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Showing 321–340 of 2058 publications.
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Nadel, James; Jabbour, Andrew; Stocker, RolandIntracellular myeloperoxidase (MPO) plays a specific role in the innate immune response; however, upon release into the extracellular space in the setting of inflammation, drives oxidative tissue injury. Extracellular MPO has recently been shown to be abundant in unstable atheroma and causally linked to plaque destabilization, erosion, and rupture, identifying it as a potential target for the surveillance and treatment of vulnerable atherosclerosis. Through the compartmentalization of MPOs protective and deleterious effects, extracellular MPO can be selectively detected using non-invasive molecular imaging and targeted by burgeoning pharmacotherapies. Given its causal relationship to plaque destabilization coupled with an ability to preserve its beneficial properties, MPO is potentially a superior translational inflammatory target compared with other immunomodulatory therapies and imaging biomarkers utilized to date. This review explores the role of MPO in plaque destabilization and provides insights into how it can be harnessed in the management of patients with vulnerable atherosclerotic plaque. The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.
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Schnabel, Renate B.; Marinelli, Elena Andreassi; Arbelo, Elena; Boriani, Giuseppe; Bova, Serge; Buckley, Claire Mary; Camm, A.John John; Casadei, Barbara; Chua, Winnie Ling; Dagres, Nikolaos; de Melis, Mirko; Desteghe, Lien; Diederichsen, Sen Za; Duncker, David; Eckardt, Lars; Eisert, Christoph; Engler, Daniel; Fabritz, Larissa; Freedman, Ben Ben; Gillet, Ludovic; Goette, Andreas; Guasch, Eduard; Svendsen, Jesper Hastrup; N. Hatem, Sthane Nicolas; Haeusler, Karl Georg; Healey, Jeff S.; Heidbuchel, H. P.; Hindricks, Gerhard; Hobbs, FD Richard; Hner, Thomas; Kotecha, Dipak; Krekler, Michael; Leclercq, Christophe; Lewalter, Thorsten; Lin, Honghuang; Linz, Dominik K.; Lip, Gregory Y.H.; Lhen, Maja Lisa; Lucassen, Wim A.M.; Malaczynska-Rajpold, Katarzyna; Massberg, Steffen; Merino, JosLuis; Meyer, Ralf; Mont, Llu; Myers, Michael C.; Neubeck, Lis; Niiranen, Teemu J.; Oeff, Michael; Oldgren, Jonas S.; Potpara, Tatjana S.; Psaroudakis, George; Perfellner, Helmut; Ravens, Ursula; Rienstra, Michiel; Rivard, La; Scherr, Daniel; Schotten, Ulrich; Shah, Dipen C.; Sinner, Moritz F.; Smolnik, Riger; Steinbeck, Gerhard; Steven, Daniel; Svennberg, Emma; Thomas, Dierk; Hills, Mellanie True; van Gelder, Isabelle C.; Vardar, Burcu; Pala, Elena; Wakili, Reza; Wegscheider, Karl; Wieloch, Mattias; Willems, Stephan; Witt, Henning; Ziegler, Andrd; Daniel Zink, Matthias; Kirchhof, Paulus F.Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI. 2022 The Author(s). Published by Oxford University Press on behalf of European Society of Cardiology.
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Naing, Pyi; Kangaharan, Nadarajah; Scalia, Gregory M.; Strange, G. A.; Playford, David A.Pulmonary hypertension (PH) is a common and debilitating medical condition with high mortality. PH research has traditionally focused on pulmonary arterial hypertension and its management in expert PH centres. Other forms of PH such as PH associated with cardiac or respiratory disease are more common, less well-understood and associated with higher mortality. Epidemiology of PH in disadvantaged, remote and rural regions, remains largely undocumented. In this review, we discuss the unique challenges in identifying PH in rural and disadvantaged populations using the Top End region of the Northern Territory of Australia as an example. We propose a simple diagnostic approach, ideally suited to regions where resource allocation is scarce, using clinical skills, echocardiography, and an escalation algorithm. The brief history, epidemiology and current literature on PH are summarised to inform the busy clinicians. We highlight two case examples from the Top End to illustrate the challenges and potential solutions. 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.
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Freedman, Ben Ben; Schnabel, Renate B.[No abstract available]
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Dupuy, Alexander; Ju, Lining Arnold; Chiu, Joyce; Passam, Freda H.Significance: How mechanical forces and biochemical cues are coupled remains a miracle for many biological processes. Integrins, well-known adhesion receptors, sense changes in mechanical forces and reduction-oxidation reactions (redox) in their environment to mediate their adhesive function. The coupling of mechanical and redox function is a new area of investigation. Disturbance of normal mechanical forces and the redox balance occurs in thromboinflammatory conditions; atherosclerotic plaques create changes to the mechanical forces in the circulation. Diabetes induces redox changes in the circulation by the production of reactive oxygen species and vascular inflammation. Recent Advances: Integrins sense changes in the blood flow shear stress at the level of focal adhesions and respond to flow and traction forces by increased signaling. Talin, the integrin-actin linker, is a traction force sensor and adaptor. Oxidation and reduction of integrin disulfide bonds regulate their adhesion. A conserved disulfide bond in integrin ?lpha IIb beta 3 (?IIb?3) is directly reduced by the thiol oxidoreductase endoplasmic reticulum protein 5 (ERp5) under shear stress. Critical Issues: The coordination of mechano-redox events between the extracellular and intracellular compartments is an active area of investigation. Another fundamental issue is to determine the spatiotemporal arrangement of key regulators of integrins' mechanical and redox interactions. How thromboinflammatory conditions lead to mechanoredox uncoupling is relatively unexplored. Future Directions: Integrated approaches, involving disulfide bond biochemistry, microfluidic assays, and dynamic force spectroscopy, will aid in showing that cell adhesion constitutes a crossroad of mechano- and redox biology, within the same molecule, the integrin. Antioxid. Redox Signal. 37, 1072-1093. Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.
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Hong, Jun Ki; Ruhoff, Alexander M.; Mathur, Kavya; Neto, Chiara; Waterhouse, AnnaBiomedical devices are prone to blood clot formation (thrombosis), and liquid-infused surfaces (LIS) are effective in reducing the thrombotic response. However, the mechanisms that underpin this performance, and in particular the role of the lubricant, are not well understood. In this work, it is investigated whether the mechanism of LIS action is related to i) inhibition of factor XII (FXII) activation and the contact pathway; ii) reduced fibrin density of clots formed on surfaces; iii) increased mobility of proteins or cells on the surface due to the interfacial flow of the lubricant. The chosen LIS is covalently tethered, nanostructured layers of perfluorocarbons, infused with thin films of medical-grade perfluorodecalin (tethered-liquid perfluorocarbon), prepared with chemical vapor deposition previously optimized to retain lubricant under flow. Results show that in the absence of external flow, interfacial mobility is inherently higher at the liquidblood interface, making it a key contributor to the low thrombogenicity of LIS, as FXII activity and fibrin density are equivalent at the interface. The findings of this study advance the understanding of the anti-thrombotic behavior of LIS-coated biomedical devices for future coating design. More broadly, enhanced interfacial mobility may be an important, underexplored mechanism for the anti-fouling behavior of surface coatings. 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
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Brandes, Axel; Stavrakis, Stavros; Freedman, Ben Ben; Antoniou, Sotiris; Boriani, Giuseppe; Camm, Alan John; Chow, Clara Kayei; DIng, Eric Y.; Engdahl, Johan; Gibson, Michael M.; Golovchiner, Gregory N.; Glotzer, Taya V.; Guo, Yutao; Healey, Jeff S.; Hills, Mellanie True; Johnson, Linda S.B.; Lip, Gregory Y.H.; Lobban, Trudie C.A.; Macfarlane, Peter W.; Marcus, Gregory Maurice; McManus, David D.; Neubeck, Lis; Orchard, Jessica Joan; Perez, Marco Valentin; Schnabel, Renate B.; Smyth, Breda; Steinhubl, Steven R.; Turakhia, Minang P.The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening. 2021 American Heart Association, Inc.
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Kavurma, Mary M.; Bursill, C. A.; Stanley, Christopher P.; Passam, Freda H.; Cartland, Si; Patel, Sanjay; Loa, Jacky; Figtree, Gemma A.; Golledge, Jonathan; Aitken, Sarah Joy; Robinson, David A.Peripheral artery disease (PAD) is caused by occluded or narrowed arteries that reduce blood flow to the lower limbs. The treatment focuses on lifestyle changes, management of modifiable risk factors and vascular surgery. In this review we focus on how Endothelial Cell (EC) dysfunction contributes to PAD pathophysiology and describe the largely untapped potential of correcting endothelial dysfunction. Moreover, we describe current treatments and clinical trials which improve EC dysfunction and offer insights into where future research efforts could be made. Endothelial dysfunction could represent a target for PAD therapy. 2022 Kavurma, Bursill, Stanley, Passam, Cartland, Patel, Loa, Figtree, Golledge, Aitken and Robinson.
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Wang, Ziyu; Mithieux, Suzanne M.; Vindin, Howard J.; Wang, Yiwei; Zhang, Miao; Liu, Linyang; Zbinden, Jacob C.; Blum, Kevin M.; Yi, Tai; Matsuzaki, Yuichi; Oveissi, Farshad; Akdemir, Reyda; Lockley, Karen M.; Zhang, Lingyue; Ma, Ke; Guan, Juan; Waterhouse, Anna; Pham, Nguyen T.H.; Hawkett, Brian S.; Shin'oka, Toshiharu K.; Breuer, Christopher K.; Weiss, Anthony StevenNative arteries contain a distinctive intima-media composed of organized elastin and an adventitia containing mature collagen fibrils. In contrast, implanted biodegradable small-diameter vascular grafts do not present spatially regenerated, organized elastin. The elastin-containing structures within the intima-media region encompass the elastic lamellae (EL) and internal elastic lamina (IEL) and are crucial for normal arterial function. Here, the development of a novel electrospun small-diameter vascular graft that facilitates de novo formation of a structurally appropriate elastin-containing intima-media region following implantation is described. The graft comprises a non-porous microstructure characterized by tropoelastin fibers that are embedded in a PGS matrix. After implantation in mouse abdominal aorta, the graft develops distinct cell and extracellular matrix profiles that approximate the native adventitia and intima-media by 8 weeks. Within the newly formed intima-media region there are circumferentially aligned smooth muscle cell layers that alternate with multiple EL similar to that found in the arterial wall. By 8 months, the developed adventitia region contains mature collagen fibrils and the neoartery presents a distinct IEL with thickness comparable to that in mouse abdominal aorta. It is proposed that this new class of material can generate the critically required, organized elastin needed for arterial regeneration. 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.
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Hosseini, Ehteramolsadat; Solouki, Amin; Haghshenas, Masood; Ghasemzadeh, Mehran; Schoenwaelder, Simone M.Background: Continuous agitation during storage slows down the platelet storage lesions. However, in special circumstances, manual-mixing can be alternatively used to store products for short time periods without compromising platelet quality. Based on this finding, and given the role of shear stress in modulating receptor expression, we were interested in comparing the levels of platelet adhesion receptor, GPVI and platelet adhesion capacity under each storage condition. Methods: Platelet concentrates (PCs) were divided into three groups: continuously-agitated PCs (CAG-PCs) with or without PP2 (Src kinase inhibitor) and manually-mixed PCs (MM-PCs). Platelet count/MPV, swirling, GPVI and P-selectin expression, GPVI shedding, platelet adhesion/spreading to collagen were examined during 5 days of storage. Results: While MM- and CAG-PCs showed similar levels of P-selectin expression, GPVI expression was significantly elevated in MM-PCs with lower GPVI shedding/expression ratios, enhanced platelet adhesion/spreading and swirling in manually-mixed PCs. Of note, CAG-PCs treated with PP2 also demonstrated lower P-selectin expression and GPVI shedding, higher GPVI expression and attenuated swirling and spreading capability. Conclusion: Given the comparable platelet activation state in MM and CAG-PCs as indicated by P-selectin expression, enhanced platelet adhesion/spreading in MM-PCs, along with relatively higher GPVI expression here, supports previous studies demonstrating a role for biomechanical forces in modulating GPVI-dependent function. Thus, lower GPVI expression in CAG-PCs may be due to shear forces induced by agitation, which keeps this receptor down-regulated while also attenuating platelet adhesion/spreading capacities during storage. Low platelet function in PP2-CAG-PCs also highlights the importance of Src-kinases threshold activity in maintaining platelets quality. 2022, The Author(s).
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Hespe, Charlotte Mary; Giskes, Katrina; Harris, Mark Fort; Peiris, David P.Background: There are discrepancies between evidence-based guidelines for screening and management of cardiovascular disease (CVD) and implementation in Australian general practice. Quality-improvement (QI) initiatives aim to reduce these gaps. This study evaluated a QI program (QPulse) that focussed on CVD assessment and management. Methods: This mixed-methods study explored the implementation of guidelines and adoption of a QI program with a CVD risk-reduction intervention in 34 general practices. CVD screening and management were measured pre- and post-intervention. Qualitative analyses examined participants Plan-Do-Study-Act (PDSA) goals and in-depth interviews with practice stakeholders focussed on barriers and enablers to the program and were analysed thematically using Normalisation Process Theory (NPT). Results: Pre- and post-intervention data were available from 15 practices (n= 19,562 and n= 20,249, respectively) and in-depth interviews from seven practices. At baseline, 45.0% of patients had their BMI measured and 15.6% had their waist circumference recorded in the past 2 years and blood pressure, lipids and smoking status were measured in 72.5, 61.5 and 65.3% of patients, respectively. Most high-risk patients (57.5%) were not prescribed risk-reducing medications. After the intervention there were no changes in the documentation and prevalence of risk factors, attainment of BP and lipid targets or prescription of CVD risk-reducing medications. However, there was variation in performance across practices with some showing isolated improvements, such as recording waist circumference (0.7-32.2% pre-intervention to 18.5-69.8% post-intervention), BMI and smoking assessment. Challenges to the program included: lack of time, need for technical support, a perceived lack of value for quality improvement work, difficulty disseminating knowledge across the practice team, tensions between the team and clinical staff and a part-time workforce. Conclusion: The barriers associated with this QI program was considerable in Australian GP practices. Findings highlighted they were not able to effectively operationalise the intervention due to numerous factors, ranging from lack of internal capacity and leadership to competing demands and insufficient external support. Trial registration: Australian New Zealand Clinical Trials Reference Number (ACTRN12615000108516), registered 06/02/2015. 2022, The Author(s).
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Rodionov, Roman Nikolaevich; Jarzebska, Natalia; Burdin, Dmitrii V.; Todorov, Vladimir T.; Martens-Lobenhoffer, Jens; Hofmann, Anja; Kolouschek, Anne; Cordasic, Nada; Jacobi, Johannes; Rubets, Elena; Morawietz, Henning; OSullivan, John F.; Markov, Alexander Georgievich; Bornstein, Stefan R.; Hilgers, Karl Friedrich; Maas, Renke; Pfluecke, Christian; Chen, Yingjie; Bode-Ber, Stefanie Margarethe; Hugo, Christian P.M.; Hohenstein, Bernd; Weiss, NorbertElevated plasma concentrations of asymmetric dimethylarginine (ADMA) are associated with an increased risk of mortality and adverse cardiovascular outcomes. ADMA can be metabolized by dimethylarginine dimethylaminohydrolases (DDAHs) and by alanine-glyoxylate aminotransferase 2 (AGXT2). Deletion of DDAH1 in mice leads to elevation of ADMA in plasma and increase inblood pressure, while overexpression of human DDAH1 is associated with a lower plasma ADMA concentration and protective cardiovascular effects. The possible role of alternative metabolism of ADMA by AGXT2 remains to be elucidated. The goal of the current study was to test the hypothesis that transgenic overexpression of AGXT2 leads to lowering of plasma levels of ADMA and protection from vascular damage in the setting of DDAH1 deficiency. We generated transgenic mice (TG) with ubiquitous overexpression of AGXT2. qPCR and Western Blot confirmed the expression of the transgene. Systemic ADMA levels were decreased by 15% in TG mice. In comparison with wild type animals plasma levels of asymmetric dimethylguanidino valeric acid (ADGV), the AGXT2 associated metabolite of ADMA, were six times higher. We crossed AGXT2 TG mice with DDAH1 knockout mice and observed that upregulation of AGXT2 lowers plasma ADMA and pulse pressure and protects the mice from endothelial dysfunction and adverse aortic remodeling. Upregulation of AGXT2 led to lowering of ADMA levels and protection from ADMA-induced vascular damage in the setting of DDAH1 deficiency. This is especially important, because all the efforts to develop pharmacological ADMA-lowering interventions by means of upregulation of DDAHs have been unsuccessful. 2022, The Author(s).
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Afrose, Dinara; Chen, Hao; Ranashinghe, Amali; Liu, Chiachi; Henessy, Annemarie; HANSBRO, Philip M.; McClements, LanaBackground: Preeclampsia is a multifactorial cardiovascular disorder of pregnancy. If left untreated, it can lead to severe maternal and fetal outcomes. Hence, timely diagnosis and management of preeclampsia are extremely important. Biomarkers of oxidative stress are associated with the pathogenesis of preeclampsia and therefore could be indicative of evolving preeclampsia and utilized for timely diagnosis. In this study, we conducted a systematic review and meta-analysis to determine the most reliable oxidative stress biomarkers in preeclampsia, based on their diagnostic sensitivities and specificities as well as their positive and negative predictive values. Methods: A systematic search using PubMed, ScienceDirect, ResearchGate, and PLOS databases (1900 to March 2021) identified nine relevant studies including a total of 343 women with preeclampsia and 354 normotensive controls. Results: Ischemia-modified albumin(IMA), uric acid(UA), and malondialdehyde(MDA) were associated with 3.38 (95% CI 2.23, 4.53), 3.05 (95% CI 2.39, 3.71), and 2.37 (95% CI 1.03, 3.70) odds ratios for preeclampsia diagnosis, respectively. The IMA showed the most promising diagnostic potential with the positive predictive ratio (PPV) of 0.852 (95% CI 0.728, 0.929) and negative predictive ratio (NPV) of 0.811 (95% CI 0.683, 0.890) for preeclampsia. Minor between-study heterogeneity was reported for these biomarkers (Higgins I2 = 015.879%). Conclusions: This systematic review and meta-analysis identified IMA, UA, and MDA as the most promising oxidative stress biomarkers associated with established preeclampsia. IMA as a biomarker of tissue damage exhibited the best diagnostic test accuracy. Thus, these oxidative stress biomarkers should be further explored in larger cohorts for preeclampsia diagnosis. Graphical Abstract: [Figure not available: see fulltext.] 2022, The Author(s).
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Coorey, Genevieve M.; Figtree, Gemma A.; Fletcher, D. F.; Snelson, Victoria J.; Vernon, Stephen Thomas; Winlaw, David S.; Grieve, Stuart M.; McEwan, Alistair Lee; Yang, Jean Yee Hwa; Qian, Pierre C.; OBrien, Kieran Robert; Orchard, Jessica Joan; Kim, Jinman; Patel, Sanjay; Redfern, JuliePotential benefits of precision medicine in cardiovascular disease (CVD) include more accurate phenotyping of individual patients with the same condition or presentation, using multiple clinical, imaging, molecular and other variables to guide diagnosis and treatment. An approach to realising this potential is the digital twin concept, whereby a virtual representation of a patient is constructed and receives real-time updates of a range of data variables in order to predict disease and optimise treatment selection for the real-life patient. We explored the term digital twin, its defining concepts, the challenges as an emerging field, and potentially important applications in CVD. A mapping review was undertaken using a systematic search of peer-reviewed literature. Industry-based participants and patent applications were identified through web-based sources. Searches of Compendex, EMBASE, Medline, ProQuest and Scopus databases yielded 88 papers related to cardiovascular conditions (28%, n = 25), non-cardiovascular conditions (41%, n = 36), and general aspects of the health digital twin (31%, n = 27). Fifteen companies with a commercial interest in health digital twin or simulation modelling had products focused on CVD. The patent search identified 18 applications from 11 applicants, of which 73% were companies and 27% were universities. Three applicants had cardiac-related inventions. For CVD, digital twin research within industry and academia is recent, interdisciplinary, and established globally. Overall, the applications were numerical simulation models, although precursor models exist for the real-time cyber-physical system characteristic of a true digital twin. Implementation challenges include ethical constraints and clinical barriers to the adoption of decision tools derived from artificial intelligence systems. 2022, The Author(s).
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Baracos, V. Elaine; Coats, Andrew J.S.; Anker, Stefan D.; Sherman, Lawrence; Klompenhouwer, TatianaBackground: Cancer cachexia negatively impacts patient outcomes, quality of life and survival. Identification and management of cancer cachexia remains challenging to healthcare professionals (HCPs). The aim of this assessment was to identify current gaps in HCPs' knowledge and practice for identifying and managing adults with cancer-related cachexia. Results may guide development of new educational programmes to close identified gaps and improve outcomes of cancer patients. Methods: An international assessment was conducted using a mixed-methods approach including focus group interviews with subject matter experts and an electronic survey of practising HCP. The assessment was led by the Society on Sarcopenia, Cachexia and Wasting Disorders (SCWD) and was supported by in-country collaborating organizations. Results: A quantitative survey of 58 multiple-choice questions was completed by physicians, nurses dietitians and other oncology HCP (N=2375). Of all respondents, 23.7% lacked confidence in their ability to provide care for patients with cancer cachexia. Patients with gastrointestinal, head and neck, pulmonary cancers and leukaemia/lymphoma were reported as those at highest risk for cachexia. Only 29.1% of respondents recognized a key criterion of cancer cachexia as >5% weight loss from baseline, but many (14.4%) did not utilize a standardized definition of cancer cachexia. Despite this, most clinicians (>84%) were able to identify causes of weight lossreduced oral intake, progressive disease, side effects of therapy and disease-related inflammation. Of all respondents, 52.7% indicated newly diagnosed patients with cancer should be screened for weight loss. In practice, 61.9% reported that patient weight was systematically tracked over time, but only 1125 (47.4%) reported they weigh their cancer patients at each visit. Treatment of cachexia focused on increasing the patient's nutritional intake by oral nutritional supplements (64.2%), energy and protein fortified foods (60.3%) and counselling by a dietitian (57.1%). Whereas many respondents (37.3%) considered cachexia inevitable, most (79.2%) believed that an interprofessional team approach could improve care and that use of standardized tools is critical. Conclusions: Findings from this international assessment highlight the challenges associated with the care of patients with cancer cachexia, opportunities for interventions to improve patient outcomes and areas of variance in care that would benefit from further analysis. 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
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Chen, Weiyu; Tumanov, Sergey; Kong, Stephanie M.Y.; Cheng, David; Michasson, Erik; Bongers, Andre; Power, Carl Andrew; Ayer, Anita; Stocker, RolandCurrently there are no established therapies to treat high-risk patients with unstable atherosclerotic lesions that are prone to rupture and can result in thrombosis, abrupt arterial occlusion, and a precipitous infarction. Rather than being stenotic, rupture-prone non-occlusive plaques are commonly enriched with inflammatory cells and have a thin fibrous cap. We reported previously that inhibition of the pro-inflammatory enzyme myeloperoxidase (MPO) with the suicide inhibitor AZM198 prevents formation of unstable plaque in the Tandem Stenosis (TS) mouse model of plaque instability. However, in our previous study AZM198 was administered to animals before unstable plaque was present and hence it did not test the significant unmet clinical need present in high-risk patients with vulnerable atherosclerosis. In the present study we therefore asked whether pharmacological inhibition of MPO with AZM198 can stabilize pre-existing unstable lesions in an interventional setting using the mouse model of plaque instability. In vivo molecular magnetic resonance imaging of arterial MPO activity using bis-5-hydroxytryptamide-DTPA-Gd and histological analyses revealed that arterial MPO activity was elevated one week after TS surgery, prior to the presence of unstable lesions observed two weeks after TS surgery. Animals with pre-existing unstable plaque were treated with AZM198 for one or five weeks. Both short- and long-term intervention effectively inhibited arterial MPO activity and increased fibrous cap thickness, indicative of a more stable plaque phenotype. Plaque stabilization was observed without AZM198 affecting the arterial content of Ly6B.2+- and CD68+-cells and MPO protein. These findings demonstrate that inhibition of arterial MPO activity converts unstable into stable atherosclerotic lesions in a preclinical model of plaque instability and highlight the potential therapeutic potency of MPO inhibition for the management of high-risk patients and the development of novel protective strategies against cardiovascular diseases. 2022 The Authors
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Stanton, Kelly M.; Wylie, Laura; Kotchetkova, Irina; Coy, A. M.Y.; Carroll, Gerard; La Gerche, AndrCrossed D.Sign; Celermajer, David S.Purpose Most studies reporting cardiac changes with exercise have been cross sectional. The few available longitudinal studies have lacked standardization for environmental confounders. We prospectively assessed the relationship between increasing exercise intensity and cardiac remodeling in a highly standardized cohort of healthy young army soldiers. Methods Sixty-three male army recruits (22 3 yr) underwent a 12-wk moderate-intensity mixed strength and endurance exercise program, followed by a further 15-wk high-intensity exercise program, with highly controlled exercise, diet, and sleep patterns. Fitness (multistage fitness test), anthropometry, and 2D echocardiography were assessed. Results Moderate-intensity exercise was associated with increased fitness and decreased body fat % (both P < 0.01). There was no significant incremental change in these parameters after high-intensity exercise. By contrast, both moderate- and high-intensity exercises were associated with dose-dependent increases in left atrial and left ventricular (LV) volumes, LV mass, and right ventricular (RV) size (all P < 0.01). At the end of high-intensity training, 51% had a dilated LV and 59% had a dilated RV compared with published normal ranges. Almost all had normal LV systolic function and strain before and after exercise training. A small number of soldiers had mildly decreased RV systolic function at baseline and after moderate-intensity exercise (3% and 6%, respectively). Conclusions We describe "soldiers' heart,"which is characterized by balanced chamber dilatation, normal LV mass, and largely normal systolic function and myocardial strain. This prospective and highly controlled longitudinal study also found that increasing intensity exercise was associated with increasing chamber dimensions, which paralleled an increase in fitness after moderate-intensity exercise. After high-intensity exercise, however, cardiac chamber size continued to increase, but fitness did not increase further. Lippincott Williams & Wilkins.
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Ngwira, Memory M.; Gadama, Luis Aaron; Shanmugalingam, Renuka; Makris, Angela; Hennessy, AnnemarieObjectives: This study investigated health care workers and key policy informant's knowledge, and barriers to the use of calcium and aspirin for preventing preeclampsia in Blantyre and Lilongwe, Malawi. Methods: A descriptive cross-sectional formative study using semi-structured In-Depth Interview (IDIs) was conducted at Queen Elizabeth Central Hospital (QECH), Reproductive Health Directorate, and the United Nations Population Development Fund (UNFPA) Office in 2021. Data was analyzed using NVIVO software. Thematic content analysis was used to analyze and interpret the findings. Emerging themes were then developed inductively and deductively. Results: Doctors had greater knowledge of the use of calcium and aspirin for prevention of preeclampsia compared to nurses and key policy informants. Lack of knowledge, patient's late presentation, scarcity of calcium tablets and delays in implementing new guidelines were the barriers to use identified. Conclusion: This study shows that there are health care worker and policy level barriers that affect the implementation of calcium and aspirin use for the prevention of preeclampsia in Malawian women. 2022 International Society for the Study of Hypertension in Pregnancy
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Tucker, Bradley; Patel, Sanjay[No abstract available]
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Koay, Yen Chin; Coster, Adelle C.F.; Chen, Daniel L.T.; Milner, Brad; Batarseh, Amani M.; OSullivan, John F.; Greenfield, Jerry R.; Samocha-Bonet, DoritThe liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the IR phenotype in a patient may guide the treatment or the prevention strategy for better health outcomes in populations at risk. Here, we performed plasma metabolomics and lipidomics in a cohort of men and women living with obesity not complicated by diabetes (mean [SD] BMI 36.0 [4.5] kg/m2, n = 62) to identify plasma signatures of metabolites and lipids that align with phenotypes of IR (muscle, liver, or adipose tissue) and abdominal fat depots. We used 2-step hyperinsulinemic-euglycemic clamp with deuterated glucose, oral glucose tolerance test, dual-energy X-ray absorptiometry and abdominal magnetic resonance imaging to assess muscle-, liver- and adipose tissue- IR, beta cell function, body composition, abdominal fat distribution and liver fat, respectively. Spearmans rank correlation analyses that passed the BenjaminiHochberg statistical correction revealed that cytidine, gamma-aminobutyric acid, anandamide, and citrate corresponded uniquely with muscle IR, tryptophan, cAMP and phosphocholine corresponded uniquely with liver IR and phenylpyruvate and hydroxy-isocaproic acid corresponded uniquely with adipose tissue IR (p < 7.2 10?4). Plasma cholesteryl sulfate (p = 0.00029) and guanidinoacetic acid (p = 0.0001) differentiated between visceral and subcutaneous adiposity, while homogentisate correlated uniquely with liver fat (p = 0.00035). Our findings may help identify diverse insulin resistance and adiposity phenotypes and enable targeted treatments in people living with obesity. 2022 by the authors.
