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2. Functionalized Protein Binders in Developmental Biology.

Author

Schnider, Sophie T., Vigano, M. Alessandra, Affolter, Markus, and Aguilar, Gustavo

Abstract

Developmental biology has greatly profited from genetic and reverse genetic approaches to indirectly studying protein function. More recently, nanobodies and other protein binders derived from different synthetic scaffolds have been used to directly dissect protein function. Protein binders have been fused to functional domains, such as to lead to protein degradation, relocalization, visualization, or posttranslational modification of the target protein upon binding. The use of such functionalized protein binders has allowed the study of the proteome during development in an unprecedented manner. In the coming years, the advent of the computational design of protein binders, together with further advances in scaffold engineering and synthetic biology, will fuel the development of novel protein binder–based technologies. Studying the proteome with increased precision will contribute to a better understanding of the immense molecular complexities hidden in each step along the way to generate form and function during development. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort

Author

Kondili, L, Quaranta, M, Cavalletto, L, Calvaruso, V, Ferrigno, L, D'Ambrosio, R, Simonelli, I, Brancaccio, G, Raimondo, G, Brunetto, M, Zignego, A, Coppola, C, Iannone, A, Biliotti, E, Verucchi, G, Massari, M, Licata, A, Barbaro, F, Persico, M, Russo, F, Morisco, F, Pompili, M, Vigano, M, Puoti, M, Santantonio, T, Villa, E, Craxi, A, Chemello, L, Panetta, V, Gaeta, G, Filomia, R, Coco, B, Monti, M, Amoruso, D, Madonia, S, Ieluzzi, D, Taliani, G, Badia, L, Migliorino, G, Giorgini, A, Masarone, M, Blanc, P, Cossiga, V, De Siena, M, Tata, X, Rumi, M, Chessa, L, Lampertico, P, Ferrari, C, Gentile, I, Parruti, G, Baiocchi, L, Ciancio, A, Invernizzi, P, Federico, A, Torti, C, Morsica, G, Andreone, P, Aghemo, A, Popoli, P, Vella, S, Kondili L. A., Quaranta M. G., Cavalletto L., Calvaruso V., Ferrigno L., D'Ambrosio R., Simonelli I., Brancaccio G., Raimondo G., Brunetto M. R., Zignego A. L., Coppola C., Iannone A., Biliotti E., Verucchi G., Massari M., Licata A., Barbaro F., Persico M., Russo F. P., Morisco F., Pompili M., Vigano M., Puoti M., Santantonio T., Villa E., Craxi A., Chemello L., Panetta V., Gaeta G. B., Filomia R., Coco B., Monti M., Amoruso D. C., Madonia S., Ieluzzi D., Taliani G., Badia L., Migliorino G. M., Giorgini A., Masarone M., Blanc P., Cossiga V., De Siena M., Tata X., Rumi M. G., Chessa L., Lampertico P., Ferrari C., Gentile I., Parruti G., Baiocchi L., Ciancio A., Invernizzi P., Federico A., Torti C., Morsica G., Andreone P., Aghemo A., Popoli P., Vella S., Kondili, L, Quaranta, M, Cavalletto, L, Calvaruso, V, Ferrigno, L, D'Ambrosio, R, Simonelli, I, Brancaccio, G, Raimondo, G, Brunetto, M, Zignego, A, Coppola, C, Iannone, A, Biliotti, E, Verucchi, G, Massari, M, Licata, A, Barbaro, F, Persico, M, Russo, F, Morisco, F, Pompili, M, Vigano, M, Puoti, M, Santantonio, T, Villa, E, Craxi, A, Chemello, L, Panetta, V, Gaeta, G, Filomia, R, Coco, B, Monti, M, Amoruso, D, Madonia, S, Ieluzzi, D, Taliani, G, Badia, L, Migliorino, G, Giorgini, A, Masarone, M, Blanc, P, Cossiga, V, De Siena, M, Tata, X, Rumi, M, Chessa, L, Lampertico, P, Ferrari, C, Gentile, I, Parruti, G, Baiocchi, L, Ciancio, A, Invernizzi, P, Federico, A, Torti, C, Morsica, G, Andreone, P, Aghemo, A, Popoli, P, Vella, S, Kondili L. A., Quaranta M. G., Cavalletto L., Calvaruso V., Ferrigno L., D'Ambrosio R., Simonelli I., Brancaccio G., Raimondo G., Brunetto M. R., Zignego A. L., Coppola C., Iannone A., Biliotti E., Verucchi G., Massari M., Licata A., Barbaro F., Persico M., Russo F. P., Morisco F., Pompili M., Vigano M., Puoti M., Santantonio T., Villa E., Craxi A., Chemello L., Panetta V., Gaeta G. B., Filomia R., Coco B., Monti M., Amoruso D. C., Madonia S., Ieluzzi D., Taliani G., Badia L., Migliorino G. M., Giorgini A., Masarone M., Blanc P., Cossiga V., De Siena M., Tata X., Rumi M. G., Chessa L., Lampertico P., Ferrari C., Gentile I., Parruti G., Baiocchi L., Ciancio A., Invernizzi P., Federico A., Torti C., Morsica G., Andreone P., Aghemo A., Popoli P., and Vella S.

Abstract

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. Conclusions: The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.

Published
2023

6. Predicting home discharge after inpatient rehabilitation of stroke patients with aphasia

Author

Ginex, V, Vigano, M, Gilardone, G, Monti, A, Gilardone, M, Corbo, M, Ginex V., Vigano M., Gilardone G., Monti A., Gilardone M., Corbo M., Ginex, V, Vigano, M, Gilardone, G, Monti, A, Gilardone, M, Corbo, M, Ginex V., Vigano M., Gilardone G., Monti A., Gilardone M., and Corbo M.

Abstract

The early identification of the discharge setting from Inpatient Rehabilitation Facilities is a primary goal in stroke-related research because of its clinical and socio-economic relevance. Several features have been identified as significant predictors of the discharge setting. Within cognitive deficits, aphasia is known to be a common and disabling condition that could influence rehabilitation outcome. However, it is often set as an exclusion criterion in stroke research. This study aims to investigate the predictive power of clinical variables, in particular specific language disturbances and nonlinguistic cognitive deficits, for discharge setting in post-acute stroke patients with aphasia after intensive multidisciplinary rehabilitation. In a sample of 158 patients, demographic, motor, language, and nonverbal cognitive data were retrospectively considered for the prediction of the discharge to home vs. another institutional setting. Univariate analysis identified relevant differences between groups and the significant variables were included in a logistic regression model. The results showed that better functional motor status, absence of dysphagia and unimpaired nonlinguistic cognitive profile independently predict the discharge to home. In particular, nonverbal cognitive functioning seemed to be specifically relevant within the aphasic population. The findings could be helpful for setting up the rehabilitation priorities and an adequate discharge arrangement.

Published
2023

7. Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept

Author

Vitale, A, Cabibbo, G, Iavarone, M, Vigano, L, Pinato, D, Ponziani, F, Lai, Q, Casadei-Gardini, A, Celsa, C, Galati, G, Gambato, M, Crocetti, L, Renzulli, M, Giannini, E, Farinati, F, Trevisani, F, Cillo, U, Baccarani, U, Brancaccio, G, Cozzolongo, R, Cucchetti, A, De Matthaeis, N, Di Sandro, S, Famularo, S, Finotti, M, Foschi, F, Ghinolfi, D, Guarracino, M, Gruttadauria, S, Guarino, M, Kostandini, A, Lenci, I, Levi Sandri, G, Manzia, T, Marasco, G, Masarone, M, Mazzarelli, C, Melandro, F, Miele, L, Morisco, F, Nicolini, D, Pagano, D, Pelizzaro, F, Pieri, G, Piscaglia, F, Plaz Torres, M, Pravisani, R, Rendina, M, Romano, F, Russo, F, Sacco, R, Sangiovanni, A, Sposito, C, Tortora, R, Tovoli, F, Vigano, M, Violi, P, Vitale A., Cabibbo G., Iavarone M., Vigano L., Pinato D. J., Ponziani F. R., Lai Q., Casadei-Gardini A., Celsa C., Galati G., Gambato M., Crocetti L., Renzulli M., Giannini E. G., Farinati F., Trevisani F., Cillo U., Baccarani U., Brancaccio G., Cozzolongo R., Cucchetti A., De Matthaeis N., Di Sandro S., Famularo S., Finotti M., Foschi F. G., Ghinolfi D., Guarracino M., Gruttadauria S., Guarino M., Kostandini A., Lenci I., Levi Sandri G. B., Manzia T. M., Marasco G., Masarone M., Mazzarelli C., Melandro F., Miele L., Morisco F., Nicolini D., Pagano D., Pelizzaro F., Pieri G., Piscaglia F., Plaz Torres M. C., Pravisani R., Rendina M., Romano F., Russo F. P., Sacco R., Sangiovanni A., Sposito C., Tortora R., Tovoli F., Vigano M., Violi P., Vitale, A, Cabibbo, G, Iavarone, M, Vigano, L, Pinato, D, Ponziani, F, Lai, Q, Casadei-Gardini, A, Celsa, C, Galati, G, Gambato, M, Crocetti, L, Renzulli, M, Giannini, E, Farinati, F, Trevisani, F, Cillo, U, Baccarani, U, Brancaccio, G, Cozzolongo, R, Cucchetti, A, De Matthaeis, N, Di Sandro, S, Famularo, S, Finotti, M, Foschi, F, Ghinolfi, D, Guarracino, M, Gruttadauria, S, Guarino, M, Kostandini, A, Lenci, I, Levi Sandri, G, Manzia, T, Marasco, G, Masarone, M, Mazzarelli, C, Melandro, F, Miele, L, Morisco, F, Nicolini, D, Pagano, D, Pelizzaro, F, Pieri, G, Piscaglia, F, Plaz Torres, M, Pravisani, R, Rendina, M, Romano, F, Russo, F, Sacco, R, Sangiovanni, A, Sposito, C, Tortora, R, Tovoli, F, Vigano, M, Violi, P, Vitale A., Cabibbo G., Iavarone M., Vigano L., Pinato D. J., Ponziani F. R., Lai Q., Casadei-Gardini A., Celsa C., Galati G., Gambato M., Crocetti L., Renzulli M., Giannini E. G., Farinati F., Trevisani F., Cillo U., Baccarani U., Brancaccio G., Cozzolongo R., Cucchetti A., De Matthaeis N., Di Sandro S., Famularo S., Finotti M., Foschi F. G., Ghinolfi D., Guarracino M., Gruttadauria S., Guarino M., Kostandini A., Lenci I., Levi Sandri G. B., Manzia T. M., Marasco G., Masarone M., Mazzarelli C., Melandro F., Miele L., Morisco F., Nicolini D., Pagano D., Pelizzaro F., Pieri G., Piscaglia F., Plaz Torres M. C., Pravisani R., Rendina M., Romano F., Russo F. P., Sacco R., Sangiovanni A., Sposito C., Tortora R., Tovoli F., Vigano M., and Violi P.

Abstract

Advances in the surgical and systemic therapeutic landscape of hepatocellular carcinoma have increased the complexity of patient management. A dynamic adaptation of the available staging-based algorithms is required to allow flexible therapeutic allocation. In particular, real-world hepatocellular carcinoma management increasingly relies on factors independent of oncological staging, including patients’ frailty, comorbid burden, critical tumour location, multiple liver functional parameters, and specific technical contraindications impacting the delivery of treatment and resource availability. In this Policy Review we critically appraise how treatment allocation strictly based on pretreatment staging features has shifted towards a more personalised treatment approach, in which expert tumour boards assume a central role. We propose an evidence-based framework for hepatocellular carcinoma treatment based on the novel concept of multiparametric therapeutic hierarchy, in which different therapeutic options are ordered according to their survival benefit (ie, from surgery to systemic therapy). Moreover, we introduce the concept of converse therapeutic hierarchy, in which therapies are ordered according to their conversion abilities or adjuvant abilities (ie, from systemic therapy to surgery).

Published
2023

8. Vaccination Recommendations in Solid Organ Transplant Adult Candidates and Recipients

Author

Vigano, M, Beretta, M, Lepore, M, Abete, R, Benatti, S, Grassini, M, Camagni, S, Chiodini, G, Vargiu, S, Vittori, C, Iachini, M, Terzi, A, Neri, F, Pinelli, D, Casotti, V, Di Marco, F, Ruggenenti, P, Rizzi, M, Colledan, M, Fagiuoli, S, Vigano M., Beretta M., Lepore M., Abete R., Benatti S. V., Grassini M. V., Camagni S., Chiodini G., Vargiu S., Vittori C., Iachini M., Terzi A., Neri F., Pinelli D., Casotti V., Di Marco F., Ruggenenti P., Rizzi M., Colledan M., Fagiuoli S., Vigano, M, Beretta, M, Lepore, M, Abete, R, Benatti, S, Grassini, M, Camagni, S, Chiodini, G, Vargiu, S, Vittori, C, Iachini, M, Terzi, A, Neri, F, Pinelli, D, Casotti, V, Di Marco, F, Ruggenenti, P, Rizzi, M, Colledan, M, Fagiuoli, S, Vigano M., Beretta M., Lepore M., Abete R., Benatti S. V., Grassini M. V., Camagni S., Chiodini G., Vargiu S., Vittori C., Iachini M., Terzi A., Neri F., Pinelli D., Casotti V., Di Marco F., Ruggenenti P., Rizzi M., Colledan M., and Fagiuoli S.

Abstract

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

Published
2023

9. Hepatotoxicity of Small Molecule Protein Kinase Inhibitors for Cancer

Author

Vigano, M, La Milia, M, Grassini, M, Pugliese, N, De Giorgio, M, Fagiuoli, S, Vigano M., La Milia M., Grassini M. V., Pugliese N., De Giorgio M., Fagiuoli S., Vigano, M, La Milia, M, Grassini, M, Pugliese, N, De Giorgio, M, Fagiuoli, S, Vigano M., La Milia M., Grassini M. V., Pugliese N., De Giorgio M., and Fagiuoli S.

Abstract

Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs, since the majority are reported to increase transaminases, and few of them (Idelalisib, Lapatinib, Pazopanib, Pexidartinib, Ponatinib, Regorafenib, Sunitinib) have a boxed label warning. The exact rate of PKI-induced hepatoxicity is not well defined due to the fact that the majority of data arise from pre-registration or registration trials on fairly selected patients, and the post-marketing data are often based only on the most severe described cases, whereas most real practice studies do not include drug-related hepatotoxicity as an end point. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing PKIs should be carefully pre-evaluated and monitored. The management of this complication requires an individually tailored reappraisal of the risk/benefit ratio, especially in patients who are responding to therapy. This review reports the currently available data on the risk and management of hepatotoxicity of all the approved PKIs.

Published
2023

10. Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial

Author

Mariani, J, Beretta, S, Diamanti, S, Versace, A, Martini, B, Vigano, M, Castiglioni, L, Sironi, L, Carone, D, Cuccione, E, Monza, L, Giussani, C, Ferrarese, C, Mariani J., Beretta S., Diamanti S., Versace A., Martini B., Vigano M., Castiglioni L., Sironi L., Carone D., Cuccione E., Monza L., Giussani C., Ferrarese C., Mariani, J, Beretta, S, Diamanti, S, Versace, A, Martini, B, Vigano, M, Castiglioni, L, Sironi, L, Carone, D, Cuccione, E, Monza, L, Giussani, C, Ferrarese, C, Mariani J., Beretta S., Diamanti S., Versace A., Martini B., Vigano M., Castiglioni L., Sironi L., Carone D., Cuccione E., Monza L., Giussani C., and Ferrarese C.

Abstract

Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; − 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.

Published
2023

11. Harmonization of sensorimotor deficit assessment in a registered multicentre pre-clinical randomized controlled trial using two models of ischemic stroke

Author

Valente, A, Mariani, J, Seminara, S, Tettamanti, M, Pignataro, G, Perego, C, Sironi, L, Pedata, F, Amantea, D, Bacigaluppi, M, Vinciguerra, A, Diamanti, S, Vigano, M, Santangelo, F, Zoia, C, Rodriguez-Menendez, V, Castiglioni, L, Rzemieniec, J, Dettori, I, Bulli, I, Coppi, E, Di Santo, C, Cuomo, O, Gullotta, G, Butti, E, Bagetta, G, Martino, G, De Simoni, M, Ferrarese, C, Fumagalli, S, Beretta, S, Valente A., Mariani J., Seminara S., Tettamanti M., Pignataro G., Perego C., Sironi L., Pedata F., Amantea D., Bacigaluppi M., Vinciguerra A., Diamanti S., Vigano M., Santangelo F., Zoia C. P., Rodriguez-Menendez V., Castiglioni L., Rzemieniec J., Dettori I., Bulli I., Coppi E., Di Santo C., Cuomo O., Gullotta G. S., Butti E., Bagetta G., Martino G., De Simoni M. -G., Ferrarese C., Fumagalli S., Beretta S., Valente, A, Mariani, J, Seminara, S, Tettamanti, M, Pignataro, G, Perego, C, Sironi, L, Pedata, F, Amantea, D, Bacigaluppi, M, Vinciguerra, A, Diamanti, S, Vigano, M, Santangelo, F, Zoia, C, Rodriguez-Menendez, V, Castiglioni, L, Rzemieniec, J, Dettori, I, Bulli, I, Coppi, E, Di Santo, C, Cuomo, O, Gullotta, G, Butti, E, Bagetta, G, Martino, G, De Simoni, M, Ferrarese, C, Fumagalli, S, Beretta, S, Valente A., Mariani J., Seminara S., Tettamanti M., Pignataro G., Perego C., Sironi L., Pedata F., Amantea D., Bacigaluppi M., Vinciguerra A., Diamanti S., Vigano M., Santangelo F., Zoia C. P., Rodriguez-Menendez V., Castiglioni L., Rzemieniec J., Dettori I., Bulli I., Coppi E., Di Santo C., Cuomo O., Gullotta G. S., Butti E., Bagetta G., Martino G., De Simoni M. -G., Ferrarese C., Fumagalli S., and Beretta S.

Abstract

Multicentre preclinical randomized controlled trials (pRCTs) are a valuable tool to improve experimental stroke research, but are challenging and therefore underused. A common challenge regards the standardization of procedures across centres. We here present the harmonization phase for the quantification of sensorimotor deficits by composite neuroscore, which was the primary outcome of two multicentre pRCTs assessing remote ischemic conditioning in rodent models of ischemic stroke. Ischemic stroke was induced by middle cerebral artery occlusion for 30, 45 or 60 min in mice and 50, 75 or 100 min in rats, allowing sufficient variability. Eleven animals per species were video recorded during neurobehavioural tasks and evaluated with neuroscore by eight independent raters, remotely and blindly. We aimed at reaching an intraclass correlation coefficient (ICC) ≥0.60 as satisfactory interrater agreement. After a first remote training we obtained ICC = 0.50 for mice and ICC = 0.49 for rats. Errors were identified in animal handling and test execution. After a second remote training, we reached the target interrater agreement for mice (ICC = 0.64) and rats (ICC = 0.69). In conclusion, a multi-step, online harmonization phase proved to be feasible, easy to implement and highly effective to align each centre’s behavioral evaluations before project’s interventional phase.

Published
2023

12. Head down tilt 15° to preserve salvageable brain tissue in acute ischemic stroke: A pre-clinical pooled analysis, with focus on cerebral hemodynamics

Author

Diamanti, S, Mariani, J, Versace, A, Riva, M, Cuccione, E, Cai, R, Monza, L, Vigano, M, Bolbos, R, Chauveau, F, Cho, T, Carone, D, Ferrarese, C, Beretta, S, Diamanti S., Mariani J., Versace A., Riva M., Cuccione E., Cai R., Monza L., Vigano M., Bolbos R., Chauveau F., Cho T. -H., Carone D., Ferrarese C., Beretta S., Diamanti, S, Mariani, J, Versace, A, Riva, M, Cuccione, E, Cai, R, Monza, L, Vigano, M, Bolbos, R, Chauveau, F, Cho, T, Carone, D, Ferrarese, C, Beretta, S, Diamanti S., Mariani J., Versace A., Riva M., Cuccione E., Cai R., Monza L., Vigano M., Bolbos R., Chauveau F., Cho T. -H., Carone D., Ferrarese C., and Beretta S.

Abstract

Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t-MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal-level data from three experimental series were combined in a study population of 104 t-MCAO rats (45 in HDT15 group and 59 in flat position group). Co-primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non-ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3, 95% CI 9.1–54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10–16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5–19.18, p = 0.0002). Mean cerebral perfusion in the non-ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI −1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t-MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non-ischemic areas.

Published
2023

13. Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid

Author

De Vincentis, A, D'Amato, D, Cristoferi, L, Gerussi, A, Malinverno, F, Lleo, A, Colapietro, F, Marra, F, Galli, A, Fiorini, C, Coco, B, Brunetto, M, Niro, G, Cotugno, R, Saitta, C, Cozzolongo, R, Losito, F, Giannini, E, Labanca, S, Marzioni, M, Marconi, G, Morgando, A, Pellicano, R, Vanni, E, Cazzagon, N, Floreani, A, Chessa, L, Morelli, O, Muratori, L, Pellicelli, A, Pompili, M, Ponziani, F, Tortora, A, Rosina, F, Russello, M, Cannavo, M, Simone, L, Storato, S, Vigano, M, Abenavoli, L, D'Anto, M, De Gasperi, E, Distefano, M, Scifo, G, Zolfino, T, Calvaruso, V, Cuccorese, G, Palitti, V, Sacco, R, Bertino, G, Frazzetto, E, Alvaro, D, Mulinacci, G, Palermo, A, Scaravaglio, M, Terracciani, F, Galati, G, Ronca, V, Zuin, M, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Vespasiani-Gentilucci, U, Carbone, M, Feletti, V, Mussetto, A, Venere, R, Bernaccioni, G, Graciella Pigozzi, M, Fagiuoli, S, Terreni, N, Pozzoni, P, Baiocchi, L, Grassi, G, Vinci, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, De Vincentis A., D'Amato D., Cristoferi L., Gerussi A., Malinverno F., Lleo A., Colapietro F., Marra F., Galli A., Fiorini C., Coco B., Brunetto M., Niro G. A., Cotugno R., Saitta C., Cozzolongo R., Losito F., Giannini E. G., Labanca S., Marzioni M., Marconi G., Morgando A., Pellicano R., Vanni E., Cazzagon N., Floreani A., Chessa L., Morelli O., Muratori L., Pellicelli A., Pompili M., Ponziani F., Tortora A., Rosina F., Russello M., Cannavo M., Simone L., Storato S., Vigano M., Abenavoli L., D'Anto M., De Gasperi E., Distefano M., Scifo G., Zolfino T., Calvaruso V., Cuccorese G., Palitti V. P., Sacco R., Bertino G., Frazzetto E., Alvaro D., Mulinacci G., Palermo A., Scaravaglio M., Terracciani F., Galati G., Ronca V., Zuin M., Claar E., Izzi A., Picardi A., Invernizzi P., Vespasiani-Gentilucci U., Carbone M., Feletti V., Mussetto A., Venere R., Bernaccioni G., Graciella Pigozzi M., Fagiuoli S., Terreni N., Pozzoni P., Baiocchi L., Grassi G., Vinci M., Bellia V., Boldizzoni R., Casella S., Omazzi B., Poggi G., De Vincentis, A, D'Amato, D, Cristoferi, L, Gerussi, A, Malinverno, F, Lleo, A, Colapietro, F, Marra, F, Galli, A, Fiorini, C, Coco, B, Brunetto, M, Niro, G, Cotugno, R, Saitta, C, Cozzolongo, R, Losito, F, Giannini, E, Labanca, S, Marzioni, M, Marconi, G, Morgando, A, Pellicano, R, Vanni, E, Cazzagon, N, Floreani, A, Chessa, L, Morelli, O, Muratori, L, Pellicelli, A, Pompili, M, Ponziani, F, Tortora, A, Rosina, F, Russello, M, Cannavo, M, Simone, L, Storato, S, Vigano, M, Abenavoli, L, D'Anto, M, De Gasperi, E, Distefano, M, Scifo, G, Zolfino, T, Calvaruso, V, Cuccorese, G, Palitti, V, Sacco, R, Bertino, G, Frazzetto, E, Alvaro, D, Mulinacci, G, Palermo, A, Scaravaglio, M, Terracciani, F, Galati, G, Ronca, V, Zuin, M, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Vespasiani-Gentilucci, U, Carbone, M, Feletti, V, Mussetto, A, Venere, R, Bernaccioni, G, Graciella Pigozzi, M, Fagiuoli, S, Terreni, N, Pozzoni, P, Baiocchi, L, Grassi, G, Vinci, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, De Vincentis A., D'Amato D., Cristoferi L., Gerussi A., Malinverno F., Lleo A., Colapietro F., Marra F., Galli A., Fiorini C., Coco B., Brunetto M., Niro G. A., Cotugno R., Saitta C., Cozzolongo R., Losito F., Giannini E. G., Labanca S., Marzioni M., Marconi G., Morgando A., Pellicano R., Vanni E., Cazzagon N., Floreani A., Chessa L., Morelli O., Muratori L., Pellicelli A., Pompili M., Ponziani F., Tortora A., Rosina F., Russello M., Cannavo M., Simone L., Storato S., Vigano M., Abenavoli L., D'Anto M., De Gasperi E., Distefano M., Scifo G., Zolfino T., Calvaruso V., Cuccorese G., Palitti V. P., Sacco R., Bertino G., Frazzetto E., Alvaro D., Mulinacci G., Palermo A., Scaravaglio M., Terracciani F., Galati G., Ronca V., Zuin M., Claar E., Izzi A., Picardi A., Invernizzi P., Vespasiani-Gentilucci U., Carbone M., Feletti V., Mussetto A., Venere R., Bernaccioni G., Graciella Pigozzi M., Fagiuoli S., Terreni N., Pozzoni P., Baiocchi L., Grassi G., Vinci M., Bellia V., Boldizzoni R., Casella S., Omazzi B., and Poggi G.

Abstract

Background & Aims: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with “advanced cirrhosis” because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. Methods: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). Results: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42–2.12), INR (1.37, 1.00–1.87), Child-Pugh score (1.79, 1.28–2.50), MELD (1.17, 1.04–1.30) and bilirubin (1.83, 1.11–3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10–3.36), lower albumin levels (0.18, 0.06–0.51), Child-Pugh score (2.43, 1.50–4.04), history of ascites (3.5, 1.85–6.5) and bilirubin (1.30, 1.05–1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. Conclusions: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.

Published
2022

14. Role of ductular reaction and ductular–canalicular junctions in identifying severe primary biliary cholangitis

Author

Overi, D, Carpino, G, Cristoferi, L, Onori, P, Kennedy, L, Francis, H, Zucchini, N, Rigamonti, C, Vigano, M, Floreani, A, D'Amato, D, Gerussi, A, Venere, R, Alpini, G, Glaser, S, Alvaro, D, Invernizzi, P, Gaudio, E, Cardinale, V, Carbone, M, Overi D., Carpino G., Cristoferi L., Onori P., Kennedy L., Francis H., Zucchini N., Rigamonti C., Vigano M., Floreani A., D'Amato D., Gerussi A., Venere R., Alpini G., Glaser S., Alvaro D., Invernizzi P., Gaudio E., Cardinale V., Carbone M., Overi, D, Carpino, G, Cristoferi, L, Onori, P, Kennedy, L, Francis, H, Zucchini, N, Rigamonti, C, Vigano, M, Floreani, A, D'Amato, D, Gerussi, A, Venere, R, Alpini, G, Glaser, S, Alvaro, D, Invernizzi, P, Gaudio, E, Cardinale, V, Carbone, M, Overi D., Carpino G., Cristoferi L., Onori P., Kennedy L., Francis H., Zucchini N., Rigamonti C., Vigano M., Floreani A., D'Amato D., Gerussi A., Venere R., Alpini G., Glaser S., Alvaro D., Invernizzi P., Gaudio E., Cardinale V., and Carbone M.

Abstract

Background & Aims: Primary biliary cholangitis (PBC) is a chronic cholangiopathy characterised by immuno-mediated injury of interlobular bile ducts leading to intrahepatic cholestasis and progressive liver fibrosis. PBC histology is characterised by portal inflammation, progressive fibrosis, ductopenia, and the appearance of the so-called ductular reaction. The aim of the present study was to investigate the pathogenetic relevance of ductular reaction in PBC. Methods: Liver biopsies were collected from naïve people with PBC (N = 87). Clinical–serological parameters were obtained at diagnosis and after 1 year of ursodeoxycholic acid (UDCA) treatment. Histological staging was performed on all slides according to multiple scoring systems and criteria for PBC. Liver samples were obtained from Mdr2−/− mice treated with or without UDCA. Samples were processed for histology, immunohistochemistry, and immunofluorescence. Results: Ductular reaction in people with PBC correlated with the disease stage and liver fibrosis, but not with disease activity; an extensive ductular reaction correlated with serum alkaline phosphatase levels at diagnosis, response to UDCA, and individuals’ estimated survival, independently from other histological parameters, including disease stage. In people with PBC, reactive ductules were associated with the establishment of junctions with bile canaliculi and with fibrogenetic cell activation. Consistently, in a mouse model of intrahepatic cholestasis, UDCA treatment was effective in reducing ductular reaction and fibrosis and increasing ductular–canalicular junctions. Conclusions: Extensive ductular reaction outlines a severe histologic phenotype in PBC and is associated with an inadequate therapy response and a worse estimated prognosis. Lay summary: In people affected by primary biliary cholangitis (PBC), the histological appearance of extensive ductular reaction identifies individuals at risk of progressive fibrosis. Ductular reaction at dia

Published
2022

15. Dysmetabolism, Diabetes and Clinical Outcomes in Patients Cured of Chronic Hepatitis C: A Real-Life Cohort Study

Author

Valenti, L, Pelusi, S, Aghemo, A, Gritti, S, Pasulo, L, Bianco, C, Iegri, C, Cologni, G, Degasperi, E, D'Ambrosio, R, del Poggio, P, Soria, A, Puoti, M, Carderi, I, Pigozzi, M, Carriero, C, Spinetti, A, Zuccaro, V, Memoli, M, Giorgini, A, Vigano, M, Rumi, M, Re, T, Spinelli, O, Colombo, M, Quirino, T, Menzaghi, B, Lorini, G, Pan, A, D'Arminio Monforte, A, Buscarini, E, Autolitano, A, Bonfanti, P, Terreni, N, Aimo, G, Mendeni, M, Prati, D, Lampertico, P, Fagiuoli, S, Valenti L., Pelusi S., Aghemo A., Gritti S., Pasulo L., Bianco C., Iegri C., Cologni G., Degasperi E., D'Ambrosio R., del Poggio P., Soria A., Puoti M., Carderi I., Pigozzi M. G., Carriero C., Spinetti A., Zuccaro V., Memoli M., Giorgini A., Vigano M., Rumi M. G., Re T., Spinelli O., Colombo M. C., Quirino T., Menzaghi B., Lorini G., Pan A., D'Arminio Monforte A., Buscarini E., Autolitano A., Bonfanti P., Terreni N., Aimo G., Mendeni M., Prati D., Lampertico P., Colombo M., Fagiuoli S., Valenti, L, Pelusi, S, Aghemo, A, Gritti, S, Pasulo, L, Bianco, C, Iegri, C, Cologni, G, Degasperi, E, D'Ambrosio, R, del Poggio, P, Soria, A, Puoti, M, Carderi, I, Pigozzi, M, Carriero, C, Spinetti, A, Zuccaro, V, Memoli, M, Giorgini, A, Vigano, M, Rumi, M, Re, T, Spinelli, O, Colombo, M, Quirino, T, Menzaghi, B, Lorini, G, Pan, A, D'Arminio Monforte, A, Buscarini, E, Autolitano, A, Bonfanti, P, Terreni, N, Aimo, G, Mendeni, M, Prati, D, Lampertico, P, Fagiuoli, S, Valenti L., Pelusi S., Aghemo A., Gritti S., Pasulo L., Bianco C., Iegri C., Cologni G., Degasperi E., D'Ambrosio R., del Poggio P., Soria A., Puoti M., Carderi I., Pigozzi M. G., Carriero C., Spinetti A., Zuccaro V., Memoli M., Giorgini A., Vigano M., Rumi M. G., Re T., Spinelli O., Colombo M. C., Quirino T., Menzaghi B., Lorini G., Pan A., D'Arminio Monforte A., Buscarini E., Autolitano A., Bonfanti P., Terreni N., Aimo G., Mendeni M., Prati D., Lampertico P., Colombo M., and Fagiuoli S.

Abstract

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2, 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related

Published
2022

16. The Italian Aphasia Awareness Survey (IAAS): an online questionnaire about the public knowledge of aphasia in Italy, informative findings

Author

Vigano, M, Gilardone, G, Cassinelli, D, Fumagalli, F, Scialla, M, Gilardone, M, Dameno, R, Corbo, M, Monti, A, Vigano M., Gilardone G., Cassinelli D., Fumagalli F. M., Scialla M., Gilardone M., Dameno R., Corbo M., Monti A., Vigano, M, Gilardone, G, Cassinelli, D, Fumagalli, F, Scialla, M, Gilardone, M, Dameno, R, Corbo, M, Monti, A, Vigano M., Gilardone G., Cassinelli D., Fumagalli F. M., Scialla M., Gilardone M., Dameno R., Corbo M., and Monti A.

Abstract

Background: According to surveys conducted in several countries, public awareness and knowledge of aphasia are inadequately low. Persons with aphasia appoint this fact as a relevant environmental barrier. Aims: The present inquiry aims at analyzing the status of awareness and knowledge about aphasia in Italy. Methods & Procedures: An original questionnaire was distributed online through a snowball sampling method on the Italian adult population. Respondents were asked if they had heard of the term “aphasia” and subsequently tested on its definition and clinical characteristics. Similar questions regarding “celiac disease” and “Down syndrome” were asked for comparison. Demographic data and information about the source of knowledge were also recorded. Outcomes & Results: Considering 2172 respondents, 62.4% had heard of aphasia, 58.2% showed definition knowledge while 4.6% complete general knowledge. These rates were lower than those for the other medical conditions. Older age, female gender, higher education, and being a health professional were significantly associated with awareness. The questionnaire highlighted poor knowledge about the social and functional consequences of aphasia. Conclusions: Overall, the rates of aphasia awareness and knowledge were low. Despite health professionals performed better, the level of general knowledge was also poor among these respondents. These preliminary data set the need for further inquiries, undertaking appropriate methodological ameliorations.

Published
2022

18. The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma

Author

Lai, Q., De Matthaeis, N., Finotti, M., Galati, G., Marrone, G., Melandro, F., Morisco, F., Nicolini, D., Pravisani, R., Giannini, E. G., Aglitti, A., Aliberti, C., Baccarani, U., Bhoori, S., Borzio, M., Brancaccio, G., Burra, P., Cabibbo, G., Casadei Gardini, A., Carrai, P., Cillo, U., Conti, F., Cucchetti, A., D'Ambrosio, R., Dell'Unto, C., Di Costanzo, G. G., Di Sandro, S., Foschi, F. G., Fucilli, F., Gambato, M., Gasbarrini, A., Giuliante, F., Ghinolfi, D., Grieco, A., Gruttaduria, S., Guarino, M., Kostandini, A., Iavarone, M., Lenci, I., Levi Sandri, G. B., Losito, F., Lupo, L. G., Manzia, T. M., Mazzocato, S., Mescoli, C., Miele, L., Muley, M., Persico, M., Plaz Torres, M. C., Pompili, M., Ponziani, F. R., Rapaccini, G. L., Rendina, M., Renzulli, M., Rossi, M., Rreka, E., Russo, F. P., Sacco, R., Sangiovanni, A., Sessa, A., Simonetti, N., Sposito, C., Tortora, R., Trevisani, F., Vigano, L., Vigano, M., Villa, E., Vincenzi, V., Violi, P., and Vitale, A.

Subjects
clopidogrel, aspirin, Clinical Biochemistry, incidence, occurrence, survival, General Medicine, Biochemistry, Settore MED/18
Abstract

To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment.A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT.A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006).Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.

Published
2023

19. Engineered kinases as a tool for phosphorylation of selected targets in vivo

Author

Lepeta, Katarzyna, primary, Roubinet, Chantal, additional, Bauer, Milena, additional, Vigano, M. Alessandra, additional, Aguilar, Gustavo, additional, Kanca, Oguz, additional, Ochoa-Espinosa, Amanda, additional, Bieli, Dimitri, additional, Cabernard, Clemens, additional, Caussinus, Emmanuel, additional, and Affolter, Markus, additional

Published
2022
Full Text
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21. Overview of prognostic systems for hepatocellular carcinoma and ITA.LI.CA external validation of MESH and CNLC classifications

Author

Vitale, A, Farinati, F, Finotti, M, Di Renzo, C, Brancaccio, G, Piscaglia, F, Cabibbo, G, Caturelli, E, Missale, G, Marra, F, Sacco, R, Giannini, E, Trevisani, F, Cillo, U, Bhoori, S, Borzio, M, Burra, P, Casadei Gardini, A, Carrai, P, Conti, F, Cozzolongo, R, Cucchetti, A, D'Ambrosio, R, Dell'Unto, C, De Matthaeis, N, Di Costanzo, G, Di Sandro, S, Famularo, S, Foschi, F, Fucilli, F, Galati, G, Gambato, M, Gasbarrini, A, Giuliante, F, Ghinolfi, D, Grieco, A, Gruttadauria, S, Guarino, M, Iavarone, M, Kostandini, A, Lai, Q, Lenci, I, Levi Sandri, G, Losito, F, Lupo, L, Marasco, G, Manzia, T, Mazzocato, S, Masarone, M, Melandro, F, Mescoli, C, Miele, L, Morisco, F, Muley, M, Nicolini, D, Pagano, D, Persico, M, Pompili, M, Ponziani, F, Pravisani, R, Rapaccini, G, Rendina, M, Renzulli, M, Romano, F, Rossi, M, Rreka, E, Russo, F, Sangiovanni, A, Sessa, A, Simonetti, N, Sposito, C, Tortora, R, Vigano, L, Vigano, M, Villa, E, Vincenzi, V, Violi, P, Azzaroli, F, Brunetto, M, Di Marco, A, Masotto, A, Mega, A, Nardone, G, Oliveri, F, Raimondo, G, Svegliati Baroni, G, Vidili, G, Zoli, M, Vitale A., Farinati F., Finotti M., Di Renzo C., Brancaccio G., Piscaglia F., Cabibbo G., Caturelli E., Missale G., Marra F., Sacco R., Giannini E. G., Trevisani F., Cillo U., Bhoori S., Borzio M., Burra P., Casadei Gardini A., Carrai P., Conti F., Cozzolongo R., Cucchetti A., D'ambrosio R., Dell'unto C., De Matthaeis N., Di Costanzo G. G., Di Sandro S., Famularo S., Foschi F. G., Fucilli F., Galati G., Gambato M., Gasbarrini A., Giuliante F., Ghinolfi D., Grieco A., Gruttadauria S., Guarino M., Iavarone M., Kostandini A., Lai Q., Lenci I., Levi Sandri G. V., Losito F., Lupo L. G., Marasco G., Manzia T. M., Mazzocato S., Masarone M., Melandro F., Mescoli C., Miele L., Morisco F., Muley M., Nicolini D., Pagano D., Persico M., Pompili M., Ponziani F. R., Pravisani R., Rapaccini G. L., Rendina M., Renzulli M., Romano F., Rossi M., Rreka E., Russo F. P., Sangiovanni A., Sessa A., Simonetti N., Sposito C., Tortora R., Vigano L., Vigano M., Villa E., Vincenzi V., Violi P., Azzaroli F., Brunetto M. R., Di Marco A., Masotto A., Mega A., Nardone G., Oliveri F., Raimondo G., Svegliati Baroni G., Vidili G., Zoli M., Vitale, A, Farinati, F, Finotti, M, Di Renzo, C, Brancaccio, G, Piscaglia, F, Cabibbo, G, Caturelli, E, Missale, G, Marra, F, Sacco, R, Giannini, E, Trevisani, F, Cillo, U, Bhoori, S, Borzio, M, Burra, P, Casadei Gardini, A, Carrai, P, Conti, F, Cozzolongo, R, Cucchetti, A, D'Ambrosio, R, Dell'Unto, C, De Matthaeis, N, Di Costanzo, G, Di Sandro, S, Famularo, S, Foschi, F, Fucilli, F, Galati, G, Gambato, M, Gasbarrini, A, Giuliante, F, Ghinolfi, D, Grieco, A, Gruttadauria, S, Guarino, M, Iavarone, M, Kostandini, A, Lai, Q, Lenci, I, Levi Sandri, G, Losito, F, Lupo, L, Marasco, G, Manzia, T, Mazzocato, S, Masarone, M, Melandro, F, Mescoli, C, Miele, L, Morisco, F, Muley, M, Nicolini, D, Pagano, D, Persico, M, Pompili, M, Ponziani, F, Pravisani, R, Rapaccini, G, Rendina, M, Renzulli, M, Romano, F, Rossi, M, Rreka, E, Russo, F, Sangiovanni, A, Sessa, A, Simonetti, N, Sposito, C, Tortora, R, Vigano, L, Vigano, M, Villa, E, Vincenzi, V, Violi, P, Azzaroli, F, Brunetto, M, Di Marco, A, Masotto, A, Mega, A, Nardone, G, Oliveri, F, Raimondo, G, Svegliati Baroni, G, Vidili, G, Zoli, M, Vitale A., Farinati F., Finotti M., Di Renzo C., Brancaccio G., Piscaglia F., Cabibbo G., Caturelli E., Missale G., Marra F., Sacco R., Giannini E. G., Trevisani F., Cillo U., Bhoori S., Borzio M., Burra P., Casadei Gardini A., Carrai P., Conti F., Cozzolongo R., Cucchetti A., D'ambrosio R., Dell'unto C., De Matthaeis N., Di Costanzo G. G., Di Sandro S., Famularo S., Foschi F. G., Fucilli F., Galati G., Gambato M., Gasbarrini A., Giuliante F., Ghinolfi D., Grieco A., Gruttadauria S., Guarino M., Iavarone M., Kostandini A., Lai Q., Lenci I., Levi Sandri G. V., Losito F., Lupo L. G., Marasco G., Manzia T. M., Mazzocato S., Masarone M., Melandro F., Mescoli C., Miele L., Morisco F., Muley M., Nicolini D., Pagano D., Persico M., Pompili M., Ponziani F. R., Pravisani R., Rapaccini G. L., Rendina M., Renzulli M., Romano F., Rossi M., Rreka E., Russo F. P., Sangiovanni A., Sessa A., Simonetti N., Sposito C., Tortora R., Vigano L., Vigano M., Villa E., Vincenzi V., Violi P., Azzaroli F., Brunetto M. R., Di Marco A., Masotto A., Mega A., Nardone G., Oliveri F., Raimondo G., Svegliati Baroni G., Vidili G., and Zoli M.

Abstract

Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described.

Published
2021

22. Real-world experience with obeticholic acid in patients with primary biliary cholangitis

Author

D'Amato, D, De Vincentis, A, Malinverno, F, Vigano, M, Alvaro, D, Pompili, M, Picciotto, A, Palitti, V, Russello, M, Storato, S, Pigozzi, M, Calvaruso, V, De Gasperi, E, Lleo, A, Castellaneta, A, Pellicelli, A, Cazzagon, N, Floreani, A, Muratori, L, Fagiuoli, S, Niro, G, Feletti, V, Cozzolongo, R, Terreni, N, Marzioni, M, Pellicano, R, Pozzoni, P, Baiocchi, L, Chessa, L, Rosina, F, Bertino, G, Vinci, M, Morgando, A, Vanni, E, Scifo, G, Sacco, R, D'Anto, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, Cristoferi, L, Gerussi, A, Ronca, V, Venere, R, Ponziani, F, Cannavo, M, Mussetto, A, Fontana, R, Losito, F, Frazzetto, E, Distefano, M, Colapietro, F, Labanca, S, Marconi, G, Grassi, G, Galati, G, O'Donnell, S, Mancuso, C, Mulinacci, G, Palermo, A, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Carbone, M, Vespasiani-Gentilucci, U, D'Amato D., De Vincentis A., Malinverno F., Vigano M., Alvaro D., Pompili M., Picciotto A., Palitti V. P., Russello M., Storato S., Pigozzi M. G., Calvaruso V., De Gasperi E., Lleo A., Castellaneta A., Pellicelli A., Cazzagon N., Floreani A., Muratori L., Fagiuoli S., Niro G. A., Feletti V., Cozzolongo R., Terreni N., Marzioni M., Pellicano R., Pozzoni P., Baiocchi L., Chessa L., Rosina F., Bertino G., Vinci M., Morgando A., Vanni E., Scifo G., Sacco R., D'Anto M., Bellia V., Boldizzoni R., Casella S., Omazzi B., Poggi G., Cristoferi L., Gerussi A., Ronca V., Venere R., Ponziani F., Cannavo M., Mussetto A., Fontana R., Losito F., Frazzetto E., Distefano M., Colapietro F., Labanca S., Marconi G., Grassi G., Galati G., O'Donnell S. E., Mancuso C., Mulinacci G., Palermo A., Claar E., Izzi A., Picardi A., Invernizzi P., Carbone M., Vespasiani-Gentilucci U., D'Amato, D, De Vincentis, A, Malinverno, F, Vigano, M, Alvaro, D, Pompili, M, Picciotto, A, Palitti, V, Russello, M, Storato, S, Pigozzi, M, Calvaruso, V, De Gasperi, E, Lleo, A, Castellaneta, A, Pellicelli, A, Cazzagon, N, Floreani, A, Muratori, L, Fagiuoli, S, Niro, G, Feletti, V, Cozzolongo, R, Terreni, N, Marzioni, M, Pellicano, R, Pozzoni, P, Baiocchi, L, Chessa, L, Rosina, F, Bertino, G, Vinci, M, Morgando, A, Vanni, E, Scifo, G, Sacco, R, D'Anto, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, Cristoferi, L, Gerussi, A, Ronca, V, Venere, R, Ponziani, F, Cannavo, M, Mussetto, A, Fontana, R, Losito, F, Frazzetto, E, Distefano, M, Colapietro, F, Labanca, S, Marconi, G, Grassi, G, Galati, G, O'Donnell, S, Mancuso, C, Mulinacci, G, Palermo, A, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Carbone, M, Vespasiani-Gentilucci, U, D'Amato D., De Vincentis A., Malinverno F., Vigano M., Alvaro D., Pompili M., Picciotto A., Palitti V. P., Russello M., Storato S., Pigozzi M. G., Calvaruso V., De Gasperi E., Lleo A., Castellaneta A., Pellicelli A., Cazzagon N., Floreani A., Muratori L., Fagiuoli S., Niro G. A., Feletti V., Cozzolongo R., Terreni N., Marzioni M., Pellicano R., Pozzoni P., Baiocchi L., Chessa L., Rosina F., Bertino G., Vinci M., Morgando A., Vanni E., Scifo G., Sacco R., D'Anto M., Bellia V., Boldizzoni R., Casella S., Omazzi B., Poggi G., Cristoferi L., Gerussi A., Ronca V., Venere R., Ponziani F., Cannavo M., Mussetto A., Fontana R., Losito F., Frazzetto E., Distefano M., Colapietro F., Labanca S., Marconi G., Grassi G., Galati G., O'Donnell S. E., Mancuso C., Mulinacci G., Palermo A., Claar E., Izzi A., Picardi A., Invernizzi P., Carbone M., and Vespasiani-Gentilucci U.

Abstract

Background & aims: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compare

Published
2021

23. Correction to: Treat all COVID 19‐positive patients, but do not forget those negative with chronic diseases (Internal and Emergency Medicine, (2020), 15, 5, (787-790), 10.1007/s11739-020-02395-z)

Author

Vigano, M, Mantovani, L, Cozzolino, P, Harari, S, Vigano M., Mantovani L., Cozzolino P., Harari S., Vigano, M, Mantovani, L, Cozzolino, P, Harari, S, Vigano M., Mantovani L., Cozzolino P., and Harari S.

Abstract

In the original publication of the article, the given name and family name of all the author were swapped. The correct author name is given in this erratum.

Published
2021

25. Comparison of three therapeutic regimens for genotype-3 hepatitis C virus infection in a large real-life multicentre cohort

Author

Soria, A, Fava, M, Bernasconi, D, Lapadula, G, Colella, E, Valsecchi, M, Migliorino, G, D'Ambrosio, R, Landonio, S, Schiavini, M, Spinetti, A, Carriero, C, Degasperi, E, Cologni, G, Gatti, F, Vigano, P, Hasson, H, Uberti-Foppa, C, Pasulo, L, Baiguera, C, Rossotti, R, Vinci, M, Puoti, M, Giorgini, A, Menzaghi, B, Lombardi, A, Pan, A, Aghemo, A, Grossi, P, Boldizzoni, R, Colombo, S, Vigano, M, Rumi, M, Del Poggio, P, Valenti, L, Giglio, O, De Bona, A, d'Arminio Monforte, A, Colombo, A, Spinelli, O, Pigozzi, M, Molteni, C, Bonfanti, P, Terreni, N, Perini, P, Capretti, A, Bella, D, Liani, C, Polo, S, Aimo, G, Pagnucco, L, Bhoori, S, Centenaro, R, Graffeo, M, Ciaccio, A, Dionigi, E, Lazzaroni, S, Carderi, I, Di Marco, M, Rizzardini, G, Noventa, F, Lampertico, P, Fagiuoli, S, Soria A., Fava M., Bernasconi D. P., Lapadula G., Colella E., Valsecchi M. G., Migliorino G. M., D'Ambrosio R., Landonio S., Schiavini M., Spinetti A., Carriero C., Degasperi E., Cologni G., Gatti F., Vigano P., Hasson H., Uberti-Foppa C., Pasulo L., Baiguera C., Rossotti R., Vinci M., Puoti M., Giorgini A., Menzaghi B., Lombardi A., Pan A., Aghemo A., Grossi P. A., Boldizzoni R., Colombo S., Vigano M., Rumi M. G., Del Poggio P., Valenti L., Giglio O., De Bona A., d'Arminio Monforte A., Colombo A., Spinelli O., Pigozzi M. G., Molteni C., Bonfanti P., Terreni N., Perini P., Capretti A., Bella D., Liani C., Polo S., Aimo G., Pagnucco L., Bhoori S., Centenaro R., Graffeo M., Ciaccio A., Dionigi E., Lazzaroni S., Carderi I., Di Marco M., Rizzardini G., Noventa F., Lampertico P., Fagiuoli S., Soria, A, Fava, M, Bernasconi, D, Lapadula, G, Colella, E, Valsecchi, M, Migliorino, G, D'Ambrosio, R, Landonio, S, Schiavini, M, Spinetti, A, Carriero, C, Degasperi, E, Cologni, G, Gatti, F, Vigano, P, Hasson, H, Uberti-Foppa, C, Pasulo, L, Baiguera, C, Rossotti, R, Vinci, M, Puoti, M, Giorgini, A, Menzaghi, B, Lombardi, A, Pan, A, Aghemo, A, Grossi, P, Boldizzoni, R, Colombo, S, Vigano, M, Rumi, M, Del Poggio, P, Valenti, L, Giglio, O, De Bona, A, d'Arminio Monforte, A, Colombo, A, Spinelli, O, Pigozzi, M, Molteni, C, Bonfanti, P, Terreni, N, Perini, P, Capretti, A, Bella, D, Liani, C, Polo, S, Aimo, G, Pagnucco, L, Bhoori, S, Centenaro, R, Graffeo, M, Ciaccio, A, Dionigi, E, Lazzaroni, S, Carderi, I, Di Marco, M, Rizzardini, G, Noventa, F, Lampertico, P, Fagiuoli, S, Soria A., Fava M., Bernasconi D. P., Lapadula G., Colella E., Valsecchi M. G., Migliorino G. M., D'Ambrosio R., Landonio S., Schiavini M., Spinetti A., Carriero C., Degasperi E., Cologni G., Gatti F., Vigano P., Hasson H., Uberti-Foppa C., Pasulo L., Baiguera C., Rossotti R., Vinci M., Puoti M., Giorgini A., Menzaghi B., Lombardi A., Pan A., Aghemo A., Grossi P. A., Boldizzoni R., Colombo S., Vigano M., Rumi M. G., Del Poggio P., Valenti L., Giglio O., De Bona A., d'Arminio Monforte A., Colombo A., Spinelli O., Pigozzi M. G., Molteni C., Bonfanti P., Terreni N., Perini P., Capretti A., Bella D., Liani C., Polo S., Aimo G., Pagnucco L., Bhoori S., Centenaro R., Graffeo M., Ciaccio A., Dionigi E., Lazzaroni S., Carderi I., Di Marco M., Rizzardini G., Noventa F., Lampertico P., and Fagiuoli S.

Abstract

Background & Aims: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. Methods: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. Results: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P =.065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P =.007) and lower median pretreatment Log10HCV-RNA (5.87 vs 6.20, P =.001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. Conclusions: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <> genotype.

Published
2020

26. Interaction Between Recovery of Motor and Language Abilities After Stroke

Author

Ginex, V, Gilardone, G, Vigano, M, Monti, A, Judica, E, Passaro, I, Gilardone, M, Vanacore, N, Corbo, M, Ginex V., Gilardone G., Vigano M., Monti A., Judica E., Passaro I., Gilardone M., Vanacore N., Corbo M., Ginex, V, Gilardone, G, Vigano, M, Monti, A, Judica, E, Passaro, I, Gilardone, M, Vanacore, N, Corbo, M, Ginex V., Gilardone G., Vigano M., Monti A., Judica E., Passaro I., Gilardone M., Vanacore N., and Corbo M.

Abstract

Objective: To analyze the nature of the interaction between motor and language recovery in patients with motor impairment and aphasia following left hemispheric stroke and to investigate prognostic factors of best recovery, that is, the significant recovery of both functions simultaneously. Design: Retrospective cohort study. Setting: Specialized inpatient rehabilitation facility. Participants: Patients (N=435) with left hemispheric stroke in the postacute phase with motor impairment and aphasia. Intervention: Not applicable. Main Outcome Measure: Patients who reached the minimal clinically important difference in the motor-FIM (M-FIM) were classified as motor responders, patients who reached a significant change in Aachen Aphasia Test were classified as language responders, and patients who reached a simultaneous and significant improvement in both functions were classified as motor and language responders. Results: Of the sample 45% were motor responders, 58% were language responders, and 35% were motor and language responders. Responder groups showed lower motor impairment and less severe aphasia at admission and greater improvement in both functions at discharge compared with nonresponder groups. Premorbid autonomy, dysphagia, apraxia, and number of rehabilitative sessions were also significantly different between groups. A logistic regression model identified M-FIM, repetition abilities, and number of sessions of speech and language therapy as independent predictors of best response (ie, motor and language responders). Conclusions: This study provides evidence about a possible interaction between motor and language recovery after stroke. The improvement in one function was never associated with deterioration in the other. The results actually suggest a synergic effect between the amelioration of the 2 functions, with an overall increased efficiency when the 2 recovery pathways are combined.

Published
2020

27. Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study

Author

Lampertico, P, Berg, T, Buti, M, Pathil, A, Petersen, J, Ryder, S, Zoulim, F, Botros, I, Flaherty, J, Jump, B, Op den Brouw, M, van Troostenburg, A, Ramroth, H, Bourliere, M, De Ledinghen, V, Riachi, G, Loustaud-Ratti, V, Tran, A, Larrey, D, Dumortier, J, Leroy, V, Metivier, S, Sellier, P, Mauss, S, Peterson, J, Schiefke, I, Niederau, C, Teuber, G, Goeser, T, Jung, M, Grambihler, A, Pathil-Warth, A, Sprinzl, K, Von der Ohe, M, Antoni, C, Weigand, K, Andreone, P, Di Marco, V, Madonia, S, Puoti, M, Santantonio, T, Vigano, M, Ciancio, A, D'Offizi, G, Pirisi, M, Suarez Garcia, E, Pascasio Acevedo, J, Andrade, R, Gea, F, Serra Desfilis, M, Molina Perez, E, Manzano Alonso, M, Carrion, J, Aoufi Rabih, S, Planas, M, Agarwal, K, Ustianowski, A, Aspinall, R, Kennedy, P, Geretti, A, Mccorry, R, Foxton, M, Healy, B, Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S. D., Zoulim F., Botros I., Flaherty J. F., Jump B., Op den Brouw M. L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M. C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J. M., Andrade R., Gea F., Serra Desfilis M. A., Molina Perez E., Manzano Alonso M., Carrion J. A., Aoufi Rabih S., Planas M. M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A. M., McCorry R., Foxton M., Healy B., Lampertico, P, Berg, T, Buti, M, Pathil, A, Petersen, J, Ryder, S, Zoulim, F, Botros, I, Flaherty, J, Jump, B, Op den Brouw, M, van Troostenburg, A, Ramroth, H, Bourliere, M, De Ledinghen, V, Riachi, G, Loustaud-Ratti, V, Tran, A, Larrey, D, Dumortier, J, Leroy, V, Metivier, S, Sellier, P, Mauss, S, Peterson, J, Schiefke, I, Niederau, C, Teuber, G, Goeser, T, Jung, M, Grambihler, A, Pathil-Warth, A, Sprinzl, K, Von der Ohe, M, Antoni, C, Weigand, K, Andreone, P, Di Marco, V, Madonia, S, Puoti, M, Santantonio, T, Vigano, M, Ciancio, A, D'Offizi, G, Pirisi, M, Suarez Garcia, E, Pascasio Acevedo, J, Andrade, R, Gea, F, Serra Desfilis, M, Molina Perez, E, Manzano Alonso, M, Carrion, J, Aoufi Rabih, S, Planas, M, Agarwal, K, Ustianowski, A, Aspinall, R, Kennedy, P, Geretti, A, Mccorry, R, Foxton, M, Healy, B, Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S. D., Zoulim F., Botros I., Flaherty J. F., Jump B., Op den Brouw M. L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M. C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J. M., Andrade R., Gea F., Serra Desfilis M. A., Molina Perez E., Manzano Alonso M., Carrion J. A., Aoufi Rabih S., Planas M. M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A. M., McCorry R., Foxton M., and Healy B.

Abstract

Background: Limited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus–infected (CHB) patients with renal impairment (RI). Aims: To compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI. Methods: Retrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation (‘before’ subgroup [baseline = treatment initiation]) or after TDF/ETV initiation (‘after’ subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting. Results: ‘Before’ subgroup included 107 TDF- and 91 ETV-treated patients; ‘after’ subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV (‘before’: 18.7% vs 8.8%; ‘after’: 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% ‘before’; 1.9% ‘after’) as well as renal adverse events leading to treatment discontinuation (8.4% ‘before’; 7.1% ‘after’). Effectiveness was similar between treatments. Conclusions: Overall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

Published
2020

29. Reply to: Correspondence on “High rates of 30-day mortality in patients with cirrhosis and COVID-19”

Author

Iavarone, M, D'Ambrosio, R, Lampertico, P, Rimondi, A, Soria, A, Bonfanti, P, Triolo, M, Fagiuoli, S, Pugliese, N, Aghemo, A, Del Poggio, P, Perricone, G, Belli, L, Massironi, S, Luca, M, Invernizzi, P, Spinetti, A, Carriero, C, Buscarini, E, Pedaci, M, Vigano, M, Rumi, M, Iavarone M., D'Ambrosio R., Lampertico P., Rimondi A., Soria A., Bonfanti P., Triolo M., Fagiuoli S., Pugliese N., Aghemo A., Del Poggio P., Perricone G., Belli L. S., Massironi S., Luca M., Invernizzi P., Spinetti A., Carriero C., Buscarini E., Pedaci M., Vigano M., Rumi M. G., Iavarone, M, D'Ambrosio, R, Lampertico, P, Rimondi, A, Soria, A, Bonfanti, P, Triolo, M, Fagiuoli, S, Pugliese, N, Aghemo, A, Del Poggio, P, Perricone, G, Belli, L, Massironi, S, Luca, M, Invernizzi, P, Spinetti, A, Carriero, C, Buscarini, E, Pedaci, M, Vigano, M, Rumi, M, Iavarone M., D'Ambrosio R., Lampertico P., Rimondi A., Soria A., Bonfanti P., Triolo M., Fagiuoli S., Pugliese N., Aghemo A., Del Poggio P., Perricone G., Belli L. S., Massironi S., Luca M., Invernizzi P., Spinetti A., Carriero C., Buscarini E., Pedaci M., Vigano M., and Rumi M. G.

Published
2020

30. Harmonization of sensorimotor deficit assessment in a registered multicentre pre-clinical randomized controlled trial using two models of ischemic stroke

Author

Valente, A., Mariani, J., Seminara, S., Tettamanti, M., Pignataro, G., Perego, C., Sironi, L., Pedata, F., Amantea, D., Bacigaluppi, M., Vinciguerra, A., Diamanti, S., Vigano, M., Santangelo, F., Zoia, C.P., Rodriguez-Menendez, V., Castiglioni, L., Rzemieniec, J., Dettori, I., Bulli, I., Coppi, E., Di Santo, C., Cuomo, O., Gullotta, G.S., Butti, E., Bagetta, G., Martino, G., De Simoni, M.-., Ferrarese, C., Fumagalli, S., and Beretta, S.

Subjects
interrater agreement, Ischemic stroke, neurobehavior, preclinical multicentre trial, quality check, Neurology, Settore BIO/14 - Farmacologia, Settore MED/26 - Neurologia, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Multicentre preclinical randomized controlled trials (pRCTs) are a valuable tool to improve experimental stroke research, but are challenging and therefore underused. A common challenge regards the standardization of procedures across centres. We here present the harmonization phase for the quantification of sensorimotor deficits by composite neuroscore, which was the primary outcome of two multicentre pRCTs assessing remote ischemic conditioning in rodent models of ischemic stroke. Ischemic stroke was induced by middle cerebral artery occlusion for 30, 45 or 60 min in mice and 50, 75 or 100 min in rats, allowing sufficient variability. Eleven animals per species were video recorded during neurobehavioural tasks and evaluated with neuroscore by eight independent raters, remotely and blindly. We aimed at reaching an intraclass correlation coefficient (ICC) ≥0.60 as satisfactory interrater agreement. After a first remote training we obtained ICC = 0.50 for mice and ICC = 0.49 for rats. Errors were identified in animal handling and test execution. After a second remote training, we reached the target interrater agreement for mice (ICC = 0.64) and rats (ICC = 0.69). In conclusion, a multi-step, online harmonization phase proved to be feasible, easy to implement and highly effective to align each centre’s behavioral evaluations before project’s interventional phase.

Published
2023

31. Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up

Author

Nguyen, Tn, Qureshi, Mm, Klein, P, Yamagami, H, Mikulik, R, Etminan, N, Abdalkader, M, Mansour, Oy, Czlonkowska, A, Lo, H, Sathya, A, Demeestere, J, Tsivgoulis, G, Sakai, N, Sedova, P, Kristoffersen, Es, Mohammaden, M, Lereis, Vp, Scollo, Sd, Ma, A, Rahman, A, Bonnet, T, Cortier, J, De Raedt, S, Lemmens, R, Ligot, N, Hidalgo, Rct, Cuervo, Dlm, Neves, Ld, Rezende, Mts, Santiago, Ib, Sirakov, A, Sirakov, S, Cora, Ea, Kelly, Me, Lavoie, P, Peeling, L, Pikula, A, Rivera, R, Chen, Hs, Chen, Ym, Fang, Hl, Bedekovic, Mr, Budincevic, H, Strossmayer, Jj, Hrabanovska, E, Jurak, L, Cabal, M, Kadlckova, J, Karpowicz, I, Palouskova, H, Reiser, M, Klecka, L, Kovar, M, Neumann, J, Rekova, P, Sramek, M, Vitkova, E, Skorna, M, Zakova, L, Sobh, K, Alpay, K, Rautio, R, Strbian, D, Gentric, Jc, Magro, E, Naggara, O, Reiner, P, Abdulazim, A, Bohmann, Fo, Boskamp, S, Gerber, Jc, Kaiser, Dpo, Kestner, Ri, Mbroh, J, Neyazi, M, Rosenkranz, M, Sani, Af, Poli, S, Thomalla, G, Karapanayiotides, T, Kargiotis, O, Koutroulou, I, Palaiodimou, L, Guerra, Jdb, Huded, V, Nagendra, S, Prajapati, C, Krishna, A, Ghoreishi, A, Ilkhchi, Rb, Jalili, J, Sabetay, Si, Abu Raya, T, Acampa, M, Longoni, M, Bigliani, Cr, Castellan, L, Ornello, R, Renieri, L, Romoli, M, Sacco, S, Sangalli, D, Vigano, M, Zini, A, Tokimura, H, Sonoda, K, Todo, K, Fukuda, H, Fujita, K, Sakaguchi, M, Uno, M, Kan, I, Kosuke, M, Kono, R, Kimura, N, Yamamoto, N, Yamamoto, R, Doijiri, R, Shindo, S, Ohara, N, Imamura, H, Ogawa, T, Uwatoko, T, Kanamaru, T, Fujinaka, T, Takenobu, Y, Toyoda, K, Matsumaru, Y, Yazawa, Y, Sugiura, Y, Baek, Jh, Sunmonu, Ta, Kwon, Ys, Lee, Yh, Seo, Kd, Sohn, Si, Chan, Yc, Zaidi, Waw, Barrientos-Prieto, J, Gongora-Rivera, F, Martinez-Marino, M, Calderon-Vallejo, A, Groppa, S, Pavel, L, Coutinho, Jm, Dippel, D, Rinkel, L, Van Dam-Nolen, Dhk, Nwazor, Eo, Al Hashimi, Am, Ahmad, S, Rashid, U, Rodriguez-Kadota, L, Vences, Ma, Yalung, Pm, Jsh, Dy, Brola, W, Dorobek, M, Karlinski, Ma, Labuz-Roszak, Bm, Lasek-Bal, A, Sienkiewicz-Jarosz, H, Staszewski, J, Sobolewski, P, Zielinska-Turek, J, Araujo, Ap, Fonseca, L, Debiec, A, Silva, Ml, Castro, P, Rocha, M, Falup-Pecurariu, Rc, Venketasubramanian, N, Mako, Gkm, Ayo-Martin, O, Wiacek, M, Blasco, J, Cruz-Culebras, A, Hernandez-Fernandez, F, Fernandez, Cr, Lopez, Je, Rodriguez, A, Bolognese, M, Karwacki, Gm, Keller, E, Machi, P, Bernava, G, Boonyakarnkul, S, Churojana, A, Hammami, N, Bajrami, A, Senadim, S, Hussain, Si, John, S, Dow, G, Krishnan, K, Lenthall, R, Wong, K, Zhang, Lq, Altschul, D, Asif, Ks, Aziz-Sultan, Ma, Bach, I, Below, K, Biller, J, Cervantes-Arslanian, Am, Chaudhry, Sa, Chebl, A, Chen, M, Colasurdo, M, Czap, A, Dasenbrock, H, Bahiru, Z, de Havenon, Ah, Dharmadhikari, S, Dmytriw, Aa, Eskey, Cj, Etherton, M, Ezepue, C, Fink, L, Gasimova, U, Goyal, N, Grimmett, Kb, Hakemi, M, Hester, T, Inoa, V, Kan, Pt, Kasper, Em, Khandelwal, P, Khatri, R, Khoury, Nn, Kim, Bs, Kolikonda, M, Kuhn, Al, Linares, G, Linfante, I, Loochtan, Ai, Lukovits, Tg, Male, Ss, Khawaja, Am, Maali, L, Galecio-Castillo, Em, Min, Jy, Mohamed, Ga, Nalleballe, K, Ortega-Gutierrez, S, Radaideh, Y, Ramakrishnan, P, Masoud, He, Reddy, Ab, Ruland, S, Omran, Ss, Sheth, Sa, Puri, As, Rahangdale, Rh, Siegler, Je, Starosciak, Ak, Tarlov, Ne, Taylor, Ra, Tsai, J, Wang, Mj, Wong, Kh, Zaidat, Oo, Hv, Le, Phan, Ht, Ton, Md, Tran, Ad, Sirakova, K, Pham, Tn, Mohlenbruch, Ma, Nagel, S, Raymond, J, Nogueira, Rg, Neurology, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders

Subjects
Psychiatry and Mental health, SDG 3 - Good Health and Well-being, COVID-19, SUBARACHNOID HAEMORRHAGE, CEREBROVASCULAR DISEASE, Surgery, Neurology (clinical)
Abstract

BackgroundPrior studies indicated a decrease in the incidences of aneurysmal subarachnoid haemorrhage (aSAH) during the early stages of the COVID-19 pandemic. We evaluated differences in the incidence, severity of aSAH presentation, and ruptured aneurysm treatment modality during the first year of the COVID-19 pandemic compared with the preceding year.MethodsWe conducted a cross-sectional study including 49 countries and 187 centres. We recorded volumes for COVID-19 hospitalisations, aSAH hospitalisations, Hunt-Hess grade, coiling, clipping and aSAH in-hospital mortality. Diagnoses were identified by International Classification of Diseases, 10th Revision, codes or stroke databases from January 2019 to May 2021.ResultsOver the study period, there were 16 247 aSAH admissions, 344 491 COVID-19 admissions, 8300 ruptured aneurysm coiling and 4240 ruptured aneurysm clipping procedures. Declines were observed in aSAH admissions (−6.4% (95% CI −7.0% to −5.8%), p=0.0001) during the first year of the pandemic compared with the prior year, most pronounced in high-volume SAH and high-volume COVID-19 hospitals. There was a trend towards a decline in mild and moderate presentations of subarachnoid haemorrhage (SAH) (mild: −5% (95% CI −5.9% to –4.3%), p=0.06; moderate: −8.3% (95% CI −10.2% to –6.7%), p=0.06) but no difference in higher SAH severity. The ruptured aneurysm clipping rate remained unchanged (30.7% vs 31.2%, p=0.58), whereas ruptured aneurysm coiling increased (53.97% vs 56.5%, p=0.009). There was no difference in aSAH in-hospital mortality rate (19.1% vs 20.1%, p=0.12).ConclusionDuring the first year of the pandemic, there was a decrease in aSAH admissions volume, driven by a decrease in mild to moderate presentation of aSAH. There was an increase in the ruptured aneurysm coiling rate but neither change in the ruptured aneurysm clipping rate nor change in aSAH in-hospital mortality.Trial registration numberNCT04934020.

Published
2022

32. Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study

Author

Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S. D., Zoulim F., Botros I., Flaherty J. F., Jump B., Op den Brouw M. L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M. C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J. M., Andrade R., Gea F., Serra Desfilis M. A., Molina Perez E., Manzano Alonso M., Carrion J. A., Aoufi Rabih S., Planas M. M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A. M., McCorry R., Foxton M., Healy B., Lampertico P., Berg T., Buti M., Pathil A., Petersen J., Ryder S.D., Zoulim F., Botros I., Flaherty J.F., Jump B., Op den Brouw M.L., van Troostenburg A., Ramroth H., Bourliere M., De Ledinghen V., Riachi G., Loustaud-Ratti V., Tran A., Larrey D., Dumortier J., Leroy V., Metivier S., Sellier P., Mauss S., Peterson J., Schiefke I., Niederau C., Teuber G., Goeser T., Jung M.C., Grambihler A., Pathil-Warth A., Sprinzl K., Von der Ohe M., Antoni C., Weigand K., Andreone P., Di Marco V., Madonia S., Puoti M., Santantonio T., Vigano M., Ciancio A., D'Offizi G., Pirisi M., Suarez Garcia E., Pascasio Acevedo J.M., Andrade R., Gea F., Serra Desfilis M.A., Molina Perez E., Manzano Alonso M., Carrion J.A., Aoufi Rabih S., Planas M.M., Ryder S., Agarwal K., Ustianowski A., Aspinall R., Kennedy P., Geretti A.M., McCorry R., Foxton M., Healy B., Lampertico, P, Berg, T, Buti, M, Pathil, A, Petersen, J, Ryder, S, Zoulim, F, Botros, I, Flaherty, J, Jump, B, Op den Brouw, M, van Troostenburg, A, Ramroth, H, Bourliere, M, De Ledinghen, V, Riachi, G, Loustaud-Ratti, V, Tran, A, Larrey, D, Dumortier, J, Leroy, V, Metivier, S, Sellier, P, Mauss, S, Peterson, J, Schiefke, I, Niederau, C, Teuber, G, Goeser, T, Jung, M, Grambihler, A, Pathil-Warth, A, Sprinzl, K, Von der Ohe, M, Antoni, C, Weigand, K, Andreone, P, Di Marco, V, Madonia, S, Puoti, M, Santantonio, T, Vigano, M, Ciancio, A, D'Offizi, G, Pirisi, M, Suarez Garcia, E, Pascasio Acevedo, J, Andrade, R, Gea, F, Serra Desfilis, M, Molina Perez, E, Manzano Alonso, M, Carrion, J, Aoufi Rabih, S, Planas, M, Agarwal, K, Ustianowski, A, Aspinall, R, Kennedy, P, Geretti, A, Mccorry, R, Foxton, M, and Healy, B

Subjects
Male, Adult, medicine.medical_specialty, Guanine, Tenofovir, MEDLINE, Antiviral Agents, Virus, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Hepatitis B, Chronic, Retrospective Studie, Internal medicine, 80 and over, HBV, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Renal Insufficiency, Young adult, Aged, Aged, 80 and over, Female, Middle Aged, Retrospective Studies, Treatment Outcome, Chronic, Antiviral Agent, Hepatology, business.industry, Gastroenterology, virus diseases, Retrospective cohort study, Entecavir, Hepatitis B, medicine.disease, Cohort, 030211 gastroenterology & hepatology, business, medicine.drug, Human
Abstract

BackgroundLimited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus-infected (CHB) patients with renal impairment (RI).AimsTo compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI.MethodsRetrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation ('before' subgroup [baseline = treatment initiation]) or after TDF/ETV initiation ('after' subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting.Results'Before' subgroup included 107 TDF- and 91 ETV-treated patients; 'after' subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV ('before': 18.7% vs 8.8%; 'after': 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% 'before'; 1.9% 'after') as well as renal adverse events leading to treatment discontinuation (8.4% 'before'; 7.1% 'after'). Effectiveness was similar between treatments.ConclusionsOverall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

Published
2020

33. Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial

Author

Masson, R., Mazurkiewicz-Bełdzińska, M., Rose, K., Servais, L., Xiong, H., Zanoteli, E., Baranello, Giovanni, Bruno, C., Day, J. W., Deconinck, N., Klein, A., Mercuri, Eugenio Maria, Vlodavets, D., Wang, Y., Dodman, A., El-Khairi, M., Gorni, K., Jaber, B., Kletzl, H., Gaki, E., Fontoura, P., Darras, B. T., Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Gerber, M., Khwaja, O., Scalco, R. S., Seabrook, T., Koch, A., Balikova, I., Joniau, I., Accou, G., Tahon, V., Wittevrongel, S., De Vos, E., de Holanda Mendonça, R., Matsui, C., Fornazieri Darcie, A. L., Machado, C., Kiyoko Oyamada, M., Martini, J., Polido, G., Rodrigues Iannicelli, J., Caires de Oliveira Achili Ferreira, J., Hu, C., Zhu, X., Qian, C., Shen, L., Li, H., Shi, Y., Zhou, S., Xiao, Y., Zhou, Z., Wang, S., Sang, T., Wei, C., Dong, H., Cao, Y., Wen, J., Li, W., Qin, L., Barisic, N., Celovec, I., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Tomas, J., Boespflug-Tanguy, O., De Lucia, S., Seferian, A., Barreau, E., Mnafek, N., Peche, H., Grange, A., Trang Nguyen, D., Milascevic, D., Tachibana, S., Pagliano, E., Bianchi Marzoli, S., Santarsiero, D., Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Dosi, C., Zanin, R., Schembri, V., Brolatti, N., Rao, G., Tassara, E., Morando, S., Tacchetti, P., Pedemonte, M., Priolo, E., Sposetti, L., Baranello G., Mercuri E. (ORCID:0000-0002-9851-5365), Masson, R., Mazurkiewicz-Bełdzińska, M., Rose, K., Servais, L., Xiong, H., Zanoteli, E., Baranello, Giovanni, Bruno, C., Day, J. W., Deconinck, N., Klein, A., Mercuri, Eugenio Maria, Vlodavets, D., Wang, Y., Dodman, A., El-Khairi, M., Gorni, K., Jaber, B., Kletzl, H., Gaki, E., Fontoura, P., Darras, B. T., Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Gerber, M., Khwaja, O., Scalco, R. S., Seabrook, T., Koch, A., Balikova, I., Joniau, I., Accou, G., Tahon, V., Wittevrongel, S., De Vos, E., de Holanda Mendonça, R., Matsui, C., Fornazieri Darcie, A. L., Machado, C., Kiyoko Oyamada, M., Martini, J., Polido, G., Rodrigues Iannicelli, J., Caires de Oliveira Achili Ferreira, J., Hu, C., Zhu, X., Qian, C., Shen, L., Li, H., Shi, Y., Zhou, S., Xiao, Y., Zhou, Z., Wang, S., Sang, T., Wei, C., Dong, H., Cao, Y., Wen, J., Li, W., Qin, L., Barisic, N., Celovec, I., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Tomas, J., Boespflug-Tanguy, O., De Lucia, S., Seferian, A., Barreau, E., Mnafek, N., Peche, H., Grange, A., Trang Nguyen, D., Milascevic, D., Tachibana, S., Pagliano, E., Bianchi Marzoli, S., Santarsiero, D., Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Dosi, C., Zanin, R., Schembri, V., Brolatti, N., Rao, G., Tassara, E., Morando, S., Tacchetti, P., Pedemonte, M., Priolo, E., Sposetti, L., Baranello G., and Mercuri E. (ORCID:0000-0002-9851-5365)

Abstract

Background: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. Methods: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural his

Published
2022

34. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial

Author

Mercuri, Eugenio Maria, Deconinck, N., Mazzone, Elena Stacy, Nascimento, A., Oskoui, M., Saito, K., Vuillerot, C., Baranello, Giovanni, Boespflug-Tanguy, O., Goemans, N., Kirschner, J., Kostera-Pruszczyk, A., Servais, L., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Staunton, H., Yeung, W. Y., Martin, Craig, Fontoura, P., Day, J. W., Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Fuerst-Recktenwald, S., Marquet, A., Mulhardt, N., Trundell, D., Daron, A., Delstanche, S., Romain, B., Dal Farra, F., Schneider, O., Balikova, I., Delbeke, P., Joniau, I., Tahon, V., Wittevrongel, S., De Vos, E., Casteels, I., De Waele, L., Cassiman, C., Prove, L., Kinoo, D., Vancampenhout, L., Van Den Hauwe, M., Van Impe, A., Prufer de Queiroz Campos Araujo, A., Chacon Pereira, A., Nardes, F., Haefeli, L., Rossetto, J., Almeida Pereira, J., Ferreira Rebel, M., Campbell, C., Sharan, S., Mcdonald, W., Scholtes, C., Mah, J., Sframeli, M., Chiu, A., Hagel, J., Beneish, R., Pham, C., Toffoli, D., Arpin, S., Turgeon Desilets, S., Wang, Y., Hu, C., Huang, J., Qian, C., Shen, L., Xiao, Y., Zhou, Z., Li, H., Wang, S., Xiong, H., Chang, X., Dong, H., Liu, Y., Sang, T., Wei, C., Wen, J., Cao, Y., Lv, X., Zhao, J., Li, W., Qin, L., Barisic, N., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Gidaro, T., Seferian, A., De Lucia, Sara Sofia, Barreau, E., Mnafek, N., Momtchilova, M. M., Peche, H., Valherie, C., Grange, A., Lilien, C., Milascevic, D., Tachibana, S., Ravelli, C., Cardas, R., Vanden Brande, L., Davion, J. -B., Coopman, S., Bouacha, I., Debruyne, P., Defoort, S., Derlyn, G., Leroy, F., Danjoux, L., Guilbaud, J., Desguerre, I., Barnerias, C., Semeraro, M., Bremond-Gignac, D., Bruere, L., Rateaux, M., Deladriere, E., Germa, V., Pereon, Y., Magot, A., Mercie, S., Billaud, F., Le Goff, L., Letellier, G., Portefaix, A., Fontaine, S., De-Montferrand, C., Le-Goff, L., Saidi, M., Bouzid, N., Barriere, A., Tinat, M., Dreesbach, M., Lagreze, W., Michaelis, B., Molnar, F., Seger, D., Vogt, S., Bertini, Enrico Silvio, D'Amico, Adele, Petroni, S., Bonetti, A. M., Carlesi, A., Mizzoni, I., Bruno, C., Priolo, E., Rao, G., Morando, S., Tacchetti, P., Zuffi, A., Comi, G. P., Brusa, R., Corti, Serafino, Daniele, V., Govoni, A., Magri, F., Minorini, V., Osnaghi, S. G., Abbati, F., Fassini, F., Foa, M., Lopopolo, A., Meneri, M., Zoppas, F., Parente, V., Masson, R., Bianchi Marzoli, Stefania, Santarsiero, Rocco Domenico, Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Zanin, Renata, Amorelli, Giulia Maria, Barresi, C., D'Amico, Guglielmo, Orazi, Lorenzo, Coratti, Giorgia, Haginoya, K., Kato, A., Morishita, Y., Kira, R., Akiyama, K., Goto, M., Mori, Y., Okamoto, M., Tsutsui, S., Takatsuji, Y., Tanaka, A., Komaki, H., Suzuki, I., Takeuchi, M., Todoroki, D., Watanabe, S., Omori, M., Matsubayashi, T., Inakazu, E., Nagura, H., Suzuki, A., Osaka, H., Ohashi, M., Ishikawa, N., Harada, Y., Fudeyasu, K., Hirata, K., Michiue, K., Ueda, K., Yashiro, S., Seki, M., Sano, N., Uemura, A., Fukuyama, K., Matsumoto, Y., Miyazaki, H., Shibata, M., Kobayashi, K., Nakamura, Y., Takeshima, Y., Kuma, M., Fraczek, A., Jedrzejowska, M., Lusakowska, A., Czeszyk-Piotrowicz, A., Hautz, W., Rakusiewicz, K., Burlewicz, M., Gierlak-Wojcicka, Z., Kepa, M., Sikorski, A., Sobieraj, M., Mazurkiewicz-Beldzinska, M., Lemska, A., Modrzejewska, S., Koberda, M., Stodolska-Koberda, U., Waskowska, A., Kolendo, J., Sobierajska-Rek, A., Steinborn, B., Dalz, M., Grabowska, J., Hajduk, W., Janasiewicz-Karachitos, J., Klimas, M., Stopa, M., Gajewska, E., Pusz, B., Vlodavets, D., Melnik, E., Leppenen, N., Yupatova, N., Monakhova, A., Papina, Y., Shidlovsckaia, O., Milic Rasic, V., Brankovic, V., Kosac, A., Djokic, O., Jaksic, V., Pepic, A., Martinovic, J., Munell Casadesus, F., Tizzano, E., Martin Begue, N., Wolley Dod, C., Subira, O., Planas Pascual, B., Toro Tamargo, E., Madruga Garrido, M., Medina Romero, J. D., Salinas, M. P., Nascimento Osorio, A., Diaz Cortes, A., Jimenez Ganan, E., Suh, S. D., Medina Cantillo, J., Moya, O., Padros, N., Roca Urraca, S., Gonzalez Valdivia, H., Pascual Pascual, S., de Manuel, S., Noval Martin, S., Burnham, P., Espinosa Garcia, S., Martinez Moreno, M., Topaloglu, H., Oncel, I., Eroglu Ertugrul, N., Konuskan, B., Eldem, B., Kadayifcilar, S., Alemdaroglu, I., Ayse Karaduman, A., Tunca Yilmaz, O., Bilgin, N., Sari, S., Chiriboga, C., Kane, S., Lee, J., Rome-Martin, D., Beres, S., Duong, T., Gee, R., Dunaway Young, S., Mercuri E. (ORCID:0000-0002-9851-5365), Mazzone E. S., Baranello G., Martin C., De Lucia S., Bertini E., D'Amico A., Corti S., Bianchi Marzoli S., Santarsiero D., Zanin R., Amorelli G. M., D'Amico G., Orazi L., Coratti G. (ORCID:0000-0001-6666-5628), Mercuri, Eugenio Maria, Deconinck, N., Mazzone, Elena Stacy, Nascimento, A., Oskoui, M., Saito, K., Vuillerot, C., Baranello, Giovanni, Boespflug-Tanguy, O., Goemans, N., Kirschner, J., Kostera-Pruszczyk, A., Servais, L., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Staunton, H., Yeung, W. Y., Martin, Craig, Fontoura, P., Day, J. W., Volpe, J. J., Posner, J., Kellner, U., Quinlivan, R., Fuerst-Recktenwald, S., Marquet, A., Mulhardt, N., Trundell, D., Daron, A., Delstanche, S., Romain, B., Dal Farra, F., Schneider, O., Balikova, I., Delbeke, P., Joniau, I., Tahon, V., Wittevrongel, S., De Vos, E., Casteels, I., De Waele, L., Cassiman, C., Prove, L., Kinoo, D., Vancampenhout, L., Van Den Hauwe, M., Van Impe, A., Prufer de Queiroz Campos Araujo, A., Chacon Pereira, A., Nardes, F., Haefeli, L., Rossetto, J., Almeida Pereira, J., Ferreira Rebel, M., Campbell, C., Sharan, S., Mcdonald, W., Scholtes, C., Mah, J., Sframeli, M., Chiu, A., Hagel, J., Beneish, R., Pham, C., Toffoli, D., Arpin, S., Turgeon Desilets, S., Wang, Y., Hu, C., Huang, J., Qian, C., Shen, L., Xiao, Y., Zhou, Z., Li, H., Wang, S., Xiong, H., Chang, X., Dong, H., Liu, Y., Sang, T., Wei, C., Wen, J., Cao, Y., Lv, X., Zhao, J., Li, W., Qin, L., Barisic, N., Galiot Delic, M., Ivkic, P. K., Vukojevic, N., Kern, I., Najdanovic, B., Skugor, M., Gidaro, T., Seferian, A., De Lucia, Sara Sofia, Barreau, E., Mnafek, N., Momtchilova, M. M., Peche, H., Valherie, C., Grange, A., Lilien, C., Milascevic, D., Tachibana, S., Ravelli, C., Cardas, R., Vanden Brande, L., Davion, J. -B., Coopman, S., Bouacha, I., Debruyne, P., Defoort, S., Derlyn, G., Leroy, F., Danjoux, L., Guilbaud, J., Desguerre, I., Barnerias, C., Semeraro, M., Bremond-Gignac, D., Bruere, L., Rateaux, M., Deladriere, E., Germa, V., Pereon, Y., Magot, A., Mercie, S., Billaud, F., Le Goff, L., Letellier, G., Portefaix, A., Fontaine, S., De-Montferrand, C., Le-Goff, L., Saidi, M., Bouzid, N., Barriere, A., Tinat, M., Dreesbach, M., Lagreze, W., Michaelis, B., Molnar, F., Seger, D., Vogt, S., Bertini, Enrico Silvio, D'Amico, Adele, Petroni, S., Bonetti, A. M., Carlesi, A., Mizzoni, I., Bruno, C., Priolo, E., Rao, G., Morando, S., Tacchetti, P., Zuffi, A., Comi, G. P., Brusa, R., Corti, Serafino, Daniele, V., Govoni, A., Magri, F., Minorini, V., Osnaghi, S. G., Abbati, F., Fassini, F., Foa, M., Lopopolo, A., Meneri, M., Zoppas, F., Parente, V., Masson, R., Bianchi Marzoli, Stefania, Santarsiero, Rocco Domenico, Garcia Sierra, M., Tremolada, G., Arnoldi, M. T., Vigano, M., Zanin, Renata, Amorelli, Giulia Maria, Barresi, C., D'Amico, Guglielmo, Orazi, Lorenzo, Coratti, Giorgia, Haginoya, K., Kato, A., Morishita, Y., Kira, R., Akiyama, K., Goto, M., Mori, Y., Okamoto, M., Tsutsui, S., Takatsuji, Y., Tanaka, A., Komaki, H., Suzuki, I., Takeuchi, M., Todoroki, D., Watanabe, S., Omori, M., Matsubayashi, T., Inakazu, E., Nagura, H., Suzuki, A., Osaka, H., Ohashi, M., Ishikawa, N., Harada, Y., Fudeyasu, K., Hirata, K., Michiue, K., Ueda, K., Yashiro, S., Seki, M., Sano, N., Uemura, A., Fukuyama, K., Matsumoto, Y., Miyazaki, H., Shibata, M., Kobayashi, K., Nakamura, Y., Takeshima, Y., Kuma, M., Fraczek, A., Jedrzejowska, M., Lusakowska, A., Czeszyk-Piotrowicz, A., Hautz, W., Rakusiewicz, K., Burlewicz, M., Gierlak-Wojcicka, Z., Kepa, M., Sikorski, A., Sobieraj, M., Mazurkiewicz-Beldzinska, M., Lemska, A., Modrzejewska, S., Koberda, M., Stodolska-Koberda, U., Waskowska, A., Kolendo, J., Sobierajska-Rek, A., Steinborn, B., Dalz, M., Grabowska, J., Hajduk, W., Janasiewicz-Karachitos, J., Klimas, M., Stopa, M., Gajewska, E., Pusz, B., Vlodavets, D., Melnik, E., Leppenen, N., Yupatova, N., Monakhova, A., Papina, Y., Shidlovsckaia, O., Milic Rasic, V., Brankovic, V., Kosac, A., Djokic, O., Jaksic, V., Pepic, A., Martinovic, J., Munell Casadesus, F., Tizzano, E., Martin Begue, N., Wolley Dod, C., Subira, O., Planas Pascual, B., Toro Tamargo, E., Madruga Garrido, M., Medina Romero, J. D., Salinas, M. P., Nascimento Osorio, A., Diaz Cortes, A., Jimenez Ganan, E., Suh, S. D., Medina Cantillo, J., Moya, O., Padros, N., Roca Urraca, S., Gonzalez Valdivia, H., Pascual Pascual, S., de Manuel, S., Noval Martin, S., Burnham, P., Espinosa Garcia, S., Martinez Moreno, M., Topaloglu, H., Oncel, I., Eroglu Ertugrul, N., Konuskan, B., Eldem, B., Kadayifcilar, S., Alemdaroglu, I., Ayse Karaduman, A., Tunca Yilmaz, O., Bilgin, N., Sari, S., Chiriboga, C., Kane, S., Lee, J., Rome-Martin, D., Beres, S., Duong, T., Gee, R., Dunaway Young, S., Mercuri E. (ORCID:0000-0002-9851-5365), Mazzone E. S., Baranello G., Martin C., De Lucia S., Bertini E., D'Amico A., Corti S., Bianchi Marzoli S., Santarsiero D., Zanin R., Amorelli G. M., D'Amico G., Orazi L., and Coratti G. (ORCID:0000-0001-6666-5628)

Abstract

Background: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. Methods: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2–25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing ≥20 kg) or 0·25 mg/kg (for individuals weighing <20 kg), or daily oral placebo (matched to risdiplam in colour and taste). Randomisation was conducted by permutated block randomisation with a computerised system run by an external party. Patients, investigators, and all individuals in direct contact with patients were masked to treatment assignment. The primary endpoint was the change from baseline in the 32-item Motor Function Measure total score at month 12. All individuals who were randomly assigned to risdiplam or placebo, and who did not meet the prespecified missing item criteria for exclusion, were included in the primary efficacy analysis. Individuals who received at least one dose of risdiplam or placebo were included in the safety analysis. SUNFISH is registered with ClinicalTrials.gov, NCT02908685. Recruitment is closed; the study is ongoing. Findings: Between Oct 9, 2017, and Sept 4, 2018, 180 patients were rand

Published
2022

35. Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units

Author

Zanella, A., Florio, G., Antonelli, M., Bellani, G., Berselli, A., Bove, T., Cabrini, L., Carlesso, E., Castelli, G. P., Cecconi, M., Citerio, G., Coloretti, I., Corti, D., Dalla Corte, F., De Robertis, E., Foti, G., Fumagalli, R., Girardis, M., Giudici, R., Guiotto, L., Langer, T., Mirabella, L., Pasero, D., Protti, A., Ranieri, M. V., Rona, R., Scudeller, L., Severgnini, P., Spadaro, S., Stocchetti, N., Vigano, M., Pesenti, A., Grasselli, G., Aspesi, M., Baccanelli, F., Bassi, F., Bet, A., Biagioni, E., Biondo, A., Bonenti, C., Bottino, N., Brazzi, L., Buquicchio, I., Busani, S., Calini, A., Calligaro, P., Cantatore, L. P., Carelli, S., Carsetti, A., Cavallini, S., Cimicchi, G., Coppadoro, A., Dall'Ara, L., Di Gravio, V., Erba, M., Evasi, G., Facchini, A., Fanelli, V., Feliciotti, G., Fusarini, C. F., Ferraro, G., Garberi, R., Gay, H., Giacche, L., Grieco, D., Guzzardella, A., Longhini, F., Manzan, A., Maraggia, D., Milani, A., Mischi, A., Montalto, C., Mormina, S., Noseda, V., Paleari, C., Pedeferri, M., Pezzi, A., Pizzilli, G., Pozzi, M., Properzi, P., Rauseo, M., Russotto, V., Saccarelli, L., Servillo, G., Spano, S., Tagliabue, P., Tonetti, T., Tullo, L., Vetrugno, L., Vivona, L., Volta, C. A., Zambelli, V., Zanoni, A, Brazzi, L, Gagliardi, G., Zanella A., Florio G., Antonelli M., Bellani G., Berselli A., Bove T., Cabrini L., Carlesso E., Castelli G.P., Cecconi M., Citerio G., Coloretti I., Corti D., Dalla Corte F., De Robertis E., Foti G., Fumagalli R., Girardis M., Giudici R., Guiotto L., Langer T., Mirabella L., Pasero D., Protti A., Ranieri M.V., Rona R., Scudeller L., Severgnini P., Spadaro S., Stocchetti N., Vigano M., Pesenti A., Grasselli G., Aspesi M., Baccanelli F., Bassi F., Bet A., Biagioni E., Biondo A., Bonenti C., Bottino N., Brazzi L., Buquicchio I., Busani S., Calini A., Calligaro P., Cantatore L.P., Carelli S., Carsetti A., Cavallini S., Cimicchi G., Coppadoro A., Dall'Ara L., Di Gravio V., Erba M., Evasi G., Facchini A., Fanelli V., Feliciotti G., Fusarini C.F., Ferraro G., Gagliardi G., Garberi R., Gay H., Giacche L., Grieco D., Guzzardella A., Longhini F., Manzan A., Maraggia D., Milani A., Mischi A., Montalto C., Mormina S., Noseda V., Paleari C., Pedeferri M., Pezzi A., Pizzilli G., Pozzi M., Properzi P., Rauseo M., Russotto V., Saccarelli L., Servillo G., Spano S., Tagliabue P., Tonetti T., Tullo L., Vetrugno L., Vivona L., Volta C.A., Zambelli V., Zanoni A., Zanella, A, Florio, G, Antonelli, M, Bellani, G, Berselli, A, Bove, T, Cabrini, L, Carlesso, E, Castelli, G, Cecconi, M, Citerio, G, Coloretti, I, Corti, D, Dalla Corte, F, De Robertis, E, Foti, G, Fumagalli, R, Girardis, M, Giudici, R, Guiotto, L, Langer, T, Mirabella, L, Pasero, D, Protti, A, Ranieri, M, Rona, R, Scudeller, L, Severgnini, P, Spadaro, S, Stocchetti, N, Viganò, M, Pesenti, A, and Grasselli, G

Subjects
Male, Original, Critical Illness, Socio-culturale, Retrospective Studie, Risk Factors, Humans, Intensive care unit, Prospective Studies, Mortality, Aged, Retrospective Studies, COVID-19, Longitudinal models, Predictors, Time course, SARS-CoV-2, Risk Factor, Respiration, Intensive Care Units, Italy, Middle Aged, Respiration, Artificial, Prospective Studie, Longitudinal model, Artificial, Predictor, Human
Abstract

Purpose To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06495-y.

Published
2021

36. Correction to: Treat all COVID 19‑positive patients, but do not forget those negative with chronic diseases (Internal and Emergency Medicine, (2020), 15, 5, (787-790), 10.1007/s11739-020-02395-z)

Author

Vigano M., Mantovani L., Cozzolino P., Harari S., Vigano, M, Mantovani, L, Cozzolino, P, and Harari, S

Subjects
COVID-19
Abstract

In the original publication of the article, the given name and family name of all the author were swapped. The correct author name is given in this erratum.

Published
2021

37. Real life experiences in HCV management in 2018

Author

Vigano, M, Andreoni, M, Perno, C, Craxi, A, Aghemo, A, Alberti, A, Andreone, P, Babudieri, S, Bonora, S, Brunetto, M, Bruno, R, Bruno, S, Calvaruso, V, Caporaso, N, Cartabellotta, F, Ceccherini-Silberstein, F, Cento, V, Ciancio, A, Colombatto, P, Coppola, N, Di Marco, V, Di Perri, G, Fagiuoli, S, Gaeta, G, Gasbarrini, A, Lampertico, P, Pellicelli, A, Prestileo, T, Puoti, M, Raimondo, G, Rizzardini, G, Taliani, G, Zignego, A, Vigano M., Andreoni M., Perno C. F., Craxi A., Aghemo A., Alberti A., Andreone P., Babudieri S., Bonora S., Brunetto M. R., Bruno R., Bruno S., Calvaruso V., Caporaso N., Cartabellotta F., Ceccherini-Silberstein F., Cento V., Ciancio A., Colombatto P., Coppola N., Di Marco V., Di Perri G., Fagiuoli S., Gaeta G. B., Gasbarrini A., Lampertico P., Pellicelli A., Prestileo T., Puoti M., Raimondo G., Rizzardini G., Taliani G., Zignego A. L., Vigano, M, Andreoni, M, Perno, C, Craxi, A, Aghemo, A, Alberti, A, Andreone, P, Babudieri, S, Bonora, S, Brunetto, M, Bruno, R, Bruno, S, Calvaruso, V, Caporaso, N, Cartabellotta, F, Ceccherini-Silberstein, F, Cento, V, Ciancio, A, Colombatto, P, Coppola, N, Di Marco, V, Di Perri, G, Fagiuoli, S, Gaeta, G, Gasbarrini, A, Lampertico, P, Pellicelli, A, Prestileo, T, Puoti, M, Raimondo, G, Rizzardini, G, Taliani, G, Zignego, A, Vigano M., Andreoni M., Perno C. F., Craxi A., Aghemo A., Alberti A., Andreone P., Babudieri S., Bonora S., Brunetto M. R., Bruno R., Bruno S., Calvaruso V., Caporaso N., Cartabellotta F., Ceccherini-Silberstein F., Cento V., Ciancio A., Colombatto P., Coppola N., Di Marco V., Di Perri G., Fagiuoli S., Gaeta G. B., Gasbarrini A., Lampertico P., Pellicelli A., Prestileo T., Puoti M., Raimondo G., Rizzardini G., Taliani G., and Zignego A. L.

Abstract

Introduction: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Treatment of chronic hepatitis C has considerably improved in the last few years thanks to the introduction of direct-acting antivirals able to achieve sustained virological response in more than 95% of patients. Successful anti-HCV treatment can halt liver disease progression and solve the HCV-related extra-hepatic manifestations, eventually reducing liver-related and overall mortality. Areas covered: With the aim to respond to unmet needs in patient’s identification, universal access to antiviral therapy and treatment optimization in specific setting of HCV-infected patients, a group of Italian experts met in Stresa in May 2018. The summary of the considerations arising from this meeting and the final statements are reported in this paper. Expert commentary: All the advances on HCV cure may have a real clinical impact not only in individual patients but also at the social health level if they are applied to all infected patients, independently from the stage of liver disease. Further improvements are needed in order to attain HCV elimination, such as the development of an enhanced screening program working in parallel to the present treatment options.

Published
2019

38. Effectiveness and safety of switching to entecavir hepatitis B patients developing kidney dysfunction during tenofovir

Author

Vigano, M, Loglio, A, Labanca, S, Zaltron, S, Castelli, F, Andreone, P, Messina, V, Ganga, R, Coppola, N, Marrone, A, Russello, M, Marzano, A, Tucci, A, Taliani, G, Fasano, M, Fagiuoli, S, Villa, E, Bronte, F, Santantonio, T, Brancaccio, G, Occhipinti, V, Facchetti, F, Grossi, G, Rumi, M, Lampertico, P, Vigano M., Loglio A., Labanca S., Zaltron S., Castelli F., Andreone P., Messina V., Ganga R., Coppola N., Marrone A., Russello M., Marzano A., Tucci A., Taliani G., Fasano M., Fagiuoli S., Villa E., Bronte F., Santantonio T., Brancaccio G., Occhipinti V., Facchetti F., Grossi G., Rumi M., Lampertico P., Vigano, M, Loglio, A, Labanca, S, Zaltron, S, Castelli, F, Andreone, P, Messina, V, Ganga, R, Coppola, N, Marrone, A, Russello, M, Marzano, A, Tucci, A, Taliani, G, Fasano, M, Fagiuoli, S, Villa, E, Bronte, F, Santantonio, T, Brancaccio, G, Occhipinti, V, Facchetti, F, Grossi, G, Rumi, M, Lampertico, P, Vigano M., Loglio A., Labanca S., Zaltron S., Castelli F., Andreone P., Messina V., Ganga R., Coppola N., Marrone A., Russello M., Marzano A., Tucci A., Taliani G., Fasano M., Fagiuoli S., Villa E., Bronte F., Santantonio T., Brancaccio G., Occhipinti V., Facchetti F., Grossi G., Rumi M., and Lampertico P.

Abstract

Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFR MDRD ) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter. Results: During 46 (4-115) months of ETV treatment, all patients’ renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFR MDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFR MDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV-R. The 5-year cumulative probability of ETV-R was 0% in LMV-naïve patients, and 11% in LMV-R patients (P = 0.018). Conclusions: Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long-term TDF treatment.

Published
2019

40. Protocol for generating in-frame seamless knockins in Drosophilausing the SEED/Harvest technology

Author

Aguilar, Gustavo, Bauer, Milena, Vigano, M. Alessandra, Guerrero, Isabel, and Affolter, Markus

Abstract

The generation of knockins is fundamental to dissect biological systems. SEED/Harvest, a technology based on CRISPR-Cas9, offers a powerful approach for seamless genome editing in Drosophila. Here, we present a protocol to tag any gene in the Drosophilagenome using SEED/Harvest technology. We describe knockin design, plasmid preparation, injection, and insertion screening. We then detail procedures for germline harvesting. The technique combines straightforward cloning and robust screening of insertions, while still resulting in scarless gene editing.

Published
2024
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41. Pulsed electromagnetic fields improve the healing process of Achilles tendinopathy: A pilot study in a rat model

Author

Perucca Orfei, C, Lovati, A, Lugano, G, Vigano, M, Bottagisio, M, D'Arrigo, D, Sansone, V, Setti, S, de Girolamo, L, Lovati, AB, Perucca Orfei, C, Lovati, A, Lugano, G, Vigano, M, Bottagisio, M, D'Arrigo, D, Sansone, V, Setti, S, de Girolamo, L, and Lovati, AB

Abstract

Aims In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy. Methods A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol. Results The daily exposure to PEMFs generally provided an improvement in the fibre organization, a decrease in cell density, vascularity, and fat deposition, and a restoration of the physiological cell morphology compared to untreated tendons. These improvements were more evident when the tendons were exposed to PEMFs during the mid-acute phase of the pathology (7 days after induction) rather than during the early (1 day after induction) or the late acute phase (15 days after induction). Moreover, the exposure to PEMFs for 14 days during the mid-acute phase was more effective than for 7 days. Conclusion PEMFs exerted a positive role in the tendon healing process, thus representing a promising conservative treatment for tendinopathy, although further investigations regarding the clinical evaluation are needed.

Published
2020

43. Treatment of Hepatitis C virus infection in Italy: A consensus report from an expert panel

Author

Vigano, M, Perno, C, Craxi, A, Aghemo, A, Alberti, A, Andreone, P, Andreoni, M, Bonora, S, Brunetto, M, Bruno, R, Bruno, S, Calvaruso, V, Caporaso, N, Ceccherini-Silberstein, F, Cento, V, Ciancio, A, Colombatto, P, Degasperi, E, Di Marco, V, Di Perri, G, D'Offizi, G, Fagiuoli, S, Ferrari, C, Gaeta, G, Pellicelli, A, Petta, S, Piovesan, S, Puoti, M, Raimondo, G, Russo, F, Taliani, G, Trama, U, Villa, E, Zignego, A, Vigano M., Perno C. F., Craxi A., Aghemo A., Alberti A., Andreone P., Andreoni M., Bonora S., Brunetto M. R., Bruno R., Bruno S., Calvaruso V., Caporaso N., Ceccherini-Silberstein F., Cento V., Ciancio A., Colombatto P., Degasperi E., Di Marco V., Di Perri G., D'offizi G., Fagiuoli S., Ferrari C., Gaeta G. B., Pellicelli A., Petta S., Piovesan S., Puoti M., Raimondo G., Russo F. P., Taliani G., Trama U., Villa E., Zignego A. L., Vigano, M, Perno, C, Craxi, A, Aghemo, A, Alberti, A, Andreone, P, Andreoni, M, Bonora, S, Brunetto, M, Bruno, R, Bruno, S, Calvaruso, V, Caporaso, N, Ceccherini-Silberstein, F, Cento, V, Ciancio, A, Colombatto, P, Degasperi, E, Di Marco, V, Di Perri, G, D'Offizi, G, Fagiuoli, S, Ferrari, C, Gaeta, G, Pellicelli, A, Petta, S, Piovesan, S, Puoti, M, Raimondo, G, Russo, F, Taliani, G, Trama, U, Villa, E, Zignego, A, Vigano M., Perno C. F., Craxi A., Aghemo A., Alberti A., Andreone P., Andreoni M., Bonora S., Brunetto M. R., Bruno R., Bruno S., Calvaruso V., Caporaso N., Ceccherini-Silberstein F., Cento V., Ciancio A., Colombatto P., Degasperi E., Di Marco V., Di Perri G., D'offizi G., Fagiuoli S., Ferrari C., Gaeta G. B., Pellicelli A., Petta S., Piovesan S., Puoti M., Raimondo G., Russo F. P., Taliani G., Trama U., Villa E., and Zignego A. L.

Abstract

Hepatitis C virus (HCV) infection remains one of the main causes of chronic liver disease worldwide. The advent of direct-acting antivirals (DAAs) has significantly improved the course of patients with chronic HCV infection (CHC), due to the ability of these drugs to achieve high rates of sustained virological response (SVR). These exceedingly high rates of SVR and the excellent safety data have been confirmed in real life practice. Evolving guidelines have been issued by national and international scientific societies in accordance with the progression of clinical knowledge and the availability of new DAAs. These recommendations, however, may not be applied universally because of delays in drugs reimbursability in different countries and because some National Health Systems identify only patients with advanced disease as a treatment priority. Italy in this regard is a prototype about DAAs treatment of CHC patients. With the aim to assess the Italian treatment experience with DAAs and to respond to unmet needs in treatment optimization of antiviral therapy in specific settings of CHC patients, a group of Italian experts met in Stresa in February 2017. The summary of the considerations arising from this two-day meeting and some statements regarding a few open issues are reported in this position paper.

Published
2017

44. Correction: DARPins recognizing mTFP1 as novel reagents for and protein manipulations (doi:10.1242/bio.036749)

Author

Vigano, M Alessandra, Bieli, Dimitri, Schaefer, Jonas V, Jakob, Roman P, Matsuda, Shinya, Maier, Timm, Plückthun, Andreas, Affolter, Markus, and University of Zurich

Subjects
1300 General Biochemistry, Genetics and Molecular Biology, 10019 Department of Biochemistry, 570 Life sciences, biology, 610 Medicine & health, 1100 General Agricultural and Biological Sciences
Published
2018

47. Predictors of Serious Adverse Event and Non-response in Cirrhotic Patients With Primary Biliary Cholangitis under Obeticholic Acid

Author

De Vincentis, A., D'Amato, D., Cristoferi, L., Gerussi, A., Malinverno, F., Lleo, A., Colapietro, F., Marra, F., Galli, A., Fiorini, C., Coco, B., Brunetto, M., Niro, G.A., Cotugno, R., Saitta, C., Cozzolongo, R., Losito, F., Giannini, E.G., Labanca, S., Marzioni, M., Marconi, G., Morgando, A., Pellicano, R., Vanni, E., Cazzagon, N., Floreani, A., Chessa, L., Morelli, O., Muratori, L., Pellicelli, A., Pompili, M., Ponziani, F., Rosina, F., Russello, M., Cannavò, M., Simone, L., Storato, S., Viganò, M., Abenavoli, L., D'Antò, M., De Gasperi, E., Distefano, M., Scifo, G., Zolfino, T., Calvaruso, V., Cuccorese, G., Pace Palitti, V., Sacco, R., Bertino, G., Frazzetto, E., Alvaro, D., Mulinacci, G., Palermo, A., Galati, G., Ronca, V., Zuin, M., Claar, E., Izzi, A., Picardi, A., Invernizzi, P., Vespasiani-Gentilucci, U., and Carbone, M.

Published
2022
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48. From current status to optimization of HCV treatment: Recommendations from an expert panel

Author

Craxi, A, Perno, C, Vigano, M, Ceccherini-Silberstein, F, Petta, S, Aghemo, A, Alberti, A, Andreone, P, Andreoni, M, Bonora, S, Brunetto, M, Bruno, S, Caporaso, N, Chirianni, A, Ciancio, A, Degasperi, E, Di Perri, G, Fagiuoli, S, Ferrari, C, Gaeta, G, Pellicelli, A, Puoti, M, Raimondo, G, Taliani, G, Villa, E, Zignego, A, Craxi A., Perno C. F., Vigano M., Ceccherini-Silberstein F., Petta S., Aghemo A., Alberti A., Andreone P., Andreoni M., Bonora S., Brunetto M. R., Bruno S., Caporaso N., Chirianni A., Ciancio A., Degasperi E., Di Perri G., Fagiuoli S., Ferrari C., Gaeta G. B., Pellicelli A., Puoti M., Raimondo G., Taliani G., Villa E., Zignego A. L., Craxi, A, Perno, C, Vigano, M, Ceccherini-Silberstein, F, Petta, S, Aghemo, A, Alberti, A, Andreone, P, Andreoni, M, Bonora, S, Brunetto, M, Bruno, S, Caporaso, N, Chirianni, A, Ciancio, A, Degasperi, E, Di Perri, G, Fagiuoli, S, Ferrari, C, Gaeta, G, Pellicelli, A, Puoti, M, Raimondo, G, Taliani, G, Villa, E, Zignego, A, Craxi A., Perno C. F., Vigano M., Ceccherini-Silberstein F., Petta S., Aghemo A., Alberti A., Andreone P., Andreoni M., Bonora S., Brunetto M. R., Bruno S., Caporaso N., Chirianni A., Ciancio A., Degasperi E., Di Perri G., Fagiuoli S., Ferrari C., Gaeta G. B., Pellicelli A., Puoti M., Raimondo G., Taliani G., Villa E., and Zignego A. L.

Abstract

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper.

Published
2016

49. DARPins recognize mTFP1 as novel reagents for and protein manipulations

Author

Vigano, M Alessandra, Bieli, Dimitri, Schaefer, Jonas V, Jakob, Roman P, Matsuda, Shinya, Maier, Timm, Plückthun, Andreas, Affolter, Markus, University of Zurich, and Affolter, Markus

Subjects
1300 General Biochemistry, Genetics and Molecular Biology, 10019 Department of Biochemistry, 570 Life sciences, biology, 610 Medicine & health, 1100 General Agricultural and Biological Sciences
Published
2018

50. Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?

Author

Lazzari, C, Karachaliou, N, Bulotta, A, Vigano, M, Mirabile, A, Brioschi, E, Santarpia, M, Gianni, L, Rosell, R, and Gregorc, V

Subjects
immune checkpoint inhibitors, PD-L1, PD-L1 inhibitors, PD-1 inhibitors, chemotherapy, immune resistance, non-small cell lung cancer, radiotherapy, immune evasion
Abstract

Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy. The current review provides an overview on the molecular rationale for the investigation of combinatorial approaches with chemotherapy or radiotherapy. Moreover, the results of completed clinical studies will be reported.

Published
2018

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