Circadian regulator BMAL1::CLOCK promotes cell proliferation in hepatocellular carcinoma by controlling apoptosis and cell cycle.

Hepatocellular carcinoma (HCC) remains a global health challenge whose incidence is growing worldwide. Previous evidence strongly supported the notion that the circadian clock controls physiological homeostasis of the liver and plays a key role in hepatocarcinogenesis. Despite the progress, cellular and molecular mechanisms underpinning this HCC-clock crosstalk remain unknown. Addressing this knowledge gap, we show here that although the human HCC cells Hep3B, HepG2, and Huh7 displayed variations in circadian rhythm profiles, all cells relied on the master circadian clock transcription factors, BMAL1 and CLOCK, for sustained cell growth. Down-regulating Bmal1 or Clock in the HCC cells induced apoptosis and arrested cell cycle at the G2/M phase. Mechanistically, we found that inhibiting Bmal1/Clock induced dysregulation of the cell cycle regulators Wee1 and p21 which cooperatively contribute to tumor cell death. Bmal1/Clock knockdown caused downregulation of Wee1 that led to apoptosis activation and upregulation of p21 which arrested the cell cycle at the G2/M phase. Collectively, our results suggest that the circadian clock regulators BMAL1 and CLOCK promote HCC cell proliferation by controlling Wee1 and p21 levels, thereby preventing apoptosis and cell cycle arrest. Our findings shed light on cellular impact of the clock proteins for maintaining HCC oncogenesis and provide proof-of-principle for developing cancer therapy based on modulation of the circadian clock.

Cell-permeable JNK-inhibitory peptide regulates intestinal barrier function and inflammation to ameliorate necrotizing enterocolitis.

Intestinal dysbiosis is believed to play a role in the development of necrotizing enterocolitis (NEC). The efficacy of JNK-inhibitory peptide (CPJIP) in treating NEC was assessed. Treatment with CPJIP led to a notable reduction in p-JNK expression in IEC-6 cells and NEC mice. Following LPS stimulation, the expression of RNA and protein of claudin-1, claudin-3, claudin-4 and occludin was significantly decreased, with this decrease being reversed by CPJIP administration, except for claudin-3, which remained consistent in NEC mice. Moreover, the expression levels of the inflammatory factors TNF-α, IL-1ß and IL-6 were markedly elevated, a phenomenon that was effectively mitigated by the addition of CPJIP in both IEC-6 cells and NEC mice. CPJIP administration resulted in improved survival rates, ameliorated microscopic intestinal mucosal injury, and increased the total length of the intestines and colon in NEC mice. Additionally, CPJIP treatment led to a reduction in serum concentrations of FD-4, D-lactate and DAO. Furthermore, our results revealed that CPJIP effectively inhibited intestinal cell apoptosis and promoted cell proliferation in the intestine. This study represents the first documentation of CPJIP's ability to enhance the expression of tight junction components, suppress inflammatory responses, and rescue intestinal cell fate by inhibiting JNK activation, ultimately mitigating intestinal severity. These findings suggest that CPJIP has the potential to serve as a promising candidate for the treatment of NEC.

Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report.

BACKGROUND: Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature. CASE PRESENTATION: A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH. CONCLUSIONS: Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.

Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Endovascular reconstruction of high cervical and long-segment carotid artery dissections with Leo plus stent.

PURPOSE: Endovascular reconstruction has emerged as a viable alternative for carotid artery dissections (CADs) that are unresponsive to antithrombotic therapy. However, high cervical and long-segment CADs pose challenges during endovascular treatment due to their distal location and tortuous anatomy. We presented our experiences using endovascular reconstruction with the Leo plus stent for this type of CAD. METHODS: We conducted a retrospective review of patients with high cervical and long-segment CADs treated using the Leo plus stent. We analyzed patient demographics, clinical presentations, procedural features, complications, and follow-up outcomes. RESULTS: A total of 17 patients (mean age, 48.1 years) with 17 CADs were identified. Seven of these dissections were accompanied by pseudoaneurysm. The mean length of the dissection was 5.7 cm, and the mean degree of stenosis was 92.3%. A single Leo plus stent was deployed in 15 patients, while another Wallstent carotid stent was used in 2 cases. All stents were successfully positioned in their intended sites. The average degree of residual stenosis was 22.2%. There were no perioperative complications. With a median follow-up duration of 29 months, no ischemic stroke events occurred. All but one Leo plus stent remained patent during follow-up, and all 7 pseudoaneurysms had disappeared at the last radiological assessment. CONCLUSION: Our experience in treating high cervical and long-segment CADs with the Leo plus stent demonstrates that this approach is practical, safe, and effective, as evidenced by long-term observations. The Leo Plus stent appears to be a suitable option for managing this type of CAD.

Lacidipine Inhibits NF-κB and Notch Pathways and Mitigates DSS-Induced Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with a global incidence that is rising. Despite the increasing prevalence, effective treatment options for UC remain limited. METHODS: We utilized an NF-κB promoter dual fluorescence reporter system to screen for compounds that could inhibit p65 and IκBα phosphorylation. The anti-hypertension drug lacidipine was identified as a candidate. Its efficacy was further evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. The analysis included the assessment of colon lesions, inflammation markers, and signal pathway activation, with a focus on NF-κB and Notch signaling. RESULTS: Lacidipine effectively inhibited p65 and IκBα phosphorylation in the reporter system. In the DSS-induced colitis murine model, lacidipine treatment led to a reduction in colon lesions and inflammatory markers. Target analysis showed significant enrichment of the Notch signaling pathway. Additionally, lacidipine inhibited both NF-κB and Notch activation in DSS-stimulated colons. CONCLUSION: Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC.

CancerMIRNome: an interactive analysis and visualization database for miRNome profiles of human cancer.

MicroRNAs (miRNAs), which play critical roles in gene regulatory networks, have emerged as promising diagnostic and prognostic biomarkers for human cancer. In particular, circulating miRNAs that are secreted into circulation exist in remarkably stable forms, and have enormous potential to be leveraged as non-invasive biomarkers for early cancer detection. Novel and user-friendly tools are desperately needed to facilitate data mining of the vast amount of miRNA expression data from The Cancer Genome Atlas (TCGA) and large-scale circulating miRNA profiling studies. To fill this void, we developed CancerMIRNome, a comprehensive database for the interactive analysis and visualization of miRNA expression profiles based on 10 554 samples from 33 TCGA projects and 28 633 samples from 40 public circulating miRNome datasets. A series of cutting-edge bioinformatics tools and machine learning algorithms have been packaged in CancerMIRNome, allowing for the pan-cancer analysis of a miRNA of interest across multiple cancer types and the comprehensive analysis of miRNome profiles to identify dysregulated miRNAs and develop diagnostic or prognostic signatures. The data analysis and visualization modules will greatly facilitate the exploit of the valuable resources and promote translational application of miRNA biomarkers in cancer. The CancerMIRNome database is publicly available at http://bioinfo.jialab-ucr.org/CancerMIRNome.

Takotsubo syndrome is a coronary microvascular disease: experimental evidence.

BACKGROUND AND AIMS: Takotsubo syndrome (TTS) is a conundrum without consensus about the cause. In a murine model of coronary microvascular dysfunction (CMD), abnormalities in myocardial perfusion played a key role in the development of TTS. METHODS AND RESULTS: Vascular Kv1.5 channels connect coronary blood flow to myocardial metabolism and their deletion mimics the phenotype of CMD. To determine if TTS is related to CMD, wild-type (WT), Kv1.5-/-, and TgKv1.5-/- (Kv1.5-/- with smooth muscle-specific expression Kv1.5 channels) mice were studied following transaortic constriction (TAC). Measurements of left ventricular (LV) fractional shortening (FS) in base and apex, and myocardial blood flow (MBF) were completed with standard and contrast echocardiography. Ribonucleic Acid deep sequencing was performed on LV apex and base from WT and Kv1.5-/- (control and TAC). Changes in gene expression were confirmed by real-time-polymerase chain reaction. MBF was increased with chromonar or by smooth muscle expression of Kv1.5 channels in the TgKv1.5-/-. TAC-induced systolic apical ballooning in Kv1.5-/-, shown as negative FS (P < 0.05 vs. base), which was not observed in WT, Kv1.5-/- with chromonar, or TgKv1.5-/-. Following TAC in Kv1.5-/-, MBF was lower in LV apex than in base. Increasing MBF with either chromonar or in TgKv1.5-/- normalized perfusion and function between LV apex and base (P = NS). Some genetic changes during TTS were reversed by chromonar, suggesting these were independent of TAC and more related to TTS. CONCLUSION: Abnormalities in flow regulation between the LV apex and base cause TTS. When perfusion is normalized between the two regions, normal ventricular function is restored.

Boosting predictabilities of agronomic traits in rice using bivariate genomic selection.

The multivariate genomic selection (GS) models have not been adequately studied and their potential remains unclear. In this study, we developed a highly efficient bivariate (2D) GS method and demonstrated its significant advantages over the univariate (1D) rival methods using a rice dataset, where four traditional traits (i.e. yield, 1000-grain weight, grain number and tiller number) as well as 1000 metabolomic traits were analyzed. The novelty of the method is the incorporation of the HAT methodology in the 2D BLUP GS model such that the computational efficiency has been dramatically increased by avoiding the conventional cross-validation. The results indicated that (1) the 2D BLUP-HAT GS analysis generally produces higher predictabilities for two traits than those achieved by the analysis of individual traits using 1D GS model, and (2) selected metabolites may be utilized as ancillary traits in the new 2D BLUP-HAT GS method to further boost the predictability of traditional traits, especially for agronomically important traits with low 1D predictabilities.

Extended application of genomic selection to screen multiomics data for prognostic signatures of prostate cancer.

Prognostic tests using expression profiles of several dozen genes help provide treatment choices for prostate cancer (PCa). However, these tests require improvement to meet the clinical need for resolving overtreatment, which continues to be a pervasive problem in PCa management. Genomic selection (GS) methodology, which utilizes whole-genome markers to predict agronomic traits, was adopted in this study for PCa prognosis. We leveraged The Cancer Genome Atlas (TCGA) database to evaluate the prediction performance of six GS methods and seven omics data combinations, which showed that the Best Linear Unbiased Prediction (BLUP) model outperformed the other methods regarding predictability and computational efficiency. Leveraging the BLUP-HAT method, an accelerated version of BLUP, we demonstrated that using expression data of a large number of disease-relevant genes and with an integration of other omics data (i.e. miRNAs) significantly increased outcome predictability when compared with panels consisting of a small number of genes. Finally, we developed a novel stepwise forward selection BLUP-HAT method to facilitate searching multiomics data for predictor variables with prognostic potential. The new method was applied to the TCGA data to derive mRNA and miRNA expression signatures for predicting relapse-free survival of PCa, which were validated in six independent cohorts. This is a transdisciplinary adoption of the highly efficient BLUP-HAT method and its derived algorithms to analyze multiomics data for PCa prognosis. The results demonstrated the efficacy and robustness of the new methodology in developing prognostic models in PCa, suggesting a potential utility in managing other types of cancer.

Observation of Electronic Strong Correlation in VTe_{2}-2sqrt[3]×2sqrt[3] Monolayer.

Strong electron correlation under two-dimensional limit is intensely studied in the transition metal dichalcogenides monolayers, mostly within their charge density wave (CDW) states that host a star of David period. Here, by using scanning tunneling microscopy and spectroscopy and density functional theory calculations with on-site Hubbard corrections, we study the VTe_{2} monolayer with a different 2sqrt[3]×2sqrt[3] CDW period. We find that the dimerization of neighboring Te-Te and V-V atoms occurs during the CDW transition, and that the strong correlation effect opens a Mott-like full gap at Fermi energy (E_{F}). We further demonstrate that such a Mott phenomenon is ascribed to the combination of the CDW transition and on-site Coulomb interactions. Our work provides a new platform for exploring Mott physics in 2D materials.

Iron Vacancy Tunable Superconductor-Insulator Transition in FeSe/SrTiO_{3} Monolayer.

The Fe_{4}Se_{5} with a sqrt[5]×sqrt[5] Fe vacancy order is suggested to be a Mott insulator and the parent state of bulk FeSe superconductor. The iron vacancy ordered state has been considered as a Mott insulator and the parent compound of bulk FeSe-based superconductors. However, for the superconducting FeSe/SrTiO_{3} monolayer (FeSe/STO) with an interface-enhanced high transition temperature (T_{c}), the electronic evolution from its Fe vacancy ordered parent phase to the superconducting state, has not been explored due to the challenge to realize an Fe vacancy order in the FeSe/STO monolayer, even though important to the understanding of superconductivity mechanism. In this study, we developed a new method to generate Fe vacancies within the FeSe/STO monolayer in a tunable fashion, with the assistance of atomic hydrogen. As a consequence, an insulating sqrt[5]×sqrt[5] Fe vacancy ordered monolayer is realized as the parent state. By using scanning tunneling microscopy and scanning tunneling spectroscopy, the spectral evolution from superconductivity to insulator is fully characterized. Surprisingly, a prominent spectral weight transfer occurs, thus implying a strong electron correlation effect. Moreover, the Fe vacancy induced insulating gap exhibits no Mott gap-like features. This work provides new insights in understanding the high-T_{c} superconductivity in FeSe/STO monolayer.

Injectable Colloidal Hydrogels of N-Vinylformamide Microgels Dispersed in Covalently Interlinked pH-Responsive Methacrylic Acid-Based Microgels.

Injectable hydrogels offer great potential to augment damaged or degenerated soft tissues. A key criterion for such gels is that their modulus is as close as possible to that of the target tissue. The majority of synthetic hydrogels have used low molecular weight polymer chains which may cause problems if they diffuse away from the injection site and/or increase the local osmotic pressure. We previously introduced a different approach of injecting preformed ultra-high molecular weight pH-responsive microgels (MGs) that interlink to form hydrogels. MGs are crosslinked polymer colloid particles that swell when the pH approaches the particle pKa. These colloidal hydrogels are termed doubly crosslinked microgels (DX MGs). The gel moduli of previous DX MGs were much greater than that reported for human nucleus pulposus (NP) tissue of the spinal intervertebral disk. Here, we replace some of the pH-responsive poly(ethyl acrylate-co-methacrylic acid) (PEA-MAA) MGs with hydrophilic non-ionic MGs based on poly(N-vinylformamide) (NVF). We investigate the morphology and mechanical properties of these new injectable composite DX MGs and show that the mechanical properties can be tuned by systematically varying the NVF MG content. Using this approach, the gel moduli close to that for NP tissue are achieved. These injectable new pH-responsive gels exhibit low cytotoxicity. Our work provides a potential new system for minimally invasive intervertebral disk augmentation.

Predictors of malignant middle cerebral artery infarction after endovascular thrombectomy: results of DIRECT-MT trial.

OBJECTIVES: Predictors of malignant middle cerebral artery infarction (mMCAi) in patients after intravenous thrombolysis were well documented, but the risk factors of mMCAi after endovascular thrombectomy (EVT) were not fully explored. Therefore, the present study aimed to investigate the predictors of mMCAi after EVT in stroke patients. METHODS: This was a secondary analysis of the DIRECT-MT trial. Patients who underwent EVT for the occlusions of MCA and/or intracranial internal carotid artery were analyzed. Primary outcome was the occurrence of mMCAi after EVT. Demographic, clinical, imaging, and treatment data were recorded, and multivariate logistic regression analysis was used to identify independent predictors. All of the candidate predictors were included, and forward elimination was applied to establish the most effective predictive model. Predictive ability and calibration of the model were assessed using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test, respectively. RESULTS: Of 559 enrolled patients, 74 (13.2%) patients developed mMCAi. Predictors of mMCAi included unsuccessful reperfusion, higher serum glucose, lower Alberta Stroke Project Early Computed Tomography Change Score (ASPECTS), higher clot burden score (CBS), lower collateral score, and higher pass number of thrombectomy device. AUC of predictive model integrating all independent variables was 0.836. The Hosmer-Lemeshow test showed appropriate calibration (p = 0.859). CONCLUSIONS: Reperfusion, serum glucose, ASPECTS, CBS, collateral, and pass number of thrombectomy device were associated with the occurrence of mMCAi in stroke patients after EVT, while alteplase treatment was not. Our findings might facilitate the early identification and management of stroke patients at a high risk of mMCAi. KEY POINTS: • A total of 13.2% of stroke patients with large vessel occlusion of anterior circulation developed mMCAi after EVT. • The occurrence of mMCAi had a definite negative impact on the outcome for stroke patients. • Reperfusion, serum glucose, ASPECTS, CBS, collateral score, and the pass number of thrombectomy device were associated with the occurrence of mMCAi after EVT in stroke patients.

Subcortical infarcts on admission CTP predict poor outcome despite excellent reperfusion in delayed time windows.

PURPOSE: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows. METHODS: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study. RESULTS: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately. CONCLUSION: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts.

A nomogram for predicting thrombus composition in stroke patients with large vessel occlusion: combination of thrombus density and perviousness with clinical features.

PURPOSE: To establish a nomogram incorporating pretreatment imaging parameters and clinical characteristics for predicting the thrombus composition of acute ischemic stroke (AIS) with large vessel occlusion (LVO). METHODS: We retrospectively enrolled patients with occlusion of the Middle Cerebral Artery (MCA) who underwent Mechanical Thrombectomy (MT). Retrieved thrombi were stained with Hematoxylin and Eosin (H&E) and Martius Scarlet Blue (MSB). Thrombi are assigned to the Fibrin-rich or RBC-rich group based on the relative fractions of Red Blood Cells (RBC), fibrin, and platelet. The independent risk factors for Fibrin-rich clots were determined via univariate and multivariate logistic regression analysis and were then integrated to establish a nomogram. RESULTS: In total, 98 patients were included in this study. Patients with fibrin-rich clots had worse functional outcome [modified Rankin scale (mRS) 0-2, 34.7% vs 63.2%, p = 0.005], longer procedure time (76.8 min vs 50.8 min, p = 0.001), and increased maneuvers of MT (1.84 vs 1.46, p = 0.703) than those with RBC-rich clots. The independent risk factors for Fibrin-rich clots were lower perviousness measured by Non-Contrast Computer Tomography (NCCT) and CT Angiography (CTA), lower thrombus relative attenuation on NCCT, elevated Platelet-WBC ratio (PWR) of admission peripheral blood, and previous antithrombotic medication. The nomogram showed good discrimination with an area under the Receiver Operating Characteristic (ROC) curve (AUC) of 0.852 (95% CI: 0.778-0.926). The calibration curve and decision curve analysis also displayed satisfactory accuracy and clinical utility. CONCLUSION: This study has developed and internally validated an easy-to-use nomogram which can help predict clot composition and optimize therapeutic strategies for thrombectomy.

Design and Validation of a Novel Evaluation Scale to Predict Inpatient Large Vessel Occlusion Strokes: Clinical Assessment Stroke Severity for Inpatient Scale.

OBJECTIVES: A large quantity of ischemic stroke events occur in patients hospitalized for non-stroke-related reason. No scale has been developed to identify the large vessel occlusion (LVO) among inpatient stroke alerts. We aimed to develop a novel evaluation scale to predict LVO from in-hospital stroke alerts. METHODS: Data from consecutive in-hospital stroke alerts were analyzed at a single high volume stroke center between January 2016 and October 2020. We developed a predictive scale based on the first half of patients (training group) using multivariate logistic regression and evaluated it in the remaining half of patients (validation group) adopting receiver operating curve. Receiver operating characteristics of the scale were analyzed to evaluate its value for the detection of LVO. RESULTS: A total of 243 patients were enrolled for further study, among them, 94 (38.7%) had confirmed LVO. Three risk factors independently predicted the presence of LVO: recent cardiac or pulmonary procedure (1 point), neurological deficit scale (≥1: 2 points), and history of atrial fibrillation (1 point). The CAPS scale was generated based on predictive factors and demonstrated highly effective discrimination in identifying the presence of LVO in the training group (area under curve = 0.956) and the validation group (area under curve = 0.940). When the score ≥2, CAPS scale showed 97.9% sensitivity, 79.2% specificity, 74.8% positive predictive value, and 98.3% negative predictive value for discriminating LVO. CONCLUSIONS: CAPS scale was developed for identifying LVO among inpatient stroke alerts with high sensitivity and specificity, which may help to quickly prompt responses by appropriate stroke teams.

Effect of Truncal-Type Occlusion Based on Multiphase or Single-Phase Computed Tomographic Angiography in Predicting Intracranial Atherosclerotic Stenosis-Related Acute Middle Cerebral Artery Occlusion.

OBJECTIVE: To investigate whether truncal-type occlusion based on multiphase computed tomographic angiography (mpCTA) was more effective for predicting intracranial atherosclerotic stenosis-related occlusion (ICAS-O) than occlusion type based on single-phase computed tomographic angiography (spCTA) in patients with acute ischemic stroke with large-vessel occlusion (AIS-LVO) in the middle cerebral artery (MCA). METHODS: Data were retrospectively collected from 72 patients with AIS-LVO in the MCA between January 2018 and December 2019. The occlusion types included truncal-type and branching-site occlusions. The association between ICAS-O and occlusion type based on the 2 computed tomographic angiography patterns was analyzed, and receiver operating characteristic curves were plotted for assessment. The areas under the curve were compared to determine the difference between the predictive powers of truncal-type occlusion based on mpCTA and spCTA. RESULTS: Among the 72 patients, 16 were classified as having ICAS-O and 56 as having embolisms. In univariate analysis, truncal-type occlusion was significantly associated with ICAS-O ( P < 0.001 for mpCTA and P = 0.001 for spCTA). After multivariable analysis, truncal-type occlusion based on both mpCTA and spCTA remained independently associated with ICAS-O ( P = 0.002 for mpCTA and P = 0.029 for spCTA). The areas under the curve were 0.821 for mpCTA and 0.683 for spCTA; this difference was statistically significant ( P = 0.024). CONCLUSIONS: In patients with AIS-LVO in the MCA, truncal-type occlusion based on mpCTA enables more accurate detection of ICAS-O than that based on spCTA.

Early plasma D-dimer as a predictor of acute intracranial atherosclerosis-related large vessel occlusion in acute ischemic stroke.

BACKGROUND: Intracranial atherosclerosis-related large vessel occlusion (ICAS+LVO) poses an important technical challenge for endovascular thrombectomy (EVT). PURPOSE: To evaluate the value of D-dimer in predicting ICAS+LVO alone and in combination with other clinical and imaging predictors. MATERIAL AND METHODS: Consecutive patients who underwent EVT at our center between January 2018 and June 2021 were retrospectively reviewed. Patients were classified to the ICAS+LVO or ICAS-LVO group according to angiographic findings. Collateral gradings were evaluated based on computed tomography angiography and categorized as follows: score 0-1 unfavorable collaterals and score 2-3 favorable collaterals. Receiver operating characteristic curve was analyzed to evaluate the predictive value of D-dimer and the combination of other predictors for ICAS+LVO. RESULTS: A total of 374 patients were enrolled, among them, 107 (28.6%) had an ICAS+LVO, while ICAS-LVO was determined in 267 (71.4%) patients. Median D-dimer levels were lower (0.36 vs. 1.18 mg/L; P < 0.001) while the proportion of favorable collaterals was higher (85.0% vs. 22.5%; P < 0.001) in the ICAS+LVO group than the ICAS-LVO group. After multivariable analysis, D-dimer (adjusted odds ratio [OR]=0.32, 95% confidence interval [CI]=0.21-0.50; P < 0.001) and collaterals (adjusted OR=16.25, 95% CI=7.58-34.84; P < 0.001) remained independent predictors of ICAS+LVO. The area under the curve of D-dimer, collaterals, and combination for identification of ICAS+LVO was 0.82, 0.85, and 0.92, respectively. CONCLUSION: Low early plasma D-dimer levels are a significant and independent predictor of ICAS+LVO, and predictive value strengthens when in a combined model using D-dimer and collateral grading.

Radiomics features on computed tomography reflect thrombus histological age prior to endovascular treatment of acute ischemic stroke.

PURPOSE: To investigate the role of radiomics features in thrombus age identification and establish a CT-based radiomics model for predicting thrombus age of large vessel occlusion stroke patients. METHODS: We retrospectively reviewed patients with middle cerebral artery occlusion receiving mechanical thrombectomy from July 2020 to March 2022 at our center. The retrieved clots were stained with Hematoxylin and Eosin (H&E) and determined as fresh or older thrombi based on coagulation age. Clot-derived radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression analysis, by which selected radiomics features were integrated into the Rad-score via the corresponding coefficients. The prediction performance of Rad-score in thrombus age was evaluated with the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 104 patients were included in our analysis, with 52 in training and 52 in validation cohort. Older thrombi were characterized with delayed procedure time, worse functional outcome and marginally associated with more attempts of device. We extracted 982 features from NCCT images. Following T test and LASSO analysis in training cohort, six radiomics features were selected, based on which the Rad-score was generated by the linear combination of features. The Rad-score showed satisfactory performance in distinguishing fresh with older thrombi, with the AUC of 0.873 (95 %CI: 0.777-0.956) and 0.773 (95 %CI: 0.636-0.910) in training and validation cohort, respectively. CONCLUSION: This study established and validated a CT-based radiomics model that could accurately differentiate fresh with older thrombi for stroke patients receiving mechanical thrombectomy.