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1. Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis

Author

Nerviani, Alessandra, Boutet, Marie-Astrid, Ghirardi, Giulia Maria, Goldmann, Katriona, Sciacca, Elisabetta, Rivellese, Felice, Pontarini, Elena, Prediletto, Edoardo, Abatecola, Federico, Caliste, Mattia, Pagani, Sara, Mauro, Daniele, Bellan, Mattia, Cubuk, Cankut, Lau, Rachel, Church, Sarah E., Hudson, Briana M., Humby, Frances, Bombardieri, Michele, Lewis, Myles J., and Pitzalis, Costantino

Published
2024
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2. Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response

Author

Corsiero, Elisa, Caliste, Mattia, Jagemann, Lucas, Fossati-Jimack, Liliane, Goldmann, Katriona, Cubuk, Cankut, Ghirardi, Giulia M., Prediletto, Edoardo, Rivellese, Felice, Alessandri, Cristiano, Hopkinson, Mark, Javaheri, Behzad, Pitsillides, Andrew A., Lewis, Myles J., Pitzalis, Costantino, and Bombardieri, Michele

Subjects
Complications and side effects, Physiological aspects, Development and progression, Health aspects, Autoimmunity -- Health aspects, Monoclonal antibodies -- Health aspects, Connective tissue cells -- Health aspects -- Physiological aspects, Arthritis -- Development and progression -- Complications and side effects, Autoantigens -- Health aspects
Abstract

Introduction Rheumatoid arthritis (RA) is the most common inflammatory, erosive polyarthritis and affects approximately 0.5%-1.5% of the worldwide population. RA is characterized by breach of self-tolerance and production of several [...], Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant monoclonal antibodies (RA- rmAbs) derived from single, locally differentiated rheumatoid arthritis (RA) synovial B cells, which specifically recognize fibroblast-like synoviocytes (FLSs). Here, we aimed to identify the specificity of FLS-derived autoantigens fueling local autoimmunity and the functional role of anti-FLS antibodies in promoting chronic inflammation. A subset of anti-FLS RA- rmAbs reacting with a 60 kDa band from FLS extracts demonstrated specificity for HSP60 and partial cross-reactivity to other stromal autoantigens (i.e., calreticulin/vimentin) but not to citrullinated fibrinogen. Anti-FLS RA-rmAbs, but not anti-neutrophil extracellular traps rmAbs, exhibited pathogenic properties in a mouse model of collagen-induced arthritis. In patients, anti-HSP60 antibodies were preferentially detected in RA versus osteoarthritis (OA) synovial fluid. Synovial HSPD1 and CALR gene expression analyzed using bulk RNA-Seq and GeoMx-DSP closely correlated with the lympho-myeloid RA pathotype, and HSP60 protein expression was predominantly observed around ELS. Moreover, we observed a significant reduction in synovial HSP60 gene expression followed B cell depletion with rituximab that was strongly associated with the treatment response. Overall, we report that synovial stromal-derived autoantigens are targeted by pathogenic autoantibodies and are associated with specific RA pathotypes, with potential value for patient stratification and as predictors of the response to B cell-depleting therapies.

Published
2024
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4. The role of the Epstein Barr Virus in B cell tolerance loss in rheumatoid arthritis disease

Author

Prediletto, Edoardo

Subjects
616.7
Abstract

Although many efforts have been done in understanding the aetiology of rheumatoid arthritis (RA), the Epstein-Barr Virus (EBV) remains one of the strongest candidates to be investigated as possible environmental factors in inducing RA. Of relevance, a high percentage of RA patients are characterised by a strong immune response to EBV, with high blood DNAviral load and circulating cross-reactive (auto)antibodies reacting against self-citrullinated antigens (ACPA) and viral proteins. Due to its lymphotropic behaviour, EBV might be able to rescue an autoreactive B cell phenotype and thus eludes the immune system checkpoints. Also, the virus and the infected B cells have been proposed as a possible source of citrullinated epitopes triggering the disease. To obtain long-standing EBV-infected B cells, I setup an in vitro co-culture system whereby RA fibroblasts-like synoviocytes (RA-FLS) obtained from synovial fluid and synovial tissue of patient were cultured with CD19+B cells for 28 days. RA-FLS were used as feeding environment for the CD19+B cells obtained from ACPA+ RA patients and healthy donor. CpG was added to induce plasmacells differentiation to test the presence of ACPA antibodies. B cells were then recovered, and analysed trough fluorescence activated cell sorting (Facs). Finally, molecular biology analysis has been performed to detect and quantify specific EBV-related gene such as the BamH1-W repeat region. Also, RA-FLS were recovered in order to investigate any possible modification induced by the CD19+B cells in the system. Preliminary data suggested that the EBV+ CD19+B cells population has a higher proliferation rate when incubated with RA-FLS, although this is not exclusive of RA patient since such proliferation was detected also in healthy donor. Nevertheless, this might reflect an in vivo mechanism in 6 which the EBV+ CD19+B cells from the peripheral compartment might find a preferential proliferating niche in the synovium, due to the RA-FLS. Furthermore, I am proposing a new method to obtain naturally EBV+ RACD19+ B cells in order to develop a better tool to study the role of the virus in RA pathogenesis.

Published
2021

5. Assessment of the alveolar volume when sampling exhaled gas at different expired volumes in the single breath diffusion test

Author

Catapano Giosuè, Fornai Edo, Prediletto Renato, and Carli Cristina

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Alveolar volume measured according to the American Thoracic Society-European Respiratory Society (ATS-ERS) guidelines during the single breath diffusion test can be underestimated when there is maldistribution of ventilation. Therefore, the alveolar volume calculated by taking into account the ATS-ERS guidelines was compared to the alveolar volume measured from sequentiallly collected samples of the expired volume in two groups of individuals: COPD patients and healthy individuals. The aim of this study was to investigate the effects of the maldistribution of ventilation on the real estimate of alveolar volume and to evaluate some indicators suggestive of the presence of maldistribution of ventilation. Methods Thirty healthy individuals and fifty patients with moderate-severe COPD were studied. The alveolar volume was measured either according to the ATS-ERS guidelines or considering the whole expired volume subdivided into five quintiles. An index reflecting the non-uniformity of the distribution of ventilation was then derived (DeltaVA/VE). Results Significant differences were found when comparing the two measurements and the alveolar volume by quintiles appeared to have increased progressively towards residual volume in healthy individuals and much more in COPD patients. Therefore, DeltaVA/VE resulted in an abnormal increase in COPD. Conclusion The results of our study suggest that the alveolar volume during the single breath diffusion test should be measured through the collection of a sample of expired volume which could be more representative of the overall gas composition, especially in the presence of uneven distribution of ventilation. Further studies aimed at clarifying the final effects of this way of calculating the alveolar volume on the measure of DLCO are needed. DeltaVA/VE is an index that can help assess the severity of inhomogeneity in COPD patients.

Published
2007
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7. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial

Author

Rivellese, Felice, Surace, Anna E. A., Goldmann, Katriona, Sciacca, Elisabetta, Çubuk, Cankut, Giorli, Giovanni, John, Christopher R., Nerviani, Alessandra, Fossati-Jimack, Liliane, Thorborn, Georgina, Ahmed, Manzoor, Prediletto, Edoardo, Church, Sarah E., Hudson, Briana M., Warren, Sarah E., McKeigue, Paul M., Humby, Frances, Bombardieri, Michele, Barnes, Michael R., Lewis, Myles J., and Pitzalis, Costantino

Published
2022
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10. Early awake proning in critical and severe COVID-19 patients undergoing noninvasive respiratory support: A retrospective multicenter cohort study

Author

Tonelli, Roberto, Pisani, Lara, Tabbì, Luca, Comellini, Vittoria, Prediletto, Irene, Fantini, Riccardo, Marchioni, Alessandro, Andrisani, Dario, Gozzi, Filippo, Bruzzi, Giulia, Manicardi, Linda, Busani, Stefano, Mussini, Cristina, Castaniere, Ivana, Bassi, Ilaria, Carpano, Marco, Tagariello, Federico, Corsi, Gabriele, d’Amico, Roberto, Girardis, Massimo, Nava, Stefano, and Clini, Enrico

Published
2022
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12. COVID-19 Pneumonia and ROX index: Time to set a new threshold for patients admitted outside the ICU

Author

María Laura Vega, Roberto Dongilli, Gustavo Olaizola, Nicolás Colaianni, Mauro Castro Sayat, Lara Pisani, Micaela Romagnoli, Greta Spoladore, Irene Prediletto, Guillermo Montiel, and Stefano Nava

Subjects
High flow nasal cannula, HFNC, Non invasive respiratory support, ROX index, Acute hypoxemic respiratory failure, AHRF, Diseases of the respiratory system, RC705-779
Abstract

High flow nasal cannula (HFNC) is used to treat acute hypoxemic respiratory failure (AHRF) even outside the ICU and the ROX index (pulse oximetry/fraction of inspired oxygen/respiratory rate) may predict HFNC failure. Objective: The purpose of this investigation was therefore to verify whether the ROX index is an accurate predictor of HFNC failure for COVID-19 patients treated outside the intensive care unit (ICU) and to evaluate the validity of the previously suggested threshold. Design: Multicenter study. Retrospective observational analysis of prospectively collected data. Setting: 3 centres specialized in non-invasive respiratory support (Buenos Aires, Argentina; Bolzano and Treviso, Italy). Patients treated outside the ICU were analysed Measurements: The variables to calculate the ROX index were collected during the first day of therapy at 2, 6, 12 and 24 hours and then recorded every 24 hours. HFNC failure was defined as escalation of respiratory support to invasive mechanical ventilation (IMV) or death. Main results: A total of 35 (29%) patients failed HFNC and required intubation. ROC analysis identified the 12-hour ROX index as the best predictor of intubation with an AUC of 0.7916[CI 95% 0.6905-0.8927] and the best threshold to be 5.99[Specificity 96% Sensitivity 62%]. In the survival analysis, a ROX value

Published
2022
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13. Health-related quality of life profiles, trajectories, persistent symptoms and pulmonary function one year after ICU discharge in invasively ventilated COVID-19 patients, a prospective follow-up study

Author

Tartaglione, Marco, Chiarini, Valentina, Buldini, Virginia, Coniglio, Carlo, Moro, Federico, Orlando, Silvia, Fecarotti, Daniele, Cilloni, Nicola, Giuntoli, Lorenzo, Bellocchio, Angela, Matteo, Emanuele, Pizzilli, Giacinto, Siniscalchi, Antonio, Tartivita, Chiara, Cavalli, Irene, Castelli, Andrea, Marchio, Annalisa, Bacchilega, Igor, Bernabé, Laura, Facondini, Francesca, Morini, Luca, Bissoni, Luca, Viola, Lorenzo, Meconi, Tommaso, Pavoni, Vittorio, Venni, Angelica, Pagni, Aline, Cleta, Patrizia Pompa, Cavagnino, Marco, Guzzo, Alessia, Malfatto, Anna, Adduci, Angelina, Pareschi, Silvia, Bertellini, Elisabetta, Maccieri, Jessica, Marinangeli, Elisa, Racca, Fabrizio, Verri, Marco, Falò, Giulia, Marangoni, Elisabetta, Ottaviani, Irene, Boni, Francesco, Felloni, Giulia, Baccarini, Federico Domenico, Terzitta, Marina, Maitan, Stefano, Tutino, Lorenzo, Senzi, Angelo, Consales, Guglielmo, Becherucci, Filippo, Imbriani, Michele, Orlandi, Paolo, Candini, Silvia, Golfieri, Rita, Ciccarese, Federica, Poerio, Antonio, Muratore, Francesco, Ferrari, Fabio, Mughetti, Martina, Giampalma, Emanuela, Franchini, Loredana, Neziri, Ersenad, Miceli, Marco, Minguzzi, Maria Teresa, Mellini, Lorenzo, Piciucchi, Sara, Monari, Matteo, Valli, Michele, Daniele, Federico, Ferioli, Martina, Nava, Stefano, Lazzari Agli, Luigi Arcangelo, Valentini, Ilaria, Bernardi, Eva, Balbi, Bruno, Contoli, Marco, Padovani, Marianna, Oldani, Stefano, Ravaglia, Claudia, Goti, Patrizio, Gamberini, Lorenzo, Mazzoli, Carlo Alberto, Prediletto, Irene, Sintonen, Harri, Scaramuzzo, Gaetano, Allegri, Davide, Colombo, Davide, Tonetti, Tommaso, Zani, Gianluca, Capozzi, Chiara, Dalpiaz, Giorgia, Agnoletti, Vanni, Cappellini, Iacopo, Melegari, Gabriele, Damiani, Federica, Fusari, Maurizio, Gordini, Giovanni, Laici, Cristiana, Lanza, Maria Concetta, Leo, Mirco, Marudi, Andrea, Papa, Raffaella, Potalivo, Antonella, Montomoli, Jonathan, Taddei, Stefania, Mazzolini, Massimiliano, Ferravante, Anna Filomena, Nicali, Roberta, Ranieri, Vito Marco, Russo, Emanuele, Volta, Carlo Alberto, and Spadaro, Savino

Published
2021
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17. Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Author

Caneva, Jorge, Tuhay, Graciela, Diez, Mirta, Talavera, Maria Lujan, Acosta, Adriana, Vulcano, Norberto, Bosio, Martin, Maldonado, Lorena, Deleo, Sabino, Melatini, Luciano, Keogh, Anne, Kotlyar, Eugene, Feenstra, John, Dwyer, Nathan, Adams, Heath, Stevens, Wendy, Steele, Peter, Proudman, Susanna, Minson, Robert, Reeves, Glenn, Lavender, Melanie, Ng, Benjamin, Mackenzie, Michele, Barry, Lisa, Gruenberger, Margarethe, Huber, Charlotte, Lang, Irene, Tilea, Ioana, Sadushi-Kolici, Roela, Löffler-Ragg, Judith, Feistmantl, Lisa-Theresa, Evrard, Patrick, Louis, Renaud, Guiot, Julien, Naldi, Marco, De Pauw, Michel, Mehta, Sanjay, Camacho, Rafael Conde, Tovar, Patricia Parada, Londoño, Alejandro, Campo, Felipe, Garcia, Paula, Lema, Camila, Orozco-Levi, Mauricio, Martinez, William, Gomez, Juan Esteban, Nielsen-Kudsk, Jens Erik, Mellemkjaer, Soren, Anton, Ly, Altraja, Alan, Vihinen, Tapani, Vasankari, Tuija, Sitbon, Olivier, Cottin, Vincent, Têtu, Laurent, Noël-Savina, Elise, Shearman, Nicole, Tayler, Susanne, Olzik, Ilona, Kulka, Christine, Grimminger, Jan, Simon, Marcel, Nolde, Anna, Oqueka, Tim, Harbaum, Lars, Egenlauf, Benjamin, Ewert, Ralf, Schulz, Christian, Regotta, Sabine, Kramer, Tilmann, Knoop-Busch, Susanne, Gerhardt, Felix, Konstantinides, Stavros, Pitsiou, Georgia, Stanopoulos, Ioannis, Sourla, Evdokia, Mouratoglou, Sofia, Karvounis, Haralambos, Pappas, Athanasios, Georgopoulos, Dimitrios, Fanaridis, Michail, Mitrouska, Ioanna, Michalis, Lampros, Pappas, Konstantinos, Kotsia, Anna, Gaine, Sean, Vizza, Carmine Dario, Manzi, Giovanna, Poscia, Roberto, Badagliacca, Roberto, Agostoni, Piergiuseppe, Bruno, Noemi, Farina, Stefania, D'Alto, Michele, Argiento, Paola, Correra, Anna, Di Marco, Giovanni Maria, Cresci, Chiara, Vannucchi, Vieri, Torricelli, Elena, Garcea, Alessio, Pesci, Alberto, Sardella, Luca, Paciocco, Giuseppe, Pane, Federico, D'Armini, Andrea Maria, Pin, Maurizio, Grazioli, Valentina, Massola, Giulia, Sciortino, Antonio, Prediletto, Renato, Bauleo, Carolina, Airò, Edoardo, Ndreu, Rudina, Pavlickova, Ivana, Lunardi, Claudio, Mulè, Massimiliano, Farruggio, Silvia, Costa, Serena, Galgano, Giuseppe, Petruzzi, Mario, De Luca, Anna, Lombardi, Francesco, Roncon, Loris, Conte, Luca, Picariello, Claudio, Wirtz, Gil, Alexandre, Myriam, Vonk-Noordegraaf, A., Boogaard, H., Mager, J., Reesink, H., van den Toorn, Leon M., Boomars, Karin, Andreassen, Arne K., Castro, Graça, Tania, Gonçalves, Baptista, Rui, Marinho, António, Shiang, Teresa, Oliveira, Ana, Coutinho, Daniel, Sousa, Joana, Loureiro, Maria José, Repolho, Débora, Martins Jesus, Susana Maria, Capinha, Marta, Agostinho, João, Cardoso, Tania, Rocha, Andreia, Espinha, Mafalda, Ivanov, Kyundyul Ivanovich, Alexeeva, Dalyana Eduardovna, Batalina, Marina Vadimovna, Hegya, Daria Viktorovna, Zvereva, Tatyana Nikolaevna, Avdeev, Sergey Nikolaevich, Tsareva, Natalia Anatolievna, Galyavich, Albert Sarvatovich, Nikolaevich, Bykov Aleksander, Filippov, Evgeny Vladimirovich, Yakovleva, Olga Eduardovna, Pavlova, Olga Borisovna, Skripkina, Elena Sergeevna, Martynyuk, Tamila Vitalievna, Bukatova, Irina Fedorovna, Tregubova, Anna Viktorovna, Platonov, Dmitry Yurievich, Kolomeytseva, Tatyana Mikhaylovna, Al Dalaan, Abdullah, Abdelsayed, Abeer Abeer, Weheba, Ihab, Saleemi, Sarferaz, Sakkijha, Hussam, Bohacekova, Marcela, Valkovicova, Tatiana, Farkasova, Iveta, Quezada, Carlos Andres, Piccari, Lucilla, Blanco, Isabel, Sebastian, Laura, Roman, Antonio, Lopez, Manuel, Otero, Remedios, Elias, Teresa, Jara, Luis, Asencio, Isabel, Arjona, Josefa Jiménez, Almagro, Raúl Menor, Cárdenas, Salvador López, García, Salvador Alcaraz, Rodríguez, Patricia Villanueva, Lopez, Raquel, Garcia, Alberto, Avilés, Francisco Fernandez, De La Pava, Sebastian, Yotti, Raquel, Peñate, Gregorio Pérez, Marrero, Fernando León, Cifrián Martínez, José Manuel, Martinez-Meñaca, Amaya, Alonso, Lecue Pilar, Rozas, Sonia Fernandez, Fernandez, David Iturbe, Cuesta, Victor Mora, Söderberg, Stefan, Bartfay, Sven-Erik, Rundqvist, Bengt, Alfetlawi, Monthir, Wodlin, Peter, Schwarz, Esther Irene, Speich, Rudolf, Lador, Frédéric, Rochat, Thierry, Gasche-Soccal, Paola, Hsu, Chih-Hsin, Lin, Tsung-Hsien, Su, Ho-Ming, Lai, Wen-Ter, Chu, Chun Yuan, Hsu, Po-Chao, Voon, Wen-Chol, Yen, Hsueh-Wei, Yih-Jer Wu, Jacob, Wu, Shu-Hao, Huang, Wen-Pin, Fong, Man-Cai, Huang, Chien-Lung, Kuo, Ping-Hung, Lin, Yen-Hung, Lin, Jiunn-Lee, Hung, Chi-Sheng, Wu, Cho-Kai, Sung, Shih-Hsien, Huang, Wei-Chun, Cheng, Chin-Chang, Kuo, Shu-Hung, Wang, Wen-Hwa, Ho, Wan-Jing, Hsu, Tsu-Shiu, Mutlu, Bülent, Atas, Halil, Ongen, Gul, Un, Zeynep, Okumus, Gulfer, Hanta, Ismail, Corris, Paul, Peacock, Andrew, Church, Colin, Toshner, Mark, Newnham, Michael, Ghofrani, Hossein-Ardeschir, Gomez Sanchez, Miguel-Angel, Humbert, Marc, Pittrow, David, Simonneau, Gérald, Gall, Henning, Grünig, Ekkehard, Klose, Hans, Halank, Michael, Langleben, David, Snijder, Repke J., Escribano Subias, Pilar, Mielniczuk, Lisa M., Lange, Tobias J., Vachiéry, Jean-Luc, Wirtz, Hubert, Helmersen, Douglas S., Tsangaris, Iraklis, Barberá, Joan A., Pepke-Zaba, Joanna, Boonstra, Anco, Rosenkranz, Stephan, Ulrich, Silvia, Steringer-Mascherbauer, Regina, Delcroix, Marion, Jansa, Pavel, Šimková, Iveta, Giannakoulas, George, Klotsche, Jens, Williams, Evgenia, Meier, Christian, and Hoeper, Marius M.

Published
2021
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18. Follicular dendritic cell differentiation is associated with distinct synovial pathotype signatures in rheumatoid arthritis

Author

Mohey Eldin M. El Shikh, Riham El Sayed, Nesreen Amer Ramadan Aly, Edoardo Prediletto, Rebecca Hands, Liliane Fossati-Jimack, Michele Bombardieri, Myles J. Lewis, and Costantino Pitzalis

Subjects
rheumatoid arthritis, synovial pathotypes, follicular dendritic cells (FDCs), platelet-derived growth factor (PDGF), tumor necrosis factor-α (TNF-α), ectopic lymphoid-like structures (ELSs), Medicine (General), R5-920
Abstract

Follicular dendritic cells (FDCs) fundamentally contribute to the formation of synovial ectopic lymphoid-like structures in rheumatoid arthritis (RA) which is associated with poor clinical prognosis. Despite this critical role, regulation of FDC development in the RA synovium and its correlation with synovial pathotype differentiation remained largely unknown. Here, we demonstrate that CNA.42+ FDCs distinctively express the pericyte/fibroblast-associated markers PDGFR-β, NG2, and Thy-1 in the synovial perivascular space but not in established follicles. In addition, synovial RNA-Seq analysis revealed that expression of the perivascular FDC markers was strongly correlated with PDGF-BB and fibroid synovitis, whereas TNF-α/LT-β was significantly associated with lymphoid synovitis and expression of CR1, CR2, and FcγRIIB characteristic of mature FDCs in lymphoid follicles. Moreover, PDGF-BB induced CNA.42+ FDC differentiation and CXCL13 secretion from NG2+ synovial pericytes, and together with TNF-α/LT-β conversely regulated early and late FDC differentiation genes in unsorted RA synovial fibroblasts (RASF) and this was confirmed in flow sorted stromal cell subsets. Furthermore, RASF TNF-αR expression was upregulated by TNF-α/LT-β and PDGF-BB; and TNF-α/LT-β-activated RASF retained ICs and induced B cell activation in in vitro germinal center reactions typical of FDCs. Additionally, FDCs trapped peptidyl citrulline, and strongly correlated with IL-6 expression, and plasma cell, B cell, and T cell infiltration of the RA synovium. Moreover, synovial FDCs were significantly associated with RA disease activity and radiographic features of tissue damage. To the best of our knowledge, this is the first report describing the reciprocal interaction between PDGF-BB and TNF-α/LT-β in synovial FDC development and evolution of RA histological pathotypes. Selective targeting of this interplay could inhibit FDC differentiation and potentially ameliorate RA in clinically severe and drug-resistant patients.

Published
2022
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19. Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

Author

Caneva, Jorge, Tuhay, Graciela, Diez, Mirta, Talavera, Maria Lujan, Acosta, Adriana, Vulcano, Norberto, Bosio, Martin, Maldonado, Lorena, Deleo, Sabino, Melatini, Luciano, Keogh, Anne, Kotlyar, Eugene, Feenstra, John, Dwyer, Nathan, Adams, Heath, Stevens, Wendy, Steele, Peter, Proudman, Susanna, Minson, Robert, Reeves, Glenn, Lavender, Melanie, Ng, Benjamin, Mackenzie, Michele, Barry, Lisa, Gruenberger, Margarethe, Huber, Charlotte, Lang, Irene, Tilea, Ioana, Sadushi-Kolici, Roela, Löffler-Ragg, Judith, Feistmantl, Lisa-Theresa, Evrard, Patrick, Guiot, Julien, Naldi, Marco, De Pauw, Michel, Louis, Renaud, Mehta, Sanjay, Camacho, Rafael Conde, Tovar, Patricia Parada, Londoño, Alejandro, Campo, Felipe, Garcia, Paula, Lema, Camila, Orozco-Levi, Mauricio, Martinez, William, Gomez, Juan Esteban, Nielsen-Kudsk, Jens Erik, Mellemkjaer, Soren, Anton, Ly, Altraja, Alan, Vihinen, Tapani, Vasankari, Tuija, Sitbon, Olivier, Cottin, Vincent, Têtu, Laurent, Noël-Savina, Elise, Shearman, Nicole, Tayler, Susanne, Olzik, Ilona, Kulka, Christine, Grimminger, Jan, Simon, Marcel, Nolde, Anna, Oqueka, Tim, Harbaum, Lars, Egenlauf, Benjamin, Ewert, Ralf, Schulz, Christian, Regotta, Sabine, Kramer, Tilmann, Knoop-Busch, Susanne, Gerhardt, Felix, Konstantinides, Stavros, Pitsiou, Georgia, Stanopoulos, Ioannis, Sourla, Evdokia, Mouratoglou, Sofia, Karvounis, Haralambos, Pappas, Athanasios, Mitrouska, Ioanna, Georgopoulos, Dimitrios, Fanaridis, Michail, Michalis, Lampros, Pappas, Konstantinos, Kotsia, Anna, Gaine, Sean, Vizza, Carmine Dario, Manzi, Giovanna, Poscia, Roberto, Badagliacca, Roberto, Agostoni, Piergiuseppe, Bruno, Noemi, Farina, Stefania, D'Alto, Michele, Argiento, Paola, Correra, Anna, Di Marco, Giovanni Maria, Cresci, Chiara, Vannucchi, Vieri, Torricelli, Elena, Garcea, Alessio, Pesci, Alberto, Sardella, Luca, Paciocco, Giuseppe, Pane, Federico, D'Armini, Andrea Maria, Pin, Maurizio, Grazioli, Valentina, Massola, Giulia, Sciortino, Antonio, Prediletto, Renato, Bauleo, Carolina, Airò, Edoardo, Ndreu, Rudina, Pavlickova, Ivana, Lunardi, Claudio, Farruggio, Silvia, Costa, Serena, Mulè, Massimiliano, Galgano, Giuseppe, Petruzzi, Mario, De Luca, Anna, Lombardi, Francesco, Roncon, Loris, Conte, Luca, Picariello, Claudio, Wirtz, Gil, Alexandre, Myriam, Vonk-Noordegraaf, A., Boogaard, H., Mager, J., Reesink, H., van den Toorn, Leon M., Boomars, Karin, Andreassen, Arne K., Castro, Graça, Tania, Gonçalves, Baptista, Rui, Marinho, António, Shiang, Teresa, Oliveira, Ana, Coutinho, Daniel, Sousa, Joana, Loureiro, Maria José, Repolho, Débora, Martins Jesus, Susana Maria, Capinha, Marta, Agostinho, João, Cardoso, Tania, Rocha, Andreia, Espinha, Mafalda, Ivanov, Kyundyul Ivanovich, Alexeeva, Dalyana Eduardovna, Batalina, Marina Vadimovna, Hegya, Daria Viktorovna, Zvereva, Tatyana Nikolaevna, Avdeev, Sergey Nikolaevich, Tsareva, Natalia Anatolievna, Galyavich, Albert Sarvatovich, Nikolaevich, Bykov Aleksander, Filippov, Evgeny Vladimirovich, Yakovleva, Olga Eduardovna, Pavlova, Olga Borisovna, Skripkina, Elena Sergeevna, Martynyuk, Tamila Vitalievna, Bukatova, Irina Fedorovna, Tregubova, Anna Viktorovna, Platonov, Dmitry Yurievich, Kolomeytseva, Tatyana Mikhaylovna, Al Dalaan, Abdullah, Abdelsayed, Abeer Abeer, Weheba, Ihab, Saleemi, Sarferaz, Sakkijha, Hussam, Bohacekova, Marcela, Valkovicova, Tatiana, Farkasova, Iveta, Quezada, Carlos Andres, Piccari, Lucilla, Blanco, Isabel, Sebastian, Laura, Roman, Antonio, Lopez, Manuel, Otero, Remedios, Elias, Teresa, Jara, Luis, Asencio, Isabel, Arjona, Josefa Jiménez, Almagro, Raúl Menor, Cárdenas, Salvador López, García, Salvador Alcaraz, Rodríguez, Patricia Villanueva, Lopez, Raquel, Garcia, Alberto, Avilés, Francisco Fernandez, De La Pava, Sebastian, Yotti, Raquel, Peñate, Gregorio Pérez, Marrero, Fernando León, Cifrián Martínez, José Manuel, Martinez-Meñaca, Amaya, Alonso, Lecue Pilar, Rozas, Sonia Fernandez, Fernandez, David Iturbe, Cuesta, Victor Mora, Söderberg, Stefan, Bartfay, Sven-Erik, Rundqvist, Bengt, Alfetlawi, Monthir, Wodlin, Peter, Schwarz, Esther Irene, Speich, Rudolf, Lador, Frédéric, Rochat, Thierry, Gasche-Soccal, Paola, Hsu, Chih-Hsin, Lin, Tsung-Hsien, Su, Ho-Ming, Lai, Wen-Ter, Chu, Chun Yuan, Hsu, Po-Chao, Voon, Wen-Chol, Yen, Hsueh-Wei, Yih-Jer Wu, Jacob, Wu, Shu-Hao, Huang, Wen-Pin, Fong, Man-Cai, Huang, Chien-Lung, Kuo, Ping-Hung, Lin, Yen-Hung, Lin, Jiunn-Lee, Hung, Chi-Sheng, Wu, Cho-Kai, Sung, Shih-Hsien, Huang, Wei-Chun, Cheng, Chin-Chang, Kuo, Shu-Hung, Wang, Wen-Hwa, Ho, Wan-Jing, Hsu, Tsu-Shiu, Mutlu, Bülent, Atas, Halil, Ongen, Gul, Un, Zeynep, Okumus, Gulfer, Hanta, Ismail, Corris, Paul, Peacock, Andrew, Church, Colin, Toshner, Mark, Newnham, Michael, Hoeper, Marius M., Gomez Sanchez, Miguel-Angel, Humbert, Marc, Pittrow, David, Simonneau, Gérald, Gall, Henning, Grünig, Ekkehard, Klose, Hans, Halank, Michael, Langleben, David, Snijder, Repke J., Escribano Subias, Pilar, Mielniczuk, Lisa M., Lange, Tobias J., Vachiéry, Jean-Luc, Wirtz, Hubert, Helmersen, Douglas S., Tsangaris, Iraklis, Barberà, Joan A., Pepke-Zaba, Joanna, Boonstra, Anco, Rosenkranz, Stephan, Ulrich, Silvia, Steringer-Mascherbauer, Regina, Delcroix, Marion, Jansa, Pavel, Šimková, Iveta, Giannakoulas, George, Klotsche, Jens, Williams, Evgenia, Meier, Christian, and Ghofrani, Hossein-Ardeschir

Published
2021
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20. Hemodynamics and risk assessment 2 years after the initiation of upfront ambrisentan‒tadalafil in pulmonary arterial hypertension

Author

D'Alto, Michele, Badagliacca, Roberto, Lo Giudice, Francesco, Argiento, Paola, Casu, Gavino, Corda, Marco, Correale, Michele, Ghio, Stefano, Greco, Alessandra, Lattanzio, Mariangela, Mercurio, Valentina, Paciocco, Giuseppe, Papa, Silvia, Prediletto, Renato, Romeo, Emanuele, Russo, Maria Giovanna, Tayar, Alessandro, Vitulo, Patrizio, Vizza, Carmine Dario, Golino, Paolo, and Naeije, Robert

Published
2020
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21. Musculoskeletal syndrome treated with global postural re-education in double-redo lung transplantation: a case report with an 8-month follow-up

Author

M. Polastri, G.M. Paganelli, G. Dolci, E. Di Ciaccio, and I. Prediletto

Subjects
Dyspnea, exercise, global postural re-education, physiotherapy, lung transplantation., Medicine, Internal medicine, RC31-1245
Abstract

Postoperative pain and persisting fatigue represent critical concerns for patients receiving lung transplantation. The purpose of this study was to illustrate the trajectory of symptoms in a patient who presented with a posttransplant musculoskeletal syndrome after double redo-lung transplantation and attended therapeutic sessions of global postural re-education during the symptomatic phase. A 32-year-old woman with interstitial lung disease underwent double lung transplantation. At 23 months, functional parameters deteriorated, and the patient was placed on the active list for a second double-lung transplantation. Twenty months after re-transplantation, the patient reported continuous thoracic-lumbar musculoskeletal pain exacerbated by moving or performing the standard motor activities. Lower body flexibility improved during the observation period changed from -10 cm to 0 cm at the Chair Sitand- Reach Test. Leg strength improved as well, and the patient was able to perform more repetitions at the Squat Test, improving from 14 to 39. Pain intensity changed from 7 to 4 on a numerical rating scale. We observed that outcomes strictly related to treatment, with lower body flexibility, pain intensity, and physical function improving over time. As a result global postural re-education proved to be effective in this patient.

Published
2022
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23. Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study

Author

Lara Pisani, Sara Betti, Carlotta Biglia, Luca Fasano, Vito Catalanotti, Irene Prediletto, Vittoria Comellini, Letizia Bacchi-Reggiani, and Stefano Nava FERS

Subjects
Chronic obstructive pulmonary disease, High flow nasal cannula, Persistent hypercapnia, Long term non invasive ventilation, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Persistent hypercapnia after COPD exacerbation is associated with excess mortality and early rehospitalization. High Flow Nasal cannula (HFNC), may be theoretically an alternative to long-term noninvasive ventilation (NIV), since physiological studies have shown a reduction in PaCO2 level after few hours of treatment. In this clinical study we assessed the acceptability of HFNC and its effectiveness in reducing the level of PaCO2 in patients recovering from an Acute Hypercapnic Respiratory Failure (AHRF) episode. We also hypothesized that the response in CO2 clearance is dependent on baseline level of hypercapnia. Methods Fifty COPD patients recovering from an acute exacerbation and with persistent hypercapnia, despite having attained a stable pH (i.e. pH > 7,35 and PaCO2 > 45 mmHg on 3 consecutive measurements), were enrolled and treated with HFNC for at least 8 h/day and during the nighttime Results HFNC was well tolerated with a global tolerance score of 4.0 ± 0.9. When patients were separated into groups with or without COPD/OSA overlap syndrome, the “pure” COPD patients showed a statistically significant response in terms of PaCO2 decrease (p = 0.044). In addition, the subset of patients with a lower pH at enrolment were those who responded best in terms of CO2 clearance (score test for trend of odds, p = 0.0038). Conclusions HFNC is able to significantly decrease the level of PaCO2 after 72 h only in “pure” COPD patients, recovering from AHRF. No effects in terms of CO2 reduction were found in those with overlap syndrome. The present findings will help guide selection of the best target population and allow a sample size calculation for future long-term randomized control trials of HFNC vs NIV. Trial registration This study is registered with www. clinicaltrials.gov with identifier number NCT03759457.

Published
2020
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25. Operative Use of Thoracic Ultrasound in Respiratory Medicine: A Clinical Study

Author

Gino Soldati, Renato Prediletto, Marcello Demi, Stefano Salvadori, and Massimo Pistolesi

Subjects
diagnosis, lung, respiratory medicine, sonography, ultrasound, Medicine (General), R5-920
Abstract

For over 15 years, thoracic ultrasound has been applied in the evaluation of numerous lung diseases, demonstrating a variable diagnostic predictive power compared to traditional imaging techniques such as chest radiography and CT. However, in unselected pulmonary patients, there are no rigorous scientific demonstrations of the complementarity of thoracic ultrasound with traditional and standardized imaging techniques that use radiation. In this study 101 unselected pulmonary patients were evaluated blindly with ultrasound chest examinations during their hospital stay. Other instrumental examinations, carried out during hospitalization, were standard chest radiography, computed tomography (CT), and, when needed, radioisotopic investigation and cardiac catheterization. The operator who performed the ultrasound examinations was unaware of the anamnestic and clinical data of the patients. Diffuse fibrosing disease was detected with a sensitivity, specificity and diagnostic accuracy of 100%, 95% and 97%, respectively. In pleural effusions, ultrasound showed a sensitivity, specificity and diagnostic accuracy of 100%. In consolidations, the sensitivity, specificity and diagnostic accuracy were 83%, 98% and 93%, respectively. Low values of sensitivity were recorded for surface nodulations of less than one centimeter. Isolated subpleural ground glass densities were identified as White Lung with a sensitivity of 72% and a specificity of 86%. Only the associations Diffuse ultrasound findings/Definitive fibrosing disease, Ultrasound Consolidation/Definitive consolidation and non-diffuse ultrasound artefactual features/Definitive vascular pathology (pulmonary hypertension, embolism) were statistically significant with adjusted residuals of 7.9, 7 and 4.1, respectively. The obtained results show how chest ultrasound is an effective complementary diagnostic tool for the pulmonologist. When performed, as a complement to the patient’s physical examination, it can restrict the diagnostic hypothesis in the case of pleural effusion, consolidation and diffuse fibrosing disease of the lung.

Published
2022
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28. What Role Do Immunological and Inflammatory Biomarkers Play on Mortality and Exacerbations in COPD Patients?

Author

Anna Maria Romanelli, Mauro Raciti, Angela Papa, and Renato Prediletto

Subjects
Ocean Engineering
Abstract

Background: COPD phenotypes have been identified according to patient clinical characteristics and, more recently, to their immunological markers. However, the role of these biomarkers in relation to exacerbations in different COPD phenotypes is not yet clear. Thus it is important to continue investigating this topic to plan the most appropriate treatment, to contrast the decline of respiratory function and to reduce subsequent exacerbations in COPD patients. Therefore the aim of this study was to assess whether biomarkers are only predictors of exacerbations and mortality in COPD patients or instead play a causal role in these adverse COPD developments. Methods: COPD phenotypes were identified according to patient clinical characteristics or immunological markers. Immunological and inflammatory biomarkers were identified as predictors of mortality and exacerbations. COPD patients were identified from the hospital discharge register of Pisa (Italy) in 2000-2006, on the basis of diagnoses and a FEV1/FVC < 0.70, and enrolled in 2003-2006 according to a longitudinal approach. They were characterized at enrollment by age, sex, comorbidities, immunological and inflammatory biomarkers. The phenotype was assigned at enrollment as eosinophilic (eosinophils>2%) or neutrophilic (leukocytes>11.0x109/L and/or neutrophils>65%). Mortality and exacerbations registered in the period 2003-2012 were assessed by phenotype and other possible predictors in regression models. Results: Mortality rates reached 43.3% in COPD patients: 69.1% and 36.5% in neutrophilic and eosinophilic, respectively. The exacerbation rate was higher in neutrophilic (54.4%) than in eosinophilic patients (48.4%). Uni-variable regression confirmed that mortality was related to age, Congestive Heart Failure (CHF), Ischemic Heart Disease (IHD), elevated neutrophil count and Neutrophil to Lymphocyte Ratio (NLR). At multivariable analysis only age was associated with mortality, whereas inflammatory biomarkers induced exacerbations. Conclusion: Mortality was influenced by phenotype and age, exacerbations by COPD severity and NLR to suggest that an appropriate treatment and the biomarker’s monitoring might help prevent exacerbations.

Published
2022
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29. Spontaneous Evolution of COVID-19 Lung Sequelae: Results from a Double-Step Follow-Up

Author

Martina Ferioli, Irene Prediletto, Serena Bensai, Sara Betti, Federico Daniele, Valerio Di Scioscio, Cecilia Modolon, Maria Rita Rimondi, Chiara De Molo, Carla Serra, Stefano Nava, Luca Fasano, Ferioli, Martina, Prediletto, Irene, Bensai, Serena, Betti, Sara, Daniele, Federico, Di Scioscio, Valerio, Modolon, Cecilia, Rimondi, Maria Rita, De Molo, Chiara, Serra, Carla, Nava, Stefano, and Fasano, Luca

Subjects
Pulmonary and Respiratory Medicine, SARS-CoV-2, Respiratory infection, Follow-up, Clinical Investigations, Sequelae, COVID-19, Humans, Pneumonia, respiratory system, Lung, Follow-Up Studies
Abstract

Background: Few studies have reported a double-step follow-up of patients after hospitalization for COVID-19. Objectives: We designed an observational double-step follow-up study with a clinical, functional, and radiological evaluation at 2 and 6 months after COVID-19. The primary outcome was to describe symptoms, spirometry, and 6-minute walking test (6MWT) at 2 and 6 months. Secondary outcomes were to identify if the lowest PaO2/FiO2 during hospitalization is related with functional and radiological evolution and to assess the correlation between radiological and functional abnormalities at 6 months. Methods: Symptoms, spirometry, and 6MWT were assessed at 2 and 6 months; arterial blood gas, chest x-ray, and lung ultrasound were performed at 2 months; body plethysmography, diffusing capacity for carbon monoxide (DLCO), and CT scan were performed at 6 months. Results: Sixty-four per cent and 42% of patients reported at least one symptom at 2 and 6 months, respectively. The most common 6-month functional alteration was DLCO impairment (57% of patients). An improvement of FEV1, FVC, and 6MWT was observed between 2 and 6 months (p < 0.001). Patients with PaO2/FiO2 p < 0.05) and reported more extended radiological abnormalities at 6 months (p < 0.001) compared with patients with PaO2/FiO2>200. At 6 months, more extended radiological abnormalities were related with worse 6MWT, DLCO, and total lung capacity (p < 0.05). Discussion: DLCO and 6MWT impairment seem to be the functional hallmark of COVID-19 and are related with the severity of acute pneumonia. At 6 months, radiological abnormalities were related to functional impairment.

Published
2022
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30. Effects of early rehabilitation on motor function, dyspnoea intensity, respiratory muscle performance and handgrip strength in patients with COVID-19: an observational study

Author

Massimiliano Polastri, Paolo Carbonara, Irene Prediletto, Aldo Gardini, Francesca Venturoli, Federico Tagariello, Lucia Neri, Marco Carpano, Angela Maria Grazia Pacilli, and Stefano Nava

Subjects
Rehabilitation, Physical Therapy, Sports Therapy and Rehabilitation
Abstract

Background/Aims Although an increasing volume of research is emerging, rehabilitative treatment of patients with COVID-19 still continues to be a matter of great importance that must be explored further. The purpose of the present study was to describe the effects of inpatient rehabilitation in acute patients treated in a sub-intensive hospital setting during the COVID-19 pandemic. Methods A retrospective analysis was conducted based on the prospectively collected data of 192 patients with COVID-19 undergoing a physiotherapeutic regimen during their hospitalisation. Patients were admitted because of COVID-19-related pneumonia from the periods of 25 March–12 June 2020 and 2 November 2020–9 June 2021. This study investigated dyspnoea intensity using the modified Borg scale, motor function through the 1-minute sit-to-stand test, and daily walked distance. In a subset of 57 patients, handgrip strength and respiratory muscle function was also evaluated. Measurements were taken at baseline and discharge. Results Patients were classified according to the severity of their ratio of arterial oxygen partial pressure to fractional inspired oxygen (mean 225 ± 82 mmHg). At discharge to home or to another hospital facility, patients performed a mean of 12 repetitions (1-minute sit-to-stand test); dyspnoea intensity was 1.4 (modified Borg scale), and they were able to walk a mean distance of 266.7 metres. The mean handgrip strength of the dominant hand was 29.3 kg, the maximal inspiratory pressure was 43.5 cmH2O, and the maximal expiratory pressure was 59.1 cmH2O. Overall, significant differences before and after treatment were detected for all clinical variables. Dyspnoea improved by 0.7 points; walked distance by 200 metres; the number of repetitions at the 1-minute sit-to-stand test by 5.6; the handgrip strength by 1.2 kg (right hand) and 1.7 kg (left hand); maximal inspiratory pressure by 7.7 cmH2O; and maximal expiratory pressure by 9.5 cmH2O. Conclusions Patients obtained significant improvements in functional capacity, dyspnoea perception, handgrip strength and respiratory muscle function. In addition, the treatment was feasible and well tolerated by patients, and no adverse related events were observed in a sub-intensive care setting.

Published
2022
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36. Idiopathic pulmonary fibrosis management: caring is sparing

Author

Stefano Nava, Irene Prediletto, Nava S., and Prediletto I.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, MEDLINE, medicine.disease, humanities, Idiopathic pulmonary fibrosis, Editorial, Text mining, medicine, IPF- lung function - quality of life, Original Article, Intensive care medicine, business
Abstract

BACKGROUND: Canadian and international guidelines recommend specialized, multidisciplinary teams for the treatment of patients with idiopathic pulmonary fibrosis (IPF). The objective of this cross-sectional clinical study was to investigate the effect of a care coordinator on IPF patient satisfaction and quality of life. METHODS: Forty IPF patients were enrolled from the practices of two physicians (n=20/physician), with either low (LCU) or high-coordinator use (HCU). Patient satisfaction was measured with modified FAMCARE and IPF Care UK Patient Support Program (UK-CARE) surveys. Health related quality of life (HRQoL) was assessed with the living with IPF impacts (L-IPFi) survey. An economic model assessed the impact of the coordinator; staff surveys informed patient management requirements, and costs were derived from published literature. RESULTS: Patient satisfaction was similar between the clinics; a trend (P=0.1) towards increased satisfaction among HCU patients was observed. Patients in the HCU clinic reported increased satisfaction (P

Published
2020
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38. Early awake proning in critical and severe COVID-19 patients undergoing noninvasive respiratory support: A retrospective multicenter cohort study

Author

Luca Tabbì, Giulia Bruzzi, Enrico Clini, Linda Manicardi, Stefano Nava, Stefano Busani, Gabriele Corsi, Cristina Mussini, Irene Prediletto, Vittoria Comellini, Roberto D'Amico, Ilaria Bassi, Riccardo Fantini, Ivana Castaniere, Federico Tagariello, Massimo Girardis, Filippo Gozzi, Marco Carpano, Lara Pisani, Alessandro Marchioni, Roberto Tonelli, Dario Andrisani, Tonelli R., Pisani L., Tabbi L., Comellini V., Prediletto I., Fantini R., Marchioni A., Andrisani D., Gozzi F., Bruzzi G., Manicardi L., Busani S., Mussini C., Castaniere I., Bassi I., Carpano M., Tagariello F., Corsi G., d'Amico R., Girardis M., Nava S., and Clini E.

Subjects
Pulmonary and Respiratory Medicine, Coronavirus disease 2019 (COVID-19), ARF, acute respiratory failure, Vt, tidal volume, medicine.medical_treatment, RR, respiratory rate, Acute respiratory failure, NRS, non-invasive respiratory support, law.invention, Cohort Studies, 03 medical and health sciences, Prone position, 0302 clinical medicine, Randomized controlled trial, law, ICU, Intensive Care Unit, medicine, Humans, Intubation, 030212 general & internal medicine, Wakefulness, APACHE II, acute physiology and chronic health evaluation II score, HFNC, High Flow Nasal Cannulae, Retrospective Studies, COVID-19, Acute respiratory failure, Non-invasive mechanical ventilation, Prone position, NIV, non-invasive mechanical ventilation, business.industry, ETI, endotracheal intubation, CPAP, continuous positive airways pressure, Confounding, COVID-19, MV, mechanical ventilation, Retrospective cohort study, SAPS II, simplified acute physiology score, PSV, pressure support ventilation, HR, hazard ratio, SOFA, subsequent organ failure assessment, OR, odds ratio, 030228 respiratory system, PEEP, positive end expiratory pressure, Anesthesia, Breathing, Original Article, Non-invasive mechanical ventilation, Respiratory Insufficiency, business, Cohort study
Abstract

BACKGROUND/MATERIALS AND METHODS: This retrospective cohort study was conducted in two teaching hospitals over a 3-month period (March 2010-June 2020) comparing severe and critical COVID-19 patients admitted to Respiratory Intensive Care Unit for non-invasive respiratory support (NRS) and subjected to awake prone position (PP) with those receiving standard care (SC). Primary outcome was endotracheal intubation (ETI) rate. In-hospital mortality, time to ETI, tracheostomy, length of RICU and hospital stay served as secondary outcomes. Risk factors associated to ETI among PP patients were also investigated. RESULTS: A total of 114 patients were included, 76 in the SC and 38 in the PP group. Unadjusted Kaplan-Meier estimates showed greater effect of PP compared to SC on ETI rate (HR = 0.45 95% CI [0.2-0.9], p = 0.02) even after adjustment for baseline confounders (HR = 0.59 95% CI [0.3-0.94], p = 0.03). After stratification according to non-invasive respiratory support, PP showed greater significant benefit for those on High Flow Nasal Cannulae (HR = 0.34 95% CI [0.12-0.84], p = 0.04). Compared to SC, PP patients also showed a favorable difference in terms of days free from respiratory support, length of RICU and hospital stay while mortality and tracheostomy rate were not significantly different. CONCLUSIONS: Prone positioning in awake and spontaneously breathing Covid-19 patients is feasible and associated with a reduction of intubation rate, especially in those patients undergoing HFNC. Although our results are intriguing, further randomized controlled trials are needed to answer all the open questions remaining pending about the real efficacy of PP in this setting.

Published
2022

45. A novel echocardiographic method for estimation of pulmonary artery wedge pressure and pulmonary vascular resistance

Author

M. Ciardetti, Vladislav Chubuchny, Christina Petersen, Michele Coceani, Carolina Bauleo, Alberto Giannoni, Valentina Spini, Andrea Barison, Claudia Taddei, Edoardo Airò, Carlo Lombardi, Emilio Pasanisi, Luigi Emilio Pastormerlo, Michele Emdin, Nicola Riccardo Pugliese, Bruno Formichi, Elisa Poggianti, and R. Prediletto

Subjects
Male, lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Echocardiography, Pulmonary artery wedge pressure, Pulmonary hypertension, Pulmonary vascular resistance, Right heart catheterization, 030204 cardiovascular system & hematology, Inferior vena cava, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, Original Research Articles, Internal medicine, Humans, Medicine, Original Research Article, Pulmonary Wedge Pressure, 030212 general & internal medicine, Pulmonary wedge pressure, Aged, Aged, 80 and over, Ejection fraction, Receiver operating characteristic, business.industry, Stroke Volume, Middle Aged, medicine.disease, Confidence interval, medicine.anatomical_structure, medicine.vein, lcsh:RC666-701, Heart failure, Cardiology, Vascular resistance, Vascular Resistance, Cardiology and Cardiovascular Medicine, business
Abstract

Aims This study aimed to evaluate a novel echocardiographic algorithm for quantitative estimation of pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR) in patients with heart failure and pulmonary hypertension (PH) scheduled to right heart catheterization (RHC). Methods and results In this monocentric study, 795 consecutive patients (427 men; age 68.4 ± 12.1 years) undergoing echocardiography and RHC were evaluated. Multiple regression analysis was performed to identify echocardiographic predictors of PAWP and PVR measured by RHC in the derivation group (the first 200 patients). The diagnostic accuracy of the model was then tested in the validation group (the remaining 595 patients). PH was confirmed by RHC in 507 (63.8%) patients, with 192 (24.2%) cases of precapillary PH, 248 (31.2%) of postcapillary PH, and 67 (8.4%) of combined PH. At regression analysis, tricuspid regurgitation maximal velocity, mitral E/e′ ratio, left ventricular ejection fraction, right ventricular fractional area change, inferior vena cava diameter, and left atrial volume index were included in the model (R = 0.8, P

Published
2021
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46. Epidemiology of systemic sclerosis: a multi-database population-based study in Tuscany (Italy)

Author

Alessio Coi, Simone Barsotti, Michele Santoro, Fabio Almerigogna, Elena Bargagli, Marzia Caproni, Giacomo Emmi, Bruno Frediani, Serena Guiducci, Marco Matucci Cerinic, Marta Mosca, Paola Parronchi, Renato Prediletto, Enrico Selvi, Gabriele Simonini, Antonio Gaetano Tavoni, the Rare Diseases Working Group, Fabrizio Bianchi, and Anna Pierini

Subjects
Male, medicine.medical_specialty, Survival, Population, lcsh:Medicine, Comorbidity, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Disease registry, Neoplasms, Epidemiology, Prevalence, medicine, Humans, Mortality risk, Pharmacoepidemiology, Rare disease, Systemic sclerosis, Pharmacology (medical), 030212 general & internal medicine, education, Genetics (clinical), Systemic sclerosis, Survival, Mortality risk, Comorbidity, Disease registry, Rare disease, Pharmacoepidemiology, 030203 arthritis & rheumatology, education.field_of_study, Scleroderma, Systemic, Database, business.industry, Research, Incidence, Incidence (epidemiology), lcsh:R, General Medicine, medicine.disease, Italy, Cohort, Female, business, computer
Abstract

Background Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions. Results The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6–37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17–2.35), congestive heart failure (HR = 2.76, CI 95% 1.80–4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21–4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06–2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008–2017 period. Conclusions The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.

Published
2021

47. Effects of asymmetric nasal high-flow cannula on carbon dioxide in hypercapnic patients: A randomised crossover physiological pilot study

Author

Lara Pisani, Maria Laura Vega, Elisa Ageno, Irene Prediletto, Roberto Dongilli, Vito Catalanotti, Gilda Giancotti, and Stefano Nava

Subjects
asymmetric cannula, carbon dioxide, copd, nasal high flow, hypercapnic respiratory failure, Diseases of the respiratory system, RC705-779
Abstract

Nasal high flow (NHF) therapy is an established form of non invasive respiratory support used in acute and chronic care. Recently, a new high flow nasal cannula with asymmetric prongs was approved for clinical use. The clinical benefits of the new cannula have not yet been defined and no evidence are available on the use of asymmetric NHF support in patient with Chronic Obstructive Pulmonary Disease (COPD). We conducted a single-centre, prospective, physiologic, crossover, randomised study to investigate the effects on partial pressure of carbon dioxide (PaCO2) levels of two different nasal cannula (“asymmetric” vs “standard” nasal interface) in 20 COPD hypercapnic patients. All patients were recovering from an acute exacerbation that required hospitalisation and had persistent hypercapnia, despite having attained a stable pH. After enrolment, two 90-min trials with the asymmetric nasal high flow interface (Optiflow + Duet, Fisher & Paykel Healthcare Ltd., New Zealand) or the standard interface (Optiflow, Fisher & Paykel Healthcare Ltd., New Zealand) were randomly applied and a washout period of 60 min between the two treatments was performed for minimising the carryover effect. Study results suggested that the asymmetrical cannula did not significantly decrease PaCO2 compared with the standard cannula. Similar performances were also observed in terms of diaphragm activity, dyspnoea and patient’s comfort. Interestingly, asymmetric NHF cannula performed significantly better in reducing the dead space ventilation and increasing the ventilatory efficiency in more advanced COPD patients with more severe hypercapnia higher baseline PaCO2 values (PaCO2 ≥ 65 mmHg at baseline).

Published
2025
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48. Effects of early rehabilitation on motor function, dyspnoea intensity, respiratory muscle performance and handgrip strength in patients with COVID-19: an observational study

Author

Polastri, Massimiliano, primary, Carbonara, Paolo, additional, Prediletto, Irene, additional, Gardini, Aldo, additional, Venturoli, Francesca, additional, Tagariello, Federico, additional, Neri, Lucia, additional, Carpano, Marco, additional, Pacilli, Angela Maria Grazia, additional, and Nava, Stefano, additional

Published
2022
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