Characteristics and Outcomes of Patients in the Emergency Department with Left Ventricular Assist Devices

Introduction: Left ventricular assist devices (LVAD) are increasingly common among patients with heart failure. The unique physiologic characteristics of patients with LVADs present a challenge to emergency clinicians making treatment and disposition decisions. Despite the increasing prevalence of LVADs, literature describing emergency department (ED) visits among this population is sparse. We aimed to describe clinical characteristics and outcomes among patients with LVADs seen in two quaternary-care EDs in a five-year period. Secondarily, we sought to evaluate mortality rates and ED return rates for bridge to transplant (BTT) and destination therapy (DT) patients.Methods: We conducted a retrospective cohort study of adult patients known to have an LVAD who were evaluated in two quaternary-care EDs from 2013–2017. Data were collected from the electronic health record and summarized with descriptive statistics. We assessed patient outcomes with mixed-effects logistic regression models including a random intercept to account for patients with multiple ED visits.Results: During the five-year study period, 290 ED visits among 107 patients met inclusion criteria. The median patient age was 61 years. The reason for LVAD implantation was BTT in 150 encounters (51.7%) and DT in 140 (48.3%). The most common presenting concerns were dyspnea (21.7%), bleeding (18.6%), and chest pain (11.4%). Visits directly related to the LVAD were infrequent (7.9%). Implantable cardioverter-defibrillator discharge was reported in 3.4% of visits. A majority of patients were dismissed home from the ED (53.8%), and 4.5% required intensive care unit admission. Among all patients, 37.9%returned to the ED within 30 days, with similar rates between DT and BTT patients (32.1 vs 43.3%; P = 0.055). The LVAD was replaced in three cases (1.0%) during hospitalization. No deaths occurred in the ED, and the mortality rate within 30 days was 2.1% among all patients.Conclusion: In this multicenter cohort study of ED visits among patients with an LVAD, dyspnea, bleeding, and chest pain were the most common presenting concerns. Visits directly related to the LVAD were uncommon. Approximately half of patients were dismissed home, although return ED visits were common

Unraveling the functional dark matter through global metagenomics

Metagenomes encode an enormous diversity of proteins, reflecting a multiplicity of functions and activities1,2. Exploration of this vast sequence space has been limited to a comparative analysis against reference microbial genomes and protein families derived from those genomes. Here, to examine the scale of yet untapped functional diversity beyond what is currently possible through the lens of reference genomes, we develop a computational approach to generate reference-free protein families from the sequence space in metagenomes. We analyse 26,931 metagenomes and identify 1.17 billion protein sequences longer than 35 amino acids with no similarity to any sequences from 102,491 reference genomes or the Pfam database3. Using massively parallel graph-based clustering, we group these proteins into 106,198 novel sequence clusters with more than 100 members, doubling the number of protein families obtained from the reference genomes clustered using the same approach. We annotate these families on the basis of their taxonomic, habitat, geographical and gene neighbourhood distributions and, where sufficient sequence diversity is available, predict protein three-dimensional models, revealing novel structures. Overall, our results uncover an enormously diverse functional space, highlighting the importance of further exploring the microbial functional dark matter

Population genomics of post-glacial western Eurasia

Western Eurasia witnessed several large-scale human migrations during the Holocene1,2,3,4,5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.info:eu-repo/semantics/publishedVersio