Song structure and singing activity of two separate humpback whales populations wintering off the coast of Caño Island in Costa Rica.

Central American (CA) and Breeding Stock-G (BSG) humpback whales are known to winter off Caño Island, Costa Rica at different times of the year. To study their singing behavior, autonomous underwater recorders were used to record the whales. Song detection for BSG whales was higher than CA whales, and song structure was distinct for each population. No strong evidence for cross-equatorial connectivity was found. This study provides the first humpback whale song reference for both populations in Costa Rica, which can help advance understanding of CA and BSG whale song rate of change and connectivity with other wintering areas.

Isolation of Mesenchymal Stromal Cells From Peripheral Blood of ST Elevation Myocardial Infarction Patients.

Bone marrow mesenchymal stromal cells (MSCs) have shown therapeutic potential in the treatment of myocardial infarction patients. However, bone marrow requires invasive harvesting techniques. Therefore, the aim was to carry out a feasibility study of using autologous peripheral blood (PB) as a source for MSCs and platelet lysate (PL), a potential novel therapeutic intervention in acute ST elevation myocardial infarction (STEMI) patients. Autologous PL and MSCs were prepared from STEMI patient and healthy control blood. MSCs were analyzed by trilineage differentiation and flow cytometry. PB MSCs were isolated from 83% of patients (n = 6) but not from controls. The use of PL was feasible in the first passage but not in subsequent ones due to volume. To conclude, PB is a promising alternative to bone marrow. It negates the need for invasive harvesting techniques, and reduces hemorrhagic risk in this patient population routinely managed with anticoagulant and antiplatelet agents.

The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.

AIMS: Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. METHODS AND RESULTS: A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31-29.64); placebo group, 43.5 mg day/L (31.15-60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32-0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65-4.62): placebo; 2.21 mg/L (1.67-2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. CONCLUSION: IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. CLINICAL TRIAL REGISTRATION EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.

Clinical Outcomes and OCT Analysis After Culotte Stenting With 2nd- and 3rd-Generation Everolimus-Eluting Stents: Two-Year Follow-Up of the CELTIC Bifurcation Study.

PURPOSE: The aim of this study was to provide 2-year clinical outcomes for patients with Medina 1,1,1 bifurcation lesions treated with a culotte technique, comparing Synergy and Xience drug eluting stent (DES) platforms. A sub-group analysis of 9-month Optical Coherence Tomography (OCT) was performed to assess stent healing. METHODS: A total of 170 patients with non-left main stem Medina 1,1,1 lesions, were randomized to treatment with Synergy or Xience DES. The primary outcome was a composite of death, myocardial infarction, stroke, target vessel failure, stent thrombosis and angiographic restenosis. Qualitative and quantitative analyses of 30 bifurcations were carried out on OCT images taken at 9-month follow-up. RESULTS: After 2 years, the primary outcome had occurred in 17.7% of patients in the Synergy group and 18.8% of patients in the Xience group. The non-inferiority test was met (p = 0.0055). MACCE occurred in 7.3% of all patients by 2 years. OCT analysis found smaller stent and lumen areas in patients treated with Synergy stents. There was a higher proportion of malapposed struts in patients treated with Xience stents. CONCLUSIONS: The first report of the CELTIC bifurcation study demonstrated a low MACCE rate after 9 months. There was little accrual of events after this timepoint. There was no difference in clinical outcomes between the platforms tested. OCT analysis demonstrated excellent healing of both platforms.

Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.

AIMS: To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients. METHODS & FINDINGS: A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data. CONCLUSION: Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.

Photodecaging from 9-substituted 2,7-dihydroxy and dimethoxyfluorenes: competition between heterolytic and homolytic pathways.

2,7-Dihydroxy-9-fluorenol (9), 2,7-dimethoxy-9-fluorenol (10), and 2,7-dimethoxy-9-acetoxyfluorene (11) were prepared and their photochemistry was studied in methanol and aqueous methanol solution in the hopes of observing efficient expulsion of the substituents positioned at the 9-position. For all three compounds, the primary photoproducts were 2,7-disubstituted-9-fluorenes and 2,7-disubstituted-9-methoxyfluorenes. A mechanism of reaction is proposed for production of these products, and involves competing homolytic and heterolytic pathways that produce radical and carbocation intermediates. Reaction quantum yields (for substrate disappearance) ranged between 0.21 and 0.31.

Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.

AIMS: European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients. METHODS: We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge. RESULTS: Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target. CONCLUSION: There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.

Red blood cell storage duration and mortality in patients undergoing percutaneous coronary intervention.

BACKGROUND: Blood transfusion has been associated with an increased mortality in patients undergoing percutaneous coronary intervention (PCI). Although the reasons for this remain unclear, it may be related to the structural and functional changes occurring within red blood cells (RBCs) during storage. We investigated whether RBC storage duration was associated with mortality in patients requiring transfusion after PCI. METHODS: We collected data on all RBC transfusions occurring within 10 days of PCI (excluding those related to cardiac surgery) using the British Columbia Cardiac Registry and Central Transfusion Registry. Transfusion details were analyzed according to 30-day survival. RESULTS: From a total of 32,580 patients undergoing PCI, 909 (2.8%) patients received RBCs with a mean storage duration of 25 +/- 10 days. In these 909 patients, mean transfusion volumes were lower in survivors (2.8 +/- 2.1 vs 3.8 +/- 2.9 U, P = .002) than those who died within 30 days. In a multivariate analysis to adjust for baseline risk, mean RBC storage age (HR 1.02 [95% CI 1.01-1.04], P = .002) and transfusion volume (HR 1.26 [95% CI 1.18-1.34], P < .001) both predicted 30-day mortality. Transfused patients who received only older blood (RBC min age >28 days) appeared to be at greater risk of death (HR 2.49 [95% CI 1.45-4.25], P = .001). CONCLUSION: Red blood cell transfusion is associated with increased 30-day mortality in patients undergoing PCI. Although current transfusion practice permits RBC storage for up to 42 days, the use of older red cells may pose an additional hazard to this patient group.

Culotte stenting for coronary bifurcation lesions with 2nd and 3rd generation everolimus-eluting stents: the CELTIC Bifurcation Study.

AIMS: The aim of this study was to provide contemporary outcome data for patients with de novo coronary disease and Medina 1,1,1 lesions who were treated with a culotte two-stent technique, and to compare the performance of two modern-generation drug-eluting stent (DES) platforms, the 3-connector XIENCE and the 2-connector SYNERGY. METHODS AND RESULTS: Patients with Medina 1,1,1 bifurcation lesions who had disease that was amenable to culotte stenting were randomised 1:1 to treatment with XIENCE or SYNERGY DES. A total of 170 patients were included. Technical success and final kissing balloon inflation occurred in >96% of cases. Major adverse cardiovascular or cerebrovascular events (MACCE: a composite of death, myocardial infarction [MI], cerebrovascular accident [CVA] and target vessel revascularisation [TVR]) occurred in 5.9% of patients by nine months. The primary endpoint was a composite of death, MI, CVA, target vessel failure (TVF), stent thrombosis and binary angiographic restenosis. At nine months, the primary endpoint occurred in 19% of XIENCE patients and 16% of SYNERGY patients (p=0.003 for non-inferiority for platform performance). CONCLUSIONS: MACCE rates for culotte stenting using contemporary everolimus-eluting DES are low at nine months. The XIENCE and SYNERGY stents demonstrated comparable performance for the primary endpoint.

Statins inhibit secretion of metalloproteinases-1, -2, -3, and -9 from vascular smooth muscle cells and macrophages.

OBJECTIVE: Production of several metalloproteinases (MMPs) from smooth muscle cells (SMCs) and macrophages causes matrix destruction and atherosclerotic plaque instability. Statins, which inhibit HMG-CoA reductase and hence cholesterol and isoprenoid synthesis, stabilize plaques. We investigated whether statins inhibit MMP secretion from SMCs and macrophages. METHODS AND RESULTS: We used human saphenous vein and rabbit aortic SMC and foamy macrophages from cholesterol-fed rabbits. Cerivastatin (50 nmol/L) inhibited inducible MMP-1, -3, and -9 secretion from human SMC by 52+/-19%, 71+/-18%, and 73+/-17%, respectively (P<0.01, n=3). Similar dose-related effects of cerivastatin (50 to 500 nmol/L), simvastatin (1 to 20 micromol/L), and lovastatin (5 to 20 micromol/L) were consistent with their relative potencies against HMG-CoA reductase. Statins also inhibited inducible MMP-1, -3, and -9 and constitutive MMP-2 secretion but not TIMP-1 or -2 secretion from rabbit SMC. Statins also dose-dependently inhibited MMP-1, -3, and -9 secretion from rabbit foam cells; cerivastatin (50 nmol/L) inhibited by 68+/-18%, 74+/-14%, and 74+/-14%, respectively (P<0.01, n=4). Statins similarly decreased collagenolytic, caseinolytic, and gelatinolytic activity. Mevalonate and geranylgeranylpyrophosphate but not squalene reversed the effects, showing dependence on isoprenoid, not cholesterol depletion. Statins did not affect MMP mRNA levels. CONCLUSIONS: Statins inhibit secretion of a several MMPs from both SMCs and macrophages, which could therefore contribute to their plaque-stabilizing effects.

Non-red blood cell transfusion as a risk factor for mortality following percutaneous coronary intervention.

BACKGROUND: Bleeding following percutaneous coronary intervention (PCI) is common and may lead to transfusion and death. Although previous work has examined the effect of red blood cell (RBC) transfusion in patients with coronary disease, no study had investigated whether transfusion of non-RBC components was associated with mortality following PCI. METHODS: All subjects transfused in the 10 days following PCI were identified using the British Columbia Cardiac and Central Transfusion Registries. Patients undergoing cardiac surgery following PCI were excluded as transfusion was assumed to be due to surgical related bleeding. Transfusion products were categorised as RBC and non-RBC comprising platelets, plasma and cryoprecipitate. Blood product use was compared according to thirty day mortality using multivariate regression and propensity adjustment for confounding variables. RESULTS: From a total of 32,580 patients who underwent PCI, 952 patients received at least 1 blood product within 10 days of PCI. Non-RBC transfusion occurred more commonly in the cohort of transfused patients dying within 30 days (p<0.001). After adjustment for baseline risk, transfusion of plasma/cryoprecipitate (HR 5.17; 95% C.I. 2.87-9.32, p<0.001) and platelets (HR 2.13; 95% C.I. 1.10-4.13, p=0.03) was associated with increased 30 day mortality. In a propensity risk adjusted model, transfusion of plasma/cryoprecipitate and RBC transfusion volume remained as significant predictors of 30-day mortality (p<0.001). CONCLUSIONS: Transfusion following PCI appears to be associated with an increased risk of death within 30 days. We now report that transfusion with plasma rich non-RBC products may confer an additional mortality risk to patients undergoing PCI.