Decrease of CA 19–9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer

Chemotherapy with gemcitabine has been shown to be an effective regimen in advanced or metastatic pancreatic cancer with improvement of both quality of life and survival time. The response of the tumour marker CA 19–9 to chemotherapy with gemcitabine was studied in order to find out whether it is related to survival time of patients. Forty-three consecutive patients (median age 61 years, range 39–76 years; 20 males, 23 females) suffering from histologically proven locally advanced or metastatic pancreatic adenocarcinoma and a baseline Karnofsky-index ≥ 60 were treated with gemcitabine in a dose of 1000 mg m−2weekly × 7 followed by 1 week of rest during the first cycle and thereafter 1000 mg m−2weekly × 3 followed by 1 week of rest until progression. In 36 of 43 patients serial measurements of CA 19–9 could be performed. Patients with a decrease of > 20% of the baseline CA 19–9 level after 8 weeks of treatment (n = 25) had a significantly better median survival than patients with a rise or a decrease ≤ 20% (n = 11) (268 vs 110 days;P< 0.001). The response of CA 19–9 was the strongest independent predictor of survival (P< 0.001) in the multivariate analysis. In conclusion, a decrease of CA 19–9 > 20% during the first weeks of chemotherapy with gemcitabine is associated with a better survival of patients with locally advanced or metastatic pancreatic cancer. Serial measurements of CA 19–9 are useful to decide whether further chemotherapy after the first weeks of treatment is indicated. © 2000 Cancer Research Campaig

Transcriptomic characterization of the larval stage in gilthead seabream (Sparus aurata) by 454 pyrosequencing

Gilthead seabream (Sparus aurata) is a teleost belonging to the family Sparidae with a high economical relevance in the Mediterranean countries. Although genomic tools have been developed in this species in order to investigate its physiology at the molecular level and consequently its culture, genomic information on post-embryonic development is still scarce. In this study, we have investigated the transcriptome of a marine teleost during the larval stage (from hatching to 60 days after hatching) by the use of 454 pyrosequencing technology. We obtained a total of 68,289 assembled contigs, representing putative transcripts, belonging to 54,606 different clusters. Comparison against all S. aurata expressed sequenced tags (ESTs) from the NCBI database revealed that up to 34,722 contigs, belonging to about 61% of gene clusters, are sequences previously not described. Contigs were annotated through an iterative Blast pipeline by comparison against databases such as NCBI RefSeq from Danio rerio, SwissProt or NCBI teleost ESTs. Our results indicate that we have enriched the number of annotated sequences for this species by more than 50% compared with previously existing databases for the gilthead seabream. Gene Ontology analysis of these novel sequences revealed that there is a statistically significant number of transcripts with key roles in larval development, differentiation, morphology, and growth. Finally, all information has been made available online through user-friendly interfaces such as GBrowse and a Blast server with a graphical frontend

Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Molecular characterization of Miraflores peach variety and relatives using SSRs

The definitive version is published in: http://www.sciencedirect.com/science/journal/03044238Some traditional peach varieties, originated from the region of Aragón (Spain), were analysed by SSRs (Simple Sequence Repeats). The aim of this research was to characterize 19 clones related to ‘Miraflores’ variety, with unknown pedigrees, to assess their genetic diversity and to elucidate their possible relationships with 10 traditional peach varieties. Twenty SSR primer pairs with high levels of polymorphism, which have been previously developed for peach, were used in this study. A total of 46 alleles were obtained for all the microsatellites studied, ranging from one to six alleles per locus, with a mean value of 2.3 alleles per locus. Fourteen SSRs were polymorphic in the set of varieties studied and permitted to distinguish 16 different genotypes out of the 30 initially studied, although fourteen ‘Miraflores’ clones showed identical gel profiles. The genetic distance matrix was used to construct Neighbor joining cluster and to perform principal coordinate analysis which allowed the arrangement of all the genotypes according to their genetic relationships. The genetic relationships among these traditional peach varieties, and in particular among ‘Miraflores’ clones are discussed. The obtained results confirm that microsatellite markers are very useful for these purposes.We are thankful to T.N. Zhebentyayeva and G.L. Reighard for helpful comments on the manuscript. This research was funded by CICYT (Comisión Interministerial de Ciencia y Tecnología, AGL2002-04219 and AGL 2005-05533), INIA (Instituto Nacional de Investigación y Tecnología Agraria y Alimentación, RF03-014-C2), Bilateral Spain-France (HF03-273) and DGA (A28, A44) projects and co-funded by the European Regional Development Fund. M. Bouhadida was supported by a fellowship from the AECI (Agencia Española de Cooperación Internacional) of the Spanish Ministry of Foreign Affairs.Peer reviewe

Incisional hernia after upper abdominal surgery: A randomised controlled trial of midline versus transverse incision

Objectives: To determine whether a transverse incision is an alternative to a midline incision in terms of incisional hern

Randomized Clinical Trial of Laparoscopic Versus Open Repair of the Perforated Peptic Ulcer: The LAMA Trial

Background: Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open appr