Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

BackgroundThere is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.Methods and findingsWe conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.Trial registrationClinicalTrials.gov - {"type":"clinical-trial","attrs":{"text":"NCT03507309","term_id":"NCT03507309"}}NCT03507309

Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes.     

A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages

The aims of the work were (1) to develop statistical tests to identify whether substitution takes place under a covariotide model in sequences used for phylogenetic inference and (2) to determine the influence of covariotide substitution on phylogenetic trees inferred for photosynthetic and other organisms. (Covariotide and covarion models are ones in which sites that are variable in some parts of the underlying tree are invariable in others and vice versa.) Two tests were developed. The first was a contingency test, and the second was an inequality test comparing the expected number of variable sites in two groups with the observed number. Application of these tests to 16S rDNA and tufA sequences from a range of nonphotosynthetic prokaryotes and oxygenic photosynthetic prokaryotes and eukaryotes suggests the occurrence of a covariotide mechanism. The degree of support for partitioning of taxa in reconstructed trees involving these organisms was determined in the presence or absence of sites showing particular substitution patterns. This analysis showed that the support for splits between (1) photosynthetic eukaryotes and prokaryotes and (2) photosynthetic and nonphotosynthetic organisms could be accounted for by patterns arising from covariotide substitution. We show that the additional problem of compositional bias in sequence data needs to be considered in the context of patterns of covariotide/covarion substitution. We argue that while covariotide or covarion substitution may give rise to phylogenetically informative patterns in sequence data, this may not always be so.      

A component of the side tail fiber of Escherichia coli bacteriophage lambda can functionally replace the receptor-recognizing part of a long tail fiber protein of the unrelated bacteriophage T4.

The distal part of the long tail fiber of Escherichia coli bacteriophage T4 consists of a dimer of protein 37. Dimerization requires the catalytic action of protein 38, which is encoded by T4 and is not present in the virion. It had previously been shown that gene tfa of the otherwise entirely unrelated phage lambda can functionally replace gene 38. Open reading frame (ORF) 314, which encodes a protein that exhibits homology to a COOH-terminal area of protein 37, is located immediately upstream of tfa. The gene was cloned and expressed in E. coli. An antiserum against the corresponding polypeptide showed that it was present in phage lambda. The serum also reacted with the long tail fibers of phage T4 near their free ends. An area of the gene encoding a COOH-terminal region of ORF 314 was recombined, together with tfa, into the genome of T4, thus replacing gene 38 and a part of gene 37 that codes for a COOH-terminal part of protein 37. Such T4-lambda hybrids, unlike T4, required the presence of outer membrane protein OmpC for infection of E. coli B. An ompC missense mutant of E. coli K-12, which was still sensitive to T4, was resistant to these hybrids. We conclude that the ORF 314 protein represents a subunit of the side tail fibers of phage lambda which probably recognize the OmpC protein. ORF 314 was designated stf (side tail fiber). The results also offer an explanation for the very unusual fact that, despite identical genomic organizations, T4 and T2 produce totally different proteins 38. An ancestor of T4 from the T2 lineage may have picked up tfa and stf from a lambdoid phase, thus possibly demonstrating horizontal gene transfer between unrelated phage species.     

Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis

Data from population- and clinic-based epidemiologic studies of rheumatoid arthritis patients suggest that individuals with rheumatoid arthritis are at risk for developing clinically evident congestive heart failure. Many established risk factors for congestive heart failure are over-represented in rheumatoid arthritis and likely account for some of the increased risk observed. In particular, data from animal models of cytokine-induced congestive heart failure have implicated the same inflammatory cytokines produced in abundance by rheumatoid synovium as the driving force behind maladaptive processes in the myocardium leading to congestive heart failure. At present, however, the direct effects of inflammatory cytokines (and rheumatoid arthritis therapies) on the myocardia of rheumatoid arthritis patients are incompletely understood.     

Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells

Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was beta-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells.     

Importance of lateral row perforator vessels in deep inferior epigastric perforator flap harvesting

Free flaps based on perforator vessels, and in particular the deep inferior epigastric perforator (DIEP) flap, are currently being applied in abdominal reconstruction. However, one of the main disadvantages is the operative complexity. Through anatomical study and clinical experience with the DIEP flap in breast reconstruction, the intramuscular path of the perforator vessels was comparatively studied, to establish the main anatomical parameters that favor procedure planning. Thirty DIEP flaps from 15 fresh cadavers were used. The number, location, and intramuscular course of the perforator vessels were determined. In addition, an initial clinical study was performed in 31 patients using 35 DIEP flaps in breast reconstruction. The number, location, and the intramuscular course of the perforators were assessed. In the cadaver study, 191 perforator vessels were detected (6.4 vessels per flap). Thirty-four percent were located in the lateral row, and the rectilinear course was observed in 79.2 percent of these vessels. In the medial row, only 18.2 percent of the perforator vessels presented this configuration (p = 0.001). Thirty-one patients underwent DIEP flap breast reconstruction, with 26 immediate and four bilateral reconstructions. In 22 of 35 flaps (62.9 percent), two perforators were used. In 25 flaps (71.4 percent), the lateral row perforators with a rectilinear course were observed. Mean operative time was 7 hours and 37 minutes. Two total flap losses and two partial necroses were observed. The majority of the lateral row perforators presented a rectilinear intramuscular course, which was shorter than that of the medial row perforators. This anatomical characteristic favors dissection with reduced operative time and vascular lesion morbidity, resulting in an important anatomical parameter for DIEP flap harvesting.     

Identification and strain differentiation of 'Bacteroides fragilis group' species and Prevotella bivia by PCR fingerprinting

Using single consensus primers of genomic nucleotide sequences, PCR-generated fingerprints were used for identification and differentiation of the Bacteroides fragilis group (B. fragilis, B. thetaiotaomicron, B. ovatus, B. distasonis, B. vulgatus) and Prevotella bivia (B. bivius) by comparing the DNA profiles with those of reference strains from the American Type Culture Collection and German Culture Collection. When primed by a single primer phage M13 core sequence, intra-species specific differences and species-specific bands were detected. Using primers derived from the evolutionarily conserved tRNA gene sequence, species-specific patterns were produced. A computer program, GelManager, was used to analyze the profiles and generate dendrograms. The correlation coefficients determined from the DNA fingerprint profiles of the clinical isolates (using the M13 core primer) fell within a narrow range, reflecting a high level of homology within the species. Based on the dendrograms, strains of one species were clearly differentiated from strains of other species. For comparison, SDS-PAGE analysis of whole cell extracts was also performed to obtain protein band patterns of various strains. Because of the simplicity of the PCR fingerprinting method and the ease of performance of computerized evaluation of data, this technique is a useful method for both species and strain differentiation, as well as for characterization of Bacteroides species and Prevotella bivia.     

Length‐weight and length‐length relationships of three tidepool fish species in the Amazon Coastal Zone of Brazil

Length‐weight relationships (LWR) and length‐length relationships (LLR) were analyzed for three species inhabiting tidepools in the Amazon Coastal Zone, two of them non‐native. Tidepools were sampled in five beaches along the Amazon Coastal Zone in 2011, and samplings were carried out using hand nets. The coefficients of allometry and proportionality were within the ranges estimated for fishes. All three species exhibited coefficients of allometry (b) higher than 3 in the LWR.