Subjects
Severe combined immunodeficiency, Hepatology, Regulatory T cell, Gastroenterology, FOXP3, Dendritic cell, Autoimmune hepatitis, Biology, medicine.disease, Regulatory T Cells, 3. Good health, IBD-Associated Liver Inflammation, Liver disease, medicine.anatomical_structure, Immunology, medicine, lcsh:Diseases of the digestive system. Gastroenterology, Liver Sinusoidal Endothelial Cells, Ileitis, lcsh:RC799-869, SAMP1/YitFc Mice, Antigen-presenting cell, Hepatic CD4+ T Cells
Abstract

Background & Aims: Liver inflammation is a common extraintestinal manifestation of inflammatory bowel disease (IBD), but whether liver involvement is a consequence of a primary intestinal defect or results from alternative pathogenic processes remains unclear. Therefore, we sought to determine the potential pathogenic mechanism(s) of concomitant liver inflammation in an established murine model of IBD. Methods: Liver inflammation and immune cell subsets were characterized in ileitis-prone SAMP1/YitFc (SAMP) and AKR/J (AKR) control mice, lymphocyte-depleted SAMP (SAMPxRag-1â/â), and immunodeficient SCID recipient mice receiving SAMP or AKR donor CD4+ T cells. Proliferation and suppressive capacity of CD4+ T-effector (Teff) and T-regulatory (Treg) cells from gut-associated lymphoid tissue (GALT) and livers of SAMP and AKR mice were measured. Results: Surprisingly, prominent inflammation was detected in 4-week-old SAMP livers before histologic evidence of ileitis, whereas both disease phenotypes were absent in age-matched AKR mice. SAMP liver disease was characterized by abundant infiltration of lymphocytes, required for hepatic inflammation to occur, a TH1-skewed environment, and phenotypically activated CD4+ T cells. SAMP intrahepatic CD4+ T cells also had the ability to induce liver and ileal inflammation when adoptively transferred into SCID recipients, whereas GALT-derived CD4+ T cells produced milder ileitis but not liver inflammation. Interestingly, SAMP intrahepatic CD4+ Teff cells showed increased proliferation compared with both SAMP GALT- and AKR liver-derived CD4+ Teff cells, and SAMP intrahepatic Tregs were decreased among CD4+ T cells and impaired in in vitro suppressive function compared with AKR. Conclusions: Activated intrahepatic CD4+ T cells induce liver inflammation and contribute to experimental ileitis via locally impaired hepatic immunosuppressive function. Keywords: Hepatic CD4+ T Cells, IBD-Associated Liver Inflammation, Liver Sinusoidal Endothelial Cells, Regulatory T Cells, SAMP1/YitFc Mice

Published
2015
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45. Edoxaban versus warfarin in patients with atrial fibrillation

Author

Robert P. Giugliano, Christian T. Ruff, Eugene Braunwald, Sabina A. Murphy, Stephen D. Wiviott, Jonathan L. Halperin, Albert L. Waldo, Michael D. Ezekowitz, Jeffrey I. Weitz, Jind?ich ?pinar, Witold Ruzyllo, Mikhail Ruda, Yukihiro Koretsune, Joshua Betcher, Minggao Shi, Laura T. Grip, Shirali P. Patel, Indravadan Patel, James J. Hanyok, Michele Mercuri, Elliott M. Antman, Braunwald E, Antman EM, Giugliano RP, Ruff CT, Morin SE, Hoffman EB, Murphy SA, Deenadayalu N, Grip L, Mercuri M, Lanz H, Patel I, Curt V, Duggal A, Hanyok J, Davé J, Morgan D, Choi Y, Shi M, Jin J, Xie J, Crerand W, Kappelhof J, Maxwell W, Skinner M, Patel S, Betcher J, Selicato G, Otto C. Jr, Reissner C, Smith K, Ostroske J, Ron A, Giugliano R, Connolly S, Camm J, Ezekowitz M, Halperin J, Waldo A, Paolasso E, Aylward P, Heidbuchel H, Nicolau JC, Goudev A, Roy D, Weitz J, Corbalán R, Yang Y, Botero R, Bergovec M, Ŝpinar J, Grande P, Hassager C, Voitk J, Huikuri H, Nieminen M, Blanc JJ, LeHeuzey JY, Mitrovic V, Alexopoulos D, Sotomora G, Kiss R, SomaRaju B, Lewis B, Merlini P, Metra M, Koretsune Y, Yamashita T, García Castillo A, Ophuis T, White H, Atar D, Horna M, Babilonia N, Ruzyllo W, Morais J, Dorobantu M, Ruda M, Ostojic M, Duris T, Dalby A, Chung N, Zamorano JL, Juul Möller S, Moccetti T, Chen SA, Sritara P, Oto A, Parkhomenko A, Senior R, Verheugt F, Skene A, Anderson J, Bauer K, Easton JD, Goto S, Wiviott S, Lowe C, Awtry E, Berger CJ, Croce K, Desai A, Gelfand E, Goessling W, Greenberger NJ, Ho C, Leeman DE, Link MS, Norden AD, Pande A, Rost N, Ruberg F, Silverman S, Singhal A, Vita JA, Vogelmann O, Gonzalez C, Ahuad Guerrero R, Rodriguez M, Albisu J, Rosales E, 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Pazier P, Riofrio K, Braun D, Robinson J, Cherrico M, Roehll W, Hollihan P, Rosado, Barnhorst M, Rosado J, Bamhorst M, Rosen R, Martin C, Ross S, Freeman R, Ruoff G, Nelson T, Sacco J, Ball E, Samal A, Schomburg J, Sandberg J, Lafave J, Savin V, Clifton R, Schaefer S, Fekete A, Schneider R, Schneider W, Schulman D, Mercer S, Seals A, Ullig T, Holt A, Seide H, Mather N, Shah G, Witt P, Shalaby A, Seese M, Shanes J, Fleets J, Shaoulian E, Hren A, Sheikh K, Hengerer T, Shih H, Browning J, Shoukfeh M, Stephenson L, Siler T, Champagne M, Simpson P, Meyer R, Singh N, Turner K, Singh V, Nelson M, Skierka R, Hughes B, Keene R, Smith R, Hodnett P, Spangenthal S, Thomason L, Sperling M, Vasquez E, Spivack E, McCartney P, Staniloae C, Liu M, Steljes A, Cox C, Struble R, Vittitow T, Suresh D, Frost J, Swerchowsky V, Freemyer D, Szulawski I, Herwehe S, Tahirkheli N, Springer K, Takata T, Bruton T, Talano J, Leo L, Tami L, Corchado D, Tatarko M, Swauger M, Tawney K, Dastoli K, Teague S, Young K, Tee H, Mitchell T, Teixeira J, Southam D, Torres M, Tucker P, Salas L, Updegrove J, Hanna K, Val Mejias J, Harrelson KG, Vemireddy D, Cardoza T, Verma S, Parsons T, Vicari R, Warren K, Vijay N, Washam M, Vossler M, Kilcup S, Walsh R, Renaud K, Ward S, Locklear T, Waxman F, Sanchez G, Weiss R, St Laurent B, Westcott J, Williams D, Gibson C, Williams R, Dowling C, Willis J, VonGerichten S, Wood K, Capasso Gulve E, Worley S, Pointer S, Yarows S, Sheehan T, Yasin M, Yi J, Dongas B, Yousuf K, Zakhary B, Curtis S, Zeig S, Mason T, Zellner C, Harden M, Roper E, Waseem M, Grammer M., PERRONE FILARDI, PASQUALE, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai [New York] (MSSM), University Hospitals Case Medical Center (CLEVELAND - UHCMC), University Hospitals Case Medical Center, Jefferson Medical College (JMC), Thomas Jefferson University Hospitals, Thrombosis and Atherosclerosis Research Institute (TARI), McMaster University [Hamilton, Ontario], University Hospital Brno, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Cardiology Research Center (MOSCOU - CRC), Cardiology Research Center, National Hopital Organization (OSAKA - NHO), Osaka National Hospital, Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Graduate School, Endocrinology, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Nursing, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, General Internal Medicine, Giugliano, Rp, Ruff, Ct, Braunwald, E, Murphy, Sa, Wiviott, Sd, Halperin, Jl, Waldo, Al, Ezekowitz, Md, Weitz, Ji, Špinar, J, Ruzyllo, W, Ruda, M, Koretsune, Y, Betcher, J, Shi, M, Grip, Lt, Patel, Sp, Patel, I, Hanyok, Jj, Mercuri, M, Antman, Em, Comi, Giancarlo, ENGAGE AF TIMI 48, Investigators, Robert P., Giugliano, Christian T., Ruff, Eugene, Braunwald, Sabina A., Murphy, Stephen D., Wiviott, Jonathan L., Halperin, Albert L., Waldo, Michael D., Ezekowitz, Jeffrey I., Weitz, Jind?ich, ?pinar, Witold, Ruzyllo, Mikhail, Ruda, Yukihiro, Koretsune, Joshua, Betcher, Minggao, Shi, Laura T., Grip, Shirali P., Patel, Indravadan, Patel, James J., Hanyok, Michele, Mercuri, Elliott M., Antman, Morin, Se, Hoffman, Eb, Deenadayalu, N, Grip, L, Lanz, H, Curt, V, Duggal, A, Hanyok, J, Davé, J, Morgan, D, Choi, Y, Jin, J, Xie, J, Crerand, W, Kappelhof, J, Maxwell, W, Skinner, M, Patel, S, Selicato, G, Otto C., Jr, Reissner, C, Smith, K, Ostroske, J, Ron, A, Giugliano, R, Connolly, S, Camm, J, Ezekowitz, M, Halperin, J, Waldo, A, Paolasso, E, Aylward, P, Heidbuchel, H, Nicolau, Jc, Goudev, A, Roy, D, Weitz, J, Corbalán, R, Yang, Y, Botero, R, Bergovec, M, Ŝpinar, J, Grande, P, Hassager, C, Voitk, J, Huikuri, H, Nieminen, M, Blanc, Jj, Leheuzey, Jy, Mitrovic, V, Alexopoulos, D, Sotomora, G, Kiss, R, Somaraju, B, Lewis, B, Merlini, P, Metra, M, Yamashita, T, García 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M, Marar, I, Rabadi Marar, D, Marenberg, M, Bedenko, E, Massin, E, Hicks, T, Mccartney, M, Stubbs, L, Mcgarvey, J, Schwarz, L, Mcguire, K, Mckenzie, M, Rodkey, K, Mcknight, T, Paul, J, Mclaurin, B, Lack, A, Mega, J, Marti, J, Meholick, A, Skinner, J, Mehrle, A, Wall, J, Mendelson, R, Cervellione, K, Mercado, A, Cajulis, C, Michlin, B, Romero Colon, J, Milas, J, Sanders, D, Miller, R, Sanchez, S, Miller, S, Gryczan, J, Mody, F, Strugatsky, S, Moran, J, Garner, S, Morledge, J, Bowman, B, Mouhaffel, A, Parrott, N, Mounsey, P, Schuler, C, Mowdy, M, Todd, S, Mullen, P, Raziano, S, Murphy, A, Oehmann, V, Nadar, V, Parker, A, Naidu, J, West, M, Nallasivan, M, Goza, J, Nguyen, T, Nomanee, S, Nielsen, R, Wilmot, M, Oberoi, M, Thakkar, N, Oppenheimer, K, Mccormick, J, Orchard, R, Garcia, L, Osborne, J, Gonzalez, M, Oza, S, Joseph, L, Patnam, S, Dennison, K, Pavon, H, Gorry, N, Pearlstein, R, Montayne, S, Pentz, W, Duncan, D, Peters, P, Chacon, L, Petruzziello, F, Morlando, F, Pettis, K, Brown, F, Pezzella, S, Kirk, D, Poulathas, A, Cush, S, Pratt, R, Neeper, L, Pribble, A, Lowe, K, Pudi, K, Sham, L, Pugeda, J, Ebert, J, Quadrel, M, Rafla, E, Quinlan, E, Reed, C, Quinn, J, Hemmen, C, Rama, P, Domingo, D, Redondo, V, Wroblewski, J, Renzi, M, Stanley, E, Richwine, R, Pazier, P, Riofrio, K, Braun, D, Robinson, J, Cherrico, M, Roehll, W, Hollihan, P, Rosado, Barnhorst, M, Rosado, J, Bamhorst, M, Rosen, R, Martin, C, Ross, S, Freeman, R, Ruoff, G, Nelson, T, Sacco, J, Ball, E, Samal, A, Schomburg, J, Sandberg, J, Lafave, J, Savin, V, Clifton, R, Schaefer, S, Fekete, A, Schneider, R, Schneider, W, Schulman, D, Mercer, S, Seals, A, Ullig, T, Holt, A, Seide, H, Mather, N, Shah, G, Witt, P, Shalaby, A, Seese, M, Shanes, J, Fleets, J, Shaoulian, E, Hren, A, Sheikh, K, Hengerer, T, Shih, H, Browning, J, Shoukfeh, M, Stephenson, L, Siler, T, Champagne, M, Simpson, P, Meyer, R, Singh, N, Turner, K, Singh, V, Nelson, M, Skierka, R, Hughes, B, Keene, R, Smith, R, Hodnett, P, Spangenthal, S, 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Grammer, M.

Subjects
Male, Pyridines, [SDV]Life Sciences [q-bio], Embolism, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Edoxaban, Atrial Fibrillation, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Warfarin, Stroke, MESH: Aged, MESH: Middle Aged, Cardiovascular diseases [NCEBP 14], Hazard ratio, General Medicine, MESH: Follow-Up Studies, Middle Aged, 3. Good health, MESH: Atrial Fibrillation, Cardiovascular Diseases, Anesthesia, Cardiology, Female, Adult, Aged, Anticoagulants, Double-Blind Method, Follow-Up Studies, Hemorrhage, Humans, Thiazoles, Warfarin, MESH: Hemorrhage, Andexanet alfa, medicine.drug, medicine.medical_specialty, MESH: Enoxaparin, MESH: Anticoagulants, MESH: Stroke, Dabigatran, 03 medical and health sciences, Internal medicine, medicine, MESH: Kaplan-Meier Estimate, Rivaroxaban, MESH: Humans, business.industry, MESH: Cardiovascular Diseases, MESH: Adult, medicine.disease, Confidence interval, MESH: Male, chemistry, business, MESH: Female, MESH: Embolism
Abstract

Contains fulltext : 125374.pdf (Publisher’s version ) (Open Access) BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P

Published
2013

46. Portal Vein Thrombosis Relevance on Liver Cirrhosis: Italian Venous Thrombotic Events Registry

Author

Violi F., Corazza R. G., Caldwell S. H., Perticone F., Gatta A., Angelico M., Farcomeni A., Masotti M., Napoleone L., Vestri A., Raparelli V., Basili S., Palasciano G., D'Alitto F., Palmieri V. O., Santovito D., Di Michele D., Croce G., Sacerdoti D., Brocco S., Fasolato S., Cecchetto L., Bombonato G., Bertoni M., Restuccia R., Andreozzi P., Liguori L. M., Caroleo B., Perticone M., Staltari O., Manfredini R., De Giorgi A., Averna M., Giammanco A., Granito A., Pettinari I., Marinelli S., Bolondi L., Falsetti L., Salvi A., Durante-Mangoni E., Cesaro F., Farinaro V., Ragone E., Morana I., Andriulli A., Ippolito A., Iacobellis A., Niro G., Merla A., Raimondo G., Maimone S., Cacciola I., Varvara D., Drenaggi D., Staffolani S., Picardi A., Vespasiani-Gentilucci U., Galati G., Gallo P., Davi G., Schiavone C., Santilli F., Tana C., Licata A., Soresi M., Bianchi B. G., Carderi I., Pinto A., Tuttolomondo A., Ferrari G., Gresele P., Fierro T., Morelli O., Laffi G., Romanelli R. G., Arena U., Cristina S., Gasbarrini A., Gargovich M., Zocco Z. M., Riccardi L., Ainora M. E., Capeci W., Martino M. G., Lorenzo N., Cavallo M., Frugiuele P., Greco A., Pietrangelo A., Ventura P., Cuoghi C., Marcacci M., Serviddio G., Vendemiale G., Villani R., Gargano R., Vidili G., Di Cesare V., Masala M., Delitala G., Invernizzi P., Di Minno G., Tufano A., Purrello F., Privitera G., Forgione A., Curigliano V., Senzolo M., Rodriguez-Castro K. -I., Giannelli G., Serra C., Neri S., Pignataro P., Rizzetto M., Debernardi V. W., Svegliati B. G., Bergamaschi G., Costanzo F., Angelico F., Del Ben M., Polimeni L., Talerico G., Proietti M., Romiti G. F., Ruscio E., Toriello F., Violi, F., Corazza, R. G., Caldwell, S. H., Perticone, F., Gatta, A., Angelico, M., Farcomeni, A., Masotti, M., Napoleone, L., Vestri, A., Raparelli, V., Basili, S., Palasciano, G., D'Alitto, F., Palmieri, V. O., Santovito, D., Croce, G., Sacerdoti, D., Brocco, S., Fasolato, S., Cecchetto, L., Bombonato, G., Restuccia, R., Andreozzi, P., Liguori, L. M., Perticone, M., Staltari, O., Manfredini, R., De Giorgi, A., Averna, M., Giammanco, A., Granito, A., Marinelli, S., Bolondi, L., Falsetti, L., Salvi, A., Durante-Mangoni, E., Cesaro, F., Farinaro, V., Ragone, E., Morana, I., Andriulli, A., Ippolito, A., Iacobellis, A., Niro, G., Merla, A., Raimondo, G., Maimone, S., Cacciola, I., Varvara, D., Drenaggi, D., Staffolani, S., Picardi, A., Vespasiani-Gentilucci, U., Galati, G., Gallo, P., Davi, G., Schiavone, C., Santilli, F., Tana, C., Licata, A., Soresi, M., Bianchi, B. G., Carderi, I., Pinto, A., Tuttolomondo, A., Ferrari, G., Gresele, P., Fierro, T., Morelli, O., Laffi, G., Romanelli, R. G., Arena, U., Cristina, S., Gasbarrini, A., Gargovich, M., Zocco, Z. M., Riccardi, L., Ainora, M. E., Capeci, W., Martino, M. G., Lorenzo, N., Cavallo, M., Frugiuele, P., Greco, A., Pietrangelo, A., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Di Cesare, V., Masala, M., Delitala, G., Invernizzi, P., Di Minno, G., Tufano, A., Purrello, F., Privitera, G., Forgione, A., Curigliano, V., Senzolo, M., Rodriguez-Castro, K. -I., Giannelli, G., Serra, C., Neri, S., Pignataro, P., Rizzetto, M., Debernardi, V. W., Svegliati, B. G., Bergamaschi, G., Costanzo, F., Angelico, F., Del Ben, M., Polimeni, L., Talerico, G., Proietti, M., Romiti, G. F., Ruscio, E., Toriello, F., Violi, F, Corazza, R, Caldwell, S, Perticone, F, Gatta, A, Angelico, M, Farcomeni, A, Masotti, M, Napoleone, L, Vestri, A, Raparelli, V, Basili, S, Palasciano, G, D'Alitto, F, Palmieri, V, Santovito, D, Di Michele, D, Croce, G, Sacerdoti, D, Brocco, S, Fasolato, S, Cecchetto, L, Bombonato, G, Bertoni, M, Restuccia, R, Andreozzi, P, Liguori, L, Caroleo, B, Perticone, M, Staltari, O, Manfredini, R, De Giorgi, A, Averna, M, Giammanco, A, Granito, A, Pettinari, I, Marinelli, S, Bolondi, L, Falsetti, L, Salvi, A, Durante-Mangoni, E, Cesaro, F, Farinaro, V, Ragone, E, Morana, I, Andriulli, A, Ippolito, A, Iacobellis, A, Niro, G, Merla, A, Raimondo, G, Maimone, S, Cacciola, I, Varvara, D, Drenaggi, D, Staffolani, S, Picardi, A, Vespasiani-Gentilucci, U, Galati, G, Gallo, P, Davi, G, Schiavone, C, Santilli, F, Tana, C, Licata, A, Soresi, M, Bianchi, B, Carderi, I, Pinto, A, Tuttolomondo, A, Ferrari, G, Gresele, P, Fierro, T, Morelli, O, Laffi, G, Romanelli, R, Arena, U, Cristina, S, Gasbarrini, A, Gargovich, M, Zocco, Z, Riccardi, L, Ainora, M, Capeci, W, Martino, M, Lorenzo, N, Cavallo, M, Frugiuele, P, Greco, A, Pietrangelo, A, Ventura, P, Cuoghi, C, Marcacci, M, Serviddio, G, Vendemiale, G, Villani, R, Gargano, R, Vidili, G, Di Cesare, V, Masala, M, Delitala, G, Invernizzi, P, Di Minno, G, Tufano, A, Purrello, F, Privitera, G, Forgione, A, Curigliano, V, Senzolo, M, Rodriguez-Castro, K, Giannelli, G, Serra, C, Neri, S, Pignataro, P, Rizzetto, M, Debernardi, V, Svegliati, B, Bergamaschi, G, Costanzo, F, Angelico, F, Del Ben, M, Polimeni, L, Talerico, G, Proietti, M, Romiti, G, Ruscio, E, Toriello, F, Violi F., Corazza R.G., Caldwell S.H., Perticone F., Gatta A., Angelico M., Farcomeni A., Masotti M., Napoleone L., Vestri A., Raparelli V., Basili S., Palasciano G., D'Alitto F., Palmieri V.O., Santovito D., Di Michele D., Croce G., Sacerdoti D., Brocco S., Fasolato S., Cecchetto L., Bombonato G., Bertoni M., Restuccia R., Andreozzi P., Liguori L.M., Caroleo B., Perticone M., Staltari O., Manfredini R., De Giorgi A., Averna M., Giammanco A., Granito A., Pettinari I., Marinelli S., Bolondi L., Falsetti L., Salvi A., Durante-Mangoni E., Cesaro F., Farinaro V., Ragone E., Morana I., Andriulli A., Ippolito A., Iacobellis A., Niro G., Merla A., Raimondo G., Maimone S., Cacciola I., Varvara D., Drenaggi D., Staffolani S., Picardi A., Vespasiani-Gentilucci U., Galati G., Gallo P., Davi G., Schiavone C., Santilli F., Tana C., Licata A., Soresi M., Bianchi B.G., Carderi I., Pinto A., Tuttolomondo A., Ferrari G., Gresele P., Fierro T., Morelli O., Laffi G., Romanelli R.G., Arena U., Cristina S., Gasbarrini A., Gargovich M., Zocco Z.M., Riccardi L., Ainora M.E., Capeci W., Martino M.G., Lorenzo N., Cavallo M., Frugiuele P., Greco A., Pietrangelo A., Ventura P., Cuoghi C., Marcacci M., Serviddio G., Vendemiale G., Villani R., Gargano R., Vidili G., Di Cesare V., Masala M., Delitala G., Invernizzi P., Di Minno G., Tufano A., Purrello F., Privitera G., Forgione A., Curigliano V., Senzolo M., Rodriguez-Castro K.-I., Giannelli G., Serra C., Neri S., Pignataro P., Rizzetto M., Debernardi V.W., Svegliati B.G., Bergamaschi G., Costanzo F., Angelico F., Del Ben M., Polimeni L., Talerico G., Proietti M., Romiti G.F., Ruscio E., and Toriello F.

Subjects
Registrie, Liver Cirrhosis, Male, Cirrhosis, Hepatocellular carcinoma, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Esophageal varices, Prevalence, Medicine, Prospective Studies, Registries, Prospective cohort study, Multivariate Analysi, Venous Thrombosis, Portal Vein, Anticoagulants, Liver failure, Splanchnic venous thrombosis, Emergency Medicine, Internal Medicine, Middle Aged, Portal vein thrombosis, Venous thrombosis, Splanchnic venous thrombosis , Anticoagulants , Liver failure , Hepatocellular carcinoma , Esophageal varices, Italy, Liver, Female, 030211 gastroenterology & hepatology, medicine.symptom, Settore SECS-S/01 - Statistica, Human, medicine.medical_specialty, Liver Cirrhosi, Socio-culturale, Asymptomatic, 03 medical and health sciences, Anticoagulants, Esophageal varices, Hepatocellular carcinoma, Liver failure, Splanchnic venous thrombosis, Internal medicine, Humans, Aged, Hepatology, Esophageal varice, business.industry, Anticoagulant, Splanchnic venous thrombosi, medicine.disease, Surgery, Prospective Studie, Splanchnic venous thrombosis, Anticoagulants, Liver failure, Hepatocellular carcinoma, Esophageal varices, Multivariate Analysis, Upper gastrointestinal bleeding, Complication, business
Abstract

Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the “Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry” (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68% men; 64±12years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44%) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child–Pugh score; hepatocellular carcinoma was present in 20%. The prevalence of ultrasound-detected portal vein thrombosis was 17% (n=126); it was asymptomatic in 43% of the cases. Notably, more than half of the portal vein thrombosis patients (n=81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis (p&nbsp

Published
2016

47. Reconstruction and Rehabilitation of Severe Mandibular Atrophy Using Distraction Osteogenesis Technique: A Case Report

Author

Alberto Merlini, Matteo Simonetti, Nicola Laffi, Joseph Garibaldi, Albino Triaca, and Paolo Balbi

Subjects
Mandibular symphysis, medicine.medical_treatment, education, Osteogenesis, Distraction, Dentistry, Bone grafting, behavioral disciplines and activities, Atrophy, Distraction, Radiography, Panoramic, medicine, Humans, Mandibular Diseases, Rehabilitation, business.industry, Middle Aged, medicine.disease, humanities, Implant placement, medicine.anatomical_structure, Otorhinolaryngology, Removable prosthesis, Distraction osteogenesis, Female, Surgery, Oral Surgery, business, psychological phenomena and processes
Abstract

Purpose The purpose of this article is to describe a rehabilitation technique for patients with severe anterior atrophy using a combination of distraction osteogenesis and implants to support fixed or removable prostheses. Materials and Methods The surgical technique involves the use of an extraosseous distraction device followed by more than 14 mm of distraction of the mandibular symphysis. Results The patient was successfully treated by the application of 4 implants in the region of the mandibular symphysis, stabilized by an Ackerman bar, and a removable prosthesis. Conclusion Osseous distraction techniques, when possible, are preferable to block bone grafting techniques because they present considerable advantages for patients and surgeons. The combination of distraction and implant placement can rehabilitate patients with severe defects.

Published
2014

48. Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events Findings From ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)

Author

Pan, Y. F., Lim, G., Desire, A., Tseng, W. K., Rost, Natalia S., Grammer, M., Khetarpal, S., Waseem, M., Zellner, C., Roper, E., Amin, M., Harden, M., Sababathi, R., Valpas, S., Bourlios, P., Kawaguchi, A., Mavronasiou, E., Pandurangi, U., Shams, S., Dichristin, U., Purayil, M. Padinhare, Munemasa, M., Angel, J., Gurusamy, P., Berni, A., Platner, N., Zeltser, D., El Jarroudi, M., Kisos, D., Haruna, T., Bernhardt, P., Coisne, D., Nakahara, Y., Li, W. M., Karamitsos, C., Tziortziotis, A., Essop, M., Nunkoo, T., Gani, M., Wilson, L., Kelfkens, Y., Mitha, I., Taljaard, J., Naidoo, D., Duki, Y., Snyders, F., Munnik, M., Soma, P., Johnston, H., Patki, N., Jasani, B., Van Der Merwe, N., Goosen, Y., Van Zyl, L., Le Roux, M., Venter, T., Wessels, L., Bae, H. J., Han, M. G., Cha, J. K., Kim, D. H., Cho, B. R., Ryu, D. R., Choi, H. H., Hong, K. S., Chung, W. S., Oh, Y. S., Han, S. H., Lee, K. H., Hong, T. J., Lee, H. W., Hyon, M. S., Jung, J. W., Jeon, H. K., Lee, J. M., Kang, D. H., Choi, K. J., Kim, C. J., Jin, E. S., Kim, D. S., Seo, J. S., Kim, H. S., Cha, M. J., Kim, J. T., Park, M. S., Kim, J. H., Park, J. H., Kim, J. S., Parekh, P., Vicente, C., Simoes, M., Carraro, A., Sobral Filho, D., Lustosa, E., Boas, F. Villas, Almeida, M., Zimmermann, S., Zimmermann, E. Burger, Kunkelova, V., Berka, L., Brodova, P., Bar, M., Bergovec, M., Vrazic, H., Matsushita, C., Premchand, R., Boyer, M., Bakliza, Z., Sutalo, K., Kirner, D., Steiner, R., Cvitkusic Lukenda, K., Samardzic, P., Buksa, B., Kartsagkoulis, E., Kaplan, P., Sopher, M., Young, G., Senior, R., Roberts, J., Mackin, A., Moriarty, A., Olympios, C., Green, M., Shandra, T., Zhurba, S., Logvinov, Y., Zharinov, O., Mudruk, I., Yena, L., Nahrebetskyy, V., Kraiz, I., Chompalova, B., Parishev, G., Kharalkar, H., Knezevic, A., Denchev, S., Usan, N., Kraydashenko, O., Milcheva, N., Stets, R., Donova, T., Gergova, V., Georgiev, B., Kostova, E., Goudev, A., Jaksic Jurinjak, S., Kinova, E., Hergeldjieva, V., Yagensky, A., Kamenova, P., Manolova, A., Vasilev, I., Mihov, A., Miteva, B., Kupnovytska, I., Mincheva, V., Jelic, V., Stoyanovski, V., Makar Ausperger, K., Nikolov, F., Vasilev, D., Pencheva, G., Kostov, K., Petranov, S., Boriani, G., Milusheva, T., Popov, A., Staneva, A., Momchilova-Lozeva, D., Francetic, I., Todorov, G., Nyagina, M., Tumbev, H., Tumbeva, D., Tzekova, M., Kitova, M., Manoylov, E., Dicker, D., Giovannelli, F., Archibald, J., Antle, S., Bhargava, R., Stafford, C., Bose, S., Hundseth, M., Cha, J., Otis, J., Romic, I., Ferri Certic, J., Chehayeb, R., Lepage, C., Tusek, S., Ciglenecki, N., Jeric, M., Chilvers, M., Car, S., Carevic, V., Vansickle, L., Kyyak, Y., Serik, S., Cleveland, D., Valley, S., Constance, C., Gauthier, M., Lasri, E., Costi, P., Masson, C., Coutu, B., Denis, I., du Preez, M., Kubanska, A., Dufresne, M., Krider, J., Eikelboom, J., Zondag, M., Fortin, C., Viau, C., Houbraken, D., Hatheway, R., Mabee, J., Bagatin, J., Lizogub, V., Atar, S., Heath, J., Scott, L., Ho, K., Perdomo Mejia, I., Ho, V., Hoag, G., Standring, R., Huynh, T., Perkins, L., Kouz, S., Roy, M., Labonte, R., Fuki, Y., Dewar, C., Lainesse, A., St-Germain, L., Lam, S., Lam, H., Lichtenstein, T., Roberts, P., Luton, R., Douglas, S., Sanchez Vallejo, G., Ma, P., Seib, M., MacCallum, C., Matthews, J., Malette, P., Vaillancourt, T., Maranda, C., Studenikow, E., Mawji, A., Morely, A., Morrison, D., Roth, M., Mucha, M., Volkov, V., Goncharov, O., Vizir, V., Sklyanna, O., Vatutin, M., Drapchak, I., Vakaliuk, I., Dharmarao, A., Zanwar, I., Thakur, B., Vinod, M. Vijan, Kaur, A., Marciano, C., Varma, S., Tykhonova, S., Kuznetsov, I., Tseluyko, V., Najarali, A., Lamoureux, U., Nicholson, R., O'Hara, G., Banville, P., O'Mahony, W., Bolton, R., Parkash, R., Carroll, L., Pesant, Y., Sardin, V., Polasek, P., Turri, L., Qureshi, A., Nethercott, C., Ricci, J., Gonzales, C., Gorna, O., Bozek, B., Rupka, D., Malynovsky, Y., Quintero, A., Belhassane, A., Fonseca, J., Orozco Linares, L., Marchand, C., Shu, D., Silverio, G., St-Hilaire, R., Fedotov, S., Morissette, A., Sussman, J., Ostrovska, L., Kailey, P., Syan, G., Lopez Giraldo, D., Moncada Corredor, M., Bobbie, C., Rivera Rodriguez, E., Talajic, M., David, D., Manzur, F., Talbot, P., Tremblay, M., Teitelbaum, I., Teitelbaum, J., Velthuysen, G., Giesbrecht, L., Wahby, R., Morley, A., Wharton, S., Caterini, T., Builes, A., Dimitra, K., Ajioka, M., Woodford, T., Balboa, W., Ushakova-Sokolova, L., Parkhomenko, A., Dovgan, N., Potapenko, P., Nekrasa, A., Prokhorov, O., Leonidova, V., Rebrov, B., Gamachek, O., Jaramillo Munoz, C., Daskalaki, A., Thankaraj, L., Moschos, N., Delgado, P., Hernandez, H., Aldana Diaz, I., Fernandez Ruiz, R., Arroyave, C., Delgado Restrepo, J., Leon Pineda, L., Srinivas, A., Cano, N., Accini, M., Accini, J., Zhang, Y. L., Zhou, S. X., Li, B. G., Zheng, Z. Q., Wang, J. Q., Zhao, X. L., Rishko, M., Chendey, T., Han, R. J., Zhao, R. P., Retamal Matus, L., Bugueno, C., Mondaca Mondaca, P., Cobos, J., Obreque, C., Corbalan, R., Parada, A., Kang, H., Gupta, R., Singh, G., Lyzohub, S., Florenzano, F., Arratia Diaz, P., Lopetegui, M., Rebolledo, C., Manriquez, L., Manriquez Silva, L., Martinez, D., Romero Llamas, R., Opazo, M., Carmona Perez, M., Pincetti, C., Torres Carrasco, G., Zhang, Z., Lin, Y. N., Rudyk, I., Zhang, H. Q., Qiang, H., Yuan, Z. Y., Li, L. L., Yu, B., Potthoff, S., Zapata Staub, J., Rodriguez, M., Campisto, Y., Xu, Y. P., Stockins, B., Lara Lara, C., Yovaniniz, P., Grandon Azua, M., Bai, F., Xu, G. L., Chen, J. Z., Xie, X. D., Chen, X. P., Zhang, X., Yin, Y. H., Gao, M., Dong, Y. G., Feng, C., Fu, G. S., Zhang, P., Miyauchi, Y., Hong, K., You, Z. G., Shatilo, V., Ishchuk, V., Zheng, Y., Hong, L., Zheng, X., Qiu, Y., Yang, Y. J., Shcherbak, V., Sudheer, R., Shetty, G., Li, A. Y., Goncharova, I., Yang, K., Liang, Y. Z., Xu, Y. M., Gu, J. Y., Xu, J. H., Li, Y. E., Wu, S. L., Huang, D., Wei, M., Shvetz, N., Shi, X. J., Wang, G. P., Qi, S. Y., Wang, D. M., Yang, Z. Y., Ma, S. M., Lu, Z. H., Liu, L., Gu, X. J., Sychov, O., Liao, D. N., Liu, Y., Zamlynskyy, M., Sirenko, Y., Stanislavchuk, M., Sethia, S., Sethia, A., Jiang, X. J., Li, Z. Q., Qu, Z., Li, L., Perebetiuk, L., Liu, H., Kandekar, B., Li, T. F., Liu, B., Raut, N., Kong, Y. Q., Hashimoto, Y., Jakala, P., Shimazu, Y., Hiasa, Y., Berger, N., Kale, V., Alexopoulos, D., Wurow, A., Filardi, P. Perrone, Al-Zoebi, A., Hoffmann, S., Viitaniemi, J., Dias, P., Oomaan, A., Murata, J., Natarajan, S., Narendra, J., Shelke, S., Duprat, C., Winter, K., Roudaut, R., Wolde, C., Buelow-Johansen, B., Oga, Y., Namjoshi, D., Lee, M. H., Leparree, S., Poulard, J., Nagai, Y., Sakata, Y., Naito, S., Oyama, H., Nishi, Y., Nagase, T., Ochiai, J., Junko, H., Ogawa, T., Sugeno, M., Oguro, H., Tanabe, M., Okada, K., Corbut, S., Moriyama, Y., Okajima, K., Nakashima, M., Okazaki, O., Wada, H., Kacet, S., Okishige, K., Kitani, S., Okumura, K., Deruche, E., Hermida, J., Dorn, S., Tsalihin, D., Hoffmann, U., Dieckheuer, U., Heuer, H., Winkelmann, B., Peitz, M., Hartmann, A., Otto, A., Grigat, C., Antman, Elliott M., Mercuri, Michele F., Ito, Y., Onishi, M., Iwade, K., SomaRaju, Bhupathi, Nicolau, Jose C., Singhal, Aneesh B., Silverman, Scott, Norden, Andrew D., Crompton, Andrea E., Murphy, Sabina A., Ruff, Christian T., Giugliano, Robert P., Narita, Y., Onaka, H., Moriyama, H., Ozaki, Y., Tanikawa, I., Sakagami, S., Nakano, A., Sakuragi, S., Hayashi, N., Sakurai, S., Ooki, H., Sasaki, T., Braunwald, Eugene, Oosawa, N., Satoh, A., Fujimoto, E., Seino, Y., Narumi, M., Shirai, T., Shigenari, M., Shoji, Y., Ueda, J., Manuela, W., Fuchs, R., Schneider, K., Sakuma, Y., Forck-Boedeker, K., Arfaoui, M., Dinanian, S., Joshi, H., Faghih, M., Weyland, K., Park, S. 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Horvathne, Lupkovics, G., Di Lenarda, A., Kovacs, Z., Gadepalli, R., Mariani, M., Kumagai, S., Luttermann, M., Krishnan, H., Dart, A., Venneklaas, U., Kay, S., Lueders, S., De Servi, S., Grosse, B., Davis, S., Baranyai, M., Silver, G., Flecknoe-Brown, S., Gates, P., Kovacs, I., Salminen, O., Koczka, M., Jakal, A., Jones, S., Pirelli, S., Lohrbaecher-Kozak, I., Bauch, F., Koenig, H., Lehman, R., Kiss, R., Saha, D., Barai, A., Roy, D., Bekal, S., Feil, J. Felfoldine, Meusel, P., Morrison, H., Biscardi, R., Kis, E., Hirayama, A., Allison, J., Godsey, W., Aliyar, P., Genova-Peeva, E., Kosztyu, M., Kleinecke-Pohl, U., Alexander, J., Brubaker, S., Akhter, F., Schoen, B., Reddy, R., Shankar, A. Ravi, Jungmair, W., Schmid, S., Junggeburth, J., De Pace, D., Ahmadpour, H., De Caterina, R., Hussain, A., Kaik, J., Ahmad, A., Beck, P., Zoghi, M., Batushkin, V., Fink, P., Reiling, S., Miyamoto, N., Adler, P., McKeirnan, M., Li, J., Paul, V., Batta, C., Serup-Hansen, K., Vuriya, A., Horacek, T., Schuppe, M., Kanakaridisz, N., Varga, A., Kimizu, T., Purnell, P., Perrett, L., Kishore, R., Szto, G., O'Shea, V., Capiau, L., Banaeian, F., De Bleecker, J., de Koning, K., De Tollenaere, M., Kara, M., Fiok, J., Szatmari, J., De Bruyne, L., Edes, I., Tsukimine, A., Muskoczki, E., Wiggers, H., Jakobsen, U., Torp-Pedersen, C., Forgione, C., Harada, K., Dioszeghy, P., Almaraz, S. Padilla, Desfontaines, P., Tincani, G., Heidbuchel, H., Camas, L. Velasquez, Cuccia, C., Meeusen, K., Herzet, J., Malmendier, D., Guerra, L., Mairesse, G., Raepers, M., Parque, J., Clinckemaille, N., Scavee, C., Samayoa, C. Sanchez, Pozuelos, J. Mayen, Arakawa, S., Huyberechts, D., Stockman, D., Jacobs, C., Vandekerckhove, Y., Svenningsen, A., Sand, N., Azhdari, M., Derycker, K., Peruzzotti, L., Comi, G., Vanwelden, J., Mino, K., Cervi, E., Sanchez, M., Gilat, T., van Welden, J., Vervoort, G., Mestdagh, I., Vrolix, M., Bazylevych, A., Vlasyuk, Z., Raae, D., Raymond, I., Beerts, C., Wollaert, B., Denie, D., Vincenzo de Paola, A. Amato, Coutinho, E., Lotufo, P. Andrade, de Melo, R. Ferreira, Atie, J., Motta, C., Alves da Costa, F. Augusto, Lahav, M., Estrada, M. Rodas, Ferraz, R. Franchin, Precoma, D. Bertolim, Guevara, S., Contzen, C., Weihrauch, D., Sehnem, E., Botelho, R., Cunha, S., Brondani, R., Fleck, N., Buhr, M., Kandekar, S., Ladenburger, K., Lavagnino, A. Ovando, Braun, R., Ishimaru, S., Chaves Junior, H., Silva, J., Costantini, C., Barroso, D., Jimenez, T., De Patta, M., Pereira, V., Duda, N., Bereznyakov, I., Laimer, R., Tomita, H., Ishii, Y., Dutra, O., Morgado, S., Saporito, W. Faustino, Seroqui, M., Ferreira, L., Araujo, E., Finimundi, H., Daitz, C., Gagliardi, R., Pereira, G., Gomes, M., Gomes, A., Guimaraes, A., Lebedynskaya, M., Petrovic, V., Overgaard, K., Ninho, L., Olsen, R., Nielsen, H., Jaeger, C., Barash, B., Veng-Olsen, T., Dotsenko, S., Pereira, L., Iversen, H., Madsen, H., Kulynych, R., Dzyak, G., Vasilyeva, L., Faynyk, A., Sorokivskyy, M., Gavrysyuk, V., Schnelzer, P., Ibsen, H., Adler, J., Dzublik, Y., Horbach, L., Husyev, V., Bouzo, M., Babbar, A., Loof, A., Blanc, J., Godlevska, O., Melgar, I. Guzman, Marcoviciu, D., Ramirez, V. de Leon, Sehr, B., Beyer-Westendorf, J., Vierbeck, S., Decoulx, E., Samburg, Y., Jorge, J., Cury, C., Karpenko, O., Hassager, C., Milla, O. Ayau, Kaiser, S., Christensen, L., Christensen, H., Dodt, K., Zidkova, E., Samkova, D., Vodnansky, P., Almeida, A., Kalil, C., Radaelli, G., Sebba Barroso de Souza, W. Kunz, Morales, K., Labrova, R., Nevolina, I., Karpenko, Y., Leaes, P., Luiz, R. 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Rossi, Pagnan, L. Goncalves, Sampaio, R., do Val, R., Saraiva, J., Francek, L., Florian, J., Ferkl, R., Elbl, L., Cermak, O., Burianova, H., Brtko, M., Pinto, B., and Yalcin, R.

Subjects
Male, medicine.medical_specialty, Pyridines, medicine.medical_treatment, 030204 cardiovascular system & hematology, Brain Ischemia, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Recurrence, Edoxaban, Internal medicine, Atrial Fibrillation, parasitic diseases, Secondary Prevention, medicine, Humans, Myocardial infarction, cardiovascular diseases, Stroke, Aged, Advanced and Specialized Nursing, business.industry, Hazard ratio, Warfarin, Anticoagulants, Atrial fibrillation, Thrombolysis, Middle Aged, medicine.disease, nervous system diseases, Thiazoles, Treatment Outcome, chemistry, Anesthesia, Cardiology, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, TIMI, medicine.drug
Abstract

Background and Purpose— Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with versus without previous IS/TIA. Methods— ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio, 2.0–3.0; median time-in-therapeutic range, 68.4%) versus once-daily edoxaban (higher-dose edoxaban regimen [HDER], 60/30 mg; lower-dose edoxaban regimen, 30/15 mg) with 2.8-year median follow-up. Primary end points included all stroke/systemic embolic events (efficacy) and major bleeding (safety). Because only HDER is approved, we focused on the comparison of HDER versus warfarin. Results— Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS 2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132 without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; P P P P =0.02). No treatment subgroup interactions were found for primary efficacy ( P =0.86) or for intracranial hemorrhage ( P =0.28). Conclusions— Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding. HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.

Published
2016

49. Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)

Author

Jones, D., Gu, X. J., Liu, L., Grammer, M., Waseem, M., Roper, E., Harden, M., Zellner, C., Mason, T., Zeig, S., Curtis, S., Zakhary, B., Yousuf, K., Wharton, S., VonGerichten, S., Willis, J., Dowling, C., Williams, R., Gibson, C., Williams, D., Truva, C., Westcott, J., St Laurent, B., Weiss, R., Sanchez, G., Waxman, F., Locklear, T., Ward, S., Renaud, K., Walsh, R., Kilcup, S., Vossler, M., Washam, M., Vijay, N., Warren, K., Vicari, R., Parsons, T., Verma, S., Cardoza, T., Vemireddy, D., Harrelson, K. Gonzalez, Val-Mejias, J., Hanna, K., Updegrove, J., Salas, L., Tucker, P., Romero, N., Torres, M., Southam, D., Teixeira, J., Mitchell, T., Tee, H., Young, K., Teague, S., Dastoli, K., Tawney, K., Swauger, M., Tatarko, M., Corchado, D., Tami, L., Leo, L., Talano, J., Bruton, T., Takata, T., Springer, K., Tahirkheli, N., Herwehe, S., Szulawski, I., Freemyer, D., Swerchowsky, V., Frost, J., Suresh, D., Vittitow, T., Struble, R., Cox, C., Steljes, A., Liu, M., Staniloae, C., McCartney, P., Spivack, E., Vasquez, E., Sperling, M., Thomason, L., Spangenthal, S., Hodnett, P., Smith, R., Keene, R., Smith, S., Hughes, B., Skierka, R., Nelson, M., Singh, V., Turner, K., Singh, N., Meyer, R., Simpson, P., Champagne, M., Siler, T., Stephenson, L., Shoukfeh, M., Browning, J., Shih, H., Hengerer, T., Sheikh, K., Hren, A., Shaoulian, E., Fleets, J., Shanes, J., Seese, M., Shalaby, A., Witt, P., Shah, G., Mather, N., Seide, H., Holt, A., Ullig, T., Seals, A., Mercer, S., Schulman, D., Schneider, W., Schneider, R., Fekete, A., Schaefer, S., Clifton, R., Savin, V., Lafave, J., Sandberg, J., Schomburg, J., Samal, A., Ball, E., Sacco, J., Nelson, T., Ruoff, G., Freeman, R., Ross, S., Martin, C., Rosen, R., Barnhorst, M., Rosado, J., Hollihan, P., Roehll, W., Cherrico, M., Robinson, J., Braun, D., Riofrio, K., Roberts, J., Pazier, P., Richwine, R., Stanley, E., Renzi, M., Wroblewski, J., Redondo, V., Domingo, D., Rama, P., Hemmen, C., Quinn, J., Reed, C., Quinlan, E., Rafla, E., Quadrel, M., Ebert, J., Pugeda, J., Sham, L., Pudi, K., Lowe, K., Pribble, A., Neeper, L., Pratt, R., Cush, S., Poulathas, A., Kirk, D., Yovaniniz, P., Pezzella, S., Brown, F., Pettis, K., Morlando, F., Petruzziello, F., Chacon, L., Peters, P., Duncan, D., Pentz, W., Montayne, S., Pearlstein, R., Gorry, N., Pavon, H., Dennison, K., Patnam, S., Joseph, L., Oza, S., Gonzalez, M., Osborne, J., Garcia, L., Orchard, R., McCormick, J., Oppenheimer, K., Thakkar, N., Oberoi, M., Wilmot, M., Nielsen, R., Nomanee, S., Nguyen, T., Goza, J., Nallasivan, M., West, M., Naidu, J., Parker, A., Nadar, V., Oehmann, V., Murphy, A., Raziano, S., Mullen, P., Todd, S., Mowdy, M., Schuler, C., Mounsey, P., Parrott, N., Mouhaffel, A., Bowman, B., Morledge, J., Garner, S., Moran, J., Strugatsky, S., Mody, F., Gryczan, J., Miller, S., Sanchez, S., Miller, R., Sanders, D., Milas, J., Romero-Colon, J., Michlin, B., Cajulis, C., Mercado, A., Cervellione, K., Mendelson, R., Wall, J., Mehrle, A., Skinner, J., Meholick, A., Marti, J., Mega, J., Lack, A., McLaurin, B., Paul, J., McKnight, T., Rodkey, K., McKenzie, M., Miranda, J., McGuire, K., Schwarz, L., McGarvey, J., Stubbs, L., McCartney, M., Hicks, T., Massin, E., Bedenko, E., Marenberg, M., Rabadi-Marar, D., Marar, I., Hernandez, S., Mandviwala, M., Casas, R., Makam, S., Lisiecki, B., Mainigi, S., Doctor, A., Magee, A., Bush, D., Macomber, J., Edelstein, J., Lurie, M., Wright, H., Lui, H., Ault, S., Looby, R., Davids, M., Lone, B., Shah, D., Lomnitz, D., Wofford, E., Littlefield, R., Murphy, R., Ling, L., Miller, D., Lillestol, M., Bonds, C., Lewis, D., Hartley, L., Lesser, M., Smith, D., Lentz, M., Royse, H., Ledbetter, L., Faucett, S., Langevin, E., Simmons, T., Lang, J., Ferguson, D., Landau, C., Coyle, G. 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Subjects
Male, medicine.medical_specialty, medicine.drug_mechanism_of_action, Pyridines, medicine.medical_treatment, Factor Xa Inhibitor, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Edoxaban, Risk Factors, Physiology (medical), Internal medicine, Thromboembolism, Atrial Fibrillation, Medicine, Humans, atrial fibrillation, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Stroke, Aged, business.industry, Warfarin, Anticoagulants, Atrial fibrillation, Thrombolysis, thromboembolism, bleeding, medicine.disease, mortality, stroke, Thiazoles, Treatment Outcome, chemistry, Anesthesia, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, TIMI, medicine.drug, Factor Xa Inhibitors
Abstract

Background— Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results— The 21 105 patients were categorized as having paroxysmal (P -adj =0.015) and permanent AF (1.95%/year; P -adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P -adj P -adj Conclusions— In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.

Published
2016

50. P1707QT interval in cirrhosis: dynamic changes during exercise suggest abnormal modulation of potassium currents

Author

Roberto Giulio Romanelli, Giuseppe Barletta, Fabio Marra, M R Del Bene, Francesco Venditti, and Giacomo Laffi

Subjects
medicine.medical_specialty, Cirrhosis, business.industry, Potassium, chemistry.chemical_element, medicine.disease, Endocrinology, chemistry, Modulation, Internal medicine, medicine, Interval (graph theory), Cardiology and Cardiovascular Medicine, business
Published
2017

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