Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.Fil: Efe, Cumali. Harran University Hospita; TurquíaFil: Lammert, Craig. University School of Medicine Indianapolis; Estados UnidosFil: Taşçılar, Koray. Universitat Erlangen-Nuremberg; AlemaniaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Ebik, Berat. Gazi Yasargil Education And Research Hospital; TurquíaFil: Higuera de la Tijera, Fatima. Hospital General de México; MéxicoFil: Calışkan, Ali R.. No especifíca;Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. Università degli Studi di Milano; ItaliaFil: Massoumi, Hatef. No especifíca;Fil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Purnak, Tugrul. University of Texas; Estados UnidosFil: Rigamonti, Cristina. Università del Piemonte Orientale ; ItaliaFil: Aldana, Andres J. G.. Fundacion Santa Fe de Bogota; ColombiaFil: Khakoo, Nidah. Miami University; Estados UnidosFil: Nazal, Leyla. Clinica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training And Research Hospital; TurquíaFil: Irak, Kader. Kanuni Sultan Suleyman Training And Research Hospital; TurquíaFil: Melekoğlu Ellik, Zeynep. Ankara University Medical Faculty; TurquíaFil: Kacmaz, Hüseyin. Adıyaman University; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Atay, Kadri. No especifíca;Fil: Eren, Fatih. No especifíca;Fil: Alvares da-Silva, Mario R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Cristoferi, Laura. Università degli Studi di Milano; ItaliaFil: Urzua, Álvaro. Universidad de Chile; ChileFil: Eşkazan, Tuğçe. Cerrahpaşa School of Medicine; TurquíaFil: Magro, Bianca. No especifíca;Fil: Snijders, Romee. No especifíca;Fil: Barutçu, Sezgin. No especifíca;Fil: Lytvyak, Ellina. University of Alberta; CanadáFil: Zazueta, Godolfino M.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Demirezer Bolat, Aylin. Ankara City Hospital; TurquíaFil: Aydın, Mesut. Van Yuzuncu Yil University; TurquíaFil: Amorós Martín, Alexandra Noemí. No especifíca;Fil: De Martin, Eleonora. No especifíca;Fil: Ekin, Nazım. No especifíca;Fil: Yıldırım, Sümeyra. No especifíca;Fil: Yavuz, Ahmet. No especifíca;Fil: Bıyık, Murat. Necmettin Erbakan University; TurquíaFil: Narro, Graciela C.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Bıyık, Murat. Uludag University; TurquíaFil: Kıyıcı, Murat. No especifíca;Fil: Kahramanoğlu Aksoy, Evrim. No especifíca;Fil: Vincent, Maria. No especifíca;Fil: Carr, Rotonya M.. University of Pennsylvania; Estados UnidosFil: Günşar, Fulya. No especifíca;Fil: Reyes, Eira C.. Hepatology Unit. Hospital Militar Central de México; MéxicoFil: Harputluoğlu, Murat. Inönü University School of Medicine; TurquíaFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Gatselis, Nikolaos K.. University Hospital Of Larissa; GreciaFil: Üstündağ, Yücel. No especifíca;Fil: Brahm, Javier. Clinica Las Condes; ChileFil: Vargas, Nataly C. E.. Hospital Nacional Almanzor Aguinaga Asenjo; PerúFil: Güzelbulut, Fatih. No especifíca;Fil: Garcia, Sandro R.. Hospital Iv Víctor Lazarte Echegaray; PerúFil: Aguirre, Jonathan. Hospital Angeles del Pedregal; MéxicoFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Ratusnu, Natalia. Hospital Regional de Ushuaia; ArgentinaFil: Hatemi, Ibrahim. No especifíca;Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Floreani, Annarosa. Università di Padova; ItaliaFil: Fagiuoli, Stefano. No especifíca;Fil: Silva, Marcelo. Universidad Austral; ArgentinaFil: Idilman, Ramazan. No especifíca;Fil: Satapathy, Sanjaya K.. No especifíca;Fil: Silveira, Marina. University of Yale. School of Medicine; Estados UnidosFil: Drenth, Joost P. H.. No especifíca;Fil: Dalekos, George N.. No especifíca;Fil: N.Assis, David. University of Yale. School of Medicine; Estados UnidosFil: Björnsson, Einar. No especifíca;Fil: Boyer, James L.. University of Yale. School of Medicine; Estados UnidosFil: Yoshida, Eric M.. University of British Columbia; CanadáFil: Invernizzi, Pietro. Università degli Studi di Milano; ItaliaFil: Levy, Cynthia. University of Miami; Estados UnidosFil: Montano Loza, Aldo J.. University of Alberta; CanadáFil: Schiano, Thomas D.. No especifíca;Fil: Ridruejo, Ezequiel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Wahlin, Staffan. No especifíca

Position statement on the use of albumin in liver cirrhosis

Cirrhosis is characterized by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Proinflammatory cytokines and pro-oxidant molecules are key in the development of organ dysfunction. Cirrhosis progression and worsening of portal hypertension bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic Inflammation. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic, and endothelial stabilizing properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options, capable of targeting several physiopathological aspects of cirrhosis. For the elaboration of the present manuscript on the uses of albumin in liver cirrhosis, several experts in the field of hepatology in Mexico were divided into 5 working groups to summarise and formulate, when appropriate, position statements: 1)pathophysiology of cirrhosis and properties of albumin; 2)proven uses of albumin [large-volume paracentesis, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS)]; 3)controversial/emerging uses of albumin (long-term use, acute decompensation, liver transplant, non-HRS kidney injury, muscle cramps, non-SBP infections, hyponatremia, encephalopathy); 4)use of albumin in acute-on-chronic liver failure, immunomodulation, and systemic Inflammation; 5)pharmacoeconomics

Speciation in the deep : genomics and morphology reveal a new species of beaked whale Mesoplodon eueu

This work was supported by ONR grants N000141613017 to E.L.C. and N.A. and N00014-18-1-2808 to C.S.B.; funds from the NMNH Rebecca G. Mead and James G. Mead Marine Mammal Endowment, NSF (USA) grant no. DEB-1457735 to M.S.S., P.A.M. and J.G.; Brothers Hartmann Foundation grant no. AB28148 to M.T.O.; NMFS, BOEM, and USA Navy funding to D.Ch. under the Atlantic Marine Assessment Program for Protected Species. M.L.M. was funded under the Marie Skłodowska-Curie grant agreement no 801199; E.L.C. by a Rutherford Discovery Fellowship from the Royal Society of New Zealand Te Apārangi. Irish Whale and Dolphin Group Cetacean Stranding scheme is part-funded by the National Parks and Wildlife Service.The deep sea has been described as the last major ecological frontier, as much of its biodiversity is yet to be discovered and described. Beaked whales (ziphiids) are among the most visible inhabitants of the deep sea, due to their large size and worldwide distribution, and their taxonomic diversity and much about their natural history remain poorly understood. We combine genomic and morphometric analyses to reveal a new Southern Hemisphere ziphiid species, Ramari's beaked whale, Mesoplodon eueu, whose name is linked to the Indigenous peoples of the lands from which the species holotype and paratypes were recovered. Mitogenome and ddRAD-derived phylogenies demonstrate reciprocally monophyletic divergence between M. eueu and True's beaked whale (M. mirus) from the North Atlantic, with which it was previously subsumed. Morphometric analyses of skulls also distinguish the two species. A time-calibrated mitogenome phylogeny and analysis of two nuclear genomes indicate divergence began circa 2 million years ago (Ma), with geneflow ceasing 0.35–0.55 Ma. This is an example of how deep sea biodiversity can be unravelled through increasing international collaboration and genome sequencing of archival specimens. Our consultation and involvement with Indigenous peoples offers a model for broadening the cultural scope of the scientific naming process.Publisher PDFPeer reviewe

Speciation in the deep: genomics and morphology reveal a new species of beaked whale

Earth’s deep oceans remains less well understood than the surface of Mars. Beaked whales (ziphiids) are among the most visible inhabitants of the abyss, due to their large size and worldwide distribution, yet their diversity and ecology remain obscure. We combine genomic and morphometric analyses to reveal a new Southern Hemisphere ziphiid species, Ramari’s beaked whale, Mesoplodon eueu, whose name is linked to the Indigenous people of the lands from which the species holotype and paratypes were recovered. Mitogenome and ddRAD-derived phylogenies demonstrate reciprocally monophyletic divergence between M. eueu and North Atlantic True’s beaked whale (M. mirus), with which it was subsumed. Revised morphometric analyses of skulls separate the species. A time-calibrated mitogenome phylogeny and analysis of two nuclear genomes indicate divergence began ca 2 million years ago (Ma), with geneflow ceasing 0.35-0.55 Ma. This is an example of how deep-sea biodiversity can be unravelled through increasing international collaboration and genome sequencing of archival specimens. Our consultation and involvement with Indigenous groups offers a model for broadening the cultural scope of the scientific naming process.,See article supplementary materials for methods and sample IDs.

Congreso científico 2016

La Universidad Autónoma de Chiriquí (UNACHI), continuando con el fortalecimiento de las políticas institucionales, correspondientes al Factor 2: Investigación e innovación, presenta a la consideración de los estamentos universitarios y a la sociedad panameña, el presente volumen, Avances en Investigación 2016, en el cual se recogen los resultados preliminares y los productos de las investigaciones, impulsadas desde las unidades académicas y la Vicerrectoría de Investigación y Posgrado (VIP), durante el período 2015-2016. Cumpliendo con el compromiso de responsabilidad social, el equipo de gestión administrativa de la Rectora Magnífica, Etelvina Medianero de Bonagas, rinde cuentas de los principales logros, los impactos sociales y las proyecciones generadas desde el quehacer investigativo institucional. La realización del II Congreso Científico comprende el desarrollo de conferencias magistrales, conferencias cortas, ponencias, un panel y la exposición de murales. En su conjunto, es un evento académico, a través del cual se procura ofrecer una visión holística de la investigación, desde las perspectivas de las diversas disciplinas, con el propósito de contribuir a un mejor entendimiento del saber humano, a que se realicen aportaciones a las teorías del conocimiento y se propongan soluciones a los grandes temas de interés nacional. Es a partir de esta visión, que en el congreso se abordan temáticas pertinentes con la gestión de la investigación; las estrategias para la colaboración internacional; las tendencias de la investigación científica; los indicadores de ciencia, tecnología e innovación; la energía y el desarrollo sustentable; el emprendimiento y la innovación; los desafíos de la agricultura, ante la soberanía alimentaria; el plan estratégico del agro panameño; la educación y las pruebas PISA; los estudios del virus del Zika y las investigaciones virológicas; los retos en la salud y el bienestar humano; la seguridad y desarrollo humano y el rol del periodismo en tiempos actuales, entre otros temas. Algunas de las instituciones nacionales e internacionales que comparten sus experiencias en el Congreso, son la Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT); la Universidad Tecnológica de Panamá (UTP); el Instituto Conmemorativo Gorgas de Estudios de la Salud (ICGES); el Ministerio de Educación (MEDUCA); la Caja de Seguro Social (CSS); la Universidad Estatal a Distancia (UNED); el Instituto Interamericano de Ciencias Agrícolas (IICA) y el Programa LASPAU, afiliado a la Universidad de Harvard. Por la UNACHI, se cuenta con decidida participación de sus investigadores, institutos y centros de investigación. Los países de los cuales proceden los conferencistas son, los Estados Unidos, Guatemala, Colombia, Bolivia y Perú; además, del país sede, Panamá

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

To access publisher's full text version of this article click on the hyperlink belowBackground: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH. Keywords: SARS-CoV-2; autoimmunity; azathioprine; budesonide; liver transplantation; mercaptopurine.Ministry of Education, Universities and Research (MIUR

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world’s largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ~30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death