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201. Long term longitudinal follow-up of an AD-HIES cohort: the impact of early diagnosis and enrollment to IPINet centers on the natural history of Job’s syndrome

Author

Maria Carrabba, Rosa Maria Dellepiane, Manuela Cortesi, Lucia Augusta Baselli, Annarosa Soresina, Emilia Cirillo, Giuliana Giardino, Francesca Conti, Laura Dotta, Andrea Finocchi, Caterina Cancrini, Cinzia Milito, Lucia Pacillo, Bianca Laura Cinicola, Fausto Cossu, Rita Consolini, Davide Montin, Isabella Quinti, Andrea Pession, Giovanna Fabio, Claudio Pignata, Maria Cristina Pietrogrande, and Raffaele Badolato

Subjects
AD-HIES, Job’s syndrome, Immunodeficiency, Inborn errors of immunity, STAT3, Pneumatocele, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Job’s syndrome, or autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES, STAT3-Dominant Negative), is a rare inborn error of immunity (IEI) with multi-organ involvement and long-life post-infective damage. Longitudinal registries are of primary importance in improving our knowledge of the natural history and management of these rare disorders. This study aimed to describe the natural history of 30 Italian patients with AD-HIES recorded in the Italian network for primary immunodeficiency (IPINet) registry. This study shows the incidence of manifestations present at the time of diagnosis versus those that arose during follow up at a referral center for IEI. The mean time of diagnostic delay was 13.7 years, while the age of disease onset was

Published
2023
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205. Nonperturbative infrared finiteness in super-renormalisable scalar quantum field theory

Author

Cossu, Guido, Del Debbio, Luigi, Juttner, Andreas, Kitching-Morley, Ben, Lee, Joseph K. L., Portelli, Antonin, Rocha, Henrique Bergallo, and Skenderis, Kostas

Subjects
High Energy Physics - Lattice, Condensed Matter - Statistical Mechanics, High Energy Physics - Theory
Abstract

We present a study of the IR behaviour of a three-dimensional super-renormalisable quantum field theory (QFT) consisting of a scalar field in the adjoint of $SU(N)$ with a $\varphi^4$ interaction. A bare mass is required for the theory to be massless at the quantum level. In perturbation theory the critical mass is ambiguous due to infrared (IR) divergences and we indeed find that at two-loops in lattice perturbation theory the critical mass diverges logarithmically. It was conjectured long ago in [Jackiw 1980, Appelquist 1981] that super-renormalisable theories are nonperturbatively IR finite, with the coupling constant playing the role of an IR regulator. Using a combination of Markov-Chain-Monte-Carlo simulations of the lattice-regularised theory, both frequentist and Bayesian data analysis, and considerations of a corresponding effective theory we gather evidence that this is indeed the case., Comment: Version accepted for publication in PRL, added references, updated plots, extended discussion of IR behaviour in perturbation theory and EFT

Published
2020
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206. Evaluation of tilt control for wind-turbine arrays in the atmospheric boundary layer

Author

Cossu, Carlo

Subjects
Physics - Fluid Dynamics
Abstract

Wake redirection is a promising approach designed to mitigate turbine-wake interactions which have a negative impact on the performance and lifetime of wind farms. It has recently been found that substantial power gains can be obtained by tilting the rotors of spanwise-periodic wind-turbine arrays. Rotor tilt is associated to the generation of coherent streamwise vortices which deflect wakes towards the ground and, by exploiting the vertical wind shear, replace them with higher-momentum fluid (high-speed streaks). The objective of this work is to evaluate power gains that can be obtained by tilting rotors in spanwise-periodic wind-turbine arrays immersed in the atmospheric boundary layer and, in particular, to analyze the influence of the rotor size on power gains in the case where the turbines emerge from the atmospheric surface layer. We show that, for the case of wind-aligned arrays, large power gains can be obtained for positive tilt angles of the order of 30{\deg}. Power gains are substantially enhanced by operating tilted-rotor turbines at thrust coefficients higher than in the reference configuration. These power gains initially increase with the rotor size reaching a maximum for rotor diameters of the order of 3.6 boundary layer momentum thicknesses (for the considered cases) and decrease for larger sizes. Maximum power gains are obtained for wind-turbine spanwise spacings which are very similar to those of large-scale and very large scale streaky motions which are naturally amplified in turbulent boundary layers. These results are all congruent with the findings of previous investigations of passive control of canonical boundary layers for drag-reduction applications where high-speed streaks replaced wakes of spanwise-periodic rows of wall-mounted roughness elements., Comment: submitted to Wind Energy Science (revised version)

Published
2020

207. High-resolution timing electronics for fast pixel sensors

Author

Lai, Adriano and Cossu, Gian Matteo

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

Detectors based on pixels with timing capabilities are gaining increasing importance in the last years. Next-to-come high-energy physics experiments at colliders requires the use of time information in tracking, due to the increasing levels of track densities in the foreseen experimental conditions. Various different developments are ongoing on solid state sensors to gain high-resolution performance at the sensor level, as for example LGAD sensors or 3D sensors. Intrinsic sensor time resolution around 20 ps have been recently obtained. The increasing performance on the sensor side strongly demands an adequate development on the front-end electronics side, which now risks to become the performance bottle-neck in a tracking or vertex-detecting system. This paper aims to analyse the ultimate possible performance in timing of a typically-used front-end circuit, the Trans-Impedance Amplifier, considering different possible circuit configurations. Evidence to the preferable modes of operation in sensor read-out for timing measurement will be given., Comment: Prepared for submission to JINST

Published
2020

208. Idempotent factorization of matrices over a Pr\'ufer domain of rational functions

Author

Cossu, Laura

Subjects
Mathematics - Commutative Algebra, Mathematics - Rings and Algebras, 15A23, 13F05, 13A15
Abstract

We consider the smallest subring $D$ of $\mathbb{R}(X)$ containing every element of the form $1/(1+x^2)$, with $x\in \mathbb{R}(X)$. $D$ is a Pr\"ufer domain called the minimal Dress ring of $\mathbb{R}(X)$. In this paper, addressing a general open problem for Pr\"ufer non B\'ezout domains, we investigate whether $2\times 2$ singular matrices over $D$ can be decomposed as products of idempotent matrices. We show some conditions that guarantee the idempotent factorization in $M_2(D)$.

Published
2020
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209. Replacing wakes with streaks in wind turbine arrays

Author

Cossu, Carlo

Subjects
Physics - Fluid Dynamics
Abstract

Wind turbine wakes negatively impact downwind turbines in wind farms reducing their global efficiency. The reduction of wake-turbine interactions by actuating control on yaw angles and induction factors is an active area of research. In this study, the capability of spanwise-periodic wind turbine arrays with tilted rotors to reduce negative turbine-wakes interaction is investigated by means of large-eddy simulations. It is shown that by means of rotor tilt it is possible to replace turbine far wakes with high-speed streaks where the streamwise velocity exceeds the freestream velocity at hub height. Considering three aligned arrays of wind turbines, it is found that the global power extracted from the wind can be increased by tilting rotors of upwind turbine arrays similarly to what already known for the case of a single row of aligned turbines. It is further shown that global tilt-induced power gains can be significantly increased by operating the tilted turbines at higher induction rates. Power gains can be further increased by increasing the ratio of the rotor diameters and turbine spacing to the boundary layer thickness. All these findings are consistent with those of previous studies where streamwise streaks were artificially forced by means of arrays of wall-mounted roughness elements in order to control canonical boundary layers for drag-reduction purposes., Comment: revised version

Published
2020

210. Effects of Oxidation of Top and Bottom Interfaces on the Electric, Magnetic, and Spin-Orbit Torque Properties of Pt/Co/AlOx Trilayers

Author

Feng, Junxiao, Grimaldi, Eva, Avci, Can Onur, Baumgartner, Manuel, Cossu, Giovanni, Rossi, Antonella, and Gambardella, Pietro

Subjects
Physics - Applied Physics, Condensed Matter - Materials Science
Abstract

Oxidation strongly influences the properties of magnetic layers employed in spintronic devices. We study the effect of oxidation on the structural, magnetic, and electrical properties as well as current-induced spin-orbit torques (SOTs) in Pt/Co/AlOx, Pt/CoOx/Co/AlOx, and PtOx/Co/AlOx layers. We show how the saturation magnetization, perpendicular magnetic anisotropy, anomalous Hall resistance, and SOT are systematically affected by the degree of oxidation of both the Pt/Co and Co/Al interfaces. Oxidation of the Co/Al interface results in a 21% and 42% variation of the dampinglike and fieldlike SOT efficiencies, which peak at 0.14 and 0.07, respectively. The insertion of a paramagnetic CoOx layer between Pt and Co maintains a very strong perpendicular magnetic anisotropy and improves the dampinglike and fieldlike SOT efficiencies, up to 0.26 and 0.20, respectively. In contrast with recent reports, we do not find that the oxidation of Pt leads to a significant enhancement of the torques. Rather, we find that oxygen migrates from Pt to the Co and Al layers, leading to a time-dependent oxidation profile and an effective spin Hall conductivity that decreases with increasing oxygen concentration. Finally, we study current-induced switching in Pt/Co/AlOx with different degrees of oxidation and find a linear relationship between the critical switching current and the effective magnetic anisotropy controlled by the oxidation of Al. These results highlight the importance of interfaces and oxidation effects on the SOT and magnetotransport properties of heavy metal/ferromagnet/oxide trilayers and provide information on how to improve the SOT efficiency and magnetization-switching characteristics of these systems.

Published
2020
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211. Self-sustained large-scale motions in the asymptotic suction boundary layer

Author

Azimi, Sajjad, Cossu, Carlo, and Schneider, Tobias M.

Subjects
Physics - Fluid Dynamics
Abstract

Large-scale motions, also known as superstructures, are dynamically relevant coherent structures in a wall-bounded turbulent flow, that span the entire domain in wall-normal direction and significantly contribute to the global energy and momentum transport. Recent investigations in channel and Couette flow, suggest that these large-scale motions are self-sustained, implying they are not driven by small-scale motions at the wall. Whether large-scale motions are self-sustained has however not yet been answered for open boundary layers, which are relevant for many applications. Here, using the asymptotic suction boundary layer flow at the friction Reynolds number $Re_\tau = 1\,168$ as a testbed, we show that large-scale motions are self-sustained also in boundary layers. Together with the previous investigations in confined flows, this observation provides strong evidence of the robust and general nature of coherent self-sustained processes in turbulent wall-bounded flows. The dynamics of the large-scale self-sustained process involving the growth, breakdown and regeneration of quasi-streamwise coherent streaks and vortices within the boundary layer shows temporal phase relations reminiscent of bursting as observed in buffer layer structures. The dynamics however differs from the quasi-periodic large-scale streak-vortex regeneration cycle observed in confined flows. Based on the similarity of the dynamics of large-scale motions in boundary layers and of small-scale buffer layer structures, we conjecture that the bursting behaviour is associated with the dynamical relevance of only one wall, while two confining walls lead to the quasi-periodic cycle.

Published
2020

212. Continual Learning with Gated Incremental Memories for sequential data processing

Author

Cossu, Andrea, Carta, Antonio, and Bacciu, Davide

Subjects
Computer Science - Machine Learning, Computer Science - Neural and Evolutionary Computing, Statistics - Machine Learning
Abstract

The ability to learn in dynamic, nonstationary environments without forgetting previous knowledge, also known as Continual Learning (CL), is a key enabler for scalable and trustworthy deployments of adaptive solutions. While the importance of continual learning is largely acknowledged in machine vision and reinforcement learning problems, this is mostly under-documented for sequence processing tasks. This work proposes a Recurrent Neural Network (RNN) model for CL that is able to deal with concept drift in input distribution without forgetting previously acquired knowledge. We also implement and test a popular CL approach, Elastic Weight Consolidation (EWC), on top of two different types of RNNs. Finally, we compare the performances of our enhanced architecture against EWC and RNNs on a set of standard CL benchmarks, adapted to the sequential data processing scenario. Results show the superior performance of our architecture and highlight the need for special solutions designed to address CL in RNNs., Comment: Accepted as a conference paper at 2020 International Joint Conference on Neural Networks (IJCNN 2020). Part of 2020 IEEE World Congress on Computational Intelligence (IEEE WCCI 2020)

Published
2020
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213. Axial U(1) symmetry and mesonic correlators at high temperature in $N_f=2$ lattice QCD

Author

Suzuki, Kei, Aoki, Sinya, Aoki, Yasumichi, Cossu, Guido, Fukaya, Hidenori, Hashimoto, Shoji, and Rohrhofer, Christian

Subjects
High Energy Physics - Lattice, High Energy Physics - Phenomenology
Abstract

We investigate the high-temperature phase of QCD using lattice QCD simulations with $N_f = 2$ dynamical M\"obius domain-wall fermions. On generated configurations, we study the axial $U(1)$ symmetry, overlap-Dirac spectra, screening masses from mesonic correlators, and topological susceptibility. We find that some of the observables are quite sensitive to lattice artifacts due to a small violation of the chiral symmetry. For those observables, we reweight the M\"obius domain-wall fermion determinant by that of the overlap fermion. We also check the volume dependence of observables. Our data near the chiral limit indicates a strong suppression of the axial $U(1)$ anomaly at temperatures $\geq$ 220 MeV., Comment: 7 pages, 4 figures, 1 table; Proceedings of the 37th International Symposium on Lattice Field Theory (Lattice 2019), 16-22 June 2019, Wuhan, China

Published
2020

214. Intweetive Text Summarization

Author

Cossu, Jean Valère, Torres-Moreno, Juan-Manuel, SanJuan, Eric, and El-Bèze, Marc

Subjects
Computer Science - Computation and Language, Computer Science - Information Retrieval
Abstract

The amount of user generated contents from various social medias allows analyst to handle a wide view of conversations on several topics related to their business. Nevertheless keeping up-to-date with this amount of information is not humanly feasible. Automatic Summarization then provides an interesting mean to digest the dynamics and the mass volume of contents. In this paper, we address the issue of tweets summarization which remains scarcely explored. We propose to automatically generated summaries of Micro-Blogs conversations dealing with public figures E-Reputation. These summaries are generated using key-word queries or sample tweet and offer a focused view of the whole Micro-Blog network. Since state-of-the-art is lacking on this point we conduct and evaluate our experiments over the multilingual CLEF RepLab Topic-Detection dataset according to an experimental evaluation process., Comment: 8 pages, 4 tables

Published
2020

215. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

Author

Gentilcore Giusy, Madonna Gabriele, Mozzillo Nicola, Ribas Antoni, Cossu Antonio, Palmieri Giuseppe, and Ascierto Paolo A

Subjects
BRAF inhibitor, Dabrafenib, Growth inhibition, Melanoma therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients) appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436), has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Methods Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Results Our experiments demonstrated an effective action of Dabrafenib (GSK2118436) and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. Conclusion These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.

Published
2013
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217. Implementing Deep Reinforcement Learning (DRL)-based Driving Styles for Non-Player Vehicles

Author

Luca Forneris, Alessandro Pighetti, Luca Lazzaroni, Francesco Bellotti, Alessio Capello, Marianna Cossu, and Riccardo Berta

Subjects
Reinforcement Learning, Automotive Driving, Serious Games, Autonomous Agents, Racing Games, Driving Styles, Education, Electronic computers. Computer science, QA75.5-76.95, Computer software, QA76.75-76.765
Abstract

We propose a new, hierarchical architecture for behavioral planning of vehicle models usable as realistic non-player vehicles in serious games related to traffic and driving. These agents, trained with deep reinforcement learning (DRL), decide their motion by taking high-level decisions, such as “keep lane”, “overtake” and “go to rightmost lane”. This is similar to a driver’s high-level reasoning and takes into account the availability of advanced driving assistance systems (ADAS) in current vehicles. Compared to a low-level decision making system, our model performs better both in terms of safety and speed. As a significant advantage, the proposed approach allows to reduce the number of training steps by more than one order of magnitude. This makes the development of new models much more efficient, which is key for implementing vehicles featuring different driving styles. We also demonstrate that, by simply tweaking the reinforcement learning (RL) reward function, it is possible to train agents characterized by different driving behaviors. We also employed the continual learning technique, starting the training procedure of a more specialized agent from a base model. This allowed significantly to reduce the number of training steps while keeping similar vehicular performance figures. However, the characteristics of the specialized agents are deeply influenced by the characteristics of the baseline agent.

Published
2023
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218. Worldwide barriers to genetic testing for movement disorders

Author

Gatto, Emilia M, Walker, Ruth H, Gonzalez, Claudio, Cesarini, Martin, Cossu, Giovanni, Stephen, Christopher D, Balint, Bettina, Rodríguez‐Violante, Mayela, Jankovic, Joseph, Morgante, Francesca, Jinnah, Hyder A, Albanese, Alberto, Amorin, Ignacio, Bhatia, Kailash, Brandabur, Melanie, Canals, Francisca, Cardoso, Francisco, Cardozo, Adriana, Carvalho, Vanessa, Chade, Anabel, Chana, Pedro, Darling, Alejandra, Correia Guedes, Leonor, De la Cerda, Andrés, de Koning‐Tijssen, Marina, Della Coletta, Marcus V, Duquette, Antoine, Espay, Alberto, Etcheverry, Jose, Ferreira, Joaquim, Friedman, Jennifer, Fung, Victor, Ganos, Christos, Ruiz, Pedro Garcia, Gershanik, Oscar, Gross, Kenneth BV, Han‐Joon, Kim, Kaji, Ruyji, Kotschet, Katya, Rosa, Andres Lescano Da, Litvan, Irene, Lubarr, Naomi, Marano, Massimo, Josep Martí, Maria, Martinez Ramirez, Daniel, Miyasaki, Janis, Münchau, Alexander, Chesta, Daniela Muñoz, Pal, Pramod, Peralta, María Cecilia, Phielipp, Nicolás, Maria Riboldi, Giulietta, Oroz, María Cruz Rodríguez, Rodriguez‐Porcel, Federico, Sarva, Harini, Schoels, Ludger, Stamelou, Maria, and Uribe Roca, Claudia

Subjects
Neurodegenerative, Genetic Testing, Clinical Research, Neurosciences, Genetics, Neurological, Asia, Europe, Humans, Middle East, Movement Disorders, Rare Movement Disorders Study Group of the International Parkinson Disease, Movement Disorders Society, Parkinson's disease, chorea, dystonia, genetic and inherited disorders, genetic diagnosis, genetic testing, movement disorders, whole exome sequencing, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeDespite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization.MethodsThe Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members.ResultsSurvey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe.ConclusionsThis survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.

Published
2021

219. Symmetries of the light hadron spectrum in high temperature QCD

Author

Rohrhofer, C., Aoki, Y., Cossu, G., Fukaya, H., Gattringer, C., Glozman, L. Ya., Hashimoto, S., Lang, C. B., and Suzuki, K.

Subjects
High Energy Physics - Lattice, High Energy Physics - Phenomenology
Abstract

Properties of QCD matter change significantly around the chiral crossover temperature, and the effects on $U(1)_A$ and topological susceptibilities, as well as the meson spectrum have been studied with much care. Baryons and the effect of parity doubling in this temperature range have been analyzed previously by various other groups employing different setups. Here we construct suitable operators to investigate chiral and axial $U(1)_A$ symmetries in the baryon spectrum. Measurements for different volumes and quark-masses are done with two flavors of chirally symmetric domain-wall fermions at temperatures above the critical one. The possibility of emergent $SU(4)$ and $SU(2)_{CS}$ symmetries is discussed., Comment: 7 pages, 4 figures, talk presented at the 37th International Symposium on Lattice Field Theory (Lattice 2019), 16-22 June 2019, Wuhan, China. Updated numerical data in Fig. 1 and Fig. 2

Published
2019

220. Idempotent factorizations of singular $2\times 2$ matrices over quadratic integer rings

Author

Cossu, Laura and Zanardo, Paolo

Subjects
Mathematics - Commutative Algebra, Mathematics - Rings and Algebras
Abstract

Let $D$ be the ring of integers of a quadratic number field $\mathbb{Q}[\sqrt{d}]$. We study the factorizations of $2 \times 2$ matrices over $D$ into idempotent factors. When $d < 0$ there exist singular matrices that do not admit idempotent factorizations, due to results by Cohn (1965) and by the authors (2019). We mainly investigate the case $d > 0$. We employ Vaser\v{s}te\u{\i}n's result (1972) that $SL_2(D)$ is generated by elementary matrices, to prove that any $2 \times 2$ matrix with either a null row or a null column is a product of idempotents. As a consequence, every column-row matrix admits idempotent factorizations.

Published
2019
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221. MASLD, hepatic steatosis and fibrosis are associated with the prevalence of chronic kidney disease and retinopathy in adults with type 1 diabetes mellitus

Author

Mantovani, A, Morieri, M, Aldigeri, R, Palmisano, L, Masulli, M, Bonomo, K, Baroni, M, Cossu, E, Cimini, F, Cavallo, G, Buzzetti, R, Mignogna, C, Leonetti, F, Bacci, S, Trevisan, R, Pollis, R, Cas, A, de Kreutzenberg, S, Targher, G, Mantovani, Alessandro, Morieri, Mario Luca, Aldigeri, Raffaella, Palmisano, Luisa, Masulli, Maria, Bonomo, Katia, Baroni, Marco Giorgio, Cossu, Efisio, Cimini, Flavia Agata, Cavallo, Gisella, Buzzetti, Raffaella, Mignogna, Carmen, Leonetti, Frida, Bacci, Simonetta, Trevisan, Roberto, Pollis, Riccardo Maria, Cas, Alessandra Dei, de Kreutzenberg, Saula Vigili, Targher, Giovanni, Mantovani, A, Morieri, M, Aldigeri, R, Palmisano, L, Masulli, M, Bonomo, K, Baroni, M, Cossu, E, Cimini, F, Cavallo, G, Buzzetti, R, Mignogna, C, Leonetti, F, Bacci, S, Trevisan, R, Pollis, R, Cas, A, de Kreutzenberg, S, Targher, G, Mantovani, Alessandro, Morieri, Mario Luca, Aldigeri, Raffaella, Palmisano, Luisa, Masulli, Maria, Bonomo, Katia, Baroni, Marco Giorgio, Cossu, Efisio, Cimini, Flavia Agata, Cavallo, Gisella, Buzzetti, Raffaella, Mignogna, Carmen, Leonetti, Frida, Bacci, Simonetta, Trevisan, Roberto, Pollis, Riccardo Maria, Cas, Alessandra Dei, de Kreutzenberg, Saula Vigili, and Targher, Giovanni

Abstract

Aim: We examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM). Methods: We performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants. Results: Patients with MASLD and significant fibrosis (n = 93) had a remarkably higher prevalence of CKD and diabetic retinopathy than their counterparts with MASLD without fibrosis (n = 578) and those without steatosis (n = 738). After adjustment for sex, diabetes duration, hemoglobin A1c, hypertension, and use of antihypertensive or lipid-lowering medications, patients with SLD and significant fibrosis had a higher risk of prevalent CKD (adjusted-odds ratio 1.76, 95 % confidence interval 1.05–2.96) than those without steatosis. Patients with MASLD without fibrosis had a higher risk of prevalent retinopathy (adjusted-odds ratio 1.49, 95 % CI 1.13–1.46) than those without steatosis. Conclusion: This is the largest cross-sectional study showing that MASLD with and without coexisting significant fibrosis was associated, independently of potential confounders, with an increased risk of prevalent CKD and retinopathy in adults with T1DM.

Published
2024

222. Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study

Author

Borgonovo, F, Lovaglio, P, Mariani, C, Berta, P, Cossu, M, Rizzardini, G, Vittadini, G, Capetti, A, Borgonovo, Fabio, Lovaglio, Pietro Giorgio, Mariani, Chiara, Berta, Paolo, Cossu, Maria Vittoria, Rizzardini, Giuliano, Vittadini, Giorgio, Capetti, Amedeo Ferdinando, Borgonovo, F, Lovaglio, P, Mariani, C, Berta, P, Cossu, M, Rizzardini, G, Vittadini, G, Capetti, A, Borgonovo, Fabio, Lovaglio, Pietro Giorgio, Mariani, Chiara, Berta, Paolo, Cossu, Maria Vittoria, Rizzardini, Giuliano, Vittadini, Giorgio, and Capetti, Amedeo Ferdinando

Abstract

OBJECTIVE: To define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome. DESIGN: A single-centre longitudinal prospective cohort study conducted from May 2020 to October 2022. SETTING: The study was conducted at Luigi Sacco University Hospital in Milan (Italy). In May 2020, we activated the ARCOVID (Ambulatorio Rivalutazione COVID) outpatient service for the follow-up of long COVID. PARTICIPANTS: Hospitalised and non-hospitalised patients previously affected by COVID-19 were either referred by specialists or general practitioners or self-referred. INTERVENTION: During the first visit, a set of questions investigated the presence and the duration of 11 symptoms (palpitations, amnesia, headache, anxiety/panic, insomnia, loss of smell, loss of taste, dyspnoea, asthenia, myalgia and telogen effluvium). The follow-up has continued until the present time, by sending email questionnaires every 3 months to monitor symptoms and health-related quality of life. PRIMARY AND SECONDARY OUTCOME MEASURES: Measurement of synthetic scores (aggregation of symptoms based on occurrence and duration) that may reveal the presence of long COVID in different clinical macro symptoms. To this end, a mixed supervised and empirical strategy was adopted. Moreover, we aimed to identify predictive factors for post-COVID-19 macro symptoms. RESULTS: In the first and second waves of COVID-19, 575 and 793 patients (respectively) were enrolled. Three different post-COVID-19 macro symptoms (neurological, sensorial and physical) were identified. We found significant associations between post-COVID-19 symptoms and (1) the patients' comorbidities, and (2) the medications used during the COVID-19 acute phase. ACE inhibitors (OR=2.039, 95% CI: 1.095 to 3.892), inhaled steroids (OR=4.08, 95% CI: 1.17 to 19.19) and COVID therapies were associated with increased incidence of the neurological macro symptoms. Age (OR=1.02, 95% CI

Published
2024

223. Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort

Author

d’Arminio Monforte, A, Tavelli, A, Di Biagio, A, Sarmati, L, Marchetti, G, Bai, F, Cingolani, A, Quiros Roldan, E, Mussini, C, Lichtner, M, Vergori, A, Piconi, S, Orofino, G, Fusco, F, Bandera, A, Nozza, S, Castagna, A, Antinori, A, Antinori, S, Cauda, R, Di Perri, G, Girardi, E, Iardino, R, Lazzarin, A, Quiros-Roldan, E, Suligoi, B, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Gori, A, Lo Caputo, S, Maggiolo, F, Puoti, M, Perno, C, Torti, C, Bonora, S, Calcagno, A, Canetti, D, Cervo, A, Cinque, P, Gagliardini, R, Giacomelli, A, Gianotti, N, Guaraldi, G, Lanini, S, Lapadula, G, Lai, A, Madeddu, G, Malagnino, V, Mondi, A, Mazzotta, V, Pinnetti, C, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Spagnuolo, V, Squillace, N, Svicher, V, Taramasso, L, De Benedittis, S, Fanti, I, Giotta, M, Rodano’, A, Bove, A, Cernuschi, M, Cosmaro, L, Errico, M, Perziano, A, Calvino, V, Augello, M, Carrara, S, Graziano, S, Prota, G, Truffa, S, Vincenti, D, Rovito, R, Giacometti, A, Costantini, A, Barocci, V, Santoro, C, Milano, E, Comi, L, Suardi, C, Badia, L, Cretella, S, Erne, E, Pieri, A, Focà, E, Minardi, C, Menzaghi, B, Abeli, C, Chessa, L, Pes, F, Maggi, P, Alessio, L, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Dal Zoppo, S, Segala, D, Di Pietro, M, Costa, C, Ferrara, S, Bassetti, M, Pontali, E, Blanchi, S, Bobbio, N, Mazzarello, G, Fondaco, L, Molteni, C, Canavesi, G, Nunnari, G, Pellicanò, G, Rizzardini, G, Bono, V, Cossu, M, Lolatto, R, Moioli, M, Pezzati, L, Diotallevi, S, Tincati, C, Puzzolante, C, Bonfanti, P, Sangiovanni, V, Gentile, I, Esposito, V, Coppola, N, Di Filippo, G, Rizzo, V, Sangiovanni, N, Martini, S, Cattelan, A, Leoni, D, Cascio, A, Colomba, C, Francisci, D, Schiaroli, E, Parruti, G, Sozio, F, Blanc, P, Bonelli, S, Lazzaretti, C, Corsini, R, Mastroianni, C, Latini, A, Lamonica, S, Capozzi, M, Rivano Capparuccia, M, Iaiani, G, Stingone, C, Gianserra, L, Paulicelli, J, Plazzi, M, D’Ettore, G, Fusto, M, Coledan, I, De Vito, A, Fabbiani, M, Montagnani, F, Franco, A, Fontana Del Vecchio, R, Pasticci, B, Di Giuli, C, Calleri, G, Accardo, G, Tascini, C, Londero, A, Manfrin, V, Battagin, G, Starnini, G, Farinacci, D, Null, N, d’Arminio Monforte, Antonella, Tavelli, Alessandro, Di Biagio, Antonio, Sarmati, Loredana, Marchetti, Giulia C, Bai, Francesca, Cingolani, Antonella, Quiros Roldan, Eugenio, Mussini, Cristina, Lichtner, Miriam, Vergori, Alessandra, Piconi, Stefania, Orofino, Giancarlo, Fusco, Francesco Maria, Bandera, Alessandra, Nozza, Silvia, Castagna, Antonella, Antinori, Andrea, Marchetti, G C, Perno, C F, Santoro, M M, Erne, E M, Di Pietro, M A, Cossu, M V, Moioli, M C, Fusco, F M, Cattelan, A M, Bonelli, S I, Plazzi, M M, d’Ettore, G, Pasticci, B M, Orofino, G C, null, null, d’Arminio Monforte, A, Tavelli, A, Di Biagio, A, Sarmati, L, Marchetti, G, Bai, F, Cingolani, A, Quiros Roldan, E, Mussini, C, Lichtner, M, Vergori, A, Piconi, S, Orofino, G, Fusco, F, Bandera, A, Nozza, S, Castagna, A, Antinori, A, Antinori, S, Cauda, R, Di Perri, G, Girardi, E, Iardino, R, Lazzarin, A, Quiros-Roldan, E, Suligoi, B, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Gori, A, Lo Caputo, S, Maggiolo, F, Puoti, M, Perno, C, Torti, C, Bonora, S, Calcagno, A, Canetti, D, Cervo, A, Cinque, P, Gagliardini, R, Giacomelli, A, Gianotti, N, Guaraldi, G, Lanini, S, Lapadula, G, Lai, A, Madeddu, G, Malagnino, V, Mondi, A, Mazzotta, V, Pinnetti, C, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Spagnuolo, V, Squillace, N, Svicher, V, Taramasso, L, De Benedittis, S, Fanti, I, Giotta, M, Rodano’, A, Bove, A, Cernuschi, M, Cosmaro, L, Errico, M, Perziano, A, Calvino, V, Augello, M, Carrara, S, Graziano, S, Prota, G, Truffa, S, Vincenti, D, Rovito, R, Giacometti, A, Costantini, A, Barocci, V, Santoro, C, Milano, E, Comi, L, Suardi, C, Badia, L, Cretella, S, Erne, E, Pieri, A, Focà, E, Minardi, C, Menzaghi, B, Abeli, C, Chessa, L, Pes, F, Maggi, P, Alessio, L, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Dal Zoppo, S, Segala, D, Di Pietro, M, Costa, C, Ferrara, S, Bassetti, M, Pontali, E, Blanchi, S, Bobbio, N, Mazzarello, G, Fondaco, L, Molteni, C, Canavesi, G, Nunnari, G, Pellicanò, G, Rizzardini, G, Bono, V, Cossu, M, Lolatto, R, Moioli, M, Pezzati, L, Diotallevi, S, Tincati, C, Puzzolante, C, Bonfanti, P, Sangiovanni, V, Gentile, I, Esposito, V, Coppola, N, Di Filippo, G, Rizzo, V, Sangiovanni, N, Martini, S, Cattelan, A, Leoni, D, Cascio, A, Colomba, C, Francisci, D, Schiaroli, E, Parruti, G, Sozio, F, Blanc, P, Bonelli, S, Lazzaretti, C, Corsini, R, Mastroianni, C, Latini, A, Lamonica, S, Capozzi, M, Rivano Capparuccia, M, Iaiani, G, Stingone, C, Gianserra, L, Paulicelli, J, Plazzi, M, D’Ettore, G, Fusto, M, Coledan, I, De Vito, A, Fabbiani, M, Montagnani, F, Franco, A, Fontana Del Vecchio, R, Pasticci, B, Di Giuli, C, Calleri, G, Accardo, G, Tascini, C, Londero, A, Manfrin, V, Battagin, G, Starnini, G, Farinacci, D, Null, N, d’Arminio Monforte, Antonella, Tavelli, Alessandro, Di Biagio, Antonio, Sarmati, Loredana, Marchetti, Giulia C, Bai, Francesca, Cingolani, Antonella, Quiros Roldan, Eugenio, Mussini, Cristina, Lichtner, Miriam, Vergori, Alessandra, Piconi, Stefania, Orofino, Giancarlo, Fusco, Francesco Maria, Bandera, Alessandra, Nozza, Silvia, Castagna, Antonella, Antinori, Andrea, Marchetti, G C, Perno, C F, Santoro, M M, Erne, E M, Di Pietro, M A, Cossu, M V, Moioli, M C, Fusco, F M, Cattelan, A M, Bonelli, S I, Plazzi, M M, d’Ettore, G, Pasticci, B M, Orofino, G C, and null, null

Abstract

Objectives: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. Methods: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. Results: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. Conclusions: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

Published
2024

224. Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Author

Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. 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F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. 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D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., and Celentano V.

Abstract

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy. Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of ≥ 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site. Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of ≥ 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P < 0.001) and MEDIUM-volume (OR 0.72, 95% c.i. 0.62-0.83, P < 0.001) centres was lower than in VERY HIGH-volume centres. Of the 4676 rectal cancer patients, the rate of ≥ 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH). Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes.

Published
2024

225. Surge of Mpox cases in Lombardy region, Italy, October 2023 - January 2024

Author

Moschese, D, Raccagni, A, Giacomelli, A, Piralla, A, Rossotti, R, Raimondi, A, Tesoro, D, Vezzosi, L, Gulletta, M, Clementi, N, Venturelli, S, Benardon, S, Ricaboni, D, Bernacchia, D, Mancon, A, Rovida, F, Attanasi, F, Cereda, D, Gismondo, M, Gori, A, Rizzardini, G, Antinori, S, Baldanti, F, Marzano, A, Marchetti, G, Castelli, F, Castagna, A, Nozza, S, Mileto, D, Bonfanti, P, Biasioli, L, Bruno, R, Vittoria Cossu, M, Fusetti, C, Lazzarin, S, Locatelli, M, Morosi, M, Piscaglia, M, Pusterla, L, Pozza, G, Ramoni, S, Rusconi, S, Rizzi, M, Rizzo, A, Sabaini, F, Salari, F, Sampaolo, M, Puoti, M, Tirani, M, Rachele Tomasoni, L, Null, N, Moschese, Davide, Raccagni, Angelo Roberto, Giacomelli, Andrea, Piralla, Antonio, Rossotti, Roberto, Raimondi, Alessandro, Tesoro, Daniele, Vezzosi, Luigi, Gulletta, Maurizio, Clementi, Nicola, Venturelli, Serena, Benardon, Susanna, Ricaboni, Davide, Bernacchia, Dario, Mancon, Alessandro, Rovida, Francesca, Attanasi, Federica, Cereda, Danilo, Gismondo, Maria Rita, Gori, Andrea, Rizzardini, Giuliano, Antinori, Spinello, Baldanti, Fausto, Marzano, Angelo Valerio, Marchetti, Giulia, Castelli, Francesco, Castagna, Antonella, Nozza, Silvia, Mileto, Davide, Bonfanti, Paolo, Biasioli, Lorenzo, Bruno, Raffaele, Vittoria Cossu, Maria, Fusetti, Chiara, Lazzarin, Samuel, Locatelli, Massimo, Morosi, Manuela, Piscaglia, Marco, Pusterla, Luigi, Pozza, Giacomo, Ramoni, Stefano, Rusconi, Stefano, Rizzi, Marco, Rizzo, Alberto, Sabaini, Federico, Salari, Federica, Sampaolo, Michela, Puoti, Massimo, Tirani, Marcello, Rachele Tomasoni, Lina, null, null, Moschese, D, Raccagni, A, Giacomelli, A, Piralla, A, Rossotti, R, Raimondi, A, Tesoro, D, Vezzosi, L, Gulletta, M, Clementi, N, Venturelli, S, Benardon, S, Ricaboni, D, Bernacchia, D, Mancon, A, Rovida, F, Attanasi, F, Cereda, D, Gismondo, M, Gori, A, Rizzardini, G, Antinori, S, Baldanti, F, Marzano, A, Marchetti, G, Castelli, F, Castagna, A, Nozza, S, Mileto, D, Bonfanti, P, Biasioli, L, Bruno, R, Vittoria Cossu, M, Fusetti, C, Lazzarin, S, Locatelli, M, Morosi, M, Piscaglia, M, Pusterla, L, Pozza, G, Ramoni, S, Rusconi, S, Rizzi, M, Rizzo, A, Sabaini, F, Salari, F, Sampaolo, M, Puoti, M, Tirani, M, Rachele Tomasoni, L, Null, N, Moschese, Davide, Raccagni, Angelo Roberto, Giacomelli, Andrea, Piralla, Antonio, Rossotti, Roberto, Raimondi, Alessandro, Tesoro, Daniele, Vezzosi, Luigi, Gulletta, Maurizio, Clementi, Nicola, Venturelli, Serena, Benardon, Susanna, Ricaboni, Davide, Bernacchia, Dario, Mancon, Alessandro, Rovida, Francesca, Attanasi, Federica, Cereda, Danilo, Gismondo, Maria Rita, Gori, Andrea, Rizzardini, Giuliano, Antinori, Spinello, Baldanti, Fausto, Marzano, Angelo Valerio, Marchetti, Giulia, Castelli, Francesco, Castagna, Antonella, Nozza, Silvia, Mileto, Davide, Bonfanti, Paolo, Biasioli, Lorenzo, Bruno, Raffaele, Vittoria Cossu, Maria, Fusetti, Chiara, Lazzarin, Samuel, Locatelli, Massimo, Morosi, Manuela, Piscaglia, Marco, Pusterla, Luigi, Pozza, Giacomo, Ramoni, Stefano, Rusconi, Stefano, Rizzi, Marco, Rizzo, Alberto, Sabaini, Federico, Salari, Federica, Sampaolo, Michela, Puoti, Massimo, Tirani, Marcello, Rachele Tomasoni, Lina, and null, null

Published
2024

229. Association between different modalities of insulin administration and metabolic dysfunction-associated fatty liver disease in adults with type 1 diabetes mellitus

Author

Csermely, Alessandro, Mantovani, Alessandro, Morieri, Mario Luca, Palmisano, Luisa, Masulli, Maria, Cossu, Efisio, Baroni, Marco Giorgio, Bonomo, Katia, Cimini, Flavia Agata, Cavallo, Gisella, Buzzetti, Raffaella, Mignogna, Carmen, Leonetti, Frida, Bacci, Simonetta, Trevisan, Roberto, Pollis, Riccardo Maria, Aldigeri, Raffaella, Cas, Alessandra Dei, de Kreutzenberg, Saula Vigili, and Targher, Giovanni

Published
2023
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231. Do cerebrovascular risk factors impact the clinical expression of idiopathic isolated adult-onset dystonia?

Author

Zaccone, Claudio, Cerne, Denise, Idone, Giovanni, Ferrazzano, Gina, Rinaldo, Sara, Humaidan, Kais, Devigili, Grazia, Polidori, Luigi, Mazzucchi, Sonia, Ramella, Marina, Ledda, Claudia, Petracca, Martina, Oppo, Valentina, Contaldi, Elena, Turla, Marinella, Gigante, Angelo Fabio, Valentino, Francesca, Cassano, Daniela, Modugno, Nicola, Tambasco, Nicola, Aguggia, Marco, Romano, Marcello, Marinelli, Lucio, Mascia, Marcello Mario, Belvisi, Daniele, Esposito, Marcello, Pellicciari, Roberta, Trinchillo, Assunta, Terranova, Carmen, Bertino, Salvatore, Avanzino, Laura, Di Biasio, Francesca, Bono, Francesco, Laterza, Vincenzo, Lettieri, Christian, Eleopra, Roberto, Fabbrini, Giovanni, Barbero, Pierangelo, Bertolasi, Laura, Altavista, Maria Concetta, Erro, Roberto, Ceravolo, Roberto, Castagna, Anna, Zibetti, Maurizio, Bentivoglio, Anna Rita, Cossu, Giovanni, Magistrelli, Luca, Scaglione, Cesa, Albanese, Alberto, Cotelli, Maria Sofia, Misceo, Salvatore, Pisani, Antonio, Schirinzi, Tommaso, Maderna, Luca, Squintani, Giovanna, Berardelli, Alfredo, and Defazio, Giovanni

Published
2023
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236. Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia

Author

Palomba Grazia, Colombino Maria, Contu Antonio, Massidda Bruno, Baldino Giovanni, Pazzola Antonio, Ionta MariaTeresa, Capelli Francesca, Trova Vittorio, Sedda Tito, Sanna Giovanni, Tanda Francesco, Budroni Mario, Palmieri Giuseppe, and Cossu Antonio

Subjects
Colorectal carcinoma, KRAS gene, BRAF gene, PIK3CA gene, Mutation analysis, Cancer genetic heterogeneity, Medicine
Abstract

Abstract Background Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia. Methods From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. Results Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (pBRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (pKRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy. Conclusions Our findings support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.

Published
2012
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237. Gene expression profiling of Mycobacterium avium subsp. paratuberculosis in simulated multi-stress conditions and within THP-1 cells reveals a new kind of interactive intramacrophage behaviour

Author

Cossu Andrea, Sechi Leonardo, Zanetti Stefania, and Rosu Valentina

Subjects
Mycobacterium avium subsp. paratuberculosis, functional genomics, DNA-microarray, simulated intra-phagosomal multi-stress, macrophage infection, Microbiology, QR1-502
Abstract

Abstract Background Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, it is necessary a thorough understanding of MAP's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic and therapeutic tools. Results In order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures. Conclusions These results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health.

Published
2012
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238. Can We Use Online Technology to Rejig the Traditional Laboratory Experience to Improve Student Engagement?

Author

Cossu, Remo, Awidi, I., and Nagy, J.

Abstract

This experimental-mixed methods investigates the impact of shifting from a traditional laboratory model to a hybrid laboratory model. The hybrid model consisted of (1) online instructions and pre-laboratory test, (2) compressed face-to-face laboratory time, and (3) post-laboratory data analysis. This study analyses whether student perceptions of a targeted intervention were correlated to a range of student performance indicators. Only a fractional improvement in student performance was observed, but evidence suggests that the use of online content led to more frequent student interaction with the learning material. The pre-laboratory tests encouraged a better preparation for the laboratory. Splitting the laboratory intervention into different phases was generally better perceived by students than the traditional style. The findings are expected to encourage course coordinators and developers to adopt concepts used in the delivery of hybrid solutions which is important due to the current emphasis on the use of online models of instruction.

Published
2022
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239. Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies

Author

Sechi Mario, Posadino Anna, Cossu Annalisa, Pintus Gianfranco, Mariani Alberto, Alzari Valeria, Marceddu Salvatore, Sanna Vanna, Roggio Anna, and Uzzau Sergio

Subjects
Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Abstract Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug. In the present study, two novel biodegradable block-copolymers, poly(lactide-co-caprolactone) (PLA-PCL) and poly(lactide-co-caprolactone-co-glycolide) (PLGA-PCL), were explored for the formulation of Dtx-loaded NPs and compared with PLA- and PLGA-NPs. The nanosystems were prepared by an original nanoprecipitation method, using Pluronic F-127 as surfactant agent, and were characterized in terms of morphology, size distribution, encapsulation efficiency, crystalline structure, and in vitro release. To evaluate the potential anticancer efficacy of a nanoparticulate system, in vitro cytotoxicity studies on human prostate cancer cell line (PC3) were carried out. NPs were found to be of spherical shape with an average diameter in the range of 100 to 200 nm and a unimodal particle size distribution. Dtx was incorporated into the PLGA-PCL NPs with higher (p < 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. In vitro drug release study showed that release profiles of Dtx varied on the bases of characteristics of polymers used for formulation. PLA-PCL and PLGA-PCL drug loaded NPs shared an overlapping release profiles, and are able to release about 90% of drug within 6 h, when compared with PLA- and PLGA-NPs. Moreover, cytotoxicity studies demonstrated advantages of the Dtx-loaded PLGA-PCL NPs over pure Dtx in both time- and concentration-dependent manner. In particular, an increase of 20% of PC3 growth inhibition was determined by PLGA-PCL NPs with respect to free drug after 72 h incubation and at all tested Dtx concentration. In summary, PLGA-PCL copolymer may be considered as an attractive and promising polymeric material for the formulation of Dtx NPs as delivery system for prostate cancer treatment, and can also be pursued as a validated system in a more large context.

Published
2011

243. Molecular alterations in key-regulator genes among patients with T4 breast carcinoma

Author

Massidda Bruno, Sini MariaCristina, Budroni Mario, Atzori Francesco, Deidda MariaCristina, Pusceddu Valeria, Perra MariaTeresa, Sirigu Paola, Cossu Antonio, Palomba Grazia, Ionta MariaTeresa, and Palmieri Giuseppe

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period. Methods A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK1-2 proteins as well as in amplification of CyclinD1 and h-prune genes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis. Results Overall, patients carrying increased expression of pERK1-2 (p = 0.027) and survivin (p = 0.008) proteins as well as amplification of h-prune gene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series. Conclusions Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients.

Published
2010
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244. Atomic scale interfacial magnetism and origin of metal-insulator transition in (LaNiO $$_3$$ 3 ) $$_n$$ n /(CaMnO $$_3$$ 3 ) $$_m$$ m superlattices: a first principles study

Author

J. Jilili, I. Tolbatov, F. Cossu, A. Rahaman, B. Fiser, and M. Upadhyay. Kahaly

Subjects
Medicine, Science
Abstract

Abstract Interfacial magnetism and metal-insulator transition at LaNiO $$_3$$ 3 -based oxide interfaces have triggered intense research efforts, because of the possible implications in future heterostructure device design and engineering. Experimental observation lack in some points a support from an atomistic view. In an effort to fill such gap, we hereby investigate the structural, electronic, and magnetic properties of (LaNiO $$_3$$ 3 ) $$_n$$ n /(CaMnO $$_3$$ 3 ) $$_m$$ m superlattices with varying LaNiO $$_3$$ 3 thickness (n) using density functional theory including a Hubbard-type effective on-site Coulomb term. We successfully capture and explain the metal-insulator transition and interfacial magnetic properties, such as magnetic alignments and induced Ni magnetic moments which were recently observed experimentally in nickelate-based heterostructures. In the superlattices modeled in our study, an insulating state is found for n=1 and a metallic character for n=2, 4, with major contribution from Ni and Mn 3d states. The insulating character originates from the disorder effect induced by sudden environment change for the octahedra at the interface, and associated to localized electronic states; on the other hand, for larger n, less localized interfacial states and increased polarity of the LaNiO $$_3$$ 3 layers contribute to metallicity. We discuss how the interplay between double and super-exchange interaction via complex structural and charge redistributions results in interfacial magnetism. While (LaNiO $$_3$$ 3 ) $$_n$$ n /(CaMnO $$_3$$ 3 ) $$_m$$ m superlattices are chosen as prototype and for their experimental feasibility, our approach is generally applicable to understand the intricate roles of interfacial states and exchange mechanism between magnetic ions towards the overall response of a magnetic interface or superlattice.

Published
2023
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246. Liposomal bupivacaine reduces opioid requirements following Ravitch repair for pectus excavatum

Author

Rania K Abbasi, Anne E Cossu, Brandon Tanner, Peter Castelluccio, Matthew Hamilton, John Brown, and Jeremy Herrmann

Subjects
liposomal bupivacaine, pectus excavatum, ravitch procedure, Anesthesiology, RD78.3-87.3, Pharmacy and materia medica, RS1-441
Abstract

Background and Aims: The management of post-operative pain after surgical repair of pectus excavatum with the Ravitch procedure is challenging. Although previous studies have compared various methods of pain control in these patients, few have compared different local anesthetics. This retrospective analysis compares the use of bupivacaine to its longer-acting form, liposomal bupivacaine, in patients who had undergone pectus excavatum repair with the Ravitch method. Material and Methods: Eleven patients who received local infiltration with liposomal bupivacaine were matched to 11 patients who received local infiltration utilizing bupivacaine with epinephrine. The primary outcome was total morphine milligram equivalents per kilogram body weight (MME/kg) over the complete length of hospital stay. Secondary outcomes included total cumulative diazepam, acetaminophen, ondansetron, and NSAID dose per kilogram body weight (mg/kg) over the course of the hospital stay, chest tube drainage (ml/kg body weight), number of post-operative hours until the first bowel movement, Haller Index, patient request for magnesium hydroxide, average pain scores from post-operative day 1 to post-operative day 5, and length of hospital stay. Continuous variables were reported as medians with inter-quartile ranges, and categorical values were reported as percentages and frequencies. Results: The total MME/kg [1.7 (1.2-2.4) vs 2.9 (2.0-3.9), P = 0.007] and hydromorphone (mg/kg) [0.1 (0.0-0.2) vs 0.3 (0.1-0.4), P = 0.006] use in the liposomal bupivacaine group versus bupivacaine with epinephrine was significantly reduced over total length of hospital stay. Similarly, there was a reduction in diazepam use in the liposomal bupivacaine group versus the bupivacaine group [0.4 (0.1-0.8) vs 0.6 (0.4-0.7), P = 0.249], but this did not reach statistical significance. The total dose of ondansetron (mg/kg) was not statistically different when comparing the liposomal bupivacaine group to the bupivacaine group [0.3 (0.0-0.5) vs 0.3 (0.2-0.6), P = 0.332]. Interestingly, the total dose of acetaminophen (mg/kg) was statistically increased in the liposomal bupivacaine group compared to the bupivacaine with epinephrine group [172 (138-183) vs 74 (55-111), P = 0.007]. Additionally, the total chest tube drainage (ml/kg) was significantly reduced in the liposomal bupivacaine group [9.3 (7.5-10.6) vs 12.8 (11.3-18.5), P = 0.027]. Finally, the percentage of patients without requests for magnesium hydroxide to promote laxation was significantly higher in the liposomal bupivacaine group than in the bupivacaine group (63.6% vs 18.2%, P = 0.027). Conclusion: The use of liposomal bupivacaine for local infiltration in patients who undergo the Ravitch procedure for pectus repair offers advantages over plain bupivacaine, including reduced opioid consumption and opioid-related side effects. However, more data are needed to understand the significance of these findings.

Published
2023
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247. La resilienza del soccorritore 'tutore di resilienza'. Uno speciale incontro tra 'il Maestro' e 'un’allieva'

Author

Daniel Lumera and Ersilia Cossu

Subjects
resilience, meditation, healthy eating, exercise, Therapeutics. Psychotherapy, RC475-489
Abstract

In this article the authors, teacher and student, will give their point of view about the importance of wellness in the daily lives of people, at the individual, interpersonal and social level. They shared an extraordinary experience in the wonderful lugar, at the foot of Pyrenees Mountains, a 3-day retreat dedicated to the “three pillars of wellness”; meditation, healthy nutrition and exercise. The article is intended for all people who want to achieve the maximum desired level of wellness in their lives. Readers of this journal, emergency psychologists, humanitarian workers and civil protection rescue workers are invited to read the following with the awareness that their care and well-being in the specific context of intervention is essential for resilience as professionals. Caring for yourself and your well-being is the basis for taking care of others. Furthermore, with reference to the most recent studies on resilience in the helping professions, we will highlight the importance of using coping strategies for stressful events with an innovative approach (theory of appraisal) not only in emergency situations but also in daily life. Preserving the well-being and mental health of people and rescue workers is possible using an adaptive mode of processing the stressful event, we will explain how. From “me” to “us”, a new perspective; we have understood that the action of each individual, combined with that of millions of people, can really change things. We model good practices that are beneficial to our planet, we circulate information, we use science to support arguments, we are kind to others and to nature. Our new way of living this millennium should never forget that everything is interconnected. The aim is to find a balance, and it is our task to preserve it.

Published
2023

248. Gene’s expression underpinning the divergent predictive value of [18F]F-fluorodeoxyglucose and prostate-specific membrane antigen positron emission tomography in primary prostate cancer: a bioinformatic and experimental study

Author

Matteo Bauckneht, Cecilia Marini, Vanessa Cossu, Cristina Campi, Mattia Riondato, Silvia Bruno, Anna Maria Orengo, Francesca Vitale, Sonia Carta, Silvia Chiola, Sabrina Chiesa, Alberto Miceli, Francesca D’Amico, Giuseppe Fornarini, Carlo Terrone, Michele Piana, Silvia Morbelli, Alessio Signori, Paola Barboro, and Gianmario Sambuceti

Subjects
Prostate cancer, Glucose metabolism, Prostate-specific membrane antigen, Positron emission tomography, Prognosis, Medicine
Abstract

Abstract Background Positron Emission Tomography (PET) imaging with Prostate-Specific Membrane Antigen (PSMA) and Fluorodeoxyglucose (FDG) represent promising biomarkers for risk-stratification of Prostate Cancer (PCa). We verified whether the expression of genes encoding for PSMA and enzymes regulating FDG cellular uptake are independent and additive prognosticators in PCa. Methods mRNA expression of genes involved in glucose metabolism and PSMA regulation obtained from primary PCa specimens were retrieved from open-source databases and analyzed using an integrative bioinformatics approach. Machine Learning (ML) techniques were used to create predictive Progression-Free Survival (PFS) models. Cellular models of primary PCa with different aggressiveness were used to compare [18F]F-PSMA-1007 and [18F]F-FDG uptake kinetics in vitro. Confocal microscopy, immunofluorescence staining, and quantification analyses were performed to assess the intracellular and cellular membrane PSMA expression. Results ML analyses identified a predictive functional network involving four glucose metabolism-related genes: ALDOB, CTH, PARP2, and SLC2A4. By contrast, FOLH1 expression (encoding for PSMA) did not provide any additive predictive value to the model. At a cellular level, the increase in proliferation rate and migratory potential by primary PCa cells was associated with enhanced FDG uptake and decreased PSMA retention (paralleled by the preferential intracellular localization). Conclusions The overexpression of a functional network involving four glucose metabolism-related genes identifies a higher risk of disease progression since the earliest phases of PCa, in agreement with the acknowledged prognostic value of FDG PET imaging. By contrast, the prognostic value of PSMA PET imaging is independent of the expression of its encoding gene FOLH1. Instead, it is influenced by the protein docking to the cell membrane, regulating its accessibility to tracer binding.

Published
2023
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249. Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

Author

Canzanella Sergio, Stanganelli Ignazio, Pagani Elena, Ascierto Paolo A, Caracò Corrado, Budroni Mario, Cossu Antonio, Muggiano Antonio, Casula Milena, Sini MariaCristina, Palomba Grazia, and Palmieri Giuseppe

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. Methods A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2A genes. Results For melanoma susceptibility, investigations at germline level indicated that p16CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2A silencing). Conclusion Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis.

Published
2009
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250. A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

Author

Lovicu Mario, Pisano Marina, Floris Carlo, Orrù Sandra, Farris Antonio, Tanda Francesco, Contu Antonio, Budroni Mario, Cossu Antonio, Gabbas Attilio, Piras Giovanna, Fancello Patrizia, Uras Antonella, Loi Angela, Palomba Grazia, Santona Maria, Landriscina Gennaro, Crisponi Laura, Palmieri Giuseppe, and Monne Maria

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. Methods Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. Results and Conclusion Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.

Published
2009
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