Intravascular ultrasound findings in the multicenter, randomized, double-blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon- expandable stent in the treatment of patients with de novo native coronary artery Lesions) trial

BACKGROUND: The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. METHODS AND RESULTS: In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2+/-5 versus 37+/-28 mm3) and percent of volume obstruction (1+/-3% versus 29+/-20%) at 6 months between the 2 groups was highly significant (P<0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition

Angiographic Findings of the Multicenter Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL)

BACKGROUND: Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, approximately 40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents. METHODS AND RESULTS: Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into tertiles according to their reference diameter (RD; stratum I, RD 2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01+/-0.25 versus 0.80+/-0.43 mm in stratum I, 0.01+/-0.38 versus 0.88+/-0.57 mm in stratum II, and -0.06+/-0.35 versus 0.74+/-0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P<0.001) and postprocedural MLD (P= 0.008). CONCLUSIONS: Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group

Five-year outcomes of chronic total occlusion treatment with a biolimus A9-eluting biodegradable polymer stent versus a sirolimus-eluting permanent polymer stent in the LEADERS all-comers trial

Background: Few data are available on long-term follow-up of drug-eluting stents in the treatment of chronic total occlusion (CTO). The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9™-eluting stent (BES) with a sirolimus-eluting stent (SES).Methods: Among 1,707 patients enrolled in the prospective, multi-center, all-comers LEADERS trial, 81 with CTOs were treated with either a BES (n = 45) or a SES (n = 36). The primary endpoint was the occurrence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI) and clinically-indicated target vessel revascularization (TVR).Results: At 5 years, the rate of MACE was numerically higher in the CTO group than in the non-CTO group (29.6% vs. 23.3%; p = 0.173), with a significant increase in the incidence of target lesion revascularization (TLR) (21.0 vs. 12.6; p = 0.033), but no difference in stent thrombosis (ST). Patients with CTO receiving a BES demonstrated a lower incidence of MACE (22.2% vs. 38.9%; p = 0.147) with a significant reduction in TLR compared to patients receiving a SES (11.1% vs. 33.3%, p = 0.0214) with an incidence similar to that observed in the non-CTO group treated with BES (11.6%). Definite ST at 5 years nearly halved in the BES group (4.4% vs. 8.3%, p = 0.478) with no ST in the BES group after the first year (0% vs. 8.3%, p for interaction = 0.009).Conclusions: The use of a BES showed a reduction in MACE, TVR, TLR, and ST over time in the CTO subset with similar outcome as for non-CTO lesions

Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting for Diabetics with Multivessel Coronary Artery Disease: The Korean Multicenter Revascularization Registry (KORR)

This study was designed to assess the relative merits of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in multivessel coronary artery disease (MVCAD), particularly for Korean diabetics. Among 3,279 patients with MVCAD who were recommended for revascularization were enrolled from nine centers in Korea, 2,154 were selected after statistical adjustments for the disparities between two groups. Survival rates were not significantly different for three years between two groups. Among diabetic patients, the three-year mortality rate in PCI group was 1.9-fold higher than that of CABG group, although it was not statistically significant (PCI 19.8%, CABG 11.4%, p=0.14). The three-year mortality rate was similar between the two groups in non-diabetics (PCI 8.3%, CABG 10.0%, p=0.50). The 30-day rate of cerebrovascular event was higher in CABG group, for both diabetic (CABG 3.6%, PCI 0.0%, p<0.001) and non-diabetic patients (CABG 2.4%, PCI 0.0%, p<0.001). Short- and long-term revascularization rates were higher in PCI group than in CABG group. As a conclusion, this Korean registry demonstrates that PCI was associated with comparable survival rates and lower short-term morbidity, but a greater requirement for repeated revascularization compared with CABG in Korean diabetics

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Five-year outcomes of chronic total occlusion treatment with a biolimus A9-eluting biodegradable polymer stent versus a sirolimus-eluting permanent polymer stent in the LEADERS all-comers trial

Background: Few data are available on long-term follow-up of drug-eluting stents in the treatment of chronic total occlusion (CTO). The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9™-eluting stent (BES) with a sirolimus-eluting stent (SES). Methods: Among 1,707 patients enrolled in the prospective, multi-center, all-comers LEADERS trial, 81 with CTOs were treated with either a BES (n = 45) or a SES (n = 36). The primary endpoint was the occurrence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI) and clinically-indicated target vessel revascularization (TVR). Results: At 5 years, the rate of MACE was numerically higher in the CTO group than in the non-CTO group (29.6% vs. 23.3%; p = 0.173), with a significant increase in the incidence of target lesion revascularization (TLR) (21.0 vs. 12.6; p = 0.033), but no difference in stent thrombosis (ST). Patients with CTO receiving a BES demonstrated a lower incidence of MACE (22.2% vs. 38.9%; p = 0.147) with a significant reduction in TLR compared to patients receiving a SES (11.1% vs. 33.3%, p = 0.0214) with an incidence similar to that observed in the non-CTO group treated with BES (11.6%). Definite ST at 5 years nearly halved in the BES group (4.4% vs. 8.3%, p = 0.478) with no ST in the BES group after the first year (0% vs. 8.3%, p for interaction = 0.009). Conclusions: The use of a BES showed a reduction in MACE, TVR, TLR, and ST over time in the CTO subset with similar outcome as for non-CTO lesions

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS)

Background: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4–7 weeks depending on tolerance to up-dosing of bisoprolol/placebo—these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers. Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally. Trial registration: Current controlled trials ISRCTN10497306. Registered on 16 August 201

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Carbon budget for 1.5 and 2oC targets lowered by natural wetland and permafrost feedbacks

Methane emissions from natural wetlands and carbon release from permafrost thaw have a positive feedback on climate, yet are not represented in most state-of-the-art climate models. Furthermore, a fraction of the thawed permafrost carbon is released as methane, enhancing the combined feedback strength. We present simulations with an intermediate complexity climate model which follow prescribed global warming pathways to stabilisation at 1.5°C or 2.0°C above pre-industrial levels by the year 2100, and that incorporates a state-of-the-art global land surface model with updated descriptions of wetland and permafrost carbon release. We demonstrate that the climate feedbacks from those two processes are substantial. Specifically, permissible anthropogenic fossil fuel CO2 emission budgets are reduced by 17-23% (47-56 GtC) for stabilisation at 1.5°C, and 9-13% (52-57 GtC) for 2.0°C stabilisation. In our simulations these feedback processes respond faster at temperatures below 1.5°C, and the differences between the 1.5°C and 2°C targets are disproportionately small. This key finding is due to our interest in transient emission pathways to the year 2100 and does not consider the longer term implications of these feedback processes. We conclude that natural feedback processes from wetlands and permafrost must be considered in assessments of transient emission pathways to limit global warming