Treatment With Methotrexate Inhibits Atherogenesis in Cholesterol-Fed Rabbits

A decrease in the number of cardiovascular events in patients with rheumatoid arthritis or psoriasis treated with methotrexate (MTX) has been observed in the literature. The aim of this study was to test whether MTX could promote anti-inflammatory effects and reduce the atherosclerotic lesions in rabbits with atherosclerosis induced by cholesterol feeding. Twenty male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 of cholesterol feeding, 10 animals were treated with 4 weekly intravenous injections of MTX (4 mg/kg) and 10 with 4 weekly saline solution injections for 30 days. MTX reduced the size of the lesion areas of cholesterol-fed animals by 75% and intima-media ratio 2- fold. The drug inhibited macrophage migration into the intima by 50% and the presence of apoptotic cells by 84% but did not inhibit the intimal proliferation of smooth muscle cells. MTX treatment also diminished the positive staining area of metalloproteinase 9 in the intima, which is probably beneficial. In the tumor necrosis factor-alpha-treated human umbilical vein endothelial cell line, incubation with MTX led to downregulation of 5 pro-inflammatory genes, TNF-alpha, VAP-1, IL-1 beta, CXCL2, and TLR2, and upregulation of the antiinflammatory TGF-beta 1 gene, thus showing endothelium-protective properties. In conclusion, MTX showed direct in vivo anti-atherosclerotic action and may have potential in the treatment of this disorder.

Effect of heat and moisture exchangers on the prevention of ventilator-associated pneumonia in critically ill patients

Ventilator-associated pneumonia (VAP) remains one of the major causes of infection in the intensive care unit (ICU) and is associated with the length of hospital stay, duration of mechanical ventilation, and use of broad-spectrum antibiotics. We compared the frequency of VAP 10 months prior to (pre-intervention group) and 13 months after (post-intervention group) initiation of the use of a heat and moisture exchanger (HME) filter. This is a study with prospective before-and-after design performed in the ICU in a tertiary university hospital. Three hundred and fourteen patients were admitted to the ICU under mechanical ventilation, 168 of whom were included in group HH (heated humidifier) and 146 in group HME. The frequency of VAP per 1000 ventilator-days was similar for both the HH and HME groups (18.7 vs 17.4, respectively; P = 0.97). Duration of mechanical ventilation (11 vs 12 days, respectively; P = 0.48) and length of ICU stay (11 vs 12 days, respectively; P = 0.39) did not differ between the HH and HME groups. The chance of developing VAP was higher in patients with a longer ICU stay and longer duration of mechanical ventilation. This finding was similar when adjusted for the use of HME. The use of HME in intensive care did not reduce the incidence of VAP, the duration of mechanical ventilation, or the length of stay in the ICU in the study population.

Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing ventilator-associated pneumonia after cardiac surgery: an observational study

Abstract Background The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery. Methods This was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1. Results Thirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29). Conclusion Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.