Benefit of onsite reperfusion therapy or transfer to primary PCI in STEMI patients admitted to hospitals without catheterization laboratory. Results of the MITRA PLUS Registry

The optimal reperfusion strategy in elderly patients with ST-segment elevation myocardial infarction (STEMI) remains a topic of debate. Therefore, we investigated in the MITRA PLUS registry clinical outcome variables in 5455 patients aged>70 years and STEMI on admission at hospitals without the facilities of coronary catheterization and PCI. Outcome was compared after thrombolysis, transfer to PCI and after no reperfusion therapy. Data of this registry in STEMI patients older than 70 years, who were transferred to another hospital for PCI, showed a strong trend for lower in-hospital mortality rates compared with a strategy with sole fibrinolysis and significantly lower in hospital death rates compared with a conservative treatment without (medical or mechanical) reperfusion. Additionally, the PCI group also had a reduced incidence of the combined events: death, myocardial reinfarction, stroke in comparison with both other infarct groups. Data of the presented MITRA PLUS registry in STEMI patients older than 70 years support data of several other studies, that patients with STEMI benefit from a transfer to primary PCI even after a time delay of symptom onset to hospital admission of more than 2 h compared with a strategy using sole fibrinolytic therapy.     

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

AIM:To study the inflammatory bowel disease-5 locus（IBD5）and interleukin-23 receptor（IL23R）gene variants in UC patients and test for gene-gene interaction.METHODS:The study population（n=625）was comprised of 320 unrelated ulcerative colitis（UC）patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus（IGR2198a₁ rs11739135,IGR2096a₁ rs12521868,IGR2230a₁ rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367）and two of the IL23R gene（rs1004819,rs2201841）were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency（P=0.032）in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers（P=0.004,OR=1.606;95%CI:1.160-2.223）and the SNP rs2201841 for homozygotes（P=0.030,OR=1.983;95%CI:1.069-3.678）.Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a₁ C or IGR2096a₁ T allele,the highest OR was calculated in the presence of SLC22A4T allele（P=0.005,OR=2.015;95%CI:1.230-3.300）.There was no association with UC for any combinations of rs1004819 and IGR2230a₁.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.     

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research.     

Phylogenetic analysis of rabbit haemorrhagic disease and European brown hare syndrome viruses by comparison of sequences from the capsid protein gene

Summary.  A 398 bp fragment of the capsid protein (VP60) gene of 39 clinical samples of rabbit haemorrhagic disease virus (RHDV) and 17 of European brown hare syndrome virus (EBHSV), collected between 1981 and 1995 from 17 countries, was amplified by PCR and directly sequenced. The alignment of the nucleotide sequences and the subsequently constructed phylogenetic tree clearly separated RHDV from EBHSV as phylogenetic entities. The nucleotide homology rates between the RHDV and EBHSV groups ranged between 52.6% and 60.0%. The homology rates within the groups were much higher, 89.4% to 100% for the RHDV samples, and 89.4% to 100% for the EBHSV specimens. No intermediate viruses were found. Despite the high homology, three main branches could be identified in the phylogenetic tree of the RHDV samples, corresponding to the epizootiological data, while the EBHSV dendrogram did not show such well defined branches. The present results support the classification of RHDV and EBHSV as two distinct members of the Caliciviridae family. Nevertheless, a comparison with previously determined sequences of other caliciviruses shows that RHDV and EBHSV are more closely related to each other than to any other calicivirus. Received July 30, 1996 Accepted October 25, 1996     

Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome

Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia and HELLP syndrome.