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2. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author

Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., Protti G., Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., and Protti G.

Abstract

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's

Published
2023

5. Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing

Author

Bassetti, M., Vena, A., Giacobbe, D. R., Falcone, M., Tiseo, G., Giannella, M., Pascale, R., Meschiari, M., Digaetano, M., Oliva, A., Rovelli, C., Carannante, N., Losito, A. R., Carbonara, S., Mariani, M. F., Mastroianni, A., Angarano, G., Tumbarello, M., Tascini, C., Grossi, P., Mastroianni, C. M., Mussini, C., Viale, P., Menichetti, F., Viscoli, C., Russo, A., Verdenelli, S., Fabiani, S., Castaldo, N., Pecori, D., Carnellutti, A., Givone, F., Graziano, E., Merelli, M., Cadeo, B., Peghin, M., Cattelan, A., Cipriani, L., Coletto, D., Gianluca, R., Ciardi, M. R., Ajassa, C., Tieghi, T., Pontino, P., Raffaelli, F., Artioli, S., Caruana, G., Luzzati, R., Bontempo, G., Petrosillo, N., Capone, A., Rizzardini, G., Coen, M., Passerini, M., Guadagnino, G., Urso, F., Borgia, G., Gentile, I., Maraolo, A. E., Crapis, M., Venturini, S., Parruti, G., Trave, F., Girardis, M., Cascio, A., Gioe, C., Anselmo, M., Malfatto, E., Bassetti, Matteo, Vena, Antonio, Giacobbe, Daniele Roberto, Falcone, Marco, Tiseo, Giusy, Giannella, Maddalena, Pascale, Renato, Meschiari, Marianna, Digaetano, Margherita, Oliva, Alessandra, Rovelli, Cristina, Carannante, Novella, Losito, Angela Raffaella, Carbonara, Sergio, Mariani, Michele Fabiano, Mastroianni, Antonio, Angarano, Gioacchino, Tumbarello, Mario, Tascini, Carlo, Grossi, Paolo, Mastroianni, Claudio Maria, Mussini, Cristina, Viale, Pierluigi, Menichetti, Francesco, Viscoli, Claudio, Russo, Alessandro, Bassetti M., Vena A., Giacobbe D.R., Falcone M., Tiseo G., Giannella M., Pascale R., Meschiari M., Digaetano M., Oliva A., Rovelli C., Carannante N., Losito A.R., Carbonara S., Mariani M.F., Mastroianni A., Angarano G., Tumbarello M., Tascini C., Grossi P., Mastroianni C.M., Mussini C., Viale P., Menichetti F., Viscoli C., Russo A., Verdenelli S., Fabiani S., Castaldo N., Pecori D., Carnellutti A., Givone F., Graziano E., Merelli M., Cadeo B., Peghin M., Cattelan A., Cipriani L., Coletto D., Gianluca R., Ciardi M.R., Ajassa C., Tieghi T., Pontino P., Raffaelli F., Artioli S., Caruana G., Luzzati R., Bontempo G., Petrosillo N., Capone A., Rizzardini G., Coen M., Passerini M., Guadagnino G., Urso F., Borgia G., Gentile I., Maraolo A.E., Crapis M., Venturini S., Parruti G., Trave F., Girardis M., Cascio A., Gioe C., Anselmo M., Malfatto E., Russo, Alessandro &amp, and Luzzati, R.

Subjects
medicine.medical_specialty, ceftolozane/tazobactam, medicine.medical_treatment, CRRT, Tazobactam, Enterobacterales, Enterobacterale, Internal medicine, ESBL, septic shock, Major Article, medicine, Clinical endpoint, Renal replacement therapy, business.industry, Septic shock, Retrospective cohort study, Odds ratio, medicine.disease, Ceftolozane/tazobactam, AcademicSubjects/MED00290, Infectious Diseases, Oncology, Ceftolozane, business, Empiric therapy, medicine.drug
Abstract

Background Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. Methods A multicenter retrospective study was performed in Italy (June 2016–June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. Results C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9–3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8–7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9–5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01–0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14–0.55; P < .001) were associated with clinical success. Conclusions Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.

Published
2020

10. Pancreaticoduodenal arteries aneurysms: Evaluation of frequency and association with celiac artery stenosis due to compression by median arcuate ligament

Author

Caruana G., Cannella R., Giambelluca D., Picone D., Lo Re G., Grassedonio E., Midiri M., Salvaggio G., Caruana G., Cannella R., Giambelluca D., Picone D., Lo Re G., Grassedonio E., Midiri M., and Salvaggio G.

Subjects
Superior mesenteric artery, Median arcuate ligament syndrome, Celiac artery, Computed tomography angiography, Aneurysm
Abstract

The aim of the study is to evaluate the prevalence of pancreaticoduodenal arteries (PDA) aneurysms in a large population, and to define possible correlations with celiac artery stenosis due to compression by the median arcuate ligament. Radiological reports of abdominal contrast-enhanced CT scans of 18,180 patients were scrutinized to identify patients with true PDA aneurysms. Two abdominal radiologists classified the aneurysms according to size, location and morphology and scored the presence of celiac artery stenosis due to either median arcuate ligament compression or atherosclerotic disease. Eleven true PDA aneurysms were identified in 10 patients. Nine out of 10 patients had stenosis of the celiac artery, in which 8 cases (80%) was due to compression by the median arcuate ligament of the diaphragm, which likely represents the most common underlying etiology. In our population, the prevalence of reported PDA aneurysms was 0.055.

Published
2019

28. Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole Glomeruli.

Author

Bertram J.F., Cullen-McEwen L.A., Caruana G., Hokke S.N., Li J., Firth S.D., Harper I.S., Nikolic-Paterson D.J., Schulze K.E., van der Wolde J.W., Puelles V.G., Short K.M., Wong M.N., Bensley J.G., Bertram J.F., Cullen-McEwen L.A., Caruana G., Hokke S.N., Li J., Firth S.D., Harper I.S., Nikolic-Paterson D.J., Schulze K.E., van der Wolde J.W., Puelles V.G., Short K.M., Wong M.N., and Bensley J.G.

Abstract

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.Copyright © 2016 by the American Society of Nephrology.

Published
2017

29. Validation of a three-dimensional method for counting and sizing podocytes in whole glomeruli.

Author

Hokke S.N., Nikolic-Paterson D.J., Firth S.D., Cullen-McEwen L.A., Caruana G., Li J., Bertram J.F., Harper I.S., Puelles V.G., Van Der Wolde J.W., Schulze K.E., Short K.M., Wong M.N., Bensley J.G., Hokke S.N., Nikolic-Paterson D.J., Firth S.D., Cullen-McEwen L.A., Caruana G., Li J., Bertram J.F., Harper I.S., Puelles V.G., Van Der Wolde J.W., Schulze K.E., Short K.M., Wong M.N., and Bensley J.G.

Abstract

Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.Copyright © 2016 by the American Society of Nephrology.

Published
2017

30. High risk Gleason patterns at prostate biopsy and body mass index

Author

SERRETTA, Vincenzo, FRANCO, Vito, Caruana, G, Sommatino, F, Torretta, F, Scurria, S, Serretta, V, Caruana, G, Sommatino, F, Torretta, F, Scurria, S, and Franco, V

Subjects
Prostate cancer, BMI, Gleason score, Settore MED/24 - Urologia
Published
2014

33. gSched: A resource aware Hadoop scheduler for heterogeneous cloud computing environments

Author

Caruana, G, Li, M, Qi, M, Khan, M, and Rana, O

Subjects
Resource Awareness, MapReduce, Cloud Computing, Cost Effective Computing, Task Scheduling
Abstract

MapReduce has become a major programming model for data-intensive applications in cloud computing environments. Hadoop, an open source implementation of MapReduce, has been adopted by an increasingly wide user community. However, Hadoop suffers from task scheduling performance degradation in heterogeneous contexts because of its homogeneous design focus. This paper presents gSched, a resource-aware Hadoop scheduler that takes into account both the heterogeneity of computing resources and provisioning charges in task allocation in cloud computing environments. gSched is initially evaluated in an experimental Hadoop cluster and demonstrates enhanced performance compared with the default Hadoop scheduler. Further evaluations are conducted on the Amazon EC2 cloud that demonstrates the effectiveness of gSched in task allocation in heterogeneous cloud computing environments.

Published
2016

34. Mechanical and microstructural evolution of a 3xxx aluminium alloy made by hazelett process

Author

Salvador, M. D., Amigó, V., Reig, L., Bloem, C., Carsí, M., and Caruana, G.

Subjects
lcsh:TN1-997, propiedades mecánicas, Mining engineering. Metallurgy, Propiedades mecánicas, AA3005, aa3005, TN1-997, Recristalización, Recrystallization, Mechanical properties, proceso hazelett, Proceso Hazelett, Precipitation, Microstructural characterization, Caracterización microestructural, recristalización, precipitación, Precipitación, caracterización microestructural, Hazelett process, lcsh:Mining engineering. Metallurgy
Abstract

10 páginas, 9 figuras, 3 tablas., [ES] El presente trabajo expone los resultados del estudio térmico, microestructural y mecánico realizado en una aleación AA3005 sometida a los diferentes estados del proceso Hazelett. Se estudia, desde la salida de la colada continua, pasando por distintos estados de deformación plástica en caliente, hasta alcanzar en la última laminación un espesor de 1,5 mm. Se realiza la observación por microscopia óptica y electrónica de barrido de las diferentes planchas procedentes tanto de la colada como de las posteriores laminaciones. Así mismo, la aplicación de la calorimetría diferencial de barrido ha permitido conocer los diferentes estados térmicos de las chapas, completando dicha información mediante su observación en el microscopio electrónico de transmisión. La interacción entre los diferentes procesos que ocurren en el material durante su producción determina el estado microestructural final de la lámina, condicionante tanto de sus propiedades mecánicas, determinadas mediante ensayos de dureza y tracción, como de los posteriores procesos de conformado. La evolución de los procesos de recristalización y precipitación provocan un incremento de las propiedades mecánicas a lo largo del proceso de fabricación., [EN] This paper presents the thermal, microstructural and mechanical changes of a AA3005 aluminium alloy during the different stages of manufacturing process, from continuous cast billet (20 mm thick) , along the different plastic deformation stages, till the last lamination (1.5 mm thick). The optical and scanning electron microscopy study of the different sheets obtained both in the cast and after each lamination, as well as the differential scanning calorimetry study has allowed us to identify the different thermal states of the sheets. The information provided by this technique was completed by transmision electron microscopy analysis. The interaction between the different processes occurred in the material during its manufacturing determines its final microstructural state, its mechanical properties, evaluated with hardness and tensile tests, as well as its behaviour for later forming processes. The recrystallization and precipitation phenomena increase mechanical properties during the manufacturing process.

Published
2007

35. Fibronectin (FN), Epidermal Growth Factor-Receptor (EGF-R) and Heparin-Binding Epidermal Growth Factor-Like Growth Factor (HB-EGF) expressions in relation to toxicity of adjuvant intravesical therapy for non-muscle invasive bladder cancer

Author

Caruana, G, Chiapparrone, G, Alonge, V, Scalici Gesolfo, C, Mastrocinque, G, Caruso, S, RUSSO, Antonio, Torretta, F., SERRETTA, Vincenzo, Caruana, G, Serretta, V, Chiapparrone, G, Alonge, V, Scalici Gesolfo, C, Mastrocinque, G, Caruso, S, Russo, A, and Torretta, F

Subjects
Fibronectin, markers, bladder cancer, EGF, Settore MED/24 - Urologia
Published
2013

37. Studio pilota sul valore predittivo dei livelli plasmatici di 9 fattori angiogenetici nella selezione di pazienti candidati alla biopsia prostatica

Author

SERRETTA, Vincenzo, SCURRIA, Salvatore, DISPENSA, Nino, CARUSO, Stefano, BRONTE, Giuseppe, CICERO, Giuseppe, RUSSO, Antonio, Caruana, G, Chiapparrone, G, Provenzano, S, PROVENZANO, Sandro, Serretta, V, Scurria, S, Caruana, G, Dispensa, N, Chiapparrone, G, Provenzano, S, Caruso, S, Bronte, G, Cicero, G, and Russo, A

Subjects
Prostate cancer, Prostate biopsy, Angiogenetic biomarker, Leptin, Settore MED/24 - Urologia
Abstract

To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potential cut-off level was computed. Fifty patients were entered. Median PSA was 6.8 ng/mL. A prostate nodule was palpable in 18 (36%) patients. The median number of biopsy cores was 12. Prostate cancer was detected in 25 (50%) and ASAP and PIN in 2 more patients (4%) respectively. Among the 9 considered biomarkers, only leptin showed an interesting diagnostic performance with an AUC of 0.781, at a cut-off value of 2.11 ng/mL, demonstrating a sensitivity of 78%, a specificity of 77% and a positive predictive value of 85%. Main limitations of our study are the exploratory design and the criteria adopted for patients' selection determining a detection rate for prostate cancer above the usual range. Leptin only, in our preliminary study, shows promising diagnostic accuracy for the selection of patients candidate to prostate biopsy. Further studies are required to confirm its diagnostic value and its relation with BMI.

Published
2013

39. Espianto di protesi peniena Flexiflater® AMS e contemporaneo impianto di protesi tricomponente idraulica Titan ® Alpha 1, con tecnica a doppia incisione in paziente con trapianto di rene e pancreas

Author

PAVONE, Carlo, ABBADESSA, Daniela, LETO, Gioacchino, GIAIMO, Rosa Maria, ASCOLI, Riccardo, Usala, M., Caruana,G, Pavone, C, Abbadessa, D, Leto, G, Giaimo, R.M., Ascoli, R., Usala, M., and Caruana,G.

Subjects
Protesi peniena, Deficit erettile, Espianto protesi peniena, Flexiflate®, Titan® Alpha 1, Settore MED/24 - Urologia
Abstract

Introduction and Objectives. We treated a 45 years old patient, suffering from diabetes mellitus since childhood, with retinal, neurovascular and kidney complications. In 1988, for erectile dysfunction (ED) resistant to medical injective treatment, the patient underwent ligation of the dorsal vein of the penis without any result. In 1989 a Flexiflate® hydraulic prosthesis was implanted with resolution of ED. In 2005 the patient underwent simultaneous kidney and pancreas transplant with a trans-laparotomic approach for end stage renal disease and diabetes mellitus. In 2009, because of the Flexiflate® Surgitek malfunction, the patient underwent explantation of the Flexiflate® prosthesis and simultaneous implantation of a Titan® Alpha 1 prosthesis with a double surgical approach.?Material and Methods. After a peno-scrotal incision and the explant of the Flexiflate® Surgitek, a Titan® Alpha 1 prosthesis was implanted with a double incision technique. The placement of two inflatable cylinders and the pump was performed by peno-scrotal approach. Instead, the prosthesis’ reservoir was placed with a separate infra-pubic incision to avoid possible injury from a single trans-inguinal approach, due to the previous laparotomy. Results. After follow-up at 9 months and 1 year the prosthesis was working well and the patient satisfied. Conclusions. We couldn’t find any related paper in the literature and as far as we know this is the only report on a simultaneous explant/implant of penile prosthesis with a double surgical approach in a patient with kidney and pancreas transplant.?

Published
2011

40. SAFETY AND TOLERABILITY OF LOCAL TREATMENT WITH ILOPROST, A PROSTACYCLIN ANALOGUE, IN PATIENTS WITH PEYRONIE'S DISEASE. A PHASE I STUDY

Author

PAVONE, Carlo, ABBADESSA, Daniela, Napoli, G, Caruana, G, Alonge, V, Usala, M, Pavone, C, Napoli, G, Caruana, G, Alonge, V, Usala, M, and Abbadessa, D

Subjects
PEYRONIE'S DISEASE, ILOPROST, INTRALESIONAL THERAPY, NON SURGICAL THERAPY, Settore MED/24 - Urologia
Abstract

Objective. To assess the possibility of intralesional therapy for the treatment of Peyronie's disease, we have verified the safety and tolerability of intralesional injections of Iloprost ( an I 2 Prostacyclin analogue) for its property to suppress the production of CTFG in fibroblasts. CTFG is a connective tissue growth factor that acts in concert with TGF-β to stimulate the fibrotic process. Materials and methods. 38 patients with Peyronie’s disease were preliminarily evaluated by considering the symptoms, the degree of penile curvature, and the size of the plaque. Each patient received weekly intralesional injections of 200 ng of Iloprost in 1 ml normal saline for 5 weeks. If tolerated, the single dose was increased weekly to the maximum of 400 ng (2ml). All patients tolerated well a Iloprost dose of 200 ng; 19 of them reached a 300 ng dose and 14 tolerated a 400 ng dose without showing side effects. There was no placebo control group in this phase I study. Results. To evaluate the efficacy of the treatment, all the patients were preliminarily evaluated by an at-home photography. Two months after the end of the treatment they were re-evaluated. Almost all patients showed mild side effects (burning or pain) during the treatment at the site of injection. 29% of the patients showed an improvement in curvature. Conclusion. According to the results, therapy with intralesional Iloprost (prostacyclin drug with antifibrotic properties) in Peyronie’s disease seems to be an encouraging alternative to surgery.

Published
2011

42. LOP13

Author

Caruana, G. and Raposio, E.

Published
2014

44. Anatomie pathologique : le groupe des techniciens de Midi-Pyrénées

Author

Caruana, G., primary, Candotti, M., additional, Cesca, M., additional, Thuries, V., additional, Crampe, S., additional, Demay, L., additional, Giacomin, S., additional, Boutges, A., additional, Germain, S., additional, Pistre, C., additional, Lagriffoul, L., additional, Baud, M., additional, Campse, T., additional, Darre, K., additional, Jalabert, L., additional, Perez, G., additional, Gaston, A., additional, Estival, A., additional, Gordien, K., additional, and Silvagni, C., additional

Published
2016
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45. Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes insulin resistance.

Author

Li J., Nikolic-Paterson D.J., Jiang X., Ren Y., Fu P., Puelles V.G., Caruana G., Bertram J.F., Sleeman M.W., Sun Y.B.Y., Qu X., Howard V., Dai L., Li J., Nikolic-Paterson D.J., Jiang X., Ren Y., Fu P., Puelles V.G., Caruana G., Bertram J.F., Sleeman M.W., Sun Y.B.Y., Qu X., Howard V., and Dai L.

Abstract

Signaling by TGF-beta/Smad3 plays a key role in renal fibrosis. As obesity is one of the major risk factors of chronic and end-stage renal disease, we studied the role of Smad3 signaling in the pathogenesis of obesity-related renal disease. After switching to a high fat diet, the onset of Smad3 C-terminal phosphorylation, increase in albuminuria, and the early stages of peripheral and renal insulin resistance occurred at 1 day, and 4 and 8 weeks, respectively, in C57BL/6 mice. The loss of synaptopodin, a functional marker of podocytes, and phosphorylation of the Smad3 linker region (T179 and S213) appeared after 4 weeks of the high fat diet. This suggests a temporal pattern of Smad3 signaling activation leading to kidney injury and subsequent insulin resistance in the development of obesity-related renal disease. In vivo, Smad3 knockout attenuated the high fat diet-induced proteinuria, renal fibrosis, overall podocyte injury, and mitochondrial dysfunction in podocytes. In vitro palmitate caused a rapid activation of Smad3 in 30 min, loss of synaptopodin in 2 days, and impaired insulin signaling in 3 days in isolated mouse podocytes. Blockade of either Smad3 phosphorylation by SIS3 (a Smad3 inhibitor) or T179 phosphorylation by flavopiridol (a CDK9 inhibitor) prevented the palmitate-induced loss of synaptopodin and mitochondrial function in podocytes. Thus, Smad3 signaling plays essential roles in obesity-related renal disease and may be a novel therapeutic target.Copyright © 2015 International Society of Nephrology.

Published
2015

46. The SMAD3/SMAD4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obetruction.

Author

Caruana G., Bertram J.F., Li J., Qu X., Jiang M., Sun Y.B., Nikolic-Paterson D.J., Jiang X., Caruana G., Bertram J.F., Li J., Qu X., Jiang M., Sun Y.B., Nikolic-Paterson D.J., and Jiang X.

Abstract

Aim: To investigate the functional roles of Smad3/Smad4/CDK9 complex in the pathogenesis of renal fibrosis in mice with Unilateral Ureteral Obstruction (UUO). Background(s): TGF-beta1/Smad signalling plays a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes the functions of which are poorly understood. Smad3 consists of MH1 and MH2 domains which are connected by a linker region. In vitro studies have demonstrated that CDK9-driven Smad3 linker phosphorylation is Smad4-dependent and requires Smad3 C-terminal phosphorylation. Thus Smad3, Smad4 and CDK9 may form transcriptional complexes. Method(s): The functional roles of Smad3/Smad4/CDK9 complex were investigated in renal fibroblasts and in UUO. Result(s): Mice heterozygous for Smad3&4 (Smad3/4+/-) exhibited substantial protection from renal fibrosis on day 7 UUO, whereas Smad2/3+/- and Smad2/4+/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following UUO in wild type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Smad3 or Smad4 deficiency significantly decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation as well as renal fibrosis but at different degrees. In vitro, TGF-beta1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and over-expression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and a specific Smad3 inhibitor achieved better protection from TGF-beta1-induced fibrotic response in vitro and renal interstitial fibrosis in UUO than administration of a single inhibitor. Conclusion(s): We have identified that the formation of Smad3/Smad4/CDK9 complex drives renal fibrosis in the UUO model. Formation of this complex represents a novel target for anti-fibrotic therapies.

Published
2015

47. Podocyte adaptation in a mouse model of conditional podocyte depletion.

Author

Cullen-Mcewen L.M., Nikolic-Paterson D.J., Van Der Wolde J., Bertram J.F., Caruana G., Puelles V.G., Hokke S.N., Cullen-Mcewen L.M., Nikolic-Paterson D.J., Van Der Wolde J., Bertram J.F., Caruana G., Puelles V.G., and Hokke S.N.

Abstract

Aim: To determine the adaptive capacity of podocytes in the context of podocyte depletion. Background(s): Podocyte depletion plays a central role in the development and progression of the majority of glomerular diseases. However, the ability of remaining podocytes to adapt and preserve glomerular function in the setting of podocyte depletion remains unclear. Method(s): PodCreiDTR mice, which express the human diphtheria toxin (DT) receptor exclusively in podocytes, were injected with DT (30 or 50 ng/kg) to induce mild (<30%) or severe (>40%) podocyte depletion, respectively. Albumin to creatinine ratio (ACR) was measured in spot urine samples. Mice were killed on day 0, 8 or 35 for podocyte analysis (n = 2-6). Total podocyte number and mean podocyte volume were measured in complete glomeruli contained in 800 mum thick slices using immunofluorescence, tissue clearing and confocal microscopy. Result(s): PodCreiDTR mice given 30 ng/kg DT (mild podocyte depletion) showed a 6-fold increase in ACR on days 6-8 that returned to normal by day 20 with an increase in mean podocyte volume of 27% (P = 0.03 vs control iDTR mice) by day 35. In contrast, 50 ng/kg DT (severe podocyte depletion) induced a 13-fold increase in ACR in days 6-8, which did not resolve and was associated with the development of glomerulosclerosis and a doubling in mean podocyte volume (P < 0.001 vs control iDTR mice) by day 35. Conclusion(s): Combining the PodCreiDTR mouse model with novel analysis of complete glomeruli provides a powerful approach to defining the adaptive capacity of podocytes. The resolution of albuminuria following mild podocyte depletion is associated with mild podocyte hypertrophy. However, even with a substantial podocyte hypertrophic response, severe podocyte depletion leads to persistent albuminuria and glomerulosclerosis.

Published
2015

48. Copy-number variation associated with congenital anomalies of the kidney and urinary tract.

Author

James P.A., Bertram J.F., Caruana G., Wong M.N., Walker A., Heloury Y., Webb N., Johnstone L., Burgess T., James P.A., Bertram J.F., Caruana G., Wong M.N., Walker A., Heloury Y., Webb N., Johnstone L., and Burgess T.

Abstract

Background: The most common cause of end-stage renal disease in children can be attributed to congenital anomalies of the kidney and urinary tract (CAKUT). Despite this high incidence of disease, the genetic mutations responsible for the majority of CAKUT cases remain unknown. Method(s): To identify novel genomic regions associated with CAKUT, we screened 178 children presenting with the entire spectrum of structural anomalies associated with CAKUT for submicroscopic chromosomal imbalances (deletions or duplications) using single-nucleotide polymorphism (SNP) microarrays. Result(s): Copy-number variation (CNV) was detected in 10.1 % (18/178) of the patients; in 6.2 % of the total cohort, novel duplications or deletions of unknown significance were identified, and the remaining 3.9 % harboured CNV of known pathogenicity. CNVs were inherited in 90 % (9/10) of the families tested. In this cohort, patients diagnosed with multicystic dysplastic kidney (30 %) and posterior urethral valves (24 %) had a higher incidence of CNV. Conclusion(s): The genes contained in the altered genomic regions represent novel candidates for CAKUT. This study has demonstrated that a significant proportion of patients with CAKUT harbour submicroscopic chromosomal imbalances, warranting screening in clinics for CNV.Copyright © 2014, IPNA.

Published
2015

49. The Smad3/Smad4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obstruction.

Author

Qu X., Nikolic-Paterson D.J., Li J., Bertram J.F., Caruana G., Dai L., Wang D., Ren Y., Fu P., Jiang X., Sun Y.B.Y., Jiang M., Qu X., Nikolic-Paterson D.J., Li J., Bertram J.F., Caruana G., Dai L., Wang D., Ren Y., Fu P., Jiang X., Sun Y.B.Y., and Jiang M.

Abstract

Transforming growth factor-beta1 (TGF-beta1)/Smad signaling has a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes, the functions of which are poorly understood. Here we studied Smad complex function in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice heterozygous for Smad3/4 (Smad3/4 +/-) exhibited substantial protection from renal fibrosis through day 7 of obstruction, whereas Smad2/3 +/- and Smad2/4 +/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following obstruction in wild-type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4 deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF-beta1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and Smad3-specific inhibition achieved better protection from TGF-beta1-induced fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral obstruction. Formation of this complex represents a novel target for antifibrotic therapies.Copyright © 2015 International Society of Nephrology.

Published
2015

50. A protocol for the identification and validation of novel genetic causes of kidney disease

Author

Mallett, A, Patel, C, Maier, B, McGaughran, J, Gabbett, M, Takasato, M, Cameron, A, Trnka, P, Alexander, SI, Rangan, G, Tchan, MC, Caruana, G, John, G, Quinlan, C, McCarthy, HJ, Hyland, V, Hoy, WE, Wolvetang, E, Taft, R, Simons, C, Healy, H, Little, M, Mallett, A, Patel, C, Maier, B, McGaughran, J, Gabbett, M, Takasato, M, Cameron, A, Trnka, P, Alexander, SI, Rangan, G, Tchan, MC, Caruana, G, John, G, Quinlan, C, McCarthy, HJ, Hyland, V, Hoy, WE, Wolvetang, E, Taft, R, Simons, C, Healy, H, and Little, M

Abstract

BACKGROUND: Genetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10 % of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD. METHODS/DESIGN: This study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra-renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed. DISCUSSION: This investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology.

Published
2015

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