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1. Characterization of compliance phenotypes in COVID-19 acute respiratory distress syndrome

Author

Zacchetti, L, Longhi, L, Bianchi, I, Di Matteo, M, Russo, F, Gandini, L, Manesso, L, Monti, M, Cosentini, R, Di Marco, F, Fagiuoli, S, Grazioli, L, Gritti, P, Previdi, F, Senni, M, Ranieri, M, Lorini, L, Rota, A, Martinelli, A, Pugni, P, Marino, A, Colombo, G, Damiani, M, Ferrari, D, Bonacina, D, Corbella, D, Poli, G, Cantu, D, Ferri, F, Brivio, M, Bonanomi, E, Fabretti, F, Benigni, A, Brambillasca, P, Scarpa, L, Marchesi, F, Zacchetti L., Longhi L., Bianchi I., Di Matteo M., Russo F., Gandini L., Manesso L., Monti M., Cosentini R., Di Marco F., Fagiuoli S., Grazioli L., Gritti P., Previdi F., Senni M., Ranieri M., Lorini L., Rota A., Martinelli A., Pugni P., Marino A., Colombo G., Damiani M., Ferrari D., Bonacina D., Corbella D., Poli G., Cantu D., Ferri F., Brivio M., Bonanomi E., Fabretti F., Benigni A., Brambillasca P., Scarpa L., Marchesi F., Zacchetti, L, Longhi, L, Bianchi, I, Di Matteo, M, Russo, F, Gandini, L, Manesso, L, Monti, M, Cosentini, R, Di Marco, F, Fagiuoli, S, Grazioli, L, Gritti, P, Previdi, F, Senni, M, Ranieri, M, Lorini, L, Rota, A, Martinelli, A, Pugni, P, Marino, A, Colombo, G, Damiani, M, Ferrari, D, Bonacina, D, Corbella, D, Poli, G, Cantu, D, Ferri, F, Brivio, M, Bonanomi, E, Fabretti, F, Benigni, A, Brambillasca, P, Scarpa, L, Marchesi, F, Zacchetti L., Longhi L., Bianchi I., Di Matteo M., Russo F., Gandini L., Manesso L., Monti M., Cosentini R., Di Marco F., Fagiuoli S., Grazioli L., Gritti P., Previdi F., Senni M., Ranieri M., Lorini L., Rota A., Martinelli A., Pugni P., Marino A., Colombo G., Damiani M., Ferrari D., Bonacina D., Corbella D., Poli G., Cantu D., Ferri F., Brivio M., Bonanomi E., Fabretti F., Benigni A., Brambillasca P., Scarpa L., and Marchesi F.

Abstract

Background: Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the “classic ARDS”, showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. Methods: This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. Results: We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32–47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. Conclusions: In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mecha

Published
2022

2. Extent and Distribution of Parenchymal Abnormalities in Baseline CT-Scans Do Not Predict Awake Prone Positioning Response in COVID-19 Related ARDS

Author

Raimondi, F, Cazzaniga, S, Annibali, S, Novelli, L, Brivio, M, Pappacena, S, Malandrino, L, Bonaffini, P, Bianco, I, Liggeri, N, Gritti, P, Lorini, F, Sironi, S, Di Marco, F, Raimondi F., Cazzaniga S., Annibali S., Novelli L., Brivio M., Pappacena S., Malandrino L., Bonaffini P. A., Bianco I., Liggeri N., Gritti P., Lorini F. L., Sironi S., Di Marco F., Raimondi, F, Cazzaniga, S, Annibali, S, Novelli, L, Brivio, M, Pappacena, S, Malandrino, L, Bonaffini, P, Bianco, I, Liggeri, N, Gritti, P, Lorini, F, Sironi, S, Di Marco, F, Raimondi F., Cazzaniga S., Annibali S., Novelli L., Brivio M., Pappacena S., Malandrino L., Bonaffini P. A., Bianco I., Liggeri N., Gritti P., Lorini F. L., Sironi S., and Di Marco F.

Abstract

Prone positioning is frequently used for non-intubated hypoxemic patients with COVID-19, although conclusive evidence is still lacking. The aim of the present study was to investigate whether baseline CT-scans could predict the improvement in oxygenation in COVID-19 related Acute respira-tory syndrome (ARDS) patients when pronated. Methods: A retrospective study of COVID-19 patients who underwent non-invasive ventilation (NIV) and prone positioning was conducted. Results: Forty-five patients were included. On average, 50% of the overall lung volume was affected by the disease, as observed in the CT-scans, with ground glass opacities (GGOs) and consolidations accounting for 44% and 4%, respectively. The abnormalities were mainly posterior, as demonstrated by posterior/anterior distribution ratios of 1.5 and 4.4 for GGO and consolidation, respectively. The median PaO2/FiO2 ratio during NIV in a supine position (SP1) was 140 [IQR 108–169], which improved by 67% (+98) during prone positioning, on average. Once supine positioning was resumed (SP2), the improvement in oxygenation was maintained in 28 patients (62% of the overall population, categorized as “responders”). We found no significant differences between responders and non-responders in terms of the extent (p = 0.92) and the distribution of parenchymal abnormalities seen in the baseline CT (p = 0.526). Conclusion: Despite the lack of a priori estimation of the sample size, considering the absence of any trends in the differences and correlations, we can reasonably conclude that the baseline chest CT-scan does not predict a gas-exchange response in awake prone-positioned patients with COVID-19 related ARDS. Physicians dealing with this category of patients should not rely on the imaging at presentation when evaluating whether to pronate patients.

Published
2022

4. Amount and distribution of parenchymal abnormalities at CT-scan do not predict awake prone position outcome in Covid-19

Author

Raimondi, F, primary, Pappacena, S, additional, Novelli, L, additional, Annibali, S, additional, Bianco, I, additional, Malandrino, L, additional, Cazzaniga, S, additional, Brivio, M, additional, Trapasso, R, additional, Bonetti, S, additional, Caglioni, F, additional, Catani, C, additional, Allegri, C, additional, Biza, R, additional, Anelli, M, additional, and Di Marco, F, additional

Published
2022
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5. Characterization of compliance phenotypes in COVID-19 acute respiratory distress syndrome

Author

Zacchetti L., Longhi L., Bianchi I., Di Matteo M., Russo F., Gandini L., Manesso L., Monti M., Cosentini R., Di Marco F., Fagiuoli S., Grazioli L., Gritti P., Previdi F., Senni M., Ranieri M., Lorini L., Rota A., Martinelli A., Pugni P., Marino A., Colombo G., Damiani M., Ferrari D., Bonacina D., Corbella D., Poli G., Cantu D., Ferri F., Brivio M., Bonanomi E., Fabretti F., Benigni A., Brambillasca P., Scarpa L., Marchesi F., Zacchetti, L, Longhi, L, Bianchi, I, Di Matteo, M, Russo, F, Gandini, L, Manesso, L, Monti, M, Cosentini, R, Di Marco, F, Fagiuoli, S, Grazioli, L, Gritti, P, Previdi, F, Senni, M, Ranieri, M, Lorini, L, Rota, A, Martinelli, A, Pugni, P, Marino, A, Colombo, G, Damiani, M, Ferrari, D, Bonacina, D, Corbella, D, Poli, G, Cantu, D, Ferri, F, Brivio, M, Bonanomi, E, Fabretti, F, Benigni, A, Brambillasca, P, Scarpa, L, and Marchesi, F

Subjects
Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, Acute respiratory distress syndrome, Coronaviru, COVID-19, Prone positioning, Respiration, Artificial, Coronavirus, Positive-Pressure Respiration, Phenotype, Sars coronaviru, Settore ING-INF/04 - Automatica, Acute lung injury, Lung compliance, Sars coronavirus, Humans, Lung Compliance
Abstract

Background Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the “classic ARDS”, showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. Methods This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. Results We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32–47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. Conclusions In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs.

Published
2022

6. Correction to: Post-operative cognitive decline (POCD) after gynaecologic surgery: current opinions and future applications (Archives of Gynecology and Obstetrics, (2018), 297, 3, (551-554), 10.1007/s00404-017-4630-3)

Author

Zarbo C., Zarbo, C, Brivio, M, Brugnera, A, Malandrino, C, Trezzi, G, Rabboni, M, Bondi, E, Compare, A, Frigerio, L, Zarbo C., Brivio M., Brugnera A., Malandrino C., Trezzi G., Rabboni M., Bondi E., Compare A., Frigerio L., Zarbo C., Zarbo, C, Brivio, M, Brugnera, A, Malandrino, C, Trezzi, G, Rabboni, M, Bondi, E, Compare, A, Frigerio, L, Zarbo C., Brivio M., Brugnera A., Malandrino C., Trezzi G., Rabboni M., Bondi E., Compare A., and Frigerio L.

Abstract

The original version of this article unfortunately contained a mistake. The given names and family names of all authors were interchanged. The correct authorship is given below. Cristina Zarbo1· Michela Brivio1· Agostino Brugnera1· Chiara Malandrino2· Gaetano Trezzi2· Massimo Rabboni3· Emi Bondi3· Angelo Compare1· Luigi Frigerio2 The original article has been corrected.

Published
2018

11. Post-operative cognitive decline (POCD) after gynaecologic surgery: current opinions and future applications

Author

Zarbo, C, Brivio, M, Brugnera, A, Malandrino, C, Trezzi, G, Rabboni, M, Bondi, E, Compare, A, Frigerio, L, Zarbo, Cristina, Brivio, Michela, Brugnera, Agostino, Malandrino, Chiara, Trezzi, Gaetano, Rabboni, Massimo, Bondi, Emi, Compare, Angelo, Frigerio, Luigi, Zarbo, C, Brivio, M, Brugnera, A, Malandrino, C, Trezzi, G, Rabboni, M, Bondi, E, Compare, A, Frigerio, L, Zarbo, Cristina, Brivio, Michela, Brugnera, Agostino, Malandrino, Chiara, Trezzi, Gaetano, Rabboni, Massimo, Bondi, Emi, Compare, Angelo, and Frigerio, Luigi

Abstract

Objective: Postoperative cognitive decline (POCD) is known to occur quite frequently after a cardiac surgery, especially in older population. Few studies specifically focused on its incidence and characteristics in gynecological setting. Methods: Current opinions and future applications of POCD studies in gynecological setting have been discussed. Result: There are still many questions and issues about POCD in gynecological setting that remain unanswered as well as numerous research fields that have not been still explored. In particular, from this article emerges the need of further studies in gynecological setting focusing on: (a) the evaluation of long-term effect of POCD (e.g. over 3 months after surgery); (b) elderly population; (c) a wide range of cognitive functions (memory, attention, concentration, orientation, etc.); (d) the evaluation of risk and protective factors for subsequent POCD development; (e) the relationships between POCD and previous psychological or neuroendocrine factors; (f) the difference on POCD outcomes between different anaesthesia and disorders. Conclusion: Promoting studies on this topic is significant for the reduction of sociosanitary costs, mortality rates, social dependences and the likelihood of comorbidity.

Published
2018

12. Albumin replacement in patients with severe sepsis or septic shock

Author

Gattinoni L, Caironi P, Pesenti A, Fumagalli R, Tognoni G, Romero M, Latini R, Masson S, Vincent JL, Suter PM, Valsecchi MG, Santosuosso A, Cavana M, Ortu A, Gabini R, Perno S, Anelli A, Amoruso R, Ferraris S, Borelli M, Massei R, Riva I, Poli G, Papagni G, Bortone F, Mamprin F, Keim R, Brivio M, Colageo U, Mimii EP, Sangiorgi G, Siniscalchi A, Pierucci E, Giovannitti A, Gentile C, Pascucci F, Antonini B, Zummo U, Valsecchi R, Cerisara M, Trezzi T, Dossena A, Ribola A, Tamayo L, Zoppellari R, Volta CA, Mangani V, Fanfani E, Chelazzi C, Bartoli T, Parrini V, Oggioni R, Fedele A, Molin A, Berri C, Guarino A, Isetta M, Bonfiglio M, Tissino F, Silvestri L, Milanesi M, Sbrana G, Motta E, Iannaco I, Casadio MC, Pasetti GS, Palandini A, Cascione C, Puscio D, Cellai F, Boccalatte D, Silvestri S, Fausto CI, Lupo V, Zompanti V, Iacobone E, Gattari D, Ronzoni G, Beck E, Francesconi S, Colombo R, Raimondi F, Castelli A, De Gasperi A, Radrizzani D, Ferla LE, Giudici R, Bellato V, Bordone G, Gavazzeni V, Lesmo A, Ripamonti D, Vesconi S, Papoff A, Rossi A, Noto A, Pezzi A, Zanforlin G, Kandil H, Ballotta A, Bettini F, Vaghi GM, Rossi S, Pessina C, Casagrande D, Trivellato A, Costagli V, Moise G, Furla M, Marelli S, Caspani L, Panigada M, Bruzzone P, Isgrò S, Abbruzzese C, Tagliabue P, Solca M, Bonazzi M, Cattaneo A, Rossi N, Andreoni P, Pasetto A, Girardis M, Barbieri E, Piazza O, Zagara G, Bono M, Galzerano A, Garzilli T, Dentini N, Bindi M, Biancofiore G, Mercante WP, Disconzi MM, Todesco N, Lunardi S, Sani E, Carli M, Bracciotti G, Gori V, Braccini P, Maggio G, Braschi A, Bottazzi A, Iotti G, Nicora B, Salati G, Salsi P, Antonelli M, Pennisi MA, Bello G, Caccese R, D'Ambrosio M, Rocco M, Sanseverino M, Gatta A, Nastasi M, Corsi A, Facondini F, Franchi F, Mongelli P, Ferrario M, Carulli F, Del Curto S, Schiappacasse G, Dalpiaz C, Armani S, Verderosa I, Marzullo A, Tonetti F, De Piero ME, Livigni S, Fiore G, Cerutti A, Erbetta S, Napolitano R, Pastorelli M, Bona F, Debernardi F, Gallo M, Segala V, Parigi L, Perzolla D, Marson F, Chiarandini P, Cammarano C, Sermann G, De Lucia S, Frigerio A, Distaso F, Franco R, Bossi E, Laudi C, De Nardin M, Violo T, Lazzari F, Vestali A, Della Mora E, Polati E, Martini A, Cristallini S, Totaro C, Milan B, Dan M, Ruberti S, Danzi V., GIARRATANO, Antonino, RAINERI, Santi Maurizio, CORTEGIANI, Andrea, Caironi, P, Tognoni, G, Masson, S, Fumagalli, R, Pesenti, A, Romero, M, Fanizza, C, Caspani, L, Faenza, S, Grasselli, G, Iapichino, G, Antonelli, M, Parrini, V, Fiore, G, Latini, R, Gattinoni, L, Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L, Vincent JL, Suter PM, Valsecchi MG, Santosuosso A, Cavana M, Ortu A, Gabini R, Perno S, Anelli A, Amoruso R, Ferraris S, Borelli M, Massei R, Riva I, Poli G, Papagni G, Bortone F, Mamprin F, Keim R, Brivio M, Colageo U, Mimii EP, Sangiorgi G, Siniscalchi A, Pierucci E, Giovannitti A, Gentile C, Pascucci F, Antonini B, Zummo U, Valsecchi R, Cerisara M, Trezzi T, Dossena A, Ribola A, Tamayo L, Zoppellari R, Volta CA, Mangani V, Fanfani E, Chelazzi C, Bartoli T, Oggioni R, Fedele A, Molin A, Berri C, Guarino A, Isetta M, Bonfiglio M, Tissino F, Silvestri L, Milanesi M, Sbrana G, Motta E, Iannaco I, Casadio MC, Pasetti GS, Palandini A, Cascione C, Puscio D, Cellai F, Boccalatte D, Silvestri S, Fausto CI, Lupo V, Zompanti V, Iacobone E, Gattari D, Ronzoni G, Beck E, Francesconi S, Colombo R, Raimondi F, Castelli A, De Gasperi A, Radrizzani D, Ferla LE, Giudici R, Bellato V, Bordone G, Gavazzeni V, Lesmo A, Ripamonti D, Vesconi S, Papoff A, Rossi A, Noto A, Pezzi A, Zanforlin G, Kandil H, Ballotta A, Bettini F, Vaghi GM, Rossi S, Pessina C, Casagrande D, Trivellato A, Costagli V, Moise G, Furla M, Marelli S, Panigada M, Bruzzone P, Isgrò S, Abbruzzese C, Tagliabue P, Solca M, Bonazzi M, Cattaneo A, Rossi N, Andreoni P, Pasetto A, Girardis M, Barbieri E, Piazza O, Giarratano A, Raineri SM, Cortegiani A, Zagara G, Bono M, Galzerano A, Garzilli T, Dentini N, Bindi M, Biancofiore G, Mercante WP, Disconzi MM, Todesco N, Lunardi S, Sani E, Carli M, Bracciotti G, Gori V, Braccini P, Maggio G, Braschi A, Bottazzi A, Iotti G, Nicora B, Salati G, Salsi P, Pennisi MA, Bello G, Caccese R, D'Ambrosio M, Rocco M, Sanseverino M, Gatta A, Nastasi M, Corsi A, Facondini F, Franchi F, Mongelli P, Ferrario M, Carulli F, Del Curto S, Schiappacasse G, Dalpiaz C, Armani S, Verderosa I, Marzullo A, Tonetti F, De Piero ME, Livigni S, Cerutti A, Erbetta S, Napolitano R, Pastorelli M, Bona F, Debernardi F, Gallo M, Segala V, Parigi L, Perzolla D, Marson F, Chiarandini P, Cammarano C, Sermann G, De Lucia S, Frigerio A, Distaso F, Franco R, Bossi E, Laudi C, De Nardin M, Violo T, Lazzari F, Vestali A, Della Mora E, Polati E, Martini A, Cristallini S, Totaro C, Milan B, Dan M, Ruberti S, and Danzi V

Subjects
Male, medicine.medical_specialty, ALBUMIN, SEPSIS, SEVERE SEPSIS, SEPTIC SHOCK, Sepsi, Serum albumin, Settore MED/41 - Anestesiologia, Aged, Albumins, Female, Humans, Isotonic Solutions, Middle Aged, Rehydration Solutions, Sepsis, Serum Albumin, Shock, Septic, Survival Rate, Treatment Outcome, Intensive care, medicine, albumin replacement, Survival rate, Isotonic Solution, Medicine (all), SEPSIS, biology, business.industry, Septic shock, Rehydration Solution, Septic, Albumin, SEPTIC SHOCK, Organ dysfunction, Shock, General Medicine, medicine.disease, Surgery, Anesthesia, Relative risk, biology.protein, medicine.symptom, business, Human
Abstract

BACKGROUND: Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS: In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS: During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P = 0.03) and lower net fluid balance (P

Published
2014

16. Kinetic study of an on-chip isocyanate derivatization reaction by on-line nano-esi ms

Author

Brivio, M., Liesner, A., Oosterbroek, R.E., Verboom, Willem, Karst, U., van den Berg, Albert, Reinhoudt, David, Jensen, K.F, Han, J., Harrison, D.J., Voldman, J., Faculty of Science and Technology, and Molecular Nanofabrication

Subjects
Micro-reactor, EWI-19992, nano-ESI MS, METIS-224693, real-time monitoring, IR-52865, Reaction kinetics
Abstract

A high-throughput method is presented for the study of reaction kinetics by nano- electrospray ionization mass spectrometry (nano-ESI MS). The reaction of propyl isocyanate (2), benzyl isocyanate (3), and toluene-2,4-diisocyanate (4) with 4-nitro-7- piperazino-2,1,3-benzoxadiazole (NBDPZ) (1) to yield the corresponding urea derivatives (5) was carried out in a continuous flow glass microchip. Real-time monitoring of the reactions was done by nano-ESI MS. Rate constants of 1.6 ⿣ 104 M-1 min-1, 5.2 ⿣ 104 M-1 min-1, and 2.5 ⿣ 104 M-1 min-1 were determined for isocyanate 2, 3 and 4, respectively.

Published
2005

17. Real-time studies of chemical reactions in lab-on-a-chip devices

Author

Brivio, M., Reinhoudt, David Nicolaas, and Verboom, Willem

Subjects
IR-50281
Abstract

The realization of a lab-on-a-chip system in which chemical reactions are carried out in a continuous flow mode and monitored on-line by a suitable analytical technique is the main topic of this thesis. Two types of a lab-on-a-chip were realized, both using mass spectrometry (MS) as the on-line detection technique, viz. electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) MS.

Published
2005

19. Glass-surface as in-situ catalyst in reaction chips

Author

Brivio, M., Oosterbroek, R. E., Willem Verboom, Goedbloed, M. H., Albert van den Berg, David Reinhoudt, Faculty of Science and Technology, and Molecular Nanofabrication

Subjects
METIS-217145, IR-41067
Published
2003

24. Simultaneous Estimation of Epidermal Growth Factor Receptors and Steroid Receptors in a Series of 136 Resectable Primary Breast Tumors.

Author

Cappelletti, V., Brivio, M., Miodini, P., Granata, G., Coradini, D., and Di Fronzo, G.

Abstract

Human breast cancer cell lines, as well as human breast cancer biopsies, possess specific high-affinity epidermal growth factor receptors (EGF-r). However, reports on the presence of EGF-r in human breast cancer biopsies are still controversial, especially concerning the relationship between EGF-r and other biological variables whose prognostic relevance is well known, such as the estrogen (ER) and progesterone (PgR) receptors. In the present study, the EGF-r content was estimated in a series of 136 unselected breast cancer primaries along with cytoplasmic (ERc) and nuclear (ERn) ER and cytoplasmic PgR. EGF-binding activity consisted of a single class of high-affinity binding sites (Kd = 0.55 nM) and ranged from 0 to 275 fmol/mg protein. We observed a strong inverse association between EGF-r and ERc (p < 0.001); in fact, about two thirds of the tumors were ERc-positive/EGF-r-negative or ERc-negative/EGF-r-positive. The same type of association was found between EGF-r and either ERn or PgR.Kendall's rank correlation test confirmed that the EGF-r concentrations were correlated with the levels of ERc (τ = -0.291, p < 0.0001), ERn (τ = -0.27, p < 0.0005) and PgR (τ = -0.162, p < 0.01). The EGF-r content was significantly higher (p < 0.0001) in the ERc-negative tumors (72.6 ± 54.4 fmol/mg protein) as compared to the ERc-positive ones (33.0 ± 37.4 fmol/mg protein). Similarly, the subset of PgR-positive tumors was characterized by lower EGF-r mean concentrations when compared to PgR-negative cases (35.4 ± 54.4 vs. 63.8 ± 54.4 fmol/mg protein). These results confirm the previously described inverse relationship between EGF-r and steroid receptors. Moreover, they suggest the existence of an interaction between steroid hormones and EGF and support the need for further studies to better understand their respective roles in modulating breast cancer growth. Copyright © 1988 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
1988
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26. Low cost and highly integrated cop monolithic liquid flow controlling system

Author

Etxebarria, J., Berganzo, J., Anduaga, J., Besteiro, J., Brivio, M., Han Gardeniers, Ezkerra, A., and Mesoscale Chemical Systems

Subjects
Micro flow control, Monolithic, Polymer
Abstract

In this work a polymer monolithic liquid flow controlling system (LFCS) at micro-scale is presented, which enables regulation between 30-230 μl/min with excellent reproducibility and accuracy. The device is made in a single piece by Hot Embossing in Cyclic Olefin Polymer, sealed with a single membrane by solvent bonding and metalized, after sealing, to render a fully functional microfluidic control system with on-chip flow sensing. The fabrication process shows industrial-like quality in terms of dimensional control and reproducibility, enabling direct transition of validated prototypes into mass-production means i.e. injection molding.

29. A hedgehog-like signal is involved in slow muscle differentation in Sepia officinalis (Mollusca)

Author

Grimaldi, A., Gianluca Tettamanti, Guidali, M. L., Brivio, M. F., Valvassori, R., and Eguilor, M.

Subjects
animal structures, mollusc, lcsh:Biology (General), embryonic structures, Development, Helical and cross-striated fibres, Hh-like protein, Mollusc, Muscle differentiation, muscle differentiation, musculoskeletal system, helical and cross-striated fibres, tissues, development, lcsh:QH301-705.5
Abstract

In the tentacle of Sepia officinalis, smooth-like, helical and cross-striated fibres deriving from different populations of myoblasts are present. Myoblasts appear at different times during the development and express two muscle-specific transcription factors: Myf5-like and MyoD-like factors. Myoblasts expressing Myf5 give rise to slow fibres, whereas fast fibres derive from MyoD+ myoblasts. We found that a Hedgehog (Hh)-like signal was present in the central nerve cord of the tentacle from the early stages of development and in a specific population of myoblasts which are the precursors of slow muscle fibres. The model showed interesting similarities with vertebrates, in which Sonic hedgehog is a protein secreted by axial structures (the notochord and neurotube) and is involved in slow muscle differentiation and in survival of muscle precursors.

32. On-Chip integration of sample pretreatment and Multiplex polymerase chain reaction (PCR) for DNA analysis

Author

Brivio, M., Snakenborg, D., Søgaard, E., Ahlford, A., Syvänen, A. C., Kutter, J. P., and Anders Wolff

Abstract

In this paper we present a modular lab-on-a-chip system for integrated samplepre-treatment (PT) by magnetophoresis and DNA amplification by polymerase chainreaction (PCR). It consists of a polymer-based microfluidic chip mounted on a custom-made thermocycler (Figure 1) and includes a simple and efficient method forswitching the liquid flow between the PT and PCR chamber. Purification of humangenomic DNA from EDTA-treated blood and multiplex PCR were successfully carriedout on-chip using the developed lab-on-a-chip system.

36. Modular Synthetic Routes to Fluorine-Containing Halogenated Phenazine and Acridine Agents That Induce Rapid Iron Starvation in Methicillin-Resistant Staphylococcus aureus Biofilms

Author

Ke Liu, Massimiliano Brivio, Tao Xiao, Verrill M. Norwood, Young S. Kim, Shouguang Jin, Antonio Papagni, Luca Vaghi, Robert W. Huigens, Liu, K, Brivio, M, Xiao, T, Norwood, V, Kim, Y, Jin, S, Papagni, A, Vaghi, L, and Huigens, R

Subjects
Methicillin-Resistant Staphylococcus aureus, chemical synthesi, antibacterial agent, Iron, Fluorine, Article, iron starvation, Anti-Bacterial Agents, halogenated phenazine, Infectious Diseases, Biofilms, biofilm-eradicating agent, CHIM/06 - CHIMICA ORGANICA, Acridines, Phenazines, halogenated acridine
Abstract

During infection, bacteria use an arsenal of resistance mechanisms to negate antibiotic therapies. In addition, pathogenic bacteria form surface-attached biofilms bearing enriched populations of metabolically dormant persister cells. Bacteria develop resistance in response to antibiotic insults; however, nonreplicating biofilms are innately tolerant to all classes of antibiotics. As such, molecules that can eradicate antibiotic-resistant and antibiotic-tolerant bacteria are of importance. Here, we report modular synthetic routes to fluorine-containing halogenated phenazine (HP) and halogenated acridine (HA) agents with potent antibacterial and biofilm-killing activities. Nine fluorinated phenazines were rapidly accessed through a synthetic strategy involving (1) oxidation of fluorinated anilines to azobenzene intermediates, (2) S(N)Ar with 2-methoxyaniline, and (3) cyclization to phenazines upon treatment with trifluoroacetic acid. Five structurally related acridine heterocycles were synthesized using S(N)Ar and Buchwald–Hartwig approaches. From this focused collection, phenazines 5g, 5h, 5i, and acridine 9c demonstrated potent antibacterial activities against Gram-positive pathogens (MIC = 0.04–0.78 μM). Additionally, 5g and 9c eradicated Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis biofilms with excellent potency (5g, MBEC = 4.69–6.25 μM; 9c, MBEC = 4.69–50 μM). Using real-time quantitative polymerase chain reaction (RT-qPCR), 5g, 5h, 5i, and 9c rapidly induce the transcription of iron uptake biomarkers isdB and sbnC in methicillin-resistant S. aureus (MRSA) biofilms, and we conclude that these agents operate through iron starvation. Overall, fluorinated phenazine and acridine agents could lead to ground-breaking advances in the treatment of challenging bacterial infections.

Published
2022

37. Post-operative cognitive decline (POCD) after gynaecologic surgery: current opinions and future applications

Author

Angelo Compare, Gaetano Trezzi, Chiara Malandrino, Michela Brivio, Massimo Rabboni, Luigi Frigerio, Cristina Zarbo, Agostino Brugnera, Emi Bondi, Zarbo, C, Brivio, M, Brugnera, A, Malandrino, C, Trezzi, G, Rabboni, M, Bondi, E, Compare, A, and Frigerio, L

Subjects
Male, medicine.medical_specialty, Cognitive decline, Cognition, Gynecology, POCD, Surgery, Older population, 03 medical and health sciences, Gynaecologic surgery, Gynecologic Surgical Procedures, Postoperative Complications, 0302 clinical medicine, 030202 anesthesiology, Settore M-PSI/08 - Psicologia Clinica, medicine, Humans, Anesthesia, Post operative, Intensive care medicine, Aged, business.industry, Mortality rate, Incidence (epidemiology), Obstetrics and Gynecology, General Medicine, medicine.disease, Comorbidity, Treatment Outcome, Female, Cognition Disorders, business, 030217 neurology & neurosurgery
Abstract

Objective: Postoperative cognitive decline (POCD) is known to occur quite frequently after a cardiac surgery, especially in older population. Few studies specifically focused on its incidence and characteristics in gynecological setting. Methods: Current opinions and future applications of POCD studies in gynecological setting have been discussed. Result: There are still many questions and issues about POCD in gynecological setting that remain unanswered as well as numerous research fields that have not been still explored. In particular, from this article emerges the need of further studies in gynecological setting focusing on: (a) the evaluation of long-term effect of POCD (e.g. over 3 months after surgery); (b) elderly population; (c) a wide range of cognitive functions (memory, attention, concentration, orientation, etc.); (d) the evaluation of risk and protective factors for subsequent POCD development; (e) the relationships between POCD and previous psychological or neuroendocrine factors; (f) the difference on POCD outcomes between different anaesthesia and disorders. Conclusion: Promoting studies on this topic is significant for the reduction of sociosanitary costs, mortality rates, social dependences and the likelihood of comorbidity.

Published
2017

38. Early suppression of immune response in Heliothis virescens larvae by the endophagous parasitoid Toxoneuron nigriceps

Author

Ferrarese, R., MAURIZIO FRANCESCO BRIVIO, Congiu, T., Falabella, P., Grimaldi, A., Mastore, M., Perletti, G., Pennacchio, F., Sciacca, L., Tettamanti, G., Valvassori, R., Eguileor, M., Ferrarese, P., Brivio, M., Congiu, T., Falabella, P., Grimaldi, A., Mastoie, M., Perletti, G., Pennacchio, Francesco, Sciacca, L., Tettamanti, G., Valvassori, R., and DE EGUILEOR, M.

Subjects
Insects, lcsh:Biology (General), Immune defenses, fungi, insect, Parasitoid, lcsh:QH301-705.5
Abstract

Toxoneuron nigriceps is an endophagous parasitoid of larval stages of the noctuid moth Heliothis virescens. As all parasitoids, this wasp avoid host immune reaction by a combination of several passive and active mechanisms. Secretions injected by ovipositing females, which contain venom, calyx fluid and polydnaviruses, are the most probably factors actively disrupting Heliothis virescens immune system. This paper describes the main alterations of the host immune response observed shortly after oviposition by T. nigriceps. A transient block of prophenoloxidase activity is registered along with changes in hemocyte number, adhesion and structure, which suggest the occurrence of apoptosis. In contrast, the host plasmatocytes appear structurally unaltered, but unable to produce a capsule in vitro.

Published
2005

39. Lung donor bronchoalveolar lavage positivity: Incidence, risk factors, and lung transplant recipients' outcome.

Author

Fumagalli J, Punzi V, Scaravilli V, Passamonti SM, Morlacchi LC, Rossetti V, Maraschini A, Matinato C, Brivio M, Righi I, Blasi F, Bandera A, Rosso L, Panigada M, Zanella A, and Grasselli G

Subjects
Humans, Male, Retrospective Studies, Female, Risk Factors, Incidence, Adult, Middle Aged, Bronchoalveolar Lavage methods, Transplant Recipients, Lung Transplantation, Tissue Donors, Bronchoalveolar Lavage Fluid microbiology
Abstract

Background: Inconsistent data exists regarding the risk factors for bronchoalveolar lavage (BAL) positivity in lung donors, the incidence of donor-derived infections (DDI), and the effect of BAL positivity on lung transplant (LuTx) recipients' outcome., Methods: A retrospective analysis was conducted on consecutive LuTx at a single center from January 2016 to December 2022. Donors' data, including characteristics, graft function and BAL samples were collected pre-procurement. Recipients underwent BAL before LuTx and about the 3rd, 7th and 14th day after LuTx. A DDI was defined as BAL positivity (bacterial growth ≥10 4 colony forming units) for identical bacterial species between donor and recipient. Recipients' pre-operative characteristics, intra-operative management, and post-operative outcomes were assessed. Two recipient cohorts were identified based on lung colonization status before undergoing LuTx., Results: Out of 188 LuTx procedures performed, 169 were analyzed. Thirty-six percent of donors' BAL tested positive. Donors' characteristics and graft function at procurement were not associated with BAL positivity. Fourteen DDI were detected accounting for 23% of recipients receiving a graft with a positive BAL. Only among uncolonized recipients, receiving a graft with positive BAL is associated with higher likelihood of requiring invasive ventilation at 72 hours after LuTx on higher positive end-expiratory pressure levels having lower PaO 2 /FiO 2 , prolonged duration of mechanical ventilation and longer ICU stay. No difference in hospital length of stay was observed., Conclusions: Receiving a graft with a positive BAL, which is poorly predicted by donors' characteristics, carries the risk of developing a DDI and is associated to a worse early graft function among uncolonized recipients., Competing Interests: Conflicts of interest The authors certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter discussed in this manuscript., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Published
2024
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40. The Effect of Positive Pressure Ventilation on Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: An Observational Study.

Author

Zacchetti L, Brivio M, Mezzapesa M, Martinelli A, Punzi V, Monti M, Marchesi F, Scarpa L, Zangari R, Longhi L, Raimondi F, Novelli L, Gritti P, Grazioli L, Villa G, and Lorini LF

Subjects
Humans, Kidney, Positive-Pressure Respiration adverse effects, Retrospective Studies, Intensive Care Units, Risk Factors, COVID-19 complications, COVID-19 therapy, Acute Kidney Injury etiology, Acute Kidney Injury therapy, Acute Kidney Injury diagnosis, Respiratory Distress Syndrome therapy, Respiratory Distress Syndrome complications
Abstract

Introduction: Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS., Methods: This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected., Results: A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively., Conclusions: In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function., (© 2024 S. Karger AG, Basel.)

Published
2024
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41. The Role of Cell Cycle Arrest Biomarkers for Predicting Acute Kidney Injury in Critically Ill COVID-19 Patients: A Multicenter, Observational Study.

Author

Weiss R, von Groote T, Ostermann M, Lumlertgul N, Weerapolchai K, Garcia MIM, Cano JMM, Del Corral BD, Broch-Porcar MJ, Perez Carrasco M, De la Vega Sanchez A, Sousa E, Catarino A, Roig AJB, Martinez de Irujo JB, de Rosa S, de la Peña MG, Tomasa T, Brivio M, De Molina FJG, Gerss J, Kellum JA, Wempe C, Leidereiter A, Meersch M, and Zarbock A

Subjects
Humans, Tissue Inhibitor of Metalloproteinase-2, Prospective Studies, Critical Illness, Biomarkers, Cell Cycle Checkpoints, Insulin-Like Growth Factor Binding Proteins, COVID-19 complications, Acute Kidney Injury diagnosis, Acute Kidney Injury etiology
Abstract

Objectives: Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) have a high risk for developing acute kidney injury (AKI) which is associated with an increased risk of death and persistent renal failure. Early prediction of AKI is crucial in order to implement preventive strategies. The purpose of this study was to investigate the predictive performance of tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 (TIMP-2) × (IGFBP7) in critically ill patients with COVID-19-associated ARDS., Design: Multicenter, prospective, observational study., Setting: Twelve centers across Europe and United Kingdom., Patients: Patients with moderate or severe COVID-19-associated ARDS were included and serial measurements of (TIMP-2) × (IGFBP7) were performed., Interventions: None., Measurements and Main Results: The primary endpoint was the development of moderate or severe AKI according to the Kidney Disease: Improving Global Outcomes definition. Three hundred patients were available for the primary analysis, and 39 met the primary endpoint. At enrollment, urinary (TIMP-2) × (IGFBP7) had high predictive value for the primary endpoint with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.84-0.93). (TIMP-2) × (IGFBP7) was significantly higher in endpoint-positive patients at enrollment and at 12 hours., Conclusions: Urinary (TIMP-2) × (IGFBP7) predicts the occurrence of AKI in critically ill patients with COVID-19-associated ARDS., Competing Interests: Dr. Ostermann received research funding from BioMérieux and Baxter. Dr. Garcia received funding from Edwards Lifesciences. Dr. Cano disclosed work for hire. Dr. Broch-Porcar disclosed that she participated in a lecture in Nephroweek with economical compensation from BioMereiux. Drs. de la Peña, Meersch, and Zarbock received funding from Baxter. Dr. Brivio received funding from Jafron and Bbraun. Dr. de Rosa received lectures fees from ESTOR SpA. Drs. Kellum’s and Zarbock’s institutions received funding from BioMereiux. Drs. Kellum, Meersch, and Zarbock received funding from BioMereiux. Dr. Meersch received funding from FMC and Baxter. Dr. Gerss received honoraria from TESARO, QUIRIS Healthcare, Ecker+Ecker, Dr August Wolff, Roche, University Clinics Schleswig-Holstein, and RWTH Aachen University. Dr. von Groote was supported by a rotational position of KFO 342, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)–ZA428/18-1. Dr. Zarbock’s institution received funding from DFG, Baxter, and Fresenius; he received funding from AM Pharma, Novartis, Alexion, Bayer, Guard Therapeutics, Paion, and Fresenius as well as independent research grants from the German Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Published
2023
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42. Combined Effect of Awake Prone Position and Noninvasive Ventilation on Respiratory Effort and Gas Exchange in Severe COVID-19-Related Pneumonia.

Author

Bianchi IM, Zacchetti L, Punzi V, Raimondi F, Novelli L, Brivio M, Grazioli LS, Mojoli F, Marco FD, and Lorini LF

Subjects
Humans, Prone Position, Wakefulness, Respiration, Artificial, Patient Positioning, COVID-19 therapy, Noninvasive Ventilation
Abstract

Competing Interests: The authors have disclosed no conflicts of interest.

Published
2023
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44. Extent and Distribution of Parenchymal Abnormalities in Baseline CT-Scans Do Not Predict Awake Prone Positioning Response in COVID-19 Related ARDS.

Author

Raimondi F, Cazzaniga S, Annibali S, Novelli L, Brivio M, Pappacena S, Malandrino L, Bonaffini PA, Bianco I, Liggeri N, Gritti P, Lorini FL, Sironi S, and Di Marco F

Abstract

Prone positioning is frequently used for non-intubated hypoxemic patients with COVID-19, although conclusive evidence is still lacking. The aim of the present study was to investigate whether baseline CT-scans could predict the improvement in oxygenation in COVID-19 related Acute respira-tory syndrome (ARDS) patients when pronated., Methods: A retrospective study of COVID-19 patients who underwent non-invasive ventilation (NIV) and prone positioning was conducted., Results: Forty-five patients were included. On average, 50% of the overall lung volume was affected by the disease, as observed in the CT-scans, with ground glass opacities (GGOs) and consolidations accounting for 44% and 4%, respectively. The abnormalities were mainly posterior, as demonstrated by posterior/anterior distribution ratios of 1.5 and 4.4 for GGO and consolidation, respectively. The median PaO 2 /FiO 2 ratio during NIV in a supine position (SP1) was 140 [IQR 108-169], which improved by 67% (+98) during prone positioning, on average. Once supine positioning was resumed (SP2), the improvement in oxygenation was maintained in 28 patients (62% of the overall population, categorized as "responders"). We found no significant differences between responders and non-responders in terms of the extent ( p = 0.92) and the distribution of parenchymal abnormalities seen in the baseline CT ( p = 0.526)., Conclusion: Despite the lack of a priori estimation of the sample size, considering the absence of any trends in the differences and correlations, we can reasonably conclude that the baseline chest CT-scan does not predict a gas-exchange response in awake prone-positioned patients with COVID-19 related ARDS. Physicians dealing with this category of patients should not rely on the imaging at presentation when evaluating whether to pronate patients.

Published
2022
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45. Modular Synthetic Routes to Fluorine-Containing Halogenated Phenazine and Acridine Agents That Induce Rapid Iron Starvation in Methicillin-Resistant Staphylococcus aureus Biofilms.

Author

Liu K, Brivio M, Xiao T, Norwood VM 4th, Kim YS, Jin S, Papagni A, Vaghi L, and Huigens RW 3rd

Subjects
Acridines pharmacology, Anti-Bacterial Agents pharmacology, Biofilms, Fluorine, Iron, Phenazines pharmacology, Methicillin-Resistant Staphylococcus aureus
Abstract

During infection, bacteria use an arsenal of resistance mechanisms to negate antibiotic therapies. In addition, pathogenic bacteria form surface-attached biofilms bearing enriched populations of metabolically dormant persister cells. Bacteria develop resistance in response to antibiotic insults; however, nonreplicating biofilms are innately tolerant to all classes of antibiotics. As such, molecules that can eradicate antibiotic-resistant and antibiotic-tolerant bacteria are of importance. Here, we report modular synthetic routes to fluorine-containing halogenated phenazine (HP) and halogenated acridine (HA) agents with potent antibacterial and biofilm-killing activities. Nine fluorinated phenazines were rapidly accessed through a synthetic strategy involving (1) oxidation of fluorinated anilines to azobenzene intermediates, (2) S N Ar with 2-methoxyaniline, and (3) cyclization to phenazines upon treatment with trifluoroacetic acid. Five structurally related acridine heterocycles were synthesized using S N Ar and Buchwald-Hartwig approaches. From this focused collection, phenazines 5g , 5h , 5i , and acridine 9c demonstrated potent antibacterial activities against Gram-positive pathogens (MIC = 0.04-0.78 μM). Additionally, 5g and 9c eradicated Staphylococcus aureus , Staphylococcus epidermidis and Enterococcus faecalis biofilms with excellent potency ( 5g , MBEC = 4.69-6.25 μM; 9c , MBEC = 4.69-50 μM). Using real-time quantitative polymerase chain reaction (RT-qPCR), 5g , 5h , 5i , and 9c rapidly induce the transcription of iron uptake biomarkers isdB and sbnC in methicillin-resistant S. aureus (MRSA) biofilms, and we conclude that these agents operate through iron starvation. Overall, fluorinated phenazine and acridine agents could lead to ground-breaking advances in the treatment of challenging bacterial infections.

Published
2022
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46. Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study.

Author

Pellegrini D, Kawakami R, Guagliumi G, Sakamoto A, Kawai K, Gianatti A, Nasr A, Kutys R, Guo L, Cornelissen A, Faggi L, Mori M, Sato Y, Pescetelli I, Brivio M, Romero M, Virmani R, and Finn AV

Subjects
Aged, COVID-19 pathology, Coronary Thrombosis pathology, Coronary Thrombosis virology, Coronary Vessels pathology, Coronary Vessels virology, Female, Heart virology, Humans, Italy, Male, Middle Aged, SARS-CoV-2, ST Elevation Myocardial Infarction epidemiology, ST Elevation Myocardial Infarction virology, COVID-19 virology, Coronary Thrombosis etiology, Myocardial Infarction pathology, Myocardial Infarction virology, Myocardium pathology
Abstract

Background: Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain., Methods: We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 in Bergamo, Italy, to determine the pathological mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury., Results: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and have shorter symptom onset to admission. The incidence of severe coronary artery disease (ie, >75% cross-sectional narrowing) was not significantly different between those with and without necrosis. Three of 14 (21.4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction, defined as ≥1 cm 2 area of necrosis, whereas 11 of 14 (78.6%) showed evidence of focal (>20 necrotic myocytes with an area of ≥0.05 mm 2 but <1 cm 2 ) myocyte necrosis. Cardiac thrombi were present in 11 of 14 (78.6%) cases with necrosis, with 2 of 14 (14.2%) having epicardial coronary artery thrombi, whereas 9 of 14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19-positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19-infected patients presenting with ST-segment-elevation myocardial infarction. Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining compared with intramyocardial thromboemboli from COVID-19-negative subjects and with aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction., Conclusions: The most common pathological cause of myocyte necrosis was microthrombi. Microthrombi were different in composition from intramyocardial thromboemboli from COVID-19-negative subjects and from coronary thrombi retrieved from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. Tailored antithrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.

Published
2021
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47. Pathological Evidence for SARS-CoV-2 as a Cause of Myocarditis: JACC Review Topic of the Week.

Author

Kawakami R, Sakamoto A, Kawai K, Gianatti A, Pellegrini D, Nasr A, Kutys B, Guo L, Cornelissen A, Mori M, Sato Y, Pescetelli I, Brivio M, Romero M, Guagliumi G, Virmani R, and Finn AV

Subjects
Biopsy, Humans, Myocarditis pathology, Myocardium pathology, COVID-19 pathology, Myocarditis virology
Abstract

To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors' experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection. Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy. Although polymerase chain reaction-detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)-infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart. It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis. Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19., Competing Interests: Author Disclosures This study was supported by the CVPath Institute, a 501(c)(3) foundation. CVPath Institute has received institutional research support from R01 HL141425 Leducq Foundation Grant, 480 Biomedical, 4C Medical, 4Tech, Abbott, Accumedical, Amgen, Biosensors, Boston Scientific, Cardiac Implants, Celonova, Claret Medical, Concept Medical, Cook, CSI, DuNing, Inc, Edwards LifeSciences, Emboline, Endotronix, Envision Scientific, Lutonix/Bard, Gateway, Lifetech, Limflo, MedAlliance, Medtronic, Mercator, Merill, Microport Medical, Microvention, Mitralign, MitrAssist, NAMSA, Nanova, Neovasc, NIPRO, Novogate, Occulotech, OrbusNeich Medical, Phenox, Profusa, Protembis, Qool, Recor, Senseonics, Shockwave, Sinomed, Spectranetics, Surmodics, Symic, Vesper, W.L. Gore, and Xeltis. Dr. Cornelissen has received research grants from University Hospital RWTH Aachen. Dr. Guagliumi has received institutional research grants from Abbott Vascular, Boston Scientific, and Infraredx; and has served as a consultant for Abbott Vascular and Boston Scientific. Dr. Virmani has received honoraria from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Cook Medical, Cordis, CSI, Lutonix Bard, Medtronic, OrbusNeich Medical, CeloNova, SINO Medical Technology, Recor Medical, Terumo Corporation, W. L. Gore, and Spectranetics; and has served as a consultant for Abbott Vascular, Boston Scientific, Celonova, Cook Medical, Cordis, CSI, Edwards Lifesciences, Lutonix Bard, Medtronic, OrbusNeich Medical, ReCore, Sinomedical Technology, Spectranetics, Surmodics, Terumo Corporation, W. L. Gore, and Xeltis. Dr. Finn has received honoraria from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Cook Medical, CSI, Lutonix Bard, Sinomed, and Terumo Corporation; and has served as a consultant to Amgen, Abbott Vascular, Boston Scientific, Celonova, Cook Medical, Lutonix Bard, and Sinomed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Published
2021
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49. Post-operative cognitive decline (POCD) after gynaecologic surgery: current opinions and future applications.

Author

Zarbo C, Brivio M, Brugnera A, Malandrino C, Trezzi G, Rabboni M, Bondi E, Compare A, and Frigerio L

Subjects
Aged, Cognition Disorders psychology, Female, Gynecologic Surgical Procedures psychology, Humans, Male, Treatment Outcome, Anesthesia, Cognition physiology, Cognition Disorders etiology, Gynecologic Surgical Procedures adverse effects, Postoperative Complications etiology
Abstract

Objective: Postoperative cognitive decline (POCD) is known to occur quite frequently after a cardiac surgery, especially in older population. Few studies specifically focused on its incidence and characteristics in gynecological setting., Methods: Current opinions and future applications of POCD studies in gynecological setting have been discussed., Result: There are still many questions and issues about POCD in gynecological setting that remain unanswered as well as numerous research fields that have not been still explored. In particular, from this article emerges the need of further studies in gynecological setting focusing on: (a) the evaluation of long-term effect of POCD (e.g. over 3 months after surgery); (b) elderly population; (c) a wide range of cognitive functions (memory, attention, concentration, orientation, etc.); (d) the evaluation of risk and protective factors for subsequent POCD development; (e) the relationships between POCD and previous psychological or neuroendocrine factors; (f) the difference on POCD outcomes between different anaesthesia and disorders., Conclusion: Promoting studies on this topic is significant for the reduction of sociosanitary costs, mortality rates, social dependences and the likelihood of comorbidity.

Published
2018
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50. Integration of an optical CMOS sensor with a microfluidic channel allows a sensitive readout for biological assays in point-of-care tests.

Author

Van Dorst B, Brivio M, Van Der Sar E, Blom M, Reuvekamp S, Tanzi S, Groenhuis R, Adojutelegan A, Lous EJ, Frederix F, and Stuyver LJ

Subjects
Antibodies chemistry, Biological Assay, Colorimetry methods, Humans, Metals chemistry, Microfluidic Analytical Techniques instrumentation, Oxides chemistry, Peptides chemistry, Point-of-Care Testing, Proteins chemistry, Semiconductors, Antibodies isolation & purification, Biosensing Techniques, Microfluidic Analytical Techniques methods, Peptides isolation & purification, Proteins isolation & purification
Abstract

In this manuscript, a microfluidic detection module, which allows a sensitive readout of biological assays in point-of-care (POC) tests, is presented. The proposed detection module consists of a microfluidic flow cell with an integrated Complementary Metal-Oxide-Semiconductor (CMOS)-based single photon counting optical sensor. Due to the integrated sensor-based readout, the detection module could be implemented as the core technology in stand-alone POC tests, for use in mobile or rural settings. The performance of the detection module was demonstrated in three assays: a peptide, a protein and an antibody detection assay. The antibody detection assay with readout in the detection module proved to be 7-fold more sensitive that the traditional colorimetric plate-based ELISA. The protein and peptide assay showed a lower limit of detection (LLOD) of 200 fM and 460 fM respectively. Results demonstrate that the sensitivity of the immunoassays is comparable with lab-based immunoassays and at least equal or better than current mainstream POC devices. This sensitive readout holds the potential to develop POC tests, which are able to detect low concentrations of biomarkers. This will broaden the diagnostic capabilities at the clinician's office and at patient's home, where currently only the less sensitive lateral flow and dipstick POC tests are implemented., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Published
2016
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