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Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet. 亲代低蛋白饮食小鼠后代肾功能障碍的早期代谢和血液动力学指标
IF 2.4 Q1 PEDIATRICS Pub Date : 2024-10-16 DOI: 10.1186/s40348-024-00184-8
Fabiola Diniz, Francesca Edgington-Giordano, Samir S El-Dahr, Giovane G Tortelote

Background: Parental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet.

Methods: Using a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension.

Results: The offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD.

Conclusion: Our findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

背景:父母营养不良,尤其是低蛋白饮食(LPD),会在婴儿出生时导致少肾病,并使后代日后易患高血压和慢性肾病。成人肾病的发病因遗传和环境因素而异,肾功能的亚临床改变往往被忽视。本研究旨在检测低蛋白饮食小鼠后代肾功能显著下降前肾脏形态的变化:我们结合使用组织学分析、肾脏代谢和血液动力学面板评估以及线性判别分析(LDA)和主成分分析(PCA)等先进的统计技术,研究了母体低蛋白饮食(LPD)对肾脏发育和功能的初步影响。我们的研究利用了高血压发病前喂食低蛋白饮食(LPD)或正常蛋白饮食(NPD)的 F0 亲本的 12 周大 F1 小鼠:结果:喂食低蛋白饮食(LPD)的亲代(F0 代)的后代(F1 代)从出生到 20 岁体重一直下降。与喂食 NPD 的亲代 F1 后代相比,肾脏重量也有所减少。12 周龄时,体重恢复正常,但肾脏重量仍然很低。喂食LPD的亲本的后代肾脏形态异常,包括肾小管扩张、少肾病和充满液体的囊肿,并且随着年龄的增长而恶化。12 周时进行的肾脏代谢面板分析显示,尿白蛋白、血浆肌酐、平均尿素和 BUN 浓度略有上升,但上升幅度一致。虽然没有观察到血液动力学变量的明显变化,但有 2/12 只小鼠(均为雄性)的收缩压发生了变化,这表明在将 F1 小鼠与喂食两种食物的 F0 小鼠进行比较时,存在性别特异性效应。总体而言,肾脏代谢变化与亲代LPD密切相关:我们的研究结果表明,在血压发生任何可检测到的变化之前,亲代喂养低密度脂蛋白饮食的 F1 代必须积累大量肾脏损伤。我们的研究表明,肾脏代谢功能的微小变化可能预示着早期肾脏损伤,因此不应忽视这些营养不良小鼠的后代以及可能的人类。
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引用次数: 0
Fatty acids from nutrition sources for preterm infants and their effect on plasma fatty acid profiles. 早产儿营养来源中的脂肪酸及其对血浆脂肪酸谱的影响。
IF 2.4 Q1 PEDIATRICS Pub Date : 2024-10-12 DOI: 10.1186/s40348-024-00183-9
Gerhard Fusch, Naomi H Fink, Niels Rochow, Christoph Fusch

Background: In preterm infants, IV administration of fat is less well tolerated compared to intake via the enteral route, often resulting in hypertriglyceridemia. It is therefore recommended that parenteral fat intake should not exceed 3.5 to 4.0 g/kg/d whereas human milk can provide up to 8 g/kg/d. It is unknown whether such hypertriglyceridemic conditions are caused by a uniform increase of all fatty acids or it is linked to an elevation of distinct fatty acids due to an unbalanced intake. Obviously, both scenarios could potentially influence the formulation of novel lipid solutions for preterm infants. Objective of this exploratory study was to compare fatty acid profiles between a) different nutritional sources and corresponding plasma samples, b) plasma of infants fed breast milk versus those receiving lipid emulsion, and c) plasma of infants with normal versus elevated triglyceride levels.

Methods: Forty-seven preterm infants < 36 weeks of gestation were included; fatty acid profiles were measured in serum samples and corresponding nutritional sources (breast milk and lipid emulsion) using gas chromatography/mass spectrometry.

Results: Compared to breast milk levels, plasma contained significantly lower C8:0, C10:0, C12:0, C14:0, C19:1n9, C18:3n3 (p < 0.0001). In contrast, relative abundance of C16:0, C18:0 and C20:4n6 was higher in plasma than in corresponding breast milk samples (p < 0.001) and lipid emulsion (p < 0.01). Compared to the corresponding lipid emulsion, the abundance of C18:2n6 and C18:3n3 was significantly lower in plasma (p < 0.001). Fatty acid profiles in plasma of infants fed breast milk compared to lipid emulsion were not markedly different. Hypertriglyceridemic samples showed elevated levels for C18:1n9 and C16:0 when compared with normotriglyceridemic samples.

Conclusions: Our study reveals that lipid levels in plasma show both depletion and enrichment of distinct fatty acids which do not seem to be closely related to dietary intake. A more detailed understanding of fatty acid flux rates is needed, like the understanding of amino acid metabolism and is supported by the finding that hypertriglyceridemia might be a state of selective fatty acid accumulation. This would allow to develop more balanced diets for intensive care and potentially improve clinical outcomes.

背景:在早产儿中,静脉注射脂肪的耐受性不如通过肠道途径摄入,往往会导致高甘油三酯血症。因此,建议肠外脂肪摄入量不应超过每公斤 3.5 至 4.0 克/天,而母乳可提供高达每公斤 8 克/天的脂肪。目前还不清楚这种高甘油三酯血症是由所有脂肪酸的均匀增加引起的,还是与摄入不均衡导致的不同脂肪酸的增加有关。显然,这两种情况都有可能影响早产儿新型脂质解决方案的配制。这项探索性研究的目的是比较 a)不同营养来源和相应血浆样本之间的脂肪酸谱;b)喂养母乳和接受脂质乳剂的婴儿血浆之间的脂肪酸谱;c)甘油三酯水平正常和升高的婴儿血浆之间的脂肪酸谱:结果:与母乳水平相比,血浆中的 C8:0、C10:0、C12:0、C14:0、C19:1n9 和 C18:3n3 含量明显降低(p 结论:我们的研究揭示了早产儿血浆中的脂质水平:我们的研究表明,血浆中的脂质水平显示出不同脂肪酸的消耗和富集,这似乎与膳食摄入量没有密切关系。就像了解氨基酸代谢一样,我们需要更详细地了解脂肪酸的通量,而高甘油三酯血症可能是一种选择性脂肪酸蓄积状态的发现也支持了这一点。这将有助于为重症监护开发更均衡的饮食,并有可能改善临床结果。
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引用次数: 0
Description of bone health in adolescents and young persons with Klinefelter syndrome – results from a pilot study 描述患有 Klinefelter 综合征的青少年的骨骼健康状况--一项试点研究的结果
Q1 PEDIATRICS Pub Date : 2024-09-17 DOI: 10.1186/s40348-024-00182-w
Julia Spiekermann, Jakob Höppner, Eliena Ibnukhsein, Kathrin Sinningen, Beatrice Hanusch, Cordula Kiewert, Heide Siggelkow, Corinna Grasemann
In adults with Klinefelter syndrome (KS), impaired bone health with reduced bone mineral density (BMD) has been described even in the presence of testosterone replacement therapy. The aim of the present study was to characterize bone health in young patients with KS. 20 participants aged 16.10 ± 4.28 years with KS (7 with testosterone replacement therapy) were included in the KliBONE study (DRKS 00024870). Medical history, clinical, radiographic and biochemical parameters of bone health and metabolism were obtained. Radiographic bone health index (BHI) was assessed via automated digital X-ray radiogrammetry of the left hand or via dual energy X-ray absorptiometry (DXA) of the lumbar spine and left femur in participants ≥ 16 years. Peripheral blood mononuclear cells were differentiated into osteoclasts and quantified in 7 participants and 7 healthy controls. Mean BHI SDS was − 1.42 ± 1.22 and mean BMD z-score at the lumbar vertebrae (L1-4) was − 0.92 ± 1.00. 25-OH-vitamin D levels < 20 ng/ml were detected in 8/20. Other parameters of bone metabolism (bone-specific alkaline phosphatase, PTH, ß-crosslaps and osteocalcin) were within age-appropriate reference ranges. Serum leptin SDS was elevated (mean 2.15 ± 1.19). The number of osteoclasts in participants with KS did not differ from that of controls. BHI SDS and BMD z-scores were lower than expected in young individuals with KS despite age-appropriate bone turnover markers and no apparent pathology in osteoclast differentiation. The cause of the early-onset bone phenotype requires further investigation.
在患有 Klinefelter 综合征(KS)的成年人中,即使在接受睾酮替代治疗的情况下,也会出现骨健康受损和骨矿物质密度(BMD)降低的情况。本研究旨在了解 KS 年轻患者的骨骼健康状况。KliBONE 研究(DRKS 00024870)共纳入了 20 名 KS 患者,年龄为 16.10 ± 4.28 岁(其中 7 人接受了睾酮替代治疗)。研究人员采集了病史、临床、放射和生化指标,以了解骨骼健康和新陈代谢情况。对于年龄≥ 16 岁的参与者,通过左手自动数字 X 射线放射测量法或腰椎和左股骨双能 X 射线吸收测量法(DXA)评估放射骨健康指数(BHI)。对 7 名参与者和 7 名健康对照者的外周血单核细胞进行破骨细胞分化和量化。平均 BHI SDS 为 - 1.42 ± 1.22,腰椎(L1-4)平均 BMD z 分数为 - 0.92 ± 1.00。有 8/20 人的 25-OH 维生素 D 水平低于 20 ng/ml。骨代谢的其他参数(骨特异性碱性磷酸酶、PTH、ß-交叉重叠和骨钙素)均在与年龄相适应的参考范围内。血清瘦素 SDS 升高(平均值为 2.15 ± 1.19)。KS 患者的破骨细胞数量与对照组没有差异。尽管KS患者的骨转换标志物与年龄相符,破骨细胞分化也无明显病理变化,但他们的BHI SDS和BMD z分数却低于预期。早发性骨表型的原因需要进一步研究。
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引用次数: 0
Monogenic lupus – from gene to targeted therapy 单基因狼疮--从基因到靶向治疗
Q1 PEDIATRICS Pub Date : 2024-09-12 DOI: 10.1186/s40348-024-00181-x
Katharina Menzel, Kateryna Novotna, Nivya Jeyakumar, Christine Wolf, Min Ae Lee-Kirsch
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by loss of tolerance to nuclear antigens. The formation of autoantibodies and the deposition of immune complexes trigger inflammatory tissue damage that can affect any part of the body. In most cases, SLE is a complex disease involving multiple genetic and environmental factors. Despite advances in the treatment of SLE, there is currently no cure for SLE and patients are treated with immunosuppressive drugs with significant side effects. The elucidation of rare monogenic forms of SLE has provided invaluable insights into the molecular mechanisms underlying systemic autoimmunity. Harnessing this knowledge will facilitate the development of more refined and reliable biomarker profiles for diagnosis, therapeutic monitoring, and outcome prediction, and guide the development of novel targeted therapies not only for monogenic lupus, but also for complex SLE.
系统性红斑狼疮(SLE)是一种典型的自身免疫性疾病,其特点是对核抗原失去耐受性。自身抗体的形成和免疫复合物的沉积会引发炎性组织损伤,可影响身体的任何部位。在大多数情况下,系统性红斑狼疮是一种涉及多种遗传和环境因素的复杂疾病。尽管系统性红斑狼疮的治疗取得了进展,但目前尚无根治的方法,患者需要服用具有明显副作用的免疫抑制剂。罕见的单基因型系统性红斑狼疮的发现,为人们深入了解系统性自身免疫的分子机制提供了宝贵的资料。利用这些知识将有助于开发更精细、更可靠的生物标志物,用于诊断、治疗监测和结果预测,并指导新型靶向疗法的开发,这些疗法不仅适用于单基因狼疮,也适用于复杂型系统性红斑狼疮。
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引用次数: 0
B cell academy of the gut: an update on gut associated germinal centre B cell dynamics. 肠道 B 细胞学院:肠道相关生殖中心 B 细胞动态的最新进展。
IF 2.4 Q1 PEDIATRICS Pub Date : 2024-08-16 DOI: 10.1186/s40348-024-00180-y
Christopher Wichmann, Elisa Wirthgen, Carla R Nowosad, Jan Däbritz

Background: The gut is an environment in which the immune system closely interacts with a vast number of foreign antigens, both inert such as food and alive, from the viral, bacterial, fungal and protozoal microbiota. Within this environment, germinal centres, which are microanatomical structures where B cells affinity-mature, are chronically present and active.

Main body: The functional mechanism by which gut-associated germinal centres contribute to gut homeostasis is not well understood. Additionally, the role of T cells in class switching to immunoglobulin A and the importance of B cell affinity maturation in homeostasis remains elusive. Here, we provide a brief overview of the dynamics of gut-associated germinal centres, T cell dependency in Immunoglobulin A class switching, and the current state of research regarding the role of B cell selection in germinal centres in the gut under steady-state conditions in gnotobiotic mouse models and complex microbiota, as well as in response to immunization and microbial colonization. Furthermore, we briefly link those processes to immune system maturation and relevant diseases.

Conclusion: B cell response at mucosal surfaces consists of a delicate interplay of many dynamic factors, including the microbiota and continuous B cell influx. The rapid turnover within gut-associated germinal centres and potential influences of an early-life window of immune system imprinting complicate B cell dynamics in the gut.

背景:肠道是免疫系统与来自病毒、细菌、真菌和原生动物微生物群的大量外来抗原密切接触的环境。在这种环境中,B 细胞亲和成熟的微解剖结构--生殖中心长期存在并活跃:肠道相关生殖中心促进肠道平衡的功能机制尚不十分清楚。此外,T细胞在免疫球蛋白A类转换中的作用以及B细胞亲和性成熟在平衡中的重要性仍然难以捉摸。在此,我们简要概述了肠道相关生发中心的动态、T 细胞在免疫球蛋白 A 类转换中的依赖性、在无生物小鼠模型和复杂微生物群的稳态条件下肠道生发中心中 B 细胞选择作用的研究现状,以及对免疫和微生物定植的反应。此外,我们还简要地将这些过程与免疫系统成熟和相关疾病联系起来:结论:粘膜表面的 B 细胞反应由许多动态因素的微妙相互作用组成,其中包括微生物群和持续的 B 细胞流入。肠道相关生殖中心内的快速更替以及生命早期免疫系统印记窗口的潜在影响使肠道中的 B 细胞动态变得复杂。
{"title":"B cell academy of the gut: an update on gut associated germinal centre B cell dynamics.","authors":"Christopher Wichmann, Elisa Wirthgen, Carla R Nowosad, Jan Däbritz","doi":"10.1186/s40348-024-00180-y","DOIUrl":"10.1186/s40348-024-00180-y","url":null,"abstract":"<p><strong>Background: </strong>The gut is an environment in which the immune system closely interacts with a vast number of foreign antigens, both inert such as food and alive, from the viral, bacterial, fungal and protozoal microbiota. Within this environment, germinal centres, which are microanatomical structures where B cells affinity-mature, are chronically present and active.</p><p><strong>Main body: </strong>The functional mechanism by which gut-associated germinal centres contribute to gut homeostasis is not well understood. Additionally, the role of T cells in class switching to immunoglobulin A and the importance of B cell affinity maturation in homeostasis remains elusive. Here, we provide a brief overview of the dynamics of gut-associated germinal centres, T cell dependency in Immunoglobulin A class switching, and the current state of research regarding the role of B cell selection in germinal centres in the gut under steady-state conditions in gnotobiotic mouse models and complex microbiota, as well as in response to immunization and microbial colonization. Furthermore, we briefly link those processes to immune system maturation and relevant diseases.</p><p><strong>Conclusion: </strong>B cell response at mucosal surfaces consists of a delicate interplay of many dynamic factors, including the microbiota and continuous B cell influx. The rapid turnover within gut-associated germinal centres and potential influences of an early-life window of immune system imprinting complicate B cell dynamics in the gut.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":"11 1","pages":"7"},"PeriodicalIF":2.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of multistrain Bifidobacteria and Lactobacillus probiotics on HMO compositions after supplementation to pregnant women at threatening preterm delivery: design of the randomized clinical PROMO trial. 有早产危险的孕妇补充多株双歧杆菌和乳酸杆菌益生菌后对 HMO 组成的影响:随机临床 PROMO 试验的设计。
IF 2.4 Q1 PEDIATRICS Pub Date : 2024-08-01 DOI: 10.1186/s40348-024-00179-5
A Welp, E Laser, K Seeger, A Haiß, K Hanke, K Faust, G Stichtenoth, C Fortmann-Grote, J Pagel, J Rupp, W Göpel, M Gembicki, J L Scharf, A Rody, E Herting, C Härtel, I Fortmann

Background: As an indigestible component of human breast milk, Human Milk Oligosaccharides (HMOs) play an important role as a substrate for the establishing microbiome of the newborn. They have further been shown to have beneficial effects on the immune system, lung and brain development. For preterm infants HMO composition of human breast milk may be of particular relevance since the establishment of a healthy microbiome is challenged by multiple disruptive factors associated with preterm birth, such as cesarean section, hospital environment and perinatal antibiotic exposure. In a previous study it has been proposed that maternal probiotic supplementation during late stages of pregnancy may change the HMO composition in human milk. However, there is currently no study on pregnancies which are threatened to preterm birth. Furthermore, HMO composition has not been investigated in association with clinically relevant outcomes of vulnerable infants including inflammation-mediated diseases such as sepsis, necrotizing enterocolitis (NEC) or chronic lung disease.

Main body: A randomized controlled intervention study (PROMO = probiotics for human milk oligosaccharides) has been designed to analyze changes in HMO composition of human breast milk after supplementation of probiotics (Lactobacillus acidophilus, Bifidobacterium lactis and Bifidobacterium infantis) in pregnancies at risk for preterm birth. The primary endpoint is HMO composition of 3-fucosyllactose and 3'-sialyllactose in expressed breast milk. We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. As secondary outcomes we will measure preterm infants' clinical outcomes (preterm birth, sepsis, weight gain growth, gastrointestinal complications) and effects on microbiome composition in the rectovaginal tract of mothers at delivery and in the gut of term and preterm infants by sequencing at high genomic resolution. Therefore, we will longitudinally collect bio samples in the first 4 weeks after birth as well as in follow-up investigations at 3 months, one year, and five years of age.

Conclusions: We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. The PROMO study will gain insight into the microbiome-HMO interaction at the fetomaternal interface and its consequences for duration of pregnancy and outcome of infants.

背景:人乳低聚糖(HMOs)是母乳中一种不易消化的成分,在新生儿微生物组的建立过程中发挥着重要作用。此外,它们还被证明对免疫系统、肺部和大脑发育有益。对于早产儿来说,母乳中的 HMO 成分可能具有特别重要的意义,因为健康微生物群的建立受到与早产有关的多种干扰因素(如剖腹产、医院环境和围产期抗生素接触)的挑战。之前的一项研究提出,在妊娠晚期补充母体益生菌可能会改变母乳中的 HMO 组成。然而,目前还没有关于早产孕妇的研究。此外,HMO 成分与易感婴儿的临床相关结果(包括败血症、坏死性小肠结肠炎(NEC)或慢性肺部疾病等炎症介导的疾病)之间的关系也未进行过研究:一项随机对照干预研究(PROMO = 母乳低聚糖益生菌)旨在分析有早产风险的孕妇在补充益生菌(嗜酸乳杆菌、乳双歧杆菌和婴儿双歧杆菌)后母乳中 HMO 成分的变化。主要终点是母乳中 3-岩藻糖乳糖和 3'-sialyllactose 的 HMO 成分。根据治疗组和对照组之间的标准化平均差,我们估计益生菌干预将使这两种 HMO 水平提高 50%。作为次要结果,我们将测量早产儿的临床结果(早产、败血症、体重增长、胃肠道并发症),以及通过高分辨率基因组测序对母亲分娩时直肠阴道和足月儿及早产儿肠道微生物组组成的影响。因此,我们将在婴儿出生后 4 周内以及 3 个月、1 岁和 5 岁时的随访调查中纵向收集生物样本:我们估计,根据治疗组和对照组之间的标准化平均差异,益生菌干预将使这两种 HMO 水平提高 50%。PROMO研究将深入了解胎儿与母体界面上微生物组与HMO的相互作用及其对妊娠期和婴儿结局的影响。
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引用次数: 0
Immune-mediated inflammatory diseases (IMIDs) in children: key research questions and some answers. 儿童免疫介导的炎症性疾病(IMIDs):关键研究问题和一些答案。
Q1 PEDIATRICS Pub Date : 2024-06-05 DOI: 10.1186/s40348-024-00177-7
Tilmann Kallinich, Marcus A Mall
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引用次数: 0
Changes in vitamins and trace elements after initiation of highly effective CFTR modulator therapy in children and adults with cystic fibrosis - a real-life insight. 囊性纤维化儿童和成人在开始接受高效 CFTR 调节剂治疗后维生素和微量元素的变化 - 现实生活的启示。
Q1 PEDIATRICS Pub Date : 2024-05-08 DOI: 10.1186/s40348-024-00178-6
Dorit Fabricius, Tina Knieling, Noelle Zurmuehl, Leandra Makedon, Joachim Freihorst, Hanna Schmidt, Sebastian Bode

Background: Highly-effective CFTR-modulator therapy with elexa-/teza-/ivacaftor (ETI) has led to improvements in pulmonary outcomes, sweat chloride, body mass index (BMI) and quality of life in people with cystic fibrosis (CF). Improved uptake of fat-soluble vitamins and micronutrients has been reported for CFTR-modulators but data regarding ETI therapy is lacking.

Methods: This single-center retrospective study evaluated forced expiratory volume in one second (FEV-1), sweat chloride, BMI, transaminases (AST, ALT), bilirubin, vitamins A, D, E, zinc and selenium in children and adults eligible for ETI. Parameters were assessed before and up to one year after initiation of ETI.

Results: 58 patients (median age m = 28 years, SD ± 11.6 years, 51.7% female14 < 18 years old) were included. FEV-1 and sweat chloride improved significantly after ETI. There were no changes in BMI or AST. ALT was increased significantly after 4 weeks of ETI but returned to normal levels in further course. Bilirubin levels remained elevated after ETI. Vitamin A was significantly higher 12 months after ETI. No changes were found for vitamins D, E, zinc and selenium.

Conclusions: This study adds to the evidence that improvements of some fat-soluble vitamin levels can be found after ETI. No changes regarding micronutrients were noted. Individualized follow-up and supplementation are recommended.

背景:使用依来沙/替扎/伊伐卡夫托(ETI)进行高效的CFTR调节剂治疗可改善囊性纤维化(CF)患者的肺功能、汗液氯化物、体重指数(BMI)和生活质量。有报道称,CFTR调节剂可改善脂溶性维生素和微量营养素的吸收,但缺乏有关ETI疗法的数据:这项单中心回顾性研究评估了符合 ETI 治疗条件的儿童和成人的一秒用力呼气容积(FEV-1)、汗液氯化物、体重指数、转氨酶(AST、ALT)、胆红素、维生素 A、D、E、锌和硒。在开始 ETI 之前和之后一年内对各项参数进行评估:结果:58 名患者(中位年龄 m = 28 岁,SD ± 11.6 岁,51.7% 为女性)14 结论:这项研究为 ETI 后某些脂溶性维生素水平的改善提供了更多证据。微量营养素没有发生变化。建议进行个体化随访和补充。
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引用次数: 0
Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both? 打破自身免疫的平衡:调节性 t 细胞是病因、治疗方法,还是两者兼而有之?
Q1 PEDIATRICS Pub Date : 2024-03-20 DOI: 10.1186/s40348-024-00176-8
Matthias Hardtke-Wolenski, Sybille Landwehr-Kenzel
Regulatory T cells (Tregs) are a specialized subgroup of T-cell lymphocytes that is crucial for maintaining immune homeostasis and preventing excessive immune responses. Depending on their differentiation route, Tregs can be subdivided into thymically derived Tregs (tTregs) and peripherally induced Tregs (pTregs), which originate from conventional T cells after extrathymic differentiation at peripheral sites. Although the regulatory attributes of tTregs and pTregs partially overlap, their modes of action, protein expression profiles, and functional stability exhibit specific characteristics unique to each subset. Over the last few years, our knowledge of Treg differentiation, maturation, plasticity, and correlations between their phenotypes and functions has increased. Genetic and functional studies in patients with numeric and functional Treg deficiencies have contributed to our mechanistic understanding of immune dysregulation and autoimmune pathologies. This review provides an overview of our current knowledge of Treg biology, discusses monogenetic Treg pathologies and explores the role of Tregs in various other autoimmune disorders. Additionally, we discuss novel approaches that explore Tregs as targets or agents of innovative treatment options.
调节性 T 细胞(Tregs)是 T 细胞淋巴细胞的一个特殊亚群,对维持免疫平衡和防止过度免疫反应至关重要。根据其分化途径,Tregs 又可分为胸腺衍生 Tregs(tTregs)和外周诱导 Tregs(pTregs)。虽然 tTregs 和 pTregs 的调控属性部分重叠,但它们的作用模式、蛋白表达谱和功能稳定性显示出每个亚群独有的特性。在过去几年中,我们对 Treg 的分化、成熟、可塑性及其表型和功能之间的相关性有了更多的了解。对 Treg 数量和功能缺陷患者进行的遗传和功能研究有助于我们从机理上理解免疫失调和自身免疫性病症。本综述概述了我们目前对 Treg 生物学的了解,讨论了单基因 Treg 病理学,并探讨了 Tregs 在其他各种自身免疫性疾病中的作用。此外,我们还讨论了将 Tregs 作为创新治疗方案的靶点或药物的新方法。
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引用次数: 0
Adverse effects of remdesivir for the treatment of acute COVID-19 in the pediatric population: a retrospective observational study. 雷米替韦治疗儿童急性 COVID-19 的不良反应:一项回顾性观察研究。
Q1 PEDIATRICS Pub Date : 2024-02-21 DOI: 10.1186/s40348-024-00175-9
Abigail Schulz, Natalie Huynh, Margaret Heger, Mustafa Bakir

Background: Although the severity of coronavirus disease 2019 (COVID-19) tends to be lower in children, it can still lead to severe illness, particularly among those with chronic medical conditions. While remdesivir (RDV) is one of the few approved antiviral treatments for COVID-19 in children in many countries, the available data on the safety of RDV in this population is limited.

Methods: To address this knowledge gap, a multicenter study involving 65 patients retrospectively analyzed the clinical data from individuals aged <18 who were hospitalized due to severe COVID-19 (defined as SpO2 < 94% or requiring supplemental oxygen) and received at least one dose of RDV. Additionally, the study encompassed 22 patients with mild-moderate COVID-19 who were considered at high risk of developing severe disease.

Results: Nineteen children (29%) experienced mild-to-moderate adverse events (AEs) attributed to RDV, including transaminitis in 20% of children, bradycardia in 8%, and hypotension in 5%. AEs did not require discontinuation of RDV, except in one patient who developed premature ventricular contractions. The rate of AEs did not differ between patients with severe COVID-19 and those with mild-moderate COVID-19 but at high risk for severe disease. All but one patient were discharged within 23 days of admission, and no fatalities were recorded. Among high-risk patients with mild-moderate disease, only 2 (9%) progressed to the point of needing supplemental oxygen.

Conclusions: Our data suggests that RDV is safe in children, with no reported serious AEs. However, the absence of a control group limits the extent to which conclusions can be drawn. RDV may contribute to clinical improvement, particularly in high-risk patients.

背景:尽管冠状病毒病2019(COVID-19)在儿童中的严重程度往往较低,但它仍可能导致严重的疾病,尤其是那些患有慢性疾病的儿童。虽然雷米替韦(RDV)是许多国家批准的少数几种治疗儿童 COVID-19 的抗病毒药物之一,但有关 RDV 在这一人群中安全性的现有数据却很有限:为了填补这一知识空白,一项涉及 65 名患者的多中心研究回顾性分析了年龄在 2 岁以下(94% 或需要补充氧气)、至少接受过一次 RDV 治疗的患者的临床数据。此外,该研究还包括22名轻度-中度COVID-19患者,他们被认为具有发展成重症的高风险:19名儿童(29%)出现了由RDV引起的轻度至中度不良事件(AEs),其中20%的儿童出现转氨酶炎,8%的儿童出现心动过缓,5%的儿童出现低血压。除一名患者出现室性早搏外,其他不良反应均无需停用 RDV。重度 COVID-19 患者与轻度-中度 COVID-19 但重症风险较高的患者之间的 AEs 发生率没有差异。除一名患者外,所有患者均在入院后23天内出院,没有死亡记录。在患有轻中度疾病的高危患者中,只有2人(9%)病情恶化到需要补充氧气的地步:我们的数据表明,RDV 对儿童是安全的,没有严重不良反应的报道。结论:我们的数据表明,RDV 对儿童是安全的,没有出现严重不良反应的报道。然而,由于没有对照组,因此无法得出结论。RDV 可能有助于临床改善,尤其是在高危患者中。
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Molecular and cellular pediatrics
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