[Etiology composition and prognosis of pediatric chronic critical illness in a pediatric intensive care unit]. / å„¿ç«¥é‡ç—‡ç›‘æŠ¤å®¤å„¿ç«¥æ ¢æ€§å±é‡ç—‡çš„ç— å› ç»„æˆåŠé¢„åŽåˆ†æž.

OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.

[Effect of sequential sedation and analgesia in preventing delirium and withdrawal symptoms in children after ventilator weaning]. / åºè´¯é•‡ç—›é•‡é™å¯¹é¢„é˜²è¡Œæœºæ¢°é€šæ°”æ²»ç–—æ‚£å„¿æ’¤æœºåŽè°µå¦„åŠæ’¤è¯ååº”çš„æ•ˆæžœç ”ç©¶.

OBJECTIVES: To investigate the effect of sequential sedative and analgesic drugs in preventing delirium and withdrawal symptoms in children after ventilator weaning. METHODS: A retrospective analysis was performed on 61 children who were admitted and received mechanical ventilation support for ≥5 days in the Pediatric Intensive Care Unit of Dongguan Children's Hospital Affiliated to Guangdong Medical University from December 2019 to September 2021. The children were divided into a control group (30 children with no maintenance of analgesic and sedative drugs after ventilator weaning) and an observation group (31 children with sequential sedative and analgesic drugs maintained for 48 hours after ventilator weaning). The two groups were compared in terms of the Sophia Observation Withdrawal Symptoms Scale (SOS) score, the Pediatric Delirium Scale (PD) score, the Richmond Agitation-Sedation Scale (RASS) score, and the incidence rates of delirium or withdrawal symptoms at 24 and 72 hours after ventilator weaning. RESULTS: There was no significant difference in the incidence rate of delirium at 24 hours and 72 hours after ventilator weaning between the two groups (P>0.05). Compared with the control group, the observation group had significantly lower incidence rate of withdrawal symptoms and scores of SOS, PD, and RASS scales at 24 hours and 72 hours after ventilator weaning (P<0.01). CONCLUSIONS: Sequential sedation and analgesia after ventilator weaning can reduce the incidence of withdrawal symptoms within 72 hours after ventilator weaning, but it cannot reduce the incidence rate of delirium.

[Application of ultrasound-guided central venous catheterization at various sites in infants with shock]. / è¶ å£°å¼•å¯¼ä¸‹ä¸åŒéƒ¨ä½ä¸­å¿ƒé™è„‰ç½®ç®¡åœ¨å©´å¹¼å„¿ä¼‘å ‹ä¸­çš„åº”ç”¨åŠä¸´åºŠåˆ†æž.

OBJECTIVES: To study the clinical characteristics of ultrasound-guided central venous catheterization at various sites in infants with shock, and to explore how to quickly select the site for central venous puncture in infants with shock. METHODS: The medical data of 112 infants who were diagnosed with shock and underwent central venous catheterization in the Pediatric Intensive Care Unit, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from January 2016 to December 2020 were reviewed retrospectively. The patients were divided into an ultrasound group (n=70) and a body surface location group (n=42) according to whether the catheterization was carried out under ultrasound guidance. The application of ultrasound-guided catheterization at various sites in infants was summarized and analyzed, and the success rate of one-time puncture, overall success rate, catheterization time, and complications were compared between these sites. RESULTS: Compared with the body surface location group, the ultrasound group had a significantly higher success rate of one-time puncture, a significantly shorter catheterization time, and a significantly reduced incidence rate of complications in internal jugular vein and femoral vein catheterizations (P<0.05). In the ultrasound group, the proportion of internal jugular vein catheterization was the highest (51%, 36/70), followed by femoral vein catheterization (33%, 23/70), and subclavian vein catheterization (16%, 11/70). For the comparison between different puncture sites under ultrasound guidance, internal jugular vein catheterization showed the shortest time of a successful catheterization [5.5 (5.0, 6.5) minutes] (P<0.05). There was no significant difference in the incidence rate of complications among the different puncture sites groups (P>0.05). CONCLUSIONS: In infants with shock, ultrasound-guided internal jugular vein catheterization can be used as the preferred catheterization method for clinicians.

Case Report: A Novel Intronic Mutation in AIFM1 Associated With Fatal Encephalomyopathy and Mitochondrial Disease in Infant.

Background: The AIFM1 gene is located on chromosome Xq26.1 and encodes a flavoprotein essential for nuclear disassembly in apoptotic cells. Mutations in this gene can cause variable clinical phenotypes, but genotype-phenotype correlations of AIFM1-related disorder have not yet been fully determined because of the clinical scarcity. Case Presentation: We describe a 4-month-old infant with mitochondrial encephalopathy, carrying a novel intronic variant in AIFM1 (NM_004208.4: c.1164 + 5G > A). TA cloning of the complementary DNA (cDNA) and Sanger sequencing revealed the simultaneous presence of an aberrant transcript with exon 11 skipping (89 bp) and a normal transcript through analysis of mRNA extracted from the patient's fibroblasts, which is consistent with direct RNA sequencing results. Conclusion: We verified the pathogenic effect of the AIFM1 c.1164 + 5G > A splicing variant, which disturbed normal mRNA splicing. Our findings expand the mutation spectrum of AIFM1 and point out the necessity of intronic sequence analysis and the importance for integrative functional studies in the interpretation of sequence variants.

Effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury undergoing continuous renal replacement therapy. / ä¸åŒæ¶²ä½“è´Ÿè·çŠ¶æ€å¯¹æŒç»­è‚¾æ›¿ä»£æ²»ç–—è„“æ¯’ç—‡ç›¸å ³æ€¥æ€§è‚¾æŸä¼¤æ‚£å„¿é¢„åŽçš„å½±å“.

OBJECTIVES: To evaluate the effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). METHODS: A total of 121 children who underwent CRRT for sepsis-associated AKI from August 2018 to March 2021 were enrolled in the retrospective study. According to the fluid load from admission or disease progression to CRRT, they were divided into three groups: low fluid load (fluid load: <5%; n=35), high fluid load (fluid load: 5% - <10%; n=35), and fluid overload (fluid load: ≥10%; n=51). Baseline data and clinical biochemical data before CRRT were collected for comparison and analysis. The Kaplan-Meier survival curve analysis was used for comparison of 28-day survival between groups. The multivariate logistic regression model was used to identify the influencing factors for the prognosis of the children. RESULTS: The survival analysis showed that the fluid overload group had a significantly higher 28-day mortality rate than the low fluid load and high fluid load groups (P<0.05). The multivariate logistic regression analysis showed that an increase in fluid overload volume was a risk factor for increased 28-day mortality in the fluid overload group, while earlier initiation of CRRT was a protective factor (P<0.05). CONCLUSIONS: Fluid overload before CRRT may increase the mortality in children with sepsis-associated AKI, and CRRT should be performed for these children as early as possible.

A novel nonsense mutation of ZEB2 gene in a Chinese patient with Mowat-Wilson syndrome.

BACKGROUND: Mowat-Wilson syndrome (MWS) is a rare genetic disorder characterized by intellectual disability, distinctive facial features, and multiple anomalies caused by haploinsufficiency of the ZEB2 gene. We investigated the genetic causes of MWS in a 14-year-old girl who had characteristic features of MWS. METHODS: Clinical data and peripheral blood DNA samples were collected from the proband. Following extraction of genomic DNA, whole-exome sequencing was conducted to detect genetic variants. Bioinformatics analysis was carried out to predict the function of the mutant gene. RESULTS: Mutation analysis of the proband identified a novel nonsense mutation (c.250G > T, p.E84*) within exon 3 of the ZEB2 gene. This novel alteration resulted in a termination codon at amino acid position 84, which was predicted to encode a truncated protein. This variant was not present in unrelated healthy control samples that were obtained from the exome sequence databases ExAc browser (http://exac.broadinstitute.org/) and gnomAD browser (http://gnomad.broadinstitute.org/). It is a novel variant that was determined to be a deleterious mutation according to the variant interpretation guidelines of the ACMG. The results of our study suggest that the p.E84* mutation in the ZEB2 gene was probably the pathogenic mutation that caused MWS in the proband. CONCLUSIONS: This study reports the novel mutation in the proband will provide a basic foundation for further investigations to elucidate the ZEB2-related mechanisms of MWS.

A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family.

BACKGROUND: Due to inconsistencies with reported myofibrillar myopathy (MFM), including autosomal dominant inheritance, late onset and a slowly progressive course, the severe, recessively inherited form of CRYAB (alpha-B crystallin) gene-related infantile MFM has been suggested. Here, we report an infant in a Chinese family with fatal neonatal-onset hypertonic MFM with a novel CRYAB homozygous variant (c.3G > A (p.Met1?)). METHODS: Muscle biopsy indicated that muscle fibers showed a uniformly small diameter, cell atrophy, and visible focal muscle fiber degeneration and necrosis consistent with myogenic myopathy. We performed the whole exome sequencing of pathogenic genes and identified it as MFM. RESULTS: The proband presented with profound muscle stiffness, progressive respiratory distress and a concurrent abnormal increase in myocardial enzymogram, and the patient died in the 17th month of life. Muscle biopsy and electron microscopy results were consistent with ultramicroscopic myogenic damage and pathological changes. Mutation analysis of the proband identified a novel rare homozygous mutation in the initiation codon of the CRYAB gene, which was inherited from currently asymptomatic, heterozygous carrier parents, and his heterozygous biological brother is unaffected. CONCLUSIONS: This article reports one infant with CRYAB-related neonatal onset MFM with a novel homozygous variant in CRYAB. To our knowledge, this is the first reported case of infantile alpha-Bcrystallinopathy in the Chinese population.

A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family.

BACKGROUND: Genetic defects in the mitochondrial aminoacyl-tRNA synthetase are important causes of mitochondrial disorders. VARS2 is one of the genes encoding aminoacyl-tRNA synthetases. Recently, an increasing number of pathogenic variants of VARS2 have been reported. CASE PRESENTATION: We report the novel compound heterozygous pathogenic VARS2 mutations c.643 C > T (p. His215Tyr) and c.1354 A > G (p. Met452Val) in a female infant who presented with poor sucking at birth, poor activity, hyporeflexia, hypertonia, persistent pulmonary hypertension of newborn (PPHN), metabolic acidosis, severe lactic acidosis, expansion and hypertrophic cardiomyopathy. These heterozygous mutations were carried individually by the proband's parents and elder sister; the two mutations segregated in the family and were the cause of the disease in the proband.The c.643 C > T (p. His215Tyr) mutation was not described in the ExaC, GNomAD and 1000 Genomes Project databases, and the frequency of c.1354 A > G (p. Met452Val) was < 0.001 in these gene databases.The two mutated amino acids were located in a highly conserved region of the VARS2 protein that is important for its interaction with the cognate tRNA. The two missense mutations were predicted by online tools to be damaging and deleterious. CONCLUSIONS: Our report expands the spectrum of known pathogenicVARS2 variants associated with mitochondrial disorders in humans.VARS2 deficiency may cause a severe neonatal presentation with structural cardiac abnormalities.

Concurrent Genetic and Standard Screening for Hearing Impairment in 9317 Southern Chinese Newborns.

OBJECTIVE: The goal of this study was to investigate the use of concurrent genetic screening together with standard newborn hearing screening (NHS) in an effort to provide a scientific basis for the beneficial use of concurrent genetic hearing screening in newborns. Our aim was to improve the neonatal detection rate of hearing impairment and the potential for hearing loss, allowing for increased early intervention and potentially allowing for prevention of later onset hearing loss. This information could also be used to increase the effectiveness of genetic counseling regarding hearing impairment. METHODS: A total of 9317 neonates from Children's Hospital of Dongguan and Dongguan People's Hospital were included in this study between January 2015 and October 2015. Twenty hotspot hearing-associated mutations of four common deafness- susceptibility genes (GJB2, GJB3, SLC26A4, and MTRNR1) were analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The results of genetic screening and NHS were concurrently analyzed. RESULTS: A total of 129 infants (1.38%) exhibited hearing loss as determined by otoacoustic emission (OAE) testing. The genetic screening revealed that 348 (3.74%) individuals had at least one mutant allele. In total, 34 (0.36%) of the neonates carried a causal complement of mutations. The overwhelming majority of the genetically referred newborns passed the OAE hearing screening, but could be at risk for later hearing loss. CONCLUSION: This study furthers the understanding of the etiology of hearing loss and proves that it is beneficial to use genetic screening along with OAE screening of neonates to improve detection rates of at-risk infants. Our results show that this concurrent testing allows for better early identification of infants at risk for hearing loss, which may occur before speech and language development. Prevention of hearing loss can be achieved by avoiding the use of antibiotics containing amino glycosides in infants whose mutations make them extremely sensitive to these antibiotics. This information is also useful in genetic counseling, providing region-specific mutation information.

Large cohort screening of G6PD deficiency and the mutational spectrum in the Dongguan District in Southern China.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymatic disorder of the erythrocytes that affects 400 million people worldwide. We developed a PCR-reverse dot blot (RDB) assay to screen twenty genotypes of seventeen Chinese G6PD mutations and investigate the spectrum of G6PD deficiency mutations in Dongguan District, Guangdong Province, in southern China. METHOD: The PCR-RDB assay consists of multiplex PCR amplification of seven fragments in the G6PD target sequence of wild-type and mutant genomic DNA samples followed by hybridization to a test strip containing allele-specific oligonucleotide probes. A total of 16,464 individuals were analyzed by a combination of phenotypic screening and genotypic detection using the PCR-RDB assay and DNA sequence analysis. RESULTS: The PCR-RDB assay had a detection rate of 98.1%, which was validated by direct sequencing in a blind study with 100% concordance. The G6PD deficiency incidence rate in Dongguan District is 4.08%. Thirty-two genotypes from 469 individuals were found. The two most common variants were c.1376G>T and c.1388G>A, followed by c.95A>G, c.871G>A, c.392G>T, and c.1024 C>T. In addition, two rare mutations (c.703C>A and c.406C>T) were detected by DNA sequencing analysis. In our study, 65 cases harbored the C1311T/IVS polymorphism and 67 cases were homozygote. CONCLUSION: The PCR-RDB assay we established is a reliable and effective method for screening G6PD mutations in the Chinese population. Data on the spectrum of mutations in the Dongguan District is beneficial to the clinical diagnosis and prevention of G6PD deficiency.