Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome

BACKGROUND: Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH). OBJECTIVES: This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing. METHODS: Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Dutch Lipid Clinic (DLC) and Simon Broome (SB) FH clinical criteria were also applied. RESULTS: The prevalence of genetically confirmed FH was 8.7% (95% confidence interval [CI]: 4.3% to 16.4%; n = 9); 29% (95% CI: 18.5% to 42.1%; n = 18) of patients without FH variants had a score highly suggestive of polygenic hypercholesterolemia. The prevalence of probable to definite FH according to DLC criteria was 27.2% (95% CI: 19.1% to 37.0%; n = 28), whereas SB criteria identified 27.2% of patients (95% CI: 19.1% to 37.0%; n = 28) with possible to definite FH. DLC and SB algorithms failed to diagnose 4 (44%) and 3 (33%) patients with genetically confirmed FH, respectively. Cascade genetic testing in first-degree relatives identified 6 additional individuals with FH. CONCLUSIONS: The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%). FH clinical algorithms do not accurately classify patients with FH. Genetic testing should be advocated in young patients with ACS and high LDL-C levels to allow prompt identification of patients with FH and relatives at risk.This research was supported in part by the Instituto de Salud Carlos III (grants RD012/0042/0066 and CB16/11/00432), Spanish Ministry of Economy and Competitiveness (grant SAF2015-71863-REDT), and Alexion through an Investigator Initiated Research Grant. Grants from the Instituto de Salud Carlos III and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 European Regional Development Fund (FEDER), "A way of making Europe." The sponsors played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Drs. Castillo, Lluis-Ganella, and Quintana are employees of Gendiag.exe/Ferrer inCode.S

SOCIB: the impact of new marine infrastructures in understanding and forecasting the coastal oceans: some examples from the Balearic Islands in the Mediterranean Sea

New monitoring technologies are being progressively implemented in coastal ocean observatories. As an example, gliders allow high resolution sampling, showing the existence of new features, such as submesoscale eddies with intense vertical motions that significantly affect upper ocean biogeochemical exchanges, an issue of worldwide relevance in a climate change context. SOCIB, is one of such systems, a new facility of facilities (covering from the coast to the open sea, and including among others a nearshore beach monitoring facility, HF radar, gliders and AUV’s, moorings, satellite, drifters and ARGO profilers, modelling), a scientific and technological infrastructure which is providing free, open, quality controlled and timely streams of oceanographic and coastal data and also modelling services. SOCIB takes profit of the strategic position of the Balearic Island at the Atlantic/Mediterranean transition area, one of the ‘hot spots’ of biodiversity in the world’s oceans. As an example of on-going SOCIB operations, since January 2011 sustained glider operations are in place in the Ibiza and Mallorca channels. The data centre is the core of SOCIB. The data management system created for gliders is an example of the new informatics capabilities for real time definition of mission planning, including adaptive sampling and real time monitoring using a Web tool that allows quick visualization and download. This type of new infrastructures, combined with new technologies and careful scientific analysis will allow new ways of international cooperation leading to major science breakthroughs in the very near future and new ways of science based coastal and ocean management.Peer Reviewe

High resolution altimeter gridded fields for coastal and regional studies: applications in the Western Mediterranean

Previousstudies(Pascualetal.2006)haveshownthatthemergingofmultiplealtimetermissionsprovideimproveddescriptionofthemesoscalevariabilitybuttheyhavealsopointedouttatthepresentconfigurationstilllacksofenoughresolutionforcorrectlysamplingregionalandcoastalfeatures.Inthiscontext,wedevelopandtestalternativemethodstogeneratehighresolutionaltimetermapsbyusingatwostepmethodinwhichsmallerscalesareaddedclosetohealtimetertracks.Peer Reviewe

Post myocardial infarction left bundle branch block disappearing with levosimendan

A 51 year old man presented with a Killip III acute anterior myocardial infarction due to a very late thrombosis of a stent in the proximal left anterior descending artery. The EKG after being admitted to the coronary care unit following primary PCI showed a new onset left bundle branch block (LBBB) (Figure 1: A). In spite of the initial favorable evolution throughout the first two days under treatment with diuretics and ACE inhibitors, the LBBB persisted. During the third day congestive signs worsened, together with a reduction in diuresis and worsening of the renal function. At that point, treatment with 0.1 mcg/kg/ min levosimendan perfusion was administered for 24 hours. During the first hours of perfusion the LBBB disappeared in the monitor and the EKG at the end of the perfusion showed narrow QRS with persistent ST elevation (Figure 1: B)

[ES] Avances recientes en la caracterización de la mesoescala en la cuenca mediterránea occidental: Sinergias entre altimetría y otros sistemas de observación

Satellite altimetry is a key component of the global observing system and plays a major role in the study of the mesoscale processes that drive most of the ocean circulation variability at middle and high latitudes. However, satellite altimetry alone provides only surface information at a limited spatio-temporal resolution. To address these limitations and to better describe the mesoscale three-dimensional variability, it is necessary to complement altimetry data with additional remote and in situ measurements. This study provides an update of the recent advances in the study of the mesoscale variability using a combination of altimetry and other independent observations, with an emphasis on the results obtained for the western Mediterranean Sea. The circulation in this area is complex because of the presence of multiple interacting scales, including basin-scale, sub-basin-scale and mesoscale structures. Thus, characterizing these processes requires high-resolution observations and multi-sensor approaches. Accordingly, multi-platform experiments and analyses have been designed and undertaken in the different sub-basins of the western Mediterranean Sea. These studies have demonstrated the advantages of synergetic approaches that use a combination of observation techniques and are able to resolve different spatio-temporal scales with the aim of better understanding mesoscale dynamics.Peer Reviewe

The Impact of New Multi-platform Observing Systems in Science, Technology Development and Response to Society Needs; from Small to Large Scales

Tintoré, Joaquín et al.Capítulo en: MORENO-DÍAZ, Roberto; PICHLER, Franz; QUESADA-ARENCIBIA, Alexis (eds.). Computer Aided Systems Theory-EUROCAST 2013 : 14th International Conference, Las Palmas de Gran Canaria, Spain, February 10-15, 2013. Revised Selected Papers, Part II. Berlin: Springer, 2013, p.341-348 (Lecture Notes in Computer Science ; 8112)New monitoring technologies are key components of ocean observatories, also called marine research infrastructures being implemented in the worlds oceans. As a result, new capabilities to characterise, in quasi-real time, the ocean state and its variability at small scales exist today. The challenge is the integration of theses multiplatform observing and forecasting systems to (a) monitor the variability at small scales (e.g. mesoscale/weeks) in order to (b) resolve the sub-basin/seasonal and inter-annual variability and by this (c) establish the decadal variability, understand the associated biases and correct them. The challenge is also to change focus and now monitor from small to large scales. SOCIB is leading this new small to large-scale multi-platform approach in ocean observation. Some examples are presented and discussed together with initial ideas on the optimal design of an observational network in the world oceans, responding to science priorities, technology development and response to strategic society needsPeer Reviewe

Short- and Long-Term Prognostic Relevance of Cardiogenic Shock in Takotsubo Syndrome: Results From the RETAKO Registry.

This study sought to describe the incidence, determinants, and prognostic impact of cardiogenic shock (CS) in takotsubo syndrome (TTS). TTS can be associated with severe hemodynamic instability. The prognostic implication of CS has not been well characterized in large studies of TTS. We analyzed patients with a definitive TTS diagnosis (modified Mayo criteria) who were recruited for the National RETAKO (Registry on Takotsubo Syndrome) trial from 2003 to 2016. Cox and competing risk regression models were used to identify factors associated with mortality and recurrences. A total of 711 patients were included, 81 (11.4%) of whom developed CS. Male sex, QTc interval prolongation, lower left ventricular ejection fraction at admission, physical triggers, and presence of "a significant" left intraventricular pressure gradient, were associated with CS (C index = 0.85). In-hospital complication rates, including mortality, were significantly higher in patients with CS. Over a median follow-up of 284 days (interquartile range: 94 to 929 days), CS was the strongest independent predictor of long-term, all-cause mortality (hazard ratio [HR]: 5.38; 95% confidence interval [CI]: 2.60 to 8.38); cardiovascular (CV) death (sub-HR: 4.29; 95% CI: 2.40 to 21.2), and non-CV death (sub-HR: 3.34; 95% CI: 1.70 to 6.53), whereas no significant difference in the recurrence rate was observed between groups (sub-HR: 0.76; 95% CI: 0.10 to 5.95). Among patients with CS, those who received beta-blockers at hospital discharge experienced lower 1-year mortality compared with those who did not receive a beta-blocker (HR: 0.52; 95% CI: 0.44 to 0.79; pinteraction = 0.043). CS is not uncommon and is associated with worse short- and long-term prognosis in TTS. CS complicating TTS may constitute a marker of underlying disease severity and could identify a masked heart failure phenotype with increased vulnerability to catecholamine-mediated myocardial stunning

Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial

IMPORTANCE Dysregulated metabolism is a hallmark of renal cell carcinoma (RCC). Glutaminase is a key enzyme that fuels tumor growth by converting glutamine to glutamate. Telaglenastat is an investigational, first-in-class, selective, oral glutaminase inhibitor that blocks glutamine utilization and downstream pathways. Preclinically, telaglenastat synergized with cabozantinib, a VEGFR2/MET/AXL inhibitor, in RCC models.OBJECTIVE To compare the efficacy and safety of telaglenastat plus cabozantinib (Tela + Cabo) vs placebo plus cabozantinib (Pbo + Cabo).DESIGN, SETTING, AND PARTICIPANTS CANTATA was a randomized, placebo-controlled, double-blind, pivotal trial conducted at sites in the US, Europe, Australia, and New Zealand. Eligible patients had metastatic clear-cell RCC following progression on 1 to 2 prior lines of therapy, including 1 or more antiangiogenic therapies or nivolumab plus ipilimumab. The data cutoff date was August 31, 2020. Data analysis was performed from December 2020 to February 2021.INTERVENTIONS Patients were randomized 1:1 to receive oral cabozantinib (60mg daily) with either telaglenastat (800mg twice daily) or placebo until disease progression or unacceptable toxicity.MAIN OUTCOMES AND MEASURES The primary end pointwas progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1) assessed by blinded independent radiology review.RESULTS A total of 444 patients were randomized: 221 to Tela + Cabo (median [range] age, 61 [21-81] years; 47 [21%] women and 174 [79%] men) and 223 to Pbo + Cabo (median [range] age, 62 [29-83] years; 68 [30%] women and 155 [70%] men). A total of 276 (62%) patients had received prior immune checkpoint inhibitors, including 128 with prior nivolumab plus ipilimumab, 93 of whom had not received prior antiangiogenic therapy. Median progression-free survival was 9.2 months for Tela + Cabo vs 9.3 months for Pbo + Cabo (HR, 0.94; 95% CI, 0.74-1.21; P =.65). Overall response rates were 31% (69 of 221) with Tela + Cabo vs 28%(62 of 223) with Pbo + Cabo. Treatment-emergent adverse event (TEAE) rates were similar between arms. Grade 3 to 4 TEAEs occurred in 160 patients (71%) with Tela + Cabo and 172 patients (79%) with Pbo + Cabo and included hypertension (38 patients [17%] vs 40 patients [18%]) and diarrhea (34 patients [15%] vs 29 patients [13%]). Cabozantinib was discontinued due to AEs in 23 patients (10%) receiving Tela + Cabo and 33 patients (15%) receiving Pbo + Cabo.CONCLUSIONS AND RELEVANCE In this randomized clinical trial, telaglenastat did not improve the efficacy of cabozantinib in metastatic RCC. Tela + Cabo was well tolerated with AEs consistent with the known risks of both agents

Prognostic Utility of Society for Cardiovascular Angiography and Interventions Shock Stage Approach for Classifying Cardiogenic Shock Severity in Takotsubo Syndrome

Background Cardiogenic shock (CS) is a significant complication of Takotsubo syndrome (TTS), contributing to heightened mortality and morbidity. Despite this, the Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks validation in patients with TTS and CS. This study aimed to characterize a patient cohort with TTS using the SCAI staging system and assess its utility in cases of TTS complicated by CS. Methods and Results From a TTS national registry, 1591 consecutive patients were initially enrolled and stratified into 5 SCAI stages (A through E). Primary outcome was all‐cause in‐hospital mortality; secondary end points were TTS‐related in‐hospital complications and 1‐year all‐cause mortality. After exclusions, the final cohort comprised 1163 patients, mean age 71.0±11.8 years, and 87% were female. Patients were categorized across SCAI shock stages as follows: A 72.1%, B 12.2%, C 11.2%, D 2.7%, and E 1.8%. Significant variations in baseline demographics, comorbidities, clinical presentations, and in‐hospital courses were observed across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage showed a significant association with increased in‐hospital mortality (adjusted odds ratio: 1.77–29.31) compared with SCAI shock stage A. Higher SCAI shock stages were also associated with increased 1‐year mortality. Conclusions In a large multicenter patient cohort with TTS, the functional SCAI shock stage classification effectively stratified mortality risk, revealing a continuum of escalating shock severity with higher stages correlating with increased in‐hospital mortality. This study highlights the applicability and prognostic value of the SCAI staging system in TTS‐related CS

Las grandes infraestructuras de investigación, motor de conocimiento, de transferencia de productos tecnológicos y de tecnologías de gestión para el sector público y privado

Trabajo presentado en ForoTec2011, III Foro Tecnológico de las Islas Baleares, celebrado el 24 y 25 de noviembre de 2011 en Palma de Mallorca (España), y organizado por la Dirección General de Universidades, Investigación y Transferencia del Conocimiento del Govern de las Illes Balears, la Universitat de les Illes Balears y el Instituto de Innovación Empresarial de les Illes BalearsPeer Reviewe