Comparison of five-year outcome of octogenarians undergoing percutaneous coronary intervention with drug-eluting versus bare-metal stents (from the RESEARCH and T-SEARCH Registries)

Although octogenarians are increasingly referred for percutaneous coronary intervention (PCI), data are lacking on long-term safety and efficacy of drug-eluting stents in this high-risk subpopulation. The aim of this study was to evaluate 5-year clinical outcome of octogenarians who underwent PCI using sirolimus-eluting stents (SESs) or paclitaxel-eluting stents (PESs) compared to bare-metal stents (BMSs). From January 2000 to December 2005, 319 consecutive octogenarian patients who underwent PCI with BMSs (n = 93, January 2000 to April 2002), SESs (n = 52, April 2002 to February 2003), or PESs (n = 174, February 2003 to December 2005) were included prospectively. Primary study end points were all-cause mortality and major adverse cardiac events (MACEs), defined as all-cause death, any myocardial infarction, or any revascularization. Mean age of the study population was 83 ± 2 years and 51% of patients were men. Median follow-up duration was 5.4 years (range 3 to 9). Five-year mortality rates in the BMS, SES, and PES cohorts were similar (41%, 42%, and 41%, respectively). Cumulative 5-year MACE-free survival in the BMS, SES, and PES cohorts were 44%, 52%, and 48%, respectively. Compared to the BMS cohort, adjusted hazard ratios for MACEs in the SES and PES cohorts were 0.5 (95% confidence interval [CI] 0.3 to 0.9, p <0.05) and 0.5 (95% CI 0.2 to 1.4, p = 0.2), respectively. Overall, use of drug-eluting stents was associated with fewer MACEs (adjusted hazard ratio 0.5, 95% CI 0.3 to 0.9, p <0.05) and a trend toward less target vessel revascularization (adjusted hazard ratio 0.5, 95% CI 0.2 to 1.2, p = 0.1). In conclusion, PCI with drug-eluting stents in octogenarians was found to be safe and more effective compared to PCI with BMSs.     

Impact of completeness of revascularization on the five-year outcome in percutaneous coronary intervention and coronary artery bypass graft patients (from the ARTS-II study)

The aim of this study was to compare clinical outcome at 5 years in patients with complete and incomplete revascularization treated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stents. Baseline and procedural angiograms and surgical case-record forms were centrally assessed for completeness of revascularization. Patients treated with PCI for incomplete revascularization were stratified according to Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score tertiles. Complete revascularization was achieved in 360 of 588 patients (61.2%) in the PCI with sirolimus-eluting stent group and 477 of 567 patients (84.1%) in the CABG group (p <0.05). There was no significant difference in 5-year survival without major adverse cardiac and cerebrovascular events (MACCEs; death, cerebrovascular accident, myocardial infarction, and any revascularization) between patients with complete and incomplete revascularization treated with PCI or CABG. Survival free from MACCEs in patients with incomplete revascularization treated with PCI was significantly lower than those with complete revascularization treated with CABG (hazard ratio 1.66, 0.96 to 1.80, log-rank p = 0.001). The 5-year MACCE-free survival in patients with incomplete revascularization treated with PCI stratified according to SYNTAX score tertiles showed a significantly lower MACCE survival in the higher SYNTAX tertile compared to the low (hazard ratio 0.56, 0.32 to 0.96, log-rank p = 0.04) and intermediate (hazard ratio 0.50, 0.28 to 0.91, log-rank p = 0.02) tertiles, whereas survival between the low and intermediate SYNTAX tertiles was not significantly different (hazard ratio 1.13, 0.60 to 2.13, log-rank p = 0.71). In conclusion, this study suggests that patients with complex coronary disease, in whom complete revascularization cannot be achieved with PCI, should be offered surgical revascularization. However, in those patients with less complex disease, PCI is a valid alternative even if complete revascularization cannot be achieved.     

Ultra-violet irradiation induces apoptosis via mitochondrial pathway in pancreatic cancer cells

Pancreatic cancer is a highly lethal disease and gemcitabine is considered to be the standard of care for the treatment of advanced pancreatic cancer. However, the outcome of the patients treated with gemcitabine is still unstatisfactory and further development of new treatments is required. We recently found that short wavelength ultra-violet (UV-C) suppresses cell proliferation with downregulation of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells, but not in normal pancreatic epithelial (PE) cells. In this study, we investigated the effect of UV-C on apoptosis in several cell lines derived from the pancreas. UV-C induced poly(ADP-ribose) polymerase (PARP) cleavage, which is a marker of cells undergoing apoptosis, in Panc1, MiaPaca2, KP3 and BxPC3 pancreatic cancer cells, but not in PE cells. We also observed similar effects in Hoechst 33258 staining, which shows DNA fragmentation. While p53, a tumor suppressor protein, plays a critical role in UV-C-induced cell damage, we did not observe the correlation between the sensitivity to UV-C and p53 status. Thapsigargin, an agent that promotes endoplasmic reticulum (ER) stress by depletion of lumenal calcium stores, as well as cis-diamineplatinum (II) dichloride, a classical anti-cancer drug that causes DNA damage, induced PARP cleavage even in PE cells. Moreover, UV-C-induced apoptosis in Panc1 and KP3 cells was associated with the release of cytochrome c, indicating that it was mediated via mitochondrial pathway. Taken together, UV-C has a potent anti-cancer effect on pancreatic cancer cells without adverse effect on normal cells and it could be useful for the treatment of human pancreatic cancers.     

Coronary calcification is associated with lower bone formation rate in CKD patients not yet in dialysis treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4–2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone‐formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p = .009; odd ratio (OR) = 0.15; 95% confidence interval (CI) 0.036–0.619]. This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone‐formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients. © 2010 American Society for Bone and Mineral Research     

Investigation of potential carbohydrate antigen targets for human and baboon antibodies

Yeh P, Ezzelarab M, Bovin N, Hara H, Long C, Tomiyama K, Sun F, Ayares D, Awwad M, Cooper DKC. Investigation of potential carbohydrate antigen targets for human and baboon antibodies. Xenotransplantation 2010; 17: 197–206. © 2010 John Wiley & Sons A/S. Abstract: Background: The continued presence of a primate antibody‐mediated response to cells and organs from α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs indicates that there may be antigens other than Galα1,3Gal (αGal) against which primates have xenoreactive antibodies. Human and baboon sera were tested for reactivity against a panel of saccharides that might be potential antigen targets for natural anti‐non‐αGal antibodies. Methods: Human sera (n = 16) and baboon sera (n = 15) of all ABO blood types were tested using an enzyme‐linked immunoadsorbent assay for binding of IgM and IgG to a panel of synthetic polyacrylamide‐linked saccharides (n = 15). Human sera were also tested after adsorption on αGal immunoaffinity beads. Sera from healthy wild‐type (WT, n = 6) and GTKO (n = 6) pigs and from baboons (n = 4) sensitized to GTKO pig organ or artery transplants (of blood type O) were also tested. Forssman antigen expression on baboon and pig tissues was investigated by immunohistochemistry. Results: Both human and baboon sera showed high IgM and IgG binding to αGal saccharides, α‐lactosamine, and Forssman disaccharide. Human sera also demonstrated modest binding to N‐glycolylneuraminic acid (Neu5Gc). When human sera were adsorbed on αGal oligosaccharides, there was a reduction in binding to αGal and α‐lactosamine, but not to Forssman. WT and GTKO pig sera showed high binding to Forssman, and GTKO pig sera showed high binding to αGal saccharides. Baboon sera sensitized to GTKO pigs showed no significant increased binding to any specific saccharide. Staining for Forssman was negative on baboon and pig tissues. Conclusions: We were unable to identify definitively any saccharides from the selected panel that may be targets for primate anti‐non‐αGal antibodies. The high level of anti‐Forssman antibodies in humans, baboons, and pigs, and the absence of Forssman expression on pig tissues, suggest that the Forssman antigen does not play a role in the primate immune response to pigs.     

Surgical treatment of patients with stenosis of the central airway due to tracheal tumours

This study retrospectively evaluated bronchoscopic and surgical treatments for patients with central airway stenosis due to tracheal tumours. Seven patients treated by resection and reconstruction of the trachea for tracheal tumours between 1994 and 2008 were retrospectively reviewed. The most common histological finding was thyroid carcinoma (n = 3), followed by adenoid cystic carcinoma (n = 2), a metastatic thyroid tumour (n = 1), and a benign granular cell tumour (n = 1). Three of the patients required preoperative laser treatment (Nd:YAG) for recanalization. Five patients underwent end-to-end anastomosis for reconstruction. There was no postoperative mortality or morbidity such as anastomotic insufficiency of the reconstructed trachea. Three patients with a microscopic residual tumour required postoperative external radiotherapy. Surgical resection of malignant tracheal tumours is recommended not only for curative purposes, but also for reduction of the risk of smothering.