The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P < 0.001 for both variables). There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P < 0.001). These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage

CAF-derived MFAP5 is a novel transcription regulator for immune checkpoint CD47 in ovarian cancer

https://openworks.mdanderson.org/sumexp23/1115/thumbnail.jp

Application of a Multidisciplinary Enhanced Recovery After Surgery Pathway to Improve Patient Outcomes After Transcatheter Aortic Valve Implantation

Enhanced recovery after surgery (ERAS) protocols have proven effective in a variety of surgical specialties. Published reports on these pathways within cardiac surgery and interventional cardiology are limited. Invasive aortic valve replacement procedures are increasingly being performed by hybrid groups of interventional cardiologists and surgeons through transcatheter aortic valve implantation (TAVI). The TAVI patient population is at a higher surgical risk compared with those undergoing surgical aortic valve replacement since they are older, frailer, and have significant co-morbidities which result in an increased risk of perioperative complications. ERAS protocols have the potential to help these patients undergoing TAVI procedures. In conclusion, we propose a TAVI ERAS protocol with a call-to-action for other centers to implement an ERAS protocol to improve hospital and cardiac outcomes

Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

Adequacy of Protein and Energy Intake in Critically Ill Adults Following Liberation From Mechanical Ventilation Is Dependent on Route of Nutrition Delivery

This is the peer reviewed version of the following article: Moisey, L. L., Pikul, J., Keller, H., Yeung, C. Y., Rahman, A., Heyland, D. K., &amp; Mourtzakis, M. (2020). Adequacy of protein and energy intake in critically ill adults following liberation from mechanical ventilation is dependent on route of Nutrition Delivery. Nutrition in Clinical Practice, 36(1), 201–212, which has been published in final form at https://doi.org/10.1002/ncp.10558. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Background: Studies examining nutrition intake of critically ill patients following liberation from mechanical ventilation (LMV) are scarce. The objectives of this prospective, observational feasibility study were to quantify and assess protein and energy intake in hospitalized, critically ill patients following LMV, to determine barriers to optimal intake, and to report on the feasibility of recruiting and retaining patients into this study. Methods: Adult patients requiring MV for >72 hours in a medical/surgical intensive care unit (ICU) were recruited. Protein and energy intakes were quantified up to 14 days following LMV. Patients also identified barriers to eating. Results: Nineteen patients (mean age, 60 years [SD, 12 years]) were studied over 125 days. Over all study days, the median amounts of protein and energy consumed in comparison with amounts prescribed by dietitians were 46% (interquartile range [IQR], 26-100) and 71% (IQR, 38-100), respectively. When stratified by route of nutrition delivery, on days (n = 54) when patients consumed an oral diet as the sole nutrition source, median amounts of protein and energy consumed in comparison with those prescribed were only 27% (IQR, 15-41) and 47% (IQR, 29-66), respectively. The most frequently reported barriers to eating were poor appetite, early satiety, and taste changes. Conclusions: Protein and calorie intake is below prescribed amounts for patients whose enteral nutrition is discontinued and an oral diet prescribed as sole nutrition source following LMV. Acceptable strategies to enhance nutrition intake in post-ICU patients during the recovery stages of critical illness are needed.This research was funded by a research grant from the Canadian Foundation for Dietetic Research. L.L. Moisey was supported by a Canadian Institutes for Health Research Doctoral Research Award

A systematic review and meta-analysis of thigmotactic behaviour in the open field test in rodent models associated with persistent pain

Thigmotaxis is an innate predator avoidance behaviour of rodents. To gain insight into how injury and disease models, and analgesic drug treatments affect thigmotaxis, we performed a systematic review and meta-analysis of studies that assessed thigmotaxis in the open field test. Systematic searches were conducted of 3 databases in October 2020, March and August 2022. Study design characteristics and experimental data were extracted and analysed using a random-effects meta-analysis. We also assessed the correlation between thigmotaxis and stimulus-evoked limb withdrawal. This review included the meta-analysis of 165 studies We report thigmotaxis was increased in injury and disease models associated with persistent pain and this increase was attenuated by analgesic drug treatments in both rat and mouse experiments. Its usefulness, however, may be limited in certain injury and disease models because our analysis suggested that thigmotaxis may be associated with the locomotor function. We also conducted subgroup analyses and meta-regression, but our findings on sources of heterogeneity are inconclusive because analyses were limited by insufficient available data. It was difficult to assess internal validity because reporting of methodological quality measures was poor, therefore, the studies have an unclear risk of bias. The correlation between time in the centre (type of a thigmotactic metric) and types of stimulus-evoked limb withdrawal was inconsistent. Therefore, stimulus-evoked and ethologically relevant behavioural paradigms should be viewed as two separate entities as they are conceptually and methodologically different from each other

IRF5 promotes influenza-induced inflammatory responses in human iPSC-derived myeloid cells and murine models.

Recognition of Influenza A virus (IAV) by the innate immune system triggers pathways that restrict viral replication, activates innate immune cells, and regulates adaptive immunity. However, excessive innate immune activation can exaggerate disease. The pathways promoting excessive activation are incompletely understood, with limited experimental models to investigate mechanisms driving influenza-induced inflammation in humans. Interferon regulatory factor (IRF5) is a transcription factor that plays important roles in induction of cytokines after viral sensing. In an in vivo model of IAV infection, IRF5 deficiency reduced IAV-driven immune pathology and associated inflammatory cytokine production, specifically reducing cytokine-producing myeloid cell populations in Irf5-/- mice, but not impacting type 1 IFN production or virus replication. Using cytometry by time-of-flight (CyTOF), we identified that human lung IRF5 expression was highest in cells of the myeloid lineage. To investigate the role of IRF5 in mediating human inflammatory responses by myeloid cells to IAV, we employed human induced pluripotent stem cells (hIPSCs) with biallelic mutations in IRF5, demonstrating for the first time iPS-derived dendritic cells (iPS-DCs) with biallelic mutations can be used to investigate regulation of human virus-induced immune responses. Using this technology, we reveal that IRF5 deficiency in human DCs, or macrophages, corresponded with reduced virus-induced inflammatory cytokine production, with IRF5 acting downstream of TLR7 and, possibly, RIG-I after viral sensing. Thus, IRF5 acts as a regulator of myeloid cell inflammatory cytokine production during IAV infection in mice and humans, and drives immune-mediated viral pathogenesis independently of type 1 IFN and virus replication.ImportanceThe inflammatory response to Influenza A virus (IAV) participates in infection control but contributes to disease severity. After viral detection intracellular pathways are activated, initiating cytokine production, but these pathways are incompletely understood. We show that interferon regulatory factor 5 (IRF5) mediates IAV-induced inflammation and, in mice, drives pathology. This was independent of antiviral type 1 IFN and virus replication, implying that IRF5 could be specifically targeted to treat influenza-induced inflammation. We show for the first time that human iPSC technology can be exploited in genetic studies of virus-induced immune responses. Using this technology, we deleted IRF5 in human myeloid cells. These IRF5-deficient cells exhibited impaired influenza-induced cytokine production and revealed that IRF5 acts downstream of Toll-like receptor 7 and possibly retinoic acid-inducible gene-I. Our data demonstrate the importance of IRF5 in influenza-induced inflammation, suggesting genetic variation in the IRF5 gene may influence host susceptibility to viral diseases.This work was supported by The Wellcome Trust. This work was funded by a Wellcome 641 Trust Senior Research Fellowship to Ian Humphreys (207503/Z/17/Z); Medical Research 642 Council, United Kingdom (MR/L018942/1 and MRC Human Immunology Unit Core); 643 Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences 644 (CIFMS), China (grant number: 2018-I2M-2-002). The Wellcome Trust Sanger Institute was 645 the source of the Kolf2 human induced pluripotent cell line which was generated under the 646 Human Induced Pluripotent Stem Cell Initiative funded by a grant from the Wellcome Trust Downloaded from http://jvi.asm.org/ on March 2, 2020 at CAMBRIDGE UNIV27 and Medical Research Council, supported 647 by the Wellcome Trust (WT098051) and the 648 NIHR/Wellcome Trust Clinical Research Facility, and Life Science Technologies 649 Corporation provided Cytotune for reprogramming. We thank the Wellcome Trust Sanger Institute Gene editing pipeline for generation of IRF5-/- 650 iPSCs and the Mass spectrometry 651 Facility at the Weatherall Institute of Molecular Medicine for help with CyTOF experiments