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The prediction of refractory Mycoplasma pneumoniae pneumonia (RMPP) remains a clinically significant challenge. This study aimed to develop an early predictive model utilizing artificial intelligence (AI)-derived quantitative assessment of lung lesion extent on initial computed tomography (CT) scans and clinical indicators for RMPP in pediatric inpatients. A retrospective cohort study was conducted on patients with M. pneumoniae pneumonia (MP) admitted to the Children's Hospital of Nanjing Medical University, China from January 2019 to December 2020. An early prediction model was developed by stratifying the patients with Mycoplasma pneumoniae pneumonia (MPP) into two cohorts according to the presence or absence of refractory pneumonia. A retrospective cohort of 126 children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) was utilized as a training set, with 85 cases classified as RMPP. Subsequently, a prospective cohort comprising 54 MPP cases, including 37 instances of RMPP, was assembled as a validation set to assess the performance of the predictive model for RMPP from January to December 2021. We defined a constant Φ which can combine the volume and CT value of pulmonary lesions and be further used to calculate the logarithm of Φ to the base of 2 (Log2Φ). A clinical-imaging prediction model was then constructed utilizing Log2Φ and clinical characteristics. Performance was evaluated by the area under the receiver operating characteristic curve (AUC). The clinical model demonstrated AUC values of 0.810 and 0.782, while the imaging model showed AUC values of 0.764 and 0.769 in the training and test sets, respectively. The clinical-imaging model, incorporating Log2Φ, temperature(T), aspartate aminotransferase (AST), preadmission fever duration (PFD), and preadmission macrolides therapy duration (PMTD), achieved the highest AUC values of 0.897 and 0.895 in the training and test sets, respectively. A prognostic model developed through automated quantification of lung disease on CT scans, in conjunction with clinical data in MPP may be utilized for the early identification of RMPP. [ABSTRACT FROM AUTHOR]

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease. NEW & NOTEWORTHY Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis.

Objective: To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China., Methods: A prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study., Results: Out of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15-0.84; P  = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17-1.61; P  < .001). Conversely, early rehabilitation intervention was negatively associated with the risk of PMV death (OR = 0.45; 95% CI: 0.22-0.93; P  = .032). Furthermore, the tracheotomy timing emerged as an independent predictor of failure to wean from PMV, with an OR of 1.08, (95% CI: 1.01-1.16; P   =  .030)., Conclusions: The study revealed a 5.3% incidence of PMV in children requiring mechanical ventilation in China. The use of vasoactive agents and a higher PELOD-2 score at PMV diagnosis were significantly associated with an increased risk of PMV death, whereas early rehabilitation intervention was identified as crucial for improving patient outcomes. The timing of tracheostomy was identified as a high-risk factor for failure to wean from mechanical ventilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Cai, Ming, Huang, Liu, Ren, Qu, Gao, Cheng, Zhang, Yang, Xu, Miao, Liu, Liu, Lu and Chen.)