Polimorfismo de nucleotídeo único da il-28b rs12979860 e il-28b rs8099917 e infecção do citomegalovírus em pacientes submetidos a transplante de células-tronco hematopoiéticas

Orientadora: Profa. Dra. Sonia Mara RaboniDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde. Defesa : Curitiba, 11/09/2018Inclui referênciasResumo: Introdução: A infecção pelo Citomegalovírus (CMV) após o Transplante de Células Tronco Hematopoiéticas (TCTH) ocorre em até 80% dos pacientes e impacta em aumento de mortalidade não relacionada a recidiva. A principal estratégia para redução do risco de doença pelo CMV é a terapia preemptiva, que consiste no monitoramento periódico e início precoce de antiviral. Apesar de eficaz, esta estratégia possui efeitos tóxicos e aumento nos custos. Estudos recentes sugerem que Polimorfismos de Nucleotídeo Único (PNU) da IL-28B modulam a infecção do CMV, o que poderia orientar o uso racional da terapia preemptiva. Objetivos: Identificar os genótipos dos PNU da IL-28B rs12979860 e IL-28B rs8099917 em pacientes submetidos à TCTH e associação com infecção do CMV. Métodos: Estudo analítico, observacional, longitudinal, prospectivo, não intervencionista. Foram avaliados os PNU descritos e correlacionados com a incidência de infecção e cinética viral do CMV e com a incidência de outras virais além de fúngicas e bacterianas. Os dados foram coletados do prontuário do paciente. Resultados: Os genótipos C/T (49,6%) da IL- 28B rs12979860 e o T/T (76,7%) da IL-28B rs8099917 foram os mais comuns. Não houve diferença significativa entre os grupos que tiveram infecção ou não do CMV quanto aos polimorfismos ou às variáveis estudadas. Os genótipos contendo alelos menores tanto da IL-28B rs12979869 quanto da IL-28B rs8099917 apresentaram uma menor progressão ao pico de antigenemia (p<0,05). O genótipo de alelo maior do receptor da IL-28B rs8099917 foi relacionado a menor incidência de infecção fúngica invasiva. Conclusão: O achado de uma menor progressão ao pico sugere que o alelo menor pode conferir uma melhor resposta imunológica após a infecção pelo CMV. Pode haver impacto, também, nas infecções fúngicas nesse contexto. Mais trabalhos são necessários para confirmar esses achados.Abstract: Introduction: Cytomegalovirus Infection after Hematopoietic Stem Cell Transplantation (HSCT) occurs in 60-80% of patients and impacts in higher nonrelapse- mortality. The main strategy for CMV disease prevention is preemptive therapy, which consists of periodic monitoring and early initiation of antiviral therapy. Although effective, this strategy has toxic effects and increased costs. Recent studies suggest that IL-28B Single Nucleotide Polymorphisms (SNP) modulate CMV infection, which could guide the rational use of preemptive therapy. Objectives: To identify the IL-28B SNP rs12979860 and IL-28B rs8099917 genotypes in patients undergoing HSCT and study their association with CMV infection. Methods: Analytical, observational, longitudinal, prospective, noninterventional study. To describe the SNU genotypes and correlated with CMV's infection incidence viral kinetics and with other viral infections incidence besides bacterial and fungal infections. Data were collected from patient's chart. Results: The IL-28B rs12979860 C/T(49.6%) and IL-28B rs8099917 T/T (76.7%) genotypes were the most common. There was no significant difference between groups with and without CMV infection regarding the SNP or variables studied. Genotypes containing minor alleles of both IL-28B rs12979869 and IL-28B rs8099917 showed a slower progression to the antigenemia peak (p <0.05). Recipient IL-28B rs8099917 genotype containing major alleles was related to lower incidence of invasive fungal infection. Conclusion: The finding of a smaller progression to the peak suggests that the minor allele may confer a better immune response after CMV infection in HSCT subjects. There may also be impact on fungal infections. More studies are needed to confirm these findings

Pseudomonas aeruginosa bloodstream infections in patients with cancer: differences between patients with hematological malignancies and solid tumors

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006-May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p &lt; 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p &lt; 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p &lt; 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p &lt; 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p &lt; 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p &lt; 0.001) and 30-day (49% vs. 37.3%; p &lt; 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.Funding: This study was supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC) (CB21/13/00009; CB21/13/00079; CB21/13/00054; CB21/13/00086), Madrid, Spain. Acknowledgments: We thank the ESCMID Study Group for Bloodstream Infections, Endocarditis, and Sepsis (ESGBIES) and the ESCMID Study Group for Immunocompromised Hosts (ESGICH) for supporting the study. We thank the Centres de Recerca de Catalunya (CERCA) Program and Generalitat de Catalunya for the institutional support. We thank the Spanish Network for Research in Infectious Diseases and the Río Hortega program of the Instituto de Salud Carlos III for the financial support of pre-doctoral student J. Laporte-Amargós and A. Bergas

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006-May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 x 10(9) cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population

Adelante / Endavant

Séptimo desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere "Purificación Escribano" de la Universitat Jaume

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

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 &lt; 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

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Polimorfismo de nucleotídeo único da il-28b rs12979860 e il-28b rs8099917 e infecção do citomegalovírus em pacientes submetidos a transplante de células-tronco hematopoiéticas

Orientadora: Profa. Dra. Sonia Mara RaboniDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde. Defesa : Curitiba, 11/09/2018Inclui referênciasResumo: Introdução: A infecção pelo Citomegalovírus (CMV) após o Transplante de Células Tronco Hematopoiéticas (TCTH) ocorre em até 80% dos pacientes e impacta em aumento de mortalidade não relacionada a recidiva. A principal estratégia para redução do risco de doença pelo CMV é a terapia preemptiva, que consiste no monitoramento periódico e início precoce de antiviral. Apesar de eficaz, esta estratégia possui efeitos tóxicos e aumento nos custos. Estudos recentes sugerem que Polimorfismos de Nucleotídeo Único (PNU) da IL-28B modulam a infecção do CMV, o que poderia orientar o uso racional da terapia preemptiva. Objetivos: Identificar os genótipos dos PNU da IL-28B rs12979860 e IL-28B rs8099917 em pacientes submetidos à TCTH e associação com infecção do CMV. Métodos: Estudo analítico, observacional, longitudinal, prospectivo, não intervencionista. Foram avaliados os PNU descritos e correlacionados com a incidência de infecção e cinética viral do CMV e com a incidência de outras virais além de fúngicas e bacterianas. Os dados foram coletados do prontuário do paciente. Resultados: Os genótipos C/T (49,6%) da IL- 28B rs12979860 e o T/T (76,7%) da IL-28B rs8099917 foram os mais comuns. Não houve diferença significativa entre os grupos que tiveram infecção ou não do CMV quanto aos polimorfismos ou às variáveis estudadas. Os genótipos contendo alelos menores tanto da IL-28B rs12979869 quanto da IL-28B rs8099917 apresentaram uma menor progressão ao pico de antigenemia (p<0,05). O genótipo de alelo maior do receptor da IL-28B rs8099917 foi relacionado a menor incidência de infecção fúngica invasiva. Conclusão: O achado de uma menor progressão ao pico sugere que o alelo menor pode conferir uma melhor resposta imunológica após a infecção pelo CMV. Pode haver impacto, também, nas infecções fúngicas nesse contexto. Mais trabalhos são necessários para confirmar esses achados.Abstract: Introduction: Cytomegalovirus Infection after Hematopoietic Stem Cell Transplantation (HSCT) occurs in 60-80% of patients and impacts in higher nonrelapse- mortality. The main strategy for CMV disease prevention is preemptive therapy, which consists of periodic monitoring and early initiation of antiviral therapy. Although effective, this strategy has toxic effects and increased costs. Recent studies suggest that IL-28B Single Nucleotide Polymorphisms (SNP) modulate CMV infection, which could guide the rational use of preemptive therapy. Objectives: To identify the IL-28B SNP rs12979860 and IL-28B rs8099917 genotypes in patients undergoing HSCT and study their association with CMV infection. Methods: Analytical, observational, longitudinal, prospective, noninterventional study. To describe the SNU genotypes and correlated with CMV's infection incidence viral kinetics and with other viral infections incidence besides bacterial and fungal infections. Data were collected from patient's chart. Results: The IL-28B rs12979860 C/T(49.6%) and IL-28B rs8099917 T/T (76.7%) genotypes were the most common. There was no significant difference between groups with and without CMV infection regarding the SNP or variables studied. Genotypes containing minor alleles of both IL-28B rs12979869 and IL-28B rs8099917 showed a slower progression to the antigenemia peak (p <0.05). Recipient IL-28B rs8099917 genotype containing major alleles was related to lower incidence of invasive fungal infection. Conclusion: The finding of a smaller progression to the peak suggests that the minor allele may confer a better immune response after CMV infection in HSCT subjects. There may also be impact on fungal infections. More studies are needed to confirm these findings

Sepsis risk assessment: a retrospective analysis after a cognitive risk management robot (Robot Laura®) implementation in a clinical-surgical unit

Abstract Introduction This study aimed at evaluating the impact of the implementation of a cognitive robot (Robot Laura™) on processes related to the identification and care of patients with risk of sepsis in a clinical-surgical unit of a private hospital in Curitiba-PR. Methods The study data were obtained from the retrospective review of medical records of patients identified with infection and/or sepsis, in the period of six months before and after the implementation of such technology in the hospital. In addition, the Average Attendance Time (AAT) was obtained from the autonomous reading of the robot. Results The average time/median until antibiotic prescription from the first identified sign of infection, with or without sepsis, was 390/77 and 109/58 minutes, respectively, in the six months before and after implementation of the technology. However, this difference was not statistically significant (p = 0.85). Regarding AAT, it was possible to observe a reduction from 305 to 280 minutes when comparing the periods of six months before and after the implementation of the technology (p = 0.02). Conclusion Technologies such as this may be promising in helping healthcare professionals to identify risky situations for patients, as well as in assisting them to optimize the care required. However, further studies, with a greater number of subjects and with different scenarios, are necessary to consistently validate the results found