Pub Date : 2024-10-18eCollection Date: 2024-01-01DOI: 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。
{"title":"Antiphospholipid syndrome onset with hemolytic anemia and accompanied cardiocerebral events: a case report.","authors":"Jie Zheng, Zhao-Yu Wei, Shi-Chao Lin, Yong Wang, Xin Fang","doi":"10.3389/fped.2024.1370285","DOIUrl":"https://doi.org/10.3389/fped.2024.1370285","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Case presentation: </strong>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.</p><p><strong>Conclusion: </strong>Pediatricians should be familiar with various presentations of pediatric APS to promptly detect possible aPL-related complications and initiate appropriate management strategies early on.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566913","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}
Pub Date : 2024-10-17eCollection Date: 2024-01-01DOI: 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.
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]。
{"title":"Clinical prognostic models in children with sepsis in low- and middle-income countries: a systematic review and meta-analysis.","authors":"Jessica Jordan, Celinie M Nguyen, Lauren M Fletcher, Stephanie C Garbern","doi":"10.3389/fped.2024.1463986","DOIUrl":"10.3389/fped.2024.1463986","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340126, PROSPERO [CRD42022340126].</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/PMC11524808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557742","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}
Pub Date : 2024-10-17eCollection Date: 2024-01-01DOI: 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.
{"title":"Case Report: Functional characterization of a missense variant in <i>INSR</i> associated with hypoketotic hypoglycemia.","authors":"Herodes Guzman, Lauren M Mitteer, Pan Chen, Christine A Juliana, Kara Boodhansingh, Katherine Lord, Arupa Ganguly, Diva D De Leon","doi":"10.3389/fped.2024.1493280","DOIUrl":"10.3389/fped.2024.1493280","url":null,"abstract":"<p><p>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 <i>INSR</i> 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 <i>INSR</i>. 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 <i>INSR</i> compared to cells expressing wild type <i>INSR</i>. Thus, herein we present a heterozygous missense variant in <i>INSR</i> (c.1151A>G, p.Asn384Ser) that results in constitutive and increased activation of the human insulin receptor, leading to both fasting and postprandial hypoglycemia.</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/PMC11524959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557741","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}
Pub Date : 2024-10-17eCollection Date: 2024-01-01DOI: 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.
{"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}
Pub Date : 2024-10-17eCollection Date: 2024-01-01DOI: 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.
{"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}
Pub Date : 2024-10-17eCollection Date: 2024-01-01DOI: 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.
{"title":"Decreased TREC and KREC levels in newborns with trisomy 21.","authors":"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","doi":"10.3389/fped.2024.1468635","DOIUrl":"10.3389/fped.2024.1468635","url":null,"abstract":"<p><p>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.</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/PMC11526121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557743","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}
Pub Date : 2024-10-17eCollection Date: 2024-01-01DOI: 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.
{"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}
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}
Pub Date : 2024-10-16eCollection Date: 2024-01-01DOI: 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.
{"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}