Aims To quantify thoracic lymphatic burden in paediatric Fontan patients using MRI and correlate with clinical status. Methods and results Paediatric Fontan patients (<18-years-old) with clinical cardiac MRI that had routine lymphatic 3D T2 fast spin echo (FSE) imaging performed from May 2017 to October 2019 were included. 'Lymphatic burden' was quantified by thresholding-based segmentation of the 3D T2 FSE maximum intensity projection image and indexed to body surface area, performed by two independent readers blinded to patient status. There were 48 patients (27 males) with median age at MRI of 12.9 (9.4-14.7) years, time from Fontan surgery to MRI of 9.1 (5.9-10.4) years, and follow-up time post-Fontan surgery of 9.4 (6.6-11.0) years. Intraclass correlation coefficient between two observers for lymphatic burden was 0.96 (0.94-0.98). Greater lymphatic burden correlated with post-Fontan operation hospital length of stay and duration of chest tube drainage (r(s) = 0.416, P = 0.004 and r(s) = 0.439, P = 0.002). Median lymphatic burden was greater in patients with chylous effusions immediately post-Fontan (178 (118-393) vs. 113 (46-190) mL/m(2), P = 0.028), and in patients with composite adverse Fontan status (n = 13) defined by heart failure (n = 3), transplant assessment (n = 2), recurrent effusions (n = 6), Fontan thrombus (n = 2), and/or PLE (n = 6) post-Fontan (435 (137-822) vs. 114 (51-178) mL/m(2), P = 0.003). Lymphatic burden > 600 mL/m(2) was associated with late adverse Fontan status with sensitivity of 57% and specificity of 95%. Conclusion Quantification of MR lymphatic burden is a reliable tool to assess the lymphatics post-Fontan and is associated with clinical status.

Drug resistance in cancer has been classified as innate resistance or acquired resistance, which were characterized by apoptotic defects and ABC transporters overexpression respectively. Therefore, to preclude or reverse these resistance mechanisms could be a promising strategy to improve chemotherapeutic outcomes. In this study, a natural product from Osage Orange, pomiferin, was identified as a novel autophagy activator that circumvents innate resistance by triggering autophagic cell death via SERCA inhibition and activation of the CaMKKβ-AMPK-mTOR signaling cascade. In addition, pomiferin also directly inhibited the P-gp (MDR1/ABCB1) efflux and reversed acquired resistance by potentiating the accumulation and efficacy of the chemotherapeutic agent, cisplatin. In vivo study demonstrated that pomiferin triggered calcium-mediated tumor suppression and exhibited an anti-metastatic effect in the LLC-1 lung cancer-bearing mouse model. Moreover, as an adjuvant, pomiferin potentiated the anti-tumor effect of the chemotherapeutic agent, cisplatin, in RM-1 drug-resistant prostate cancer-bearing mouse model by specially attenuating ABCB1-mediated drug efflux, but not ABCC5, thereby promoting the accumulation of cisplatin in tumors. Collectively, pomiferin may serve as a novel effective agent for circumventing drug resistance in clinical applications.

Commonsense generation aims to generate a plausible sentence containing all given unordered concept words. Previous methods focusing on this task usually directly concatenate these words as the input of a pre-trained language model (PLM). However, in PLMs’ pre-training process, the inputs are often corrupted sentences with correct word order. This input distribution discrepancy between pre-training and fine-tuning makes the model difficult to fully utilize the knowledge of PLMs. In this paper, we propose a two-stage framework to alleviate this issue. Firstly, in pre-training stage, we design a new format of input to endow PLMs the ability to deal with masked sentences with incorrect word order. Secondly, during fine-tuning, we insert the special token [MASK] between two consecutive concept words to make the input distribution more similar to the input distribution in pre-training. We conduct extensive experiments and provide thorough analysis to demonstrate the effectiveness of our proposed method.

Introduction Type 2 diabetes (T2D) is increasingly prevalent and associated with increased risk for cardiovascular and renal disease. After lifestyle modification, metformin is usually the first-line pharmacotherapy and sulfonylureas are traditionally added after metformin failure. However, with newer glucose lowering drugs that may have less risk of hypoglycemia or that may reduce cardiovascular and renal events, the position of sulfonylureas is being reevaluated. Areas covered In this article, the authors review relevant publications related to the use of sulfonylureas. Expert opinion Sulfonylureas are potent glucose lowering drugs. The risk of hypoglycemia varies with different drugs within the class and can be minimized by using the safer drugs, possibly in lower doses. Cardiovascular events do not appear to be increased with some of the newer generation drugs. The durability of glycemic control also appears comparable to other newer agents. Sulfonylureas are the preferred treatment for some types of monogenic diabetes and selection of T2D patients who may have greater benefit from sulfonylureas based on certain phenotypes and genotypes is likely to be refined further by precision medicine. Sulfonylureas are inexpensive and readily available everywhere and they are still the most frequently used second-line treatment for T2D in many parts of the world.

Dry eye is currently one of the most common ocular surface disease. It can lead to ocular discomfort and even cause visual impairment, which greatly affects the work and quality of life of patients. With the increasing incidence of dry eye disease (DED) in recent years, the disease is receiving more and more attention, and has become one of the hot research fields in ophthalmology research. Recently, with the in-depth research on the etiology, pathogenesis and treatment of DED, it has been shown that defects in immune regulation is one of the main pathological mechanisms of DED. Since the non-specific and specific immune response of the ocular surface are jointly regulated, a variety of immune cells and inflammatory factors are involved in the development of DED. The conventional treatment of DED is the application of artificial tears for lubricating the ocular surface. However, for moderate-to-severe DED, treatment with anti-inflammatory drugs is necessary. In this review, the immunomodulatory mechanisms of DED and the latest research progress of its related treatments including Chinese medicine will be discussed.

ABSTRACT Introduction Type 2 diabetes (T2D) is a progressive condition, and sequential additions of therapy are usually required to maintain glycemic control. The options for glucose lowering therapies have increased considerably in recent years. Fixed-dose combinations such as alogliptin with pioglitazone provide a convenient choice which can improve medication adherence. Areas covered The authors performed a literature search to identify publications describing the efficacy and safety of alogliptin and pioglitazone when used separately and in combinations. Expert opinion Pioglitazone activates peroxisome proliferator-activated receptor-gamma which improves insulin sensitivity and helps to preserve β-cell function with a durable improvement in glycemic control. Pioglitazone can retard the progression of atherosclerosis and reduce cardiovascular events, but it is associated with adverse events including weight gain, fluid retention, and increased risk of fractures. Alogliptin improves glycemic control and appears neutral in terms of cardiovascular events. It does not appear to increase the adverse events associated with pioglitazone and use of the combination may permit the use of lower doses of pioglitazone with reduced adverse effects. There are no cardiovascular outcome studies with the combination but the cardiovascular benefits of pioglitazone and additional glucose lowering effects of alogliptin provide a useful combination with convenient once daily dosing.

Allergic rhinitis (AR) is a highly prevalent allergic disease induced by immunoglobulin (Ig) E-mediated hypersensitivity reaction at the nasal epithelium against inhaled allergens. Previous studies have demonstrated that Pentaherbs formula (PHF), a modified herbal formula comprising five herbal medicines (Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis), could suppress various immune effector cells to exert anti-inflammatory and anti-allergic effects in allergic asthma and atopic dermatitis. The present study aimed to further determine the anti-inflammatory activities of PHF in an ovalbumin (OVA)-induced AR BALB/c mouse model. Nasal symptoms such as sneezing and nose rubbing were recorded and the serum total IgE and OVA-specific IgG1, as well as interleukin (IL)-4, IL-5, IL-10, IL-13, chemokines CXCL9 CXCL10, and tumor necrosis factor (TNF)-α concentrations in nasal lavage fluid (NALF) were measured during different treatments. Effects of PHF on the expression of inflammatory mediators in the sinonasal mucosa were quantified using real-time QPCR. PHF was found to suppress allergic symptoms, infiltration of inflammatory cells, and hyperplasia of goblet cells in the nasal epithelium of the OVA-induced AR mice. PHF could reduce OVA-specific IgG1 level in serum, and TNF-α and IL-10 in nasal lavage fluid (NALF), significantly up-regulate the splenic regulatory T (Treg) cell level, increase the Type 1 helper T cell (Th1)/Type 2 helper T cell (Th2) ratio, and reduce the Th17 cells (all p < 0.05). PHF could also alleviate in situ inflammation in sinonasal mucosa of OVA-induced AR mice. In conclusion, oral treatment of PHF showed immuno-modulatory activities in the OVA-induced AR mice by regulating the splenic T cell population to suppress the nasal allergy symptoms and modulating inflammatory mediators, implicating that PHF could be a therapeutic strategy for allergic rhinitis.

The pulmonary circulation after one and one-half ventricle repair is complex because of the direct connection of two sources of blood flow. Associated pulmonary regurgitation further complicates the pulmonary circulation. We report the complex hemodynamics depicted by phase-contrast magnetic resonance imaging in a patient with one and one-half ventricle circuit and severe pulmonary regurgitation. Antegrade superior vena caval flow occurred almost exclusively during diastole and regurgitated into the right ventricle. Consequently, the entire systemic venous return reached the right ventricle during diastole and is pumped back into the pulmonary arteries in systole. The case highlights the importance of analyzing flow patterns phase-by phase throughout the cardiac cycle instead of relying on the net flow volumes through each source of pulmonary blood flow.

Remdesivir (RDV) has generated much anticipation for its moderate effect in treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the unsatisfactory survival rates of hospitalized patients limit its application to the treatment of coronavirus disease 2019 (COVID-19). Therefore, improvement of antiviral efficacy of RDV is urgently needed. As a typical nucleotide analog, the activation of RDV to bioactive triphosphate will affect the biosynthesis of endogenous ribonucleotides (RNs) and deoxyribonucleotides (dRNs), which are essential to RNA and DNA replication in host cells. The imbalance of RN pools will inhibit virus replication as well. In order to investigate the effects of RDV on cellular nucleotide pools and on RNA transcription and DNA replication, cellular RNs and dRNs concentrations were measured by the liquid chromatography-mass spectrometry method, and the synthesis of RNA and DNA was monitored using click chemistry. The results showed that the IC 50 values for BEAS-2B cells at exposure durations of 48 and 72 h were 25.3 ± 2.6 and 9.6 ± 0.7 μM, respectively. Ten (10) μM RDV caused BEAS-2B arrest at S-phase and significant suppression of RNA and DNA synthesis after treatment for 24 h. In addition, a general increase in the abundance of nucleotides and an increase of specific nucleotides more than 2 folds were observed. However, the variation of pyrimidine ribonucleotides was relatively slight or even absent, resulting in an obvious imbalance between purine and pyrimidine ribonucleotides. Interestingly, the very marked disequilibrium between cytidine triphosphate (CTP) and cytidine monophosphate might result from the inhibition of CTP synthase. Due to nucleotides which are also precursors for the synthesis of viral nucleic acids, the perturbation of nucleotide pools would block viral RNA replication. Considering the metabolic vulnerability of endogenous nucleotides, exacerbating the imbalance of nucleotide pools imparts great promise to enhance the efficacy of RDV, which possibly has special implications for treatment of COVID-19.

Introduction Inclisiran is a small interfering RNA that inhibits hepatic production of proprotein convertase subtilisin/kexin type 9 (PCSK9) which results in reduction of circulating low-density lipoprotein cholesterol (LDL-C). It can be used alone or in combination with statins or other lipid-lowering therapy. Areas covered In this article, we review the pharmacokinetics, pharmacodynamics and clinical efficacy of inclisiran based on the published literature. Expert opinion Inclisiran is a chemically stabilized duplex RNA conjugated with triantennary N-acetylgalactosamine which facilitates rapid and selective liver uptake and the drug is almost entirely removed from the circulation within 24 hours after subcutaneous injection. The duration of action is impressively prolonged and after doses of 300 mg on days one and 90, the dose can be repeated every six months to maintain a durable reduction of LDL-C by about 50%. The efficacy and safety are similar to the monoclonal antibodies targeting PCSK9, evolocumab and alirocumab, and injection site reactions are infrequent and generally mild. The cardiovascular outcome study with inclisiran is ongoing and other long term safety data are keenly awaited. The infrequent dosing regimen offers a major advantage to improve long term compliance and inclisiran may be extensively adopted depending on the cost.

Neonatal ductus arteriosus aneurysm (DAA) is a rare abnormality that is typically diagnosed at fetal third trimester or early postnatal echocardiography. While echocardiography is usually adequate for diagnosis and clinical decision-making, cross-sectional imaging, including CT or cardiac MRI, may be necessary to clarify the diagnosis or delineate associated complications. Severe complications include thromboembolism, infection, compression of adjacent structures, airway erosion, and aneurysm rupture. This imaging essay reviews the pathophysiology and depicts the spectrum of cross-sectional imaging appearances of neonatal DAAs. Most neonatal DAAs will spontaneously regress and can be managed conservatively. Keywords: CT, MRI, Cardiac, Aneurysms, Congenital Supplemental material is available for this article. ©RSNA, 2021.

Study Objective: To evaluate the diagnostic performance of a Volume and Solid Vascular Tissue Score (VSVTS) for preoperative risk assessment of pediatric and adolescent adnexal masses. Design: A retrospective cohort study comprised of all female individuals who presented with an adnexal mass that was managed surgically between April 2011 and March 2016. Setting: The Hospital for Sick Children (Toronto, Ontario, Canada). Participants: Female individuals 1-18 years of age who presented to a large tertiary pediatric hospital with an adnexal mass that was managed surgically. Main Outcome Measures: Main outcome measures included diagnostic performance of the VSVTS for malignancy via sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and receiver operating characteristic area-under-the-curve (AUC) analysis. Results: A total of 179 masses in 169 subjects were included. The malignancy rate was 10.6%. The AUC for the VSTVS was 0.919. A VSTVS cut-off value of 4 achieved a sensitivity of 79% (95% CI 0.54-0.93), specificity of 88% (95% CI 0.82-0.93), PPV of 0.44 (95% CI 0.33-0.56), NPV of 0.97 (95% CI 0.94-0.99), LR+ of 6.77 (95% CI 4.18-10.97), and LR-of 0.24 (95% CI 0.10-0.57). Conclusions: A sonographic scoring system based on the volume and presence of solid vascular tissue improves PPV for preoperative risk stratification of adnexal masses in the pediatric and adolescent population compared to existing ultrasound-only approaches. Further prospective research is needed to determine how best to incorporate components of such scoring systems into clinical management algorithms.

Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the liver in pediatric Fontan patients often shows peripheral reticular areas of hypoenhancement, which has not been studied in detail. To semiquantitatively score the hepatic MR perfusion abnormality seen in pediatric Fontan patients, and to correlate the perfusion abnormality with functional clinical and hemodynamic parameters. All children (< 18 years old) after Fontan palliation with combined clinical cardiac and liver MRI performed between May 2017 and April 2019 were considered for inclusion. A semiquantitative perfusion score was used to assess the severity of the hepatic reticular pattern seen on dynamic contrast-enhanced liver imaging. The liver was divided into four sections: right posterior, right anterior, left medial and left lateral. Each liver section was assigned a score from 0 to 4 depending on the amount of abnormal reticular hypoenhancement. Scoring was assigned for each section of the liver across eight successive dynamic contrast-enhanced modified spoiled gradient echo runs. Scores were correlated with clinical and hemodynamic parameters. All Fontan children showed hepatic reticular hypoenhancement by MRI, most severe in the early portal venous phase with a median maximum total perfusion abnormality score of 12 (range: 9–14). All perfusion abnormalities progressively resolved during the hepatic venous phase. Perfusion abnormality scores were greatest in the right compared to left hepatic lobes (7 range: [6–8] vs. 5 [range: 3–6], P < 0.01). The maximum left hepatic lobe perfusion abnormality scores were greatest in children with versus without imaging signs of portal hypertension (8 [range: 7–8] vs. 4 [range: 3–5], P < 0.01). High unconjugated bilirubin and low platelets correlated with greater perfusion abnormality (R = 0.450, P = 0.024, and R =  − 0.458, P < 0.01, respectively). Age at MRI, time from Fontan, focal liver lesions and cardiac MRI hemodynamic parameters did not show significant correlations with the severity of the liver perfusion abnormality. All Fontan children have hepatic reticular hypoenhancement abnormalities seen with MRI that are most severe in the right hepatic lobe and universally show gradual resolution through the hepatic venous phase. Perfusion abnormality in the left hepatic lobe is worse in children with portal hypertension.

INTRODUCTION:Type 2 diabetes mellitus (T2DM) is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD) which is partly related to atherogenic dyslipidemia with raised triglycerides, reduced high-density lipoprotein cholesterol levels, and accompanying lipid changes. Treatment of this dyslipidemia is regarded as a priority to reduce the ASCVD risk in T2DM.AREAS COVERED:This article reviews the relevant studies and guidelines from the publications related to this area.EXPERT OPINION:Lifestyle modification should always be encouraged, and statin treatment is indicated in most patients with T2DM based on the outcome of randomized controlled trials. If LDL-C goals are not achieved, first, ezetimibe and subsequently proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors should be added. Patients with T2DM derive greater benefits from ezetimibe and PCSK9 inhibitors due to their higher absolute ASCVD risk compared to patients without T2DM. If triglyceride levels remain elevated, a high dose of eicosapentaenoic acid ethyl ester should be added. Fibrates should be used for severe hypertriglyceridemia to prevent acute pancreatitis. Novel treatments including pemafibrate and inclisiran are undergoing cardiovascular outcome trials, and RNA-based therapies may help to target residual hypertriglyceridemia and high lipoprotein(a) with the long acting treatments offering potential improved adherence to therapy.

BACKGROUND:Atopic dermatitis (AD) is a chronic relapsing inflammatory and pruritic skin disease, affecting 10-20% of the population worldwide. Paeonia suffruticosa Andrews (Paeoniaceae) (Cortex Moutan) and Mentha haplocalyx Briq. (Labiatae) (Herba Menthae) have shown beneficial effects on AD. Calendula officinalis L. (Asteraceae) is commonly used for treating skin rashes and wounds. PURPOSE:In the present study, a three-herbs formula including Cortex Moutan and Herba Menthae, together with C. officinalis at 1:1:1 weight ratio was used as a topical agent and its therapeutic effects on AD was investigated. METHODS:In vitro effects of individual herbs and three-herbs formula (0.125-1 mg/ml) were examined using cytokine release assay on human mast HMC-1 cells, inflammation test on murine macrophage RAW cells and human keratinocyte (HaCaT) cells, and migration scratch assay on human umbilical vein endothelial cells (HUVEC). The contributing functional pathway of three-herbs formula in AD was explored using Western Blot assay in HMC-1 cells. Oxazolone-induced AD-like mice model was also used to investigate the in vivo therapeutic effect of the topical application of the three-herbs formula. RESULTS:Herba Menthae, Cortex Moutan, and three-herbs formula significantly reduced the production of IL-6 and tumor necrosis factor (TNF)-α in HMC-1 cells, inhibited the expression of IL-6, IL-8 and CCL2 in TNF-α/IFN-γ stimulated HaCaT cells, and suppressed the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. Moreover, Herba Menthae and three-herbs formula significantly suppressed CCL2 and TNF-α production in LPS-induced RAW 264.7 cells. C. officinalis and three-herbs formula promoted wound healing in HUVEC. For intracellular mechanisms, three-herbs formula inhibited the expressions of molecules in STAT1 and STAT3-dependent pathways. In vivo model showed that topical application of three-herbs formula on challenged ear reduced ear swelling and mice scratching frequencies. H&E and toluidine blue staining of the challenged ear tissue demonstrated that three-herbs formula reduced the epidermal thickness and mast cell infiltration, respectively. CONCLUSION:The three-herbs formula of Cortex Moutan, Herba Menthae and C. officinalis at 1:1:1 (w/w) exhibited anti-inflammatory effect and promotion of cell migration in vitro. It also alleviated ear redness, swelling, epidermal thickness and inflammation of the OXA-induced AD mice. These findings suggest a potential beneficial role of the topical application of the three-herbs formula for treatment of AD.

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.

Background: Left ventricular dysfunction in Ebstein’s anomaly (EA) is associated with higher mortality. The health of the left ventricular myocardium in children and adolescents with EA has not been investigated in detail. Methods: Patients with unrepaired EA who had undergone cardiac magnetic resonance imaging including T1 mapping were retrospectively reviewed. Patients were compared with age- and sex-matched controls. EA severity index was calculated using volumetric measurements at end diastole ([right atrial+atrialized right ventricular volumes]/[functional right ventricular+left atrial+left ventricular volumes]). Global circumferential and radial strain and as well as strain rate were examined using cardiac magnetic resonance feature tracking. Results: Twelve EA patients and an equal number of controls were included. Functional and atrialized right ventricular end-diastolic volumes were 84±15 and 21±13 mL/m 2 , respectively. Late gadolinium enhancement, confined to the right ventricle, was found in 2 patients (16%). Left ventricular native T1 values and extracellular volume fractions were higher in patients compared with controls (1026±47 versus 956±40 ms, P =0.0004 and 28.5±3.4% versus 22.5±2.6%, P <0.001, respectively). Native T1 times correlated inversely with patients’ age, body surface area, and O 2 saturations (r=−0.63, −0.62, and −0.91, respectively; P =0.02, P =0.02, and P <0.0001, respectively). EA severity index ranged between 0.15 and 0.94 and correlated with T1 values (r=0.76, P =0.003). Native T1 correlated with global circumferential strain (r=0.58, P =0.04) but not ejection fraction (EF). EA patients had reduced maximum oxygen uptake (V o 2 max). V o 2 max correlated inversely with T1 values (r=−0.79, P =0.01). Conclusions: Children and adolescents with EA experience an abnormal degree of diffuse myocardial fibrosis. Its association with O 2 saturation points toward a role of hypoxemia in the pathogenesis of fibrosis. Larger and prospective studies are needed to evaluate the value of T1 mapping for risk stratification and monitoring in EA.