Succinate 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. We 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. These 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.

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.

: 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.

The primary objective was to observe the relationship between serum levels of BNP, Ca-125, C-reactive protein and uric acid as prognostic and functional markers in patients with chronic Chagas cardiomyopathy (CCC). Circulating levels of cytokines: IL-1β, TNFα, IL-10, IL6, IL-8 and IL-12 were determined and investigated regarding their association with hemodynamic parameters, clinical signs of heart failure and outcome. Chagas is still a neglected disease that affects numerous individuals, many of them in their most productive years. CCC with left ventricular dysfunction is the most severe presentation of Chagas Disease. BNP is a well-recognized prognostic and clinical biomarker, not only in chronic heart failure patients but also in patients with CCC. Previous studies have shown Ca-125, C-reactive protein, and uric acid to be potentially good prognostic markers in heart failure (HF). Fifty patients with left ventricular fraction less (LVEF) than 55% were selected and followed for a mean period of 18 ± 8.3 months. Patient’s mean age was 43.42 ± 10.3 years (32 male), their BNP was 293 (160–530) pg/mL, Ca-125 8.5 (5.5–16.75) U/mL, uric acid 6.2 ± 2 mg/dL, and C- reactive protein 4.5 (4.5–7.3) mg/L. Patients who had LVEF less than 35% had higher BNP (p = 0.0023), Ca-125 (p = 0.027) and uric acid (p = 0.01) serum levels. Patients who died also showed higher BNP (p = 0.01), uric acid (p = 0.05) and a trend towards higher Ca-125 serum levels (p = 0.056). All markers: BNP, Ca-125, uric acid and C-reactive had good predictability of death in Cox-regression univariate analysis, however, not on the final multivariate model. Of the inflammatory cytokines, IL-8 and IL-12 showed a relation to LVEF of less than 35%. IL-12 was related to adverse cardiovascular events and non-survival. IL-1β was a good predictor of mortality in the final Cox regression model. Determination of Ca-125, uric acid levels and C-reactive protein may add useful clinical and prognostic information and may help clinical decision making for patients with CCC.

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.