Liposomes loaded with everolimus and coated with hyaluronic acid: A promising approach for lung fibrosis

Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells

Respiratory failure due to concomitant interstitial lung disease and diaphragmatic involvement in a patient with anti-MDA5 dermatomyositis: a case report

Diaphragm myositis is a rare manifestation of idiopathic inflammatory myopathies, barely portrayed in literature despite its potential severity. We describe a 57-year-old Caucasian male with anti-MDA5 positive dermatomyositis, that had a 4-month history of progressive dyspnoea requiring oxygen-therapy, scarcely responsive to prednisolone. Chest high resolution computed tomography (HRCT) showed mild interstitial lung disease (ILD), whereas pulmonary function tests evidenced severe restrictive syndrome with high lung ultrasound score. Diaphragm ultrasound revealed a marked diaphragm dysmotility, confirmed by electromyography (EMG). The patient was treated with intravenous immunoglobulins and mofetil mycophenolate with progressive improvement of dyspnoea, lung volumes and ILD at CT scan. Ultrasound examination also revealed marked improvement of the diaphragmatic disfunction and a reduction of lung ultrasound score. The use of ultrasound may provide a valuable tool in the diagnosis of diaphragm myositis, which may play a major role in the respiratory impairment of these patients. A combined lung and diaphragm examination allowed bedside monitoring of the improvements in both lung aeration and diaphragm contractility

A Proof-of-Concept Analysis of Plasma-Derived Exosomal microRNAs in Interstitial Pulmonary Fibrosis Secondary to Antisynthetase Syndrome

Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the positivity of autoantibodies against different aminoacyl transfer RNA (tRNA) synthetases. Morbidity and mortality of this disease are highly affected by interstitial lung disease (ILD) which is present in about 80% of patients. In this study, we investigated possible differences in 84 immune-related circulating miRNAs between ASSD patients with and without ILD; we enrolled 15 ASSD patients, 11 with ILD (ILD+) and 4 without ILD (ILD-), and 5 patients with idiopathic pulmonary fibrosis (IPF) as an additional control group. All patients were at disease onset and not on therapy at the time of inclusion. Differentially expressed miRNAs were identified in plasma-derived exosomes, using an miRNA PCR array (MIHS-111ZG, Qiagen, Hilden, Germany); miR-30a-5p and miR-29c-3p were upregulated in ASSD-ILD patients compared to patients without lung involvement (adjusted p-value < 0.05). IPF patients showed higher miR-29c-3p expression levels with respect to both ASSD and ASSD-ILD (p = 0.0005), whereas levels of miR-30a-5p were not different. miR-29c-3p and miR-30a-5p are overexpressed in ASSD-ILD+ patients compared with ILD−. These miRNAs are involved in the regulation of inflammation and fibrosis through their action on NF-κB and TGF-β1. Although the mechanistic role of these miRNAs in ASSD-ILD development has to be elucidated, we suggest that their exosome levels could be useful in identifying patients at risk of ILD

Correction to: Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy (Internal and Emergency Medicine, (2021), 16, 5, (1141-1152), 10.1007/s11739-020-02550-6)

none238noIn the original publication of the article, the names of the COVID-19 Task Force were not listed as contributors.noneMelazzini F.; Colaneri M.; Fumoso F.; Freddi G.; Lenti M.V.; Pieri T.C.; Piloni D.; Noris P.; Pieresca C.; Preti P.S.; Russo M.; Corsico A.; Tavazzi G.; Baldanti F.; Triarico A.; Mojoli F.; Bruno R.; Di Sabatino A.; Aronico N.; Bergamaschi G.; Bertolino G.; Codega S.; Costanzo F.; Cresci R.; Delliponti A.; Derosa G.; Di Stefano M.; Falaschi F.; Iadarola C.; Lovati E.; Lucotti P.C.; Martignoni A.; Mengoli C.; Miceli E.; Mugellini A.; Muggia C.; Pagani E.; Palumbo I.; Pecci A.; Perrone T.; Sgarlata C.; Siciliani L.; Staniscia A.; Vjera F.T.; Achilli G.; Agostinelli A.; Antoci V.; Ballesio A.; Banfi F.; Barteselli C.; Benedetti I.; Borrelli de Andreis F.; Brattoli M.; Calabretta F.; Cambie G.; Canta R.; Conca F.; Coppola L.; Cremonte E.M.; Croce G.; Del Rio V.; Di Terlizzi F.; Ferrari M.G.; Ferrari S.; Fiengo A.; Forni T.; Frigerio C.; Fusco A.; Gabba M.; Garolfi M.; Gentile A.; Gori G.; Grandi G.; Grimaldi P.; Lampugnani A.; Lapia F.; Lepore F.; Lettieri G.; Mambella J.; Mercanti C.; Merli S.; Morda F.; Nardone A.; Pace L.; Padovini L.; Parodi A.; Pellegrino I.; Pitotti L.; Reduzzi M.; Rigano G.; Romito G.; Rotola G.; Sabatini U.; Salvi L.; Santacroce G.; Savioli J.; Soriano S.; Spataro C.; Stefani D.; Aliberti A.R.; Amatu A.; Anfossi L.; Arisi E.; Baldi C.; Belliato M.; Bellini L.; Benzi A.; Bichisao G.; Bolongaro A.; Bottazzi A.; Broglia F.; Bruschi G.; Caneva L.; Capaccio E.; Carboni V.; Cavalloro F.; Ciceri M.; Civardi L.; Delmonte M.P.; Domenegati E.L.; Ferrari F.; Ferrari F.; Ferrari M.; Fuardo M.; Gerletti M.M.; Gualdana S.; Ilardi M.; Lo Coco C.; Maggio G.; Mascia M.B.; Mencherini S.; Merati P.M.; Mongodi S.; Mori A.M.; Morgante F.; Niebel T.L.; Noli S.; Orlando A.; Pagani M.; Passador D.; Pellicori S.; Perotti L.; Picchioni R.; Poma S.; Pozzi M.; Preti E.; Puce R.; Radolovich D.K.; Ragni G.; Repossi F.; Riccardi F.; Rizzardi R.; Rodi G.; Roldi E.; Romito G.; Rossi C.; Sala Gallini G.; Sciutti F.; Sportiello D.; Ticozzelli G.; Visconti F.; Zizzi S.; Bagliani A.; Belotti C.; Bossi C.; Colombo A.; Colombo C.N.J.; Cremascoli L.; Dammassa V.; Discepoli R.; Garlando M.A.; Grandini F.; Pellegrini A.; Quaranta C.; Stella A.; Torresani F.; Mondelli M.; Brunetti E.; Di Matteo A.; Seminari E.; Maiocchi L.; Zuccaro V.; Pagnucco L.; Mariani B.; Ludovisi S.; Lissandrin R.; Parisi A.; Sacchi P.; Patruno S.F.A.; Michelone G.; Gulminetti R.; Zanaboni D.; Novati S.; Maserati R.; Orsolini P.; Vecchia M.; Asperges E.; Di Filippo A.; Sambo M.; Biscarini S.; Lupi M.; Roda S.; Gallazzi I.; Sachs M.; Valsecchi P.; Ferrari A.; Mariani B.; Bosio M.; Cascina A.; Conio V.; Di Domenica R.; Donnetta A.; Fraolini E.; Gualtieri G.; Mangiarotti P.; Mariani F.; Meloni F.; Oggionni T.; Pasturenzi L.; Ronzoni V.; Saracino L.; Stella G.; Tomaselli S.; Abbate T.; Accordino G.; Bertuccio F.; Burattini C.; Cacciatore E.; Cattaneo E.; Chino V.; Coretti M.; Della Zoppa M.; Infusino C.; Lettieri S.; Maccabruni V.; Mancinelli S.; Tirelli C.; Vertui V.Melazzini, F.; Colaneri, M.; Fumoso, F.; Freddi, G.; Lenti, M. V.; Pieri, T. C.; Piloni, D.; Noris, P.; Pieresca, C.; Preti, P. S.; Russo, M.; Corsico, A.; Tavazzi, G.; Baldanti, F.; Triarico, A.; Mojoli, F.; Bruno, R.; Di Sabatino, A.; Aronico, N.; Bergamaschi, G.; Bertolino, G.; Codega, S.; Costanzo, F.; Cresci, R.; Delliponti, A.; Derosa, G.; Di Stefano, M.; Falaschi, F.; Iadarola, C.; Lovati, E.; Lucotti, P. C.; Martignoni, A.; Mengoli, C.; Miceli, E.; Mugellini, A.; Muggia, C.; Pagani, E.; Palumbo, I.; Pecci, A.; Perrone, T.; Sgarlata, C.; Siciliani, L.; Staniscia, A.; Vjera, F. T.; Achilli, G.; Agostinelli, A.; Antoci, V.; Ballesio, A.; Banfi, F.; Barteselli, C.; Benedetti, I.; Borrelli de Andreis, F.; Brattoli, M.; Calabretta, F.; Cambie, G.; Canta, R.; Conca, F.; Coppola, L.; Cremonte, E. M.; Croce, G.; Del Rio, V.; Di Terlizzi, F.; Ferrari, M. G.; Ferrari, S.; Fiengo, A.; Forni, T.; Frigerio, C.; Fusco, A.; Gabba, M.; Garolfi, M.; Gentile, A.; Gori, G.; Grandi, G.; Grimaldi, P.; Lampugnani, A.; Lapia, F.; Lepore, F.; Lettieri, G.; Mambella, J.; Mercanti, C.; Merli, S.; Morda, F.; Nardone, A.; Pace, L.; Padovini, L.; Parodi, A.; Pellegrino, I.; Pitotti, L.; Reduzzi, M.; Rigano, G.; Romito, G.; Rotola, G.; Sabatini, U.; Salvi, L.; Santacroce, G.; Savioli, J.; Soriano, S.; Spataro, C.; Stefani, D.; Aliberti, A. R.; Amatu, A.; Anfossi, L.; Arisi, E.; Baldi, C.; Belliato, M.; Bellini, L.; Benzi, A.; Bichisao, G.; Bolongaro, A.; Bottazzi, A.; Broglia, F.; Bruschi, G.; Caneva, L.; Capaccio, E.; Carboni, V.; Cavalloro, F.; Ciceri, M.; Civardi, L.; Delmonte, M. P.; Domenegati, E. L.; Ferrari, F.; Ferrari, F.; Ferrari, M.; Fuardo, M.; Gerletti, M. M.; Gualdana, S.; Ilardi, M.; Lo Coco, C.; Maggio, G.; Mascia, M. B.; Mencherini, S.; Merati, P. M.; Mongodi, S.; Mori, A. M.; Morgante, F.; Niebel, T. L.; Noli, S.; Orlando, A.; Pagani, M.; Passador, D.; Pellicori, S.; Perotti, L.; Picchioni, R.; Poma, S.; Pozzi, M.; Preti, E.; Puce, R.; Radolovich, D. K.; Ragni, G.; Repossi, F.; Riccardi, F.; Rizzardi, R.; Rodi, G.; Roldi, E.; Romito, G.; Rossi, C.; Sala Gallini, G.; Sciutti, F.; Sportiello, D.; Ticozzelli, G.; Visconti, F.; Zizzi, S.; Bagliani, A.; Belotti, C.; Bossi, C.; Colombo, A.; Colombo, C. N. J.; Cremascoli, L.; Dammassa, V.; Discepoli, R.; Garlando, M. A.; Grandini, F.; Pellegrini, A.; Quaranta, C.; Stella, A.; Torresani, F.; Mondelli, M.; Brunetti, E.; Di Matteo, A.; Seminari, E.; Maiocchi, L.; Zuccaro, V.; Pagnucco, L.; Mariani, B.; Ludovisi, S.; Lissandrin, R.; Parisi, A.; Sacchi, P.; Patruno, S. F. A.; Michelone, G.; Gulminetti, R.; Zanaboni, D.; Novati, S.; Maserati, R.; Orsolini, P.; Vecchia, M.; Asperges, E.; Di Filippo, A.; Sambo, M.; Biscarini, S.; Lupi, M.; Roda, S.; Gallazzi, I.; Sachs, M.; Valsecchi, P.; Ferrari, A.; Mariani, B.; Bosio, M.; Cascina, A.; Conio, V.; Di Domenica, R.; Donnetta, A.; Fraolini, E.; Gualtieri, G.; Mangiarotti, P.; Mariani, F.; Meloni, F.; Oggionni, T.; Pasturenzi, L.; Ronzoni, V.; Saracino, L.; Stella, G.; Tomaselli, S.; Abbate, T.; Accordino, G.; Bertuccio, F.; Burattini, C.; Cacciatore, E.; Cattaneo, E.; Chino, V.; Coretti, M.; Della Zoppa, M.; Infusino, C.; Lettieri, S.; Maccabruni, V.; Mancinelli, S.; Tirelli, C.; Vertui, V