Drug-eluting versus bare-metal stents for saphenous vein graft lesions.

A best evidence topic was written addressing the question 'in patients with saphenous vein graft lesions requiring percutaneous coronary intervention, do long-term clinical outcomes differ between drug-eluting and bare-metal stents?' Altogether 1466 papers were found, of which seven represented the best evidence. Although one major recent randomised trial was neutral, the weight of earlier evidence supports drug-eluting stents as standard of care. Bare-metal stents may represent a reasonable, efficacious, and less expensive alternative to drug-eluting stents in well selected patient groups.

Peripheral Arterial Disease.

Peripheral arterial disease (PAD) affects 15% of the Australian population and is a powerful and serious predictor of cardiovascular mortality yet continues to be under-recognised and undertreated. Diagnosis is simple and management is centred upon symptom relief and risk minimisation. While novel and specialised therapies play a role, the bulk of management is approachable and feasible. In this review, we cover the epidemiology, risk factors, associated conditions, classification, and natural history of PAD. We then discuss current diagnostic and therapeutic options as well as emerging therapies for this common condition.

A review of the impact and potential of intermittent aeration on continuous flow nitrifying activated sludge.

Intermittent aeration of activated sludge plants (ASPs) is a potential strategy that may help deliver reduced operational costs while providing an adequate effluent quality. This review paper critically assesses the implications of temporary turning aeration offin continuous flow nitrifying ASPs, including impact on dissolved oxygen concentrations, process biology and operational parameters. The potential savings and pitfalls of the approach are further illustrated through an example scenario. Findings from this review indicate rapid dissolved oxygen depletion times of 1-60 minutes and a significant reduction of nitrification rates from 0.12 to less than 0.04 g NH4-N/g VSS/d. Further negative impacts include a potential increase in nitrous oxide emissions from 0.07% to 27% N2O-N per mole of NH4-N oxidized; enhanced filamentous bacteria growth; a noticeable increase in effluent turbidity developing within one hour of air supply interruption; and, if no mechanical mixing is in place, risk of mixed liquor suspended solids settling in the bioreactor within short times (23-53 min). However, the potential savings in terms of aeration costs could amount to 33%-45% if instrumentation adequacy and impact on process biology and carbon equivalent emissions are excluded from the economic analysis. Further research on the areas of nitrous oxide emissions and the use of hybrid systems to provide resilience and robustness to the intermittent operation of continuous flow nitrifying ASPs is recommended.

Predicting the potential of sludge dewatering liquors to recover nutrients as struvite biominerals.

Phosphorus and nutrient recovery from wastewater as mineral salts can support local replenishment of fertilisers and reduce mining, contributing to the circular economy. Wastewater and related streams are rich in nutrients, however; there is need to develop bio-based processes to recover them. This study investigates the fractions of phosphorus (P) used by Brevibacterium antiquum to form struvite biominerals (bio-struvite) in wastewater sludge dewatering liquors. After 72h of incubation, 25.6 mg P/L were recovered as bio-struvite from 12.4 mg P/L organic plus condensed P and 13.2 mg P/L of ortho-phosphate. The potential of sludge dewatering liquors to recover nutrients as struvite was investigated by characterising ten types of sludge liquors (originating from primary, secondary sludge, feed to anaerobic digester and digestate, from 3 types of wastewater treatment plants) for their P fractions together with other parameters relevant for B. antiquum growth. Results indicated that liquors obtained from primary sludge, feed to anaerobic digesters and digestate were the most suitable to produce bio-struvite, as these were found to frequently have a high content of organic and condensed P, between to 276-732 mg P/L. Liquors, from all the investigated sites, presented a higher potential for bio-struvite production than with conventional struvite precipitation. This study demonstrated that B. antiquum could convert organic and condensed P into bio-struvite, and this opens up a completely new way to recover forms of phosphorus that are not typically available for nutrient recovery in a single process.

The impact of polymer selection and dose on the incorporation of ballasting agents onto wastewater aggregates.

Ballasted flocculation is an efficient high-rate sedimentation process getting more attention as an advanced P removal technology for levels below 0.1 mg/L. The process is well-known yet only very few studies have investigated the interactions, within the matrix of wastewater, of coagulant, polymer and ballast, especially when it comes to polymer doses and types which are, in the industry, rather based on recommendations than scientific evidence. In this work, the impact of anionic and cationic polymers has been investigated on P removal and floc properties. Anionic polymers showed to be superior to cationic ones when it comes to P removal and doses even as low as 0.01 mg/L yield better results than coagulant alone. There appears to be a "best-case" floc size with which very good P removal (>90%) can be achieved and flocs of sufficient strength can be generated.

Enhancing the anaerobic digestion process through carbon dioxide enrichment: initial insights into mechanisms of utilization.

Carbon dioxide (CO2) enrichment of anaerobic digesters (ADs) without hydrogen addition has been demonstrated to provide a potential solution to manage CO2 streams generated in the water and organic waste sectors, with concomitant increases in methane (CH4) production. This study investigates the CO2 utilization mechanisms, by considering chemical and biological pathways in food waste and sewage sludge ADs. Methanosaetaceae was observed to be the dominant methanogen in sewage sludge ADs (Abundance of 83.8-98.8%) but scarce in food waste units (3.5-5.8%). Methanosarcinaceae was dominant in food waste (14.3-32.4%), likely due to a higher tolerance to the free ammonia nitrogen concentration recorded (885 mg L-1). RMethanosaetaceae (ratio of Methanosaetaceae fluorescence signal between test and control) of 1.45 and 1.79 were observed for sludge ADs enriched once and periodically with CO2, respectively (p-value < .05), suggesting a higher Methanosaetaceae activity associated with CO2 enrichment. Reduction of CO2 by homoacetogenesis followed by acetoclastic methanogenesis was proposed as a CO2 utilization mechanism, which requires validation by radiolabelling or carbon isotope analysis.

Understanding the growth of the bio-struvite production Brevibacterium antiquum in sludge liquors.

Biological struvite (bio-struvite) production through biomineralization has been suggested as an alternative to chemically derived struvite production to recover phosphorus from wastewater streams. In this study, statistical experimental design techniques were used to find the optimal growth rate (µ) of Brevibacterium antiquum in sludge liquors. Acetate, oleic acid, NaCl, NH4-N, and Ca2+ were shown to affect the growth rate of B. antiquum. The growth rate reached 3.44 1/d when the bacteria were supplemented with 3.0% w/v NaCl and 1124 mg chemical oxygen demand/L as acetate. However, NaCl was found to hinder the biomineralization of bio-struvite. A two-stage experiment demonstrated that bio-struvite was produced in the presence of acetate. Bio-struvite production was confirmed with X-ray spectroscopy and crystal morphology (prismatic, tabular, and twinned crystal habit) through electron microscope analysis. The bio-struvite production was estimated by measuring phosphate content of the recovered precipitates, reaching 9.6 mg P/L as bio-struvite. Overall, these results demonstrated the optimal conditions required to achieve high growth rates as well as bio-struvite production with B. antiquum. The results obtained in this study could be used to develop a process to grow B. antiquum in wastewater streams in mixed cultures and recover phosphorus-rich products such as struvite.

The role of pH on the biological struvite production in digested sludge dewatering liquors.

Struvite production mediated by bacteria has opened up a new route for phosphorus recovery from wastewater streams but its application to digested sludge dewatering liquors is not yet well understood. This study investigates the growth and biological struvite production of selected bacteria in wastewater liquors with pHs between 5.7 to 9.1. The bacterial growth was assessed through flow cytometry. Bacillus pumilus, Halobacterium salinarum and Brevibacterium antiquum remained viable at pHs between 5.7 to 9.1 but B. antiquum was able to grow at pHs between 7.3 to 7.8. Further analysis allowed the identification of crystals as struvite in tests between pH 7.3 to 8.3. All strains were capable of producing struvite at a range of pHs, but the highest production of 135-198 mg/L was observed for pHs between 7.3 to 8.3. At pHs > 8.3, precipitation of struvite and calcium compounds was observed in inoculated and non-inoculated tests. This study demonstrates that biological struvite production can occur at a wide range of pHs, hence significantly different from chemical struvite precipitation that occurs at pH > 8.3, making it a potentially viable process for phosphorus recovery as struvite from wastewater streams and sludge liquors without strict pH control.

Impacts of coagulation-flocculation treatment on the size distribution and bioavailability of trace metals (Cu, Pb, Ni, Zn) in municipal wastewater.

This study investigated the impact of coagulation-flocculation treatment on metal form and bioavailability in municipal wastewater. Real humus effluent samples were separated into particulate, colloidal and truly dissolved fractions before and after treatment with either ferric chloride (FeCl3) or the biopolymer Floculan. Results revealed that both reagents effectively (≥48%) eliminated Cu, Pb and Zn from the particulate fraction and removed Cu and Zn from the colloidal fraction in conjunction with colloidal organic carbon (COC). Although organics in the truly dissolved fraction were resistant to removal, Floculan reduced Cu in this fraction by 72% owing to the complexation of free Cu ions to phenol and amino groups along the polymeric chains, revealing an additional removal pathway. In fact, COC removed in the CF process by Floculan was replaced with truly dissolved compounds, input as a result of this reagents organic composition. Floculan, therefore, reduced the soluble concentration of Cu and Zn without changing the DOC concentration, thus reducing the bioavailability of these metals in treated effluent. FeCl3 did not reduce the bioavailability of target metals, thus did not deliver any environmental benefit. This work provides important information for the selection and development of high performance coagulants to improve metal removal.

Distribution of trace metals (Cu, Pb, Ni, Zn) between particulate, colloidal and truly dissolved fractions in wastewater treatment.

The distribution of Cu, Pb, Ni and Zn between particulate, colloidal and truly dissolved size fractions in wastewater from a trickling filter treatment plant was investigated. Samples of influent, primary effluent, humus effluent, final effluent and sludge holding tank returns were collected and separated into particulate (i.e. > 0.45 µm), colloidal (i.e. 1 kDa to 0.45 µm), and truly dissolved (i.e. < 1 kDa) fractions using membrane filters. In the influent, substantial proportions of Cu (60%), Pb (67%), and Zn (32%) were present in the particulate fraction which was removed in conjunction with suspended particles at the works in subsequent treatment stages. In final effluent, sizeable proportions of Cu (52%), Pb (32%), Ni (44%) and Zn (68%) were found within the colloidal size fraction. Calculated ratios of soluble metal to organic carbon suggest the metal to be adsorbed to or complexed with non-humic macromolecules typically found within the colloidal size range. These findings suggest that technologies capable of removing particles within the colloidal fraction have good potential to enhance metals removal from wastewater.

Performance and stability of sewage sludge digestion under CO2 enrichment: A pilot study.

Carbon dioxide (CO2) injection in anaerobic digestion has recently been proposed as an interesting possibility to boost methane (CH4) recovery from sludge and organic waste by converting a greenhouse gas into a renewable resource. This research assessed the effects of exogenous CO2 injection on performance and process stability of single-phase continuous anaerobic digesters. Two pilot scale reactors treating sewage sludge were operated for 130days. One reactor was periodically injected with CO2 while the other acted as control. Two injection frequencies and injection devices were tested. The results indicated that CO2 enrichment allowed an increase in CH4 production of ca. 12%, with a CH4 production rate of 371±100L/(kgVSfed·d) and a CH4 concentration of ca. 60% when dissolved CO2 levels inside the test reactor were increased up to 1.9-fold. Results also indicated an improvement in process resilience to temporary overloads and no impacts on stability parameters.

Mercury and antimony in wastewater: fate and treatment.

It is important to understand the fate of Hg and Sb within the wastewater treatment process so as to examine potential treatment options and to ensure compliance with regulatory standards. The fate of Hg and Sb was investigated for an activated sludge process treatment works in the UK. Relatively high crude values (Hg 0.092 µg/L, Sb 1.73 µg/L) were observed at the works, whilst low removal rates within the primary (Hg 52.2 %, Sb 16.3 %) and secondary treatment stages (Hg 29.5 %, Sb -28.9 %) resulted in final effluent concentrations of 0.031 µg/L for Hg and 2.04 µg/L for Sb. Removal of Hg was positively correlated with suspended solids (SS) and chemical oxygen demand (COD) removal, whilst Sb was negatively correlated. Elevated final effluent Sb concentrations compared with crude values were postulated and were suggested to result from Sb present in returned sludge liquors. Kepner Tregoe (KT) analysis was applied to identify suitable treatment technologies. For Hg, chemical techniques (specifically precipitation) were found to be the most suitable whilst for Sb, adsorption (using granulated ferric hydroxide) was deemed most appropriate. Operational solutions, such as lengthening hydraulic retention time, and treatment technologies deployed on sludge liquors were also reviewed but were not feasible for implementation at the works.

Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia.

BACKGROUND: This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina. METHODS AND RESULTS: A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61+/-2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 microg (n=9), 800 microg (n=9), or 2000 microg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (-1.3 versus -0.1, P=0.04). Remaining efficacy end points--including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by > or =2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data--all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment. CONCLUSIONS: This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.

Plasma vascular endothelial growth factor (VEGF) levels after intramuscular and intramyocardial gene transfer of VEGF-1 plasmid DNA.

The purpose of this study was to document the kinetics of vascular endothelial growth factor (VEGF) protein release into the systemic circulation after phVEGF gene transfer for therapeutic angiogenesis. VEGF plasma levels were measured by ELISA in 64 patients undergoing gene transfer of plasmid DNA: intramuscular in 34 patients with peripheral artery disease, and intramyocardial in 30 patients with coronary disease. Baseline plasma VEGF was highly variable and not normally distributed. After intramuscular gene transfer, median plasma VEGF rose slightly, although significantly, by 7 days (38 to 41 pg/ml, p < 0.05), but was not different from baseline at 14, 21, or 28 days. After intramyocardial gene transfer, median plasma VEGF levels were significantly elevated compared with baseline on days 2, 3, and 7 (39, 38, and 45 pg/ml, respectively, each p < 0.05 vs. baseline value of 21 pg/ml). Day 7 plasma levels did not differ significantly as a function of phVEGF dose, or between intramyocardial and intramuscular injections (1.8 and 1.3 times baseline levels, respectively, p = 0.6), despite an almost 10-fold difference in mean phVEGF dose. Intramuscular and intramyocardial phVEGF injections result in significant, although modest, elevations of circulating gene product for <14 days, with no relationship to injected dose. While a statistically significant increase in circulating VEGF level can provide evidence of successful gene transfer for groups of patients, interpretation of results for individual subjects is complicated by wide variation in baseline VEGF and low circulating levels compared with baseline after gene transfer.

Angiogenic gene therapy: pre-clinical studies and phase I clinical data.

Over the last three decades, significant progress has been made in the management of patients with atherosclerotic coronary and peripheral vascular diseases using medical, surgical, and percutaneous therapies. Despite these advances, there remains a significant population of patients who are not optimal candidates for surgical or percutaneous revascularization. These patients continue to suffer from the debilitating symptoms of their disease and remain at risk for myocardial infarction, limb loss, or death. It was this clinical need, coupled with the advances in the understanding of angiogenesis, that has led to efforts to develop angiogenic therapies for patients with peripheral and myocardial ischemia. In general, these conditions are characterized by local hypovascularity, and the approach to treatment is therefore focused on stimulating neovascularization.

Therapeutic angiogenesis by gene transfer in critical limb and myocardial ischemia.

Cardiovascular atherosclerotic diseases remain leading causes of morbidity and mortality in the world. Despite the significant progress that has been made in the management of these diseases using medical, surgical and percutaneous therapies over the last three decades, there remains a significant population of patients who are not optimal candidates for surgical or percutaneous revascularization. Substantial research has focused on the administration of angiogenic growth factors, either as recombinant protein or by gene transfer, to promote the development of supplemental collateral blood vessels that will constitute endogenous bypass conduits around occluded native arteries; a strategy termed "therapeutic angiogenesis". While many cytokines have angiogenic activity, the best studied both in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). This review will discuss gene transfer strategies for therapeutic angiogenesis in critical limb and myocardial ischemia.

One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients.

This phase I open label, dose-escalating study shows that gene transfer of vascular endothelial growth factor-2 naked deoxyribonucleic acid by direct myocardial injection by way of thoracotomy in patients with Canadian Cardiovascular Society class 3 or 4 angina is feasible and safe. The procedure is well tolerated, with few major adverse cardiac events at 1 year, and without complications directly related to gene expression. In this prospective, nonblinded study, the procedure is associated with clinical improvement; however, there was no angiographic evidence of angiogenesis and there is a great potential for a sham or placebo effect in the study patients. A randomized phase III trial is underway that will help determine the efficacy of vascular endothelial growth factor-2 gene transfer in "no-option" patients.

Nitrous oxide emissions and dissolved oxygen profiling in a full-scale nitrifying activated sludge treatment plant.

This paper reports findings from online, continuous monitoring of dissolved and gaseous nitrous oxide (N2O), combined with dissolved oxygen (DO) and ammonia loading, in a full-scale nitrifying activated sludge plant. The study was conducted over eight weeks, at a 210,000 population equivalent sewage treatment works in the UK. Results showed diurnal variability in the gaseous and dissolved N2O emissions, with hourly averages ranging from 0 to 0.00009 kgN2O-N/h for dissolved and 0.00077-0.0027 kgN2O-N/h for gaseous nitrous oxide emissions respectively, per ammonia loading, depending on the time of day. Similarly, the spatial variability was high, with the highest emissions recorded immediately after the anoxic zone and in the final pass of the aeration lane, where ammonia concentrations were typically below 0.5 mg/L. Emissions were shown to be negatively correlated to dissolved oxygen, which fluctuated between 0.5 and 2.5 mgO2/L, at the control set point of 1.5 mgO2/L. The resulting dynamic DO conditions are known to favour N2O production, both by autotrophic and heterotrophic processes in mixed cultures. Average mass emissions from the lane were greater in the gaseous (0.036% of the influent total nitrogen) than in the dissolved (0.01% of the influent total nitrogen) phase, and followed the same diurnal and spatial patterns. Nitrous oxide emissions corresponded to over 34,000 carbon dioxide equivalents/year, adding 13% to the carbon footprint associated with the energy requirements of the monitored lane. A clearer understanding of emissions obtained from real-time data can help towards finding the right balance between improving operational efficiency and saving energy, without increasing N2O emissions.

Long-term (2-year) clinical events following transthoracic intramyocardial gene transfer of VEGF-2 in no-option patients.

BACKGROUND: The short-term clinical impact of intramyocardial gene transfer (GT) of the angiogenic protein vascular endothelial growth factor-2 (VEGF-2) has been previously reported to significantly reduce Canadian Cardiovascular Society (CCS) angina class and to prolong exercise treadmill test (ETT) time. We describe the safety and long-term events (>1 year) in consecutive, nonrandomized, patients who received intramyocardial VEGF-2. METHODS: Thirty patients with intractable CCS class III or IV angina and no options for revascularization underwent direct intramyocardial GT of VEGF-2 naked DNA via limited thoracotomy at total doses of 0.2, 0.8, or 2.0 mg. Patients were followed for clinical events after 1 year by hospital records, follow-up visits or telephone contact. Due to one perioperative death, 29 patients were followed. RESULTS: At a mean follow-up of 751 +/- 102.5 days (range 459-959) there were four deaths (13.8%), five myocardial infarctions (MIs) (17.2%), and seven revascularization procedures (24.1%). There were 15 hospitalizations in 12 patients. At the end of the follow-up period no patient (0%) had CCS class IV angina, 3 patients (11.5%) had class III angina, and 23 (88.5%) had class I to II angina. There were two new diagnoses of cancer. CONCLUSION: Transthoracic intramyocardial injection of VEGF-2 is associated with an improvement of symptoms of angina in the majority of patients beyond the first year of treatment. Major clinical events such as death, MI, and repeat revascularization are uncommon during the first year but more frequent after 1 year at a rate consistent with the severity of underlying disease in this population with advanced atherosclerosis. The majority of events were the result of progression of disease in areas of the heart remote from the site of GT. A large randomized trial is planned to determine the efficacy of intramyocardial VEGF-2 injections in inoperable patients.

Factores de crecimiento para la angiogénesis terapéutica en las enfermedades cardiovasculares / Growth Factors for Therapeutic Angiogenesis in Cardiovascular Diseases

La angiogénesis terapéutica basada en la administración de factores de crecimiento con actividad angiogénica sirve para promover el desarrollo de vasos sanguíneos colaterales capaces de suplir la deficiencia de perfusión secundaria a la obstrucción de las arterias nativas. En la actualidad, este tipo de terapia se dirige a aquellos pacientes en los que los tratamientos convencionales (revascularización quirúrgica o percutánea) han fallado o no son viables. Los factores de crecimiento angiogénicos que han sido objeto de un estudio más exhaustivo son el factor de crecimiento del endotelio vascular (VEGF) y el factor de crecimiento de fibroblastos (FGF). Estas citocinas se pueden administrar en forma de proteína recombinante o de genes que codifican para estas proteínas. Cada uno de estos enfoques presenta una serie de ventajas e inconvenientes que están siendo investigados en detalle, tanto en modelos animales como en ensayos clínicos con humanos. Aunque los ensayos clínicos se han basado en series reducidas de pacientes, a menudo no aleatorizadas, los resultados preliminares son muy prometedores. Así, por ejemplo, en la isquemia miocárdica se han obtenido evidencias objetivas de aumento de la perfusión tisular, y en la enfermedad arterial periférica se ha documentado una mejoría significativa del dolor en reposo y de las úlceras isquémicas después de la administración de VEGF y FGF. Contrariamente a lo esperado, los efectos colaterales de este tipo de intervenciones han sido pocos, aunque será necesario incluir un mayor número de pacientes en los ensayos clínicos para probar la seguridad y efectividad de este tipo de terapia. Parece claro, sin embargo, que es posible inducir una angiogénesis terapéutica en pacientes seleccionados capaz de modular las alteraciones vasculares sin que se produzca una toxicidad asociada significativa (AU)