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06 November 2023, Volume 38 Issue 11 Previous Issue   

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Chinese expert consensus on the diagnosis and treatment of children with idiopathic short stature The Subspecialty Group of Endocrinology, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association, Adolescent Health and Medical Professional Committee, Chinese Medical Doctor Association, Futang Research Center of Pediatric Development, et al 2023, 38(11): 801-813.  DOI: 10.19538/j.ek2023110601 Abstract ( )   Idiopathic short stature（ISS）is a group of highly heterogeneous disorders that cause short stature but have no known etiology. ISS describes a state of short stature of unknown causes. To diagnose ISS，clinicians should exclude all known diseases by a complete evaluation，which is based on a combination of clinical history，physical examination，complete routine and endocrine laboratory tests and imaging examinations，and genetic testing with informed consent（recommend）. After a comprehensive and systematic diagnostic evaluation，the short stature still with unknown causes is defined as ISS. The treatment of ISS should involve the pediatric endocrinologist and the child's family in the decision-making of the treatment plan and course of treatment. In 2021，China's National Medical Products Administration （NMPA） approved human growth hormone （hGH） treatment for ISS. Treatment is recommended to be adjusted according to the growth response （the rate of height growth）. Gonadotropin-releasing hormone analogues （GnRHa） or aromatase inhibitors or recombinant insulin-like growth factor-1 （rhIGF-1） in combination with hGH are insufficient in evidence-based evidence for the treatment of ISS and are not recommended for routine use.

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Development of child growth charts and its application in China LI Hui 2023, 38(11): 814-817.  DOI: 10.19538/j.ek2023110602 Abstract ( )   Growth evaluation and monitoring is the basis of child health care and pediatric clinical practice. Using growth chart for dynamic monitoring and evaluation is the most appropriate technical tool. Through more than 200 years of development，growth charts have demonstrated their important role in promoting children's health，detecting abnormalities early，assisting disease diagnosis，and evaluating the efficacy of intervention treatments. Even though the research and development of growth charts in China has reached a relatively perfect and advanced level，the correct interpretation and appropriate use of these charts require continuous training，practice and verification.

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Advances in the genetics of idiopathic short stature in children YING Yan-qin, LIANG Yan 2023, 38(11): 818-822.  DOI: 10.19538/j.ek2023110603 Abstract ( )   Idiopathic short stature is a diagnosis for a group of highly heterogeneous short stature in children with unclear etiology. With the progress of molecular diagnostic technology，more and more idiopathic short stature are excluded due to the identification of genetic causes. Understanding the genetic mechanism of idiopathic short stature is helpful to the diagnosis and treatment in clinical practice.

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Primary growth disorders related to growth plate in children ZHU Gao-Hui, ZHU Min 2023, 38(11): 823-828.  DOI: 10.19538/j.ek2023110604 Abstract ( )   Growth plate，a cartilage tissue，is located between the epiphyses and diaphysis，and is composed of chondrocytes and extracellular matrix. Growth plate is the critical part of longitudinal growth of bones in cartilage. Recent findings have revealed that the GH-IGF-1 axis is just one of many regulatory systems that control chondrogenesis in the growth plate. Consequently，normal growth in children depends not only on GH and IGF-I but on multiple hormones，paracrine factors，extracellular matrix molecules，and intracellular proteins that regulate growth plate chondrocytes. Linear bone growth results from co-action of chondrocyte proliferation，hypertrophy and extracellular matrix secretion，and is perfectly coordinated by macro-scale regulating factors（mechanical stress，age，et al.）and micro-scale regulating factors（local paracrine，endocrine factors，extracellular matrix，et al.）. Damaged structure and function of the growth plate due to abnormal regulation is related to growth disorders in children.

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Short stature associated with skeletal dysplasia in children：Skeletal dysplasia patients with COMP gene variants GONG Chun-xiu, ZHENG Yan-nan, CHEN Jia-jia 2023, 38(11): 829-834.  DOI: 10.19538/j.ek2023110605 Abstract ( )   Skeletal dysplasia with short stature in children is a primary growth disorder characterized by abnormal bone and cartilage，some of which also involve muscles，ligaments，and tendons，often presenting as asymmetric short stature. With the wide application of molecular detection technology，more and more patients have obtained a clear etiological diagnosis，and it has been found that the same bone disease can be caused by the variation of several genes，and the variation of different sites of the same gene can cause several bone abnormalities. Among them，skeletal dysplasia caused by COMP gene variation in children are rare diseases and easily misdiagnosedwith the main complaint of short stature，which needs to be distinguished from some relatively common skeletal dysplasia diseases with obvious clinical characteristics. COMP gene variation can lead topseudoachondroplasia （PSACH） and multiple epiphyseal dysplasia （MED）. Both diseases often came to the hospitals with chief complaints of short stature. Clinically，abnormal signs of metacarpal bone，phalangeal bone and epiphysis can be found by taking bone age X-ray films of the left wrist and hand. However，early detection and diagnosis are difficult due to phenotypes differ greatly and clinical understanding is insufficient. The expert writing mainly discusses the spectrum of children with short stature with skeletal dysplasia caused by COMP gene mutation，aiming at strengthening the underst-anding of this disease.

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Diagnosis and assessment of short stature in children CHENG Xin-ran, DU Si-hong, LENG Jie 2023, 38(11): 834-838.  DOI: 10.19538/j.ek2023110606 Abstract ( )   Short stature is an important and complex disease in the field of pediatric endocrinology，so detailed evaluation and diagnosis are essential. Children with short stature need to be comprehensively evaluated from height，symmetry and growth rate，combined with detailed medical history collection，physical examination，laboratory tests and imaging examination. With the development of molecular genetic technology，the etiology of short stature has been greatly enriched，and accurate diagnosis has been further realized. The etiology of short stature is complex，and appropriate means should be selected according to the actual situation to clarify the diagnosis.

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History of growth hormone in the treatment of idiopathic short stature CHEN Rui-min, AI Zhuan-zhuan, CAI Bin-bin 2023, 38(11): 838-842.  DOI: 10.19538/j.ek2023110607 Abstract ( )   Idiopathic short stature （ISS） is a general term of a group of short stature diseases of unknown etiology，The recognition to ISS can be traced back to the 1970s. Growth hormone （GH） has been approved by countries such as the United States，Belgium，Sweden，and China to be used used to improve the height of children with ISS.  In this article，the history of recognition and treatment of GHin ISS is reviewed，in order to provide reference for clinical work.

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Diagnostic value of IGF-1 in children with short stature DAI Yang-li, DONG Guan-ping 2023, 38(11): 842-845.  DOI: 10.19538/j.ek2023110608 Abstract ( )   Short stature in children is one of the risk factors for physical and psychological problems，and early diagnosis and treatment are required. However，the etiology of children's short stature is complex，so a comprehensive evaluation is required to determine the cause. Insulin-like growth factor-1 is an important index in the evaluation of the etiology of short stature in children，especially for growth hormone deficiency and growth hormone resistance. Insulin-like growth factor-1 level is not only influenced by GH，but also by other factors，and immunoassays for IGF-1 suffer from poor concordance among platforms，which limits the broad application of insulin-like growth factor-1.

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Efficacy and safety of fluticasone propionate nebuliser suspension in acute attack of asthma children aged 2 to 4 years：A clinical multicenter study CHENG Qi, ZHANG Han, SHANG Yun-xiao, et al 2023, 38(11): 846-852.  DOI: 10.19538/j.ek2023110609 Abstract ( )   Objective    To observe the efficacy and safety of fluticasone propionate nebuliser suspension （FP nebuliser） in the treatment of acute asthma attack in children aged 2～4 years. Methods    A randomized，active drug controlled，multicenter clinical study design was adopted. Totally 245 children aged 2 to 4 years old with acute asthma in 10 hospitals from June 2022 to February 2023 were randomly divided into FP nebulizer group and Budesonide suspension for inhalation （BUD nebuliser） group according to the ratio of 1.5：1. Observe the daily daytime and nighttime clinical symptom scores，respiratory index scores，and differences from baseline in two groups，as well as the use of other asthma relief drugs to evaluate effectiveness. Use the difference between the daytime clinical symptom scores and baseline on the third day as the main efficacy indicator，and further conduct subgroup analysis based on the severity of asthma. Evaluate safety by observing changes in blood and biochemical indicators （routine blood，liver function，myocardial enzyme，kidney function electrocardiogram）before and after medication，as well as the incidence of adverse events. Finally 239 cases completed the 5～7-day study. Results    There was no statistically significant difference in the main efficacy indicators between the two groups  （P>0.05）. The difference between clinical symptoms and baseline on the second day at night in the FP nebuliser group was higher than that in the BUD nebuliser group  （P<0.05）. The clinical symptom scores of FP nebuliser group on the 4th day were higher than those of BUD nebuliser group （P<0.05）. At other time points，there was no statistically significant difference between the two groups in daytime symptom scores，nighttime clinical symptom scores，respiratory index scores，or differences  trom baseline （P>0.05）. There was no statistically significant difference in the number and frequency of concurrent use of systemic glucocorticoids between the FP nebuliser group and the BUD nebuliser group  （P>0.05）. In children with mild asthma attacks，the difference between the nighttime clinical symptom scores and baseline in the FP nebuliser group on the 2nd and 4th day was greater than that in the BUD nebuliser group  （P<0.05），and there was no significant difference in the other differences. All subjects had no oral candidiasis or hoarse voice. There was no significant difference in routine blood，liver and kidney function，myocardial enzymes，or electrocardiogram between the two groups before and after medication  （P>0.05）.  Conclusion FP nebuliser suspension （0.5 mg） has no difference in efficacy compared to BUD suspension（1 mg）  in the asthma at acute attack period in 2～4-year old children，and has good safety. FP nebuliser is superior to BUD nebuliser in controlling nocturnal asthma symptoms on the 2nd day of treatment；FP nebuliser is superior to BUD nebuliser in controlling nocturnal asthma symptoms on the 2nd and 4th day of mild asthma attacks.

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Clinical study on the relationship between RSV loading and severity of acute lower respiratory tract infection  in children MO Rong-hao, CHEN Jie-lin, XU Lin, et al 2023, 38(11): 853-857.  DOI: 10.19538/j.ek2023110610 Abstract ( )   Objective    To investigate the clinical value of respiratory syncytial virus （RSV） viral load in children with acute lower respiratory tract infection （ALRTI） and analyze its correlation with severe infection. Methods    The clinical data of 123 children with RSV nucleic acid or antigen positive ALRTI admitted to our hospital from July 2020 to December 2021 were collected，viral load detection and immune response characteristics were analyzed，and they were divided into mild infection group，moderate infection group and severe infection group. The clinical data of the three groups were compared. The correlation of viral load in ALRTI disease grading was analyzed. Results    A total of 123 cases were included，including 78 males （63.4%） and 45 females （36.6%），with a male to female ratio of 1.73∶1.00. There were 45 cases （36.6%） in the mild infection group，33 cases （26.8%） in the moderate infection group，and 45 cases （36.6%） in the severe infection group. Statistical analysis of data: RSV viral load was statistically significant between ALRTI severe infection group and moderate infection group，and between severe infection group and mild infection group （P<0.001）；CD4+ T cells increased in severe and moderate infection groups compared with mild infection group （P<0.05），and CD8+ T cells decreased compared with mild infection group （P<0.05）. Gender，age of onset and CD3+ T cells were not statistically significant in groups （P>0.05）. Conclusion    High viral load can easily cause severe RSV infection，and severe infection may occur in different ages and genders. Viral load detection and lymphocyte subsets analysis at the early stage of RSV infection can predict the severity of the disease to a certain extent，which is conducive to taking effective measures in time.

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Risk factors for death of 390 hospitalized children with severe pneumonia ZHOU Shao-yu, LI Shu, XU Ming, et al 2023, 38(11): 858-862.  DOI: 10.19538/j.ek2023110611 Abstract ( )   Objective    To analyze the risk factors for death of severe pneumonia in children in Wenzhou. Methods    A retrospective analysis was conducted on pediatric patients diagnosed with severe pneumonia and admitted to the Yuying Children's Hospital，the Second Affiliated Hospital of Wenzhou Medical University，between January 2018 and December 2019. Clinical records encompassing patients' demographic details，clinical manifestations，laboratory examinations，radiological findings，therapeutic interventions，and short-term prognoses （survival and mortality） were collected. According to，a binary logistic regression model was formulated to assess the risk factors underpinning mortality in pediatric severe pneumonia cases. Results    A total of 613 cases of severe pneumonia in pediatric patients were assembled；after the exclusion of cases with incomplete data，390 cases were included in the study cohort. Among these，233 cases （59.7%） were male，with a median age of 9.0 months. Underlying diseases were present in 213 cases （54.6%），and 260 cases （66.7%） were admitted to the Pediatric Intensive Care Unit （PICU），with 32 cases （8.2%） resulting in mortality. At least one pathogen was detected in 254 cases （65.1%），bacterial cultures were positive in 135 cases （34.6%），respiratory viruses were detected in 118 cases （30.3%），and Mycoplasma pneumoniae was identified in 48 cases （12.3%）. The parameters with statistically significant differences between the survival group and mortality group  included underlying diseases，fever，cyanosis，procalcitonin levels，alanine aminotransferase levels，lactate dehydrogenase levels，PICU admission，and mechanical ventilation requirement. The multifactorial logistic regression analysis revealed the following results： the need for mechanical ventilation （OR=7.78，95% CI： 2.83，22.00） and underlying diseases （OR=5.28，95% CI： 1.65，23.20） were identified as risk factors for mortality in pediatric severe pneumonia. Conclusion    The need for mechanical ventilation and the presence of underlying diseases are risk factors for death in pediatric severe pneumonia in Wenzhou.

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Influencing factors of ambulatory blood pressure in 106 relapsing children with primary nephrotic syndrome         SHEN Xiao-yu, YIN Lei, SHA Sha, et al 2023, 38(11): 863-868.  DOI: 10.19538/j.ek2023110612 Abstract ( )   Objective    To explore and analyze the influencing factors of ambulatory blood pressure（ABP） in relapsing children with primary nephrotic syndrome（PNS）. Methods    Reports 24 h ABP of 106 relapsing children with PNS in our hospital from December 2015 to August 2021 were retrospectively analyzed to explore the relationship between blood pressure and gender，age of onset，course of disease，renal function，body mass index （BMI），cholesterol，clinical type and response to corticosteroid therapy. Results    ABP parameters ［24hSBP and 24hDBP and their load，daytime SBP（dSBP） and daytime DBP（dDBP） and their load，nighttime SBP（nSBP）and nighttime DBP（nDBP） and their load］ levels in 3 groups： SRNS（steroid-resistant nephrotic syndrome） group > SDNS（steroid-dependent nephrotic syndrome） group > SSNS（steroid-sensitive nephrotic syndrome） group. There were statistical differences between SRNS group and SSNS group except Δ24hDBP and ΔnDBP（P<0.05）. And there were statistical differences between SRNS and SDNS group only in ΔdDBP and dSBP load（P<0.05）. Conclusion    Hypercholesterolemia and obesity affect SBP，while nephritis NS is prone to abnormal DBP.The The characteristics of ABP parameters in SRNS group were similar those in the SDNS group，but significantly different from  those in SSNS group.

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Auxiliary effects of Heling emollient in children with mild atopic dermatitis CHEN Li-xin, WANG Ying, GUAN Zhi-wei, et al 2023, 38(11): 869-872.  DOI: 10.19538/j.ek2023110613 Abstract ( )   Objective    To observe the auxiliary role of topical emollient in children with mild atopic dermatitis （ AD） . Methods    Using a self-controlled and study design，90 children aged 0.5～ 12 years with mild AD attending Department of Dermatology，Tianjin Children′s Hospital form Novemher 2022 to March 2023 were enrolled. The tested site was given emollient Heling twice a day，symptom severity assessment，non-invasive skin parameter testing，and skin microbial sampling were conducted on the first day （D0） and the 14th day （D14） of enrollment，respectively. Results    Totally 90 children aged 0.5～12 years with mild AD were enrolled in the study，and 76 children who were followed up were included in the analysis. After 14 days of treatment，the SCORAD score and PP-NRS itching score of the two groups decreased compared to before treatment，and the difference was statistically significant （P<0.05）；the pH value and stratum corneum water content of the tested site improved significantly compared to before treatment （P<0.05）；the distribution of bacterial communities in the lesion area significantly improved，and the diversity of bacterial communities increased，with statistically significant differences （P<0.05）. The proportion of Staphylococcus aureus in the lesion area decreased，while the abundance of other bacterial communities significantly increased compared to before treatment. Conclusion    In children with mild AD，Heling emollients，as an auxiliary therapy，can effectively alleviate the clinical symptoms ，and help to repair the skin barrier.

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Progress on the mechanism of probiotics in the treatment of functional abdominal pain in children FANG Kai-Li, LU Xiao-ying, ZHANG Xiao-mei 2023, 38(11): 873-876.  DOI: 10.19538/j.ek2023110614 Abstract ( )   Functional abdominal pain （FAP） is a common disease with abdominal pain as the main symptom in children，which seriously affects the children's quality of life. FAP is caused mainly by changes in brain-gut axis，resulting in gastrointestinal barrier dysfunction，disturbed gastrointestinal motility，visceral hypersensitivity，intestinal dysbacteriosis and so on. Probiotics， as an important means of non-drug treatment，has obvious effect in the treatment of FAP. This article reviews the mechanism of probiotics in the treatment of FAP in children.

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Retroperitoneal Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon and hemorrhagic asc-ites in a girl ZHENG Xue-fang, CAI Bao-huan, ZHOU Sheng, et al 2023, 38(11): 877-880.  DOI: 10.19538/j.ek2023110615 Abstract ( )   Kaposiform hemangioendothelioma （KHE） is a rare borderline vascular tumor   and has a high mortality in infants and young children with Kasabach-Merritt phenomenon （KMP）. Retroperitoneal lesions are rare. A case of retroperitoneal Kaposiform hemangioendothelioma complicated with Kasabach-Merritt and hemorrhagic ascites is reported. A girl aged 3 months presented with considerable reduction of platelets and hemoglobin for a month and progressive enlargement of abdominal circumference for a week， and gastrointestinal bleeding developed on admission to hospital. Laboratory examinations showed fibrin-related markers increased continuously. Platelets and megakaryocytes were easy to find in bone marrow smear. Abdominal CT showed multiple anomalistic and slightly low-density shadows in retroperitoneum and mesentery. Hemorrhagic ascites was drained by peritoneocentesis. Empirical treatment with corticosteroids and immunoglobulin was given with poor effect. Retroperitoneal lesion biopsy as further examination suggested kaposiform hemangioendothelioma which was the final diagnosis. Hemorrhagic ascites was suspected to be associated with Kaposiform hemangioendothelioma. Treatment with corticosteroids，Sirolimus and vincristine was successful，the abnormal laboratory examinations reached normal level，tumor disappeared，and no recurrence was observed for 1 year. For children with intractable thrombocytopenia and persistent coagulation dysfunction，Kasabach-Merritt phenomenon needs to be considered. Imaging examination is necessary to find lesions，and athological biopsy should be done if necessary to help diagnose and select appropriate treatment to improve the prognosis of those children.