Fernando Antônio Botoni

Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation

BackgroundSuccinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.ResultsWe found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases.ConclusionsThese results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.

Corneal injuries: incidence and risk factors in the Intensive Care Unit

Patients hospitalized in the Intensive Care Unit (ICU) may present risk for corneal injury due to sedation or coma. This study aimed to estimate the incidence of corneal injuries; to identify the risk factors and to propose a risk prediction model for the development of corneal injury, in adult patients, in an intensive care unit of a public hospital. This is a one year, prospective cohort study with 254 patients. The data were analyzed using descriptive statistics, univariate and logistic regression. Of the 254 patients, 59.4% had corneal injuries and the mean time to onset was 8.9 days. The independent variables that predispose to risk for punctate type corneal injury were: duration of hospitalization, other ventilatory support device, presence of edema and blinking less than five times a minute. The Glasgow Coma Scale and exposure of the ocular globe were the variables related to corneal ulcer type corneal injury. The injury frequencies were punctate type (55.1%) and corneal ulcers (11.8%). Risk prediction models for the development of punctate and corneal ulcer type corneal injury were established.Pacientes internados en Unidad de Terapia Intensiva (UTI) pueden presentar riesgo de lesion en la cornea debido a la sedacion o al coma. Este estudio tuvo por objetivo estimar la incidencia de las lesiones en la cornea; identificar los factores de riesgo y proponer un modelo de prediccion de riesgo para el desarrollo de lesion en la cornea, en pacientes adultos, en Unidad de Terapia Intensiva, de un hospital publico. Estudio de cohorte prospectivo de un ano con 254 pacientes. Los datos fueron analizados por estadistica descriptiva, univariada y de regresion logistica. De los 254 pacientes, 59,4% tuvieron lesion en la cornea y el tiempo promedio para su aparicion fue de 8,9 dias. Las variables independientes que predisponen al riesgo de lesion en la cornea tipo punteada fueron: tiempo de internacion, otro dispositivo de asistencia ventilatoria, presencia de edema y parpadeo de ojos menor que cinco veces por minuto. La escala de coma de Glasgow y la exposicion del globo ocular fueron las variables relacionadas a la lesion en la cornea del tipo ulcera de cornea. Las lesiones fueron del tipo punteada (55,1%) y ulceras de cornea (11,8%). Modelos de prediccion de riesgo para lesiones en la cornea del tipo punteada y ulcera fueron establecidos.

Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources.

Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX®, UpToDate®, Medscape® and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss’ kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211–0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292–0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality.

A technical modification for percutaneous tracheostomy: prospective case series study on one hundred patients

The purpose of this study is to describe a technical modification of percutaneous tracheostomy that combines principles of the Percu Twist™ and the Griggs-Portex® methods in a reusable kit. One hundred patients underwent the procedure. There were no false passage, tube misplacement, or deaths related to the procedure. There were two minor bleedings managed conservatively. The technical modification described in this study is safe and simple to execute.

The behavior and diagnostic utility of procalcitonin and five other inflammatory molecules in critically ill patients with respiratory distress and suspected 2009 influenza a H1N1 infection

OBJECTIVES: During the 2009 influenza A H1N1 pandemic, it became difficult to differentiate viral infections from other conditions in patients admitted to the intensive care unit. We sought to evaluate the behavior and diagnostic utility of procalcitonin, C-reactive protein and four other molecules in patients with suspected 2009 Influenza A H1N1 infection. METHODS: The serum levels of procalcitonin, C-reactive protein, tumor necrosis factor α, interferon γ, interleukin 1β, and interleukin 10 were tested on admission and on days 3, 5, and 7 in 35 patients with suspected 2009 H1N1 infection who were admitted to two ICUs. RESULTS: Twelve patients had confirmed 2009 influenza A H1N1 infections, 6 had seasonal influenza infections, and 17 patients had negative swabs. The procalcitonin levels at inclusion and on day 3, and the C-reactive protein levels on day 3 were higher among subjects with 2009 influenza A H1N1 infections. The baseline levels of interleukin 1β were higher among the 2009 influenza A H1N1 patients compared with the other groups. The C-reactive protein levels on days 3, 5, and 7 and procalcitonin on days 5 and 7 were greater in non-surviving patients. CONCLUSION: Higher levels of procalcitonin, C-reactive protein and interleukin-1β might occur in critically ill patients who had a 2009 H1N1 infection. Neither procalcitonin nor CRP were useful in discriminating severe 2009 H1N1 pneumonia. Higher levels of CRP and procalcitonin appeared to identify patients with worse outcomes.

Is atrial function in Chagas dilated cardiomyopathy more impaired than in idiopathic dilated cardiomyopathy

AIMS Atrial function is an important component in overall cardiovascular performance. However, information on atrial function in dilated cardiomyopathy is limited. This study aimed to assess atrial function in dilated cardiomyopathy and to investigate if parameters of atrial function are more impaired in Chagas dilated cardiomyopathy (CDC) than in idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS Seventy-two patients with dilated cardiomyopathy (36 with CDC and 36 with IDC) and 32 healthy controls were evaluated by tissue Doppler, Doppler-based strain and strain rate (SR) imaging of the left atrium (LA) and right atrium (RA). Peak atrial strain during systole and SR during systole, early and late diastolic SR, were measured at the interatrial septum, LA inferior wall and at the lateral wall of the RA. The clinical characteristics and the parameters of LV function were similar between patients with CDC and IDC. Myocardial deformation indices during the reservoir phase of both RA and LA were lower in patients with dilated cardiomyopathy than in controls, suggesting atrial dysfunction in cardiomyopathies. However, LA and RA deformation parameters did not differ between CDC and IDC patients (interatrial septal strain during the reservoir phase: -25.2 ± 14.8 vs. -24.9 ± 16.0%, P = NS; strain rate during the reservoir phase: -1.3 ± 0.7 vs. -1.5 ± 0.9/s, P = NS). CONCLUSIONS Atrial myocardial deformation properties are abnormal in patients with dilated cardiomyopathy. CDC does not seem to have more atrial involvement than IDC.

Lesões na córnea: incidência e fatores de risco em Unidade de Terapia Intensiva

Patients hospitalized in the Intensive Care Unit (ICU) may present risk for corneal injury due to sedation or coma. This study aimed to estimate the incidence of corneal injuries; to identify the risk factors and to propose a risk prediction model for the development of corneal injury, in adult patients, in an intensive care unit of a public hospital. This is a one year, prospective cohort study with 254 patients. The data were analyzed using descriptive statistics, univariate and logistic regression. Of the 254 patients, 59.4% had corneal injuries and the mean time to onset was 8.9 days. The independent variables that predispose to risk for punctate type corneal injury were: duration of hospitalization, other ventilatory support device, presence of edema and blinking less than five times a minute. The Glasgow Coma Scale and exposure of the ocular globe were the variables related to corneal ulcer type corneal injury. The injury frequencies were punctate type (55.1%) and corneal ulcers (11.8%). Risk prediction models for the development of punctate and corneal ulcer type corneal injury were established.Pacientes internados en Unidad de Terapia Intensiva (UTI) pueden presentar riesgo de lesion en la cornea debido a la sedacion o al coma. Este estudio tuvo por objetivo estimar la incidencia de las lesiones en la cornea; identificar los factores de riesgo y proponer un modelo de prediccion de riesgo para el desarrollo de lesion en la cornea, en pacientes adultos, en Unidad de Terapia Intensiva, de un hospital publico. Estudio de cohorte prospectivo de un ano con 254 pacientes. Los datos fueron analizados por estadistica descriptiva, univariada y de regresion logistica. De los 254 pacientes, 59,4% tuvieron lesion en la cornea y el tiempo promedio para su aparicion fue de 8,9 dias. Las variables independientes que predisponen al riesgo de lesion en la cornea tipo punteada fueron: tiempo de internacion, otro dispositivo de asistencia ventilatoria, presencia de edema y parpadeo de ojos menor que cinco veces por minuto. La escala de coma de Glasgow y la exposicion del globo ocular fueron las variables relacionadas a la lesion en la cornea del tipo ulcera de cornea. Las lesiones fueron del tipo punteada (55,1%) y ulceras de cornea (11,8%). Modelos de prediccion de riesgo para lesiones en la cornea del tipo punteada y ulcera fueron establecidos.

Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock

Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock.

The Presentation of Respiratory Failure in Elderly Individuals

Respiratory failure (RF) is a prevalent condition whose presence in elderly patients may be complex and require specific and specialized intervention. A multidimensional evaluation is necessary to choose the best treatment, taking into consideration functional capacity and frailty. Cardiogenic pulmonary edema, community-acquired pneumonia, pulmonary embolism, bronchitis, and acute asthma are the main causes of RF in this patient population. Despite the limited availability of studies and data, including systematic reviews, regarding RF treatment in elderly patients, in this update, we synthesize data to guide diagnosis, treatment, and health care decision making.

Iron metabolism in chronic Chagas cardiomyopathy

É notória uma intensa resposta inflamatória em indivíduos infectados com a doença de Chagas (Trypanosoma cruzi), enfermidade crônica degenerativa na qual estão envolvidos eventos inflamatórios que atingem um dos principais órgãos-alvo, o coração, com demonstrados efeitos colaterais cardiometabólicos.1 De fato, segundo relatos de Pinto2 e confirmado em estudos, a deficiência de ferro potencializa o processo infeccioso, levando a acentuada piora no prognóstico dos pacientes com essa enfermidade.3 Análise feita em pacientes com insuficiência cardíaca revela alterações no metabolismo do ferro, sendo este fato intrínseco ao mecanismo patofisiológico da insuficiência cardíaca.4 O complexo questionamento paradoxal de um estudo de revisão Pinto2, chama a atenção e leva a hipóteses levantadas em outros estudos, em que a infecção pelo T. Cruzi ativa uma cascata imunológica. Nesse contexto, há um hormônio chamado hepcidina, que é estimulado por células específicas do sistema imunológico, tendo, portanto, participação nos mecanismos reguladores do metabolismo do ferro5. Diante disso, o paralelo entre o metabolismo do ferro descrito durante a resposta inflamatória perpassa pelo eixo hepcidina-IL-6 (citocina pró-inflamatória). Pacientes chagásicos exibem disseminação sistêmica do T. cruzi acompanhada por uma intensa resposta imune, a qual permite não apenas o controle do parasito, mas também leva a uma massiva infiltração de células mononucleares nos tecidos atingidos, especialmente no miocárdio, conduzindo à produção local e sistêmica de citocinas, quimiocinas e outros mediadores inflamatórios, tais como o óxido nítrico (NO).6 Interessantemente relatado por Pinto2, a deficiência de ferro conduz a um estado de imunocompêtencia, tornando os pacientes suscetíveis à infecção, uma vez que o ferro é essencial para fluidos orgânicos e teciduais, atuando no requerimento de energia celular e no metabolismo7. Neste sentido, sua homeostase tem sido de fundamental importância para a regulação do sistema imune.8 A importância da suplementação do ferro em grupos específicos como crianças e gestantes, bem explicitado em artigo publicado recentemente por Pinto,2 é de fato uma necessidade para amenizar problemas de carência nutricional e fortalecimento do sistema imunológico Nanas et al.9. Não obstante, estudos relatam a necessidade de suplementação do aminoácido ferro quelado em ratos infectados pelo T. cruzi, para amenizar a infecção parasitária e promover diminuta estocagem do ferro pelo sistema reticuloendotelial e macrofagocítico Rocha et al.10 Iron metabolism in chronic Chagas cardiomyopathy