The Use of Angiotensin II for the Treatment of Post-cardiopulmonary Bypass Vasoplegia

PURPOSE: Vasoplegia is a common complication after cardiac surgery and is related to the use of cardiopulmonary bypass (CPB). Despite its association with increased morbidity and mortality, no consensus exists in terms of its treatment. In December 2017, angiotensin II (AII) was approved by the Food and Drug Administration (FDA) for use in vasodilatory shock; however, except for the ATHOS-3 trial, its use in vasoplegic patients that underwent cardiac surgery on CPB has mainly been reported in case reports. Thus, the aim of this review is to collect all the clinically relevant data and describe the pharmacologic mechanism, efficacy, and safety of this novel pharmacologic agent for the treatment of refractory vasoplegia in this population. METHODS: Two independent reviewers performed a systematic search in PubMed, Embase, Web of Science, and Cochrane Library using relevant MeSH terms (Angiotensin II, Vasoplegia, Cardiopulmonary Bypass, Cardiac Surgical Procedures). RESULTS: The literature search yielded 820 unique articles. In total, 9 studies were included. Of those, 2 were randomized clinical trials (RCTs) and 6 were case reports and 1 was a retrospective cohort study. CONCLUSIONS: AII appears to be a promising means of treatment for patients with post-operative vasoplegia. It is demonstrated to be effective in raising blood pressure, while no major adverse events have been reported. It remains uncertain whether this agent will be broadly available and whether it will be more advantageous in the clinical management of vasoplegia compared to other available vasopressors. For that reason, we should contain our eagerness and enthusiasm regarding its use until supplementary knowledge becomes available. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10557-020-07098-3) contains supplementary material, which is available to authorized users

Robotic mitral valve repair surgery: where do we go from here?

Surgical mitral valve repair through median sternotomy has long presented the treatment of choice for degenerative mitral valve disease. In recent decades, minimal invasive surgical techniques have been developed and are now gaining widespread popularity. Robotic cardiac surgery presents an emerging field, initially adopted only by selected centres, mostly in the United States. In recent years, the number of centers interested in robotic mitral valve surgery has grown with an increasing adoption in Europe as well. Increasing interest and surgical experience gained are stimulating further developments in the field and the full potential of robotic mitral valve surgery remains to be developed.Thoracic Surger

eComment. Posterior mitral valve leaflet prolapse: one term, several different meanings

Thoracic Surger

Leukocyte migration in experimental inflammatory bowel disease

Emigration of leukocytes from the circulation into tissue by transendothelial migration, is mediated subsequently by adhesion molecules such as selectins, chemokines and integrins. This multistep paradigm, with multiple molecular choices at each step, provides a diversity in signals. The influx of neutrophils, monocytes and lymphocytes into inflamed tissue is important in the pathogenesis of chronic inflammatory bowel disease. The importance of each of these groups of adhesion molecules in chronic inflammatory bowel disease, either in human disease or in animal models, will be discussed below. Furthermore, the possibilities of blocking these different steps in the process of leukocyte extravasation in an attempt to prevent further tissue damage, will be taken into account

Stronger than your voices:A cognitive behavioral therapy for youth suffering from auditory verbal hallucinations

Objective: Auditory verbal hallucinations (AVHs) are a common feature in youth and mostly transient. Nevertheless, while present, AVH can cause considerable distress. Children and adolescents seeking help for distressing AVH represent a heterogeneous group in terms of underlying factors, yet they consistently suffer from their AVH. Until now, a youth-specific psychotherapeutic intervention for AVH was lacking. Experts in the field of treating AVH in both adults and youngsters collaborated with service users to develop the cognitive behavioral therapy (CBT) "Stronger Than Your Voices" (STYV). We investigated feasibility and clinical outcomes of the STYV therapy. Methods: Patients were derived from children and adolescents seeking help for AVH at the UMC Utrecht outpatient clinic with an indication for STYV therapy. Therapists preferably originated from referring health care facilities and were required to have sufficient general knowledge and experience with CBT. They received a short individual training to apply STYV. After, patients and their therapists could participate this naturalistic pilot study, assessing feasibility, tolerability, and clinical change when applying the STYV therapy. Results: Six participants (10-16 years old), all suffering from comorbid psychopathology, provided pre and post measures, all completing STYV therapy without experiencing an aggravation of symptoms. AVH total impact decreased 40% with Cohen's d within-group effect size (1.28) also suggesting clinically meaningful change. Therapists were positive about STYV therapy and manual. Conclusion: The STYV therapy is feasible for youth with distressing AVH. First results indicate that STYV may be clinically effective. A trial to further test effectiveness in a larger sample is needed

Microinvasive mitral valve surgery: current status and status quo

Surgical mitral valve repair, performed either through median sternotomy or minimal invasive approach, presents the gold standard treatment for degenerative mitral valve disease. In dedicated centres, high repair and low complication rates have been established with excellent valve repair durability. Recently, new techniques have been introduced, that allow mitral valve repair to be performed through small surgical incisions and while avoiding cardio-pulmonary bypass. These new techniques, however, conceptually differ significantly when compared to surgical repair and it remains questionable whether they are capable of reproducing the results of surgical treatment.Thoracic Surger

Jak-STAT regulation of cyst stem cell development in the Drosophila testis

Establishment and maintenance of functional stem cells is critical for organ development and tissue homeostasis. Little is known about the mechanisms underlying stem establishment during organogenesis. Drosophila testes are among the most thoroughly characterized systems for studying stem cell behavior, with germline stem cells (GSCs) and somatic cyst stem cells (CySCs) cohabiting a discrete stem cell niche at the testis apex. GSCs and CySCs are arrayed around hub cells that also comprise the niche and communication between hub cells, GSCs, and CySCs regulates the balance between stem cell maintenance and differentiation. Recent data has shown that functional, asymmetrically dividing GSCs are first established at similar to 23 h after egg laying during Drosophila testis morphogenesis (Sheng et al., 2009). This process correlates with coalescence of the hub, but development of CySCs from somatic gonadal precursors (SGPs) was not examined. Here, we show that functional CySCs are present at the time of GSC establishment, and that Jak-STAT signaling is necessary and sufficient for CySC maintenance shortly thereafter. Furthermore, hyper-activation of Jak in CySCs promotes expansion of the GSC population, while ectopic Jak activation in the germline induces GSC gene expression in GSC daughter cells but does not prevent spermatogenic differentiation. Together, these observations indicate that, similar to adult testes, Jak-STAT signaling from the hub acts on both GSCs and CySC to regulate their development and differentiation, and that additional signaling from CySCs to the GSCs play a dominant role in controlling GSC maintenance during niche formation. (c) 2012 Elsevier Inc. All rights reserved

The role of long-term mechanical circulatory support in patients with advanced heart failure

In patients with end-stage heart failure, advanced therapies such as heart transplantation and long-term mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) have to be considered. LVADs can be implanted as a bridge to transplantation or as an alternative to heart transplantation: destination therapy. In the Netherlands, long-term LVAD therapy is gaining importance as a result of increased prevalence of heart failure together with a low number of heart transplantations due to shortage of donor hearts. As a result, the difference between bridge to transplantation and destination therapy is becoming more artificial since, at present, most patients initially implanted as bridge to transplantation end up receiving extended LVAD therapy. Following LVAD implantation, survival after 1, 2 and 3 years is 83%, 76% and 70%, respectively. Quality of life improves substantially despite important adverse events such as device-related infection, stroke, major bleeding and right heart failure. Early referral of potential candidates for long-term MCS is of utmost importance and positively influences outcome. In this review, an overview of the indications, contraindications, patient selection, clinical outcome and optimal time of referral for long-term MCS is given

Functional analysis of four LDLR 5'UTR and promoter variants in patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disease characterised by increased low-density lipoprotein cholesterol (LDL-C) levels. The functionality of four novel variants within the LDLR 5'UTR and promoter located at c.-13A>G, c.-101T>C, c.-121T>C and c.-215A>G was investigated using in silico and in vitro assays, and a systemic bioinformatics analysis of all 36 reported promoter variants are presented. Bioinformatic tools predicted that all four variants occurred in sites likely to bind transcription factors and that binding was altered by the variant allele. Luciferase assay was performed for all the variants. Compared with wild type, the c.-101T>C and c.-121T>C variants showed significantly lower mean (±SD) luciferase activity (64±8 and 72±8%, all PG or c.-215A>G variants (96±15 and 100±12%), suggesting these variants are not FH causing. Similar results were seen for the c.-101T>C and c.-121T>C variants in lipid-depleted serum. However, a significant reduction in luciferase activity was seen in the c.-215A>G variant in lipid-depleted serum. Electrophoretic-mobility shift assays identified allele-specific binding of liver (hepatoma) nuclear proteins to c.-121T>C and suggestive differential binding to c.-101T>C but no binding to c.-215A>G. These data highlight the importance of in vitro testing of reported LDLR promoter variants to establish their role in FH. The functional assays performed suggest that the c.-101T>C and c.-121T>C variants are pathogenic, whereas c.-13A>G variant is benign, and the status of c.-215A>G remains unclear.European Journal of Human Genetics advance online publication, 24 September 2014; doi:10.1038/ejhg.2014.199

The use of design activity for research into Computer Supported Co-operative Working (CSCW)

This paper describes current research at Loughborough University in the field of Computer Supported Co-operative Working (CSCW). The project, which is funded by the Information Engineering Directorate (IED) within the Science and Engineering Research Council (SERC), is titled 'Establishing the Communicational Requirements of Information Technology (IT) Systems that Support Humans Co-operating Remotely'. The research group have adopted a less cumbersome acronym for the project - ROCOCO which is derived from REmote COoperation and COmmunication. Design activity has been proposed as offering a suitable context for a study of co-operation and at the time of writing the first phase of the experiments - involving face to face or proximal co-operation - has been undertaken and the analysis begun. The ROCOCO project is about to embark on phase two involving remote co-operation. This paper presents, in some detail, the construction and operation of a pilot study that allowed project members to assess and adjust the experimental design prior to the start of Phase One. A selection of initial findings illustrate the nature of the investigation to be undertaken. The paper also seeks to highlight the importance of CSCW research for the design community. The substance of the paper is concerned with a presentation of issues involved in an analysis of co-operation, involving as it does, verbal and non-verbal communication