[Establishment of a nomogram model for predicting the risk of early-onset sepsis in very preterm infants]. / 预测极早产儿早发型败血症发生风险的列线图模型的构建.

OBJECTIVES: To identify risk factors associated with early-onset sepsis (EOS) in very preterm infants and develop a nomogram model for predicting the risk of EOS. METHODS: A retrospective analysis was conducted on 344 very preterm infants delivered at the First Affiliated Hospital of Zhengzhou University and admitted to the Department of Neonatology between January 2020 and December 2022. These infants were randomly divided into a training set (241 infants) and a validating set (103 infants) in a 7:3 ratio. The training set was further divided into two groups based on the presence or absence of EOS: EOS (n=64) and non-EOS (n=177). Multivariate logistic regression analysis was performed to identify risk factors for EOS in the very preterm infants. The nomogram model was developed using R language and validated using the validating set. The discriminative ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis revealed that gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis were risk factors for EOS in very preterm infants (P<0.05). The area under the ROC curve for the training set was 0.925 (95%CI: 0.888-0.963), and that for the validating set was 0.796 (95%CI: 0.694-0.898), confirming the model's good discrimination. The Hosmer-Lemeshow goodness-of-fit test suggested that the model was well-fitting (P=0.621). The calibration curve analysis and decision curve analysis demonstrated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis are significantly associated with the development of EOS in very preterm infants.The nomogram model for predicting the risk of EOS in very preterm infants, constructed based on these factors, has high predictive efficacy and clinical applicability.

[Risk factors for recurrence after intravitreal anti-vascular endothelial growth factor injection for retinopathy of prematurity]. / çŽ»ç’ƒä½“è ”å† æ³¨å°„æŠ—è¡€ç®¡å† çš®ç”Ÿé•¿å› å­æ²»ç–—æ—©äº§å„¿è§†ç½‘è†œç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS: Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.

Walking alone milestone combined reading-frame rule improves early prediction of Duchenne muscular dystrophy.

Objective: To explore the potential of walking alone milestone combined reading-frame rule to improve the early diagnosis of Duchenne muscular dystrophy (DMD). Method: To retrospectively describe the genotype and phenotype of Duchenne and Becker muscular dystrophies (BMD) patients with deletions and duplicates in the dystrophin gene. The sensitivity and specificity of the reading frame rule were calculated and compared to that of the combined reading frame rule and walking alone milestone. The diagnostic coincidence rate of two different methods was analyzed. Result: One hundred sixty-nine male DMD/BMD patients were enrolled, including 17 cases of BMD and 152 cases of DMD. The diagnostic coincidence rate, diagnostic sensitivity, and specificity of the reading-frame rule for DMD/BMD were 85.2, 86.8, and 70.59%, respectively. The sensitivity and specificity of the reading frame principle combined with the walking alone milestone for DMD/BMD were 96.05 and 70.59%, respectively. The diagnostic coincidence rate increased to 93.49%, significantly different from that predicted by reading- frame rule (P < 0.05). Conclusion: The reading-frame rule combined with the walking alone milestone significantly improved the early diagnosis rate of DMD.

[A comparison of auditory brainstem responses and otoacoustic emissions in hearing screening of high-risk neonates].

OBJECTIVE: Otoacoustic emissions (OAE) and auditory brainstem responses (ABR) are tests widely used in neonatal hearing screening. This study aimed to investigate the differences and clinical value of distortion product otoacoustic emissions (DPOAE) and ABR in hearing screening of high-risk neonates admitted to a neonatal intensive care unit (NICU). METHODS: DPOAE and ABR were measured with the Smart-OAE analyser and the Smart-EP brain-stem electric response audiometry apparatus, respectively, in 600 high-risk neonates (1,200 ears). The testing results of DPOAE and ABR were compared. RESULTS: Of the 600 neonates (1,200 ears), the incidence of ABR abnormality (78.6%, 943/1,200) was remarkably higher than that of DPOAE abnormality (22.3%, 268/1,200). Two hundred and forty-one ears (20.8%) were negative and 252 (21%) were positive in both DPOAE and ABR tests. A total of 707 ears (58.9%) presented with a discordant result in DPOAE and ABR. The false positive and false negative rates of the DPOAE test were 6.0% (16/268) and 74.1% (691/932) respectively. CONCLUSIONS: In high-risk neonates the diagnostic value of DPOAE for identification of hearing loss, when used alone, is limited. The ABR test appears to be more reliable for hearing screening in high-risk neonates. It is suggested that hearing screening for high-risk neonates should be conducted with ABR first, followed by OAE after failure on ABR.

[Distribution and drug resistance of pathogens in lower respiratory tract infection in neonates].

OBJECTIVE: To investigate the epidemiological characteristics of pathogens and their antimicrobial susceptibility in neonates with lower respiratory tract infection (LRTI). METHODS: Sputum specimens for bacterial cultures were collected from 1173 neonates with LRTL between January 2005 and December 2006. Antibiotic susceptibility tests were performed after bacteria had been identified. RESULTS: A total of 707 pathogenic strains (60.3%) were identified, including 521 (73.7%) Gram-negative bacilli, 106 (15.0%) Gram-positive bacilli, and 80 (11.3%) fungi. E Coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and enteric bacilli were common cultured Gram-negative bacilli. Most strains of Gram-negative bacilli were susceptible to meropenem, piperacillin/tazobactam, the fourth generation cephalosporin, cebfoperazone/sulbactam and amikacin. Staphylococcus aureus and coagula-negative staphylococci (CNS) were common in the cultured Gram-positive bacilli. Staphylococcus aureus and CNS were susceptible to vancomycin, ciprofloxacin and piperacillin/tazobactam but were resistant to Penicillin. CONCLUSIONS: Gram-negative bacilli predominate the pathogens of LRTI in neonates. E Coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are major pathogens.

[Neuroprotective effect of hypothermia on hypoxic-ischemic brain injury in mice].

OBJECTIVE: The study was to investigate the effect of different temperatures during hypoxia on brain injury in mice of different ages. METHODS: Newborn C57/BL6 mice at 7 days or 21 days of life were subjected to left carotid artery ligation followed by exposure with 10% oxygen. The mice were kept in a incubator with a predetermined, constant temperature, either 34 degrees centigrade (Hypothermia group) or 36 degrees centigrade (Normothermia group). Brain injury was evaluated 7 days after hypoxia-ischemia (HI). Active caspase-3 and apoptosis-inducing factor (AIF) expressions in the brain tissue were detected by immunohistochemistry and Western Blot was used to evaluate the phosphor-Akt (P-Akt) expression in the brain tissue at 24 hrs post-HI. RESULTS: Brain injuries, including the cortex, hippocampus, striatum and thalamus injuries, occurred in the Normothermia group at 7 days post-HI. The brain cortex showed cystic cavitation in the postnatal day (P)7 pups mice and laminar infarct of the brain cortex was observed in P21 mice. In the Hypothermia group, the P7 mice did not present with laminar infarct of the cortex and had lower scores of neuropathological lesions in cortex, hippocampus, striatum and thalamus than P7 mice from the Normothermia group (P < 0.01); the cortex injuries were significantly relieved but the injuries of hippocampus, striatum and thalamus in P21 mice were similar to those from the Normothermia group. Active caspase-3 (7.0 +/- 5.6) and AIF positive cells (3.7 +/- 6.2) in the cortex of P7 mice from the Hypothermia group were significantly lower than those of the Normothermia group (51.5 +/- 23.2 and 31.8 +/- 22.4) at 24 hrs post-HI (P < 0.01). Wetstern Blot showed the P-Akt expression was obviously decreased in the ipsilateral hemisphere to the occlusion compared with that of the contralateral hemisphere after HI in the Normothermia group (P < 0.05), while in the Hypothermia group the P-Akt expression was not significantly different between the two hemispheres. CONCLUSIONS: Hypothermia has protective effects against HI insults. The protection was more pronounced for the immature brain than the mature brain.

[Expression of p53 in neonatal mice following hypoxia-ischemia and effects of its inhibitor on neonatal brain injury].

OBJECTIVE: p53-induced apoptosis is crucial in the development of hypoxic-ischemia (HI) brain damage and neurodegenerative disorders. Some experimental research has shown that a synthetic inhibitor of p53 can protect neurons against apoptosis. This study aimed to explore the expression of p53 in neonatal mice following HI brain damage and the effect of p53 inhibitor (pifithrin-alpha, PFT-alpha) on brain damage. METHODS: HI was induced in 9-day-old mice pups by ligation of left carotid artery and 10% oxygen exposure for 55 minutes. The pups were sacrificed and the brains were taken out at 3, 8, 24, and 72 hrs post-HI. The brains were sectioned and stained with antibody against p53 and microtubule-associated protein 2 (MAP-2). PFT-alpha was injected intraperitoneally: in experiment 1, immediately after HI with different dosages (1, 2 and 8 mg/kg); in experiment 2, 2 mg/kg at different HI times (1 hr before HI, and immediately and 1 hr after HI). Control animals without HI received injections of 0.5% dimethyl sulfoxide. Brain damage was evaluated by gross morphology scoring at 72 hrs after HI. RESULTS: The number of p53 positive cells in the cortex, hippocampus and striatum of the ipsilateral hemisphere increased significantly and peaked at 3-8 hrs post-HI when compared with those of contralateral hemisphere as well as normal controls. The positive cells distributed mainly in the MAP-2 negative area. Both different dosages and different injection time PFT-alpha treatment did not reduce the extent of brain damage. CONCLUSIONS: The immunoactivity of p53 increased significantly as early as 3 hrs post-HI. The distribution area of p53 expression was consistent with that of brain damage. The p53 inhibitor PFT-alpha has no protective effects against HI brain damage in neonatal mice.

Application of NT-proBNP in ventilator weaning for preterm infants with RDS.

OBJECTIVE: To evaluate the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels along with spontaneous breathing trial (SBT) in the prediction of ventilator weaning outcome among respiratory distress syndrome (RDS) preterm infants ready to wean. METHODS: NT-proBNP along with plasma albumin concentration, serum sodium, serum potassium, and hematocrit were measured immediately before SBT in preterm infants (≤32 weeks) mechanically ventilated due to RDS. Extubation was considered successful if infants remained extubated >48 hr. Either SBT failure or extubation failure was considered weaning failure. RESULTS: Sixty-three of 88 infants passed the SBT and were subsequently extubated. Of these, two (3.2%) cases rapidly developed laryngeal dyspnea imposing reintubation (excluded from analysis). Of the remaining 61 infants, 45 (73.8%) cases had successful extubation, and 16 (26.2%) cases were reintubated. Infants who failed weaning had lower gestational age, birth weight, and plasma albumin concentrations, higher NT-proBNP, doses of surfactant, occurrence of ventilator-associated pneumonia, and occurrence of pulmonary arterial hypertension than those who did not. NT-proBNP was the only independent factor that could predict weaning failure (OR = 1.872; P = 0.044). The ROC-AUC for NT-proBNP to predict weaning failure was 0.977 (95% CI 0.918-0.997; P < 0.001). The cut-off of NT-proBNP level 18,500 pg/ml to predict weaning failure had a positive likelihood ratio of 25.180. The addition of NT-proBNP to SBT in prediction of weaning failure significantly improved the net reclassification improvement (NRI = 0.224; P = 0.034). CONCLUSION: NT-proBNP is an independent factor that could predict weaning failure. Measurement of NT-proBNP prior to SBT may be helpful in promoting successful ventilator weaning along with SBT.

[Cytochrome C release and apoptosis in neonatal rat cerebral hypoxia-ischemia].

OBJECTIVE: To study the relation of cytochrome C release from mitochondria to cytosol and neuronal apoptosis after cerebral hypoxia-ischemia (HI) in neonatal rats. METHODS: Hypoxia-ischemia was induced in 7-day-old rat pups by ligation of left carotid artery and 7.7% oxygen was inhaled for 55 min. The pups were sacrificed and the brains were taken out at different recovery time. Some of the brains were homogenized and cellular fraction of mitochondria and cytosol was isolated with different speed centrifugation. The cellular fraction was used for Western blotting. Some of the brains were sectioned and stained with antibody against cytochrome C and TUNEL as well as double labeling with different combinations. RESULTS: Western blots showed that cytochrome C in mitochondria was not reduced significantly at 1 h, but reduced markedly at 14 h in ipsilateral hemisphere post-HI. However, the immunoreactivity of cytochrome C in cytosol was increased markedly at 1 h post-HI and reached peak at 14 h post-HI. The number of cytochrome C positive cells in the cortex was increased significantly at 1 h (8.4 +/- 1.8/visual field) compared to normal control (1.5 +/- 0.8/visual field) (P < 0.01) and reached peak at 14 h (29.0 +/- 5.2/visual field) post-HI. The number of TUNEL positive cells increased significantly at 1 h post-HI (14 +/- 3/visual field) compared to normal control (1.5 +/- 0.8/visual field) (P < 0.01) and reached peak at 24 h (286 +/- 86/visual field). The double labeling of cytochrome C and active caspase-3 showed that they colocalized well at 3 h after HI. Furthermore, the positive cells showed nuclei condensation. There were more active caspase-3 positive cells at late recovery (24 h and on) after HI. The double labeling of cytochrome C and TUNEL showed only part of Positive cells colocalized. The cells with cytochrome C strong staining showed TUNEL negative or weakly positive. The cells with TUNEL strong staining showed weakly cytochrome C staining. CONCLUSION: Cytochrome C release is one of the early biochemical changes of neuronal apoptosis after hypoxia-ischemia in neonatal rat brain.

[Neuroprotective effect and mechanisms of hypothermia in neonatal rat cerebral hypoxic-ischemic damages].

OBJECTIVE: Recent studies suggest that hypothermia may be a potential treatment for perinatal hypoxic-ischemic (HI) brain damage. But the mechanisms of this effect are not well known. In the present study, the protective effect of systemic hypothermia as well as effect on apoptosis and associated biochemical events were investigated on neonatal rats with HI brain damage. METHODS: Seven-day-old Wistar rats were subjected to left carotid artery ligation and hypoxia was persisted for 60 min. Immediately at the end of hypoxia, the animals were maintained either at 36 degrees C or 30 degrees C for 10 h at random. Caspase-2, 3 activity in brain homogenate was detected with Western blotting at 24 h post-HI (n = 8 for each group). Immunoactivity of microtubule-associated protein-2 (MAP-2), active caspase-3, apoptosis inducing factor (AIF) and oligonucleotide hairpin probe staining were detected at 72 h post-HI. The infarct volume, neuronal loss in CA(1) sector of hippocampus as well as brain injury scoring were calculated according to MAP-2 staining and hematoxylin and eosin staining. RESULTS: Caspase-2, 3 activities were much higher in the normothermia group [(27.7 +/- 14.7), (94.9 +/- 53.1) pmol/(min.mg protein)] at 24 h post-HI than those of hypothermia [(7.9 +/- 3.4), (21.1 +/- 18.7) pmol/(min.mg protein)] and normal control groups [(7.6 +/- 0.7), (12.9 +/- 0.5) pmol/(min x mg protein)] (P < 0.01). The activities were not significantly different between hypothermia group and normal control group. Western blotting showed that caspase-3 activation process was blocked by hypothermia. The number of active caspase-3 and AIF positive cells in the cortex of ipsilateral hemisphere was much higher in the normothermia group (median: 148.5; 22/field) than that of hypothermia group (median: 48.5; 9/field) (P < 0.05). The number of apoptotic cells as judged by oligonucleotide hairpin probe labeling was much higher in normothermia group (median: 144/field) than that of hypothermia group (median: 133/field) (P < 0.05). The brain injury scoring, infarct volume and neuronal loss in CA(1) area of hippocampus were much less in the hypothermia group [10.4 +/- 2.9; 40.5 +/- 34.8)mm(3); 25.7 +/- 11.5] than that of normothermia group [14.2 +/- 3.5; (73.9 +/- 22.4) mm(3); 37.4 +/- 10.6, P < 0.05]. CONCLUSIONS: Systemic hypothermia for 10 h after hypoxia-ischemia seemed to be effective in reducing brain damage and the mechanism is associated with alteration of apoptotic pathway.