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1. Antithrombotic Treatment in Antiphospholipid Syndrome: A Review

Author: Carmine Siniscalchi, Francesca Futura Bernardi, Pierpaolo Di Micco, Alessandro Perrella, Tiziana Meschi, and Ugo Trama
Subjects: antiphospholipid syndrome, catastrophic antiphospholipid syndrome, aspirin, heparins, warfarin, direct anticoagulant, Medicine
Abstract: Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid-binding proteins. APS is an autoimmune disorder associated with recurrent thrombosis of arterial or venous vessels and/or recurrent obstetric complications as miscarriages. APS can be divided into primary or secondary clinical syndrome because of the possible association with other autoimmune systemic diseases as systemic lupus erythematosus (SLE). Vitamin K antagonists remain the mainstay of treatment for most patients with APS and, based on current data, appear superior to the more targeted direct oral anticoagulants. However, the choice of the type of antithrombotic drug is based on the anamnesis of affected patients: patients with previous arterial or venous thrombosis may benefit from anticoagulants, while patients with previous obstetric diseases may benefit from aspirin, but several clinical exceptions may be evaluated. This short review is dedicated to underlining the main clinical evidence for patients affected by APS or CAPS (catastrophic antiphospholipid syndrome) in order to prevent recurrent thrombosis.
Published: 2024
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2. Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry

Author: Dominique Farge-bancel, R Marqués, M Ortiz, Paolo Prandoni, J Roa, Manuel Monreal, F Couturaud, J Gutierrez, J Pagan, Peter Verhamme, A Aujayeb, Laurent Bertoletti, P Verhamme, M Monreal, S Fonseca, S Pinto, S Soler, A Lorenzo, R Lecumberri, R Otero, P DI MICCO, F Rivera-Cívico, A Molino, P Suchon, C Grange, JA Caprini, J Osorio, Henri Bounameaux, R Valle, F Negro, A Tufano, Remedios Otero, Aitor Ballaz, G Kenet, I Francisco, F Uresandi, G Barillari, Marijan Bosevski, F García-Bragado, E Grau, D Jiménez, A Maestre, A Visonà, J Criado, R Chopard, I Weinberg, M Lumbierres, B Leclercq, H Bounameaux, Farid Rashidi, Abílio Reis, Lucia Mazzolai, P Llamas, MJ Núñez-Fernández, F Dentali, O Espitia, C Siniscalchi, Rosaria Del Giorno, Sanjiv Keller, Carmine Siniscalchi, Luciano Lopez-Jimenez, Ana Cristina Montenegro, Benjamin Brenner, Raquel Barb, Pierpaolo Di Micco, Sebastian Schellong, Inna Tzoran, Radovan Malý, Joseph A. Caprini, Hanh My Bui, MD Adarraga, A Alberich-Conesa, J Aibar, A Alda-Lozano, J Alfonso, C Amado, M Angelina-García, JI Arcelus, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón-Andrés, F Beddar-Chaib, A Blanco-Molina, JC Caballero, J Carrillo-Alonso, G Castellanos, L Chasco, C De Ancos, J Del Toro, P Demelo-Rodríguez, C De Juana-Izquierdo, MC Díaz-Pedroche, JA Díaz-Peromingo, A Dubois-Silva, JC Escribano, C Falgá, AI Farfán-Sedano, C Fernández-Aracil, C Fernández-Capitán, B Fernández-Jiménez, JL Fernández-Reyes, MA Fidalgo, C Gabara, F Galeano-Valle, C García-González, A García-Ortega, O Gavín-Sebastián, MA Gil-De Gómez, A Gil-Díaz, C Gómez-Cuervo, A González-Munera, L Guirado, L Hernández-Blasco, L Jara-Palomares, MJ Jaras, I Jou, MD Joya, JL Lobo, L López-Jiménez, P López-Miguel, H López-Brull, JJ López-Núñez, A López-Ruiz, JB LópezSáez, O Madridano, PJ Marchena, M Marcos, M Martín del Pozo, F Martín-Martos, R Martínez-Prado, JM Maza, E Mena, MI Mercado, J Moisés, MV Morales, MS Navas, JA Nieto, M Olid, L Ordieres-Ortega, S Otálora, N Pacheco-Gómez, AC Palomeque, E Paredes, P Parra-Caballero, P Parra-Rosado, JM Pedrajas, C Pérez-Ductor, M Pérez-Pinar, MA Pérez-Jacoiste, ML Peris, ML Pesce, JA Porras, R Puchades, A Rodríguez-Cobo, M Romero-Brugera, P Ruiz-Artacho, N Ruiz-Giménez, J Ruiz-Ruiz, G Salgueiro, T Sancho, V Sendín, P Sigüenza, A Steinherr, S Suárez-Fernández, R Tirado, A TorrentsVilar, MI Torres, J Trujillo-Santos, JF Varona, A Villalobos, P Villares, C Ay, S Nopp, I Pabinger, C Van Edom, A Verstraete, Yoo HHB, AC Montenegro, SN Morales, J Hirmerova, R Malý, L Bertoletti, A BuraRiviere, J Catella, R Le Mao, I Mahé, F Moustafa, L Plaisance, G Sarlon-Bartoli, E Versini, S Schellong, B Brenner, I Tzoran, P Sadeghipour, F Rashidi, A Abenante, M Basaglia, M Bertoni, F Bilora, B Brandolin, M Ciammaichella, D Colaizzo, E Grandone, E Imbalzano, R Pesavento, A Poz, P Prandoni, B Taflaj, B Zalunardo, A Skride, D Kigitovica, J Meireles, M Bosevski, M Zdraveska, L Mazzolai, and HM Bui
Subjects: Medicine
Abstract: Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.
Published: 2024
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3. Elemental and isotopic analysis of leaves predicts nitrogen-fixing phenotypes

Author: Joshua R. Doby, Carolina M. Siniscalchi, Mariela Pajuelo, John Krigbaum, Douglas E. Soltis, Robert P. Guralnick, and Ryan A. Folk
Subjects: Medicine, Science
Abstract: Abstract Nitrogen (N)-fixing symbiosis is critical to terrestrial ecosystems, yet possession of this trait is known for few plant species. Broader presence of the symbiosis is often indirectly determined by phylogenetic relatedness to taxa investigated via manipulative experiments. This data gap may ultimately underestimate phylogenetic, spatial, and temporal variation in N-fixing symbiosis. Still needed are simpler field or collections-based approaches for inferring symbiotic status. N-fixing plants differ from non-N-fixing plants in elemental and isotopic composition, but previous investigations have not tested predictive accuracy using such proxies. Here we develop a regional field study and demonstrate a simple classification model for fixer status using nitrogen and carbon content measurements, and stable isotope ratios (δ15N and δ13C), from field-collected leaves. We used mixed models and classification approaches to demonstrate that N-fixing phenotypes can be used to predict symbiotic status; the best model required all predictors and was 80–94% accurate. Predictions were robust to environmental context variation, but we identified significant variation due to native vs. non-native (exotic) status and phylogenetic affinity. Surprisingly, N content—not δ15N—was the strongest predictor, suggesting that future efforts combine elemental and isotopic information. These results are valuable for understudied taxa and ecosystems, potentially allowing higher-throughput field-based N-fixer assessments.
Published: 2024
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4. Noi refertiamo così… voi? Guida rapida per la valutazione sonologica della stenosi carotidea.

Author: Giovanni Malferrari, Andrea Zini, Giorgia Arnone, Ludovica Migliaccio, Matteo Paolucci, Giorgia Gentile, Mariateresa Lefemine, Franco Accorsi, Attilia Maria Pizzini, Mauro Silingardi, Nicola Carraro, Vittoria Maria Sarra, Giorgio Meneghetti, Claudio Baracchini, Giuseppe Pistollato, Patrizio Prati, Luciano Paolo Marchionno, Daniela Monaco, Maria Vittoria De Angelis, Chiara Vincenzi, Simone Quintana, Amedeo Bianchini, Giuseppe Pulito, Donatella Mastria, Francesco Paolo Sellitti, Fabrizio Calliada, Domenico Laterza, Lorenzo Coppo, Daniela Mastroiacovo, Francesco Prada, Sabrina Rossi, Cristiano Azzini, Nicola Merli, Maura Pugliatti, Francesco Ciccirillo, Antonio Siniscalchi, Enzo Sanzaro, Fabio Melis, Michele Pacilli, and Vincenzo Inchingolo
Subjects: stenosi carotidea, eco color Doppler, NASCET, ECST, stenosi carotidee classificazioni, neu-rosonologia clinica., Medicine, Therapeutics. Pharmacology, RM1-950
Abstract: Da oltre quarant’anni si utilizzano gli ultrasuoni per rilevare una placca carotidea e per seguire nel tempo la sua evoluzione. I protocolli terapeutici hanno ridotto enormemente il suo impatto sulla salute delle persone ma la scelta fra terapia medica e chirurgica si fonda su una valutazione clinica e strumentale che è solo apparentemente semplice. Nei referti di un esame ultrasonografico riportiamo il più delle volte delle percentuali di stenosi, a volte puntuali, a volte in termini di range oppure ci esprimiamo con aggettivi che descrivono la gravità della stenosi ma spesso ci facciamo confondere dai numeri e dalle differenti modalità di calcolo del range di stenosi ed è indubbio che, a volte, le conclusioni risultano ambigue ed estremamente dipendenti dall’interpretazione dell’operatore. Il problema è che l’angiografia digitale, gold standard diagnostico per la stenosi carotidea, adotta delle metriche non del tutto riproducibili con gli ultrasuoni. Con questo documento vogliamo condividere la ricerca di un linguaggio comune, a partire dal referto dei nostri esami. Noi refertiamo così… voi?
Published: 2024
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5. Catastrophic Antiphospholipid Syndrome: A Review

Author: Carmine Siniscalchi, Manuela Basaglia, Michele Riva, Michele Meschi, Tiziana Meschi, Giampiero Castaldo, and Pierpaolo Di Micco
Subjects: catastrophic antiphospholipid syndrome, antiphospholipid syndrome, antiphospholipid antibodies, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, Medicine
Abstract: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in individuals who have persistent antiphospholipid antibodies. Catastrophic antiphospholipid syndrome (CAPS) is a rare and potentially fatal form of APS characterized by severe thrombotic complications occurring in multiple organs over a short period of time or simultaneously. CAPS is associated with a high (50%) death rate. Infections, multi-organ failure, and cerebral and heart thrombosis represent the main complications of this syndrome. Generally, anticoagulants, glucocorticoids, therapeutic plasmapheresis (TPE), and intravenous immunoglobulin (IVIG) are used in combination for treatment. Multidisciplinary care involving different specialists from hematology, rheumatology, nephrology, infectious disease, critical care, and obstetrics is often required due to the complexity of the disease. Recent data emphasize the effectiveness of biologics such as anti-TNF-a monoclonal antibodies (adalimumab, certolizumab), anti-CD38 monoclonal antibody (daratumumab), BAFF/Blys inhibitor (belimumab), and BTK inhibitor (zanubrutinib) against CAPS. In order to understand the underlying causes of CAPS, one future possibility involves investigating and characterizing the hereditary and acquired risk factors associated with CAPS.
Published: 2023
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6. Relationship between asymmetric nostril use and human emotional odours in cats

Author: Serenella d’Ingeo, Marcello Siniscalchi, Valeria Straziota, Gianluca Ventriglia, Raffaella Sasso, and Angelo Quaranta
Subjects: Medicine, Science
Abstract: Abstract Cat social behaviour and cognition has received a growing interest during the last decades. Recent studies reported that cats efficiently engage in interspecific communication with humans and suggest that cats are sensitive to human emotional visual and auditory cues. To date, there is no evidence on the social and informative role of human emotional odours, which may affect human-cat communication. In this study, we presented cats with human odours collected in different emotional contexts (fear, happiness, physical stress and neutral) and evaluated the animals’ behavioural responses. We found that “fear” odours elicited higher stress levels than “physical stress” and “neutral”, suggesting that cats perceived the valence of the information conveyed by “fear” olfactory signals and regulate their behaviour accordingly. Moreover, the prevalent use of the right nostril (right hemisphere activation) with the increase of stress levels, particularly in response to “fear” odours, provides first evidence of lateralized emotional functions of olfactory pathways in cats.
Published: 2023
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7. Bacterial Porins and Their Procoagulant Role: Implication in the Pathophysiology of Several Thrombotic Complications during Sepsis

Author: Carmine Siniscalchi, Alessandro Perrella, Ugo Trama, Francesca Futura Bernardi, Egidio Imbalzano, Giuseppe Camporese, Vincenzo Russo, Olga Scudiero, Tiziana Meschi, and Pierpaolo Di Micco
Subjects: porins, thromboembolism, bacteria, sepsis, Medicine
Abstract: The association between sepsis and thrombotic complications is still not well known. Different mechanisms have been shown to be involved in the sepsis-induced prothrombotic state, but clinical scenarios may differ. In this review, we have summarized the role that bacterial products such as porins and toxins can have in the induction of the prothrombotic state during sepsis and the interaction that they can have with each other. Furthermore, the above-mentioned mechanisms might be involved in the pattern of the clinical presentation of thrombotic events during bacterial sepsis, which would secondarily explain the association between sepsis and venous thromboembolism, the association between sepsis and disseminated intravascular coagulation, and the association between sepsis and microangiopathic venous thromboembolism.
Published: 2024
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8. Real World Use of Tixagevimab/Cilgavimab Pre-Exposure Prophylaxis of COVID-19 in Immunocompromised Individuals: Data from the OCTOPUS Study

Author: Alessandra Vergori, Giulia Matusali, Eleonora Cimini, Licia Bordi, Paola Borrelli, Simone Lanini, Roberta Palazzi, Jessica Paulicelli, Davide Mariotti, Valentina Mazzotta, Stefania Notari, Rita Casetti, Massimo Francalancia, Silvia Rosati, Alessandra D’Abramo, Cosmina Mija, Paola Mencarini, Eugenia Milozzi, Emanuela Caraffa, Simona Sica, Elisabetta Metafuni, Federica Sorà, Angela Rago, Agostina Siniscalchi, Elisabetta Abruzzese, Mariagrazia Garzia, Giovanni Luzi, Roberta Battistini, Luca Prosperini, Antonella Cingolani, Enrico Girardi, Fabrizio Maggi, and Andrea Antinori
Subjects: passive pre-prophylaxis, SARS coronavirus, cell mediated immunity, humoral immunity, Medicine
Abstract: Objective. We aimed to report the real-world use and outcomes over time in immunocompromised individuals receiving tixagevimab/cilgavimab (T/C) pre-exposure prophylaxis (PrEP). Methods. This observational study included participants who received T/C PrEP, categorized into three groups: (i) No COVID-19 (NoC), i.e., participants who never had COVID-19; (ii) Hybrids (H), i.e., participants who had COVID-19 before PrEP; and (iii) Break-through Infections (BTIs), i.e., participants who had COVID-19 after PrEP. The study measured several immune markers at the administration of T/C (T0) at 3 (T1), 6 (T2), and 9 (T3) months afterward. These markers included: anti-receptor-binding domain (RBD) IgG antibodies; BA.5-neutralizing antibodies (nAbs); mucosal IgG; and T cell immunity. The incidence rate ratios for BTIs were analyzed using a Poisson regression model. Results. A total of 231 participants with a median age of 63 years (IQR 54.0–73.0). were included. Among these, 84% had hematological diseases and received a median of three vaccine doses. N = 72 participants belonged to the NoC group, N = 103 to the H group, and n = 56 to the BTI group (24%), with most BTIs being mild/moderate. The incidence rate (IR) of BTIs was 4.2 per 100 patient-months (95% CI 3.2–5.4), with no associated risk factors identified. There was a significant increase in anti-RBD IgG levels 3 months after the T/C administration in all groups, followed by a decline at 6 months, whereas at the same time points, geometric mean titers (GMTs) of anti-BA.5 nAbs were low for all groups and were around or below the detection threshold. No significant changes were observed in IFN-γ levels. The mucosal immune response was observed only 3 months after the PrEP administration. Conclusion. We provided a real-world experience model on the clinical efficacy of T/C PrEP in preventing severe COVID-19 during the Omicron wave through a comprehensive virological and immunological study. While waiting for the arrival of new monoclonal antibodies that can effectively neutralize the most recent variants, T/C PrEP remains the only viable strategy in the available armamentarium today to prevent COVID-19 complications in an extremely fragile population with suboptimal immune responses to COVID-19 vaccines.
Published: 2024
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9. A landscape of mouse mitochondrial small non-coding RNAs

Author: Chiara Siniscalchi, Armando Di Palo, Giuseppe Petito, Rosalba Senese, Francesco Manfrevola, Ilenia De Leo, Nicola Mosca, Teresa Chioccarelli, Veronica Porreca, Giovanna Marchese, Maria Ravo, Rosanna Chianese, Gilda Cobellis, Antonia Lanni, Aniello Russo, and Nicoletta Potenza
Subjects: Medicine, Science
Published: 2024

10. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes

Author: Raffaele Marfella, Celestino Sardu, Nunzia D’Onofrio, Carlo Fumagalli, Lucia Scisciola, Ferdinando Carlo Sasso, Mario Siniscalchi, Ludovica Vittoria Marfella, Davide D’Andrea, Fabio Minicucci, Giuseppe Signoriello, Arturo Cesaro, Maria Consiglia Trotta, Chiara Frigé, Francesco Prattichizzo, Maria Luisa Balestrieri, Antonio Ceriello, Paolo Calabrò, Ciro Mauro, Luca del Viscovo, and Giuseppe Paolisso
Subjects: Restenosis, Type 2 diabetes, SGLT-2 inhibitors, Major adverse cardiovascular events, Glycemic control, Medicine
Abstract: Abstract Background No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Methods We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. Results Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. Conclusions SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.
Published: 2023
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11. A review on management of antiphospholipid syndrome in clinical practice

Author: Carmine Siniscalchi, Pietro Rossetti, Gaetano Carolla, Pierpaolo Di Micco, Adriano Stella, and Michele Riva
Subjects: Antiphospholipid syndrome, antiphospholipid antibodies, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein 1 antibodies, Medicine
Abstract: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic or obstetric events occurring in patients with persistent antiphospholipid antibodies. Thrombotic APS is characterized by venous, arterial, or microvascular thrombosis. The diagnosis is accepted when both one clinical and one laboratory criteria according to the updated Sapporo classification are established. APS may occur in combination with other autoimmune diseases, mainly systemic lupus erythematosus, or in its primary form. Long-term anticoagulation with a vitamin K antagonist is the standard of care for patients who develop thrombosis, considering the high rate of recurrent thrombosis. The current international guidelines are not in favor of recommending direct oral anticoagulants for secondary prevention of thrombotic antiphospholipid syndrome, especially in the context of arterial thrombosis and triple-positive antiphospholipid patients. The most common approach, endorsed by the American College of Chest Physicians guidelines is the combination of heparin and low-dose aspirin (75-100 mg) daily for women who fulfill the clinical and serologic criteria for obstetric APS. New potential therapeutic approaches are under evaluation but actually the anticoagulation remains the cornerstone of treatment.
Published: 2023
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12. Facial asymmetry in dogs with fear and aggressive behaviors towards humans

Author: Marcello Siniscalchi, Serenella d’Ingeo, Michele Minunno, and Angelo Quaranta
Subjects: Medicine, Science
Abstract: Abstract There is now scientific evidence that, in dogs, distinctive facial actions are produced in response to different emotionally-arousing stimuli suggesting a relationship between lateralized facial expressions and emotional states. Although in humans, relationships between facial asymmetry and both emotional and physiological distress have been reported, there are currently no data on the laterality of dogs’ facial expressions in response to social stimuli with respect to canine behavioral disorders. The aim of the present work was to investigate the facial asymmetries of dogs with fear and aggressive behavior towards humans during two different emotional situations: (1) while the dogs were alone in the presence of their owners and (2) during the approach of an unfamiliar human being. Overall, our results demonstrated high levels of asymmetries in facial expressions of dogs displaying fear and aggressive behaviors towards humans indicating that measuring facial asymmetries in dogs could prove to be a useful non-invasive tool for investigating physiology-based behavioral disorders.
Published: 2022
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13. Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

Author: Joachim Gerss, Javier Ripollés-Melchor, Emmanuel Futier, Melanie Meersch, Carola Wempe, Detlef Kindgen-Milles, Alexander Zarbock, Markus W Hollmann, Sigismond Lasocki, Thomas Rimmele, Tim Rahmel, Michael Adamzik, Hartmuth Nowak, Ingeborg Welters, Brian Johnston, Ane Abad-motos, Alfredo Abad-gurumeta, Marc Moritz Berger, Davide Ricci, Maurizio Cecconi, Gudrun Kunst, Christian Stoppe, Christian Putensen, Marlies Ostermann, Sascha Ott, Brijesh Patel, Gabriele Baldini, Antoine Lamblin, Karen Williams, Elena Mancini, Christian Arndt, Hinnerk Wulf, Marc Irqsusi, Wim Vandenberghe, John Kellum, Raphael Weiss, Jackie Donovan, Lui G Forni, Giacomo Monti, Céline Monard, Markus A Weigand, Thorsten Brenner, Ulrich Jaschinski, Carlos Lopez, Maxime Leger, Emmanuel Rineau, Philipp Simon, María Gómez-Rojo, Lars Bergmann, Alicia Waite, Savino Spadaro, Alexander Wolf, Andrew Spence, Simon Dubler, Alexander PJ Vlaar, Patrick Schober, Ben C Creagh-Brown, Nandor Marczin, Emilio Maseda, Christian Strauss, Stefano Romagnoli, Christian Nusshag, Ulrich Gobel, Ángel Candela-Toha, Jon Silversides, Nuttha Lumlertgul, Khaschayar Saadat-Gilani, Vincent Legros, Timo Brandenburger, Thomas Dimski, Laura Huthmann, Claude Pelletier, Manon Schleß, Peter Rosenberger, Helene Häberle, Jan Gerrit Haaker, Matthias Gründel, Lucia Cattin, Laura Villarino Villa, Juan Victor Lorente, Christine Martin, Jan Larmann, Wolfgang Bauer, Giovanni Borghi, Benjamin O’Brien, Thilo von Groote, Antoine Guillaume Schneider, Silvia De Rosa, Diego Parise, Alice Bernard, Paula Fernández-Valdes-Bango, Irene Romero Bhathal, A Suarez-de-la-Rica, Gianluca Villa, Raquel García-Álvarez, Antonio Siniscalchi, Richard Ellerkmann, Florian Espeter, Christian Porschen, Mahan Sadjadi, Michael Storck, Tobias Brix, Dana Meschede, Wida Amini, Carina Stenger, Julius Freytag, Jens Brands, Matthias Unterberg, Britta Marko, Fabian Dusse, Wolfgang A Wetsch, Sandra E Stoll, Hendrik Drinhaus, Bernd W Böttiger, Onnen Mörer, Lars-Olav Harnisch, Roswitha Lubjuhn, Daniel Heise, Christian Bode, Andrea Sauer, Konrad Peukert, Lennart Wild, Philippe Kruse, Jan Menzenbach, Valbona Mirakaj, Sabine Hermann, Stefanie Decker, Mona Jung-König, Tobias Hölle, Sarah Dehne, Jörg Reutershan, Thomas Prüfer, Stefan Pielmeier, Indra Wimmelmeier, Michaela Scholz, Andrea Paris, Isabel Christina Gallego Zapata, Holger Pohl, Nirmeen Fayed, Kai Dielmann, Evelyn Martin, Tilo Koch, Alexander Mück, Philipp Deetjen, Ngoc Bich Mehlmann, Peter M Spieth, Andreas Güldner, Axel Rand, Maximillian Ragaller, Martin Mirus, Rebecca Bockholt, Marc Herzog, Maren Kleine-Brüggeney, Ant Isabelle Cristiani, Marion Ohl, Monica Vieira Da Silva, Gilda Filipe de Castro Reblo, Matthias Hilty, Katharina Spanaus, Benedetta Mura, Eleonora Terreni, Francesco Magiotti, Lorenzo Turi, Cristiana Laici, Chiara Capozzi, Andrea Castelli, Massimiliano Greco, Antonio Messina, Gianluca Castellani, Romina Aceto, Vinicio Danzi, Alessandro Rigobello, Massimo De Cal, Monica Zanella, Gaetano Scaramuzzo, Riccardo La Rosa, Paolo Priani, Alberto Volta Carlo, Stefano Turi, Martina Baiardo Redaelli, Marilena Marmiere, Kittisak Weerapolchai, Shelley Lorah, Fabiola D’Amato, Aneta Bociek, Rosario Lim, Benjie Cendreda, Reynaldo Dela Cuesta, Eirini Kosifidou, Zoka Milan, Juliana Fernanda, Emma Clarey, Daveena Meeks, Nicholas J Lees, Marco Scaramuzzi, Orinta Kviatkovske, Adam Glass, Christine Turley, Charlotte Quinn, Syeda Haider, Adam Rossiter, Syed Nasser, Ned Gilbert-Kawai, Tatjana Besse-Hammer, Eric Hoste, Hannah Schaubroeck, Jan De Waele, Jenni Breel, Eline de Klerk, Harm-Jan de Grooth, Lothar Schwarte, Alexander Loer, Alicia Ruiz-Escobar, Diana Fernández-García, Nerea Gómez-Pérez, Pascual Crespo-Aliseda, Cristina Cerro-Zaballos, Cristina Fernández-Martín, Eduardo Martín-Montero, Alejandro Suarez de la Rica, Héctor Berges Gutiérrez, Maria del Pino Heredia Pérez, Maria de los Reyes Bellido Fernández, Liena Izquierdo López, Javier Valiente Lourtau, Ma Angeles Ferre Colomer, Ma Azucena Pajares Moncho, Maria Jesús Montero Hernández, Esther Pérez Sancho, Silvia Polo Matínez, Pedro Rivera Soria, Maider Puyada Jáuregui, Hugo Rivera Ramos, Marta Antelo Adrán, Ramón Adalia Bartolomé, Patricia Galán Menéndez, Laura Llinares Espin, Yuri Santiago Loaiza Aldean, Víctor MoralesAriza, Rosalía Navarro-Perez, Luis Santé-Serna, Pedro de la Calle-Elguezabal, Rubén Sánchez-Martín, Inés De Soto, Pau Vallhonrat Alcántara, Laura Perelló Cerdà, Gal·la Rouras Hurtado, Paula Rodriguez Nieto, John Narros Sicluna, Angel Molero Molinero, Juan Pablo Nocete, Elena Murcia Sánchez, Stanislas Abrard, Marie-Luce Parrouffe, Frank Bidar, Lucie Aupetitgendre, Ugo Schiff, Bertille Paquette, Gaëlle Sellier, Nathalie Borgnetta, Benjamin Brochet, Thierry Floch, Julien Coffinet, and Marion Leclercq-Rouget
Subjects: Medicine
Abstract: Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysis The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and dissemination The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration number NCT04647396.
Published: 2023
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14. Therapeutic option for patients with severe hallux rigidus

Author: Diego Javier Yearson, Ignacio Melendez, Federico Anain, Santiago Siniscalchi, and Juan Drago
Subjects: Hallux rigidus, Metatarsal bone, Metatarsophalangeal joint, Osteotomy, Medicine, Orthopedic surgery, RD701-811
Abstract: Objective: Subclassify grade III of Hattrup and Johnson classification into two groups, according to the remaining percentage of plantar articular cartilage, and propose a treatment option other than arthrodesis for some of these patients. Methods: Twenty-one patients with grade III hallux rigidus were operated on between February 2015 and January 2020. The radiographic Hattrup and Johnson’s classification was used, and grade III patients were submitted to frontal, lateral, and oblique radiographs. Eventually, a computed tomography (CT) was performed. The viable surface of the plantar cartilage and the percentage of the total joint was determined: if there is up to 50% of remaining plantar articular cartilage, the joint was preserved, indicating Weil osteotomy of the first metatarsal, associated with wide dorsal cheilectomy (type 3A); if less than 50%, metatarsophalangeal arthrodesis was indicated (type 3B). Patients with the first metatarsal at least 5 mm shorter than the second on frontal radiograph were excluded from the study. Results: A mean postoperative American Orthopaedic Foot & Ankle Society (AOFAS) score of 91 was obtained. To date, no patient has needed arthrodesis, and all patients have increased joint range of motion. Shortening the central metatarsals was not necessary as a second procedure due to transfer metatarsalgia. Conclusion: Some joints classified as grade III can be treated with an osteotomy without needing arthrodesis. Level of Evidence IV; Therapeutic Study; Case Series.
Published: 2022
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15. Comparative analyses of Mikania (Asteraceae: Eupatorieae) plastomes and impact of data partitioning and inference methods on phylogenetic relationships

Author: Verônica A. Thode, Caetano T. Oliveira, Benoît Loeuille, Carolina M. Siniscalchi, and José R. Pirani
Subjects: Medicine, Science
Abstract: Abstract We assembled new plastomes of 19 species of Mikania and of Ageratina fastigiata, Litothamnus nitidus, and Stevia collina, all belonging to tribe Eupatorieae (Asteraceae). We analyzed the structure and content of the assembled plastomes and used the newly generated sequences to infer phylogenetic relationships and study the effects of different data partitions and inference methods on the topologies. Most phylogenetic studies with plastomes ignore that processes like recombination and biparental inheritance can occur in this organelle, using the whole genome as a single locus. Our study sought to compare this approach with multispecies coalescent methods that assume that different parts of the genome evolve at different rates. We found that the overall gene content, structure, and orientation are very conserved in all plastomes of the studied species. As observed in other Asteraceae, the 22 plastomes assembled here contain two nested inversions in the LSC region. The plastomes show similar length and the same gene content. The two most variable regions within Mikania are rpl32-ndhF and rpl16-rps3, while the three genes with the highest percentage of variable sites are ycf1, rpoA, and psbT. We generated six phylogenetic trees using concatenated maximum likelihood and multispecies coalescent methods and three data partitions: coding and non-coding sequences and both combined. All trees strongly support that the sampled Mikania species form a monophyletic group, which is further subdivided into three clades. The internal relationships within each clade are sensitive to the data partitioning and inference methods employed. The trees resulting from concatenated analysis are more similar among each other than to the correspondent tree generated with the same data partition but a different method. The multispecies coalescent analysis indicate a high level of incongruence between species and gene trees. The lack of resolution and congruence among trees can be explained by the sparse sampling (~ 0.45% of the currently accepted species) and by the low number of informative characters present in the sequences. Our study sheds light into the impact of data partitioning and methods over phylogenetic resolution and brings relevant information for the study of Mikania diversity and evolution, as well as for the Asteraceae family as a whole.
Published: 2021
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16. External column lengthening with peek cage and modified single approach

Author: Diego Yearson, Ignacio Melendez, Federico Anain, Santiago Siniscalchi, and Juan Drago
Subjects: flatfoot/surgery, foot deformities, acquired, osteotomy, calcaneus/surgery, bone screws, treatment outcome, Medicine, Orthopedic surgery, RD701-811
Abstract: Objective: To show the results obtained with the treatment of stage 2B flatfoot according to Myerson classification (reducible and flexible), through external column lengthening with interposition of a peek cage filled with spongious graft taken from the same calcaneus, without osteosynthesis, combined with medial slide calcaneal osteotomy with step plate, both using the a single approach. Medial time was associated with latero-lateral transfer of common flexor tendon of toes to posterior tibial. Methods: Sixteen patients were assessed from 2015 to 2018, of which 11 were women and 5 were men. In all cases, surgery was performed with a first lateral time for osteotomies and a second time for tendon repair. Mean patients’ follow-up was 28 months. Results: All patients achieved consolidation of both osteotomies at nearly 12 postoperative weeks. No patient presented signs of peek cage migration due to lack of stability or dorsal cutaneous nerve branch injuries resulting from this modified single approach. Two patients evolved with wound dehiscence and only one with calcaneocuboid pain so far. No patient required reoperation. Conclusion: The modified single tuberosity approach for the two osteotomies has shown to be a simple procedure that prevents damages to dorsal cutaneous nerve branches described with dorsal approach. Leve lof Evidence IV; Therapeutic Studies; Case Series.
Published: 2021
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17. A geo-chemo-mechanical study of a highly polluted marine system (Taranto, Italy) for the enhancement of the conceptual site model

Author: F. Cotecchia, C. Vitone, F. Sollecito, M. Mali, D. Miccoli, R. Petti, D. Milella, G. Ruggieri, O. Bottiglieri, F. Santaloia, P. De Bellis, F. Cafaro, M. Notarnicola, F. Todaro, F. Adamo, A. Di Nisio, A. M. L. Lanzolla, M. Spadavecchia, M. Moretti, G. Agrosì, F. De Giosa, P. Fago, M. Lacalamita, S. Lisco, P. Manzari, E. Mesto, G. Romano, G. Scardino, E. Schingaro, A. Siniscalchi, G. Tempesta, E. Valenzano, G. Mastronuzzi, N. Cardellicchio, A. Di Leo, L. Spada, S. Giandomenico, M. Calò, V. F. Uricchio, G. Mascolo, G. Bagnuolo, R. Ciannarella, A. Tursi, G. Cipriano, P. Cotugno, L. Sion, R. Carlucci, G. Capasso, G. De Chiara, G. Pisciotta, R. Velardo, and V. Corbelli
Subjects: Medicine, Science
Abstract: Abstract The paper presents the results of the analysis of the geo-chemo-mechanical data gathered through an innovative multidisciplinary investigation campaign in the Mar Piccolo basin, a heavily polluted marine bay aside the town of Taranto (Southern Italy). The basin is part of an area declared at high environmental risk by the Italian government. The cutting-edge approach to the environmental characterization of the site was promoted by the Special Commissioner for urgent measures of reclamation, environmental improvements and redevelopment of Taranto and involved experts from several research fields, who cooperated to gather a new insight into the origin, distribution, mobility and fate of the contaminants within the basin. The investigation campaign was designed to implement advanced research methodologies and testing strategies. Differently from traditional investigation campaigns, aimed solely at the assessment of the contamination state within sediments lying in the top layers, the new campaign provided an interpretation of the geo-chemo-mechanical properties and state of the sediments forming the deposit at the seafloor. The integrated, multidisciplinary and holistic approach, that considered geotechnical engineering, electrical and electronical engineering, geological, sedimentological, mineralogical, hydraulic engineering, hydrological, chemical, geochemical, biological fields, supported a comprehensive understanding of the influence of the contamination on the hydro-mechanical properties of the sediments, which need to be accounted for in the selection and design of the risk mitigation measures. The findings of the research represent the input ingredients of the conceptual model of the site, premise to model the evolutionary contamination scenarios within the basin, of guidance for the environmental risk management. The study testifies the importance of the cooperative approach among researchers of different fields to fulfil the interpretation of complex polluted eco-systems.
Published: 2021
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18. Hallux valgus: Patología tridimensional. Nuevo enfoque terapéutico

Author: Diego Javier Yearson, Ignacio Melendez, Federico Anain, Santiago Siniscalchi, and Juan Drago
Subjects: hallux valgus, rotacional, crecientica, chevron, Medicine, Orthopedic surgery, RD701-811
Abstract: Introducción: el hallux valgus es la deformidad musculoesquelética más frecuente. La laxitud y la hipermovilidad tarso metatarsiana favorecen su desarrollo. El objetivo de este trabajo es plantear una patología tridimensional, y elaborar un algoritmo quirúrgico para cada patrón de deformidad, incorporando el componente rotacional del metatarsiano. Materiales y métodos: evaluamos prospectivamente una serie de 89 casos entre febrero de 2020 y febrero 2021, 80 mujeres y 9 hombres. Nivel de evidencia IV. La edad promedio fue 39 años y el seguimiento 11.3 meses. Utilizamos la clasificación de Hardy-Clapham y separamos 2 grupos, los hallux sin componente rotacional (tipo 1 a 3), y aquellos con componente rotacional (tipo 4 a 7). Resultados: el 59% entraron en el primer grupo, a los cuales se realizó osteotomía distal en chevron acorde a la deformidad en el plano frontal. El 41 % restante tuvo componente rotacional, y se realizó una osteotomía distal en chevron rotacional, crecientica en la base, o artrodesis de Lapidus modificada, según la deformidad en plano frontal o inestabilidad asociada. Consolidaron todos pacientes. AOFAS 94.5%, VAS 0.71 y 100% de satisfacción. Discusión: el componente rotacional es fundamental en la interpretación del hallux valgus, pero no es el único para tener en cuenta. El mismo puede no estar presente o no ser trascendente, y se alcanzan excelentes resultados como los publicados por décadas. Es fundamental diferenciar los pacientes con componente rotacional para realizar el tratamiento adecuado. Conclusión: considerando el hallux valgus una patología tridimensional, proponemos un protocolo de tratamiento acorde para cada paciente.
Published: 2021
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19. Mobilization protocol and early postoperative weight-bearing in transyndesmal ankle fractures

Author: Diego Yearson, Ignacio Melendez, Federico Anain, Santiago Siniscalchi, and Juan Drago
Subjects: Fractures, bone, Ankle, Range of motion, articular, Early ambulation, Electrophoretic mobility shift assay, Medicine, Orthopedic surgery, RD701-811
Abstract: Objective: To disseminate a rehabilitation protocol with early mobilization and ambulation, with no external supports, reducing the time until full weight-bearing and providing greater postoperative comfort. Methods: We prospectively assessed a series of 68 patients, with level of evidence IV, mean age of 33.3 years. We performed open reduction with ankle lateral approach (Kocher) and internal fixation with an interfragmentary compression screw and a one-third locked tubular plate for neutralization. All patients were subjected to a rehabilitation protocol with early mobilization and weight-bearing. Results: No fracture displacements were observed on the postoperative radiographic controls, neither loosening nor ruptures of implants. There was no need to change rehabilitation guidelines either due to pain or to other subjective limitation. Conclusion: We can state that early joint mobilization and controlled progressive support, with appropriate osteosynthesis, resulting in an early return to everyday activities, both work and sports ones. Level of Evidence IV; Therapeutic Studies; Case Series.
Published: 2021
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20. Extremely low nucleotide diversity among thirty-six new chloroplast genome sequences from Aldama (Heliantheae, Asteraceae) and comparative chloroplast genomics analyses with closely related genera

Author: Benoit Loeuille, Verônica Thode, Carolina Siniscalchi, Sonia Andrade, Magdalena Rossi, and José Rubens Pirani
Subjects: Complete plastome, Compositae, ycf2 gene, rbcL positive selection, Species-level plastome evolution, Medicine, Biology (General), QH301-705.5
Abstract: Aldama (Heliantheae, Asteraceae) is a diverse genus in the sunflower family. To date, nearly 200 Asteraceae chloroplast genomes have been sequenced, but the plastomes of Aldama remain undescribed. Plastomes in Asteraceae usually show little sequence divergence, consequently, our hypothesis is that species of Aldama will be overall conserved. In this study, we newly sequenced 36 plastomes of Aldama and of five species belonging to other Heliantheae genera selected as outgroups (i.e., Dimerostemma asperatum, Helianthus tuberosus, Iostephane heterophylla, Pappobolus lanatus var. lanatus, and Tithonia diversifolia). We analyzed the structure and gene content of the assembled plastomes and performed comparative analyses within Aldama and with other closely related genera. As expected, Aldama plastomes are very conserved, with the overall gene content and orientation being similar in all studied species. The length of the plastome is also consistent and the junction between regions usually contain the same genes and have similar lengths. A large ∼20 kb and a small ∼3 kb inversion were detected in the Large Single Copy (LSC) regions of all assembled plastomes, similarly to other Asteraceae species. The nucleotide diversity is very low, with only 1,509 variable sites in 127,466 bp (i.e., 1.18% of the sites in the alignment of 36 Aldama plastomes, with one of the IRs removed, is variable). Only one gene, rbcL, shows signatures of positive selection. The plastomes of the selected outgroups feature a similar gene content and structure compared to Aldama and also present the two inversions in the LSC region. Deletions of different lengths were observed in the gene ycf2. Multiple SSRs were identified for the sequenced Aldama and outgroups. The phylogenetic analysis shows that Aldama is not monophyletic due to the position of the Mexican species A. dentata. All Brazilian species form a strongly supported clade. Our results bring new understandings into the evolution and diversity of plastomes at the species level.
Published: 2021
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21. Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury.

Author: Erika Cione, Antonio Siniscalchi, Pietro Gangemi, Lucio Cosco, Manuela Colosimo, Federico Longhini, Filippo Luciani, Giovambattista De Sarro, G&SP Working Group, Liberato Berrino, Bruno D'Agostino, and Luca Gallelli
Subjects: Medicine, Science
Abstract: The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren's method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P
Published: 2021
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22. Posterior malleolar fractures. New classification and treatment algorithm

Author: Diego Yearson, Ignacio Melendez, Federico Anain, Santiago Siniscalchi, and Juan Drago
Subjects: Ankle fractures/classification, Algorithms, Treatment outcomes, Medicine, Orthopedic surgery, RD701-811
Abstract: Objective: This study proposes a new classification of posterolateral malleolar fractures and a treatment algorithm. Methods: We divided the posterolateral malleolus, which we considered as the posterior malleolus, from the posteromedial one, which we considered as being part of the medial malleolus fracture. The experience with 77 patients treated from February 2017 to February 2020 was assessed. All of them were assessed by frontal and profile radiographies and computed tomography (CT). Among the parameters to classify these fractures, we believe the most determining ones are fracture size, followed by presence of fracture displacement. Results: Fractures were divided into those whose posterior fragment was 25% smaller than the tibial joint surface and those that compromised more than 25% of this joint. The first group underwent syndesmotic opening and was subclassified into 1A (stable fractures), which do not require surgical treatment, and 1B (unstable), which require syndesmotic stabilization. The second group, which comprised the larger fractures, was subclassified into 2 A (non-displaced fractures, or with a displacement below 2 mm), which underwent percutaneous osteosynthesis, 2B (displaced fractures), and 2C (comminuted fractures), which underwent open reduction and internal fixation using a posterior approach. Conclusion: The classifications published so far are anatomic or descriptive, but none of them proposes a therapeutic algorithm for each type of fracture. We believe it will be helpful for its interpretation and decision-making on the need to perform a posterior approach, prioritizing the anatomical reduction of the joint fragment and resolution of syndesmotic instability linked to each fracture pattern using the most simple and effective method. Level of Evidence IV; Therapeutic Studies; Case Series.
Published: 2020
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23. Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism

Author: G. Pellejero, Jose Gutierrez, R. Malý, M. Basaglia, L. Chasco, P. Suchon, R. Le Mao, Laurent Bertoletti, F. Martins, J. Caprini, A. Braester, F. Galeano-Valle, Hanh My Bui, J. Alonso, Y. Sato, G. Vidal, Y. Nishimoto, C. Tolosa, E. Nofuentes-Pérez, A.M. Díaz-Brasero, N. Ait Abdallah, M.D. Adarraga, R. Sánchez-Martínez, L. Font, Raquel López-Reyes, Inna Tzoran, Karine Lacut, J. del Toro, Andris Skride, Ana Jaureguizar, Joseph A. Caprini, C. Amado, R. García de la Garza, A.M. Camon, S. Merla, Luciano López-Jiménez, G. Salgueiro, Sebastian Schellong, Alfonso Muriel, F. Bilora, S. Lainez-Justo, B. Suárez-Rodríguez, Carme Font, F. Beddar Chaib, I. Francisco, C. Jiménez-Alfaro, P. Azcarate-Agüero, Maurizio Ciammaichella, J.A. Porras, N. Vo Hong, F. Martín-Martos, Dominique Farge-Bancel, D. Farge-Bancel, José Luis Lobo, M. Giménez-Suau, E. Grau, F. García-Bragado, Ángeles Blanco-Molina, Carmen Fernández-Capitán, María del Carmen Díaz-Pedroche, C. Grange, Adriana Visonà, L. Guirado, P. Villares, P. López-Miguel, José María Pedrajas, S. Accassat, Beatriz Valero, B. Crichi, Juan J. López-Núñez, Luis Jara-Palomares, G. Sarlon-Bartoli, J. Lima, C. Bortoluzzi, Alicia Lorenzo, C. de Ancos, M.A. Fidalgo, Philippe Debourdeau, Pablo Javier Marchena, C. Rodríguez-Matute, A.I. Farfán-Sedano, José Luis Fernández-Reyes, J.C. Escribano, Juan I. Arcelus, M. Barrón, I. Quere, Remedios Otero, A. De Angelis, P. Morange, Peter Verhamme, G. Kenet, P. Prandoni, Pedro Ruiz-Artacho, C. Siniscalchi, A. Zaicenko, M. Olid-Velilla, C. García-Díaz, B. Barrón-Andrés, T. Sancho, Fernando Uresandi, Javier Trujillo-Santos, A. Muñoz-Blanco, A. Villalobos, A. Dubois-Silva, J. Moisés, J. Osorio, M.I. Mercado, J.M. Suriñach, M.A. Aibar, M.D. Joya, Cihan Ay, J.A. Díaz-Peromingo, H. Bounameaux, Diego Martínez-Urbistondo, Thomas Vanassche, L. Bertoletti, Marijan Bosevski, Farès Moustafa, M. Martín del Pozo, J.F. Sánchez-Muñoz-Torrero, H.M. Bui, Ingrid Pabinger, M.C. Olivares, M. García de Herreros, M.J. Núñez-Fernández, B. Zalunardo, J.F. Varona, Stephan Nopp, Behnood Bikdeli, B. Brandolin, B. Bikdeli, Olga Madridano, Manuel Monreal, M.J. Jaras, Alessandra Bura-Rivière, Abílio Reis, J. Portillo, O. Espitia, J. Catella, Aitor Ballaz, F. Esposito, R. Barba, R. Valle, H. Helfer, I. Tzoran, J.B. López-Sáez, P. Ruiz-Artacho, M.A. García, J. Aibar, C. Gómez-Cuervo, C. Gabara, A. Latorre, J. Ruiz-Ruiz, Benjamin Brenner, S. Fonseca, S. Schellong, Raffaele Pesavento, Barry M. Brenner, Silvia Soler, Paolo Prandoni, Victor F. Tapson, Ana Maestre, Pierpaolo Di Micco, M. Muñoz, J. Criado, D. Jiménez, Antonella Tufano, G. Krstevski, B. Valero, Henri Bounameaux, M.I. Torres, G. Poenou, Isabelle Mahé, Aída Gil-Díaz, A. Asuero, S. Otalora, V. Rosa, L. Vela, E. Imbalzano, C. Vandenbriele, C. Barbagelata, Jana Hirmerova, J. Meireles, David Jiménez, Lucia Mazzolai, L. Hernández-Blasco, M. Bosevski, Gili Kenet, C. Mella, M. Monreal, J.R. Vela, P. Di Micco, Carlos Zamora, K. Flores, P. Demelo-Rodríguez, Radovan Malý, J. Birzulis, J.A. Nieto, J. Castro, M.V. Di Campli, Francis Couturaud, Raquel Barba, Jaureguizar, A., Jimenez, D., Bikdeli, B., Ruiz-Artacho, P., Muriel, A., Tapson, V., Lopez-Reyes, R., Valero, B., Kenet, G., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Verhamme, P., Caprini, J. A., Bui, H. M., Adarraga, M. D., Aibar, J., Aibar, M. A., Alonso, J., Amado, C., Arcelus, J. I., Asuero, A., Azcarate-Aguero, P., Ballaz, A., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Beddar Chaib, F., Camon, A. M., Castro, J., Chasco, L., Criado, J., de Ancos, C., del Toro, J., Demelo-Rodriguez, P., Diaz-Brasero, A. M., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Di Campli, M. V., Dubois-Silva, A., Escribano, J. C., Esposito, F., Farfan-Sedano, A. I., Fernandez-Capitan, C., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, C., Font, L., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia de Herreros, M., Garcia de la Garza, R., Garcia-Diaz, C., Gil-Diaz, A., Gomez-Cuervo, C., Gimenez-Suau, M., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Jimenez-Alfaro, C., Joya, M. D., Lainez-Justo, S., Latorre, A., Lima, J., Lobo, J. L., Lopez-Jimenez, L., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Saez, J. B., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Urbistondo, D., Mella, C., Mercado, M. I., Moises, J., Munoz, M., Munoz-Blanco, A., Nieto, J. A., Nofuentes-Perez, E., Nunez-Fernandez, M. J., Olid-Velilla, M., Olivares, M. C., Osorio, J., Otalora, S., Otero, R., Pedrajas, J. M., Pellejero, G., Porras, J. A., Portillo, J., Rodriguez-Matute, C., Rosa, V., Ruiz-Ruiz, J., Salgueiro, G., Sanchez-Martinez, R., Sanchez-Munoz-Torrero, J. F., Sancho, T., Soler, S., Suarez-Rodriguez, B., Surinach, J. M., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valle, R., Varona, J. F., Vela, L., Vela, J. R., Vidal, G., Villalobos, A., Villares, P., Zamora, C., Ay, C., Nopp, S., Pabinger, I., Vanassche, T., Vandenbriele, C., Hirmerova, J., Accassat, S., Ait Abdallah, N., Bura-Riviere, A., Catella, J., Couturaud, F., Crichi, B., Debourdeau, P., Espitia, O., Grange, C., Helfer, H., Lacut, K., Le Mao, R., Mahe, I., Morange, P., Moustafa, F., Poenou, G., Sarlon-Bartoli, G., Suchon, P., Quere, I., Braester, A., Basaglia, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., De Angelis, A., Imbalzano, E., Merla, S., Pesavento, R., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Nishimoto, Y., Sato, Y., Birzulis, J., Skride, A., Zaicenko, A., Fonseca, S., Martins, F., Meireles, J., Krstevski, G., and Mazzolai, L.
Subjects: Male, Registrie, Pulmonary and Respiratory Medicine, medicine.medical_specialty, pulmonary embolism, Critical Care and Intensive Care Medicine, Logistic regression, Heart Rate, Internal medicine, Heart rate, medicine, In patient, Aged, Aged, 80 and over, business.industry, medicine.disease, mortality, Pulmonary embolism, Prospective Studie, Increased risk, Spain, Cardiology, Positive relationship, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract: Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.
Published: 2022
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24. Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

Author: Antonio Siniscalchi, Luca Gallelli, Erika Cione, Gianfranco Vasta, Antonio Guerra, Andrea Scaramuzzino, Lucia Longo, Lucia Muraca, Giovambattista De Sarro, null 'G & SP' Working Group, Giacomo Leuzzi, Antonio Gerace, Antonio Scuteri, Piero Vasapollo, Vincenzo Natale, Stefania Zampogna, and Filippo Luciani
Subjects: Male, medicine.medical_specialty, Skin Neoplasms, Toxicology, Hydrochlorothiazide, Internal medicine, medicine, Humans, Pharmacology (medical), Basal cell carcinoma, In patient, Antihypertensive Agents, Retrospective Studies, Pharmacology, business.industry, Significant difference, Retrospective cohort study, Odds ratio, medicine.disease, Carcinoma, Basal Cell, Female, Skin cancer, business, medicine.drug, Non melanoma
Abstract: Aims: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Background: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. Objective: To evaluate the statistically significant difference (P Methods: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. Results: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. Conclusions: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.
Published: 2022
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25. Biomarkers in Unstable Carotid Plaque: Physiopathology and Prediction

Author: Giovambattista De Sarro, Sean M. Murphy, Antonio Siniscalchi, Luca Gallelli, and Cleona Gray
Subjects: Carotid Artery Diseases, medicine.medical_specialty, Cochrane Library, medicine.disease_cause, Drug treatment, Risk Factors, Carotid artery disease, Internal medicine, Humans, Medicine, Stroke, Pharmacology, business.industry, Hematology, medicine.disease, Vulnerable plaque, Inflammatory biomarkers, Plaque, Atherosclerotic, Pathophysiology, Stenosis, Carotid Arteries, Cardiology, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Aims: To study the role of cytokines and vascular inflammatory biomarkers in unstable carotid plaque Background: Clinical studies showed that not only the degree of stenosis but also the type of carotid plaque can be responsible for ipsilateral ischemic stroke. Objective: The objective of this study is to suggest a role for vulnerable carotid atherosclerotic disease in the occurrence of ischemic stroke. Methods: PubMed, Embase, Cochrane library, and reference lists have been used to evaluate articles published until February 15, 2021. Results: Several factors may be involved in unstable plaque. Clinical studies support the involvement of brain inflammatory biomarkers as well as cytokines in the unstable carotid plaque. Conclusions: Biomarkers could help to stratify patients with a vulnerable carotid plaque and to personalize the drug treatment. In this review, we briefly discuss the characteristics of vulnerable plaque and the role of biomarkers in the vulnerable carotid plaque.
Published: 2022
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26. Isolated Hand Palsy in National Institutes of Health Stroke Scale (NIHSS): Is It Useful?

Author: Antonio Siniscalchi, Piergiorgio Lochner, Paolo Perrotta, Stefano Rizzuto, Giovambattista De Sarro, and Luca Gallelli
Subjects: Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2018
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27. microRNA‐377‐3p downregulates the oncosuppressor T‐cadherin in colorectal adenocarcinoma cells

Author: Chiara Siniscalchi, Aniello Russo, Nicoletta Potenza, Aurora Daniele, Rita Polito, Armando Di Palo, Ersilia Nigro, Di Palo, A., Siniscalchi, C., Polito, R., Nigro, E., Russo, A., Daniele, A., and Potenza, N.
Subjects: 0301 basic medicine, Untranslated region, Colorectal cancer, Short Communication, Down-Regulation, Biology, 03 medical and health sciences, 0302 clinical medicine, microRNA, medicine, Humans, cancer, Genes, Tumor Suppressor, Receptor, RNA, Cancer, Cell Biology, General Medicine, Cadherins, medicine.disease, T-cadherin, MicroRNAs, 030104 developmental biology, Cell culture, 030220 oncology & carcinogenesis, Cancer research, Caco-2 Cells, Colorectal Neoplasms, HT29 Cells
Abstract: Colorectal cancer (CRC) is the second leading cause of death of malignant tumors worldwide. Recent studies point to a role for adiponectin-receptor axis in colorectal carcinogenesis, and in particular to the oncosuppressive properties of T-cadherin receptor. In addition, the loss of T-cadherin expression in tumor tissues has been linked to cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of microRNAs in CRC, this work explores their possible contribution to the down-regulation of T-cadherin. A systematic bioinformatics analysis, restricted by microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top-ranking target miRNA sites within the 3' UTR of T-cadherin. Experimental validation analyses based on luciferase reporter constructs and miRNA mimic or miRNA inhibitor transfections toward colorectal adenocarcinoma cell lines indicated that miR-377-3p was able to directly bind to the T-cadherin sequence, and thus down-regulating its expression. Given the oncogenic activity of miR-377 and the oncosuppressive activity of T-cadherin in CRC, the regulatory circuit highlighted in this work may add new insights into molecular mechanisms driving colorectal carcinogenesis, and perspectively it could be exploited to identify novel biomarkers and therapeutic targets. This article is protected by copyright. All rights reserved.
Published: 2021
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28. Does poor glycaemic control affect the immunogenicity of the COVID-19 vaccination in patients with type 2 diabetes: The CAVEAT study

Author: Giovanni Napolitano, Gianpaolo Papaccio, Fabrizio Turriziani, Celestino Sardu, Marilena Galdiero, Antonio Papa, Luigi Salemme, Giuseppe Paolisso, Lucia Scisciola, Nicola Coppola, Eugenio Basile, Carmela Papa, Paolo Maggi, Michelangela Barbieri, Ferdinando Carlo Sasso, Ciro Romano, F. Russo, Maria Rosaria Rizzo, Maria Luisa Balestrieri, Raffaele Marfella, Mario Siniscalchi, Claudio Napoli, Vincenzo Messina, Nunzia D'Onofrio, Ludovica Vittoria Marfella, Maria Vittoria Montemurro, Italo F. Angelillo, Virginia Tirino, Marco Boccalatte, Francesco Frascaria, Mauro Maniscalco, Marfella, Raffaele, D'Onofrio, Nunzia, Sardu, Celestino, Scisciola, Lucia, Maggi, Paolo, Coppola, Nicola, Romano, Ciro, Messina, Vincenzo, Turriziani, Fabrizio, Siniscalchi, Mario, Maniscalco, Mauro, Boccalatte, Marco, Napolitano, Giovanni, Salemme, Luigi, Marfella, Ludovica Vittoria, Basile, Eugenio, Montemurro, Maria Vittoria, Papa, Carmela, Frascaria, Francesco, Papa, Antonio, Russo, Ferdinando, Tirino, Virginia, Papaccio, Gianpaolo, Galdiero, Marilena, Sasso, Ferdinando Carlo, Barbieri, Michelangela, Rizzo, Maria Rosaria, Balestrieri, Maria Luisa, Angelillo, Italo Francesco, Napoli, Claudio, Paolisso, Giuseppe, Marfella, R., D'Onofrio, N., Sardu, C., Scisciola, L., Maggi, P., Coppola, N., Romano, C., Messina, V., Turriziani, F., Siniscalchi, M., Maniscalco, M., Boccalatte, M., Napolitano, G., Salemme, L., Marfella, L. V., Basile, E., Montemurro, M. V., Papa, C., Frascaria, F., Papa, A., Russo, F., Tirino, V., Papaccio, G., Galdiero, M., Sasso, F. C., Barbieri, M., Rizzo, M. R., Balestrieri, M. L., Angelillo, I. F., Napoli, C., and Paolisso, G.
Subjects: Blood Glucose, medicine.medical_specialty, Glycated Hemoglobin A, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), COVID-19 Vaccine, Endocrinology, Diabetes and Metabolism, MEDLINE, Type 2 diabetes, Glycemic Control, Affect (psychology), Endocrinology, Immunogenicity, Vaccine, Internal medicine, Research Letter, Internal Medicine, medicine, Humans, In patient, Poor glycaemic control, Glycated Hemoglobin, business.industry, Immunogenicity, COVID-19, medicine.disease, Research Letters, Vaccination, Diabetes Mellitus, Type 2, business, Human
Published: 2021

29. Liver transplantation in Italy in the era of COVID 19: reorganizing critical care of recipients

Author: Siniscalchi, Antonio, Vitale, Giovanni, Morelli, Maria Cristina, Ravaioli, Matteo, Laici, Cristiana, Bianchini, Amedeo, Del Gaudio, Massimo, Conti, Fabio, Vizioli, Luca, Cescon, Matteo, Siniscalchi A., Vitale G., Morelli M.C., Ravaioli M., Laici C., Bianchini A., Del Gaudio M., Conti F., Vizioli L., and Cescon M.
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Donors, Pneumonia, Viral, 030204 cardiovascular system & hematology, Liver transplantation, law.invention, End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, law, Pandemic, Health care, Recipient, Internal Medicine, medicine, Healthcare personnel, Humans, Intensive care unit, 030212 general & internal medicine, Liver transplant, Pandemics, Coronavirus Infection, business.industry, Mortality rate, COVID-19, Middle Aged, Im - Original, Liver Transplantation, Transplantation, Intensive Care Units, Crowding, Italy, Emergency medicine, Emergency Medicine, Recipients, Female, business, Coronavirus Infections, Donor, Human
Abstract: Transplant programs have been severely disrupted by the COVID-19 pandemic. Italy was one of the first countries with the highest number of deaths in the world due to SARS-CoV-2. Here we propose a management model for the reorganization of liver transplant (LT) activities and policies in a local intensive care unit (ICU) assigned to liver transplantation affected by restrictions on mobility and availability of donors and recipients as well as health personnel and beds. We describe the solutions implemented to continue transplantation activities throughout a given pandemic: management of donors and recipients’ LT program, ICU rearrangement, healthcare personnel training and monitoring to minimize mortality rates of patients on the waiting list. Transplantation activities from February 22, 2020, the data of first known COVID-19 case in Italy’s Emilia Romagna region to June 30, 2020, were compared with the corresponding period in 2019. During the 2020 study period, 38 LTs were performed, whereas 41 were performed in 2019. Patients transplanted during the COVID-19 pandemic had higher MELD and MELD-Na scores, cold ischaemia times, and hospitalization rates (p < 0.05); accordingly, they spent fewer days on the waitlist and had a lower prevalence of hepatocellular carcinoma (p < 0.05). No differences were found in the provenance area, additional MELD scores, age of donors and recipients, BMI, re-transplant rates, and post-transplant mortality. No transplanted patients contracted COVID-19, although five healthcare workers did. Ultimately, our policy allowed us to continue the ICU’s operations by prioritizing patients hospitalized with higher MELD without any case of transplant infection due to COVID-19.
Published: 2020

30. What microRNAs could tell us about the human X chromosome

Author: Chiara Siniscalchi, Aniello Russo, Claus Højbjerg Gravholt, Nicoletta Potenza, Armando Di Palo, Mariacarolina Salerno, Di Palo, A., Siniscalchi, C., Salerno, M., Russo, A., Gravholt, C. H., and Potenza, N.
Subjects: SEX-DIFFERENCES, Turner syndrome, Aneuploidy, Computational biology, Review, Biology, CELL-PROLIFERATION, X chromosome, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Klinefelter syndrome, microRNA, Turner syndrome, X chromosome, microRNA, RAPID EVOLUTION, medicine, NONCODING RNA, TUMOR-SUPPRESSOR, Klinefelter syndrome, Molecular Biology, 030304 developmental biology, GENE-EXPRESSION, Pharmacology, 0303 health sciences, Cell Biology, medicine.disease, CANCER, KLINEFELTER-SYNDROME, CARDIOVASCULAR-DISEASE, 030220 oncology & carcinogenesis, Molecular Medicine, INACTIVATION
Abstract: MicroRNAs (miRNA) are small-non coding RNAs endowed with great regulatory power, thus playing key roles not only in almost all physiological pathways, but also in the pathogenesis of several diseases. Surprisingly, genomic distribution analysis revealed the highest density of miRNA sequences on the X chromosome; this evolutionary conserved mammalian feature equips females with a larger miRNA machinery than males. However, miRNAs contribution to some X-related conditions, properties or functions is still poorly explored. With the aim to support and focus research in the field, this review analyzes the literature and databases about X-linked miRNAs, trying to understand how miRNAs could contribute to emerging gender-biased functions and pathological mechanisms, such as immunity and cancer. A fine map of miRNA sequences on the X chromosome is reported, and their known functions are discussed; in addition, bioinformatics functional analyses of the whole X-linked miRNA targetome (predicted and validated) were performed. The emerging scenario points to different gaps in the knowledge that should be filled with future experimental investigations, also in terms of possible implications and pathological perspectives for X chromosome aneuploidy syndromes, such as Turner and Klinefelter syndromes. Electronic supplementary material The online version of this article (10.1007/s00018-020-03526-7) contains supplementary material, which is available to authorized users.
Published: 2020
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31. The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017

Author: Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, Mg, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Tarasconi, A, Sella, M, Auriemma, S, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Margola, A, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Giani, A, Famularo, S, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Ballestrero, A, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, De, F, Pietrogrande, L, De, B, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Bianchetti, A, Crucitti, A, Di Francesco, V, Fontana, G, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cannistrà, U, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambara, V, Saitta, A, Corica, F, Braga, M, Ettorre, E, Camellini, C, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuari, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, D'Imporzano, E, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samy Salama Fahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Pezzoni, D, Gentile, S, Platto, C, D'Ambrosio, V, Faraci, B, Brambilla, C, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Confente, S, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, C Boffelli S, Corsini, Filippi, A, Delpin, K, Bertoletti, E, Vannucci, M, Tesi, F, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Riva, E, Dell'Acqua, D, Cottino, M, Vezzadini, G, Avanzi, S, Orini, S, Sgrilli, F, Mello, A, Lombardi, L, Muti, E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, A Millul A, Barelli, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cat, C, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Scapigliati, A, Cortegiani, A, Vitale, F, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D., Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, M, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Citerio, G, Zucchelli, Alberto, Valsecchi, M G, and A Tarasconi, M Sella, S Auriemma, G Paternò, G Faggian, C Lucarelli, N De Grazia, C Alberto, A Margola, L Porcella, I Nardiello, E Chimenti, M Zeni, A Giani, S Famularo, E Romairone, C Minaglia, C Ceccotti, G Guerra, G Mantovani, F Monacelli, C Minaglia, T Candiani, A Ballestrero, C Minaglia, F Santolini, C Minaglia, M Rosso, V Bono, S Sibilla, P Dal Santo, M Ceci, P Barone, T Schirinzi, A Formenti, G Nastasi, G Isaia, D Gonella, A Battuello, S Casson, D Calvani, F Boni, A Ciaccio, R Rosa, G Sanna, S Manfredini, L Cortese, M Rizzo, R Prestano, A Greco, M Lauriola, G Gelosa, V Piras, M Arena, D Cosenza, A Bellomo, M LaMontagna, L Gabbani, L Lambertucci, S Perego, G Parati, G Basile, V Gallina, G Pilone, C Giudice, F De, L Pietrogrande, B De, M Mosca, I Corazzin, P Rossi, V Nunziata, F D'Amico, A Grippa, S Giardini, R Barucci, A Cossu, L Fiorin, M Arena, M Distefano, M Lunardelli, M Brunori, I Ruffini, E Abraham, A Varutti, E Fabbro, A Catalano, G Martino, D Leotta, A Marchet, G Dell'Aquila, A Scrimieri, M Davoli, M Casella, A Cartei, G Polidori, G Basile, D Brischetto, S Motta, R Saponara, P Perrone, G Russo, D Del, C Car, T Pirina, S Franzoni, A Cotroneo, F Ghiggia, G Volpi, C Menichetti, M Bo, A Panico, P Calogero, G Corvalli, M Mauri, E Lupia, R Manfredini, F Fabbian, A March, M Pedrotti, M Veronesi, E Strocchi, A Bianchetti, A Crucitti, V Di Francesco, G Fontana, L Bonanni, F Barbone, C Serrati, G Ballardini, M Simoncelli, G Ceschia, C Scarpa, R Brugiolo, S Fusco, T Ciarambino, C Biagini, E Tonon, M Porta, D Venuti, M DelSette, M Poeta, G Barbagallo, G Trovato, A Delitala, P Arosio, F Reggiani, G Zuliani, B Ortolani, E Mussio, A Girardi, A Coin, G Ruotolo, A Castagna, M Masina, R Cimino, A Pinciaroli, G Tripodi, U Cannistrà, F Cassadonte, M Vatrano, F Cassandonte, L Scaglione, P Fogliacco, C Muzzuilini, F Romano, A Padovani, L Rozzini, A Cagnin, F Fragiacomo, G Desideri, E Liberatore, A Bruni, G Orsitto, M Franco, L Bonfrate, M Bonetto, N Pizio, G Magnani, G Cecchetti, A Longo, V Bubba, L Marinan, M Cotelli, M Turla, M Brunori, M Sessa, L Abruzzi, G Castoldi, D LoVetere, C Musacchio, M Novello, A Cavarape, A Bini, A Leonardi, F Seneci, W Grimaldi, F Fimognari, V Bambara, A Saitta, F Corica, M Braga, E Ettorre, C Camellini, A Marengoni, A Bruni, A Crescenzo, G Noro, R Turco, M Ponzetto, L Giuseppe, B Mazzei, G Maiuri, D Costaggiu, R Damato, E Fabbro, G Patrizia, L Santuari, M Gallucci, C Minaglia, M Paragona, P Bini, D Modica, C Abati, M Clerici, I Barbera, F NigroImperiale, A Manni, C Votino, C Castiglioni, M Di, M Degl'Innocenti, G Moscatelli, S Guerini, C Casini, D Dini, S DeNotariis, F Bonometti, C Paolillo, A Riccardi, A Tiozzo, A SamySalamaFahmy, A Riccardi, C Paolillo, M DiBari, S Vanni, A Scarpa, D Zara, P Ranieri, P Calogero, G Corvalli, D Pezzoni, S Gentile, A Morandi, C Platto, V D'Ambrosio, B Faraci, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, S Confente, M Bonetto, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, E Bertoletti, M Vannucci, F Tesi, P Crippa, A Malighetti, C Caltagirone, S DiSant, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D'Amico, A Grippa, A Mazzone, E Riva, D Dell'Acqua, M Cottino, G Vezzadini, S Avanzi, S Orini, F Sgrilli, A Mello, L Lombardi, E Muti, B Dijk, S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, F De, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul, G De, G Morrone, M Bigolari, C Minaglia, M Macchi, F Zambon, F D'Amico, F D'Amico, C Pizzorni, G DiCasaleto, G Menculini, M Marcacci, G Catanese, D Sprini, T DiCasalet, M Bocci, S Borga, P Caironi, C Cat, E Cingolani, L Avalli, G Greco, G Citerio, L Gandini, G Cornara, R Lerda, L Brazzi, F Simeone, M Caciorgna, D Alampi, S Francesconi, E Beck, B Antonini, K Vettoretto, M Meggiolaro, E Garofalo, A Bruni, S Notaro, R Varutti, F Bassi, G Mistraletti, A Marino, R Rona, E Rondelli, I Riva, A Scapigliati, A Cortegiani, F Vitale, L Pistidda, R D'Andrea, L Querci, P Gnesin, M Todeschini, M Lugano, G Castelli, M Ortolani, A Cotoia, S Maggiore, L DiTizio, R Graziani, I Testa, E Ferretti, C Castioni, F Lombardi, R Caserta, M Pasqua, S Simoncini, F Baccarini, M Rispoli, F Grossi, L Cancelliere, M Carnelli, F Puccini, G Biancofiore, A Siniscalchi, C Laici, E Mossello, M Torrini, G Pasetti, S Palmese, R Oggioni, V Mangani, S Pini, M Martelli, E Rigo, F Zuccalà, A Cherri, R Spina, I Calamai, N Petrucci, A Caicedo, F Ferri, P Gritti, N Brienza, R Fonnesu, M Dessena, G Fullin, D Saggioro
Subjects: Male, Aging, medicine.medical_specialty, Sarcopenia, medicine.medical_treatment, Socio-culturale, Older person, Logistic regression, Delirium, Older persons, Sarcopenia, Internal medicine, mental disorders, Delirium, Older persons, medicine, Dementia, Humans, LS4_4, Muscle, Skeletal, Pathological, Aged, Rehabilitation, business.industry, Area under the curve, Settore MED/23 - Chirurgia Cardiaca, Skeletal, medicine.disease, Skeletal muscle mass, Cross-Sectional Studies, Italy, Muscle, Female, Geriatrics and Gerontology, medicine.symptom, business
Abstract: Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.
Published: 2022

32. Transcranial Doppler Ultrasonography in Pre-hospital Management of Stroke: Can it make a Difference?

Author: Sandro Sanguigni, Giovanni Malferrari, Piergiorgio Lochner, and Antonio Siniscalchi
Subjects: medicine.medical_specialty, Stroke patient, Ultrasonography, Doppler, Transcranial, business.industry, medicine.disease, Hospitals, Transcranial Doppler ultrasonography, Transcranial Doppler, Stroke, Internal medicine, Occlusion, medicine, Cardiology, Humans, Radiology, Nuclear Medicine and imaging, Ultrasonography, Doppler, Color, business, Acute ischemic stroke
Abstract: The aim of this paper is to discuss the use of transcranial doppler in the pre-hospital management of stroke. In the pre-hospital organization, neurological defect scales are used, but they are often indicative of the occlusions of anterior circulation and not of the posterior circulation. Patients with posterior circulation stroke are sometimes not diagnosed and clinically treated. In the pre-hospital phase, the transcranial doppler may identify an occlusion of the large cerebral vessels and be useful for stroke patients, in particular those with posterior occlusions, for a more precise diagnosis and consequently for adequate treatment in the excellence centers for stroke.
Published: 2021
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33. Bleeding risk in hospitalized patients with COVID‐19 receiving intermediate‐ or therapeutic doses of thromboprophylaxis

Author: Pablo Demelo‐Rodriguez, Ana Isabel Farfán‐Sedano, José María Pedrajas, Pilar Llamas, Patricia Sigüenza, María Jesús Jaras, Manuel Quintana‐Diaz, Carmen Fernández‐Capitán, Behnood Bikdeli, David Jiménez, Manuel Monreal, Adarraga D, Aibar J, Baeza C, Ballaz A, Barba R, Blanco‐Molina A, Botella E, Criado J, Demelo‐Rodríguez P, Díaz‐Brasero AM, de Ancos C, del Toro J, Farfán‐Sedano AI, Fernández‐Capitán C, Fidalgo A, Flores K, Gabara C, Galeano‐Valle F, Gavín‐Sebastián O, Gil‐Díaz A, Jaras MJ, Jara‐Palomares L, Jiménez R, Lainez‐Justo S, Latorre A, Lecumberri R, Llamas P, Lobo JL, López‐Jiménez L, Loureiro B, Madridano O, Mancebo‐Plaza AB, Martín del Pozo M, Monreal M, Muñoz‐Rivas N, Núñez‐Fernández MJ, Olivera PE, Ordieres‐Ortega L, Padín‐Paz EM, Pedrajas JM, Quintana‐Díaz M, Ríos‐Prego M, Rodríguez‐Chiaradía DA, Ruiz‐Artacho P, Sigüenza P, Suriñach JM, Trujillo‐Santos J, Zamora C, Bucherini E, Di Micco P, Imbalzano E, Siniscalchi C, Bosevski M, Stevanovic M, Paz‐Rios L, and Weinberg I
Subjects: anticoagulants, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Hospitalized patients, 030204 cardiovascular system & hematology, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, death, Internal medicine, medicine, Humans, Retrospective Studies, SARS-CoV-2, business.industry, Mortality rate, Incidence (epidemiology), Hazard ratio, COVID-19, Venous Thromboembolism, Original Articles, Hematology, Confidence interval, Original Article, prognosis, hemorrhage, business, Cohort study
Abstract: Introduction Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID‐19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown. Methods We performed a cohort study of patients hospitalized for COVID‐19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding. Results During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate‐ and 618 (31%) therapeutic‐dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non‐major bleeding. The 30‐day all‐cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%‐54%) and for non‐major bleeding 32% (95% CI: 24%‐40%). Multivariable analysis showed increased risk for in‐hospital major bleeding associated with D‐dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38–3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02–3.95), critical illness (HR, 1.91; 95% CI, 1.14–3.18), and therapeutic‐intensity anticoagulation (HR, 1.43; 95% CI, 1.01–1.97). Conclusions Among patients hospitalized with COVID‐19 receiving intermediate‐ or therapeutic‐intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic‐intensity anticoagulation, critical illness, and elevated D‐dimer or ferritin levels at admission were associated with increased risk for major bleeding.
Published: 2021
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34. A Heart Surgery Simulator With an Integrated Supervision System for Self-Learning the Key Steps and Pitfalls of the Mitral Valve Repair

Author: Piergiorgio Tozzi, Enrico Ferrari, Alessandra Solida, and Giuseppe Siniscalchi
Subjects: Mitral valve repair, medicine.medical_specialty, Epidemiology, Computer science, medicine.medical_treatment, Medicine (miscellaneous), Mitral ring, Surgery simulator, Education, Cardiac surgery, medicine.anatomical_structure, Interactivity, Modeling and Simulation, Mitral valve, medicine, Key (cryptography), Medical physics, Surgical education
Abstract: INTRODUCTION Over the years, surgical education has dramatically improved and has become increasingly innovative. Almost all educational programs in surgery now rely on sophisticated training boxes and simulators that enable surgical instruments to be handled and surgical procedures to be trained in a safe environment. However, simulators need constant feedback from supervising senior surgeons, who only have limited teaching time available. We describe a cardiac surgery simulator with an integrated supervision system for self-learning how to repair a mitral valve. METHODS We developed a mitral surgery simulator with integrated sensors to generate, record, and display quantitative data on trainee performance in relation with the mitral valve repair procedure. A team of experienced cardiac surgeons defined critical areas of the model and an algorithm to identify inconsistent movements, in terms of error types and out-of-bound actions. The device provided real-time feedback on the accuracy of the stitches placed. Four experienced cardiac surgeons and 3 advanced cardiac-surgery used the simulator and were asked to evaluate specific parameters of the system on a scale ranging from 1 to 10. RESULTS All surgeons completed a P2 resection, followed by implanting a 32-mm mitral ring. The simulator detected 2 stitches that were placed in dangerous zones and another stitch that was placed in an inappropriate position. Users scored the real tissue feeling and interactivity of the model 9.5/10. CONCLUSIONS This heart-surgery simulator offers a real-life model for learning about and training in mitral valve surgery, which could potentially replace the experienced surgeon's teaching role.
Published: 2021
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35. Isolated Tongue Angioedema after Alteplase Infusion in Acute Ischemic Stroke

Author: Furio Stancati, Ermanno Pisani, Carmen Gaudiano, Alfredo Petrone, and Antonio Siniscalchi
Subjects: Pharmacology, Angioedema, medicine.drug_class, business.industry, Indapamide, Toxicology, medicine.disease, Anesthesia, ACE inhibitor, medicine, Perindopril, Pharmacology (medical), Amlodipine, medicine.symptom, Antihypertensive drug, Adverse effect, business, Anaphylaxis, medicine.drug
Abstract: Background: Angioedema, like anaphylaxis, has been reported as a rare adverse event of alteplase infusion in acute ischemic stroke. Objective: We report the case of a patient with acute ischemic stroke who, after treatment of alteplase, developed angioedema. Methods: We report the case of an 81-year-old woman who presented to our observation with acute ischemic stroke. The patient was on therapy with 100 mg acetylsalicylic acid and a triple combination antihypertensive drug (perindopril 10 mg + 2.5 mg indapamide + 5 mg amlodipine). The patient was treated with alteplase infusion. Results: Five minutes after the end of the alteplase infusion (0.9 mg/kg for 1 hour), the patient developed isolated angioedema of the lips and tongue. Conclusion: Although the incidence of alteplase-induced angioedema in these patients is rare, this case report suggests the need for a routine inspection of the tongue in an acute ischemic patient in treatment with alteplase infusion, especially in female patients in treatment with ACE inhibitors.
Published: 2022
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36. Ultrasound Diagnostic Method in Vascular Dementia: Current Concepts

Author: Giovanni Malferrari, Cleona Gray, and Antonio Siniscalchi
Subjects: medicine.medical_specialty, Diagnostic methods, Ultrasonography, Doppler, Transcranial, business.industry, Dementia, Vascular, Ultrasound, Hemodynamics, Cochrane Library, Vascular risk, medicine.disease, Transcranial Doppler, Risk Factors, Cerebral hemodynamics, Internal medicine, medicine, Cardiology, Humans, Radiology, Nuclear Medicine and imaging, business, Vascular dementia, Pathological, Aged
Abstract: Background: Increasing interest in identifying of cerebral hemodynamics alterations as cause of possible onset or worsening of cognitive impairment in elderly patients with vascular risk factors. Introduction: Intracranial ultrasound is a non-invasive, repeatable inexpensive method for recording variation of the cerebral vascular tree in physiological and pathological conditions as well in the diagnosis of vascular dementia (VaD). Methods: PubMed, Embase, Cochrane library and reference lists have been searched for articles published until March 30, 2020. Results: Clinical studies reported different Transcranial Doppler (TCD) parameters and subsequently transcranial duplex with color code (TCCD) in patients affected by vascular dementia. The number of studies using TCCD remains limited and most of available data are still based on TCD. However, the use of transcranial Doppler could better stratify elderly patients with initial signs of cognitive impairment. Conclusion: Intracranial ultrasound employment to detect cerebral hemodynamic changes in VaD patients has been briefly discussed in this review.
Published: 2021
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37. Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Author: Behnood Bikdeli, David Jiménez, Jorge del Toro, Gregory Piazza, Agustina Rivas, José Luis Fernández‐Reyes, Ángel Sampériz, Remedios Otero, José María Suriñach, Carmine Siniscalchi, Javier Miguel Martín‐Guerra, Joaquín Castro, Alfonso Muriel, Gregory Y. H. Lip, Samuel Z. Goldhaber, Manuel Monreal, Paolo Prandoni, Benjamin Brenner, Dominique Farge‐Bancel, Raquel Barba, Pierpaolo Di Micco, Laurent Bertoletti, Sebastian Schellong, Inna Tzoran, Abilio Reis, Marijan Bosevski, Henri Bounameaux, Radovan Malý, Peter Verhamme, Joseph A. Caprini, Hanh My Bui, María Dolores Adarraga, María Agud, Jesús Aibar, Miguel Ángel Aibar, Cristina Amado, Juan Ignacio Arcelus, Carlos Baeza, Aitor Ballaz, Cristina Barbagelata, Manuel Barrón, Belén Barrón‐Andrés, Ángeles Blanco‐Molina, Ernesto Botella, Ana María Camon, Inmaculada Cañas, Ignacio Casado, Leyre Chasco, Juan Criado, Cristina de Ancos, Javier de Miguel, Pablo Demelo‐Rodríguez, José Antonio Díaz‐Peromingo, Mario Virgilio Di Campli, Javier Díez‐Sierra, Irene Milagros Domínguez, José Carlos Escribano, Conxita Falgá, Ana Isabel Farfán‐Sedano, Carmen Fernández‐Capitán, Jose Luis Fernández‐Reyes, María Ángeles Fidalgo, Katia Flores, Carme Font, Llorenç Font, Iria Francisco, Cristina Gabara, Francisco Galeano‐Valle, David Galindo, María Angelina García, Ferrán García‐Bragado, Marta García de Herreros, Raquel García‐Hernáez, María Mar García‐Mullor, Arantxa García‐Raso, Olga Gavín‐Sebastián, Aida Gil‐Díaz, Covadonga Gómez‐Cuervo, Enric Grau, Leticia Guirado, Javier Gutiérrez, Luis Hernández‐Blasco, Elena Hernando, Miguel Herreros, Luis Jara‐Palomares, María Jesús Jaras, Rafael Jiménez, Maria Dolores Joya, José Manuel León, Jorge Lima, Pilar Llamas, José Luis Lobo, Luciano López‐Jiménez, Patricia López‐Miguel, Juan José López‐Núñez, Raquel López‐Reyes, Antonio López‐Ruiz, Juan Bosco López‐Sáez, Alicia Lorenzo, Olga Madridano, Ana Maestre, Pablo Javier Marchena, Mar Martín del Pozo, Francisco Martín‐Martos, Carmen Mella, Meritxell Mellado, Maria Isabel Mercado, Jorge Moisés, María del Valle Morales, Arturo Muñoz‐Blanco, Nuria Muñoz‐Rivas, María Sierra Navas, Jose Antonio Nieto, Manuel Jesús Núñez‐Fernández, Berta Obispo, Mónica Olid, María Carmen Olivares, José Luis Orcastegui, Clara Ortega‐Michel, Jeisson Osorio, Sonia Otalora, Pedro Parra, Virginia Parra, José María Pedrajas, Galadriel Pellejero, José Antonio Porras, José Portillo, Antoni Riera‐Mestre, Francisco Rivera‐Civico, Diego Agustín Rodríguez‐Chiaradía, Ana Rodríguez‐Cobo, Consolación Rodríguez‐Matute, Jacobo Rogado, Sonia Roig, Vladimir Rosa, Pedro Ruiz‐Artacho, Nuria Ruiz‐Giménez, Justo Ruiz‐Ruiz, Pablo Ruiz‐Sada, Giorgina Salgueiro, Rosario Sánchez‐Martínez, Juan Francisco Sánchez‐Muñoz‐Torrero, Teresa Sancho, Merçe Sirisi, Silvia Soler, Raimundo Tirado, María Isabel Torres, Carles Tolosa, Javier Trujillo‐Santos, Fernando Uresandi, Beatriz Valero, Reina Valle, Jerónimo Ramón Vela, Gemma Vidal, Paula Villares, Carles Zamora, Paula Gutiérrez, Fernando Javier Vázquez, Matthias Engelen, Thomas Vanassche, Jana Hirmerova, Estuardo Salgado, Nassim Ait Abdallah, Alessandra Bura‐Riviere, Benjamin Crichi, Philippe Debourdeau, Espitia Olivier, Nicolas Falvo, Silvia Galliazzo, Hélène Helfer, Isabelle Mahé, Farès Moustafa, Geraldine Poenou, Andrei Braester, Franca Bilora, Eugenio Bucherini, Maurizio Ciammaichella, Egidio Imbalzano, Rosa Maida, Daniela Mastroiacovo, Federica Pace, Raffaele Pesavento, Fulvio Pomero, Roberto Quintavalla, Anna Rocci, Roberta Romualdi, Antonella Tufano, Adriana Visonà, Beniamino Zalunardo, Valdis Gibietis, Dana Kigitovica, Andris Skride, Samuel Fonseca, Filipa Martins, Jose Meireles, Lucia Mazzolai, Alfonso J. Tafur, Cassius Iyad Ochoa‐Chaar, Ido Weinberg, Hannah Wilkins, Institut Català de la Salut, [Bikdeli B] Cardiovascular Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Yale/YNHH Center for Outcomes Research & Evaluation, New Haven, CT. Cardiovascular Research Foundation (CRF), New York, NY. [Jiménez D] Respiratory Department, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain. Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. [Del Toro J] Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Piazza G] Cardiovascular Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. [Rivas A] Department of Pneumonology, Hospital Universitario Araba, Álava, Spain. [Fernández-Reyes JL] Department of Internal Medicine, Complejo Hospitalario de Jaén, Jaén, Spain. [Suriñach JM] Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Bikdeli, B., Jimenez, D., Toro, J. D., Piazza, G., Rivas, A., Fernandez-Reyes, J. L., Samperiz, A., Otero, R., Surinach, J. M., Siniscalchi, C., Martin-Guerra, J. M., Castro, J., Muriel, A., Lip, G. Y. H., Goldhaber, S. Z., Monreal, M., and Tufano, A
Subjects: Registrie, medicine.medical_specialty, Embolism, enfermedades cardiovasculares::enfermedades cardíacas::arritmias cardíacas::fibrilación atrial [ENFERMEDADES], Otros calificadores::/diagnóstico [Otros calificadores], Vascular Medicine, Risk Factors, Internal medicine, Other subheadings::Other subheadings::Other subheadings::/mortality [Other subheadings], Atrial Fibrillation, medicine, Other subheadings::/diagnosis [Other subheadings], Diseases of the circulatory (Cardiovascular) system, Humans, Registries, Cor - Malalties - Diagnòstic, Mortality, Original Research, Outcome, Otros calificadores::Otros calificadores::Otros calificadores::/mortalidad [Otros calificadores], business.industry, Risk Factor, Pulmonary embolism, Thrombosis, Atrial fibrillation, medicine.disease, Cardiovascular Diseases::Vascular Diseases::Embolism and Thrombosis::Embolism::Pulmonary Embolism [DISEASES], Stroke, Embòlia pulmonar - Mortalitat, RC666-701, Acute Disease, Cardiology, Avaluació de resultats (Assistència sanitària), Cardiology and Cardiovascular Medicine, business, enfermedades cardiovasculares::enfermedades vasculares::embolia y trombosis::embolia::embolia pulmonar [ENFERMEDADES], Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Atrial Fibrillation [DISEASES], Human
Abstract: Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90‐day and 1‐year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90‐day all‐cause (odds ratio [OR], 2.81; 95% CI, 2.33–3.38) and PE‐related mortality (OR, 2.38; 95% CI, 1.37–4.14) and increased 1‐year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10–9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all‐cause mortality (OR, 1.91; 95% CI, 1.57–2.32) but not PE‐related mortality (OR, 1.50; 95% CI, 0.85–2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90‐day all‐cause (OR, 2.28; 95% CI, 1.75–2.97) and PE‐related (OR, 3.64; 95% CI, 2.01–6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.
Published: 2021
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38. Long term results of down-staging and liver transplantation for patients with hepatocellular carcinoma beyond the conventional criteria

Author: Massimo Del Gaudio, Guido Fallani, Antonietta D'Errico, Valentina Rosa Bertuzzo, Maria Cristina Morelli, Alberta Cappelli, Antonio Siniscalchi, Edoardo G. Giannini, Matteo Ravaioli, Matteo Cescon, Franco Trevisani, Rita Golfieri, Alessandro Cucchetti, Fabio Farinati, Fabio Piscaglia, Vanessa De Pace, Antonio Daniele Pinna, Francesca Ciccarese, Federica Odaldi, Maria Di Marco, Flavia Neri, and Matteo Ravaioli, Federica Odaldi, Alessandro Cucchetti, Franco Trevisani, Fabio Piscaglia, Vanessa De Pace, Valentina Rosa Bertuzzo, Flavia Neri, Rita Golfieri, Alberta Cappelli, Antonietta D’Errico, Matteo Cescon, Massimo Del Gaudio, Guido Fallani, Antonio Siniscalchi, Maria Cristina Morelli, Francesca Ciccarese, Maria Di Marco, Fabio Farinati, Edoardo Giovanni Giannini, Antonio Daniele Pinna
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Time Factors, medicine.medical_treatment, Down staging, lcsh:Medicine, Milan criteria, Liver transplantation, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Internal medicine, Carcinoma, medicine, Humans, lcsh:Science, Survival rate, Aged, Multidisciplinary, business.industry, Liver Neoplasms, lcsh:R, Middle Aged, medicine.disease, Liver Transplantation, Survival Rate, 030104 developmental biology, Hepatocellular carcinoma, Female, lcsh:Q, down-staging, liver transplantation, hepatocellular carcinoma, criteria, Outcomes research, Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p
Published: 2019
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39. A Relapsing Meningeal Acute Myeloid Leukaemia FLT3-ITD+ Responding to Gilteritinib

Author: Roberta Siniscalchi, Salvatore Perrone, Maria Teresa Voso, Federica Viola, Giuseppe Cimino, Maria C. Scerpa, Elena Cipollone, Elettra Ortu La Barbera, and Tiziana Ottone
Subjects: Pathology, medicine.medical_specialty, Central nervous system, Acute myeloid leukaemia, Lumbar, Cerebrospinal fluid, Bone Marrow, hemic and lymphatic diseases, Drug Discovery, Myeloid sarcoma, medicine, Humans, Pharmacology (medical), Protein Kinase Inhibitors, CPX-351, Pharmacology, Aniline Compounds, medicine.diagnostic_test, business.industry, Brain, Gilteritinib, Magnetic resonance imaging, General Medicine, Settore MED/15, medicine.disease, Magnetic Resonance Imaging, Minimal residual disease, Leukemia, Myeloid, Acute, Treatment Outcome, Infectious Diseases, medicine.anatomical_structure, fms-Like Tyrosine Kinase 3, Oncology, Pyrazines, Mutation, Reflex, Bone marrow, Neoplasm Recurrence, Local, business
Abstract: A patient with a therapy-related acute myeloid leukaemia (AML), NPM1mut, and FLT3-ITD+ was treated with induction and consolidation with CPX-351, obtaining a complete response (CR) but minimal residual disease persisted positive. Later, she complained progressive burning leg pain, weakening of the right hand and leg muscles, associated with absence of osteotendinous leg reflexes. Examination of cerebrospinal fluid (CSF) showed a meningeal relapse of AML. Moreover, a magnetic resonance imaging (MRI) showed 2 right meningeal implants of myeloid sarcoma and bone marrow revealed haematologic relapse of disease. She was treated with medicated lumbar punctures (LPs) followed by an FLA-Ida scheme, and she achieved a 2nd CR. Unfortunately, the patient developed hyperleucocytosis and reappearance of meningeal myeloid sarcoma at MRI. For this reason, a monotherapy with gilteritinib (an FLT3 inhibitor) was started: after 3 months of therapy, central nervous system (CNS)-disease shrunken and then faded, while AML in the bone marrow achieved only a partial response. This is the 1st report of a positive biological effect of gilteritinib on CNS (meningeal) myeloid sarcoma. There are no studies of gilteritinib concentration into CSF and penetration of gilteritinib into the blood-brain barrier should be further studied, given the paucity of drugs active on CNS relapse of AML. In patients receiving CPX-351 only, diagnostic LP should be considered after induction.
Published: 2021
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40. Symptomatic subsegmental versus more central pulmonary embolism: Clinical outcomes during anticoagulation

Author: Carmen Fernández‐Capitán, Ana Rodriguez Cobo, David Jiménez, Olga Madridano, Maurizio Ciammaichella, Esther Usandizaga, Remedios Otero, Pierpaolo Di Micco, Farès Moustafa, Manuel Monreal, M.D. Adarraga, M.A. Aibar, M. Alfonsa, J.I. Arcelus, P. Azcarate‐Agüero, A. Ballaz, P. Baños, R. Barba, M. Barrón, B. Barrón‐Andrés, J. Bascuñana, A. Blanco‐Molina, A.M. Camón, L. Chasco, A.J. Cruz, R. del Pozo, J. de Miguel, J. del Toro, M.C. Díaz‐Pedroche, J.A. Díaz‐Peromingo, J.C. Escribano, C. Falgá, C. Fernández‐Aracil, M.A. Fidalgo, C. Font, L. Font, M.A. García, F. García‐Bragado, M. García‐Morillo, A. García‐Raso, A.I. García‐Sánchez, O. Gavín, I. Gaya, C. Gómez, V. Gómez, J. González, E. Grau, R. Guijarro, J. Gutiérrez, G. Hernández‐Comes, L. Hernández‐Blasco, E. Hernando, L. Jara‐Palomares, M.J. Jaras, D. Jiménez, M.D. Joya, J. Lima, P. Llamas, J.L. Lobo, R. López‐Reyes, J.B. López‐Sáez, M.A. Lorente, A. Lorenzo, M. Lumbierres, A. Maestre, P.J. Marchena, F. Martín‐Martos, M. Martín‐Romero, M.V. Morales, J.A. Nieto, S. Nieto, A. Núñez, M.J. Núñez, M. Odriozola, M.C. Olivares, S. Otalora, J.M. Pedrajas, G. Pellejero, C. Pérez‐Ductor, M.L. Peris, I. Pons, J.A. Porras, L. Ramírez, O. Reig, A. Riera‐Mestre, D. Riesco, A. Rivas, M.A. Rodríguez‐Dávila, V. Rosa, P. Ruiz‐Artacho, J.C. Sahuquillo, M.C. Sala‐Sainz, A. Sampériz, R. Sánchez‐Martínez, S. Soler, B. Sopeña, J.M. Suriñach, C. Tolosa, M.I. Torres, J. Troya, J. Trujillo‐Santos, F. Uresandi, B. Valero, R. Valle, J. Vela, L. Vela, G. Vidal, A. Villalobos, T. Vanassche, C. Vandenbriele, P. Verhamme, H.H.B. Yoo, P. Wells, J. Hirmerova, R. Malý, E. Salgado, L. Bertoletti, A. Bura‐Riviere, N. Falvo, D. Farge‐Bancel, A. Hij, I. Mahé, I. Quere, A. Braester, B. Brenner, M. Ellis, I. Tzoran, G. Antonucci, G. Barillari, F. Bilora, C. Bortoluzzi, E. Bucherini, A. Camerota, C. Cattabiani, F. Dentali, R. Duce, M. Giorgi‐Pierfranceschi, E. Grandone, E. Imbalzano, G. Lessiani, R. Maida, D. Mastroiacovo, F. Pace, R. Pesavento, M. Pesavento, R. Poggio, P. Prandoni, R. Quintavalla, A. Rocci, C. Siniscalchi, E. Tiraferri, D. Tonello, A. Visonà, B. Zalunardo, V. Gibietis, A. Skride, B. Vitola, A. Alatri, H. Bounameaux, L. Calanca, and L. Mazzolai
Subjects: Subsegmental, medicine.medical_specialty, anticoagulant, deep vein thrombosis, outcomes, pulmonary embolism, subsegmental, medicine.drug_class, Deep vein, Outcomes, Deep vein thrombosis, Internal medicine, medicine, First episode, lcsh:RC633-647.5, business.industry, Pulmonary embolism, Hazard ratio, Anticoagulant, Anticoagulants, lcsh:Diseases of the blood and blood-forming organs, Hematology, Heparin, Original Articles ‐ Thrombosis, medicine.disease, Thrombosis, Confidence interval, medicine.anatomical_structure, Cardiology, Original Article, business, medicine.drug
Abstract: The RIETE Investigators., [Background] The optimal therapy of patients with acute subsegmental pulmonary embolism (PE) is controversial., [Methods] We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic PE recurrences during anticoagulation in patients with subsegmental, segmental, or more central PEs. [Results] Among 15 963 patients with a first episode of symptomatic PE, 834 (5.2%) had subsegmental PE, 3797 (24%) segmental, and 11 332 (71%) more central PE. Most patients in all subgroups received initial therapy with low‐molecular‐weight heparin, and then most switched to vitamin K antagonists. Median duration of therapy was 179, 185, and 204 days, respectively. During anticoagulation, 183 patients developed PE recurrences, 131 developed deep vein thrombosis (DVT), 543 bled, and 1718 died (fatal PE, 135). The rate of PE recurrences was twofold higher in patients with subsegmental PE than in those with segmental (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.16‐3.85) or more central PE (HR, 1.89; 95% CI, 1.12‐3.13). On multivariable analysis, patients with subsegmental PE had a higher risk for PE recurrences than those with central PE (adjusted HR, 1.75; 95% CI, 1.02‐3.03). After stratifying patients with subsegmental PE according to ultrasound imaging in the lower limbs, the rate of PE recurrences was similar in patients with DVT, in patients without DVT, and in those with no ultrasound imaging. [Conclusions] Our study reveals that the risk for PE recurrences in patients with segmental PE is not lower than in those with more central PE, thus suggesting that the risk of PE recurrences is not influenced by the anatomic location of PE.
Published: 2021
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41. Pharmacokinetic drug-drug interaction and their implication in clinical management

Author: Palleria Caterina, Di Paolo Antonello, Giofrè Chiara, Caglioti Chiara, Leuzzi Giacomo, Siniscalchi Antonio, De Sarro Giovambattista, and Gallelli Luca
Subjects: Absorption, adverse drug reaction, distribution, drug-drug interactions, excretion, metabolism, poly-therapy, Medicine
Abstract: Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.
Published: 2013

42. Edoxaban for the Long‐Term Therapy of Venous Thromboembolism: Should the Criteria for Dose Reduction be Revised?

Author: Camporese, G., Simioni, P., Di Micco, P., Fernandez-Capitan, C., Rivas, A., Font, C., Sahuquillo, J. C., Villares, P., Prandoni, P., Monreal, M., Adarraga, M. D., Agud, M., Aibar, J., Aibar, M. A., Alfonso, J., Amado, C., Arcelus, J. I., Baeza, C., Ballaz, A., Barba, R., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Camon, A. M., Castro, J., Caudevilla, M. A., Cerda, P., Chasco, L., Criado, J., de Ancos, C., de Miguel, J., del Toro, J., Demelo-Rodriguez, P., Diaz-Peromingo, J. A., Diez-Sierra, J., Dominguez, I. M., Encabo, M., Escribano, J. C., Falga, C., Farfan, A. I., Fernandez de Roitegui, K., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, L., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia-Mullor, M. M., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Joya, M. D., Jou, I., Lacruz, B., Lalueza, A., Lecumberri, R., Lima, J., Lobo, J. L., Lopez-Brull, H., Lopez-Jimenez, L., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Loring, M., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Baquerizo, C., Mella, C., Mellado, M., Mercado, M. I., Moises, J., Morales, M. V., Munoz-Blanco, A., Munoz-Guglielmetti, D., Munoz-Rivas, N., Nart, E., Nieto, J. A., Nunez, M. J., Olivares, M. C., Ortega-Recio, M. D., Osorio, J., Otalora, S., Otero, R., Paredes, D., Parra, P., Parra, V., Pedrajas, J. M., Pellejero, G., Peris, M. L., Pesantez, D., Porras, J. A., Portillo, J., Ramos, E., Reig, L., Riera-Mestre, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rogado, J., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Gimenez, N., Ruiz-Ruiz, J., Ruiz-Sada, P., Salgueiro, G., Samperiz, A., Sanchez-Munoz-Torrero, J. F., Sancho, T., Siguenza, P., Sirisi, M., Soler, S., Suarez, S. Surinach J. M., Tiberio, G., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J. R., Vidal, G., Vilar, C., Zamora, C., Gutierrez, P., Vazquez, F. J., Vanassche, T., Vandenbriele, C., Verhamme, P., Hirmerova, J., Maly, R., Salgado, E., Benzidia, I., Bertoletti, L., Bura-Riviere, A., Crichi, B., Debourdeau, P., Espitia, O., Farge-Bancel, D., Helfer, H., Mahe, I., Moustafa, F., Poenou, G., Schellong, S., Braester, A., Brenner, B., Tzoran, I., Amitrano, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., Colaizzo, D., Dentali, F., Giammarino, E., Grandone, E., Mangiacapra, S., Mastroiacovo, D., Maida, R., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Make, K., Meilanden, K., Skride, A., Ferreira, M., Fonseca, S., Martins, F., Meireles, J., Bosevski, M., Zdraveska, M., Bounameaux, H., Mazzolai, L., Caprini, J. A., Tafur, A. J., Weinberg, I., Wilkins, H., Bui, H. M., and UAM. Departamento de Medicina
Subjects: Male, medicine.medical_specialty, Time Factors, Dose, Medicina, Pyridines, Hemorrhage, General Biochemistry, Genetics and Molecular Biology, Article, chemistry.chemical_compound, Edoxaban, Recurrence, Internal medicine, medicine, Humans, Prospective Studies, Registries, General Pharmacology, Toxicology and Pharmaceutics, Long term therapy, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Drug Tapering, business.industry, lcsh:Public aspects of medicine, General Neuroscience, Mortality rate, Research, lcsh:RM1-950, Hazard ratio, Anticoagulants, lcsh:RA1-1270, General Medicine, Articles, Venous Thromboembolism, Middle Aged, Confidence interval, Thiazoles, lcsh:Therapeutics. Pharmacology, chemistry, Practice Guidelines as Topic, Dose reduction, Female, business, Venous thromboembolism, Follow-Up Studies
Abstract: Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12–42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63–262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54–133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated., No funding was received for this work
Published: 2020

43. Myocardial Scar by Pulse-Cancellation Echocardiography Is Independently Associated with Appropriate Defibrillator Intervention for Primary Prevention after Myocardial Infarction

Author: Nicola Gaibazzi, Valentina Lorenzoni, Silvia Garibaldi, Gregg S. Pressman, Sergio Suma, Daniele Sartorio, and Carmine Siniscalchi
Subjects: medicine.medical_specialty, Myocardial Infarction, Contrast Media, Gadolinium, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, Coronary artery disease, Cicatrix, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, Primary prevention, medicine, Humans, Radiology, Nuclear Medicine and imaging, Myocardial infarction, Retrospective Studies, Ejection fraction, Receiver operating characteristic, Pulse (signal processing), business.industry, Ultrasound, Area under the curve, medicine.disease, Defibrillators, Implantable, Primary Prevention, Echocardiography, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Myocardial scar burden impacts prognosis in patients with coronary artery disease who have experienced a myocardial infarction (MI). This has been demonstrated by late gadolinium enhancement cardiac magnetic resonance. Clinical experience with echocardiography suggests that the reflected ultrasound signal is enhanced in infarcted myocardial segments. Scar imaging with an ultrasound multipulse scheme (eScar) has been preliminarily validated in prior studies.To assess whether scar burden, as detected by eScar, is associated with implantable cardioverter-defibrillator (ICD) shocks in post-MI patients.We retrospectively selected 50 post-MI patients with an ejection fraction35% who received an ICD for primary prevention and subsequently had at least one appropriate shock (cases). These were compared with 50 post-MI patients, matched for clinical variables and ejection fraction, who never experienced an appropriate defibrillator shock (controls). Subjects were assessed with the eScar technique at the time of implantation or during follow-up.An eScar was present in ≥1 segment in 40 of 50 (80%) cases vs 26 of 50 (52%) controls and was associated with appropriate ICD shocks (P = .004). Receiver operating characteristic curve analysis, using a threshold of ≥3 segments by eScar, showed an area under the curve (AUC) of 0.715. On models including clinical and echocardiographic variables, eScar remained significantly associated with ICD shocks (P = .050 or P = .033 depending on the model). Adding eScar to a multivariate logistic regression model including indexed left ventricular end-systolic volume led to an increase in AUC from 0.734 to 0.782 (P = .049), while substituting indexed left ventricular end-diastolic volume for indexed left ventricular end-systolic volume resulted in a nonsignificant increase in AUC from 0.747 to 0.785 (P = .098).Presence and extent of eScar were independently associated with appropriate ICD shocks in this study of patients with prior MI and reduced ejection fraction. However, the addition of eScar assessment to the clinical multivariable model that included also indexed left ventricular end-diastolic volume did not provide significant incremental value.
Published: 2020
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44. Different Types of Statins and All-Cause Mortality during Anticoagulation for Venous Thromboembolism: Validation Study from RIETE Registry

Author: Siniscalchi, Carmine, Suriñach, José M, Visonà, Adriana, Fernández-Reyes, José L, Gómez-Cuervo, Covadonga, Verhamme, Peter, Marchena, Pablo J, Farge-Bancel, Dominique, Moisés, Jorge, Monreal, Manuel, and and the RIETE Investigators
Subjects: lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Statin, medicine.drug_class, Atorvastatin, venous thromboembolism, 030204 cardiovascular system & hematology, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, death, medicine, simvastatin, Rosuvastatin, cardiovascular diseases, business.industry, Hazard ratio, nutritional and metabolic diseases, atorvastatin, medicine.disease, Confidence interval, Pulmonary embolism, lcsh:RC666-701, Cohort, lipids (amino acids, peptides, and proteins), Original Article, business, rosuvastatin, 030217 neurology & neurosurgery, medicine.drug
Abstract: Introduction We previously reported that during the course of anticoagulation for venous thromboembolism (VTE) patients using statins were at a lower risk to die than nonusers. Methods We used the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry to validate our previous findings in a subsequent cohort of patients and to compare the risk of death according to the use of different types of statins. Results From January 2018 to December 2019, 19,557 patients with VTE were recruited in RIETE. Of them, 4,065 (21%) were using statins (simvastatin, 1,406; atorvastatin, 1,328; rosuvastatin, 246; and others, 1,085). During anticoagulation (192 vs.182 days, for statin and no statin users respectively), 500 patients developed a VTE recurrence, 519 suffered major bleeding, and 1,632 died (fatal pulmonary embolism [PE], 88 and fatal bleeding, 78). On multivariable analysis, statin users were at a lower risk to die (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.59–0.79) than nonusers. When separately analyzing the drugs, on multivariable analysis, patients using simvastatin (HR = 0.64; 95% CI: 0.52–0.80), atorvastatin (HR 0.72; 95% CI: 0.58–0.89), or other statins (HR = 0.67; 95% CI: 0.52–0.87) were at a lower risk to die than nonusers. For those using rosuvastatin, difference was not statistically significant (HR = 0.77; 95% CI: 0.50–1.19), maybe due to the sample size. Conclusion Our data validate previous findings and confirm that VTE patients using statins at baseline are at a lower risk to die than nonusers. No statistically differences were found according to type of statins.
Published: 2020

45. Use of Panax Quinquefolius and Acetylcarnitine Supplement (FORT UP®) Against Fatigue in Cancer Patients Admitted to Hospice Palliative Care

Author: Massimo Bonucci, S. Dell’Arte, A. Siniscalchi, and G. Spinelli
Subjects: medicine.medical_specialty, Palliative care, business.industry, Guideline, Internal medicine, medicine, Panax quinquefolium, General Earth and Planetary Sciences, In patient, medicine.symptom, business, Acetylcarnitine, Cancer-related fatigue, General Environmental Science, medicine.drug
Abstract: For cancer patients, fatigue is one of the most frequent and disabling symptoms. Fatigue is a mix of symptoms like muscle pain, mental cognitive dysfunction, neurological disorders that make the patient completely inactive and into a state of complete abandonment. At this time not exist anything for treatment and today there is no specific guideline; only a very few substances can alleviate this situation. In our study, we’ve used two scales of VAS to better deeply understand the severity of symptoms. For treatment, we used a supplement (Fort up® - Gamfarma Italy) made with two active principles, Panax quinquefolium and acetyl-carnitine, in 56 cancer patients admitted to hospice palliative care, administered for three weeks to assess the effect in medium to severe asthenia. Both active principles have demonstrated activity in clinical studies against cancer-related fatigue with tonic and energizing action. At the end of study 46 out of 56 patients (82%) had an improvement of symptoms and in 18 patients (4 in low, 11 in medium and 3 in severe asthenia) (32%) these symptoms there resolved. The study aimed was to investigate the efficacy of this product on cancer-related fatigue in patients admitted to hospital palliative care. Our study demonstrated that this product can relieve cancer-related fatigue in this setting of cancer patients.
Published: 2020
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46. Venous outflow in partial heterotopic liver transplantation with spleen replacement: Evidence of no chronic venous hypertension

Author: Matteo Ravaioli, Matteo Serenari, Francesco Vasuri, Matteo Renzulli, Enrico Prosperi, Guido Fallani, Antonio Siniscalchi, Lorenzo Maroni, Federica Odaldi, Matteo Cerri, Giuliana Germinario, Matteo Cescon, Ravaioli M., Germinario G., Cerri M., Prosperi E., Fallani G., Vasuri F., Serenari M., Odaldi F., Maroni L., Siniscalchi A., Cescon M., and Renzulli M.
Subjects: medicine.medical_specialty, Transplantation, Heterotopic, medicine.medical_treatment, Spleen, Economic shortage, Liver transplantation, clinical research/practice, Liver disease, liver transplantation: auxiliary, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Venous hypertension, Transplantation, business.industry, medicine.disease, Liver Transplantation, Surgery, medicine.anatomical_structure, Liver, Hypertension, Hepatectomy, liver disease, business, liver transplantation/hepatology
Abstract: We recently described the first case of partial heterotopic liver transplantation replacing the spleen with delayed recipient hepatectomy to overcome the problem of organ shortage and to make possible debated indications for liver transplantation.1,2 The surgical technique of the RAVAS procedure was described in different steps: before planning the operation1 and after the first procedure performed, with a case report and video of the technique.
Published: 2022
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47. Restoration of portal flow with varix in liver transplantation for patients with total portal vein thrombosis: An effective strategy in the largest center experience

Author: Antonio Daniele Pinna, Matteo Cescon, Antonio Siniscalchi, Giacomo Frascaroli, Lorenzo Maroni, Enrico Prosperi, Federica Odaldi, Guido Fallani, Matteo Ravaioli, Matteo Serenari, Ravaioli M., Prosperi E., Pinna A., Siniscalchi A., Fallani G., Frascaroli G., Maroni L., Odaldi F., Serenari M., and Cescon M.
Subjects: medicine.medical_specialty, Blood transfusion, Left gastric vein, medicine.medical_treatment, portal reconstruction, 030230 surgery, Anastomosis, Liver transplantation, Varicose Veins, gastric varix, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, portal vein thrombosi, Venous Thrombosis, Transplantation, Varix, liver transplantation, Portal Vein, business.industry, Liver Neoplasms, portal hypertension, Gastric varices, medicine.disease, coronary-portal anastomosi, Portal vein thrombosis, Surgery, Liver Neoplasm, Portal hypertension, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business, Human, Varicose Vein
Abstract: Introduction: Postoperative complications and worse prognosis still burden liver transplantations (LT) with complex portal vein thrombosis (CPVT). When an engorged left gastric vein (LGV) is present, the portal inflow is restorable with an anastomosis between the graft portal vein and the LGV of the recipient. We analyzed short- and long-term results of this procedure in 12 LT with CPVT. Methods: Between 2005 and 2019, 55 patients with CPVT underwent LT. We applied this technique in 12 patients. In six cases, we placed a vascular graft to obtain a tension-free structure. We evaluated patency, short- and long-term results. Results: No intraoperative complication was observed. The median duration of LT, blood transfusion, deceased donor age, and MELD score of the recipients were 7h, 1250mL, 72years, and 19. Seven patients were affected by hepatocellular carcinoma. No major complications or PVT recurrence were observed. One patient required a liver re-transplantation for primary non-functioning syndrome. The mean hospital stay was 20days. The actuarial patient survival was 85% with a mean FU of 4years. The two late deaths were due to hepatocellular carcinoma recurrence and sepsis for cholangitis. Conclusions: This technique in presence of both CPVT and engorged LGV is feasible and safe for patients, with good short- and long-term results.
Published: 2021
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48. COVID-19 in IBD: The experience of a single tertiary IBD center

Author: Nikolas Dussias, Gilberto Poggioli, Paolo Gionchetti, Fernando Rizzello, Carlo Calabrese, Laura Melotti, Andrea Belluzzi, Eleonora Filippone, Matteo Rottoli, Eleonora Scaioli, G. Peruzzi, Hana Privitera, Silvio Laureti, L. Calandrini, Marco Salice, Anastasio Decorato, Antonio Siniscalchi, and Fernando Rizzello, Carlo Calabrese, Marco Salice, Lucia Calandrini, Hana Privitera, Laura Melotti, Giulia Peruzzi, Nikolas Dussias, Andrea Belluzzi, Eleonora Scaioli, Anastasio Decorato, Antonio Siniscalchi, Eleonora Filippone, Silvio Laureti, Matteo Rottoli, Gilberto Poggioli, Paolo Gionchetti
Subjects: Covid-*19, Male, Disease, Inflammatory bowel disease, Tertiary Care Centers, chemistry.chemical_compound, 0302 clinical medicine, Deprescriptions, Crohn Disease, biological treatment, Mesalamine, Aged, 80 and over, education.field_of_study, Incidence (epidemiology), Gastroenterology, Middle Aged, Hospitalization, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Covid-19, Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Adolescent, IBD, Population, Antibodies, Monoclonal, Humanized, Article, Time-to-Treatment, 03 medical and health sciences, Young Adult, Mesalazine, Gastrointestinal Agents, Internal medicine, medicine, Humans, Risk factor, education, Aged, Biological Products, Hepatology, business.industry, SARS-CoV-2, medicine.disease, Inflammatory Bowel Diseases, Sulfasalazine, chemistry, Observational study, Colitis, Ulcerative, Tumor Necrosis Factor Inhibitors, business
Abstract: Background Italy has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID‐19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19. Methods This was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020. Results 1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p Conclusions Our data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse.
Published: 2021
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49. Delirium and Clusters of Older Patients Affected by Multimorbidity in Acute Hospitals

Author: Monacelli, F, Signori, A, Marengoni, A, Di Santo, S, Rossi, E, Valsecchi, Mg, Morandi, A, Bellelli, G, Tarasconi, A, Sella, M, Auriemma, S, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Giani, A, Famularo, S, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Candiani, T, Ballestrero, A, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, Pietrogrande, L, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Bo, M, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Borghi, C, Bianchetti, A, Crucitti, A, Difrancesco, V, Fontana, G, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cannistrà, U, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambara, V, Saitta, A, Corica, F, Braga, M, Ettorre, E, Camellini, C, Annoni, G, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuari, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, D'Imporzano, E, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samy Salama Fahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Alessandro, M, Pezzoni, D, Platto, C, D'Ambrosio, V, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Confente, S, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, Corsini, C, Boffelli, S, Filippi, A, Delpin, K, Faraci, B, Bertoletti, E, Vannucci, M, Tesi, F, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Riva, E, Dell'Acqua, D, Cottino, M, Vezzadini, G, Avanzi, S, Brambilla, C, Orini, S, Sgrilli, F, Mello, A, Lombardi, L, Muti, E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, Barelli, A, Millul, A, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Cortegiani, A, Vitale, F, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Mossello, E, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D., Monacelli, F, Signori, A, Marengoni, A, Di Santo, S, Rossi, E, Valsecchi, M, Morandi, A, and Bellelli, G
Subjects: medicine.medical_specialty, multimorbidity, Delirium, multimorbidity, Socio-culturale, Older patients, mental disorders, Medicine, Dementia, Multimorbidity, Humans, Medical history, LS4_4, General Nursing, Aged, Aged, 80 and over, Routine screening, business.industry, Health Policy, Delirium, General Medicine, Targeted interventions, medicine.disease, Hospitals, Cross-Sectional Studies, Charlson comorbidity index, Emergency medicine, Geriatrics and Gerontology, medicine.symptom, business
Abstract: Objectives Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition. Design This is a cross-sectional study nested in the 2017 Delirium Day project. Setting and Participants The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium. Methods Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity. Results The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults. Conclusions and Implications Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis.
Published: 2022

50. Prevalence of aneurysm of the interatrial septum in the general population and in patients with a recent episode of cryptogenetic ischemic stroke: a tissue harmonic imaging transthoracic ecocardiography study in 5.631 patients

Author: O. Serafini, G. Misuraca, A. Siniscalchi, M.T. Manes, G. Meringolo, C. Tomaselli, M. Chiatto, and A. Buffon
Subjects: aneurysm of the interatrial septum, transthoracic echocardiography, patent foramen ovale, cerebral ischemia, Medicine
Abstract: Cerebral ischemia is among the principal causes of mortality and morbidity in industrialized countries being responsible of 10-12% of all deaths and of an elevated number of permanent disability. The cardioembolic forms may be responsible of the 30-35% of cerebrovascular acute syndrome, nevertheless in a significant percentage of cases, especially among young people, cerebral ischemic episodes are not induced by these cardiembolic forms: these cases are defined as cryptogenetic stroke/TIA. In these patients cardiac abnormalities represented by an aneurysm of the interatrial septum (ASA) and by a patent foramen ovale (PFO) have been frequently observed. The purpose of our prospective study was to evaluate, through transthoracic ecocardiography and tissue harmonic imaging (ETT-THI), the prevalence of ASA in the general population (group A) and the prevalence of ASA-FOP in a subgroup of patients with recent episode of cryptogenetic ischemic stroke/TIA (group B). We studied in a prospective manner from January 1 2003 to October 31t 2004 n. 5.631 patients. The presence of ASA was found in 3,2% of patients of group A, while in patients of group B we identifyed an ASA in 32% and a POF in 42% of the cases. Using a ETT-THI, our study shows in a wide range of a non selected population a prevalence of ASA greater than in previous studies. Such high prevalence in the general population of patients submitted to echocardiography and the higher frequency in subjects with recent cryptogenetic stroke, suggests to search carefully these abnormalities at the level of the interatrial septum using the harmonic imaging method.
Published: 2016
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