Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age>65 years, antiviral treatment and for severe disease, lactate dehydrogenase >300 mg/dL

Computational techniques are valuable tools for the discovery of protein-protein interaction inhibitors: the 14-3-3s case

Targeting the binding site of 14-3-3 proteins lets the release of partner proteins involved in cell cycle progression, apoptosis, cytoskeletal rearrangement and transcriptional regulation and may therefore be regarded as an alternative strategy to integrate conventional therapeutic approaches against cancer. In the present work, we report the identification of two new small molecule inhibitors of 14-3-3σ/c-Abl protein-protein interaction (BV01 and BV101) discovered by means of computational methods. The most interesting compound (BV01) showed a lethal dose (LD 50) in the low micromolar range against Ba/F3 murine cell lines expressing the Imatinib (IM)-sensitive wild type Bcr-Abl construct and the IM-resistant Bcr-Abl mutation T315I. BV01 interaction with 14-3-3σ was demonstrated by NMR studies and elucidated by docking. It blocked the binding domain of 14-3-3σ, hence promoting the release of the partner protein c-Abl (the one not involved in Bcr rearrangement), and its translocation to both the nuclear compartment and mitochondrial membranes to induce a pro-apoptotic response. Our results advance BV01 as a confirmed hit compound capable of eliciting apoptotic death of Bcr-Abl-expressing cells by interfering with 14-3-3σ/c-Abl protein-protein interaction

Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion.

Cultures of human CD34pos cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus few macrophages (~3%, 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169pos macrophages established multiple rapid “loose” interactions with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169neg macrophages established tight interactions with mature erythroblasts and phagocytosed these cells. Loose interactions of CD169pos macrophages were associated with proerythroblast cytokinesis (the M phase of cell cycle) suggesting that these interactions may promote proerythroblast duplication. This hypothesis was tested by experiments indicating that as few as 103 macrophages significantly increased levels of 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide incorporation, frequency in S/G2/M and cytokinesis expressed by proerythroblasts over 24 hours culture. These effects were observed also when macrophages were co-cultured with dexamethasone directly conjugated to a macrophage-specific CD163 antibody. In conclusion, in addition to promoting proerythroblast proliferation directly, dexamethasone stimulates expansion of these cells indirectly by stimulating maturation and cytokinesis supporting activity of macrophages

SARS Cov-2 infection in a renal-transplanted patient: A case report

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can \u201cbe protective\u201d as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection

Rapid response to COVID-19 outbreak in Northern Italy: how to convert a classic infectious disease ward into a COVID-19 response centre

none133noopenAsperges E.; Novati S.; Muzzi A.; Biscarini S.; Sciarra M.; Lupi M.; Sambo M.; Gallazzi I.; Peverini M.; Lago P.; Mojoli F.; Perlini S.; Bruno R.; Mondelli M.U.; Brunetti E.; Di Matteo A.; Seminari E.; Maiocchi L.; Zuccaro V.; Pagnucco L.; Mariani B.; Ludovisi S.; Parisi R.L.A.; Sacchi P.; Patruno S.F.A.; Michelone G.; Gulminetti R.; Zanaboni D.; Maserati R.; Orsolini P.; Vecchia M.; Colaneri M.; Di Filippo A.; Roda S.; Pieri T.C.; Sachs M.; Valsecchi P.; Alfano C.; Bonzano M.; Briganti F.; Crescenzi G.; Falchi A.G.; Guarnone R.; Guglielmana B.; Maggi E.; Martino I.; Pettenazza P.; Pioli di Marco S.; Quaglia F.; Sabena A.; Salinaro F.; Speciale F.; Zunino I.; De Lorenzo M.; Secco G.; Dimitry L.; Cappa G.; Maisak I.; Chiodi B.; Sciarrini M.; Barcella B.; Resta F.; Moroni L.; Vezzoni G.; Scattaglia L.; Boscolo E.; Zattera C.; Fidel T.M.; Vincenzo C.; Vignaroli D.; Bazzini M.; Iotti G.; Belliato M.; Perotti L.; Mongodi S.; Tavazzi G.; Marseglia G.; Licari A.; Brambilla I.; Daniela B.; Antonella B.; Patrizia C.; Giulia C.; Giuditta C.; Marta C.; Rossana D.; Milena F.; Bianca M.; Roberta M.; Enza M.; Stefania P.; Maurizio P.; Elena P.; Antonio P.; Francesca R.; Antonella S.; Maurizio Z.; Guy A.; Laura B.; Ermanna C.; Giuliana C.; Luca D.; Gabriella F.; Gabriella G.; Alessia G.; Viviana L.; Claudia L.; Valentina M.; Simona P.; Marta P.; Alice B.; Giacomo C.; Irene C.; Corcione A.; di Martino R.; di Napoli A.; Alessandro F.; Guglielmo F.; Loretta F.; Federica G.; Alessandra M.; Federica N.; Giacomo R.; Beatrice R.; Maria S.I.; Monica T.; Edoardo V.N.; Calvi M.; Tizzoni M.; Nicora C.; Triarico A.; Petronella V.; Marena C.Asperges, E.; Novati, S.; Muzzi, A.; Biscarini, S.; Sciarra, M.; Lupi, M.; Sambo, M.; Gallazzi, I.; Peverini, M.; Lago, P.; Mojoli, F.; Perlini, S.; Bruno, R.; Mondelli, M. U.; Brunetti, E.; Di Matteo, A.; Seminari, E.; Maiocchi, L.; Zuccaro, V.; Pagnucco, L.; Mariani, B.; Ludovisi, S.; Parisi, R. L. A.; Sacchi, P.; Patruno, S. F. A.; Michelone, G.; Gulminetti, R.; Zanaboni, D.; Maserati, R.; Orsolini, P.; Vecchia, M.; Colaneri, M.; Di Filippo, A.; Roda, S.; Pieri, T. C.; Sachs, M.; Valsecchi, P.; Alfano, C.; Bonzano, M.; Briganti, F.; Crescenzi, G.; Falchi, A. G.; Guarnone, R.; Guglielmana, B.; Maggi, E.; Martino, I.; Pettenazza, P.; Pioli di Marco, S.; Quaglia, F.; Sabena, A.; Salinaro, F.; Speciale, F.; Zunino, I.; De Lorenzo, M.; Secco, G.; Dimitry, L.; Cappa, G.; Maisak, I.; Chiodi, B.; Sciarrini, M.; Barcella, B.; Resta, F.; Moroni, L.; Vezzoni, G.; Scattaglia, L.; Boscolo, E.; Zattera, C.; Fidel, T. M.; Vincenzo, C.; Vignaroli, D.; Bazzini, M.; Iotti, G.; Belliato, M.; Perotti, L.; Mongodi, S.; Tavazzi, G.; Marseglia, G.; Licari, A.; Brambilla, I.; Daniela, B.; Antonella, B.; Patrizia, C.; Giulia, C.; Giuditta, C.; Marta, C.; Rossana, D.; Milena, F.; Bianca, M.; Roberta, M.; Enza, M.; Stefania, P.; Maurizio, P.; Elena, P.; Antonio, P.; Francesca, R.; Antonella, S.; Maurizio, Z.; Guy, A.; Laura, B.; Ermanna, C.; Giuliana, C.; Luca, D.; Gabriella, F.; Gabriella, G.; Alessia, G.; Viviana, L.; Claudia, L.; Valentina, M.; Simona, P.; Marta, P.; Alice, B.; Giacomo, C.; Irene, C.; Corcione, A.; di Martino, R.; di Napoli, A.; Alessandro, F.; Guglielmo, F.; Loretta, F.; Federica, G.; Alessandra, M.; Federica, N.; Giacomo, R.; Beatrice, R.; Maria, S. I.; Monica, T.; Edoardo, V. N.; Calvi, M.; Tizzoni, M.; Nicora, C.; Triarico, A.; Petronella, V.; Marena, C

Emergency Department and Out-of-Hospital Emergency System (112\u2014AREU 118) integrated response to Coronavirus Disease 2019 in a Northern Italy centre

Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating \u201cout-of-hospital\u201d and \u201chospital\u201d activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The \u201cout-of-hospital\u201d response was analysed in terms of calls, rescues and missions, whereas the \u201chospital\u201d response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5 weeks of the Covid-19 outbreak (February 21\u2013March 26, 2020) were compared with a reference time window referring to the previous 5 weeks (January 17\u2013February 20, 2020) and with the corresponding historical average data from the previous 5 years (February 21\u2013March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+ 440%). After 5 weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+ 48% and + 10%, respectively) and the historical control (+ 53% and + 22%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants, + 108%). To minimize the possibility of intra-hospital spreading of the infection, a separate \u201cEmergency Department\u2014Infective Disease\u201d was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n = 720) were admitted in general wards (n = 629) or intensive care unit (n = 91). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the \u201cout-of-hospital\u201d and \u201cin-hospital\u201d systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future