Validated Risk Score for Predicting 6-Month Mortality in Infective Endocarditis.

Background Host factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6-month mortality in IE. Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ICE]-Prospective Cohort Study [PCS], 2000-2006, n=4049), a model to predict 6-month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry (ICE-PLUS, 2008-2012, n=1197). The 6-month mortality was 971 of 4049 (24.0%) in the ICE-PCS cohort and 342 of 1197 (28.6%) in the ICE-PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left-sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6-month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62-0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six-month mortality after IE is 25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in I

HIV and Chagas Disease Coinfection, a Tractable Disease?

We present 2 patients born in Argentina who were newly diagnosed with advanced HIV disease and Chagas disease reactivation with central nervous system involvement. The patients received concurrent benznidazole treatment and antiretroviral therapy, showing good response. Improvement in morbidity and mortality due to early treatment makes this treatment appropriate for coinfected patients

Chagas' disease and solid organ transplantation

Fil: Lattes, Roberta. Instituto de Nefrología; Argentina.Fil: Altclas, Javier. Sanatorio de la Trinidad Mitre. Enfermedades Infecciosas; Argentina.Fil: Arselán, Sergio. Clínica Privada Velez Sarfield. Sección Enfermedades Infecciosas; Argentina.Fil: Barcán, Laura. Hospital Italiano. Sección Enfermedades Infecciosas; Argentina.Fil: Diez, Mirta. Hospital Universitario de la Fundación Favaloro. Trasplante de corazón; Argentina.Fil: Gadano, Adrian. Hospial Italiano. Trasplante de Hígado; Argentina.Fil: Jacob, Néstor. Hospital Austral. Sección Enfermedades Infecciosas; Argentina.Fil: Maiolo, Elena. Hospital Argerich. Enfermedades Infecciosas; Argentina.Fil: Nagel, Claudia. Hospital Universitario de la Fundación Favaloro. Enfermedades Infecciosas; Argentina.Fil: Riarte, Adelina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Rodriguez, Viviana. Hospital Alemán. Enfermedades Infecciosas; Argentina.Fil: Schiavelli, Ruben. Hospital Argerich. Trasplante de riñón; Argentina.Fil: Schijman, Alejandro G. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular. Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Vigliano, Carlos. Hospital Universitario de la Fundación Favaloro. Patología; Argentina.This review summarizes relevant published data on transplant recipients with Chagas' disease and of naïve recipients transplanted with organs from infected donors. Unpublished experience from some of the largest transplant centers in Argentina is also included. The review outlines the guidelines for pretransplant evaluation and for posttransplant management formulated by the Chagas Disease Argentine Collaborative Transplant Consortium

Validated Risk Score for Predicting 6-Month Mortality in Infective Endocarditis

Host factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6-month mortality in IE.Background-Host factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6-month mortality in IE. Methods and Results-Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ICE]-Prospective Cohort Study [PCS], 2000-2006, n=4049), a model to predict 6-month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry (ICE-PLUS, 2008-2012, n=1197). The 6-month mortality was 971 of 4049 (24.0%) in the ICE-PCS cohort and 342 of 1197 (28.6%) in the ICE-PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left-sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6-month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62-0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions-Six-month mortality after IE is 25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE

Validated Risk Score for Predicting 6-Month Mortality in Infective Endocarditis.

Background Host factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6-month mortality in IE. Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ICE]-Prospective Cohort Study [PCS], 2000-2006, n=4049), a model to predict 6-month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry (ICE-PLUS, 2008-2012, n=1197). The 6-month mortality was 971 of 4049 (24.0%) in the ICE-PCS cohort and 342 of 1197 (28.6%) in the ICE-PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left-sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6-month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62-0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six-month mortality after IE is 25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in I

Health care-associated native valve endocarditis: importance of non-nosocomial acquisition.

BACKGROUND: The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined. OBJECTIVE: To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis. DESIGN: Prospective cohort study. SETTING: 61 hospitals in 28 countries. PATIENTS: Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005. MEASUREMENTS: Clinical and echocardiographic findings, microbiology, complications, and mortality. RESULTS: Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]). LIMITATIONS: Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use. CONCLUSION: More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection. PRIMARY FUNDING SOURCE: None

Recommendations for management of Chagas disease in organ and hematopoietic tissue transplantation programs in nonendemic areas

Fil: Pinazo, María-Jesús. Tropical Medicine Unit, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic/IDIBAPS, Universitat de Barcelona, CIBER Epidemiología y Salud Pública (CIBERESP), Roselló, 132. 4th. 08036 Barcelona; España.Fil: Miranda, Blanca. Headship of Transplant Services Foundation and Coordination Unit of Transplant, Hospital Clínic, Villarroel, 170 08036 Barcelona; España.Fil: Rodríguez-Villar, Camino. Donors Unit, Hospital Clínic, Villarroel, 170 08036 Barcelona; España.Fil: Altclas, Javier. Headship of Infectology, Sanatorio de la Trinidad Mitre and Sanatorio Anchorena, Bartolome Mitre 2553 Buenos Aires; Argentina.Fil: Brunet Serra, Mercè. University of Barcelona, Pharmacology and Toxicology Laboratory, Centro de Diagnóstico Biomédico, Hospital Clínic, IDIBAPS, CIBERehd, Villarroel 170 08036 Barcelona; España.Fil: García-Otero, Elías Cañas. International Health Unit, Infectious Diseases Department, Virgen del Rocío University Hospitals, Manuel Siurot avenue, s/n. 41013 Sevilla; España.Fil: de Almeida, Eros Antonio. Infectious Diseases Unit, Department of Clínica Médica, University of Campinas, UNICAMP, Albert Fleming, 40 13083–970 Campinas-SP; Brasil.Fil: de la Mata García, Manuel. Digestive Disorders Unit, Reina Sofía University Hospital, Menéndez Pidal avenue, s/n 14004 Córdoba; España.Fil: Gascon, Joaquim. Tropical Medicine Unit, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic/IDIBAPS, Universitat de Barcelona, CIBER Epidemiología y Salud Pública (CIBERESP), Roselló, 132. 4th. 08036 Barcelona; España.Fil: García Rodríguez, Magdalena. International Health Unit and pre-travel counseling, Infectious Diseases Department, Consorcio Hospital General Universitario de Valencia, Tres Cruces avenue s/n 46014 Valencia; España.Fil: Manito, Nicolás. Heart Failure and Heart Transplant, Bellvitge University Hospital, Feixa Llarga, s/n, 08907 L'Hospitalet del LLobregat, Barcelona; España.Fil: Moreno Camacho, Asunción. Infectious Diseases Department, Hospital Clinic, University of Barcelona, Villarroel, 170, 08036 Barcelona; España.Fil: Oppenheimer, Federico. Kidney Transplant Unit, Nefrology and Kidney Transplant Department, Hospital Clínic, Villarroel 170, 08036 Barcelona; España.Fil: Puente Puente, Sabino. Tropical Medicine Unit, Hospital Carlos III, Valdevarnes, 33, 28039 Madrid; España.Fil: Riarte, Adelina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Salas Coronas, Joaquín. Tropical Medicine Unit, Hospital de Poniente, Almerimar road s/n 04700 El Ejido, Almería; España.Fil: Salavert Lletí, Miguel. Infectious Diseases Unit, La Fe University Hospital, Campanar 21, 46009 Valencia; España.Fil: Sanz, Guillermo F. Hematology Department, La Fe University Hospital, Campanar 21, 46009 Valencia; España.Fil: Torrico, Faustino. Facultad de Medicina, Universidad Mayor de San Simón, Aniceto Arce 371, Cochabamba; Bolivia.Fil: Torrús Tendero, Diego. Imported Disease and Parasitology Unit, Internal Medicine Department, Hospital General Universitario de Alicante, Pintor Baeza 12, 03010 Alicante; España.Fil: Ussetti, Piedad. Puerta de Hierro University Hospital, Donantes de sangre s/n, Madrid; España.Fil: Shikanai-Yasuda, Maria Aparecida. Department of Infectious and Parasitic Diseases, Infections in Imunossupressed Host Group, Faculdade de Medicina da Universidade de São Paulo, Dr Enéias de Carvalho Aguiar, 500, 04303 010 São Paulo; Brasil.The substantial immigration into Spain from endemic areas of Chagas disease such as Latin America has increased the number of potential donors of organs and tissues. In addition, an increasing number of patients with advanced Chagas heart disease may eventually be eligible to receive a heart transplant, a universally accepted therapeutic strategy for the advanced stages of this disease. Therefore, it is necessary to establish protocols for disease management. This document is intended to establish the guidelines to be followed when a potential donor or a tissue or organ recipient is potentially affected by Chagas disease and summarizes the action criteria against the possibility of Chagas disease transmission through the donation of organs, tissues, or hematopoietic stem cells and aims to help professionals working in this field. A single registry of transplants in Trypanosoma cruzi infected donors and/or recipients will provide and disseminate experience in this area, which has shown a low recorded incidence to date

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial

Background: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. Methods: In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027. Findings: Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of -2·7 percentage points (95% CI -7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41-0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47-0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. Interpretation: Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19