BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

Objective: To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL). Methods: A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams. Results: There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor.

This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in de novo acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of de novo AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing.We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. FLT3-ITD was the most common mutated gene (16.2%, 42/259), followed by CEBPA (15.1%, 39/259), NRAS (14.7%, 38/259), and NPM1 (13.5%, 35/259). Concurrence was observed in 97.1% of the NPM1 mutated cases and in 29.6% of the double mutated CEBPA cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the IDH2 gene: R140 mutations were associated with NPM1 and/or FLT3-ITD mutations, whereas R172 mutations co-occurred with DNMT3A mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with NPM1 mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.
Adolescent ; Adult ; Aged ; CCAAT-Enhancer-Binding Proteins ; genetics ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Female ; GTP Phosphohydrolases ; genetics ; Gene Expression Profiling ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute ; genetics ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Phenotype ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

Obgective To observe the effect of Milrinone combined with Esmolol in the treatment of severe hand-foot-and-mouth disease (HFMD) so as to improve the prognosis.Methods Eighty-two cases of children with critically severe HFMD,who were hospitalized in the Intensive Care Unit of Xuzhou Children's Hospital,were enrolled in the study from may of 2013 to June of 2014,and were randomly divided into a control group and an observation group.The control group was given intravenous Milrinone,and the observation group was given Milrinone combined with Esmolol.The heart rate (HR),systolic blood pressure (SBP),cardiac output (CO),left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP),norepinephrine (NE) were detected on admission and checked again 1 hour and 48 hours again after treatment.The changes in the above indicators were compared before and after therapy to evaluate the clinical curative effect.Results (1) There was no significant difference in the HR,SBP,CO,LVEF,BNP and NE between the 2 groups before treatment(all P ＞ 0.05).(2) The HR,SBP,CO and LVEF of 2 groups were significantly improved after 1 hour treatment compared with those before treatment (all P ＜ 0.05),and the BNP and NE of the control group were not obviously improved compared with those before therapy (all P ＞ 0.05),but the significant changes were seen in the observation group (all P ＜ 0.05).Forty-eight hours after the treatment,all the observed indicators in 2 groups were significantly improved compared with those before treatment(all P ＜ 0.01).(3)Compared with control group,the HR,SBP,CO,LVEF and BNP of the observation group were significantly improved after 1 hour treatment (t =2.08,2.12,-2.11,-2.37,2.07,all P ＜ 0.05),but the NE of the observation group had no obvious improvement (t =0.83,P ＞ 0.05).All the observed indicators of the observation group were significantly improved compared with the control group after 48 hours treatment(t =3.76,2.48,-2.70,-2.27,5.37,2.74,all P ＜ 0.05).Conclusions Milrinone combined with Esmolol can significantly improve the cardiac function and the vital signs of the children with critically severe HFMD,which can be recommended clinically.

Objective: To investigate the relation between proliferation, apoptosis and Bcl-2 in human tongue squamous cell carcinoma(TSCC). Methods: Apoptosis, prolifexation and Bcl-2 protein expression were examined in 7 cases of normal tongue mucosa, 20(10 of Han and 10 of Uygur people) of tongue squamous cell papilloma (TSCP) and 42 of TSCC (30 of well-differentiated and 12 of middle-differentiated ) with immunohistochemical and in situ cell death detection technique. Results: The apoptosis index (TI) and the proliferation index (PI) showed no significant difference between Han and Uygur people or between male and femae, TI and PI in human TSCP were heigher than those in normal tongue mucosa, The proliferation was enhanced and apoptosis was inhibited according to dysplasia degree(P