CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver

IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells have been implicated in immune-mediated liver diseases, but the molecular basis for their recruitment and positioning within the liver is unknown.

New insights regarding the incidence, presentation and treatment options of aorto-oesophageal fistulation after thoracic endovascular aortic repair: the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To review the incidence, clinical presentation, definite management and 1-year outcome in patients with aorto-oesophageal fistulation (AOF) following thoracic endovascular aortic repair (TEVAR). METHODS International multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2011 with a total caseload of 2387 TEVAR procedures (17 centres). RESULTS Thirty-six patients with a median age of 69 years (IQR 56-75), 25% females and 9 patients (19%) following previous aortic surgery were identified. The incidence of AOF in the entire cohort after TEVAR in the study period was 1.5%. The primary underlying aortic pathology for TEVAR was atherosclerotic aneurysm formation in 53% of patients and the median time to development of AOF was 90 days (IQR 30-150). Leading clinical symptoms were fever of unknown origin in 29 (81%), haematemesis in 19 (53%) and shock in 8 (22%) patients. Diagnosis could be confirmed via computed tomography in 92% of the cases with the leading sign of a new mediastinal mass in 28 (78%) patients. A conservative approach resulted in a 100% 1-year mortality, and 1-year survival for an oesophageal stenting-only approach was 17%. Survival after isolated oesophagectomy was 43%. The highest 1-year survival rate (46%) could be achieved via an aggressive treatment including radical oesophagectomy and aortic replacement [relative risk increase 1.73 95% confidence interval (CI) 1.03-2.92]. The survival advantage of this aggressive treatment modality could be confirmed in bootstrap analysis (95% CI 1.11-3.33). CONCLUSIONS The development of AOF is a rare but lethal complication after TEVAR, being associated with the need for emergency TEVAR as well as mediastinal haematoma formation. The only durable and successful approach to cure the disease is radical oesophagectomy and extensive aortic reconstruction. These findings may serve as a decision-making tool for physicians treating these complex patients.

Clinical outcomes after zotarolimus and everolimus drug eluting stent implantation in coronary artery bifurcation lesions: insights from the RESOLUTE All Comers Trial

OBJECTIVE We investigated clinical outcomes after treatment of coronary bifurcation lesions with second generation drug eluting stents (DES). DESIGN Post hoc analysis of a randomised, multicentre, non-inferiority trial. SETTING Multicentre study. PATIENTS All comers study with minimal exclusion criteria. INTERVENTIONS Patients were treated with either zotarolimus or everolimus eluting stents. The patient population was divided according to treatment of bifurcation or non-bifurcation lesions and clinical outcomes were compared between groups. MAIN OUTCOMES MEASURES Clinical outcomes within 2-year follow-up. RESULTS A total of 2265 patients were included in the present analysis. Two-year follow-up data were available in 2223 patients: 1838 patients in the non-bifurcation group and 385 patients in the bifurcation group. At 2-year follow-up the bifurcation and the non-bifurcation lesion groups showed no significant differences in terms of cardiac death (2.3 vs 2.1, p=0.273), target lesion failure (9.7% vs 13.8%, p=0.255), major adverse cardiac events (11.5% vs 15.1%, p=0.305), target lesion revascularisation (4.7% vs 6.0%, p=0.569), and definite or probable stent thrombosis (1.6% vs 1.8%, p=0.419). CONCLUSIONS The use of second generation DES for the treatment of coronary bifurcation lesions was associated with similar long term mortality and clinical outcomes compared with non-bifurcation lesions.

The edge vascular response following implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold and the XIENCE V metallic everolimus-eluting stent. First serial follow-up assessment at six months and two years: insights from the first-in-man ABSORB Cohort B and SPIRIT II trials

AIMS To assess serially the edge vascular response (EVR) of a bioresorbable vascular scaffold (BVS) compared to a metallic everolimus-eluting stent (EES). METHODS AND RESULTS Non-serial evaluations of the Absorb BVS at one year have previously demonstrated proximal edge constrictive remodelling and distal edge changes in plaque composition with increase of the percent fibro-fatty (FF) tissue component. The 5 mm proximal and distal segments adjacent to the implanted devices were investigated serially with intravascular ultrasound (IVUS), post procedure, at six months and at two years, from the ABSORB Cohort B1 (n=45) and the SPIRIT II (n=113) trials. Twenty-two proximal and twenty-four distal edge segments were available for analysis in the ABSORB Cohort B1 trial. In the SPIRIT II trial, thirty-three proximal and forty-six distal edge segments were analysed. At the 5-mm proximal edge, the vessels treated with an Absorb BVS from post procedure to two years demonstrated a lumen loss (LL) of 6.68% (-17.33; 2.08) (p=0.027) with a trend toward plaque area increase of 7.55% (-4.68; 27.11) (p=0.06). At the 5-mm distal edge no major changes were evident at either time point. At the 5-mm proximal edge the vessels treated with a XIENCE V EES from post procedure to two years did not show any signs of LL, only plaque area decrease of 6.90% (-17.86; 4.23) (p=0.035). At the distal edge no major changes were evident with regard to either lumen area or vessel remodelling at the same time point. CONCLUSIONS The IVUS-based serial evaluation of the EVR up to two years following implantation of a bioresorbable everolimus-eluting scaffold shows a statistically significant proximal edge LL; however, this finding did not seem to have any clinical implications in the serial assessment. The upcoming imaging follow-up of the Absorb BVS at three years is anticipated to provide further information regarding the vessel wall behaviour at the edges.

The Regulatory Framework for Nanomaterials at a Global Level: SAICM and WTO Insights

The regulation of nanomaterials is being discussed at various levels. This article offers a historical description of governmental activities concerning the safety of nanomaterials at the United Nations (UN) level since 2006, with a focus on the UN Strategic Approach to International Chemicals Management (SAICM). The outcomes of the SAICM process were a nanospecific resolution and the addition of new activities on nanotechnologies and manufactured nanomaterials to the SAICM’s Global Plan of Action. The article discusses the implications of these decisions for multilateral environmental agreements. In addition, it studies the consequences of the regulation of nanotechnologies activities on trade governance, in particular the relationship between the SAICM to the legally binding World Trade Organization (WTO) agreements (notably the General Agreement on Tariffs and Trade and the Agreement on Technical Barriers to Trade). The article concludes that the SAICM decisions on manufactured nanomaterials are compatible with WTO law.

Environment and climate of the last 51,000 years – new insights from the Potrok Aike maar lake Sediment Archive Drilling prOject (PASADO)

In this introductory paper we summarize the history and achievements of the Potrok Aike maar lake Sediment Archive Drilling prOject (PASADO), an interdisciplinary project embedded in the International Continental Scientific Drilling Program (ICDP). The stringent multiproxy approach adopted in this research combined with radiocarbon and luminescence dating provided the opportunity to synthesize a large body of hydrologically relevant data from Laguna Potrok Aike (southern Patagonia, Argentina). At this site, lake level was high from 51 ka until the early Holocene when the Southern Hemisphere Westerlies (SHW) were located further to the north. At 9.3 ka cal. BP the SHW moved southward and over the latitude of the study area (52 degrees S) causing a pronounced negative water balance with a lake level decrease of more than 50 m. Two millennia later, the SHW diminished in intensity and lake level rose to a subsequent maximum during the Little Ice Age. Since the 20th century, a strengthening of the SHW increased the evaporative stress resulting in a more negative water balance. A comparison of our data with other hydrological fluctuations at a regional scale in south-eastern Patagonia, provides new insights and also calls for better chronologies and high-resolution records of climate variability.

The Regulatory Framework for Nanomaterials at a Global Level: SAICM and WTO Insights

The regulation of nanomaterials is being discussed at various levels. This article offers a historical description of governmental activities concerning the safety of nanomaterials at the United Nations (UN) level since 2006, with a focus on the UN Strategic Approach to International Chemicals Management (SAICM). The outcomes of the SAICM process were a nanospecific resolution and the addition of new activities on nanotechnologies and manufactured nanomaterials to the SAICM’s Global Plan of Action. The article discusses the implications of these decisions for multilateral environmental agreements. In addition, it studies the consequences of the regulation of nanotechnologies activities on trade governance, in particular the relationship between the SAICM to the legally binding World Trade Organization (WTO) agreements (notably the General Agreement on Tariffs and Trade and the Agreement on Technical Barriers to Trade). The article concludes that the SAICM decisions on manufactured nanomaterials are compatible with WTO law.

Adolescence and parental history of alcoholism: insights from the sleep EEG

BACKGROUND Disrupted sleep is a common complaint of individuals with alcohol use disorder and in abstinent alcoholics. Furthermore, among recovering alcoholics, poor sleep predicts relapse to drinking. Whether disrupted sleep in these populations results from prolonged alcohol use or precedes the onset of drinking is not known. The aim of this study was to examine the sleep electroencephalogram (EEG) in alcohol-naïve, parental history positive (PH+), and negative (PH-) boys and girls. METHODS All-night sleep EEG recordings in 2 longitudinal cohorts (child and teen) followed at 1.5 to 3 year intervals were analyzed. The child and teen participants were 9/10 and 15/16 years old at the initial assessment, respectively. Parental history status was classified by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria applied to structured interviews (DIS-IV) resulting in 14 PH- and 10 PH+ children and 14 PH- and 10 PH+ teens. Sleep data were visually scored in 30-second epochs using standard criteria. Power spectra were calculated for EEG derivations C3/A2, C4/A1, O2/A1, O1/A2 for nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. RESULTS We found no difference between PH+ and PH- individuals in either cohort for any visually scored sleep stage variable. Spectral power declined in both cohorts across assessments for NREM and REM sleep in all derivations and across frequencies independent of parental history status. With regard to parental history, NREM sleep EEG power was lower for the delta band in PH+ teens at both assessments for the central derivations. Furthermore, power in the sigma band for the right occipital derivation in both NREM and REM sleep was lower in PH+ children only at the initial assessment. CONCLUSIONS We found no gross signs of sleep disruption as a function of parental history. Modest differences in spectral EEG power between PH+ and PH- children and teens indicate that a marker of parental alcohol history may be detectable in teens at risk for problem drinking.

At the Interface of Culture, Development, and Forests: Insights from Bolivia and Kenya

The first part summarises the origins, definitions and debates around the general notions of development, culture and associated more specific concepts such as identity, tradition, exogenous and endogenous knowledge, institutions, governance or territoriality. A second part highlights how culture and development got related to the debates around sustainable governance of natural resources and forests. The third part illustrates on the basis of a case study from Kenya and Bolivia how culture as a transversal element of forest governance is expressed in empirical terms. Moreover it is shown how the cultural dimension affects positively or negatively the outcomes of culturally shaped forest governance outcomes and the role these effects play in shaping the sustainability of the socio-ecological systems of forests in Africa and South America.

Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: insights from the PLATelet inhibition and patient outcomes (PLATO) trial

BACKGROUND Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. METHODS Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG. CONCLUSIONS Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

AIMS Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. METHODS Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. RESULTS A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). CONCLUSION Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD.

A propensity score-matched comparison between Cardia and Amplatzer PFO closure devices - insights from the SOLUTION registry (Swiss percutaneOus patent foramen ovale cLosUre in recurrent clinical events prevenTION)

Aims: To compare clinical outcome of Amplatzer PFO (APFO) to Cardia PFO (CPFO) occluder. Percutaneous patent foramen ovale (PFO) closure prevents stroke recurrence in stroke due to paradoxical embolism. Methods and results: The primary endpoint was a composite of stroke, TIA, or peripheral embolism at follow-up. The secondary endpoint was residual shunt. Outcome was compared among 934 (APFO: 712; CPFO: 222) patients, and in 297 propensity score-matched patients. The primary endpoint occurred in 29 patients (0.71/100 patient-years): four (2%) with the CPFO (0.31/100 patient-years), and 25 (4%) with the APFO (0.89/100 patient-years) (p=0.20). Residual shunt at six months was more frequent with the CPFO (31% versus 9%, p<0.001). No differences in residual shunts were seen at the last available echocardiographic follow-up (9±18 months): APFO 11%, CPFO 14%, p=0.22. Conclusions: This study suggests that PFO closure with APFO or CPFO is equally effective for the prevention of recurrent events. Residual shunt was more frequent at six months with CPFO, but was similar to APFO at later follow-up.