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1. Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Yeoh, Su-Ann, Gianfrancesco, Milena, Lawson-Tovey, Saskia, Hyrich, Kimme L, Strangfeld, Anja, Gossec, Laure, Carmona, Loreto, Mateus, Elsa F, Schäfer, Martin, Richez, Christophe, Hachulla, Eric, Holmqvist, Marie, Scirè, Carlo Alberto, Lorenz, Hanns-Martin, Voll, Reinhard E, Hasseli, Rebecca, Jayatilleke, Arundathi, Hsu, Tiffany Y-T, D’Silva, Kristin M, Pimentel-Quiroz, Victor R, del Mercado, Monica Vasquez, Shinjo, Samuel Katsuyuki, dos Reis Neto, Edgard Torres, da Rocha, Laurindo Ferreira, de Oliveira e Silva Montandon, Ana Carolina, Pons-Estel, Guillermo J, Ornella, Sofía, Exeni, Maria Eugenia D'Angelo, Velozo, Edson, Jordan, Paula, Sirotich, Emily, Hausmann, Jonathan S, Liew, Jean W, Jacobsohn, Lindsay, Gore-Massy, Monique, Sufka, Paul, Grainger, Rebecca, Bhana, Suleman, Wallace, Zachary, Robinson, Philip C, Yazdany, Jinoos, and Machado, Pedro M

Subjects
Aging, Autoimmune Disease, Rare Diseases, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, COVID-19, COVID-19 Testing, Female, Humans, Male, Myositis, Physicians, Prednisolone, Registries, Rheumatology, Rituximab, polymyositis, dermatomyositis, outcome assessment, health care, epidemiology, COVID-19 Global Rheumatology Alliance, outcome assessment, health care, Clinical Sciences
Abstract

ObjectivesTo investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death.ResultsOf 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65-1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51-0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively).ConclusionsThis is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with IIM.

Published
2022

2. A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Author

Fernandez-Jimenez, Nora, Fore, Ruby, Cilleros-Portet, Ariadna, Lepeule, Johanna, Perron, Patrice, Kvist, Tuomas, Tian, Fu-Ying, Lesseur, Corina, Binder, Alexandra M, Lozano, Manuel, Martorell-Marugán, Jordi, Loke, Yuk J, Bakulski, Kelly M, Zhu, Yihui, Forhan, Anne, Sammallahti, Sara, Everson, Todd M, Chen, Jia, Michels, Karin B, Belmonte, Thalia, Carmona-Sáez, Pedro, Halliday, Jane, Daniele Fallin, M, LaSalle, Janine M, Tost, Jorg, Czamara, Darina, Fernández, Mariana F, Gómez-Martín, Antonio, Craig, Jeffrey M, Gonzalez-Alzaga, Beatriz, Schmidt, Rebecca J, Dou, John F, Muggli, Evelyne, Lacasaña, Marina, Vrijheid, Martine, Marsit, Carmen J, Karagas, Margaret R, Räikkönen, Katri, Bouchard, Luigi, Heude, Barbara, Santa-Marina, Loreto, Bustamante, Mariona, Hivert, Marie-France, and Bilbao, Jose Ramon

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Prevention, Pregnancy, Maternal Health, Conditions Affecting the Embryonic and Fetal Periods, Women's Health, Childhood Obesity, Pediatric, Human Genome, Obesity, Nutrition, Genetics, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Reproductive health and childbirth, Good Health and Well Being, Infant, Newborn, Child, Humans, Female, Body Mass Index, DNA Methylation, Placenta, Mothers, Child Health, Biological sciences, Biomedical and clinical sciences
Abstract

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

Published
2022

3. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry

Author

Sparks, Jeffrey A, Wallace, Zachary S, Seet, Andrea M, Gianfrancesco, Milena A, Izadi, Zara, Hyrich, Kimme L, Strangfeld, Anja, Gossec, Laure, Carmona, Loreto, Mateus, Elsa F, Lawson-Tovey, Saskia, Trupin, Laura, Rush, Stephanie, Katz, Patricia, Schmajuk, Gabriela, Jacobsohn, Lindsay, Wise, Leanna, Gilbert, Emily L, Duarte-García, Ali, Valenzuela-Almada, Maria O, Pons-Estel, Guillermo J, Isnardi, Carolina A, Berbotto, Guillermo A, Hsu, Tiffany Y-T, D’Silva, Kristin M, Patel, Naomi J, Kearsley-Fleet, Lianne, Schäfer, Martin, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Tidblad, Liselotte, Scirè, Carlo Alberto, Raffeiner, Bernd, Thomas, Thierry, Flipo, René-Marc, Avouac, Jérôme, Seror, Raphaèle, Bernardes, Miguel, Cunha, Maria Margarida, Hasseli, Rebecca, Schulze-Koops, Hendrik, Müller-Ladner, Ulf, Specker, Christof, de Souza, Viviane Angelina, da Mota, Licia Maria Henrique, Gomides, Ana Paula Monteiro, Dieudé, Philippe, Nikiphorou, Elena, Kronzer, Vanessa L, Singh, Namrata, Ugarte-Gil, Manuel F, Wallace, Beth, Akpabio, Akpabio, Thomas, Ranjeny, Bhana, Suleman, Costello, Wendy, Grainger, Rebecca, Hausmann, Jonathan S, Liew, Jean W, Sirotich, Emily, Sufka, Paul, Robinson, Philip C, Machado, Pedro M, Yazdany, Jinoos, Dahou, Brahim, Quintana, Rosana, Gómez, Gimena, Roberts, Karen, Baez, Roberto Miguel, Coello, Vanessa Castro, Salinas, María Haye, Maldonado, Federico Nicolas, Reyes, Alvaro Andres, Alle, Gelsomina, Tanten, Romina, Ficco, Hernán Maldonado, Nieto, Romina, Gobbi, Carla, Tissera, Yohana, Pisoni, Cecilia, Paula, Alba, Albiero, Juan Alejandro, Schmid, Maria Marcela, Cosatti, Micaela, Gamba, Maria Julieta, Leandro, Carlevaris, Cusa, María Alejandra, German, Noelia, Bellomio, Veronica, Takashima, Lorena, Pera, Mariana, Cogo, Karina, Elkin, Maria Soledad, Medina, María Alejandra, Savio, Veronica, Tessel, Ivana Romina, Alamino, Rodolfo Perez, Werner, Marina Laura, Ornella, Sofía, and Casalla, Luciana

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Coronaviruses, Emerging Infectious Diseases, Infectious Diseases, Arthritis, Rheumatoid Arthritis, Autoimmune Disease, 6.1 Pharmaceuticals, Inflammatory and immune system, Good Health and Well Being, Aged, Antirheumatic Agents, Arthritis, Rheumatoid, COVID-19, Female, Humans, Male, Middle Aged, Registries, SARS-CoV-2, Severity of Illness Index, COVID-19 Global Rheumatology Alliance, Covid-19, abatacept, rheumatoid arthritis, rituximab, tumour necrosis factor inhibitors, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveTo investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Published
2021

4. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Strangfeld, Anja, Schäfer, Martin, Gianfrancesco, Milena A, Lawson-Tovey, Saskia, Liew, Jean W, Ljung, Lotta, Mateus, Elsa F, Richez, Christophe, Santos, Maria J, Schmajuk, Gabriela, Scirè, Carlo A, Sirotich, Emily, Sparks, Jeffrey A, Sufka, Paul, Thomas, Thierry, Trupin, Laura, Wallace, Zachary S, Al-Adely, Sarah, Bachiller-Corral, Javier, Bhana, Suleman, Cacoub, Patrice, Carmona, Loreto, Costello, Ruth, Costello, Wendy, Gossec, Laure, Grainger, Rebecca, Hachulla, Eric, Hasseli, Rebecca, Hausmann, Jonathan S, Hyrich, Kimme L, Izadi, Zara, Jacobsohn, Lindsay, Katz, Patricia, Kearsley-Fleet, Lianne, Robinson, Philip C, Yazdany, Jinoos, Machado, Pedro M, Dahou, Brahim, Pinheiro, Marcelo, Ribeiro, Francinne M, Chassin-Trubert, Anne-Marie, Ibáñez, Sebastián, Dong, Lingli, Cajas, Lui, Hamoud, Hesham, Avouac, Jérôme, Belin, Véronique, Borie, Raphaël, Chazerain, Pascal, Chevalier, Xavier, Claudepierre, Pascal, Clavel, Gaëlle, Colette-Cedoz, Marie-Eve, Combe, Bernard, Constant, Elodie, Costedoat-Chalumeau, Nathalie, Desmurs, Marie, Devauchelle-Pensec, Valérie, Devaux, Mathilde, Dhote, Robin, Dieudonné, Yannick, Domont, Fanny, Duret, Pierre-Marie, Ebbo, Mikaël, Ebstein, Esther, Mahou, Soumaya El, Fautrel, Bruno, Felten, Renaud, Flipo, René-Marc, Foltz, Violaine, Froissart, Antoine, Galland, Joris, Gaud-Listrat, Véronique, Georgin-Lavialle, Sophie, Giraud-Morelet, Aude, Quitrec, Jeanine S Giraudet-Le, Goupille, Philippe, Govindaraju-Audouard, Sophie, Grados, Franck, Guillaume-Czitrom, Séverine, Hermet, Marion, Hittinger-Roux, Ambre, Hudry, Christophe, Kone-Paut, Isabelle, La Batide Alanore, Sylvain, Lafforgue, Pierre, Lahalle, Sophie, Lambrecht, Isabelle, Langlois, Vincent, Larbre, Jean-Paul, Ledoult, Emmanuel, Leroux, Christophe, Liote, Frédéric, Maria, Alexandre TJ, Marotte, Hubert, Mekinian, Arsène, Melki, Isabelle, Messer, Laurent, Michel, Catherine, and Morel, Gauthier

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Autoimmune Disease, Infectious Diseases, Coronaviruses, Arthritis, Emerging Infectious Diseases, Inflammatory and immune system, Cardiovascular, Good Health and Well Being, Aged, Antirheumatic Agents, COVID-19, Comorbidity, Female, Global Health, Glucocorticoids, Humans, Male, Middle Aged, Odds Ratio, Registries, Rheumatic Diseases, Rheumatology, SARS-CoV-2, antirheumatic agents, autoimmune diseases, epidemiology, glucocorticoids, outcome assessment, health care, COVID-19 Global Rheumatology Alliance, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectivesTo determine factors associated with COVID-19-related death in people with rheumatic diseases.MethodsPhysician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.ResultsOf 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.ConclusionAmong people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Published
2021

5. Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity

Author

Fernández-Tussy, Pablo, Rodríguez-Agudo, Rubén, Fernández-Ramos, David, Barbier-Torres, Lucía, Zubiete-Franco, Imanol, Davalillo, Sergio López de, Herraez, Elisa, Goikoetxea-Usandizaga, Naroa, Lachiondo-Ortega, Sofia, Simón, Jorge, Lopitz-Otsoa, Fernando, Juan, Virginia Gutiérrez-de, McCain, Misti V, Perugorria, Maria J, Mabe, Jon, Navasa, Nicolás, Rodrigues, Cecilia MP, Fabregat, Isabel, Boix, Loreto, Sapena, Victor, Anguita, Juan, Lu, Shelly C, Mato, José M, Banales, Jesus M, Villa, Erica, Reeves, Helen L, Bruix, Jordi, Reig, Maria, Marin, Jose JG, Delgado, Teresa C, and Martínez-Chantar, María L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Liver Disease, Digestive Diseases, Liver Cancer, Rare Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Animals, Apoptosis, Cell Death, Female, Humans, Liver Neoplasms, Mice, Mice, Nude, MicroRNAs, Mitochondria, Biochemistry and Cell Biology, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Dysregulation of miRNAs is a hallmark of cancer, modulating oncogenes, tumor suppressors, and drug responsiveness. The multi-kinase inhibitor sorafenib is one of the first-line drugs for advanced hepatocellular carcinoma (HCC), although the outcome for treated patients is heterogeneous. The identification of predictive biomarkers and targets of sorafenib efficacy are sorely needed. Thus, selected top upregulated miRNAs from the C19MC cluster were analyzed in different hepatoma cell lines compared to immortalized liver human cells, THLE-2 as control. MiR-518d-5p showed the most consistent upregulation among them. Thus, miR-518d-5p was measured in liver tumor/non-tumor samples of two distinct cohorts of HCC patients (n = 16 and n = 20, respectively). Circulating miR-518d-5p was measured in an independent cohort of HCC patients receiving sorafenib treatment (n = 100), where miR-518d-5p was analyzed in relation to treatment duration and patient's overall survival. In vitro and in vivo studies were performed in human hepatoma BCLC3 and Huh7 cells to analyze the effect of miR-518d-5p inhibition/overexpression during the response to sorafenib. Compared with healthy individuals, miR-518d-5p levels were higher in hepatic and serum samples from HCC patients (n = 16) and in an additional cohort of tumor/non-tumor paired samples (n = 20). MiR-518d-5p, through the inhibition of c-Jun and its mitochondrial target PUMA, desensitized human hepatoma cells and mouse xenograft to sorafenib-induced apoptosis. Finally, serum miR-518d-5p was assessed in 100 patients with HCC of different etiologies and BCLC-stage treated with sorafenib. In BCLC-C patients, higher serum miR-518d-5p at diagnosis was associated with shorter sorafenib treatment duration and survival. Hence, hepatic miR-518d-5p modulates sorafenib resistance in HCC through inhibition of c-Jun/PUMA-induced apoptosis. Circulating miR-518d-5p emerges as a potential lack of response biomarker to sorafenib in BCLC-C HCC patients.

Published
2021

6. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Gianfrancesco, Milena, Hyrich, Kimme L, Al-Adely, Sarah, Carmona, Loreto, Danila, Maria I, Gossec, Laure, Izadi, Zara, Jacobsohn, Lindsay, Katz, Patricia, Lawson-Tovey, Saskia, Mateus, Elsa F, Rush, Stephanie, Schmajuk, Gabriela, Simard, Julia, Strangfeld, Anja, Trupin, Laura, Wysham, Katherine D, Bhana, Suleman, Costello, Wendy, Grainger, Rebecca, Hausmann, Jonathan S, Liew, Jean W, Sirotich, Emily, Sufka, Paul, Wallace, Zachary S, Yazdany, Jinoos, Machado, Pedro M, and Robinson, Philip C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Autoimmune Disease, Emerging Infectious Diseases, Infectious Diseases, Arthritis, 6.1 Pharmaceuticals, Inflammatory and immune system, Good Health and Well Being, Adolescent, Adult, Aged, Anti-Inflammatory Agents, Non-Steroidal, Antimalarials, Antirheumatic Agents, Arthritis, Psoriatic, Arthritis, Rheumatoid, Betacoronavirus, Biological Products, COVID-19, Coronavirus Infections, Female, Glucocorticoids, Hospitalization, Humans, Janus Kinase Inhibitors, Lupus Erythematosus, Systemic, Male, Middle Aged, Multivariate Analysis, Pandemics, Pneumonia, Viral, Prednisone, Protective Factors, Registries, Rheumatic Diseases, Risk Factors, SARS-CoV-2, Severity of Illness Index, Spondylarthropathies, Tumor Necrosis Factor Inhibitors, Vasculitis, Young Adult, COVID-19 Global Rheumatology Alliance, arthritis, rheumatoid, hydroxychloroquine, lupus erythematosus, systemic, methotrexate, tumor necrosis factor inhibitors, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectivesCOVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease.MethodsCase series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed.ResultsA total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed.ConclusionsWe found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

Published
2020

7. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian’an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, and Trier, Caecilie

Subjects
Biological Sciences, Genetics, Cardiovascular, Perinatal Period - Conditions Originating in Perinatal Period, Nutrition, Prevention, Preterm, Low Birth Weight and Health of the Newborn, Pediatric, Obesity, Conditions Affecting the Embryonic and Fetal Periods, Infant Mortality, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Birth Weight, Blood Pressure, Body Height, Diabetes Mellitus, Type 2, Female, Fetal Development, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Diseases, Humans, Infant, Newborn, Male, Maternal Inheritance, Maternal-Fetal Exchange, Metabolic Diseases, Models, Genetic, Polymorphism, Single Nucleotide, Pregnancy, Risk Factors, EGG Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Published
2019

8. The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Author

Verbitsky, Miguel, Westland, Rik, Perez, Alejandra, Kiryluk, Krzysztof, Liu, Qingxue, Krithivasan, Priya, Mitrotti, Adele, Fasel, David, Batourina, Ekaterina, Sampson, Matthew, Bodria, Monica, Werth, Max, Kao, Charlly, Martino, Jeremiah, Capone, Valentina, Vivante, Asaf, Shril, Shirlee, Kil, Byum, Marasà, Maddalena, Zhang, Jun, Na, Young-Ji, Lim, Tze, Ahram, Dina, Weng, Patricia, Heinzen, Erin, Carrea, Alba, Piaggio, Giorgio, Gesualdo, Loreto, Manca, Valeria, Masnata, Giuseppe, Gigante, Maddalena, Cusi, Daniele, Izzi, Claudia, Scolari, Francesco, van Wijk, Joanna, Saraga, Marijan, Santoro, Domenico, Conti, Giovanni, Zamboli, Pasquale, White, Hope, Drozdz, Dorota, Zachwieja, Katarzyna, Miklaszewska, Monika, Tkaczyk, Marcin, Tomczyk, Daria, Krakowska, Anna, Sikora, Przemyslaw, Jarmoliński, Tomasz, Borszewska-Kornacka, Maria, Pawluch, Robert, Szczepanska, Maria, Adamczyk, Piotr, Mizerska-Wasiak, Malgorzata, Krzemien, Grazyna, Szmigielska, Agnieszka, Zaniew, Marcin, Dobson, Mark, Darlow, John, Puri, Prem, Barton, David, Furth, Susan, Warady, Bradley, Gucev, Zoran, Lozanovski, Vladimir, Tasic, Velibor, Pisani, Isabella, Allegri, Landino, Rodas, Lida, Campistol, Josep, Jeanpierre, Cécile, Alam, Shumyle, Casale, Pasquale, Wong, Craig, Lin, Fangming, Miranda, Débora, Oliveira, Eduardo, Simões-E-Silva, Ana, Barasch, Jonathan, Levy, Brynn, Wu, Nan, Hildebrandt, Friedhelm, Ghiggeri, Gian, Latos-Bielenska, Anna, Materna-Kiryluk, Anna, Zhang, Feng, Hakonarson, Hakon, Papaioannou, Virginia, Mendelsohn, Cathy, Gharavi, Ali, and Sanna-Cherchi, Simone

Subjects
Chromosome Deletion, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney, Male, Urinary Tract, Urogenital Abnormalities, Vesico-Ureteral Reflux
Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

Published
2019

9. Sex differences in smoking cessation: a retrospective cohort study in a psychosocial care unit in Brazil

Author

Bruna Beatriz Sales Guimarães-Pereira, Anderson Sousa Martins-da-Silva, Danielle Ruiz Lima, Carlos Felipe Cavalcanti Carvalho, Aline Rodrigues Loreto, Lucas Pequeno Galvão, Fernanda Piotto Frallonardo, Flavia Ismael, Julio Torales, Antonio Ventriglio, Arthur Guerra de Andrade, and João Mauricio Castaldelli-Maia

Subjects
Tobacco use cessation, female, tobacco use disorder, Psychiatry, RC435-571
Abstract

Abstract Introduction Despite the results of epidemiological and psychometric studies reporting comparable levels of tobacco dependence among males and females, some clinical studies have detected disparities. Some smoking cessation studies based on clinical setting programs reported poorer outcomes among women than men. Methods This retrospective cohort study aimed to compare treatment success and retention between men and women on a smoking cessation program (n = 1,014) delivered at a CAPS-AD unit in Brazil. The psychological intervention lasted 6 weeks for each group of 15 patients. Each patient had to participate in weekly group cognitive-behavioral therapy (CBT) sessions and individual medical appointments during this period. These appointments were focused on the possibility of prescribing pharmacological treatment (i.e., nicotine replacement therapy, bupropion, or nortriptyline) as adjuvants to group therapy. Results The women had lower smoking severity at baseline, more clinical symptoms, and lower prevalence of alcohol and drug use disorders and were older than the men. Females had significantly higher levels of success (36.6% vs. 29.7%) and retention (51.6% vs. 41.4%) than males. Sensitivity analysis showed that female gender was significantly associated with both retention and success, among those without drug use disorders only. Conclusion Depending on the smoking cessation setting (i.e., low and middle-income countries and mental health and addiction care units), females can achieve similar and even higher quit rates than males. Previous drug use disorder was an important confounding variable in the gender outcomes analyses. Future studies should try to replicate these positive smoking cessation effects of CBT-based group therapy plus pharmacotherapy in women.

Published
2023
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10. Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania

Author

Santos, Susana, Eekhout, Iris, Voerman, Ellis, Gaillard, Romy, Barros, Henrique, Charles, Marie-Aline, Chatzi, Leda, Chevrier, Cécile, Chrousos, George P, Corpeleijn, Eva, Costet, Nathalie, Crozier, Sarah, Doyon, Myriam, Eggesbø, Merete, Fantini, Maria Pia, Farchi, Sara, Forastiere, Francesco, Gagliardi, Luigi, Georgiu, Vagelis, Godfrey, Keith M, Gori, Davide, Grote, Veit, Hanke, Wojciech, Hertz-Picciotto, Irva, Heude, Barbara, Hivert, Marie-France, Hryhorczuk, Daniel, Huang, Rae-Chi, Inskip, Hazel, Jusko, Todd A, Karvonen, Anne M, Koletzko, Berthold, Küpers, Leanne K, Lagström, Hanna, Lawlor, Debbie A, Lehmann, Irina, Lopez-Espinosa, Maria-Jose, Magnus, Per, Majewska, Renata, Mäkelä, Johanna, Manios, Yannis, McDonald, Sheila W, Mommers, Monique, Morgen, Camilla S, Moschonis, George, Murínová, Ľubica, Newnham, John, Nohr, Ellen A, Andersen, Anne-Marie Nybo, Oken, Emily, Oostvogels, Adriëtte JJM, Pac, Agnieszka, Papadopoulou, Eleni, Pekkanen, Juha, Pizzi, Costanza, Polanska, Kinga, Porta, Daniela, Richiardi, Lorenzo, Rifas-Shiman, Sheryl L, Roeleveld, Nel, Santa-Marina, Loreto, Santos, Ana C, Smit, Henriette A, Sørensen, Thorkild IA, Standl, Marie, Stanislawski, Maggie, Stoltenberg, Camilla, Thiering, Elisabeth, Thijs, Carel, Torrent, Maties, Tough, Suzanne C, Trnovec, Tomas, van Gelder, Marleen MHJ, van Rossem, Lenie, von Berg, Andrea, Vrijheid, Martine, Vrijkotte, Tanja GM, Zvinchuk, Oleksandr, van Buuren, Stef, and Jaddoe, Vincent WV

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Health Sciences, Women's Health, Obesity, Perinatal Period - Conditions Originating in Perinatal Period, Clinical Research, Contraception/Reproduction, Pediatric, Nutrition, Pregnancy, Prevention, Maternal Health, Reproductive health and childbirth, Good Health and Well Being, Adult, Body Mass Index, Europe, Female, Gestational Weight Gain, Humans, North America, Oceania, Pregnancy Complications, Pregnancy Outcome, Risk Factors, Weight gain, Charts, References, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundGestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.MethodsWe used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.ResultsWe observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.ConclusionsGestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

Published
2018

11. Cortical sources of resting state EEG rhythms are related to brain hypometabolism in subjects with Alzheimer's disease: an EEG-PET study

Author

Babiloni, Claudio, Del Percio, Claudio, Caroli, Anna, Salvatore, Elena, Nicolai, Emanuele, Marzano, Nicola, Lizio, Roberta, Cavedo, Enrica, Landau, Susan, Chen, Kewei, Jagust, William, Reiman, Eric, Tedeschi, Gioacchino, Montella, Patrizia, De Stefano, Manuela, Gesualdo, Loreto, Frisoni, Giovanni B, and Soricelli, Andrea

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Acquired Cognitive Impairment, Brain Disorders, Biomedical Imaging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Alzheimer's Disease, Neurosciences, Aging, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Brain, Electroencephalography, Female, Humans, Male, Neuroimaging, Positron-Emission Tomography, Rest, Alzheimer's disease, Brain hypometabolism, Fluorodeoxyglucose positron emission tomography, Low resolution brain electromagnetic tomography, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Cortical sources of resting state electroencephalographic (EEG) delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms show abnormal activity (i.e., current density) in patients with dementia due to Alzheimer's disease (AD). Here, we hypothesized that abnormality of this activity is related to relevant disease processes as revealed by cortical hypometabolism typically observed in AD patients by fluorodeoxyglucose positron emission tomography. Resting state eyes-closed EEG data were recorded in 19 AD patients with dementia and 40 healthy elderly (Nold) subjects. EEG frequency bands of interest were delta and low-frequency alpha. EEG sources were estimated in these bands by low-resolution brain electromagnetic tomography (LORETA). Fluorodeoxyglucose positron emission tomography images were recorded only in the AD patients, and cortical hypometabolism was indexed by the so-called Alzheimer's discrimination analysis tool (PALZ) in the frontal association, ventromedial frontal, temporoparietal association, posterior cingulate, and precuneus areas. Results showed that compared with the Nold group, the AD group pointed to higher activity of delta sources and lower activity of low-frequency alpha sources in a cortical region of interest formed by all cortical areas of the PALZ score. In the AD patients, there was a positive correlation between the PALZ score and the activity of delta sources in the cortical region of interest (p < 0.05). These results suggest a relationship between resting state cortical hypometabolism and synchronization of cortical neurons at delta rhythms in AD patients with dementia.

Published
2016

12. Rationale and design of a long term follow-up study of women who did and did not receive HPV 16/18 vaccination in Guanacaste, Costa Rica.

Author

Gonzalez, Paula, Hildesheim, Allan, Herrero, Rolando, Katki, Hormuzd, Wacholder, Sholom, Porras, Carolina, Safaeian, Mahboobeh, Jimenez, Silvia, Schiller, John, Ocampo, Rebeca, Schussler, John, Lowy, Douglas, Guillen, Diego, Stoler, Mark, Quint, Wim, Morales, Jorge, Avila, Carlos, Rodriguez, Ana, Kreimer, Aimée, Cortes, Bernal, Befano, Brian, Schiffman, Mark, Carvajal, Loreto, Palefsky, Joel, and Darragh, Teresa

Subjects
Human papillomavirus, Long term follow-up, Methods, Vaccines, Adult, Costa Rica, Cross-Over Studies, Early Detection of Cancer, Female, Follow-Up Studies, Hepatitis A Vaccines, Human papillomavirus 16, Human papillomavirus 18, Humans, Papillomavirus Infections, Papillomavirus Vaccines, Research Design, Time Factors, Uterine Cervical Diseases, Uterine Cervical Neoplasms, Vaccination, Young Adult, Uterine Cervical Dysplasia
Abstract

The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participation in LTFU. To provide underlying rates of HPV acquisition and cervical disease among unvaccinated women to compare with the HPV-arm during LTFU, a new unvaccinated control group (UCG) of women who are beyond the age generally recommended for routine vaccination was enrolled, and will be followed by cervical cancer screening over 6 years. To form the UCG, 5000 women were selected from a local census, of whom 2836 women (61% of eligible women) agreed to participate. Over 90% of participants complied with an interview, blood and cervical specimen collection. Evaluation of comparability between the original (Hepatitis-A arm of CVT) and new (UCG) control groups showed that womens characteristics, as well as their predicted future risk for cervical HPV acquisition, were similar, thus validating use of the UCG. LTFU is poised to comprehensively address many important questions related to long-term effects of prophylactic HPV vaccines.

Published
2015

13. Mutations in DSTYK and Dominant Urinary Tract Malformations

Author

Sanna-Cherchi, Simone, Sampogna, Rosemary V, Papeta, Natalia, Burgess, Katelyn E, Nees, Shannon N, Perry, Brittany J, Choi, Murim, Bodria, Monica, Liu, Yan, Weng, Patricia L, Lozanovski, Vladimir J, Verbitsky, Miguel, Lugani, Francesca, Sterken, Roel, Paragas, Neal, Caridi, Gianluca, Carrea, Alba, Dagnino, Monica, Materna-Kiryluk, Anna, Santamaria, Giuseppe, Murtas, Corrado, Ristoska-Bojkovska, Nadica, Izzi, Claudia, Kacak, Nilgun, Bianco, Beatrice, Giberti, Stefania, Gigante, Maddalena, Piaggio, Giorgio, Gesualdo, Loreto, Vukic, Durdica Kosuljandic, Vukojevic, Katarina, Saraga-Babic, Mirna, Saraga, Marijan, Gucev, Zoran, Allegri, Landino, Latos-Bielenska, Anna, Casu, Domenica, State, Matthew, Scolari, Francesco, Ravazzolo, Roberto, Kiryluk, Krzysztof, Al-Awqati, Qais, D'Agati, Vivette D, Drummond, Iain A, Tasic, Velibor, Lifton, Richard P, Ghiggeri, Gian Marco, and Gharavi, Ali G

Subjects
Urologic Diseases, Pediatric, Congenital Structural Anomalies, Human Genome, Kidney Disease, Biotechnology, Genetics, Clinical Research, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, Renal and urogenital, Adult, Animals, Base Sequence, Child, Exome, Female, Gene Knockdown Techniques, Genetic Linkage, Genome-Wide Association Study, Heterozygote, Humans, Infant, Kidney, Male, Mice, Molecular Sequence Data, Mutation, Pedigree, RNA, Small Interfering, Receptor-Interacting Protein Serine-Threonine Kinases, Urinary Tract, Urogenital Abnormalities, Young Adult, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundCongenital abnormalities of the kidney and the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and the etiologic factors are poorly understood.MethodsWe performed genomewide linkage analysis and whole-exome sequencing in a family with an autosomal dominant form of congenital abnormalities of the kidney or urinary tract (seven affected family members). We also performed a sequence analysis in 311 unrelated patients, as well as histologic and functional studies.ResultsLinkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single, rare, deleterious variant within these linkage intervals, a heterozygous splice-site mutation in the dual serine-threonine and tyrosine protein kinase gene (DSTYK). This variant, which resulted in aberrant splicing of messenger RNA, was present in all affected family members. Additional, independent DSTYK mutations, including nonsense and splice-site mutations, were detected in 7 of 311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in developmental defects in multiple organs, which suggested loss of fibroblast growth factor (FGF) signaling. Consistent with this finding is the observation that DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated phosphorylation of extracellular-signal-regulated kinase (ERK), the principal signal downstream of receptor tyrosine kinases.ConclusionsWe detected independent DSTYK mutations in 2.3% of patients with congenital abnormalities of the kidney or urinary tract, a finding that suggests that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling. (Funded by the National Institutes of Health and others.).

Published
2013

14. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010

Author

Vos, Theo, Flaxman, Abraham D, Naghavi, Mohsen, Lozano, Rafael, Michaud, Catherine, Ezzati, Majid, Shibuya, Kenji, Salomon, Joshua A, Abdalla, Safa, Aboyans, Victor, Abraham, Jerry, Ackerman, Ilana, Aggarwal, Rakesh, Ahn, Stephanie Y, Ali, Mohammed K, AlMazroa, Mohammad A, Alvarado, Miriam, Anderson, H Ross, Anderson, Laurie M, Andrews, Kathryn G, Atkinson, Charles, Baddour, Larry M, Bahalim, Adil N, Barker-Collo, Suzanne, Barrero, Lope H, Bartels, David H, Basáñez, Maria-Gloria, Baxter, Amanda, Bell, Michelle L, Benjamin, Emelia J, Bennett, Derrick, Bernabé, Eduardo, Bhalla, Kavi, Bhandari, Bishal, Bikbov, Boris, Bin Abdulhak, Aref, Birbeck, Gretchen, Black, James A, Blencowe, Hannah, Blore, Jed D, Blyth, Fiona, Bolliger, Ian, Bonaventure, Audrey, Boufous, Soufiane, Bourne, Rupert, Boussinesq, Michel, Braithwaite, Tasanee, Brayne, Carol, Bridgett, Lisa, Brooker, Simon, Brooks, Peter, Brugha, Traolach S, Bryan-Hancock, Claire, Bucello, Chiara, Buchbinder, Rachelle, Buckle, Geoffrey, Budke, Christine M, Burch, Michael, Burney, Peter, Burstein, Roy, Calabria, Bianca, Campbell, Benjamin, Canter, Charles E, Carabin, Hélène, Carapetis, Jonathan, Carmona, Loreto, Cella, Claudia, Charlson, Fiona, Chen, Honglei, Cheng, Andrew Tai-Ann, Chou, David, Chugh, Sumeet S, Coffeng, Luc E, Colan, Steven D, Colquhoun, Samantha, Colson, K Ellicott, Condon, John, Connor, Myles D, Cooper, Leslie T, Corriere, Matthew, Cortinovis, Monica, de Vaccaro, Karen Courville, Couser, William, Cowie, Benjamin C, Criqui, Michael H, Cross, Marita, Dabhadkar, Kaustubh C, Dahiya, Manu, Dahodwala, Nabila, Damsere-Derry, James, Danaei, Goodarz, Davis, Adrian, De Leo, Diego, Degenhardt, Louisa, Dellavalle, Robert, Delossantos, Allyne, Denenberg, Julie, Derrett, Sarah, Jarlais, Don C Des, and Dharmaratne, Samath D

Subjects
Epidemiology, Biomedical and Clinical Sciences, Public Health, Health Sciences, Pain Research, Mental Health, Infectious Diseases, Prevention, Rare Diseases, Aetiology, 2.2 Factors relating to the physical environment, 2.4 Surveillance and distribution, Good Health and Well Being, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Global Health, Health Status, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Prevalence, Quality-Adjusted Life Years, Sex Factors, Wounds and Injuries, Young Adult, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundNon-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs).MethodsOf the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis.FindingsGlobal prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa.InterpretationRates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world.FundingBill & Melinda Gates Foundation.

Published
2012

15. Serum metal levels in a population of Spanish pregnant women

Author

Michael Levi, Loreto Santa-Marina, Ferran Ballester, Sabrina Llop, Mikel Ayerdi, Mario Murcia, Amaia Molinuevo, Miren Begoña Zubero, Manuel Lozano, and Amaia Irizar

Subjects
Iron, Population, trace elements, chemistry.chemical_element, Physiology, Calcium, Overweight, Selenium, Pregnancy, medicine, Animals, Humans, Magnesium, Vitamin B12, education, education.field_of_study, business.industry, Iron levels, Public Health, Environmental and Occupational Health, Vitamins, Anthropometry, medicine.disease, Trace Elements, Zinc, Cross-Sectional Studies, chemistry, Female, Pregnant Women, pregnancy, medicine.symptom, business, serum, Copper
Abstract

Objective: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. Method: Cross-sectional study with 1279 participants from the INMA cohorts. Results: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p = 0.026), for cop-per with excess body weight (p < 0.01), low social class (p = 0.03) and being multipara (p < 0.01), for magnesium with being over 35 years old (p = 0.001), high social class (p = 0.044), primiparous status (p = 0.002) and low daily intake of bread (p = 0.009) and legumes (p = 0.020); for zinc with university edu-cation (p = 0.039) and residence in Gipuzkoa (p < 0.01), and for selenium with residence in Valencia (p < 0.01), university education (p = 0.001), vitamin B6 supplementation (p = 0.006), fish intake (> 71 g/day) (p = 0.014) and having been born in Spain (p = 0.001). Further, lower iron levels were associated with being overweight (p = 0.021) or obese (p < 0.001) and vitamin B12 supplementation (p = 0.006). Conclusions: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables. This study is part of the INMA (Infancia y Medio Ambiente) project. It was supported by grants from Instituto de Salud Carlos III (FIS-FEDER: 06/0867, 09/00090, 13/1944, 16/1288, 19/1338; Miguel Servet-FEDER: CP15/0025; Miguel Servet-FSE: MS15/0025) , by the Council of Gipuzkoa (DFG15/009) and by the Health Department of the Basque Government.

Published
2022
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16. Dropped abdominal pressure at void in women

Author

Juan Pablo Valdevenito, Alejandro Mercado-Campero, Luis López-Fando, Carlos Ignacio Calvo, Valentín Manríquez, and Loreto Medina

Subjects
Urinary Bladder Neck Obstruction, Urodynamics, Cross-Sectional Studies, Urinary Incontinence, Stress, Urology, Humans, Urination, Obstetrics and Gynecology, Female, Retrospective Studies
Abstract

"Dropped pRetrospective cross-sectional study of non-neurological consecutive symptomatic women. The following definitions were used: "dropped pA total of 360 women were analyzed. Ninety-five percent of the women had a variation in pApproximately one-quarter of women had "dropped p

Published
2022
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17. Household income, fetal size and birth weight: an analysis of eight populations

Author

Steve Turner, Anke G Posthumus, Eric A P Steegers, Amel AlMakoshi, Bahauddin Sallout, Sheryl L Rifas-Shiman, Emily Oken, Ben Kumwenda, Fatemah Alostad, Catherine Wright-Corker, Laura Watson, Diane Mak, Hiu Ching Cheung, Alice Judge, Lorna Aucott, Vincent W V Jaddoe, Isabella Annesi Maesano, Munawar Hussain Soomro, Peter Hindmarsh, Geir Jacobsen, Torstein Vik, Isolina Riaño-Galan, Ana Cristina Rodríguez-Dehli, Aitana Lertxundi, Loreto Santa Marina Rodriguez, Martine Vrijheid, Jordi Julvez, Ana Esplugues, Carmen Iñiguez, Obstetrics & Gynecology, Erasmus MC other, and Pediatrics

Subjects
Epidemiology, Pregnancy Trimester, Third, EMBRYONIC AND FETAL DEVELOPMENT, Infant, Newborn, Public Health, Environmental and Occupational Health, Ultrasonography, Prenatal, POVERTY, Fetal Development, Cross-Sectional Studies, BIRTH WEIGHT, SDG 3 - Good Health and Well-being, Pregnancy, Pregnancy Trimester, Second, EPIDEMIOLOGY, Birth Weight, Humans, Female
Abstract

BackgroundThe age at onset of the association between poverty and poor health is not understood. Our hypothesis was that individuals from highest household income (HI), compared to those with lowest HI, will have increased fetal size in the second and third trimester and birth.Methods.Second and third trimester fetal ultrasound measurements and birth measurements were obtained from eight cohorts. Results were analysed in cross-sectional two-stage individual patient data (IPD) analyses and also a longitudinal one-stage IPD analysis.ResultsThe eight cohorts included 21 714 individuals. In the two-stage (cross-sectional) IPD analysis, individuals from the highest HI category compared with those from the lowest HI category had larger head size at birth (mean difference 0.22 z score (0.07, 0.36)), in the third trimester (0.25 (0.16, 0.33)) and second trimester (0.11 (0.02, 0.19)). Weight was higher at birth in the highest HI category. In the one-stage (longitudinal) IPD analysis which included data from six cohorts (n=11 062), head size was larger (mean difference 0.13 (0.03, 0.23)) for individuals in the highest HI compared with lowest category, and this difference became greater between the second trimester and birth. Similarly, in the one-stage IPD, weight was heavier in second highest HI category compared with the lowest (mean difference 0.10 (0 .00, 0.20)) and the difference widened as pregnancy progressed. Length was not linked to HI category in the longitudinal model.ConclusionsThe association between HI, an index of poverty, and fetal size is already present in the second trimester.

Published
2022
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18. Kidney failure prediction models

Author

Ramspek, Chava L, Evans, Marie, Wanner, Christoph, Drechsler, Christiane, Chesnaye, Nicholas C, Szymczak, Maciej, Krajewska, Magdalena, Torino, Claudia, Porto, Gaetana, Hayward, Samantha, Caskey, Fergus, Dekker, Friedo W, Jager, Kitty J, van Diepen, Merel, EQUAL Study Investigators: Adamasco Cupisti, Adelia Sagliocca, Alberto Ferraro, Aleksandra Musiała, Alessandra Mele, Alessandro Naticchia, Alex Còsaro, Alistair Woodman, Andrea Ranghino, Andrea Stucchi, Andreas Jonsson, Andreas Schneider, Angelo Pignataro, Anita Schrander, Anke Torp, Anna McKeever, Anna Szymczak, Anna-Lena Blom, Antonella De Blasio, Antonello Pani, Aris Tsalouichos, Asad Ullah, Barbara McLaren, Bastiaan van Dam, Beate Iwig, Bellasi Antonio, Biagio Raffaele Di Iorio, Björn Rogland, Boris Perras, Butti Alessandra, Camille Harron, Carin Wallquist, Carl Siegert, Carla Barrett, Carlo Gaillard, Carlo Garofalo, Cataldo Abaterusso, Charles Beerenhout, Charlotte O'Toole, Chiara Somma, Christian Marx, Christina Summersgill, Christof Blaser, Claudia D'alessandro, Claudia Emde, Claudia Zullo, Claudio Pozzi, Colin Geddes, Cornelis Verburgh, Daniela Bergamo, Daniele Ciurlino, Daria Motta, Deborah Glowski, Deborah McGlynn, Denes Vargas, Detlef Krieter, Domenico Russo, Dunja Fuchs, Dympna Sands, Ellen Hoogeveen, Ellen Irmler, Emöke Dimény, Enrico Favaro, Eva Platen, Ewelina Olczyk, Ewout Hoorn, Federica Vigotti, Ferruccio Ansali, Ferruccio Conte, Francesca Cianciotta, Francesca Giacchino, Francesco Cappellaio, Francesco Pizzarelli, Fredrik Sundelin, Fredrik Uhlin, Gaetano Greco, Geena Roy, Gaetana Porto, Giada Bigatti, Giancarlo Marinangeli, Gianfranca Cabiddu, Gillian Hirst, Giordano Fumagalli, Giorgia Caloro, Giorgina Piccoli, Giovanbattista Capasso, Giovanni Gambaro, Giuliana Tognarelli, Giuseppe Bonforte, Giuseppe Conte, Giuseppe Toscano, Goffredo Del Rosso, Gunilla Welander, Hanna Augustyniak-Bartosik, Hans Boots, Hans Schmidt-Gürtler, Hayley King, Helen McNally, Hendrik Schlee, Henk Boom, Holger Naujoks, Houda Masri-Senghor, Hugh Murtagh, Hugh Rayner, Ilona Miśkowiec-Wiśniewska, Ines Schlee, Irene Capizzi, Isabel Bascaran Hernandez, Ivano Baragetti, Jacek Manitius, Jane Turner, Jan-Willem Eijgenraam, Jeroen Kooman, Joachim Beige, Joanna Pondel, Joanne Wilcox, Jocelyn Berdeprado, Jochen Röthele, Jonathan Wong, Joris Rotmans, Joyce Banda, Justyna Mazur, Kai Hahn, Kamila Jędrzejak, Katarzyna Nowańska, Katja Blouin, Katrin Neumeier, Kirsteen Jones, Kirsten Anding-Rost, Knut-Christian Gröntoft, Lamberto Oldrizzi, Lesley Haydock, Liffert Vogt, Lily Wilkinson, Loreto Gesualdo, Lothar Schramm, Luigi Biancone, Łukasz Nowak, Maarten Raasveld, Magdalena Durlik, Manuela Magnano, Marc Vervloet, Marco Ricardi, Margaret Carmody, Maria Di Bari, Maria Laudato, Maria Luisa Sirico, Maria Stendahl, Maria Svensson, Maria Weetman, Marjolijn van Buren, Martin Joinson, Martina Ferraresi, Mary Dutton, Merel van Diepen, Michael Matthews, Michele Provenzano, Monika Hopf, Moreno Malaguti, Nadja Wuttke, Neal Morgan, Nicola Palmieri, Nikolaus Frischmuth, Nina Bleakley, Paola Murrone, Paul Cockwell, Paul Leurs, Paul Roderick, Pauline Voskamp, Pavlos Kashioulis, Pawlos Ichtiaris, Peter Blankestijn, Petra Kirste, Petra Schulz, Phil Mason, Philip Kalra, Pietro Cirillo, Pietro Dattolo, Pina Acampora, Rincy Sajith, Rita Nigro, Roberto Boero, Roberto Scarpioni, Rosa Sicoli, Rosella Malandra, Sabine Aign, Sabine Cäsar, Sadie van Esch, Sally Chapman, Sandra Biribauer, Santee Navjee, Sarah Crosbie, Sharon Brown, Sheila Tickle, Sherin Manan, Silke Röser, Silvana Savoldi, Silvio Bertoli, Silvio Borrelli, Siska Boorsma, Stefan Heidenreich, Stefan Melander, Stefania Maxia, Stefano Maffei, Stefano Mangano, Stephanie Palm, Stijn Konings, Suresh Mathavakkannan, Susanne Schwedler, Sylke Delrieux, Sylvia Renker, Sylvia Schättel, Szyszkowska Dorota, Teresa Cicchetti, Teresa Nieszporek, Theresa Stephan, Thomas Schmiedeke, Thomas Weinreich, Til Leimbach, Tiziana Rappa, Tora Almquist, Torsten Stövesand, Udo Bahner, Ulrika Jensen, Valentina Palazzo, Walter De Simone, Wolfgang Seeger, Ying Kuan, Zbigniew Heleniak, Zeynep Aydin, Internal Medicine, Chava L, Ramspek, Marie, Evan, Christoph, Wanner, Christiane, Drechsler, Nicholas C, Chesnaye, Maciej, Szymczak, Magdalena, Krajewska, Claudia, Torino, Gaetana, Porto, Samantha, Hayward, Fergus, Caskey, Friedo W, Dekker, Kitty J, Jager, Merel, van Diepen, Study Investigators: Adamasco Cupisti, Equal, Sagliocca, Adelia, Ferraro, Alberto, Musiała, Aleksandra, Mele, Alessandra, Naticchia, Alessandro, Còsaro, Alex, Woodman, Alistair, Ranghino, Andrea, Stucchi, Andrea, Jonsson, Andrea, Schneider, Andrea, Pignataro, Angelo, Schrander, Anita, Torp, Anke, Mckeever, Anna, Szymczak, Anna, Blom, Anna-Lena, De Blasio, Antonella, Pani, Antonello, Tsalouichos, Ari, Ullah, Asad, Mclaren, Barbara, van Dam, Bastiaan, Iwig, Beate, Antonio, Bellasi, Raffaele Di Iorio, Biagio, Rogland, Björn, Perras, Bori, Alessandra, Butti, Harron, Camille, Wallquist, Carin, Siegert, Carl, Barrett, Carla, Gaillard, Carlo, Garofalo, Carlo, Abaterusso, Cataldo, Beerenhout, Charle, O'Toole, Charlotte, Somma, Chiara, Marx, Christian, Summersgill, Christina, Blaser, Christof, D'Alessandro, Claudia, Emde, Claudia, Zullo, Claudia, Pozzi, Claudio, Geddes, Colin, Verburgh, Corneli, Bergamo, Daniela, Ciurlino, Daniele, Motta, Daria, Glowski, Deborah, Mcglynn, Deborah, Vargas, Dene, Krieter, Detlef, Russo, Domenico, Fuchs, Dunja, Sands, Dympna, Hoogeveen, Ellen, Irmler, Ellen, Dimény, Emöke, Favaro, Enrico, Platen, Eva, Olczyk, Ewelina, Hoorn, Ewout, Vigotti, Federica, Ansali, Ferruccio, Conte, Ferruccio, Cianciotta, Francesca, Giacchino, Francesca, Cappellaio, Francesco, Pizzarelli, Francesco, Sundelin, Fredrik, Uhlin, Fredrik, Greco, Gaetano, Roy, Geena, Porto, Gaetana, Bigatti, Giada, Marinangeli, Giancarlo, Cabiddu, Gianfranca, Hirst, Gillian, Fumagalli, Giordano, Caloro, Giorgia, Piccoli, Giorgina, Capasso, Giovanbattista, Gambaro, Giovanni, Tognarelli, Giuliana, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Giuseppe, Del Rosso, Goffredo, Welander, Gunilla, Augustyniak-Bartosik, Hanna, Boots, Han, Schmidt-Gürtler, Han, King, Hayley, Mcnally, Helen, Schlee, Hendrik, Boom, Henk, Naujoks, Holger, Masri-Senghor, Houda, Murtagh, Hugh, Rayner, Hugh, Miśkowiec-Wiśniewska, Ilona, Schlee, Ine, Capizzi, Irene, Bascaran Hernandez, Isabel, Baragetti, Ivano, Manitius, Jacek, Turner, Jane, Eijgenraam, Jan-Willem, Kooman, Jeroen, Beige, Joachim, Pondel, Joanna, Wilcox, Joanne, Berdeprado, Jocelyn, Röthele, Jochen, Wong, Jonathan, Rotmans, Jori, Banda, Joyce, Mazur, Justyna, Hahn, Kai, Jędrzejak, Kamila, Nowańska, Katarzyna, Blouin, Katja, Neumeier, Katrin, Jones, Kirsteen, Anding-Rost, Kirsten, Gröntoft, Knut-Christian, Oldrizzi, Lamberto, Haydock, Lesley, Vogt, Liffert, Wilkinson, Lily, Gesualdo, Loreto, Schramm, Lothar, Biancone, Luigi, Nowak, Łukasz, Raasveld, Maarten, Durlik, Magdalena, Magnano, Manuela, Vervloet, Marc, Ricardi, Marco, Carmody, Margaret, Di Bari, Maria, Laudato, Maria, Luisa Sirico, Maria, Stendahl, Maria, Svensson, Maria, Weetman, Maria, van Buren, Marjolijn, Joinson, Martin, Ferraresi, Martina, Dutton, Mary, van Diepen, Merel, Matthews, Michael, Provenzano, Michele, Hopf, Monika, Malaguti, Moreno, Wuttke, Nadja, Morgan, Neal, Palmieri, Nicola, Frischmuth, Nikolau, Bleakley, Nina, Murrone, Paola, Cockwell, Paul, Leurs, Paul, Roderick, Paul, Voskamp, Pauline, Kashioulis, Pavlo, Ichtiaris, Pawlo, Blankestijn, Peter, Kirste, Petra, Schulz, Petra, Mason, Phil, Kalra, Philip, Cirillo, Pietro, Dattolo, Pietro, Acampora, Pina, Sajith, Rincy, Nigro, Rita, Boero, Roberto, Scarpioni, Roberto, Sicoli, Rosa, Malandra, Rosella, Aign, Sabine, Cäsar, Sabine, van Esch, Sadie, Chapman, Sally, Biribauer, Sandra, Navjee, Santee, Crosbie, Sarah, Brown, Sharon, Tickle, Sheila, Manan, Sherin, Röser, Silke, Savoldi, Silvana, Bertoli, Silvio, Borrelli, Silvio, Boorsma, Siska, Heidenreich, Stefan, Melander, Stefan, Maxia, Stefania, Maffei, Stefano, Mangano, Stefano, Palm, Stephanie, Konings, Stijn, Mathavakkannan, Suresh, Schwedler, Susanne, Delrieux, Sylke, Renker, Sylvia, Schättel, Sylvia, Dorota, Szyszkowska, Cicchetti, Teresa, Nieszporek, Teresa, Stephan, Theresa, Schmiedeke, Thoma, Weinreich, Thoma, Leimbach, Til, Rappa, Tiziana, Almquist, Tora, Stövesand, Torsten, Bahner, Udo, Jensen, Ulrika, Palazzo, Valentina, De Simone, Walter, Seeger, Wolfgang, Kuan, Ying, Heleniak, Zbigniew, Aydin, Zeynep, Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Quality of Care, and APH - Global Health

Subjects
Male, progression of chronic renal failure, medicine.medical_specialty, Time Factors, epidemiology and outcome, 030232 urology & nephrology, Risk Assessment, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Older patients, external validation, Predictive Value of Tests, medicine, Humans, Failure risk, Clinical Epidemiology, In patient, comprehensive external validation, 030212 general & internal medicine, Statistic, Aged, Aged, 80 and over, Kidney, Models, Statistical, business.industry, External validation, General Medicine, prediction, kidney failure, Europe, prediction model, medicine.anatomical_structure, chronic kidney disease, epidemiology and outcomes, prognosis, Nephrology, Emergency medicine, Disease Progression, Kidney Failure, Chronic, Female, business, prognostic, Predictive modelling, prognosi, Cohort study
Abstract

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Published
2021
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19. Update of Robotic Surgery in Benign Gynecological Pathology: Systematic Review

Author

Vito Andrea Capozzi, Elisa Scarpelli, Giulia Armano, Luciano Monfardini, Angela Celardo, Gaetano Maria Munno, Nicola Fortunato, Primo Vagnetti, Maria Teresa Schettino, Giulia Grassini, Domenico Labriola, Carla Loreto, Marco Torella, Stefano Cianci, Capozzi, V. A., Scarpelli, E., Armano, G., Monfardini, L., Celardo, A., Munno, G. M., Fortunato, N., Vagnetti, P., Schettino, M. T., Grassini, G., Labriola, D., Loreto, C., Torella, M., and Cianci, S.

Subjects
United State, endometriosi, Endometriosis, General Medicine, pelvic organ prolapse, Hysterectomy, United States, Gynecologic Surgical Procedures, Robotic Surgical Procedures, Gynecologic Surgical Procedure, Gynecology, robotic surgery, Humans, Female, Laparoscopy, myomectomy, minimally invasive surgery, Human
Abstract

Background and Objectives: Since the Food and Drug Administration’s (FDA) approval in 2005, the application of robotic surgery (RS) in gynecology has been adopted all over the world. This study aimed to provide an update on RS in benign gynecological pathology by reporting the scientific recommendations and high-value scientific literature available to date. Materials and Methods: A systematic review of the literature was performed. Prospective randomized clinical trials (RCT) and large retrospective trials were included in the present review. Results: Twenty-two studies were considered eligible for the review: eight studies regarding robotic myomectomy, five studies on robotic hysterectomy, five studies about RS in endometriosis treatment, and four studies on robotic pelvic organ prolapse (POP) treatment. Overall, 12 RCT and 10 retrospective studies were included in the analysis. In total 269,728 patients were enrolled, 1721 in the myomectomy group, 265,100 in the hysterectomy group, 1527 in the endometriosis surgical treatment group, and 1380 patients received treatment for POP. Conclusions: Currently, a minimally invasive approach is suggested in benign gynecological pathologies. According to the available evidence, RS has comparable clinical outcomes compared to laparoscopy (LPS). RS allowed a growing number of patients to gain access to MIS and benefit from a minimally invasive treatment, due to a flattened learning curve and enhanced dexterity and visualization.

Published
2022

20. A sense of community at school and the subjective well‐being of Chilean students

Author

Alejandra Villarroel, Fernando Reyes, Gisela Carrillo, Jaime Alfaro, and Loreto Ditzel

Subjects
Male, Schools, Social Psychology, Student life, Emotions, education, Sense of community, Life satisfaction, Sample (statistics), Surveys and Questionnaires, Scale (social sciences), Humans, Female, Chile, Dimension (data warehouse), Descriptive research, Subjective well-being, Child, Students, Psychology, Social psychology
Abstract

Understand the degree to which a Sense of Community at School can predict the Life Satisfaction of Chilean students in the fifth and seventh grades. The classroom and school components will be presented separately. The research was designed as a descriptive study using a survey with a probabilistic sample made up of 1959 students (52.6% male and 47.4% female) in the fifth and seventh grades at elementary schools in the cities of Concepción and Santiago in Chile. A multiple linear regression analysis was done using the Multidimensional Scales of School Sense of Community (SOC-S) and Classroom Sense of Community (SOC-C) as predictors of life satisfaction measured with the Student Life Satisfaction Scale (SLSS). Multigroup analysis was conducted to make comparisons by sex and grade. The dimension of "sense of belonging and emotional connection" of the SOC-C and the dimension of "belonging" of the SOC-S predict life satisfaction for fifth grade students. The additional dimension of "emotional connection" of the SOC-S scale was included for the seventh-grade students. The sense that one is part of the school community is a dimension that affects childhood life satisfaction. Its level of contribution varies by age, with the sense of belonging and emotional connection variables being the relevant ones.

Published
2021
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21. Mucocutaneous Manifestations in Autoimmune Gastritis: A Prospective Case-Control Study

Author

Natalia Sabatini, Juan Carlos Roa, Arnoldo Riquelme, Javiera Torres, Gonzalo Latorre, Shailja C. Shah, Sara Maquilon, Lorena Montoya, Loreto Paredes, Alberto Espino, Agustín González, and Marianne Kolbach

Subjects
Male, medicine.medical_specialty, Autoimmune Gastritis, Biopsy, Mucocutaneous zone, Autoimmunity, Vitiligo, Gastroenterology, Article, Parietal Cells, Gastric, Internal medicine, medicine, Humans, Endoscopy, Digestive System, Prospective Studies, Autoantibodies, Hepatology, biology, business.industry, Stomach, Case-control study, Odds ratio, Middle Aged, Alopecia areata, Helicobacter pylori, medicine.disease, biology.organism_classification, Confidence interval, Diabetes Mellitus, Type 1, Case-Control Studies, Gastritis, Female, business, Follow-Up Studies
Abstract

Introduction Autoimmune gastritis (AIG) is associated with nutritional deficiencies, autoimmune diseases, and gastric malignancies. The aims of the study were to test the hypothesis that mucocutaneous (MC) manifestations occur more often in patients with vs without AIG and to delineate patterns of MC manifestations in AIG. Methods A single-center, prospective 2:1 case-control study was conducted. Cases were patients with the diagnosis of AIG based on consistent serologic and histologic findings. Controls had a normal gastric biopsy. MC manifestations were independently evaluated by 3 experienced dermatologists. We conducted a multivariable logistic regression model adjusted for age, sex, Helicobacter pylori, tobacco use, and alcohol consumption to estimate the association between AIG (vs no AIG) and MC manifestations (adjusted odds ratio; 95% confidence interval). Results We prospectively enrolled 60 cases and 30 controls (mean age 53.5 ± 15.8 vs 53.4 ± 14.5 years; 75% vs 73.3% women). The pooled prevalence of MC immune-mediated diseases was higher in patients with vs without AIG (66.7% vs 23.3%; adjusted odds ratio 12.01 [95% confidence interval: 3.51-41.13]). In patients with AIG, seropositive vs seronegative anti-intrinsic factor antibodies more often had concomitant immunological diseases with MC manifestations (100% vs 58.5%; P = 0.016). The most common MC immune-mediated diseases in AIG were Sjogren syndrome (n = 5, 8.3%), alopecia areata (n = 5, 8.3%), and vitiligo (n = 4, 6.7%). Nutritional deficiency-related MC findings, mainly xerosis, lingual, and nail disorders, were also more common in AIG. Discussion This is the first comparative study specifically designed to evaluate MC manifestations in AIG. We demonstrated that AIG is more frequently associated with both immune- and nutritional deficiency-related MC manifestations, which might have both diagnostic and therapeutic clinical implications.

Published
2021
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22. OncomiRs miR-106a and miR-17 negatively regulate the nucleoside-derived drug transporter hCNT1

Author

Mireia Martín-Satué, Marçal Pastor-Anglada, Loreto Boix, Clara Boces-Pascual, Aida Mata-Ventosa, Meritxell Gironella, and Sandra Pérez-Torras

Subjects
Male, Nucleoside analog, Context (language use), Nucleoside transporter, Apoptosis, Biology, medicine.disease_cause, Cellular and Molecular Neuroscience, Nucleòsids, Downregulation and upregulation, Pancreatic cancer, microRNA, medicine, Biomarkers, Tumor, Tumor Cells, Cultured, Humans, Non-coding RNA, Molecular Biology, Càncer de pàncrees, Pancreas cancer, Aged, Cell Proliferation, Pharmacology, CNT1, Cancer, Membrane Transport Proteins, Nucleosides, Cell Biology, Middle Aged, medicine.disease, Prognosis, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Survival Rate, MicroRNAs, Tumor progression, Cancer research, biology.protein, Molecular Medicine, Original Article, Female, Carcinogenesis, Colorectal Neoplasms, Chemoresistance, Carcinoma, Pancreatic Ductal
Abstract

Graphic abstract High-affinity uptake of natural nucleosides as well as nucleoside derivatives used in anticancer therapies is mediated by human concentrative nucleoside transporters (hCNTs). hCNT1, the hCNT family member that specifically transports pyrimidines, is also a transceptor involved in tumor progression. In particular, oncogenesis appears to be associated with hCNT1 downregulation in some cancers, although the underlying mechanisms are largely unknown. Here, we sought to address changes in colorectal and pancreatic ductal adenocarcinoma—both of which are important digestive cancers—in the context of treatment with fluoropyrimidine derivatives. An analysis of cancer samples and matching non-tumoral adjacent tissues revealed downregulation of hCNT1 protein in both types of tumor. Further exploration of the putative regulation of hCNT1 by microRNAs (miRNAs), which are highly deregulated in these cancers, revealed a direct relationship between the oncomiRs miR-106a and miR-17 and the loss of hCNT1. Collectively, our findings provide the first demonstration that hCNT1 inhibition by these oncomiRs could contribute to chemoresistance to fluoropyrimidine-based treatments in colorectal and pancreatic cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03959-8.

Published
2021

23. SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

Author

Anja Strangfeld, Ana M. Rodrigues, Loreto Carmona, Ludovic Trefond, Charalampos Papagoras, Laure Gossec, N Roux, Kimme L. Hyrich, Saskia Lawson-Tovey, Bernd Raffeiner, Elsa F Mateus, Gözde Kübra Yardımcı, Pedro Machado, Xavier Mariette, NIHR Manchester Biomedical Research Centre [Manchester] (BRC [Manchester]), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Centre for Genetics and Genomics Versus Arthritis, Centre for Epidemiology Versus Arthritis, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Instituto de Salud Musculoesqueletica (InMusc), Central Hospital of Bolzano, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital privé Robert-Schuman, Metz, France., Sociedade Portuguesa de Reumatologia [Lisboa], Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Democritus University of Thrace (DUTH), Liga Portuguesa Contra as Doenças Reumaticas (LPCDR), EULAR PARE [Zurich, Switzerland], Université Paris-Saclay, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, University College of London [London] (UCL), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University College London Hospitals (UCLH), London North West University Healthcare NHS Trust (LNWH), European Alliance of Associations for Rheumatology, Service de Rhumatologie [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Molé, Christine

Subjects
Male, medicine.medical_specialty, COVID-19 Vaccines, Immunology, Population, Comorbidity, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Rheumatic Diseases, Internal medicine, Epidemiology, medicine, Humans, Immunology and Allergy, Registries, Adverse effect, education, Aged, Aged, 80 and over, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, education.field_of_study, business.industry, Abatacept, COVID-19, Middle Aged, vaccination, Vaccine efficacy, Vaccination, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Hypertension, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, epidemiology, Rituximab, business, medicine.drug
Abstract

Patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs) are often treated with immunomodulatory or immunosuppressive medications; consequently, they have been excluded alongside other immunocompromised patients from late stages of SARS-CoV-2 vaccine trials. SARS-CoV-2 vaccine efficacy in this population is unclear, though initial data are reassuring overall. However, a slightly lower SARS-CoV-2 immunogenicity of vaccines has been documented in some patients with iRMD.1 2 Some common rheumatic and musculoskeletal disease (RMD) medications have been highlighted as possible influential factors on immunogenicity, particularly rituximab (RTX), mycophenolate mofetil (MMF), methotrexate (MTX), abatacept and glucocorticoids.3–7 The European Alliance of Associations for Rheumatology (EULAR) launched a COVID-19 registry in March 2020, capturing COVID-19 outcomes in the European RMD population. Questions on reinfection and vaccination were added in January 2021. A further EULAR registry (COVAX) was launched in February 2021 to collect data on COVID-19 vaccination and related adverse events among patients with RMD. Here we describe a series of patients who contracted SARS-CoV-2 infection after COVID-19 vaccination between 19 January 2021 and 27 July 2021. The series consists of 38 adults with iRMDs, 8 from the COVID-19 registry (

Published
2021
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24. Prognostic factors and perinatal outcomes in early-onset intrauterine growth restriction due to placental insufficiency

Author

Silvia de Lourdes Loreto Faquini, Gláucia Virgínia de Queiroz Lins Guerra, Isabela Melo Buarque de Gusmão, Alex Sandro Rolland Souza, Lycia Siqueira Vilela, and Marília Wanderley de Siqueira Galindo

Subjects
medicine.medical_specialty, Fetal Growth Retardation, Obstetrics, business.industry, Perinatal Death, Placenta, Infant, Newborn, Obstetrics and Gynecology, Intrauterine growth restriction, Placental insufficiency, medicine.disease, Placental Insufficiency, Prognosis, Oxygen, Neonatal outcomes, Pregnancy, Pediatrics, Perinatology and Child Health, medicine, Humans, Birth Weight, Female, business, Early onset, Retrospective Studies
Abstract

To determine the principal prognostic factors and neonatal outcomes associated with perinatal death in cases of early-onset intrauterine growth restriction (IUGR) due to placental insufficiency and to define the cutoff point for the risk of perinatal death. A retrospective cohort study conducted with 198 pregnant women with a diagnosis of early-onset IUGR (as detected before the 32nd week of gestational age). The association between the dependent variable (perinatal death) and the independent variables was investigated using a multivariate logistic regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of the adjusted model. A significance level of 5% was established for the entire statistical analysis. Perinatal deaths occurred in 89 (44.9%) of the 198 fetuses with early-onset IUGR. Birthweight p < .001), postnatal need for mechanical ventilation (OR: 24.56; 95%CI: 5.58–108.08; p < .001) and postnatal use of an oxygen hood (OR: 0.09; 95%CI: 0.02–0.39; p = .001) remained significantly associated with neonatal death in the multivariate model. The sensitivity, specificity, positive and negative predictive values for birthweight

Published
2022

25. Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study

Author

Zara Izadi, Milena A Gianfrancesco, Gabriela Schmajuk, Lindsay Jacobsohn, Patricia Katz, Stephanie Rush, Clairissa Ja, Tiffany Taylor, Kie Shidara, Maria I Danila, Katherine D Wysham, Anja Strangfeld, Elsa F Mateus, Kimme L Hyrich, Laure Gossec, Loreto Carmona, Saskia Lawson-Tovey, Lianne Kearsley-Fleet, Martin Schaefer, Samar Al-Emadi, Jeffrey A Sparks, Tiffany Y-T Hsu, Naomi J Patel, Leanna Wise, Emily Gilbert, Alí Duarte-García, Maria O Valenzuela-Almada, Manuel F Ugarte-Gil, Lotta Ljung, Carlo A Scirè, Greta Carrara, Eric Hachulla, Christophe Richez, Patrice Cacoub, Thierry Thomas, Maria J Santos, Miguel Bernardes, Rebecca Hasseli, Anne Regierer, Hendrik Schulze-Koops, Ulf Müller-Ladner, Guillermo Pons-Estel, Romina Tanten, Romina E Nieto, Cecilia N Pisoni, Yohana S Tissera, Ricardo Xavier, Claudia D Lopes Marques, Gecilmara C S Pileggi, Philip C Robinson, Pedro M Machado, Emily Sirotich, Jean W Liew, Jonathan S Hausmann, Paul Sufka, Rebecca Grainger, Suleman Bhana, Monique Gore-Massy, Zachary S Wallace, Jinoos Yazdany, Brahim Dahou, Gimena Gómez, Karen Roberts, Roberto M Baez, Vanessa V Castro Coello, María J Haye Salinas, Federico N Maldonado, Alvaro A Reyes, Gelsomina Alle, Hernán Maldonado Ficco, Romina Nieto, Carla Gobbi, Yohana Tissera, Cecilia Pisoni, Alba Paula, Juan A Albiero, Maria M Schmid, Micaela Cosatti, Maria J Gamba, Carlevaris Leandro, María A Cusa, Noelia German, Veronica Bellomio, Lorena Takashima, Mariana Pera, Karina Cogo, Maria S Gálvez Elkin, María A Medina, Veronica Savio, Romina Rojas Tessel, Rodolfo P Alamino, Marina L Werner, Sofía Ornella, Luciana Casalla, Maria de la Vega, María Severina, Mercedes García, Luciana Gonzalez Lucero, Cecilia Romeo, Sebastián Moyano, Tatiana Barbich, Ana Bertoli, Andrea Baños, Sandra Petruzzelli, Carla Matellan, Silvana Conti, Maria A Lazaro, Gustavo F Rodriguez Gil, Fabian Risueño, Maria I Quaglia, Julia Scafati, Natalia L Cuchiaro, Jonathan E Rebak, Susana I Pineda, María E Calvo, Eugenia Picco, Josefina G Yanzi, Pablo Maid, Debora Guaglianone, Julieta S Morbiducci, Sabrina Porta, Natalia Herscovich, José L Velasco Zamora, Boris Kisluk, Maria S Castaños Menescardi, Rosana Gallo, María V Martire, Carla Maldini, Cecilia Goizueta, Sabrina S de la Vega Fernandez, Carolina Aeschlimann, Gisela Subils, Eva Rath, Yves Piette, Mieke Devinck, Bea Maeyaert, Francinne Machado Ribeiro, Sandra L Euzebio Ribeiro, Marcelo Pinheiro, Sebastián Ibáñez, Anne-Marie Chassin Trubert, Lingli Dong, Lui Cajas, Marko Barešić, Branimir Anić, Melanie-Ivana Ćulo, Tea A Pavelić, Kristina K Stranski, Boris Karanovic, Jiri Vencovsky, Marta Píchová, Maria Filkova, Hesham Hamoud, Dimitrios Vassilopoulos, Gabriela M Guzman Melgar, Ho So, Márta Király, Mahdi Vojdanian, Alexandra Balbir Gurman, Fatemah Abutiban, Julija Zepa, Inita Bulina, Loreta Bukauskiene, Beatriz E Zazueta Montiel, Angel A Castillo Ortiz, Erick Zamora Tehozol, David Vega Morales, Diana Cervántes Rosete, Eduardo Martín Nares, Tatiana S Rodriguez Reyna, Marina Rull Gabayet, Deshiré Alpízar Rodríguez, Fedra Irazoque, Xochitl Jimenez, Lenny Geurts van Bon, Theo Zijlstra, Monique Hoekstra, Nasra Al Adhoubi, Babur Salim, Enrique Giraldo, Ariel Salinas, Manuel Ugarte Gil, Jarosław Nowakowski, Richard Conway, Rachael Flood, Geraldine McCarthy, Ioana Felea, Ileana Filipescu, Simona Rednic, Laura Groseanu, Maria M Tamas, Vanda Mlynarikova, Martina Skamlova, Martin Zlnay, Dagmar Mičeková, Lubica Capova, Zelmira Macejova, Emőke Šteňová, Helena Raffayova, Gabriela Belakova, Eva Strakova, Marieta Senčarová, Soňa Žlnayová, Anna Sabová, Daniela Spisakova, Mária Oetterová, Olga Lukacova, Martina Bakosova, Alojzija Hocevar, Natalia de la Torre Rubio, Juan J Alegre Sancho, Montserrat Corteguera Coro, Juan C Cobeta Garcia, Maria C Torres Martin, Jose Campos, Jose A Gomez Puerta, Gozd K Yardimci, Servet Akar, Ozan C Icacan, Selda ÇELİK, Viktoriia Vasylets, Su-Ann Yeoh, Claire Vandevelde, Sasha Dunt, Jane Leeder, Elizabeth Macphie, Rosaria Salerno, Christine Graver, Katie Williams, Sheila O'Reilly, Kirsty Devine, Jennifer Tyler, Elizabeth Warner, James Pilcher, Samir Patel, Elena Nikiphorou, Laura Chadwick, Caroline M Jones, Beverley Harrison, Lucy Thornton, Diana O'Kane, Lucia Fusi, Audrey Low, Sarah Horton, Shraddha Jatwani, Sara Baig, Hammad Bajwa, Vernon Berglund, Angela Dahle, Walter Dorman, Jody Hargrove, Maren Hilton, Nicholas Lebedoff, Susan Leonard, Jennifer Morgan, Emily Pfeifer, Archibald Skemp, Jeffrey Wilson, Anne Wolff, Eduardo Cepeda, Derrick Todd, Denise Hare, Cassandra Calabrese, Christopher Adams, Arezou Khosroshahi, Adam Kilian, Douglas White, Melanie Winter, Theodore Fields, Caroline Siegel, Nicole Daver, Melissa Harvey, Neil Kramer, Concetta Lamore, Suneya Hogarty, Karen Yeter, Faizah Siddique, Byung Ban, Tamar Tanner, Eric Ruderman, William Davis, Robert Quinet, Evangeline Scopelitis, Karen Toribio, Tameka Webb Detiege, Jerald Zakem, Khurram Abbass, Gilbert Kepecs, Lilliam Miranda, Michael Guma, Ammar Haikal, Sushama Mody, Daric Mueller, Arundathi Jayatilleke, JoAnn Zell, Alison Bays, Kathryn Dao, Fatemeh Ezzati, Deborah Parks, David Karp, Guillermo Quiceno, Izadi, Z, Gianfrancesco, M, Schmajuk, G, Jacobsohn, L, Katz, P, Rush, S, Ja, C, Taylor, T, Shidara, K, Danila, M, Wysham, K, Strangfeld, A, Mateus, E, Hyrich, K, Gossec, L, Carmona, L, Lawson-Tovey, S, Kearsley-Fleet, L, Schaefer, M, Al-Emadi, S, Sparks, J, Hsu, T, Patel, N, Wise, L, Gilbert, E, Duarte-Garcia, A, Valenzuela-Almada, M, Ugarte-Gil, M, Ljung, L, Scire, C, Carrara, G, Hachulla, E, Richez, C, Cacoub, P, Thomas, T, Santos, M, Bernardes, M, Hasseli, R, Regierer, A, Schulze-Koops, H, Muller-Ladner, U, Pons-Estel, G, Tanten, R, Nieto, R, Pisoni, C, Tissera, Y, Xavier, R, Lopes Marques, C, Pileggi, G, Robinson, P, Machado, P, Sirotich, E, Liew, J, Hausmann, J, Sufka, P, Grainger, R, Bhana, S, Gore-Massy, M, Wallace, Z, Yazdany, J, Dahou, B, Gomez, G, Roberts, K, Baez, R, Castro Coello, V, Haye Salinas, M, Maldonado, F, Reyes, A, Alle, G, Maldonado Ficco, H, Gobbi, C, Paula, A, Albiero, J, Schmid, M, Cosatti, M, Gamba, M, Leandro, C, Cusa, M, German, N, Bellomio, V, Takashima, L, Pera, M, Cogo, K, Galvez Elkin, M, Medina, M, Savio, V, Rojas Tessel, R, Alamino, R, Werner, M, Ornella, S, Casalla, L, de la Vega, M, Severina, M, Garcia, M, Gonzalez Lucero, L, Romeo, C, Moyano, S, Barbich, T, Bertoli, A, Banos, A, Petruzzelli, S, Matellan, C, Conti, S, Lazaro, M, Rodriguez Gil, G, Risueno, F, Quaglia, M, Scafati, J, Cuchiaro, N, Rebak, J, Pineda, S, Calvo, M, Picco, E, Yanzi, J, Maid, P, Guaglianone, D, Morbiducci, J, Porta, S, Herscovich, N, Velasco Zamora, J, Kisluk, B, Castanos Menescardi, M, Gallo, R, Martire, M, Maldini, C, Goizueta, C, de la Vega Fernandez, S, Aeschlimann, C, Subils, G, Rath, E, Piette, Y, Devinck, M, Maeyaert, B, Machado Ribeiro, F, Euzebio Ribeiro, S, Pinheiro, M, Ibanez, S, Chassin Trubert, A, Dong, L, Cajas, L, Baresic, M, Anic, B, Culo, M, Pavelic, T, Stranski, K, Karanovic, B, Vencovsky, J, Pichova, M, Filkova, M, Hamoud, H, Vassilopoulos, D, Guzman Melgar, G, So, H, Kiraly, M, Vojdanian, M, Balbir Gurman, A, Abutiban, F, Zepa, J, Bulina, I, Bukauskiene, L, Zazueta Montiel, B, Castillo Ortiz, A, Zamora Tehozol, E, Vega Morales, D, Cervantes Rosete, D, Martin Nares, E, Rodriguez Reyna, T, Rull Gabayet, M, Alpizar Rodriguez, D, Irazoque, F, Jimenez, X, Geurts van Bon, L, Zijlstra, T, Hoekstra, M, Al Adhoubi, N, Salim, B, Giraldo, E, Salinas, A, Ugarte Gil, M, Nowakowski, J, Conway, R, Flood, R, Mccarthy, G, Felea, I, Filipescu, I, Rednic, S, Groseanu, L, Tamas, M, Mlynarikova, V, Skamlova, M, Zlnay, M, Micekova, D, Capova, L, Macejova, Z, Stenova, E, Raffayova, H, Belakova, G, Strakova, E, Sencarova, M, Zlnayova, S, Sabova, A, Spisakova, D, Oetterova, M, Lukacova, O, Bakosova, M, Hocevar, A, de la Torre Rubio, N, Alegre Sancho, J, Corteguera Coro, M, Cobeta Garcia, J, Torres Martin, M, Campos, J, Gomez Puerta, J, Yardimci, G, Akar, S, Icacan, O, Celik, S, Vasylets, V, Yeoh, S, Vandevelde, C, Dunt, S, Leeder, J, Macphie, E, Salerno, R, Graver, C, Williams, K, O'Reilly, S, Devine, K, Tyler, J, Warner, E, Pilcher, J, Patel, S, Nikiphorou, E, Chadwick, L, Jones, C, Harrison, B, Thornton, L, O'Kane, D, Fusi, L, Low, A, Horton, S, Jatwani, S, Baig, S, Bajwa, H, Berglund, V, Dahle, A, Dorman, W, Hargrove, J, Hilton, M, Lebedoff, N, Leonard, S, Morgan, J, Pfeifer, E, Skemp, A, Wilson, J, Wolff, A, Cepeda, E, Todd, D, Hare, D, Calabrese, C, Adams, C, Khosroshahi, A, Kilian, A, White, D, Winter, M, Fields, T, Siegel, C, Daver, N, Harvey, M, Kramer, N, Lamore, C, Hogarty, S, Yeter, K, Siddique, F, Ban, B, Tanner, T, Ruderman, E, Davis, W, Quinet, R, Scopelitis, E, Toribio, K, Webb Detiege, T, Zakem, J, Abbass, K, Kepecs, G, Miranda, L, Guma, M, Haikal, A, Mody, S, Mueller, D, Jayatilleke, A, Zell, J, Bays, A, Dao, K, Ezzati, F, Parks, D, Karp, D, Quiceno, G, and Repositório da Universidade de Lisboa

Subjects
health care disparity, Immunology, air pollution, cohort analysi, mortality rate, Autoimmune Disease, Article, coronavirus disease 2019, biocontainment, Rheumatology, male, cardiovascular disease, environmental factor, death, geographic distribution, Immunology and Allergy, follow up, controlled study, human, population density, outcome assessment, rheumatic disease, diabetes mellitu, adult, Prevention, market, temperature, mortality, United Kingdom, Europe, aged, female, workplace, Good Health and Well Being, human development, particulate matter 2.5, statistical analysi, North America, incidence, life expectancy, social aspect, COVID-19 Global Rheumatology Alliance Registry, observational study, demographic
Abstract

Published by Elsevier Ltd., Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p, MAG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534 [JY]). KDW is supported by the Department of Veterans Affairs and the Rheumatology Research Foundation Scientist Development award. JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253, and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). AD-G is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. RH was supported by the Justus-Liebig University Giessen Clinician Scientist Program in Biomedical Research to work on this registry. JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155).

Published
2022

26. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

Author

Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesús, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James, Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia, Zhang, Yu, Snow, Andrew, Holland, Steven, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna, Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila, Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel, Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam, Kennelly, Sean, Bourke, Nollaig, Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald, Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András, Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard, Mane, Shrikant, Anderson, Mark, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine, Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charles, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter, Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi, Su, Helen, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles, Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, Cobat, Aurélie, Zhang, Peng, Seeleuthner, Yoann, Talouarn, Estelle, Marchal, Astrid, Matuozzo, Daniela, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Albisures, Jonathan Antonio Roblero, Aldave, Juan, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Allardet-Servent, Jerome, Allende, Luis, Alonso-Arias, Rebeca, Alshahrani, Mohammed, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzaghi, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P., Bukhari, Huda, Bustamante, Jacinta, Agra, Juan José Cáceres, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew, Clavé, Pere, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, de Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Godínez, Karen Alejandra Cifuentes, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-Ki, Holanda-Peña, María Soledad, Horcajada, Juan, Hraiech, Sami, Humbert, Linda, Hung, Ivan, Iglesias, Alejandro, Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Kanık-Yüksek, Saliha, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Daganou, Maria, Koukaki, Evangelia, Koutsoukou, Antonia, Rapti, Vasiliki, Syrigos, Konstantinos, Król, Zbigniew, Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur, Kwan, Yat Wah M., Kwok, Janette, Lam, David, Conti, Francesca, Pession, Andrea, Lampropoulou, Vicky, Lanternier, Fanny, Bourgeois, Fleur Le, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José, Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa Rb, Matthews, Gail, Mayaux, Julien, Mclaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paz-Artal, Estela, Pedraza-Sánchez, Sigifredo, Gálvez-Romero, José Luis, Pellecer, Nancy Carolina González, Pellegrini, Silvia, Diego, Rebeca Pérez De, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Planas-Serra, Laura, Ploin, Dominique, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rivet, Nadia, Rocamora-Blanch, Gemma, Rodero, Mathieu, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Gallego, Carlos, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Prado, Maria Yolanda Ruiz Del, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Tsang, Owen, Tserel, Liina, Tso, Eugene, Tucci, Alessandra, Öz, Şadiye Kübra Tüter, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, van den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Veliz, Silvia Patricia Zuniga, Viel, Sébastien, Villain, Cédric, Vilaire-Meunier, Marie, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby, Yükselmiş, Ufuk, Ghirardello, Stefano, Zuccaro, Valentina, Andrés, Ana De, van Praet, Jens, Lambrecht, Bart, van Braeckel, Eva, Bosteels, Cédric, Hoste, Levi, Hoste, Eric, Bauters, Fré, Clercq, Jozefien De, Heijmans, Cathérine, Slabbynck, Hans, Naesens, Leslie, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey, Dobbs, Kerry, Kashyap, Anuj, Ding, Li, Dalgard, Clifton, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Bettini, Laura Rachele, D’angio, Mariella, Beretta, Ilaria, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Batten, Isabella, Reddy, Conor, Mcelheron, Matt, Noonan, Claire, Connolly, Emma, Fallon, Aoife, Storgaard, Merete, Jørgensen, Sofie, Pedersen, Ole Birger, Sørensen, Erik, Mikkelsen, Susan, Dinh, Khoa Manh, Larsen, Margit Anita Hørup, Paulsen, Isabella Worlewenut, von Stemann, Jakob Hjorth, Hansen, Morten Bagge, Ostrowski, Sisse Rye, Townsend, Liam, Ni Cheallaigh, Cliona, Bergin, Colm, Martin-Loeches, Ignacio, Dunne, Jean, Conlon, Niall, O’farrelly, Cliona, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behillill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouscambert-Duchamp, Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, D’ortenzio, Eric, de Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farase, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, van der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Jaïs, Jean-Philippe, Pelet, Anna, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly, Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Michel, Frédérique, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Bourgeon, Marilou, Lefèvre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David, Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave, Dujardin, Romein, Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin, Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine, Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe, de Jong, Menno, Lim, Endry, van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther, Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan, van der Poll, Tom, Preckel, Bennedikt, Prins, Jan, Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits, Schinkel, Michiel, Schultz, Marcus, Schrauwen, Femke, Schuurman, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen, Smeele, Patrick, Smit, Marry, Stijnis, Cornelis, Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa, Tuinman, Pieter, van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke, van Vugt, Michèle, Wouters, Dorien, Zwinderman, A., Brouwer, Matthijs, Wiersinga, W. Joost, Vlaar, Alexander, Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés, Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos, Butte, Manish, Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan, Cooper, Megan, Desai, Murkesh, Drolet, Beth, El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah, Hsieh, Elena, Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich, Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie, Maniatis, Tom, Maródi, László, Milner, Joshua, Mironska, Kristina, Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Perez-Tur, Jordi, Arkin, Lisa, Asano, Takaki, Oriol, Roger Colobran, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Tayoun, Ahmad Abou, Ramaswamy, Sathishkumar, Turvey, Stuart, Uddin, K., Uddin, Mohammed, von Bernuth, Horst, Zawadzki, Pawel, Grimbacher, Bodo, Pape, Jean, Perlin, David, Pesole, Graziano, García, Paula Andrea Gaviria, López, Gustavo Andrés Salguero, Rojas-Villaraga, Adriana, Vélez, Verónica Posada, Landinez, Lina Marcela Acevedo, Correales, Luisa Paola Duarte, Gómez, Oscar, Guaqueta, Jeser Santiago Grass, Pérez, Cristian Alejandro Ricaurte, Carrillo, Jorge, Vergara, José Alejandro Daza, Landinez, Sandra, Mantilla, Rubén, Yepes, Jairo David Torres, Ricaurte, Oscar Andrés Briceño, Pérez-Díaz, Carlos, Mateus, Yady Nataly, Navarro, Laura Mancera, Rodríguez, Yhojan, Acosta-Ampudia, Yeny, Monsalve, Diana, Rojas, Manuel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Got, Stéphane Le, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, CHU Henri Mondor, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospital Universitario Infanta Leonor [Madrid], Hospices Civils de Lyon (HCL), Grand Hôpital de l'Est Francilien (GHEF), Vall d'Hebron University Hospital [Barcelona], Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), National Institutes of Health [Bethesda] (NIH), Tokyo Medical and Dental University [Japan] (TMDU), Universitat de Barcelona (UB), Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute for Systems Biology [Seattle] (ISB), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidad del Rosario [Bogota], Hospital Universitario de Gran Canaria Dr Negrin, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Uniformed Services University of the Health Sciences (USUHS), University of British Columbia (UBC), CHU Necker - Enfants Malades [AP-HP], Spanish National Research Council (CSIC), Ghent University Hospital, Goce Delchev University (UGD), Invitae Corporation, Bilkent University [Ankara], Necmettin Erbakan University [Konya, Turquie], Centre Hospitalier Universitaire Hassan II (CHU HII), CHU Ibn Rochd [Casablanca], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institute, Réseau International des Instituts Pasteur (RIIP), Tel Aviv Sourasky Medical Center [Te Aviv], The Feinstein Institute for Medical Research, IRCCS San Raffaele Scientific Institute [Milan, Italie], IRCCS Ospedale San Raffaele [Milan, Italy], Universidade de São Paulo = University of São Paulo (USP), Fundacion Rioja Salud, Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Shupyk National Medical Academy of Postgraduate Education [Kiev] (SNMAPE), I.Horbachevsky Ternopil State Medical University, Ternopil, Ukraine, Hospital Donostia, Garvan Institute of medical research, Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Charles University [Prague] (CU), University Hospital Motol [Prague], Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology [Moscow, Russia], The University of Hong Kong (HKU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of La Sabana = Universitad de la Sabana, Hôpital Robert Ballanger [Aulnay-sous-Bois], Sackler Faculty of Medicine, Tel Aviv University (TAU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Tallaght Hospital, Trinity College Dublin, University of Sharjah (UoS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire CERBA [Saint Ouen l'Aumône], King Fahad University, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), McGill University = Université McGill [Montréal, Canada], Aarhus University [Aarhus], Instituto de Pesquisa Pelé Pequeno Principe, Hôpital Jean Verdier [AP-HP], Ecole Polytechnique Fédérale de Lausanne (EPFL), Yale University [New Haven], University of California [San Francisco] (UC San Francisco), University of California (UC), Academy of Athens, Institució Catalana de Recerca i Estudis Avançats (ICREA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), IrsiCaixa (Institut de Recerca de la Sida), Hôpital Foch [Suresnes], Etablissement Français du Sang, EFS, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), George Mason University, Yale University, National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Scientific Committee on Oceanic Research, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondation Bettencourt Schueller, Centro de Investigación Biomédica en Red Enfermedades Raras (España), European Commission, G. Harold & Leila Y. Mathers Foundation, Hospital Universitario Infanta Leonor, National Institute of Allergy and Infectious Diseases (US), National Institute of Dental and Craniofacial Research (US), Estonian Research Council, Al Jalila Foundation, American University of Sharjah, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Regione Lombardia, Instituto de Salud Carlos III, Japan Agency for Medical Research and Development, Sorbonne Université, Université de Bordeaux, National Cancer Institute (US), Research Foundation - Flanders, Hellenic Foundation for Research and Innovation, Sao Paulo Research Foundation, The Meath Foundation, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), INSERM UMRS-1144, Université Paris Cité, Réanimation Médicale et Toxicologique, Hôpital Lariboisière, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the NIH (Grants R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Awards program (Grant UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (Grant S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (Grant ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (Grant EQU201903007798), the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05), the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects, the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e co-morbidità'). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program 'Cohortes et collections de données biologiques.' S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1, AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID), by the Katholieke Universiteit Leuven C1 Grant C16/18/007, by a Flanders Institute for Biotechnology-Grand Challenges - PID grant, by the FWO Grants G0C8517N, G0B5120N, and G0E8420N, and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation., HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest Group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank Investigators, COVID Human Genetic Effort, CP-COVID-19 Group, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement Français du Sang Study group, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-19-CE15-0009,CNSVIRGEN,Déficits immunitaires innés dans les infections sévères du tronc cérébral(2019), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), Manry, J, Bastard, P, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Michailidis, E, Hoffmann, H, Eto, S, Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Mégarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de Beek, D, Sahanic, S, Tancevski, I, Stepanovskyy, Y, Boyarchuk, O, Nukui, Y, Tsumura, M, Vidaur, L, Tangye, S, Burrel, S, Duffy, D, Quintana-Murci, L, Klocperk, A, Kann, N, Shcherbina, A, Lau, Y, Leung, D, Coulongeat, M, Marlet, J, Koning, R, Reyes, L, Chauvineau-Grenier, A, Venet, F, Monneret, G, Nussenzweig, M, Arrestier, R, Boudhabhay, I, Baris-Feldman, H, Hagin, D, Wauters, J, Meyts, I, Dyer, A, Kennelly, S, Bourke, N, Halwani, R, Sharif-Askari, F, Dorgham, K, Sallette, J, Sedkaoui, S, Alkhater, S, Rigo-Bonnin, R, Morandeira, F, Roussel, L, Vinh, D, Erikstrup, C, Condino-Neto, A, Prando, C, Bondarenko, A, Spaan, A, Gilardin, L, Fellay, J, Lyonnet, S, Bilguvar, K, Lifton, R, Mane, S, Anderson, M, Boisson, B, Béziat, V, Zhang, S, Andreakos, E, Hermine, O, Pujol, A, Peterson, P, Mogensen, T, Rowen, L, Mond, J, Debette, S, de Lamballerie, X, Burdet, C, Bouadma, L, Zins, M, Soler-Palacin, P, Colobran, R, Gorochov, G, Solanich, X, Susen, S, Martinez-Picado, J, Raoult, D, Vasse, M, Gregersen, P, Piemonti, L, Rodríguez-Gallego, C, Notarangelo, L, Su, H, Kisand, K, Okada, S, Puel, A, Jouanguy, E, Rice, C, Tiberghien, P, Zhang, Q, Casanova, J, Abel, L, Cobat, A, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Graduate School, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Gunst, Jan, Acibadem University Dspace, Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesú, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine M, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charle, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, Cobat, Aurélie, Vougny, Marie-Christine, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
Adult, Male, Risk, infection fatality rate, [SDV.IMM] Life Sciences [q-bio]/Immunology, autoantibodies, chronic mucocutaneous candidiasis, CHRONIC MUCOCUTANEOUS CANDIDIASIS, Autoimmunity, IMMUNITY, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, DISEASE, Basic medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, INFECTION, Medicine and Health Sciences, Humans, IMUNOLOGIA, Aged, Autoantibodies, Aged, 80 and over, disease, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, SARS-CoV-2, type I IFNs, Age Factors, COVID-19, Type I IFNs, Middle Aged, autoantibodie, immunity, Antibodies, Neutralizing, infection, Infection fatality rate, Relative risk, relative risk, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, type I IFN
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.

Published
2022
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27. Early diarrhoea under sorafenib as a marker to consider the early migration to second‐line drugs

Author

Marco Sanduzzi-Zamparelli, Loreto Boix, Maria Reig, Alejandro Forner, Carmen Ayuso, Gemma Iserte, Victor Sapena, Ernest Belmonte, Sergio Muñoz-Martínez, Cassia Guedes, Anna Darnell, Ferran Torres, Jordi Bruix, Leonardo G Da Fonseca, Jordi Rimola, Neus Llarch, and Álvaro Díaz-González

Subjects
Male, Cancer cells, Time Factors, Gastroenterology, Tyrosine-kinase inhibitor, Proteïna-tirosina-fosfatasa, tyrosine kinase inhibitor, Second line, Protein kinases, Survival analysis (Biometry), Protein-tyrosine phosphatase, Inhibition, Liver Neoplasms, digestive, oral, and skin physiology, Hazard ratio, hepatocellular carcinoma, Middle Aged, Sorafenib, Prognosis, Survival Rate, Treatment Outcome, Oncology, Hepatocellular carcinoma, Cèl·lules canceroses, Female, Original Article, Liver cancer, medicine.drug, Diarrhea, medicine.medical_specialty, Carcinoma, Hepatocellular, Bevacizumab, medicine.drug_class, Antineoplastic Agents, survival, Càncer de fetge, resistance, Anàlisi de supervivència (Biometria), Atezolizumab, Internal medicine, medicine, Humans, Adverse effect, Protein Kinase Inhibitors, neoplasms, Resistència als medicaments, Aged, Proportional Hazards Models, Hepatology, business.industry, medicine.disease, Hepatologia, Proteïnes quinases, diarrhoea, Inhibició, Drug Resistance, Neoplasm, Drug resistance, Hepatobiliary, Diarrea, business
Abstract

Background Despite atezolizumab and bevacizumab (A + B) is currently the first‐line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors. Objective To characterize the early diarrhoea development as prognostic factor in 344 HCC patients. Methods The development of early diarrhoea in sorafenib treatment defined as patients who developed diarrhoea and needed dose modification within the first 60 days of treatment (e‐diarrhoea) and 3‐grouping variables were analysed: Patients with e‐diarrhoea, patients who developed diarrhoea after the first 60 days of treatment (L‐diarrhoea) and patients that never developed diarrhoea (never diarrhoea). Results The median overall survival in sorafenib treated patients was significantly different across groups (6.8 months for e‐diarrhoea, 26.7 months for L‐diarrhoea and 13.3 months for never‐diarrhoea). The emergence of e‐diarrhoea was associated with poor outcomes (hazard ratio [HR] 1.84 [95%CI 1.15–2.95]), while there was no increased/decreased risk of dismal evolution in patients with L‐diarrhoea (HR 0.66 [95%CI 0.42–1.03]). Conclusion The emergence of e‐diarrhoea in HCC patients treated with sorafenib is an early predictor of dismal evolution under this therapy. Thus, prompt identification of these non‐responders may be useful for an early switch to second‐line therapies., Key Summary Established knowledge on this subject Diarrhoea is a frequent adverse event of sorafenib and its emergence has been associated to better outcomes. What are the significant and/or new findings of this study? Early diarrhoea (e‐diarrhoea) in hepatocellular carcinoma patients treated with sorafenib is an early predictor of dismal evolution.Diarrhoea under sorafenib should not be taken as a predictive parameter of lack of benefit.E‐diarrhoea could be used as clinical biomarker for switching to second‐line therapies.

Published
2021
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28. Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Children With Chronic HCV: Part 2 of the DORA Study

Author

Daniel H. Leung, Andrew Topp, Cornelia Feiterna-Sperling, Antonio Del Valle-Segarra, John Marcinak, Regino P. Gonzalez-Peralta, Steven Lobritto, Rakesh Tripathi, Vishakha Sabharwal, Simon C. Ling, Susan Gilmour, Jessica Wen, Loreto Hierro, Hoi Kei Lon, Yuri Lobzin, Maureen M. Jonas, Deirdre Kelly, Etienne Sokal, Michael R. Narkewicz, Tatsuki Mizuochi, and Susan Rhee

Subjects
Male, medicine.medical_specialty, Pyrrolidines, Cirrhosis, Genotyping Techniques, Hepacivirus, Antiviral Agents, Gastroenterology, Virus, Pharmacokinetics, Chronic hepatitis, Quinoxalines, Internal medicine, Genotype, medicine, Humans, Child, Sulfonamides, Hepatology, business.industry, Glecaprevir, Hepatitis C, Chronic, medicine.disease, Pibrentasvir, Drug Combinations, Treatment Outcome, Child, Preschool, Cohort, Benzimidazoles, Female, business, Rapid Communication
Abstract

Background and Aims Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic HCV‐infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, open‐label study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of GLE and PIB in children ages 3 to < 12 years. Approach and Results Children with chronic HCV infection, genotype 1‐6, with or without compensated cirrhosis, were divided into three cohorts by age—cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)—and given weight‐based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were sustained virologic response at posttreatment week 12 (SVR12) and steady‐state exposure; secondary endpoints were rates of persistent viremia, relapse, and reinfection. Safety and laboratory abnormalities were assessed. Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 to < 30 kg), and 150 mg GLE + 60 mg PIB (12 to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by posttreatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two nonresponders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug‐related serious AEs occurred. Pharmacokinetic exposures were comparable to those of adults. Conclusions A pediatric formulation of GLE/PIB was highly efficacious and well tolerated in chronic HCV‐infected children 3 to < 12 years old.

Published
2021
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29. Hyperventilation maneuver during EEG in children with epilepsy after the COVID‐19 pandemic. Is a routine procedure necessary?

Author

Loreto Ríos-Pohl, Macarena Franco, and Magdalena Gonzalez

Subjects
Male, clinical seizure, generalized epileptiform discharges, Pediatrics, medicine.medical_specialty, Adolescent, Coronavirus disease 2019 (COVID-19), hyperventilation, Diagnostic Techniques, Neurological, Electroencephalography, Preliminary Report, Sensitivity and Specificity, absence childhood epilepsy, Epilepsy, Ambulatory care, Seizures, Hyperventilation, Ambulatory Care, medicine, Humans, Chile, COVID‐19, SARS‐CoV‐2, EEG activation, Child, RC346-429, Retrospective Studies, Ambulatory electroencephalogram, medicine.diagnostic_test, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, medicine.disease, Epilepsy, Absence, Neurology, Ambulatory, Female, Neurology (clinical), Neurology. Diseases of the nervous system, medicine.symptom, business
Abstract

Objective Hyperventilation (HV) is one of the main and basic activation methods during ambulatory electroencephalogram (EEG), unless medical reasons contraindicate it. During the COVID‐19 pandemic, with the high risk of human‐to‐human infection, local guidelines and recommendations have been developed that suggest not to perform the HV maneuver routinely. Our objective was to characterize patients who present positive HV in an epilepsy center. Methods We analyzed retrospectively all the ambulatory EEGs performed during one year in our specialized ambulatory child and adolescent epilepsy center, and describe patients with positive maneuver. Results A total of 305 EEGs were performed. Patients under 3 years and 11 months were excluded as well as all patients that did not fill up the criteria for epilepsy diagnosis. From the 252 EEGs that were included in the study, 194 EEGs (77%) were classified as abnormal and 58 (23%) as normal. From these same 252 EEGs, 150 EEG finished correctly the HV maneuver. Physiological slowing response was found in 54 EEGs (36%), no changes (negative) in 83 (55%), and abnormal response (positive) in 13 EEGs (9%). The 13 HV‐positive EEGs showed 4 patients with an increase of epileptiform activity, 3 patients experienced an increase of basal preregistered abnormal slowing, and 6 EEGs showed trigger of bilaterally synchronous and symmetric 2‐4 Hz spike‐and‐slow wave discharges and absences. None of these last 6 patients needed more than 3 minutes to elicit the paroxysmal discharge. Significance Based on these findings and according with other studies, the low positivity and high specificity of the HV maneuver support the idea that HV could be excluded during the COVID‐19 pandemic situation, and also reevaluate whether it could be changed to a complementary maneuver, restricted only for cases where absence epilepsy is suspected. Larger studies will be needed to reaffirm this proposal.

Published
2021

30. Neurotoxin-mediated --potent activation of the axon degeneration regulator SARM1

Author

Loreto, Andrea, Angeletti, Carlo, Gu, Weixi, Osborne, Andrew, Nieuwenhuis, Bart, Gilley, Jonathan, Merlini, Elisa, Arthur-Farraj, Peter, Amici, Adolfo, Luo, Zhenyao, Hartley-Tassell, Lauren, Ve, Thomas, Desrochers, Laura M, Wang, Qi, Kobe, Bostjan, Orsomando, Giuseppe, Coleman, Michael, Loreto, Andrea [0000-0001-6535-6436], Nieuwenhuis, Bart [0000-0002-2065-2271], Arthur-Farraj, Peter [0000-0002-1239-9392], Coleman, Michael [0000-0002-9354-532X], Apollo - University of Cambridge Repository, Gu, Weixi [0000-0002-1185-3557], Gilley, Jonathan [0000-0002-9510-7956], Amici, Adolfo [0000-0002-1081-7749], Kobe, Bostjan [0000-0001-9413-9166], and Orsomando, Giuseppe [0000-0001-6640-097X]

Subjects
Male, SARM1, QH301-705.5, Science, Neurotoxins, vacor, chemical biology, General Biochemistry, Genetics and Molecular Biology, neuroscience, Mice, Biochemistry and Chemical Biology, Animals, biochemistry, Biology (General), mouse, Armadillo Domain Proteins, General Immunology and Microbiology, General Neuroscience, Phenylurea Compounds, Rodenticides, General Medicine, VMN, NAD, Axons, axon degeneration, Cytoskeletal Proteins, nervous system, environmental neurotoxin, Nerve Degeneration, Medicine, Female, Research Article
Abstract

Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the NAD-consuming enzyme SARM1. Here, we report a novel activator of SARM1, a metabolite of the pesticide and neurotoxin vacor. Removal of SARM1 completely rescues mouse neurons from vacor-induced neuron and axon death in vitro and in vivo. We present the crystal structure of the Drosophila SARM1 regulatory domain complexed with this activator, the vacor metabolite VMN, which as the most potent activator yet known is likely to support drug development for human SARM1 and NMNAT2 disorders. This study indicates the mechanism of neurotoxicity and pesticide action by vacor, raises important questions about other pyridines in wider use today, provides important new tools for drug discovery, and demonstrates that removing SARM1 can robustly block programmed axon death induced by toxicity as well as genetic mutation.

Published
2021

31. Improvement in quality of life with sacubitril/ /valsartan in cardiac resynchronization non-responders: The RESINA (RESynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry

Author

Belén Arroyo Rivera, Hugo del Castillo, José Manuel Rubio Campal, Mikel Taibo Urquia, José Tuñón Fernández, Ángel Miracle Blanco, Loreto Bravo Calero, Pepa Sánchez Borque, Carmen de Juan Bitriá, and David Martí Sánchez

Subjects
Male, medicine.medical_specialty, Angiotensins, medicine.medical_treatment, Cardiac resynchronization therapy, Cardiomyopathy, Tetrazoles, Clinical Cardiology, Ventricular Function, Left, Sacubitril, Cardiac Resynchronization Therapy, Angiotensin Receptor Antagonists, Quality of life, Internal medicine, medicine, Humans, Registries, Aged, Aged, 80 and over, Heart Failure, Ejection fraction, business.industry, Aminobutyrates, Biphenyl Compounds, Stroke Volume, General Medicine, medicine.disease, Drug Combinations, Treatment Outcome, Valsartan, Heart failure, Quality of Life, Cardiology, Female, Neprilysin, Cardiology and Cardiovascular Medicine, business, Sacubitril, Valsartan, medicine.drug
Abstract

Background: Clinical management of cardiac resynchronization therapy (CRT) non-responders is difficult, and their prognosis is poor. The aim of the present study was to evaluate whether treatment with sacubitril/valsartan can improve quality of life (QoL) parameters in these patients. Methods: Thirty five non-responders to CRT were included (75 ± 7 years, 28% females, mean left ventricular ejection fraction 28 ± 8%, 54% non-ischemic cardiomyopathy) with maximally optimized drug therapy and New York Heart Association class II–III. They were all on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and were switched to sacubitril/valsartan. One week before and 6 months after initiation of the therapy they completed both the Minnesota Living with Heart Failure (MLWHF) and the 12-item Kansas City Cardiomyopathy Questionnaires (KCCQ-12). The primary outcome was the effect of sacubitril/valsartan on the physical, clinical, social and emotional QoL parameters and number of hospitalizations. Results: The mean total scores of both questionnaires improved from baseline to the follow-up visit at 6-months (KCCQ-12 40 ± 10 to 47 ± 10; p < 0.001; MLWHF 40 ± 15 to 29 ± 15; p < 0.001). The best results were seen in the KCCQ-12 total symptom domains (77% improvement), the MLWHF physical domain (81% improvement), and the MLWHF emotional domain (71% improvement). Two patients died during follow-up. The mean number of hospitalizations reduced significantly (1 ± 0.6 vs. 0.5 ± 0.8; p = 0.003) Conclusions: In CRT non-responders, sacubitril/valsartan significantly improved overall QoL, physical limitations and emotional domains and reduced the number of hospitalizations.

Published
2021
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32. Impact of Social Isolation on People with Dementia and Their Family Caregivers

Author

Marcos Sorbara, Ricardo F. Allegri, Daniela Thumala, Adriana Peredo Rossetti, Lílian Viana Dos Santos Azevedo, Lucia Crivelli, Ludmila Vivas, Paulo Caramelli, Ludmilla Aparecida Cardoso Pinto, Andrea Slachevsky, Caíssa Bezerra de Andrade, Maira Tonidandel Barbosa, Héctor Gastón Graviotto, Alana Barroso Generoso, Ismael Calandri, Alejandra Pinto, Karoline Carvalho Carmona, Tania Guajardo, Maria Carolina Santos Vieira, Cecilia Serrano, Claudia Miranda-Castillo, and Loreto Olavarria

Subjects
Adult, Male, medicine.medical_specialty, Activities of daily living, media_common.quotation_subject, Physical Distancing, Argentina, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Activities of Daily Living, mental disorders, Pandemic, Humans, Medicine, Dementia, 030212 general & internal medicine, Chile, Social isolation, Psychiatry, Pandemics, Aged, media_common, Aged, 80 and over, business.industry, Family caregivers, General Neuroscience, COVID-19, General Medicine, Middle Aged, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Caregivers, Social Isolation, Feeling, Severe dementia, Anxiety, Female, Geriatrics and Gerontology, medicine.symptom, business, Brazil, 030217 neurology & neurosurgery
Abstract

Background: People with dementia and their family caregivers may face a great burden through social isolation due to the COVID-19 pandemic, which can be manifested as various behavioral and clinical symptoms. Objective: To investigate the impacts of social isolation due to the COVID-19 pandemic on individuals with dementia and their family caregivers. Methods: Two semi-structured questionnaires were applied via telephone to family caregivers of people diagnosed with dementia in three cities in Argentina, Brazil, and Chile, in order to assess clinical and behavioral changes in people with dementia and in their caregivers. Results: In general, 321 interviews were conducted. A significant decline in memory function has been reported among 53.0%of people with dementia. In addition, 31.2%of individuals with dementia felt sadder and 37.4%had increased anxiety symptoms. These symptoms of anxiety were greater in individuals with mild to moderate dementia, while symptoms of agitation were greater in individuals with severe dementia. Moreover, compulsive-obsessive behavior, hallucinations, increased forgetfulness, altered appetite, and increased difficulty in activities of daily living were reported more frequently among individuals with moderate to severe dementia. Caregivers reported feeling more tired and overwhelmed during this period and these symptoms were also influenced by the severity of dementia. Conclusion: Social isolation during the COVID-19 pandemic triggered a series of negative behavioral repercussions, both for people with dementia and for their family caregivers in these three South American countries.

Published
2021
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33. Relation of the Serum Levels of DKK-1 and Osteoprotegerin with Bone Mass in Tightly Controlled Rheumatoid Arthritis

Author

Andrea Zacarías, Javier Narváez, Estíbaliz Loza, Carmen Gómez-Vaquero, Irene Martín, Loreto Carmona, and Pedro Alía

Subjects
Adult, Male, musculoskeletal diseases, medicine.medical_specialty, Bone density, Osteoporosis, Gastroenterology, Arthritis, Rheumatoid, Rheumatology, Osteoprotegerin, Bone Density, Internal medicine, medicine, Humans, Femur, Aged, Femoral neck, Bone mineral, business.industry, Middle Aged, medicine.disease, medicine.anatomical_structure, Rheumatoid arthritis, Intercellular Signaling Peptides and Proteins, Female, business, Bone mass
Abstract

Objective: To analyze the association between serum levels of osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and the annual percent change (Δ%) in bone mineral density (BMD) in patients with tightly controlled rheumatoid arthritis (RA). Methods: Observational mixed-study. RA patients followed-up with a tight-control strategy were included. Bone densitometries were performed at baseline (T0) and follow-up (T1) and serum levels of OPG and DKK-1 were measured by ELISA also in T0 and T1; additional clinical variables included disease activity measures, and treatment for RA and osteoporosis. Descriptive bivariate and multivariate analyses, stratified by gender, were performed. Results: We included 97 RA patients (70% female, with a mean age of 53 years, and 76% with low activity by DAS28); 95% were treated with DMARDs and 37% with anti-osteoporotic drugs. Mean time between T0 and T1 was 2.7 years. Most patients had their BMD improved. The mean Δ%BMD was +0.42% for lumbar spine, +0.15% for femoral neck and +0.91% for total femur. In men, baseline OPG was significantly associated with higher BMD loss (β coefficient -0.64) at the femoral neck. In women, DKK-1 was associated with higher BMD loss at the femoral neck (β coefficient -0.09), and total femur (β coefficient -0.11); however, DKK-1 was associated with lower BMD loss at the lumbar spine (β coefficient 0.06). Conclusion: In tightly controlled RA patients, we have found no evidence of bone loss. The role of DKK1 and OPG seems small and might be related to sex and location.

Published
2021
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34. Association of retinal detachment with age 50 years or younger at onset in patients with acute retinal necrosis

Author

Luz Elena Concha-Del-Río, Victor Velasquez, Lourdes Arellanes-Garcia, Rodrigo Anguita, Loreto Cuitino, Jared E. Knickelbein, Sergio Morales, H. Nida Sen, Cristhian A. Urzua, Uriel Moreno, and Francisco A Villarroel

Subjects
Adult, Male, medicine.medical_specialty, Visual Acuity, Acyclovir, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Risk groups, Prednisone, Internal medicine, medicine, Humans, In patient, Retrospective Studies, business.industry, Retinal Detachment, Retinal detachment, Retinal Necrosis Syndrome, Acute, Middle Aged, medicine.disease, Sensory Systems, Predictive factor, Ophthalmology, 030221 ophthalmology & optometry, Female, Acute retinal necrosis, Complication, business, 030217 neurology & neurosurgery, medicine.drug, Guarded prognosis
Abstract

Due to the guarded prognosis of acute retinal necrosis (ARN), it is relevant to develop a strategy to early categorize those patients in a higher risk of worse outcomes. The purpose of this study is to describe clinical features and predictive factors for retinal detachment (RD) in patients with ARN. Retrospective observational case series of 34 adult patients (38 eyes) with ARN examined between January 2005 and July 2015 in the National Eye Institute (Bethesda, USA), the Department of Ophthalmology, University of Chile (Santiago, Chile), and APEC (CDMX, Mexico). A total of 16 males and 18 females with a mean age at presentation of 44.5 ± 16.8 years were included. Twenty-seven patients (79.4%) received intravenous acyclovir as first-line treatment, and 7 patients received either oral antiviral (4 patients) or oral plus intravitreal antiviral (3 patients). All subjects were treated with prednisone, with a mean initial dose of 57.7 ± 16.3 mg per day. Seventeen patients (50.0%) developed retinal detachment. An association of retinal detachment with age at onset was observed (p = 0.04), with patients younger than 50 years presenting a higher risk (OR = 14.86, p = 0.0009). Additionally, patients in this higher risk group had more inflammation in both anterior chamber and vitreous (p = 0.04 and 0.03, respectively). No other predictive factor for retinal detachment was found in the present study. RD represents an important complication in patients with ARN. Younger patients may be at higher risk of this complication, possibly secondary to the presence of a higher level of inflammation.

Published
2021
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35. Adherence to subcutaneous biological therapies in patients with inflammatory rheumatic diseases and inflammatory bowel disease: a systematic review

Author

Carlos Marras, Luis Cea-Calvo, Juan C Nieto, Claudia Arajol, and Loreto Carmona

Subjects
Adult, Male, medicine.medical_specialty, Injections, Subcutaneous, Immunology, Inflammatory bowel disease, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Rheumatic Diseases, Internal medicine, medicine, Humans, Immunology and Allergy, In patient, 030212 general & internal medicine, 030203 arthritis & rheumatology, Biological Products, Biological therapies, business.industry, Gold standard, Inflammatory Bowel Diseases, medicine.disease, Biological Therapy, Medication possession ratio, Study heterogeneity, Family member, Oncology, Female, Immune-mediated inflammatory diseases, business
Abstract

Aim: To assess adherence to subcutaneous biologicals in adults with inflammatory rheumatic diseases or inflammatory bowel disease and evaluate factors possibly associated with adherence. Materials & methods: Systematic searches were conducted of main databases from January 2000 to June 2019. Results: 41 articles (32 full papers and nine abstracts) were included in the review. Among studies which used a medication possession ratio threshold of ≥80% as the end point, adherence varied from 28.8 to 89.4%. Possible predictors of adherence were older age, professional or family member support, belief in medication necessity, lower concerns about medication and monthly versus weekly administration. Conclusion: Considerable variability in adherence rates across published studies reflects study heterogeneity and the absence of a ‘gold standard’ to measure adherence.

Published
2021
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36. DElayed COloRectal cancer care during COVID-19 Pandemic (DECOR-19): Global perspective from an international survey

Author

Santoro, Giulio A., Grossi, Ugo, Murad-Regadas, Sthela, Nunoo-Mensah, Joseph W., Mellgren, Anders, Di Tanna, Gian Luca, Gallo, Gaetano, Tsang, Charles, Wexner, Steven D, LA TORRE, Filippo, Abary Ryan Rainiel, A, Philippines, Abdelwahab Khaled M, Egypt, Abellán Antonio M, Spain, Abraham Ned, Australia, Achkasov Sergey I, Russia, Adamina Michel, Switzerland, Adamo Vincenzo, Italy, Agapov Mikhail, Russia, Agarwal Amit, Usa, Aguado López Héctor, Spain, Aguilar Werner, Chile, AguilarMartínez María Del Mar AM, Spain, Aguilera Asuncion, Spain, Ahmed Jamil, Uk, Aiello Domenico, Italy, Akagi Tomonori, Japan, Akcakaya Adem, Turkey, Akhtar Khalid I, Pakistan, Akiba Ricardo, Brazil, Akrami Majid, Iran, Akyol Cihangir, Turkey, Alaamer Ohood H, Saudi Arabia, Alapati Kishore, India, Alasari Sami, Saudi Arabia, Albastaki Sara, Uae, Albergaria Diogo, Portugal, Alconchel Felipe, Spain, Alerta-Torre Andrea J, Philippines, Alex Ochsner, Switzerland, Alexander Herold, Germany, Alfaro Samuel, El Salvador, Ali Jehangir F, Pakistan, Aliyazicioglu Tolga, Turkey, Almgla Naser, South Africa, Alonsopoza Alfredo, Spain, Al-Radjid Jamiri, Philippines, Alselaim Nahar A, Saudi Arabia, Altaf Kiran K, Uk, Althebaity Rasha, Saudi Arabia, Altinel Yuksel, Turkey, Altiparmak Basak, Turkey, Altomare Donato F, Italy, Alvandipour Mina, Iran, Alvarez-Gallego Mario, Spain, Alyami Mohammad, Saudi Arabia, Amado Sandra, Portugal, Amato Antonio, Italy, Amodio Pietro M, Italy, Ana-Maria Mușină, Romania, Andrade Luis, Chile, Andreas Kohler, Switzerland, Angelini Giulio, Italy, Angenete Eva, Sweden, Annicchiarico Alfredo, Italy, Antelo Galarza Renan, Bolivia, Anwer Mariyah, Pakistan, Aparício David J, Portugal, Arciniega Jose A, Mexico, Arezzo Alberto, Italy, Argenio Giulio, Italy, Arenas Mara, Belgium, Arnaud Alves AA, France, Arredondo Jorge, Spain, Arslan Baha, Turkey, Arya Shobhit, Uk, Aselmann Heiko, Germany, Aumann Georg, Germany, Avanzolini Andrea, Italy, Avendano Rodolfo, Chile, Awedew Atalel F, Ethiopia, Ayantunde Abraham, Uk, Aycan Ilker, Turkey, Aytac Erman, Turkey, Azevedo Constança TM, Portugal, Ba Am, Iraq, Bader Fg, Germany, Baehrle Markus, Germany, Bagaglini Giulia, Italy, Balaban Vladimir, Russia, Balciscueta Zutoia, Spain, Balciscueta Izaskun, Spain, Baldazzi Gianandrea, Italy, Balik Emre, Turkey, Bandolon Robert, Philippines, Barberis Andrea, Italy, Barisic Goran I, Serbia, Barrera Alejandro, Chile, Barros Inês MSF, Portugal, Basaran Betul, Turkey, Basilio Pedro C, Brazil, Bech Flemming, Denmark, Behboo Roubik, Iran, Behboudi Behnam, Iran, Beitia Ivan E, Panama, Bellato Vittoria, Italy, Bellolio Felipe, Chile, Benli Sami, Turkey, Bernal Jc, Spain, Bernante Paolo, Italy, Berrospi Francisco E, Peru, Bertelson Noelle, Usa, Bevan Katharine, Uk, Bhama Anuradha, Usa, Bianco Francesco, Italy, Bievel Radulescu Raluca, Romania, Bintraiki Thamer, Saudi Arabia, Bisgin Tayfun, Turkey, Bislenghi Gabriele, Belgium, Blaslaina Juanluis, Spain, Bloom Itm, Uk, Boehm Gabriele, Germany, Bogoni Selene, Italy, Bohlooli Mehrdad, Iran, Bondurri Andrea, Italy, Boni Luigi, Italy, Bonomi Alessandro Michele, Italy, Booning Nitikun, Thailand, Boonpipattanapong Teeranut, Thailand, Bordeianou Liliana, Usa, Bossard Kerrie, Usa, Botelho Maria, Portugal, Boto Carlos, Portugal, Bottini Corrado, Italy, Bouchagier Konstantinos, Greece, Boutall Adam, South Africa, Bowers Dan, Usa, Bozbiyik Osman, Turkey, Brambilla Eduardo, Brazil, Brisinda Giuseppe, Italy, Brizzi Maria Pia, Italy, Brizzolari Marco, Italy, Brusciano Luigi, Italy, Bucci Luigi, Italy, Buchwald Pam, Sweden, Bugra Dursun, Turkey, Bui Andrew, Australia, Buldanlı Mehmet Zeki, Turkey, Bulut Orhan, Denmark, Cagigas Fernandez Carmen, Spain, Cai Yuankun, China, Calcerrada Alises Enrique, Spain, Caldes Pedro, Portugal, Calussi Marco, Italy, Calvo Espino Pablo, Spain, Campanelli Michela, Italy, Campbell Ken, Uk, Campennì Paola, Italy, Canda Arasemre, Turkey, Capolupo Gabriella T, Italy, Caravana Jorge, Portugal, Carballo Federico HE, Argentina, Carbone Fabio, Italy, Carcamo Leonardo C, Chile, Cardoso Paulo, Portugal, Cariati Maria, Italy, Caricato Marco, Italy, Carmona Maria, Spain, Carpelan Holmstrom Monika, Finland, Carrié Augusto J, Argentina, Carrino Francesco, Italy, Cartucho Daniel DF, Portugal, Carvalho Marcia, Portugal, Carvas João M, Portugal, Casagranda Biagio, Italy, Casimiro Carlos, Portugal, Castro Anyely, Dominican Republic, Catiwala-An Michael T, Philippines, Caushaj Philip F, Usa, Cavallo Debora, Italy, Cedermas Mariela, Argentina, Celayir Fevzi, Turkey, Celentano Valerio, Uk, Cengiz Fevzi, Turkey, Chaisomboon Nopdanai, Thailand, Chenghua Luo, China, Cherepenin Mikhail, Russia, Chessa Antonella, Italy, Chierici Andrea, France, Chok Aikyong, Singapore, Chouliaras Christos, Greece, Chowchankit Irin, Thailand, Christou Niki, France, Chun Hokyung, South Korea, Cillara Nicola, Italy, Cinza Margarida, Portugal, Cione Gianpiero, Italy, Cipe Gokhan, Turkey, Ciprian Duta, Romania, Cirocco William, Usa, Citgez Bulent, Turkey, Clark Jill E, Usa, Clementi Ilaria IC, Italy, Clerc Daniel, Switzerland, Clermonts Journal Pre-proof 39 Stefan HEM, Netherlands, Cobellis Luigi, Italy, Colak Tahsin, Turkey, Colao Garcia Laura, Spain, Colombo Francesco, Italy, Comba Andrea, Italy, Coret Franco Alba CFA, Spain, Correa Bonito Alba, Spain, Cosman Bard, Usa, Costa Susana GS, Portugal, Costa Marta RP, Portugal, Costa Pereira Joaquim, Portugal, Cózar Lozano Coral, Spain, Cravero Francesca, Italy, Creavin Ben, Ireland, Cross Katie LR, Uk, Cruz Arturo, Spain, Cui Junhui, China, Cunha Miguel F, Portugal, Curado Antonio, Portugal, D'Ugo Stefano, Italy, Dajti Irida, Albania, Dalessandro Antonio, France, Dal Monte Giorgio, Italy, Danelli Piergiorgio, Italy, Daniels Ian R, Uk, Dar Asif M, India, Davies Richard J, Uk, De Andrés Beatriz, Spain, De Angelis Marsilio, Italy, De Falco Nadia, Italy, De Luca Maurizio, Italy, De Luca Raffaele, Italy, De Nardi Paola, Italy, De Rosa Michele, Italy, De Silva Kaluthanthiri Patabanadi VR, Sri Lanka, De Simone Veronica, Italy, De Wilt Johannes HW, Netherlands, De-León-Rendón Jorge Luis, Mexico, Dean Phillip, Usa, Deangelis Nicola, France, Dedemadi Georgia, Greece, Delgadillo Xavier, Switzerland, Delgadillo Edgar, Switzerland, D’Elia Antonio, Italy, Delibegovic Samir, Bosnia and Herzegovina, Delis S, Greece, Della Porta Massimiliano, Italy, Del Rio Paolo, Italy, De Marano Gaetano, Italy, Demey Karel, Belgium, Demirli Atıcı Semra, Turkey, Denoya Paula I, Usa, Derebey Murat, Turkey, De Santis Mariangela, France, Devezas Vítor BS, Portugal, Dhaif Ali, Bahrain, Diaconescu Bogdan, Romania, Di Candido Francesca, Italy, Die Javier, Spain, Dieguez Beatriz, Spain, Dieter Hahnloser, Switzerland, Diez Alonso Manuel, Spain, Dimaren Ishmael, Philippines, Disimone Massimo, Italy, Doerner Johannes, Germany, Domingos Hugo VG, Portugal, Dominguez Rubén RD, Paraguay, Dorenbusch Michael, Usa, Doulias Triantafyllos A, Uk, Duff Sarah, Uk, Dulskas Audrius, Lithuania, Dunn Gary, Usa, Duque-Mallén Victoria, Spain, Dusek Tomas, Czech Republic, Dusitanond Navara, Thailand, Dzulkarnaen Zakaria Andee, Malaysia, Dworkin Michael, United Kingdom, Dybau Aleh, Belarus, Dziakova Jana, Spain, Dziki Lukasz, Poland, Dziki Adam, Poland, Efetov Sergey K, Russia, Eisa Mohamed, Egypt, Eisenstat Ted, Usa, El Sorogy Mohamed, Egypt, El-Hussuna Alaa, Denmark, Elfeki Hossam, Egypt, Elhussuna Alaa, Denmark, Eliasrabelo Fernanda, Brazil, Ellis Tyler, Usa, Elzalabany Tamer, Egypt, Emile Sameh H, Egypt, Emiroglu Mustafa, Turkey, Emmanuel Odet, France, Enomoto Masanobu, Japan, Epifani Angelo Gabriele, Italy, Erenler Ilknur, Turkey, Erkan Arman, Usa, Erol Timuçin, Turkey, Erturk Suphan, Turkey, Escalante Ricardo, Venezuela, Escartin Jorg, Spain, Escrevente Ricardo, Portugal, Espin-Basany Eloy, Spain, Estaire-Gomez Mercedes, Spain, Falaschi Federica, Italy, Falken Ylva, Sweden, Fantini Corrado, Italy, Fantozzi Mauricio, Argentina, Farid Asim, Usa, Farina Pablo, Argentina, Farmer Russ, Usa, Farmer Martin, Uk, Faul Eleanor M, Ireland, Favara Andrea, Italy, Febra Pedro, Portugal, Fenner Lyra Junior Humberto, Brazil, Fermani Claudio, Argentina, Fernandes Fábio FN, Portugal, Fernandes Miguel, Portugal, Ferracci Federica, Italy, Ferrara Francesco, Italy, Ferrari Giovanni, Italy, Ferrario Luca, Italy, Ferreira Rita, Portugal, Ferreira Carlos, Portugal, Ferris Jeff, Usa, Ferronetti Antonio, Italy, Fialho Guilherme L, Portugal, Fichera Alessandro, Usa, Figueiredo Odete, Portugal, Filipe Vieira Pedro JG, Portugal, Fiore Felicia, Italy, Folliero Cristina, Italy, Folstad Torbjorn, Norway, Forerotorres Alexander, Spain, Forgan Timothy R, South Africa, Franceschilli Marzia, Italy, Frizelle Frank, New Zealand, Froehner Junior Ilario, Brazil, Frois Miguel, Portugal, Frontali Alice, France, Fu Chuangang, China, Fulginiti Serena, Italy, Galiffa Giampaolo, Italy, Gallagher Hugh J, Uk, Gallardo Cristian, Chile, Galleano Raffaele, Italy, Gama Barbara, Portugal, Garcia Conde Maria, Spain, Garcia Granero Alvaro, Spain, Garcia Esther, Spain, García Sánchez Felipe, Spain, Garcia Septiem Javier, Spain, Garcia Walter, Argentina, Garcia-Urena Miguel Angel, Spain, Garmanova Tatiana N, Russia, Garofalo Thomas, Usa, Garoufalia Zoe, Greece, Garulli Gianluca, Italy, Gatti Matteo, Italy, Gecim Ethem, Turkey, Gellona Jose, Chile, Gercek Yuksel, Uk, Ghignone Federico, Italy, Gianchandani Moorjani Rajesh, Spain, Gianfrancisco James A, Usa, Giani Iacopo, Italy, Gibert Juan, Spain, Gilles Manceau, France, Gilmore Andrew, Australia, Gilsanz Carlos, Spain, Gilshtein Hayim, Usa, Girgin Behic, Turkey, Giria Joao, Portugal, Giuffrida Maria Carmela, Italy, Giuliani Antonio, Italy, Goi Gloria, Italy, Golovina Anastasiya, Russia, Gomez Rosado Juan Carlos, Spain, González Enrique, Spain, Granada Nemesio, Philippines, Grimme Frederike, Netherlands, Grobler Stephen, South Africa, Guaitoli Eleonora, Italy, Guerci Claudio, Italy, Guerra Daniel, Mexico, Guerreiro José MM, Portugal, Guido Jutten, Belgium, Gulcu Baris, Turkey, Gunay Emre, Turkey, Gundes Ebubekir, Turkey, Gurbuz Bulent, Turkey, Gurjar Shashank, Uk, Hainsworth Alison J, Uk, Hall Nigel, Uk, Hamed Hosam H, Egypt, Hammer Clare, Uk, Hannon Rob, Ireland, Harmston Christopher, New Zealand, Harran Nadine, South Africa, Hartendorp Paul, Usa, Hassan Iyad, Uae, Hassan Imran, Usa, Hawkins Alexander T, Usa, Hayssen Theresa, Usa, Hendren Samantha, Usa, Hernandez Garcia Miguel, Spain, Hershman Michael, Journal Pre-proof 40 UK, Hild Stefanie, Germany, Hilton Joanna, Uk, Hiranyakas Art, Thailand, Ho Ming, Australia, Hollington Paul, Australia, Holubar Stefan, Usa, Hompes Roel, Netherlands, Houcine Maghrebi, Tunisia, Hovsepyan Vardges, Armenia, Hul Rene, Netherlands, Hunt Louise E, Uk, Hyder Zargham, Uk, Ibrahim Aini F, Malaysia, Iglesias Gustavo, Brazil, Iesalnieks Igors, Germany, Ilkanich Andrei, Russia, Imanova Nargiz, Azerbaijan, Isik Arda, Turkey, Jayathilaka Buddika, Uk, Jimenez Virginia, Spain, Jimenez-Gomez Luis Miguel, Spain, Jitmungngan Romyen, Thailand, Joelsson Magnus, Sweden, Joshi Heman, Uk, Juloski Jovan T, Serbia, Juwid Abdallah E, Libya, Kanjanasilp Prapon, Thailand, Kannappa Lava, Uk, Kanno Danilo, Brazil, Kaplan Esin, Turkey, Kara Yasin, Turkey, Kartal Abdulcabbar, Turkey, Kawamura Junichiro, Japan, Kaya Tayfun, Turkey, Kazemi Nava Andrea, Italy, Kazachenko Ekaterina A, Russia, Kelkar Ashish, Uk, Kelly Michael E, Ireland, Keramati Mohammad Reza, Iran, Kerawala Asad, Pakistan, Khalil Mohammad I, Bangladesh, Khan Jim S, Uk, Khan Rbn, Uk, Khitaryan Alexander, Russia, Kinjo Tatsuya, Japan, Kirilova Tanya N, Bulgaria, Kirmizi Yasemin, Turkey, Klaristenfeld Daniel, Usa, Knapp Jens, Norway, Koc Mehmet A, Turkey, Kocián Petr, Czechia, Konishi Tsuyoshi, Japan, Konstantoudakis Georgios, Cyprus, Konsten Joop, Netherlands, Kontovounisios Christos, Uk, Korkmaztoker Melike, Turkey, Kørner, Hartwig, Norway, Krdzic Igor, D, Serbia, Krivokapic Zoran, Serbia, Kumar Sanjeev, India, Kumar Sandip, Malaysia, Kushtrim Shala, Germany, Kynaston James, Uk, Langmayr Johannes, Austria, La Torre Marco, Italy, La Torre Filippo, Italy, Labalde Maria, Spain, Lagopoulos Vasileios, Greece, Lal Roshan, Uk, Landaluce- Olavarria Aitor, Spain, Langone Antonio, Italy, Lapolla Pierfrancesco, Italy, Larach Sergio, Usa, Larach, Andres, Chile, Larsson, Peranders, Sweden, Lasala Alfred, Philippines, Lauretta Andrea, Italy, Leao Pedro, Portugal, Lee Pamela C, Usa, Lee Suk-Hwan, South Korea, Lee Wooyong, South Korea, Lefevre Jeremie H, France, Leite Julio, Portugal, Lemaire Julien, Belgium, Lemma Maria, Italy, Lemme Gustavo Nestor, Argentina, Lenna Giovanni, Italy, Leo Cosimo Alex, Uk, Leventoglu Sezai, Turkey, Licardie Eugenio, Spain, Lienert Mark, Germany, Lima Sergio, Brazil, Limbert Manuel CSB, Portugal, Lisi Giorgio, Italy, Litta Francesco, Italy, Littaua Dennis, Philippines, Liu Fanlong, China, Liyanage Chris, New Zealand, Llovera Antony, Cuba, Lo Oswens, China, Lo Dico Rea, France, Lobascio Pierluigi, Italy, Lohsiriwat Varut, Thailand, Lombana Luis, Colombia, Lopez Marc, Philippines, Lopez Jose, Mexico, Lopez Francisco, Chile, Lorber Julie, Usa, Losada Manuel, Spain, Lowenfeld Lea, Usa, Lucci Enrico, Italy, Luglio Gaetano, Italy, Lynch Craig, Australia, Luqman, Pakistan, Machairas Nikolaos, Uk, Maciel João MRP, Portugal, Madbouly Khaled, Egypt, Madhoun, Nisreen, Usa, Maffioli, Anna, Italy, Magbojos Christian Raymond S, Philippines, Magistro Carmelo CM, Italy, Magrino Thomas, Usa, Makhoul Rami, Usa, Mallmann Karen DP, Brazil, Manatakis Dimitrios K, Greece, Mancini Stefano, Italy, Manfredelli Simone, France, Mangione John, Usa, Manso Antonio, Portugal, Marakutsa Eugen V, Moldova, Marano Alessandra, Italy, Marchesi Federico, Italy, Marchiori Mauro, Brazil, Marfan Michael, Australia, Marianelli Raphael, Brazil, Mariani Nicolò M, Italy, Marimuthu Kalimuthu, Uk, Marinello Franco, Spain, Marinis Athanasios, Greece, Marino Marco V, Italy, Markides Georgios, Cyprus, Marquez Lucila, Spain, Marra Angelo A, Italy, Martín Navarro Fabian, Mexico, Martin-Martin Gonzalo P, Spain, Martinez Javier, Spain, Martinez-Iglesias Marta A, Uk, Martins Ruben AFP, Portugal, Martins Ana RG, Portugal, Mascali Davide DM, Italy, Massucco Paolo, Italy, Matas Fernando, Spain, Mathew Alexander, Usa, Matzel Klaus E, Germany, Maun Dipen, Usa, Maurus Christine F, Switzerland, McCormick Jim, Usa, McIntyre Robert, Uk, McKinley Aileen, Uk, McLemore Lisa, Usa, McNeil Jennifer, Usa, McNevin Shane, Usa, Medich David, Usa, Medina Cesar, Mexico, Medina Quintana Rita E, Spain, Melo Ingrid, Paraguay, Melstrom Kurt A, Usa, Mendoza-Moreno Fernando, Spain, Menna Maria Paola, Italy, Mentz Ricardo, Argentina, Merlini David A, Italy, Mihmanli Mehmet, Turkey, Mike Spencer, Usa, Millan Monica, Spain, Miller Jerad, Usa, Milone Marco, Italy, Minahi Ilyas, Uk, Minaya-Bravo Ana María, Spain, Mingoli Andrea, Italy, Minicozzi Annamaria, Uk, Miranda Pedro, Portugal, Miro Antonio, Italy, Miskovic Danilo, Uk, Mistrangelo Massimiliano, Italy, Mitra Rajarshi, Uae, Mittal Rohin, India, Mladenovikj Dragoslav P, North Macedonia, Moctezuma Velázquez Paulina, Mexico, Mohamed Kamil Nil Amri, Malaysia, Mohammed Mohammed MH, Egypt, Mohsen Yasser MA, Uk, Monami Benoit N, Belgium, Monroe Justin, Usa, Monroy Hermogenes DJ, Philippines, Montori Giulia, Italy, Montuori Mauro, Italy, Mora-Guzmán Ismael, Spain, Moraes Ana, Brazil, Morales Carlos, Usa, Morelli Luca, Italy, Moreno Almudena, Spain, Moretto Gianluigi, Italy, Morici Riccardo, Italy, Morini Andrea, Italy, Moro-Valdezate David, Spain, Moroni Eliana, Italy, Morton Dion, Uk, Moura Catarina, Portugal, Moysidis Moysis M, Greece, Mozo Ana S, Spain, Nacion Aeris Jane D, Philippines, Nada Mohamed, Journal Pre-proof 41 Egypt, Nagasaki Toshiya, Japan, Nakamoto Yoshihiko, Japan, Neary Peter, Ireland, Negoi Ionut, Romania, Neijenhuis Peter A, Niger, Ng Simon SM, China, Niazi Samiullah, Pakistan, Nikoupour Hamed, Iran, Nogueiro Jorge PM, Portugal, Noguera Jose, Spain, Nova Carlos, Portugal, Nunes Amadeu, Portugal, O'Riordain Micheal G, Ireland, Oke Olatunbosun A, Nigeria, Okkabaz Nuri, Turkey, Oliva Cristiano, Italy, Oliveira Olga, Portugal, Oliveira Manuel, Portugal, Oliveira Antonio, Portugal, Oliveira Lucia CC, Brazil, Olivier James B, Uk, Olivier Pittet, Switzerland, Omejc Mirko, Slovenia, Ong Loreto B, Philippines, Ong David, Malaysia, Onglao Mark, Philippines, Onody Peter, Hungary, Orefice Raffaele, Italy, Ortega David, Peru, Ozben Volkan, Turkey, Ozcan Onder, Turkey, Ozturk Ersin, Turkey, Pacheco Andre, Portugal, Paci Marco, France, Paczosa Marcin, Poland, Padmanabhan Anantha, Usa, Pai Ajit, India, Palmer Gabriella, Sweden, Pandey Diwakar, India, Panis Yves, France, Pantel, Haddon, Paonariang Krisada, Thailand, Papa Mario V, Italy, Papadopoulos Aristeidis, Greece, Papagni Vincenzo, Italy, Papp Andras, Sweden, Parello Angelo, Italy, Parente Alessandro, Uk, Parra Pedro, Spain, PascualMigueláñez Isabel, Spain, Pata Francesco, Italy, Patel Nikhil, Usa, Patel Reeya, Uk, Pattyn Paul RL, Belgium, Paul Bikram, Usa, Pavanello Maurizio, Italy, Pedro Luis E, Argentina, Pellino Gianluca, Spain, Peltrini Roberto, Italy, Peña Ros Emilio, Spain, Pennacchi Luca UC, Italy, Pereira André, A Portugal, Pereira Bela, Portugal, Perez Guillermo, Ecuador, Perez Horacio, Portugal, Perez Natalia, Spain, Perez Flecha Marina, Spain, Perinotti Roberto, Italy, Pernazza Graziano, Italy, Perra Teresa, Italy, Pertile Davide, Italy, Pessia Beatrice, Italy, Pessoa Joana, Brazil, Petagna Lorenzo, Italy, Peters Walter, Usa, Petit Mindy, Usa, Petracca Gabriele Luciano, Italy, Pezzolla Francesco, Italy, Philp Matthew, Usa, Pianim Nana, Usa, Picciariello Arcangelo, Italy, Piccinini Pablo E, Argentina, Piccinni Giuseppe, Italy, Piccolo Davide, Italy, Pigalarga, Rodolfo, Pikarsky Alon J, Israel, Pimentel Alice, Portugal, Pinchot Scott, Usa, Pinotti Enrico, Italy, Pinto Diogo, Portugal, Pirozzi Felice, Italy, Plastiras Aris, Greece, Platto Marco, Italy, Plerhoples Tim, Usa, Podda Mauro, Italy, Poggi Luis, Peru, Polastri Roberto, Italy, Porcu Alberto, Italy, Porter Michael, Usa, Poskus Eligijus, Lithuania, Potolicchio Analia I, Argentina, Poylin Vitaliy, Usa, Pozzo Mauro, Italy, Pramateftakis Manos, Greece, Pravosudov Igor V, Russia, Praxedes Vanessa P, Portugal, Primoromaguera Vicent, Spain, Progno Valerio C, Italy, Proud David M, Australia, Pucciarelli Salvatore, Italy, Qadir Abdul, Uk, Qayoom Hina, Pakistan, Quindos Patricia, Spain, Quintanilha Rui, Portugal, Quinteros Francisco A, Usa, Qureshi Nafees, Uk, Rachadell Juan J, Portugal, Ralf Schmidt, Germany, Raman Shankar, Usa, Ramos Diego, Spain, Ramos Jose, Portugal, Ramwell, Andrew, Randazzo, Valentina, Rattanarpichart Patsaporn, Thailand, Ratto Carlo, Italy, Rautio Tero, Finland, Raviolo Carla, Italy, Read Thomas, Usa, Real Joao, Portugal, Rega Daniela, Italy, Regadas Francisco, Brazil, Regenbogen Scott, Usa, Reia Marta, Portugal, Reina Angel, Spain, Rems Miran, Slovenia, Rencuzogullari Ahmet, Turkey, Renwick Andrew A, Uk, Reyes Juan C, Colombia, Reyes Jeryl Anne Silvia R, Philippines, Ribeiro Jr Ulysses, Brazil, Ridzuan Farouk, Singapore, Ripetti Valter, Italy, Ripoll Cristina, Mexico, Ripollés-Melchor Javier, Spain, Rizal Rizal, Indonesia, Rizk Mariam, Uk, Rizvi Irfan, Usa, Robinson Jonathan, Uk, Rodimov Sergei, Russia, Rodrigues João VL, Brazil, Rodriguez Javier, Mexico, Rodriguez Cristian, Argentina, Rodriguez Homero, Panama, Rodriguez Garcia Jaime, Mexico, Roig Jose, Spain, Rojanasakul Arun, Thailand, Rojas Julio, Chile, Romanelli Elena, France, Rosa Fausto, Italy, Rosato Guillermo, Argentina, Rosenberg Robert, Switzerland, Rosete Manuel, Portugal, Roslani April C, Malaysia, Rottoli Matteo, Italy, Roxas Manuel Francisco Roxas T, Philippines, Roxburgh Campbell S, Uk, Ruan Joseph, Usa, Rubbini Michele M, Italy, Rubio Eduardo, Spain, Ruddy Theresa, Usa, Rueda Camilo, Spain, Ruiztovar Jaime, Spain, Rusconi Andrea, Italy, Rutegård Martin, Sweden, Sá Milene RRM, Portugal, Saad Luiz Henrique Cury, Brazil, Sadien Iannish D, Uk, Sadowski Brian M, Usa, Saeed Mirza Faraz, Bahrain, Safiyeva Aynur K, Azerbaijan, Sagap Ismail, Malaysia, Sahnan Kapil, Uk, Sairafi Rami, Saudi Arabia, Saklami Avanish P, India, Salgado-Nesme Noel NSN, Mexico, Salman Nevriye, Turkey, Samalavicius Narimantas E, Lithuania, Sambucci Daniele, Italy, Sanchez Noel, Usa, Sanchez Robles Juan Carlos, Mexico, Sanmiguel Carlos, Spain, Santacruz Eduardo, Paraguay, Santoni Simone, Italy, Santos Pedro MD, Portugal, Santos Brian U, Argentina, Santos Carlos, Portugal, Sapienza Paolo, Italy, Saracoglu Ayten, Turkey, Saracoglu Kemal T, Turkey, Sardinas Carlos, Venezuela, Sari Ramazan, Turkey, Sarma Diwakar, Uk, Sartori Alberto A, Italy, Sasia Diego, Italy, Sbaih Mohammed H, Saudi Arabia, Scabini Stefano, Italy, Scaringi Stefano, Italy, Scheinin Tom M, Finland, Schiavo Marcello, Italy, Schizas Alexis, Uk, Sciaudone Guido, Italy, Scognamillo Fabrizio, Italy, Scott Kelley, Usa, Scow Jeffrey S, Usa, Sechi Raffaele, Italy, Seehra Harkiran, Uk, Segering Joerg, Germany, Selcuk Mehtap, Turkey, Journal Pre-proof 42 Selemane Carlos, Mozambique, Seltman Ann, Usa, Selvaggi Francesco, Italy, Sensi Bruno, Italy, SeowChoen Francis, Singapore, Sernagiotto Carlo, Italy, Serralta De Colsa Daniel, Spain, Serrano González Javier, Spain, Sert Ismail, Turkey, Serventi Alberto, Italy, Sforza Sergio, Italy, Shabbir Jamshed, Uk, Shabeeb Fadel, Uae, Shafik Ali, Egypt, Shalaby Mostafa, Egypt, Shanker Bethann, Usa, Shanmugam Venkatesh, Uk, Shariff Umar, Uk, Shehta Ahmed, Egypt, Shelton Andrew, Usa, Shintaro Akamoto, Japan, Shlyk Daria, Russia, Shukla Amit, Uk, Sibio Simone, Italy, Sietze Koopal, Netherlands, Sigurdardottir Johanna, Sweden, Silva Jorge, Mexico, Silva Anaisa, Portugal, Simianu Val, Usa, Singh Baljit, Uk, Siragusa Leandro, Italy, Sirikurnpiboon Siripong, Thailand, Sivrikoz Emre, Turkey, Sizonenko Nikolay, Russia, Slavchev Mihail T, Bulgaria, Sniuolis Pranas, Lithuania, Soares Duarte, Qatar, Sojar Valentin, Slovenia, Sokmen Selman, Turkey, Sokol Thomas, Usa, Soldatov Denis, Russia, Soncini Stefania, Italy, Sordo Ricardo, Mexico, Sosa María V, Spain, Sousa Xavier, Portugal, Sozutek Alper, Turkey, Spiezio Giovanni, Italy, Spinelli Antonino, Italy, Stahl Etienne, Mexico, Stanojevic Goran Z, Serbia, Steckel Brian, Usa, Stefan Neagu, Romania, Stefanescu Victor, Romania, Steinhagen Randolph, Usa, Stella Marco, Italy, Stephensen Bree D, Australia, Stevenson Andrew RL, Australia, Stitzenberg Karyn, Usa, Strombom Paul, Usa, Sturiale Alessandro, Italy, Suhail Anjum, Pakistan, Sungurtekin Ugur, Turkey, Sutton Jeffrey M, Usa, Suwannakij Chanchai, Thailand, Szczepkowski Marek, Poland, Sztipits Tamas, Hungary, Takashi Akiyoshi, Japan, Takkenberg Marijn, Netherlands, Tallon-Aguilar Luis, Spain, Tam Michael, Usa, Tamburini Andrea M, Italy, Tamini Nicolò, Italy, Tammaro Pasquale, Italy, Tan Kerkan, Singapore, Tan Teerasan, Thailand, Tanal Mert, Turkey, Tanda Cinzia, Italy, Tang Jinghua, China, Tapiolas Ingrid, Uk, Täreby Magnus, Sweden, Tariverdiev Andrey, Russia, Tayar Serkan, Turkey, Tejedor Patricia, Spain, Terrosu Giovanni, Italy, Testa Alessandro, Italy, Tewari Shirish, Uk, Thabet Waleed, Egypt, Thakur Sukesh, India, Thomas Ehmann, Germany, Thomas Kuruc, Germany, Tiesi Vincenzo, Italy, Tin Moemoetin, Myanmar, Tita Agustin C, Argentina, Titu Liviu V, Uk, Tkachenko Fedot, Ukraine, Tonello Paolo, Italy, Tooley Richard, Usa, Torres Juan, Spain, Troci Albert, Italy, Trompetto Mario, Italy, Troncoso Pereira Paula, Spain, Tropeano Francesca Paola FP, Italy, Trostchansky Ivan, Uruguay, Tsujinaka Shingo, Japan, Tufo Andrea, Italy, Tulina Inna, Russia, Turati Luca, Italy, Turchina Catalin, Sweden, Turina Matthias, Switzerland, Tutino Roberta, Italy, Tyler Km, Usa, Uemura Mamoru, Japan, Unal Ayse G, Turkey, Uraiqat Ahmad, Jordan, Uribe Sebastián, Chile, V Duke, Usa, Vailati Bruna, Brazil, Vaingurt Mariano, Argentina, Valente Michael, Usa, Van Dellen Jonathan, Uk, Van Ramshorst Gabrielle H, Belgium, Vannelli Alberto, Italy, Vanriel W, Belgium, Varabei Aliaksandr, Belarus, Varcada Massimo, Uk, Varela Cristopher L, Venezuela, Varma Madhulika G, Usa, Vasapollo Leoluca F, Italy, Venn Mary L, Uk, Vercillo Kristin, Usa, Vergara-Fernandez Omar, Mexico, Veronesi Paolo, Italy, Vicente Aline, Brazil, Victor Tomulescu, Romania, Vieiradesousa Paulo, Portugal, Vignali Andrea, Italy, Vigorita Vincenzo, Spain, Vilchis Jose, Mexico, Villaverde Kathia, Peru, Vindevoghel Koen, Belgium, Violante Tommaso, Italy, Vitoopinyoparb Kasidin, Thailand, Voutsarakis Athanasios, Uk, Wainstein Ricardo, Argentina, Wakefield Simon, Uk, Wallon Conny, Sweden, Wang Yongbing, China, Wang Xiaodong, China, Wang Xiaofeng, China, Warden Claire, South Africa, Wei Rockson, China, Wheeler Matthew, Usa, Willem Bemelman, Netherlands, Wilson Matthew, Usa, Winter Des C, Ireland, Wongwiwatseree Yongsun, Thailand, Woon Kyung Jeong, South Korea, Wright Danette B, Australia, Wu Jiong, China, Wuraola Funmilola O, Nigeria, Xenaki Sofia A, Greece, Xiaohua Jiang, China, Xiaoqiang Jia, China, Xue Yahong, China, Xynos Evangelos, Greece, Yamada Kazunosuke, Japan, Yanar Hakan, Turkey, Yang Bolin, China, Yanishev Alexey, Russia, Yildirim Ali C, Turkey, Yildiz Ufukmete, Turkey, Yildiz Alp, Turkey, Yilmaz Mehmet, Turkey, Younis Muhammad Umar MUY, Uae, Yousef Zeyad, Saudi Arabia, Yu Dongsheng, China, Zalucki James, Usa, Zaman Ahamaduz, Bangladesh, Zamora Aída T, Spain, Zampitis Nikolaos, Cyprus, Zanus Giacomo, Italy, Zapata Gonzalo H, Argentina, Zelic Marko, Croatia, Zenger Serkan, Turkey, Zheng Jianyong, China, Zigiotto Daniele, Italy, Zmora Oded, Israel, Zoikas Athanasios, Greece, Zorcolo Luigi, Italy, Zucchella Martino, Italy, Zuhdy, Mohammad, Santoro G.A., Grossi U., Murad-Regadas S., Nunoo-Mensah J.W., Mellgren A., Di Tanna G.L., Gallo G., Tsang C., Rottoli M., and Wexner S.D.

Subjects
Male, medicine.medical_specialty, Delayed Diagnosis, Internationality, Colorectal cancer, colorectal surgery - COVID-19 - delay - treatment - outcomes, MEDLINE, colorectal cancer, 030230 surgery, medicine.disease_cause, Article, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Pandemic, medicine, Humans, Practice Patterns, Physicians', Elective surgery, Personal protective equipment, SARS-CoV-2, COVID-19, delayed surgery, Coronavirus, Infection Control, business.industry, Outbreak, medicine.disease, 030220 oncology & carcinogenesis, Preparedness, Emergency medicine, Female, Surgery, Colorectal Neoplasms, business, Colorectal Surgery
Abstract

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

Published
2021
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37. Conservative Treatment for Cervical Adenocarcinoma In Situ: Long-Term Results

Author

Ermelinda Monti, Edgardo Somigliana, Daniela Alberico, Veronica Boero, Maria Iorio, Eugenia Di Loreto, Andrea Dell'acqua, and Carlo Antonio Liverani

Subjects
Treatment Outcome, Electrosurgery, Obstetrics and Gynecology, Humans, Uterine Cervical Neoplasms, Female, General Medicine, Adenocarcinoma in Situ, Conservative Treatment, Uterine Cervical Dysplasia, Retrospective Studies
Abstract

This study aimed to evaluate the effectiveness of conservative treatment for cervical adenocarcinoma in situ (AIS).This is a retrospective study on women with histologically confirmed AIS on cervical loop electrosurgical excision procedure specimen, treated conservatively between 2008 and 2020 in our center, Ospedale Maggiore Policlinico, Milan. The main outcome investigated was the risk of recurrence defined as a subsequent finding of recurrent AIS or invasive adenocarcinoma in a long-term follow-up. The disease-free survival curve was computed using the Kaplan-Meyer method. All patients underwent colposcopy with endocervical curettage and cytology every 6 months for the first 2 years after initial surgery and then annual cytology.Thirty women, aged 26 to 51 years, with histologically proven AIS on excisional specimen with negative margins, negative apex, and negative endocervical curettage were included. The median follow-up was 5.4 years. One woman had a recurrence of AIS after 8 years of follow-up and underwent total hysterectomy. No invasive cervical disease was detected during surveillance.Women with cervical AIS can be managed conservatively by an excisional procedure, provided that the margins are free and a close and long-term follow-up is guaranteed.

Published
2022

38. Validation of a Parent-Reported Physical Activity Questionnaire by Accelerometry in European Children Aged from 6 to 12 Years Old

Author

Daniel Prieto-Botella, Desirée Valera-Gran, Loreto Santa-Marina, Izaro Babarro, Mikel Subiza-Pérez, Maribel Casas, Mónica Guxens, Gabriela Cárdenas-Fuentes, Barbara Heude, Jonathan Y. Bernard, Rosemary R. C. McEachan, Judith García-Aymerich, Martine Vrijheid, Eva-María Navarrete-Muñoz, Miguel Hernandez University (UMH), CIBER de Epidemiología y Salud Pública (CIBERESP), BIODonostia Research Institute, Ministry of Health of the Basque Government, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bradford Institute for Health Research [Bradford, UK], Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-FISABIO), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Bernard, Jonathan, European Commission, and Child and Adolescent Psychiatry / Psychology

Subjects
Male, Health, Toxicology and Mutagenesis, moderate-to-vigorous physical activity, validity measures, measurement, childhood, Public Health, Environmental and Occupational Health, moderate to vigorous physical activity, World Health Organization, Leisure Activities, SDG 3 - Good Health and Well-being, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Surveys and Questionnaires, Accelerometry, Humans, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Exercise
Abstract

Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children's Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland-Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman's partial correlations. ROC curve analysis was also used to explore the questionnaire's capability to identify active children based on the World Health Organization guidelines. A moderate correlation was found between parent-reported and accelerometer MVPA (rho = 0.41, p < 0.001). The child's sex (girl) was statistically associated with the mean MVPA difference between methods. However, this questionnaire accurately identified physically active children (area under the curve = 83.8% and 82.7% for boys and girls, cut-points = 68.6 and 45.4 min/day in MVPA, respectively). Consequently, this questionnaire is suitable for classifying active children in order to monitor public health interventions regarding PA. This study was supported by funding from the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement no. 308333—the HELIX project. INMA data collections were supported by grants from the Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds; PI15/00118 incl. FEDER funds; CP16/00128 incl. FEDER funds; PI16/00118 incl. FEDER funds; PI16/00261 incl. FEDER funds; PI17/01340 incl. FEDER funds; PI18/00547 incl. FEDER funds, PI18/01237 incl. FEDER funds, PI18/00825 incl. FEDER funds); Generalitat Valenciana (GVA/2021/191); CIBERESP; and the Generalitat de Catalunya-CIRIT 1999SGR 00241; Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090430). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program, Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (1262C0010; EST-2016 RF-21), EU Commission (261357, 308333, 603794 and 634453); and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). M.C. and M.G. hold Miguel Servet fellowships (CP16/00128, CPII18/00018) funded by Instituto de Salud Carlos III and co-funded by European Social Fund “Investing in your future”. R.R.C.M. received funding from the National Institute for Health Research Applied Research Collaboration for Yorkshire and Humber.

Published
2022
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39. Maternal occupational exposures and fetal growth in a Spanish birth cohort

Author

Jennifer Ish, David Gimeno Ruiz de Porras, Elaine Symanski, Ferran Ballester, Maribel Casas, George L. Delclos, Mònica Guxens, Jesús Ibarluzea, Carmen Iñiguez, Loreto Santa-Marina, Michael D. Swartz, Kristina W. Whitworth, Child and Adolescent Psychiatry / Psychology, European Commission, Ish, Jennifer, Gimeno Ruiz de Porras, David, Symanski, Elaine, Ballester Díez, Ferran, Casas Sanahuja, Maribel, Delclos, George L., Guxens Junyent, Mònica, Ibarluzea, Jesús, Iñiguez, Carmen, Santa Marina, Loreto, Swartz, Michael D., and Whitworth, Kristina W.

Subjects
Multidisciplinary, Antigen-presenting cells, Infant, Newborn, Gestational Age, Jobs, occupational exposure, Endocrine Disruptors, Ultrasonography, Prenatal, infant, newborn, Fetal Development, Phthalates, Psychological stress, Maternal Exposure, Pregnancy, maternal exposure, Occupational Exposure, Birth, Cohort studies, Birth Weight, Humans, Birth Cohort, Female, pregnancy, Chemical disruption, ultrasonography, prenatal
Abstract

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers' employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We calculated z-scores from longitudinal growth curves representing trajectories from 0-12, 12-20 and 20-34 gestational weeks for abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW). Linear mixed models clustered by IMNA region (i.e., Gipuzkoa, Sabadell, Valencia) were used to examine associations between occupational exposures and fetal growth. Effect estimates are presented as percentage change in fetal growth. There was limited evidence of associations between work-related non-chemical stressors and fetal growth. We observed associations of similar magnitude between multiple EDC groups and decreased EFW trajectories during 20-34 gestational weeks (phthalates: -1.4% [-3.5, 0.6%]; alkylphenolic compounds (APCs): -1.1% [-2.3, 0.1%]; miscellaneous chemicals: -1.5% [-3.7, 0.8%]), while miscellaneous chemicals were associated with increased BPD from 12-20 weeks (2.1% [0.8, 3.5%]). Notably, 67% of women exposed to phthalates were hairdressers; 68% of women exposed to APCs worked as domestic cleaners. In conclusion, we found limited evidence that maternal occupational exposures impact fetal growth. Further research should consider the combined impact of multiple workplace exposures. This work was supported by grants from the National Institutes of Health/National Institute of Environmental Health Sciences (R01ES028842, PI: KWW), Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663, FIS-PI18/01142 incl. FEDER funds; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, CPII18/00018, and CP16/00128), Generalitat de Catalunya-CIRIT 1999SGR 00241, EU Commission (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249) and Conselleria d’Educació AICO/2020/285, and Alicia Koplowitz Foundation 2017, Department of Health of the Basque Government (2005111093), Provincial Government of Gipuzkoa (DFG06/002), and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). We also acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. JI, DGRdP, and GLD were partly supported by the Southwest Center for Occupational and Environmental Health (SWCOEH), the Centers for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) Education and Research Center (T42OH008421) at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health. KWW and ES were supported in part by the by the Gulf Coast Center for Precision Environmental Health (GC-CPEH) at Baylor College of Medicine (P30ES030285). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2021

40. COVID-19 hospital outbreaks: Protecting healthcare workers to protect frail patients. An Italian observational cohort study

Author

Luigi De Maria, Loreto Gesualdo, Marco Quarato, Giovanni Migliore, Pasquale Stefanizzi, Silvio Tafuri, Maria Chironna, Antonio Caputi, Stefania Sponselli, Maria Celeste Delfino, F. I. M. Fucilli, Domenica Cavone, and Luigi Vimercati

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Prevention protocol, Group based, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Frail Elderly, Health Personnel, 030106 microbiology, Article, Disease Outbreaks, lcsh:Infectious and parasitic diseases, Cohort Studies, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Health care, Prevalence, Humans, Medicine, Healthcare workers, lcsh:RC109-216, 030212 general & internal medicine, Aged, Cross Infection, SARS-CoV-2, business.industry, Risk of infection, Infection prevalence, Outbreak, COVID-19, General Medicine, Middle Aged, University hospital, Infectious Diseases, Italy, Female, business, Cohort study
Abstract

Highlights • This study included 3570 healthcare workers underwent naso and oropharyngeal swabs. • The workers were divided into two groups based on COVID-19 patient contact type. • SARS-CoV-2 infection prevalence is 0.45% (25 workers of 5750 subjected to protocol). • We found 0.52% positive in the low-risk group, 13.16% in the high-risk group. • Prevention procedures reduce the risk related to SARS-CoV-2 for healthcare workers., Objectives to determine the prevalence of SARS-CoV-2 infection among exposed HCWs after preventive protocol implementation. Methods 5750 HCWs. Those in contact with COVID-19 patients were allocated into a high-risk or a low-risk group based on contact type (PPE- or non-PPE-protected); high risk workers underwent nasopharyngeal swab tests, while for low-risk workers swab tests were carried out only for symptomatic workers (active surveillance). The prevalence was determined by real-time reverse transcriptase–polymerase chain reaction on nasopharyngeal samples. Results 3570 HCWs had contact with 1065 COVID-19 patients. Among them, 3494 were subjected to active surveillance (low-risk group); 2886 (82.60%) were subjected to a swab test and 15 were positive (0.52%). 76 HCWs (2.13% of exposed) were included in the high-risk group, and a swab test was mandatory for each participant. Overall, 66 (86.84% of high-risk) were negative, and 10 positive (13.16%), resulting in a higher risk of infection than in the low-risk group [OR = 29.00; 95% CI:12.56-66.94; p

Published
2021

41. Midwives’ experiences with screening for intimate partner violence in Santiago, Chile

Author

Ashley Rizzieri, Loreto Pantoja Manzanarez, Savannah Gray, Jennifer Foster, Chelsea Marie Medina, Matthew Revilla, and Lorena Binfa

Subjects
Research, education, Intimate Partner Violence, social sciences, Midwifery, behavioral disciplines and activities, Global issue, Nursing, Pregnancy, mental disorders, General Health Professions, Humans, Mass Screening, population characteristics, Domestic violence, Female, Chile, Psychology, Healthcare providers
Abstract

Although intimate partner violence (IPV) is well-established as a highly prevalent global issue, research examining the experience of health providers who screen women at risk for IPV is scarce. We aimed to explore the experience of midwives in primary health care centers in Santiago, Chile, regarding identification of at-risk women and barriers to screening. We highlight the intersection of complex issues of global relevance, such as culture, language, provider-patient relationships, and allocation of time and resources. In our results, we illustrate the importance of providing midwives extended time, interpreter services, and cross-cultural education to address IPV in their transcultural context.

Published
2020
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42. Progression of chronic kidney disease in familial LCAT deficiency: a follow-up of the Italian cohort

Author

Tiziano Lucchi, Tiziana Sampietro, Giuliano Boscutti, Fabrizio Veglia, Alice Ossoli, Loreto Gesualdo, Marcello Arca, Laura Calabresi, Laura D'Erasmo, and Chiara Pavanello

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, lecithin:cholesterol acyltransferase, kidney transplantation, Renal function, cholesterol/metabolism, Disease, QD415-436, 030204 cardiovascular system & hematology, Biochemistry, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, High-density lipoprotein, Lecithin Cholesterol Acyltransferase Deficiency, renal disease, familial lecithin:cholesterol acyltransferase deficiency, medicine, Humans, Renal Insufficiency, Chronic, Kidney transplantation, Kidney, business.industry, Genetic disorder, Cell Biology, Middle Aged, medicine.disease, lipoproteins, Cholesterol, 030104 developmental biology, medicine.anatomical_structure, Italy, chemistry, high density lipoprotein, Cohort, Female, Patient-Oriented and Epidemiological Research, business, Follow-Up Studies, Kidney disease
Abstract

Familial LCAT deficiency (FLD) is a rare genetic disorder of HDL metabolism, caused by loss-of-function mutations in the LCAT gene and characterized by a variety of symptoms including corneal opacities and kidney failure. Renal disease represents the leading cause of morbidity and mortality in FLD cases. However, the prognosis is not known and the rate of deterioration of kidney function is variable and unpredictable from patient to patient. In this article, we present data from a follow-up of the large Italian cohort of FLD patients, who have been followed for an average of 12 years. We show that renal failure occurs at the median age of 46 years, with a median time to a second recurrence of 10 years. Additionally, we identify high plasma unesterified cholesterol level as a predicting factor for rapid deterioration of kidney function. In conclusion, this study highlights the severe consequences of FLD, underlines the need of correct early diagnosis and referral of patients to specialized centers, and highlights the urgency for effective treatments to prevent or slow renal disease in patients with LCAT deficiency.

Published
2020

43. High levels of gut-homing immunoglobulin A+ B lymphocytes support the pathogenic role of intestinal mucosal hyperresponsiveness in immunoglobulin A nephropathy patients

Author

Anna Gallone, Claudia Curci, Renato C. Monteiro, Loreto Gesualdo, Chiara Divella, Fabio Sallustio, Angela Picerno, Sanae Ben Mkaddem, Luigi Macchia, Giulia Fontò, Gabriella Lauriero, Vincenzo Di Leo, Maria De Angelis, Nada Chaoul, and Francesco Pesce

Subjects
Adult, Male, 0301 basic medicine, Immunoglobulin A, medicine.medical_treatment, 030232 urology & nephrology, CCR9, Gut flora, urologic and male genital diseases, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Intestinal Mucosa, B-cell activating factor, AcademicSubjects/MED00340, Immunity, Mucosal, Inflammation, B-Lymphocytes, Transplantation, B cells, Errata, biology, gut microbiota, business.industry, commensal bacteria, Glomerulonephritis, IGA, Glomerulonephritis, Original Articles, IgA nephropathy, Middle Aged, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, 030104 developmental biology, Cytokine, Basic Research, Nephrology, Case-Control Studies, Immunology, biology.protein, Cytokines, Female, Tumor necrosis factor alpha, business, glomerulonephritis
Abstract

Background Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis. The role of the microbiota and mucosal immunity in the pathogenesis of IgAN remains a key element. To date, the hypothetical relationship between commensal bacteria, elevated tumour necrosis factor (TNF) superfamily member 13 [also known as B-cell activating factor (BAFF)] levels, perturbed homoeostasis of intestinal-activated B cells and intestinal IgA class switch has not been clearly shown in IgAN patients. Methods We studied the intestinal–renal axis connections, analysing levels of BAFF, TNF ligand superfamily member 13 (APRIL) and intestinal-activated B cells in IgAN patients, healthy subjects (HSs) and patients with non-IgA glomerulonephritides. Results IgAN patients had increased serum levels of BAFF cytokine, correlating with higher amounts of five specific microbiota metabolites, and high APRIL cytokine serum levels. We also found that subjects with IgAN have a higher level of circulating gut-homing (CCR9+ β7 integrin+) regultory B cells, memory B cells and IgA+ memory B cells compared with HSs. Finally, we found that IgAN patients had high levels of both total plasmablasts (PBs) and intestinal-homing PBs. Interestingly, PBs significantly increased in IgAN but not in patients with other glomerulonephritides. Conclusions Our results demonstrate a significant difference in the amount of intestinal-activated B lymphocytes between IgAN patients and HSs, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in IgAN. The intestinal–renal axis plays a crucial role in IgAN and several factors may contribute to its complex pathogenesis and provide an important area of research for novel targeted therapies to modulate progression of the disease., Graphical Abstract

Published
2020

44. EULAR/eumusc.net standards of care for rheumatoid arthritis

Author

Rachelle, Meisters, Polina, Putrik, Sofia, Ramiro, Monika, Hifinger, Andras P, Keszei, Yvonne, van Eijk-Hustings, Anthony D, Woolf, Josef S, Smolen, Tanja A, Stamm, Michaela, Stoffer-Marx, Till, Uhlig, Rikke Helene, Moe, Maarten, de Wit, Argjend, Tafaj, Vahan, Mukuchyan, Paul, Studenic, Patrick, Verschueren, Russka, Shumnalieva, Paraskevi, Charalambous, Jiří, Vencovský, Melpomeni, Varvouni, Mart, Kull, Kari, Puolakka, Laure, Gossec, Nino, Gobejishvili, Jacqueline, Detert, Prodromos, Sidiropoulos, Márta, Péntek, David, Kane, Carlo Alberto, Scirè, Uri, Arad, Daina, Andersone, Mart, van de Laar, Annette, van der Helm-van Mil, Piotr, Głuszko, Luís, Cunha-Miranda, Florian, Berghea, Nemanja S, Damjanov, Matija, Tomšič, Loreto, Carmona, Carl, Turesson, Adrian, Ciurea, Surayo, Shukurova, Nevsun, Inanc, Suzanne Mm, Verstappen, Annelies, Boonen, Edi, Rembeci, Meisters, R, Putrik, P, Ramiro, S, Hifinger, M, Keszei, A, Van Eijk-Hustings, Y, Woolf, A, Smolen, J, Stamm, T, Stoffer-Marx, M, Uhlig, T, Moe, R, De Wit, M, Tafaj, A, Mukuchyan, V, Studenic, P, Verschueren, P, Shumnalieva, R, Charalambous, P, Vencovsky, J, Varvouni, M, Kull, M, Puolakka, K, Gossec, L, Gobejishvili, N, Detert, J, Sidiropoulos, P, Pentek, M, Kane, D, Scire, C, Arad, U, Andersone, D, Van De Laar, M, Van Der Helm-Van Mil, A, Gluszko, P, Cunha-Miranda, L, Berghea, F, Damjanov, N, Tomsic, M, Carmona, L, Turesson, C, Ciurea, A, Shukurova, S, Inanc, N, Verstappen, S, Boonen, A, Health Services Research, RS: CAPHRI - R2 - Creating Value-Based Health Care, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, Health promotion, Interne Geneeskunde, MUMC+: KIO Kemta (9), MUMC+: MA Reumatologie (9), and Psychology, Health & Technology

Subjects
Adult, Male, medicine.medical_specialty, arthritis, health services research, health care, outcome and process assessment, Rheumatology, Standard of Care, rheumatoid, Immunology, Arthritis, General Biochemistry, Genetics and Molecular Biology, Gross domestic product, NO, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Surveys and Questionnaires, Health care, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Registries, GUIDELINE DISSEMINATION, Aged, 030203 arthritis & rheumatology, business.industry, Health services research, Standard of Care, Middle Aged, medicine.disease, outcome and process assessment, health care, n/a OA procedure, health services research, Multilevel logistic regression, Europe, arthriti, Cross-Sectional Studies, arthritis, Rheumatoid arthritis, Family medicine, Female, HEALTH, Rheumatologists, business, Rheumatism
Abstract

ObjectiveAs part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe.MethodsTwo cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0–10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0–100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementationResultsOverall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients.ConclusionsMany problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.

Published
2020
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45. Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren’s syndrome?

Author

Ivan Giovannini, Michele Lorenzon, Alen Zabotti, Enrico Pegolo, Cathryn Anne Scott, Alessandro Tel, Chiara Zuiani, Carla Di Loreto, Sara Zandonella Callegher, Massimo Robiony, and Salvatore De Vita

Subjects
Male, medicine.medical_specialty, Open biopsy, Biopsy, Submandibular Gland, salivary gland, Salivary Glands, Sialadenitis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Major Salivary Gland, Humans, Parotid Gland, Medicine, Pharmacology (medical), Prospective Studies, Ultrasonography, Interventional, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, US-guided core needle biopsy, ultrasonography, Middle Aged, medicine.disease, Submandibular gland, Parotid gland, Sjogren's Syndrome, medicine.anatomical_structure, Sjögren’s syndrome, histopathology, 030220 oncology & carcinogenesis, Female, Histopathology, Biopsy, Large-Core Needle, Sarcoidosis, Radiology, business
Abstract

Objective Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. Methods Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). Results Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. Conclusion US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement.

Published
2020
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46. Treatment of COVID-19 atypical pneumonia by early Tocilizumab administration in 'non-critically-ill' patients on hemodialysis

Author

Giuseppe Castellano, Giovanni Stallone, Loreto Gesualdo, Mauro Forcella, Barbara Infante, Sharon Cox, Gaetano Serviddio, and Silvia Mercuri

Subjects
Nephrology, Adult, Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, chemistry.chemical_compound, Tocilizumab, Renal Dialysis, Internal medicine, medicine, Humans, Dialysis, Aged, IL-6, business.industry, Critically ill, COVID-19, Middle Aged, medicine.disease, COVID-19 Drug Treatment, Lesson for the Clinocal Nephrologist, chemistry, Atypical pneumonia, Female, Kidney Diseases, Hemodialysis, business
Published
2020

47. Effect of an abdominal hypopressive technique programme on pelvic floor muscle tone and urinary incontinence in women: a randomised crossover trial

Author

L. Soriano, M.M. Álvarez Sáez, R. Curbelo, Loreto Carmona, and C. González-Millán

Subjects
Adult, 030506 rehabilitation, medicine.medical_specialty, Psychological intervention, Physical Therapy, Sports Therapy and Rehabilitation, Urinary incontinence, Pelvic Floor Muscle, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Humans, Medicine, 030212 general & internal medicine, Aged, Cross-Over Studies, Random assignment, business.industry, Outcome measures, Pelvic Floor, Middle Aged, Tone (literature), Crossover study, Confidence interval, Exercise Therapy, Urinary Incontinence, Muscle Tonus, Physical therapy, Female, medicine.symptom, 0305 other medical science, business
Abstract

To test the effect of a structured abdominal hypopressive technique (AHT) programme on pelvic floor muscle (PFM) tone and urinary incontinence (UI) in women.Crossover trial with random assignment of women to one of two groups: Group 1 (AHT followed by rest) and Group 2 (rest followed by AHT).Two cultural centres in Madrid, Spain.Women aged 20-65 years.Two months of supervised AHT exercises compared with 2 months of rest.Variation in PFM tone and score on the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)].Forty-two women were randomised to two groups (both n=21). No sequence or period effect was noted. The mean difference in PFM tone after the 2-month AHT programme was 59g/cm² [95% confidence interval (CI) 37 to 82]; the between-group difference was 83g/cm² (95% CI 50 to 116; P0.001). After 2 months, the between-group difference in the ICIQ-SF score was 3.3 points (P0.001). The majority of participants reported improved body image and sense of well-being.A structured 2-month AHT programme for women showed short-term benefits in PFM tone and UI. In addition, study participants reported improved body image and sense of well-being, and programme satisfaction, as demonstrated by questionnaire at the end of the intervention period. Further research is needed to test the long-term effects and effectiveness of AHT compared with other PFM exercises. ClinicalTrials.gov Identifier NCT0221241.

Published
2020
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48. Manifest preexcitation with a prolonged PR interval: What is the mechanism?

Author

José Manuel Rubio Campal, Ángel Miracle Blanco, Loreto Bravo Calero, and Pepa Sánchez Borque

Subjects
Adult, Bundle of His, medicine.medical_specialty, Pre-Excitation Syndromes, business.industry, Accessory pathway, Accessory Atrioventricular Bundle, Past history, Electrocardiography, QRS complex, Heart Rate, Internal medicine, Av conduction, Palpitations, medicine, Cardiology, Humans, Female, Sinus rhythm, cardiovascular diseases, medicine.symptom, PR interval, Cardiology and Cardiovascular Medicine, business, Surgical ablation
Abstract

A 44-year-old woman with a past history of surgical ablation of an accessory pathway presented to our facility with episodes of palpitations and dizziness. An ECG showed sinus rhythm with a prolonged PR interval and a preexcited QRS complex. An EP study revealed AV conduction through a postero-septal accessory pathway and a prolonged PR interval due to severe intra-atrial conduction delay.

Published
2020
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49. Patients' perceptions on shared decision making during prescription of subcutaneous biological drug treatments for inflammatory arthritis: The RHEU‐LIFE survey

Author

Sabela Fernández, Luis Cea-Calvo, Teresa Otón, María J. Arteaga, Loreto Carmona, Javier de Toro, and Carlos M. González

Subjects
Male, medicine.medical_specialty, Nursing (miscellaneous), Inflammatory arthritis, Decision Making, Physical Therapy, Sports Therapy and Rehabilitation, Disease, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Spondyloarthritis, Health care, medicine, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, Rheumatoid arthritis, Medical prescription, Survey, Shared decision making, 030203 arthritis & rheumatology, Response rate (survey), Biological Products, Physician-Patient Relations, Descriptive statistics, business.industry, Arthritis, Rehabilitation, Middle Aged, medicine.disease, Preference, Subcutaneous biological drugs, Prescriptions, Family medicine, Female, Perception, Chiropractics, Patient Participation, business, Decision Making, Shared
Abstract

Short report [Abstract] Objectives: The aim of this study was to explore the preferences of patients with rheumatic diseases and their perceived experience regarding participation in shared decision making (SDM) when they were prescribed a subcutaneous (SC) biological drug. Methods: A printed survey was handed to 1,000 patients with inflammatory rheumatic diseases treated with SC biological drug. The survey included closed questions about preferences regarding decision making and about patients' experience when they were prescribed an SC biological drug. Descriptive statistics were performed with stratification by patient profiles, using chi-square for comparisons between groups. Results: A total of 592 surveys were received (response rate 59.2%, mean age 51.7 years, 57.6% women). Some 28.2% of patients reported preferring to take part in treatment selection, a percentage that was higher in younger patients, in those with higher academic degree and in those who search information in sources different to that of health care professionals. Over half of patients (56.3%) perceived that the rheumatologist considered their opinion when prescribing an SC biological drug, a percentage higher in younger people. Only in 40.8% of cases did the patients' preference match their perception of their participation in the process. No differences were observed by sex, disease or number of biologics. Conclusions: Patients with inflammatory rheumatic diseases want information about their treatments but mostly leave the prescription decision to the rheumatologist. Younger people, or those with higher academic degree, more often want to participate in the SDM. There are discrepancies between patient preferences and perceptions of this process.

Published
2020
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50. Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER)

Author

Torrente-Segarra, Vicenç, Salman-Monte, Tarek C, Rúa-Figueroa, Íñigo, Del Campo, Víctor, López-Longo, Francisco Javier, Galindo-Izquierdo, María, Calvo-Alén, Jaime, Olivé-Marqués, Alejandro, Mouriño-Rodríguez, Coral, Horcada, Loreto, Bohórquez, Cristina, Montilla, Carlos, Salgado, Eva, Díez-Álvarez, Elvira, Blanco, Ricardo, Andreu, José Luis, Fernández-Berrizbeitia, Olaia, Expósito, Lorena, Gantes, Marian, Hernández-Cruz, Blanca, Pecondón-Español, Ángela, Lozano-Rivas, Nuria, Bonilla, Gema, Lois Iglesias, Ana, Rubio-Muñoz, Paula, Ovalles, Juan, Tomero, Eva, Boteanu, Alina, Narvaez, Javier, Freire, Mercedes, Vela, Paloma, Quevedo-Vila, Víctor, Juan Mas, Antonio, Muñoz-Fernández, Santiago, Raya, Enrique, Moreno, Mireia, Velloso-Feijoo, M L, Soler, Gregorio, Vázquez-Rodríguez, Tomás Ramón, Pego-Reigosa, José M, and RELESSER Study Group of the Spanish Society of Rheumatology (SER) and the Study Group of Systemic Autoimmune Diseases of the SER (EAS-SER)

Subjects
Adult, Male, RELESSER, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Splenectomy, Serious infection, Infections, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Adrenal Cortex Hormones, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Registries, 030212 general & internal medicine, Serious Infections, Child, skin and connective tissue diseases, Retrospective Studies, 030203 arthritis & rheumatology, Juvenile-onset Systemic Lupus Erythematosus, Systemic lupus erythematosus, business.industry, Incidence, Incidence (epidemiology), Retrospective cohort study, medicine.disease, 3. Good health, Large cohort, Cross-Sectional Studies, Anesthesiology and Pain Medicine, Juvenile onset, Female, business, Immunosuppressive Agents, Follow-Up Studies
Abstract

Objective: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. Methods: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet >= 4 ACR-97 SLE criteria and disease onset = 6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2-4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. Conclusions: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy. (C) 2020 Elsevier Inc. All rights reserved.

Published
2020
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