Ciguatera poisoning in French Polynesia: A review of the distribution and toxicity of Gambierdiscus spp., and related impacts on food web components and human health.

Ciguatera Poisoning (CP) is a seafood poisoning highly prevalent in French Polynesia. This illness results from the consumption of seafood contaminated with ciguatoxins (CTXs) produced by Gambierdiscus, a benthic dinoflagellate. Ciguatera significantly degrades the health and economic well-being of local communities largely dependent on reef fisheries for their subsistence. French Polynesia has been the site of rich and active CP research since the 1960's. The environmental, toxicological, and epidemiological data obtained in the frame of large-scale field surveys and a country-wide CP case reporting program conducted over the past three decades in the five island groups of French Polynesia are reviewed. Results show toxin production in Gambierdiscus in the natural environment may vary considerably at a temporal and spatial scale, and that several locales clearly represent Gambierdiscus spp. "biodiversity hotspots". Current data also suggest the "hot" species G. polynesiensis could be the primary source of CTXs in local ciguateric biotopes, pending formal confirmation. The prevalence of ciguatoxic fish and the CTX levels observed in several locales were remarkably high, with herbivores and omnivores often as toxic as carnivores. Results also confirm the strong local influence of Gambierdiscus spp. on the CTX toxin profiles characterized across multiple food web components including in CP-prone marine invertebrates. The statistics, obtained in the frame of a long-term epidemiological surveillance program established in 2007, point towards an apparent decline in the number of CP cases in French Polynesia as a whole; however, incidence rates remain dangerously high in some islands. Several of the challenges and opportunities, most notably those linked to the strong cultural ramifications of CP among local communities, that need to be considered to define effective risk management strategies are addressed.

An oscillator-driven, time-resolved optical pump/NIR supercontinuum probe spectrometer.

We present a novel, to the best of knowledge, time-resolved, optical pump/NIR supercontinuum probe spectrometer suitable for oscillators. A NIR supercontinuum probe spectrum (850-1250 nm) is generated in a photonic crystal fiber, dispersed across a digital micromirror device (DMD), and then raster scanned into a single element detector at a 5 Hz rate. Dual modulation of pump and probe beams at disparate frequencies permits simultaneous measurement of both the bare reflectance R and its photoinduced change ΔR through lock-in detection, allowing for continuously self-normalized measurement of ΔR/R. Example data are presented on a germanium wafer sample that demonstrate for signals of order ΔR/R ∼ 10-3, a 2.87 nm spectral resolution and ≲400 fs temporal resolution pre-recompression, and comparable sensitivity to standard time-resolved, amplifier-based pump-probe techniques.

Geographical distribution, molecular and toxin diversity of the dinoflagellate species Gambierdiscus honu in the Pacific region.

An increase in cases of ciguatera poisoning (CP) and expansion of the causative species in the South Pacific region highlight the need for baseline data on toxic microalgal species to help identify new areas of risk and manage known hot spots. Gambierdiscus honu is a toxin producing and potential CP causing dinoflagellate species, first described in 2017. Currently no high-resolution geographical distribution, intraspecific genetic variation or toxin production diversity data is available for G. honu. This research aimed to further characterize G. honu by investigating its distribution using species-specific real-time polymerase chain reaction assays at 25 sites in an area spanning ∼8000 km of the Coral Sea/Pacific Ocean, and assessing intraspecific genetic variation, toxicity and toxin production of isolated strains. Assessment of genetic variation of the partial rRNA operon of isolates demonstrated no significant intraspecific population structure, in addition to a lack of adherence to isolation by distance (IBD) model of evolution. The detected distribution of G. honu in the Pacific region was within the expected tropical to temperate latitudinal ranges of 10° to -30° and extended from Australia to French Polynesia. In the lipophilic fractions, the neuroblastoma cell-based assay (CBA-N2a) showed no ciguatoxin (CTX)-like activity for nine of the 10 isolates, and an atypical pattern for CAWD233 isolate which showed cytotoxic activity in OV- and OV+ conditions. In the same way, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis confirmed no Pacific-CTXs (CTX-3B, CTX-3C, CTX-4A, CTX-4B) were produced by the ten strains. The CBA-N2a assessment of the hydrophilic fractions showed moderate to high cytotoxicity in both OV- and OV+ condition for all the strains showing a cytotoxic profile similar to that of gambierone. Indeed, this study is the first to show the cytotoxic activity of gambierone on mouse neuroblastoma cells while no cytotoxicity was observed when 44-MG was analysed at the same concentrations using the CBA-N2a. Analysis of the hydrophilic via LC-MS/MS confirmed production of gambierone in all isolates, ranging from 2.1 to 38.1 pg/cell, with 44-methylgambierone (44-MG) also produced by eight of the isolates, ranging from 0.3 to 42.9 pg/cell. No maitotoxin-1 was detected in any of the isolates. Classification of the G. honu strains according to the quantities of gambierone produced aligned with the classification of their cytotoxicity using the CBA-N2a. Finally, no maitotoxin-1 (MTX) was detected in any of the isolates. This study shows G. honu is widely distributed within the Pacific region with no significant intraspecific population structure present. This aligns with the view of microalgal populations as global metapopulations, however more in-depth assessment with other genetic markers could detect further structure. Toxicity diversity across 10 isolates assessed did not display any geographical patterns.

Direct Measurement of Helicoid Surface States in RhSi Using Nonlinear Optics.

Despite the fundamental nature of the edge state in topological physics, direct measurement of electronic and optical properties of the Fermi arcs of topological semimetals has posed a significant experimental challenge, as their response is often overwhelmed by the metallic bulk. However, laser-driven currents carried by surface and bulk states can propagate in different directions in nonsymmorphic crystals, allowing for the two components to be easily separated. Motivated by a recent theoretical prediction G. Chang et al., Phys. Rev. Lett. 124, 166404 (2020)PRLTAO0031-900710.1103/PhysRevLett.124.166404, we have measured the linear and circular photogalvanic effect currents deriving from the Fermi arcs of the nonsymmorphic, chiral Weyl semimetal RhSi over the 0.45-1.1 eV incident photon energy range. Our data are in good agreement with the predicted spectral shape of the circular photogalvanic effect as a function of photon energy, although the direction of the surface photocurrent departed from the theoretical expectation over the energy range studied. Surface currents arising from the linear photogalvanic effect were observed as well, with the unexpected result that only two of the six allowed tensor element were required to describe the measurements, suggesting an approximate emergent mirror symmetry inconsistent with the space group of the crystal.

Weyl-mediated helical magnetism in NdAlSi.

Emergent relativistic quasiparticles in Weyl semimetals are the source of exotic electronic properties such as surface Fermi arcs, the anomalous Hall effect and negative magnetoresistance, all observed in real materials. Whereas these phenomena highlight the effect of Weyl fermions on the electronic transport properties, less is known about what collective phenomena they may support. Here, we report a Weyl semimetal, NdAlSi, that offers an example. Using neutron diffraction, we found a long-wavelength helical magnetic order in NdAlSi, the periodicity of which is linked to the nesting vector between two topologically non-trivial Fermi pockets, which we characterize using density functional theory and quantum oscillation measurements. We further show the chiral transverse component of the spin structure is promoted by bond-oriented Dzyaloshinskii-Moriya interactions associated with Weyl exchange processes. Our work provides a rare example of Weyl fermions driving collective magnetism.

Ciguatera poisonings: A global review of occurrences and trends.

Ciguatera Poisoning (CP) is the most prevalent, phycotoxin related seafood poisoning across the globe, affecting between 10,000 and 50,000 people annually. This illness results from the consumption of seafood contaminated with lipid soluble toxins known as ciguatoxins (CTXs) that are produced by benthic dinoflagellates in the genera Gambierdiscus and Fukuyoa. The present work reviews the global occurrence of CP events and outbreaks, based on both scientific and gray literature. Ciguatera prevalence is significantly underestimated due to a lack of recognition of ciguatera symptoms, limited collection of epidemiological data on a global level, and reticence to report ciguatera in CP-endemic regions. Analysis of the time-series data available for a limited number of countries indicates the highest incidence rates are consistently reported from two historical CP-endemic areas i.e., the Pacific and Caribbean regions, a situation due in part to the strong reliance of local communities on marine resources. Ciguatera-related fatalities are rare (<0.1% of reported cases). The vast majority of outbreaks involve carnivorous fish including snappers, groupers, wrasses, and barracudas. Since 2000, an expansion of the geographical range of CP has been observed in several areas like Macaronesia and east and southeast Asia. In some of these locales, random surveys confirmed the presence of CTXs in locally sourced fish, consistent with the concurrent report of novel CP incidents (e.g., Canary Islands, Madeira, Selvagens Islands, New South Wales). One characteristic of outbreaks occurring in Asia is that they often present as large disease clusters due to group consumption of a single contaminated fish. Similar observations are reported from the Indian Ocean in the form of shark poisoning outbreaks which often lead to singular types of CP characterized by a high fatality rate. Other atypical forms of CP linked to the consumption of marine invertebrates also have been documented recently. Owing to the significant health, socioeconomic and socio-cultural impacts of ciguatera, there is an urgent need for increased, standardized, coordinated efforts in ciguatera education, monitoring and research programs. Several regional and international initiatives have emerged recently, that may help improve patients' care, data collection at a global scale, and risk monitoring and management capabilities in countries most vulnerable to CP's toxic threat.

Helicity-dependent photocurrents in the chiral Weyl semimetal RhSi.

Weyl semimetals are crystals in which electron bands cross at isolated points in momentum space. Associated with each crossing point (or Weyl node) is a topological invariant known as the Berry monopole charge. The circular photogalvanic effect (CPGE), whereby circular polarized light generates a helicity-dependent photocurrent, is a notable example of a macroscopic property that emerges directly from the topology of the Weyl semimetal band structure. Recently, it was predicted that the amplitude of the CPGE associated with optical transitions near a Weyl node is proportional to its monopole charge. In chiral Weyl systems, nodes of opposite charge are nondegenerate, opening a window of wavelengths where the CPGE resulting from uncompensated Berry charge can emerge. Here, we report measurements of CPGE in the chiral Weyl semimetal RhSi, revealing a CPGE response in an energy window that closes at 0.65 eV, in agreement with the predictions of density functional theory.

The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

Ciguatera poisoning in French Polynesia: insights into the novel trends of an ancient disease.

Ciguatera is a non-bacterial seafood poisoning highly prevalent in French Polynesia where it constitutes a major health issue and a major threat to food sustainability and food security for local populations. Ciguatera results from the bioaccumulation in marine food webs of toxins known as ciguatoxins, originating from benthic dinoflagellates in the genera Gambierdiscus and Fukuyoa. Ciguatera is characterized by a complex array of gastrointestinal, neurological and cardiovascular symptoms. The effective management of patients is significantly hampered by the occurrence of atypical forms and/or chronic sequelae in some patients, and the lack of both a confirmatory diagnosis test and a specific antidote. In addition, recent findings have outlined the implication of novel species of the causative organisms as well as new vectors, namely marine invertebrates, in ciguatera outbreaks. Another novel trend relates to the geographical expansion of this disease to previously unaffected areas, not only in certain island groups of French Polynesia but also in temperate regions worldwide, as a likely consequence of the effects of climate change.

Fast reflective optic-based rotational anisotropy nonlinear harmonic generation spectrometer.

We present a novel Rotational Anisotropy Nonlinear Harmonic Generation (RA-NHG) apparatus based primarily upon reflective optics. The data acquisition scheme used here allow for fast accumulation of RA-NHG traces, mitigating low frequency noise from laser drift, while permitting real-time adjustment of acquired signals with significantly more data points per unit angle rotation of the optics than other RA-NHG setups. We discuss the design and construction of the optical and electronic components of the device and present example data taken on a GaAs test sample at a variety of wavelengths. The RA-second harmonic generation data for this sample show the expected four-fold rotational symmetry across a broad range of wavelengths, while those for RA-third harmonic generation exhibit evidence of cascaded nonlinear processes possible in acentric crystal structures.

[Antithrombotic treatment in acute coronary syndrome and atrial fibrillation]. / Antithrombotische Therapie bei akutem Koronarsyndrom und Vorhofflimmern.

The number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and indications for oral anticoagulation (OAC) for the prevention of stroke, who need dual antiplatelet treatment (DAPT) with acetylsalicylic acid (ASA) plus a P2Y12 inhibitor because of an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is also increasing. In the past these patients received a triple therapy (TT) for 3-12 months. This TT has never been studied for efficacy; however, the rate of bleeding complications in comparison to a simple OAC or DAPT is significantly higher. Registries and smaller trials showed that DAPT with an OAC plus a platelet inhibitor may be sufficient to prevent stroke and stent thromboses/myocardial infarctions. These questions were investigated in various prospective and randomized studies involving all four non-vitamin K oral anticoagulants (NOAC) approved for stroke prevention in AF. The NOACs were tested against vitamin K antagonists (VKA) involving single antiplatelet therapy without using DAPT. The trials with rivaroxaban (PIONEER AF-PCI) and dabigatran (RE-DUAL PCI) have already been published but the investigations involving apixaban (AUGUSTUS) and edoxaban (ENTRUST-AF PCI) are still ongoing. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with VKA with respect to bleeding complications without any obvious disadvantage due to increases in stroke cases or cardiac ischemia. The international guidelines already permit treatment without TT in cases where the bleeding risk is prevalent. In this situation it is recommended to prescribe a NOAC plus a single antiplatelet therapy. Thus, TT no longer seems to be indicated for most patients with AF and after ACS or PCI.

Soluble CD93 is an apoptotic cell opsonin recognized by αx ß2.

Efferocytosis is essential for homeostasis and prevention of the inflammatory and autoimmune diseases resulting from apoptotic cell lysis. CD93 is a transmembrane glycoprotein previously implicated in efferocytosis, with mutations in CD93 predisposing patients to efferocytosis-associated diseases. CD93 is a cell surface protein, which is proteolytically shed under inflammatory conditions, but it is unknown how CD93 mediates efferocytosis or whether its efferocytic activity is mediated by the soluble or membrane-bound form. Herein, using cell lines and human monocytes and macrophages, we demonstrate that soluble CD93 (sCD93) potently opsonizes apoptotic cells but not a broad range of microorganisms, whereas membrane-bound CD93 has no phagocytic, efferocytic, or tethering activity. Using mass spectrometry, we identified αx ß2 as the receptor that recognizes sCD93, and via deletion mutagenesis determined that sCD93 binds to apoptotic cells via its C-type lectin-like domain and to αx ß2 by its EGF-like repeats. The bridging of apoptotic cells to αx ß2 markedly enhanced efferocytosis by macrophages and was abrogated by αx ß2 knockdown. Combined, these data elucidate the mechanism by which CD93 regulates efferocytosis and identifies a previously unreported opsonin-receptor system utilized by phagocytes for the efferocytic clearance of apoptotic cells.

Investigation of ciguatoxins in invasive lionfish from the greater caribbean region: Implications for fishery development.

Lionfish, native to reef ecosystems of the tropical and sub-tropical Indo-Pacific, were introduced to Florida waters in the 1980s, and have spread rapidly throughout the northwestern Atlantic, Caribbean Sea and the Gulf of Mexico. These invasive, carnivorous fish significantly reduce other fish and benthic invertebrate biomass, fish recruitment, and species richness in reef ecosystems. Fisheries resource managers have proposed the establishment of a commercial fishery to reduce lionfish populations and mitigate adverse effects on reef communities. The potential for a commercial fishery for lionfish is the primary reason to identify locations where lionfish accumulate sufficient amounts of ciguatoxin (CTX) to cause ciguatera fish poisoning (CFP), the leading cause of non-bacterial seafood poisoning associated with fish consumption. To address this issue, an initial geographic assessment of CTX toxicity in lionfish from the Caribbean and Gulf of Mexico was conducted. Lionfish samples (n = 293) were collected by spearfishing from 13 locations (74 sampling sites) around the Caribbean and Gulf of Mexico between 2012 and 2015. The highest frequencies of lionfish containing measurable CTX occurred in areas known to be high-risk regions for CFP in the central to eastern Caribbean (e.g., 53% British Virgin Islands and 5% Florida Keys). Though measurable CTX was found in some locations, the majority of the samples (99.3%) contained CTX concentrations below the United States Food and Drug Administration guidance level of 0.1 ppb Caribbean ciguatoxin-1 (C-CTX-1) equivalents (eq.). Only 0.7% of lionfish tested contained more than 0.1 ppb C-CTX-1 eq. As of 2018, there has been one suspected case of CFP from eating lionfish. Given this finding, current risk reduction techniques used to manage CTX accumulating fish are discussed.

[Hemorrhage under direct oral anticoagulants : Occurrence and treatment in intensive care patients]. / Blutungen unter direkten oralen Antikoagulanzien : Auftreten und Therapie bei Intensivpatienten.

The use of anticoagulants is associated with an increased risk of bleeding and nevertheless bleeding complications can be lifethreatening. The focus is on bleeding under direct oral anticoagulants (DOAC) because antidotes and specific measures are lacking for some DOACs. Furthermore, routinely carried out clotting tests cannot be used to determine the degree of anticoagulation under DOACs. Therefore, it becomes difficult to determine whether the coagulation inhibition effect is present. This article presents the treatment of hemorrhage in patients with DOACs in the intensive care unit. Further, the indications for DOACS and details of administration and monitoring are presented.

Experimental evidence of dietary ciguatoxin accumulation in an herbivorous coral reef fish.

Ciguatoxins (CTXs) are potent algal toxins that cause widespread ciguatera poisoning and are found ubiquitously in coral reef food webs. Here we developed an environmentally-relevant, experimental model of CTX trophic transfer involving dietary exposure of herbivorous fish to the CTX-producing microalgae Gambierdiscus polynesiensis. Juvenile Naso brevirostris were fed a gel-food embedded with microalgae for 16 weeks (89 cells g-1 fish daily, 0.4 µg CTX3C equiv kg-1 fish). CTXs in muscle tissue were detectable after 2 weeks at levels above the threshold for human intoxication (1.2 ±â€¯0.2 µg CTX3C equiv kg-1). Although tissue CTX concentrations stabilized after 8 weeks (∼3 ±â€¯0.5 µg CTX3C equiv kg-1), muscle toxin burden (total µg CTX in muscle tissue) continued to increase linearly through the end of the experiment (16 weeks). Toxin accumulation was therefore continuous, yet masked by somatic growth dilution. The observed CTX concentrations, accumulation rates, and general absence of behavioural signs of intoxication are consistent with field observations and indicate that this method of dietary exposure may be used to develop predictive models of tissue-specific CTX uptake, metabolism and depuration. Results also imply that slow-growing fish may accumulate higher CTX flesh concentrations than fast-growing fish, which has important implications for global seafood safety.

Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA2DS2-VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk-benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4 weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Fourier domain rotational anisotropy-second harmonic generation.

We describe a novel scheme of detecting rotational anisotropy-second harmonic generation (RA-SHG) signals using a lock-in amplifier referenced to a fast scanning RASHG apparatus. The method directly measures the nth harmonics of the scanning frequency corresponding to SHG signal components of Cn symmetry that appear in a Fourier series expansion of a general RA-SHG signal. GaAs was used as a test sample allowing comparison of point-by-point averaging with the lock-in based method. When divided by the C∞ signal component, the lock-in detected data allowed for both self-referenced determination of ratios of Cn components of up to 1 part in 104 and significantly more sensitive measurement of the relative amount of different Cn components when compared with conventional methods.

Toward broadband mechanical spectroscopy.

Diverse material classes exhibit qualitatively similar behavior when made viscous upon cooling toward the glass transition, suggesting a common theoretical basis. We used seven different measurement methods to determine the mechanical relaxation kinetics of a prototype molecular glass former over a temporal range of 13 decades and over a temperature range spanning liquid to glassy states. The data conform to time-temperature superposition for the main (alpha) process and to a scaling relation of schematic mode-coupling theory. The broadband mechanical measurements demonstrated have fundamental and practical applications in polymer science, geophysics, multifunctional materials, and other areas.

[NOAC: Real-life data and the role of antidotes for the treatment of bleeding]. / NOAK: Real-life-Daten und Therapie von Blutungen mit Antidots.

The non-vitamin K antagonists (NOAC) are an integral component of our antithrombotic prevention and therapy. For four of the NOAC, their non-inferiority or even superiority versus vitamin K antagonists (VKA) has been proven. Thus, the management of special patient cohorts or the management of active bleeding complications is a focus of current discussion.In addition to prospective trials, numerous retrospective analyses of health insurers or public health provider data have been analyzed and published as "real life" or "real-world evidence" data. In almost all data sets the results of the NOAC approval trials were confirmed, demonstrating their non-inferiority or even superiority versus VKA. Attempts to compare the various NOAC with each other must be viewed critically since the real-world evidence (RWE) analysis provides very divergent results depending on the cohorts analyzed. Thus, a substantial prescriber-bias must be taken into account and never be excluded.In order to improve the management of bleeding complications, NOAC antidotes were developed. While the factors Xa antidote, andexanet alpha, a modified coagulation factor deleted of an intrinsic activity, will not be available before 2018, the dabigatran antidote idarucizumab is already in clinical use. Idarucizumab, a monoclonal antibody fragment directed against dabigatran, is able to completely antagonize the effect of dabigatran within minutes. Therefore, the drug has the potential to terminate life-threatening bleeding complications earlier and make emergency surgical or interventional procedures possible without an elevated bleeding risk.

[Bleeding in patients receiving dual antiplatelet therapy after acute coronary syndrome - significance, prevention and interdisciplinary management]. / Interdisziplinäres Management von Blutungen unter dualer antithrombozytärer Therapie nach akutem Koronarsyndrom.

For secondary prevention of acute coronary syndrome, guidelines recommend dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 receptor antagonist such as clopidogrel, prasugrel or ticagrelor for a period of 12 months. Premature discontinuation of dual antiplatelet therapy is associated with an increased risk of ischaemic events. However, antiplatelet therapy is also associated with an increased risk of bleeding that should not be under- or overestimated. To ensure an optimal care of patients receiving dual antiplatelet therapy after an acute coronary syndrome, an interdisciplinary group of experienced experts in the fields of cardiology, cardiac surgery, gastroenterology, anaesthesiology, intensive care and haemostaseology gathered bleeding-related information and developed recommendations relevant to daily clinical practice. These include the significance of bleeding events in the course of treatment, measures for bleeding prevention and the adequate care of patients with bleedings.