Development and validation of radiology-clinical statistical and machine learning model for stroke-associated pneumonia after first intracerebral haemorrhage.

BACKGROUND: Society is burdened with stroke-associated pneumonia (SAP) after intracerebral haemorrhage (ICH). Cerebral small vessel disease (CSVD) complicates clinical manifestations of stroke. In this study, we redefined the CSVD burden score and incorporated it into a novel radiological-clinical prediction model for SAP. MATERIALS AND METHODS: A total of 1278 patients admitted to a tertiary hospital between 1 January 2010 and 31 December 2019 were included. The participants were divided into training and testing groups using fivefold cross-validation method. Four models, two traditional statistical models (logistic regression and ISAN) and two machine learning models (random forest and support vector machine), were established and evaluated. The outcomes and baseline characteristics were compared between the SAP and non-SAP groups. RESULTS: Among the of 1278 patients, 281(22.0%) developed SAP after their first ICH. Multivariate analysis revealed that the logistic regression (LR) model was superior in predicting SAP in both the training and testing groups. Independent predictors of SAP after ICH included total CSVD burden score (OR, 1.29; 95% CI, 1.03-1.54), haematoma extension into ventricle (OR, 2.28; 95% CI, 1.87-3.31), haematoma with multilobar involvement (OR, 2.14; 95% CI, 1.44-3.18), transpharyngeal intubation operation (OR, 3.89; 95% CI, 2.7-5.62), admission NIHSS score ≥ 10 (OR, 2.06; 95% CI, 1.42-3.01), male sex (OR, 1.69; 95% CI, 1.16-2.52), and age ≥ 67 (OR, 2.24; 95% CI, 1.56-3.22). The patients in the SAP group had worse outcomes than those in the non-SAP group. CONCLUSION: This study established a clinically combined imaging model for predicting stroke-associated pneumonia and demonstrated superior performance compared with the existing ISAN model. Given the poor outcomes observed in patients with SAP, the use of individualised predictive nomograms is vital in clinical practice.

A dynamic online nomogram predicting prostate cancer short-term prognosis based on 18F-PSMA-1007 PET/CT of periprostatic adipose tissue: a multicenter study.

BACKGROUND: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT. METHODS: Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA. RESULTS: The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram. CONCLUSION: The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.

Discriminating atypical parotid carcinoma and pleomorphic adenoma utilizing extracellular volume fraction and arterial enhancement fraction derived from contrast-enhanced CT imaging: A multicenter study.

OBJECTIVES: To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation. METHODS: From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. RESULTS: Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). CONCLUSIONS: ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.

Enhanced Prediction of Malignant Cerebral Edema in Large Vessel Occlusion with Successful Recanalization Through Automated Weighted Net Water Uptake.

BACKGROUND: Malignant cerebral edema (MCE) is associated with both net water uptake (NWU) and infarct volume. We hypothesized that NWU weighted by the affected Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions could serve as a quantitative imaging biomarker of aggravated edema development in acute ischemic stroke with large vessel occlusion (LVO). The aim of this study was to evaluate the performance of weighted NWU (wNWU) to predict MCE in patients with mechanical thrombectomy (MT). METHODS: We retrospectively analyzed consecutive patients who underwent MT due to LVO. NWU was computed from nonenhanced computed tomography scans upon admission using automated ASPECTS software. wNWU was derived by multiplying NWU with the number of affected ASPECTS regions in the ischemic hemisphere. Predictors of MCE were assessed through multivariate logistic regression analysis and receiver operating characteristic curves. RESULTS: NWU and wNWU were significantly higher in MCE patients than in non-MCE patients. Vessel recanalization status influenced the performance of wNWU in predicting MCE. In patients with successful recanalization, wNWU was an independent predictor of MCE (adjusted odds ratio 1.61; 95% confidence interval [CI] 1.24-2.09; P < 0.001). The model integrating wNWU, National Institutes of Health Stroke Scale, and collateral score exhibited an excellent performance in predicting MCE (area under the curve 0.80; 95% CI 0.75-0.84). Among patients with unsuccessful recanalization, wNWU did not influence the development of MCE (adjusted odds ratio 0.99; 95% CI 0.60-1.62; P = 0.953). CONCLUSIONS: This study revealed that wNWU at admission can serve as a quantitative predictor of MCE in LVO with successful recanalization after MT and may contribute to the decision for early intervention.

Novel anthropometric indicators of visceral obesity predict the severity of hyperlipidemic acute pancreatitis.

BACKGROUND: Obesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP. METHOD: The body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test. RESULTS: Patients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678-0.784. CONCLUSIONS: This study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP.

Low blood flow ratio is associated with hemorrhagic transformation secondary to mechanical thrombectomy in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: A significant decrease of cerebral blood flow (CBF) is a risk factor for hemorrhagic transformation (HT) in acute ischemic stroke (AIS). This study aimed to ascertain whether the ratio of different CBF thresholds derived from computed tomography perfusion (CTP) is an independent risk factor for HT after mechanical thrombectomy (MT). METHODS: A retrospective single center cohort study was conducted on patients with AIS undergoing MT at the First Affiliated Hospital of Wenzhou Medical University from August 2018 to December 2023. The perfusion parameters before thrombectomy were obtained according to CTP automatic processing software. The low blood flow ratio (LFR) was defined as the ratio of brain volume with relative CBF <20 % over volume with relative CBF <30 %. HT was evaluated on the follow-up CT images. Binary logistic regression was used to analyze the correlation between parameters that differ between the two groups with regards to HT occurrence. The predictive efficacy was assessed utilizing the receiver operating characteristic curve. RESULTS: In total, 243 patients met the inclusion criteria. During the follow-up, 46.5 % of the patients (113/243) developed HT. Compared with the Non-HT group, the HT group had a higher LFR (0.47 (0.34-0.65) vs. 0.32 (0.07-0.56); P < 0.001). According to the binary logistic regression analysis, the LFR (aOR: 6.737; 95 % CI: 1.994-22.758; P = 0.002), Hypertension history (aOR: 2.231; 95 % CI: 1.201-4.142; P = 0.011), plasma FIB levels before MT (aOR: 0.641; 95 % CI: 0.456-0.902; P = 0.011), and the mismatch ratio (aOR: 0.990; 95 % CI: 0.980-0.999; P = 0.030) were independently associated with HT secondary to MT. The area under the curve of the regression model for predicting HT was 0.741. CONCLUSION: LFR, a ratio quantified via CTP, demonstrates potential as an independent risk factor of HT secondary to MT.

Space-confined manganese oxides nanosheets for efficient catalytic decomposition of ozone.

Ground-level ozone has long posed a substantial menace to human well-being and the ecological milieu. The widely reported manganese-based catalysts for ozone decomposition still facing the persisting issues encompass inefficiency and instability. To surmount these challenges, we developed a mesoporous silica thin films with perpendicular nanochannels (SBA(⊥)) confined Mn3O4 catalyst (Mn3O4@SBA(⊥)). Under a weight hourly space velocity (WHSV) of 500,000 mL g-1 h-1, the Mn3O4@SBA(⊥) catalyst exhibited 100% ozone decomposition efficiency in 5 h and stability across a wide humidity range, which exceed the performance of bulk Mn3O4 and Mn3O4 confine in commonly reported SBA-15. Rapidly decompose 20 ppm O3 to a safety level below 100 µg m-3 in the presence of dust in smog chamber (60 × 60 × 60 cm) was also realized. This prominent catalytic performance can be attributed to the unique confined structure engenders the highly exposed active sites, facilitate the reactant-active sites contact and impeded the water accumulation on the active sites. This work offers new insights into the design of confined structure catalysts for air purification.

Association of follow-up neutrophil-to-lymphocyte ratio and systemic inflammation response index with stroke-associated pneumonia and functional outcomes in cerebral hemorrhage patients: a case-controlled study.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) at admission are independent diagnostic biomarkers in stroke-associated pneumonia (SAP). Our study aimed to investigate the association between NLR, SIRI, specifically follow-up NLR and SIRI, and SAP, as well as their relationship with functional outcomes. PATIENTS AND METHODS: We retrospectively included 451 consecutive intracerebral hemorrhage patients from May 2017 to May 2019. We conducted univariate and multivariable analyses to identify the factors independently associated with SAP and poor functional outcomes. RESULTS: Compared to 127 (28.16%) patients diagnosed with SAP, those without SAP had both lower baseline and follow-up NLR and SIRI values ( P <0.001). After adjustments, we found that baseline NLR [OR, 1.039 (95% CI, 1.003-1.077); P =0.036] and follow-up NLR [OR, 1.054 (95% CI, 1.011-1.098); P =0.012] were independently associated with SAP. The follow-up NLR was also associated with a higher mRS [OR, 1.124 (95% CI, 1.025-1.233); P =0.013] and lower ADL-MBI score [OR, 1.167 (95% CI, 1.057-1.289); P =0.002] at discharge. Multivariable analysis indicated that advanced age and nasogastric tube feeding were independently associated with SAP ( P <0.05). We constructed a dynamic nomogram to identify SAP risk. Further subgroup analysis revealed that baseline NLR [OR, 1.062 (95% CI, 1.007-1.120); P =0.026] is independently associated with SAP in the nasogastric feeding group, while follow-up NLR [OR, 1.080 (95% CI, 1.024-1.139); P =0.005] was associated with the occurrence of SAP in non-nasogastric feeding patients. CONCLUSIONS: We found elevated baseline and follow-up NLR values were associated with SAP occurrence, and increasing follow-up NLR indicated poor functional outcomes. Inflammatory markers at different stages may offer individualized guidance for patients receiving various treatments.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Multimodal radiomics based on 18F-Prostate-specific membrane antigen-1007 PET/CT and multiparametric MRI for prostate cancer extracapsular extension prediction.

OBJECTIVES: To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. METHODS: We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. RESULTS: AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P < .05). CONCLUSION: The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. ADVANCES IN KNOWLEDGE: This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE.

An Online Dynamic Radiomics-Clinical Nomogram to Predict Recurrence in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Radiomics can reflect the heterogeneity within the focus. We aim to explore whether radiomics can predict recurrent intracerebral hemorrhage (RICH) and develop an online dynamic nomogram to predict it. METHODS: This retrospective study collected the clinical and radiomics features of patients with spontaneous intracerebral hemorrhage seen in our hospital from October 2013 to October 2016. We used the minimum redundancy maximum relevancy and the least absolute shrinkage and selection operator methods to screen radiomics features and calculate the Rad-score. We use the univariate and multivariate analyses to screen clinical predictors. Optimal clinical features and Rad-score were used to construct different logistics regression models called the clinical model, radiomics model, and combined-logistic regression model. DeLong testing was performed to compare performance among different models. The model with the best predictive performance was used to construct an online dynamic nomogram. RESULTS: Overall, 304 patients with intracerebral hemorrhage were enrolled in this study. Fourteen radiomics features were selected to calculate the Rad-score. The patients with RICH had a significantly higher Rad-score than those without (0.5 vs. -0.8; P< 0.001). The predictive performance of the combined-logistic regression model with Rad-score was better than that of the clinical model for both the training (area under the receiver operating curve, 0.81 vs. 0.71; P = 0.02) and testing (area under the receiver operating curve, 0.65 vs. 0.58; P = 0.04) cohorts statistically. CONCLUSIONS: Radiomics features were determined related to RICH. Adding Rad-score into conventional clinical models significantly improves the prediction efficiency. We developed an online dynamic nomogram to accurately and conveniently evaluate RICH.

The effect of shikonin on the metabolism of lapatinib in vitro, and in vivo.

PURPOSE: The purpose of this study was to develop an assay for simultaneous determination of lapatinib and its metabolites (N-dealkylated lapatinib and O-dealkylated lapatinib) by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), and to determine the interaction between shikonin and lapatinib in vitro, in vivo, in silico and its mechanism of action. METHODS: A new UPLC-MS/MS method for the determination of the concentrations of lapatinib and its metabolites was developed. In vivo, Sprague-Dawley (SD) rats were given lapatinib with or without shikonin. In vitro, to study the interaction mechanism, rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4.1 were used for determining enzyme kinetics. Lastly, we used in silico molecular docking to investigate the molecular mechanism of inhibition. RESULTS: The selectivity, precision, accuracy, stability, matrix effect and recovery of UPLC-MS/MS all met the requirements of quantitative analysis of biological samples. Administration of lapatinib combined with shikonin resulted in significantly increased pharmacokinetic parameters (AUC(0-t) and Cmax) of lapatinib, indicating that shikonin increased the exposure of lapatinib in rats. Moreover, in vitro kinetic measurements indicated that shikonin was a time-independent inhibitor, which inhibited the metabolism of lapatinib through a competitive mechanism in RLMs, while noncompetitive inhibition type in both HLMs and CYP3A4.1. Molecular docking analysis further verified the non-competitive inhibition of shikonin on lapatinib in CYP3A4.1. CONCLUSION: We developed an UPLC-MS/MS assay for simultaneous determination of lapatinib and its metabolites. It could be successfully applied to the study of pharmacokinetic interaction of shikonin on the inhibition of lapatinib metabolism in vivo and in vitro. In the end, further studies are needed to determine if such interactions are indeed valid in humans and if the interaction is clinically relevant.

Development and validation of a nomogram based on CT texture analysis for discriminating minimally invasive adenocarcinoma from glandular precursor lesions in sub­centimeter pulmonary ground glass nodules.

In a recent reclassification, adenocarcinoma in situ has been redefined as a glandular precursor lesion (GPL), alongside adenomatous hyperplasia. This updated classification necessitates corresponding adaptations in clinical diagnostic and therapeutic protocols. Consequently, the present study aimed to construct and validate a nomogram utilizing computed tomography (CT) texture features to effectively discriminate between minimally invasive adenocarcinoma (MIA) and GPL within sub-centimeter pulmonary ground glass nodules (GGNs). To achieve this objective, the present study employed rigorous statistical methodologies, including the Mann-Whitney U test and binary logistic regression analysis, to identify distinguishing features and establish predictive models. Subsequently, the diagnostic performance of these models underwent evaluation through receiver operating characteristic (ROC) curves. The area under the curve (AUC) in ROC curves was compared using DeLong's test. Additionally, the nomogram was constructed using R software and its diagnostic performance was validated through calibration curves. Within both the training and validation datasets, the AUCs were observed to be 0.992 [95% confidence interval (CI): 0.980-1.000] and 0.975 (95% CI: 0.935-1.000), respectively. DeLong's test revealed significant disparities in the AUCs between the nomogram and single-parameter models (P<0.001). Furthermore, calibration curves demonstrated concordance between the training and validation datasets. In conclusion, the application of a CT texture-based nomogram model has demonstrated aptitude in differentiating between MIA and GPL within sub-centimeter GGNs. This model streamlines the identification of optimal surgical interventions and enhances the sphere of clinical decision-making and management.

Acute Phase Blood Glucose Levels and Functional Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.

Objective: Post-stroke hyperglycemia as a common phenomenon is associated with unfavorable outcomes. Focusing on admission hyperglycemia, other markers of dysglycemia were overlooked. This study aimed to explore the contribution of acute phase blood glucose levels in combination with other radiological signs to the prognostication of functional outcomes in patients with spontaneous intracerebral hemorrhage (sICH). Methods: Consecutive patients with sICH with at least five random plasma glucose measurements and complete radiological data during hospitalization were included. We calculated the average, maximum, minimum, standard deviation, and coefficient of variation of blood glucose levels for each patient. Radiological data, including island, black hole, blend, and satellite signs were collected. Functional outcomes were evaluated using the Barthel index. Unfavorable outcomes were defined as a Barthel index score ≤ 60. Univariate and multivariate analyses were performed to identify independent predictors of unfavorable outcomes. Results: Two hundred and thirty-eight patients (mean age 58.5, 163 men and 75 women) were included, and 71 had a history of diabetes. Unfavorable outcomes occurred in 107 patients (45.0%) at 3 months. Multivariate logistic regression analysis demonstrated that maximum blood glucose levels (odds ratio, 1.256; 95% confidence interval, 1.124‒1.404; p < 0.001) and island sign (odds ratio, 2.701; 95% confidence interval, 1.322‒5.521; p = 0.006) were independent predictors of unfavorable outcomes in the nondiabetic group. Meanwhile, patients without diabetes who experienced hematoma expansion had higher average (p = 0.036) and maximum blood glucose levels (p = 0.014). Interpretation: Maximum blood glucose levels and island sign were independently associated with unfavorable outcomes in patients without diabetes, whereas no glycemic variability indices were associated with unfavorable outcomes. Glucose levels influenced hematoma expansion and functional outcomes, particularly in patients without diabetes with sICH. Thus, clinical management of blood glucose levels should be strengthened for patients with sICH with or without a history of diabetes.

Predicting very early recurrence in intrahepatic cholangiocarcinoma after curative hepatectomy using machine learning radiomics based on CECT: A multi-institutional study.

BACKGROUND: Even after curative resection, the prognosis for patients with intrahepatic cholangiocarcinoma (iCCA) remains disappointing due to the extremely high incidence of postoperative recurrence. METHODS: A total of 280 iCCA patients following curative hepatectomy from three independent institutions were recruited to establish the retrospective multicenter cohort study. The very early recurrence (VER) of iCCA was defined as the appearance of recurrence within 6 months. The 3D tumor region of interest (ROI) derived from contrast-enhanced CT (CECT) was used for radiomics analysis. The independent clinical predictors for VER were histological stage, AJCC stage, and CA199 levels. We implemented K-means clustering algorithm to investigate novel radiomics-based subtypes of iCCA. Six types of machine learning (ML) algorithms were performed for VER prediction, including logistic, random forest (RF), neural network, bayes, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). Additionally, six clinical ML (CML) models and six radiomics-clinical ML (RCML) models were developed to predict VER. Predictive performance was internally validated by 10-fold cross-validation in the training cohort, and further evaluated in the external validation cohort. RESULTS: Approximately 30 % of patients with iCCA experienced VER with extremely discouraging outcome (Hazard ratio (HR) = 5.77, 95 % Confidence Interval (CI) = 3.73-8.93, P < 0.001). Two distinct iCCA subtypes based on radiomics features were identified, and subtype 2 harbored a higher proportion of VER (47.62 % Vs 25.53 %) and significant shorter survival time than subtype 1. The average AUC values of the CML and RCML models were 0.744 ± 0.018, and 0.900 ± 0.014 in the training cohort, and 0.769 ± 0.065 and 0.929 ± 0.027 in the external validation cohort, respectively. CONCLUSION: Two radiomics-based iCCA subtypes were identified, and six RCML models were developed to predict VER of iCCA, which can be used as valid tools to guide individualized management in clinical practice.

Predicting the formation of mixed pattern hemorrhages in ruptured middle cerebral artery aneurysms based on a decision tree model: A multicenter study.

OBJECTIVE: Mixed-pattern hemorrhages (MPH) commonly occur in ruptured middle cerebral artery (MCA) aneurysms and are associated with poor clinical outcomes. This study aimed to predict the formation of MPH in a multicenter database of MCA aneurysms using a decision tree model. METHODS: We retrospectively reviewed patients with ruptured MCA aneurysms between January 2009 and June 2020. The MPH was defined as subarachnoid hemorrhages with intracranial hematomas and/or intraventricular hemorrhages and/or subdural hematomas. Univariate and multivariate logistic regression analyses were used to explore the prediction factors of the formation of MPH. Based on these prediction factors, a decision tree model was developed to predict the formation of MPH. Additional independent datasets were used for external validation. RESULTS: We enrolled 436 patients with ruptured MCA aneurysms detected by computed tomography angiography; 285 patients had MPH (65.4%). A multivariate logistic regression analysis showed that age, aneurysm size, multiple aneurysms, and the presence of a daughter dome were the independent prediction factors of the formation of MPH. The areas under receiver operating characteristic curves of the decision tree model in the training, internal, and external validation cohorts were 0.951, 0.927, and 0.901, respectively. CONCLUSION: Age, aneurysm size, the presence of a daughter dome, and multiple aneurysms were the independent prediction factors of the formation of MPH. The decision tree model is a useful visual triage tool to predict the formation of MPH that could facilitate the management of unruptured aneurysms in routine clinical work.

Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.

Itraconazole is a triazole anti-infective drug that has been proven to prevent and treat a variety of fungal and viral infections and has been considered to be a potential therapeutic remedy for COVID-19 treatment. In this study, we aimed to completely evaluate the impacts of Cytochrome P450 3A4 (CYP3A4) variant proteins and drug interactions on the metabolism of itraconazole in recombinant insect microsomes, and to characterize the potential mechanism of substrate selectivity. Incubations with itraconazole (0.2-15 µM) in the presence/absence of lopinavir or darunavir were assessed by CYP3A4 variants, and the metabolite hydroxyitraconazole concentrations were measured by UPLC-MS/MS. Our data showed that when compared with CYP3A4.1, 4 variants (CYP3A4.9, .10, .28 and .34) displayed no significant differences, and 3 variants (CYP3A4.14, .15 and .19) exhibited increased intrinsic clearance (CLint), whereas the remaining 17 variant proteins showed decreased enzyme activities for the catalysis of itraconazole. Moreover, the inhibitory effects of lopinavir and darunavir on itraconazole metabolism varied in different degrees. Furthermore, different changed trend of the kinetic parameters in ten variants (CYP3A4.5, .9, .10, .16, .19, .24, .28, .29, .31, and .33) were observed, especially CYP3A4.5 and CYP3A4.16, and this may be related to the metabolic site-heme iron atom distance. In the present study, we functionally analyzed the effects of 25 CYP3A4 protein variants on itraconazole metabolism for the first time, and provided comprehensive data on itraconazole metabolism in vitro. This may help to better assess the metabolism and elimination of itraconazole in clinic to improve the safety and efficacy of its clinical treatment and also provide new possibilities for the treatment of COVID-19.

The interaction of global small vessel disease burden and Alzheimer's disease pathologies do not change the independent association of amyloid-beta with hippocampal volume: A longitudinal study on mild cognitive impairment subjects.

The purpose of this study was to investigate whether the co-existence of global small vessel disease (SVD) burdens and Alzheimer's disease (AD) pathologies change hippocampal volume (HV) and cognitive function of mild cognitive impairment (MCI) subjects. We obtained MRI images, cerebrospinal fluid biomarkers (Aß1-42 and p-tau), and neuropsychological tests of 310 MCI subjects from ADNI. The global SVD score was assessed. We used linear regression and linear mixing effect to analyze the effects of global SVD burdens, AD pathologies, and their interactions (SVD*AD) on baseline and longitudinal HV and cognition respectively. We used simple mediation effect to analyze the influencing pathways. After adjusting for global SVD and SVD*AD, Aß remained independently correlated with baseline and longitudinal HV (std ß = 0.294, p = .007; std ß = 0.292, p < .001), indicating that global SVD did not affect the correlation between Aß and HV. Global SVD score was correlated with longitudinal but not baseline HV (std ß = 0.470, p = .050), suggesting that global SVD may be more representative of long-term permanent impairment. Global SVD, AD pathologies, and SVD*AD were independently correlated with baseline and longitudinal cognitions, in which the association of Aß (B = 0.005, 95% CI: 0.005; 0.024) and p-tau (B = -0.002, 95% CI: -0.004; -0.000) with cognition were mediated by HV, suggesting that HV is more likely to explain the progression caused by AD pathology than SVD. The co-existence of global SVD and AD pathologies did not affect the individual association of Aß on HV; HV played a more important role in the influence of AD pathology on cognition than in SVD.

Machine learning prediction model for the rupture status of middle cerebral artery aneurysm in patients with hypertension: a Chinese multicenter study.

Background: Hypertension is a common comorbidity in patients with unruptured intracranial aneurysms and is closely associated with the rupture of aneurysms. However, only a few studies have focused on the rupture risk of aneurysms comorbid with hypertension. This retrospective study aimed to construct prediction models for the rupture of middle cerebral artery (MCA) aneurysm associated with hypertension using machine learning (ML) algorithms, and the constructed models were externally validated with multicenter datasets. Methods: We included 322 MCA aneurysm patients comorbid with hypertension who were being treated in four hospitals. All participants underwent computed tomography angiography (CTA), and aneurysm morphological features were measured. Clinical characteristics included sex, age, smoking, and hypertension history. Based on the clinical and morphological characteristics, the training datasets (n=277) were used to fit the ML algorithms to construct prediction models, which were externally validated with the testing datasets (n=45). The prediction performances of the models were assessed by receiver operating characteristic (ROC) curves. Results: The areas under the ROC curve (AUCs) of the k-nearest-neighbor (KNN), neural network (NNet), support vector machine (SVM) and logistic regression (LR) models in the training datasets were 0.83 [95% confidence interval (CI): 0.78-0.88], 0.87 (95% CI: 0.82-0.92), 0.91 (95% CI: 0.88-0.95), and 0.83 (95% CI: 0.77-0.88), respectively, and in the testing datasets were 0.74 (95% CI: 0.59-0.89), 0.82 (95% CI: 0.69-0.94), 0.73 (95% CI: 0.58-0.88), and 0.76 (95% CI: 0.61-0.90), respectively. The aspect ratio (AR) was ranked as the most important variable in the ML models except for NNet. Further analysis showed that the AR had good diagnostic performance, with AUC values of 0.75 in the training datasets and 0.77 in the testing datasets. Conclusions: The ML models performed reasonably accurately in predicting MCA aneurysm rupture comorbid with hypertension. AR was demonstrated as the leading predictor for the rupture of MCA aneurysm with hypertension.