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1. HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.

Author

Tedesco, Barbara, Vendredy, Leen, Adriaenssens, Elias, Cozzi, Marta, Asselbergh, Bob, Crippa, Valeria, Cristofani, Riccardo, Rusmini, Paola, Ferrari, Veronica, Casarotto, Elena, Chierichetti, Marta, Mina, Francesco, Pramaggiore, Paola, Galbiati, Mariarita, Piccolella, Margherita, Baets, Jonathan, Baeke, Femke, De Rycke, Riet, Mouly, Vincent, Laurenzi, Tommaso, Eberini, Ivano, Vihola, Anna, Udd, Bjarne, Weiss, Lan, Timmerman, Vincent, Poletti, Angelo, and Kimonis, Virginia

Subjects
BAG3, CASA, HSPA, HSPB8, misfolding, myopathy, neuromuscular disorders, neuropathy, protein quality control, Humans, Sequestosome-1 Protein, Autophagy, Heat-Shock Proteins, Neuromuscular Diseases, Charcot-Marie-Tooth Disease, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Molecular Chaperones
Abstract

Chaperone-assisted selective autophagy (CASA) is a highly selective pathway for the disposal of misfolding and aggregating proteins. In muscle, CASA assures muscle integrity by favoring the turnover of structural components damaged by mechanical strain. In neurons, CASA promotes the removal of aggregating substrates. A crucial player of CASA is HSPB8 (heat shock protein family B (small) member 8), which acts in a complex with HSPA, their cochaperone BAG3, and the E3 ubiquitin ligase STUB1. Recently, four novel HSPB8 frameshift (fs) gene mutations have been linked to neuromyopathies, and encode carboxy-terminally mutated HSPB8, sharing a common C-terminal extension. Here, we analyzed the biochemical and functional alterations associated with the HSPB8_fs mutant proteins. We demonstrated that HSPB8_fs mutants are highly insoluble and tend to form proteinaceous aggregates in the cytoplasm. Notably, all HSPB8 frameshift mutants retain their ability to interact with CASA members but sequester them into the HSPB8-positive aggregates together with two autophagy receptors SQSTM1/p62 and TAX1BP1. This copartitioning process negatively affects the CASA capability to remove its clients and causes a general failure in proteostasis response. Further analyses revealed that the aggregation of the HSPB8_fs mutants occurs independently of the other CASA members or from the autophagy receptors interaction, but it is an intrinsic feature of the mutated amino acid sequence. HSPB8_fs mutants aggregation alters the differentiation capacity of muscle cells and impairs sarcomere organization. Collectively, these results shed light on a potential pathogenic mechanism shared by the HSPB8_fs mutants described in neuromuscular diseases.Abbreviations : ACD: α-crystallin domain; ACTN: actinin alpha; BAG3: BAG cochaperone 3; C: carboxy; CASA: chaperone-assisted selective autophagy; CE: carboxy-terminal extension; CLEM: correlative light and electron microscopy; CMT2L: Charcot-Marie-Tooth type 2L; CTR: carboxy-terminal region; dHMNII: distal hereditary motor neuropathy type II; EV: empty vector; FRA: filter retardation assay; fs: frameshift; HSPA/HSP70: heat shock protein family A (Hsp70); HSPB1/Hsp27: heat shock protein family B (small) member 1; HSPB8/Hsp22: heat shock protein family B (small) member 8; HTT: huntingtin; KO: knockout; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MD: molecular dynamics; MTOC: microtubule organizing center; MYH: myosin heavy chain; MYOG: myogenin; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; NSC34: Neuroblastoma X Spinal Cord 34; OPTN: optineurin; polyQ: polyglutamine; SQSTM1/p62: sequestosome 1; STUB1/CHIP: STIP1 homology and U-box containing protein 1; TARDBP/TDP-43: TAR DNA binding protein; TAX1BP1: Tax1 binding protein 1; TUBA: tubulin alpha; WT: wild-type.

Published
2023

2. Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder

Author

Rosser, Anne E, members, on behalf of SC4HD, Busse, Monica E, Gray, William P, Badin, Romina Aron, Perrier, Anselme L, Wheelock, Vicki, Cozzi, Emanuele, Martin, Unai Perpiña, Salado-Manzano, Cristina, Mills, Laura J, Drew, Cheney, Goldman, Steven A, Canals, Josep M, and Thompson, Leslie M

Subjects
Huntington's Disease, Orphan Drug, Genetics, Brain Disorders, Regenerative Medicine, Rare Diseases, Neurodegenerative, Biotechnology, Neurosciences, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Neurological, Animals, Brain, Cell- and Tissue-Based Therapy, Humans, Huntington Disease, Neurodegenerative Diseases, cell therapy, stem cells, clinical translation, neurodegeneration, Huntington's, Huntington’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington's disease as a specific example, and suggest potential strategies to address these challenges. Huntington's disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington's disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington's Disease and the European Huntington's Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington's disease.

Published
2022

3. The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration

Author

Senage, Thomas, Paul, Anu, Le Tourneau, Thierry, Fellah-Hebia, Imen, Vadori, Marta, Bashir, Salam, Galiñanes, Manuel, Bottio, Tomaso, Gerosa, Gino, Evangelista, Arturo, Badano, Luigi P, Nassi, Alberto, Costa, Cristina, Cesare, Galli, Manji, Rizwan A, Cueff de Monchy, Caroline, Piriou, Nicolas, Capoulade, Romain, Serfaty, Jean-Michel, Guimbretière, Guillaume, Dantan, Etienne, Ruiz-Majoral, Alejandro, Coste du Fou, Guénola, Leviatan Ben-Arye, Shani, Govani, Liana, Yehuda, Sharon, Bachar Abramovitch, Shirley, Amon, Ron, Reuven, Eliran Moshe, Atiya-Nasagi, Yafit, Yu, Hai, Iop, Laura, Casós, Kelly, Kuguel, Sebastián G, Blasco-Lucas, Arnau, Permanyer, Eduard, Sbraga, Fabrizio, Llatjós, Roger, Moreno-Gonzalez, Gabriel, Sánchez-Martínez, Melchor, Breimer, Michael E, Holgersson, Jan, Teneberg, Susann, Pascual-Gilabert, Marta, Nonell-Canals, Alfons, Takeuchi, Yasuhiro, Chen, Xi, Mañez, Rafael, Roussel, Jean-Christian, Soulillou, Jean-Paul, Cozzi, Emanuele, and Padler-Karavani, Vered

Subjects
Biomedical and Clinical Sciences, Immunology, Heart Disease, Cardiovascular, 5.3 Medical devices, Development of treatments and therapeutic interventions, Animals, Antibody Formation, Aortic Valve, Aortic Valve Stenosis, Bioprosthesis, Calcinosis, Galactose, Humans, Immunoglobulin G, Mice, Polysaccharides, Prospective Studies, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in

Published
2022

4. Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study.

Author

Bashir, Salam, Fezeu, Leopold K, Leviatan Ben-Arye, Shani, Yehuda, Sharon, Reuven, Eliran Moshe, Szabo de Edelenyi, Fabien, Fellah-Hebia, Imen, Le Tourneau, Thierry, Imbert-Marcille, Berthe Marie, Drouet, Emmanuel B, Touvier, Mathilde, Roussel, Jean-Christian, Yu, Hai, Chen, Xi, Hercberg, Serge, Cozzi, Emanuele, Soulillou, Jean-Paul, Galan, Pilar, and Padler-Karavani, Vered

Subjects
Animals, Humans, Mice, Neoplasms, Neuraminic Acids, Carbohydrates, Antibodies, Cohort Studies, Prospective Studies, Middle Aged, France, Female, Male, Cancer, Red meat, Sialic acid, Digestive Diseases, Prevention, Clinical Research, Nutrition, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundHigh consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in "human-like" mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown.MethodsWe used world global data to demonstrate that colorectal cancer incidence and mortality are associated with increased national meat consumption. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records (aged 45-60, Q1-Q4; aged > 60, Q1 and Q4; 10 men/women per quartile).ResultsWe found that high-Neu5Gc diet, gender, and age affect the specificity, levels, and repertoires of anti-Neu5Gc IgG immune responses, but not their affinity. Men consumed more Neu5Gc than women, mostly from red meat (p = 0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94 ng/μl versus 2.22 ng/μl, respectively; p = 0.039). Detailed glycan microarray analysis against 56 different glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without an increase in antibody affinity, in individuals consuming higher Neu5Gc levels. Furthermore, in a high-meat diet, antibody diversity patterns on glycan microarrays shifted towards Neu5Gcα3-linked glycans, increasing the α3/α6-glycans ratio score.ConclusionsWe found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.

Published
2020

5. Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study

Author

Judd, Ali, Zangerle, Robert, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Julia, Del Amo, Obel, Niels, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella d’Arminio, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miró, Jose M, Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Quiros-Roldan, Eugenia, Sabin, Caroline, Teira, Ramon, Garrido, Myriam, Haerry, David, de Wit, Stéphane, Costagliola, Dominique, d’Arminio-Monforte, Antonella, del Amo, Julia, Raben, Dorthe, Chêne, Geneviève, Rojo, Conejo Pablo, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Grabar, Sophie, Guiguet, Marguerite, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Miro, Jose M, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, and Schomaker, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Sexually Transmitted Infections, Rare Diseases, Emerging Infectious Diseases, Infectious Diseases, HIV/AIDS, Infection, Adolescent, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Risk Factors, Sarcoma, Kaposi, Viral Load, Young Adult, AIDS-defining Cancer Project Working Group for IeDEA and COHERE in EuroCoord, HIV, Kaposi sarcoma, antiretroviral therapy, cohort study, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundWe compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America.MethodsWe included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs).ResultsWe included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were

Published
2017

6. Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy

Author

Cain, Lauren E, Saag, Michael S, Petersen, Maya, May, Margaret T, Ingle, Suzanne M, Logan, Roger, Robins, James M, Abgrall, Sophie, Shepherd, Bryan E, Deeks, Steven G, Gill, M John, Touloumi, Giota, Vourli, Georgia, Dabis, François, Vandenhende, Marie-Anne, Reiss, Peter, van Sighem, Ard, Samji, Hasina, Hogg, Robert S, Rybniker, Jan, Sabin, Caroline A, Jose, Sophie, del Amo, Julia, Moreno, Santiago, Rodríguez, Benigno, Cozzi-Lepri, Alessandro, Boswell, Stephen L, Stephan, Christoph, Pérez-Hoyos, Santiago, Jarrin, Inma, Guest, Jodie L, Monforte, Antonella D’Arminio, Antinori, Andrea, Moore, Richard, Campbell, Colin NJ, Casabona, Jordi, Meyer, Laurence, Seng, Rémonie, Phillips, Andrew N, Bucher, Heiner C, Egger, Matthias, Mugavero, Michael J, Haubrich, Richard, Geng, Elvin H, Olson, Ashley, Eron, Joseph J, Napravnik, Sonia, Kitahata, Mari M, Van Rompaey, Stephen E, Teira, Ramón, Justice, Amy C, Tate, Janet P, Costagliola, Dominique, Sterne, Jonathan AC, Hernán, Miguel A, and Systems, and the HIV-CAUSAL Collaboration on behalf of the Antiretroviral Therapy Cohort Collaboration the Centers for AIDS Research Network of Integrated Clinical

Subjects
Epidemiology, Health Sciences, Clinical Trials and Supportive Activities, Infectious Diseases, Sexually Transmitted Infections, HIV/AIDS, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Observational Studies as Topic, Randomized Controlled Trials as Topic, Survival Analysis, United Kingdom, Viral Load, HIV, antiretroviral therapy, inverse-probability weighting, observational studies, mortality, dynamic strategies, Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems, and the HIV-CAUSAL Collaboration, Statistics, Public Health and Health Services, Public health
Abstract

BackgroundWhen a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).MethodsWe review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.ResultsOf 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.ConclusionsAlthough our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.

Published
2016

7. Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy

Author

Grund, Birgit, Baker, Jason V, Deeks, Steven G, Wolfson, Julian, Wentworth, Deborah, Cozzi-Lepri, Alessandro, Cohen, Calvin J, Phillips, Andrew, Lundgren, Jens D, and Neaton, James D

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, HIV/AIDS, Clinical Research, Infectious Diseases, Prevention, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Adult, Antiretroviral Therapy, Highly Active, Biomarkers, C-Reactive Protein, Endpoint Determination, Female, Fibrin Fibrinogen Degradation Products, HIV Seropositivity, Humans, Interleukin-6, Kaplan-Meier Estimate, Male, Middle Aged, Morbidity, Risk Reduction Behavior, INSIGHT SMART/ESPRIT/SILCAAT Study Group, General Science & Technology
Abstract

BackgroundDespite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts.MethodsIn HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR) adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability) were used to predict risk reductions in serious non-AIDS conditions or death associated with lower "usual" levels of IL-6 and D-dimer.ResultsOver 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63), 1.28 (95% CI: 1.14 to 1.44), and 1.17 (95% CI: 1.09 to 1.26) per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower "usual" IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46%) in the risk of serious non-AIDS conditions or death if the relationship is causal.ConclusionsBoth IL-6 and D-dimer are independently associated with serious non-AIDS conditions or death among HIV-positive adults with suppressed virus. This suggests that treatments that reduce IL-6 and D-dimer levels might substantially decrease morbidity and mortality in patients on suppressive ART. Clinical trials are needed to test this hypothesis.

Published
2016

8. Prevalence and features of delirium in older patients admitted to rehabilitation facilities

Author

Sidoli, Chiara, Zambon, Antonella, Tassistro, Elena, Rossi, Emanuela, Mossello, Enrico, Inzitari, Marco, Cherubini, Antonio, Marengoni, Alessandra, Morandi, Alessandro, Bellelli, Giuseppe, Tarasconi, A, Sella, M, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, Pietrogrande, L, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D’Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell’Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Bo, M, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Borghi, C, Bianchetti, A, Crucitti, A, Difrancesco, V, Fontana, G, Geriatria, A, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambar, V, Saitta, A, Corica, F, Braga, M, Servi, Null, Ettorre, E, Camellini Bellelli, C G, Annoni, G, Marengoni, A, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuar, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl’Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samysalamafahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Alessandro, M, Di, F, Pezzoni, D, Platto, C, D’Ambrosio, V, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, Corsini, C, Boffelli, S, Filippi, A, Delpin, K, Faraci, B, Bertoletti, E, Vannucci, M, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Cottino, M, Vezzadini, G, Avanzi, S, Brambilla, C, Orini, S, Sgrilli, F, Mello, A, Lombardi Muti, L E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, Barelli, A, Millul, A, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cat, C, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Cortegiani, A, Pistidda, L, D’Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Mossello, E, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D, Sidoli, Chiara, Zambon, Antonella, Tassistro, Elena, Rossi, Emanuela, Mossello, Enrico, Inzitari, Marco, Cherubini, Antonio, Marengoni, Alessandra, Morandi, Alessandro, Bellelli, Giuseppe, A Tarasconi, M Sella, G Paternò, G Faggian, C Lucarelli, N De Grazia, C Alberto, L Porcella, I Nardiello, E Chimenti, M Zeni, E Romairone, C Minaglia, C Ceccotti, G Guerra, G Mantovani, F Monacelli, C Minaglia, T Candiani, F Santolini, C Minaglia, M Rosso, V Bono, S Sibilla, P Dal Santo, M Ceci, P Barone, T Schirinzi, A Formenti, G Nastasi, G Isaia, D Gonella, A Battuello, S Casson, D Calvani, F Boni, A Ciaccio, R Rosa, G Sanna, S Manfredini, L Cortese, M Rizzo, R Prestano, A Greco, M Lauriola, G Gelosa, V Piras, M Arena, D Cosenza, A Bellomo, M LaMontagna, L Gabbani, L Lambertucci, S Perego, G Parati, G Basile, V Gallina, G Pilone, C Giudice, L Pietrogrande, M Mosca, I Corazzin, P Rossi, V Nunziata, F D’Amico, A Grippa, S Giardini, R Barucci, A Cossu, L Fiorin, M Arena , M Distefano, M Lunardelli, M Brunori, I Ruffini, E Abraham, A Varutti, E Fabbro, A Catalano, G Martino, D Leotta, A Marchet, G Dell’Aquila, A Scrimieri, M Davoli, M Casella, A Cartei, G Polidori, G Basile, D Brischetto, S Motta, R Saponara, P Perrone, G Russo, D Del, C Car, T Pirina, S Franzoni, A Cotroneo, F Ghiggia, G Volpi, C Menichetti, M Bo, A Panico, P Calogero, G Corvalli, M Mauri, E Lupia, R Manfredini, F Fabbian, A March, M Pedrotti, M Veronesi, E Strocchi, C Borghi, A Bianchetti, A Crucitti, V DiFrancesco, G Fontana, A Geriatria, L Bonanni, F Barbone, C Serrati, G Ballardini, M Simoncelli, G Ceschia, C Scarpa, R Brugiolo, S Fusco, T Ciarambino, C Biagini, E Tonon, M Porta , D Venuti, M DelSette, M Poeta, G Barbagallo, G Trovato, A Delitala, P Arosio, F Reggiani, G Zuliani, B Ortolani, E Mussio, A Girardi, A Coin, G Ruotolo, A Castagna, M Masina, R Cimino, A Pinciaroli, G Tripodi, F Cassadonte, M Vatrano, L Scaglione, P Fogliacco, C Muzzuilini, F Romano, A Padovani, L Rozzini, A Cagnin, F Fragiacomo, G Desideri, E Liberatore, A Bruni, G Orsitto, M Franco, L Bonfrate, M Bonetto, N Pizio, G Magnani, G Cecchetti, A Longo, V Bubba, L Marinan, M Cotelli, M Turla, M Brunori, M Sessa, L Abruzzi, G Castoldi, D LoVetere, C Musacchio, M Novello, A Cavarape, A Bini, A Leonardi, F Seneci, W Grimaldi, F Seneci, F Fimognari, V Bambar, A Saitta, F Corica, M Braga, Servi, E Ettorre , C G Camellini Bellelli, G Annoni, A Marengoni, A Bruni, A Crescenzo, G Noro, R Turco, M Ponzetto, L Giuseppe, B Mazzei, G Maiuri, D Costaggiu, R Damato, E Fabbro, M Formilan, G Patrizia, L Santuar , M Gallucci, C Minaglia, M Paragona, P Bini, D Modica, C Abati, M Clerici, I Barbera, F NigroImperiale, A Manni, C Votino, C Castiglioni, M Di, M Degl’Innocenti, G Moscatelli, S Guerini, C Casini, D Dini, S DeNotariis, F Bonometti, C Paolillo, A Riccardi, A Tiozzo, A SamySalamaFahmy, A Riccardi, C Paolillo, M DiBari, S Vanni, A Scarpa, D Zara, P Ranieri, M Alessandro, P Calogero, G Corvalli, F Di, D Pezzoni, C Platto, V D’Ambrosio, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, M Bonetto, M Grasso, E Troisi, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, B Faraci, E Bertoletti, M Vannucci, P Crippa, A Malighetti, C Caltagirone, S DiSant, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D’Amico, A Grippa , A Mazzone, M Cottino, G Vezzadini, S Avanzi, C Brambilla, S Orini, F Sgrilli, A Mello, L E Lombardi Muti, B Dijk , S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul , G De, G Morrone, M Bigolari, C Minaglia, M Macchi, F Zambon, F D’Amico, F D’Amico, C Pizzorni, G DiCasaleto, G Menculini, M Marcacci, G Catanese, D Sprini, T DiCasalet, M Bocci, S Borga, P Caironi, C Cat, E Cingolani, L Avalli, G Greco, G Citerio, L Gandini, G Cornara, R Lerda, L Brazzi, F Simeone, M Caciorgna, D Alampi, S Francesconi, E Beck, B Antonini, K Vettoretto, M Meggiolaro, E Garofalo, A Bruni, S Notaro, R Varutti, F Bassi, G Mistraletti, A Marino, R Rona, E Rondelli, I Riva, A Cortegiani, L Pistidda, R D’Andrea, L Querci, P Gnesin, M Todeschini, M Lugano, G Castelli, M Ortolani, A Cotoia, S Maggiore, L DiTizio, R Graziani, I Testa, E Ferretti, C Castioni, F Lombardi, R Caserta, M Pasqua, S Simoncini, F Baccarini, M Rispoli, F Grossi, L Cancelliere, M Carnelli, F Puccini, G Biancofiore, A Siniscalchi, C Laici, E Mossello, M Torrini, G Pasetti, S Palmese, R Oggioni, V Mangani, S Pini, M Martelli, E Rigo, F Zuccalà , A Cherri, R Spina, I Calamai, N Petrucci, A Caicedo, F Ferri, P Gritti, N Brienza, R Fonnesu, M Dessena, G Fullin & D Saggioro, VU University medical center, Sidoli, C, Zambon, A, Tassistro, E, Rossi, E, Mossello, E, Inzitari, M, Cherubini, A, Marengoni, A, Morandi, A, Bellelli, G, Tarasconi, A, Sella, M, Paterno, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, Pietrogrande, L, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Bo, M, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Borghi, C, Bianchetti, A, Crucitti, A, Difrancesco, V, Fontana, G, Geriatria, A, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambar, V, Saitta, A, Corica, F, Braga, M, Servi, Ettorre, E, Camellini Bellelli, C, Annoni, G, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuar, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samysalamafahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Alessandro, M, Di, F, Pezzoni, D, Platto, C, D'Ambrosio, V, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, Corsini, C, Boffelli, S, Filippi, A, Delpin, K, Faraci, B, Bertoletti, E, Vannucci, M, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Cottino, M, Vezzadini, G, Avanzi, S, Brambilla, C, Orini, S, Sgrilli, F, Mello, A, Lombardi Muti, L, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Ricco, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, Barelli, A, Millul, A, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cat, C, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Cortegiani, A, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccala, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, and Saggioro, D

Subjects
Aging, Disability, Rehabilitation, Delirium, Dementia, Physical restraint, Cross-Sectional Studies, Activities of Daily Living, mental disorders, Prevalence, Humans, Geriatrics and Gerontology, Aged
Abstract

Background: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. Aim: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. Methods: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Results: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17–1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08–2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62–2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10–1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02–1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68–3.36, p value < 0.0001). Conclusion: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Published
2022

9. During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

Author

Ruggiero, Alessandra, De Spiegelaere, Ward, Cozzi-Lepri, Alessandro, Kiselinova, Maja, Pollakis, Georgios, Beloukas, Apostolos, Vandekerckhove, Linos, Strain, Matthew, Richman, Douglas, Phillips, Andrew, Geretti, Anna Maria, Group, ERAS Study, Vitiello, Paola, Mackie, Nicola, Ainsworth, Jonathan, Waters, Anele, Post, Frank, Edwards, Simon, and Fox, Julie

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Genetics, Clinical Research, Infectious Diseases, Infection, Adult, Antiretroviral Therapy, Highly Active, CD8-Positive T-Lymphocytes, DNA, Viral, Female, HIV-1, HLA-DP Antigens, HLA-DQ Antigens, HLA-DR Antigens, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Viral Load, Suppression, Reservoir, Persistence, Integration, Activation, ERAS Study Group, 2-LTR, 2-long terminal repeats, ART, Anti-retroviral therapy, CMV, cytomegalovirus virus, CRN, Clinical Research Network, EBV, Epstein-Bar virus, ELISA, enzyme-linked immune-enzymatic assay, HIC, HIV-1 controllers, HIV-1 VL, HIV-1 viral load, HIV-1, Human Immunodeficiency Virus type 1, HLA, Human Leukocyte Antigen, LPS, lipopolysaccharide, NIHR, National Institute for Health Research, NNRTI, Non-nucleoside reverse-transcriptase inhibitors, NRTI, nucleoside/nucleotide reverse transcriptase inhibitors, PBMCs, Peripheral blood mononuclear cells, PCR, Polymerase chain reaction, PFA, paraformaldehyde, VLS, Viral Load Suppression, WHO, World Health Organisation, sCD14, soluble CD14, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundCharacterising the correlates of HIV persistence improves understanding of disease pathogenesis and guides the design of curative strategies. This study investigated factors associated with integrated HIV-1 DNA load during consistently suppressive first-line antiretroviral therapy (ART).MethodTotal, integrated, and 2-long terminal repeats (LTR) circular HIV-1 DNA, residual plasma HIV-1 RNA, T-cell activation markers, and soluble CD14 (sCD14) were measured in peripheral blood of 50 patients that had received 1-14 years of efavirenz-based or nevirapine-based therapy.ResultsIntegrated HIV-1 DNA load (per 10(6) peripheral blood mononuclear cells) was median 1.9 log10 copies (interquartile range 1.7-2.2) and showed a mean difference of 0.2 log10 copies per 10 years of suppressive ART (95% confidence interval - 0.2, 0.6; p = 0.28). It was positively correlated with total HIV-1 DNA load and frequency of CD8(+)HLA-DR/DP/DQ(+) cells, and was also higher in subjects with higher sCD14 levels, but showed no correlation with levels of 2-LTR circular HIV-1 DNA and residual plasma HIV-1 RNA, or the frequency of CD4(+)CD38(+) and CD8(+)CD38(+) cells. Adjusting for pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, and sCD14 levels, integrated HIV-1 DNA load was mean 0.5 log10 copies higher for each 50% higher frequency of CD8(+)HLA-DR/DP/DQ(+) cells (95% confidence interval 0.2, 0.9; p = 0.01).ConclusionsThe observed positive association between integrated HIV-1 DNA load and frequency of CD8(+)DR/DP/DQ(+) cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.

Published
2015

10. Long-Term IgG Response to Porcine Neu5Gc Antigens without Transmission of PERV in Burn Patients Treated with Porcine Skin Xenografts

Author

Scobie, Linda, Padler-Karavani, Vered, Le Bas-Bernardet, Stephanie, Crossan, Claire, Blaha, Josef, Matouskova, Magda, Hector, Ralph D, Cozzi, Emanuele, Vanhove, Bernard, Charreau, Beatrice, Blancho, Gilles, Bourdais, Ludovic, Tallacchini, Mariachiara, Ribes, Juan M, Yu, Hai, Chen, Xi, Kracikova, Jitka, Broz, Ludomir, Hejnar, Jiri, Vesely, Pavel, Takeuchi, Yasuhiro, Varki, Ajit, and Soulillou, Jean-Paul

Subjects
Biotechnology, Prevention, Clinical Research, Autoimmune Disease, Adolescent, Adult, Aged, Animals, Antigens, Heterophile, Burns, Child, Endogenous Retroviruses, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin G, Infant, Male, Middle Aged, RNA, Viral, Reverse Transcriptase Polymerase Chain Reaction, Sialic Acids, Skin Transplantation, Swine, Transplantation, Heterologous, Immunology
Abstract

Acellular materials of xenogenic origin are used worldwide as xenografts, and phase I trials of viable pig pancreatic islets are currently being performed. However, limited information is available on transmission of porcine endogenous retrovirus (PERV) after xenotransplantation and on the long-term immune response of recipients to xenoantigens. We analyzed the blood of burn patients who had received living pig-skin dressings for up to 8 wk for the presence of PERV as well as for the level and nature of their long term (maximum, 34 y) immune response against pig Ags. Although no evidence of PERV genomic material or anti-PERV Ab response was found, we observed a moderate increase in anti-αGal Abs and a high and sustained anti-non-αGal IgG response in those patients. Abs against the nonhuman sialic acid Neu5Gc constituted the anti-non-αGal response with the recognition pattern on a sialoglycan array differing from that of burn patients treated without pig skin. These data suggest that anti-Neu5Gc Abs represent a barrier for long-term acceptance of porcine xenografts. Because anti-Neu5Gc Abs can promote chronic inflammation, the long-term safety of living and acellular pig tissue implants in recipients warrants further evaluation.

Published
2013

11. Differences in Long-Term Progression of Atrophy between Neovascular and Nonneovascular Age-Related Macular Degeneration

Author

Matteo Airaldi, Federico Corvi, Mariano Cozzi, Muneeswar Gupta Nittala, Giovanni Staurenghi, and SriniVas R. Sadda

Subjects
Macular Degeneration, Ophthalmology, Geographic Atrophy, Disease Progression, Humans, Atrophy, Fluorescein Angiography, Retrospective Studies
Abstract

To compare the enlargement rates of geographic atrophy (GA) over 5 years of follow-up with those of macular atrophy (MA) associated with macular neovascularization (MNV).Retrospective, longitudinal, comparative case series.Consecutive series of patients with age-related macular degeneration and GA (dry) or with MA and MNV.Atrophic regions detected on serial registered fundus autofluorescence images were semiautomatically delineated, and the measurements of these areas were recorded every 6 ± 3 months for the first 2 years of follow-up and at yearly intervals for up to 5 years.Annual raw and square root-transformed rates of atrophy growth.The study included 117 eyes of 95 patients (61 in the GA cohort and 56 in the MA cohort); 100% and 38.5% of the eyes completed 2 and 5 years of follow-up, respectively. The mean size of lesions at baseline was similar between the 2 groups (raw: 1.74 vs. 1.53 mmThe presence of MNV was associated with a slower rate of expansion, resulting in overall smaller areas of atrophy over time. These findings support the hypothesis that MNV may protect against the progression of atrophy.

Published
2022

12. Common genetic variation and the control of HIV-1 in humans.

Author

Fellay, Jacques, Ge, Dongliang, Shianna, Kevin V, Colombo, Sara, Ledergerber, Bruno, Cirulli, Elizabeth T, Urban, Thomas J, Zhang, Kunlin, Gumbs, Curtis E, Smith, Jason P, Castagna, Antonella, Cozzi-Lepri, Alessandro, De Luca, Andrea, Easterbrook, Philippa, Günthard, Huldrych F, Mallal, Simon, Mussini, Cristina, Dalmau, Judith, Martinez-Picado, Javier, Miro, José M, Obel, Niels, Wolinsky, Steven M, Martinson, Jeremy J, Detels, Roger, Margolick, Joseph B, Jacobson, Lisa P, Descombes, Patrick, Antonarakis, Stylianos E, Beckmann, Jacques S, O'Brien, Stephen J, Letvin, Norman L, McMichael, Andrew J, Haynes, Barton F, Carrington, Mary, Feng, Sheng, Telenti, Amalio, Goldstein, David B, and NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)

Subjects
NIAID Center for HIV/AIDS Vaccine Immunology, Humans, HIV-1, HIV Infections, Disease Progression, Viral Load, Major Histocompatibility Complex, Genotype, Phenotype, Polymorphism, Single Nucleotide, Alleles, Adult, Female, Male, Genetic Variation, Kaplan-Meier Estimate, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.

Published
2009

13. Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from the EUSTAR cohort

Author

Elisabetta Zanatta 1, Dörte Huscher 2, Augusta Ortolan 1, Jérôme Avouac 3, Paolo Airò 4, Alexandra Balbir-Gurman 5, Elise Siegert 6, Marco Matucci Cerinic 7, Franco Cozzi 8, Gabriela Riemekasten 9, Anna-Maria Hoffmann-Vold 10, Oliver Distler 11, Armando Gabrielli 12, Stefan Heitmann 13, Nicolas Hunzelmann 14, Carlomaurizio Montecucco 15, Jadranka Morovic-Vergles 16, Camillo Ribi 17, Andrea Doria 1, Yannick Allanore 3, EUSTAR collaborators, Giovanna Cuomo, Gianluca Moroncini, Jiri Stork, Fiorenzo Iannone, Ulrich Walker, Eugenia Bertoldo, Dorota Krasowska, Maria João Salvador, Mohammed Tikly, Eric Hachulla, Valeria Riccieri, Ami Sha, Ana Maria Gheorghiu, Cord Sunderkötter, Francesca Ingegnoli, Luc Mouthon, Vanessa Smith, Francesco Paolo Cantatore, Kilian Eyerich, Piotr Wiland, Marie Vanthuyne, Branimir Anic, Maria Üprus, Brigitte Granel, Alessandra Vacca, Cristina-Mihaela Tanaseanu, Paloma García de la Peña Lefebvre, Jean Sibilia, Ira Litinsky, Lesley Ann Saketkoo, Eduardo Kerzberg, Massimiliano Limonta, Doron Rimar, Petros Sfikakis, Maurizio Cutolo, Patricia E Carreira, Rosario Foti, Srdan Novak, Michele Iudici, Mislav Radic, Raffaele Pellerito, Carlo Francesco Selmi, Lidia P Ananieva, Gabriela Szücs, Carlos de la Puente, Ruxandra Maria Ionescu, Jörg Distler, Maria Rosa Pozzi, Juan Jose Alegre-Sancho, Kristine Herrmann, Ellen De Langhe, Sule Yavuz, Carolina de Souza Müller, Svetlana Agachi, Douglas Veale, Esthela Loyo, Mengtao Li, Edoardo Rosato, Britta Maurer, Ivan Castellví, François Spertini, Kamal Solanki, Nicoletta Del Papa, Gerard Espinosa, László Czirják, Bernard Coleiro, Dominique Farge Bancel, Christopher Denton, Nemanja Damjanov, Jörg Henes, Vera Ortiz Santamaria, Michaela Kohm, Bojana Stamenkovic, 1, Elisabetta Zanatta, 2, Dörte Huscher, 1, Augusta Ortolan, 3, Jérôme Avouac, 4, Paolo Airò, 5, Alexandra Balbir-Gurman, 6, Elise Siegert, 7, Marco Matucci Cerinic, 8, Franco Cozzi, 9, Gabriela Riemekasten, Hoffmann-Vold 10, Anna-Maria, Distler 11, Oliver, Gabrielli 12, Armando, Heitmann 13, Stefan, Hunzelmann 14, Nicola, Montecucco 15, Carlomaurizio, Morovic-Vergles 16, Jadranka, Ribi 17, Camillo, 1, Andrea Doria, 3, Yannick Allanore, Collaborators, Eustar, Cuomo, Giovanna, Moroncini, Gianluca, Stork, Jiri, Iannone, Fiorenzo, Walker, Ulrich, Bertoldo, Eugenia, Krasowska, Dorota, João Salvador, Maria, Tikly, Mohammed, Hachulla, Eric, Riccieri, Valeria, Sha, Ami, Maria Gheorghiu, Ana, Sunderkötter, Cord, Ingegnoli, Francesca, Mouthon, Luc, Smith, Vanessa, Paolo Cantatore, Francesco, Eyerich, Kilian, Wiland, Piotr, Vanthuyne, Marie, Anic, Branimir, Üprus, Maria, Granel, Brigitte, Vacca, Alessandra, Tanaseanu, Cristina-Mihaela, García de la Peña Lefebvre, Paloma, Sibilia, Jean, Litinsky, Ira, Ann Saketkoo, Lesley, Kerzberg, Eduardo, Limonta, Massimiliano, Rimar, Doron, Sfikakis, Petro, Cutolo, Maurizio, E Carreira, Patricia, Foti, Rosario, Novak, Srdan, Iudici, Michele, Radic, Mislav, Pellerito, Raffaele, Francesco Selmi, Carlo, P Ananieva, Lidia, Szücs, Gabriela, de la Puente, Carlo, Maria Ionescu, Ruxandra, Distler, Jörg, Rosa Pozzi, Maria, Jose Alegre-Sancho, Juan, Herrmann, Kristine, De Langhe, Ellen, Yavuz, Sule, de Souza Müller, Carolina, Agachi, Svetlana, Veale, Dougla, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Maurer, Britta, Castellví, Ivan, Spertini, Françoi, Solanki, Kamal, Del Papa, Nicoletta, Espinosa, Gerard, Czirják, László, Coleiro, Bernard, Farge Bancel, Dominique, Denton, Christopher, Damjanov, Nemanja, Henes, Jörg, Ortiz Santamaria, Vera, Kohm, Michaela, and Stamenkovic, Bojana

Subjects
interstitial lung disease, Scleroderma, Systemic, Hypertension, Pulmonary, disease subset, anti-topoisomerase I, Scleroderma, Systemic sclerosis, cutaneous form, outcome, Phenotype, Rheumatology, Scleroderma, Limited, Antibodies, Antinuclear, Scleroderma, Diffuse, Humans, Pharmacology (medical), Lung Diseases, Interstitial
Abstract

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Published
2022

14. Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy

Author

Chammartin, F., Lodi, S., Logan, R., Ryom, L., Mocroft, A., Kirk, O., D'Arminio Monforte, A., Reiss, P., Phillips, A., El-Sadr, W., Hatleberg, C. I., Pradier, C., Bonnet, F., Law, M., De Wit, S., Sabin, C., Lundgren, J. D., Bucher, H. C., Calvo, G., Dabis, F., Morfeldt, L., Weber, R., Lind-Thomsen, A., Salbol Brandt, R., Hillebreght, M., Zaheri, S., Wit, F. W. N. M., Scherrer, A., Schoni-Affolter, F., Rickenbach, M., Tavelli, A., Fanti, I., Leleux, O., Mourali, J., Le Marec, F., Boerg, E., Thulin, E., Sundstrom, A., Bartsch, G., Thompsen, G., Necsoi, C., Delforge, M., Fontas, E., Caissotti, C., Dollet, K., Mateu, S., Torres, F., Petoumenos, K., Blance, A., Huang, R., Puhr, R., Gronborg Laut, K., Kristensen, D., Kamara, D. A., Smith, C. J., Raben, D., Matthews, C., Bojesen, A., Grevsen, A. L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Smit, C., Ross, M., Fux, C. A., Morlat, P., Friis-Moller, N., Kowalska, J., Bohlius, J., Bower, M., Fatkenheuer, G., Grulich, A., Sjol, A., Meidahl, P., Iversen, J. S., Hillebregt, M., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T. M., Godfried, M. H., Van Der Poll, T., Nellen, F. J. B., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., Van Der Valk, M., Goorhuis, A., Hovius, J. W., Van Eden, J., Henderiks, A., Van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., Van Den Berge, M., Stegeman, A., Baas, S., Hage De Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., Van Der Plas, A., Weijsenfeld, A. M., Van Der Ende, M. E., de Vries-Sluijs, T. E. M. S., van Gorp, E. C. M., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Van Der Feltz, M., Bassant, N., Van Beek, J. E. A., Vriesde, M., Van Zonneveld, L. M., De Oude-Lubbers, A., Van Den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., De Zeeuw-De Man, M., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Driessen, G. J. A., van Rossum, A. M. C., Van Der Knaap, L. C., Visser, E., Branger, J., Rijkeboer-Mes, A., Duijf-Van De Ven, C. J. H. M., Schippers, E. F., van Nieuwkoop, C., van IJperen, J. M., Geilings, J., van der Hut, G., Franck, P. F. H., Van Eeden, A., Brokking, W., Groot, M., Elsenburg, L. J. M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., Van Den Berg, J. F., Van Hulzen, A. G. W., Van Der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., Kroon, F. P., De Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Van Holten, N., Claas, E. C. J., Wessels, E., Den Hollander, J. G., Pogany, K., Roukens, A., Kastelijns, M., Smit, J. V., Smit, E., Struik-Kalkman, D., Tearno, C., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A. M. L., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg-Maes, B., van Loo, I. H. M., Havenith, T. R. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Smits, P. H. M., Weijer, S., El Moussaoui, R., Bosma, A. S., van Vonderen, M. G. A., van Houte, D. P. F., Kampschreur, L. M., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-Van de Plas, M., Heins, H., Lucas, E., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., van Truijen-Oud, F. A., van der Reijden, W. A., Jansen, R., Brinkman, K., van den Berk, G. E. L., Blok, W. L., Frissen, P. H. J., Lettinga, K. D., Schouten, W. E. M., Veenstra, J., Brouwer, J. C., Geerders, F. G., Hoeksema, K., Kleene, J. M., van der Meche, B. I., Spelbrink, M., Sulman, H., Toonen, A. J. M., Wijnands, S., Kwa, D., Witte, E., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, J. B., Stelma, F. F., Rahamat-Langendoen, J., Burger, D., Richter, C., Gisolf, H. E., Hassing, J. R., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., van der Swaluw, J., Bermon, N., Herpers, B. L., Veenendaal, D., Verhagen, W. D. M., van Wijk, M., van Kasteren, M. E. E., Brouwer, E. A., de Kruijf-Van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, H. J., Buiting, A. G. M., Kabel, J. P., Bierman, W. F. W., Scholvinck, H., Wilting, R. K., Stienstra, Y., de Groot-De Jonge, H., van der Meulen, A. P., de Weerd, A. D., Ludwig-Roukema, J., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Knoester, M., Hoepelman, A. I. M., Mudrikova, T., Ellerbroek, M. P., Oosterheert, J. J., Arends, E. J., Barth, E. R., Wassenberg, M. W. M., Schadd, M. E., van Elst-Laurijssen, D. H. M., van Oers-Hazelzet, B. E., Vervoort, S., van Berkel, M., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, A. M., Bomers, M., de Vocht, J., Heitmuller, M., Laan, M. L., Pettersson, M. A., Vandenbroucke-Grauls, C. M. J. E., Ang, W. C., Geelen, S. P. M., Wolfs, T. F. W., Bont, J. L., Nauta, N., Bezemer, O. D., van Sighem, I. A., Boender, S. T., de Jong, A., Bergsma, D., Hoekstra, P., de Lang, A., Grivell, S., Jansen, A., Rademaker, J. M., Raethke, M., Meijering, R., Schnorr, S., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., van de Sande, L., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Dupon, M., Gaborieau, V., Lacoste, D., Malvy, D., Mercie, P., Neau, D., Pellegrin, L. J., Tchamgoue, S., Lazaro, E., Cazanave, C., Vandenhende, M., Vareil, O. M., Gerard, Y., Blanco, P., Bouchet, S., Breilh, D., Fleury, H., Pellegrin, I., Chene, G., Thiebaut, R., Wittkop, L., Lawson-Ayayi, S., Gimbert, A., Desjardin, S., Lacaze-Buzy, L., Petrov-Sanchez, V., Andre, N., Bernard, K., Caubet, O., Caunegre, L., Chossat, I., Courtault, C., Dauchy, A. F., Dondia, D., Duffau, P., Dutronc, H., Farbos, S., Faure, I., Ferrand, H., Greib, C., Hessamfar, M., Imbert, Y., Lataste, P., Marie, J., Mechain, M., Monlun, E., Ochoa, A., Pistone, T., Raymond, I., Receveur, C. M., Rispal, P., Sorin, L., Valette, C., Viallard, J. F., Wille, H., Wirth, G., Lafon, M., Trimoulet, P., Bellecave, P., Tumiotto, C., Haramburu, F., Miremeont-Salame, G., Blaizeau, J. M., Decoin, M., Hannapier, C., Lenaud, E., Pougetoux, A., Delveaux, S., D'Ivernois, C., Diarra, F., Uwamaliya-Nziyumvira, B., Palmer, G., Conte, V., Sapparrart, V., Moore, R., Edwards, S., Hoy, J., Watson, K., Roth, N., Lau, H., Bloch, M., Baker, D., Carr, A., Cooper, D., O'Sullivan, M., Nolan, D., Guelfi, G., Domingo, P., Sambeat, A. M., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaque, A., Clumeck, N., Gennotte, F. A., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, C. M., Semaille, P., Van Laethem, Y., Neaton, J., El-Sadr, M. W., Krum, E., Thompson, G., Wentworth, D., Luskin-Hawk, R., Telzak, E., Abrams, I. D., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, R. L., Sampson, J., Baxter, J., Gazzard, B., Horban, A., Karpov, I., Pedersen, C., Ristola, M., Rockstroh, J., Peters, L., Fischer, H. A., Larsen, F. J., Podlekareva, D., Cozzi-Lepri, A., Shepherd, L., Schultze, A., Amele, S., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Vassilenko, A., Mitsura, M. V., Paduto, D., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Moller, F. N., Ostergaard, L., Wiese, L., Nielsen, N. L., Zilmer, K., Smidt, J., Aho, I., Viard, J. P., Girard, P. M., Duvivier, C., Schmidt, R., Degen, O., Stellbrink, J. H., Stefan, C., Bogner, J., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Armenis, K., Sambatakou, H., Szlavik, J., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, M. Z., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Miro, M. J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Gutierrez, M., Mateo, G., Laporte, M. J., Falconer, K., Thalme, A., Sonnerborg, A., Blaxhult, A., Flamholc, L., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Kyselyova, G., Sluzhynska, M., Johnson, A. M., Simons, E., Orkin, C., Weber, J., Scullard, G., Clarke, A., Leen, C., Thulin, G., Akerlund, B., Koppel, K., Karlsson, A., Hakangard, C., Castelli, F., Cauda, R., Di Perri, G., Iardino, R., Ippolito, G., Marchetti, C. G., Perno, F. C., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Bonora, S., Borderi, M., Calcagno, A., Calza, L., Capobianchi, R. M., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petrone, F., Prota, G., Quartu, S., Truffa, S., Giacometti, A., Costantini, A., Barocci, V., Angarano, G., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, E. P., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Pan, A., Lorenzotti, S., Sighinolfi, L., Segala, D., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Milini, P., Rizzardini, G., Moioli, C. M., Piolini, R., Ridolfo, L. A., Salpietro, S., Tincati, C., Puzzolante, C., Abrescia, N., Chirianni, A., Borgia, G., Orlando, R., Bonadies, G., Di Martino, F., Gentile, I., Maddaloni, L., Cattelan, M. A., Marinello, S., Cascio, A., Colomba, C., Baldelli, F., Schiaroli, E., Parruti, G., Sozio, F., Magnani, G., Ursitti, A. M., Cristaudo, A., Baldin, G., Capozzi, M., Cicalini, S., Fontanelli Sulekova, L., Iaiani, G., Latini, A., Mastrorosa, I., Savinelli, S., Vergori, A., Cecchetto, M., Viviani, F., Bagella, P., Rossetti, B., Franco, A., Fontana Del Vecchio, R., Francisci, D., Di Giuli, C., Caramello, P., Orofino, C. G., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Starnini, G., Ialungo, A., Dellamonica, P., Bernard, E., Courjon, J., Cua, E., De Salvador-Guillouet, F., Durant, J., Etienne, C., Ferrando, S., Mondain-Miton, V., Naqvi, A., Perbost, I., Pillet, S., Prouvost-Keller, B., Pugliese, P., Rio, V., Risso, K., Roger, M. P., Aubert, V., Bernasconi, E., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Gunthard, F. H., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, D. R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, J. K., Muller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Speck, R., Stockle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Yerly, S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Chammartin F., Lodi S., Logan R., Ryom L., Mocroft A., Kirk O., D'Arminio Monforte A., Reiss P., Phillips A., El-Sadr W., Hatleberg C.I., Pradier C., Bonnet F., Law M., De Wit S., Sabin C., Lundgren J.D., Bucher H.C., Calvo G., Dabis F., Morfeldt L., Weber R., Lind-Thomsen A., Salbol Brandt R., Hillebreght M., Zaheri S., Wit F.W.N.M., Scherrer A., Schoni-Affolter F., Rickenbach M., Tavelli A., Fanti I., Leleux O., Mourali J., Le Marec F., Boerg E., Thulin E., Sundstrom A., Bartsch G., Thompsen G., Necsoi C., Delforge M., Fontas E., Caissotti C., Dollet K., Mateu S., Torres F., Petoumenos K., Blance A., Huang R., Puhr R., Gronborg Laut K., Kristensen D., Kamara D.A., Smith C.J., Raben D., Matthews C., Bojesen A., Grevsen A.L., Powderly B., Shortman N., Moecklinghoff C., Reilly G., Smit C., Ross M., Fux C.A., Morlat P., Friis-Moller N., Kowalska J., Bohlius J., Bower M., Fatkenheuer G., Grulich A., Sjol A., Meidahl P., Iversen J.S., Hillebregt M., Prins J.M., Kuijpers T.W., Scherpbier H.J., Van Der Meer J.T.M., Godfried M.H., Van Der Poll T., Nellen F.J.B., Geerlings S.E., Van Vugt M., Pajkrt D., Bos J.C., Wiersinga W.J., Van Der Valk M., Goorhuis A., Hovius J.W., Van Eden J., Henderiks A., Van Hes A.M.H., Mutschelknauss M., Nobel H.E., Pijnappel F.J.J., Jurriaans S., Back N.K.T., Zaaijer H.L., Berkhout B., Cornelissen M.T.E., Schinkel C.J., Thomas X.V., Van Den Berge M., Stegeman A., Baas S., Hage De Looff L., Versteeg D., Pronk M.J.H., Ammerlaan H.S.M., de Munnik E.S., Jansz A.R., Tjhie J., Wegdam M.C.A., Deiman B., Scharnhorst V., Van Der Plas A., Weijsenfeld A.M., Van Der Ende M.E., de Vries-Sluijs T.E.M.S., van Gorp E.C.M., Schurink C.A.M., Nouwen J.L., Verbon A., Rijnders B.J.A., Bax H.I., Van Der Feltz M., Bassant N., Van Beek J.E.A., Vriesde M., Van Zonneveld L.M., De Oude-Lubbers A., Van Den Berg-Cameron H.J., Bruinsma-Broekman F.B., de Groot J., De Zeeuw-De Man M., Boucher C.A.B., Koopmans M.P.G., van Kampen J.J.A., Pas S.D., Driessen G.J.A., van Rossum A.M.C., Van Der Knaap L.C., Visser E., Branger J., Rijkeboer-Mes A., Duijf-Van De Ven C.J.H.M., Schippers E.F., van Nieuwkoop C., van IJperen J.M., Geilings J., van der Hut G., Franck P.F.H., Van Eeden A., Brokking W., Groot M., Elsenburg L.J.M., Damen M., Kwa I.S., Groeneveld P.H.P., Bouwhuis J.W., Van Den Berg J.F., Van Hulzen A.G.W., Van Der Bliek G.L., Bor P.C.J., Bloembergen P., Wolfhagen M.J.H.M., Ruijs G.J.H.M., Kroon F.P., De Boer M.G.J., Bauer M.P., Jolink H., Vollaard A.M., Dorama W., Van Holten N., Claas E.C.J., Wessels E., Den Hollander J.G., Pogany K., Roukens A., Kastelijns M., Smit J.V., Smit E., Struik-Kalkman D., Tearno C., Bezemer M., van Niekerk T., Pontesilli O., Lowe S.H., Oude Lashof A.M.L., Posthouwer D., Ackens R.P., Schippers J., Vergoossen R., Weijenberg-Maes B., van Loo I.H.M., Havenith T.R.A., Leyten E.M.S., Gelinck L.B.S., van Hartingsveld A., Meerkerk C., Wildenbeest G.S., Mutsaers J.A.E.M., Jansen C.L., Mulder J.W., Vrouenraets S.M.E., Lauw F.N., van Broekhuizen M.C., Paap H., Vlasblom D.J., Smits P.H.M., Weijer S., El Moussaoui R., Bosma A.S., van Vonderen M.G.A., van Houte D.P.F., Kampschreur L.M., Dijkstra K., Faber S., Weel J., Kootstra G.J., Delsing C.E., van der Burg-Van de Plas M., Heins H., Lucas E., Kortmann W., van Twillert G., Cohen Stuart J.W.T., Diederen B.M.W., van Truijen-Oud F.A., van der Reijden W.A., Jansen R., Brinkman K., van den Berk G.E.L., Blok W.L., Frissen P.H.J., Lettinga K.D., Schouten W.E.M., Veenstra J., Brouwer J.C., Geerders F.G., Hoeksema K., Kleene J.M., van der Meche B.I., Spelbrink M., Sulman H., Toonen A.J.M., Wijnands S., Kwa D., Witte E., Koopmans P.P., Keuter M., van der Ven A.J.A.M., ter Hofstede H.J.M., Dofferhoff A.S.M., van Crevel R., Albers M., Bosch M.E.W., Grintjes-Huisman K.J.T., Zomer J.B., Stelma F.F., Rahamat-Langendoen J., Burger D., Richter C., Gisolf H.E., Hassing J.R., ter Beest G., van Bentum P.H.M., Langebeek N., Tiemessen R., Swanink C.M.A., van Lelyveld S.F.L., Soetekouw R., Hulshoff N., van der Prijt L.M.M., van der Swaluw J., Bermon N., Herpers B.L., Veenendaal D., Verhagen W.D.M., van Wijk M., van Kasteren M.E.E., Brouwer E.A., de Kruijf-Van de Wiel B.A.F.M., Kuipers M., Santegoets R.M.W.J., van der Ven B., Marcelis H.J., Buiting A.G.M., Kabel J.P., Bierman W.F.W., Scholvinck H., Wilting R.K., Stienstra Y., de Groot-De Jonge H., van der Meulen A.P., de Weerd A.D., Ludwig-Roukema J., Niesters H.G.M., Riezebos-Brilman A., van Leer-Buter C.C., Knoester M., Hoepelman A.I.M., Mudrikova T., Ellerbroek M.P., Oosterheert J.J., Arends E.J., Barth E.R., Wassenberg M.W.M., Schadd M.E., van Elst-Laurijssen D.H.M., van Oers-Hazelzet B.E., Vervoort S., van Berkel M., Schuurman R., Verduyn-Lunel F., Wensing A.M.J., Peters E.J.G., van Agtmael A.M., Bomers M., de Vocht J., Heitmuller M., Laan M.L., Pettersson M.A., Vandenbroucke-Grauls C.M.J.E., Ang W.C., Geelen S.P.M., Wolfs T.F.W., Bont J.L., Nauta N., Bezemer O.D., van Sighem I.A., Boender S.T., de Jong A., Bergsma D., Hoekstra P., de Lang A., Grivell S., Jansen A., Rademaker J.M., Raethke M., Meijering R., Schnorr S., de Groot L., van den Akker M., Bakker Y., Claessen E., El Berkaoui A., Koops J., Kruijne E., Lodewijk C., Munjishvili L., Peeck B., Ree C., Regtop R., Ruijs Y., Rutkens T., van de Sande L., Schoorl M., Timmerman A., Tuijn E., Veenenberg L., van der Vliet S., Wisse A., Woudstra T., Tuk B., Dupon M., Gaborieau V., Lacoste D., Malvy D., Mercie P., Neau D., Pellegrin L.J., Tchamgoue S., Lazaro E., Cazanave C., Vandenhende M., Vareil O.M., Gerard Y., Blanco P., Bouchet S., Breilh D., Fleury H., Pellegrin I., Chene G., Thiebaut R., Wittkop L., Lawson-Ayayi S., Gimbert A., Desjardin S., Lacaze-Buzy L., Petrov-Sanchez V., Andre N., Bernard K., Caubet O., Caunegre L., Chossat I., Courtault C., Dauchy A.F., Dondia D., Duffau P., Dutronc H., Farbos S., Faure I., Ferrand H., Greib C., Hessamfar M., Imbert Y., Lataste P., Marie J., Mechain M., Monlun E., Ochoa A., Pistone T., Raymond I., Receveur C.M., Rispal P., Sorin L., Valette C., Viallard J.F., Wille H., Wirth G., Lafon M., Trimoulet P., Bellecave P., Tumiotto C., Haramburu F., Miremeont-Salame G., Blaizeau J.M., Decoin M., Hannapier C., Lenaud E., Pougetoux A., Delveaux S., D'Ivernois C., Diarra F., Uwamaliya-Nziyumvira B., Palmer G., Conte V., Sapparrart V., Moore R., Edwards S., Hoy J., Watson K., Roth N., Lau H., Bloch M., Baker D., Carr A., Cooper D., O'Sullivan M., Nolan D., Guelfi G., Domingo P., Sambeat A.M., Gatell J., Del Cacho E., Cadafalch J., Fuster M., Codina C., Sirera G., Vaque A., Clumeck N., Gennotte F.A., Gerard M., Kabeya K., Konopnicki D., Libois A., Martin C., Payen C.M., Semaille P., Van Laethem Y., Neaton J., El-Sadr M.W., Krum E., Thompson G., 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O, D'Arminio Monforte, A, Reiss, P, Phillips, A, El-Sadr, W, Hatleberg, C, Pradier, C, Bonnet, F, Law, M, De Wit, S, Sabin, C, Lundgren, J, Bucher, H, Calvo, G, Dabis, F, Morfeldt, L, Weber, R, Lind-Thomsen, A, Salbol Brandt, R, Hillebreght, M, Zaheri, S, Wit, F, Scherrer, A, Schoni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundstrom, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Gronborg Laut, K, Kristensen, D, Kamara, D, Smith, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Moller, N, Kowalska, J, Bohlius, J, Bower, M, Fatkenheuer, G, Grulich, A, Sjol, A, Meidahl, P, Iversen, J, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, Van Der Meer, J, Godfried, M, Van Der Poll, T, Nellen, F, Geerlings, S, Van Vugt, M, 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M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, Van Den Berg, J, Van Hulzen, A, Van Der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, De Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, Van Holten, N, Claas, E, Wessels, E, Den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Cohen Stuart, J, Diederen, B, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, J, Geerders, F, Hoeksema, K, Kleene, J, van der Meche, B, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, J, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, H, Hassing, J, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der Prijt, L, van der Swaluw, J, Bermon, N, Herpers, B, Veenendaal, D, Verhagen, W, van Wijk, M, van Kasteren, M, Brouwer, E, de Kruijf-Van de Wiel, B, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, H, Buiting, A, Kabel, J, Bierman, W, Scholvinck, H, Wilting, R, Stienstra, Y, de Groot-De Jonge, H, van der Meulen, A, de Weerd, A, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter, C, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, M, Oosterheert, J, Arends, E, Barth, E, Wassenberg, M, Schadd, M, van Elst-Laurijssen, D, van Oers-Hazelzet, B, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael, A, Bomers, M, de Vocht, J, Heitmuller, M, Laan, M, Pettersson, M, Vandenbroucke-Grauls, C, Ang, W, Geelen, S, Wolfs, T, Bont, J, Nauta, N, Bezemer, O, van Sighem, I, Boender, S, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, J, Raethke, M, Meijering, R, Schnorr, S, de Groot, L, van den Akker, M, Bakker, Y, Claessen, E, El Berkaoui, A, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, van de Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, van der Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercie, P, Neau, D, Pellegrin, L, Tchamgoue, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, O, Gerard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chene, G, Thiebaut, R, Wittkop, L, Lawson-Ayayi, S, Gimbert, A, Desjardin, S, Lacaze-Buzy, L, Petrov-Sanchez, V, Andre, N, Bernard, K, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, A, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, C, Rispal, P, Sorin, L, Valette, C, Viallard, J, Wille, H, Wirth, G, Lafon, M, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont-Salame, G, Blaizeau, J, Decoin, M, Hannapier, C, Lenaud, E, Pougetoux, A, Delveaux, S, D'Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Carr, A, Cooper, D, O'Sullivan, M, Nolan, D, Guelfi, G, Domingo, P, Sambeat, A, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaque, A, Clumeck, N, Gennotte, F, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, C, Semaille, P, Van Laethem, Y, Neaton, J, El-Sadr, M, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, I, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, R, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Pedersen, C, Ristola, M, Rockstroh, J, Peters, L, Fischer, H, Larsen, F, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Losso, M, Kundro, M, Schmied, B, Zangerle, R, Vassilenko, A, Mitsura, M, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Moller, F, Ostergaard, L, Wiese, L, Nielsen, N, Zilmer, K, Smidt, J, Aho, I, Viard, J, Girard, P, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, J, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlavik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, M, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak-Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Panteleev, A, Panteleev, O, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Miro, M, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, M, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, A, Simons, E, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Akerlund, B, Koppel, K, Karlsson, A, Hakangard, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, C, Perno, F, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, R, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marcotullio, S, Monno, L, Nozza, S, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, E, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, C, Piolini, R, Ridolfo, L, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, M, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, A, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Fontanelli Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Fontana Del Vecchio, R, Francisci, D, Di Giuli, C, Caramello, P, Orofino, C, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, M, Aubert, V, Bernasconi, E, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Gunthard, F, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hosli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, D, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, J, Muller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stockle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Internal medicine, Pediatric surgery, Medical Microbiology and Infection Prevention, Amsterdam Gastroenterology Endocrinology Metabolism, Faculteit Medische Wetenschappen/UMCG, Microbes in Health and Disease (MHD), and Molecular Pharmacology

Subjects
Male, HIV AIDS, HIV Infections, 0302 clinical medicine, Interquartile range, Risk Factors, Neoplasms, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 0303 health sciences, Incidence, Absolute risk reduction, Drugs, General Medicine, Middle Aged, Viral Load, Antiretroviral therapy, 3. Good health, AIDS, Cancer treatment, Prevention policy and public health, Cohort, Infectious diseases, Cohort studies, Female, Viral load, Adult, medicine.medical_specialty, Anti-HIV Agents, HIV Infections/drug therapy, Socio-culturale, Time-to-Treatment, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, Internal Medicine, Humans, Adverse effect, 030306 microbiology, business.industry, HIV, Cancer, medicine.disease, CD4 Lymphocyte Count, Anti-HIV Agents/therapeutic use, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Neoplasms/epidemiology
Abstract

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Published
2021

15. Impact of COVID-19 Pandemic on Non-Melanoma Skin Cancer's Tumor Burden and Care: a Multi-Center Study Based in Northern Italy

Author

Cozzi Silvia, Codazzi Denis, Cherubino Mario, Valdatta Luigi, Tamborini Federico, and Carminati Marcello

Subjects
Skin Neoplasms, Italy, COVID-19, Humans, Surgery, Pandemics, Retrospective Studies, Tumor Burden
Abstract

The brisk remodeling in healthcare delivery observed after the COVID-19 outbreak led us to evaluate how the pandemic affected non-melanoma skin cancer's (NMSC) care and tumor burden. To address this topic, we set up a retrospective real-life multi-center study based on the cities of Bergamo and Varese, whose provinces were the worst hit in Italy by the pandemic. We analyzed medical and pathological data from patients that underwent surgery in the two months preceding the outbreak in Italy and compared them to those who did in the corresponding bimester of the following year, reaching 214 patients and 274 lesions. We observed a considerable and significant increase in NMSC's diameter, as well as in the proportion of squamous cell carcinomas. Both the average waiting time to obtain an evaluation visit and the average time in the surgical waiting list was shorter after the COVID-19 outbreak: the reason is that we evaluated and operated near-exclusive patients affected by high-priority lesions, who benefited from "fast-track" referrals. Conversely, less-concerning lesions were, and still are, left on hold, until they will become advanced enough to be labeled as "urgent". Plastic surgery departments should evade as soon as possible from this downward spiral, in order to provide our patients with timely cancer care and to be able to treat all plastic surgery-requiring pathologies.

Published
2022

16. Urinary incontinence in systemic sclerosis: a prospective multicentre cohort study

Author

Gregor John, Elisabetta Zanatta, Pamela Polito, Silvia Piantoni, Micaela Fredi, Yann Coattrenec, Romain Guemara, Franco Franceschini, Marie-Elise Truchetet, Franco Cozzi, Paolo Airò, and Carlo Chizzolini

Subjects
Quality of life, Scleroderma, Systemic, Death, Hospital admission, Natural history, Scleroderma, Urinary incontinence, Immunology, Rheumatology, Surveys and Questionnaires, Waxes, Humans, Immunology and Allergy, Prospective Studies, Diuretics
Abstract

Investigate the natural history of urinary incontinence (UI) in systemic sclerosis (SSc) and assess its impact on quality of life (QoL). A longitudinal, international observational study followed 189 patients with SSc for a median duration of 5 years (IQR: 4.8–5.3). Presence, subtype and severity of UI, hospital admission and QoL were assessed using serial self-administered questionnaires. Mortality data came from national death registries. Multilevel mixed-effect logistic regressions explored factors associated with UI. Cox models adjusted the effects of UI on hospitalization and death for age, sex and subtype of SSc. Mean annual rates of new-onset UI and remission were 16.3% (95%CI 8.3%–24.2%) and 20.8% (95%CI 12.6–29.1), respectively. Among UI patients, 57.9% (95%CI 51.8–64.0) changed from one UI subtype to another. Between annual questionnaires, the severity of UI was the same in 51.1% (95%CI 40.8–61.4), milder or resolved in 35.2% (95%CI 25.3–44.9), and worse in 13.8% (95%CI 6.7–20.9). Anti-centromere antibodies, digestive symptoms, sex, age, neurological or urological comorbidities, diuretics and puffy fingers were all associated with UI. The two strongest predictors of UI and UI subtypes were a recent UI episode and the subtype of previous leakage episodes. UI at inclusion was not associated with hospital admission (adjusted HR: 1.86; 95%CI 0.88–3.93), time to death (aHR: 0.84; 95%CI 0.41–1.73) or change in QoL over time. Self-reported UI among SSc patients is highly dynamic: it waxes and wanes, changing from one subtype to another over time.

Published
2022

17. Phenotypic and genetic characterizations of the Milan cohort of von Willebrand disease type 2

Author

Omid Seidizadeh, Luciano Baronciani, Maria Teresa Pagliari, Giovanna Cozzi, Paola Colpani, Andrea Cairo, Simona Maria Siboni, Eugenia Biguzzi, and Flora Peyvandi

Subjects
Male, von Willebrand Diseases, Genotype, Mutation, von Willebrand Factor, Humans, Female, von Willebrand Disease, Type 2, Hematology
Abstract

von Willebrand disease (VWD) type 2 is caused by qualitative abnormalities of von Willebrand factor (VWF). This study aimed to determine the genotypic and phenotypic characterizations of a large VWD type 2 cohort from Milan. We included 321 patients (54% female) within 148 unrelated families from 1995 to 2021. Patients were fully characterized using laboratory phenotypic tests, and the genotypic diagnosis was confirmed by target genetic analysis using Sanger sequencing. Patients were diagnosed with type 2A (n = 98; 48 families), 2B (n = 85; 38 families), 2M (n = 112; 50 families), or 2N (n = 26; 12 families). Eighty-two unique VWF variants, including 8 novel variants, were found. The potential pathogenic effect of novel variants was assessed by in silico analysis. Most patients were heterozygous for a single variant (n = 259; 81%), whereas 37 cases (11%) had 2 variants (4 homozygous, 9 in trans, and 24 in cis). Twenty-five patients (8%) had ≥3 variants, mainly as a result of gene conversions. Among the 82 distinct variants identified, 5 different types, including missense (n = 64), gene conversion (n = 10), synonymous (n = 1), deletion (n = 4), and splice (n = 3), were observed. The results from this large cohort showed that VWD type 2 is invariably due to variants that do not prevent the synthesis of the protein, and a vast majority of patients (88%) had missense variants. Given the complexity of type 2 diagnosis and the necessity of performing several phenotypic tests, genetic analysis for patients suspected of having type 2 is beneficial to establish the correct diagnosis.

Published
2022

18. Prevalence, management, and outcome of cryptorchidism associated with gastroschisis: A systematic review and meta-analysis

Author

Silvia Ceccanti, Corrado De Vito, Denis A. Cozzi, and Giuseppe Migliara

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Population, Context (language use), testicular atrophy, Cryptorchidism, Testis, Prevalence, Humans, Medicine, Orchiopexy, education, Retrospective Studies, Gastroschisis, education.field_of_study, Testicular atrophy, business.industry, Obstetrics, Abdominal wall defect, Infant, undescended testis, General Medicine, medicine.disease, Hypoplasia, Meta-analysis, Pediatrics, Perinatology and Child Health, Surgery, neonate, prolapsed testis, business, cryptorchidism, gastroschisis, orchiopexy
Abstract

Purpose Cryptorchidism associated with gastroschisis has been poorly investigated. We aimed to assess the prevalence of this association, and to address the management and outcome of cryptorchidism in this context. Materials and methods In this systematic review, we searched electronic databases (PubMed, Web of Science, and Google Scholar), without language restrictions from inception to March 31, 2021, for studies on cryptorchidism and gastroschisis co-occurrence. Random effects meta-analysis was used to calculate pooled prevalence estimates of cryptorchidism in gastroschisis and spontaneous testicular descent in this population. Results Twenty-five studies were included for the systematic review. All were retrospective case reports or series for a total of 175 patients. Pooled prevalence estimate for cryptorchidism in gastroschisis was 19% (95% CI 13–26). Complete data sets for management and outcome analysis were available in 94 patients, involving 120 undescended testes [63 (52.5%) nonpalpable, 34 (28.3%) prolapsed outside the abdominal wall defect, and 23 (19.2%) palpable]. Fifty-five descended spontaneously, with a pooled prevalence estimate of 50% (95% CI 31–69). Twelve testes/remnants were primarily removed or absent, while 49 testes underwent orchiopexy (success rate, 63%). Excluding 4 testes still awaiting orchiopexy, 30 of the remaining 116 (25.8%) testes had a dismal outcome, including testicular loss (19), hypoplasia (8) or recurrent cryptorchidism (3). Conclusion Cryptorchidism in gastroschisis appears to occur more frequently than in the normal population. The overall mediocre testicular outcome seems to reflect the most unfavorable presentation of cryptorchidism in gastroschisis, which is represented by originally intrabdominal or prolapsed testis in the majority of cases. Level of evidence IV.

Published
2022

19. O-RADS MRI: A Systematic Review and Meta-Analysis of Diagnostic Performance and Category-wise Malignancy Rates

Author

Stefania Rizzo, Andrea Cozzi, Miriam Dolciami, Filippo Del Grande, Angela L. Scarano, Andrea Papadia, Benedetta Gui, Nicoletta Gandolfo, Carlo Catalano, and Lucia Manganaro

Subjects
Settore MED/06 - Oncologia Medica, ovarian neoplasms, retrospective studies, female, Settore MED/36 - Diagnostica per Immagini e Radioterapia, adnexa uteri, adnexal diseases, humans, magnetic resonance imaging, sensitivity and specificity, ultrasonograph, Settore MED/40 - Ginecologia e Ostetricia, Radiology, Nuclear Medicine and imaging
Abstract

Background US-indeterminate adnexal lesions remain an important indication for gynecologic surgery. MRI can serve as a problem-solving tool through the use of the Ovarian-Adnexal Imaging Reporting and Data System (O-RADS) MRI lexicon, which is based on the ADNEX MR scoring system. Purpose To perform a systematic review and meta-analysis of the diagnostic performance of pelvic MRI interpreted using the ADNEX or O-RADS MRI stratification systems to characterize US-indeterminate adnexal lesions and of the category-wise malignancy rates. Materials and Methods A systematic literature search from May 2013 (publication of the ADNEX MR score) to September 2022 was performed. Studies reporting the use of pelvic MRI interpreted with the ADNEX or O-RADS MRI systems to characterize US-indeterminate adnexal lesions, with pathologic examination and/or follow-up as the reference standard, were included. Summary estimates of diagnostic performance were obtained with the bivariate random-effects model, while category-wise summary malignancy rates of O-RADS MRI 2, 3, 4, and 5 lesions were obtained with a random-effects model. Effects of covariates on heterogeneity and diagnostic performance were investigated through meta-regression. Results Thirteen study parts from 12 studies (3731 women, 4520 adnexal lesions) met the inclusion criteria. Diagnostic performance meta-analysis for 4012 lesions found a 92% summary sensitivity (95% CI: 88, 95) and a 91% summary specificity (95% CI: 89, 93). The meta-analysis of malignancy rates for 3641 lesions showed summary malignancy rates of 0.1% (95% CI: 0, 1) among O-RADS MRI 2 lesions, 6% (95% CI: 3, 9) among O-RADS MRI 3 lesions, 60% (95% CI: 52, 67) among O-RADS MRI 4 lesions, and 96% (95% CI: 92, 99) among O-RADS MRI 5 lesions. Conclusion Pelvic MRI interpreted with the Ovarian-Adnexal Reporting and Data System (O-RADS) MRI lexicon had high diagnostic performance for the characterization of US-indeterminate adnexal lesions. Summary estimates of malignancy rates in the O-RADS MRI 4 and O-RADS MRI 5 categories were higher than predicted ones. © RSNA, 2022

Published
2023

20. Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report

Author

Garzone, Davide, Terheyden, Jan Henrik, Morelle, Olivier, Wintergerst, Maximilian W.M., Saßmannshausen, Marlene, Schmitz-Valckenberg, Steffen, Pfau, Maximilian, Thiele, Sarah, Poor, Stephen, Leal, Sergio, Holz, Frank G., Finger, Robert P., Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J.F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Fletcher, E., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Lechanteur, Y. T.E., Luhmann, U. F.O., Lüning, A., Schmid, M., Ophthalmology, Amsterdam Neuroscience - Complex Trait Genetics, Agostini, H., Altay, L., Atia, R., Bandello, F., Basile, P. G., Behning, C., Belmouhand, M., Berger, M., Binns, A., Boon, C. J. F., Böttger, M., Bouchet, C., Brazier, J. E., Butt, T., Carapezzi, C., Carlton, J., Carneiro, A., Charil, A., Coimbra, R., Cozzi, M., Crabb, D. P., Cunha-Vaz, J., Dahlke, C., de Sisternes, L., Dunbar, H., Fletcher, E., Francisco, C., Gutfleisch, M., Hogg, R., Hoyng, C. B., Kilani, A., Krätzschmar, J., Kühlewein, L., Larsen, M., Lechanteur, Y. T. E., Luhmann, U. F. O., Lüning, A., Marques, I., Martinho, C., Montesano, G., Mulyukov, Z., Paques, M., Parodi, B., Parravano, M., Penas, S., Peters, T., Peto, T., Priglinger, S., Rowen, D., Rubin, G. S., Sahel, J., Sánchez, C., Sander, O., Schmid, M., Schrinner-Fenske, H., Siedlecki, J., Silva, R., Skelly, A., Souied, E., Staurenghi, G., Stöhr, L., Taylor, D. J., Tufail, A., Varano, M., Vieweg, L., Wintergerst, L., Wolf, A., and Zakaria, N.

Subjects
diagnosis [Macular Degeneration], methods [Tomography, Optical Coherence], Fovea Centralis, Multidisciplinary, Humans, ddc:600, Retina, Software
Abstract

Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study. We assessed OCT scans from Cirrus (200 × 200 macular cube, 6 × 6 mm; Zeiss Meditec, CA) and Spectralis (20° × 20°, 25 B-scans; 30° × 25°, 241 B-scans; Heidelberg Engineering, Germany) devices. Sensitivity and specificity for drusen detection and differences between modalities were assessed with intra-class correlation coefficients (ICCs) and mean difference in a 5 mm diameter fovea-centered circle. Specificity was > 90% in the three modalities. In eAMD, we observed highest sensitivity in the denser Spectralis scan (68.1). The two different Spectralis modalities showed a significantly higher agreement in quantifying drusen volume in iAMD (ICC 0.993 [0.991–0.994]) than the dense Spectralis with Cirrus scan (ICC 0.807 [0.757–0.847]). Formulae for drusen volume conversion in iAMD between the two devices are provided. Automated drusen volume measures are not interchangeable between devices and softwares and need to be interpreted with the used imaging devices and software in mind. Accounting for systematic difference between methods increases comparability and conversion formulae are provided. Less dense scans did not affect drusen volume measurements in iAMD but decreased sensitivity for medium drusen in eAMD.Trial registration: ClinicalTrials.gov NCT03349801. Registered on 22 November 2017.

Published
2022

21. Oxidative Stress in Structural Valve Deterioration: A Longitudinal Clinical Study

Author

Galiñanes, Manuel, Casós, Kelly, Blasco-Lucas, Arnau, Permanyer, Eduard, Máñez, Rafael, Le Tourneau, Thierry, Barquinero, Jordi, Schwartz, Simon, Bottio, Tomaso, Roussel, Jean Christian, Fellah-Hebia, Imen, Sénage, Thomas, Evangelista Masip, Arturo, Badano, Luigi P., Ruiz-Majoral, Alejandro, Galli, Cesare, Padler-Karavani, Vered, Soulillou, Jean-Paul, Vidal Guitart, Xavier, Cozzi, Emanuele, Costa, Cristina, Universitat Autònoma de Barcelona, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], Vall d’Hebron Research Institute (VHIR), Llobregat Hospital [Barcelona], Quironsalud Teknon Heart Institute [Barcelona, Spain] (QTHI), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Bellvitge University Hospital [Barcelona, Spain], Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Università degli Studi di Padova = University of Padua (Unipd), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Avantea [Cremona, Italy], Tel Aviv University (TAU), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Institut Català de la Salut [Barcelona, Spain] (ICS), L’Hospitalet de Llobregat [Barcelona, Spain], The project was funded by the European Commission (FP7/2007–2013, Grant Agreement 603049: accessed on 1 September 2013, and PERIS SLT002/16/00445 funded by the Department of Health of the Generalitat de Catalunya, both granted to C.C., and cofunded by FEDER funds, a way to build Europe. IDIBELL benefits from the support of CERCA., European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), KERANDEL-DION, Céline, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID, Galinanes, M, Casos, K, Blasco-Lucas, A, Permanyer, E, Manez, R, Le Tourneau, T, Barquinero, J, Schwartz, S, Roussel, T, Fellah-Hebia, I, Senage, T, Evangelista, A, Badano, L, Ruiz-Majoral, A, Galli, C, Padler-Karavani, V, Soulillou, J, Vidal, X, Cozzi, E, and Costa, C

Subjects
Estrès oxidatiu, [SDV]Life Sciences [q-bio], Structural valve deterioration, Lipid peroxidation, Prosthesis Design, Biochemistry, structural valve deterioration, aortic valve, biological heart valves, lipid peroxidation, oxidative stress, protein nitration, transcatheter aortic valve implantation, Humans, Aortic valve, Molecular Biology, Heart valve prosthesis, Heart valves, oxidative stre, Transcatheter aortic valve implantation, Pròtesis valvulars cardíaques, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Aortic Valve Stenosis, Vàlvules cardíaques, biological heart valve, Prosthesis Failure, [SDV] Life Sciences [q-bio], Treatment Outcome, Oxidative stress, Heart Valve Prosthesis, Biological heart valves, Protein nitration
Abstract

International audience; The cause of structural valve deterioration (SVD) is unclear. Therefore, we investigated oxidative stress markers in sera from patients with bioprosthetic heart valves (BHVs) and their association with SVD. Blood samples were taken from SVD (Phase A) and BHV patients during the first 24 (Phase B1) and >48 months (Phase B2) after BHV implantation to assess total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrotyrosine (NT). The results show that MDA levels increased significantly 1 month after surgery in all groups but were higher at 6 months only in incipient SVD patients. NT levels increased gradually for the first 24 months after implantation in the BHV group. Patients with transcatheter aortic valve implantation (TAVI) showed even higher levels of stress markers. After >48 months, MDA and NT continued to increase in BHV patients with a further elevation after 60–72 months; however, these levels were significantly lower in the incipient and established SVD groups. In conclusion, oxidative stress may play a significant role in SVD, increasing early after BHV implantation, especially in TAVI cases, and also after 48 months’ follow-up, but decreasing when SVD develops. Oxidative stress potentially represents a target of therapeutic intervention and a biomarker of BHV dysfunction.

Published
2022
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22. Contrast-enhanced mammography-guided biopsy: why, when, and where we need it

Author

Andrea Cozzi and Simone Schiaffino

Subjects
Settore MED/36 - Diagnostica per Immagini e Radioterapia, Biopsy, Humans, Feasibility Studies, Female, Breast Neoplasms, Radiology, Nuclear Medicine and imaging, General Medicine, Magnetic Resonance Imaging, Early Detection of Cancer, Mammography
Abstract

• The use of CEM-guided biopsy is spreading after initial experiences in a few pilot centers.• CEM-guided biopsy has the potential to ensure fast, low-cost, and effective tissue sampling of MRI-detected and CEM-detected lesions that do not have a corresponding finding at morphological imaging.• The need and utility of CEM-guided biopsy are warranted by the impending expansion of morpho-functional imaging towards breast cancer screening for women with extremely dense breasts.

Published
2022

23. Autophagy Dysfunction in ALS: from Transport to Protein Degradation

Author

Veronica Ferrari and Marta Cozzi

Subjects
Motor Neurons, Proteins, Neurodegenerative Diseases, General Medicine, Amyotrophic lateral sclerosis, Settore BIO/09 - Fisiologia, Animal models, Cellular and Molecular Neuroscience, Settore BIO/13 - Biologia Applicata, Proteolysis, Autophagy, Humans, Mutations
Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motor neurons (MNs). Since the identification of the first ALS mutation in 1993, more than 40 genes have been associated with the disorder. The most frequent genetic causes of ALS are represented by mutated genes whose products challenge proteostasis, becoming unable to properly fold and consequently aggregating into inclusions that impose proteotoxic stress on affected cells. In this context, increasing evidence supports the central role played by autophagy dysfunctions in the pathogenesis of ALS. Indeed, in early stages of disease, high levels of proteins involved in autophagy are present in ALS MNs; but at the same time, with neurodegeneration progression, autophagy-mediated degradation decreases, often as a result of the accumulation of toxic protein aggregates in affected cells. Autophagy is a complex multistep pathway that has a central role in maintaining cellular homeostasis. Several proteins are involved in its tight regulation, and importantly a relevant fraction of ALS-related genes encodes products that directly take part in autophagy, further underlining the relevance of this key protein degradation system in disease onset and progression. In this review, we report the most relevant findings concerning ALS genes whose products are involved in the several steps of the autophagic pathway, from phagophore formation to autophagosome maturation and transport and finally to substrate degradation.

Published
2022

24. Quantitative autofluorescence findings in patients undergoing hydroxychloroquine treatment

Author

Salvatore Parrulli, Mariano Cozzi, Matteo Airaldi, Francesco Romano, Francesco Viola, Piercarlo Sarzi‐Puttini, Giovanni Staurenghi, and Alessandro Invernizzi

Subjects
Adult, Ophthalmology, Retinal Diseases, Antirheumatic Agents, Humans, Female, Fluorescein Angiography, Middle Aged, Tomography, Optical Coherence, Hydroxychloroquine
Abstract

To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment5 years or daily HCQ dose5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAFThirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAFThese results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.

Published
2022

25. Systemic Emergencies in COVID-19 Patient: A Pictorial Review

Author

Marco Albanesi, Diletta Cozzi, Edoardo Cavigli, Chiara Moroni, Gianluca Frezzetti, Lina Bartolini, and Vittorio Miele

Subjects
SARS-CoV-2, COVID-19, Humans, Radiology, Nuclear Medicine and imaging, Emergencies, World Health Organization, Disease Outbreaks
Abstract

Since the first report of the outbreak in Wuhan, China in December 2019, as of 1 September 2021, the World Health Organization has confirmed more than 239 million cases of the novel coronavirus (SARS-CoV-2) infectious disease named coronavirus disease 2019 (COVID-19), with more than 4.5 million deaths. Although SARS-CoV-2 mainly involves the respiratory tract, it is considered to be a systemic disease. Imaging plays a pivotal role in the diagnosis of all manifestations of COVID-19 disease, as well as its related complications. The figure of the radiologist is fundamental in the management and treatment of the patient. The authors try to provide a systematic approach based on an imaging review of major multi-organ manifestations of this infection.

Published
2022

27. Climate changes modulated the history of Arctic iodine during the Last Glacial Cycle

Author

Juan Pablo Corella, Niccolo Maffezzoli, Andrea Spolaor, Paul Vallelonga, Carlos A. Cuevas, Federico Scoto, Juliane Müller, Bo Vinther, Helle A. Kjær, Giulio Cozzi, Ross Edwards, Carlo Barbante, Alfonso Saiz-Lopez, Danish Research Council, European Commission, National Science Foundation (US), Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (Germany), Spolaor, Andrea [0000-0001-8635-9193], Cuevas, Carlos A. [0000-0002-9251-5460], Scoto, Federico [0000-0003-2498-3227], Müller, Juliane [0000-0003-0724-4131], Kjær, Helle A. [0000-0002-3781-9509], Cozzi, Giulio [0000-0001-8796-4176], Barbante, Carlo [0000-0003-4177-2288], Saiz-Lopez, A. [0000-0002-0060-1581], Spolaor, Andrea, Cuevas, Carlos A., Scoto, Federico, Müller, Juliane, Kjær, Helle A., Cozzi, Giulio, Barbante, Carlo, and Saiz-Lopez, A.

Subjects
Multidisciplinary, Arctic Regions, Atmosphere, Climate Change, Science, Climate, Greenland, General Physics and Astronomy, General Chemistry, Palaeoclimate, History, 21st Century, History, Medieval, Article, General Biochemistry, Genetics and Molecular Biology, Ozone, Arctic, Settore GEO/04 - Geografia Fisica e Geomorfologia, Humans, Ice Cover, Seawater, History, Ancient, Climate sciences, geographic locations, Iodine
Abstract

9 pags., 4 figs., Iodine has a significant impact on promoting the formation of new ultrafine aerosol particles and accelerating tropospheric ozone loss, thereby affecting radiative forcing and climate. Therefore, understanding the long-term natural evolution of iodine, and its coupling with climate variability, is key to adequately assess its effect on climate on centennial to millennial timescales. Here, using two Greenland ice cores (NEEM and RECAP), we report the Arctic iodine variability during the last 127,000 years. We find the highest and lowest iodine levels recorded during interglacial and glacial periods, respectively, modulated by ocean bioproductivity and sea ice dynamics. Our sub-decadal resolution measurements reveal that high frequency iodine emission variability occurred in pace with Dansgaard/Oeschger events, highlighting the rapid Arctic ocean-ice-atmosphere iodine exchange response to abrupt climate changes. Finally, we discuss if iodine levels during past warmer-than-present climate phases can serve as analogues of future scenarios under an expected ice-free Arctic Ocean. We argue that the combination of natural biogenic ocean iodine release (boosted by ongoing Arctic warming and sea ice retreat) and anthropogenic ozone-induced iodine emissions may lead to a near future scenario with the highest iodine levels of the last 127,000 years., This study received funding from the European Research Council (ERC) Executive Agency under the European Union´s Horizon 2020 Research and Innovation programme (Project ‘ERC-2016-COG 726349 CLIMAHAL’). The RECAP ice coring effort was financed by the Danish Research Council through a Sapere Aude grant, the NSF through the Division of Polar Programmes, the Alfred Wegener Institute, and the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement 610055 through the Ice2Ice project and the Early Human Impact project (267696).

Published
2022
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28. Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients' subgroups

Author

Domenico Olivo, E. Pigatto, Francesca La Gualana, Giorgio Amato, Ilaria Cavazzana, Rosario Foti, Antonio Tavoni, Raffaele Brittelli, Tommaso Ferrari, Francesco Masini, Marcella Visentini, Stefano Angelo Santini, Dilia Giuggioli, Franco Franceschini, Vincenzo Raimondo, Laura Gragnani, Giuseppa Pagano Mariano, Poupak Fallahi, Vincenzo Aiello, Lorenzo Puccetti, C. Naclerio, Riccardo Meliconi, Giovanna Cuomo, Amelia Spinella, Ylenia Dal Bosco, Alessandro Antonelli, Daniela Scorpiniti, M. Vadacca, Piero Ruscitti, Milvia Casato, Elisa Visalli, Florenzo Iannone, Maurizio Caminiti, Fabio Cacciapaglia, Francesco Ursini, Clodoveo Ferri, T. Urraro, Rodolfo Caminiti, Monica Monti, Massimo L'Andolina, Giovanni Rechichi, Anna Linda Zignego, Roberto Giacomelli, Giuseppe Varcasia, Roberta Pellegrini, Franco Cozzi, Pietro Gigliotti, Giusy Elia, Ferri, C., Ursini, F., Gragnani, L., Raimondo, V., Giuggioli, D., Foti, R., Caminiti, M., Olivo, D., Cuomo, G., Visentini, M., Cacciapaglia, F., Pellegrini, R., Pigatto, E., Urraro, T., Naclerio, C., Tavoni, A., Puccetti, L., Varcasia, G., Cavazzana, I., L'Andolina, M., Ruscitti, P., Vadacca, M., Gigliotti, P., La Gualana, F., Cozzi, F., Spinella, A., Visalli, E., Dal Bosco, Y., Amato, G., Masini, F., Pagano Mariano, G., Brittelli, R., Aiello, V., Caminiti, R., Scorpiniti, D., Rechichi, G., Ferrari, T., Monti, M., Elia, G., Franceschini, F., Meliconi, R., Casato, M., Iannone, F., Giacomelli, R., Fallahi, P., Santini, S. A., Zignego, A. L., Antonelli, A., Ferri C., Ursini F., Gragnani L., Raimondo V., Giuggioli D., Foti R., Caminiti M., Olivo D., Cuomo G., Visentini M., Cacciapaglia F., Pellegrini R., Pigatto E., Urraro T., Naclerio C., Tavoni A., Puccetti L., Varcasia G., Cavazzana I., L'Andolina M., Ruscitti P., Vadacca M., Gigliotti P., La Gualana F., Cozzi F., Spinella A., Visalli E., Dal Bosco Y., Amato G., Masini F., Pagano Mariano G., Brittelli R., Aiello V., Caminiti R., Scorpiniti D., Rechichi G., Ferrari T., Monti M., Elia G., Franceschini F., Meliconi R., Casato M., Iannone F., Giacomelli R., Fallahi P., Santini S.A., Zignego A.L., and Antonelli A.

Subjects
Male, History, Polymers and Plastics, Binding Antibody Units, BAU, Antibodies, Viral, Gastroenterology, Industrial and Manufacturing Engineering, Cryoglobulinemic vasculitis, CV, Scleroderma, Systemic sclerosi, Systemic lupu, Anti-citrullinated protein antibodies, ACPA, Systemic vasculitis, Lupus Erythematosus, Systemic, Immunology and Allergy, Medicine, Viral, Prospective Studies, Prospective cohort study, Neutralizing, education.field_of_study, Autoimmune systemic diseases, COVID-19 vaccine, Cryoglobulinemic vasculitis, Neutralizing antibodies, Rheumatoid arthritis, Systemic lupus, Systemic sclerosis, Immunogenicity, Vaccination, Middle Aged, Neutralizing antibody, NAb, Rheumatoid factor, RF, Italy, Female, Rituximab, Systemic sclerosis, SSc, Adverse events, AEs, 2019-nCoV Vaccine mRNA-1273, Human, medicine.drug, medicine.medical_specialty, Systemic lupus erythematosus, SLE, Immunology, Population, Autoimmune systemic disease, Autoimmune Disease, Article, Antibodies, Autoimmune Diseases, Internal medicine, Neutralizing antibodie, Humans, Business and International Management, Seroconversion, education, Settore BIO/10 - BIOCHIMICA, Vaccine Potency, Rheumatoid arthriti, BNT162 Vaccine, Scleroderma, Systemic, Lupus Erythematosus, Cryoglobulinemic vasculiti, SARS-CoV-2, business.industry, Systemic, Systemic Vasculiti, COVID-19, medicine.disease, Antibodies, Neutralizing, Autoimmune systemic diseases, ASD, Prospective Studie, World Health Organization, WHO, Rheumatoid arthritis, RA, Systemic Vasculitis, business
Abstract

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals.

Published
2022

29. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author

Rossella, De Angelis, Dilia, Giuggioli, Gianluigi, Bajocchi, Lorenzo, Dagna, Giovanni, Zanframundo, Rosario, Foti, Fabio, Cacciapaglia, Giovanna, Cuomo, Alarico, Ariani, Edoardo, Rosato, Serena, Guiducci, Francesco, Girelli, Valeria, Riccieri, Elisabetta, Zanatta, Silvia, Bosello, Ilaria, Cavazzana, Francesca, Ingegnoli, Maria De, Santis, Giuseppe, Murdaca, Giuseppina, Abignano, Nicoletta, Romeo, Alessandra, Della Rossa, Maurizio, Caminiti, Annamaria, Iuliano, Giovanni, Ciano, Lorenzo, Beretta, Gianluca, Bagnato, Ennio, Lubrano, Ilenia, De Andres, Alessandro, Giollo, Marta, Saracco, Cecilia, Agnes, Federica, Lumetti, Amelia, Spinella, Luca, Magnani, Corrado, Campochiaro, Giacomo, De Luca, Veronica, Codullo, Elisa, Visalli, Francesco, Masini, Antonietta, Gigante, Silvia, Bellando-Randone, Greta, Pellegrino, Erika, Pigatto, Francesca, Dall'Ara, Maria Grazia, Lazzaroni, Elena, Generali, Gianna, Mennillo, Simone, Barsotti, Giuseppa Pagano, Mariano, Francesca, Calabrese, Federica, Furini, Licia, Vultaggio, Simone, Parisi, Clara Lisa, Peroni, Anna Maria, Risa, Davide, Rozza, Anna, Zanetti, Greta, Carrara, Giampiero, Landolfi, Carlo Alberto, Scirè, Gerolamo, Bianchi, Enrico, Fusaro, Gian Domenico, Sebastiani, Marcello, Govoni, Salvatore, D'Angelo, Franco, Cozzi, Andrea, Doria, Florenzo, Iannone, Carlo, Salvarani, Marco, Matucci-Cerinic, Clodoveo, Ferri, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, S., Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, Giacomo., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, G. D., Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., De Angelis, Rossella, Giuggioli, Dilia, Bajocchi, Gianluigi, Dagna, Lorenzo, Zanframundo, Giovanni, Foti, Rosario, Cacciapaglia, Fabio, Cuomo, Giovanna, Ariani, Alarico, Rosato, Edoardo, Guiducci, Serena, Girelli, Francesco, Riccieri, Valeria, Zanatta, Elisabetta, Bosello, Silvia, Cavazzana, Ilaria, Ingegnoli, Francesca, De Santis, Maria, Murdaca, Giuseppe, Abignano, Giuseppina, Romeo, Nicoletta, Della Rossa, Alessandra, Caminiti, Maurizio, Iuliano, Annamaria, Ciano, Giovanni, Beretta, Lorenzo, Bagnato, Gianluca, Lubrano, Ennio, De Andres, Ilenia, Giollo, Alessandro, Saracco, Marta, Agnes, Cecilia, Lumetti, Federica, Spinella, Amelia, Magnani, Luca, Campochiaro, Corrado, De Luca, Giacomo, Codullo, Veronica, Visalli, Elisa, Masini, Francesco, Gigante, Antonietta, Bellando-Randone, Silvia, Pellegrino, Greta, Pigatto, Erika, Dall'Ara, Francesca, Lazzaroni, Maria Grazia, Generali, Elena, Mennillo, Gianna, Barsotti, Simone, Pagano Mariano, Giuseppa, Calabrese, Francesca, Furini, Federica, Vultaggio, Licia, Parisi, Simone, Peroni, Clara Lisa, Risa, Anna Maria, Rozza, Davide, Zanetti, Anna, Carrara, Greta, Landolfi, Giampiero, Scirè, Carlo Alberto, Bianchi, Gerolamo, Fusaro, Enrico, Sebastiani, Gian Domenico, Govoni, Marcello, D'Angelo, Salvatore, Cozzi, Franco, Doria, Andrea, Iannone, Florenzo, Salvarani, Carlo, Matucci-Cerinic, Marco, and Ferri, Clodoveo

Subjects
Male, medicine.medical_specialty, Vital capacity, Settore MED/16 - REUMATOLOGIA, Cross-sectional study, Immunology, Left, Socio-culturale, scleroderma, sex, systemic sclerosis, Disease, Ventricular Function, Left, Scleroderma, Systemic sclerosi, Rheumatology, Internal medicine, Sicca syndrome, Sex, Systemic sclerosis, Cross-Sectional Studies, Female, Humans, Italy, Registries, Sex Characteristics, Stroke Volume, Scleroderma, Systemic, Sjogren's Syndrome, medicine, LS8_2, Immunology and Allergy, Ventricular Function, Honeycombing, skin and connective tissue diseases, Ejection fraction, integumentary system, business.industry, Systemic, medicine.disease, Cohort, business
Abstract

ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Published
2022

30. SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern

Author

Giorgio Cozzi, Antimo Tessitore, Manuela Giangreco, Paola Cogo, Elena Valentini, Simona Salis, Paola Pascolo, Egidio Barbi, Cozzi, Giorgio, Tessitore, Antimo, Giangreco, Manuela, Cogo, Paola, Valentini, Elena, Salis, Simona, Pascolo, Paola, and Barbi, Egidio

Subjects
Emergency department, Infant, General Medicine, Gut feeling, Bacterial Infections, Abnormal respiratory pattern, Severe bacterial infection, Paediatric patients, Italy, Child, Preschool, Pediatrics, Perinatology and Child Health, Humans, Paediatric patient, Prospective Studies, Pediatricians, Child, Emergency Service, Hospital
Abstract

According to the Italian national statistical institute, severe bacterial infections (SBI) in Italy are responsible for 1.7% of mortality under 5 years of age and their recognition is often challenging, especially in the first stages of the disease. We tried to estimate the prevalence of SBI in our target population and to identify signs and symptoms that could guide in the initial evaluation of a child with a possible SBI.We designed a prospective, multicentre study and enrolled patients aged 0-14 years at the first evaluation to the emergency department with an acute illness lasting a maximum of 5 days. The presence of variables suggestive of SBI was collected for every enrolled patient. One week after the enrolment, every patient was followed up by telephone.SBI is more likely to be detected with the 'gut feeling' in both univariate and multivariate models (univariate OR: 7.16, 95% CI: 4.08-12.56; multivariate OR: 5.34, 95% CI: 2.78-10.25), while abnormal breathing pattern resulted significative only in univariate model (OR 3.83, 95% CI: 1.98-7.40). Nevertheless, their associated sensitivity is low.SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern.

Published
2022

31. Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV

Author

Alessandra, Vergori, Alessandro, Cozzi Lepri, Stefania, Cicalini, Giulia, Matusali, Veronica, Bordoni, Simone, Lanini, Silvia, Meschi, Roberta, Iannazzo, Valentina, Mazzotta, Francesca, Colavita, Ilaria, Mastrorosa, Eleonora, Cimini, Davide, Mariotti, Lydia, De Pascale, Alessandra, Marani, Paola, Gallì, AnnaRosa, Garbuglia, Concetta, Castilletti, Vincenzo, Puro, Chiara, Agrati, Enrico, Girardi, Francesco, Vaia, Andrea, Antinori, Eleonora, Tartaglia, Vergori, Alessandra, Cozzi Lepri, Alessandro, Cicalini, Stefania, Matusali, Giulia, Bordoni, Veronica, Lanini, Simone, Meschi, Silvia, Iannazzo, Roberta, Mazzotta, Valentina, Colavita, Francesca, Mastrorosa, Ilaria, Cimini, Eleonora, Mariotti, Davide, De Pascale, Lydia, Marani, Alessandra, Gallì, Paola, Garbuglia, Annarosa, Castilletti, Concetta, Puro, Vincenzo, Agrati, Chiara, Girardi, Enrico, Vaia, Francesco, and Antinori, Andrea

Subjects
COVID-19 Vaccines, Multidisciplinary, SARS-CoV-2, COVID-19 Vaccine, COVID-19, General Physics and Astronomy, HIV Infections, General Chemistry, Middle Aged, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Immunogenicity, Vaccine, Humans, HIV Infection, BNT162 Vaccine, 2019-nCoV Vaccine mRNA-1273, Human
Abstract

HIV infection may affect the immune response to vaccination. Here the authors show that humoral response in persons living with HIV after the third dose of a SARS-CoV-2 vaccine is strong and higher than that achieved with the second dose, while cell-mediated immunity remains stable.In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-gamma production in 216 PLWH on ART with advanced disease (CD4 count 2 log(2) difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.

Published
2022

32. Treatment and prevention of viral hepatitis in pregnancy

Author

Gabriella D. Cozzi, Basile Njei, Alan T.N. Tita, Ricardo A. Franco, and Jodie Dionne-Odom

Subjects
Hepatitis B virus, Pediatrics, medicine.medical_specialty, Sexual transmission, Antiviral Agents, Article, Hepatitis B, Chronic, Pregnancy, medicine, Humans, Lactation, Hepatitis B Vaccines, Pregnancy Complications, Infectious, Transmission (medicine), business.industry, Infant, Newborn, Obstetrics and Gynecology, Hepatitis A, Hepatitis C, Viral Load, Jaundice, Hepatitis B, medicine.disease, Infectious Disease Transmission, Vertical, Immunoglobulin G, Female, medicine.symptom, Viral hepatitis, business, Viral load
Abstract

Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.

Published
2022

33. Contrast-enhanced Mammography: A Systematic Review and Meta-Analysis of Diagnostic Performance

Author

Andrea Cozzi, Veronica Magni, Moreno Zanardo, Simone Schiaffino, and Francesco Sardanelli

Subjects
Reviews and Commentary, Contrast Media, Humans, Breast Neoplasms, Female, Radiology, Nuclear Medicine and imaging, Mammography
Abstract

Background Contrast-enhanced mammography (CEM) is a promising technique for breast cancer detection, but conflicting results have been reported in previous meta-analyses. Purpose To perform a systematic review and meta-analysis of CEM diagnostic performance considering different interpretation methods and clinical settings. Materials and Methods The MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were systematically searched up to July 15, 2021. Prospective and retrospective studies evaluating CEM diagnostic performance with histopathology and/or follow-up as the reference standard were included. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Summary diagnostic odds ratio and area under the receiver operating characteristic curve were estimated with the hierarchical summary receiver operating characteristic (HSROC) model. Summary estimates of sensitivity and specificity were obtained with the hierarchical bivariate model, pooling studies with the same image interpretation approach or focused on the same findings. Heterogeneity was investigated through meta-regression and subgroup analysis. Results Sixty studies (67 study parts, 11 049 CEM examinations in 10 605 patients) were included. The overall area under the HSROC curve was 0.94 (95% CI: 0.91, 0.96). Pooled diagnostic odds ratio was 55.7 (95% CI: 42.7, 72.7) with high heterogeneity (τ

Published
2022

34. Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis

Author

Salvatore Cozzi, Masoumeh Najafi, Marzieh Gomar, Patrizia Ciammella, Cinzia Iotti, Corrado Iaccarino, Massimo Dominici, Giacomo Pavesi, Chiara Chiavelli, Ali Kazemian, and Amin Jahanbakhshi

Subjects
Survival, Brain Neoplasms, Checkpoint inhibitor, Vaccination, Humans, Dendritic cell vaccination, Glioblastoma, Immunotherapy, Dendritic Cells
Abstract

Background: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients’ long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. Methods: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “glioblastoma multiforme”, “dendritic cell”, “vaccination”, “immunotherapy”, “immune system”, “immune response”, “chemotherapy”, “recurrence”, and “temozolomide”. Among the 157 screened, only 15 articles were eligible for the final analysis. Results: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822–2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882–2.248, p = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396–2.85, p = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291–5.879, p = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively. Conclusion: Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.

Published
2022

35. Radiomics-based prognosis classification for high-risk prostate cancer treated with radiotherapy

Author

Ciro Franzese, Luca Cozzi, Marco Badalamenti, Davide Baldaccini, Giuseppe D’Agostino, Antonella Fogliata, Pierina Navarria, Davide Franceschini, Tiziana Comito, Elena Clerici, Giacomo Reggiori, Stefano Tomatis, and Marta Scorsetti

Subjects
Male, Prostate cancer, Radiomics, Oncology, Outome prediction, Metastatic progression prediction, Prostate, Humans, Prostatic Neoplasms, Seminal Vesicles, Androgen Antagonists, Radiology, Nuclear Medicine and imaging, Prognosis
Abstract

Objective:The present study aimed to investigate if CT-based radiomics features could correlate to the risk of metastatic progression in high-risk prostate cancer patients treated with radical RT and long-term androgen deprivation therapy (ADT). Materials and methods:A total of 157 patients were investigated and radiomics features extracted from the contrast-free treatment planning CT series. Three volumes were segmented: the prostate gland only (CTV_p), the prostate gland with seminal vesicles (CTV_psv), and the seminal vesicles only (CTV_sv). The patients were split into two subgroups of 100 and 57 patients for training and validation. Five clinical and 62 radiomics features were included in the analysis. Considering metastases-free survival (MFS) as an endpoint, the predictive model was used to identify the subgroups with favorable or unfavorable prognoses (separated by a threshold selected according to the Youden method). Pure clinical, pure radiomic, and combined predictive models were investigated. Results:With a median follow-up of 30.7 months, the MFS at 1 and 3 years was 97.2% ± 1.5 and 92.1% ± 2.0, respectively. Univariate analysis identified seven potential predictors for MFS in the CTV_p group, 11 in the CTV_psv group, and 9 in the CTV_sv group. After elastic net reduction, these were 4 predictors for MFS in the CTV_p group (positive lymph nodes, Gleason score, H_Skewness, and NGLDM_Contrast), 5 in the CTV_psv group (positive lymph nodes, Gleason score, H_Skewnesss, Shape_Surface, and NGLDM_Contrast), and 6 in the CTV_sv group (positive lymph nodes, Gleason score, H_Kurtosis, GLCM_Correlation, GLRLM_LRHGE, and GLZLM_SZLGE). The patients' group of the training and validation cohorts were stratified into favorable and unfavorable prognosis subgroups. For the combined model, for CTV_p, the mean MFS was 134 ± 14.5 vs. 96.9 ± 22.2 months for the favorable and unfavorable subgroups, respectively, and 136.5 ± 14.6 vs. 70.5 ± 4.3 months for CTV_psv and 150.0 ± 4.2 vs. 91.1 ± 8.6 months for CTV_sv, respectively. Conclusion:Radiomic features were able to predict the risk of metastatic progression in high-risk prostate cancer. Combining the radiomic features and clinical characteristics can classify high-risk patients into favorable and unfavorable prognostic groups.

Published
2022

36. Recovery characteristics and parental satisfaction in pediatric procedural sedation

Author

Luisa Cortellazzo Wiel, Lorenzo Monasta, Paola Pascolo, Alessia Giuseppina Servidio, Laura Levantino, Silvia Fasoli, Alessia Saccari, Giorgio Cozzi, and Egidio Barbi

Subjects
Parents, Respiratory Distress Syndrome, Sleepiness, Hallucinations, Vomiting, Midazolam, Conscious Sedation, Personal Satisfaction, Anesthesiology and Pain Medicine, Pediatrics, Perinatology and Child Health, Humans, Hypnotics and Sedatives, Ketamine, Child, Propofol, Dexmedetomidine
Abstract

Despite being a standard of care for children undergoing stressful procedures, little data exist on parental perception of pediatric sedation.This study aimed to investigate recovery characteristics and parental satisfaction for pediatric sedations performed with four widely used sedative regimens.A prospective observational study was conducted at the Institute for Maternal and Child Health of Trieste, Italy, enrolling children undergoing procedural sedation with one of the following pharmacological regimens: propofol, propofol + midazolam, ketamine + propofol, and dexmedetomidine + midazolam. A questionnaire was used to assess the occurrence of symptoms upon recovery from sedation and the following day, and the caregivers' satisfaction for both the recovery pattern and the overall sedation experience, according to a numerical rating scale (0-10). Answers were collected through a telephone survey. The primary outcome was the difference in the quality of the recovery as perceived by caregivers; the secondary and tertiary outcomes were the perceived quality of the overall sedation experience and the frequency of sedation-related adverse events, respectively.Data from 655 patients, 149 receiving propofol, 245 propofol + midazolam, 134 ketamine + propofol, and 127 dexmedetomidine + midazolam, were analyzed. The level of parents' satisfaction for both the recovery and the sedation experience was overall high and increased with the patients' age in all the pharmacological groups (Spearman's rank correlation, ρ .083, p = .033, and ρ .087, p = .026, respectively), with no statistically significant differences between groups when adjusting for age. The occurrence of irritability, prolonged sleepiness, hyperactivity, unsteadiness, hallucinations, emesis, and respiratory distress at any moment negatively affected parental satisfaction.In this study, caregivers' satisfaction with pediatric sedation was high, regardless of the regimen used. Lower parental satisfaction was associated with younger age, irritability after sedation, prolonged sleepiness, hyperactivity, unsteadiness, hallucinations, emesis, and respiratory distress.

Published
2022

37. Thoracic non-traumatic cardiovascular diseases: current perspective and multi-detectors Computed Tomography protocols optimization in the emergency setting

Author

Palumbo, P, Cannizzaro, E, Bracci, A, Bruno, F, Arrigoni, F, Splendiani, A, Danti, G, Cozzi, D, Pradella, S, Grassi, F, Grassi, R, Dell'Aversana, F, Brunese, M C, Cutolo, C, Ravo, L, Fusco, R, Galdiero, R, Granata, V, Masciocchi, C, Di Cesare, E, Palumbo, P, Cannizzaro, E, Bracci, A, Bruno, F, Arrigoni, F, Splendiani, A, Danti, G, Cozzi, D, Pradella, S, Grassi, F, Grassi, R, Dell'Aversana, F, Brunese, M C, Cutolo, C, Ravo, L, Fusco, R, Galdiero, R, Granata, V, Masciocchi, C, and Di Cesare, E

Subjects
Pulmonary embolism, Non-traumatic, CCTA, Heart, Humans, Review Literature as Topic, Tomography, X-Ray Computed, Cardiovascular Diseases, Cardiovascular System, Thoracic Diseases, Cardiovascular disease, X-Ray Computed, Thoracic emergency, Acute aortic syndrome, Triple-rule-out, CTPA, Acute coronary syndrome, Tomography, CT
Abstract

Cardiovascular diseases (CVDs) are among the most common causes of access to the Emergency Department and among the leading causes of death worldwide. Accurate diagnostic algorithms are mandatory to ensure a rapid life-saving treatment. However, non-specific clinical presentation and unnecessary referrals to other subspecialties may lead to misinterpretation of the diagnosis and delays. In recent years, the development of imaging technologies has allowed Computed Tomography (CT) to play a prominent role in the concepts of CVD rule-in and rule-out. An optimization strategy for CT protocols is needed to reduce variability and improve image quality. A correct diagnostic suspicion is crucial, as different districts (i.e., heart, aorta and pulmonary circulation) may require different investigation techniques. Additionally, the CVD pre-test probability assessment is highly correlated with CT accuracy. The purpose of this narrative review is to analyze the current role of CT in the approach to the CVDs in the ED, and to analyze the main strategies of CT optimization.

Published
2022

38. Increased use of high-flow nasal cannulas after the pandemic in bronchiolitis: a more severe disease or a changed physician's attitude?

Author

Sergio Ghirardo, Giorgio Cozzi, Giovanna Tonin, Francesco Maria Risso, Laura Dotta, Alessandro Zago, Daniela Lupia, Paola Cogo, Nicola Ullmann, Antonella Coretti, Raffaele Badolato, Alessandro Amaddeo, Egidio Barbi, Renato Cutrera, Ghirardo, Sergio, Cozzi, Giorgio, Tonin, Giovanna, Risso, Francesco Maria, Dotta, Laura, Zago, Alessandro, Lupia, Daniela, Cogo, Paola, Ullmann, Nicola, Coretti, Antonella, Badolato, Raffaele, Amaddeo, Alessandro, Barbi, Egidio, and Cutrera, Renato

Subjects
Attitude of Health Personnel, SARS-CoV-2, High-flow nasal cannula (HFNC), Oxygen Inhalation Therapy, COVID-19 pandemic, COVID-19, Infant, Bronchiolitis, Non-invasive ventilation (NIV), Respiratory syncytial virus (RSV), Oxygen, Physicians, Pediatrics, Perinatology and Child Health, Cannula, Humans, Bronchioliti, Child, Pandemics, Retrospective Studies
Abstract

After the SARS-CoV-2 pandemic, we noticed a marked increase in high-flow nasal cannula use for bronchiolitis. This study aims to report the percentage of children treated with high-flow nasal cannula (HFNC) in various seasons. The secondary outcomes were admissions for bronchiolitis, virological results, hospital burden, and NICU/PICU need. We conducted a retrospective study in four Italian hospitals, examining the medical records of all infants (p p Conclusion: This study shows a marked increase in respiratory support and intensive care admissions this last winter. While these severity indexes were all driven by medical choices, more reliable indexes such as intubation rate and length of stay did not change. Therefore, we suggest that there is a more aggressive treatment attitude rather than a more severe disease. What is Known:• COVID-19 pandemic deeply impacted bronchiolitis epidemiology, reducing hospitalizations to onetenth. In the 2021-2022 winter, bronchiolitis resurged to pre-pandemic numbers in Europe. What is New:• Bronchiolitis hospitalization rose much faster in the 2021-2022 winter period, peaking at a higher level. Respiratory supports and high-flow nasal cannula increased significantly compared to the pre-pandemic era.

Published
2022

39. Optimization of CT protocol in polytrauma patients: an update

Author

Flammia, F, Chiti, G, Trinci, M, Danti, G, Cozzi, D, Grassi, R, Palumbo, P, Bruno, F, Agostini, A, Fusco, R, Granata, V, Giovagnoni, A, Miele, V, Flammia, F, Chiti, G, Trinci, M, Danti, G, Cozzi, D, Grassi, R, Palumbo, P, Bruno, F, Agostini, A, Fusco, R, Granata, V, Giovagnoni, A, and Miele, V

Subjects
Review Literature as Topic, Multiple Trauma, Dual energy CT, Radiologists, Humans, Polytrauma, Tomography, X-Ray Computed, Computed tomography, Whole body CT
Abstract

Radiologists play a key role in the management of trauma patients. With the improvement of computed tomography (CT), radiologist makes an important contribution to the timely diagnosis of trauma-related findings and the choice of the most suitable treatment, improving patient outcomes. It is important to select the most appropriate imaging technique, which in the trauma patient is CT, and especially the most appropriate CT protocol, to correctly characterize trauma injuries. Currently, there is no agreement on what the optimal protocol is, acquisition times and number of contrast enhanced phases are not standardized. This is a review of the most recent literature on optimizing the CT protocol in polytrauma, with the intent of giving a useful tool for radiologists in the management of trauma patients.

Published
2022

40. Robot-Assisted Radical Cystectomy for Nonmetastatic Urothelial Carcinoma of Urinary Bladder: A Comparison Between Intracorporeal Versus Extracorporeal Orthotopic Ileal Neobladder

Author

Gabriele Cozzi, Michele Catellani, Antonio Brescia, Giovanni Cordima, Antonio Cioffi, Claudia Collà Ruvolo, A. Conti, Ottavio De Cobelli, Vincenzo Mirone, Matteo Ferro, Deliu Victor Matei, Ettore Di Trapani, Roberto Bianchi, Danilo Bottero, Stefano Luzzago, Francesco A. Mistretta, F. Verweij, Gennaro Musi, Mistretta, F. A., Musi, G., Colla Ruvolo, C., Conti, A., Luzzago, S., Catellani, M., Di Trapani, E., Cozzi, G., Bianchi, R., Ferro, M., Cioffi, A., Cordima, G., Brescia, A., Verweij, F., Bottero, D., Matei, D. V., Mirone, V., and De Cobelli, O.

Subjects
robotic, medicine.medical_specialty, Urology, medicine.medical_treatment, 030232 urology & nephrology, complication, Urinary Diversion, Cystectomy, Extracorporeal, 03 medical and health sciences, 0302 clinical medicine, Robotic Surgical Procedures, Humans, Medicine, Complication rate, Retrospective Studies, Urothelial carcinoma, Urinary bladder, business.industry, Continent Urinary Reservoir, continent urinary reservoir, Robotics, Treatment Outcome, medicine.anatomical_structure, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, Neoplasm Recurrence, Local, business
Abstract

Introduction: To compare surgical, oncologic, functional outcomes and complication rate between intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) orthotopic ileal neobladder of robot-assisted radical cystectomy (RARC) in patients with nonmetastatic bladder carcinoma (BC). Materials and Methods: From 2014 to 2019, we prospectively collected and retrospectively analyzed 101 patients with nonmetastatic BC treated with RARC and ortothopic neobladder. Chi-squared test estimated differences in proportions of functional and oncologic outcomes. Multivariable logistic regression models (MLRMs) focused on overall, early (30 days from discharge) in ICNB vs ECNB. Results: Of all patients, 57 (56.4%) ICNB and 44 (43.6%) ECNB patients were identified. At least one complication occurred in 75.4% vs 72.7% in ICNB vs ECNB, respectively (p = 0.9). In MLRMs, focusing on complication rate, there was no statistically significant difference between ICNB vs ECNB for overall (p = 0.8), early (p = 0.6), and late complications (p = 0.8). No statistically significant differences were recorded for tumor relapse rate, cancer-specific and other cause mortality. No positive surgical margins were recorded in both groups. Daytime and nighttime continence recovery were 89.4% vs 87.1% (p = 1.0) and 63.8% vs 51.6% (p = 1.0) for ICNB vs ECNB. Potency recovery was 59.1% vs 54.3% (p = 0.5) for ICNB vs ECNB. Conclusions: No statistically significant differences in complication rate (overall, early, or late) were identified, when ICNB and ECNB were compared. Similarly, no statistically significant difference was found in oncologic and functional outcomes.

Published
2021

41. Pathogenic mechanism and modeling of neuroferritinopathy

Author

Anna Cozzi, Paolo Santambrogio, Maddalena Ripamonti, Sonia Levi, Ermanna Rovida, Cozzi, A., Santambrogio, P., Ripamonti, M., Rovida, E., and Levi, S.

Subjects
Iron metabolism disorder, Neurodegeneration with brain iron accumulation, Iron, Iron deposition, Neuroaxonal Dystrophies, Neuroferritinopathy, Disease models, medicine.disease_cause, Cellular and Molecular Neuroscience, Extrapyramidal symptoms, Oxidative damage, medicine, Ferroptosis, Animals, Humans, Molecular Biology, Pharmacology, biology, Mechanism (biology), Neurodegenerative diseases, Cell Biology, Iron metabolism, medicine.disease, Iron Metabolism Disorders, Ferritin, Apoferritins, biology.protein, Molecular Medicine, medicine.symptom, Neuroscience, Oxidative stress
Abstract

Neuroferritinopathy is a rare autosomal dominant inherited movement disorder caused by alteration of the L-ferritin gene that results in the production of a ferritin molecule that is unable to properly manage iron, leading to the presence of free redox-active iron in the cytosol. This form of iron has detrimental effects on cells, particularly severe for neuronal cells, which are highly sensitive to oxidative stress. Although very rare, the disorder is notable for two reasons. First, neuroferritinopathy displays features also found in a larger group of disorders named Neurodegeneration with Brain Iron Accumulation (NBIA), such as iron deposition in the basal ganglia and extrapyramidal symptoms; thus, the elucidation of its pathogenic mechanism may contribute to clarifying the incompletely understood aspects of NBIA. Second, neuroferritinopathy shows the characteristic signs of an accelerated process of aging; thus, it can be considered an interesting model to study the progress of aging. Here, we will review the clinical and neurological features of neuroferritinopathy and summarize biochemical studies and data from cellular and animal models to propose a pathogenic mechanism of the disorder.

Published
2021

42. IgG antibodies against SARS-CoV-2 decay but persist 4 months after vaccination in a cohort of healthcare workers

Author

C. Caffau, Agostino Steffan, Maria Rita Cozzi, Elena Muraro, Chiara Corso, Mariateresa Casarotto, Marcella Montico, Federico Ronchese, Stefania Zanussi, Roberto Vettori, Chiara Evangelista, Matteo Turetta, and Giulia Brisotto

Subjects
COVID-19, COronaVIrus Disease 19, COVID-19 Vaccines, HCW, HealthCare Workers, Health Personnel, Clinical Biochemistry, Vaccine Efficacy, Ig, Immunoglobulin, Biochemistry, Article, Immunoglobulin G, Serology, Immune system, Immunity, Humans, Medicine, BNT162 Vaccine, biology, SARS-CoV-2, business.industry, mRNA vaccination, Vaccination, Biochemistry (medical), AU, Arbitrary Units, COVID-19, RBD, Receptor Binding Domain, General Medicine, Vaccine efficacy, antibody decay, IQR, InterQuartile Range, Cohort, Immunology, biology.protein, IgG antibodies, mRNA Vaccines, Antibody, business, 2019-nCoV Vaccine mRNA-1273
Abstract

Background and aims Monitoring the immune response against SARS-CoV-2 is pivotal in the evaluation of long-term vaccine efficacy. Immunoglobulin G (IgG) antibodies represent an advisable tool to reach this goal, especially for the still poorly defined antibody trend induced by the new class of mRNA vaccines against SARS-CoV-2. Materials and methods Anti-Spike RBD IgG antibodies were monitored in a cohort of healthcare workers at CRO Aviano, National Cancer Institute, through MAGLUMI® chemiluminescence assay, at 1 and 4 months after full-schedule of BNT162b2 or mRNA-1273 vaccination. Results At 1 month after vaccination, 99.9% of 767 healthcare workers showed a reactive antibody response, which was inversely correlated with age, and positively associated with a previous history of COVID-19, and mRNA-1273 vaccination. Serological response was maintained in 99.6% of the 516 subjects monitored also at follow-up. An antibody decay from 559.8 AU/mL (IQR 359.7–845.7) to 92.7 AU/mL (IQR 65.1–148.6; p

Published
2021

43. Trabecular titanium cups in acetabular revision arthroplasty: analysis of 10-year survivorship, restoration of center of rotation and osteointegration

Author

Andrea Cozzi Lepri, Marco Villano, Roberto Civinini, Alberto Galeotti, Matteo Innocenti, and Christian Carulli

Subjects
Reoperation, medicine.medical_specialty, Rotation, Arthroplasty, Replacement, Hip, Radiography, Dentistry, Survivorship, Osseointegration, Survivorship curve, medicine, Humans, Orthopedics and Sports Medicine, Instant centre of rotation, Survival rate, Pelvis, Retrospective Studies, Titanium, business.industry, Acetabulum, General Medicine, Prosthesis Failure, medicine.anatomical_structure, Harris Hip Score, Orthopedic surgery, Surgery, Hip Prosthesis, business, Follow-Up Studies
Abstract

In case of severe bone loss, acetabular revision can be challenged using extra porous pure trabecular titanium (TT) revision cups designed to ensure enhanced iliac and ischiatic purchase. Aim of the study is to report on the clinical and radiological results of a TT acetabular component, evaluating functional outcome, restoration of the hip center of rotation and osteointegration.85 patients, who underwent acetabular revision with a TT revision cup system between October 2009 and December 2018, were included in a retrospective study. Clinical outcome were assessed with Harris Hip Score (HHS). The hip rotation center was measured using the Pierchon method on the AP pelvis film. Loosening of the cup was determined according to the Kosashvili modification of Gill's criteria. Kaplan- Meier survivorship curve was performed. Results The mean follow-up was 6.12 years. The average HHS improved from 54.7 points to 89.7 points (p 0.05). Two acetabular components (2.3%) were re-revised after a mean of 5.6 years, for aseptic loosening and for infection, with a progressive radiolucency and a 5 mm vertical migration, respectively. The radiographic evaluation of the position of the hip rotation center revealed a statistically significant difference (p 0.05) between the pre- and post-operative values. The hip rotation center was correctly restored within 5% of the reference Pierchon values in a percentage of 85.4% relative to horizontal parameters and within 8% in a percentage of 66.7% relative to vertical parameters. 5-year and 10-year survivorships were, respectively, 100% and 88%.In case of severe bone loss, TT revision cup system allows for good restoration of center of rotation and osteointegration showing good 10-year survival rate.

Published
2021

44. Volumetric modulated arc therapy versus intensity-modulated proton therapy in the irradiation of infra diaphragmatic Hodgkin Lymphoma in female patients

Author

Peter Borchmann, Antonella Fogliata, Luca Cozzi, Alessandro Clivio, Andrés Vásquez-Torres, Christian Baues, Johannes Rosenbrock, and Simone Marnitz

Subjects
Organs at Risk, Diaphragmatic breathing, immune system diseases, hemic and lymphatic diseases, Female patient, Proton Therapy, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Irradiation, Proton therapy, business.industry, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, Hematology, General Medicine, medicine.disease, Hodgkin Disease, Volumetric modulated arc therapy, Lymphoma, Intensity (physics), body regions, Oncology, Hodgkin lymphoma, Female, Radiotherapy, Intensity-Modulated, business, Nuclear medicine
Abstract

To investigate the role of infra diaphragmatic intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for female Hodgkin Lymphoma (HL) patients and to estimate the risk of secondary cancer and ovarian failure.A comparative treatment planning study was performed on 14 patients, and the results were compared according to conventional dose-volume metrics. In addition, estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the bowel, the bladder and the rectum. For the ovaries, the risk of ovarian failure was estimated.The dosimetric findings demonstrate the equivalence between VMAT and IMPT in terms of target coverage. A statistically significant reduction of the mean and near-to-maximum doses was proven for the organs at risk. The EAR ratio estimated for IMPT to VMAT was 0.51 ± 0.32, 0.32 ± 0.35 and 0.05 ± 0.11 for the bowel, bladder and rectum, respectively. Concerning the risk of ovarian failure for the chronologic age ranging from 18 to 46 years, the expected net loss in fertility years ranged from 4.8 to 3.0 years for protons and 12.0 to 5.7 years for photons.This in-silico study confirmed the beneficial role of IMPT from a dosimetric point of view. Mathematical models suggested that the use of protons might be further advantageous due to the expected reduction of the risk of secondary cancer induction and its milder impact on the reduction of fertility.

Published
2021

45. Impact of the first COVID-19 lockdown on the relationship with parents and peers in a cohort of adolescents with somatic symptom disorder

Author

Andrea Trombetta, Laura De Nardi, Giorgio Cozzi, Luca Ronfani, Lara Bigolin, Egidio Barbi, Matteo Bramuzzo, Giuseppe Abbracciavento, Trombetta, A, De Nardi, L, Cozzi, G, Ronfani, L, Bigolin, L, Barbi, E, Bramuzzo, M, Abbracciavento, G., Trombetta, Andrea, De Nardi, Laura, Cozzi, Giorgio, Ronfani, Luca, Bigolin, Lara, Barbi, Egidio, Bramuzzo, Matteo, and Abbracciavento, Giuseppe

Subjects
Coping strategies, Cross-Sectional Studie, Parents, Adolescent, Adolescent Health, COVID-19, Mental health, Somatic symptom disorder, Communicable Disease Control, Cross-Sectional Studies, Humans, Medically Unexplained Symptoms, Coping strategie, Parent, Human
Abstract

To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown.This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies.We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers.The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group.The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013).Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group.

Published
2021

46. The Effect of Filters on CPAP Delivery by Helmet

Author

Daniele Privitera, Nicolò Capsoni, Francesco Zadek, Paolo Vailati, Chiara Airoldi, Mattia Cozzi, Federico Pierotti, Roberto Fumagalli, Andrea Bellone, Thomas Langer, Privitera, D, Capsoni, N, Zadek, F, Vailati, P, Airoldi, C, Cozzi, M, Pierotti, F, Fumagalli, R, Bellone, A, and Langer, T

Subjects
Pulmonary and Respiratory Medicine, Hot Temperature, emergency department, Continuous Positive Airway Pressure, CPAP, respiratory insufficiency, noninvasive ventilation, Humans, General Medicine, Critical Care and Intensive Care Medicine, Noise
Abstract

BACKGROUND: When helmet CPAP is performed using a Venturi system, filters are frequently interposed in the respiratory circuit to reduce noise within the helmet. The effect of the interposition of these filters on delivered fresh gas flow and the resulting FIO2 is currently unknown. METHODS: In a bench study, 2 different Venturi systems (WhisperFlow and Harol) were used to generate 3 different gas flow/FIO2 combinations (80 L/min-FIO2 0.6, 100 L/min-FIO2 0.5, 120 L/min-FIO2 0.4). Different combinations of filters were applied at the flow generator input line and/or at the helmet inlet port. Two types of filters were used for this purpose: a heat and moisture exchanger filter and an electrostatic filter. The setup without filters was used as baseline. Gas flow and FIO2 were measured for each setup. RESULTS: Compared to baseline, the interposition of filters reduced the gas flow between 1–13% (P < .001). The application of a filter at the Venturi system or at the helmet generated a comparable flow reduction (-3 ± 2% vs-4 ± 2%, P = .12), whereas a greater flow reduction (-7 ± 4%) was observed when filters were applied at both sites (P < .001). An increase in FIO2 up to 5% was observed with filters applied. A strong inverse linear relationship (P < .001) was observed between the resulting gas flow and FIO2. CONCLUSIONS: The use of filters during helmet CPAP reduced the flow delivered to the helmet and, consequently, modified FIO2. If filters are applied, an adequate gas flow should be administered to guarantee a constant CPAP during the entire respiratory cycle and avoid rebreathing. Moreover, it might be important to measure the effective FIO2 delivered to the patient to guarantee a precise assessment of oxygenation.

Published
2022

47. Massive iron accumulation in PKAN-derived neurons and astrocytes: light on the human pathological phenotype

Author

Paolo Santambrogio, Maddalena Ripamonti, Anna Cozzi, Marzia Raimondi, Chiara Cavestro, Ivano Di Meo, Alicia Rubio, Stefano Taverna, Valeria Tiranti, Sonia Levi, Santambrogio, P., Ripamonti, M., Cozzi, A., Raimondi, M., Cavestro, C., Di Meo, I., Rubio, A., Taverna, S., Tiranti, V., and Levi, S.

Subjects
Neurons, Phosphotransferases (Alcohol Group Acceptor), Cancer Research, Cellular and Molecular Neuroscience, Phenotype, Astrocytes, Iron, Immunology, Humans, Coenzyme A, Cell Biology, Pantothenate Kinase-Associated Neurodegeneration
Abstract

Neurodegeneration associated with defective pantothenate kinase-2 (PKAN) is an early-onset monogenic autosomal-recessive disorder. The hallmark of the disease is the massive accumulation of iron in the globus pallidus brain region of patients. PKAN is caused by mutations in the PANK2 gene encoding the mitochondrial enzyme pantothenate kinase-2, whose function is to catalyze the first reaction of the CoA biosynthetic pathway. To date, the way in which this alteration leads to brain iron accumulation has not been elucidated. Starting from previously obtained hiPS clones, we set up a differentiation protocol able to generate inhibitory neurons. We obtained striatal-like medium spiny neurons composed of approximately 70–80% GABAergic neurons and 10–20% glial cells. Within this mixed population, we detected iron deposition in both PKAN cell types, however, the viability of PKAN GABAergic neurons was strongly affected. CoA treatment was able to reduce cell death and, notably, iron overload. Further differentiation of hiPS clones in a pure population of astrocytes showed particularly evident iron accumulation, with approximately 50% of cells positive for Perls staining. The analysis of these PKAN astrocytes indicated alterations in iron metabolism, mitochondrial morphology, respiratory activity, and oxidative status. Moreover, PKAN astrocytes showed signs of ferroptosis and were prone to developing a stellate phenotype, thus gaining neurotoxic features. This characteristic was confirmed in iPS-derived astrocyte and glutamatergic neuron cocultures, in which PKAN glutamatergic neurons were less viable in the presence of PKAN astrocytes. This newly generated astrocyte model is the first in vitro disease model recapitulating the human phenotype and can be exploited to deeply clarify the pathogenetic mechanisms underlying the disease.

Published
2022

48. The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017

Author

Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, Mg, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Tarasconi, A, Sella, M, Auriemma, S, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Margola, A, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Giani, A, Famularo, S, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Ballestrero, A, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, De, F, Pietrogrande, L, De, B, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Bianchetti, A, Crucitti, A, Di Francesco, V, Fontana, G, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cannistrà, U, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambara, V, Saitta, A, Corica, F, Braga, M, Ettorre, E, Camellini, C, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuari, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, D'Imporzano, E, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samy Salama Fahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Pezzoni, D, Gentile, S, Platto, C, D'Ambrosio, V, Faraci, B, Brambilla, C, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Confente, S, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, C Boffelli S, Corsini, Filippi, A, Delpin, K, Bertoletti, E, Vannucci, M, Tesi, F, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Riva, E, Dell'Acqua, D, Cottino, M, Vezzadini, G, Avanzi, S, Orini, S, Sgrilli, F, Mello, A, Lombardi, L, Muti, E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, A Millul A, Barelli, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cat, C, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Scapigliati, A, Cortegiani, A, Vitale, F, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D., Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, M, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Citerio, G, Zucchelli, Alberto, Valsecchi, M G, and A Tarasconi, M Sella, S Auriemma, G Paternò, G Faggian, C Lucarelli, N De Grazia, C Alberto, A Margola, L Porcella, I Nardiello, E Chimenti, M Zeni, A Giani, S Famularo, E Romairone, C Minaglia, C Ceccotti, G Guerra, G Mantovani, F Monacelli, C Minaglia, T Candiani, A Ballestrero, C Minaglia, F Santolini, C Minaglia, M Rosso, V Bono, S Sibilla, P Dal Santo, M Ceci, P Barone, T Schirinzi, A Formenti, G Nastasi, G Isaia, D Gonella, A Battuello, S Casson, D Calvani, F Boni, A Ciaccio, R Rosa, G Sanna, S Manfredini, L Cortese, M Rizzo, R Prestano, A Greco, M Lauriola, G Gelosa, V Piras, M Arena, D Cosenza, A Bellomo, M LaMontagna, L Gabbani, L Lambertucci, S Perego, G Parati, G Basile, V Gallina, G Pilone, C Giudice, F De, L Pietrogrande, B De, M Mosca, I Corazzin, P Rossi, V Nunziata, F D'Amico, A Grippa, S Giardini, R Barucci, A Cossu, L Fiorin, M Arena, M Distefano, M Lunardelli, M Brunori, I Ruffini, E Abraham, A Varutti, E Fabbro, A Catalano, G Martino, D Leotta, A Marchet, G Dell'Aquila, A Scrimieri, M Davoli, M Casella, A Cartei, G Polidori, G Basile, D Brischetto, S Motta, R Saponara, P Perrone, G Russo, D Del, C Car, T Pirina, S Franzoni, A Cotroneo, F Ghiggia, G Volpi, C Menichetti, M Bo, A Panico, P Calogero, G Corvalli, M Mauri, E Lupia, R Manfredini, F Fabbian, A March, M Pedrotti, M Veronesi, E Strocchi, A Bianchetti, A Crucitti, V Di Francesco, G Fontana, L Bonanni, F Barbone, C Serrati, G Ballardini, M Simoncelli, G Ceschia, C Scarpa, R Brugiolo, S Fusco, T Ciarambino, C Biagini, E Tonon, M Porta, D Venuti, M DelSette, M Poeta, G Barbagallo, G Trovato, A Delitala, P Arosio, F Reggiani, G Zuliani, B Ortolani, E Mussio, A Girardi, A Coin, G Ruotolo, A Castagna, M Masina, R Cimino, A Pinciaroli, G Tripodi, U Cannistrà, F Cassadonte, M Vatrano, F Cassandonte, L Scaglione, P Fogliacco, C Muzzuilini, F Romano, A Padovani, L Rozzini, A Cagnin, F Fragiacomo, G Desideri, E Liberatore, A Bruni, G Orsitto, M Franco, L Bonfrate, M Bonetto, N Pizio, G Magnani, G Cecchetti, A Longo, V Bubba, L Marinan, M Cotelli, M Turla, M Brunori, M Sessa, L Abruzzi, G Castoldi, D LoVetere, C Musacchio, M Novello, A Cavarape, A Bini, A Leonardi, F Seneci, W Grimaldi, F Fimognari, V Bambara, A Saitta, F Corica, M Braga, E Ettorre, C Camellini, A Marengoni, A Bruni, A Crescenzo, G Noro, R Turco, M Ponzetto, L Giuseppe, B Mazzei, G Maiuri, D Costaggiu, R Damato, E Fabbro, G Patrizia, L Santuari, M Gallucci, C Minaglia, M Paragona, P Bini, D Modica, C Abati, M Clerici, I Barbera, F NigroImperiale, A Manni, C Votino, C Castiglioni, M Di, M Degl'Innocenti, G Moscatelli, S Guerini, C Casini, D Dini, S DeNotariis, F Bonometti, C Paolillo, A Riccardi, A Tiozzo, A SamySalamaFahmy, A Riccardi, C Paolillo, M DiBari, S Vanni, A Scarpa, D Zara, P Ranieri, P Calogero, G Corvalli, D Pezzoni, S Gentile, A Morandi, C Platto, V D'Ambrosio, B Faraci, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, S Confente, M Bonetto, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, E Bertoletti, M Vannucci, F Tesi, P Crippa, A Malighetti, C Caltagirone, S DiSant, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D'Amico, A Grippa, A Mazzone, E Riva, D Dell'Acqua, M Cottino, G Vezzadini, S Avanzi, S Orini, F Sgrilli, A Mello, L Lombardi, E Muti, B Dijk, S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, F De, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul, G De, G Morrone, M Bigolari, C Minaglia, M Macchi, F Zambon, F D'Amico, F D'Amico, C Pizzorni, G DiCasaleto, G Menculini, M Marcacci, G Catanese, D Sprini, T DiCasalet, M Bocci, S Borga, P Caironi, C Cat, E Cingolani, L Avalli, G Greco, G Citerio, L Gandini, G Cornara, R Lerda, L Brazzi, F Simeone, M Caciorgna, D Alampi, S Francesconi, E Beck, B Antonini, K Vettoretto, M Meggiolaro, E Garofalo, A Bruni, S Notaro, R Varutti, F Bassi, G Mistraletti, A Marino, R Rona, E Rondelli, I Riva, A Scapigliati, A Cortegiani, F Vitale, L Pistidda, R D'Andrea, L Querci, P Gnesin, M Todeschini, M Lugano, G Castelli, M Ortolani, A Cotoia, S Maggiore, L DiTizio, R Graziani, I Testa, E Ferretti, C Castioni, F Lombardi, R Caserta, M Pasqua, S Simoncini, F Baccarini, M Rispoli, F Grossi, L Cancelliere, M Carnelli, F Puccini, G Biancofiore, A Siniscalchi, C Laici, E Mossello, M Torrini, G Pasetti, S Palmese, R Oggioni, V Mangani, S Pini, M Martelli, E Rigo, F Zuccalà, A Cherri, R Spina, I Calamai, N Petrucci, A Caicedo, F Ferri, P Gritti, N Brienza, R Fonnesu, M Dessena, G Fullin, D Saggioro

Subjects
Male, Aging, medicine.medical_specialty, Sarcopenia, medicine.medical_treatment, Socio-culturale, Older person, Logistic regression, Delirium, Older persons, Sarcopenia, Internal medicine, mental disorders, Delirium, Older persons, medicine, Dementia, Humans, LS4_4, Muscle, Skeletal, Pathological, Aged, Rehabilitation, business.industry, Area under the curve, Settore MED/23 - Chirurgia Cardiaca, Skeletal, medicine.disease, Skeletal muscle mass, Cross-Sectional Studies, Italy, Muscle, Female, Geriatrics and Gerontology, medicine.symptom, business
Abstract

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

Published
2022

49. The orbitofrontal cortex of the sheep. Topography, organization, neurochemistry, digital tensor imaging and comparison with the chimpanzee and human

Author

Tommaso Gerussi, Jean-Marie Graïc, Annamaria Grandis, Antonella Peruffo, Bruno Cozzi, Gerussi, Tommaso, Graïc, Jean-Marie, Grandis, Annamaria, Peruffo, Antonella, and Cozzi, Bruno

Subjects
Histology, Chimpanzee, Sheep, Pan troglodytes, Animal, General Neuroscience, Pan troglodyte, Brain, Prefrontal Cortex, Neurochemistry, DTI, Human, Orbitofrontal cortex, Animals, Humans, Diffusion Tensor Imaging, nervous system, Anatomy, psychological phenomena and processes
Abstract

Areas dedicated to higher brain functions such as the orbitofrontal cortex (OFC) are thought to be unique to hominidae. The OFC is involved in social behavior, reward and punishment encoding and emotional control. Here, we focused on the putative corresponding area in the sheep to assess its homology to the OFC in humans. We used classical histology in five sheep (Ovis aries) and four chimpanzees (Pan troglodytes) as a six-layered-cortex primate, and Diffusion Tensor Imaging (DTI) in three sheep and five human brains. Nissl’s staining exhibited a certain alteration in cortical lamination since no layer IV was found in the sheep. A reduction of the total cortical thickness was also evident together with a reduction of the prevalence of layer one and an increased layer two on the total thickness. Tractography of the sheep OFC, on the other hand, revealed similarities both with human tracts and those described in the literature, as well as a higher number of cortico-cortical fibers connecting the OFC with the visual areas in the right hemisphere. Our results evidenced the presence of the basic components necessary for complex abstract thought in the sheep and a pronounced laterality, often associated with greater efficiency of a certain function, suggested an evolutionary adaptation of this prey species.

Published
2022

50. Computation of contrast-enhanced perfusion using only two CT scan phases: a proof-of-concept study on abdominal organs

Author

Massimo Cressoni, Andrea Cozzi, Simone Schiaffino, Paolo Cadringher, Paolo Vitali, Gianpaolo Basso, Davide Ippolito, Francesco Sardanelli, Cressoni, M, Cozzi, A, Schiaffino, S, Cadringher, P, Vitali, P, Basso, G, Ippolito, D, and Sardanelli, F

Subjects
Male, Carcinoma, Hepatocellular, Contrast media, Liver Neoplasms, Carcinoma, Settore MED/37 - Neuroradiologia, Hepatocellular, Perfusion imaging, Carcinoma (hepatocellular), Tomography (x-ray computed), X-Ray Computed, Perfusion, Humans, Radiology, Nuclear Medicine and imaging, Tomography, X-Ray Computed, Tomography, Retrospective Studies
Abstract

Background Computed tomography perfusion imaging (CTPI) by repeated scanning has clinical relevance but implies relatively high radiation exposure. We present a method to measure perfusion from two CT scan phases only, considering tissue enhancement, feeding vessel (aortic) peak enhancement, and bolus shape. Methods CTPI scans (each with 40 frames acquired every 1.5 s) of 11 patients with advanced hepatocellular carcinoma (HCC) enrolled between 2012 and 2016 were retrospectively analysed (aged 69 ± 9 years, 8/11 males). Perfusion was defined as the maximal slope of the time-enhancement curve divided by the peak enhancement of the feeding vessel (aorta). Perfusion was computed two times, first using the maximum slope derived from all data points and then using the peak tissue enhancement and the bolus shape obtained from the aortic curve. Results Perfusion values from the two methods were linearly related (r2 = 0.92, p r2 = 0.55, p Conclusions This proof-of-concept study showed that perfusion values of HCC, kidney, and pancreas could be computed using enhancement measured only with two CT scan phases, if aortic peak enhancement and bolus shape are known.

Published
2022

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