Journal of Clinical Pediatrics

Phenotypic characteristics and treatment strategies of severe bronchopulmonary dysplasia

XIA Hongping, ZHANG Yongjun

Journal of Clinical Pediatrics. 2022, 40(6): 401-406. doi:10.12372/jcp.2022.22e0605

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Bronchopulmonary dysplasia (BPD) is one of the commonest and most serious complications in premature infants. Severe BPD (sBPD) is defined as premature infants receiving oxygen inhalation for at least 28 days and requiring oxygen concentration >30% or positive pressure ventilation at 36 weeks of corrected gestational age. Infants with sBPD may cause longterm death, cardiopulmonary dysfunction, failure to thrive, impaired cognitive development and motor retardation. With the improvement of survival rate of extremely premature infants in China, the incidence of sBPD has increased gradually. Due to the different pathophysiological mechanisms of different children, the phenotypes of diseases are greatly different, which brings considerable challenges to clinical diagnosis and treatment. In recent years, the diagnosis and treatment consensus at home and abroad has put forward the comprehensive management of the infants with sBPD through multidisciplinary team cooperation. In this review, the mechanism and clinical features of three disease components were introduced, including moderate-severe parenchymal disease, large airway disease and pulmonary hypertension. Respiratory support strategy, tracheostomy and drug treatment of pulmonary hypertension were also described. Neonatologists are expected to further improve the survival rate and prognosis of sBPD patients by strengthening the understanding of key pathophysiological and phenotypic characteristics of sBPD, establishing multidisciplinary team consultation mechanism and adopting targeted treatment strategies.

Phenotypic evolution of bronchopulmonary dysplasia in premature infants

DING Yingxue

Journal of Clinical Pediatrics. 2022, 40(6): 407-412. doi:10.12372/jcp.2022.22e0360

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Bronchopulmonary dysplasia (BPD) is the commonest chronic lung disease in preterm infants, and is associated with increased infant mortality and respiratory incidence rate. With the progress of neonatal intensive care medicine, the phenotype of BPD has evolved from fibrocystic disease affecting late preterm infants to lung parenchyma damage and vascular growth disorder mainly affecting infants born 28 weeks ago. In this article, we evaluated the evolution of the definition, pathophysiology, imaging and clinical phenotypes of BPD in order to find new evidence-based prevention and management strategies, to improve the classification of disease phenotypes, to early identify the clinical characteristics of high-risk premature infants and improve their prognosis.

Concerns about diagnosis and treatment of bronchopulmonary dysplasia

LI Fang, LIU Liting

Journal of Clinical Pediatrics. 2022, 40(6): 413-419. doi:10.12372/jcp.2022.22e0333

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Bronchopulmonary dysplasia (BPD) is the commonest chronic lung disease in premature infants, especially in very and extremely low birth weight infant. BPD affects the survival rate and the quality of life of premature infants. At present, the incidence of BPD remains high. With the in-depth understanding of BPD, the diagnostic criteria of BPD are constantly revised, and the treatment methods are constantly improved and perfected. However, the selection of diagnostic criteria for BPD, the selection of respiratory support mode in treatment and the use of glucocorticoids are still problems that clinicians are confused and concerned about. This manuscript compared the different diagnostic criteria of BPD, which are all commonly used in the last decade. In addition, we discussed respiratory support management and glucocorticoid use in the prevention and treatment of BPD in neonates.

Clinical characteristics of bronchopulmonary dysplasia in preterm infants with gestational age <32 weeks

XU Ruzheng, JIANG Xu, SUN Bin

Journal of Clinical Pediatrics. 2022, 40(6): 420-424. doi:10.12372/jcp.2022.21e0945

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Objective To analyze the epidemiological characteristics of children with bronchopulmonary dysplasia (BPD) for 6 years and clinical characteristics changes of BPD in different periods. Methods Clinical data of children with confirmed BPD after birth and during the mother's pregnancy from January 2015 to December 2020 were retrospectively collected. The children were grouped according to the gestational age and birth weight, and the trend of BPD incidence in each group was compared. According to the time of diagnosis, the children were divided into group 2015-2017 and group 2018-2020 and the clinical characteristics of the two groups were compared. Results From 2015 to 2020, a total of 1237 premature infants with gestational age <32 weeks were admitted to our hospital, including 155 infants with BPD (12.5%). There was significant difference in the incidence of BPD among different gestational age groups (P<0.001). The incidence of BPD among premature infants ≤26 weeks was the highest, and the incidence of BPD decreased with the increase of gestational age. From 2015 to 2020, the gestational age distribution of children with BPD showed statistically significant differences among different years (P=0.001). In 2015 and 2016, the proportion of patients with gestational age of 28 to 32 weeks was higher. The proportion of patients with gestational age of 26-29⁺⁶ weeks from 2017 to 2020 was higher. The incidence of BPD among different birth weight groups was significantly different (P<0.001). The incidence of BPD among premature infants ≤750g was the highest, and the incidence of BPD decreased with the increase of birth weight. From 2015 to 2020, there were statistically significant differences in the birth weight distribution of BPD children in different years (P<0.05). In 2015 and 2016, the proportion of patients with birth weight of 1001-1500g was higher. In 2017 and 2018, the proportion of patients with birth weight of 751-1500 g was higher. In 2019 and 2020, the proportion of patient with birth weight of 751-1250g was higher. Compared with group 2015-2017, BPD children in group 2018-2020 had lower gestational age, lower birth weight and NCIS score, lower proportion of physical body weight decline ≥10%, higher proportion of maternal smoking or exposure to polluted air, higher proportion of respiratory failure and anemia, longer time to start enteral nutrition and to reach complete enteral nutrition. The difference between the two groups was statistically significant (P<0.05). Conclusions BPD happens in early gestational age and cause low birth weight of children. For children with maternal exposure to smoking or air pollution, respiratory failure and anemia after birth, BPD should be considered in clinical work.

Application of volume guaranteed ventilation in preterm infants with respiratory distress syndrome

LIU Wenqiang, WANG Jun, YE Lili, YANG Qianqian, XU Yan

Journal of Clinical Pediatrics. 2022, 40(6): 425-430. doi:10.12372/jcp.2022.21e1289

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Objective To compare the effects of volume guaranteed (VG) ventilation and pressure controlled (PC) ventilation in premature infants with respiratory distress syndrome (RDS). Methods RDS premature infants with gestational age <32 weeks or birth weight <1500g and requiring invasive mechanical ventilation from March 2017 to April 2021 were prospectively enrolled in the study. Patients were divided into VG group and PC group by simple random method. Before extubation, ventilator parameters, arterial blood gas, invasive mechanical ventilation time, total respiratory support time, average hospital stay, incidence of complications and mortality were compared between the two groups. Results Finally, 79 premature infants with RDS (46 boys and 33 girls) completed the study, the average gestational age was (30.1±1.2) weeks and the average birth weight was (1239.0±158.0) g. There were 36 patients in the VG group and 43 patients in the PC group. Compared with the PC group, the average airway pressure before extubation was lower in the VG group, and invasive mechanical ventilation time, total respiratory support time and average hospital stay were shortened, with statistically significant differences (P<0.05). Conclusions For premature infants with RDS, the VG mode may be a safer and more effective mode of mechanical ventilation. However, multi-center clinical trials with large sample sizes are needed to verify the results of our current study.

Effect of L-carnitine on lipid and bilirubin metabolism in extremely premature infants

YU Yanliang, CHEN Xueyu, FAN Guoqing, CHEN Chun, LIN Bingchun, ZHAO Jie, HUANG Zhifeng, YANG Chuanzhong

Journal of Clinical Pediatrics. 2022, 40(6): 431-435. doi:10.12372/jcp.2022.21e0730

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Objective To investigate the effect of L-carnitine on lipid and bilirubin metabolism in extremely premature infants (EPI). Methods The clinical data of preterm infants with gestational age <28 weeks hospitalized from August 2016 to December 2019 were retrospectively analyzed. Preterm infants were divided into L-carnitine group and non-L-carnitine group according to the prophylactic use of L-carnitine within 72 hours after admission, and the levels of lipids and bilirubin were compared between the two groups. Results A total of 261 EPI (151 boys and 110 girls) were enrolled, and the mean gestational age was (26.5±1.3) weeks and the mean birth weight was (907.3±175.9) g. There were 139 patients in L-carnitine group and 122 in non-L-carnitine group. The 1-minute Apgar score and the proportion of prenatal dexamethasone use in L-carnitine group were higher than those in non-L-carnitine group, and the differences were statistically significant (P<0.05). Compared with non-L-carnitine group, L-carnitine group had lower total bilirubin level at week 1 and 2, higher bile acid level at week 2, lower direct bilirubin level at week 4, higher triglyceride level at week 1, lower blood urea nitrogen and creatinine levels and higher alanine aminotransferase level at week 1 and 2, and the differences were statistically significant (P<0.05). Among 261 patients, 66 had parenteral nutrition associated cholestasis (PNAC), including 33 patients (23.7%) in the L-carnitine group and 33 (27.0%) in the non-L-carnitine group. Binary logistic regression analysis showed that triacylglycerol level at the fourth week of hospitalization was a risk factor for PNAC (P<0.05). There was no significant correlation between prophylactic use of L-carnitine and the occurrence of PNAC (P>0.05). Conclusions Early prophylactic use of L-carnitine in EPI can regulate bilirubin and lipid metabolism, but it will not reduce the incidence of PNAC, nor affect liver and kidney function.

The effect of phototherapy on intestinal flora and drug-resistant genes in jaundiced neonates

ZHANG Kun, FAN Sainan, ZHENG Fang, ZHANG Jiahui, WU Zhimin, LYU Anping, MA Yanan, FANG Xiaohui, ZHANG Jinping

Journal of Clinical Pediatrics. 2022, 40(6): 436-441. doi:10.12372/jcp.2022.21e0643

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Objective To analyze the changes of intestinal microflora and drug-resistant genes in jaundiced neonates receiving phototherapy, and to explore its clinical significance. Methods Metagenomic sequencing was used to analyze the changes of intestinal flora and drug-resistant genes in neonates with jaundice after phototherapy. Results There was no significant difference in the α- and β-diversity of the intestinal microflora abundance after 24 and 48 hours of phototherapy (P>0.05). At the species level, the relative abundance of some species increased, including Clostridium bolteae, Enterococcus faecium and Streptococcus thermophilus (P<0.01). The intestinal flora of jaundiced neonates carried a large number of drug-resistant genes, a total of 242 genes, mainly tetracycline, β-lactams, macrolides, sulfonamides and aminoglycosides, and more resistant genes of Escherichia coli were also found. With the prolongation of phototherapy time, some drug resistance genes changed significantly. The main increased resistance genes were β-lactam resistance gene (CTX-M-14), aminoglycoside resistance gene (aadA2), tetracycline resistance gene [tet(59)], efflux pump gene (efmA), quinolone resistance gene (QnrS2), carbapenemase gene (OXA-347) and sulfonamide resistance gene (dfrA1), while the abundance of mgrA in Staphylococcus aureus decreased after phototherapy, and the differences were significant (P<0.05). After 48 hours of phototherapy, the species abundance of the following intestinal microflora showed a significant positive correlation with drug resistance genes: Clostridium and aminoglycoside resistance gene [APH(3')-Ia], Bacteroides uniformis and β-lactam resistance gene (CfxA6), Enterobacter cloacae and fosfomycin resistance gene (UhpT), Streptococcus parahaemolyticus and macrolide resistance gene (mefA) (P<0.01); while the species abundance of Enterococcus faecalis was negatively correlated with aminoglycoside resistance gene [ANT(2") -Ia] (P<0.01). Conclusions Phototherapy can change the relative abundance of some bacterial species in the intestinal microflora of neonates and significantly increase the abundance of some drug-resistant genes. Whether the disruption of bacterial homeostasis is related to the adverse reactions of phototherapy and its clinical significance needs further study.

Neonatal severe hyperparathyroidism caused by novel variation in CASR gene: a case report

WANG Yingcan, TAN Jintong, CHEN Yan, HUANG Qi, XIA Hongping

Journal of Clinical Pediatrics. 2022, 40(6): 442-445. doi:10.12372/jcp.2022.21e1090

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To improve the understanding of neonatal severe hyperparathyroidism (NSHPT). The clinical data, gene test result, treatment and prognosis of a child with NSHPT were retrospectively analyzed. A 14-day-old female infant presented with hyperbilirubinemia, poor feeding, lethargy, hypotonia, severe hypercalcemia and hyperparathyroidism 4 days after birth. She was found to carry novel compound heterozygous mutations of c.888C > A (p. Ser296Arg) (from father) and c.1576G > T (p. Glu526Ter) (from mother) in the CASR gene. The infant received multiple-dose intravenous zoledronate. After the drug treatment, symptoms improved including sucking, reaction and muscle tension. Serum calcium decreased obviously at first, but increased again after one week. Unilateral parathyroidectomy was performed 54 days after birth. Postoperative serum calcium reduced and the patient was discharged 64 days after birth. At 17 months of follow-up, the patient showed delayed growth and neurodevelopmental retardation. NSHPT is caused by an inactivation variation of the CASR gene and is characterized by severe hypercalcemia and hyperparathyroidism with growth retardation. Total parathyroidectomy is the first choice of treatment, bisphosphonates may have a certain effect.

Clinical analysis of 23 HIV-negative children with Talaromyces marneffei infections

ZENG Senqiang, FAN Huifeng, LIN Haiyang, LIANG Yufeng, ZHANG Dongwei, LU Gen

Journal of Clinical Pediatrics. 2022, 40(6): 446-449. doi:10.12372/jcp.2022.21e1072

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Objective To explore clinical characteristics and treatment of Talaromyces marneffei (T. marneffei) infection in HIV-negative children, so as to improve the diagnosis of T. marneffei infection in children. Methods The clinical data of 23 HIV-negative children with T. marneffei infection were retrospectively analyzed, and the demographic characteristics, clinical manifestations, laboratory tests, complications, treatment and outcome were summarized. Results Twenty-three children (15 boys and 8 girls) were included, with a median age of 22 months (3 months to 13 years). The main clinical features were fever (22/23, 95.7%), cough (18/23,78.3%) and hepatomegaly (18/23,78.3%), and skin involvement was found in 9 cases (39.1%). Common severe complications included septic shock (13/23, 56.5%), hemophagocytic syndrome (12/23, 52.2%), acute respiratory distress syndrome (11/23, 47.8%) and multiple organ dysfunction syndrome (10/23, 43.5%). Serum IgG decreased in 7 cases, IgM increased in 6 cases, IgE increased in 9 cases, and NK cell count decreased in 13 cases. Eleven children were tested by genetic testing and 6 of them were found to have primary immunodeficiency disease. T. marneffei was cultured from specimens of blood in 87% cases (20/23). Nine of them were also confirmed by bone marrow culture. Another two cases were diagnosed by skin biopsies and next-generation sequencing (NGS) of alveolar lavage fluid, respectively. Twenty cases received antifungal therapy. Twelve cases (52.2%) died at last, though 9 of them had received antifungal therapy. Conclusions The clinical manifestations of HIV-negative children with T. marneffei infection were not typical with serious complications and high mortality rate. Early identification and blood culture and bone marrow culture can improve the detection rate, and fluid NGS, especially alveolar lavage fluid, is a promising detection method. Early detection and timely treatment may help to improve the prognosis of T. marneffei infection.

Clinical diagnosis and treatment of 5 cases with congenital mesoblastic nephroma and literature review

ZHANG Dongdong, DONG Youhong, YUAN Xiaojun

Journal of Clinical Pediatrics. 2022, 40(6): 450-455. doi:10.12372/jcp.2022.21e1185

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Objective The clinical characteristics, treatment strategies and clinical outcomes of congenital mesoblastic nephroma (CMN) were retrospectively analyzed and CMN diagnosis and treatment were summarized. Methods The age at onset, tumor size, pathological classification, ETV6-NTRK fusion gene, treatment regimens and clinical outcomes of children newly diagnosed with CMN admitted to the Department of Pediatric Hematology/Oncology, Xinhua Hospital from January 2013 to December 2020 were analyzed. Results A total of 5 children with CMN were admitted in 7 years, including 4 boys and 1 girl. The median age of diagnosis was 4.5 months (0.3-11 months). In 3 patients, renal mass was found during obstetric examination, and CMN was diagnosed early after birth, and ETV6-NTRK fusion gene was negative. The CMN diagnosis age was older than 6 months in 2 patients, and the ETV6-NTRK fusion gene was positive. The tumor stages were stageⅠ (1 case), StageⅡ (1 case), and stage Ⅲ (3 cases). Pathological classification was as follows: 1 case was classical, 2 cases were cellular (stageⅡchild with epithelioid type), and 2 cases were mixed. All the children underwent surgery. One child received surgical resection after 2 cycles of neoadjuvant chemotherapy. The stage Ⅲ children received 9 cycles of VAC chemotherapy after surgery. The median follow-up time was 19 months (11-34 months). One stageⅡchild relapsed 1 year after the completion of combined treatment with surgery and chemotherapy, while the rest of the children were disease-free. Conclusions Most children with CMN have a good prognosis after surgery combined with adjuvant chemotherapy. The age of diagnosis is generally less than 1 year old, and some children can be diagnosed early because of obstetric examination. Surgery is still the main treatment, and postoperative follow-up can be applied for stage Ⅰ and Ⅱ patients. Postoperative adjuvant chemotherapy can reduce the recurrence rate in stage Ⅲ cases.

T lymphocyte subsets and serum neuron-specific enolase levels in children with tic disorder and their clinical significance

LI Weiqin, ZHANG Zilu, QIN Zhuo, ZHANG Liya, GUO Yue

Journal of Clinical Pediatrics. 2022, 40(6): 456-460. doi:10.12372/jcp.2022.21e1478

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Objective To investigate the association of T lymphocyte subsets and serum neuron-specific enolase (NSE) levels with the severity of tic symptoms and clinical types in Tic disorders (TD) children, and to analyze its clinical significance. Methods Clinical data of children with TD who attended one neurology clinic from June 2020 to June 2021 were collected. According to the Yale Global Tic Severity Scale (YGTSS), the children were divided into the mild TD group and the moderate to severe TD group. According to the DSM-V clinical classification standard, the TD group is divided into transient tic disorder group (TTD group), chronic exercise or vocal tic disorder group (CTD group), Tourette syndrome group (TS group). T lymphocyte subsets and NSE levels were compared between TD children and healthy children who underwent routine physical examination at the same time. Results A total of 180 TD children (TD group) were enrolled, including 141 boys and 39 girls, and the mean age was (7.3±2.3) years. There were 150 children (115 boys and 35 girls) in the control group, and the mean age was (7.4±2.2 years). The levels of CD3⁺, CD3⁺CD4⁺ and CD4⁺/CD8⁺ in TD group were lower than those in the control group, and the NSE level in TD group was higher than that in the control group, and the difference was statistically significant (P<0.001). The differences in CD3⁺, CD3⁺CD4⁺, CD4⁺/CD8⁺ and NSE levels between the mild TD group (n=73), the moderate to severe TD group (n=107) and the control group were statistically significant (P<0.05). The CD3⁺ level in the moderate to severe TD group was lower than that in the mild TD group and the control group, the NSE level in the moderate to severe TD group was higher than that in the mild TD group and the control group, and the difference was statistically significant (P<0.05). The NSE levels were significantly positively correlated with TD severity (r=0.82, P<0.001). The differences in CD3⁺, CD3⁺CD4⁺, CD4⁺/CD8⁺ and NSE levels between the TTD group (n=115), CTD group (n=42), TS group (n=23) and the control group were statistically significant (P<0.05). The levels of CD3⁺, CD3⁺, CD4⁺, CD4⁺/CD8⁺ in the TTD group, CTD group and TS group were lower than those in the control group, the NSE level was higher than that in the control group, and the differences were statistically significant (P<0.05). Conclusions T lymphocyte immunity disorder was found in TD children. The level of NSE increased, and the degree of elevation was related to the severity of the disease, but not to the clinical classification of the disease.

Retrospective analysis of 698 children with chronic spontaneous urticaria

LIN Xiao, ZHENG Bingjie, CHEN Li, CHEN Xilan, HUANG Ying, QIAN Qiufang

Journal of Clinical Pediatrics. 2022, 40(6): 461-464. doi:10.12372/jcp.2022.21e1750

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Objective To summarize the clinical characteristics of chronic spontaneous urticaria (CSU) in children. Methods The clinical data of children with CSU from January 2020 to June 2021 were retrospectively analyzed. Results A total of 698 children (356 boys and 342 girls) with CSU were enrolled, and the median age was 4.0 (2.0-7.0) years. The commonest age group was 1-7 years old (474 cases, 67.9%). The median course of disease was 6.0 (3.0-12.0) months. There were predisposing factors such as infection, food and vaccine in 119 children (17.1%) and there were 211 children (30.2%) with atopic diseases. Antinuclear antibody (ANA) test was performed in 79 patients, and 16 patients (20.3%) were positive. A total of 84 children with CSU were tested for 25-(OH) D, and the median level of 25-(OH) D was 55.1 nmol/L (26.3-80.6 nmol/L), compared with 70.2 nmol/L (55.9-93.5 nmol/L) in the control group, the difference between the two groups was statistically significant (P<0.01). Conclusion Chronic spontaneous urticaria in children has its own clinical characteristics. There is a certain proportion of positive antinuclear antibody and 25-hydroxyvitamin D deficiency, which deserves attention.

Lesch-Nyhan syndrome caused by HPRT1 gene variation: a case report

LI Fengchao, ZHANG Yinhong, LYU Tao, ZHU Baosheng, HAN Siqi, CAI Shiyan, LI Li

Journal of Clinical Pediatrics. 2022, 40(6): 465-468. doi:10.12372/jcp.2022.21e0944

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Lesch-Nyhan syndrome is a rare X-linked recessive genetic disease. Before the occurrence of self-injury, it could be misdiagnosed as cerebral palsy. The proband, male, 8 years and 7 months old, was admitted to the clinic due to over 8 years of developmental retardation and abnormal muscle tone. Multiple blood biochemical tests showed that uric acid was increased. Genetic analysis results confirmed that the patient had c.200 _ 201delTG variation of HPRT1 gene, which was rated as a suspected pathogenic variation by ACMG. Sanger sequencing confirmed that the variation was inherited from the mother and was an unreported new variation, thus the child was diagnosed with HPRT1 gene-associated Lesch-Nyhan syndrome. After oral allopurinol tablets and sodium bicarbonate tablets for 6 months, the level of uric acid decreased significantly, and there was no self-injury behavior. In patients with unexplained cerebral palsy, genetic examination should be performed as early as possible to help early diagnosis and genetic counseling.

Comments on KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease of Children

ZHANG Pei, GAO Chunlin, XIA Zhengkun

Journal of Clinical Pediatrics. 2022, 40(6): 469-474. doi:10.12372/jcp.2022.21e1610

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Hypertension is an important complication of chronic kidney disease (CKD) and substantial cause for the occurrence and progression of CKD. In 2021, the Kidney Disease: Improving Global Outcomes (KDIGO) published clinical practice guideline for the management of blood pressure in CKD, which is mainly applicable to CKD patients who have not undergone dialysis. The content includes methods, control objectives and treatment of blood pressure measurement in CKD children. This article interprets the relevant content of the blood pressure management of CKD children in the guideline.

The research progress of acute lymphoblastic leukemia with thromboembolism in children

LI Beiduo, SHAO Jingbo

Journal of Clinical Pediatrics. 2022, 40(6): 475-480. doi:10.12372/jcp.2022.22e0158

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Acute lymphoblastic leukemia (ALL) is the commonest hematological malignancy in children, and also the commonest malignant tumor associated with thrombosis. Thromboembolism and abnormal coagulation function in children are related to chemotherapy drugs, infection, deep vein catheterization and genetic factors, and can endanger life in severe cases. This article reviewed the pathogenesis, clinical characteristics, risk factors and treatment progress of thromboembolism in children with ALL, in order to improve the understanding of thromboembolism in children with ALL.

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