Mid-term outcomes for Endoscopic versus Open Vein Harvest: a case control study

<p>Abstract</p> <p>Background</p> <p>Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years.</p> <p>Methods</p> <p>We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed.</p> <p>Results</p> <p>Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06).</p> <p>Conclusions</p> <p>While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.</p

LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer

<p>Abstract</p> <p>Background</p> <p>There is no cure for castration-recurrent prostate cancer (CRPC) and the mechanisms underlying this stage of the disease are unknown.</p> <p>Methods</p> <p>We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC <it>in vivo </it>using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC.</p> <p>Results</p> <p>Three million tags were sequenced using <it>in vivo </it>samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor (<it>CCNH, CUEDC2, FLNA, PSMA7</it>), steroid synthesis and metabolism (<it>DHCR24, DHRS7</it>, <it>ELOVL5, HSD17B4</it>, <it>OPRK1</it>), neuroendocrine (<it>ENO2, MAOA, OPRK1, S100A10, TRPM8</it>), and proliferation (<it>GAS5</it>, <it>GNB2L1</it>, <it>MT-ND3</it>, <it>NKX3-1</it>, <it>PCGEM1</it>, <it>PTGFR</it>, <it>STEAP1</it>, <it>TMEM30A</it>), but neither supported nor discounted a role for cell survival genes.</p> <p>Conclusions</p> <p>The <it>in vivo </it>gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.</p

Mood stabilizing drugs regulate transcription of immune, neuronal and metabolic pathway genes in Drosophila

Abstract: Lithium and valproate (VPA) are drugs used in the management of bipolar disorder. Even though they reportedly act on various pathways, the transcriptional targets relevant for disease mechanism and therapeutic effect remain unclear. Furthermore, multiple studies used lymphoblasts of bipolar patients as a cellular proxy, but it remains unclear whether peripheral cells provide a good readout for the effects of these drugs in the brain. We used Drosophila culture cells and adult flies to analyze the transcriptional effects of lithium and VPA and define mechanistic pathways. Transcriptional profiles were determined for Drosophila S2-cells and adult fly heads following lithium or VPA treatment. Gene ontology categories were identified using the DAVID functional annotation tool with a cut-off of p < 0.05. Significantly enriched GO terms were clustered using REVIGO and DAVID functional annotation clustering. Significance of overlap between transcript lists was determined with a Fisher's exact hypergeometric test. Treatment of cultured cells and adult flies with lithium and VPA induces transcriptional responses in genes with similar ontology, with as most prominent immune response, neuronal development, neuronal function, and metabolism. (i) Transcriptional effects of lithium and VPA in Drosophila S2 cells and heads show significant overlap. (ii) The overlap between transcriptional alterations in peripheral versus neuronal cells at the single gene level is negligible, but at the gene ontology and pathway level considerable overlap can be found. (iii) Lithium and VPA act on evolutionarily conserved pathways in Drosophila and mammalian models