Objective:To analyze the clinical efficacy and safety of carglumic acid in the treatment of neonatal hyperammonemia caused by organic acidemia.Methods:A case summary was made.Six cases of neonatal hyperammonemia caused by organic acidemia treated at the Neonatal Intensive Care Unit of Henan Children′s Hospital from March to September in 2024 were included.They received comprehensive ammonia-lowering treatment in combination with oral carglumic acid dispersible tablets.The clinical data of the children were collected and analyzed retrospectively.Changes in blood ammonia levels, blood gas parameters, and complete blood count before and after treatment with carglumic acid were analyzed using the Wilcoxon test.The incidence of adverse reactions and clinical regression during the treatment with carglumic acid was observed.Results:There were 2 females and 4 males in the 6 patients included.Four children suffered from isolated methylmalonic acidemia caused by MUT gene mutations, and the other 2 had propionic acidemia.The clinical manifestations were poor breastfeeding in 6 cases, vomiting in 2 cases, poor response in 6 cases, weight loss in 6 cases, and convulsions in 3 cases.Acute metabolic decompensation abnormalities were presented in all children, such as metabolic acidosis, hyperammonemia, leukopenia and thrombocytopenia.The first dose of carglumic acid was 62-255 mg/kg, the second dose was 75-172 mg/kg.The blood ammonia level decreased from 411.7 (339.7, 623.8) μmol/L before treatment to 108.1 (35.5, 229.1) μmol/L after 48 hours of treatment, showing a statistically significant reduction ( Z=2.20, P<0.05).Three cases with a blood ammonia level higher than 400 μmol/L, it was effectively reduced after treatment with carglumic acid.Two cases did not undergo hemodialysis or peritoneal dialysis.One case underwent hemodialysis but died after withdrawing the treatment.After administration of carglumic acid, metabolic acidosis was corrected in all children, and 2 patients ultimately died after discontinuing the treatment.No causal relationship was identified between adverse events and carglumic acid treatment.The examinations at discharge and during the follow-up period (2-7 months) showed that most laboratory abnormalities (including leukopenia, anemia, thrombocytopenia, hyperlactatemia, hyponatremia, hyperkalemia, elevated myocardial enzymes, and hyperbilirubinemia) returned to normal. Conclusions:Carglumic acid can effectively reduce neonatal hyperammonemia caused by organic academia, improve metabolic disorders, and reduce the need for blood purification or peritoneal dialysis, with good safety.

Objective:To analyze the clinical efficacy and safety of carglumic acid in the treatment of neonatal hyperammonemia caused by organic acidemia.Methods:A case summary was made.Six cases of neonatal hyperammonemia caused by organic acidemia treated at the Neonatal Intensive Care Unit of Henan Children′s Hospital from March to September in 2024 were included.They received comprehensive ammonia-lowering treatment in combination with oral carglumic acid dispersible tablets.The clinical data of the children were collected and analyzed retrospectively.Changes in blood ammonia levels, blood gas parameters, and complete blood count before and after treatment with carglumic acid were analyzed using the Wilcoxon test.The incidence of adverse reactions and clinical regression during the treatment with carglumic acid was observed.Results:There were 2 females and 4 males in the 6 patients included.Four children suffered from isolated methylmalonic acidemia caused by MUT gene mutations, and the other 2 had propionic acidemia.The clinical manifestations were poor breastfeeding in 6 cases, vomiting in 2 cases, poor response in 6 cases, weight loss in 6 cases, and convulsions in 3 cases.Acute metabolic decompensation abnormalities were presented in all children, such as metabolic acidosis, hyperammonemia, leukopenia and thrombocytopenia.The first dose of carglumic acid was 62-255 mg/kg, the second dose was 75-172 mg/kg.The blood ammonia level decreased from 411.7 (339.7, 623.8) μmol/L before treatment to 108.1 (35.5, 229.1) μmol/L after 48 hours of treatment, showing a statistically significant reduction ( Z=2.20, P<0.05).Three cases with a blood ammonia level higher than 400 μmol/L, it was effectively reduced after treatment with carglumic acid.Two cases did not undergo hemodialysis or peritoneal dialysis.One case underwent hemodialysis but died after withdrawing the treatment.After administration of carglumic acid, metabolic acidosis was corrected in all children, and 2 patients ultimately died after discontinuing the treatment.No causal relationship was identified between adverse events and carglumic acid treatment.The examinations at discharge and during the follow-up period (2-7 months) showed that most laboratory abnormalities (including leukopenia, anemia, thrombocytopenia, hyperlactatemia, hyponatremia, hyperkalemia, elevated myocardial enzymes, and hyperbilirubinemia) returned to normal. Conclusions:Carglumic acid can effectively reduce neonatal hyperammonemia caused by organic academia, improve metabolic disorders, and reduce the need for blood purification or peritoneal dialysis, with good safety.

Objective:To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks.Methods:The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children′s Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria.Results:The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria ( Z=0.02, P=0.984). Conclusion:The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

Background::Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods::This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Na?ve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.Results::The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. Conclusions::Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Objective:To compare the results of clinical diagnosis and severity grading in preterm infants with bronchopulmonary dysplasia (BPD) using three different diagnostic criteria and the consistency of two new diagnostic criteria.Methods:From January to December, 2020, infants with gestational age <32 w admitted to neonatal intensive care unit of our hospital were retrospectively enrolled in this cohort study. The patients were diagnosed and graded according to the 2001, 2018 and 2019 criteria of BPD. Chi-square test was used to compare the differences of BPD diagnostic rate and mortality rate using three criteria and Kappa coefficient test was used to compare the consistency between the two new criteria of 2018 NICHD and 2019 NRN.Results:A total of 231 preterm infants were enrolled, including 130 males (56.3%) and 101 females. 9 patients were dead. According to 2018 NICHD criteria, 97 cases (42.0%) were diagnosed with BPD, including 16 gradeⅠ, 44 grade Ⅱ, 31 grade Ⅲ and 6 grade ⅢA. The remaining 134 cases were not BPD (58.0%). No significant differences existed ( P>0.05) among the diagnostic rates of 2001 criteria (112/231, 48.5%), 2018 criteria (97/231, 42.0%) and 2019 criteria (91/231, 39.4%). For grade Ⅲ BPD, the diagnostic rate of 2001 criteria was significantly higher than the 2018 criteria (including grade Ⅲ and grade ⅢA, 16.0%) and 2019 criteria (6.5%) and the diagnostic rate of 2018 criteria was also significantly higher than 2019 criteria ( P<0.05). No significant differences existed in the overall mortality rate of BPD among three criteria ( P>0.05), however, the case mortality rate of grade Ⅲ BPD of 2001 criteria (3.9%) was significantly lower than 2018 criteria (24.3%) and 2019 criteria (20.0%) ( P<0.05). The 2018 and 2019 criteria were highly consistent in the overall diagnostic rate of BPD (Kappa value = 0.946), the positive consistency rate was 93.8% (95% CI 85.5%~97.5%) and the negative consistency rate was 100.0% (95% CI 96.5%~100.0%). But the consistency of severity grading for BPD was weak (Kappa value = 0.597) between the two criteria. Conclusions:The 2001 NICHD BPD criteria is no longer valid because it tends to overdiagnose severe BPD, thus underestimate the case mortality. The 2018 NICHD criteria is comprehensive and detailed and the 2019 NRN criteria is simple and practical. The two new criteria are highly consistent in the overall diagnosis of BPD, but the consistency of severity grading is weak.

Objective:To investigate the possible causative factors of central core disease(CCD), the clinical features of a neonatal case with CCD and five patients in the pedigree line were analyzed for RYR1 gene variant.Methods:Medical and family history inquiries and detailed clinical examinations were performed in the proband . High-throughput sequencing technology was applied to analyze the gene variant of the proband , and Sanger sequencing was applied to verify the pedigree distribution of the variant.Results:The whole exon sequencing results showed that the proband has a missense variant of c. 14591 A>C (p.Tyr4864Ser) in the RYR1 gene which was unreported previously; Sanger sequencing results showed that the father, grandfather, the eldest aunt and second aunt of the proband all carried the same variant. The c. 14591 A>C variant of RYR1 gene was predicted to be a likely pathogenic (PM2+ PM5+ PP1+ PP3) according to the American College of Medical Genetics and Genomics standards and guidelines. Conclusions:The RYR1 gene c. 14591 A >C (p.Tyr4864Ser) variant may be the genetic cause of the pedigree and genetic testing helps to clarify the diagnosis. Identification of this variant has enriched the variant spectrum of the RYR1 gene.

Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis often presents with a mental disorder as the first symptom, which is more common in middle-aged and older men. However, adolescent females suffer from CASPR2 antibody-related encephalitis, while schizophrenia is rarely reported. This article reports a case of CASPR2 antibody-related encephalitis, ovarian cyst, and schizophrenia in a young female. Due to the complexity of clinical symptoms, the particularity of the course of the disease, and the richness of the diagnosis and treatment process, through the detection, diagnosis, and treatment of this disease, The process description of the case is expected to increase doctors′ experience in diagnosis and treatment of such comorbidities, and to increase the attention to adolescents suffering from CASPR2 antibody-related encephalitis.

Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis often presents with a mental disorder as the first symptom, which is more common in middle-aged and older men. However, adolescent females suffer from CASPR2 antibody-related encephalitis, while schizophrenia is rarely reported. This article reports a case of CASPR2 antibody-related encephalitis, ovarian cyst, and schizophrenia in a young female. Due to the complexity of clinical symptoms, the particularity of the course of the disease, and the richness of the diagnosis and treatment process, through the detection, diagnosis, and treatment of this disease, The process description of the case is expected to increase doctors′ experience in diagnosis and treatment of such comorbidities, and to increase the attention to adolescents suffering from CASPR2 antibody-related encephalitis.

Objective:To investigate the clinical characteristics of severe purulent meningitis in neonates.Methods:A retrospective study was conducted.One hundred and sixty-nine newborns with purulent meningitis diagnosed at the neonatal center of our hospital from January 2014 to December 2017 were selected.According to the severity of the disease, the cases were divided into severe group and mild group.The clinical data of all children were collected and analyzed, and the characteristics of severe purulent meningitis were summarized.Results:Among 169 cases of neonatal purulent meningitis, 43 cases(25.4%)were in severe group, and 126 cases(74.6%)were in mild group.Twenty-one cases were cured in severe group, 10 cases had complications, 9 cases abandoned and 3 cases died.Ninty-eight cases were cured in the mild group, 17 cases had complications and 11 cases were discharged automatically and 2 cases died.There were significant differences in respiratory failure requiring mechanical ventilation, convulsion, consciousness disorder, blood C-reactive protein, positive cerebrospinal fluid culture, severe abnormality of amplitude integrated electroencephalogram, cerebrospinal fluid/serum glucose ratio, the incidence rate of complications and mortality between two groups( P<0.05). Conclusion:Severe purulent meningitis not only has the manifestation of mild meningitis, but also often has the clinical characteristics of brain parenchymal damage and/or brain failure with more complications and higher mortality.

OBJECTIVE: To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results. RESULTS: The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found to harbor pathogenic variants of the AVPR2/AQP2 gene, which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC, two missense mutations of c.541C>T and c.419C>A, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 and 7 were a pair of twins. Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene, which was known to be pathogenic. CONCLUSION AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.
Aquaporin 2/genetics* ; Child ; Diabetes Insipidus, Nephrogenic/genetics* ; Diabetes Mellitus ; Humans ; Infant, Newborn ; Male ; Molecular Biology ; Mutation ; Pedigree ; Receptors, Vasopressin/genetics*