Pubblicazioni recenti - pediatric cardiac
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Single-cell Transcriptomics Reveal Different Maturation Stages and Sublineages Commitment of Human Thymic Invariant Natural Killer T cells.
J Leukoc Biol2023 Sep;():. doi: qiad113.
Maas-Bauer Kristina, Köhler Natalie, Stell Anna-Verena, Zwick Melissa, Acharya Swati, Rensing-Ehl Anne, König Christoph, Kroll Johannes, Baker Jeanette, Koßmann Stefanie, Pradier Amandine, Wang Sisi, Docquier Mylène, Lewis David B, Negrin Robert S, Simonetta Federico,
Abstract
Invariant natural killer T (iNKT) cells are a rare, heterogeneous T-cell subset with cytotoxic and immunomodulatory properties. During thymic development, murine iNKT cells go through different maturation stages differentiating into distinct sublineages, namely iNKT1, iNKT2, and iNKT17 cells. Recent reports indicate that iNKT2 cells display immature properties and give rise to other subsets, whereas iNKT1 cells seem to be terminally differentiated. Whether human iNKT cells follow a similar differentiation model is still unknown. To define the maturation stages and assess the sublineage commitment of human iNKT cells during thymic development, in this study we performed scRNAseq analysis on human V?24+ V?11?+?iNKT cells isolated from thymocytes. We show that these iNKT cells displayed heterogeneity and our unsupervised analysis identified five clusters representing different maturation stages, from an immature profile with high expression of genes important for iNKT cell development and proliferation to a mature, fully differentiated profile with high levels of cytotoxic effector molecules. Evaluation of expression of sublineage-defining gene sets revealed mainly cells with an iNKT2 signature in the most immature cluster, whereas the more differentiated ones displayed an iNKT1 signature. Combined analysis with a publicly available scRNAseq dataset of human iNKT cells from peripheral blood suggested that the two main subsets exist both in thymus and in the periphery, while a third more immature one was restricted to the thymus. Our data point to the existence of different maturation stages of human thymic iNKT cells and provide evidence for sublineage commitment of iNKT cells in the human thymus.
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology.
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Risk Factors and Nomogram Model of Postoperative Delirium in Children with Congenital Heart Disease: A Single-Center Prospective Study.
Pediatr Cardiol2023 Sep;():. doi: 10.1007/s00246-023-03297-5.
Mao Dou, Fu Lijuan, Zhang Wenlan,
Abstract
Delirium is a common postoperative complication in children with congenital heart disease, which affects their postoperative recovery. The purpose of this study is to explore the risk factors of delirium and construct a nomogram model to provide novel references for the prevention and management of postoperative delirium in children with congenital heart disease. 470 children after congenital heart surgery treated in the cardiac intensive care unit (CICU) of Shanghai Children's Medical Center were divided into a model and a validation cohort according to the principle of 7:3 distribution temporally. Then, the delirium-related influencing factors of 330 children in the training cohort were analyzed, and the nomogram model was established by a combination of Lasso regression and logistic regression. The data of 140 children in the validation cohort were used to verify the effectiveness of the model. Multivariable logistic regression analysis showed that age, disease severity, non-invasive ventilation after extubation, delayed chest closure, phenobarbital dosage, promethazine dosage, mannitol usage, and elevated temperature were independent risk factors for postoperative delirium. The area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.864 and the Brier value was 0.121. Regarding the validation of the model's effect, our results showed that 51 cases were predicted by the model and 34 cases actually occurred, including 4 cases of false negative and 21 cases of false positive. The positive predictive value of the model was 58.8%, and its negative predictive value was 95.5%. The nomogram model established in this study showed acceptable performance in predicting postoperative delirium in children with congenital heart disease.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Comparison of hemodynamic effects of chest compression delivered via machine or human in asphyxiated piglets.
Pediatr Res2023 Sep;():. doi: 10.1038/s41390-023-02827-4.
O'Reilly Megan, Lee Tze-Fun, Cheung Po-Yin, Schmölzer Georg M,
Abstract
BACKGROUND:
High-quality chest compressions (CC) are an important factor of neonatal resuscitation. Mechanical CC devices may provide superior CC delivery and improve resuscitation outcomes. We aimed to compare the hemodynamic effects of CC delivered by machine and human using a neonatal piglet model.
METHODS:
Twelve asphyxiated piglets were randomized to receive CC during resuscitation using an automated mechanical CC device ("machine") or the two-thumb encircling technique ("human"). CC was superimposed with sustained inflations.
RESULTS:
Twelve newborn piglets (age 0-3 days, weight 2.12?±?0.17?kg) were included in the study. Machine-delivered CC resulted in an increase in stroke volume, and minimum and maximum rate of left ventricle pressure change (dp/dt and dp/dt) compared to human-delivered CC.
CONCLUSIONS:
During machine-delivered CC, stroke volume and left ventricular contractility were significantly improved. Mechanical CC devices may provide improved cardiopulmonary resuscitation outcomes in neonatal cardiac arrest induced by asphyxia.
IMPACT:
Machine chest compression leads to changes in hemodynamic parameters during resuscitation of asphyxiated neonatal piglets, namely greater stroke volume and left ventricular contractility, compared with standard two-thumb compression technique. Mechanical chest compression devices may provide improved cardiopulmonary resuscitation outcomes in neonatal and pediatric asphyxia-induced cardiac arrest.
© 2023. The Author(s).
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Point-of-Care Ultrasound of the Airway in the Diagnosis of a High-Riding Innominate Artery Before Percutaneous Tracheostomy.
J Cardiothorac Vasc Anesth2023 Aug;():. doi: S1053-0770(23)00722-X.
Pandompatam Govind, Waldron Nathan, Townsley Matthew M, Kalagara Hari,
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Genetic Variants and Effect Modifiers of QT Interval Prolongation in Patients with Sickle Cell Disease.
Gene2023 Sep;():147824. doi: 10.1016/j.gene.2023.147824.
Zhang Mengna, Hillegass William B, Yu Xue, Majumdar Suvankar, Daryl Pollard J, Jackson Erin, Knudson Jarrod, Wolfe Douglas, Kato Gregory J, Maher Joseph F, Mei Hao,
Abstract
BACKGROUND:
Sickle cell disease (SCD) is a common inherited blood disorder among African Americans (AA), with premature mortality which has been associated with prolongation of the heart rate-corrected QT interval (QTc), a known risk factor for sudden cardiac death. Although numerous genetic variants have been identified as contributors to QT interval prolongation in the general population, their impact on SCD patients remains unclear. This study used an unweighted polygenic risk score (PRS) to validate the previously identified associations between SNPs and QTc interval in SCD patients, and to explore possible interactions with other factors that prolong QTc interval in AA individuals with SCD.
METHODS:
In SCD patients, candidate genetic variants associated with the QTc interval were genotyped. To identify any risk SNPs that may be correlated with QTc interval prolongation, linear regression was employed, and an unweighted PRS was subsequently constructed. The effect of PRS on the QTc interval was evaluated using linear regression, while stratification analysis was used to assess the influence of serum alanine transaminase (ALT), a biomarker for liver disease, on the PRS effect. We also evaluated the PRS with the two subcomponents of QTc, the QRS and JTc intervals.
RESULTS:
Out of 26 candidate SNPs, five risk SNPs were identified for QTc duration under the recessive model. For every unit increase in PRS, the QTc interval prolonged by 4.0ms (95% CI: [2.0, 6.1]; p-value:
CONCLUSION:
Several candidate genetic variants are associated with QTc interval prolongation in SCD patients, and serum ALT acts as a modifying factor. The association of a CPS1 gene variant in both QTc and JTc duration adds to NOS1AP as evidence of involvement of the urea cycle and nitric oxide metabolism in cardiac repolarization in SCD. Larger replication studies are needed to confirm these findings and elucidate the underlying mechanisms.
Copyright © 2023. Published by Elsevier B.V.
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Efficacy and safety of fluticasone propionate/salmeterol and fluticasone propionate monotherapy in step-up treatment of childhood asthma: A systematic review and meta-analysis.
Heart Lung2023 Sep;63():23-34. doi: 10.1016/j.hrtlng.2023.09.004.
Li Hua, Dong Tao, Luan Jinling,
Abstract
BACKGROUND:
Asthma is a chronic respiratory disease that affects millions of children worldwide and can impair their quality of life and development. Inhaled glucocorticoids are the mainstay of asthma treatment, but some children require step-up therapy with additional drugs to achieve symptom control. Fluticasone propionate and salmeterol (FSC) has been shown to reduce asthma exacerbations and improve lung function in adults. However, the evidence for its efficacy and safety in children is limited.
OBJECTIVE:
This study aims to provide a comprehensive basis for treatment selection by summarizing existing clinical randomized controlled trials (RCTs) on the efficacy of FSC compared to fluticasone propionate (FP) monotherapy in children with asthma who require step-up treatment.
METHODS:
Five online databases and three clinical trial registration platforms were systematically searched. The effect size and corresponding 95% confidence interval (CI) were calculated based on the heterogeneity among the included studies.
RESULTS:
Twelve RCTs were identified and a total of 9, 859 patients were involved. The results of the meta-analysis revealed that the use of FSC was associated with a greater reduction in the incidence of asthma exacerbations than FP alone when the dose of FP was the same or when the duration of treatment exceeded 12 weeks. In addition, FSC resulted in a greater proportion of time with asthma-free and without the use of albuterol compared to FP alone when the duration of treatment exceeded 12 weeks. No significant differences were observed between FSC and FP alone in the incidence of drug-related adverse events and other adverse events.
CONCLUSION:
Both FSC and FP alone are viable options for the initial selection of step-up treatment in asthmatic children. While, FSC treatment demonstrates a greater likelihood of reducing asthma exacerbations which is particularly important for reducing the personnel, social and economic burden in children requiring step-up asthma treatment.
Copyright © 2023. Published by Elsevier Inc.
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Four-dimensional imaging of double drainage of fetal infracardiac total anomalous pulmonary venous connection.
Ultrasound Obstet Gynecol -
Management of Junctional Rhythm in Patients After the Fontan Operation: A Multicenter Congenital Cardiology Survey.
Pediatr Cardiol2023 Sep;():. doi: 10.1007/s00246-023-03296-6.
Balaji Seshadri, Evers Patrick D, Batra Anjan S, Moore Jeremy,
Abstract
Sinus node dysfunction with concomitant junctional rhythm (JR) is frequently observed among Fontan patients and has been recognized as a contributor to heart failure. The impact and management of JR is unclear. A survey was mailed to all members of the Pediatric and Congenital Electrophysiology society (PACES) and members were asked to forward the questionnaire to their non-electrophysiology colleagues. Responses were received from 154 physicians (88 electrophysiologists (EP's) and 66 non-EP's (46 pediatric cardiologists and 20 adult congenital cardiologists). There were few differences in the response between EP's and non-EP's. Overall, 57% recommended an annual ambulatory ECG (AECG). A significant majority (80%) opted to continue to follow patients with significant periods of JR on AECG as long as the patients were asymptomatic, and showed no echocardiographic signs of cardiac decompensation. However, 84% would place a pacemaker in a patient with JR who was having open chest surgery for other reasons. Finally, pacemaker placement would be performed by 91% if a patient with JR showed signs of heart failure. Most congenital cardiologists would not recommend pacemaker placement in asymptomatic Fontan patients with JR. Further studies are needed on the Fontan population to determine the impact of SND and JR on longer term outcomes and to determine the role and optimal timing of pacemaker placement in these patients.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Comparing the efficacy and safety of low, medium, and high dosages of selexipag for treating pulmonary hypertension: A systematic review and meta-analysis.
Animal Model Exp Med2023 Sep;():. doi: 10.1002/ame2.12347.
Wang Shang, Yan Yi, Zhang Jian, Yuan Ping, Luo Ci-Jun, Qiu Hong-Ling, Li Hui-Ting, Xu Jian, Wang Lan, Li Tian-Lan, Jiang Rong,
Abstract
BACKGROUND:
The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta-analysis.
METHODS:
Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO-FC), six-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO ), were included.
RESULTS:
Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20?m, 95% CI: 10.74-37.67), NT-proBNP (SMD: -0.41, 95% CI: -0.79-0.04), CI (MD: 0.47?L/min/m , 95% CI: 0.17-0.77) and WHO-FC (OR: 0.564, 95% CI: 0.457-0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30?L/min/m , 95% CI: 0.15-0.46) and WHO-FC (OR: 0.589, 95% CI: 0.376-0.922). Within 6?months of treatment, only the WHO-FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380-0.993; MD: 0.30?L/min/m , 95% CI: 0.16-0.45, respectively). More than 6?months of treatment significantly improved the 6MWD, WHO-FC and NT-proBNP (MD: 40.87?m, 95% CI: 10.97-70.77; OR: 0.557, 95% CI: 0.440-0.705; SMD: -0.61, 95% CI: -1.17-0.05, respectively).
CONCLUSIONS:
Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6?months, selexipag exerted obvious effects, even in the low-dosage group. This finding is important for guiding individualized treatments.
© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.
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Functional Aortic Annulus Remodelling-Revisited.
Eur J Cardiothorac Surg2023 Sep;():. doi: ezad320.
Jasinski Marek J, Nowicki Rafal, Jasinski Jakub, Bielicki Grzegorz, Rachwalik Maciej, Berezowski Mikolaj,
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Health related quality of life during dialysis modality transitions: a qualitative study.
BMC Nephrol2023 Sep;24(1):282. doi: 10.1186/s12882-023-03330-y.
Dumaine Chance S, Fox Danielle E, Ravani Pietro, Santana Maria J, MacRae Jennifer M,
Abstract
BACKGROUND:
Modality transitions represent a period of significant change that can impact health related quality of life (HRQoL). We explored the HRQoL of adults transitioning to new or different dialysis modalities.
METHODS:
We recruited eligible adults (??18) transitioning to dialysis from pre-dialysis or undertaking a dialysis modality change between July and September 2017. Nineteen participants (9 incident and 10 prevalent dialysis patients) completed the KDQOL-36 survey at time of transition and three months later. Fifteen participants undertook a semi-structured interview at three months. Qualitative data were thematically analyzed.
RESULTS:
Four themes and five sub-themes were identified: adapting to new circumstances (tackling change, accepting change), adjusting together, trading off, and challenges of chronicity (the impact of dialysis, living with a complex disease, planning with uncertainty). From the first day of dialysis treatment to the third month on a new dialysis therapy, all five HRQoL domains from the KDQOL-36 (symptoms, effects, burden, overall PCS, and overall MCS) improved in our sample (i.e., those who remained on the modality).
CONCLUSIONS:
Dialysis transitions negatively impact the HRQoL of people with kidney disease in various ways. Future work should focus on how to best support people during this time.
© 2023. BioMed Central Ltd., part of Springer Nature.
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Postoperative evaluation of left atrial stiffness in patients with congenital heart diseases.
Heart Vessels2023 Sep;():. doi: 10.1007/s00380-023-02313-1.
Oka Hideharu, Nakau Kouichi, Shibagaki Yuki, Ito Keita, Sasaki Yuki, Imanishi Rina, Shimada Sorachi, Takahashi Satoru,
Abstract
Left atrial (LA) stiffness is one of the most important factors involved in LA remodeling. LA stiffness has rarely been studied postoperatively in patients with congenital heart diseases (CHDs). This study aimed to evaluate LA stiffness in CHD patients postoperatively. Seventy-five patients (CHDs, 67; controls, 8; age range, 10-41 years) who underwent cardiac catheterization at our institution were included in this study. From the pulmonary artery wedge pressure waveform obtained during cardiac catheterization, the pressure range between the v wave and x trough was determined, and this value was divided by the LA reservoir strain obtained by echocardiography to calculate LA stiffness, as previously reported. LA stiffness was significantly higher in postoperative CHD patients than in controls (0.28?±?0.17 vs. 0.13?±?0.03, p?=?0.001). Nineteen of 52 (37%) patients in their teens, 8 of 11 (73%) patients in their 20 s, and 1 of 4 (25%) patients aged?>?30 years had elevated LA stiffness values. In particular, all patients with an LA reservoir strain?20% had elevated LA stiffness. In postoperative CHD patients, LA stiffness was frequently elevated from a young age. CHD patients with elevated LA stiffness should be cautious of possible LA dysfunction in the future.
© 2023. Springer Nature Japan KK, part of Springer Nature.
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Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome.
Commun Biol2023 Sep;6(1):969. doi: 10.1038/s42003-023-05344-6.
Chan Chun-Ho, Lam Yin-Yu, Wong Nicodemus, Geng Lin, Zhang Jilin, Ahola Virpi, Zare Aman, Li Ronald Adolphus, Lanner Fredrik, Keung Wendy, Cheung Yiu-Fai,
Abstract
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Ventricular dysfunction and cardiac arrhythmias are well-documented complications in patients with repaired TOF. Whether intrinsic abnormalities exist in TOF cardiomyocytes is unknown. We establish human induced pluripotent stem cells (hiPSCs) from TOF patients with and without DiGeorge (DG) syndrome, the latter being the most commonly associated syndromal association of TOF. TOF-DG hiPSC-derived cardiomyocytes (hiPSC-CMs) show impaired ventricular specification, downregulated cardiac gene expression and upregulated neural gene expression. Transcriptomic profiling of the in vitro cardiac progenitors reveals early bifurcation, as marked by ectopic RGS13 expression, in the trajectory of TOF-DG-hiPSC cardiac differentiation. Functional assessments further reveal increased arrhythmogenicity in TOF-DG-hiPSC-CMs. These findings are found only in the TOF-DG but not TOF-with no DG (ND) patient-derived hiPSC-CMs and cardiac progenitors (CPs), which have implications on the worse clinical outcomes of TOF-DG patients.
© 2023. Springer Nature Limited.
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A Pitfall in Measuring Heart Rates With Pulse Oximetry.
Ann Emerg Med2023 Oct;82(4):472-474. doi: 10.1016/j.annemergmed.2023.05.017.
Chuman Takuya, Iio Kazuki, Yanai Shun, Hagiwara Yusuke, Maeda Jun,
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Diabetic cardiomyopathy - Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways.
Toxicol Appl Pharmacol2023 Sep;():116694. doi: 10.1016/j.taap.2023.116694.
Cai Lu, Tan Yi, Watson Sara, Wintergerst Kupper,
Abstract
Oxidative stress and insulin resistance are two key mechanisms for the development of diabetic cardiomyopathy (DCM, cardiac remodeling and dysfunction). In this review, we discussed how zinc and metallothionein (MT) protect the heart from type 1 or type 2 diabetes (T1D or T2D) through its anti-oxidative function and insulin-mediated PI3K/Akt signaling activation. Both T1D and T2D-induced DCM, shown by cardiac structural remodeling and dysfunction, in wild-type mice, but not in cardiomyocyte-specific overexpressing MT mice. In contrast, mice with global MT gene deletion were more susceptible to the development of DCM. When we used zinc to treat mice with either T1D or T2D, cardiac remodeling and dysfunction were significantly prevented along with increased cardiac MT expression. To support the role of zinc homeostasis in insulin signaling pathways, treatment of diabetic mice with zinc showed the preservation of phosphorylation levels of insulin-mediated glucose metabolism-related Akt2 and GSK-3? and even rescued cardiac pathogenesis induced by global deletion of Akt2 gene in a MT-dependent manner. These results suggest the protection by zinc from DCM is through both the induction of MT and sensitization of insulin signaling. Combined our own and other works, this review comprehensively summarized the roles of zinc homeostasis in the development and progression of DCM and its therapeutic implications. At the end, we provided pre-clinical and clinical evidence for the preventive and therapeutic potential of zinc supplementation through its anti-oxidative stress and sensitizing insulin signaling actions. Understanding the intricate connections between zinc and DCM provides insights for the future interventional approaches.
Copyright © 2023. Published by Elsevier Inc.
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Aortic Root Thrombosis in Patients with HeartMate 3 Left Ventricular Assist Device Support.
J Heart Lung Transplant2023 Sep;():. doi: S1053-2498(23)02007-7.
Carey Matthew R, Marshall Dylan, Clerkin Kevin, Laracuente Ronald, Sanchez Joseph, Jain Sneha S, Raikhelkar Jayant K, Leb Jay S, Kaku Yuji, Yuzefpolskaya Melana, Naka Yoshifumi, Colombo Paolo C, Sayer Gabriel T, Takeda Koji, Uriel Nir, Topkara Veli K, Fried Justin A,
Abstract
BACKGROUND:
Aortic root thrombus (ART) formation is a complication of continuous flow left ventricular assist device (LVAD) therapy. However, the incidence and related complications of ART in HeartMate 3 (HM3) patients remains unknown.
METHODS:
Patients who underwent HM3 implantation from November 2014 through August 2020 at a quaternary academic medical center were included. Demographics and outcomes were abstracted from the medical record. Echocardiograms and contrast-enhanced CT studies were reviewed to identify patients who developed ART and/or moderate or greater aortic insufficiency (AI) on HM3 support.
RESULTS:
The study cohort included 197 HM3 patients with a median post-implant follow-up of 17.5 months. Nineteen patients (9.6%) developed ART during HM3 support, and 15 patients (7.6%) developed moderate or greater AI. Baseline age, gender, race, implantation strategy, and INTERMACS classification were similar between the ART and no-ART groups. ART was associated with an increased risk of death, stroke, or AV intervention (subhazard ratio [SHR] 3.60 [95% CI 1.71-7.56]; p=0.001) and moderate or greater AI (SHR 11.1 [CI 3.60-34.1]; p
CONCLUSION:
Nearly 10% of HM3 patients developed ART during device support. ART was associated with increased risk of a composite endpoint of death, stroke, or AV intervention as well as moderate or greater AI.
Copyright © 2023. Published by Elsevier Inc.
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BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma.
Gastroenterology2023 Sep;():. doi: S0016-5085(23)05012-6.
Feng Yuliang, Cai Liuyang, Pook Martin, Liu Feng, Chang Chao-Hui, Mouti Mai Abdel, Nibhani Reshma, Militi Stefania, Dunford James, Philpott Martin, Fan Yanbo, Fan Guo-Chang, Liu Qi, Qi Jun, Wang Cheng, Hong Wanzi, Morgan Hannah, Wang Mingyang, Sadayappan Sakthivel, Jegga Anil G, Oppermann Udo, Wang Yigang, Huang Wei, Jiang Lei, Pauklin Siim,
Abstract
BACKGROUND AND AIMS:
The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. The epigenetic mechanisms regulating CSCs are currently insufficiently understood which hampers the development of novel strategies for eliminating CSCs.
METHODS:
By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodelling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGF?/Activin-SMAD2/3 signalling pathway.
RESULTS:
Inhibition and genetic ablation of BRD9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to Gemcitabine treatment. In addition, pharmacological inhibition of BRD9 significantly reduced the tumorigenesis in patient-derived xenografts mouse models and eliminated CSCs in tumours from pancreatic cancer patients. Mechanistically, inhibition of BRD9 disrupts enhancer-promoter looping and transcription of stemness genes in CSCs.
CONCLUSIONS:
Collectively, the data suggest BRD9 as a novel therapeutic target for PDAC treatment via modulation of CSC stemness.
Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Racial Disparities in Failure to Rescue after Pediatric Heart Surgeries in the United States.
J Pediatr2023 Sep;():113734. doi: 10.1016/j.jpeds.2023.113734.
Alabbadi Sundos, Rowe Georgina, Gill George, Chikwe Joanna, Egorova Natalia,
Abstract
OBJECTIVE:
To identify the trend in failure to rescue (FTR) and risk factors contributing to racial disparities in FTR after pediatric heart surgery using contemporary nationwide data.
STUDY DESIGN:
We identified 85,267 congenital heart surgeries in patients
RESULTS:
Among 36,753 surgeries with postoperative complications, the FTR was 7.3%. The FTR decreased from 7.4% in 2009 to 6.3% in 2019 (p=0.02). FTR was higher among Black than White children for all years. The FTR was higher among girls (7.2%) vs. boys (6.6%), children aged
CONCLUSION:
Racial disparities exist in FTR after pediatric heart surgery in the United States. The racial differences in the location of care may account for almost half the disparities in FTR.
Copyright © 2023. Published by Elsevier Inc.
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ICD outcome in pediatric arrhythmogenic cardiomyopathy.
Int J Cardiol2023 Sep;():131381. doi: 10.1016/j.ijcard.2023.131381.
Cicenia Marianna, Silvetti Massimo Stefano, Cantarutti Nicoletta, Battipaglia Irma, Adorisio Rachele, Saputo Fabio Anselmo, Tamburri Ilaria, Campisi Marta, Baban Anwar, Drago Fabrizio,
Abstract
BACKGROUND:
Arrhythmogenic cardiomyopathy (ACM) is a very rare condition among pediatric patients. Sudden cardiac death (SCD) is the main complication and often requires ICD implantation. Aim of the study is the evaluation of the outcomes of ICD implanted ACM pediatric patients in terms of safety, efficacy and complications.
METHODS:
All pediatric patients (
RESULTS:
Nineteen consecutive ACM patients were implanted with ICD. Subcutaneous ICDs (S-ICD) were implanted in 15 patients (79%) while transvenous ICDs (TV-ICD) in 4 patients (21%). Mean age at implantation was 14.3?±?2.1 y.o. ICDs were implanted for secondary prevention in 4 (21%) patients, and for primary prevention in 15 (79%). During the follow-up (5.59?±?3.4?years), appropriate ICD interventions were delivered in 4 (21%) patients for sustained VTs, [2 implanted in primary prevention (13%) and 2 in secondary prevention (50%)]. No defibrillation failures occurred. Inappropriate shocks occurred in 2 cases (10.5%). Device-related complications requiring device revision occurred in 3 (16%): lead dislodgement, surgical skin erosion and sensing defect.
CONCLUSIONS:
In a pediatric ACM cohort, appropriate ICD therapies occurred in a minority of primary prevention patients and frequently in secondary prevention patients. The rate of inappropriate shocks and device-related complications were even more rare and mostly wound related. Therefore, ICD therapy in pediatric ACM is effective and safe.
Copyright © 2023. Published by Elsevier B.V.
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Social inequities impact infant mortality due to congenital heart disease.
Public Health2023 Sep;224():66-73. doi: 10.1016/j.puhe.2023.08.021.
Schwartz B N, Evans F J, Burns K M, Kaltman J R,
Abstract
OBJECTIVES:
To evaluate how educational, economic, and racial residential segregation may impact congenital heart disease infant mortality (CHD-IM).
STUDY DESIGN:
This is a population-based US ecological study.
METHODS:
This study evaluated linked live birth-infant death files from the National Center for Health Statistics for live births from 2006 to 2018 with cause of death attributed to CHD. Maternal race and education data were obtained from the live birth-infant death files, and income data were obtained from the American Community Survey. A spatial social polarization measure termed the Index of Concentration at the Extremes (ICE) was calculated and split by quintiles for maternal education, household income, and race for all US counties (n = 3142). The lowest quintile represents counties with highest concentration of disadvantaged groups (income
RESULTS:
Between 2006 and 2018, 17,489 infant deaths were due to CHD, an unadjusted CHD-IM of 0.33 deaths per 1000 live births. The risk of CHD-IM was 1.5 times greater among those in the lowest ICE-education quintile (0.41 [0.39-0.44] vs 0.28 deaths/1000 live births [0.27-0.29], P
CONCLUSIONS:
Counties with the highest concentration of lower-educated mothers and the highest concentration of low-income households were associated with higher rates of CHD-IM. Mortality as a function of race is more complicated and requires further investigation.
Published by Elsevier Ltd.
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