Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Pre-eclampsia: relationship between coagulation, fibrinolysis and inflammation

Pre-eclampsia (PE) is a multi-system disorder of human pregnancy, characterised by hypertension and proteinuria. Although the pathogenesis of PE is not fully understood, predisposition to endothelial dysfunction is thought to play a crucial part. Despite intensive research there is no reliable test for screening purposes or to inform decision making towards effective treatment for PE. Understanding the link between PE, abnormal haemostatic activation and inflammation may help to elucidate some of the patho-physiology of the disease; primary preventative measures and targeted therapies at an early stage of the disease could then be considered. In the present paper we discuss potential causal links between PE, haemostasis and inflammation. The potential implications of such interaction on the pathogenesis of PE are also addressed

Evaluation of lipid profile, high-sensitivity C-reactive protein and D-dimer in users of oral contraceptives of different types

<div><p>ABSTRACT Introduction: The use of oral contraceptives increases women's risk of developing cardiovascular and thromboembolic diseases, due to alterations in hemostatic and lipid profile. Objectives: Analyze the association between the use of different types of oral contraceptives with lipid profile and levels of serum high-sensitivity C-reactive protein (hsCRP) and plasma D-dimer. Methods: One hundred fifty-four participants were divided into the following groups: control nonusers (n = 41), medium-dose users (n= 32), third-generation low-dose users (n = 40), and fourth-generation low-dose users (n = 41). Triglycerides and total cholesterol serum levels were determined by colorimetric enzymatic method; high-density lipoprotein (HDL) cholesterol levels, by precipitation method; low-density lipoprotein (LDL) cholesterol levels, by Friedewald equation; hsCRP levels, by immunoturbidimetric method; and D-dimer levels, by fluorescence immunoassay. Results: Oral contraceptive users had higher serum levels of triglycerides, total cholesterol, HDL cholesterol (HDL-C), HDL/LDL index and hsCRP compared to controls. Medium-dose users had higher D-dimer plasma levels than controls and higher triglycerides serum levels than low-dose users. Triglycerides, hsCRP and D-dimer were positively correlated to each other. Conclusion: The use of combined oral contraceptives was associated with an unfavorable lipid profile and a chronic subclinical inflammation, with atherogenic potential. Furthermore, medium-dose contraceptives induced a higher thrombogenic potential, since they were associated with increased D-dimer levels in comparison to low-dose ones.</p></div

Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia.

BACKGROUND: Despite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-β1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE. METHODS: Plasma levels of sEng, TGF-β1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [early (n = 19) and late (n = 24)]. RESULTS: Pregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-β1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-β1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-β1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity. CONCLUSIONS: These results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

A retrospective study of the epidemiological and clinic-pathological aspects of cattle and buffaloes with degenerative joint disease (DJD) was conducted in the state of Pará, Brazil. From 1999 to 2014, eleven cattle and 24 buffaloes were evaluated. All the treated animals with suspected DJD underwent a clinical examination of the musculoskeletal system. In seven cattle and eight buffaloes with clinical signs of the disease postmortem examination was performed. The common clinical signs observed in both species were chronic lameness, stiff gait, postural changes, audible crackles in the affected limb, prolonged recumbency, difficulty in getting up and progressive weight loss. The lesions observed at necropsy were: irregular articular surfaces, erosion of the articular cartilage and the underlying bone tissue, and proliferation of the periarticular bone tissue with formation of osteophytes. The most affected joints in cattle and buffaloes wereof the hind limb. In buffaloes, the main predisposing factor to the onset of DJD was phosphorus deficiency. In cattle, defects of the anatomical conformation of the hind limbs, chronic trauma due to the activities performed, such as semen collection, and advanced age possibly contributed to the emergence of the disease

Significant correlations among sEng, TGF-β1, sTNF-R1 and sTNF-R2 levels and laboratorial parameters in preeclamptic women.

<p>The lines represent linear regression and the closed circles represent preeclamptic (PE) women. Maternal plasma sEng concentrations (nanograms/milliliter) are correlated positively with creatinine (mg/dL) (A) and aspartate aminotransferase (U/L) (B) levels in PE women. There is a positive correlation between sTNF-R1 (picograms/milliliter) and lactate dehydrogenase (U/L) levels in PE women (C).</p

Plasma levels of sEng, TGF-β1, sTNF-R1 and sTNF-R2 in non-pregnant, normotensive pregnant and preeclamptic women.

<p>NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women). Horizontal bars represent median values for sEng, TGF-β1, sTNF-R1 and mean value for sTNF-R2. *<i>p</i><0.05, **<i>p</i><0.01 and ***<i>p</i><0.001. Plasma levels of sEng (nanograms/milliliter) (A), sTNF-R1 (picograms/milliliter) (C) and sTNF-R2 (picograms/milliliter) (D) were higher in normotensive pregnant women than in non-pregnant women. When compared with normotensive pregnant women, sEng (A) and sTNF-R1 (C) were elevated in women with PE. TGF-β1 (picograms/milliliter) levels showed no significant differences among the studied groups (B).</p

Plasma levels of sEng, TGF-β1, sTNF-R1 and sTNF-R2 according to the onset-time and severity of preeclampsia.

<p>Horizontal bars represent median values for sEng and sTNF-R1 and mean values for TGF-β1 and sTNF-R2. **<i>p</i><0.01. Women with late preeclampsia (PE) had higher levels of sTNF-R1 (picograms/milliliter) (C) and sTNF-R2 (picograms/milliliter) (D) than women with early PE. No significant differences were found in sEng (nanograms/milliliter) (A) and TGF-β1 (picograms/milliliter) (B) comparing early and late PE. sEng levels were higher in severe PE than in mild PE (E) and no difference was found for TGF-β1 (F), sTNF-R1 (G) and sTNF-R2 levels (H).</p

Demographic and clinical characteristics of the three studied groups.

<p>Abbreviations: BMI (body mass index: before pregnancy for normotensive pregnant women and preeclamptic women), GWG (gestational weight gain), GA (gestational age), SBP (systolic blood pressure), DPB (diastolic blood pressure), NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women), N/A (not applicable). Note: n =  total subjects.</p>a<p>Data are presented as median (25^th–75^th percentiles); ^bData are presented as mean ± standard deviation; ^cData are presented as number (percentage). ¹Kruskal-Wallis with <i>Bonferroni</i> correction; ²ANOVA with <i>post-hoc</i> LSD;³Pearson chi-square (χ²) test. *<i>p</i><0.05, **<i>p</i><0.017.</p