Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis

Background and aims: Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC. Methods: Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients. Results: The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission. Conclusions: In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis

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

Síndrome hemolítico urémico en Chile: presentación clínica, evolución y factores pronósticos

Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Aim: To describe the characteñstics ofpatients with the diagnosis ofHUS in Chile, and to identify the most reliable early predictors oímorbidity and moñality. Material and methods: The clinical records ofpatients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. Results: A cohort of 587 patients aged 2 to 8 years, 48% males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39% of the patients, hypertension in 45% and seizures in 17%. Forty two percent required renal replacement therapy (RRT) and perítoneal dialysis was used in the majoríty of cases (78%). The most frequently isolated etiological agentwas Escherichia coli. Mortality rate was 2.9% in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC) >20.000/mm3 and requirements of renal replacement therapy (p <0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC >20.000/mm3, seizures and hypertension. Conclusions: The present study emphasizes important clinical and epidemiological aspeets ofHUSin a Chilean pediatricpopulation

A vaccine for human babesiosis: prospects and feasibility

Babesiosis is a tick-borne disease caused by intraerythrocytic Babesia parasites. It is a well-known illness in companion animals and livestock, resulting in substantial economic losses in the cattle industry. Babesiosis is also recognized as an emerging zoonosis of humans in many countries worldwide. There is no vaccine against human babesiosis. Currently, preventive measures are focused on vector avoidance. Although not always effective, treatment includes antimicrobial therapy and exchange transfusion. In this review, we discuss the host's immune response to the parasite, vaccines being used to prevent babesiosis in animals, and lessons from malaria vaccine development efforts to inform the development of a human babesiosis vaccine. An effective human vaccine would be a significant advance towards curtailing this rapidly emerging disease.No Full Tex

Evaluation of patients with virus C hepatitis treated with direct-acting antivirals in the Chilean public systemHepatitis crónica por virus C. Evaluación de los pacientes tratados con antivirales de acción directa en el sistema público de Chile

© 2021 Sociedad Medica de Santiago. All rights reserved.Background: Direct-acting antivirals (DAA) allowed a radical change in the treatment of hepatitis C virus (HCV), achieving the elimination of the virus or sustained viral response (SVR) in > 95% of patients, with good tolerance and few adverse effects. Aim: To characterize the treated population and evaluate the efficacy of DAA treatment in the Chilean public health system. Material and Methods: Retrospective analysis of data sheets of patients with chronic HCV infection collected by the Ministry of Health of Chile between 2016 and May 2019. Results: Two hundred and fifty-five patients with a mean age of 59 years (51% males) were collected. Genotype 1b was predominant, 72% patients had a diagnosis of cirrhosis at the beginning of treatment. Sofosbuvir-Velpatasvir was predominantly used in 56%. SVR was achieved in 92% of cases, only 4% persisted with detectable load at 24 weeks. A significant decrease in alanine aminotransferase values (88 and 31 U/L respectively, p < 0.01) and a significant increase in plasma albumin (3.7 and 3.9 mg/dl respectively, p = 0.02) were observed. The comparative analysis of MELD-Na before and after treatment did not show a significant variation (10.8 and 10.4 respectively, p = 0.34). Conclusions: These patients treated with DAAs presented SVR rates comparable with national and international data.ANID FONDAPCIGIDENResearch Center for Integrated Disaster Risk ManagementVRI-UCCONICYTANI

Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years Endocarditis infecciosa: Características clínicas, complicaciones y mortalidad en 506 pacientes y factores pron

Background: Rates of morbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. Aim: To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. Material and Methods: Observational prospective national cohort study of 506 consecutive patients included between June 1, 1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. Results: The main findings were the presence of Rheumatic valve disease in 22.1% of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylococcus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% of patients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28