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We aimed to evaluate the effects of dental correction on voluntary nutrient intake, time of intake, apparent digestibility and fecal particle size in Brazilian ponies. Twelve mares, with no history of previous dental treatments, housed in individual pens and fed a diet based on tifton 85 were used. The study comprised two consecutive experimental phases, pre and post dental treatment. Each phase consisted of 15 days for adaptation to the pen and treatment and 5 days for data collection, totaling 20 days. To calculate nutrient intake and digestibility coefficients, samples of diets, leftovers, and feces were analyzed for dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude fat (CF), mineral matter (MM), organic matter (OM), and non-fiber carbohydrates (NFC). Food intake time was recorded using a digital video recorder. Fecal particles were analyzed by wet sieving. Dental correction did not influence the intake of DM, CP, NDF, CF, and OM by the animals. However, there was an increase in NFC intake from 0.12 kg to 0.14 kg and in food intake time from 654.50 ± 138.98 to 774.95 ± 167.14. There was a decrease in the digestibility of CP from 0.08 kg to 0.04 kg and an increase in the digestibility of NDF from 0.65 kg to 0.82 kg. Although odontoplasty increased the time of hay intake and the digestibility of the fibrous fractions of the feed of ponies, it did not influence the intake of nutrients and the size of the fecal particles., Competing Interests: Declaration of competing interest The authors declare no competing interests. None of the authors has any financial or personal relationships with other people or organizations that could inappropriately influence or be perceived to influence the content of the paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Considerable evidence indicates that a signaling crosstalk between the brain and periphery plays important roles in neurological disorders, and that both acute and chronic peripheral inflammation can produce brain changes leading to cognitive impairments. Recent clinical and epidemiological studies have revealed an increased risk of cognitive impairment and dementia in individuals with impaired pulmonary function. However, the mechanistic underpinnings of this association remain unknown. Exposure to SiO 2 (silica) particles triggers lung inflammation, including infiltration by peripheral immune cells and upregulation of pro-inflammatory cytokines. We here utilized a mouse model of lung silicosis to investigate the crosstalk between lung inflammation and memory., Methods: Silicosis was induced by intratracheal administration of a single dose of 2.5 mg SiO 2 /kg in mice . Molecular and behavioral measurements were conducted 24 h and 15 days after silica administration. Lung and hippocampal inflammation were investigated by histological analysis and by determination of pro-inflammatory cytokines. Hippocampal synapse damage, amyloid-β (Aβ) peptide content and phosphorylation of Akt, a proxy of hippocampal insulin signaling, were investigated by Western blotting and ELISA. Memory was assessed using the open field and novel object recognition tests., Results: Administration of silica induced alveolar collapse, lung infiltration by polymorphonuclear (PMN) cells, and increased lung pro-inflammatory cytokines. Lung inflammation was followed by upregulation of hippocampal pro-inflammatory cytokines, synapse damage, accumulation of the Aβ peptide, and memory impairment in mice., Conclusion: The current study identified a crosstalk between lung and brain inflammatory responses leading to hippocampal synapse damage and memory impairment after exposure to a single low dose of silica in mice., (© 2022. The Author(s).)

Early diagnosis is essential for the appropriate management of acute kidney injury (AKI). We evaluated the impact of an electronic AKI alert together with a care bundle on the progression and mortality of AKI. This was a single-center prospective study that included AKI patients aged ≥ 18 years, whereas those in palliative care, nephrology, and transplantation departments were excluded. An AKI alert was issued in electronic medical records and a care bundle was suggested. A series of classes were administered to the multidisciplinary teams by nephrologists, and a clinical pharmacist audited prescriptions. Patients were categorized into pre-alert and post-alert groups. The baseline characteristics were comparable between the pre-alert (n = 1613) and post-alert (n = 1561) groups. The 30-day mortality rate was 33.6% in the entire cohort and was lower in the post-alert group (30.5% vs. 36.7%; p < 0.001). Age, pulmonary disease, malignancy, and ICU admission were associated with an increase in 30-day mortality. The electronic AKI alert together with a care bundle and a multidisciplinary education program was associated with a reduction in 30-day mortality in patients with AKI.

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a powerful predictor of perioperative outcomes. We evaluated the burden of CSA-AKI in patients with preserved baseline renal function., Methods: The data of 2,162 adult patients who underwent cardiac surgery from January 2005 to December 2020 were analyzed. Logistic regression models were used to determine predictors of CSA-AKI and their associations with hospital mortality up to 30 days., Results: The prevalence of acute kidney injury was 43.0%, and 2.0% of patients required renal replacement therapy. Hospital mortality rate was 5.6% (non-acute kidney injury = 2.0% vs. CSA-AKI = 10.4%, P&lt;0.001), and any degree of CSA-AKI was associated with a significant increase in death rates (stage 1 = 4.3%, stage 2 = 23.9%, stage 3 = 59.7%). Multivariable logistic regression analysis identified age, obesity, left ventricular dysfunction, previous cardiac surgery, and cardiopulmonary bypass duration as predictors of CSA-AKI. Moreover, CSA-AKI was confirmed as independent predictor of hospital mortality for stage 1 (odds ratio, 2.02; 95% confidence interval, 1.16 to 3.51; P=0.013), stage 2 (odds ratio, 9.18; 95% confidence interval, 4.54 to 18.58; P&lt;0.001), and stage 3 (odds ratio, 37.72; 95% confidence interval, 18.87 to 75.40; P&lt;0.001) patients., Conclusion: Age, obesity, left ventricular dysfunction, previous cardiac surgery, and cardiopulmonary bypass duration are independent predictors of CSA-AKI in patients with preserved baseline renal function. The development of CSA-AKI is significantly associated with worse outcomes, and there is a dose-response relationship between acute kidney injury stages and hospital mortality.

Objective: To characterize myocardial injury and cardiovascular complications and their predictors in severe and critical COVID-19 patients admitted to the intensive care unit., Methods: This was an observational cohort study of severe and critical COVID-19 patients admitted to the intensive care unit. Myocardial injury was defined as blood levels of cardiac troponin above the 99th percentile upper reference limit. Cardiovascular events considered were the composite of deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, acute limb ischemia, mesenteric ischemia, heart failure and arrhythmia. Univariate and multivariate logistic regression or Cox proportional hazard models were used to determine predictors of myocardial injury., Results: Of 567 patients with severe and critical COVID-19 admitted to the intensive care unit, 273 (48.1%) had myocardial injury. Of the 374 patients with critical COVID-19, 86.1% had myocardial injury, and also showed more organ dysfunction and higher 28-day mortality (56.6% versus 27.1%, p < 0.001). Advanced age, arterial hypertension and immune modulator use were predictors of myocardial injury. Cardiovascular complications occurred in 19.9% of patients with severe and critical COVID-19 admitted to the intensive care unit, with most events occurring in patients with myocardial injury (28.2% versus 12.2%, p < 0.001). The occurrence of an early cardiovascular event during intensive care unit stay was associated with higher 28-day mortality compared with late or no events (57.1% versus 34% versus 41.8%, p = 0.01)., Conclusion: Myocardial injury and cardiovascular complications were commonly found in patients with severe and critical forms of COVID-19 admitted to the intensive care unit, and both were associated with increased mortality in these patients.

This study aimed to evaluate the COVID-19 hospitalizations in a tertiary hospital by age group and month, considering the introduction and the advance of the vaccination against the disease. The laboratory-confirmed COVID-19-associated hospitalizations among people aged 20 years or older, that occurred between March 2020 and June 2021, were distributed by month of symptom onset and age group. The proportion of hospitalizations by age group was calculated for the year 2021. The proportions were compared using the chi-square test for trends. The marks of vaccination advances among different age groups were taken from the official website LocalizaSUS. In 2020, hospitalizations among people aged 60-80 years old were the most frequent (39.1%). From January-June 2021, when the vaccination commenced, while hospitalizations of patients aged 20 to < 40 and 40 to 60 years old showed an increasing trend, the older age groups and those with vaccination recommendations (from 60 to < 80 and from 80 or over) showed a downward trend. As of June 2021, with widespread vaccination, a drop in hospitalizations was observed in > 60 years old. At 20 to <40 and 40 to < 60, an increase in hospitalizations was observed. It demonstrates the important role of vaccination in combating the COVID-19 pandemic.

Background: The impact of left ventricular reverse remodeling (LVRR) on the prognosis of Chagas cardiomyopathy is unknown. The aim of this study was to determine whether the presence of LVRR can predict mortality in these patients., Methods: From January 2000 to December 2010, the medical charts of 159 patients were reviewed. LVRR was defined as an increase of left ventricular ejection fraction (LVEF) and a decrease of left ventricular end-diastolic diameter (LVDD) by two-dimensional echocardiography. No patient underwent cardiac resynchronization therapy or required mechanical ventricular assistance., Results: At baseline, median (25th-75th) LVDD was 64 mm (59-70), and median LVEF was 33.2% (26.4-40.1). LVRR was detected in 24.5% of patients in a 40-month (26-64) median follow-up. In the LVRR group, LVDD decreased from 64 mm (59-68) to 60 mm (56-65; p < 0.001), and LVEF increased from 31.3% (24.1-39.0) to 42.5% (32.2-47.7; p < 0.001). However, LVRR was not associated with heart failure hospitalization, cardiogenic shock, heart transplantation, or mortality (p > 0.05 for all comparisons). The Cox proportional hazard model analysis identified only cardiogenic shock (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 1.51-3.85; p < 0.001) and serum sodium level (HR: 0.91; 95% CI: 0.86-0.96; p < 0.001) as independent predictors of all-cause mortality., Conclusions: Left ventricular reverse remodeling occurs in one quarter of patients with Chagas cardiomyopathy and have no impact on the outcomes of patients with this condition.

Background Increased high-sensitivity cardiac troponin T (hs-cTnT) above the upper reference limit (URL) after noncardiac surgery identifies patients at risk for mortality. Prior studies have not analyzed hs-cTnT as a continuous variable or probed age- and sex-specific URLs. This study compared the prediction of 30-day mortality using continuous postoperative hs-cTnT levels to the use of the overall URL and age- and sex-specific URLs. Methods and Results Patients (876) >40 years of age who underwent noncardiac surgery were included. Hs-cTnT was measured on postoperative day 1. Cox proportional hazards models were used to compare associations between 30-day mortality and using hs-cTnT as a continuous variable, or above the overall or age- and sex-specific URLs. Comparisons were performed by the area under the receiver operating characteristic curve analysis. Mortality was 4.2%. For each 1 ng/L increase in postoperative hs-cTnT, there was a 0.3% increase in mortality ( P <0.001). Patients with postoperative hs-cTnT >14 ng/L were 37% of the cohort, while those above age- and sex-specific URLs were 25.3%. Both manifested higher mortality (hazard ratio [HR], 3.19; 95% CI, 1.20-8.49; P =0.020) and (HR, 2.76; P =0.009) than those with normal levels. The area under receiver operating characteristic curve was 0.89 using hs-cTnT as a continuous variable, 0.87 for age- and sex-specific URLs, and 0.86 for the overall URL. Conclusions Hs-cTnT as a continuous variable was independently associated with 30-day mortality and had the highest accuracy. Hs-cTnT elevations using overall and/or age- and sex-specific URLs were also associated with higher mortality.

Cylindrospermopsin (CYN) is a cyanotoxin of increasing worldwide environmental importance as it can harm human beings. Dexamethasone is a steroidal anti-inflammatory agent. Thus, we aimed at evaluating the pulmonary outcomes of acute CYN intoxication and their putative mitigation by dexamethasone. Male BALB/c mice received intratracheally a single dose of saline or CYN (140 μg/kg). Eighteen hours after exposure, mice instilled with either saline solution (Ctrl) or CYN were intramuscularly treated with saline (Tox) or 2 mg/kg dexamethasone (Tox + dexa) every 6 h for 48 h. Pulmonary mechanics was evaluated 66 h after instillation using the forced oscillation technique (flexiVent) to determine airway resistance (R N ), tissue viscance (G) and elastance (H). After euthanasia, the lungs were removed and separated for quantification of CYN, myeloperoxidase activity and IL-6 and IL-17 levels plus histological analysis. CYN was also measured in the liver. CYN increased G and H, alveolar collapse, PMN cells infiltration, elastic and collagen fibers, activated macrophages, peroxidase activity in lung and hepatic tissues, as well as IL-6 and IL-17 levels in the lung. Tox + Dexa mice presented total or partial reversion of the aforementioned alterations. Briefly, CYN impaired pulmonary and hepatic characteristics that were mitigated by dexamethasone., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

C 60 fullerene (C 60 ) is a nano-pollutant that can damage the respiratory system. Eugenol exhibits significant anti-inflammatory and antioxidant properties. We aimed to investigate the time course of C 60 emulsion-induced pulmonary and spermatic harms, as well as the effect of eugenol on C 60 emulsion toxicity. The first group of mice (protocol 1) received intratracheally C 60 emulsion (1.0 mg/kg BW) or vehicle and were tested at 12, 24, 72 and 96 h (F groups) thereafter. The second group of mice (protocol 2) received intratracheally C 60 emulsion or vehicle, 1 h later were gavaged with eugenol (150 mg/kg) or vehicle, and experiments were done 24 h after instillation. Lung mechanics, morphology, redox markers, cytokines and epididymal spermatozoa were analyzed. Protocol 1: Tissue damping (G) and elastance (H) were significantly higher in F24 than in others groups, except for H in F72. Morphological and inflammatory parameters were worst at 24 h and subsequently declined until 96 h, whereas redox and spermatic parameters worsened over the whole period. Eugenol eliminated the increase in G, H, cellularity, and cytokines, attenuated oxidative stress induced by C60 exposure, but had no effect on sperm. Hence, exposure to C 60 emulsion deteriorated lung morphofunctional, redox and inflammatory characteristics and increased the risk of infertility. Furthermore, eugenol avoided those changes, but did not prevent sperm damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to develop and validate a simple method for predicting long-term all-cause mortality in ambulatory patients with chronic heart failure (CHF) residing in an area where Chagas disease is endemic, which will be important not only for patients living in Latin America but also to those living in developed non-endemic countries., Methods and Results: A total of 677 patients with a wide spectrum of aetiologies for left ventricular systolic dysfunction and receiving optimized evidence-based treatment for CHF were prospectively followed for approximately 11 years. We established a risk score using Cox proportional hazard regression models. After multivariable analysis, four variables were independently associated with mortality and included in the CALL Risk Score: Chagas cardiomyopathy aetiology alone [hazard ratio, 3.36; 95% confidence interval (CI), 2.61-4.33; P < 0.001], age ≥60 years (hazard ratio, 1.36; 95% CI, 1.06-1.74; P = 0.016), left anterior fascicular block (hazard ratio, 1.64; 95% CI, 1.27-2.11; P < 0.001), and left ventricular ejection fraction <40% (hazard ratio, 1.73; 95% CI, 1.30-2.28; P < 0.001). The internal validation considered the bootstrapping, a resampling technique recommended for prediction model development. Hence, we established a scoring system attributing weights according to each risk factor: 3 points for Chagas cardiomyopathy alone, 1 point for age ≥60 years, and 2 points each for left anterior fascicular block and left ventricular ejection fraction <40%. Three risk groups were identified: low risk (score ≤2 points), intermediate risk (score of 3 to 5 points), and high risk (score ≥6 points). High-risk patients had more than two-fold increase in mortality (26.9 events/100 patient-years) compared with intermediate-risk patients (10.1 events/100 patient-years) and almost seven-fold increase compared with low-risk patients (4.3 events/100 patient-years). The CALL Risk Score data sets from the development and internal validation cohorts both displayed suitable discrimination c-index of 0.689 (95% CI, 0.688-0.690; P < 0.001) and 0.687 (95% CI, 0.686-0.688; P < 0.001), respectively, and satisfactory calibration [Greenwood-Nam-D'Agostino test (8) = 7.867; P = 0.447] and [Greenwood-Nam-D'Agostino test (8) = 10.08; P = 0.273], respectively., Conclusions: The CALL Risk Score represents a simple and validated method with a limited number of non-invasive variables that successfully predicts long-term all-cause mortality in a real-world cohort of patients with CHF. Patients with CHF stratified as high risk according to the CALL Risk Score should be monitored and aggressively managed, including those with CHF secondary to Chagas disease., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Few studies regarding chronic kidney disease (CKD) and anemia have been conducted in patients with Chagas cardiomyopathy (CC). We evaluated the risk prediction performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and anemia in CC patients., Methods: From 2000 to 2010, a total of 232 patients were studied in a single-center retrospective study. CKD was defined as creatinine clearance <60 mL/min/1.73 m 2 according to CKD-EPI equation. Anemia was defined as hemoglobin <12 g/dL (women) and <13 g/dL (men). Cox proportional hazards models were used to establish predictors for death., Results: At baseline, 98 individuals (42.2%) had criteria for CKD and 41 (17.7%) for anemia. During follow-up, 136 patients (58.6%) died. Independently, CKD and anemia were not associated with all-cause mortality. However, when they coexisted, an additional risk was attributed for these patients. Cox proportional hazard models analysis identified systolic blood pressure (hazard ratio, 0.99; 95% confidence interval (CI), 0.98 to 1.00; P =0.015), implantable cardioverter-defibrillator (hazard ratio, 0.48; 95% CI, 0.27 to 0.85; P =0.012), left anterior fascicular block (hazard ratio, 1.52; 95% CI, 1.08 to 2.13; P =0.017), left ventricular end-diastolic diameter (hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P < 0.001), and serum sodium (hazard ratio, 0.95; 95% CI, 0.92 to 0.99; P =0.020) as independent predictors for death., Conclusions: CKD and anemia are not independent predictors for long-term mortality in CC patients. However, the prognosis is poorer in individuals with both comorbidities., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Marcelo Arruda Nakazone et al.)

Silicosis is an occupational lung disease caused by inhalation of silica particles. It is characterized by intense lung inflammation, with progressive and irreversible fibrosis, leading to impaired lung function. Purinergic signaling modulates silica-induced lung inflammation and fibrosis through P2X7 receptor. In the present study, we investigate the role of P2Y 12 , the G-protein-coupled subfamily prototype of P2 receptor class in silicosis. To that end, BALB/c mice received an intratracheal injection of PBS or silica particles (20 mg), without or with P2Y 12 receptor blockade by clopidogrel (20 mg/kg body weight by gavage every 48 h) - groups CTRL, SIL, and SIL + Clopi, respectively. After 14 days, lung mechanics were determined by the end-inflation occlusion method. Lung histology was analyzed, and lung parenchyma production of nitric oxide and cytokines (IL-1β, IL-6, TNF-α, and TGF-β) were determined. Silica injection reduced animal survival and increased all lung mechanical parameters in relation to CTRL, followed by diffuse lung parenchyma inflammation, increased neutrophil infiltration, collagen deposition and increased pro-inflammatory and pro-fibrogenic cytokine secretion, as well as increased nitrite production. Clopidogrel treatment prevented silica-induced changes in lung function, and significantly reduced lung inflammation, fibrosis, as well as cytokine and nitrite production. These data suggest that inhibition of P2Y 12 signaling improves silica-induced lung inflammation, preventing lung functional changes and mortality. Our results corroborate previous observations of silica-induced lung changes and expand the understanding of purinergic signaling in this process., (Copyright © 2020 Santana, Luna-Gomes, Rangel-Ferreira, Tamura, Da Graça, Machado, Zin, Takiya, Faffe and Coutinho-Silva.)

Objective: To examine the impact of delayed transfer from the emergency room into the intensive care unit on the length of intensive care unit stay and death., Methods: This prospective, cohort study performed in a tertiary academic hospital obtained data from 1913 patients admitted to the emergency room with a documented request for admission into the intensive care unit. The patients admitted directly into the medical-surgical intensive care unit (n = 209) were categorized into tertiles according to their waiting time for intensive care unit admission (Group 1: < 637 min, Group 2: 637 to 1602 min, and Group 3: > 1602 min). Patients who stayed in the intensive care unit for longer than 3.2 days (median time of intensive care unit length of stay of all patients) were considered as having a prolonged intensive care unit stay., Results: A total of 6,176 patients were treated in the emergency room during the study period, among whom 1,913 (31%) required a bed in the intensive care unit. The median length of stay in the emergency room was 17 hours [9 to 33 hours]. Hospitalization for infection/sepsis was an independent predictor of prolonged intensive care unit stay (OR 2.75 95%CI 1.38 - 5.48, p = 0.004), but waiting time for intensive care unit admission was not. The mortality rate was higher in Group 3 (38%) than in Group 1 (31%) but the difference was not statistically significant., Conclusion: Delayed admission into the intensive care unit from the emergency room did not result in an increased intensive care unit stay or mortality.

Background:  Periprocedural myocardial injury after coronary artery bypass grafting (CABG) may affect the patient's prognosis and may be due to a different set of factors beyond the atherosclerotic plaque instability. Considering the challenges in the diagnosis of myocardial injury after CABG, the aim of this study was to determine the association between postoperative early elevation of high-sensitivity troponin T (hsTnT) and all-cause 30-day mortality after CABG., Methods:  We enrolled 600 consecutive patients who underwent CABG. The hsTnT value was measured immediately before surgery and in the morning of the first postoperative day., Results:  The baseline hsTnT was 13 ng/L (7-26 ng/L) and 273 patients (45.7%) had baseline hsTnT above the 99th percentile/upper reference limit (URL) (14 ng/L). The median for hsTnT at first postoperative day was 235 ng/L (152-425 ng/L). We calculated the postoperative hsTnT ratio to URL for each patient, representing the number of times exceeding the URL (hsTnT value divided by 14 ng/L). The multivariate analysis by Cox proportional hazard model revealed that age (years) (hazard ratio [HR] = 1.13, 95% confidence interval [CI]: 1.07-1.20; p  < 0.001) and postoperative hsTnT ratio to URL (per 10-fold increase) (HR = 1.06, 95% CI: 1.04-1.08; p  < 0.001) were independent predictors of all-cause 30-day mortality after CABG., Conclusion:  In our series, age and higher postoperative hsTnT levels were independent and reliable predictors of all-cause 30-day mortality after CABG., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Acute lung injury (ALI) remains a major cause of mortality. In lipopolysaccharide (LPS)-stimulated macrophages, eugenol reduces cyclooxygenase-2 expression, NF-κB activation, and inflammatory mediators. We examined the anti-inflammatory and anti-oxidative action of eugenol in an in vivo model of LPS-induced lung injury. Lung mechanics and histology were analyzed in mice 24 h after LPS exposure, with and without eugenol treatment at different doses. Additional animals, submited to the same protocol, were treated with eugenol at 150 mg/kg to determine its effect on inflammatory cytokines (ELISA) and oxidative markers. LPS-induced lung functional and histological changes were significantly improved by eugenol, in a dose-dependent way. Furthermore, eugenol (150 mg/kg) was able to inhibit the release of inflammatory cytokines (TNF-α, IL-1β and IL-6), NADPH oxidase activity, as well as antioxidant enzymes activity (superoxide dismutase, catalase and glutathione peroxidase). Finally, eugenol reduced LPS-induced protein oxidation. In conclusion, eugenol improved in vivo LPS-induced ALI through both anti-inflammatory and anti-oxidative effects, avoiding damage to lung structure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Several trials have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors, used to treat type 2 diabetes (T2DM), improve endothelial function. The current study investigated the effects of vildagliptin, a DPP-4 inhibitor, compared to glibenclamide on endothelial function, arterial stiffness, and blood pressure in patients with T2DM and hypertension., Methods: Patients aged over 35 years with T2DM and hypertension, but without cardiovascular disease, were randomly allocated to treatment with vildagliptin (n = 25) or glibenclamide (n = 25). Both groups took metformin. Endothelial function was evaluated by peripheral artery tonometry (Endo-PAT 2000) to calculate the reactive hyperemia index (RHI) and arterial stiffness. Primary outcome was change in the RHI after 12 weeks of treatment. Twenty-four-hour non-invasive ambulatory blood pressure monitoring was performed using a Mobil-O-Graph ® 24-h PWA monitor. Arterial stiffness was assessed using the augmentation index corrected for 75 bpm (AIx75), pulse wave velocity (PWV) and central systolic blood pressure (cSBP)., Results: There were no changes in the RHI in the vildagliptin group (before 2.35 ± 0.59; after 2.24 ± 0.60; p value = NS) or in the glibenclamide group (before 2.36 ± 0.52; after 2.34 ± 0.50; p value = NS), with no differences between groups (p value = NS). There was also no difference between vildagliptin and glibenclamide treatment in respect to AIx75 (p value = NS), cSBP (p value = NS) or PWV (p value = NS)., Conclusions: Vildagliptin and glibenclamide similarly do not change the endothelial function and arterial stiffness after 12 weeks of treatment in diabetic and hypertensive patients without cardiovascular disease. Thus, vildagliptin has a neutral effect on vascular function., Trial Registration: ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

Aim: This study assessed pulmonary outcomes generated by inhibiting key enzymes of sphingolipid metabolism pathways related to ceramide synthesis in a murine model of lung injury induced by lipopolysaccharide (LPS)., Methods: C57BL/6 male adult mice received LPS intratracheally and the expressions of acid sphingomyelinase (ASM), neutral sphingomyelinase (NSM), serine palmitoyl transferase (SPT) and dihydroceramide synthase (DS) were assessed at 2, 4, 6, 12 and 24 h after LPS instillation in lung homogenate (n = 30). The pharmacological inhibition of ASM, NSM, SPT and DS were assayed in other mice groups by three different doses of desipramine, GW4869, myriocin and fumonisin, respectively (n = 90). Their most effective doses were administered intraperitoneally 1 or 2 h before LPS to different animal groups (n = 120). Mice underwent determination of pulmonary mechanics, lung histopathological aspects and apoptosis., Results: The expression levels of the enzymes reached their peak at 2-4 h after LPS administration. ASM inhibition attenuated alveolar collapse and GW4869 decreased lung elastance, proinflammatory cytokines' levels and was more effective to improve alveolar collapse than desipramine. On the other hand, SPT blockage aggravated lung lesion and no effects it was observed with fumonisin. Moreover, simultaneous administration of inhibitors (desipramine + GW4869, myriocin + fumonisin and all inhibitors together) resulted in no changes., Conclusion: Blockage of sphingomyelinases and the de novo pathways improved and aggravated lung injury, respectively, putatively suggesting specific targets to therapeutic strategies in LPS-induced lung injury., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Continuous exposure to coal mining particles can cause a variety of lung diseases. We aimed to evaluate the outcomes of exposure to detailed characterized coal and coal fly ash (CFA) particles on DNA, lung and extrapulmonary tissues. Coal samples (COAL11 and COAL16) and CFA samples (CFA11 and CFA16) were included in this study. Intending to enhance the combustion process COAL16 was co-fired with a mixture of fuel oil and diesel oil, producing CFA16. Male BALB/c mice were intratracheally instilled with coal and CFA particles. Measurements were done 24h later. Results showed significant rigidity and obstruction of the central airways only for animals acutely exposed to coal particles. The COAL16 group also showed obstruction of the peripheral airways. Mononuclear cells were recruited in all treatment groups and expression of cytokines, particularly TNF-α and IL-1β, was observed. Only animals exposed to COAL16 showed a significant expression of IL-6 and recruitment of polymorphonuclear cells. DNA damage was demonstrated by Comet assay for all groups. Cr, Fe and Ni were detected in liver, spleen and brain, showing the efficient translocation of metals from the bloodstream to extrapulmonary organs. These effects were associated with particle composition (oxides, hydroxides, phosphates, sulfides, sulphates, silciates, organic-metalic compounds, and polycyclic aromatic hidrocarbons) rather than their size. This work provides state of knowledge on the effects of acute exposure to coal and CFA particles on respiratory mechanics, DNA damage, translocation of metals to other organs and related inflammatory processes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Murine papain-induced emphysema is a model that reproduces many of the features found in patients. Bone marrow-derived mononuclear cells (BMMC) have already been used to repair the alveolar epithelium in respiratory diseases, but not in the papain model. Thus, we hypothesized that BMMC could prevent the pathophysiological processes in papain-induced experimental emphysema. Female BALB/c mice received intratracheal instillation of 50 μL of saline (S groups) or papain (P groups, 10 IU/50 μl of saline) on days 1 and 7 of the experimental protocol. On the 14th day, 2 × 10 6 BMMC of male BALB/c mice (SC21 and PC21) or saline (SS21 and PS21) were injected by the jugular vein. Analyses were done on days 14 (S14 and P14) and 21 (SS21, PS21, SC21, and PC21) of the protocol. qPCR evaluated the presence of the Y chromosome in the lungs of BMMC recipient animals. Functional residual capacity (FRC), alveolar diameter, cellularity, elastic fiber content, concentrations of TNF-α, IL-1β, IL-6, MIP-2, KC, IFN-γ, apoptosis, mRNA expression of the dual oxidase (DUOX1 and DUOX2), production of H 2 O 2 and DUOX activity were evaluated in lung tissue. We did not detect the Y chromosome in recipients' lungs. FRC, alveolar diameter, polymorphonuclear cells (PMN) and levels of KC, MIP-2, and IFN-γ increased in P14 and PS21 groups; the changes in the latter were reverted by BMMC. TNF-α, IL-1β e IL-6 were similar in all groups. The amount of elastic fibers was smaller in P14 and PS21 than in other groups, and BMMC did not increase it in PC21 mice. PS21 animals showed increased DUOX activity and mRNA expression for DUOX1 and 2. Cell therapy reverted the activity of DUOX and mRNA expression of DUOX1. BMMC reduced mRNA expression of DUOX2. Apoptosis index was elevated in PS21 mice, which was reduced by cell therapy in PC21. Static compliance, viscoelastic component of elastance and pressure to overcome viscoelasticity were increased in P14 and PS21 groups. These changes and the high resistive pressure found on day 21 were reverted by BMMC. In conclusion, BMMC showed potent anti-inflammatory, antiapoptotic, antioxidant, and restorative roles in papain-triggered pulmonary emphysema.

Objective: The present study refers to a determination of the preoperative B-type natriuretic peptide is a predictor of short-term all-cause mortality in patients undergoing on-pump coronary artery bypass graft surgeries., Methods: Two hundred and twenty-one patients undergoing on-pump coronary artery bypass graft surgeries were evaluated prospectively during a 30-day postoperative follow-up period. Serum B-type natriuretic peptide concentration was measured without a 24-hour period prior to the surgical procedure and the value obtained was correlated with a short-term all-cause mortality., Results: Data analysis showed that all-cause mortality rates were equal to 9.5% in 30 days. Accuracy analysis by the receiver operating characteristic curve found an ideal cut-off value of B-type natriuretic peptide equal to 150 pg/mL in relation to mortality (AUC=0.82, 95% CI=0.71-0.87, P<0.001). Multivariate analysis showed that B-type natriuretic peptide value greater than or equal to 150 pg/mL (P=0.030, HR=3.99, 95% CI=1.14-13.98) was an independent predictor of all-cause mortality in a 30-day follow-up period., Conclusion: Preoperative serum B-type natriuretic peptide concentration is an independent predictor of short-term all-cause mortality in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Background: The incidence of posttraumatic osteomyelitis (PTO) is increasing despite new treatment strategies. Assessment of patients' outcomes following PTO is challenging due to multiple variables. The study goals are to determine the frequency of recurrence following PTO treatment and identify factors predisposing patients to treatment failure., Methods: Between August 01, 2007 to August 30, 2012, a single-center retrospective cohort study was performed among 193 patients diagnosed with PTO following orthopedic surgery for fracture care. Bone and soft tissues were collected for cultures and PTO was defined according to CDC/NHSN criteria. Patient, injury, surgery-associated variables, and microbiological records were reviewed for risk factors associated to recurrence of PTO. Univariate and multivariable analyses using logistic regression were performed, with p < 0.05 considered significant., Results: Thirty-eight patients (20%) of 192 diagnosed and treated for PTO failed their treatment. Factors associated with recurrence were age between 61 and 80 years [hazard ratio (HR) = 6.086, 95% confidence interval (CI) = 2.459;15.061, p  = <0.001], age above 80 years [HR = 9.975 (95% CI = 3.591;27.714), p  = <0.001], intraoperative blood transfusion [HR = 2.239 (95% CI = 1.138;4.406), p  = 0.020], and positive culture for Pseudomonas aeruginosa [HR = 2.700 (95% CI = 1.370;5.319), p  = 0.004]., Conclusions: Risk factors associated with recurrence of PTO are difficult to measure. The present study revealed that elderly patients, intraoperative blood transfusions, and infection due to P. aeruginosa were independently associated with recurrence of PTO. These factors should warn clinicians of a higher failure rate following treatment of PTO. Trial registration: ISRCTN71648577. Registered 18 May 2017. Retrospectively registered.

Objective: α-2-agonists cause sympathetic inhibition combined with parasympathetic activation and have other properties that could be beneficial during cardiac anesthesia. We evaluated the effects of dexmedetomidine as an anesthetic adjuvant compared to a control group during cardiac surgery., Methods: We performed a retrospective analysis of prospectively collected data from all adult patients (> 18 years old) undergoing cardiac surgery. Patients were divided into two groups, regarding the use of dexmedetomidine as an adjuvant intraoperatively (DEX group) and a control group who did not receive α-2-agonist (CON group)., Results: A total of 1302 patients who underwent cardiac surgery, either coronary artery bypass graft or valve surgery, were included; 796 in the DEX group and 506 in the CON group. Need for reoperation (2% vs. 2.8%, P=0.001), type 1 neurological injury (2% vs. 4.7%, P=0.005) and prolonged hospitalization (3.1% vs. 7.3%, P=0.001) were significantly less frequent in the DEX group than in the CON group. Thirty-day mortality rates were 3.4% in the DEX group and 9.7% in the CON group (P<0.001). Using multivariable Cox regression analysis with in hospital death as the dependent variable, dexmedetomidine was independently associated with a lower risk of 30-day mortality (odds ratio [OR]=0.39, 95% confidence interval [CI]: 0.24-0.65, P≤0.001). The Logistic EuroSCORE (OR=1.05, 95% CI: 1.02-1.10, P=0.004) and age (OR=1.03, 95% CI: 1.01-1.06, P=0.003) were independently associated with a higher risk of 30-day mortality., Conclusion: Dexmedetomidine used as an anesthetic adjuvant was associated with better outcomes in patients undergoing coronary artery bypass graft and valve surgery. Randomized prospective controlled trials are warranted to confirm our results., Competing Interests: No conflict of interest.

Introduction: In coronary artery bypass (CABG) surgery, the common complications are the need for reintubation, prolonged mechanical ventilation (PMV) and death. Thus, a reliable model for the prognostic evaluation of those particular outcomes is a worthwhile pursuit. The existence of such a system would lead to better resource planning, cost reductions and an increased ability to guide preventive strategies. The aim of this study was to compare different methods - logistic regression (LR) and artificial neural networks (ANNs) - in accomplishing this goal., Material and Methods: Subjects undergoing CABG (n = 1315) were divided into training (n = 1053) and validation (n = 262) groups. The set of independent variables consisted of age, gender, weight, height, body mass index, diabetes, creatinine level, cardiopulmonary bypass, presence of preserved ventricular function, moderate and severe ventricular dysfunction and total number of grafts. The PMV was also an input for the prediction of death. The ability of ANN to discriminate outcomes was assessed using receiver-operating characteristic (ROC) analysis and the results were compared using a multivariate LR., Results: The ROC curve areas for LR and ANN models, respectively, were: for reintubation 0.62 (CI: 0.50-0.75) and 0.65 (CI: 0.53-0.77); for PMV 0.67 (CI: 0.57-0.78) and 0.72 (CI: 0.64-0.81); and for death 0.86 (CI: 0.79-0.93) and 0.85 (CI: 0.80-0.91). No differences were observed between models., Conclusions: The ANN has similar discriminating power in predicting reintubation, PMV and death outcomes. Thus, both models may be applicable as a predictor for these outcomes in subjects undergoing CABG.

Silicosis is an occupational lung disease, characterized by irreversible and progressive fibrosis. Silica exposure leads to intense lung inflammation, reactive oxygen production, and extracellular ATP (eATP) release by macrophages. The P2X7 purinergic receptor is thought to be an important immunomodulator that responds to eATP in sites of inflammation and tissue damage. The present study investigates the role of P2X7 receptor in a murine model of silicosis. To that end wild-type (C57BL/6) and P2X7 receptor knockout mice received intratracheal injection of saline or silica particles. After 14 days, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage and flow cytometry analyzes were performed. Lungs were harvested for histological and immunochemistry analysis of fibers content, inflammatory infiltration, apoptosis, as well as cytokine and oxidative stress expression. Silica particle effects on lung alveolar macrophages and fibroblasts were also evaluated in cell line cultures. Phagocytosis assay was performed in peritoneal macrophages. Silica exposure increased lung mechanical parameters in wild-type but not in P2X7 knockout mice. Inflammatory cell infiltration and collagen deposition in lung parenchyma, apoptosis, TGF-β and NF-κB activation, as well as nitric oxide, reactive oxygen species (ROS) and IL-1β secretion were higher in wild-type than knockout silica-exposed mice. In vitro studies suggested that P2X7 receptor participates in silica particle phagocytosis, IL-1β secretion, as well as reactive oxygen species and nitric oxide production. In conclusion, our data showed a significant role for P2X7 receptor in silica-induced lung changes, modulating lung inflammatory, fibrotic, and functional changes.

In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Preoperatively elevated serum creatinine (SCr) is considered an independent risk factor for morbidity and mortality after cardiac surgery. The aim of this study was to apply the Kidney Disease Improving Global Outcomes classification for acute kidney injury in a population of patients with preoperatively elevated serum creatinine who underwent cardiac surgery (coronary artery bypass grafting or cardiac valve surgery) and to evaluate the acute worsening of renal function as a predictor of 30-day mortality., Methods: This was a single-center retrospective study that included patients from the Postoperative Cardiac Surgery Intensive Care Unit of the Hospital de Base, São José do Rio Preto Medical School. Demographics, type of surgery, laboratory data and pre, peri and postoperative data were obtained from a prospectively collected database. From January 2003 to June 2013, 2,878 patients underwent cardiac surgery, either coronary artery bypass grafting or cardiac valve surgery, at the Hospital de Base of São José do Rio Preto Medical School. Out of those, 918 showed elevated preoperative serum creatinine, with SCr > 1.30 mg/dL for men and > 1.00 mg/dL for women. Five hundred and forty nine patients (60%) undergoing coronary artery bypass grafting and 369 patients (40%) undergoing cardiac valve surgery. A Multivariate Cox Proportional Hazard Model (stepwise) was used to assess the relationship between AKI and mortality at 30 days., Results: Out of the 918 patients studied, 391 (43%) had postoperative AKI: 318 (35%) had Kidney Disease Improving Global Outcomes stage 1, 27 (2.9%) had Kidney Disease Improving Global Outcomes stage 2, and 46 (5.0%) had Kidney Disease Improving Global Outcomes stage 3. Patients in every stage of acute kidney injury showed progressive increase in EuroSCORE values, 30-day mortality rates, cardiopulmonary bypass duration, and intensive care length of stay. Among patients classified as Kidney Disease Improving Global Outcomes stage 3, 76% required dialysis with a 30-day mortality of 66%. The Cox proportional hazards model showed that the hazard ratio for 30-day mortality was 4.8 for Kidney Disease Improving Global Outcomes stage 1 patients, 13.5 for Kidney Disease Improving Global Outcomes stage 2 patients, and 20.8 for Kidney Disease Improving Global Outcomes stage 3 patients (P<0.001 for all). Subgroup analyses (coronary artery bypass grafting and cardiac valve surgery) had similar results., Conclusion: In this population, acute kidney injury based on the Kidney Disease Improving Global Outcomes criteria was a powerful predictor of 30-day mortality in patients with elevated preoperative serum creatinine who underwent cardiac surgery (coronary artery bypass grafting or cardiac valve surgery).

Tripoli is a microcrystalline siliceous rock used to polish metals and precious stones. Its inhalation has been associated with increased prevalence of breathing complaints and pneumoconiosis. However, its acute human exposure has not been so far studied. We aimed at evaluating the putative mechanical, morphological, biochemical and inflammatory lung damage in mice acutely exposed to Tripoli dust. BALB/c mice were randomly assigned to 2 groups: In control group (CTRL, n=6) animals received intratracheally (i.t.) 0.9% NaCl (50μl), while Tripoli group (TRIP, n=15) received 20mg of Tripoli powder diluted in 50μL of saline i.t. The experiments were done 15 days later. TRIP mice showed higher pulmonary mechanical impedance, polymorphonuclear cells, TNF-α, IL1-β and IL-6 than CTRL. TRIP presented granulomatous nodules containing collagenous fibers that occupied 35% of the lung tissue area. In conclusion, acute exposure to Tripoli dust triggered important lung damage in mice lungs that if found in human workers could trigger severe illness., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: The definition of acute renal failure has been recently reviewed, and the term acute kidney injury (AKI) was proposed to cover the entire spectrum of the syndrome, ranging from small changes in renal function markers to dialysis needs. This study was aimed to evaluate the incidence, morbidity and mortality associated with AKI (based on KDIGO criteria) in patients after cardiac surgery (coronary artery bypass grafting or cardiac valve surgery) and to determine the value of this feature as a predictor of hospital mortality (30 days)., Methods: From January 2003 to June 2013, a total of 2,804 patients underwent cardiac surgery in our service. Cox proportional hazard models were used to determine the association between the development of AKI and 30-day mortality., Results: A total of 1,175 (42%) patients met the diagnostic criteria for AKI based on KDIGO classification during the first 7 postoperative days: 978 (35%) patients met the diagnostic criteria for stage 1 while 100 (4%) patients met the diagnostic criteria for stage 2 and 97 (3%) patients met the diagnostic criteria for stage 3. A total of 63 (2%) patients required dialysis treatment. Overall, the 30-day mortality was 7.1% (2.2%) for patients without AKI and 8.2%, 31% and 55% for patients with AKI at stages 1, 2 and 3, respectively. The KDIGO stage 3 patients who did not require dialysis had a mortality rate of 41%, while the mortality of dialysis patients was 62%. The adjusted Cox regression analysis revealed that AKI based on KDIGO criteria (stages 1-3) was an independent predictor of 30-day mortality (P<0.001 for all. Hazard ratio = 3.35, 11.94 and 24.85)., Conclusion: In the population evaluated in the present study, even slight changes in the renal function based on KDIGO criteria were considered as independent predictors of 30-day mortality after cardiac surgery.

Background: Pulmonary emphysema is characterized by the loss of lung architecture. Our hypothesis is that the inhibition of 5-lipoxygenase (5-LO) production may be an important strategy to reduce inflammation, oxidative stress, and metalloproteinases in lung tissue resulting from cigarette smoke (CS)-induced emphysema., Methods: 5-LO knockout (129S2-Alox5(tm1Fun)/J) and wild-type (WT) mice (129S2/SvPas) were exposed to CS for 60days. Mice exposed to ambient air were used as Controls. Oxidative, inflammatory, and proteolytic markers were analyzed., Results: The alveolar diameter was decreased in CS 5-LO(-/-) mice when compared with the WT CS group. The CS exposure resulted in less pronounced pulmonary inflammation in the CS 5-LO(-/-) group. The CS 5-LO(-/-) group showed leukotriene B4 values comparable to those of the Control group. The expression of MMP-9 was decreased in the CS 5-LO(-/-) group when compared with the CS WT group. The expression of superoxide dismutase, catalase, and glutathione peroxidase were decreased in the CS 5-LO(-/-) group when compared with the Control group. The protein expression of nuclear factor (erythroid-derived 2)-like 2 was reduced in the CS 5-LO(-/-) group when compared to the CS WT group., Conclusion: In conclusion, we show for the first time that 5-LO deficiency protects 129S2 mice against emphysema caused by CS. We suggest that the main mechanism of pathogenesis in this model involves the imbalance between proteases and antiproteases, particularly the association between MMP-9 and TIMP-1. General significance This study demonstrates the influence of 5-LO mediated oxidative stress, inflammation, and proteolytic markers in CS exposed mice., (© 2013.)

Statins are standard therapy for the treatment of lipid disorders, and the field of redox biology accepts that statins have antioxidant properties. Our aim in this report was to consider the pleiotropic effects of atorvastatin, pravastatin and simvastatin administered prior to endotoxin-induced acute lung injury. Male mice were divided into 5 groups and intraperitoneally injected with LPS (10 mg/kg), LPS plus atorvastatin (10 mg/kg/day; A + LPS group), LPS plus pravastatin (5 mg/kg/day; P + LPS group) or LPS plus simvastatin (20 mg/kg/day; S + LPS group). The control group received saline. All mice were sacrificed one day later. There were fewer leukocytes in the P + LPS and S + LPS groups than in the LPS group. MCP-1 cytokine levels were lower in the P + LPS group, while IL-6 levels were lower in the P + LPS and S + LPS groups. TNF-α was lower in all statin-treated groups. Levels of redox markers (superoxide dismutase and catalase) were lower in the A + LPS group (p < 0.01). The extent of lipid peroxidation (malondialdehyde and hydroperoxides) was reduced in all statin-treated groups (p < 0.05). Myeloperoxidase was lower in the P + LPS group (p < 0.01). Elastance levels were significantly greater in the LPS group compared to the statin groups. Our results suggest that atorvastatin and pravastatin but not simvastatin exhibit anti-inflammatory and antioxidant activity in endotoxin-induced acute lung injury., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: We evaluated patients underwent cardiac valve surgery in the presence of infective endocarditis in an attempt to identify independent predictors of 30-day mortality., Methods: We evaluated 837 consecutive patients underwent cardiac valve surgery from January 2003 to May 2010 in a tertiary hospital in São José do Rio Preto, São Paulo (SP), Brazil. The study group comprised patients who underwent intervention in the presence of infective endocarditis and was compared to the control group (without infective endocarditis), evaluating perioperative clinical outcomes and 30-day all cause mortality., Results: In our series, 64 patients (8%) underwent cardiac valve surgery in the presence of infective endocarditis, and 37.5% of them had surgical intervention in multiple valves. The study group had prolonged ICU length of stay (16%), greater need for dialysis (9%) and higher 30-day mortality (17%) compared to the control group (7%, P=0.020; 2%, P=0.002 and 9%, P=0.038; respectively). In a Cox regression analysis, age (P = 0.007), acute kidney injury (P = 0.004), dialysis (P = 0.026), redo surgery (P = 0.026), re-exploration for bleeding (P = 0.013), tracheal reintubation (P <0.001) and type I neurological injury (P <0.001) were identified as independent predictors for death. Although the manifestation of infective endocarditis influenced on mortality in univariate analysis, multivariate Cox regression analysis did not confirm such variable as an independent predictor of death., Conclusion: Age and perioperative complications stand out as predictors of hospital mortality in Brazilian population. Cardiac valve surgery in the presence of active infective endocarditis was not confirmed itself as an independent predictor of 30-day mortality.

The development of bleomycin-induced pulmonary fibrosis (BLEO-PF) has been associated with differences in genetic background and oxidative stress status. The authors' aim was to investigate the crosstalk between the redox profile, lung histology, and respiratory function in BLEO-PF in C57BL/6, DBA/2, and BALB/c mice. BLEO-PF was induced with a single intratracheal dose of bleomycin (0.1 U/mouse). Twenty-one days after bleomycin administration, the mortality rate was over 50% in C57BL/6 and 20% in DBA/2 mice, and BLEO-PF was not observed in BALB/c. There was an increase in lung static elastance (p < .001), viscoelastic/inhomogeneous pressure (p < .05), total pressure drop after flow interruption (p < .01), and ΔE (p < .05) in C57BL/6 mice. The septa volume increased in C57BL/6 (p < .05) and DBA/2 (p < .001). The levels of IFN-γ were reduced in C57BL/6 mice (p < .01). OH-proline levels were increased in C57BL/6 and DBA/2 mice (p < .05). SOD activity and expression were reduced in C57BL/6 and DBA/2 mice (p < .001 and p < .001, respectively), whereas catalase was reduced in all strains 21 days following bleomycin administration compared with the saline groups (C57BL/6: p < .05; DBA/2: p < .01; BALB/c: p < .01). GPx activity and GPx1/2 expression decreased in C57BL/6 (p < .001). The authors conclude that BLEO-PF resistance may also be related to the activity and expression of SOD in BALB/c mice.

Cyanobacterial blooms that generate microcystins (MCYSTs) are increasingly recognized as an important health problem in aquatic ecosystems. We have previously reported the impairment of pulmonary structure and function by microcystin-LR (MCYST-LR) exposure as well as the pulmonary improvement by intraperitoneally injected (i.p.) LASSBio 596. In the present study, we aimed to evaluate the usefulness of LASSBio 596 per os on the treatment of pulmonary and hepatic injuries induced by MCYST-LR. Swiss mice received an intraperitoneal injection of 40 μl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 μg/kg). After 6 h the animals received either saline (TOX and CTRL groups) or LASSBio 596 (50 mg/kg, LASS group) by gavage. Eight hours after the first instillation, lung impedance (static elastance, elastic component of viscoelasticity and resistive, viscoelastic and total pressures) was determined by the end-inflation occlusion method. Left lung and liver were prepared for histology. In lung and hepatic homogenates MCYST-LR, TNF-α, IL-1β and IL-6 were determined by ELISA. LASSBio 596 per os (LASS mice) kept all lung mechanical parameters, polymorphonuclear (PMN) cells, pro-inflammatory mediators, and alveolar collapse similar to control mice (CTRL), whereas in TOX these findings were higher than CTRL. Likewise, liver structural deterioration (hepatocytes inflammation, necrosis and steatosis) and inflammatory process (high levels of pro-inflammatory mediators) were less evident in the LASS than TOX group. LASS and CTRL did not differ in any parameters studied. In conclusion, orally administered LASSBio 596 prevented lung and hepatic inflammation and completely blocked pulmonary functional and morphological changes induced by MCYST-LR., (Copyright © 2011. Published by Elsevier Ltd.)

Objective: To compare mechanical ventilation weaning based on a protocol using the spontaneous breathing trial against mechanical ventilation weaning without a standardized protocol in heart patients., Methods: Prospective, open, randomized study. In 2006, 36 patients undergoing mechanical ventilation for over 24 hours were randomized into two groups: control group - eighteen patients whose mechanical ventilation weaning was performed according to the different procedures adopted by the multidisciplinary team; and experimental group - eighteen patients weaned according to previously established protocol., Results: Control group patients started the weaning process sooner than experimental group patients (74.7 ± 14.7 hours vs. 185.7 ± 22.9 hours, P=0.0004). However, after the experimental group patients were ready for weaning, the extubation was carried out more rapidly than in the control group (149.1 ± 3.6 min vs. 4179.1 ± 927.8 min, P < 0.0001) with significantly lower reintubation rates (16.7% vs. 66.7%, P = 0.005)., Conclusion: The use of a specific protocol based on the spontaneous breathing trial for mechanical ventilation weaning in heart patients had better outcomes than weaning carried out without a standardized protocol, with shorter weaning times and lower reintubation rates.

We investigated the possible protective effects of the Allopurinol (A), N-(2-mercaptopropionyl)-glycine (M) and N-acetylcysteine (N) against lung injury caused by long-term exposure to cigarette smoke (CS) in mouse. C57BL6 mice were exposed to 12 cigarettes a day for 60 days and concomitantly treated with either one of the antioxidant drugs diluted in saline (CS+A-50 mg/kg; CS+M-200 mg/kg/day; CS+N-200 mg/kg/day). Control groups were sham-smoked (AA). Long-term CS exposure results in extensive parenchyma destruction in CS group. Both CS+N and CS+M groups showed preserved alveolar structure and showed preserved lung function when compared to CS group. Macrophage and neutrophil counts were decreased in CS+M, and CS+N groups when compared to CS group (p<0.05). Antioxidant enzyme activities were reduced in all treated groups. CS+A showed the highest reduction in catalase activity (-25%, p<0.01). We conclude that M treatment reduced long-term CS-induced inflammatory lung parenchyma destruction and lung function, comparable to N treatment, however, antioxidant administration did not reverse CS-induced antioxidant enzyme activity reduction., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: heart rate variability (HRV) is a noninvasive diagnostic method used in the assessment of the autonomic modulation of the heart. The assessment of HRV using nonlinear dynamics methods in the preoperative period of surgical myocardial revascularization could be predictive of morbidity such as pulmonary infections in the postoperative period., Objective: to evaluate the behavior of HRV using nonlinear dynamics in the preoperative period of surgical myocardial revascularization and its relation to the occurrence of pulmonary infections in the in-hospital postoperative period., Methods: a total of 69 patients with coronary artery disease (mean age of 58.6 ± 10.4 years) and indication for elective surgical myocardial revascularization were studied. In order to quantify the nonlinear dynamics of HRV, the following procedures were performed: detrended fluctuation analysis (DFA); analysis of the short (α1) and long-term (α2) components of DFA; approximate entropy (ApEn); Lyapunov exponent (LE); and Hurst exponent (HE) of time series of RR intervals of the ECG, as captured by the Polar S810i instrument on the day before surgery., Results: at the cut-off levels set by the ROC curve, there was a significant difference between the groups with and without pulmonary infections in the postoperative period of myocardial revascularization for total DFA, approximate entropy and Lyapunov exponent with p = 0. 0309, p = 0.0307 and p = 0.0006, respectively., Conclusion: the nonlinear dynamics methods, at their respective cut-off levels, allowed for the identification of patients developing pulmonary infection in the postoperative period of surgical myocardial revascularization, thus suggesting that these methods may have a prognostic value for this group of patients.

Background: The acute kidney injury (AKI) is a complex disease for which there is no accepted standard definition nowadays. The Acute Kidney Injury Network (AKIN) represents an attempt to standardize the criteria for diagnosis and staging of acute renal dysfunction based on recently published RIFLE criteria, that means, (Risk, Injury, Failure, Loss, and End-stage kidney disease)., Objectives: To evaluate the incidence and associated mortality of AKI in patients submitted to on-pump coronary artery bypass graft surgery (on-pump CABG)., Methods: A total of 817 patients were divided into two groups: negative AKI (-), with 421 patients (51.5%), and positive AKI (+), with 396 patients (48.5%). Increase of 0.3 mg/dL in creatinine or of 50% in creatinine's basal value was considered as AKI., Results: The rate of patient's mortality with or without AKI within 30 days after cardiac surgery was 12.6% and 1.4%, respectively (p<0.0001). In a multivariate logistic regression model, AKI after on-pump CABG was an independent predictor of death within 30 days (OR=6.7; p=0.0002). This group of patients presented a longer period of permanency in intensive care unit (ICU) [median 2 days (2 to 3) versus 3 days (2 to 5); p=0.0001] and a bigger proportion of patients with prolonged permanence in intensive care (>14 days) (14 versus 2%; p=0.0001)., Conclusion: In the studied population, even a discrete alteration in renal function, based on AKIN criteria, was an independent predictor of death in 30 days after on-pump CABG.

We report a rare case of extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum. A 72-year-old Japanese man was admitted to our hospital presenting with a 3-mo history of epigastric pain, vomiting and weight loss. On computed tomography (CT) a wall thickening of the fourth part of the duodenum was observed. Multiple biopsies obtained from the lesion showed infiltration of plasma cells and lymphocytes, but they were not conclusive. The patient underwent resection of the lesion and, on histopathological examination, the lesion consisted of a dense and diffuse infiltrate of plasma cells and a few admixed lymphocytes with reactive follicles extending to the muscular propria. An extensive deposition of amyloid was also observed. Immunohistochemical stains revealed that a few plasmacytoid cells showed lambda light chain staining, though most were kappa light chain positive. These cells also were positive for CD138 and CD56 but negative for CD20 and CD79. The findings were consistent with extramedullary plasmocytoma associated with a massive deposit of amyloid in duodenum. A subsequent workup for multiple myeloma was completely negative. The patient showed no signs of local recurrence or dissemination of the disease after 12 mo follow-up. Because of the association of plasmocytoma and amyloidosis, the patient must be followed up because of the possible systemic involvement of the neoplasm and amyloidosis in future.

Background: Several infectious agents have been investigated since the association between atherosclerosis and infection was demonstrated; however, the results of these studies are contradictory., Objective: To test the association between serum titers of anti-Chlamydia and anti-Mycoplasma antibodies in different forms of acute coronary syndromes (ACS)., Methods: One hundred and twenty-six patients were divided in 4 groups: ACS with ST-segment elevation (32 patients), ACS without ST-segment elevation (30 patients), chronic coronary artery disease (30 patients) and blood donors without known coronary disease (34 patients--control group). In the two first groups, serum samples were collected at hospital admission (first 24 hours of hospitalization) and after a 6-month follow-up. In the other two groups, only a basal sample was collected. Anti-Chlamydia and anti-Mycoplasma antibodies were measured by indirect immunofluorescence in all samples., Results: Significant differences were observed between the basal sample and the one measured after a 6-month follow-up in patients with myocardial infarction with ST-segment elevation for Chlamydia (650+/-115.7 versus 307+/-47.5, p=0.0001) as well as Mycoplasma (36.5+/-5.0 versus 21.5+/-3.5, p=0.0004). The groups with ACS had higher anti-Chlamydia and anti-Mycoplasma serum antibody levels in the basal measurement, when compared to the patients with chronic coronary disease and the control group, but the differences were not statistically significant., Conclusion: The present study showed an association between the serum titers of anti-Chlamydia and anti-Mycoplasma antibodies in the acute phase of patients with unstable angina or myocardial infarction.

Background: The aim was to demonstrate that a reduction in the nonlinear behavior of heart rate variability (HRV) in the preoperative period in patients undergoing coronary artery bypass graft (CABG) triggers higher morbidity and mortality rates in the postoperative stay., Material/method: Seventy patients (59+/-10.3 years) were included. HRV was captured by a Polar Advanced S810 heart rate monitor and analyzed using the nonlinear variables detrended fluctuation analysis (DFA), autocorrelation (tau), Lyapunov exponent (LE), and the Poincaré plot (PP). Based on two scenarios, death vs. non-death (scenario 1) and events vs. their absence (scenario 2), the occurrence of neurological complications, infections, kidney failure, arrhythmia, and death were evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio (95% CI) were recorded., Results: In scenario 1, significant differences were found for DFA, alpha-2, LE, PP[SD1], and PP[SD2], with p-values of 0.0172, 0.0343, 0.0159, 0.0069, and 0.0287, respectively. In scenario 2, differences were found for alpha-1, alfa-2, tau, LE, PP[SD1], and PP[SD2], with p-values of 0.0066, 0.0426, 0.0188, 0.0108, 0.0005, and 0.0158, respectively. The best areas under ROC curve were seen in scenario 1, with values of 0.72 (tau), 0.77 (LE), and 0.78 (PP[SD1])., Conclusions: Analysis of HRV in the nonlinear domain in the preoperative period in patients undergoing elective CABG surgery may detect subgroups with a high risk for postoperative complications, at least with the assistance of some of the variables, and it can become a new prognostic tool for assessing patients scheduled to undergo other major surgeries.

Objective: The aim of this study is to establish a cut-off value for troponin I by correlating it to occurrence of postoperative myocardial infarction., Methods: 180 consecutive patients with coronary disease referred for surgery were included. The mean age of the patients were 60.6 (+/-9.3) years, with 119 (66.1%) males and 61 (33.9%) females. The patients were divided into two groups: group without myocardial infarction (A)--170 patients--and with myocardial infarction (B)--10 patients.The troponin I was collected from each patient at the beginning of anesthesia and on the second postoperative day by correlating it to presence or not of postoperative myocardial infarction. StatsDirect 1.6.0 for Windows was used for statistical analysis., Results: Preoperative troponin I was 1.0 (+/-6) ng/ml as mean. Univariate logistic regression showed correlation of troponin I of the second postoperative day with myocardial infarction (P=0.0005). ROC curve was used to define the cutoff value, and 6.1 ng/ml (sensitivity=90.0%, specificity=82.1%, OR=49.8 with CI=95% 6.1- 410.4, P<0.0001) were found., Conclusion: The chance of a patient with postoperative myocardial infarction to present troponin I equal to or higher than 6.1 ng/ml is 49.8-fold higher than the chance of a patient without infarction to present troponin I higher than this value.

Objective: It is common to obtain femoral venous approach in patients undergoing combined heart surgery or as an alternative to superior approach (internal jugular vein or subclavian vein). The aim of this study was to compare the measures of central venous pressure (CVP) at two different sites (superior versus femoral)., Methods: We prospectively and openly allocated 60 patients who underwent heart surgery between July from November 2006. Three measures were obtained from each patient at each site (admission, 6 and 12 hours after surgery) in two different inclinations of the headboard (zero and 30 degrees) totaling 720 measures., Results: Fifty five percent of patients who underwent coronary artery bypass grafting, 38% heart valve surgery and 7% other surgeries. The mean of CVP +/- standard deviation (SD) measured in superior approach was 13.0 +/- 5.5 mmHg (zero degree) and 13.3 +/- 6.1 mmHg (30 degrees) while the measures in inferior approach were 11.1 +/- 4.9 mmHg (zero degree) and 13.7 +/- 4.6 mmHg (30 degrees). The linear correlation (r) between the measures in both sites was 0.66 (zero degree) and 0.53 (30 degrees), both with p value<0.0001., Conclusion: The CVP can be measured with accuracy in the femoral venous approach in the immediate postoperative period of heart surgery with better linear correlation obtained with the measures made with the headboard positioned at zero degree.

Syphilis is an infectious disease occurring through a series of frequently overlapping stages. It can impair the cardiovascular and neurological system. In 30% of the non treated patients, syphilis develops its tertiary form. We report a case of a 46-year-old male patient admitted due to edema pulmonary and acute coronary syndrome with left bundle branch block, submitted to fibrinolytic therapy successfully. Coronary angiography showed a 90% ostial lesion of left main coronary artery and occlusion of the right coronary artery ostium. VDRL was titrated to 1/128. The patient was undergone to CABG and was discharged after treatment with crystalline penicillin.

In patients with acute myocardial infarction (AMI), the mechanisms behind the increased mortality related to glucose levels (GL) are poorly understood. The main purpose of this study is to analyze the relationship between baseline glucose and left ventricular enlargement (LVE). We analyzed 52 patients with a first ST-elevation AMI <24 h of evolution. Glucose levels were obtained upon admission (median time, 3 h after the beginning of chest pain). The median GL was 123.5 mg/dl, and patients above this limit were considered hyperglycemic (n=26). Left ventricular enlargement was analyzed comparing two radionuclide ventriculographies, the first obtained within 4 days post-AMI (median, 55 h) and the second 6 months later (median, 188.5 days), taking into account the difference in the obtained end-systolic volumes. Myocardial reperfusion was evaluated comparing ST resolution between a first ECG done immediately upon hospital arrival with a second ECG performed 2 h after treatment. By univariate analysis, LVE correlated significantly with baseline hyperglycemia (P<.001), failed reperfusion by ECG criteria (P<.001), and no use of ACE inhibitors or AT1 blockers (P=.046) and aspirin (P=.046). A history of previous diabetes did not correlate significantly with LVE at 6 months. In the adjusted model, basal hyperglycemia (P<.001) and failed reperfusion (P=.001) were the only variables independently correlated with LVE. In conclusion, baseline glucose is a powerful and independent predictor of LVE after AMI, which reinforces the importance of a tight glucose control during the initial phase of the disease.