Translational pediatrics最新文献

Background: Preoperative fear and anxiety are prevalent in children undergoing surgery. The combination of esketamine and dexmedetomidine has been proposed as a promising premedication for enhancing preoperative sedation and analgesia. This study compared the premedication efficacy of intranasal esketamine alone and esketamine-dexmedetomidine combination in pediatric patients undergoing strabismus surgery.

Methods: One hundred and eighty preschool children aged 2-6 years scheduled for strabismus surgery were enrolled and randomly assigned to one of the three groups: intranasal premedication with esketamine 2 mg/kg (Group K), esketamine 1 mg/kg and dexmedetomidine 1 µg/kg (Group KD1), or esketamine 0.5 mg/kg and dexmedetomidine 2 µg/kg (Group KD2). The primary outcome was the level of sedation following the intervention, as measured by the modified Yale preoperative anxiety scale (mYPAS) and sedation scale (SS). Secondary outcomes included onset time of sedation, the successful rate of peripheral intravenous cannulation, parental separation anxiety scale (PSAS), mask acceptance scale (MAS), wake-up time, duration of stay in the post-anesthesia care unit (PACU), and premedication-related adverse effects.

Results: After premedication, the mYPAS score gradually decreased in the three groups, with lower values in Group K than in Group KD1 and Group KD2 patients in 1, 5, and 10 min. SS in Group KD1 and Group KD2 steadily increased until 40 min after premedication, while SS in Group K increased in the first 5 min after premedication and maintained consistent levels during the remaining time. Sedation onset was substantially faster in Group K patients (11.4±7.8 min) than Group KD1 (18.1±7.5 min, P=0.006) and Group KD2 (18.4±6.8 min, P<0.001). PSAS, separation status, the successful rate of peripheral intravenous cannulation, and MAS were comparable among groups. There was no significant difference in terms of emergence time or duration of stay in the PACU among groups. More gastrointestinal events were observed in Group K (P<0.001).

Conclusions: Intranasal premedication with 2 mg/kg esketamine produced a more rapid onset of sedation accompanied by more gastrointestinal reactions compared with a combination of esketamine and dexmedetomidine.

Trial registration: ClinicalTrials.gov identifier: NCT04757675.

Open heart surgery requires a proper understanding of the endocardial surface of the heart and vascular structures. While modern four-dimensional (4D) imaging enables excellent dynamic visualization of the blood pool, endocardial surface anatomy has not routinely been assessed. 4D image data were post-processed using commercially available virtual reality (VR) software. Using thresholding, the blood pool was segmented dynamically across the imaging volume. The segmented blood pool was further edited for correction of errors due to artifacts or inhomogeneous signal intensity. Then, a surface shell of an even thickness was added to the edited blood pool. When the cardiac valve leaflets and chordae were visualized, they were segmented separately using a different range of signal intensity for thresholding. Using an interactive cutting plane, the endocardial surface anatomy was reviewed from multiple perspectives by interactively applying a cutting plane, rotating and moving the model. In conclusions, dynamic three-dimensional (3D) endocardial surface imaging is feasible and provides realistic simulated views of the intraoperative scenes at open heart surgery. As VR is based on the use of all fingers of both hands, the efficiency and speed of postprocessing are markedly enhanced. Although it is limited, visualization of the cardiac valve leaflets and chordae is also possible.

Background: Infantile colic is common in pediatric patients, yet few probiotics effectively treat this condition. The efficacy of Lactobacillus rhamnosus GG (LGG) in managing colic remains unclear. In this meta-analysis, we aimed to evaluate the effectiveness of LGG in treating infantile colic.

Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases from their inception until January 2024. We used Version 2 of the Cochrane tool (ROB 2) to assess the risk of bias in randomized trials. Meta-analysis was conducted using RevMan 5.3 software. The inclusion criteria followed the PICOS framework: (I) participants: infants with colic; (II) intervention: LGG administration at any dose; (III) control: placebo or no treatment; (IV) outcomes: primary outcome was crying or fussing time (minutes/day) at the end of the intervention, secondary outcomes included fecal calprotectin content (µg/g) and adverse events; (V) Study type: randomized controlled trials.

Results: Four studies involving 168 infants with colic were included. The meta-analysis indicated that LGG significantly reduced daily crying time [mean difference (MD) =-32.59 minutes; 95% confidence interval (CI): -43.23 to -21.96; P<0.001] and fecal calprotectin content (MD =-103.28 µg/g; 95% CI: -149.30 to -7.26; P<0.001). Only one study reported adverse events.

Conclusions: LGG is effective in treating infantile colic. Further studies are needed to examine the effects of different doses, administration schedules, and durations of LGG treatment in infants with varying feeding methods.

Background: Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development.

Methods: We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP).

Results: The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these effects. Mice with dysbiosis displayed cognitive deficits in the MWM test. SCFAs levels decreased during dysbiosis, and increased upon microbiota recovery.

Conclusions: Neonatal dysbiosis affects the microbiota-gut-brain axis, impairing cognitive function and nervous system development. Reduced SCFAs may contribute significantly to these alterations.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition causing brain injury in newborns with unclear pathogenesis. Cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and NOD-like receptor protein 3 (NLRP3) mediated pyroptosis are thought to be involved in the pathological process of HIE, but whether these two mechanisms act independently is still unknown. Therefore, we aim to clarify whether there is any interaction between these two pathways and thus synergistically affects the progression of HIE.

Methods: The HIE model of neonatal rats was established using the Rice-Vannucci method. The potential therapeutic effect of RU.521 targeting cGAS on HIE was explored through rescue experiment. Twenty-four hours after modeling was selected as observation point, sham + vehicle group, HIE + vehicle group and HIE + RU.521 group were established. A complete medium of BV2 cells was adjusted to a glucose-free medium, and the oxygen-glucose deprivation model was established after continuous hypoxia for 4 hours and reoxygenation for 12 to 24 hours. 2,3,5-triphenyl tetrazolium chloride staining was employed to detect ischemic cerebral infarction in rat brain tissue, and hematoxylin and eosin staining was used to observe tissue injury. Immunofluorescence was applied to monitor the expression of cGAS. Real-time quantitative polymerase chain reaction and western blot were utilized to detect the expression of messenger RNA and protein.

Results: cGAS expression was increased in brain tissues of neonatal rats with HIE, and mainly localized in microglia. RU.521 administration reduced infarct size and pathological damage in rat HIE. Moreover, blocking cGAS with RU.521 significantly reduced inflammatory conditions in the brain by down-regulating STING expression, decreasing NLRP3 inflammasome activation and reducing microglial pyroptosis both in vivo and in vitro. Besides, RU.521 promoted the switching of BV2 cells towards the M2 phenotype.

Conclusions: This study revealed a link between the cGAS/STING pathway and the NLRP3/GSDMD/pyroptosis pathway in neonatal HIE. Furthermore, the small molecule compound RU.521 can negatively regulate cGAS/STING/NLRP3/pyroptosis axis and promote M2 polarization in microglia, which provides a potential therapeutic strategy for the treatment of neuroinflammation in HIE.

Background and objective: Biliary atresia (BA) is characterized by biliary inflammation and obstruction. In the later phase, liver fibrosis occurs. Although the etiology of BA is believed to be multi-factorial, genetic predisposition has been proposed to play a critical role in the pathogenesis. This review aimed to provide an updated summary of the genes that have been reported to be involved in BA-associated liver fibrosis.

Methods: The review was conducted via evaluation of MalaCards (BA disease: MalaCards-research articles, drugs, genes, clinical trials) which is a universally applied website including various human disease database. The database of genes that are involved in liver fibrosis were studied.

Key content and findings: Thirty-one genes that are associated with BA according to the disease relevance score were reviewed after further evaluations. Eleven genes (GPT, NR1H4, TGF-B1, MMP7, CCN2, TIMP1, SPP1, ADD3, KRT7, ADD3-AS1, SOX9) that are specific and with a potential association with liver fibrosis were selected for detailed description. Increased expression of GPT, TGF-B1, MMP7, CCN2, TIMP1, SPP1, ADD3, KRT7 and ADD3-AS1 maybe associated with the development of liver fibrosis in BA patients, while the expression of NR1H4 and SOX9 are more likely to suppress liver fibrosis.

Conclusions: Current scientific evidence using gene database has revealed a close association between genetic anomalies and the pathogenesis of liver fibrosis in BA. With a better understanding of these anomalies, therapy targeting these related genes may be a new therapeutic approach to alleviate liver fibrosis in BA.

Background: Understanding of multisystem inflammatory syndrome in children (MIS-C) continues to evolve with extensive evaluations, including echocardiograms, obtained in emergency departments (EDs) to assist with clinical decision making and bed allocation. We assessed the utility of obtaining echocardiograms in the ED to assist in determining bed placement for this patient population.

Methods: This 2-year retrospective single-center study of patients 0-21 years old without underlying cardiac disease hospitalized for MIS-C focused on individuals whose initial evaluation occurred in the institution's ED and whose echocardiogram was obtained either in the ED or within 24 hours of admission. Patients were placed in two cohorts-those remaining in their unit of admission without transfer (cohort WoT) and those transferred (cohort T) from their initial unit to one with a differing level of care within 24 hours. Pearson chi-square test assessed the relationship between echocardiogram status and appropriate bed placement, defined as no transfer within 24 hours.

Results: Of the 60 patients who met study criteria, no significant difference was detected in rates of transfer between patients whose echocardiograms were obtained in the ED versus those obtained within 24 hours of admission (odds ratio =2.08; 95% confidence interval: 0.58, 7.95; P=0.28).

Conclusions: Cardiac involvement is a known complication of MIS-C; however, our study yields no evidence in favor of obtaining echocardiograms in the ED to ensure appropriate bed placement. While this modality remains integral in evaluation and management, it does not appear to be requisite as part of an emergent workup prior to admission.

[This corrects the article DOI: 10.21037/tp-23-391.].