Gene expression changes associated with myocarditis and fibrosis in hearts of mice with chronic chagasic cardiomyopathy.

Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries. About 30% of Trypanosoma cruzi-infected individuals develop this severe symptomatic form of the disease, characterized by intense inflammatory response accompanied by fibrosis in the heart. We performed an extensive microarray analysis of hearts from a mouse model of this disease and identified significant alterations in expression of approximately 12% of the sampled genes. Extensive up-regulations were associated with immune-inflammatory responses (chemokines, adhesion molecules, cathepsins, and major histocompatibility complex molecules) and fibrosis (extracellular matrix components, lysyl oxidase, and tissue inhibitor of metalloproteinase 1). Our results indicate potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets in chronic Chagas disease.

Physician satisfaction with a multi-platform digital scheduling system.

OBJECTIVE: Physician shift schedules are regularly created manually, using paper or a shared online spreadsheet. Mistakes are not unusual, leading to last minute scrambles to cover a shift. We developed a web-based shift scheduling system and a mobile application tool to facilitate both the monthly scheduling and shift exchanges between physicians. The primary objective was to compare physician satisfaction before and after the mobile application implementation. METHODS: Over a 9-month period, three surveys, using the 4-point Likert type scale were performed to assess the physician satisfaction. The first survey was conducted three months prior mobile application release, a second survey three months after implementation and the last survey six months after. RESULTS: 51 (77%) of the physicians answered the baseline survey. Of those, 32 (63%) were males with a mean age of 37.8 ± 5.5 years. Prior to the mobile application implementation, 36 (70%) of the responders were using more than one method to carry out shift exchanges and only 20 (40%) were using the official department report sheet to document shift exchanges. The second and third survey were answered by 48 (73%) physicians. Forty-eight (98%) of them found the mobile application easy or very easy to install and 47 (96%) did not want to go back to the previous method. Regarding physician satisfaction, at baseline 37% of the physicians were unsatisfied or very unsatisfied with shift scheduling. After the mobile application was implementation, only 4% reported being unsatisfied (OR = 0.11, p < 0.001). The satisfaction level improved from 63% to 96% between the first and the last survey. Satisfaction levels significantly increased between the three time points (OR = 13.33, p < 0.001). CONCLUSION: Our web and mobile phone-based scheduling system resulted in better physician satisfaction.

Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial.

BACKGROUND: Liver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far. The aim of this study is to compare three transfusion strategies (routine coagulation test-guided - ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis. METHODS/DESIGN: Design and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. INCLUSION CRITERIA: adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis. DISCUSSION: This study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly reduce transfusion of blood products in this population, leading to a reduction in costs and transfusion-related adverse reactions. In this manner, this trial will add evidence in favor of reducing empirical transfusion in severely ill patients with coagulopathy. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02311985 . Retrospectively registered on 3 December 2014.

IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva / IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units

RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.

ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

Blood Lactate Levels Cutoff and Mortality Prediction in Sepsis-Time for a Reappraisal? a Retrospective Cohort Study.

The objective of this study was to identify the initial value of blood lactate that best correlates with 28-day mortality in resuscitated septic shock patients. This was a retrospective cohort study including 443 patients admitted to an intensive care unit (ICU) with severe sepsis or septic shock from the emergency department. A receiver-operating characteristic (ROC) curve was drawn to obtain the best cutoff value for initial blood lactate associated with 28-day mortality. Patients were then dichotomized according to the chosen lactate cutoff, and sensitivity, specificity, and positive and negative predictive values were calculated. Baseline blood lactate level more than 2.5 mmol/L showed the largest area under the ROC curve to predict 28-day mortality (ROC area, 0.70; 95% confidence interval [CI], 0.62-0.79), with sensitivity, specificity, and negative predictive value of 67.4%, 61.7%, and 94.2%, respectively. Mortality at 28 days was 16.9% (31/183) in patients with initial lactate more than 2.5 mmol/L and 5.8% (15/260) in patients with initial lactate at most 2.5 mmol/L (relative risk, 2.93; 95% CI, 1.63-5.28; P < 0.001). Initial blood lactate levels more than 2.5 mmol/L (hazard ratio [HR], 2.86; 95% CI, 1.53-5.33; P = 0.001) and Sepsis-related Organ Failure Assessment score at ICU admission (HR, 1.18; 95% CI, 1.09-1.27; P < 0.001) were associated with increased 28-day mortality in the adjusted Cox regression. In this retrospective cohort study, a lactate level more than 2.5 mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. Further prospective studies should address the impact on morbidity and mortality of this threshold as a trigger to resuscitation in this population of critically ill patients.

Antibiotics alone versus appendectomy to treat uncomplicated acute appendicitis in adults: what do meta-analyses say?

BACKGROUND: Primary appendectomy is the current standard of care for treating uncomplicated acute appendicitis, but interest in conservative treatment with antibiotics alone has been increasing in recent years. Clinical trials so far have shown controversial results. METHODS: A series of meta-analyses were reviewed. Studies comparing surgery versus antibiotics alone for treating uncomplicated acute appendicitis in adults were included. Descriptive statistics and data on treatment effects were retrieved and summarized. RESULTS: The conservative approach has a success rate of around 60 % and is associated with shorter pain duration, reduced analgesic medication, faster resolution of the inflammation process, lower expenses and quicker return to work. On the other hand, medical treatment leads to high (up to 20 %) readmission rates and more often requires surgery. An operative approach is associated with higher treatment success rates (>90 %) and very a low mortality rate. CONCLUSION: Based on the current body of evidence, the use of antibiotics for primary treatment of uncomplicated acute appendicitis cannot be routinely recommended. Appendectomy remains the gold-standard treatment.

[Current concepts on hemodynamic support and therapy in septic shock]. / Conceitos atuais sobre suporte hemodinâmico e terapia em choque séptico.

Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

Current concepts on hemodynamic support and therapy in septic shock.

Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

Fluid therapy for septic shock resuscitation: which fluid should be used?

Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients.

Should we treat fever in critically ill patients? A summary of the current evidence from three randomized controlled trials.

Fever is a nonspecific response to various types of infectious or non-infectious insult and its significance in disease remains an enigma. Our aim was to summarize the current evidence for the use of antipyretic therapy in critically ill patients. We performed systematic review and meta-analysis of publications from 1966 to 2013. The MEDLINE and CENTRAL databases were searched for studies on antipyresis in critically ill patients. The meta-analysis was limited to: randomized controlled trials; adult human critically ill patients; treatment with antipyretics in one arm versus placebo or non-treatment in another arm; and report of mortality data. The outcomes assessed were overall intensive care unit mortality, changes in temperature, intensive care unit length of stay, and hospital length of stay. Three randomized controlled trials, covering 320 participants, were included. Patients treated with antipyretic agents showed similar intensive care unit mortality (risk ratio 0.91, with 95% confidence interval 0.65-1.28) when compared with controls. The only difference observed was a greater decrease in temperature after 24 hours in patients treated with antipyretics (-1.70±0.40 versus - 0.56±0.25ºC; p=0.014). There is no difference in treating or not the fever in critically ill patients.

Fluid therapy for septic shock resuscitation: which fluid should be used? / Fluidoterapia para a ressuscitação no choque séptico: qual tipo de fluido deve ser utilizado?

Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients.

A ressuscitação precoce de pacientes com choque séptico tem o potencial de reduzir sua morbidade e mortalidade. Os objetivos principais da ressuscitação no choque séptico incluem expansão volêmica, manutenção da perfusão tecidual e da oferta de oxigênio para os tecidos, guiados pela pressão venosa central, pressão arterial média, saturação venosa mista ou central de oxigênio e lactato arterial. Uma ressuscitação agressiva com fluidos, possivelmente em associação com vasopressores, inotrópicos e transfusão de concentrado de hemácias, pode ser necessária para atingir estes objetivos hemodinâmicos. Todavia, embora a administração de fluidos seja uma das intervenções mais comumente realizada em pacientes graves, o tipo de fluido mais apropriado para ser utilizado permanece controverso e incerto. De acordo com os estudos clínicos mais recentes, os cristaloides são os fluidos de escolha para serem utilizados na ressuscitação inicial de pacientes com choque séptico. As soluções cristaloides balanceadas possuem vantagens teóricas em relação as não balanceadas, porém ainda não há evidências suficientes para indicá-las como tratamento de primeira escolha. Além disso, albumina humana parece ser uma alternativa segura e efetiva quando grandes quantidades de fluidos são necessárias para o restabelecimento da estabilidade hemodinâmica. O uso de soluções de hidroxetilamido deve ser evitado em pacientes sépticos, devido ao maior risco de desenvolvimento de insuficiência renal aguda, necessidade de terapia de substituição renal e aumento de mortalidade. O objetivo deste estudo foi apresentar uma revisão narrativa da literatura sobre os principais tipos de fluidos e os problemas mais importantes na ressuscitação inicial de pacientes com choque séptico.

Current concepts on hemodynamic support and therapy in septic shock / Conceitos atuais sobre suporte hemodinâmico e terapia em choque séptico

ABSTRACTSevere sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

RESUMOA sepse grave e o choque séptico são um grande desafio para a assistência médica. Grande parte da melhoria na taxa de mortalidade associada ao choque séptico está relacionada ao reconhecimento precoce em combinação com a reposição volêmica oportuna e a administração adequada de antibióticos. Os principais objetivos da reanimação do choque séptico incluem reposição intravascular, manutenção adequada da pressão de perfusão e fornecimento de oxigênio para os tecidos. Para atingir esses objetivos, a avaliação da responsividade do volume e das intervenções complementares (vasopressores, inotrópicos e transfusão de sangue) pode ser necessária. Este artigo é uma revisão da literatura para identificar as evidências disponíveis do suporte hemodinâmico inicial aos pacientes com choque séptico admitidos em sala de emergência ou unidade de terapia intensiva e as principais intervenções disponíveis para atingir essas metas, com foco em terapia com reposição de líquidos e vasopressores, transfusão de sangue e administração de inotrópicos.

Devemos tratar febre em doentes graves? Resumo da evidência atual de três ensaios clínicos randomizados / Should we treat fever in critically ill patients? A summary of the current evidence from three randomized controlled trials

A febre é uma resposta não específica a vários tipos de insultos, de origem infecciosa ou não, e sua importância em doenças continua a ser um enigma. Nosso objetivo foi resumir a evidência atual para o uso de antipiréticos em pacientes graves. Foram realizadas revisão sistemática e meta-análise de publicações entre 1966 e 2013. As bases de dados MEDLINE e CENTRAL foram pesquisadas para estudos sobre antipirese em pacientes graves. A meta-análise restringiu-se a ensaios clínicos randomizados em humanos adultos; pacientes graves; tratamento com antipiréticos em um braço contra placebo ou não tratamento no outro; e dados sobre mortalidade. Os desfechos avaliados foram: mortalidade geral na unidade de terapia intensiva, mudança de temperatura e tempo de internação na unidade de terapia intensiva e no hospital. Três ensaios clínicos randomizados com 320 participantes foram incluídos. Os pacientes tratados com antipiréticos tiveram mortalidade na unidade de terapia intensiva semelhante aos controles (razão de risco de 0,91, com intervalo de confiança de 95% de 0,65-1,28). A única diferença observada foi uma diminuição na temperatura após 24 horas em pacientes tratados com antipiréticos (-1,70±0,40 x - 0,56±0,25ºC; p=0,014). Não houve diferença entre tratar ou não a febre em pacientes graves.

Fever is a nonspecific response to various types of infectious or non-infectious insult and its significance in disease remains an enigma. Our aim was to summarize the current evidence for the use of antipyretic therapy in critically ill patients. We performed systematic review and meta-analysis of publications from 1966 to 2013. The MEDLINE and CENTRAL databases were searched for studies on antipyresis in critically ill patients. The meta-analysis was limited to: randomized controlled trials; adult human critically ill patients; treatment with antipyretics in one arm versus placebo or non-treatment in another arm; and report of mortality data. The outcomes assessed were overall intensive care unit mortality, changes in temperature, intensive care unit length of stay, and hospital length of stay. Three randomized controlled trials, covering 320 participants, were included. Patients treated with antipyretic agents showed similar intensive care unit mortality (risk ratio 0.91, with 95% confidence interval 0.65-1.28) when compared with controls. The only difference observed was a greater decrease in temperature after 24 hours in patients treated with antipyretics (-1.70±0.40 versus - 0.56±0.25ºC; p=0.014). There is no difference in treating or not the fever in critically ill patients.

Transcriptomic alterations in Trypanosoma cruzi-infected cardiac myocytes.

Trypanosoma cruzi infection is a major cause of cardiomyopathy. Previous gene profiling studies of infected mouse hearts have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 h post-infection. Statistical comparison of gene expression levels of 7624 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected substantial (>or=1.5 absolute fold changes) in 420 (5.5%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. These findings on infected cardiac myocytes in culture reveal that alterations in cardiac gene expression described in Chagas disease are the consequence of both direct infection of the myocytes themselves as well as resulting from the presence of other cell types in the myocardium and systemic effects of infection.