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Antiphospholipid syndrome onset with hemolytic anemia and accompanied cardiocerebral events: a case report. 抗磷脂综合征起病时伴有溶血性贫血和心脑事件:病例报告。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-18 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1370285
Jie Zheng, Zhao-Yu Wei, Shi-Chao Lin, Yong Wang, Xin Fang

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder that can manifest as thrombosis in the pediatric population, characterized by persistently positive antiphospholipid antibodies. APS is infrequently observed in children and could represent non-criteria manifestations.

Case presentation: A six-year-old Chinese female presented with jaundice and dark urine, leading to a diagnosis of hemolytic anemia. Prednisone therapy initially improved her complexion, but she later developed neurological symptoms. Further laboratory tests showed intravascular hemolysis, coagulation abnormalities, and a positive lupus anticoagulant (LA) test result. Magnetic resonance imaging (MRI) scan revealed abnormal signals in the pons and cerebellar hemispheres, and an occluded part of the basilar artery. She was subsequently diagnosed with autoimmune encephalitis and received IG(immunoglobulin) and high-dose glucocorticoid (GC) treatment, leading to improvement in her clinical symptoms. However, the symptoms of hemolytic anemia worsened after two years. Subsequent laboratory assessments demonstrated the presence of intravascular hemolysis, coagulation abnormalities, and positive tests of anticardiolipin, LA, and anti-beta2 glycoprotein I antibodies. Elevated troponin I and N-terminal pro-brain natriuretic peptide levels, along with electrocardiogram and echocardiogram findings, indicated a myocardial infarction and a thrombus-like mass in the left auricle. Brain MRI showed multifocal infarction and cerebrovascular obstruction. She was diagnosed with APS accompanied by hemolytic anemia, cerebrovascular obstruction, and myocardial infarction. After several weeks of treatment with GC, IG, rituximab, hydroxychloroquine alone with low-molecular-weight heparin sodium, and warfarin, there was a marked improvement in the patient's condition.

Conclusion: Pediatricians should be familiar with various presentations of pediatric APS to promptly detect possible aPL-related complications and initiate appropriate management strategies early on.

背景:抗磷脂综合征(APS)是一种全身性自身免疫性疾病,可表现为儿童血栓形成,其特点是抗磷脂抗体持续阳性。APS在儿童中并不常见,可能是非标准表现:一名六岁的中国女孩因黄疸和深色尿液就诊,诊断为溶血性贫血。泼尼松治疗最初改善了她的肤色,但后来她出现了神经系统症状。进一步的实验室检查显示,她出现了血管内溶血、凝血异常和狼疮抗凝物(LA)阳性检测结果。磁共振成像(MRI)扫描显示脑桥和小脑半球信号异常,基底动脉部分闭塞。她随后被诊断为自身免疫性脑炎,接受了免疫球蛋白(IG)和大剂量糖皮质激素(GC)治疗,临床症状有所改善。然而,两年后溶血性贫血症状加重。随后的实验室评估显示存在血管内溶血、凝血异常以及抗心磷脂、LA 和抗-beta2 糖蛋白 I 抗体检测阳性。肌钙蛋白 I 和 N 端前脑钠肽水平升高,加上心电图和超声心动图检查结果,表明患者患有心肌梗死,左心耳有血栓样肿块。脑磁共振成像显示多灶性梗死和脑血管阻塞。她被诊断为伴有溶血性贫血、脑血管阻塞和心肌梗死的 APS。在使用 GC、IG、利妥昔单抗、羟氯喹单用低分子量肝素钠和华法林治疗数周后,患者病情明显好转:儿科医生应熟悉小儿 APS 的各种表现,及时发现可能与 aPL 相关的并发症,并尽早采取适当的治疗策略。
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引用次数: 0
Clinical prognostic models in children with sepsis in low- and middle-income countries: a systematic review and meta-analysis. 中低收入国家儿童败血症临床预后模型:系统回顾和荟萃分析。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1463986
Jessica Jordan, Celinie M Nguyen, Lauren M Fletcher, Stephanie C Garbern

Introduction: Sepsis is the leading cause of child death worldwide, with the majority of these deaths occurring in low- and middle-income countries (LMICs). The aim of this systematic review and meta-analysis was to describe clinical prognostic scores and models for pediatric sepsis outcomes and assess the performance of these scores for predicting mortality in LMICs.

Methods: Ovid Medline, CINAHL, Cochrane Library, EBSCO Global Health, and Web of Science, were searched through September 2022 for citations related to the development or validation of a clinical prognostic score or model among children with sepsis, conducted in LMIC. Titles, abstracts, and full texts were screened by two independent reviewers and data extracted included population characteristics, variables included, outcomes, and model performance. Risk of bias was assessed with the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Results: 4,251 titles/abstracts and 315 full-text studies were screened, with 12 studies meeting inclusion criteria. Study countries included India, China, Egypt, Indonesia, Tanzania, and a multi-site study in Latin America. Prognostic scores/models included existing scores such as PELOD-2, pSOFA, PRISM, P-MODS, refractory shock criteria. There was high risk of bias in all studies. Meta-analysis was possible for pSOFA, PELOD-2, PRISM, and P-MODS, with pooled area under the receiver-operator characteristic curve of 0.86 (95%CI 0.78-0.94), 0.83 (95% CI 0.76-0.91), respectively.

Conclusion: Relatively few clinical scores and models have been externally validated for prognostication and risk-stratification among children with sepsis in diverse LMIC settings. Notably there were no studies from low-income countries. Some potentially relevant studies were excluded due to lack of clarity regarding the presence of sepsis in the study populations. More widespread and standardized use of sepsis criteria may aid in better understanding the burden of sepsis and prognostic model performance at the bedside among children in LMICs. Further research to externally validate, implement and adapt these models is needed to account for challenges in use of these scores in resource-limited settings.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340126, PROSPERO [CRD42022340126].

导言:败血症是全球儿童死亡的主要原因,其中大部分死亡病例发生在中低收入国家(LMICs)。本系统综述和荟萃分析旨在描述儿科脓毒症结果的临床预后评分和模型,并评估这些评分在预测中低收入国家死亡率方面的性能:方法:检索了 Ovid Medline、CINAHL、Cochrane Library、EBSCO Global Health 和 Web of Science 上截至 2022 年 9 月有关在 LMIC 地区开发或验证脓毒症患儿临床预后评分或模型的引文。标题、摘要和全文由两名独立审稿人进行筛选,提取的数据包括人群特征、包含的变量、结果和模型性能。采用预测模型偏倚风险评估工具(PROBAST)评估偏倚风险:筛选了 4,251 篇标题/摘要和 315 篇全文研究,其中 12 篇研究符合纳入标准。研究国家包括印度、中国、埃及、印度尼西亚、坦桑尼亚以及拉丁美洲的一项多站点研究。预后评分/模型包括现有评分,如 PELOD-2、pSOFA、PRISM、P-MODS、难治性休克标准。所有研究的偏倚风险都很高。pSOFA、PELOD-2、PRISM和P-MODS可进行荟萃分析,接收器-操作者特征曲线下的集合面积分别为0.86(95%CI 0.78-0.94)、0.83(95%CI 0.76-0.91):在不同的低收入与中等收入国家环境中,经外部验证可用于脓毒症患儿预后和风险分级的临床评分和模型相对较少。值得注意的是,没有来自低收入国家的研究。一些潜在的相关研究因研究人群中是否存在败血症而被排除在外。脓毒症标准的更广泛和标准化使用有助于更好地了解脓毒症的负担以及预后模型在低收入和中等收入国家儿童床旁的表现。需要进一步开展研究,从外部验证、实施和调整这些模型,以应对在资源有限的环境中使用这些评分所面临的挑战。系统综述注册:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340126,PROSPERO [CRD42022340126]。
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引用次数: 0
Case Report: Functional characterization of a missense variant in INSR associated with hypoketotic hypoglycemia. 病例报告:与低血糖有关的 INSR 错义变体的功能特征。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1493280
Herodes Guzman, Lauren M Mitteer, Pan Chen, Christine A Juliana, Kara Boodhansingh, Katherine Lord, Arupa Ganguly, Diva D De Leon

Hypoketotic hypoglycemia due to dysregulated insulin secretion is the most common cause of persistent hypoglycemia in children. However, this type of hypoglycemia can also result from defects in the insulin signaling pathway. Distinguishing between the two is important for informing treatment decisions. Here we describe the case of a 10-year-old female with fasting and postprandial hypoglycemia who was found to have a missense variant in the INSR gene, which we functionally characterized. The proband presented with fasting and postprandial hypoglycemia at age six. Diagnostic evaluation was consistent with hypoketotic hypoglycemia suspected to be due to hyperinsulinism, and she was treated with diazoxide. Whole exome sequencing identified a maternally inherited heterozygous missense variant in INSR. Phenotypic studies on the mother were consistent with postprandial hypoglycemia. Phosphorylated Akt and ERK1/2 levels were higher at baseline and in response to stimulation with insulin in 3T3-L1 cells expressing mutant INSR compared to cells expressing wild type INSR. Thus, herein we present a heterozygous missense variant in INSR (c.1151A>G, p.Asn384Ser) that results in constitutive and increased activation of the human insulin receptor, leading to both fasting and postprandial hypoglycemia.

胰岛素分泌失调导致的低酮低血糖是儿童持续性低血糖最常见的原因。然而,胰岛素信号通路缺陷也可能导致这种类型的低血糖。区分这两种情况对于做出治疗决定非常重要。在这里,我们描述了一个患有空腹和餐后低血糖症的 10 岁女性病例,她被发现患有 INSR 基因的错义变异,我们对该基因进行了功能鉴定。该患者六岁时出现空腹和餐后低血糖症。诊断评估结果与低酮低血糖症一致,怀疑是高胰岛素血症引起的,她接受了双唑醇治疗。全外显子组测序确定了INSR的母系遗传性杂合错义变异。对母亲的表型研究与餐后低血糖症一致。与表达野生型 INSR 的细胞相比,在表达突变 INSR 的 3T3-L1 细胞中,磷酸化 Akt 和 ERK1/2 水平在基线和胰岛素刺激下均较高。因此,我们在本文中提出了一种 INSR 杂合子错义变体(c.1151A>G, p.Asn384Ser),这种变体会导致人类胰岛素受体的构成性活化和活化增强,从而导致空腹和餐后低血糖。
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引用次数: 0
Editorial: Recurrent fever in pediatrics. 社论:儿科反复发烧。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1500769
Carla Gaggiano, Mohamed Tharwat Hegazy, Luca Cantarini, Gaafar Ragab
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引用次数: 0
Implementation of an automated transition readiness assessment in a pediatric rheumatology clinic. 在儿科风湿病诊所实施自动过渡准备评估。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1457651
Melissa Argraves, Elizabeth Murray, Alysha Taxter, Kelly Wise, Paul T Jensen, Alana Goldstein-Leever, Bethanne Thomas, Alexa Scott, James Gallup, Ashlee Leone, Stacy P Ardoin, Vidya Sivaraman

Background: Failure of successful transition to adult care for adolescents and young adults with chronic rheumatic diseases negatively impacts their health and wellbeing. Transition of care is a vital and complex process within pediatric rheumatology that can be difficult to execute. Use of quality improvement (QI) and clinical informatics (CI) can help implement transition programs.

Local problem: Despite efforts to improve transition of care within our pediatric rheumatology clinic, it has been difficult to implement and sustain good transition practices including assessment of transition readiness. Using QI methodology and CI, this study aimed to improve transition readiness assessment from 12 to 30% and sustain for one year by surveying transitioning patients yearly.

Methods: A transition-focused QI team utilized methods endorsed by the Institute for Healthcare Improvement and leveraged CI to improve survey completion. Control charts of survey completion rates were tracked monthly. Descriptive statistics were used to analyze survey responses.

Interventions: Interventions focused on automation of patient surveys at regularly scheduled clinic visits.

Results: 1,265 questionnaires were administered to 1,158 distinct patients. Survey completion rose from a baseline of 12% to greater than 90% and was sustained over 18 months. Identified educational needs included health insurance, scheduling appointments, obtaining care outside of rheumatology clinic business hours, Electronic Health Record messaging, and refilling medications.

Conclusions: By leveraging CI and QI methodology, we were able to assess transition readiness in more than 90% of our patients and identify gaps in self-management. Process automation can create sustainable transition practices.

背景:患有慢性风湿病的青少年如果不能成功过渡到成人护理,会对他们的健康和福祉产生负面影响。在儿科风湿病学中,护理过渡是一个重要而复杂的过程,可能很难执行。当地问题:尽管我们努力改善儿科风湿病诊所内的护理过渡,但很难实施和维持良好的过渡做法,包括评估过渡准备情况。本研究采用 QI 方法和 CI,旨在通过每年对过渡患者进行调查,将过渡准备评估率从 12% 提高到 30%,并持续一年:方法:一个以过渡为重点的 QI 小组采用了医疗保健改进研究所认可的方法,并利用 CI 来提高调查的完成率。每月跟踪调查完成率对照表。采用描述性统计对调查回复进行分析:干预措施的重点是在定期门诊时自动向患者发放调查问卷:共向 1158 名患者发放了 1265 份调查问卷。调查完成率从 12% 的基线上升到 90% 以上,并持续了 18 个月。确定的教育需求包括医疗保险、预约时间安排、在风湿病诊所营业时间以外获得护理、电子健康记录信息以及重新配药:通过利用 CI 和 QI 方法,我们能够评估 90% 以上患者的过渡准备情况,并找出自我管理方面的差距。流程自动化可以创造可持续的过渡实践。
{"title":"Implementation of an automated transition readiness assessment in a pediatric rheumatology clinic.","authors":"Melissa Argraves, Elizabeth Murray, Alysha Taxter, Kelly Wise, Paul T Jensen, Alana Goldstein-Leever, Bethanne Thomas, Alexa Scott, James Gallup, Ashlee Leone, Stacy P Ardoin, Vidya Sivaraman","doi":"10.3389/fped.2024.1457651","DOIUrl":"10.3389/fped.2024.1457651","url":null,"abstract":"<p><strong>Background: </strong>Failure of successful transition to adult care for adolescents and young adults with chronic rheumatic diseases negatively impacts their health and wellbeing. Transition of care is a vital and complex process within pediatric rheumatology that can be difficult to execute. Use of quality improvement (QI) and clinical informatics (CI) can help implement transition programs.</p><p><strong>Local problem: </strong>Despite efforts to improve transition of care within our pediatric rheumatology clinic, it has been difficult to implement and sustain good transition practices including assessment of transition readiness. Using QI methodology and CI, this study aimed to improve transition readiness assessment from 12 to 30% and sustain for one year by surveying transitioning patients yearly.</p><p><strong>Methods: </strong>A transition-focused QI team utilized methods endorsed by the Institute for Healthcare Improvement and leveraged CI to improve survey completion. Control charts of survey completion rates were tracked monthly. Descriptive statistics were used to analyze survey responses.</p><p><strong>Interventions: </strong>Interventions focused on automation of patient surveys at regularly scheduled clinic visits.</p><p><strong>Results: </strong>1,265 questionnaires were administered to 1,158 distinct patients. Survey completion rose from a baseline of 12% to greater than 90% and was sustained over 18 months. Identified educational needs included health insurance, scheduling appointments, obtaining care outside of rheumatology clinic business hours, Electronic Health Record messaging, and refilling medications.</p><p><strong>Conclusions: </strong>By leveraging CI and QI methodology, we were able to assess transition readiness in more than 90% of our patients and identify gaps in self-management. Process automation can create sustainable transition practices.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of early and treatment related deaths among children and adolescents with acute myeloid leukemia in Poland: 2005-2023. 波兰急性髓性白血病儿童和青少年早期死亡和治疗相关死亡分析:2005-2023 年。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1482720
Katarzyna Pawińska-Wąsikowska, Małgorzata Czogała, Karolina Bukowska-Strakova, Marta Surman, Monika Rygielska, Teofila Książek, Beata Sadowska, Agnieszka Pac, Jolanta Skalska-Sadowska, Magdalena Samborska, Jacek Wachowiak, Małgorzata Ciebiera, Radosław Chaber, Renata Tomaszewska, Tomasz Szczepański, Karolina Zielezińska, Tomasz Urasiński, Anna Rodziewicz-Konarska, Krzysztof Kałwak, Marta Kozłowska, Ninela Irga-Jaworska, Barbara Sikorska-Fic, Bartosz Chyżyński, Paweł Łaguna, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Paulina Deleszkiewicz, Katarzyna Drabko, Katarzyna Bobeff, Wojciech Młynarski, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Mycko, Wanda Badowska, Natalia Bartoszewicz, Jan Styczyński, Katarzyna Machnik, Weronika Stolpa, Agnieszka Mizia-Malarz, Walentyna Balwierz, Szymon Skoczeń

Background: A personalised approach to the treatment of acute myeloid leukemia (AML) in children and adolescents, as well as the development of supportive therapies, has significantly improved survival. Despite this, some patients still die before starting treatment or in an early phase of therapy before achieving remission. The study analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment related deaths (TRD) of children and adolescents with AML.

Methods: From January 2005 to November 2023, 646 children with AML treated in the centers of the Polish Pediatric Leukemia and Lymphoma Study Group according to three subsequent therapeutic protocols were evaluated: AML-BFM 2004 Interim (385 children), AML-BFM 2012 Registry (131 children) and AML-BFM 2019 (130 children).

Results: Out of 646 children, early death occurred in 30 children, including 15 girls. The median age was 10.7 years (1 day to 18 years). More than half of the patients (53%) were diagnosed with acute myelomonocytic leukemia (M5) and 13% with acute promyelocytic leukemia (M3). The ED rate for the three consecutive AML-BFM protocols was 4.9% vs. 5.3% vs. 3.1%, respectively. In 19 patients, death occurred before the 15th day of treatment, in 11 between the 15th and 42nd day. The most common cause of death before the 15th day (ED15) was leukostasis and bleeding, whereas between the 15th and 42nd day (ED15-42), infections, mainly bacterial sepsis. A significant association was found between ED15 and high leukocyte count (>10 × 109/L), M3 leukemia (p < 0.001), and ED15-42 and age <1 year (p = 0.029). In the univariate analysis only initial high leukocyte count >100 × 109/L, was a significant predictor of early death. The overall TRD for the entire study period was 3.4%. The main cause of death were infections, mainly bacterial sepsis (10 children out of 22, 45.4%).

Conclusions: Hyperleukocytosis remains significant factor of early mortality in patients with AML, despite the introduction of various cytoreductive methods. Infections are still the main cause of treatment related deaths. A more individualized approach by using new targeted drugs may be the therapeutic option of choice in the future.

背景:针对儿童和青少年急性髓性白血病(AML)的个性化治疗方法以及支持性疗法的开发,大大提高了患者的生存率。尽管如此,仍有一些患者在开始治疗前死亡,或在获得缓解前的早期治疗阶段死亡。该研究分析了急性髓细胞性白血病儿童和青少年患者早期死亡(ED)和治疗相关死亡(TRD)的频率、临床特征和风险因素:从2005年1月到2023年11月,波兰儿童白血病和淋巴瘤研究小组的中心按照随后的三种治疗方案对646名接受治疗的AML患儿进行了评估:AML-BFM2004年中期方案(385名患儿)、AML-BFM2012年登记方案(131名患儿)和AML-BFM2019年方案(130名患儿):结果:在646名患儿中,有30名患儿早逝,其中包括15名女孩。中位年龄为 10.7 岁(1 天至 18 岁)。超过一半的患者(53%)被诊断为急性粒单核细胞白血病(M5),13%被诊断为急性早幼粒细胞白血病(M3)。AML-BFM三个连续方案的ED率分别为4.9% vs. 5.3% vs. 3.1%。19名患者在治疗第15天之前死亡,11名患者在治疗第15天至第42天之间死亡。第15天前(ED15)最常见的死亡原因是白细胞增多和出血,而第15天到第42天之间(ED15-42)最常见的死亡原因是感染,主要是细菌性败血症。ED15 与高白细胞计数(>10 × 109/L)、M3 白血病之间存在明显关联(P = 0.029)。在单变量分析中,只有初始高白细胞计数(>100 × 109/L)是早期死亡的重要预测因素。在整个研究期间,总体TRD为3.4%。死亡的主要原因是感染,主要是细菌性败血症(22 名儿童中有 10 名,占 45.4%):结论:尽管采用了各种细胞吞噬方法,但高白细胞仍是急性髓细胞白血病患者早期死亡的重要因素。感染仍是治疗相关死亡的主要原因。使用新的靶向药物进行更个体化的治疗可能是未来的治疗选择。
{"title":"Analysis of early and treatment related deaths among children and adolescents with acute myeloid leukemia in Poland: 2005-2023.","authors":"Katarzyna Pawińska-Wąsikowska, Małgorzata Czogała, Karolina Bukowska-Strakova, Marta Surman, Monika Rygielska, Teofila Książek, Beata Sadowska, Agnieszka Pac, Jolanta Skalska-Sadowska, Magdalena Samborska, Jacek Wachowiak, Małgorzata Ciebiera, Radosław Chaber, Renata Tomaszewska, Tomasz Szczepański, Karolina Zielezińska, Tomasz Urasiński, Anna Rodziewicz-Konarska, Krzysztof Kałwak, Marta Kozłowska, Ninela Irga-Jaworska, Barbara Sikorska-Fic, Bartosz Chyżyński, Paweł Łaguna, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Paulina Deleszkiewicz, Katarzyna Drabko, Katarzyna Bobeff, Wojciech Młynarski, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Mycko, Wanda Badowska, Natalia Bartoszewicz, Jan Styczyński, Katarzyna Machnik, Weronika Stolpa, Agnieszka Mizia-Malarz, Walentyna Balwierz, Szymon Skoczeń","doi":"10.3389/fped.2024.1482720","DOIUrl":"10.3389/fped.2024.1482720","url":null,"abstract":"<p><strong>Background: </strong>A personalised approach to the treatment of acute myeloid leukemia (AML) in children and adolescents, as well as the development of supportive therapies, has significantly improved survival. Despite this, some patients still die before starting treatment or in an early phase of therapy before achieving remission. The study analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment related deaths (TRD) of children and adolescents with AML.</p><p><strong>Methods: </strong>From January 2005 to November 2023, 646 children with AML treated in the centers of the Polish Pediatric Leukemia and Lymphoma Study Group according to three subsequent therapeutic protocols were evaluated: AML-BFM 2004 Interim (385 children), AML-BFM 2012 Registry (131 children) and AML-BFM 2019 (130 children).</p><p><strong>Results: </strong>Out of 646 children, early death occurred in 30 children, including 15 girls. The median age was 10.7 years (1 day to 18 years). More than half of the patients (53%) were diagnosed with acute myelomonocytic leukemia (M5) and 13% with acute promyelocytic leukemia (M3). The ED rate for the three consecutive AML-BFM protocols was 4.9% vs. 5.3% vs. 3.1%, respectively. In 19 patients, death occurred before the 15th day of treatment, in 11 between the 15th and 42nd day. The most common cause of death before the 15th day (ED15) was leukostasis and bleeding, whereas between the 15th and 42nd day (ED15-42), infections, mainly bacterial sepsis. A significant association was found between ED15 and high leukocyte count (>10 × 10<sup>9</sup>/L), M3 leukemia (<i>p</i> < 0.001), and ED15-42 and age <1 year (<i>p</i> = 0.029). In the univariate analysis only initial high leukocyte count >100 × 10<sup>9</sup>/L, was a significant predictor of early death. The overall TRD for the entire study period was 3.4%. The main cause of death were infections, mainly bacterial sepsis (10 children out of 22, 45.4%).</p><p><strong>Conclusions: </strong>Hyperleukocytosis remains significant factor of early mortality in patients with AML, despite the introduction of various cytoreductive methods. Infections are still the main cause of treatment related deaths. A more individualized approach by using new targeted drugs may be the therapeutic option of choice in the future.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decreased TREC and KREC levels in newborns with trisomy 21. 21 三体综合征新生儿的 TREC 和 KREC 水平降低。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1468635
Andrey Marakhonov, Anna Mukhina, Elena Vlasova, Irina Efimova, Natalya Balinova, Yulia Rodina, Dmitry Pershin, Zhanna Markova, Marina Minzhenkova, Nadezhda Shilova, Dzhaina Mudaeva, Djamila Saydaeva, Taisiya Irbaieva, Svetlana Matulevich, Elena Belyashova, Grigoriy Yakubovskiy, Inna Tebieva, Yulia Gabisova, Murat Ikaev, Nataliya Irinina, Liya Nurgalieva, Elena Saifullina, Tatiana Belyaeva, Olga Romanova, Sergey Voronin, Rena Zinchenko, Anna Shcherbina, Sergey Kutsev

Newborn screening (NBS) for severe combined immunodeficiency (SCID) has been widely implemented to enable early detection and intervention. Trisomy 21, commonly known as Down syndrome (DS), poses unique challenges in NBS due to its frequent association with T and/or B cell lymphopenia. The pilot NBS screening program recently conducted in Russia was aimed to identify both severe T and B cell deficiencies by measuring TREC and KREC. This study aims to evaluate the incidence of DS in newborns who participated in the pilot program, assess their TREC and KREC values, and determine the proportion of DS newborns potentially identifiable through T/B lymphopenia NBS. We conducted a retrospective analysis of the data obtained during the pilot NBS program, involving 202,908 newborns from eight regions of Russia. The study identified 157 patients with trisomy 21 among the screened cohort, resulting in a DS birth prevalence of 1:1,284. Median TREC and KREC values did not significantly differ between full-term and pre-term subgroups of DS patients. TREC values in DS newborns were decreased and comparable to those of the extremely preterm newborns. DS newborns also demonstrated significant differences in KREC values as compared to the general cohort regardless of gestational age. Our data suggests abnormalities of T- and B-cell lineages development and requires further investigation. This article highlights the need for increased awareness of the intrinsic immunological defects associated with DS. The findings underscore the importance of continued follow-up and comprehensive support by healthcare teams for individuals with DS.

新生儿重症联合免疫缺陷(SCID)筛查(NBS)已被广泛实施,以实现早期检测和干预。21 三体综合征,俗称唐氏综合征(DS),由于常伴有 T 和/或 B 细胞淋巴细胞减少症,给 NBS 带来了独特的挑战。最近在俄罗斯开展的新生儿基础营养筛查试点项目旨在通过测量TREC和KREC来识别严重的T细胞和B细胞缺陷。本研究旨在评估参与试点计划的新生儿中 DS 的发病率,评估他们的 TREC 和 KREC 值,并确定通过 T/B 淋巴细胞减少 NBS 可能识别出的 DS 新生儿的比例。我们对新生儿筛查试点项目中获得的数据进行了回顾性分析,涉及俄罗斯八个地区的 202,908 名新生儿。研究在筛查人群中发现了 157 名 21 三体综合征患者,DS 出生率为 1:1,284。DS 患者中足月亚组和早产亚组的 TREC 和 KREC 中位值没有明显差异。DS新生儿的TREC值有所下降,与极早产新生儿的TREC值相当。无论胎龄大小,DS 新生儿的 KREC 值与普通人群相比也有显著差异。我们的数据表明T细胞系和B细胞系发育异常,需要进一步研究。这篇文章强调了提高对与DS相关的内在免疫缺陷认识的必要性。研究结果强调了医疗团队为 DS 患者提供持续跟踪和全面支持的重要性。
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引用次数: 0
Molecular characteristics, risk factors, and clinical outcomes of methicillin-resistant Staphylococcus aureus infections among critically ill pediatric patients in Shanghai, 2016-2021. 2016-2021年上海儿科重症患者耐甲氧西林金黄色葡萄球菌感染的分子特征、风险因素和临床结局。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1457645
Congyi Dai, Wenting Ji, Yufei Zhang, Weichun Huang, Haiying Wang, Xing Wang

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) infection in children has been on the rise, which poses a serious threat to their health and life in China. The purpose of this study was to determine the molecular characteristics, risk factors, and clinical outcomes of MRSA infections among critically ill pediatric patients.

Methods: A retrospective case-control study was performed in the pediatric intensive care unit (PICU) of a tertiary university teaching hospital. All children infected with culture-positive S. aureus in the PICU between January 2016 and December 2021 were included. Univariate and multivariable logistic regression analyses were used to identify potential risk factors for MRSA infection and clinical outcomes of S. aureus infection. All S. aureus isolates were characterized based on antimicrobial resistance, multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing.

Results: Of 3,974 patients admitted to the PICU, 280 were diagnosed with a S. aureus infection during the 6-year study period. Among them, 43.2% (121/280) were MRSA. All MRSA isolates showed significantly higher rates of resistance to penicillin, erythromycin, clindamycin and tetracycline than MSSA strains. The MRSA strains consisted of 45 spa types and 20 sequence types (STs) (20 clonal complexes), among which the most frequently represented were ST59-t437and ST398-t034. Multivariable logistic regression revealed vaginal delivery, respiratory failure, co-infection with a virus, C-reactive protein (CRP) > 8 mg/L as significant risk factors for MRSA infection. There was no significant difference in all-cause mortality during hospitalization between the MRSA group and the MSSA group. Furthermore, independent predictors for mortality in patients with S. aureus infections were the presence of hypoproteinemia, hematopathy, septic shock, respiratory failure, fever, and white blood cell (WBC) > 15.0 × 109/L.

Conclusions: The study revealed a high proportion of MRSA infections among critically ill pediatric patients, and found significant risk factors for MRSA infection and poor prognosis of S. aureus infection. Methicillin resistance did not contribute to the mortality in the current study. These findings will provide evidence-based practices to make the strategies of prevention and rational use of antibiotics for pediatric patients with S. aureus infection in the ICU.

研究目的在中国,儿童耐甲氧西林金黄色葡萄球菌(MRSA)感染呈上升趋势,严重威胁着儿童的健康和生命。本研究旨在确定儿科重症患者中 MRSA 感染的分子特征、风险因素和临床结果:方法:在一家三级大学教学医院的儿科重症监护室(PICU)开展了一项回顾性病例对照研究。研究纳入了2016年1月至2021年12月期间在PICU感染金黄色葡萄球菌培养阳性的所有患儿。采用单变量和多变量逻辑回归分析来确定MRSA感染的潜在风险因素和金黄色葡萄球菌感染的临床结局。根据抗菌药耐药性、多焦点序列分型(MLST)和金黄色葡萄球菌蛋白A(spa)分型对所有金黄色葡萄球菌分离物进行特征描述:在 6 年的研究期间,PICU 共收治了 3974 名患者,其中 280 人被确诊为金黄色葡萄球菌感染。其中,43.2%(121/280)为 MRSA。所有 MRSA 分离物对青霉素、红霉素、克林霉素和四环素的耐药率均明显高于 MSSA 菌株。MRSA菌株包括45种Spa类型和20种序列类型(ST)(20个克隆复合体),其中最常见的是ST59-t437和ST398-t034。多变量逻辑回归显示,阴道分娩、呼吸衰竭、合并病毒感染、C反应蛋白(CRP)> 8 mg/L是MRSA感染的重要风险因素。MRSA 组和 MSSA 组在住院期间的全因死亡率方面没有明显差异。此外,低蛋白血症、血液病、脓毒性休克、呼吸衰竭、发热和白细胞(WBC)> 15.0 × 109/L也是金黄色葡萄球菌感染患者死亡的独立预测因素:该研究揭示了儿科重症患者中 MRSA 感染的高比例,并发现了 MRSA 感染的重要风险因素和金黄色葡萄球菌感染的不良预后。在本次研究中,甲氧西林耐药性并未导致死亡率上升。这些研究结果将为重症监护室中金黄色葡萄球菌感染的儿科患者制定预防和合理使用抗生素的策略提供循证实践。
{"title":"Molecular characteristics, risk factors, and clinical outcomes of methicillin-resistant <i>Staphylococcus aureus</i> infections among critically ill pediatric patients in Shanghai, 2016-2021.","authors":"Congyi Dai, Wenting Ji, Yufei Zhang, Weichun Huang, Haiying Wang, Xing Wang","doi":"10.3389/fped.2024.1457645","DOIUrl":"10.3389/fped.2024.1457645","url":null,"abstract":"<p><strong>Objective: </strong>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infection in children has been on the rise, which poses a serious threat to their health and life in China. The purpose of this study was to determine the molecular characteristics, risk factors, and clinical outcomes of MRSA infections among critically ill pediatric patients.</p><p><strong>Methods: </strong>A retrospective case-control study was performed in the pediatric intensive care unit (PICU) of a tertiary university teaching hospital. All children infected with culture-positive <i>S. aureus</i> in the PICU between January 2016 and December 2021 were included. Univariate and multivariable logistic regression analyses were used to identify potential risk factors for MRSA infection and clinical outcomes of <i>S. aureus</i> infection. All <i>S. aureus</i> isolates were characterized based on antimicrobial resistance, multilocus sequence typing (MLST) and Staphylococcal protein A (<i>spa</i>) typing.</p><p><strong>Results: </strong>Of 3,974 patients admitted to the PICU, 280 were diagnosed with a <i>S. aureus</i> infection during the 6-year study period. Among them, 43.2% (121/280) were MRSA. All MRSA isolates showed significantly higher rates of resistance to penicillin, erythromycin, clindamycin and tetracycline than MSSA strains. The MRSA strains consisted of 45 <i>spa</i> types and 20 sequence types (STs) (20 clonal complexes), among which the most frequently represented were ST59-t437and ST398-t034. Multivariable logistic regression revealed vaginal delivery, respiratory failure, co-infection with a virus, C-reactive protein (CRP) > 8 mg/L as significant risk factors for MRSA infection. There was no significant difference in all-cause mortality during hospitalization between the MRSA group and the MSSA group. Furthermore, independent predictors for mortality in patients with <i>S. aureus</i> infections were the presence of hypoproteinemia, hematopathy, septic shock, respiratory failure, fever, and white blood cell (WBC) > 15.0 × 10<sup>9</sup>/L.</p><p><strong>Conclusions: </strong>The study revealed a high proportion of MRSA infections among critically ill pediatric patients, and found significant risk factors for MRSA infection and poor prognosis of <i>S. aureus</i> infection. Methicillin resistance did not contribute to the mortality in the current study. These findings will provide evidence-based practices to make the strategies of prevention and rational use of antibiotics for pediatric patients with <i>S. aureus</i> infection in the ICU.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The impact of diurnal variations on emergence delirium following general anesthesia and surgery in children. 昼夜变化对儿童全身麻醉和手术后出现谵妄的影响。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1437460
Wei Wei, Haihang Xie, Yingyi Xu, Jingwen Qin, Xinying Guo, Xingrong Song, Gaofeng Yu, Na Zhang, Daqing Ma, Yonghong Tan, Tianyun Zhao

Background: Emergence delirium (ED) is a widely recognized issue that prolongs mechanical ventilation and post-anesthesia care unit (PACU) resuscitation time, consequently increasing hospital costs and mortality. Postoperative disturbance in circadian rhythms, commonly leading to sleep disorders, has been identified as a significant risk factor for ED. However, the influence of surgery timing (morning vs. afternoon) on the incidence of ED in pediatric patients undergoing general anesthesia remains unknown.

Methods: Patients aged 2-6 years who were operated on under general anesthesia with a bispectral index value between 50 and 60 were categorized based on anesthesia start time into either the morning surgery group (Group M, 8:00-12:00) or the afternoon surgery group (Group A, 13:00-17:00). The primary outcome was the post-extubation incidence of ED assessed by the Cornell Assessment of Pediatric Delirium (CAPD) score. Secondary outcomes included extubation time, duration of PACU stay, and adverse postoperative events and complications.

Results: We recruited a total of 560 patients, 280 in group M and 280 in group A. Compared to Group M, Group A exhibited a significantly higher incidence of ED (p < 0.001), elevated CAPD scores (p < 0.001), and prolonged PACU stays (p < 0.001). Notably, there was no significant difference in extubation time and anesthesia-related adverse events or other postoperative complications between the groups.

Conclusion: Our study highlights that the time of surgery significantly affects the incidence of ED, CAPD scores, and PACU stay duration in children. Further validation of these findings may guide future strategies to reduce ED.

背景:谵妄(ED)是一个公认的问题,它会延长机械通气和麻醉后护理病房(PACU)的复苏时间,从而增加医院成本和死亡率。术后昼夜节律紊乱通常会导致睡眠失调,已被确定为引发急诊谵妄的重要风险因素。然而,手术时间(上午与下午)对接受全身麻醉的儿科患者 ED 发生率的影响仍然未知:方法:根据麻醉开始时间,将双频谱指数值在 50-60 之间的 2-6 岁全身麻醉手术患者分为上午手术组(M 组,8:00-12:00)或下午手术组(A 组,13:00-17:00)。主要结果是根据康奈尔儿童谵妄评估(CAPD)评分评估拔管后ED发生率。次要结果包括拔管时间、PACU停留时间以及术后不良事件和并发症:与 M 组相比,A 组的 ED 发生率明显更高(P P P P 结论:我们的研究强调了手术时间的重要性:我们的研究表明,手术时间对儿童 ED 发生率、CAPD 评分和 PACU 留观时间有重大影响。对这些发现的进一步验证可指导未来减少 ED 的策略。
{"title":"The impact of diurnal variations on emergence delirium following general anesthesia and surgery in children.","authors":"Wei Wei, Haihang Xie, Yingyi Xu, Jingwen Qin, Xinying Guo, Xingrong Song, Gaofeng Yu, Na Zhang, Daqing Ma, Yonghong Tan, Tianyun Zhao","doi":"10.3389/fped.2024.1437460","DOIUrl":"10.3389/fped.2024.1437460","url":null,"abstract":"<p><strong>Background: </strong>Emergence delirium (ED) is a widely recognized issue that prolongs mechanical ventilation and post-anesthesia care unit (PACU) resuscitation time, consequently increasing hospital costs and mortality. Postoperative disturbance in circadian rhythms, commonly leading to sleep disorders, has been identified as a significant risk factor for ED. However, the influence of surgery timing (morning vs. afternoon) on the incidence of ED in pediatric patients undergoing general anesthesia remains unknown.</p><p><strong>Methods: </strong>Patients aged 2-6 years who were operated on under general anesthesia with a bispectral index value between 50 and 60 were categorized based on anesthesia start time into either the morning surgery group (Group M, 8:00-12:00) or the afternoon surgery group (Group A, 13:00-17:00). The primary outcome was the post-extubation incidence of ED assessed by the Cornell Assessment of Pediatric Delirium (CAPD) score. Secondary outcomes included extubation time, duration of PACU stay, and adverse postoperative events and complications.</p><p><strong>Results: </strong>We recruited a total of 560 patients, 280 in group M and 280 in group A. Compared to Group M, Group A exhibited a significantly higher incidence of ED (<i>p</i> < 0.001), elevated CAPD scores (<i>p</i> < 0.001), and prolonged PACU stays (<i>p</i> < 0.001). Notably, there was no significant difference in extubation time and anesthesia-related adverse events or other postoperative complications between the groups.</p><p><strong>Conclusion: </strong>Our study highlights that the time of surgery significantly affects the incidence of ED, CAPD scores, and PACU stay duration in children. Further validation of these findings may guide future strategies to reduce ED.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142550064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
45,X[2]/46,X,der(Y).ish Psu idic(Y)(q11.2)[38] mosaic karyotype in mixed gonadal dysgenesis: a case report and literature review. 45,X[2]/46,X,der(Y).ish Psu idic(Y)(q11.2)[38]混合性性腺发育不良的马赛克核型:病例报告和文献综述。
IF 2.1 3区 医学 Q2 PEDIATRICS Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI: 10.3389/fped.2024.1460174
Qiang Zhang, Xiaoxiao Chen, Yanyan Cao, Yun Zhou, Yingye Liu, Lijun Liu, Lei Liu, Xiaowei Cui

Mixed gonadal dysgenesis is caused by a variety of chromosome abnormalities, most commonly Y chromosome mosaicism. An 8-year-old boy presented with short stature for possible treatment with recombinant growth hormone. He had a history of mixed gonadal dysgenesis (hypospadias, bilateral cryptorchidism, processus vaginalis, and dysplastic immature uterus) and a series of corrective surgeries. At 14 months of age, chromosomal karyotyping revealed 46,X,+mar. Upon presentation, lab testing was consistent with the male phenotype at prepuberty. Fluorescence in situ hybridization revealed 45,X[2]/46,X,der(Y).ish psu idic(Y)(q11.2)(SRY++,DYZ3++)[38] karyotype. A literature review identified eight case reports of mixed gonadal dysgenesis associated with 45,X/46,X,idic(Y)(q11.2). Neither sex phenotype nor short stature correlated with the 46,X,idic(Y)(q11.2) mosaic ratio.

混合性性腺发育不良是由多种染色体异常引起的,最常见的是 Y 染色体嵌合。一名 8 岁男孩因身材矮小前来就诊,可能需要使用重组生长激素进行治疗。他曾患有混合性性腺发育不良(尿道下裂、双侧隐睾、阴道前突和发育不良的未成熟子宫),并接受过一系列矫正手术。14 个月大时,染色体核型检查结果显示为 46,X,+mar。就诊时,实验室检测结果与青春期前的男性表型一致。荧光原位杂交显示核型为 45,X[2]/46,X,der(Y).ish psu idic(Y)(q11.2)(SRY++,DYZ3++)[38] 。文献综述发现了 8 例与 45,X/46,X,idic(Y)(q11.2)相关的混合性性腺发育不良病例报告。性表型和身材矮小均与 46,X,idic(Y)(q11.2)马赛克比率无关。
{"title":"45,X[2]/46,X,der(Y).ish Psu idic(Y)(q11.2)[38] mosaic karyotype in mixed gonadal dysgenesis: a case report and literature review.","authors":"Qiang Zhang, Xiaoxiao Chen, Yanyan Cao, Yun Zhou, Yingye Liu, Lijun Liu, Lei Liu, Xiaowei Cui","doi":"10.3389/fped.2024.1460174","DOIUrl":"10.3389/fped.2024.1460174","url":null,"abstract":"<p><p>Mixed gonadal dysgenesis is caused by a variety of chromosome abnormalities, most commonly Y chromosome mosaicism. An 8-year-old boy presented with short stature for possible treatment with recombinant growth hormone. He had a history of mixed gonadal dysgenesis (hypospadias, bilateral cryptorchidism, processus vaginalis, and dysplastic immature uterus) and a series of corrective surgeries. At 14 months of age, chromosomal karyotyping revealed 46,X,+mar. Upon presentation, lab testing was consistent with the male phenotype at prepuberty. Fluorescence <i>in situ</i> hybridization revealed 45,X[2]/46,X,der(Y).ish psu idic(Y)(q11.2)(SRY++,DYZ3++)[38] karyotype. A literature review identified eight case reports of mixed gonadal dysgenesis associated with 45,X/46,X,idic(Y)(q11.2). Neither sex phenotype nor short stature correlated with the 46,X,idic(Y)(q11.2) mosaic ratio.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Frontiers in Pediatrics
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