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1. Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease

Author

Birolini, G, Valenza, M, Ottonelli, I, Talpo, F, Minoli, L, Cappelleri, A, Bombaci, M, Caccia, C, Canevari, C, Trucco, A, Leoni, V, Passoni, A, Favagrossa, M, Nucera, M, Colombo, L, Paltrinieri, S, Bagnati, R, Duskey, J, Caraffi, R, Vandelli, M, Taroni, F, Salmona, M, Scanziani, E, Biella, G, Ruozi, B, Tosi, G, Cattaneo, E, Birolini G., Valenza M., Ottonelli I., Talpo F., Minoli L., Cappelleri A., Bombaci M., Caccia C., Canevari C., Trucco A., Leoni V., Passoni A., Favagrossa M., Nucera M. R., Colombo L., Paltrinieri S., Bagnati R., Duskey J. T., Caraffi R., Vandelli M. A., Taroni F., Salmona M., Scanziani E., Biella G., Ruozi B., Tosi G., Cattaneo E., Birolini, G, Valenza, M, Ottonelli, I, Talpo, F, Minoli, L, Cappelleri, A, Bombaci, M, Caccia, C, Canevari, C, Trucco, A, Leoni, V, Passoni, A, Favagrossa, M, Nucera, M, Colombo, L, Paltrinieri, S, Bagnati, R, Duskey, J, Caraffi, R, Vandelli, M, Taroni, F, Salmona, M, Scanziani, E, Biella, G, Ruozi, B, Tosi, G, Cattaneo, E, Birolini G., Valenza M., Ottonelli I., Talpo F., Minoli L., Cappelleri A., Bombaci M., Caccia C., Canevari C., Trucco A., Leoni V., Passoni A., Favagrossa M., Nucera M. R., Colombo L., Paltrinieri S., Bagnati R., Duskey J. T., Caraffi R., Vandelli M. A., Taroni F., Salmona M., Scanziani E., Biella G., Ruozi B., Tosi G., and Cattaneo E.

Abstract

Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing (“early treatment”) or reversing (“late treatment”) HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic (“early treatment”) or symptomatic (“late treatment”) stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments (“2 cycle treatment”) lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. Data availability: This study does not include data deposit

Published
2023

5. A Novel In Silico Benchmarked Pipeline Capable of Complete Protein Analysis: A Possible Tool for Potential Drug Discovery

Author

D. D. B. D. Perera, K. Minoli L. Perera, and Dinithi C. Peiris

Subjects
virtual screening, therapeutic targets, protein modulation, trifecta analysis, Biology (General), QH301-705.5
Abstract

Current in silico proteomics require the trifecta analysis, namely, prediction, validation, and functional assessment of a modeled protein. The main drawback of this endeavor is the lack of a single protocol that utilizes a proper set of benchmarked open-source tools to predict a protein’s structure and function accurately. The present study rectifies this drawback through the design and development of such a protocol. The protocol begins with the characterization of a novel coding sequence to identify the expressed protein. It then recognizes and isolates evolutionarily conserved sequence motifs through phylogenetics. The next step is to predict the protein’s secondary structure, followed by the prediction, refinement, and validation of its three-dimensional tertiary structure. These steps enable the functional analysis of the macromolecule through protein docking, which facilitates the identification of the protein’s active site. Each of these steps is crucial for the complete characterization of the protein under study. We have dubbed this process the trifecta analysis. In this study, we have proven the effectiveness of our protocol using the cystatin C and AChE proteins. Beginning with just their sequences, we have characterized both proteins’ structures and functions, including identifying the cystatin C protein’s seven-residue active site and the AChE protein’s active-site gorge via protein–protein and protein–ligand docking, respectively. This process will greatly benefit new and experienced scientists alike in obtaining a strong understanding of the trifecta analysis, resulting in a domino effect that could expand drug development.

Published
2021
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6. Cholesterol-laden brain-permeable nanoparticles support long-lasting cognitive recovery and motor amelioration in the slow-progressing zQ175DN mouse model of Huntington’s Disease

Author

Birolini, G., Valenza, M., Ilaria, O., Francesca, T., Minoli, L., Cappelleri, A., Mauro, B., Claudio, C., Valerio, L., Alice, P., Monica, F., Nucera, M.R., Laura, C., Paltrinieri, S., Renzo, B., Jason Thomas Duskey, Riccardo, C., Maria Angela Vandelli, Franco, T., Mario, S., Scanziani, E., Biella, G.R., Barbara, R., Tosi, G.F., and Cattaneo, E.

Subjects
Huntington, brain, cholesterol, nanoparticles, Settore BIO/14 - Farmacologia
Published
2022

7. PEGylated recombinant human hyaluronidase (PEGPH20) pre-treatment improves intra-tumour distribution and efficacy of paclitaxel in preclinical models

Author

Morosi, L, Meroni, M, Ubezio, P, Fuso Nerini, I, Minoli, L, Porcu, L, Panini, N, Colombo, M, Blouw, B, Kang, D, Davoli, E, Zucchetti, M, D'Incalci, M, Frapolli, R, Morosi L., Meroni M., Ubezio P., Fuso Nerini I., Minoli L., Porcu L., Panini N., Colombo M., Blouw B., Kang D. W., Davoli E., Zucchetti M., D'Incalci M., Frapolli R., Morosi, L, Meroni, M, Ubezio, P, Fuso Nerini, I, Minoli, L, Porcu, L, Panini, N, Colombo, M, Blouw, B, Kang, D, Davoli, E, Zucchetti, M, D'Incalci, M, Frapolli, R, Morosi L., Meroni M., Ubezio P., Fuso Nerini I., Minoli L., Porcu L., Panini N., Colombo M., Blouw B., Kang D. W., Davoli E., Zucchetti M., D'Incalci M., and Frapolli R.

Abstract

Background: Scarce drug penetration in solid tumours is one of the possible causes of the limited efficacy of chemotherapy and is related to the altered tumour microenvironment. The abnormal tumour extracellular matrix (ECM) together with abnormal blood and lymphatic vessels, reactive stroma and inflammation all affect the uptake, distribution and efficacy of anticancer drugs. Methods: We investigated the effect of PEGylated recombinant human hyaluronidase PH20 (PEGPH20) pre-treatment in degrading hyaluronan (hyaluronic acid; HA), one of the main components of the ECM, to improve the delivery of antitumor drugs and increase their therapeutic efficacy. The antitumor activity of paclitaxel (PTX) in HA synthase 3-overexpressing and wild-type SKOV3 ovarian cancer model and in the BxPC3 pancreas xenograft tumour model, was evaluated by monitoring tumour growth with or without PEGPH20 pre-treatment. Pharmacokinetics and tumour penetration of PTX were assessed by HPLC and mass spectrometry imaging analysis in the same tumour models. Tumour tissue architecture and HA deposition were analysed by histochemistry. Results: Pre-treatment with PEGPH20 modified tumour tissue architecture and improved the antitumor activity of paclitaxel in the SKOV3/HAS3 tumour model, favouring its accumulation and more homogeneous intra-tumour distribution, as assessed by quantitative and qualitative analysis. PEGPH20 also reduced HA content influencing, though less markedly, PTX distribution and antitumor activity in the BxPC3 tumour model. Conclusion: Remodelling the stroma of HA-rich tumours by depletion of HA with PEGPH20 pre-treatment, is a potentially successful strategy to improve the intra-tumour distribution of anticancer drugs, increasing their therapeutic efficacy, without increasing toxicity.

Published
2021

9. Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model

Author

Le Noci, V, Bernardo, G, Manenti, G, Infante, G, Hashemian, D, Minoli, L, Canesi, S, Bianchi, F, Triulzi, T, Arioli, S, De Cecco, L, Guglielmetti, S, Ambrogi, F, Recordati, C, Gagliano, N, Tagliabue, E, Sommariva, M, Sfondrini, L, Hashemian, DK, Le Noci, V, Bernardo, G, Manenti, G, Infante, G, Hashemian, D, Minoli, L, Canesi, S, Bianchi, F, Triulzi, T, Arioli, S, De Cecco, L, Guglielmetti, S, Ambrogi, F, Recordati, C, Gagliano, N, Tagliabue, E, Sommariva, M, Sfondrini, L, and Hashemian, DK

Abstract

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.

Published
2022

12. A Novel In Silico Benchmarked Pipeline Capable of Complete Protein Analysis: A Possible Tool for Potential Drug Discovery

Author

Dinithi Champika Peiris, K. Minoli L. Perera, and D. D. B. D. Perera

Subjects
Virtual screening, protein modulation, General Immunology and Microbiology, Drug discovery, QH301-705.5, In silico, Computational biology, Biology, Proteomics, virtual screening, therapeutic targets, trifecta analysis, General Biochemistry, Genetics and Molecular Biology, Protein tertiary structure, Conserved sequence, Docking (molecular), Macromolecular docking, Biology (General), General Agricultural and Biological Sciences
Abstract

Current in silico proteomics require the trifecta analysis, namely, prediction, validation, and functional assessment of a modeled protein. The main drawback of this endeavor is the lack of a single protocol that utilizes a proper set of benchmarked open-source tools to predict a protein’s structure and function accurately. The present study rectifies this drawback through the design and development of such a protocol. The protocol begins with the characterization of a novel coding sequence to identify the expressed protein. It then recognizes and isolates evolutionarily conserved sequence motifs through phylogenetics. The next step is to predict the protein’s secondary structure, followed by the prediction, refinement, and validation of its three-dimensional tertiary structure. These steps enable the functional analysis of the macromolecule through protein docking, which facilitates the identification of the protein’s active site. Each of these steps is crucial for the complete characterization of the protein under study. We have dubbed this process the trifecta analysis. In this study, we have proven the effectiveness of our protocol using the cystatin C and AChE proteins. Beginning with just their sequences, we have characterized both proteins’ structures and functions, including identifying the cystatin C protein’s seven-residue active site and the AChE protein’s active-site gorge via protein–protein and protein–ligand docking, respectively. This process will greatly benefit new and experienced scientists alike in obtaining a strong understanding of the trifecta analysis, resulting in a domino effect that could expand drug development.

Published
2021

13. A Novel

Author

D D B D, Perera, K Minoli L, Perera, and Dinithi C, Peiris

Subjects
protein modulation, virtual screening, therapeutic targets, trifecta analysis, Article
Abstract

Simple Summary Protein interactions govern the majority of an organism’s biological processes. Therefore, to fully understand the functionality of an organism, we must know how proteins work at a molecular level. This study assembled a protocol that enables scientists to construct a protein’s tertiary structure easily and subsequently to investigate its mechanism and function. Each step involved in prediction, validation, and functional analysis of a protein is crucial to obtain an accurate result. We have dubbed this the trifecta analysis. It was clear early in our research that no single study in the literature had previously encompassed the complete trifecta analysis. In particular, studies that recommend free, open-source tools that have been benchmarked for each step are lacking. The present study ensures that predictions are accurate and validated and will greatly benefit new and experienced scientists alike in obtaining a strong understanding of the trifecta analysis, resulting in a domino effect that could lead to drug development. Abstract Current in silico proteomics require the trifecta analysis, namely, prediction, validation, and functional assessment of a modeled protein. The main drawback of this endeavor is the lack of a single protocol that utilizes a proper set of benchmarked open-source tools to predict a protein’s structure and function accurately. The present study rectifies this drawback through the design and development of such a protocol. The protocol begins with the characterization of a novel coding sequence to identify the expressed protein. It then recognizes and isolates evolutionarily conserved sequence motifs through phylogenetics. The next step is to predict the protein’s secondary structure, followed by the prediction, refinement, and validation of its three-dimensional tertiary structure. These steps enable the functional analysis of the macromolecule through protein docking, which facilitates the identification of the protein’s active site. Each of these steps is crucial for the complete characterization of the protein under study. We have dubbed this process the trifecta analysis. In this study, we have proven the effectiveness of our protocol using the cystatin C and AChE proteins. Beginning with just their sequences, we have characterized both proteins’ structures and functions, including identifying the cystatin C protein’s seven-residue active site and the AChE protein’s active-site gorge via protein–protein and protein–ligand docking, respectively. This process will greatly benefit new and experienced scientists alike in obtaining a strong understanding of the trifecta analysis, resulting in a domino effect that could expand drug development.

Published
2021

18. Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA for the detection of drug resistance prior to starting first-line antiretroviral therapy with etravirine or efavirenz

Author

Geretti, Anna Maria, Conibear, Tim, Hill, Andrew, Johnson, Jeffrey A., Tambuyzer, Lotke, Thys, Kim, Vingerhoets, Johan, Van Delft, Yvon, Rieger, A., Vetter, N., Greil, R., Pedersen, C., Storgaard, M., Morlat, P., Katlama, C., Durant, J., Cotte, L., Duvivier, C., Rey, D., Esser, S., Stellbrink, C., Schmidt, W., Stoll, M., Stephan, C., Fatkenheuer, G., Stoehr, A., Rockstroh, J., Banhegyi, D., Itzchak, L., Shahar, E., Maayan, S., Turner, D., Lazzarin, A., Antinori, A., Carosi, G., Minoli, L., di Perri, G., Filice, G., Andreoni, M., Duiculescu, D., Rugina, S., Erscoiu, S., Streinu, A., Pronin, A., Pokrovsky, V., Gruzdev, B., Yakovlev, A., Voronin, E., Clotet, B., Gatell, J., Arribas, J., Podzamczer, D., Domingo, P., Alvarez, C. Miralles, Quero, J. Hernandez, Furrer, H., Feher, J., Johnson, M., Fox, J., Nelson, M., Fisher, M., and Orkin, C.

Published
2014
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19. Soluble stroma-related biomarkers of pancreatic cancer

Author

Resovi, A, Bani, M, Porcu, L, Anastasia, A, Minoli, L, Allavena, P, Cappello, P, Novelli, F, Scarpa, A, Morandi, E, Falanga, A, Torri, V, Taraboletti, G, Belotti, D, Giavazzi, R, Resovi A, Bani MR, Porcu L, Anastasia A, Minoli L, Allavena P, Cappello P, Novelli F, Scarpa A, Morandi E, Falanga A, Torri V, Taraboletti G, Belotti D, Giavazzi R, Resovi, A, Bani, M, Porcu, L, Anastasia, A, Minoli, L, Allavena, P, Cappello, P, Novelli, F, Scarpa, A, Morandi, E, Falanga, A, Torri, V, Taraboletti, G, Belotti, D, Giavazzi, R, Resovi A, Bani MR, Porcu L, Anastasia A, Minoli L, Allavena P, Cappello P, Novelli F, Scarpa A, Morandi E, Falanga A, Torri V, Taraboletti G, Belotti D, and Giavazzi R

Abstract

The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma-related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and 16 healthy subjects. A second confirmatory phase on an independent cohort of 131 PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and PLG Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC = 0.99, 99% CI = 0.98-1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92-0.99) and PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI = 0.88-0.99). Five molecules were associated with PanIN development in two GEM models of PDAC (PdxCre/LSL-KrasG12D and PdxCre/LSL-KrasG12D/+/LSL-Trp53R172H/+), suggesting their potential for detecting early disease. These markers were also elevated in patient-derived orthotopic PDAC xenografts and associated with response to chemotherapy. The identified stroma-related soluble biomarkers represent potential tools for PDAC diagnosis and for monitoring treatment response of PDAC patients

Published
2018

20. Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin

Author

Capasso Palmiero, U, Morosi, L, Bello, E, Ponzo, M, Frapolli, R, Matteo, C, Ferrari, M, Zucchetti, M, Minoli, L, De Maglie, M, Romanelli, P, Morbidelli, M, D'Incalci, M, Moscatelli, D, Capasso Palmiero U., Morosi L., Bello E., Ponzo M., Frapolli R., Matteo C., Ferrari M., Zucchetti M., Minoli L., De Maglie M., Romanelli P., Morbidelli M., D'Incalci M., Moscatelli D., Capasso Palmiero, U, Morosi, L, Bello, E, Ponzo, M, Frapolli, R, Matteo, C, Ferrari, M, Zucchetti, M, Minoli, L, De Maglie, M, Romanelli, P, Morbidelli, M, D'Incalci, M, Moscatelli, D, Capasso Palmiero U., Morosi L., Bello E., Ponzo M., Frapolli R., Matteo C., Ferrari M., Zucchetti M., Minoli L., De Maglie M., Romanelli P., Morbidelli M., D'Incalci M., and Moscatelli D.

Abstract

The improvement of the pharmacological profile of lipophilic drug formulations is one of the main successes achieved using nanoparticles (NPs) in medicine. However, the complex synthesis procedure and numerous post-processing steps hamper the cost-effective use of these formulations. In this work, an approach which requires only a syringe to produce self-assembling biodegradable and biocompatible poly(caprolactone)-based NPs is developed. The effective synthesis of monodisperse NPs has been made possible by the optimization of the block-copolymer synthesized via a combination of ring opening polymerization and reversible addition-fragmentation chain transfer polymerization. These NPs can be used to formulate lipophilic drugs that are barely soluble in water, such as trabectedin, a potent anticancer therapeutic. Its biodistribution and antitumor activity have been compared with the commercially available formulation Yondelis®. The results indicate that this trabectedin NP formulation performs with the same antitumor activity as Yondelis®, but does not have the drawback of severe local vascular toxicity in the injection site.

Published
2018

21. FoxO-1 contributes to the efficacy of the combination of the XPO1 inhibitor selinexor and cisplatin in ovarian carcinoma preclinical models

Author

Corno, C, Stucchi, S, De Cesare, M, Carenini, N, Stamatakos, S, Ciusani, E, Minoli, L, Scanziani, E, Argueta, C, Landesman, Y, Zaffaroni, N, Gatti, L, Perego, P, Corno C., Stucchi S., De Cesare M., Carenini N., Stamatakos S., Ciusani E., Minoli L., Scanziani E., Argueta C., Landesman Y., Zaffaroni N., Gatti L., Perego P., Corno, C, Stucchi, S, De Cesare, M, Carenini, N, Stamatakos, S, Ciusani, E, Minoli, L, Scanziani, E, Argueta, C, Landesman, Y, Zaffaroni, N, Gatti, L, Perego, P, Corno C., Stucchi S., De Cesare M., Carenini N., Stamatakos S., Ciusani E., Minoli L., Scanziani E., Argueta C., Landesman Y., Zaffaroni N., Gatti L., and Perego P.

Abstract

The XPO1/CRM1 inhibitor selinexor (KPT-330), is currently being evaluated in multiple clinical trials as an anticancer agent. XPO1 participates in the nuclear export of FoxO-1, which we previously found to be decreased in platinum-resistant ovarian carcinoma. The aim of this study was to determine whether enriching FoxO-1 nuclear localization using selinexor would increase ovarian cancer cell sensitivity to cisplatin. Selinexor, as a single agent, displayed a striking antiproliferative effect in different ovarian carcinoma cell lines. A schedule-dependent synergistic effect of selinexor in combination with cisplatin was found in cisplatin-sensitive IGROV-1, the combination efficacy being more evident in sensitive than in the resistant cells. In IGROV-1 cells, the combination was more effective when selinexor followed cisplatin exposure. A modulation of proteins involved in apoptosis (p53, Bax) and in cell cycle progression (p21WAF1) was found by Western blotting. Selinexor-treated cells exhibited enriched FoxO-1 nuclear staining. Knock-down experiments with RNA interference indicated that FOXO1-silenced cells displayed a reduced sensitivity to selinexor. FOXO1 silencing also tended to reduce the efficacy of the drug combination at selected cisplatin concentrations. Selinexor significantly inhibited tumor growth, induced FoxO-1 nuclear localization and improved the efficacy of cisplatin in IGROV-1 xenografts. Taken together, our results support FoxO-1 as one of the key factors promoting sensitivity towards selinexor and the synergistic interaction between cisplatin and selinexor in ovarian carcinoma cells with selected molecular backgrounds, highlighting the need for treatment regimens tailored to the molecular tumor features.

Published
2018

24. Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial

Author

Fätkenheuer, G., Duvivier, C., Rieger, A., Durant, J., Rey, D., Schmidt, W., Hill, A., van Delft, Y., Marks, S., Rieger, A., Vetter, N., Greil, R., Pedersen, C., Storgaard, M., Morlat, P., Katlama, C., Durant, J., Cotte, L., Duvvier, C., Rey, D., Esser, S., Stellbrink, C., Schmidt, W., Stoll, M., Stephan, C., Fatkenheuer, G., Stoehr, A., Rockstroh, J., Banhegyi, D., Itzchak, L., Shahar, E., Maayan, S., Turner, D., Lazzarin, A., Antinori, A., Carosi, G., Minoli, L., di Perri, G., Filice, G., Andreoni, M., Duiculescu, D., Rugina, S., Erscoiu, S., Streinu, A., Pronin, A., Pokrovsky, V., Gruzdev, B., Yakovlev, A., Voronin, E., Clotet, B., Gatell, J., Arribas, J., Podzamczer, D., Domingo, P., Miralles Alvarez, C., Hernandez Quero, J., Furrer, H., Feher, J., Johnson, M., Fox, J., Nelson, M., Fisher, M., and Orkin, C.

Published
2012
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26. Tumor progression and metastatic dissemination in ovarian cancer after dose-dense or conventional paclitaxel and cisplatin plus bevacizumab

Author

Bizzaro, F, Falcetta, F, D’Agostini, E, Decio, A, Minoli, L, Erba, E, Peccatori, AF, Scanziani, E, Colombo, N, Zucchetti, M, Bani, MR, Ubezio, P, Giavazzi, R, Bizzaro, F, Falcetta, F, D’Agostini, E, Decio, A, Minoli, L, Erba, E, Peccatori, A, Scanziani, E, Colombo, N, Zucchetti, M, Bani, M, Ubezio, P, and Giavazzi, R

Subjects
Ovarian Neoplasms, Cancer Research, Paclitaxel, Mice, Nude, Apoptosis, Xenograft Model Antitumor Assays, Cystadenocarcinoma, Serous, Bevacizumab, Mice, ovarian cancer, Oncology, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Tumor Cells, Cultured, Animals, Humans, metastasi, Female, xenograft, Cisplatin, Peritoneal Neoplasms, Cell Proliferation
Abstract

The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time-windows in two patient-derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short-term effects on cell cycle, tumor cell proliferation/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose-dense (with/without DDP) was superior to the conventional scheme in a dose-dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP/PTX dose-dense-high (only chemotherapy) was at least as active as DDP/PTX conventional plus bevacizumab. DDP/PTX dose-dense-high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule-dose of the treatment and help to explain the unclear benefits after bevacizumab.

Published
2017

32. OC.04.4 EMILIN1 DEFICIENCY AFFECTS EXPERIMENTAL COLITIS AND COLON CARCINOGENESIS ENHANCING LYMPHATIC DYSFUNCTION

Author

Capuano, A., primary, Bosisio, G., additional, Pivetta, E., additional, Scanziani, E., additional, Minoli, L., additional, Maiero, S., additional, Magris, R., additional, Bortoluzzi, S., additional, Gaffo, E., additional, Cannizzaro, R., additional, Doliana, R., additional, Colombatti, A., additional, and Spessotto, P., additional

Published
2019
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34. Tumor progression and metastatic dissemination in ovarian cancer after dose-dense or conventional paclitaxel and cisplatin plus bevacizumab

Author

Bizzaro, F, Falcetta, F, D’Agostini, E, Decio, A, Minoli, L, Erba, E, Peccatori, A, Scanziani, E, Colombo, N, Zucchetti, M, Bani, M, Ubezio, P, Giavazzi, R, Peccatori, AF, Bani, MR, Bizzaro, F, Falcetta, F, D’Agostini, E, Decio, A, Minoli, L, Erba, E, Peccatori, A, Scanziani, E, Colombo, N, Zucchetti, M, Bani, M, Ubezio, P, Giavazzi, R, Peccatori, AF, and Bani, MR

Abstract

The efficacy of therapeutic regimens incorporating weekly or every-3-weeks paclitaxel (PTX) for ovarian cancer is debated. We investigated the addition of bevacizumab in regimens of chemotherapy with different PTX doses and schedules in preclinical models. Treatments were cisplatin (DDP) with weekly PTX (conventional), or dose-dense-equi (every other day to the conventional cumulative dose), or dose-dense-high (total dose 1.5 times higher), with or without bevacizumab. Treatment efficacy was evaluated analyzing tumor growth in different time-windows in two patient-derived ovarian cancer xenografts with different sensitivity to cisplatin. Tumor progression, metastasis and survival were studied in ovarian cancer models growing orthotopically and disseminating in the mouse peritoneal cavity. Short-term effects on cell cycle, tumor cell proliferation/apoptosis and vasculature were evaluated by flow cytometry and immunohistochemistry. PTX dose-dense (with/without DDP) was superior to the conventional scheme in a dose-dependent manner; the high efficacy was confirmed by the lower ratio of tumor to normal cells. All schemes benefited from bevacizumab, which reduced tumor vessels. However, DDP/PTX dose-dense-high (only chemotherapy) was at least as active as DDP/PTX conventional plus bevacizumab. DDP/PTX dose-dense-high plus bevacizumab was the most effective in delaying tumor progression, though it did not prolong mouse survival and the continuous treatment with bevacizumab was associated with a malignant disease. These findings indicate that the effect of bevacizumab in combination with chemotherapy may depend on the schedule-dose of the treatment and help to explain the unclear benefits after bevacizumab

Published
2018

37. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

Author

Wilcox, M. H., Gerding, D. N., Poxton, I. R., Kelly, C., Nathan, R., Birch, T., Cornely, O. A., Rahav, G., Bouza, E., Lee, C., Jenkin, G., Jensen, W., Kim, Y. -S., Yoshida, J., Gabryelski, L., Pedley, A., Eves, K., Tipping, R., Guris, D., Kartsonis, N., Playford G, Dorr M. -B., Mcgechie, D, Iredell, J, Allworth, A, Cheng, A, Choi, Nj, Thalhammer, F, Maieron, A, Wenisch, C, Meyer, B, Jacobs, F, Delmee, M, Peetermans, W, Giot, Jb, Munhoz, Al, Kallas, Eg, Ladeira, Jp, Bernstein, Cn, Grimard, D, Mcgeer, A, Poirier, A, Valiquette, L, Miller, M, Oughton, M, Trottier, S, Dolce, P, Smyth, D, Gambra, P, Palma, S, Rojas, L, Northland, R, Arellano, Mc, Perez, J, Barreto, Mf, Gomez, Jm, Ramirez, I, Correa, A, Onate, J, Rohacova, H, Stastnik, M, Zjevikova, A, Blazek, J, Kumpel, P, Petersen, Am, Gluud, Ll, Staugaard, Hm, Tvede, M, Glerup, H, Madsen, Sm, Helms, M, Naumann, R, Karthaus, M, Reinshagen, M, Raz, R, Giladi, M, Chowers, M, Bishara, J, Quirino, T, Castelli, F, Bassetti, M, Rizzardini, G, Vismara, E, Puoti, M, Viale, P, Menichetti, F, Cauda, R, Bonfanti, P, Franzetti, F, Gori, A, Minoli, L, Noriega, Er, Mills, Gd, Ritchie, S, Burns, A, Pithie, A, dos Santos RM, Aldomiro, F, Fernando, Pb, Rola, J, Reis, E, Van Zyl JH, Aboo, N, Richards, G, Hernandez, Mj, de Medrano VA, Prunonosa, Lm, Gonzalez, Jl, Reinoso, Jc, Martinez, Ar, Cisneros, Jd, Banos, Jr, Sheridan, R, Minton, J, Williams, J, Stanley, P, Guleri, A, Llewelyn, M, Todd, N, Barlow, G, Bacon, Ae, Baird, Im, Baxter, R, Zenilman, Jm, Beshay, M, Betts, Rf, Brettholz, Em, Buitrago, Mi, Carlson, Rw, Cook, Pp, Dupont, Hl, Foley, C, Freilich, B, Giron, Ja, Golan, Y, Green, S, Hall, Mc, Johnson, Dj, Jones, Rk, Graham, Dr, Kazimir, M, Keating, M, Brumble, Lm, Kumar, Pn, Liappis, Ap, Libke, R, Mehra, Pk, Overcash, Sj, Mullane, Km, Nguyen, Mh, Patel, Mc, Powers, Ck, Pullman, J, Keegan, J, Nepal, S, English, G, Ricci, Rl, Risi, Gf, Rodriguez, M, Schmitt, Cm, Sims, Md, Kamepalli, R, Tural, A, Vazquez, Ja, Alangaden, Gj, Weavind, Lm, Young, Ma, Chen, St, Liu, E, Nguyen, Hh, Alfonso, Tb, Muse, Dd, Orenstein, R, Yacyshyn, B, Gebhard, Re, Dinges, W, Bolton, M, Rubin, M, Kuemmerle, Jf, Limaye, Ap, Friedenberg, Ka, Hiemenz, Jw, Quadri, A, Martinez, Jv, Barcan, La, Cordova, E, Mykietiuk, A, Losso, M, Fedorak, Rn, Steiner, T, Gerson, M, Weiss, K, Dlouhy, P, Vitous, A, Benes, J, Husa, P, Knizek, P, Anttila, Vj, Broas, M, Camou, F, Postil, D, Launay, O, Corroyer-Simovic, B, Meynard, Jl, Schneider, S, Molina, Jm, Neau, D, Zalcman, G, Boutoille, D, Ostermann, H, Heinz, W, Reuter, S, Oren, I, Schiff, E, Umemoto, T, Masubuchi, T, Mukawa, K, Yasuda, K, Imokawa, S, Fukuda, K, Ohta, H, Harada, N, Fujii, S, Tamaki, S, Yasui, S, Furukawa, K, Takahashi, M, Uraoka, T, Watanabe, M, Ikehara, Y, Kodaira, M, Komatsu, H, Higashi, K, Taguchi, F, Ura, N, Serizawa, Y, Fukuchi, T, Ashikawa, T, Shabana, M, Okubo, M, Matsumoto, M, Kurihara, A, Miyasaka, E, Shimizu, M, Tominaga, H, Kubota, T, Kashiwazaki, M, Masuda, Y, Terasaki, S, Okafuji, H, Mieno, H, Urabe, T, Okamoto, E, Kajimura, M, Yamagishi, Y, Rydzewska, G, Mach, T, Ciechanowski, K, Podlasin, R, Tomasiewicz, K, Janczewska-Kazek, E, Czarnobilski, K, Halota, W, Gryglewska, B, Plesniak, R, Dabrowiecki, P, Lipowski, D, Simanenkov, V, Shcheglova, L, Uspenskiy, Y, Cheganov, A, Han, Ds, Kim, Js, Hong, Sp, Kim, Ti, Jang, Bi, Byeon, Js, Kim, E, Kim, Mj, Lee, J, Pai, H, Cheong, Hj, Lee, S, Loyarte, Ja, Gonzalez, Jc, Santiago, Eb, Lopez, Jr, Baranda, Jm, Viladomiu, As, Calbo, E, Lannergard, A, Falt, J, Gardlund, B, Andersson, Lm, Fraenkel, Cj, Rombo, L, Widmer, A, Chen, Yc, Sheng, Wh, Wang, Fd, Wang, Nc, Lee, Ch, Chen, Yh, Chuang, Yc, Unal, S, Ozaras, R, Esen, S, Ural, O, Ayaz, C, Sakarya, S, Celebi, A, Mistik, R, Bedimo, R, Bressler, A, Mckinley, Mj, Quirk, D, Talansky, Al, Agronin, Me, Akhrass, Fa, Ali, M, Alrabaa, Sf, Assi, Ma, Calfee, Dp, Carson, P, Mariani, Pg, Guerrero, D, Dubberke, Er, Hardi, R, Hazan-Steinberg, S, Itani, Km, Jauregui-Peredo, El, Kasabji, A, Hameed, M, Murillo, A, Odio, Aj, Shah, P, Braun, Ti, Slim, J, Sloan, L, Srinivasan, S, Tan, Mj, Clough, La, Herr, D, Miller, Lg, Dorfmeister, J, Khan, O, and Melik-Abrahamian, F.

Subjects
0301 basic medicine, Male, Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Antibodies, Monoclonal, Antibodies, Neutralizing, Clostridium Infections, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Infusions, Intravenous, Intention to Treat Analysis, Kaplan-Meier Estimate, Middle Aged, Secondary Prevention, Young Adult, Clostridium difficile, Clinical Trial, Phase III, Antibiotics, 0302 clinical medicine, Monoclonal, 80 and over, 030212 general & internal medicine, Medicine (all), Neutralizing, education.field_of_study, Research Support, Non-U.S. Gov't, General Medicine, Multicenter Study, Randomized Controlled Trial, Combination, Broadly Neutralizing Antibodies, Intravenous, medicine.medical_specialty, Infusions, medicine.drug_class, 030106 microbiology, Population, Placebo, Antibodies, 03 medical and health sciences, Pharmacotherapy, Drug Therapy, Internal medicine, Journal Article, medicine, education, Intention-to-treat analysis, Clostridioides difficile, business.industry, Interim analysis, Surgery, Bezlotoxumab, business
Abstract

BACKGROUND: Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.METHODS: We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population.RESULTS: In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; PCONCLUSIONS: Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).

Published
2017

38. Progetti condivisi tra scuola e università

Author

Cacciapuoti, G, Milella, A, Cruciani, M, Baldo, D, Tomarchio, V, Marsico, S, Sulis, Mc, Nocentini, M, Arena, P, Capasso, L, Dragotto, F, Boaretto, N, Giacobbe, I, Belotti, B, Oliva, R, Onnis, A, Spnelli, P, Rizzo, E, Minoli, L, Basile, G, Anatra, Mg, Cerkvenic, E, Antolini, C, Ocanha, Sv, Tomasucci, R, Cario, N, Gallarate, M, Pilò, C, Giaccai, S, Cavagnoli, S, Metta, L, Strickland, E, Laterza, R, Priulla, G, Ianniciello, C, Belardi, A, Lanzon, P, Clemente, A, Fedeli, V, Marchetti, C, Miceli, E, Milito, D, Junck, L, Candiani, L, Guerrieri, L, Casilio, S, Vitelli, F, Chersi, M, and Coppola, A

Subjects
Settore L-LIN/02 - Didattica delle Lingue Moderne, Settore L-LIN/01 - Glottologia e Linguistica
Published
2017

39. Ab uno disce omnes. Che genere di dizionario?

Author

Cacciapuoti, G, Milella, A, Cruciani, M, Baldo, D, Tomarchio, V, Marsico, S, Sulis, Mc, Nocentini, M, Arena, P, Capasso, L, Boaretto, N, Giacobbe, I, Belotti, B, Oliva, R, Onnis, A, Spnelli, P, Rizzo, E, Minoli, L, Basile, G, Anatra, Mg, Cerkvenic, E, Antolini, C, Ocanha, Sv, Tomasucci, R, Cario, N, Gallarate, M, Pilò, C, Giaccai, S, Cavagnoli, S, Metta, L, Strickland, E, Laterza, R, Priulla, G, Ianniciello, C, Belardi, A, Lanzon, P, Clemente, A, Fedeli, V, Marchetti, C, Miceli, E, Milito, D, Junck, L, Candiani, L, Guerrieri, L, Casilio, S, Vitelli, F, Chersi, M, and Coppola, A

Subjects
lessico, lessicoografia, semantica, genere, Settore L-LIN/01 - Glottologia e Linguistica, genere, lessicoografia, semantica, lessico
Published
2017

41. The old patient in DAA era: Real life reports on 5925 patients from the Lombardy HCV Network

Author

Pasulo, L., primary, Aghemo, A., additional, Fargion, S., additional, Spinetti, A., additional, Cologni, G., additional, Maggiolo, F., additional, Rizzardini, G., additional, Puoti, M., additional, Bruno, R., additional, Minoli, L., additional, Zuin, M., additional, Foppa, C. Uberti, additional, Quirino, T., additional, D’Arminio Monforte, A., additional, Colli, A., additional, Rumi, M.G., additional, Iegri, C., additional, Fagiuoli, S., additional, and Colombo, M., additional

Published
2017
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42. Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitors to regimens containing NRTI plus non-NRTI or only NRTI

Author

Torti, C, d'Arminio-Monforte, A, Pozniak, A, Lapadula, G, Cologni, G, Antinori, A, De Luca, A, Mussini, C, Castagna, A, Cicconi, P, Minoli, L, Costantini, A, Carosi, G, Liang, H, Cesana, B, Torti C., d'Arminio-Monforte A., Pozniak A. L., Lapadula G., Cologni G., Antinori A., De Luca A., Mussini C., Castagna A., Cicconi P., Minoli L., Costantini A., Carosi G., Liang H., Cesana B. M., Torti, C, d'Arminio-Monforte, A, Pozniak, A, Lapadula, G, Cologni, G, Antinori, A, De Luca, A, Mussini, C, Castagna, A, Cicconi, P, Minoli, L, Costantini, A, Carosi, G, Liang, H, Cesana, B, Torti C., d'Arminio-Monforte A., Pozniak A. L., Lapadula G., Cologni G., Antinori A., De Luca A., Mussini C., Castagna A., Cicconi P., Minoli L., Costantini A., Carosi G., Liang H., and Cesana B. M.

Abstract

Background: Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce.Methods: Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after the switch, and last visit). Finally, we explored whether the CD4+ counts evolved differently in patients who switched to NNRTI or NRTI-only regimens by considering: the overall CD4+ trends, the time to CD4+≥ 500/mm3 after the switch, and the area-under-the-curve (AUC) of the CD4+ after the switch.Results: Eight hundred and ninety-six patients, followed for a median of 2,121 days, were included. At TPLR, hinges occurred in 581/844 (68.9%), but in only 40/581 (6.9%) within a time interval (180 days) compatible with a possible relationship to the switch; furthermore, in 19/40 cases, CD4+ counts appeared to decrease after the hinges. In comparison with the NNRTI group, the NRTI group showed CD4+ count greater at baseline (P = 0.0234) and before the switch (P ≤ 0.0001), superior CD4+ T-cell increases after HAART was started, lower probability of not achieving CD4+ ≥ 500/mm3 (P = 0.0024), and, finally, no significant differences in the CD4+ T-cell AUC after the switch after adjusting for possible confounders (propensity score and pre-switch AUC). Persistence at CD4+ < 200/mm3 was observed in 34/435 (7.5%) patients, and a decrease below this level was found in only 10/259 (3.9%) with baseline CD4+ ≥ 350/mm3.Conclusions: Switching from first-line PI to NNRTI- or NRTI-based regimens did not s

Published
2011

43. Predictors of AIDS-defining events among advanced naïve patients after HAART

Author

Torti, C, Lapadula, G, Maggiolo, F, Casari, S, Suter, F, Minoli, L, Pezzoli, C, Di Pietro, M, Migliorino, G, Quiros-Roldan, E, Ladisa, N, Sighinolfi, L, Gatti, F, Carosi, G, Torti C., Lapadula G., Maggiolo F., Casari S., Suter F., Minoli L., Pezzoli C., Di Pietro M., Migliorino G., Quiros-Roldan E., Ladisa N., Sighinolfi L., Gatti F., Carosi G., Torti, C, Lapadula, G, Maggiolo, F, Casari, S, Suter, F, Minoli, L, Pezzoli, C, Di Pietro, M, Migliorino, G, Quiros-Roldan, E, Ladisa, N, Sighinolfi, L, Gatti, F, Carosi, G, Torti C., Lapadula G., Maggiolo F., Casari S., Suter F., Minoli L., Pezzoli C., Di Pietro M., Migliorino G., Quiros-Roldan E., Ladisa N., Sighinolfi L., Gatti F., and Carosi G.

Abstract

Background: Baseline and follow-up predictors of new AIDS-defining events or death (ADE/death) among patients who started HAART late in their disease history have rarely been assessed simultaneously. Method: ADE and mortality rates were assessed using Cox regression analyses. Variables were tested for prediction of ADE/death within the first 3 months of therapy and from month 3, thereafter. Results: 751 HIV-infected patients with <200 CD4+/mm3 before HAART were followed for a median of 49 months. 207 new ADE occurred (7.06 [6.16-8.10] per 100 patient-years). ADE/deaths clustered within the first 3 months of treatment (106/207, 51%). Higher CD4+ T-cell counts during the follow-up (per loge cells/mm3: hazard ratio [HR] 0.51; 0.41-0.64; p < .001) and use of antiretroviral therapy (HR 0.38; 95% CI 0.21-0.69; p = .001) appeared to protect from ADE/death after month 3. Conversely, increasing follow-up with HIV RNA >400 copies/mL correlated with ADE/death (per month: HR 1.09; 95% CI 1.06-1.12; p = .001). Use of boosted protease inhibitors as first-line HAART and HCV-seropositivity were additional risk factors. Baseline CD4+ T-cell count and HIV RNA had a predominant impact in the first 3 months after HAART initiation. Conclusion: A careful monitoring of patients with low CD4+ is particularly necessary during the first few months of HAART. Length and extent of viral replication during the follow-up appeared to induce a significantly higher risk of HIV disease progression afterwards, implying that new drugs and new strategies aimed at ensuring long-term suppression of HIV RNA are of outstanding importance. © 2007 Thomas Land Publishers, Inc.

Published
2007

44. Evaluation of cytomegalovirus DNAaemia versus pp65-antigenaemia cutoff for guiding preemptive therapy in transplant recipients: a randomized study

Author

Gerna, G, Baldanti, F, Torsellini, M, Minoli, L, Vigano, M, Oggionni, T, Rampino, T, Castiglioni, B, Goglio, A, Colledan, M, Mammana, C, Nozza, F, Lilleri, D, Gerna G, Baldanti F, Torsellini M, Minoli L, Vigano M, Oggionni T, Rampino T, Castiglioni B, Goglio A, Colledan M, Mammana C, Nozza F, Lilleri D, Gerna, G, Baldanti, F, Torsellini, M, Minoli, L, Vigano, M, Oggionni, T, Rampino, T, Castiglioni, B, Goglio, A, Colledan, M, Mammana, C, Nozza, F, Lilleri, D, Gerna G, Baldanti F, Torsellini M, Minoli L, Vigano M, Oggionni T, Rampino T, Castiglioni B, Goglio A, Colledan M, Mammana C, Nozza F, and Lilleri D

Abstract

Methods: A bicentre, randomized, prospective open-label study aimed at defining a DNAaemia versus antigenaemia cutoff for guiding preemptive therapy of human cytomegalovirus (HCMV) infections in solid organ transplant recipients (SOTR) was completed. Overall, 99 patients were enrolled in the DNAaemia arm and 101 patients in the antigenaemia arm. Patients were randomized to be monitored for HCMV infection in the blood by either assay. Antiviral treatment was started in both seropositive and seronegative patients when levels greater than 300,000 DNA copies/ml blood or 100 pp65-positive leukocytes in the relevant arm were reached. Results: HCMV infection was detected in 81/99 (81.8%) patients in the DNAaemia arm and in 87/101 (86.1%) patients in the antigenaemia arm (P=ns). Antiviral treatment was given to 23/99 (23.0%) patients in the DNAaemia arm and 42/101 (41.0%) patients in the antigenaemia arm (P=0.01). In the DNAaemia arm, antiviral therapy was significantly delayed and duration of the first course of treatment was significantly greater than in the antigenaemia arm. However, total duration of treatment was comparable in the two arms. No case of HCMV disease occurred in patients treated after reaching the relevant cutoff. However, four patients (three in the antigenaemia arm, and one in the DNAaemia arm) suffered from HCMV disease prior to reaching the relevant cutoff. Conclusions: Compared with antigenaemia, a single DNAaemia cutoff: (i) significantly reduces the number of patients requiring treatment; (ii) may be safely adopted to guide preemptive therapy of both primary and reactivated HCMV infections in SOTR; and (iii) does not significantly modify the overall duration of treatment.

Published
2007

45. First case in Italy of acquired resistance to oseltamivir in an immunocompromised patient with influenza A/H1N1v infection

Author

Campanini G, Piralla A, Rovida F, Puzelli S, Facchini M, Locatelli F, Minoli L, Percivalle E, Donatelli I, Baldanti F, Surveillance Group for New Influenza A/H1N1v Investigation in Italy, D'AGARO, PIERLANFRANCO, Campanini, G, Piralla, A, Rovida, F, Puzelli, S, Facchini, M, Locatelli, F, Minolic, L, Percivalle, E, Donatelli, I, Tramuto, F, Baldanti, F, Surveillance Group for New Influenza A/H1N1v Investigation in Italy, Minoli, L, Surveillance Group for New Influenza A/H1N1v Investigation in, Italy, and D'Agaro, Pierlanfranco

Subjects
Bodily Secretions, viruses, Resistance, Drug Resistance, Settore MED/42 - Igiene Generale E Applicata, medicine.disease_cause, Pandemic, H1N1v, Oseltamivir, Resistance, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, Pandemic, Influenza A virus, Influenza A Virus, Viral, Child, Viral Load, Treatment Outcome, Infectious Diseases, Italy, Child, Preschool, RNA, Viral, Female, Viral disease, Viral load, H1N1v, Sequence Analysis, Oseltamivir, Amino Acid Substitution, Antiviral Agents, Humans, Immunocompromised Host, Influenza, Human, Molecular Sequence Data, Mutation, Missense, Neuraminidase, Nose, Sequence Analysis, DNA, Viral Proteins, Withholding Treatment, Drug Resistance, Viral, Virology, Human, Biology, Virus, resistance, medicine, H1N1 Subtype, Preschool, Influenza-like illness, DNA, Influenza, A/H1N1v, chemistry, Mutation, biology.protein, RNA, Missense
Abstract

A pandemic influenza A/H1N1v strain with the neuraminidase H274Y mutation was detected in nasal secretions of a 2-year-old leukemic patient with influenza-like illness after 18 days of treatment with oseltamivir. At baseline, no drug-resistant virus was found, while 4 days after treatment initiation a mix- ture of wild-type and mutated virus was detected. After treatment interruption, the wild type influenza virus re-emerged and became prevalent in nasal secretions after a few days, suggesting the lower fitness of the mutated virus strain. The patient slowly improved concurrently with a decrease in virus load, which resulted negative 42 days after diagnosis. No other drug-resistant influenza A/H1N1v virus strains have been detected in Italy (up to the end of November 2009) since the first case of the novel A/H1N1v virus was identified in the country (May 2009).

Published
2010

46. Influence of genotype 3 hepatitis C coinfection on liver enzyme elevation in HIV-1-positive patients after commencement of a new highly active antiretroviral regimen: Results from the EPOKA-MASTER cohort

Author

Torti, C, Lapadula, G, Puoti, M, Casari, S, Uccelli, M, Cristini, G, Bella, D, Pastore, G, Ladisa, N, Minoli, L, Sotgiu, G, Caputo, S, Bonora, S, Carosi, G, Torti C., Lapadula G., Puoti M., Casari S., Uccelli M. C., Cristini G., Bella D., Pastore G., Ladisa N., Minoli L., Sotgiu G., Caputo S. L., Bonora S., Carosi G., Torti, C, Lapadula, G, Puoti, M, Casari, S, Uccelli, M, Cristini, G, Bella, D, Pastore, G, Ladisa, N, Minoli, L, Sotgiu, G, Caputo, S, Bonora, S, Carosi, G, Torti C., Lapadula G., Puoti M., Casari S., Uccelli M. C., Cristini G., Bella D., Pastore G., Ladisa N., Minoli L., Sotgiu G., Caputo S. L., Bonora S., and Carosi G.

Abstract

Background: The independent role of hepatitis C virus (HCV) genotype 3 in liver transaminase elevation following highly active antiretroviral regimens is still controversial. Methods: Analysis of data from a cohort of 492 HIV/HCV-coinfected patients was conducted using an intention-to-treat approach. Incidence of grade ≥III liver transaminase elevation was estimated per 100 patient-years of follow-up. Univariate and multiple proportional hazards regression analysis of factors that may predict liver enzyme elevation was performed. Results: The incidence of grade ≥III hepatotoxicity was 25 per 100 patient-years among patients coinfected with HCV genotype 3 and 11 per 100 patient-years among those with other genotypes. On multiple proportional hazard regression analysis, time-to-grade ≥III liver enzyme elevation was directly correlated with HCV genotype 3 (hazards ratio [HR]: 2.0, 95% CI: 1.3 to 2.9; P = 0.001), male gender (HR: 2.7; 95% CI: 1.3 to 5.7; P = 0.007), chronic hepatitis B virus infection (HR: 2.9, 95% CI: 1.5 to 5.9; P = 0.002), and alanine aminotransferase level at baseline (per 10 IU/L HR: 1.10; 95% CI: 1.06 to 1.15; P < 0.001). In the same model, higher CD4 + T-cell counts at baseline were inversely correlated with risk of hepatotoxicity (HR: 0.998; 95% CI: 0.997 to 0.999; P = 0.036). Moreover, among patients experienced to antiretroviral drugs, previous grade ≥III hepatotoxicity (HR: 2.8; 95% CI: 1.8 to 4.3; P < 0.001) was an adjunctive independent risk factor. Conclusions: HIV-positive patients coinfected with HCV genotype 3 displayed a higher risk of relevant hepatotoxicity, independently from other clinical variables. The impact of HCV genotype outweighed the role of drugs in determining hepatotoxicity. Copyright © 2006 by Lippincott Williams & Wilkins.

Published
2006

47. Hepatotoxicity Development During Antiretroviral Therapy Containing Protease Inhibitors in Patients With HIV

Author

Aceti, A, Pasquazzi, C, Zechini, B, De Bac, C, Liverhaart, Group, Cargnel, A, Giorgi, R, Carosi, G, Torti, C, Chiodo, F, Giuliani, R, Concia, Ercole, Cainelli, F, Ghinelli, F, Roda, R, Mazzotta, F, Pierotti, L, Milazzo, F, Fagion, I, Minoli, L, Rizzi, L, Mura, Ms, Sotgiu, G, Ortona, L, Di Gianbenedetto, S, Pastore, G, Cavaliere, R, Piazza, M, Maddaloni, L, Sagnelli, E, Nacca, C, Scalise, G, Del Prete MS, Vullo, V, and Santopadre, P.

Subjects
Adult, Male, hepatotoxicity, Time Factors, Hepatitis C virus, protease inhibitors, HIV Infections, medicine.disease_cause, Antiviral Agents, Risk Factors, Prevalence, medicine, Humans, Pharmacology (medical), Protease inhibitor (pharmacology), Retrospective Studies, Hepatitis, Ritonavir, business.industry, HIV, Alanine Transaminase, Bilirubin, HIV Protease Inhibitors, Viral Load, Hepatitis B, medicine.disease, Hepatitis C, ART, hepatotoxicity, hepatitis C or B virus, HIV, protease inhibitors, Infectious Diseases, Italy, Chemical and Drug Induced Liver Injury, Chronic, Immunology, Coinfection, Regression Analysis, Female, hepatitis C or B virus, business, Viral hepatitis, Viral load, ART, medicine.drug
Abstract

To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV-infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection.

Published
2002

48. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy : not all AIDS-defining conditions are created equal

Author

Antiretroviral Therapy Cohort Collaboration Mocroft A, Sterne JA, Egger M, May M, Grabar S, Furrer H, Sabin C, Fatkenheuer G, Justice A, Reiss P, d'Arminio Monforte A, Gill J, Hogg R, Bonnet F, Kitahata M, Staszewski S, Casabona J, Harris R, Saag M, Chêne G, Costagliola D, Dabis F, D'Arminio Monforte A, de Wolf F, Ledergerber B, Mocroft A, Phillips A, Weller I, Sterne J, Abgrall S, Barin F, Bentata M, Billaud E, Boué F, Burty C, Cabié A, Cotte L, De Truchis P, Duval X, Duvivier C, Enel P, Fredouille Heripret L, Gasnault J, Gaud C, Gilquin J, Katlama C, Khuong MA, Lang JM, Lascaux AS, Launay O, Mahamat A, Mary Krause M, Matheron S, Meynard JL, Pavie J, Pialoux G, Pilorgé F, Poizot Martin I, Pradier C, Reynes J, Rouveix E, Simon A, Tattevin P, Tissot Dupont H, Viard JP, Viget N, Pariente Khayat A, Salomon V, Jacquemet N, Rivet A, Guiguet M, Kousignian I, Lanoy E, Lièvre L, Potard V, Selinger Leneman H, Bouvet E, Crickx B, Ecobichon JL, Leport C, Picard Dahan C, Yeni P, Tisne Dessus D, Weiss L, Salmon D, Sicard D, Auperin I, Roudière L, Fior R, Delfraissy JF, Goujard C, Jung C, Lesprit P, Desplanque N, Meyohas MC, Picard O, Cadranel J, Mayaud C, Bricaire F, Herson S, Clauvel JP, Decazes JM, Gerard L, Molina JM, Diemer M, Sellier P, Berthé H, Dupont C, Chandemerle C, Mortier E, Honoré P, Jeantils V, Tassi S, Mechali D, Taverne B, Gourdon F, Laurichesse H, Fresard A, Lucht F, Eglinger P, Faller JP, Bazin C, Verdon R, Boibieux A, Peyramond D, Livrozet JM, Touraine JL, Trepo C, Ravaux I, Delmont JP, Moreau J, Gastaut JA, Retornaz F, Soubeyrand J, Allegre T, Blanc PA, Galinier A, Ruiz JM, Lepeu G, Granet Brunello P, Esterni JP, Pelissier L, Cohen Valensi R, Nezri M, Chadapaud S, Laffeuillade A, May T, Rabaud C, Raffi F, Arvieux C, Michelet C, Borsa Lebas F, Caron F, Fraisse P, Rey D, Arlet Suau E, Cuzin L, Massip P, Thiercelin Legrand MF, Yasdanpanah Y, Pradinaud R, Sobesky M, Contant M, Montroni M, Scalise G, Braschi MC, Riva A, Tirelli U, Martellotta F, Pastore G, Ladisa N, Suter F, Arici C, Chiodo F, Colangeli V, Fiorini C, Carosi G, Cristini G, Torti C, Minardi C, Bertelli D, Quirino T, Manconi PE, Piano P, Cosco L, Scerbo A, Vecchiet J, D'Alessandro M, Santoro D, Pusterla L, Carnevale G, Lorenzotti S, Viganò P, Mena M, Ghinelli F, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Lo Caputo S, Grisorio B, Ferrara S, Grima P, Grima PF, Pagano G, Cassola G, Alessandrini A, Piscopo R, Toti M, Trezzi M, Soscia F, Tacconi L, Orani A, Perini P, Scasso A, Vincenti A, Chiodera F, Castelli P, Scalzini A, Palvarini L, Moroni M, Lazzarin A, Rizzardini G, Caggese L, Cicconi P, Galli A, Merli S, Pastecchia C, Moioli MC, Esposito R, Mussini C, Abrescia N, Chirianni A, Izzo CM, Piazza M, De Marco M, Viglietti R, Manzillo E, Colomba A, Abbadessa V, Prestileo T, Mancuso S, Ferrari C, Pizzaferri P, Filice G, Minoli L, Bruno R, Novati S, Baldelli F, Camanni G, Petrelli E, Cioppi A, Alberici F, Ruggieri A, Menichetti F, Martinelli C, De Stefano C, La Gala A, Ballardini G, Rizzo E, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Cauda R, Dianzani F, Ippolito G, Antinori A, Antonucci G, Ciardi M, Narciso P, Petrosillo N, Vullo V, De Luca A, Zaccarelli M, Acinapura R, De Longis P, Trotta MP, Noto P, Lichtner M, Capobianchi MR, Carletti F, Girardi E, Pezzotti P, Rezza G, Mura MS, Mannazzu M, Caramello P, Di Perri G, Orofino GC, Sciandra M, Grossi PA, Basilico C, Poggio A, Bottari G, Raise E, Ebo F, Pellizzer G, Buonfrate D, Resta F, Loso K, Cozzi Lepri A, Battegay M, Bernasconi E, Böni J, Bucher H, Bürgisser P, Cattacin S, Cavassini M, Dubs R, Elzi L, Erb P, Fischer M, Flepp M, Fontana A, Francioli P, Gorgievski M, Günthard H, Hirsch H, Hirschel B, Hösli I, Kahlert C, Kaiser L, Karrer U, Kind C, Klimkait T, Martinetti G, Martinez B, Müller N, Nadal D, Opravil M, Paccaud F, Pantaleo G, Rickenbach M, Rudin C, Schmid P, Schultze D, Schüpbach J, Speck R, Taffé P, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S, Gras LA, van Sighem AI, Smit C, Bronsveld W, Hillebrand Haverkort ME, Prins JM, Branger J, Eeftinck Schattenkerk JK, Gisolf J, Godfried MH, Lange JM, Lettinga KD, van der Meer JT, Nellen FJ, van der Poll T, Ruys TA, Steingrover R, Vermeulen JN, Vrouenraets SM, van Vugt M, Wit FW, Kuijpers TW, Pajkrt D, Scherpbier HJ, van Eeden A, Brinkman K, van den Berk GE, Blok WL, Frissen PH, Roos JC, Schouten WE, Mulder JW, van Gorp EC, Wagenaar J, Veenstra J, Danner SA, Van Agtmael MA, Claessen FA, Perenboom RM, Rijkeboer A, van Vonderen MG, Richter C, van der Berg J, Vriesendorp R, Jeurissen FJ, Kauffmann RH, Pogány K, Bravenboer B, ten Napel CH, Kootstra GJ, Sprenger HG, van Assen S, van Leeuwen JT, Doedens R, Scholvinck EH, ten Kate RW, Soetekouw R, van Houte D, Polée MB, Kroon FP, van den Broek PJ, van Dissel JT, Schippers EF, Schreij G, van der Geest S, Lowe S, Verbon A, Koopmans PP, Van Crevel R, de Groot R, Keuter M, Post F, van der Ven AJ, Warris A, van der Ende ME, Gyssens IC, van der Feltz M, Nouwen JL, Rijnders BJ, de Vries TE, Driessen G, van der Flier M, Hartwig NG, Juttman JR, van Kasteren ME, Van de Heul C, Hoepelman IM, Schneider MM, Bonten MJ, Borleffs JC, Ellerbroek PM, Jaspers CA, Mudrikove T, Schurink CA, Gisolf EH, Geelen SP, Wolfs TF, Faber T, Tanis AA, Groeneveld PH, den Hollander JG, Duits AJ, Winkel K, Back NK, Bakker ME, Berkhout B, Jurriaans S, Zaaijer HL, Cuijpers T, Rietra PJ, Roozendaal KJ, Pauw W, van Zanten AP, Smits PH, von Blomberg BM, Savelkoul P, Pettersson A, Swanink CM, Franck PF, Lampe AS, Jansen CL, Hendriks R, Benne CA, Veenendaal D, Storm H, Weel J, van Zeijl JH, Kroes AC, Claas HC, Bruggeman CA, Goossens VJ, Galama JM, Melchers WJ, Poort YA, Doornum GJ, Niesters MG, Osterhaus AD, Schutten M, Buiting AG, Swaans CA, Boucher CA, Schuurman R, Boel E, Jansz AF, Veldkamp A, Beijnen JH, Huitema AD, Burger DM, Hugen PW, van Kan HJ, Losso M, Duran A, Vetter N, Karpov I, Vassilenko A, Mitsura VM, Suetnov O, Clumeck N, De Wit S, Poll B, Colebunders R, Kostov K, Begovac J, Machala L, Rozsypal H, Sedlacek D, Nielsen J, Lundgren J, Benfield T, Kirk O, Gerstoft J, Katzenstein T, Hansen AB, Skinhøj P, Pedersen C, Oestergaard L, Zilmer K, Ristola M, Girard PM, Vanhems P, Rockstroh J, Schmidt R, van Lunzen J, Degen O, Stellbrink HJ, Bogner J, Kosmidis J, Gargalianos P, Xylomenos G, Perdios J, Panos G, Filandras A, Karabatsaki E, Sambattakou H, Banhegyi D, Mulcahy F, Yust I, Turner D, Burke M, Pollack S, Hassoun G, Maayan S, Chiesi A, Mazeu I, Pristera R, Gabbuti A, Montesarchio E, Gargiulo M, Iacomi F, Vlassi C, Finazzi R, Galli M, Ridolfo A, Rozentale B, Aldins P, Chaplinskas S, Hemmer R, Staub T, Bruun J, Maeland A, Ormaasen V, Knysz B, Gasiorowski J, Horban A, Prokopowicz D, Wiercinska Drapalo A, Boron Kaczmarska A, Pynka M, Beniowski M, Mularska E, Trocha H, Antunes F, Valadas E, Mansinho K, Maltez F, Duiculescu D, Rakhmanova A, Vinogradova E, Buzunova S, Jevtovic D, Mokrás M, Staneková D, González Lahoz J, Soriano V, Martin Carbonero L, Labarga P, Clotet B, Jou A, Conejero J, Tural C, Gatell JM, Miró JM, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Karlsson A, Persson PO, Flamholc L, Boffi E, Kravchenko E, Chentsova N, Barton S, Johnson AM, Mercey D, Johnson MA, Murphy M, Weber J, Scullard G, Fisher M, Brettle R, Gatell J, Gazzard B, Friis Møller N, Bannister W, Ellefson M, Borch A, Podlekareva D, Holkmann Olsen C, Kjaer J, Peters L, Reekie J, Raffanti S, Dieterch D, Becker S, Scarsella A, Fusco G, Most B, Balu R, Rana R, Beckerman R, Ising T, Fusco J, Irek R, Johnson B, Hirani A, DeJesus E, Pierone G, Lackey P, Irek C, Johnson A, Burdick J, Leon S, Arch J, Helm EB, Carlebach A, Müller A, Haberl A, Nisius G, Lennemann T, Stephan C, Bickel M, Mösch M, Gute P, Locher L, Lutz T, Klauke S, Knecht G, Khaykin P, Doerr HW, Stürmer M, Babacan E, von Hentig N, Beylot J, Dupon M, Longy Boursier M, Pellegrin JL, Ragnaud JM, Salamon R, Thiébaut R, Lewden C, Lawson Ayayi S, Mercié P, Moreau JF, Morlat P, Bernard N, Lacoste D, Malvy D, Neau D, Blaizeau MJ, Decoin M, Delveaux S, Hannapier C, Labarrère S, Lavignolle Aurillac V, Uwamaliya Nziyumvira B, Palmer G, Touchard D, Balestre E, Alioum A, Jacqmin Gadda H, Bonarek M, Coadou B, Gellie P, Nouts C, Bocquentin F, Dutronc H, Lafarie S, Aslan A, Pistonne T, Thibaut P, Vatan R, Chambon D, De La Taille C, Cazorla C, Ocho A, Viallard JF, Caubet O, Cipriano C, Lazaro E, Couzigou P, Castera L, Fleury H, Lafon ME, Masquelier B, Pellegrin I, Breilh D, Blanco P, Loste P, Caunègre L, Bonnal F, Farbos S, Ferrand M, Ceccaldi J, Tchamgoué S, De Witte S, Buy E, Alexander C, Barrios R, Braitstein P, Brumme Z, Chan K, Cote H, Gataric N, Geller J, Guillemi S, Harrigan PR, Harris M, Joy R, Levy A, Montaner J, Montessori V, Palepu A, Phillips E, Phillips P, Press N, Tyndall M, Wood E, Yip B, Bhagani S, Breen R, Byrne P, Carroll A, Cuthbertson Z, Dunleavy A, Geretti AM, Heelan B, Johnson M, Kinloch de Loes S, Lipman M, Madge S, Marshall N, Nair D, Nebbia G, Prinz B, Shah S, Swader L, Tyrer M, Youle M, Chaloner C, Grabowska H, Holloway J, Puradiredja J, Ransom D, Tsintas R, Bansi L, Fox Z, Harris E, Hill T, Lampe F, Lodwick R, Smith C, Amoah E, Booth C, Clewley G, Garcia Diaz A, Gregory B, Janossy G, Labbett W, Thomas M, Read R, Krentz H, Beckthold B, Schmeisser N, Alquézar A, Esteve A, Podzamczer D, Murillas J, Romero A, Agustí C, Agüero F, Ferrer E, Riera M, Segura F, Navarro G, Force L, Vilaró J, Masabeu A, García I, Guadarrama M, Montoliu A, Ortega N, Lazzari E, Puchol E, Sanchez M, Blanco JL, Garcia Alcaide F, Martinez E, Mallolas J, López Dieguez M, García Goez JF, Sirera G, Romeu J, Negredo E, Miranda C, Capitan MC, Olmo M, Barragan P, Saumoy M, Bolao F, Cabellos C, Peña C, Sala M, Cervantes M, Jose Amengual M, Navarro M, Penelo E, Barrufet P, Raper JL, Mugavero MJ, Willig JH, Schumacher J, Chang PW, Westfall AO, Cloud G, Lin HY, Acosta EP, Colette Kempf M, Allison JJ, Pisu M., NAPPA, SALVATORE, Mocroft, A, Mancuso, S, Antiretroviral Therapy Cohort Collaboration Mocroft, A, Sterne, Ja, Egger, M, May, M, Grabar, S, Furrer, H, Sabin, C, Fatkenheuer, G, Justice, A, Reiss, P, d'Arminio Monforte, A, Gill, J, Hogg, R, Bonnet, F, Kitahata, M, Staszewski, S, Casabona, J, Harris, R, Saag, M, Chêne, G, Costagliola, D, Dabis, F, D'Arminio Monforte, A, de Wolf, F, Ledergerber, B, Phillips, A, Weller, I, Sterne, J, Abgrall, S, Barin, F, Bentata, M, Billaud, E, Boué, F, Burty, C, Cabié, A, Cotte, L, De Truchis, P, Duval, X, Duvivier, C, Enel, P, Fredouille Heripret, L, Gasnault, J, Gaud, C, Gilquin, J, Katlama, C, Khuong, Ma, Lang, Jm, Lascaux, A, Launay, O, Mahamat, A, Mary Krause, M, Matheron, S, Meynard, Jl, Pavie, J, Pialoux, G, Pilorgé, F, Poizot Martin, I, Pradier, C, Reynes, J, Rouveix, E, Simon, A, Tattevin, P, Tissot Dupont, H, Viard, Jp, Viget, N, Pariente Khayat, A, Salomon, V, Jacquemet, N, Rivet, A, Guiguet, M, Kousignian, I, Lanoy, E, Lièvre, L, Potard, V, Selinger Leneman, H, Bouvet, E, Crickx, B, Ecobichon, Jl, Leport, C, Picard Dahan, C, Yeni, P, Tisne Dessus, D, Weiss, L, Salmon, D, Sicard, D, Auperin, I, Roudière, L, Fior, R, Delfraissy, Jf, Goujard, C, Jung, C, Lesprit, P, Desplanque, N, Meyohas, Mc, Picard, O, Cadranel, J, Mayaud, C, Bricaire, F, Herson, S, Clauvel, Jp, Decazes, Jm, Gerard, L, Molina, Jm, Diemer, M, Sellier, P, Berthé, H, Dupont, C, Chandemerle, C, Mortier, E, Honoré, P, Jeantils, V, Tassi, S, Mechali, D, Taverne, B, Gourdon, F, Laurichesse, H, Fresard, A, Lucht, F, Eglinger, P, Faller, Jp, Bazin, C, Verdon, R, Boibieux, A, Peyramond, D, Livrozet, Jm, Touraine, Jl, Trepo, C, Ravaux, I, Delmont, Jp, Moreau, J, Gastaut, Ja, Retornaz, F, Soubeyrand, J, Allegre, T, Blanc, Pa, Galinier, A, Ruiz, Jm, Lepeu, G, Granet Brunello, P, Esterni, Jp, Pelissier, L, Cohen Valensi, R, Nezri, M, Chadapaud, S, Laffeuillade, A, May, T, Rabaud, C, Raffi, F, Arvieux, C, Michelet, C, Borsa Lebas, F, Caron, F, Fraisse, P, Rey, D, Arlet Suau, E, Cuzin, L, Massip, P, Thiercelin Legrand, Mf, Yasdanpanah, Y, Pradinaud, R, Sobesky, M, Contant, M, Montroni, M, Scalise, G, Braschi, Mc, Riva, A, Tirelli, U, Martellotta, F, Pastore, G, Ladisa, N, Suter, F, Arici, C, Chiodo, F, Colangeli, V, Fiorini, C, Carosi, G, Cristini, G, Torti, C, Minardi, C, Bertelli, D, Quirino, T, Manconi, Pe, Piano, P, Cosco, L, Scerbo, A, Vecchiet, J, D'Alessandro, M, Santoro, D, Pusterla, L, Carnevale, G, Lorenzotti, S, Viganò, P, Mena, M, Ghinelli, F, Sighinolfi, L, Leoncini, F, Mazzotta, F, Pozzi, M, Lo Caputo, S, Grisorio, B, Ferrara, S, Grima, P, Grima, Pf, Pagano, G, Cassola, G, Alessandrini, A, Piscopo, R, Toti, M, Trezzi, M, Soscia, F, Tacconi, L, Orani, A, Perini, P, Scasso, A, Vincenti, A, Chiodera, F, Castelli, P, Scalzini, A, Palvarini, L, Moroni, M, Lazzarin, A, Rizzardini, G, Caggese, L, Cicconi, P, Galli, A, Merli, S, Pastecchia, C, Moioli, Mc, Esposito, R, Mussini, C, Abrescia, N, Chirianni, A, Izzo, Cm, Piazza, M, De Marco, M, Viglietti, R, Manzillo, E, Nappa, Salvatore, Colomba, A, Abbadessa, V, Prestileo, T, Ferrari, C, Pizzaferri, P, Filice, G, Minoli, L, Bruno, R, Novati, S, Baldelli, F, Camanni, G, Petrelli, E, Cioppi, A, Alberici, F, Ruggieri, A, Menichetti, F, Martinelli, C, De Stefano, C, La Gala, A, Ballardini, G, Rizzo, E, Magnani, G, Ursitti, Ma, Arlotti, M, Ortolani, P, Cauda, R, Dianzani, F, Ippolito, G, Antinori, A, Antonucci, G, Ciardi, M, Narciso, P, Petrosillo, N, Vullo, V, De Luca, A, Zaccarelli, M, Acinapura, R, De Longis, P, Trotta, Mp, Noto, P, Lichtner, M, Capobianchi, Mr, Carletti, F, Girardi, E, Pezzotti, P, Rezza, G, Mura, M, Mannazzu, M, Caramello, P, Di Perri, G, Orofino, Gc, Sciandra, M, Grossi, Pa, Basilico, C, Poggio, A, Bottari, G, Raise, E, Ebo, F, Pellizzer, G, Buonfrate, D, Resta, F, Loso, K, Cozzi Lepri, A, Battegay, M, Bernasconi, E, Böni, J, Bucher, H, Bürgisser, P, Cattacin, S, Cavassini, M, Dubs, R, Elzi, L, Erb, P, Fischer, M, Flepp, M, Fontana, A, Francioli, P, Gorgievski, M, Günthard, H, Hirsch, H, Hirschel, B, Hösli, I, Kahlert, C, Kaiser, L, Karrer, U, Kind, C, Klimkait, T, Martinetti, G, Martinez, B, Müller, N, Nadal, D, Opravil, M, Paccaud, F, Pantaleo, G, Rickenbach, M, Rudin, C, Schmid, P, Schultze, D, Schüpbach, J, Speck, R, Taffé, P, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Yerly, S, Gras, La, van Sighem, Ai, Smit, C, Bronsveld, W, Hillebrand Haverkort, Me, Prins, Jm, Branger, J, Eeftinck Schattenkerk, Jk, Gisolf, J, Godfried, Mh, Lange, Jm, Lettinga, Kd, van der Meer, Jt, Nellen, Fj, van der Poll, T, Ruys, Ta, Steingrover, R, Vermeulen, Jn, Vrouenraets, Sm, van Vugt, M, Wit, Fw, Kuijpers, Tw, Pajkrt, D, Scherpbier, Hj, van Eeden, A, Brinkman, K, van den Berk, Ge, Blok, Wl, Frissen, Ph, Roos, Jc, Schouten, We, Mulder, Jw, van Gorp, Ec, Wagenaar, J, Veenstra, J, Danner, Sa, Van Agtmael, Ma, Claessen, Fa, Perenboom, Rm, Rijkeboer, A, van Vonderen, Mg, Richter, C, van der Berg, J, Vriesendorp, R, Jeurissen, Fj, Kauffmann, Rh, Pogány, K, Bravenboer, B, ten Napel, Ch, Kootstra, Gj, Sprenger, Hg, van Assen, S, van Leeuwen, Jt, Doedens, R, Scholvinck, Eh, ten Kate, Rw, Soetekouw, R, van Houte, D, Polée, Mb, Kroon, Fp, van den Broek, Pj, van Dissel, Jt, Schippers, Ef, Schreij, G, van der Geest, S, Lowe, S, Verbon, A, Koopmans, Pp, Van Crevel, R, de Groot, R, Keuter, M, Post, F, van der Ven, Aj, Warris, A, van der Ende, Me, Gyssens, Ic, van der Feltz, M, Nouwen, Jl, Rijnders, Bj, de Vries, Te, Driessen, G, van der Flier, M, Hartwig, Ng, Juttman, Jr, van Kasteren, Me, Van de Heul, C, Hoepelman, Im, Schneider, Mm, Bonten, Mj, Borleffs, Jc, Ellerbroek, Pm, Jaspers, Ca, Mudrikove, T, Schurink, Ca, Gisolf, Eh, Geelen, Sp, Wolfs, Tf, Faber, T, Tanis, Aa, Groeneveld, Ph, den Hollander, Jg, Duits, Aj, Winkel, K, Back, Nk, Bakker, Me, Berkhout, B, Jurriaans, S, Zaaijer, Hl, Cuijpers, T, Rietra, Pj, Roozendaal, Kj, Pauw, W, van Zanten, Ap, Smits, Ph, von Blomberg, Bm, Savelkoul, P, Pettersson, A, Swanink, Cm, Franck, Pf, Lampe, A, Jansen, Cl, Hendriks, R, Benne, Ca, Veenendaal, D, Storm, H, Weel, J, van Zeijl, Jh, Kroes, Ac, Claas, Hc, Bruggeman, Ca, Goossens, Vj, Galama, Jm, Melchers, Wj, Poort, Ya, Doornum, Gj, Niesters, Mg, Osterhaus, Ad, Schutten, M, Buiting, Ag, Swaans, Ca, Boucher, Ca, Schuurman, R, Boel, E, Jansz, Af, Veldkamp, A, Beijnen, Jh, Huitema, Ad, Burger, Dm, Hugen, Pw, van Kan, Hj, Losso, M, Duran, A, Vetter, N, Karpov, I, Vassilenko, A, Mitsura, Vm, Suetnov, O, Clumeck, N, De Wit, S, Poll, B, Colebunders, R, Kostov, K, Begovac, J, Machala, L, Rozsypal, H, Sedlacek, D, Nielsen, J, Lundgren, J, Benfield, T, Kirk, O, Gerstoft, J, Katzenstein, T, Hansen, Ab, Skinhøj, P, Pedersen, C, Oestergaard, L, Zilmer, K, Ristola, M, Girard, Pm, Vanhems, P, Rockstroh, J, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, Hj, Bogner, J, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Sambattakou, H, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Maayan, S, Chiesi, A, Mazeu, I, Pristera, R, Gabbuti, A, Montesarchio, E, Gargiulo, M, Iacomi, F, Vlassi, C, Finazzi, R, Galli, M, Ridolfo, A, Rozentale, B, Aldins, P, Chaplinskas, S, Hemmer, R, Staub, T, Bruun, J, Maeland, A, Ormaasen, V, Knysz, B, Gasiorowski, J, Horban, A, Prokopowicz, D, Wiercinska Drapalo, A, Boron Kaczmarska, A, Pynka, M, Beniowski, M, Mularska, E, Trocha, H, Antunes, F, Valadas, E, Mansinho, K, Maltez, F, Duiculescu, D, Rakhmanova, A, Vinogradova, E, Buzunova, S, Jevtovic, D, Mokrás, M, Staneková, D, González Lahoz, J, Soriano, V, Martin Carbonero, L, Labarga, P, Clotet, B, Jou, A, Conejero, J, Tural, C, Gatell, Jm, Miró, Jm, Domingo, P, Gutierrez, M, Mateo, G, Sambeat, Ma, Karlsson, A, Persson, Po, Flamholc, L, Boffi, E, Kravchenko, E, Chentsova, N, Barton, S, Johnson, Am, Mercey, D, Johnson, Ma, Murphy, M, Weber, J, Scullard, G, Fisher, M, Brettle, R, Gatell, J, Gazzard, B, Friis Møller, N, Bannister, W, Ellefson, M, Borch, A, Podlekareva, D, Holkmann Olsen, C, Kjaer, J, Peters, L, Reekie, J, Raffanti, S, Dieterch, D, Becker, S, Scarsella, A, Fusco, G, Most, B, Balu, R, Rana, R, Beckerman, R, Ising, T, Fusco, J, Irek, R, Johnson, B, Hirani, A, Dejesus, E, Pierone, G, Lackey, P, Irek, C, Johnson, A, Burdick, J, Leon, S, Arch, J, Helm, Eb, Carlebach, A, Müller, A, Haberl, A, Nisius, G, Lennemann, T, Stephan, C, Bickel, M, Mösch, M, Gute, P, Locher, L, Lutz, T, Klauke, S, Knecht, G, Khaykin, P, Doerr, Hw, Stürmer, M, Babacan, E, von Hentig, N, Beylot, J, Dupon, M, Longy Boursier, M, Pellegrin, Jl, Ragnaud, Jm, Salamon, R, Thiébaut, R, Lewden, C, Lawson Ayayi, S, Mercié, P, Moreau, Jf, Morlat, P, Bernard, N, Lacoste, D, Malvy, D, Neau, D, Blaizeau, Mj, Decoin, M, Delveaux, S, Hannapier, C, Labarrère, S, Lavignolle Aurillac, V, Uwamaliya Nziyumvira, B, Palmer, G, Touchard, D, Balestre, E, Alioum, A, Jacqmin Gadda, H, Bonarek, M, Coadou, B, Gellie, P, Nouts, C, Bocquentin, F, Dutronc, H, Lafarie, S, Aslan, A, Pistonne, T, Thibaut, P, Vatan, R, Chambon, D, De La Taille, C, Cazorla, C, Ocho, A, Viallard, Jf, Caubet, O, Cipriano, C, Lazaro, E, Couzigou, P, Castera, L, Fleury, H, Lafon, Me, Masquelier, B, Pellegrin, I, Breilh, D, Blanco, P, Loste, P, Caunègre, L, Bonnal, F, Farbos, S, Ferrand, M, Ceccaldi, J, Tchamgoué, S, De Witte, S, Buy, E, Alexander, C, Barrios, R, Braitstein, P, Brumme, Z, Chan, K, Cote, H, Gataric, N, Geller, J, Guillemi, S, Harrigan, Pr, Harris, M, Joy, R, Levy, A, Montaner, J, Montessori, V, Palepu, A, Phillips, E, Phillips, P, Press, N, Tyndall, M, Wood, E, Yip, B, Bhagani, S, Breen, R, Byrne, P, Carroll, A, Cuthbertson, Z, Dunleavy, A, Geretti, Am, Heelan, B, Johnson, M, Kinloch de Loes, S, Lipman, M, Madge, S, Marshall, N, Nair, D, Nebbia, G, Prinz, B, Shah, S, Swader, L, Tyrer, M, Youle, M, Chaloner, C, Grabowska, H, Holloway, J, Puradiredja, J, Ransom, D, Tsintas, R, Bansi, L, Fox, Z, Harris, E, Hill, T, Lampe, F, Lodwick, R, Smith, C, Amoah, E, Booth, C, Clewley, G, Garcia Diaz, A, Gregory, B, Janossy, G, Labbett, W, Thomas, M, Read, R, Krentz, H, Beckthold, B, Schmeisser, N, Alquézar, A, Esteve, A, Podzamczer, D, Murillas, J, Romero, A, Agustí, C, Agüero, F, Ferrer, E, Riera, M, Segura, F, Navarro, G, Force, L, Vilaró, J, Masabeu, A, García, I, Guadarrama, M, Montoliu, A, Ortega, N, Lazzari, E, Puchol, E, Sanchez, M, Blanco, Jl, Garcia Alcaide, F, Martinez, E, Mallolas, J, López Dieguez, M, García Goez, Jf, Sirera, G, Romeu, J, Negredo, E, Miranda, C, Capitan, Mc, Olmo, M, Barragan, P, Saumoy, M, Bolao, F, Cabellos, C, Peña, C, Sala, M, Cervantes, M, Jose Amengual, M, Navarro, M, Penelo, E, Barrufet, P, Raper, Jl, Mugavero, Mj, Willig, Jh, Schumacher, J, Chang, Pw, Westfall, Ao, Cloud, G, Lin, Hy, Acosta, Ep, Colette Kempf, M, Allison, Jj, Pisu, M., Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Infectious diseases, Other departments, General Internal Medicine, Graduate School, Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, and Medical Microbiology and Infection Prevention

Subjects
Male, Infectious diseases and international health [NCEBP 13], Lymphoma, 030312 virology, Esophageal candidiasis, Cohort Studies, 0302 clinical medicine, Interquartile range, 030212 general & internal medicine, AIDS-Related, Lymphoma, AIDS-Related, 0303 health sciences, Mortality rate, Progressive multifocal leukoencephalopathy, Hazard ratio, Prognosis, 3. Good health, Pathogenesis and modulation of inflammation [N4i 1], Infectious Diseases, Combination, Drug Therapy, Combination, Female, Infection and autoimmunity [NCMLS 1], Human, Microbiology (medical), Adult, medicine.medical_specialty, Prognosi, Anti-HIV Agents, antiretroviral therapy, Infectious Disease, Article, AIDS-Related Opportunistic Infection, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Drug Therapy, Internal medicine, medicine, Humans, AIDS-defining event, Proportional Hazards Models, AIDS-Related Opportunistic Infections/diagnosis/ mortality, Acquired Immunodeficiency Syndrome/complications/diagnosis/drug, therapy/ mortality, Anti-HIV Agents/ therapeutic use, AIDS-Related/diagnosis/mortality, Acquired Immunodeficiency Syndrome, AIDS-Related Opportunistic Infections, business.industry, Proportional hazards model, Poverty-related infectious diseases [N4i 3], Anti-HIV Agent, medicine.disease, mortality, Confidence interval, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Contains fulltext : 80963.pdf (Publisher’s version ) (Open Access) BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in

Published
2009

49. Candida infective endocarditis: report of 15 cases from a prospective multicenter study

Author

Falcone, M, Barzaghi, N, Carosi, G, Grossi, P, Minoli, L, Ravasio, V, Rizzi, M, Suter, F, Utili, R, Viscoli, C, Venditti, M, Collaborators: Biglino A, Italian Study on E. n. d. o. c. a. r. d. i. t. i. s., Crivelli, P, Stellini, R, Magri, S, Del Bono, V, Vitale, F, Scalzini, A, Gattuso, G, Durante Mangoni, E, Ragone, E, Cuccurullo, S, Tripodi, MARIE FRANCOISE, Spoladore, G, Pasticci, Mb, Martinelli, L, Mal, Uo, Petrosillo, N, Chinello, P, Delle Foglie, P, Vaglia, A, Viale, P, Crapis, M, Tambini, R, Tomasello, L, Pellizzer, Gp, Nicolin, R, Concia, E, Del Bravo, P, Tedesco, A., Falcone, M, Barzaghi, N, Carosi, G, Grossi, P, Minoli, L, Ravasio, V, Rizzi, M, Suter, F, Utili, Riccardo, Viscoli, C, Venditti, M, and ITALIAN STUDY ON, Endocarditis

Subjects
Adult, Male, medicine.medical_specialty, Antifungal Agents, Prosthesis-Related Infections, Adolescent, Candida, infective endocarditis, italy, Echinocandins, Lipopeptides, Young Adult, chemistry.chemical_compound, Caspofungin, Epidemiology, medicine, Humans, Endocarditis, Prospective Studies, Prosthesis-Related Infection, Child, Prospective cohort study, Aged, Aged, 80 and over, yeast endocarditis, Native Valve Endocarditis, business.industry, Mortality rate, Candidiasis, General Medicine, Middle Aged, medicine.disease, Surgery, chemistry, Child, Preschool, Heart Valve Prosthesis, Infective endocarditis, Female, business
Abstract

Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted from January 2004 through December 2007.A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), 1 case of pacemaker endocarditis, and 1 case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy.Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia.

Published
2009

50. Incidence and risk factors for liver enzyme elevation during highly active antiretroviral therapy in HIV-HCV co-infected patients: Results from the Italian EPOKA-MASTER cohort

Author

Torti, C, Lapadula, G, Casari, S, Puoti, M, Nelson, M, Quiros-Roldan, E, Bella, D, Pastore, G, Ladisa, N, Minoli, L, Sotgiu, G, Mazzotta, F, Lo Caputo, S, Di Perri, G, Filice, G, Tinelli, C, Carosi, G, Torti C., Lapadula G., Casari S., Puoti M., Nelson M., Quiros-Roldan E., Bella D., Pastore G., Ladisa N., Minoli L., Sotgiu G., Mazzotta F., Lo Caputo S., Di Perri G., Filice G., Tinelli C., Carosi G., Torti, C, Lapadula, G, Casari, S, Puoti, M, Nelson, M, Quiros-Roldan, E, Bella, D, Pastore, G, Ladisa, N, Minoli, L, Sotgiu, G, Mazzotta, F, Lo Caputo, S, Di Perri, G, Filice, G, Tinelli, C, Carosi, G, Torti C., Lapadula G., Casari S., Puoti M., Nelson M., Quiros-Roldan E., Bella D., Pastore G., Ladisa N., Minoli L., Sotgiu G., Mazzotta F., Lo Caputo S., Di Perri G., Filice G., Tinelli C., and Carosi G.

Abstract

Background: The risk of hepatotoxicity associated with different highly active antiretroviral therapy (HAART) regimens (containing multiple-protease inhibitors, single-protease inhibitors or non nucleoside reverse transcriptase inhibitors) in HIV-HCV co-infected patients has not been fully assessed. Methods: Retrospective analysis of a prospective cohort of 1,038 HIV-HCV co-infected patients who commenced a new HAART in the Italian MASTER database. Patients were stratified into naïve and experienced to antiretroviral therapy before starting the study regimens. Time to grade ≥III hepatotoxicity (as by ACTG classification) was the primary outcome. Secondary outcome was time to grade IV hepatotoxicity. Results: Incidence of grade ≥III hepatotoxicity was 17.71 per 100 patient-years (p-yr) of follow up in naïve patient group and 8.22 per 100 p-yrs in experienced group (grade IV: 4.13 per 100 p-yrs and 1.08 per 100 p-yrs, respectively). In the latter group, the only independent factors associated with shorter time to the event at proportional hazards regression model were: previous liver transaminase elevations to grade ≥III, higher baseline alanine amino-transferase values, and use of a non nucleoside reverse transcriptase inhibitor based regimen. In the naive group, baseline aspartate transaminase level was associated with the primary outcome. Conclusion: Use of a single or multiple protease inhibitor based regimen was not associated with risk of hepatotoxicity in either naïve or experienced patient groups to a statistically significant extent. A cautious approach with strict monitoring should be applied in HIV-HCV co-infected experienced patients with previous liver transaminase elevations, higher baseline alanine aminotransferase values and who receive regimens containing non nucleoside reverse transcriptase inhibitors. © 2005 Torti et al; license BioMed Central Ltd.

Published
2005

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