The predictive value of lesion-specific pericoronary fat attenuation index for major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to explore the prognostic significance of the lesion-specific pericoronary fat attenuation index (FAI) in forecasting major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). METHODS: This study conducted a retrospective analysis of 304 patients diagnosed with T2DM who underwent coronary computed tomography angiography (CCTA) in our hospital from December 2011 to October 2021. All participants were followed for a period exceeding three years. Detailed clinical data and CCTA imaging features were carefully recorded, encompassing lesion-specific pericoronary FAI, FAI of the three prime coronary arteries, features of high-risk plaques, and the coronary artery calcium score (CACS). The MACE included in the study comprised cardiac death, acute coronary syndrome (which encompasses unstable angina pectoris and myocardial infarction), late-phase coronary revascularization procedures, and hospital admissions prompted by heart failure. RESULTS: Within the three-year follow-up, 76 patients with T2DM suffered from MACE. The lesion-specific pericoronary FAI in patients who experienced MACE was notably higher compared to those without MACE (-84.87 ± 11.36 Hounsfield Units (HU) vs. -88.65 ± 11.89 HU, p = 0.016). Multivariate Cox regression analysis revealed that CACS ≥ 100 (hazard ratio [HR] = 4.071, 95% confidence interval [CI] 2.157-7.683, p < 0.001) and lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.400, 95% CI 1.399-4.120, p = 0.001) were independently associated with heightened risk of MACE in patients with T2DM over a three-year period. Kaplan-Meier analysis showed that patients with higher lesion-specific pericoronary FAI were more likely to develop MACE (p = 0.0023). Additionally, lesions characterized by higher lesion-specific pericoronary FAI values were found to have a greater proportion of high-risk plaques (p = 0.015). Subgroup analysis indicated that lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.017, 95% CI 1.143-3.559, p = 0.015) was independently correlated with MACE in patients with T2DM who have moderate to severe coronary calcification. Moreover, the combination of CACS ≥ 100 and lesion-specific pericoronary FAI>-83.5 HU significantly enhanced the predictive value of MACE in patients with T2DM within 3 years. CONCLUSIONS: The elevated lesion-specific pericoronary FAI emerged as an independent prognostic factor for MACE in patients with T2DM, inclusive of those with moderate to severe coronary artery calcification. Incorporating lesion-specific pericoronary FAI with the CACS provided incremental predictive power for MACE in patients with T2DM.

A new predictor of coronary artery disease in acute ischemic stroke or transient ischemic attack patients: pericarotid fat density.

OBJECTIVES: The study aims to evaluate the incremental predictive value of pericarotid fat density (PFD) on head and neck computed tomography angiography (CTA) for the obstructive coronary artery disease (CAD) (≥ 50% stenosis) relative to a clinical risk model (Framingham risk score (FRS)) and the degree of carotid artery stenosis and plaque type in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients without a known history of CAD. METHODS: In a cohort of 134 consecutive stable patients diagnosed with AIS or TIA undergoing head and neck CTA between January 2010 and December 2021, pericarotid adipose tissue density (PFD) was quantified using a dedicated software. We collected demographic and clinical data, assessed the risk of CAD using the FRS, and analyzed coronary and carotid artery CTA images. Univariate and multivariate logistic regression analyses were performed to assess associations between FRS, PFD, CTA variables, and obstructive CAD risk. Four prediction models were established to evaluate the incremental predictive value of PFD relative to FRS, stenosis degree, and plaque types. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUC) were compared. RESULTS: Increasing FRS, stenosis degree, and PFD values were positively correlated with obstructive CAD (all p < 0.05). In the predictive models for obstructive CAD, the model incorporating carotid stenosis exhibited superior predictive performance compared to FRS alone (p < 0.05). Moreover, the predictive model integrating PFD demonstrated enhanced performance and yielded the highest AUC of the receiver operator characteristic curve (AUC = 0.783), with sensitivity and specificity values of 86.89% and 65.75%, respectively. CONCLUSION: CTA-derived PFD measurements offer supplementary predictive value for obstructive CAD beyond FRS and stenosis, thereby facilitating improved risk stratification of TIA or stroke patients without a history of CAD history. CLINICAL RELEVANCE STATEMENT: CTA-derived PFD provides incremental predictive value for obstructive coronary artery disease in acute ischemic stroke or transient ischemic attack patients without CAD history, beyond Framingham risk score and carotid artery stenosis degree, improving risk stratification. KEY POINTS: • Pericarotid fat density is associated with obstructive coronary artery disease in acute ischemic stroke or transient ischemic attack patients. • Higher pericarotid fat density corresponds to an increased risk of obstructive coronary artery disease. • Estimation of pericarotid fat density using computed tomography angiography imparts additional predictive value for obstructive CAD in risk stratification of acute ischemic stroke or transient ischemic attack patients.

LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis: A protective mechanism in the pathogenesis of atherosclerosis.

Atherosclerosis (AS), a metabolic disorder, is usually caused by chronic inflammation. LETM1 Domain-Containing Protein 1 (LETMD1) is a mitochondrial outer membrane protein required for mitochondrial structure. This study aims to evaluate the functional role of LETMD1 in endothelial pathogenesis of AS. Oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) and high-fat diet apolipoprotein E-deficient (ApoE-/-) mice were used to establish in vitro and in vivo models, respectively. Recombinant adenovirus vectors were constructed to investigate the role of LETMD1 in AS. mRNA sequencing was used to explore the effect of LETMD1 overexpression on gene expression in ox-LDL-induced HUVECs. A dual-luciferase reporting assay and chromatin immunoprecipitation (ChIP)-PCR were further conducted to verify the relationship between KLF4 and LETMD1. Results showed that LETMD1 was highly expressed in the aortas of atherosclerotic animals. LETMD1 overexpression reduced the expression of inflammatory factors, pyroptosis, ROS production, and NF-κB activation in ox-LDL-induced HUVECs, whereas LETMD1 knockdown had the opposite impact. LETMD1 overexpression was involved in regulating gene expression in ox-LDL-induced HUVECs. Overexpression of LETMD1 in mice reduced serum lipid levels as well as atherosclerotic lesions in the aortic roots. Furthermore, LETMD1 overexpression suppressed inflammatory reactions, cell pyroptosis, nuclear p65 protein level, cell apoptosis, and ROS generation in the aortas of AS mice. KLF4 (Krüppel-like factor 4) was found to be the transcriptional regulator of LETMD1. In conclusion, LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis, which is a mechanism inhibiting the development of atherosclerosis.

KPNA2 Silencing, Regulated by E3 Ubiquitin Ligase FBXW7, Alleviates Endothelial Dysfunction and Inflammation Through Inhibiting the Nuclear Translocation of p65 and IRF3: A Possible Therapeutic Approach for Atherosclerosis.

Atherosclerosis (AS), characterized by a maladaptive inflammatory response, is one of the most common causes of death among the elderly. Karyopherin subunit alpha 2 (KPNA2), a member of the nuclear transport protein family, has been reported to play a pro-inflammatory role in various pathological processes by regulating the nuclear translocation of pro-inflammatory transcription factors. However, the function of KPNA2 in AS remains unknown. ApoE-/- mice were fed high-fat diets for 12 weeks to establish an AS mice model. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish an AS cell model. We found that KPNA2 was upregulated in the aortic roots of atherosclerotic mice and LPS-stimulated cells. KPNA2 knockdown inhibited LPS-induced secretion of pro-inflammatory factors and monocyte-endothelial adhesion in HUVECs, whereas KPNA2 overexpression exerted the opposite effects. p65 and interferon regulatory factor 3 (IRF3), the transcription factors known to regulate the transcription of pro-inflammatory genes, interacted with KPNA2, and their nuclear translocations were blocked following KPNA2 silencing. Furthermore, we found that KPNA2 protein level was decreased by E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBXW7), which was downregulated in the atherosclerotic mice. FBXW7 overexpression induced ubiquitination with subsequent proteasomal degradation of KPNA2. Meanwhile, the effects of KPNA2 deficiency on atherosclerotic lesions were further confirmed by in vivo experiments. Taken together, our study indicates that KPNA2 downregulation, regulated by FBXW7, may alleviate endothelial dysfunction and related inflammation in the progression of AS by suppressing the nuclear translocation of p65 and IRF3.

Associations between the serum triglyceride-glucose index and pericoronary adipose tissue attenuation and plaque features using dual-layer spectral detector computed tomography: a cross-sectional study.

Background and aims: The triglyceride-glucose (TyG) index is a reliable alternative marker for insulin resistance (IR). Pericoronary adipose tissue (PCAT) can indirectly reflect coronary inflammation. IR and coronary inflammation play a key role in the development and progression of coronary atherosclerosis. Therefore, this study investigated the relationships between the TyG index, PCAT and atherosclerotic plaque characteristics to explore whether IR might lead to coronary artery atherosclerosis progression by inducing coronary inflammation. Methods: We retrospectively collected data on patients with chest pain who underwent coronary computed tomography angiography using spectral detector computed tomography at our institution from June to December 2021. The patients were grouped based on their TyG index levels: T1 (low), T2 (medium), and T3 (high). Each patient was assessed for total plaque volume, plaque load, maximum stenosis, the plaque component volume proportion, high-risk plaques(HRPs), and plaque characteristics (including low attenuation plaques, positive remodeling, a napkin ring sign, and spot calcification). PCAT quantification was performed on the proximal right coronary artery using the fat attenuation index (FAI) measured from a conventional multicolor computed tomography image (FAI120kVp), a spectral virtual single-energy image (FAI40keV), and the slope of the spectral HU curve (λHU). Results: We enrolled 201 patients. The proportion of patients with maximum plaque stenosis, positive remodeling, low-density plaques, and HRPs increased as the TyG index level increased. Moreover, the FAI40keV and λHU significantly differed among the three groups, and we identified good positive correlations between FAI40keV and λHU and the TyG index (r = 0.319, P <0.01 and r = 0.325, P <0.01, respectively). FAI120kVp did not significantly differ among the groups. FAI40keV had the highest area under the curve, with an optimal cutoff value of -130.5 HU for predicting a TyG index value of ≥9.13. The multivariate linear regression analysis demonstrated that FAI40keV and λHU were independently positively related to a high TyG index level (standardized regression coefficients: 0.117 [P <0.001] and 0.134 [P <0.001], respectively). Conclusions: Patients with chest pain and a higher TyG index level were more likely to have severe stenosis and HRPs. Moreover, FAI40keV and λHU had good correlations with the serum TyG index, which may noninvasively reflect PCAT inflammation under insulin resistance. These results could help explain the mechanism of plaque progression and instability in patients with insulin resistance might be related to IR-induced coronary inflammation.

Prediction of high-risk esophageal varices in patients with chronic liver disease with point and 2D shear wave elastography: a systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic performance of liver stiffness (LS) and spleen stiffness (SS) measured by point shear wave elastography (pSWE) and 2D shear wave elastography (2D-SWE) in the detection of high-risk esophageal varices (HREV) and to compare their diagnostic accuracy. METHODS: Through systematic search of PubMed, Embase, and Web of Science databases, we included 17 articles reporting the diagnostic performance of LS or SS measured by pSWE or 2D-SWE for HREV. We used a bivariate random-effects model to estimate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under summary receiver operator characteristic curve (AUSROC), and diagnostic odds ratio (DOR). RESULTS: For LS, there was no significant difference between the pooled sensitivity, 0.89 (95% confidence interval CI, 0.81-0.94) vs. 0.8 (95% CI, 0.72-0.86) (p = 0.13), and specificity, 0.81 (95% CI, 0.73-0.87) vs. 0.73 (95% CI, 0.65-0.79) (p = 0.07) of pSWE and 2D-SWE. The AUSROC and DOR of pSWE were higher than those of 2D-SWE: 0.92 (95% CI, 0.89-0.94) vs. 0.84 (95% CI, 0.80-0.87), p = 0.03, 33 (95% CI, 25-61) vs. 11 (95% CI, 5-22), (p < 0.01). For SS, there was no significant difference between the pooled sensitivity 0.91 (95% CI, 0.78-0.96) vs. 0.89 (95% CI, 0.80-0.94) (p = 0.43); specificity, 0.79 (95% CI, 0.72-0.84) vs. 0.72 (95% CI, 0.63-0.79) (p = 0.06); and DOR, 35 (95% CI, 13-100) vs. 20 (95% CI, 8-50) (p = 0.16) of pSWE and 2D-SWE. CONCLUSION: LS and SS measured by pSWE and 2D-SWE have good accuracy in predicting HREV. KEY POINTS: • There is modest difference between the diagnostic performance of LS and SS measured by pSWE and 2D-SWE. • LS and SS measured by pSWE and 2D-SWE both have high sensitivity, specificity, and AUSROC for the evaluation of HREV in patients with CLD. • pSWE and 2D-SWE are promising tools for noninvasive monitoring risk of esophageal varices bleeding of CLD patients.

Retraction notice to "Application of transthoracic shear wave elastography in evaluating subpleural pulmonary lesions" [Eur. J. Radiol. Open 8C (2021) 100364].

[This retracts the article DOI: 10.1016/j.ejro.2021.100364.].

Systematic Review and Meta-Analysis of Drug-Coated Balloon Angioplasty for In-Stent Restenosis in Femoropopliteal Artery Disease.

PURPOSE: The present meta-analysis evaluated the role of drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR) in femoropopliteal artery disease. MATERIALS AND METHODS: Cochrane Library, Embase, and PubMed were searched without language restrictions from inception to May 10, 2020. The endpoints included target lesion revascularization (TLR), recurrent ISR, clinical improvement, ankle-brachial index (ABI), and death. There were 5 randomized controlled trials with 425 patients (218 with DCB angioplasty and 207 with plain old balloon angioplasty [POBA]) were included in the meta-analysis. RESULTS: Compared with POBA, DCB angioplasty was associated with lower risk of TLR (odds ratio [OR], 0.21; 95% confidence interval [CI]: 0.09-0.49, P < .001 at 6 months and OR, 0.15; 95% CI, 0.08-0.30; P < .001 at 12 months) and recurrent ISR (OR, 0.22; 95% CI, 0.13-0.38; P < .001 at 6 months and OR, 0.31; 95% CI, 0.16-0.61; P < .001 at 12 months), and superior clinical improvement (OR, 1.98; 95% CI, 1.07-3.65; P = .03 at 6 months and OR, 2.84; 95% CI: 1.50-5.35; P = .001 at 12 months). There were no significant differences between groups in ABI and death. Subgroup analysis for patients with DCB angioplasty showed similar rates of TLR, recurrent ISR, clinical improvement, and death between the short lesion (<15 cm) and long lesion group (≥15 cm) (P > .05). CONCLUSIONS: The current meta-analysis suggests that DCB angioplasty is an improvement over POBA for femoropopliteal ISR. Future studies about the effect of lesion length on DCB performance are still needed.

Application of Transthoracic Shear Wave Elastography in Evaluating Subpleural Pulmonary Lesions.

AIM: The objective of this research was to investigate the feasibility of transthoracic shear wave elastography in the differentiation of subpleural masses. METHODS: Between December 2019 and November 2020,82 consecutive patients with radiographic evidence (including chest X ray and thoracic computed tomography CT) of single subpleural lesion enrolled in this research. The Young's modulus E (including Emean and Emax) of each lesion was detected, and the Young's modulus E of malignant lesions were compared with those of benign ones. We made diagnoses according to the results of pathology or standard clinical course for at least 3 months. Receiver operating characteristic (ROC) analysis was plotted to determine the cut-off point by maximizing the Youden index. RESULTS: The Emean and Emax of the benign and malignant group was 34.68 ± 12.12 kPa vs. 53.82 ± 11.95 kPa (p < 0.001), 57.77 ± 14.45 kPa vs. 76.62 ± 17.04 kPa (p < 0.001). The ROC of Emean showed that when the cut-off point was 43.8 kPa, the Youden index (0.53) for distinguishing benign and malignant tumors was the largest (sensitivity 80.4 %, specificity 72.2 %, AUC = 0.848, p < 0.0001). When the cut-off point recommended by Emax ROC was 73.5 kPa, the Youden index (0.44) for distinguishing benign and malignant tumors was the largest (sensitivity 76.1 %, specificity 66.7 %, AUC = 0.780, p < 0.0001). CONCLUSIONS: This study demonstrated that we can employ transthoracic shear wave elastography as a valuable instrument in differentiating benign subpleural lesions from malign ones.

Feasibility of low-dose contrast media in run-off CT angiography on dual-layer spectral detector CT.

BACKGROUND: The aim of the present study was to assess the feasibility of applying low-dose contrast media (CM), and to explore the optimal virtual monoenergetic images (VMIs) in run-off computed tomography (CT) angiography (CTA) on dual-layer spectral detector CT (SDCT). METHODS: Forty patients were randomly assigned into a control group using routine volume CM (group A) and an experimental group using half-volume CM (group B). In groups A and B, 120 kVp polychromatic conventional images were generated via hybrid iterative reconstruction algorithm defined as A1 and B1, respectively. Additionally, in group B, VMIs (range, 40-120 keV) were reconstructed via a spectral reconstruction algorithm defined as B2-B10. Vascular attenuation, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and radiation dose were evaluated. Subjective evaluation was performed using a 5-point scale. RESULTS: The patient demographics and radiation dose demonstrated no significant difference between groups A and B [dose length product (DLP): 1,823.45±512.68 vs. 2,014.40±453.25 mGy·cm, P=0.229; volume CT dose index: 14.92±3.40 vs. 16.26±2.85 mGy, P=0.208; the effective dose (ED): 10.82±3.02 vs. 11.88±2.67 mSv, P=0.229]. The mean vascular attenuation was higher in group B2 (40 keV) and was lower in group B3 (50 keV) in comparison with that in group A1 (487.07±154.21 vs. 414.35±71.66 HU, 329.90±100.25 vs. 414.35±71.66 HU, P>0.05). Compared with group A1, the mean noise was similar in group B2 (40 keV) and was lower in group B1 and groups B3-B10 (50-120 keV) (14.81±5.67 vs. 17.29±4.70 HU, P>0.05; 6.75±1.23-11.26±3.24 vs. 17.29±4.70 HU, P<0.05). The mean SNR and CNR in group B2 (40 keV), as well as the mean SNR in group B3 (50 keV), were significantly higher than those of group A1 (38.21±7.52 vs. 28.25±7.20, 32.70±7.79 vs. 24.54±6.60, 32.85±7.10 vs. 28.25±7.20, P<0.05), and the mean CNR in group B3 (50 keV) was similar to that in group A1 (26.66±7.32 vs. 24.54±6.60, P>0.05). Scores of subjective image quality (IQ) in group B2 (40 keV) and B3 (50 keV) were similar to those in group A1 {5 [4.25, 5] vs. 5 [4, 5], 5 [5, 5] vs. 5 [4, 5], P>0.05}, and showed a declining trend in group B4 (60 keV) {4 [4, 5] vs. 5 [4, 5], P>0.05}. CONCLUSIONS: It is feasible to perform run-off CTA using low-dose CM with VMI on SDCT. The VMIs at 40-50 keV were the optimal choice and did not compromise IQ.

Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2 respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3; p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p < .01), while only Definity and SonoVue increased efficacy in the low power cohort (p < .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.

Assessment of Virtual Monoenergetic Images in Run-off Computed Tomography Angiography: A Comparison Study to Conventional Images From Spectral Detector Computed Tomography.

OBJECTIVE: The aims of this study were to evaluate image quality of virtual monoenergetic images (VMIs) compared with conventional images (CIs) from spectral detector CT (SDCT) and to explore the optimal energy level in run-off computed tomography angiography (CTA). METHODS: The data sets of 35 patients who received run-off CTA on the SDCT were collected in this retrospective study. Conventional images were generated via iterative reconstruction algorithm and VMI series from 40 to 120 keV were generated via spectral reconstruction algorithm. The objective indices including vascular attenuation, noise, signal-to-noise ratio, and contrast-to-noise ratio were compared. Two readers performed subjective evaluation using a 5-point scale. RESULTS: The attenuation showed higher values compared with CIs at 40 to 60 keV (P < 0.001). The noise was similar in 60- to 80-keV VMIs and significantly decreased in 90- to 120-keV VMIs (P < 0.001) in comparison with CIs. The signal-to-noise ratio and contrast-to-noise ratio were improved in 40- to 60-keV VMIs compared with CIs (P < 0.05). The score of subjective assessment was higher than that of CIs in 50- to 70-keV VMIs (P < 0.001). CONCLUSIONS: Virtual monoenergetic images can provide improved image quality compared with CIs from SDCT in run-off CTA, and VMIs at 60 keV may be the best choice in evaluating lower extremity arteries.

[Diagnosis of glutaric acidemia type â ¡C by fetal whole exome sequencing].

OBJECTIVE: To explore the genetic basis of a fetus with enlargement and enhanced echo of the kidneys. METHODS: The imaging data of the fetus were collected, in addition with 20 mL amniotic fluid sample and 2 mL peripheral blood samples of both parents. Amniotic DNA was extracted for library construction and whole exome sequencing, and Sanger sequencing was carried out to verify candidate variant associated with the fetal phenotype. RESULTS: Prenatal ultrasound showed that the fetus had enlargement and enhanced echo of the kidneys, in addition with many small renal cysts. Whole exome sequencing showed that the fetus carried pathogenic compound heterozygous variants of the ETFDH gene, namely c.3G>C and c.1436dupA. Sanger sequencing of the family suggested that the variants were inherited from its mother and father, respectively. CONCLUSION: By combining its clinical manifestations and results of whole exome sequencing, the fetus was diagnosed as glutaric acidemia type ⅡC due to the compound heterozygous variants of the ETFDH gene. Above results have provided a basis for prenatal diagnosis and genetic counseling. Fetal exome sequencing has provided an important tool for prenatal diagnosis.

Impact of pulmonary interstitial lesions on efficacy and prognosis of EGFR-TKI-treated advanced non-small cell lung cancers.

BACKGROUND: This study aimed to assess the impact of pre-existing pulmonary interstitial lesions (PIL) on the efficacy and prognosis of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitor (TKI). METHODS: Patients with advanced NSCLC harboring EGFR exon 19 deletion (E19 del) or exon 21 (E21) L858R were enrolled in this study. All patients underwent high resolution computed tomography (HRCT) chest scans prior to EGFR-TKI treatment. Pre-existing PIL was graded according to HRCT imaging (PIL 0, 1, 2, and 3). Cox proportional-hazards regression models were used to identify the prognostic factors for progression-free survival (PFS). RESULTS: A total of 134 eligible patients were enrolled. The overall objective response rate (ORR) and median PFS were 73.1% and 10.0 months (95% CI: 7.51-12.49), respectively. There were 62 (46.3%), 25 (18.7%), 28 (20.9%), and 19 (14.1%) cases of PIL grade 0, 1, 2, and 3, respectively, with median PFS and ORR of 12.9 months and 80.6%, 11.0 months and 72.0%, 10.0 months and 71.4%, and 7.0 months and 52.6%, respectively. Multivariate analysis showed that squamous cell carcinoma (vs. adenocarcinoma, HR =4.33), E21 L858R (vs. E19 del, HR =1.57), and PIL grade 3 (vs. grade 0-2, HR =1.60-2.48) were poor prognostic factors for PFS (P<0.05 for all). CONCLUSIONS: Pre-existing PIL grade is an independent prognostic factor for predicting resistance to EGFR-TKIs in patients with EGFR-mutant advanced NSCLC. Higher PIL grade suggests higher risk of early progression.

Platelet to lymphocyte ratio predicting 6-month primary patency of drug-coated balloon for femoropopliteal disease.

BACKGROUND: Inflammatory reaction is an essential factor in the occurrence, development and prognosis of femoropopliteal disease (FPD). The ratio of platelets to lymphocytes (PLR) is a new indicator reflecting platelet aggregation and burden of systemic inflammation. Our study is to explore the association between preoperative platelet-to-lymphocyte ratio (pre-PLR) and 6-month primary patency (PP) after drug-coated balloon (DCB) in FPD. METHODS: There were 70 patients who underwent DCB for FPD contained in the study. According to 6-month PP, patients were divided into group A (PP ≥6 months, n = 54) and group B (PP < 6 months, n = 16). Logistic regression analysis was used to identify potential predictors for 6-month PP after DCB in FPD. A receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value of pre-PLR to predict 6-month PP. RESULTS: Logistic regression analysis showed that pre-PLR (OR: 1.008, 95% CI: 1.001-1.016, P = 0.031) and lesion length > 10 cm (OR: 4.305, 95% CI: 1.061-17.465, P = 0.041) were independently predictive for 6-month PP. The cutoff value of pre-PLR obtained from the ROC analysis was 127.35 to determine 6-month PP with the area of 0.839. Subgroup analysis was conducted based on the cutoff value of pre-PLR. The 6-month PP in the group of pre-PLR < 127.35 was higher than that of pre-PLR ≥ 127.35 group (p < 0.001). CONCLUSIONS: The present study indicated that an elevated pre-PLR was an effective additional indicator for predicting early PP in FPD after DCB.

Lower Limb Arterial Calcification and Acute Thrombosis Risk in Patients with Peripheral Artery Disease.

BACKGROUND: Calcification is closely related to in situ thrombosis secondary to plaque rupture in the coronary artery. However, the association between calcification in lower extremity arteries and acute thrombosis has not been assessed. We thus sought to determine whether lower limb arterial calcification (LLAC) was correlated with acute thrombosis in patients with symptomatic peripheral artery disease (PAD). METHODS: We retrospectively reviewed consecutive patients presenting with symptomatic PAD between April 2017 and March 2018 who underwent lower extremity arterial evaluation by computed tomography (CT) angiography. Patient characteristics and cardiovascular risk factors were recorded, and LLAC scores were determined by noncontrast CT scans. Univariate and multivariate logistic regression was used to identify factors associated with acute thrombosis. RESULTS: The record search identified 201 patients with symptomatic PAD, including 24 with acute thrombosis and 177 without. Patients in the acute thrombosis group were significantly younger (P = 0.04) and had less diabetes mellitus (P = 0.04). Patients with acute thrombosis had more advanced ischemia at presentation (P < 0.01) and higher amputation rate within 30 days (P < 0.01). Univariate regression showed a significant association among acute thrombosis and age, diabetes mellitus, and LLAC score; in multivariable analysis, only the LLAC score (odds ratio 0.60, 95% confidence interval 0.37-0.98) maintained an association with acute thrombosis after adjusting for relevant risk factors. CONCLUSIONS: The LLAC score is independently and inversely associated with acute thrombosis in patients with PAD.

Directional Atherectomy with Antirestenotic Therapy for Femoropopliteal Artery Disease: A Systematic Review and Meta-Analysis.

Systematic literature searches using Embase, PubMed, and Cochrane Library for directional atherectomy with antirestenotic therapy (DAART) in femoropopliteal artery disease (FPAD) from January 2003 to February 2018 were conducted to evaluate clinical safety and effectiveness. A meta-analysis was conducted using Stata software for the event rate of technical success, bailout stent placement, primary patency, and target lesion revascularization (TLR) at 12 months. Five studies with 189 patients who received DAART were included in the meta-analysis. Pooled rates of technical success and bailout stent placement were 90.4% (95% confidence interval [CI] 86.3%-94.6%) and 4.8% (95% CI 0.7%-8.9%), respectively. Primary patency and TLR at 12 months were 85.3% (95% CI 79.6%-91.1%) and 5.5% (95% CI 1.9%-9.1%), respectively. Meta-analysis of 3 comparative studies demonstrated that DAART was not superior in performance in clinical endpoints, including technical success, bailout stent placement, primary patency, and TLR at 12 months (relative risk [RR] 1.111, 95% CI 0.896-1.377, P = .337; RR 0.400, 95% CI 0.120-1.332, P = .135; RR 1.136, 95% CI 0.841-1.535, P = .405; and RR 0.722, 95% CI 0.291-1.789, P = .482). The data did not suggest that DAART was an improvement over paclitaxel-coated balloon angioplasty for FPAD. The theoretical advantages of DAART still require further confirmation.

A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma.

Purpose: The aim of this pooled analysis was to evaluate the clinical efficacy and safety of transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma (ICC). Methods: We searched the Cochrane Library, Embase, PubMed, SCI with the English language from inception to October 2018. A pooled analysis was conducted using Stata software. Results: There were 16 eligible studies included in this pooled analysis. The pooled median overall survival (OS) from 12 studies was 14.3 (95% CI: 11.9-17.1) months. Based on Response Evaluation Criteria in Solid Tumors (RECIST), no complete response was reported, and the median of partial response, stable disease and progressive disease were 11.5% (range: 4.8-35.3%), 61.5% (range: 42.9-81.3%) and 22.7% (range: 12.5-52.4%) respectively. The pooled disease control rate (DCR) from nine studies was 77.2% (95% CI: 70.2-84.2%). According to the type of microspheres, subgroup analysis was performed, the median OS in the glass microspheres group was 14.0 (95% CI: 9.1-21.4) months, and 14.3 (95% CI: 11.5-17.8) months in the resin microspheres group. The DCR was 77.3% (95% CI: 63.5-91.1%) and 77.4% (95% CI: 66.8-87.9%) in the glass and resin microspheres groups respectively. Most of the side effects reported in the included studies were mild and did not require intervention. Conclusion: TARE with 90Y microspheres is safe and effective for patients with unresectable ICC with acceptable side effects. And it seems that the type of microsphere has no influence on therapeutic efficacy.

Relationship Between Postoperative Neutrophil-Lymphocyte Ratio and 6-Month Primary Patency of Percutaneous Transluminal Angioplasty in Femoropopliteal disease With Drug-Coated and Uncoated Balloons.

We investigated the relationship of postoperative neutrophil-lymphocyte ratio (NLR) with 6-month primary patency of percutaneous transluminal angioplasty (PTA) in femoropopliteal disease using drug-coated balloon (DCB) or uncoated balloon (UCB). This retrospective study included 106 patients who received DCB (n = 44) or UCB (n = 62). The postoperative NLR was lower in the DCB group than that in the UCB group (2.60 vs 3.23; P = .004), and 6-month primary patency rate was significantly higher in DCB group than that in the UCB group (77.3% vs 53.2%; P = .011). Multivariate logistic analysis showed that the postoperative NLR was an independent predictor of 6-month primary patency after PTA in patients with femoropopliteal disease (odds ratio: 1.589, 95% confidence interval: 1.078-2.343; P = .019). The cutoff value of postoperative NLR was 3.05 for prediction of 6-month primary patency, with a sensitivity of 64.1% and specificity of 65.7%. The 6-month primary patency rate in the NLR ≤3.05 group was higher than that in the NLR >3.05 group (75.9% vs 47.9%; P = .003). In conclusion, DCB may improve early primary patency by inhibiting inflammation. A higher postoperative NLR was associated with early restenosis.