Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.

The residual efficacy of a cypermethrin pour-on formulation applied on goats on the mortality and blood intake of Triatoma infestans

Triatoma infestans is the main vector of Trypanosoma cruzi, the aetiological agent of Chagas disease in the Gran Chaco region of South America. As a frequent blood meal source for triatomine bugs, domestic goats play a key role in the eco-epidemiology of Chagas disease. The aim of this study was to evaluate the mortality and blood intake of T. infestans fed on goats that had been treated with different doses of pour-on insecticide. Third-instar nymphs were fed on goats that had been treated with 0 cc, 5 cc, 10 cc or 15 cc of a pour-on formulation of cypermethrin. The exposure of T. infestans to animals treated at different post-application intervals revealed a residual activity of the insecticide. The mortality rate in the treated groups was higher than in the control groups until 30 days post-insecticide application (p = 0.03), except in the group treated with 5 cc, in which no mortality was detected after seven days of insecticide application. Rainfall affected the triatomicide effect, reducing the time of residual activity. The cypermethrin pour-on treatment decreased the blood intake of T. infestans. Thirty days after the cypermethrin application, nymph mortality was 16% (± 13) with both doses (10 cc and 15 cc). The 15 cc dose did not result in higher insect mortality or increased persistence compared to the 10 cc dose.

Silver nanoparticle production by the fungus Fusarium oxysporum: nanoparticle characterisation and analysis of antifungal activity against pathogenic yeasts

The microbial synthesis of nanoparticles is a green chemistry approach that combines nanotechnology and microbial biotechnology. The aim of this study was to obtain silver nanoparticles (SNPs) using aqueous extract from the filamentous fungus Fusarium oxysporum as an alternative to chemical procedures and to evaluate its antifungal activity. SNPs production increased in a concentration-dependent way up to 1 mM silver nitrate until 30 days of reaction. Monodispersed and spherical SNPs were predominantly produced. After 60 days, it was possible to observe degenerated SNPs with in additional needle morphology. The SNPs showed a high antifungal activity against Candida and Cryptococcus , with minimum inhibitory concentration values ≤ 1.68 µg/mL for both genera. Morphological alterations of Cryptococcus neoformans treated with SNPs were observed such as disruption of the cell wall and cytoplasmic membrane and lost of the cytoplasm content. This work revealed that SNPs can be easily produced by F. oxysporum aqueous extracts and may be a feasible, low-cost, environmentally friendly method for generating stable and uniformly sized SNPs. Finally, we have demonstrated that these SNPs are active against pathogenic fungi, such as Candida and Cryptococcus .

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study.

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers' feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.

Cost-effectiveness of full-course oral levofloxacin in severe community-acquired pneumonia.

Oral levofloxacin is as efficient as sequential antibiotic treatment in community-acquired pneumonia (CAP). The current authors assessed whether oral levofloxacin treatment of patients with severe CAP, followed-up for 30 days, would save money. Over a 12-month period, 129 hospitalised patients with severe non-intensive care unit CAP were randomly assigned to receive either oral levofloxacin or sequential antibiotic treatment. Direct and indirect costs were compared over a 30-day period from several perspectives. CAP resolved in 71 out of 77 oral levofloxacin (92%) and in 34 out of 37 sequential antibiotic treatment patients (92%). Patients' characteristics, treatment duration, hospital length of stay and mortality were similar in both groups. Drug acquisition costs were 1.7-times smaller in oral levofloxacin patients, who were less often transferred to rehabilitation centres, but they used more physicians' visits during follow-up and their total costs were lower. As only a minority of patients was still active, inability to work and, hence, indirect costs were similar in both groups. In this study, oral levofloxacin for severe non-intensive care unit community-acquired pneumonia was equally effective as sequential antibiotic treatment, but did not lead to major costs savings except for drug acquisition costs. External factors linked with patients' characteristics and/or medical practice are likely to play a role and should be addressed.

Permanent pacemaker implantation after transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function.

BACKGROUND Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. METHODS AND RESULTS A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74-1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56-1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77-1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11-0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, -2.26; 95% confidence interval, -4.07 to -0.44; P=0.013; R(2)=0.121). CONCLUSIONS The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.

Do Swiss adolescents perceive the negative effects of their illegal substance use?

This study explores adolescents' perceptions of adverse consequences linked to their illegal psychoactive substance (IPS) use, as they are often thought to minimise them. From a Swiss nationally representative sample of 8740 adolescents aged 16 to 20 pursuing post-mandatory education, 2515 participants reported IPS use in the past month on a self-administered anonymous questionnaire. The percentages of participants reporting problems in four areas (individual, school, relationships and sexual) were assessed, depending on the type of IPS consumption over the last 30 days: occasional cannabis users: ≤2 times; regular cannabis users: ≥3 times; and poly-consumers: cannabis plus at least one other substance used. The percentages varied significantly across these three groups with 26.9% of occasional users, 53.8% of regular users, and 73.3% of poly-consumers reporting at least one problem. Compared to occasional cannabis users, poly-consumers were more likely to report problems in all four categories [relative risk ratio (RRR): 3.38 to 5.44], while regular cannabis users often reported only school and relationship problems [RRR: 2.43 to 3.23]. Thus, many adolescents seem to perceive the negative effects of their IPS use, with heavier consumption being associated with increasing problems. Physicians should feel confident questioning adolescents on the adverse consequences of their IPS consumption, as they are likely to be responsive on this issue.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

The SYNTAX score predicts early mortality risk in the elderly with acute coronary syndrome having primary PCI.

BACKGROUND: The SYNTAX score (SXscore), an angiographic score reflecting coronary lesion complexity, predicts clinical outcomes in patients with left main or multivessel disease, and in patients with ST-segment elevation myocardial infarction undergoing primary PCI. The clinical SXscore (CSS) integrates the SXscore and clinical variables (age, ejection fraction, serum creatinine) into a single score. We analyzed these scores in elderly patients with acute coronary syndrome (ACS) undergoing primary PCI. The purpose of this analysis was not to decide which patients should undergo PCI, but to predict clinical outcomes in this population. METHODS: The SXscore was determined in a consecutive series of 114 elderly patients (mean age, 79.6 ± 4.1 years) undergoing primary PCI for ACS. Outcomes were stratified according to SXscore tertiles: SXLOW ≤15 (n = 39), 15< SXMID <23 (n = 40), and SXHIGH ≥23 (n = 35). The primary endpoint was all-cause mortality at 30 days. Secondary endpoints were nonfatal major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and 1-year outcomes in patients discharged alive. RESULTS: Mortality at 30 days was higher in the SXHIGH group compared with the aggregate SXLOW+MID group (37.1% vs 5.1%; P<.0001), and in the CSSHIGH group compared with the aggregate CSSLOW+MID group (25.5% vs 1.4%; P=.0001). MACCE rates at 30 days were similar among SXscore tertiles. The CSS predicted 1-year MACCE rates (12.1% for CSSHIGH vs 3.1% for CSSLOW+MID; P=.03). CONCLUSIONS: The SXscore predicts 30-day mortality in elderly patients with ACS undergoing primary PCI. In patients discharged alive, the CSS predicts risk of MACCE at 1 year.

Late removal of retrievable caval filters.

The advent of retrievable caval filters was a game changer in the sense, that the previously irreversible act of implanting a medical device into the main venous blood stream of the body requiring careful evaluation of the pros and cons prior to execution suddenly became a "reversible" procedure where potential hazards in the late future of the patient lost most of their weight at the time of decision making. This review was designed to assess the rate of success with late retrieval of so called retrievable caval filters in order to get some indication about reasonable implant duration with respect to relatively "easy" implant removal with conventional means, i.e., catheters, hooks and lassos. A PubMed search (www.pubmed.gov) was performed with the search term "cava filter retrieval after 30 days clinical", and 20 reports between 1994 and 2013 dealing with late retrieval of caval filters were identified, covering approximately 7,000 devices with 600 removed filters. The maximal duration of implant reported is 2,599 days and the maximal implant duration of removed filters is also 2,599 days. The maximal duration reported with standard retrieval techniques, i.e., catheter, hook and/or lasso, is 475 days, whereas for the retrievals after this period more sophisticated techniques including lasers, etc. were required. The maximal implant duration for series with 100% retrieval accounts for 84 days, which is equivalent to 12 weeks or almost 3 months. We conclude that retrievable caval filters often become permanent despite the initial decision of temporary use. However, such "forgotten" retrievable devices can still be removed with a great chance of success up to three months after implantation. Conventional percutaneous removal techniques may be sufficient up to sixteen months after implantation whereas more sophisticated catheter techniques have been shown to be successful up to 83 months or more than seven years of implant duration. Tilting, migrating, or misplaced devices should be removed early on, and replaced if indicated with a device which is both, efficient and retrievable.

Peroxisomal and microsomal lipid pathways associated with resistance to hepatic steatosis and reduced pro-inflammatory state.

Accumulation of fat in the liver increases the risk to develop fibrosis and cirrhosis and is associated with development of the metabolic syndrome. Here, to identify genes or gene pathways that may underlie the genetic susceptibility to fat accumulation in liver, we studied A/J and C57Bl/6 mice that are resistant and sensitive to diet-induced hepatosteatosis and obesity, respectively. We performed comparative transcriptomic and lipidomic analysis of the livers of both strains of mice fed a high fat diet for 2, 10, and 30 days. We found that resistance to steatosis in A/J mice was associated with the following: (i) a coordinated up-regulation of 10 genes controlling peroxisome biogenesis and β-oxidation; (ii) an increased expression of the elongase Elovl5 and desaturases Fads1 and Fads2. In agreement with these observations, peroxisomal β-oxidation was increased in livers of A/J mice, and lipidomic analysis showed increased concentrations of long chain fatty acid-containing triglycerides, arachidonic acid-containing lysophosphatidylcholine, and 2-arachidonylglycerol, a cannabinoid receptor agonist. We found that the anti-inflammatory CB2 receptor was the main hepatic cannabinoid receptor, which was highly expressed in Kupffer cells. We further found that A/J mice had a lower pro-inflammatory state as determined by lower plasma levels and IL-1β and granulocyte-CSF and reduced hepatic expression of their mRNAs, which were found only in Kupffer cells. This suggests that increased 2-arachidonylglycerol production may limit Kupffer cell activity. Collectively, our data suggest that genetic variations in the expression of peroxisomal β-oxidation genes and of genes controlling the production of an anti-inflammatory lipid may underlie the differential susceptibility to diet-induced hepatic steatosis and pro-inflammatory state.

Validation of the potentially avoidable hospital readmission rate as a routine indicator of the quality of hospital care

BACKGROUND: The hospital readmission rate has been proposed as an important outcome indicator computable from routine statistics. However, most commonly used measures raise conceptual issues. OBJECTIVES: We sought to evaluate the usefulness of the computerized algorithm for identifying avoidable readmissions on the basis of minimum bias, criterion validity, and measurement precision. RESEARCH DESIGN AND SUBJECTS: A total of 131,809 hospitalizations of patients discharged alive from 49 hospitals were used to compare the predictive performance of risk adjustment methods. A subset of a random sample of 570 medical records of discharge/readmission pairs in 12 hospitals were reviewed to estimate the predictive value of the screening of potentially avoidable readmissions. MEASURES: Potentially avoidable readmissions, defined as readmissions related to a condition of the previous hospitalization and not expected as part of a program of care and occurring within 30 days after the previous discharge, were identified by a computerized algorithm. Unavoidable readmissions were considered as censored events. RESULTS: A total of 5.2% of hospitalizations were followed by a potentially avoidable readmission, 17% of them in a different hospital. The predictive value of the screen was 78%; 27% of screened readmissions were judged clearly avoidable. The correlation between the hospital rate of clearly avoidable readmission and all readmissions rate, potentially avoidable readmissions rate or the ratio of observed to expected readmissions were respectively 0.42, 0.56 and 0.66. Adjustment models using clinical information performed better. CONCLUSION: Adjusted rates of potentially avoidable readmissions are scientifically sound enough to warrant their inclusion in hospital quality surveillance.

Clinical predictors of prophylaxis use prior to the onset of acute venous thromboembolism in hospitalized patients SWIss Venous ThromboEmbolism Registry (SWIVTER).

BACKGROUND: We investigated clinical predictors of appropriate prophylaxis prior to the onset of venous thromboembolism (VTE). METHODS: In 14 Swiss hospitals, 567 consecutive patients (306 medical, 261 surgical) with acute VTE and hospitalization < 30 days prior to the VTE event were enrolled. RESULTS: Prophylaxis was used in 329 (58%) patients within 30 days prior to the VTE event. Among the medical patients, 146 (48%) received prophylaxis, and among the surgical patients, 183 (70%) received prophylaxis (P < 0.001). The indication for prophylaxis was present in 262 (86%) medical patients and in 217 (83%) surgical patients. Among the patients with an indication for prophylaxis, 135 (52%) of the medical patients and 165 (76%) of the surgical patients received prophylaxis (P < 0.001). Admission to the intensive care unit [odds ratio (OR) 3.28, 95% confidence interval (CI) 1.94-5.57], recent surgery (OR 2.28, 95% CI 1.51-3.44), bed rest > 3 days (OR 2.12, 95% CI 1.45-3.09), obesity (OR 2.01, 95% CI 1.03-3.90), prior deep vein thrombosis (OR 1.71, 95% CI 1.31-2.24) and prior pulmonary embolism (OR 1.54, 95% CI 1.05-2.26) were independent predictors of prophylaxis. In contrast, cancer (OR 1.06, 95% CI 0.89-1.25), age (OR 0.99, 95% CI 0.98-1.01), acute heart failure (OR 1.13, 95% CI 0.79-1.63) and acute respiratory failure (OR 1.19, 95% CI 0.89-1.59) were not predictive of prophylaxis. CONCLUSIONS: Although an indication for prophylaxis was present in most patients who suffered acute VTE, almost half did not receive any form of prophylaxis. Future efforts should focus on the improvement of prophylaxis for hospitalized patients, particularly in patients with cancer, acute heart or respiratory failure, and in the elderly.

Correlation between the infestation level of Sitophilus zeamais Motschulsky, 1855 (Coleoptera, Curculionidae) and the quality factors of stored corn, Zea mays L. (Poaceae)

This experiment was carried out in order to evaluate the effect of Sitophilus zeamais on physical, physiological and sanitary quality of stored corn. Samples of 500 g of the hybrid OC-705, in three replicates, were conditioned in glasses covered with a screened lid, and kept in chamber at 25±2ºC, 70±5% RH and 12 h of photophase, for 150 days. The infestation levels were 0, 5, 15 and 50 adults/replicate, for the storage periods of 30, 60, 90, 120 and 150 days. The moisture content, classification, weight loss, germination and internal infestation were evaluated monthly. Significant inverse correlations were verified between the number of insects and both the germination and the weight loss; also between the internal infestation and the germination and the standard type. The presence of S. zeamais showed a positive correlation with the weight loss, what means that the internal and external infestations contribute to the reduction of physiological and physical quality of corn seeds. The mean dry matter loss was 0,36%/day, corresponding to a consumption of 0,0001%/insect/month. As the result of those damages, the product suffered reduction of the commercial grade in 30 days, with significant loss in all quality factors.