Severe cardiogenic shock due to acute onset of an aorto-to-right atrial shunt in a patient with aortic valve endocarditis

AbstractINTRODUCTIONHeart failure is the most common cause of death due to infective endocarditis. We report a case of a patient presenting with severe shock due to an infection-associated left-to-right cardiac shunt.PRESENTATION OF CASEA 62-year-old man, who underwent aortic valve replacement five years previously, was admitted to ICU due to acute hemodynamic deterioration. A few days earlier, he had a septic episode with blood cultures positive for Staphylococcus aureus and clinical features of infective endocarditis. In ICU, transthoracic echocardiography revealed shunting from the aortic root to the right atrium resulting in severe cardiogenic shock.DISCUSSIONThis case report describes a near fatal complication of infective endocarditis, detected by routine use of transthoracic echocardiography.CONCLUSIONOur case outlines the relevance of early cardiac surgery strategies in patients with infective endocarditis and we briefly discuss the current literature

Agent-Based Simulation Modelling for Reflecting on Consequences of Digital Mental Health

The premise of this working paper is based around agent-based simulation models and how to go about creating them from given incomplete information. Agent-based simulations are stochastic simulations that revolve around groups of agents that each have their own characteristics and can make decisions. Such simulations can be used to emulate real life situations and to create hypothetical situations without the need for real-world testing prior. Here we describe the development of an agent-based simulation model for studying future digital mental health scenarios. An incomplete conceptual model has been used as the basis for this development. To define differences in responses to stimuli we employed fuzzy decision making logic. The model has been implemented but not been used for structured experimentation yet. This is planned as our next step

Landiolol in patients with septic shock resident in an intensive care unit (LANDI-SEP): study protocol for a randomized controlled trial

In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ae 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ae 95 bpm) despite a hemodynamic optimization period of 24-36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80-94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80-94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study

Background: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. Methods: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor–positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. Results: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. Conclusions: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. Trial registration Clinical Trials Number: CFEM345DDE1

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Enhanced underground metabolism challenges life at high temperature–metabolic thermoadaptation in hyperthermophilic Archaea

The text-book picture of a perfect, well organised metabolism with highly specific enzymes, is challenged by non-enzymatic reactions and promiscuous enzymes. This, so-called ‘underground metabolism’, is a special challenge for hyperthermophilic Archaea that thrive at temperatures above 80 °C and possess modified central metabolic pathways often with promiscuous enzymes. Hence, the question arises how extremely thermophilic Archaea can operate their unusual metabolism at temperatures where many pathway intermediates are unstable? We herein discuss current insights in the underground metabolism and metabolic thermoadaptation of (hyper)thermophilic Archaea. So far, only a few repair enzymes and salvaging pathways have been investigated in Archaea. Studies of the central carbohydrate metabolism indicate that a number of different strategies have evolved: 1) reduction of the concentration of unstable metabolites, 2) different pathway topologies are used with newly induced enzymes, and 3) damaged metabolites are removed via new metabolic pathways