Relationship between biomarkers and subsequent clinical and angiographic restenosis after paclitaxel-eluting stents for treatment of STEMI: a HORIZONS-AMI substudy

Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether the use of biomarkers might be of utility to identify patients who remain at risk for DES ISR after primary PCI has never been examined. A total of 26 biomarkers were measured at enrollment and 30 days and analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent (PES), were scheduled for routine angiographic follow-up at 13 months, and were followed for 3 years. Mean in-stent late-loss was 0.28 ± 0.57 mm, and target lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission were associated with both higher in-stent late loss and ischemia-driven TLR. Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1), and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30 days were also associated with ischemia-driven TLR. After multivariate adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30 days were associated with in-stent late loss, and only CT-1 was associated with TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were independently associated with in-stent late loss, and CT-1 was associated with TLR. Additional studies to confirm and validate the utility of these biomarkers are warranted.     

Selection and management of the lung donor

This article reviews recent developments in the selection, assessment, and management of the potential lung donor that aim to increase donor organ use. The scarcity of suitable donor organs results in long waiting times and significant mortality for those patients awaiting transplant. Strategies to expand the donor pool can substantially improve donor lung use rates. Although further long-term studies are required to confirm that long-term outcomes are not being compromised, the available evidence suggests that the traditional factors defining a lung as marginal or extended do not actually compromise outcomes within the framework of current donor management strategies.     

Developing best practice for fungal specimen management: audit of UK microbiology laboratories

This study represents an audit of microbiology laboratories in the UK to ascertain whether they are aware of, or follow, the Health Protection Agency (HPA) National Standard Methods Standard Operating Procedure (NSM SOP) for the investigation of dermatological specimens for superficial mycoses, or use a locally adapted version. A questionnaire audit was distributed to 179 NHS microbiology laboratories throughout England, Wales, Scotland and Northern Ireland. The NSM SOP was followed by 92% of laboratories for the microscopy of dermatological samples; light microscopy/ KOH digestion was used by 63% and fluorescence microscopy/KOH digestion by 29% of laboratories. Preliminary reports post-microscopy were issued by 98% of laboratories, with 93% issuing reports within 48 hours. Adherence to the NSM SOP guidelines for culture was low; only 34% of laboratories incubated microscopy-negative specimens for the recommended 14 days, while approximately 60% incubated microscopy-positive specimens for 21 days. The culture medium recommended by the NSM SOP was used in 82% of laboratories. Comments were added to culture reports by 51% of laboratories; most were added manually and comments varied between laboratories. Nail samples were the most common sample received from primary care, followed by skin and hair. These results show no significant difference in the rate of microscopy positives versus culture positives. Microscopy and culture are the easiest and cheapest methods available to UK laboratories for the investigation of suspected superficial fungal infections. Although most laboratories included in this audit claimed to follow the NSM SOP for microscopy and culture, these results show that the techniques used vary throughout the UK. To maximise the service provided to primary care, UK laboratories should use standardise methods based on the NSM SOP.     

CD8+ T-cell maturation following lung transplantation: the differential impact of CMV and acute rejection

Studies on persistent viral infections demonstrate that CD8(+) T-cells differentiate along distinct pathways following chronic antigen exposure; however the effect of stimulation with non-viral chronic antigens is poorly described. We assessed the contributions that the presence of an allograft or cytomegalovirus (CMV) has on the post-thymic differentiation of CD8(+) T-cells in both the blood and lung allograft in patients undergoing lung transplantation. CD28 expression on blood CD8(+) T-cells was reduced in CMV seropositive patients, and was further reduced following acute episodes of CMV reactivation. These viral-associated changes in phenotype were not seen in CD8(+) T-cells isolated from the lung allograft where a different pattern of CD28 expression was observed. Following transplantation there was a progressive reduction in CD28 expression on BAL CD8(+) T-cells. In contrast to what was observed in peripheral blood, reduced CD28 expression on BAL CD8(+) T-cells was associated with a reduced gamma-IFN production. Furthermore, a high proportion of CD28-CD8(+) T-cells in the BAL was associated with fewer episodes of acute allograft rejection. An expanded CD28-CD8(+) T-cell subset, with reduced function, within the lung allograft may have important prognostic implications in lung transplant recipients.