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Arginine-axis transcriptomics define three neuroblastoma subtypes and a fixed four-gene prognostic signature with immune correlations. 精氨酸轴转录组学定义了三种神经母细胞瘤亚型和与免疫相关的固定四基因预后特征。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2026-01-31 Epub Date: 2025-12-31 DOI: 10.21037/tp-2025-aw-724
Ying Zheng, Yanan Zhang, Xin Li, Lu Chen, Yuren Xia
<p><strong>Background: </strong>Metabolic plasticity shapes neuroblastoma (NB) heterogeneity and therapy response. Arginine (Arg) sits at the crossroads of the urea cycle, nitric-oxide signaling, polyamine biosynthesis, and proline-collagen metabolism, yet, pathway-level organization of the Arg/proline ("Arg-axis") program in NB and its clinical relevance remain incompletely defined. This study aimed to define Arg-axis transcriptomic subtypes in NB and to develop and externally validate an Arg-axis-derived prognostic risk score with immune correlates.</p><p><strong>Methods: </strong>We prespecified a 54-gene Arg/proline-metabolism panel and used it as the feature space for discovery in GSE49710 (microarray) and validation in E-MTAB-8248 (microarray); two immunotherapy RNA sequencing (RNA-seq) cohorts (MEL_PRJEB23709, GSE78220) were analyzed for out-of-domain evaluation. Consensus clustering delineated Arg-axis subtypes. Tumor stemness was quantified by one-class logistic regression (OCLR)-derived messenger RNA (mRNA) expression-based stemness index (mRNAsi). Cluster-derived features were reduced by random forest and entered into multivariable Cox modeling to derive a fixed-coefficient four-gene signature. Discrimination, calibration, and clinical utility were assessed by receiver operating characteristic (ROC), calibration, and decision-curve analysis (DCA). Immune contexture was inferred by Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE), Microenvironment Cell Populations-counter (MCP-counter), and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT); checkpoint response was predicted by using Tumor Immune Dysfunction and Exclusion (TIDE) [2025] and immunophenoscore (IPS). Connectivity Map (CMap 2.0) prioritized compounds using the top |log fold change| 150 up/down genes per cohort with cross-cohort aggregation.</p><p><strong>Results: </strong>Fifty of 54 panel genes were expressed in the discovery cohort. Consensus clustering supported three subtypes with stepwise overall-survival separation, higher mRNAsi in the poorest-prognosis group, and concordant clinicogenomic features [age, International Neuroblastoma Staging System (INSS) stage, MYCN]. gseGO highlighted cell-cycle/replication programs in high-risk states and antigen-presentation/T-cell-inflamed programs in favorable states. The fixed four-gene model stratified outcome in discovery and reproduced risk separation in the external NB cohort, retaining independence from age, stage, and MYCN, and showing added net benefit on DCA. Across risk strata, immune deconvolution indicated myeloid/extracellular matrix (ECM)-dominant microenvironments at higher scores <i>vs.</i> T-cell-inflamed phenotypes at lower scores; TIDE/IPS were concordant. In two immunotherapy cohorts, a higher RiskScore was associated with inferior overall survival, consistent with the in-silico response metrics. Aggregated CMap analysis nominated hi
背景:代谢可塑性影响神经母细胞瘤(NB)的异质性和治疗反应。精氨酸(Arg)位于尿素循环、一氧化氮信号、多胺生物合成和脯氨酸-胶原代谢的十字路口,然而,NB中Arg/脯氨酸(“Arg轴”)程序的通路水平组织及其临床相关性仍未完全确定。本研究旨在确定NB中arg轴转录组亚型,并开发和外部验证arg轴衍生的具有免疫相关因素的预后风险评分。方法:我们预先指定了一个54个基因的精氨酸/脯氨酸代谢面板,并将其作为在GSE49710(芯片)中发现和在E-MTAB-8248(芯片)中验证的特征空间;分析两个免疫治疗RNA测序(RNA-seq)队列(MEL_PRJEB23709, GSE78220)进行域外评价。一致聚类描述了arg轴亚型。肿瘤干性通过一类logistic回归(OCLR)衍生的信使RNA (mRNA)表达为基础的干性指数(mRNAsi)进行量化。聚类衍生的特征通过随机森林进行约简,并进入多变量Cox建模,得到固定系数的四基因特征。通过受试者工作特征(ROC)、校准和决策曲线分析(DCA)评估鉴别、校准和临床应用。通过使用表达数据(ESTIMATE)、微环境细胞群计数器(MCP-counter)和通过估计RNA转录物的相对亚群(CIBERSORT)来估计恶性肿瘤中的基质细胞和免疫细胞来推断免疫环境;通过肿瘤免疫功能障碍和排斥(TIDE)[2025]和免疫表型评分(IPS)预测检查点反应。Connectivity Map (CMap 2.0)通过跨队列聚合,利用每个队列顶部的|log fold变化| 150个上/下基因来对化合物进行优先排序。结果:54个面板基因中有50个在发现队列中表达。共识聚类支持三种亚型,它们具有逐步的总生存分离,最差预后组的mRNAsi较高,以及一致的临床基因组特征[年龄,国际神经母细胞瘤分期系统(INSS)分期,MYCN]。gseGO突出了高危状态下的细胞周期/复制程序和有利状态下的抗原呈递/ t细胞炎症程序。固定的四基因模型分层了外部NB队列中发现和再现风险分离的结果,保留了与年龄、分期和MYCN的独立性,并显示了DCA的净收益。在整个风险层中,免疫反褶积表明,评分较高的骨髓/细胞外基质(ECM)占主导地位的微环境与评分较低的t细胞炎症表型;TIDE/IPS一致。在两个免疫治疗队列中,较高的RiskScore与较差的总生存期相关,这与计算机应答指标一致。聚合CMap分析提名组蛋白去乙酰化酶(HDAC)抑制,其中依替诺他(MS-275)作为逆转高风险转录组学项目的候选药物排名最高。结论:arg轴锚定方法解决了生物学上一致的NB亚型,并产生了一个简洁的、固定系数的四基因特征,该特征在整个队列中普遍存在,与免疫背景一致,并提出了可测试的治疗假设。这些结果支持NB的代谢风险分层,并激发标准化处理、机制通量测定和合理联合研究的前瞻性验证。
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引用次数: 0
Pegaspargase-associated cerebral venous sinus thrombosis: risk factors and anticoagulation management in pediatric acute lymphoblastic leukemia-a case series. 飞马草相关脑静脉窦血栓形成:儿童急性淋巴细胞白血病的危险因素和抗凝治疗-一个病例系列。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2026-01-31 Epub Date: 2026-01-09 DOI: 10.21037/tp-2025-673
Lu Cao, Wanting Xue, Xiangying Meng, Hui Zhang, Ruixin Zhu, Hongmei Chen, Meilin Han, Zhenjiang Bai, Shaoyan Hu, Shuiyan Wu

Background: Despite improving outcomes in pediatric acute lymphoblastic leukemia (ALL), pegaspargase (PEG-ASP) carries a risk of cerebral venous sinus thrombosis (CVST), for which optimal anticoagulation management in children remains undefined. This retrospective case series aimed to analyze the incidence, associated factors, and management outcomes of PEG-ASP-associated CVST in pediatric ALL patients. Among 741 ALL patients treated at a single center over a 3-year period, the incidence of PEG-ASP-associated CVST was 1.4% (11 cases).

Case description: Eleven pediatric ALL patients who developed PEG-ASP-associated CVST were stratified by disease severity [intensive care unit (ICU) admission vs. non-ICU] and anticoagulation duration (>3 vs. ≤3 months). ICU-admitted patients received significantly higher cumulative PEG-ASP doses (4,000 IU/m2) compared to ward-managed patients (2,250 IU/m2), and a strong positive correlation (r=0.75) was observed between cumulative PEG-ASP dose and disease severity. Extended anticoagulation (>3 months) was associated with improved laboratory parameters, including notably lower triglyceride and D-dimer levels at 8 weeks, along with increased antithrombin (AT)-III levels. All patients were managed conservatively with low-molecular-weight heparin without thrombectomy or discontinuation of PEG-ASP. Outcomes were excellent, with 90.9% survival, complete neurological recovery (modified Rankin Scale grade 0), and no cases of thrombosis recurrence or leukemia relapse.

Conclusions: The study highlights a significant association between cumulative PEG-ASP dose and CVST severity in this pediatric ALL cohort. The findings support the feasibility and safety of extended anticoagulation therapy alongside continued chemotherapy, without interrupting PEG-ASP treatment, leading to favorable clinical and neurological outcomes.

背景:尽管pegaspargase (PEG-ASP)改善了儿童急性淋巴细胞白血病(ALL)的预后,但它具有脑静脉窦血栓形成(CVST)的风险,儿童的最佳抗凝治疗仍不明确。本回顾性病例系列旨在分析儿科ALL患者peg - asp相关CVST的发生率、相关因素和治疗结果。在单一中心接受治疗的741例ALL患者中,peg - asp相关CVST的发生率为1.4%(11例)。病例描述:11例发生peg - asp相关CVST的儿科ALL患者按疾病严重程度(ICU入院vs非ICU)和抗凝时间(bbbb3 vs≤3个月)进行分层。icu住院患者接受的PEG-ASP累积剂量(4,000 IU/m2)明显高于病房管理患者(2,250 IU/m2),并且在累积PEG-ASP剂量与疾病严重程度之间观察到强正相关(r=0.75)。延长抗凝时间(>3个月)与改善的实验室参数相关,包括8周时甘油三酯和d -二聚体水平显著降低,以及抗凝血酶(at)-III水平升高。所有患者均采用低分子肝素保守治疗,没有取栓或停用PEG-ASP。结果非常好,生存率为90.9%,神经功能完全恢复(改良Rankin评分0级),无血栓复发或白血病复发病例。结论:该研究强调了小儿ALL队列中累积PEG-ASP剂量与CVST严重程度之间的显著关联。研究结果支持在持续化疗的同时延长抗凝治疗的可行性和安全性,而不中断PEG-ASP治疗,导致良好的临床和神经预后。
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引用次数: 0
A regional quality-improvement collaborative to reduce early neonatal hypothermia in critically ill newborns. 区域质量改进协作,以减少危重新生儿早期新生儿体温过低。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2026-01-31 Epub Date: 2026-01-23 DOI: 10.21037/tp-2025-aw-685
Yanqing Shen, Xiang Chen, Yu Zhang, Lixiao Liu, Jiang-Qin Liu, Lei Zhang, Wangtao Sheng, Chuhan Dong, Xiafang Chen, Fei Bei

Background: Early postnatal hypothermia (EPH) remains a significant clinical concern in critically ill transported neonates. A previous regional study reported an alarming EPH incidence rate of 82.1%, with wide variation across delivery facilities, underscoring the urgent need for quality improvement (QI) in early body temperature management. This study aimed to reduce the percentage of EPH in critically ill transported newborns by 20% to 25% within 1 year.

Methods: A standardized, evidence-based thermal care bundle and comprehensive staff training were implemented using multiple Plan-Do-Study-Act (PDSA) cycles starting May 1, 2023. Neonates transported from six referral hospitals in the pre-QI phase (January 1, 2022-April 30, 2023) were compared with those in the intervention period (May 1-December 31, 2024). Clinical characteristics, EPH incidence, and early outcomes within 7 days were analyzed.

Results: A total of 1,247 neonates transferred from six referral hospitals were included, with 457 newborns in the pre-QI group and 790 in the post-QI group. Baseline characteristics were similar except for higher maternal intrapartum fever in the post-QI group (1.0% vs. 3.1%, P=0.02). Following implementation of the thermal management protocol, the incidence of EPH significantly decreased from 82.1% to 59.0% (adjusted P<0.001). A marked reduction in severe intraventricular hemorrhage (IVH) (grade ≥3) was observed, from 2.6% to 0.2% (adjusted P=0.002). No significant difference was observed in mortality, pulmonary hemorrhage, shock, hypoglycemia, disseminated intravascular coagulation (DIC), nor invasive mechanical ventilation use.

Conclusions: Implementing a standardized thermal management protocol substantially reduces EPH incidence in critically ill transported neonates. Avoiding EPH is beneficial for improving short-term outcomes.

背景:早期产后低体温(EPH)仍然是危重新生儿的重要临床问题。先前的一项区域研究报告了令人震惊的EPH发病率为82.1%,不同分娩设施的发病率差异很大,强调了早期体温管理质量改善(QI)的迫切需要。本研究旨在1年内将危重新生儿EPH的百分比降低20%至25%。方法:从2023年5月1日开始,采用多个计划-做-研究-行动(PDSA)周期实施标准化、循证热护理包和全面的员工培训。比较干预期(2024年5月1日至12月31日)前qi阶段(2022年1月1日至2023年4月30日)从6家转诊医院转来的新生儿。分析临床特征、EPH发生率及7天内的早期结局。结果:共纳入6家转诊医院的1247例新生儿,其中457例新生儿为qi前组,790例新生儿为qi后组。基线特征相似,除了qi后组产妇产时发热较高(1.0% vs 3.1%, P=0.02)。实施热管理方案后,EPH发病率从82.1%显著下降至59.0%(调整后)。结论:实施标准化热管理方案可显著降低危重新生儿EPH发病率。避免EPH有利于改善短期结果。
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引用次数: 0
Application of 3T contrast-enhanced Dixon water-fat separation coronary magnetic resonance angiography with artificial intelligence-assisted compressed sensing on coronary artery aneurysm in children with Kawasaki disease. 人工智能辅助压缩感知3T增强Dixon水脂分离冠状动脉磁共振造影在川崎病患儿冠状动脉瘤中的应用
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2026-01-31 Epub Date: 2026-01-12 DOI: 10.21037/tp-2025-aw-731
Haitang Jiang, Yali Yue, Quanli Shen, Guanke Cai, Yan Zheng, Yuanzheng Zheng, Chenxi Hu, Kai Lu, Qiong Yao, Xihong Hu

Background: Pediatric cardiac magnetic resonance imaging (MRI) examinations often present significant challenges. artificial intelligence-assisted compressed sensing (ACS) technique is widely used to reduce scan time and improve image quality. Our purpose was to explore the value of the ACS technique for detecting coronary artery aneurysms (CAA) in children with Kawasaki disease (KD), as compared to the united compressed sensing (uCS) technique.

Methods: Sixty patients with KD complicated with suspected coronary artery disease (CAD) who underwent 3T cardiovascular magnetic resonance (CMR) were recruited. Contrast-enhanced magnetic resonance angiography (MRA) images were obtained by both ACS and uCS techniques. The two sequences' scan time, subjective and objective image quality, and diagnostic performance for detecting CAA were measured and compared.

Results: Sixty participants (39 males and 21 females; mean age ± standard deviation, 7±3 years) completed two sequences. The ACS technique exhibited a significantly shorter scan time compared to the uCS technique group (230.6±35.7 vs. 335.3±70.8 seconds, P<0.001). The subjective image quality scores, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the ACS technique were significantly higher than those of the uCS technique (all P<0.05). The sensitivity of the ACS technique coronary MRA was found to be 96% (53/55), the specificity was 80% (4/5), the positive predictive value (PPV) was 98% (53/54), the negative predictive value (NPV) was 67% (4/6) and the accuracy was 95% (57/60) on the basis of each person. The area under the receiver operating characteristic curve (AUC-ROC) of the ACS technique MRA images was larger than that of the uCS technique group on a per-patient basis (0.824 vs. 0.796, P<0.001), a per-vessel basis (0.894 vs. 0.823, P<0.001) and a per-segment basis (0.897 vs. 0.836, P<0.001).

Conclusions: The ACS technique shows excellent diagnostic performance at 3T imaging with shorter scan time and better image quality compared with the uCS technique.

背景:儿童心脏磁共振成像(MRI)检查经常面临重大挑战。人工智能辅助压缩感知(ACS)技术在减少扫描时间和提高图像质量方面得到了广泛的应用。我们的目的是探讨ACS技术在川崎病(KD)患儿冠状动脉瘤(CAA)检测中的价值,并与联合压缩感知(uCS)技术进行比较。方法:选取60例KD合并疑似冠心病(CAD)患者行3T心血管磁共振(CMR)检查。对比增强磁共振血管造影(MRA)图像均由ACS和uCS技术获得。测量并比较两种序列的扫描时间、主客观图像质量以及检测CAA的诊断性能。结果:60名参与者(男性39名,女性21名,平均年龄±标准差,7±3岁)完成了两个序列。与uCS技术相比,ACS技术的扫描时间明显缩短(230.6±35.7 vs. 335.3±70.8 s, pv . 0.796, pv . 0.823, pv . 0.836, p)。结论:ACS技术在3T成像中具有较好的诊断性能,扫描时间较uCS技术短,图像质量较uCS技术好。
{"title":"Application of 3T contrast-enhanced Dixon water-fat separation coronary magnetic resonance angiography with artificial intelligence-assisted compressed sensing on coronary artery aneurysm in children with Kawasaki disease.","authors":"Haitang Jiang, Yali Yue, Quanli Shen, Guanke Cai, Yan Zheng, Yuanzheng Zheng, Chenxi Hu, Kai Lu, Qiong Yao, Xihong Hu","doi":"10.21037/tp-2025-aw-731","DOIUrl":"10.21037/tp-2025-aw-731","url":null,"abstract":"<p><strong>Background: </strong>Pediatric cardiac magnetic resonance imaging (MRI) examinations often present significant challenges. artificial intelligence-assisted compressed sensing (ACS) technique is widely used to reduce scan time and improve image quality. Our purpose was to explore the value of the ACS technique for detecting coronary artery aneurysms (CAA) in children with Kawasaki disease (KD), as compared to the united compressed sensing (uCS) technique.</p><p><strong>Methods: </strong>Sixty patients with KD complicated with suspected coronary artery disease (CAD) who underwent 3T cardiovascular magnetic resonance (CMR) were recruited. Contrast-enhanced magnetic resonance angiography (MRA) images were obtained by both ACS and uCS techniques. The two sequences' scan time, subjective and objective image quality, and diagnostic performance for detecting CAA were measured and compared.</p><p><strong>Results: </strong>Sixty participants (39 males and 21 females; mean age ± standard deviation, 7±3 years) completed two sequences. The ACS technique exhibited a significantly shorter scan time compared to the uCS technique group (230.6±35.7 <i>vs.</i> 335.3±70.8 seconds, P<0.001). The subjective image quality scores, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the ACS technique were significantly higher than those of the uCS technique (all P<0.05). The sensitivity of the ACS technique coronary MRA was found to be 96% (53/55), the specificity was 80% (4/5), the positive predictive value (PPV) was 98% (53/54), the negative predictive value (NPV) was 67% (4/6) and the accuracy was 95% (57/60) on the basis of each person. The area under the receiver operating characteristic curve (AUC-ROC) of the ACS technique MRA images was larger than that of the uCS technique group on a per-patient basis (0.824 <i>vs.</i> 0.796, P<0.001), a per-vessel basis (0.894 <i>vs.</i> 0.823, P<0.001) and a per-segment basis (0.897 <i>vs.</i> 0.836, P<0.001).</p><p><strong>Conclusions: </strong>The ACS technique shows excellent diagnostic performance at 3T imaging with shorter scan time and better image quality compared with the uCS technique.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 1","pages":"6"},"PeriodicalIF":1.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Human bocavirus 1 viremia-associated pediatric sepsis with a triphasic urinary course: a case report. 人类bocavavirus - 1病毒血症相关小儿败血症伴三期尿程:1例报告。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2026-01-31 Epub Date: 2026-01-19 DOI: 10.21037/tp-2025-aw-687
Shuwen Zhong, Wenjie Shan, Long Xiang, Ying Wang, Lei Zhang

Background: Human bocavirus 1 (HBoV1) is a common pediatric respiratory virus, yet, its potential to cause severe systemic illness as a sole pathogen and its specific effects on the urinary system are not fully recognized. This report describes the first case of pediatric sepsis, meeting the 2024 Phoenix sepsis criteria, caused by high-load HBoV1 viremia, which was characterized by a novel triphasic urinary course.

Case description: A previously healthy 4-year-old girl presented with fever and cough and developed asymptomatic sterile pyuria on illness day 4. On day 7, her condition deteriorated to sepsis (Phoenix Sepsis Score of 2), with acute respiratory distress and a depressed level of consciousness. Blood metagenomic next-generation sequencing (mNGS) identified high-load HBoV1 viremia (7,513 reads) as the sole pathogen, with negative blood and urine cultures. During the septic peak, urinary tract ultrasonography was normal; however, follow-up imaging on day 13 revealed delayed-onset, non-obstructive pyelectasis and increased post-void residual (PVR) volume. These functional abnormalities were resolved completely within 2.5 months.

Conclusions: HBoV1 can act as a sole pathogen to cause pediatric sepsis. The observed triphasic urinary course-early sterile pyuria, imaging quiescence at the sepsis peak, and delayed functional impairment-supports an inflammation-mediated pathogenesis rather than direct viral invasion. This case highlights the critical role of advanced molecular diagnostics in identifying viral etiologies in culture-negative sepsis and underscores the necessity of longitudinal functional surveillance, as clinically significant organ dysfunction may manifest after the acute inflammatory phase has resolved.

背景:人类bocavavirus 1 (HBoV1)是一种常见的儿童呼吸道病毒,然而,它作为唯一病原体引起严重全身性疾病的潜力及其对泌尿系统的特异性影响尚未得到充分认识。本报告描述了第一例儿童脓毒症,符合2024年凤凰脓毒症标准,由高负荷HBoV1病毒血症引起,其特征是一种新的三相尿过程。病例描述:一名先前健康的4岁女孩在发病第4天出现发烧和咳嗽,并出现无症状无菌脓尿症。第7天,患者病情恶化为脓毒症(凤凰脓毒症评分2分),伴有急性呼吸窘迫,意识水平下降。血液宏基因组下一代测序(mNGS)鉴定出高负荷HBoV1病毒血症(7513 reads)是唯一的病原体,血液和尿液培养均为阴性。脓毒症高峰期,尿路超声检查正常;然而,第13天的随访成像显示延迟发作,非阻塞性肾盂扩张和空洞后残留(PVR)体积增加。这些功能异常在2.5个月内完全消除。结论:HBoV1是引起小儿败血症的唯一病原菌。观察到的三期尿过程-早期无菌脓尿,败血症高峰时的成像静止和延迟的功能损伤-支持炎症介导的发病机制,而不是直接的病毒入侵。该病例强调了先进的分子诊断在确定培养阴性败血症的病毒病因方面的关键作用,并强调了纵向功能监测的必要性,因为急性炎症期消退后可能出现临床显著的器官功能障碍。
{"title":"Human bocavirus 1 viremia-associated pediatric sepsis with a triphasic urinary course: a case report.","authors":"Shuwen Zhong, Wenjie Shan, Long Xiang, Ying Wang, Lei Zhang","doi":"10.21037/tp-2025-aw-687","DOIUrl":"10.21037/tp-2025-aw-687","url":null,"abstract":"<p><strong>Background: </strong>Human bocavirus 1 (HBoV1) is a common pediatric respiratory virus, yet, its potential to cause severe systemic illness as a sole pathogen and its specific effects on the urinary system are not fully recognized. This report describes the first case of pediatric sepsis, meeting the 2024 Phoenix sepsis criteria, caused by high-load HBoV1 viremia, which was characterized by a novel triphasic urinary course.</p><p><strong>Case description: </strong>A previously healthy 4-year-old girl presented with fever and cough and developed asymptomatic sterile pyuria on illness day 4. On day 7, her condition deteriorated to sepsis (Phoenix Sepsis Score of 2), with acute respiratory distress and a depressed level of consciousness. Blood metagenomic next-generation sequencing (mNGS) identified high-load HBoV1 viremia (7,513 reads) as the sole pathogen, with negative blood and urine cultures. During the septic peak, urinary tract ultrasonography was normal; however, follow-up imaging on day 13 revealed delayed-onset, non-obstructive pyelectasis and increased post-void residual (PVR) volume. These functional abnormalities were resolved completely within 2.5 months.</p><p><strong>Conclusions: </strong>HBoV1 can act as a sole pathogen to cause pediatric sepsis. The observed triphasic urinary course-early sterile pyuria, imaging quiescence at the sepsis peak, and delayed functional impairment-supports an inflammation-mediated pathogenesis rather than direct viral invasion. This case highlights the critical role of advanced molecular diagnostics in identifying viral etiologies in culture-negative sepsis and underscores the necessity of longitudinal functional surveillance, as clinically significant organ dysfunction may manifest after the acute inflammatory phase has resolved.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"15 1","pages":"22"},"PeriodicalIF":1.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Challenge of Cupriavidus gilardii infection in an immunocompromised child: a case report. 免疫功能低下儿童吉拉第铜球菌感染的挑战:1例报告。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2025-12-31 Epub Date: 2025-12-23 DOI: 10.21037/tp-2025-592
Yue Hou, Wenqin Xie, Jinyue Duan, Xuankun Li, Zhu Wu

Background: Cupriavidus gilardii is a multidrug-resistant (MDR) pathogen found in soil and water. Human infection is extremely rare, with only two pediatric cases reported to date, and its clinical features and the antimicrobial strategies remain unclear. The pathogen's MDR nature often poses a therapeutic challenge. This case provides valuable clinical evidence regarding the management of C. gilardii infection in immunocompromised pediatric patients.

Case description: A 4-year-old boy with acute lymphoblastic leukemia developed severe immunosuppression after reinduction cyclophosphamide, cytarabine (Ara-C), mercaptopurine (CAM) chemotherapy according to the SCCCG-ALL-2023 protocol. The patient initially presented with recurrent fever, septic shock, and progressive respiratory distress. Despite an aggressive empirical antibiotic regimen including meropenem, imipenem, piperacillin-tazobactam, linezolid, and levofloxacin, his condition continued to worsen. Blood cultures and metagenomic next-generation sequencing (mNGS) subsequently confirmed C. gilardii infection. Based on susceptibility testing, therapy was adjusted to a combination of ceftazidime-avibactam (CAZ-AVI) and tigecycline. After this adjustment, the patient showed marked clinical improvement, with decreased inflammatory indicators and nearly completed clearance of the pathogen. Unfortunately, on hospital day 26, he developed sudden massive hemoptysis due to Aspergillus pulmonary artery invasion and died despite emergency treatment.

Conclusions: This case demonstrates that CAZ-AVI may offer effective antimicrobial control for C. gilardii infection in immunocompromised pediatric patients. Although the patient succumbed to secondary fungal complications, successful microbiological control demonstrates that CAZ-AVI may serve as a potential salvage therapy for rare MDR Gram-negative bacteria and provides clinical insight into the management of uncommon pediatric infections.

背景:吉拉迪铜毒杆菌(Cupriavidus gilardii)是一种在土壤和水中发现的多重耐药病原菌。人类感染极为罕见,迄今仅报告了两例儿科病例,其临床特征和抗菌策略仍不清楚。这种病原体的耐多药性常常给治疗带来挑战。本病例为免疫功能低下儿童吉拉第梭菌感染的处理提供了宝贵的临床证据。病例描述:一名患有急性淋巴细胞白血病的4岁男孩,根据SCCCG-ALL-2023方案,在再诱导环磷酰胺、阿糖胞苷(Ara-C)、巯基嘌呤(CAM)化疗后出现严重的免疫抑制。患者最初表现为反复发热、感染性休克和进行性呼吸窘迫。尽管给予积极的经经验抗生素治疗,包括美罗培南、亚胺培南、哌拉西林-他唑巴坦、利奈唑胺和左氧氟沙星,他的病情仍继续恶化。随后,血液培养和新一代宏基因组测序(mNGS)证实了吉拉第弓形虫感染。根据药敏试验,调整治疗为头孢他啶-阿维巴坦(CAZ-AVI)和替加环素联合用药。调整后,患者临床表现明显改善,炎症指标下降,病原体几乎完全清除。不幸的是,在住院的第26天,由于曲霉菌侵入肺动脉,他突然出现大量咯血,经紧急治疗后死亡。结论:本病例表明CAZ-AVI可能对免疫功能低下儿童吉拉第梭菌感染提供有效的抗菌控制。虽然患者死于继发性真菌并发症,但成功的微生物控制表明CAZ-AVI可能作为罕见耐多药革兰氏阴性菌的潜在补救疗法,并为罕见儿科感染的管理提供临床见解。
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引用次数: 0
A risk prediction model for autism spectrum disorder integrating biopsychosocial factors: a systematic review and meta-analysis with multicenter validation. 整合生物心理社会因素的自闭症谱系障碍风险预测模型:一项多中心验证的系统回顾和荟萃分析。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2025-12-31 Epub Date: 2025-12-24 DOI: 10.21037/tp-2025-620
Lu Zhang, Weicong He, Pujue Huang, Lisha Zhong

Background: Early identification of individuals at high risk for autism spectrum disorder (ASD) is crucial for optimizing intervention strategies and improving outcomes. This study aims to develop a risk prediction model integrating biopsychosocial factors through a systematic review with multicenter validation.

Methods: A comprehensive search was conducted across PubMed, Cochrane Library, and Embase for articles on biopsychosocial ASD risk factors during 2010-2023. Two reviewers independently extracted data. Meta-regression analysis of 37 systematic reviews/meta-analyses identified 18 potential risk factors by Stata 16.0. Four core variables were included in the prediction model, while 14 were excluded due to low-quality evidence or insufficient data after screening. Multivariate logistic regression with least absolute shrinkage and selection operator (LASSO) variable selection derived model weights. External validation was performed in a Chinese cohort (n=1,175) from two tertiary hospitals. Model discrimination was assessed via receiver operating characteristic (ROC) curves and clinical utility by decision curve analysis (DCA).

Results: Analysis of 37 systematic reviews identified four independent predictors of ASD risk: adverse childhood experiences (ACEs) [odds ratio (OR) =2.11; 95% confidence interval (CI): 1.61-2.77], preterm birth (OR =3.3; 95% CI: 1.24-7.60), antidepressant exposure during pregnancy (OR =1.17; 95% CI: 1.08-1.21), and perinatal antibiotic exposure (OR =1.52; 95% CI: 1.09-2.12). The risk model formula was: 0.82 × (ACEs) + 1.19 × (preterm birth) + 0.42 × (antidepressant exposure) + 0.21 × (perinatal antibiotic exposure). External validation showed excellent discrimination [area under the curve (AUC) =0.78; 95% CI: 0.75-0.81]. DCA confirmed significantly higher net clinical benefit compared to universal intervention strategies.

Conclusions: This study developed a risk prediction model integrating biopsychosocial factors, providing an evidence-based tool for early identification of individuals at high risk for ASD.

背景:早期识别自闭症谱系障碍(ASD)高危个体对于优化干预策略和改善预后至关重要。本研究旨在透过多中心验证的系统回顾,建立整合生物心理社会因素的风险预测模型。方法:综合检索PubMed、Cochrane Library和Embase,检索2010-2023年期间有关ASD生物心理社会风险因素的文章。两名审稿人独立提取数据。通过Stata 16.0对37篇系统评价/荟萃分析进行meta回归分析,确定了18个潜在的危险因素。预测模型纳入4个核心变量,筛选后因证据质量低或数据不足而排除14个核心变量。采用最小绝对收缩和选择算子(LASSO)变量选择的多元逻辑回归方法导出模型权重。在来自两家三级医院的中国队列(n= 1175)中进行了外部验证。通过受试者工作特征(ROC)曲线评估模型的判别性,通过决策曲线分析(DCA)评估模型的临床效用。结果:37项系统评价分析确定了4个独立的ASD风险预测因素:不良童年经历(ace)[优势比(OR) =2.11;95%可信区间(CI): 1.61-2.77]、早产(OR =3.3; 95% CI: 1.24-7.60)、妊娠期抗抑郁药物暴露(OR =1.17; 95% CI: 1.08-1.21)和围产期抗生素暴露(OR =1.52; 95% CI: 1.09-2.12)。风险模型公式为:0.82 × (ace) + 1.19 ×(早产)+ 0.42 ×(抗抑郁药物暴露)+ 0.21 ×(围产期抗生素暴露)。外部验证表明鉴别效果良好[曲线下面积(AUC) =0.78;95% ci: 0.75-0.81]。与通用干预策略相比,DCA证实了更高的净临床效益。结论:本研究建立了综合生物心理社会因素的风险预测模型,为ASD高危人群的早期识别提供了循证工具。
{"title":"A risk prediction model for autism spectrum disorder integrating biopsychosocial factors: a systematic review and meta-analysis with multicenter validation.","authors":"Lu Zhang, Weicong He, Pujue Huang, Lisha Zhong","doi":"10.21037/tp-2025-620","DOIUrl":"10.21037/tp-2025-620","url":null,"abstract":"<p><strong>Background: </strong>Early identification of individuals at high risk for autism spectrum disorder (ASD) is crucial for optimizing intervention strategies and improving outcomes. This study aims to develop a risk prediction model integrating biopsychosocial factors through a systematic review with multicenter validation.</p><p><strong>Methods: </strong>A comprehensive search was conducted across PubMed, Cochrane Library, and Embase for articles on biopsychosocial ASD risk factors during 2010-2023. Two reviewers independently extracted data. Meta-regression analysis of 37 systematic reviews/meta-analyses identified 18 potential risk factors by Stata 16.0. Four core variables were included in the prediction model, while 14 were excluded due to low-quality evidence or insufficient data after screening. Multivariate logistic regression with least absolute shrinkage and selection operator (LASSO) variable selection derived model weights. External validation was performed in a Chinese cohort (n=1,175) from two tertiary hospitals. Model discrimination was assessed via receiver operating characteristic (ROC) curves and clinical utility by decision curve analysis (DCA).</p><p><strong>Results: </strong>Analysis of 37 systematic reviews identified four independent predictors of ASD risk: adverse childhood experiences (ACEs) [odds ratio (OR) =2.11; 95% confidence interval (CI): 1.61-2.77], preterm birth (OR =3.3; 95% CI: 1.24-7.60), antidepressant exposure during pregnancy (OR =1.17; 95% CI: 1.08-1.21), and perinatal antibiotic exposure (OR =1.52; 95% CI: 1.09-2.12). The risk model formula was: 0.82 × (ACEs) + 1.19 × (preterm birth) + 0.42 × (antidepressant exposure) + 0.21 × (perinatal antibiotic exposure). External validation showed excellent discrimination [area under the curve (AUC) =0.78; 95% CI: 0.75-0.81]. DCA confirmed significantly higher net clinical benefit compared to universal intervention strategies.</p><p><strong>Conclusions: </strong>This study developed a risk prediction model integrating biopsychosocial factors, providing an evidence-based tool for early identification of individuals at high risk for ASD.</p>","PeriodicalId":23294,"journal":{"name":"Translational pediatrics","volume":"14 12","pages":"3219-3230"},"PeriodicalIF":1.7,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Clinical characteristics of Mycoplasma pneumoniae pneumonia in children during the post-coronavirus disease 2019 era: a retrospective study in Chongqing, China. 2019冠状病毒病后时期重庆市儿童肺炎支原体肺炎临床特征的回顾性研究
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2025-12-31 Epub Date: 2025-12-23 DOI: 10.21037/tp-2025-435
Kui-Lin Lü, Ju-Hao Yang, Zi-Yun Tang, Hong Chen

Background: Mycoplasma pneumoniae (MP), characterized by periodic outbreaks, causes community-acquired pneumonia in Chinese children. Non-pharmaceutical interventions (NPIs) during the coronavirus disease 2019 (COVID-19) pandemic significantly altered MP transmission. Following the relaxation of NPIs, MP infections rebounded globally, with trends toward younger individuals and increased severity. In this study, we aimed to identify new changes in the epidemiological characteristics, clinical phenotypes, and treatment strategies of MP infection in the post-pandemic era in China.

Methods: In this retrospective study, we analyzed the clinical data of 541 pediatric patients with MP nucleic acid samples who were treated at a general hospital in Chongqing, China between January 2018 and December 2024. Participants were divided into an observation group [2023-2024] and a control group [2018-2022] based on their hospitalization dates. Differences in the group characteristics were compared.

Results: After the relaxation of NPIs, the 2023 hospitalization rate was 5.1 times higher than that before the pandemic (11.16% vs. 2.29%). The peak age of onset shifted from 5-15 to 3-7 years. The observation group had a significantly higher proportion of severe cases (74.34% vs. 40.00%), more intense fever and cough symptoms, multilobar involvement (66.89%), and a higher post-discharge residual cough rate (64.69% vs. 20.00%). In the observation group, tetracycline usage increased (57.38% in children <8 years), glucocorticoid use increased (63.82% vs. 23.53%), and treatment duration was extended.

Conclusions: The post-pandemic era witnessed a surge in MP infections in younger patients, with more severe cases requiring adjusted treatment strategies. This study provides critical evidence for the clinical management and public health decision-making for MP pneumonia.

背景:肺炎支原体(Mycoplasma pneumoniae, MP)在中国儿童中引起社区获得性肺炎,具有周期性暴发的特点。2019冠状病毒病(COVID-19)大流行期间的非药物干预措施(npi)显着改变了MP传播。随着npi的放松,MP感染在全球范围内出现反弹,趋势是向年轻人和严重程度增加。在本研究中,我们旨在确定中国后大流行时代MP感染的流行病学特征、临床表型和治疗策略的新变化。方法:回顾性分析2018年1月至2024年12月在重庆市某综合医院就诊的541例携带MP核酸样本的儿科患者的临床资料。根据住院时间分为观察组[2023-2024]和对照组[2018-2022]。比较各组特征的差异。结果:放宽npi后,2023年住院率是疫情前的5.1倍(11.16% vs. 2.29%)。发病高峰年龄由5-15岁转移至3-7岁。观察组重症比例(74.34% vs. 40.00%)明显高于对照组,发热咳嗽症状更严重,多叶受累(66.89%),出院后残余咳嗽率(64.69% vs. 20.00%)明显高于对照组。观察组患者四环素用量增加(儿童57.38% vs. 23.53%),治疗时间延长。结论:大流行后时代,年轻患者中MP感染激增,更严重的病例需要调整治疗策略。本研究为肺炎的临床管理和公共卫生决策提供了重要依据。
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引用次数: 0
The effectiveness of TEACCH-based interventions in improving adaptive skills in children with autism spectrum disorders: a systematic review and meta-analysis. 基于教学的干预措施在提高自闭症谱系障碍儿童适应技能方面的有效性:一项系统回顾和荟萃分析。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2025-12-31 Epub Date: 2025-12-24 DOI: 10.21037/tp-2025-466
Junmin Li, Ming Chen, Raffy C F Chan, Jacqueline L M Chan, Xiao Liang, Lulu Wang
<p><strong>Background: </strong>The Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) intervention has been adopted globally for children with autism spectrum disorder (ASD). Although previous studies have investigated the effectiveness of TEACCH-based interventions for children with ASD, the impact of various experimental designs and participants' characteristics remains unclear. To address this, a systematic review and meta-analysis were conducted to examine the effectiveness of TEACCH-based interventions in improving different skills, reducing ASD severity, and decreasing parental stress across different study designs and children's characteristics.</p><p><strong>Methods: </strong>A literature search of the PubMed, Embase, MEDLINE, APA PsycInfo, Scopus, and Web of Science databases was conducted. Studies were included if the following criteria were met: (I) a diagnosis of ASD based on professional diagnostic criteria or school report; (II) an age ≤18 years; (III) studies conducted with TEACCH-based interventions explicitly described as based on the TEACCH approach, with structured teaching and environment tailored to ASD children being emphasized; (IV) changes in outcomes reported with at least one well-developed measurement; and (V) a primary study type of randomized controlled trials (RCTs) or nonrandomized controlled studies (NRSs), with pretest-posttest studies only included in the systematic analyses and not in the final meta-analysis. Data were extracted and analyzed via meta-regression and subgroup analysis, and publication bias and quality were assessed. From 1,019 initially included studies, 20, comprising 920 children, were ultimately used in the meta-analysis.</p><p><strong>Results: </strong>This analysis revealed significant improvements in communication skills (g=0.21), daily living skills (g=0.40), motor skills (g=0.19), and social skills (g=0.76) among children with ASD. Subgroup analyses highlighted the positive influence of school age (6-12 years) and parental involvement in strengthening TEACCH-based intervention outcomes. TEACCH interventions also significantly reduced ASD symptom severity (g=-0.91), improved cognitive functioning (g=0.30), and reduced parental stress (g=-0.4).</p><p><strong>Conclusions: </strong>This study demonstrates that TEACCH-based interventions can significantly enhance a range of developmental skills in children with ASD. By comparing intervention settings, durations, and levels of parental involvement, and identifying the specific conditions under which TEACCH yields the greatest benefits-namely, structured clinical environments, medium-term implementation periods, and intentional parent participation. These findings provide actionable evidence on how to optimize TEACCH-based programs in practice and emphasize the importance of context-specific adaptation and high-fidelity delivery when applying these interventions across diverse populations and service sett
背景:自闭症及相关沟通障碍儿童的治疗与教育(TEACCH)干预已被全球广泛采用。尽管之前的研究已经调查了基于teach的干预措施对ASD儿童的有效性,但各种实验设计和参与者特征的影响仍不清楚。为了解决这个问题,我们进行了一项系统回顾和荟萃分析,以检验基于教学的干预措施在不同研究设计和儿童特征中提高不同技能、降低ASD严重程度和减少父母压力方面的有效性。方法:检索PubMed、Embase、MEDLINE、APA PsycInfo、Scopus、Web of Science等数据库的文献。如果符合以下标准,则纳入研究:(I)根据专业诊断标准或学校报告诊断为ASD;(二)年龄≤18周岁;(III)采用明确描述为基于teach方法的干预措施进行的研究,强调为自闭症儿童量身定制的结构化教学和环境;(IV)通过至少一种完善的测量方法报告的结果变化;(V)随机对照试验(rct)或非随机对照研究(NRSs)的主要研究类型,前测-后测研究仅包括在系统分析中,而不包括在最终的荟萃分析中。通过meta回归和亚组分析提取数据并进行分析,评估发表偏倚和质量。从最初纳入的1019项研究中,有20项研究,包括920名儿童,最终用于荟萃分析。结果:该分析显示,ASD儿童在沟通技能(g=0.21)、日常生活技能(g=0.40)、运动技能(g=0.19)和社交技能(g=0.76)方面有显著改善。亚组分析强调了学龄(6-12岁)和家长参与对加强以教学为基础的干预结果的积极影响。teach干预还显著降低了ASD症状严重程度(g=-0.91),改善了认知功能(g=0.30),减轻了父母压力(g=-0.4)。结论:本研究表明,以教学为基础的干预可以显著提高自闭症儿童的一系列发展技能。通过比较干预设置、持续时间和家长参与程度,并确定TEACCH产生最大效益的具体条件,即结构化的临床环境、中期实施期和家长有意参与。这些发现为如何在实践中优化基于教学的项目提供了可操作的证据,并强调了在不同人群和服务环境中应用这些干预措施时,根据具体情况进行适应和高保真交付的重要性。
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引用次数: 0
Evaluation of clear aligner treatment for early permanent dentition Angle Class II Division 1 malocclusion in adolescents. 矫正器治疗青少年恒牙列早期角ⅱ类1分错的疗效评价。
IF 1.7 4区 医学 Q2 PEDIATRICS Pub Date : 2025-12-31 Epub Date: 2025-12-24 DOI: 10.21037/tp-2025-373
Miao He, Hai Feng, Yang-Dong Lin, Yong-Juan Guo, Zun-Tai Li

Background: Angle Class II Division 1 malocclusion in adolescents can impair oral health and facial aesthetics, yet evidence on clear aligner therapy is limited. This study aimed to evaluate the clinical efficacy of clear aligner therapy combined with Class II intermaxillary traction for treating Angle Class II Division 1 malocclusion in adolescents during the early permanent dentition stage.

Methods: A total of 30 adolescents (14 males and 16 females; age range, 12-15 years; mean age: 12.6 years) diagnosed with Angle Class II Division 1 malocclusion in early permanent dentition were enrolled. All patients received non-extraction treatment using clear aligners combined with Class II intermaxillary traction. Treatment outcomes were assessed by comparing pre- and post-treatment cephalometric measurements using statistical analysis.

Results: The mean treatment duration was 28.6 months. All patients achieved satisfactory occlusal outcomes, including improved overjet, overbite, and Class I molar relationship, along with notable enhancement in facial profile aesthetics. Post-treatment cephalometric analysis revealed statistically significant improvements (P<0.05) in most parameters, including sella-nasion-point B angle (SNB), point A-nasion-point B angle (ANB), gonion-pogonion distance (Go-Pog) distance, U1-SN angle, U1-NA angle, U1-L1 angle, U1-NA distance, L1-MP angle, L1-NB angle, L1-NB distance, overjet, overbite, U1-PP distance, L1-MP distance, PTM-U6 distance, upper lip to E-plane (UL-EP), lower lip to E-plane (LL-EP), nasolabial angle (NLA), and facial convexity angle (FCA). No significant changes were observed in sella-nasion-point A angle (SNA), MP-SN, or MP-FH angles (P>0.05).

Conclusions: Clear aligner therapy, when combined with Class II intermaxillary traction, is an effective approach for correcting Angle Class II Division 1 Malocclusion in adolescents. It not only improves occlusal relationships but also enhances facial soft tissue profile.

背景:青少年的Angle II类1分错会损害口腔健康和面部美观,但明确的矫正器治疗的证据有限。本研究旨在评价清牙矫正器联合II类上颌间牵引治疗青少年恒牙期早期的Angle II类1分错的临床疗效。方法:选取确诊为早期恒牙列Angleⅱ类1分错的青少年30例,其中男14例,女16例,年龄12 ~ 15岁,平均年龄12.6岁。所有患者均接受非拔牙治疗,使用清除对准器联合II类上颌间牵引。通过统计分析比较治疗前和治疗后的头颅测量结果来评估治疗结果。结果:平均治疗时间28.6个月。所有患者均获得满意的咬合结果,包括覆盖、覆盖咬合和I类磨牙关系的改善,以及面部轮廓美学的显着提高。治疗后头颅测量分析显示有统计学意义的改善(P0.05)。结论:清除矫正器治疗联合II类上颌间牵引是矫正青少年II类1节错牙合的有效方法。它不仅改善了咬合关系,而且改善了面部软组织轮廓。
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引用次数: 0
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Translational pediatrics
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