Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial-mesenchymal transition and lipid metabolism due to alterations in the NF-kappa B and MAPK signaling pathways. Tumor cells were also differentially enriched for the IL-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated ICC, whereas there was more infiltration of myeloid cells with attenuated expression of the MHC II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1-CD44 and ANXA1-FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.

Preoperative prediction of microvascular invasion risk in hepatocellular carcinoma with MRI: peritumoral versus tumor region.

OBJECTIVES: To explore the predictive performance of tumor and multiple peritumoral regions on dynamic contrast-enhanced magnetic resonance imaging (MRI), to identify optimal regions of interest for developing a preoperative predictive model for the grade of microvascular invasion (MVI). METHODS: A total of 147 patients who were surgically diagnosed with hepatocellular carcinoma, and had a maximum tumor diameter ≤ 5 cm were recruited and subsequently divided into a training set (n = 117) and a testing set (n = 30) based on the date of surgery. We utilized a pre-trained AlexNet to extract deep learning features from seven different regions of the maximum transverse cross-section of tumors in various MRI sequence images. Subsequently, an extreme gradient boosting (XGBoost) classifier was employed to construct the MVI grade prediction model, with evaluation based on the area under the curve (AUC). RESULTS: The XGBoost classifier trained with data from the 20-mm peritumoral region showed superior AUC compared to the tumor region alone. AUC values consistently increased when utilizing data from 5-mm, 10-mm, and 20-mm peritumoral regions. Combining arterial and delayed-phase data yielded the highest predictive performance, with micro- and macro-average AUCs of 0.78 and 0.74, respectively. Integration of clinical data further improved AUCs values to 0.83 and 0.80. CONCLUSION: Compared with those of the tumor region, the deep learning features of the peritumoral region provide more important information for predicting the grade of MVI. Combining the tumor region and the 20-mm peritumoral region resulted in a relatively ideal and accurate region within which the grade of MVI can be predicted. CLINICAL RELEVANCE STATEMENT: The 20-mm peritumoral region holds more significance than the tumor region in predicting MVI grade. Deep learning features can indirectly predict MVI by extracting information from the tumor region and directly capturing MVI information from the peritumoral region. KEY POINTS: We investigated tumor and different peritumoral regions, as well as their fusion. MVI predominantly occurs in the peritumoral region, a superior predictor compared to the tumor region. The peritumoral 20 mm region is reasonable for accurately predicting the three-grade MVI.

Nomograms established for predicting microvascular invasion and early recurrence in patients with small hepatocellular carcinoma.

BACKGROUND: In this study, we aimed to establish nomograms to predict the microvascular invasion (MVI) and early recurrence in patients with small hepatocellular carcinoma (SHCC), thereby guiding individualized treatment strategies for prognosis improvement. METHODS: This study retrospectively analyzed 326 SHCC patients who underwent radical resection at Wuhan Union Hospital between April 2017 and January 2022. They were randomly divided into a training set and a validation set at a 7:3 ratio. The preoperative nomogram for MVI was constructed based on univariate and multivariate logistic regression analysis, and the prognostic nomogram for early recurrence was constructed based on univariate and multivariate Cox regression analysis. We used the receiver operating characteristic (ROC) curves, area under the curves (AUCs), and calibration curves to estimate the predictive accuracy and discriminability of nomograms. Decision curve analysis (DCA) and Kaplan-Meier survival curves were employed to further confirm the clinical effectiveness of nomograms. RESULTS: The AUCs of the preoperative nomogram for MVI on the training set and validation set were 0.749 (95%CI: 0.684-0.813) and 0.856 (95%CI: 0.805-0.906), respectively. For the prognostic nomogram, the AUCs of 1-year and 2-year RFS respectively reached 0.839 (95%CI: 0.775-0.903) and 0.856 (95%CI: 0.806-0.905) in the training set, and 0.808 (95%CI: 0.719-0.896) and 0.874 (95%CI: 0.804-0.943) in the validation set. Subsequent calibration curves, DCA analysis and Kaplan-Meier survival curves demonstrated the high accuracy and efficacy of the nomograms for clinical application. CONCLUSIONS: The nomograms we constructed could effectively predict MVI and early recurrence in SHCC patients, providing a basis for clinical decision-making.

Occult coronary microvascular dysfunction and ischaemic heart disease in patients with diabetes and heart failure.

BACKGROUND: Patients with diabetes (DM) and heart failure (HF) have worse outcomes than normoglycaemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischaemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify extent of silent IHD and CMD in patients with DM presenting with HF. METHODS: Prospectively recruited outpatients undergoing assessment into the aetiology of HF underwent inline quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). RESULTS: Final analysis included 343 patients (176 normoglycaemic, 84 with pre-diabetes and 83 with DM). Prevalence of silent IHD was highest in DM (31%), then pre-diabetes (20%) then normoglycaemia (17%). Stress MBF was lowest in DM (1.53±0.52), then pre-diabetes (1.59±0.54) then normoglycaemia (1.83±0.62). MPR was lowest in DM (2.37±0.85) then pre-diabetes (2.41±0.88) then normoglycaemia (2.61±0.90). During follow up 45 patients experienced at least one MACE. On univariate Cox regression analysis MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age and left ventricular ejection fraction the associations were no longer significant. CONCLUSIONS: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for assessment of silent IHD and CMD in patients with DM presenting with HF.

Cardio- and Vasoprotective Effects of Quinacrine in an In Vivo Rat Model of Myocardial Ischemia/Reperfusion Injury.

This study aimed to investigate the cardioprotective effect of quinacrine in an in vivo model of myocardial ischemia/reperfusion injury. A 30-min regional myocardial ischemia followed by a 2-h reperfusion was modeled in anesthetized Wistar rats. Starting at the last minute of ischemia and during the first 9 min of reperfusion the rats in the control (n=8) and experimental (n=9) groups were injected with 0.9% NaCl and quinacrine solution (5 mg/kg), respectively. The area at risk and infarct size were evaluated by "double staining" with Evans blue and triphenyltetrazolium chloride. To assess vascular permeability in the area at risk zone, indocyanine green (ICG) and thioflavin S (ThS) were injected intravenously at the 90th and 120th minutes of reperfusion, respectively, to assess the no-reflow zone. The images of ICG and ThS fluorescence in transverse sections of rat hearts were obtained using a FLUM multispectral fluorescence organoscope. HR tended to decrease by 13% after intravenous administration of quinacrine and then recovered within 50 min. Quinacrine reduced the size of the necrotic zone (p=0.01), vascular permeability in the necrosis region, and the no-reflow area (p=0.027); at the same time, the area at risk did not significantly differ between the groups. Intravenous administration of quinacrine at the beginning of reperfusion of the rat myocardium reduces no-reflow phenomenon and infarct size.

Hyperoxia exposure promotes endothelial-mesenchymal transition and inhibits regulatory T cell function in human pulmonary microvascular endothelial cells.

Objective: This study aims to investigate the effects of hyperoxia exposure on TGF-ß1-induced endothelial-mesenchymal transition (EndoMT) and regulatory T cell (Treg)-mediated immunomodulation in human pulmonary microvascular endothelial cells (HPMECs), which could provide a theoretical basis for further studies of the pathogenesis of bronchopulmonary dysplasia (BPD). Methods: A BPD cell model was established by exposing HPMECs to hyperoxia. Flow cytometry was used to isolate CD4 + CD3 + CD25 + CD127- Tregs from the peripheral blood samples of preterm infants. HPMECs were divided into four groups based on whether they were exposed to hyperoxia and/or co-cultured with Tregs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to test the expression levels of TGF-ß1, α-SMA, Foxp3, IL-10, and reactive oxygen species (ROS). Results: The results showed that the expression levels of TGF-ß1 and α-SMA in HPMECs increased at 24 h, 48 h, and 72 h of hyperoxia exposure. In the co-culture group of HPMECs and Tregs, Foxp3 and IL-10 expressions decreased at 48 h and 72 h of hyperoxia exposure. ROS expression increased in the hyperoxia group of HPMECs at 24 h, 48 h, and 72 h of hyperoxia exposure, which were higher than those in the hyperoxia group of HPMECs and Tregs. Conclusion: These findings suggest that hyperoxia exposure promotes EndoMT in HMPECs and inhibits the immunosuppressive effect of Tregs. Despite this, Tregs still seem could protect HPMECs from oxidative stress injury.

Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS.

Risperidone is useful for the treatment of schizophrenia symptoms; however, it also has side effects, and an overdose can be harmful. The metabolic effects of risperidone at high therapeutic doses and its metabolites have not been elucidated. Endogenous cellular metabolites may be comprehensively analyzed using untargeted metabolomics-based liquid chromatography-mass spectrometry (LC-MS), which can reveal changes in cell regulation and metabolic pathways. By identifying the metabolites and pathway changes using a nontargeted metabolomics-based LC-MS approach, we aimed to shed light on the potential toxicological effects of high-dose risperidone on brain microvascular endothelial cells (MVECs) associated with the human blood brain barrier. A total of 42 metabolites were selected as significant putative metabolites of the toxicological response of high-dose risperidone in MVECs. Six highly correlated pathways were identified, including those involving diacylglycerol, fatty acid, ceramide, glycerophospholipid, amino acid, and tricarboxylic acid metabolism. We demonstrated that methods focused on metabolomics are useful for identifying metabolites that may be used to clarify the mechanism of drug-induced toxicity.

Risk Factors for Plate Infection, Exposure, and Removal in Mandibular Reconstruction.

OBJECTIVE: Mandibular plate reconstruction (MPR) is often indicated after tumor ablation, osteoradionecrosis excision, and traumatic bone loss to restore oral functionality and facial cosmetics. There are limited analyses identifying risk factors that lead to plate infection (PIn), exposure, and removal ("plate complications"). STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary medical center. METHODS: Patients who underwent MPR from 2013 to 2022 were identified. Risk factors for plate complications were analyzed based on demographic, clinical, intraoperative, and postoperative factors. Multivariable analysis was conducted with logistic regression. Survival analysis was conducted with a Cox model. RESULTS: Of the 188 patients analyzed, 48 (25.5%) had a plate complication [infection: 22 (11.7%); exposure: 23 (12.2%); removal: 35 (18.6%)]. Multivariate analysis revealed predictive associations between at least 1 plate complication and the following variables: smoking status, soft tissue defect size, number of plates, average screw length, and various postoperative complications. Other associations approached the threshold for significance. Prior and adjuvant radiation therapy, type of free flap, stock versus custom plates, and perioperative antibiotic prophylaxis regimens were not associated with plate complications. No plate complication was independently associated with lower overall survival. PIn (hazard ratio, HR: 7.99, confidence interval, CI [4.11, 15.54]) and exposure (HR: 3.56, CI [1.79, 7.08]) were independently associated with higher rates of plate removal. CONCLUSION: Plate complications are relatively common after MPR. Smoking history, specific disease characteristics, hardware used during surgery, and postoperative complications may help identify higher-risk patients, but additional larger-scale studies are needed to validate our findings and resolve discrepancies in the current literature.

Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes.

In this review article, we explore the interplay between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM), highlighting a significant yet often overlooked comorbidity. We delve into the pathophysiological links between OSA and diabetes, specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism. The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications. Emphasizing the importance of comprehensive management, including weight control and positive airway pressure therapy, the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA. This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR.

BACKGROUND: Coronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear. OBJECTIVES: The authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome. METHODS: Fully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery. RESULTS: Compared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (-0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (-0.25 to 1.1; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [-0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = -0.45 [95% CI: -0.05 to 0.90]; P = 0.03). CONCLUSIONS: Coronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus.

Assessment of the utility of two-dimensional shear wave elastography and superb microvascular imaging in postoperative patients with biliary atresia.

PURPOSE: We aimed to investigate whether prediction of liver fibrosis using two-dimensional shear wave elastography (2D-SWE) and vascular tree grading using superb microvascular imaging (SMI) are useful for postoperative follow-up in patients with biliary atresia (BA). METHODS: We retrospectively collected data from medical records of 134 patients who underwent ultrasound examination with 2D-SWE or SMI, including 13 postoperative patients with BA and 121 non-BA patients. We investigated the distribution of liver stiffness values with SWE and vascular tree grading with SMI and evaluated correlations between these findings and biochemical indices of liver fibrosis in postoperative BA patients. RESULTS: The SWE values of the BA group were not significantly different from that of any other disease groups in non-BA patients. In postoperative BA patients, SWE values correlated significantly with aspartate aminotransferase to platelet ratio index (Spearman rank correlation coefficient [rs] = 0.6380, p = 0.0256) and with the Fib-4 index (rs = 0.6526, p = 0.0214). SMI vascular tree grading of the BA group was significantly higher than that of the choledochal cyst group (p = 0.0008) and other hepatobiliary disorder group (p = 0.0030). In postoperative BA patients, SMI vascular tree grading was not positively correlated with any biochemical marker of fibrosis. CONCLUSION: 2D-SWE appears to be useful for follow-up in postoperative BA patients.

Ultrasound enhancing agents in cardiovascular imaging: expanding horizons beyond coronary arteries.

From its inception as a two-dimensional snapshot of the beating heart, echocardiography has become an indelible part of cardiovascular diagnostics. The integration of ultrasound enhancing agents (UEAs) marks a pivotal transition, enhancing its diagnostic acumen beyond myocardial perfusion. These agents have refined echocardiography's capacity to visualize complex cardiac anatomy and pathology with unprecedented clarity, especially in non-coronary artery disease contexts. UEAs aid in detailed assessments of myocardial viability, endocardial border delineation in left ventricular opacification, and identification of intracardiac masses. Recent innovations in UEAs, accompanied by advancements in echocardiographic technology, offer clinicians a more nuanced view of cardiac function and blood flow dynamics. This review explores recent developments in these applications and future contemplated studies.

Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction.

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10mg QD) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (Statin: n=8, 76±6 yr; Placebo: n=8, 68±9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-Minute Walk Test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under-the-curve (LBFAUC), increased following the statin intervention (pre: 60 ± 68 mL; post: 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group (P=0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre: 0.68 ± 0.10; post: 0.51 ± 0.11; P < 0.01), while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.

Factors associated with outcomes following microvascular decompression for the treatment of primary trigeminal neuralgia in adults: a systematic review and meta-analysis.

This study aimed to evaluate pain assessment strategies and factors associated with outcomes after microvascular decompression for the treatment of primary trigeminal neuralgia in adults. We conducted a systematic review and meta-analysis of English, Spanish, and French literature. We searched three databases, PubMed, Ovid, and EBSCO, from 2010 to 2022 and selected studies including patients with primary trigeminal neuralgia, clear pain assessment, and pain outcomes. Population means and standard deviations were calculated. Studies that included factors associated with postoperative outcomes were included in the meta-analysis. A total of 995 studies involving 5673 patients with primary trigeminal neuralgia following microvascular decompression were included. Patients with arteries compressing the trigeminal nerve demonstrated optimal outcomes following microvascular decompression (odds ratio [OR]= 0.39; 95% confidence interval [CI] = 0.19-0.80; X2 = 46.31; Dof = 15; I2 = 68%; P = < 0.0001). Conversely, when comparing arterial vs venous compression of the trigeminal nerve (OR = 2.72; 95% CI = 1.16-6.38; X2 = 23.23; Dof = 10; I2 = 57%; P = 0.01), venous compression demonstrated poor outcomes after microvascular decompression. Additionally, when comparing single-vessel vs multiple-vessel compression (OR = 2.72; 95% CI = 1.18-6.25; X2 = 21.17; Dof = 9; I2 = 57%; P = 0.01), patients demonstrated unfavorable outcomes after microvascular decompression. This systematic review and meta-analysis evaluated factors associated with outcomes following microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). Although MVD is an optimal treatment strategy for PTN, a gap exists in interpreting the results when considering the lack of evidence for most pain assessment strategies.

Risk factors for unsuccessful restoration of coronary flow reserve after coronary bypass surgery.

OBJECTIVES: Coronary flow reserve (CFR) is a strong predictor of cardiovascular events and prognosis in patients with coronary artery disease. This study aimed to evaluate preoperative factors associated with the unsuccessful restoration of CFR after coronary artery bypass grafting (CABG). METHODS: Included in this study were the 65 patients who presented with functionally significant left anterior descending artery (LAD) lesions confirmed by both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), and who underwent successful CABG at our hospital within the study period. After CABG, graft patency was confirmed by coronary computed tomography angiography, and CFR in the LAD artery was measured by echocardiography. We defined postoperative CFR <2.5 as impaired CFR, and CFR ≥2.5 as preserved CFR. RESULTS: Of the 65 patients, 14 patients (22%) showed impaired CFR, while 51 patients had preserved CFR. Patients with impaired CFR had significantly higher HbA1c (6.7% vs. 6.0%, P < 0.01), greater use of insulin (43% vs. 4%, P < 0.01), longer lesion length (33 mm vs. 25 mm, P = 0.044), and lower iFR (0.69 vs 0.81, P = 0.01) than those with preserved CFR, although both groups had comparable FFR (0.65 vs 0.64, P = 0.46). In receiver operating characteristic curve analysis, iFR had a significantly larger area under the curve than FFR in terms of the prediction of impaired CFR (0.74 vs 0.42, P = 0.01). CONCLUSIONS: Poorly-controlled preoperative diabetes, greater reliance on insulin, longer lesion length and lower iFR were associated with postoperative impaired CFR, suggesting the involvement of microvascular dysfunction.

Short dental implants in microvascular free flap DCIA: A case report.

Placing dental implants in microvascular bone free flaps used for reconstructing the mandible or maxilla has been previously reported. However, there is scarce information available on the restorative protocol using short dental implants placed in a deep circumflex iliac artery (DCIA) microvascular free flap and the rationale behind it. This case report describes a 18-year-old patient referred to the hospital for numbness and dull pain of the left mandible, which she observed for three months. The patient underwent mandible resection and reconstruction using the DCIA free flap due to "giant cell lesion" on the left side of the mandibular angle. Short dental implants were placed and prosthetic reconstruction of the dentition involved in the resection was performed in a young patient with two integrated abutment crowns. The placement of short dental implants did not negatively affect the vascular pedicle and vitality of free flap. In our case report, two years after the healing, excellent aesthetic and function were accomplished with the DCIA flap followed by restoration with short implants.

Breast multiparametric ultrasound: a single-center experience.

PURPOSE: To evaluate the role of multiparametric ultrasound (mpUS) in the characterization of focal breast lesions (FBLs). METHODS: This prospective study enrolled patients undergoing multiparametric breast ultrasound for FBLs. An experienced breast radiologist evaluated the following ultrasound features: US BI-RADS category, vascularization pattern (internal, vessels in rim and combined) and presence of penetrating vessels with each Doppler method (Color-Doppler, Power-Doppler, Microvascular imaging), strain ratio (SR) and Tsukuba score (TS) with Strain Elastography (SE), Emax, Emean, Emin and Eratio with 2D-shear wave elastography (2D-SWE). Core biopsy for all BI-RADS 4-5 FBLs and 24-month follow-up for all BI-RADS 2-3 FBLs were considered for standard of reference. The diagnostic performance was assessed with the area under curve (AUCs) and cut-off values were determined according to the Youden's index. RESULTS: A total of 139 FBLs were included with 75/139 (53.9%) benign and 64/139 (46.1%) malignant FBLs. Internal vascularization patterns (p < 0.001), penetrating vessels (p < 0.001), TS 4-5 (p < 0.001) and all 2D-SWE parameters (p < 0.001) were significantly different between benign and malignant FBLs. The BI-RADS score provided an AUC of 0.876 (95% CI 0.810-0.926) for the diagnosis of malignant FBLs. Among the 2D-SWE measurements, an excellent diagnostic performance was observed for Emax with an AUC of 0.915 (95% CI 0.856-0.956) and Emean of 0.908 (95% CI 0.847-0.951). Optimal cutoff for the diagnosis of malignant FBLs were US BI-RADS > 3, Strain Ratio > 2.52, Tsukuba Score > 3, Emax > 82.6 kPa, Emean > 66.0 kPa, Emin > 54.4 kPa and Eratio > 330.8. Multiparametric ultrasound, particularly SWE, can improve specificity in the characterization of FBLs.

Evaluation of coronary microvascular dysfunction using magnetocardiography: A new application to an old technology.

Background: In patients with angina and non-obstructive coronary artery disease (ANOCA), diagnosis of coronary microvascular dysfunction (CMD) remains an unmet need. Magnetocardiography (MCG), is a rest-based, non-invasive scan that can detect weak electrophysiological changes that occur at the early phase of ischemia. Objective: This study assessed the ability of MCG to detect CMD in ANOCA patients as compared to reference standard, invasive coronary flow reserve (CFR). Methods: Patients with ANOCA and invasive coronary physiologic assessment using intracoronary flow measurements with Doppler and thermodilution methods were enrolled. CMD was defined dichotomously as an invasive CFR < 2.0 by Doppler or thermodilution assessment. Noninvasive 36-channel 90-s MCG scan was performed and quantitative assessment of four distinct MCG features was completed. We evaluated the diagnostic performance of 2 or more abnormal MCG features to detect CMD in the overall cohort and performed a subgroup analysis in the subset of patients with Doppler CFR assessment. Results: Among 79 ANOCA patients, 25 were CMD positive and 54 patients were CMD negative by CFR. Using invasive CFR as reference, MCG had an ROC AUC of 0.66 with a sensitivity of 68 % and specificity of 65 % for the detection of CMD. In the subgroup with Doppler CFR assessment, MCG had an ROC AUC of 0.76 with a sensitivity of 75 % and specificity of 77 %. Conclusions: In ANOCA patients, MCG demonstrates the ability to detect CMD using a 90-second non-invasive scan without the need for an intravenous stressor or ionizing radiation. Further investigations are needed to validate an MCG-based diagnostic pathway for CMD.

Exosomes derived from endothelial progenitor cells ameliorate LPS-induced brain microvascular endothelial cells injury by delivering miR-126a-5p.

Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.