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Background ST Segment Elevation Acute myocardial infarction (STEMI) preferred treatment is culprit artery reperfusion with primary percutaneous coronary intervention (PPCI). We ought to analyze the benefit of early reperfusion vs. optimal medical therapy in STEMI before and after the set-up of a regional STEMI network that prioritizes PPCI. Methods Between January 2002 and December 2013, 1268 STEMI patients were consecutively admitted in a University Hospital. Patients were classified in two groups: pre-STEMI Network (January 2002–June 2009; n  = 670) and post-STEMI network (July 2009–December 2013; n  = 598). Vital status was available at 2-year follow-up. Results The STEMI network increased reperfusion (89.2% vs 64.4%, p  < 0.001) mainly using PCI (99.0% vs 43.9%, p  < 0.001). In univariate analysis, in-hospital mortality was significantly lower in the post-STEMI network period (2.51% vs. 7.16%, p  < 0.001). After multivariate adjustment, including age, sex, comorbidities, severity and reperfusion therapy, a trend to a lower in-hospital mortality was observed (post-Network OR: 0.50, 95% CI:0.16–1.59, p  = 0.24); this trend disappeared when optimal medical therapy was included in the model (post-Network OR: 1.14, 95% CI:0.32–4.08, p  = 0.840). No differences in 2-year mortality were observed (post-Network HR: 0.83; CI 95%: 0.55–1.25, p  = 0.37). Conclusion A STEMI network with PPCI 24/7 improved reperfusion therapy, resulting in an increase on PPCI. Despite in-hospital mortality decreased with a STEMI network, 2-year mortality remained similar in both periods, pre- and post-Network. Optimal medical therapy could be as important as reperfusion therapy in a STEMI reperfusion network.

ObjectivesGuidelines recommending 12-month dual antiplatelet therapy (DAPT) in patients with ST-elevation acute coronary syndrome (STEACS) undergoing percutaneous coronary intervention (PCI) were published in year 2012. We aimed to describe the influence of guideline implementation on the trend in 12-month persistence with DAPT between 2010 and 2015 and to evaluate its relationship with DAPT duration regimens recommended at discharge from PCI hospitals.DesignObservational study based on region-wide registry data linked to pharmacy billing data for DAPT follow-up.SettingAll PCI hospitals (10) belonging to the acute myocardial infarction (AMI) code network in Catalonia (Spain).Participants10 711 STEACS patients undergoing PCI between 2010 and 2015 were followed up.Primary and secondary outcome measuresPrimary outcome was 12-month persistence with DAPT. Calendar year quarter, publication of guidelines, DAPT duration regimen recommended in the hospital discharge report, baseline patient characteristics and significant interactions were included in mixed-effects logistic regression based interrupted time-series models.ResultsThe proportion of patients on-DAPT at 12 months increased from 58% (56–60) in 2010 to 73% (71–75) in 2015. The rate of 12-month persistence with DAPT significantly increased after the publication of clinical guidelines with a time lag of 1 year (OR=1.20; 95% CI 1.11 to 1.30). A higher risk profile, more extensive and complex coronary disease, use of drug-eluting stents (OR=1.90; 95% CI 1.50 to 2.40) and a 12-month DAPT regimen recommendation at discharge from the PCI hospital (OR=5.76; 95% CI 3.26 to 10.2) were associated with 12-month persistence.ConclusionPersistence with 12-month DAPT has increased since publication of clinical guidelines. Even though most patients were discharged on DAPT, only 73% with potential indication were on-DAPT 12 months after PCI. A guideline-based recommendation at PCI hospital discharge was highly associated with full persistence with DAPT. Establishing evidence-based, common prescribing criteria across hospitals in the AMI-network would favour adherence and reduce variability.

Macrourid fish are one of the most abundant marine species on continental margins worldwide. Although they play an important role in the ecosystem, little is known about their overall biology. We report here a large data set of the most abundant macrourid in Mediterranean waters, Trachyrincus scabrus , showing the main population and reproductive characteristics. The study was based on 3,239 specimens collected between 300 and 1,500 m depth on the northwestern Mediterranean in 2003–2004 and 2008–2009. The population showed a depth-related structure with the largest individuals at 1,100 m depth and the smallest (i.e., immature) at shallower depths. Macroscopic and microscopic analyses of the gonads showed that T. scabrus has a highly seasonal reproductive pattern. Spawning females were found during winter when the organic matter fluxes were highest on the continental slope. T. scabrus is a batch spawner with group-synchronous oocyte development and present low average fecundity of 14,191 oocytes.

The population structure and reproductive biology of deep-water continental margin Cynoglossidae is poorly known. Here, we focused on two highly abundant species of the upper slope of the NW Mediterranean Sea, Symphurus nigrescens and S. ligulatus. Megafaunal sampling of 37 hauls was conducted between April 2003 and May 2004 in the Blanes canyon and the adjacent open slope between 300–1500 m depth. The differential bathymetric distribution between the two species was surveyed by standardizing catch data per unit of swept surface and by pooling resulting densities by 100 m depth interval. Females of both species were classified into a five-stage maturity scale according to their external appearance and their gonads dissected for histological analysis. The analysis of the species' bathymetric distribution revealed a differential and only partial overlap. In both species, an increase in size with depth was observed coinciding with the dominance of females in deeper depth strata. The shallower species, S. nigrescens showed a marked spawning period with a peak in summer. In contrast, the deeper-living species, S. ligulatus, presented a longer spawning period ranging from spring to autumn. Moreover, histological examination demonstrated that the ovaries of both species had an asynchronous organization. Present results on spatial-temporal size frequency distribution, spawning temporality and oocyte size are discussed assuming interspecific competition and the different environmental conditions related to their bathymetric distribution.

The distributions of 2 congenerics, sympatric species of Mullidae (Mullus surmuletus and M. barbatus) were studied by means of abundance and length frequencies, obtained in experimental trawl surveys carried out in the springtime (1994 to 1998) throughout the Spanish Mediterranean area. From the data obtained we compared the spatial segregation between these species in relation to the bottom type and to the depth of their habitat. Although M. barbatus was the most abundant species throughout the sampling area (except at the shallowest rough-bottom sites), spatial segregation was observed between the 2 species, with the ratio between the species varying according to the bottom type on which they lived. M. barbatus showed maximum abundance and frequency on muddy bottoms in waters between 50 and 200 m deep. For M. surmuletus, maximum density and frequency were at a shallower depth (between 10 and 50 m) and largely on rough bottoms. At overlap sites, the relative abundance of M. barbatus increased on muddy bottoms and decreased on rocky and sandy bottoms. The size frequencies encountered for both species were made up by preadults and adults. Significant size differences between species existed in all the bathymetric strata studied. In all cases, except the more coastal muddy bottom stratum, M. surmuletus had a range of sizes and a mean size greater than M. barbatus. The structural heterogeneity of the Spanish continental shelf gave rise to a distribution characterised by patches. M. barbatus had a clear preference for the areas where the shelf became wider, and M. surmuletus was more abundant and frequent in narrow shelf areas

Introduction: Chondrichthyans (sharks, batoids and chimaeras) play key roles in the regulation of marine food webs dynamics. However, more than half of the assessed species in the Mediterranean are threatened, primarily by fishing pressure and compounded by habitat degradation and climate change. Nevertheless, there is an important knowledge gap in identifying the underlying drivers of their community structure and spatial distribution. Methods and Results: We provide insights into the current bycatch rates of chondrichthyans in the western Mediterranean commercial bottom trawling fishery by accurately depicting the unaltered practices of the local fleet. A total of 17 species were recorded in the studied fishing grounds (ranging from 50 to 800 m deep), including 7 sharks, 9 batoids, and 1 chimaera, although the total catch was dominated by few species. Furthermore, we tested the effect of environmental and fishing-related factors on multiple community descriptors by using analysis of community structure (multidimensional scaling and analysis of similitude) and generalized linear mixed models to further understand the drivers of the chondrichthyan community distribution and structure. This study revealed the importance of combining environmental and anthropogenic drivers to further understand the spatial distribution patterns of chondrichthyan communities. Our results indicate that depth was the main driver of the community structure, with deeper areas within the fishing grounds hosting a higher diversity. Sea bottom temperature and substrate type also influenced the distribution of the community, with substrate effects changing depending on the intensity of fishing pressure. In all cases, density, biomass, and diversity of chondrichthyans were negatively impacted by increasing fishing effort. Discussion: Understanding the drivers of the structure and distribution of the chondrichthyan community is crucial to understand the potential impacts that increased fishing pressure, habitat loss and global change may entail. The ongoing challenges that the Mediterranean chondrichthyans and their ecosystems are facing highlights the need for continued monitoring and improved chondrichthyan-focused fisheries management.

Background and importanceAlirocumab is a monoclonal antibody approved for the treatment of hypercholesterolaemia but long term clinical data are still limited.Aim and objectivesTo assess the long term efficacy, safety and adherence to alirocumab after 96 weeks of treatment in a cohort of patients with dyslipidaemia.Material and methodsThis was a retrospective observational study performed in a university tertiary hospital. All patients starting alirocumab before September 2017 in our institution and treated for at least 96 weeks were included.Demographic, clinical and alirocumab data were collected. Treatment efficacy was calculated as per cent reduction in low density lipoprotein cholesterol (LDL-c) from baseline to 96 weeks after treatment initiation. Adverse effects were collected and classified according to the common terminology criteria for adverse events (CTCAE) V.4.0 grades. Mean adherence at 96 weeks was calculated by the medication possession ratio based on pharmacy refill records.ResultsThirty-three patients started alirocumab treatment in 2017 and 31 (93.9%) were still on treatment after 96 weeks. Two patients (6.1%) discontinued therapy: one due to an active malignancy and one due to loss of follow-up.Patient characteristics were 58.1% men with a median (IQR) age of 65 (11) years. Alirocumab dose was 75 mg/2 weeks in 87.1% of patients and 150 mg/2 weeks in 12.9%. Secondary prevention was 83.9% and there was a high cardiovascular risk in 80.6%. Type of hypercholesterolaemia was heterozygous familial in 29.0% of patients, polygenic in 67.7% and combined familial hyperlipidaemia in 3.2%. Statin intolerance was found in 38.7% of patients. Comorbidities included diabetes mellitus 19.4%, hypertension 54.8% and smoking 3.2%.Median (range) adherence was 100% (81.7–100%) (only 2 patients (6.5%) with adherence <90%). Median (IQR) reduction in LDL-c reduction was 59.5 (22.6)%. Only one patient did not have a reduction in LDL from baseline (adherence 82%). A high cardiovascular risk was the only patient factor associated with 100% adherence (p=0.034). Mild adverse effects were present in 19.3% of patients (27.3% constipation, 18.2% flu-like syndrome, 18.2% pruritus and other (dizziness, palpitations, headache, dysgeusia) 9.1% each). All adverse effects (100%) were classified as CTCAE grade 1.Conclusion and relevanceMore than 90% of patients starting alirocumab persisted with treatment for 96 weeks after initiation. Alirocumab showed good long term efficacy with a median reduction in LDL of >50%. It was also well tolerated because all reported adverse events were mild and did not lead to any treatment discontinuation.References and/or acknowledgementsNo conflict of interest.

BackgroundAlirocumab and evolocumab are two monoclonal antibodies proproteinconvertasesubtilisin/kexin type 9 inhibitors (iPCSK9) approved for the treatment of hypercholesterolaemia.PurposeEvaluation of the efficacy, safety and patient acceptance of treatment with iPCSK9 in a cohort of patients with dyslipidaemia.Material and methodsRetrospective observational study performed in a university hospital. Included patients started with iPCSK9 therapy from September 2016 to June 2018.Data collected: demographic; iPCSK9 dose; prevention; indication; cardiovascular risk factors (CVRF) (excluding dyslipidaemia), cardiovascular risk (CVR) (by ESC 2016 guidelines); and statin intolerance.At baseline (pre) and 6–12 weeks after starting treatment (post), LDL value and concomitant lipid lowering agents (LLA) were collected.Additionally, reported adverse events and patient treatment were evaluated through a validated survey1 during the pharmaceutical visit.Statistics: Categorical variables: n (%), Fisher’s exact test.Quantitative variables: mean ±SD/median(rank), Mann–Whitney U test.ResultsAbstract 4CPS-024 Table 1 Baseline Alirocumab (n= 48) Evolocumab (n= 10) P-value Male29 (60.4%)9 (90.0%)Age62.6±8.655.8±8.8Initial dose:75 mg/2 weeks40 (83.3%)-Secondary prevention38 (79.2%)10 (100.0%)IndicationPolygenic-hypercholesterolaemia31 (64.6%)8 (80.0%)Familial-hypercholesterolaemia14 (29.2%)1 (10.0%)Other3 (6.3%)1 (10.0%)CVRFNone13 (27.1%)1 (10.0%)117 (35.4%)2 (20.0%)≥218 (37.5%)7 (70.0%)High-risk CVR38 (79.2%)10 (100.0%)Statin intolerance25 (52.1%)4 (40.0%)Pre LLA45 (93.7%)9 (90.0%) LDLLDL (mg/dL)Pre138.5 (92–308)111.5 (92–216)0.067Post59 (17–223)28.5 (4–59)0.002% LDL reduction57.7 (13.2–87.5)75.2 (47.3–97.3)0.015LDL post<70 mg/dL29 (60.4%)10 (100%)0.022Adverse events4 (8.3%)*0 (0%)1.000 Treatment acceptanceVery acceptable40 (83.3%)9 (90.0%)Quite acceptable6 (12.5%)0 (0%)Acceptable2 (4.2%)1 (10.0%)*Pseudogrippal syndrome (3) and constipation (1).All patients decreased LDL except 1 patient on alirocumab who was non-adherent.Post: 15 treatment changes in 13 (27.1%) patients with alirocumab (five (33.3%) alirocumab dose increase, seven (46.7%) other LLA introduction/dose increase, three (20.0%) other LLA suspension/dose decrease). With evolocumab patients, only 1 stopped ezetimibe.After the survey, all patients desired to continue with iPCSK9.ConclusionAfter 6–12 weeks of iPCSK9 treatment, all patients reduced LDL level except 1 who was non-adherent. The LDL reduction ranged between 54%–71% and all patients on evolocumab achieved a LDL <70 mg/dL.The tolerability was excellent and only mild adverse events in about 8% of patients were experienced.A high acceptance of both alirocumab and evolocumab was reported by all patients who would continue with iPCSK9 treatment.References and/or acknowledgementsNo conflict of interest.

Background When the homeostasis of the central nervous system (CNS) is altered, microglial cells become activated displaying a wide range of phenotypes that depend on the specific site, the nature of the activator, and particularly the microenvironment generated by the lesion. Cytokines are important signals involved in the modulation of the molecular microenvironment and hence play a pivotal role in orchestrating microglial activation. Among them, interleukin-6 (IL-6) is a pleiotropic cytokine described in a wide range of pathological conditions as a potent inducer and modulator of microglial activation, but with contradictory results regarding its detrimental or beneficial functions. The objective of the present study was to evaluate the effects of chronic IL-6 production on the immune response associated with CNS-axonal anterograde degeneration. Methods The perforant pathway transection (PPT) paradigm was used in transgenic mice with astrocyte-targeted IL6-production (GFAP-IL6Tg). At 2, 3, 7, 14, and 21 days post-lesion, the hippocampal areas were processed for immunohistochemistry, flow cytometry, and protein microarray. Results An increase in the microglia/macrophage density was observed in GFAP-IL6Tg animals in non-lesion conditions and at later time-points after PPT, associated with higher microglial proliferation and a major monocyte/macrophage cell infiltration. Besides, in homeostasis, GFAP-IL6Tg showed an environment usually linked with an innate immune response, with more perivascular CD11b + /CD45 high /MHCII + /CD86 + macrophages, higher T cell infiltration, and higher IL-10, IL-13, IL-17, and IL-6 production. After PPT, WT animals show a change in microglia phenotype expressing MHCII and co-stimulatory molecules, whereas transgenic mice lack this shift. This lack of response in the GFAP-IL6Tg was associated with lower axonal sprouting. Conclusions Chronic exposure to IL-6 induces a desensitized phenotype of the microglia.