Septic arthritis of the knee: clinical and laboratory comparison of groups with different etiologies

OBJECTIVES: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure

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

Septic arthritis of the knee: clinical and laboratory comparison of groups with different etiologies

OBJECTIVES: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure

Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy

International audienceAimsChagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis.Methods and ResultsWe conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5’ region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful.ConclusionsGenetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions

Correlation analysis for the rs640249 polymorphism in two different reference populations.

<p>Genotype data from the European reference population (CEU) and from the West Africa reference population (YRI) were downloaded from HapMap. A 2 Mb region surrounding the ACTC1 gene was analyzed in these two populations. The data were analyzed with Haploview Software. <b>A)</b> Correlations were assessed by calculating r² values. The rs640249 polymorphism was found to be correlated with three other polymorphisms in the CEU reference population (rs641563; rs639735; rs479623). <b>B</b>) In the West Africa reference population, the rs640249 polymorphism was correlated only with rs641563. </p

<i>In silico</i> analysis predicted differential binding patterns for rs640249 and rs641563 polymorphisms. Gel shift experiment has confirmed this differential binding for rs640249 polymorphism.

<p>The probability of these polymorphisms creating or altering DNA–protein interaction was determined by in silico analysis (<a href="http://www.gene-regulation.com/cgi-bin/pub/programs/match/bin/match.cgi" target="_blank"><u>http://www.gene-regulation.com/cgi-bin/pub/programs/match/bin/match.cgi</u></a>). An 75% threshold score (similarity matrix) was used. For each polymorphism (A, rs1800925; B, rs641563) putative bindings are described. The similarity matrix score is indicated in brackets. <b>C</b>: Electrophoretic mobility shift assays were performed in vitro as described in Materials and Methods. A differential binding pattern was detected for the rs640249A allele. </p

Relative quantification of alpha-cardiac actin 1 (ACTC1) by immunoblotting.

<div><p>Myocardial samples were obtained from the left ventricular free wall of the hearts of patients with severe CCC and end-stage heart failure, at the time of heart transplantation. Samples from five hearts from CCC patients (at least two positive results in three independent anti-<i>T</i>. <i>cruzi</i> serology tests, as indicated above), and from healthy hearts from organ donors not used for transplantation for technical reasons were used. Immunoblotting and protein quantification were done in duplicate. A. The immunoblot and the protein quantification result of the first experiment are presented here. The central line represents the median. Representative results from two experiments are shown here. A Mann-Whitney test was performed and differences were considered significant if <i>P</i><0.001.</p> <p><b>B</b>. Real-time quantitative PCR was carried out on the same samples. All the samples were tested in triplicate with GAPDH, the expression of which has been shown to vary little between human myocardial tissue samples. Data were normalized and the relative levels of each mRNA were calculated by the 2^-ΔCt method.</p></div

The rs640249A-rs641563A haplotype is associated with resistance to CCC.

<p>Based on the genotypes obtained, we performed a haplotype analysis of the rs7719175 and rs1800925 polymorphisms. Only three haplotypes were found in our study population: <b>A</b>) Distribution of the three main haplotype combinations in the CCC patients and ASY subjects: homozygous rs640249C-rs641563C (black bar); heterozygous rs640249C-rs641563C + rs640249A-rs641563A (gray bar) and homozygous rs640249A-rs641563A (white bar). <b>B</b>) Haplotype combinations between cases and controls, taking sex into account. <b>C</b>) Distribution of the three main haplotype combinations between patients with severe and moderate CCC, taking sex into account.</p

The same trends for association were detected in a small, independent replication cohort.

<p>The two main polymorphisms, rs640249 and rs641563, were genotyped in the independent replication cohort. This second cohort focused exclusively on male patients with Chagas disease, who have a higher risk of progression to CCC. This replication cohort included asymptomatic (<i>n</i> = 36) and CCC patients (<i>n</i> = 102). Of the 106 patients with CCC, 48 had severe ventricular dysfunction (left ventricular ejection fraction <40%). The rs640249 genotype distribution is illustrated in A. The results for the rs641563 polymorphism are in B. Haplotype analysis was then performed in C.</p