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1. Infections in liver and lung transplant recipients. A national prospective cohort

Author

Gagliotti, Carlo, Morsillo, Filomena, Moro, Maria Luisa, Masiero, Lucia, Procaccio, Francesco, Vespasiano, Francesca, Pantosti, Annalisa, Monaco, Monica, Errico, Giulia, Ricci, Andrea, Grossi, Paolo, Nanni Costa, Alessandro, Adorno, D., Ambretti, S., Amoroso, A., Arghittu, M., Berloco, P., Bertani, A., Bonizzoli, M., Cambieri, P., Canzonieri, M., Caprio, M., Carrara, E., Carrinola, R., Cibelli, E., Cillo, U., Colledan, M., Colombo, R., Coluccio, E., Conaldi, P. G., Cusi, M., D’Armini, A. M., da Riva, A., D’Auria, B., de Carlis, L., de Cillia, C., de Gasperi, A., Di Caro, A., Di Ciaccio, P., Dondossola, D., Farina, C., Feltrin, G., Finarelli, A. C., Fossati, L., Gaibani, P., Garcia Fernandez, A., Gesu, G., Giacometti, R., Gona, F., Gridelli, B., Henrici de Angelis, L., Landini, M. P., Maldarelli, F., Mancini, C., Marone, P., Mularoni, A., Paglialunga, G., Paladini, P., Palù, G., Parisi, S., Peris, A., Pinna, A. D., Platto, M., Pugliese, F., Puoti, F., Rago, C., Ravini, M., Rea, F., Rinaldi, M., Rossi, G., Rossi, L., Rossi, M., Salizzoni, M., Sangiorgi, G., Santambrogio, L., Spada, M., Sparacino, V., Stella, F., Torelli, R., Torresani, E., Tosi, D., Vailati, F., Valeri, M., Venuta, F., Vesconi, S., Viale, P., Vismara, C., Gagliotti, C, Morsillo, F, Moro, M, Masiero, L, Procaccio, F, Vespasiano, F, Pantosti, A, Monaco, M, Errico, G, Ricci, A, Grossi, P, Nanni Costa, A, Adorno, D, Ambretti, S, Amoroso, A, Arghittu, M, Berloco, P, Bertani, A, Bonizzoli, M, Cambieri, P, Canzonieri, M, Caprio, M, Carrara, E, Carrinola, R, Cibelli, E, Cillo, U, Colledan, M, Colombo, R, Coluccio, E, Conaldi, P, Cusi, M, D’Armini, A, da Riva, A, D’Auria, B, de Carlis, L, de Cillia, C, de Gasperi, A, Di Caro, A, Di Ciaccio, P, Dondossola, D, Farina, C, Feltrin, G, Finarelli, A, Fossati, L, Gaibani, P, Garcia Fernandez, A, Gesu, G, Giacometti, R, Gona, F, Gridelli, B, Henrici de Angelis, L, Landini, M, Maldarelli, F, Mancini, C, Marone, P, Mularoni, A, Paglialunga, G, Paladini, P, Palù, G, Parisi, S, Peris, A, Pinna, A, Platto, M, Pugliese, F, Puoti, F, Rago, C, Ravini, M, Rea, F, Rinaldi, M, Rossi, G, Rossi, L, Rossi, M, Salizzoni, M, Sangiorgi, G, Santambrogio, L, Spada, M, Sparacino, V, Stella, F, Torelli, R, Torresani, E, Tosi, D, Vailati, F, Valeri, M, Venuta, F, Vesconi, S, Viale, P, Vismara, C, Gagliotti, Carlo, Morsillo, Filomena, Moro, Maria Luisa, Masiero, Lucia, Procaccio, Francesco, Vespasiano, Francesca, Pantosti, Annalisa, Monaco, Monica, Errico, Giulia, Ricci, Andrea, Grossi, Paolo, Costa, Alessandro Nanni, Adorno, Domenico, Ambretti, Simone, Amoroso, Antonio, Arghittu, Milena, Berloco, Pasquale, Bertani, Alessandro, Bonizzoli, Manuela, Cambieri, Patrizia, Canzonieri, Marco, Caprio, Mario, Carrara, Elena, Carrinola, Rosaria, Cibelli, Eva, Cillo, Umberto, Colledan, Michele, Colombo, Rosaria, Coluccio, Elena, Conaldi, Pier Giulio, Cusi, Mariagrazia, D’Armini, Andrea Maria, Da Riva, Adelaide, D'Auria, Bianca, De Carlis, Luciano, De Cillia, Carlo, De Gasperi, Andrea, Di Caro, Antonino, Di Ciaccio, Paola, Dondossola, Daniele, Farina, Claudio, Feltrin, Giuseppe, Finarelli, Alba Carola, Fossati, Lucina, Gaibani, Paolo, Fernandez, Aurora Garcia, Gesu, Giovanni, Giacometti, Raffaella, Gona, Floriana, Gridelli, Bruno, De Angelis, Lucia Henrici, Landini, Maria Paola, Maldarelli, Federica, Mancini, Carlo, Marone, Piero, Mularoni, Alessandra, Paglialunga, Giulia, Paladini, Piero, Palù, Giorgio, Parisi, Saverio, Peris, Adriano, Pinna, Antonio Daniele, Platto, Marco, Pugliese, Francesco, Puoti, Francesca, Rago, Claudio, Ravini, Mario, Rea, Federico, Rinaldi, Mauro, Rossi, Giorgio, Rossi, Lucia, Rossi, Massimo, Salizzoni, Mauro, Sangiorgi, Gabriela, Santambrogio, Luigi, Spada, Marco, Sparacino, Vito, Stella, Franco, Torelli, Rosanna, Torresani, Erminio, Tosi, Davide, Vailati, Francesca, Valeri, Maurizio, Venuta, Federico, Vesconi, Sergio, Viale, Pierluigi, and Vismara, Chiara

Subjects
Microbiology (medical), Infectious Diseases, Male, 0301 basic medicine, medicine.medical_treatment, Drug Resistance, Transplant Recipient, 030230 surgery, Liver transplantation, Postoperative Complications, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Medicine, Cumulative incidence, Prospective Studies, Prospective cohort study, Incidence, Incidence (epidemiology), Mortality rate, Bacterial, Bacterial Infections, General Medicine, Middle Aged, lung transplant, Anti-Bacterial Agents, infectious, Italy, Female, Multiple, Adult, Bacteria, Humans, Transplant Recipients, Liver Transplantation, Lung Transplantation, Human, medicine.medical_specialty, 030106 microbiology, Bacterial Infection, Infectious Diseases, transplantation, 03 medical and health sciences, Internal medicine, Anti-Bacterial Agent, Lung transplantation, business.industry, lung transplant, liver transplant, infectious, Transplantation, Prospective Studie, liver transplant, Etiology, Postoperative Complication, business, transplantation
Abstract

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Published
2018

2. Retrospective screening of solid organ donors in Italy, 2009, reveals unpredicted circulation of West Nile virus

Author

Capobianchi, Mr, Sambri, V, Castilletti, C, Pierro, Am, Rossini, G, Gaibani, P, Cavrini, F, Selleri, M, Meschi, S, Lapa, D, Di Caro, A, Grossi, P, De Cillia, C, Venettoni, S, Landini, Mp, Ippolito, G, Nanni Costa, A, Italian Transplant Network Collaborators: Scalamogna, M, Famulari, A, Saracino, A, Giacon, B, Mancini, P, Di Florio, E, Ridolfi, L, Peressutti, R, Adorno, D, Castiglione, Ag, Vesconi, S, Testasecca, D, Amoroso, Antonio, Schena, Fp, Carcassi, C, Sparacino, V, Lippi, R, Gabardi, E, Gambelunghe, C, Calabrò, F., Capobianchi M.R., Sambri V., Castilletti C., Pierro A.M., Rossini G., Gaibani P., Cavrini F., Selleri M., Meschi S., Lapa D., Di Caro A., Grossi P., De Cillia C., Venettoni S., Landini M., Ippolito G., and Nanni Costa A.

Subjects
SOLID ORGAN TRANSPLANT, Adult, organ donor, Epidemiology, West Nile virus, animal diseases, viruses, medicine.disease_cause, Virus, Flaviviridae, West nile virus, screening, transplantation, Predictive Value of Tests, Virology, medicine, Humans, Aged, Retrospective Studies, Aged, 80 and over, biology, business.industry, Transmission (medicine), SEROPREVALENCE, Public Health, Environmental and Occupational Health, virus diseases, Retrospective cohort study, Middle Aged, biology.organism_classification, Health Surveys, Tissue Donors, nervous system diseases, Transplantation, Flavivirus, Italy, Immunology, Risk assessment, business, West Nile Fever
Abstract

Since the occurrence of West Nile virus (WNV) infection in humans in 2008 in Italy, concerns have been raised about the potential risks associated with solid organ transplantation (SOT). A nationwide retrospective survey showed that 1.2% of SOT donors in 2009 were WNV-seropositive and demonstrated that human WNV infection is distributed throughout several Italian regions. Transmission of WNV or other arboviruses through SOT is a possibility and risk assessment should be carried out before SOT to avoid infection through transplantation.

3. Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy

Author

Rosaria Carrinola, P. Paladini, A. Garcia Fernandez, M. Bonizzoli, E. Coluccio, Marco Spada, L. Henrici De Angelis, Alessandro Bertani, M. Valeri, Mauro Rinaldi, P. Di Ciaccio, Simone Ambretti, A. Ricci, Paolo Gaibani, Claudio Farina, L. De Carlis, Giulia Errico, S. D’Arezzo, F. Vailati, M. Canzonieri, M. Caprio, Antonio Daniele Pinna, E. Carrara, Giorgio Palù, G. Feltrin, Francesco Pugliese, C. Rago, M. Ravini, G. Sangiorgi, R. Colombo, P. Cambieri, C. De Cillia, Pier Giulio Conaldi, B. D’Auria, Erminio Torresani, G. P. Gesu, Alessandra Mularoni, A De Gasperi, Giorgio Rossi, A. Peris, Bruno Gridelli, Milena Arghittu, Mauro Salizzoni, Saverio Giuseppe Parisi, Paolo Grossi, M. Platto, V. Sparacino, P. Viale, Lucia Masiero, A. Nanni Costa, M. P. Landini, A. Da Riva, Daniele Dondossola, Antonio Amoroso, Carlo Gagliotti, R. Torelli, D. Adorno, M. Cusi, Floriana Gona, Luigia Rossi, P.B. Berloco, G. Paglialunga, Federico Venuta, Piero Marone, U. Cillo, Francesca Vespasiano, A C Finarelli, L. Fossati, Davide Tosi, A. Maria D’Armini, Federica Maldarelli, Massimiliano Rossi, Federico Rea, Francesco Procaccio, Michele Colledan, Annalisa Pantosti, Filomena Morsillo, C. Vismara, R. Giacometti, Sergio Vesconi, C. Mancini, C. Venditti, Francesca Puoti, Luigi Santambrogio, A. Di Caro, Maria Luisa Moro, F. Stella, E. Cibelli, Monica Monaco, Errico G., Gagliotti C., Monaco M., Masiero L., Gaibani P., Ambretti S., Landini M.P., D'Arezzo S., Di Caro A., Parisi S.G., Palu G., Vespasiano F., Morsillo F., Moro M.L., Procaccio F., Ricci A., Grossi P.A., Pantosti A., Nanni Costa A., Farina C., Vailati F., Gesu G., Vismara C., Arghittu M., Colombo R., Torresani E., Rossi L., Conaldi P.G., Gona F., Cambieri P., Marone P., Venditti C., Fernandez A.G., Mancini C., Cusi M., De Angelis L.H., Fossati L., Finarelli A.C., De Cillia C., Sangiorgi G., Pinna A.D., Stella F., Viale P., Colledan M., Platto M., Bonizzoli M., Peris A., Torelli R., Vesconi S., Cibelli E., De Carlis L., De Gasperi A., Ravini M., Carrinola R., Coluccio E., Dondossola D., Rossi G., Santambrogio L., Tosi D., Feltrin G., Rago C., Cillo U., Da Riva A., Rea F., Sparacino V., Bertani A., Canzonieri M., Gridelli B., Mularoni A., Spada M., Carrara E., D'Armini A.M., Paladini P., Adorno D., Valeri M., Caprio M., Di Ciaccio P., Puoti F., Berloco P., D'Auria B., Maldarelli F., Paglialunga G., Pugliese F., Rossi M., Venuta F., Amoroso A., Giacometti R., Rinaldi M., Salizzoni M., Errico, G, Gagliotti, C, Monaco, M, Masiero, L, Gaibani, P, Ambretti, S, Landini, M, D'Arezzo, S, Di Caro, A, Parisi, S, Palu, G, Vespasiano, F, Morsillo, F, Moro, M, Procaccio, F, Ricci, A, Grossi, P, Pantosti, A, Nanni Costa, A, Farina, C, Vailati, F, Gesu, G, Vismara, C, Arghittu, M, Colombo, R, Torresani, E, Rossi, L, Conaldi, P, Gona, F, Cambieri, P, Marone, P, Venditti, C, Fernandez, A, Mancini, C, Cusi, M, De Angelis, L, Fossati, L, Finarelli, A, De Cillia, C, Sangiorgi, G, Pinna, A, Stella, F, Viale, P, Colledan, M, Platto, M, Bonizzoli, M, Peris, A, Torelli, R, Vesconi, S, Cibelli, E, De Carlis, L, De Gasperi, A, Ravini, M, Carrinola, R, Coluccio, E, Dondossola, D, Rossi, G, Santambrogio, L, Tosi, D, Feltrin, G, Rago, C, Cillo, U, Da Riva, A, Rea, F, Sparacino, V, Bertani, A, Canzonieri, M, Gridelli, B, Mularoni, A, Spada, M, Carrara, E, D'Armini, A, Paladini, P, Adorno, D, Valeri, M, Caprio, M, Di Ciaccio, P, Puoti, F, Berloco, P, D'Auria, B, Maldarelli, F, Paglialunga, G, Pugliese, F, Rossi, M, Venuta, F, Amoroso, A, Giacometti, R, Rinaldi, M, and Salizzoni, M

Subjects
0301 basic medicine, Male, Colonization, Klebsiella pneumoniae, medicine.medical_treatment, Drug Resistance, Transplant Recipient, Liver transplantation, beta-Lactamase, Cohort Studies, 0302 clinical medicine, 80 and over, 030212 general & internal medicine, Prospective Studies, Screening cultures, Prospective cohort study, Child, Aged, 80 and over, biology, Bacterial, Enterobacteriaceae Infections, General Medicine, Middle Aged, Tissue Donors, Infectious Diseases, Italy, Child, Preschool, Female, Infection, Human, Lung Transplantation, Adult, Microbiology (medical), medicine.medical_specialty, Adolescent, 030106 microbiology, Tissue Donor, Bacterial Protein, beta-Lactamases, 03 medical and health sciences, Young Adult, Bacterial Proteins, Internal medicine, Drug Resistance, Bacterial, medicine, Humans, Preschool, Genotyping, Contraindication, Donor–recipient transmission, Aged, business.industry, CPE, Solid organ transplant, Infant, Liver Transplantation, Transplant Recipients, Carbapenem-Resistant Enterobacteriaceae, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Enterobacteriaceae Infection, Transplantation, Prospective Studie, Multilocus sequence typing, Cohort Studie, business
Abstract

Objectives A prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. Methods Between 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. Results Of 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor–recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-β-lactamase (VIM)-producing Enterobacter aerogenes. Conclusions This study showed a low risk of donor–recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres.

Published
2019

4. The histological assessment of liver fibrosis in grafts from extended criteria donors predicts the outcome after liver transplantation: A retrospective study

Author

Mattia Riefolo, Giacomo Santandrea, Carlo de Cillia, Matteo Cescon, Melissa Monica, Antonia D'Errico, Francesco Vasuri, Vanessa De Pace, Matteo Ravaioli, Matteo Serenari, D'Errico A., Riefolo M., Serenari M., De Pace V., Santandrea G., Monica M., de Cillia C., Ravaioli M., Cescon M., and Vasuri F.

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Histopathology, Context (language use), Dyslipidemic donor, Liver transplantation, Gastroenterology, Donor Selection, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Fibrosis, Cause of Death, Internal medicine, Biopsy, medicine, Humans, Early allograft dysfunction, Portal fibrosis, Aged, Dyslipidemias, Retrospective Studies, Hepatology, medicine.diagnostic_test, business.industry, Incidence, Graft Survival, Middle Aged, medicine.disease, Survival Analysis, Liver Transplantation, Treatment Outcome, surgical procedures, operative, Italy, 030220 oncology & carcinogenesis, Liver biopsy, Female, 030211 gastroenterology & hepatology, business, Dyslipidemia
Abstract

Background The use of extended criteria donors (ECD) in liver transplantation is increasing due to the organ shortage. Histological evaluation of the liver graft in the context of procurement is an important tool for extending the donor pool without affecting the quality of the transplanted organs. Macrovesicular steatosis is widely accepted as predictor of early allograft dysfunction (EAD), while other features, such as portal fibrosis, are poorly studied. Aim To identify morphological features, other than macrovesicular steatosis, that may affect recipients’ outcome. Methods Between 2014 and 2016, 132 donors with extended criteria underwent pre-transplant liver biopsy during procurement. Histological variables of the graft, donors’/recipients’ clinical data, EAD and patient/graft survival were registered. Results The recipients who received a graft with histological-proven portal fibrosis had a significant lower patient and graft survival in comparison to patients without fibrosis (P = 0.044 and P = 0.039, respectively). Donors’ dyslipidemia was significantly associated with the occurrence of EAD (P = 0.021). When dyslipidemia was combined with histological liver fibrosis a 54.5% incidence of EAD was observed (P = 0.012). Conclusions The histological assessment of liver fibrosis in pre-transplant biopsy of ECD grafts, together with donor’s clinical data, provides important information on recipients’ outcome.

Published
2020
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5. Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors

Author

Francesco Vasuri, Antonia D'Errico, Carlo de Cillia, Deborah Malvi, Matteo Ravaioli, Costantino Ricci, Massimo Cardillo, Michelangelo Fiorentino, Francesca Ambrosi, Ambrosi F., Ricci C., Malvi D., De Cillia C., Ravaioli M., Fiorentino M., Cardillo M., Vasuri F., and D'errico A.

Subjects
medicine.medical_specialty, lcsh:Internal medicine, lcsh:Specialties of internal medicine, 030232 urology & nephrology, Chromophobe cell, 030204 cardiovascular system & hematology, urologic and male genital diseases, Kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, lcsh:RC581-951, medicine, Stage (cooking), lcsh:RC31-1245, Risk assessment, Frozen section procedure, business.industry, Papillary Adenoma, Cancer, General Medicine, Cancer transmission, medicine.disease, Donor evaluation, Original Article, Radiology, business, Clear cell
Abstract

Background : We report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission. Methods : From the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs. Results : The evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed: 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients. Conclusion : Donors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists.

Published
2020

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