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Aims The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. Methods and results After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73–1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72–1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08–0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. Conclusion After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

The International Union of Geological Sciences Executive Committee (IUGS EC) voted on 13 October 2021 to ratify a proposal for the Neogene subseries/subepochs to have formal status. They are now incorporated into a six-tiered chronostratigraphic hierarchy within the International Chronostratigraphic Chart (ICC). The Lower/Early Miocene Subseries/Subepoch comprises the Aquitanian and Burdigalian stages/ages, the Middle Miocene Subseries/Subepoch comprises the Langhian and Serravallian stages/ages, the Upper/Late Miocene Subseries/Subepoch comprises the Tortonian and Messinian stages/ages, the Lower/Early Pliocene Subseries/Subepoch comprises the Zanclean Stage/Age and the Upper/Late Pliocene Subseries/Subepoch comprises the Piacenzian Stage/Age. This ratification is an important move towards both a common language in the wider Earth Sciences community and a step forward in the unification of Cenozoic chronostratigraphy, with Neogene and Quaternary subseries/subepochs now formalized.

Coronary aneurysms are rare and of various etiologies in adults. Natural history, modalities of management and clinical monitoring remain poorly known due to the lack of large studies and homogeneous diagnostic and follow-up criteria in the published data. Coronary angiography is, so far, the most common diagnostic tool but can overlook some partially thrombosed aneurysmal. Intracoronary imaging, particularly intravascular ultrasound, can differentiate aneurysms from pseudoaneurysms considered by some to be at greater risk of events, requiring a curative treatment. Intracoronary imaging can also help with etiological assessment and percutaneous treatment. With its growing use in the search for coronary atheromatous disease, coronary CT angiography has become a major diagnostic tool for coronary aneurysms. In addition, that it can incidentally detect coronary aneurysms, coronary CT angiography is particularly useful for giant aneurysms poorly visualized on coronary angiography or less well evaluated by intracoronary imaging. It specifies their relationship with adjacent anatomical structures. It is also a non-invasive modality of monitoring. These three imaging tools are currently the most relevant in current practice pending large studies evaluating the natural history of coronary aneurysms, with the identification of possible risk factors that could modify the management.

Despite an often favorable risk/benefit ratio, patients with severe chronic kidney disease are sometimes declined for interventional coronary procedures, due to the risk of acute kidney injury post-contrast (AKI-PC). A large preventive supply of intravenous fluid may be problematic in this population. The RenalGuard® system allows hyperhydration by maintaining a stable volemia through an enhanced diuresis.This work reports the evaluation of the RenalGuard® system in 25 consecutive patients with chronic kidney disease (glomerular filtration rate40 mL/min/1.73 m²) requiring an interventional coronary procedure (coronary angiography and/or percutaneous coronary intervention) and at high risk of IRA-PC. An increase in serum creatinine ≥ 26.5 µmol/L at 48-72 hours (AKI-PC definition) was observed in 4 patients (16%). The mean glomerular filtration rate was 26 ± 8 mL/min/1.73 m² at 48-72 hours versus 25 ± 8 mL/min/1.73 m² at baseline. No patient presented with an increase in serum creatinine ≥ 1.5 from baseline, stage 2 or 3 AKI, or acute pulmonary edema. No renal replacement therapy was necessary. One death unrelated to AKI-PC occurred during hospital stay.This single-center observational study suggests that the RenalGuard® system, allowing diuresis-adjusted hyperhydration, is safe and useful for patients at high risk of AKI-PC after an interventional coronary procedure.

Resume Les infections des abords vasculaires sont exceptionnelles et rarement mentionnees comme complication potentielle d’une intervention cardiovasculaire percutanee. Nous rapportons un cas d’infection d’abord vasculaire et faisons une revue de la litterature. Cette complication concerne essentiellement la voie femorale et dans certaines circonstances : introducteur laisse en place apres l’acte, ponction compliquee d’un hematome, d’une fistule arterioveineuse ou d’un faux-anevrysme, ou mise en place d’un systeme de fermeture vasculaire. Cette complication est toujours serieuse necessitant habituellement un traitement medicochirurgical, avec de possibles complications severes mettant en jeu le pronostic fonctionnel et parfois vital du patient. Des mesures preventives peuvent diminuer ce risque infectieux : amelioration de nos techniques de ponction vasculaire avec un interet de l’abord guide par echographie, changement de voie d’abord en cas d’hematome, evaluation angiographique femorale et asepsie rigoureuse en cas d’utilisation de systeme de fermeture vasculaire, et bien entendu le choix preferentiel de l’abord arteriel radial.

The freshwater Hydra polyp is a versatile model to study whole-body regeneration from a developmental as well as a cellular point of view. The outstanding regenerative capacities of Hydra are based on its three populations of adult stem cells located in the central body column of the animal. There, these three populations, gastrodermal epithelial, epidermal epithelial, and interstitial, continuously cycle in homeostatic conditions, and their activity is locally regulated after mid-gastric bisection. Moreover, they present an unusual cycling behavior with a short G1 phase and a pausing in G2. This particular cell cycle has been studied for a long time with classical microscopic methods. We describe here two flow cytometry methods that provide accurate and reproducible quantitative data to monitor cell cycle regulation in homeostatic and regenerative contexts. We also present a cell sorting procedure based on flow cytometry, whereby stem cells expressing a fluorescent reporter protein in transgenic lines can be enriched for use in applications such as transcriptomic, proteomic, or cell cycle analysis.

The recombinant antibodies AD822, AW199, AW200 and AW201 bind HEK293 cells expressing the human Fas receptor protein as assessed by flow cytometry.

The fenestration of a coronary artery hematoma is a therapeutic option in case of a life-threatening spontaneous coronary artery dissection, if the conservative treatment is not feasible. Here we present the case of a 34-year-old woman who presented three spontaneous coronary artery dissections, on three different arteries, over a period of twenty-one months. The diagnosis was confirmed by endovascular imaging. During an acute coronary syndrome, emergent percutaneous coronary intervention of the left anterior descending artery was performed, successfully, by a fenestration of the hematoma, using an AngioSculpt® scoring balloon.

International audience; Background and purpose The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial. Methods This was a planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischaemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists. Results Of 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs. 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs. 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up. Conclusions In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, in migraine patients both with and without aura.

Calcareous nannofossils are micrometric calcite platelets secreted by the photosynthetic algae named coccolithophores and incertae sedis. Calcareous nannoplankton inhabit the photic zone from coast to open-ocean and have left an abundant fossil record since the Triassic. Therefore, they constitute an interesting material for geochemical studies although they have been overlooked in comparison to foraminifera. We have analyzed manganese distribution and valence in six calcareous nannofossil species representing different ages (Recent to Jurassic) and geological settings (land sections and deep ocean core-tops) and with different structures to assess the potential of Mn as a paleobiological or paleoenvironmental proxy. Nano x -Ray Fluorescence ( xrf ) maps were established at the esrf id 22 ni and id 21 beamlines and Mn k -edge x -Ray Absorption Near Edge Structure ( xanes ) at id 21. Mn is more abundant in nannofossils from pre-Quaternary rock samples than from core-top samples. In nannofossil rock samples, Mn nano xrf maps show distributions correlated with primary crystalline organization whereas in nannofossil core-top samples, Mn is either absent or does not follow the crystal organization. X anes analyses show that Mn is in the form of MnCO3. All these observations argue for Mn incorporation within calcareous nannofossils controlled by diagenesis through overgrowth of secondary calcite (Ca, Mn)CO3. Crusts grew along the original crystal growth directions. The incorporation of Mn in some core-top samples highlights potential early diagenesis input when the detached platelet lies on the seafloor or is still in the water column. Mn should therefore be considered a critical tool to identify diagenetic overgrowth rather than primary environmental conditions.

Highlights • Sudden cardiac death (SCD), especially in young athletes, should be avoided. • Current pre-sports screening is based on history/physical exam (insufficient). • ECG is an excellent test for electrically induced SCD but requires expert review. • Screening MRI is the best tool for identifying myocardiopathies/coronary anomalies. • Results of a preliminary population-based study confirm the value of screening MRI., Preventing sudden cardiac death (SCD) in athletes is a primary duty of sports cardiologists. Current recommendations for detecting high-risk cardiovascular conditions (hr-CVCs) are history and physical examination (H&P)-based. We discuss the effectiveness of H&P-based screening versus more-modern and accurate methods. In this position paper, we review current authoritative statements and suggest a novel alternative: screening MRI (s-MRI), supported by evidence from a preliminary population-based study (completed in 2018), and a prospective, controlled study in military recruits (in development). We present: 1. Literature-Based Comparisons (for diagnosing hr-CVCs): Two recent studies using traditional methods to identify hr-CVCs in >3,000 young athletes are compared with our s-MRI-based study of 5,169 adolescents. 2. Critical Review of Previous Results: The reported incidence of SCD in athletes is presently based on retrospective, observational, and incomplete studies. H&P’s screening value seems minimal for structural heart disease, versus echocardiography (which improves diagnosis for high-risk cardiomyopathies) and s-MRI (which also identifies high-risk coronary artery anomalies). Electrocardiography is valuable in screening for potentially high-risk electrophysiological anomalies. 3. Proposed Project: We propose a prospective, controlled study (2 comparable large cohorts: one historical, one prospective) to compare: (1) diagnostic accuracy and resulting mortality-prevention performance of traditional screening methods versus questionnaire/electrocardiography/s-MRI, during 2-month periods of intense, structured exercise (in military recruits, in advanced state of preparation); (2) global costs and cost/efficiency between these two methods. This study should contribute significantly toward a comprehensive understanding of the incidence and causes of exercise-related mortality (including establishing a definition of hr-CVCs) while aiming to reduce mortality.

Retiring baby boomers are increasing the demand for Social Security Administration (SSA) services at a time when budget constraints and retiring staff are limiting its capacity to deliver these services. In theory, investing in web-based tools that people can use to serve themselves could help SSA meet the projected increases in demand, even with fewer staff. But, despite investments in tools with significant labor-saving potential, such as online benefit application, usage of these tools has stalled since 2016. This study of online claiming is based on a survey of older individuals who either claimed their Old Age and Survivor (OASI) benefit in the past five years or intend to claim within the next five years. The survey covered: 1) how they submitted (or intend to submit) their benefit application; and 2) how they communicated (or intend to communicate) with SSA during the process.

Federal law allows certain state and local government employees to be excluded from Social Security if they are covered by an employer pension of sufficient generosity. As a result, approximately one-quarter of state and local workers are not covered by Social Security on their current job. Before COVID-19, these “FICA replacement plans” all satisfied the letter of the law in terms of providing benefits of sufficient generosity. This study has three aims. The first is to document the immediate impact of COVID-19 on the financial status of FICA replacement plans. The second is to investigate whether COVID-19 has led to cuts in benefit promises among plans, as well as the likelihood of future cuts. The third is to investigate the likelihood that FICA replacement plans will exhaust their trust fund assets and default on benefit promises.

Few patients with an anomalous aortic origin of a coronary artery (AAOCA) require a correction of the congenital anomaly. Current recommendations offer surgical repair in first line therapy with a prevention of sudden cardiac death as main objective. However these guidelines are focused on children and not based on randomized controlled studies. Furthermore decision-making must be different in an adult population less exposed to the risk of sudden cardiac death. Current practices showed unwillingness to offer a surgical treatment for right AAOCA associated with ischemic symptoms or myocardial ischemia. We sought in the review to explain the rational for percutaneous coronary intervention in right AAOCA with interarterial course and to present the published results of this technique.

Aims Limited data exist regarding the incidence and aetiology of life-threatening events such as major cardiac events or exertional heat stroke during long-distance races. We aimed to provide an updated incidence, etiology and prognosis of life-threatening events during long-distance races. Methods The prospective RACE PARIS registry recorded all life-threatening events/fatal events occurring during 46 marathons, half-marathons and other long-distance races in the Paris area between 2006 and 2016, comprising 1,073,722 runners. Event characteristics were determined by review of medical records and interviews with survivors. Results The incidence of life-threatening events, exertional heat stroke and major cardiac events was 3.35 per 100,000, 1.02 per 100,000 and 2.33 per 100,000, respectively, including 18 sudden cardiac arrests (1.67 per 100,000). The main aetiology of sudden cardiac arrest was myocardial ischaemia (11/18), due to acute coronary thrombosis (6/11), stable atherosclerotic coronary artery disease (2/11), coronary dissection (1/11), anomalous connection (1/11) or myocardial bridging (1/11). A third of participants with ischaemia-related major cardiac events presented with pre-race clinical symptoms. Major cardiac events were more frequent in the case of a high pollution index (6.78 per 100,000 vs. 2.07 per 100,000, odds ratio 3.27, 95% confidence interval 1.12–9.54). Case fatality was low (0.19 per 100,000). Similarly, we report in a meta-analysis of eight long-distance race registries comprising 16,223,866 runners a low incidence of long-distance race-related sudden cardiac arrest (0.82 per 100,000) and fatality (0.39 per 100,000). Death following sudden cardiac arrest was strongly associated with initial asystole or pulseless rhythm. Conclusion Long-distance race-related life-threatening events remain rare although serious events. Better information for runners on the risk of pre-race clinical symptoms, outside air pollution and temperature may reduce their incidence.

CD19 is a B cell-specific receptor that regulates the threshold of B cell receptor (BCR)-mediated cell proliferation. A CD47xCD19 bispecific antibody (biAb) was generated to target and deplete B cells via multiple antibody-mediated mechanisms. Interestingly, the biAb, constructed of a CD19 binding arm and a CD47 binding arm, inhibited BCR-mediated B-cell proliferation with an effect even more potent than a CD19 monoclonal antibody (mAb). The inhibitory effect of the biAb was not attributable to CD47 binding because a monovalent or bivalent anti-CD47 mAb had no effect on B cell proliferation. Fluorescence resonance energy transfer analysis demonstrated that co-engaging CD19 and CD47 prevented CD19 clustering and its migration to BCR clusters, while only engaging CD19 (with a mAb) showed no impact on either CD19 clustering or migration. The lack of association between CD19 and the BCR resulted in decreased phosphorylation of CD19 upon BCR activation. Furthermore, the biAb differentially modulated BCR-induced gene expression compared to a CD19 mAb. Taken together, this unexpected role of CD47xCD19 co-ligation in inhibiting B cell proliferation illuminates a novel approach in which two B cell surface molecules can be tethered, to one another in order, which may provide a therapeutic benefit in settings of autoimmunity and B cell malignancies.

Background: \ud Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.\ud \ud Objectives: \ud This study sought to test the association between the rs9349379 genotype and SCAD.\ud \ud Methods: \ud Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.\ud \ud Results: \ud The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.\ud \ud Conclusions: \ud The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Little is known about the association between provision of post-resuscitation care and prognosis of out-of-hospital cardiac arrest (OHCA) in elderly patients. Previous studies have suggested futility after 65 years of age.We aimed to evaluate the association of early coronary angiogram (CAG) followed if necessary by percutaneous coronary intervention (PCI), with favorable outcome after OHCA among elderly patients, compared to younger patients.Using a large French registry, we included all OHCA patients with an initial shockable rhythm, transported to hospital from 2011 to 2015. Favorable outcome was defined as hospital discharge with Cerebral Performance Category (CPC) 1 or 2. and were evaluated by multivariate logistic regression. Subgroup analyses were performed according to age groups:65, 65-75 and75 years.Among 1502 included patients, 31% were older than 65 and 12% older than 75 years. An early CAG was performed in 79%, 88% and 76% of patients below 65, between 65 and 75 and above 75, respectively (P = 0.002). The rate of patients discharged with CPC1 or 2 was 42% below 65, 38% between 65 and 75 and 24% above 75 (P 0.001). Among the whole population, early CAG (OR = 6.4, 95% CI = 3.9-10.5, P 0.001) was associated with favorable outcome. In subgroups analysis, CAG was associated with favorable outcome among patients65 and 65-75. In patients75, there was a trend towards a favorable outcome (OR2.9, 95CI = 0.9-9.1).In a large registry of OHCA survivors, the early CAG use was associated with a better prognosis. This benefit was persistent up to 75 years of age, suggesting that age alone should not guide the decision for early invasive strategy.

The recombinant antibodies AC650, AC653, AC656 and AD460 detect the human CD8α protein by flow cytometry.

The Multiemployer Pension Reform Act (MPRA) allows multiemployer plans facing insolvency to apply for approval from the Treasury to cut accrued benefits of plan members to prolong plan solvency—a departure from the benefit protections of Employee Retirement Income Security Act. To assess the law's impact, this paper models Central States Teamsters – by far the largest – plan to have applied under the new law to reduce benefits. Using a stochastic model of future investment returns, the probability of insolvency within 10 years drops from 50% (without cuts) to 6% (with cuts). While benefit cuts increase the overall welfare of participants by extending the plan's life, the welfare of younger retirees (under age 75) worsens and welfare of workers improves.