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1.
Kidney Int ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32409237

RESUMO

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.

3.
Transpl Int ; 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32337774

RESUMO

A primary obligation of medical journals is the responsible, professional, and expeditious delivery of knowledge from researchers and practitioners to the wider community.1 The task of journal editors, therefore, rests not merely in selecting what to publish, but in large measure judging how it might best be communicated. The challenge of improving descriptions of kidney function and disease in medical publishing was the impetus for a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference held in June 2019. The conference goals included standardizing and refining kidney-related nomenclature used in English-language scientific articles and developing a glossary that could be used by journals.2.

4.
Kidney Int ; 97(5): 861-876, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32278617

RESUMO

Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technology-based solutions; and volume-related patient symptoms and experiences. The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32276946

RESUMO

The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 "Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors" was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a "proof-of-concept" risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate's profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32248348

RESUMO

We developed models of pulmonary artery (PA) size in Fontan patients as a function of age and body surface area (BSA) using linear regression and breakpoint analyses based on data from 43 Fontan patients divided into two groups: the extracardiac conduit (ECC) group (n = 24) and the non-ECC group (n = 19). Model predictions were compared against those of a non-Fontan control group (n = 18) and published literature. We observed strong positive correlations of the mean PA diameter with BSA (r = 0.9, p < 0.05) and age (r = 0.88, p < 0.05) in the ECC group. The absolute percentage differences between our BSA and age model predictions against published literature were less than 16% and 20%, respectively. Predicted PA size for Fontan patients was consistently smaller than the control group. These models may serve as useful references for clinicians and be utilized to construct 3D anatomic models that correspond to patient body size or age.

7.
J Hypertens ; 38(4): 723-730, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32134846

RESUMO

OBJECTIVE: Reservoir pressure parameters [e.g. reservoir pressure (RP) and excess pressure (XSP)] measured using tonometry predict cardiovascular events beyond conventional risk factors. However, the operator dependency of tonometry impedes widespread use. An operator-independent cuff-based device can reasonably estimate the intra-aortic RP and XSP from brachial volumetric waveforms, but whether these estimates are clinically relevant to preclinical phenotypes of cardiovascular risk has not been investigated. METHODS: The RP and XSP were derived from brachial volumetric waveforms measured using cuff oscillometry (SphygmoCor XCEL) in 1691 mid-life adults from the CheckPoint study (a population-based cross-sectional study nested in the Longitudinal Study of Australian Children). Carotid intima--media thickness (carotid IMT, n = 1447) and carotid--femoral pulse wave velocity (PWV, n = 1632) were measured as preclinical phenotypes of cardiovascular risk. Confounders were conventional risk factors that were correlated with both exposures and outcomes or considered as physiologically important. RESULTS: There was a modest association between XSP and carotid IMT (ß = 0.76 µm, 95% CI, 0.25-1.26 partial R = 0.8%) after adjusting for age, sex, BMI, heart rate, smoking, diabetes, high-density lipoprotein cholesterol and mean arterial pressure. Neither RP nor XSP were associated with PWV in the similarly adjusted models (ß = -0.47 cm/s, 95% CI, -1.15 to 0.20, partial R = 0.2% for RP, and ß = 0.04 cm/s, 95% CI, -0.59 to 0.67, partial R = 0.01% for XSP). CONCLUSION: Cuff-based XSP associates with carotid IMT independent of conventional risk factors, including traditional BP, but the association was weak, indicating that further investigation is warranted to understand the clinical significance of reservoir pressure parameters.

8.
J Med Internet Res ; 22(3): e16769, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32217498

RESUMO

BACKGROUND: Technological surrogate nursing (TSN) derives from the idea that nurse-caregiver substitutes can be created by technology to support chronic disease self-care. OBJECTIVE: This paper begins by arguing that TSN is a useful and viable approach to chronic disease self-care. The analysis then focuses on the empirical research question of testing and demonstrating the effectiveness and safety of prototype TSN supplied to patients with the typical complex chronic disease of coexisting type 2 diabetes and hypertension. At the policy level, it is shown that the data allow for a calibration of TSN technology augmentation, which can be readily applied to health care management. METHODS: A 24-week, parallel-group, randomized controlled trial (RCT) was designed and implemented among diabetic and hypertensive outpatients in two Hong Kong public hospitals. Participants were randomly assigned to an intervention group, supplied with a tablet-based TSN app prototype, or to a conventional self-managing control group. Primary indices-hemoglobin A1c, systolic blood pressure, and diastolic blood pressure-and secondary indices were measured at baseline and at 8, 12, 16, and 24 weeks after initiation, after which the data were applied to test TSN effectiveness and safety. RESULTS: A total of 299 participating patients were randomized to the intervention group (n=151) or the control group (n=148). Statistically significant outcomes that directly indicated TSN effectiveness in terms of hemoglobin 1c were found in both groups but not with regard to systolic and diastolic blood pressure. These findings also offered indirect empirical support for TSN safety. Statistically significant comparative changes in these primary indices were not observed between the groups but were suggestive of an operational calibration of TSN technology augmentation. Statistically significant changes in secondary indices were obtained in one or both groups, but not between the groups. CONCLUSIONS: The RCT's strong behavioral basis, as well as the importance of safety and effectiveness when complex chronic illness is proximately self-managed by layperson patients, prompted the formulation of the empirical joint hypothesis that TSN would improve patient self-care while satisfying the condition of patient self-safety. Statistical and decision analysis applied to the experimental outcomes offered support for this hypothesis. Policy relevance of the research is demonstrated by the derivation of a data-grounded operational calibration of TSN technology augmentation with ready application to health care management. TRIAL REGISTRATION: ClinicalTrials.gov NCT02799953; https://clinicaltrials.gov/ct2/show/NCT02799953.

9.
Diabetes Res Clin Pract ; 162: 108092, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32109519

RESUMO

The Guideline Workshop 2019, held in October 2019 in Munich, Germany, had the purpose of facilitating discussion on strategies for optimization of guideline processes in diabetes amongst a group of representatives of renown national and international societies in the field of diabetes, cardiology, and nephrology. Results of this panel's discussions are presented in this manuscript and comprise a variety of suggestions for improving the quality and usability of guidelines, as well as to accelerate the development and responsiveness of guidelines to newly published, relevant data from clinical trials such as cardiovascular outcome trials in diabetes mellitus. These include, but are not limited to, recommendations to optimize presentation of content in guidelines, use of the GRADE-approach to rating the quality of evidence to harmonize guidelines, and utilization of digital health technologies to accelerate, streamline, and optimize communication on relevant data and development of clinical guidelines and necessary updates, while reducing costs. Recognizing that achieving alignment in guideline development among various medical organizations will be a long-term process, representatives from cross-sectional medical organizations relevant to cardio-renal metabolic disease and experts in guideline methodology will work together in the future. Among other activities, it is planned to continue the activity and organize a Guideline Workshop in 2020.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32034901

RESUMO

OBJECTIVES: The aim of this study was to study the impact of a decision-making protocol for shunt type in the Norwood procedure for hypoplastic left heart syndrome. Our cohort extends from 2004 to 2016. In era 1 (pre-2008), there was no policy for the choice of Norwood shunt. In era 2 (post-2008), a standard protocol was implemented. The right ventricle (RV)-to-pulmonary artery conduit was utilized for low-birth weight patients (<2.5 kg). The right modified Blalock-Taussig Shunt (RBTS) was constructed for normal birth weight patients. METHODS: The records of 133 consecutive operative patients with hypoplastic left heart syndrome anatomy between 2004 and 2016 were retrospectively reviewed. Survival risk factors were analysed using the Cox proportional hazards risk model. RESULTS: The Norwood procedure was performed at a mean age of 2.9 ± 1.9 days. Bidirectional cavopulmonary shunt was performed at a median age of 99 days (interquartile range 91-107). In era 1, 38.6% (22/57) of patients received the RBTS and 61.4% (35/57) of patients received the RV-to-pulmonary artery conduit. In era 2, 86.8% (66/76) of patients received the RBTS and 13.2% (10/76) of patients received the RV-to-pulmonary artery conduit. The actuarial survival to Fontan was 72.2% (96/133). Era 1 patients were more likely to die within the 1st year (hazard ratio = 2.310, P = 0.025). CONCLUSIONS: The shunt protocol may improve outcomes in high-risk patients, and we have demonstrated the reliability of the RBTS in low-risk patients. The short- and mid-term outcomes of our Norwood population justify the continued efforts to improve surgical and perioperative management.

11.
J Appl Physiol (1985) ; 128(2): 429-439, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971471

RESUMO

Reversal of shunting across the ductus arteriosus from right-to-left to left-to-right is a characteristic feature of the birth transition. Given that immediate cord clamping (ICC) followed by an asphyxial cord clamp-to-ventilation (CC-V) interval may augment left ventricular (LV) output and central blood flows after birth, we tested the hypothesis that an asphyxial CC-V interval accelerates the onset of postnatal left-to-right ductal shunting. High-fidelity central blood flow signals were obtained in anesthetized preterm lambs (gestation 128 ± 2 days) after ICC followed by a nonasphyxial (∼40 s, n = 9) or asphyxial (∼90 s, n = 9) CC-V interval before mechanical ventilation for 30 min after birth. Left-to-right ductal flow segments were related to aortic isthmus and descending aortic flow profiles to quantify sources of ductal shunting. In the nonasphyxial group, phasic left-to-right ductal shunting was initially minor after birth, but then rose progressively to 437 ± 164 ml/min by 15 min (P < 0.001). However, in the asphyxial group, this shunting increased from 24 ± 21 to 199 ± 93 ml/min by 15 s after birth (P < 0.001) and rose further to 471 ± 190 ml/min by 2 min (P < 0.001). This earlier onset of left-to-right ductal shunting was supported by larger contributions (P < 0.001) from direct systolic LV flow and retrograde diastolic discharge from an arterial reservoir/windkessel located in the descending aorta and its major branches, and associated with increased pulmonary arterial blood flow having a larger ductal component. These findings suggest that the duration of the CC-V interval after ICC is an important modulator of left-to-right ductal shunting, LV output and pulmonary perfusion at birth.NEW & NOTEWORTHY This birth transition study in preterm lambs demonstrated that a brief (∼90 s) asphyxial interval between umbilical cord clamping and ventilation onset resulted in earlier and greater left-to-right shunting across the ductus arteriosus after birth. This greater shunting 1) resulted from an increased left ventricular output associated with a higher systolic left-to-right ductal flow and increased retrograde diastolic discharge from a lower body arterial reservoir/windkessel, and 2) was accompanied by greater lung perfusion after birth.

12.
Heart Lung Circ ; 29(1): 5-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735685

RESUMO

The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.

13.
Kidney Int ; 97(1): 42-61, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31706619

RESUMO

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas.

14.
Hum Reprod ; 35(1): 232-239, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834929

RESUMO

STUDY QUESTION: Is ART related with the association of American Heart Association (AHA) ideal cardiovascular health score and markers of subclinical atherosclerosis? SUMMARY ANSWER: The associations between AHA score and markers of subclinical atherosclerosis in ART and non-ART groups were similar in magnitude. WHAT IS KNOWN ALREADY: Long-term consequences of ART on cardiovascular health are unknown. STUDY DESIGN, SIZE, DURATION: The study cohort for the cross-sectional analyses consisted of 172 ART-conceived and 78 non-ART conceived individuals of same age (range 22-35 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Cardiovascular risk factor status was evaluated with American Heart Association (AHA) ideal cardiovascular health score consisting of seven factors (body mass index, blood pressure, total cholesterol, glucose, diet and physical activity, non-smoking). Carotid artery intima-media thickness (cIMT), arterial pulse-wave velocity (PWV) and retinal microvascular parameters were evaluated as markers of early atherosclerosis. Group comparisons in continuous variables were performed with t-tests. For categorical variables, comparisons were performed with chi-square tests. The relationships between AHA score and the markers of atherosclerosis were examined with linear regression analyses adjusted for age and sex. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in AHA ideal health score between the ART and non-ART groups; mean (SD) scores were 4.1(1.4) versus 4.0(1.5), respectively, P = 0.65. No differences were observed between groups for any individual ideal health metric (P always >0.2). AHA score was not associated with cIMT or retinal measures in either group (P always >0.05). An inverse association was observed between AHA score and PWV in the ART group (beta (95% CI) -0.18(-0.26 to -0.10)). A numerically similar relationship was observed in the smaller non-ART group (-0.19(-0.39 to 0.01)). LIMITATIONS, REASONS FOR CAUTION: Even though this cohort is among the largest ART studies with extensive cardiovascular data, the sample is still relatively small and the statistical power is limited. As the study population was still in early adulthood, we were not able to evaluate the associations with clinical cardiovascular events, but utilized non-invasive methods to assess early markers of subclinical atherosclerosis. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that ART-conceived individuals do not have increased vulnerability for cardiovascular risk factors. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a National Health & Medical Research Council Project Grant (APP1099641), The Royal Children's Hospital Research Foundation, Monash IVF Research and Education Foundation, and Reproductive Biology Unit Sperm Fund, Melbourne IVF. The authors have no conflicts of interest relevant to this article to disclose.

15.
Hypertension ; 75(1): 211-217, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735082

RESUMO

More infants born extremely preterm (<28 weeks' gestation) or extremely low birthweight (<1000 g) are surviving into adulthood in recent years. Preterm adolescents have higher blood pressure (BP) than normal birthweight controls, but how their BP changes with increasing age is not known. We compared BP at 25 years and trajectories of BP (change per year) from 18 to 25 years between survivors born <28 weeks/<1000 g and normal birthweight (>2499 g) controls born in the early 1990s, when survival rates began to rise. Participants were derived from 297 consecutive survivors born <28 weeks/<1000 g in 1991 to 1992 in Victoria, Australia, and 260 contemporaneous controls. At age 25 years, ambulatory BP was measured in 151 and 119 participants, respectively. Participants born <28 weeks/<1000 g had higher 24-hour systolic (mean difference 4.5 [95% CI, 1.2-7.7 mm Hg]), diastolic (3.4 [1.5-5.2 mm Hg]), and mean BPs (3.6 [1.4-5.8 mm Hg]) compared with the controls. Similar patterns were observed for both awake and asleep periods. Asleep ambulatory BP between 18 and 25 years increased more in participants born <28 weeks/<1000 g than in controls (systolic 0.56, diastolic 0.41, and mean 0.41 mm Hg increase per year; all P<0.05). Young adults born <28 weeks/<1000 g in the post surfactant era have higher BP and an increased trajectory of ambulatory BP compared with controls. With more survivors born <28 weeks/<1000 g now reaching adulthood, these findings are important for early detection and timely management of hypertension in this high-risk population.

16.
J Hypertens ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31790068

RESUMO

BACKGROUND: Central aortic SBP (cSBP) may have superior prognostic value compared with peripheral SBP (pSBP), but noninvasive cSBP measurement techniques have not been formally validated in children and adolescents. METHOD: This study assessed the accuracy of two automated devices and the radial tonometry/transfer function method (RT-TF) for estimating central pressures and pulse pressure amplification (PPA) in this population, with adherence to validation guidelines for central pressure devices. In 69 children/adolescents aged 3-18 years undergoing clinically indicated aortic catheterization, high fidelity ascending aortic cSBP was measured with a micromanometer-tipped wire and compared with values from SphygmoCor XCEL, Mobil-O-Graph (systolic/diastolic calibration, MoG-C1, or mean/diastolic calibration, MoG-C2) and RT-TF. Reference intra-arterial pSBP was derived from the tonometry pulse calibrated to central mean/diastolic pressures. RESULTS: XCEL, MoG-C1 and MoG-C2 overestimated cSBP by 7.9 ±â€Š6.8 mmHg (mean ±â€ŠSD), 5.7 ±â€Š10.3 mmHg, and 19.1 ±â€Š14.9 mmHg, exceeding the validation cut-off (5 ±â€Š8 mmHg). Brachial pSBP was also overestimated by XCEL (10.9 ±â€Š8.4 mmHg) and Mobil-O-Graph (11.5 ±â€Š12.3 mmHg). By contrast, central and brachial diastolic pressures were underestimated by the automated devices, albeit mostly within acceptable limits; pulse pressures were, therefore, substantially overestimated. Central-brachial PPA (4.5 ±â€Š4.4 mmHg) was overestimated by XCEL (8.7 ±â€Š3.2 mmHg) and MoG-C1 (11.1 ±â€Š6.4 mmHg), but underestimated by MoG-C2 (-3.0 ±â€Š6.6 mmHg). Given accurate pulse calibration, RT-TF achieved acceptable accuracy for cSBP (-0.2 ±â€Š4.6 mmHg) and central-radial PPA (1.9 ±â€Š5.1 mmHg). CONCLUSION: In conclusion, XCEL and Mobil-O-Graph overestimated pSBP and cSBP in children and adolescents. cSBP can be obtained via the same transfer function used in adults, but accurate pressure pulse calibration is critical.Video Abstracts: http://links.lww.com/HJH/B222.

17.
Intern Med J ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31841257

RESUMO

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry (ACOR) is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult (AYA) oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the ACOR registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical LV dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise magnetic resonance imaging (CMR) and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and AYA oncology patients exposed to cardiac toxic therapies. This article is protected by copyright. All rights reserved.

19.
Sci Rep ; 9(1): 15928, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685864

RESUMO

MicroRNAs (miRNAs) are translational regulatory molecules with recognised roles in heart development and disease. Therefore, it is important to define the human miRNA expression profile in cardiac progenitors and early-differentiated cardiomyocytes and to determine whether critical cardiac transcription factors such as NKX2-5 regulate miRNA expression. We used an NKX2-5eGFP/w reporter line to isolate both cardiac committed mesoderm and cardiomyocytes. We identified 11 miRNAs that were differentially expressed in NKX2-5 -expressing cardiac mesoderm compared to non-cardiac mesoderm. Subsequent profiling revealed that the canonical myogenic miRNAs including MIR1-1, MIR133A1 and MIR208A were enriched in cardiomyocytes. Strikingly, deletion of NKX2-5 did not result in gross changes in the cardiac miRNA profile, either at committed mesoderm or cardiomyocyte stages. Thus, in early human cardiomyocyte commitment and differentiation, the cardiac myogenic miRNA program is predominantly regulated independently of the highly conserved NKX2-5 -dependant gene regulatory network.

20.
Glob Heart ; 14(4): 367-372, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31611153

RESUMO

BACKGROUND: Pulmonary hypertension may complicate human immunodeficiency virus (HIV) infection and result in right ventricular (RV) failure and premature death. There are limited data of the effects of childhood HIV infection or antiretroviral therapy (ART) on pulmonary artery pressure (PAP). OBJECTIVES: To establish if there is an association between childhood HIV infection or its treatment and pulmonary artery pressure. METHODS: The study conducted a cross-sectional study of 102 HIV-infected (48 ART-naïve, 54 ART-exposed) and 51 HIV-uninfected children in Jakarta, Indonesia, to estimate PAP using echocardiography parameters: tricuspid regurgitation peak velocity (TRV), left ventricular systolic index and diastolic eccentricity index (EI), and RV systolic function, assessed by tricuspid annulus plane systolic excursion. The association between either ART-naive or ART-exposed HIV and PAP was explored using general linear modelling adjusted for potential confounders. RESULTS: ART-exposed HIV-infected children had higher TRV (adjusted difference: 0.36 m/s; 95% confidence interval [CI]: 0.12 to 0.60; p = 0.003) and diastolic EI (adjusted difference 0.06; 95% CI: 0.01 to 0.11; p = 0.02) than did uninfected children. The EI in ART-exposed children was significantly higher than normal. ART-naive HIV-infected children had a lower tricuspid annulus plane systolic excursion (adjusted difference: -2.2 mm; 95% CI: -3.73 to -0.71; p = 0.004), despite no difference in TRV (adjusted difference: 0.18 m/s; 95% CI: -0.06 to 0.43 m/s; p = 0.14). Seven (13%) ART-exposed and 4 (8.3%) ART-naïve HIV-infected children had pulmonary hypertension. Within-HIV group comparisons showed that accounting for lower respiratory tract infections attenuated the lower RV systolic function in ART-naïve children but not in ART-exposed children (difference: -1.1 mm; 95% CI:-2.8 to 0.7 mm; p = 0.22), but not the higher left ventricular eccentricity indexes in the ART-exposed children (systolic difference: 0.07; 95% CI: 0.02 to 0.12; p = 0.007; diastolic difference: 0.08; 95% CI: 0.02 to 0.14; p = 0.006). CONCLUSIONS: ART-exposed HIV infection is associated with higher estimated PAP. Reduced RV systolic function is seen in ART-naïve HIV infection. Lower respiratory tract infection partly explains lower systolic RV function in ART-naïve relative to ART-exposed HIV infection.

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