Comparison of clinical and MRI features of brain metastases between ALK+ and ALK- NSCLC.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is the primary cause of brain metastases (BM). This study aimed to investigate differences in clinical and magnetic resonance imaging (MRI) features of BM between anaplastic lymphoma kinase (ALK) gene fusion (ALK+) and ALK wild-type (ALK-) NSCLC, and to preliminarily assess the efficacy of radiotherapy for treating BM. METHODS: A retrospective analysis included 101 epidermal growth factor receptor (EGFR)- NSCLC patients with BM: 41 with ALK gene fusion and 60 being ALK-. The brain MRI and clinical features were compared between different ALK status using the multivariate analysis, and a nomogram was constructed to predict ALK gene fusion. Fifty-six patients who did not undergo cerebral surgery and had complete pre- and post- treatment data were further divided based on whether they received radiotherapy. Log-rank test was used to compare the short-term effect of treatment between the two groups under different genotypes. RESULTS: ALK+ BM exhibited decreased peritumoral brain edema size, lower peritumoral brain edema index (PBEI), and a more homogeneous contrast enhancement pattern compared to ALK- BM. Age (OR = 1.04; 95%CI: 1.02-1.06), time to BM (OR = 1.50; 95% CI: 1.04-2.14), PBEI (OR = 1.26; 95% CI: 0.97-1.62), smoking status (smoking index >400 vs. non-smoking status: OR = 1.42; 95% CI: 0.99-2.04) and contrast enhancement pattern (OR = 1.89; 95% CI: 1.28-2.78) were associated with ALK gene fusion. A nomogram based on these variables demonstrated acceptable predictive efficiency (AUC = 0.844). In the ALK+ group, patients who received radiotherapy did not show increased disease control rate (DCR) or progression-free survival (PFS). In contrast, in the ALK- group, those who received radiotherapy had improved objective response rate (ORR), DCR, and PFS compared to those who were only treated with systemic therapy. CONCLUSIONS: The clinical and MRI features of BM can indicate the status of ALK in NSCLC. In the ALK- group, patients who received radiotherapy showed higher ORR, DCR, and PFS compared to those who did not.

Ginsenoside Rb1 promotes the activation of PPARα pathway via inhibiting FADD to ameliorate heart failure.

PURPOSE: Ginsenoside Rb1 (GRb1), a dammarane-type triterpene saponin compound mainly distributed in ginseng (Panax ginseng), has been demonstrated to ameliorate cardiovascular diseases. However, it remains unclear whether GRb1 alleviates heart failure (HF) by maintaining cardiac energy metabolism balance. Therefore, this work aimed to investigate the cardiac benefits of GRb1 against cardiac energy deficit and explore its mechanism of action. METHODS AND RESULTS: Isoproterenol (ISO) induced HF Sprague-Dawley rats were administrated with GRb1 or fenofibrate for 6 weeks. ISO-induced primary neonatal rat cardiomyocytes (NRCMs) were used as the in vitro model. In vivo, GRb1 significantly improved the structural and metabolic disorder, as demonstrated by the restoration of cardiac function, inhibition of cardiac hypertrophy and fibrosis, and increased adenosine triphosphate (ATP) generation. In vitro, GRb1 effectively protected mitochondrial function and scavenged excessive reactive oxygen species. Moreover, in ISO-induced NRCMs, GRb1 significantly inhibited the abnormal upregulation of Fas-associated death domain (FADD), promoted transcriptional activation of peroxisome proliferator-activated receptor-alpha (PPARα), improved the aberrant expression of cardiac energy metabolism-related enzymes and cardiac fatty acid oxidation, and subsequently increased the synthesis of ATP. Noticeably, GRb1 could inhibit the increased binding between FADD and PPARα, which contributed to the activation of PPARα. Furthermore, GRb1 strengthened the thermal stabilization of FADD and might bind to FADD directly. CONCLUSIONS: Collectively, it's part of the in-depth mechanism of GRb1's cardio-protection that GRb1 could directly bind to FADD and counteract its negative role in the transcription of PPARα thus ameliorating cardiac energy derangement and HF.

Effect of bleeding risk prediction on decision making of intravenous thrombolysis before thrombectomy: a subgroup analysis of DIRECT-MT.

BACKGROUND: The major concern for bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the potentially increased risk of symptomatic intracerebral hemorrhage (sICH). Thus we conducted this study to clarify whether evaluation of individual bleeding risk could assist in the decision to perform IVT before EVT. METHODS: The study was a subgroup analysis of a randomized trial evaluating the safety and efficacy of IVT before EVT. The SEDAN (blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign, Age, and National Institutes of Health Stroke Score) score, GRASPS (Glucose, Race, Age, Sex, systolic blood Pressure, and Severity of stroke) score, and SITS-SICH (Safe Implementation of Thrombolysis in Stroke-Symptomatic Intracerebral Hemorrhage) score were used to evaluate individual bleeding risk. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Binary logistic regression with an interaction term was used to estimate treatment effect modification to clarify whether direct EVT was more beneficial in patients with a higher sICH risk, while adjunctive IVT before EVT was more beneficial in patients with a lower sICH risk. RESULTS: Among 658 randomized patients, 639 (361 men, 56.5%; median age 69 (IQR 61-76) years) were included in the study. With the SITS-SICH score as an example, adjusted OR for functional independence with EVT alone was 1.12 (95% CI 0.68 to 1.82) in patients with a lower sICH risk (SITS-SICH score 0-4) and 0.92 (0.53 to 1.60) in those with a higher sICH risk (SITS-SICH score 5-15). There were no treatment-by-bleeding-risk interactions for all dichotomized mRS outcomes based on the three scores (all p>0.05). CONCLUSIONS: We found no evidence that clinicians can decide whether to omit IVT before EVT based on an individualized assessment of bleeding risk.

Case report: Kidney perivascular epithelioid cell tumor treated with anti-VEGFR tyrosine kinase inhibitor and MTOR inhibitor.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors arising from perivascular epithelial cells. There was no standard treatment for unresectable PEComa before 2021. For a low incidence and a rarely curable disease, development of new therapy is essential. A 45-year-old female was diagnosed with malignant renal PEComa (likely with TFE3 rearrangement) that underwent rapid progression after 10 months of surgery. The patient then received the tyrosine kinase inhibitor (TKI) Apatinib, and the tumor remained stable for 15 months before another progression. The patient then received the MTOR inhibitor everolimus that alleviated her symptoms but the tumor went into remission again after another 15 months. This result suggests that antagonizing the vascular endothelial growth factor receptor (VEGFR) pathway be a useful strategy for malignant PEComas, along with the MTOR pathway inhibition that had recently been approved for the rare tumor.

Differentiating Central Lung Tumors from Atelectasis with Contrast-Enhanced CT-Based Radiomics Features.

OBJECTIVES: To evaluate the utility of radiomics features in differentiating central lung cancers and atelectasis on contrast-enhanced computed tomography (CT) images. This study is retrospective. MATERIALS AND METHODS: In this study, 36 patients with central pulmonary cancer and atelectasis between July 2013 and June 2018 were identified. A total of 1,653 2D and 2,327 3D radiomics features were extracted from segmented lung cancers and atelectasis on contrast-enhanced CT. The refined features were investigated for usefulness in classifying lung cancer and atelectasis according to the information gain, and 10 models were trained based on these features. The classification model is trained and tested at the region level and pixel level, respectively. RESULTS: Among all the extracted features, 334 2D features and 1,507 3D features had an information gain (IG) greater than 0.1. The highest accuracy (AC) of the region classifiers was 0.9375. The best Dice score, Hausdorff distance, and voxel AC were 0.2076, 45.28, and 0.8675, respectively. CONCLUSIONS: Radiomics features derived from contrast-enhanced CT images can differentiate lung cancers and atelectasis at the regional and voxel levels.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). METHODS: This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. RESULTS: Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). CONCLUSIONS: An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

Efficacy of radiofrequency catheter ablation for premature ventricular contractions in children.

PURPOSE: This study evaluated the efficacy and safety of transcatheter radiofrequency ablation (RFCA) in treating ventricular premature contractions (PVCs) in children, summarized the countermeasures during intraoperative ventricular fibrillation (VF), and improved the safety of ventricular premature treatment. METHODS: A retrospective analysis was conducted on 75 children with PVCs who received RFCA in the Second Affiliated Hospital of Wenzhou Medical University from January 2010 to April 2019. Data including age, sex, body weight, ejection fraction, left ventricular end diastolic diameter, burden and number of PVCs/24 h, origin of PVCs, and its complications were collected. Paired t test was used to compare changes in cardiac function before and after surgery. RESULTS: Among the 75 cases treated with RFCA, 68 were successfully ablated, giving a success rate of 90.67%. After ablation, the left ventricular ejection fraction (LVEF) of the children was 69.13 ± 3.81%, which was significantly higher than that before surgery (69.13 ± 3.81% vs. 66.21 ± 3.22%, P = 0.012). One of the patients experienced VF during the operation, with no other complications. The initial locus of origin was the anterior septum of the right ventricular outflow tract, but VF occurred during the ablation process. Mean follow-up time was 39 ± 33 months, with two recurrent cases (2.94%). CONCLUSIONS: Performing RFCA in children is safe and effective, with a low recurrence rate and few complications. VF is not an indication to cease surgery; the key to eliminating complications is repositioning the catheter and finding a more accurate origin point.

Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy.

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

MiR-215 modulates gastric cancer cell proliferation by targeting RB1.

Growing evidence indicates that miRNAs play critical roles in tumorigenesis and cancer progression. Here, we report that miR-215 is significantly up-regulated in gastric cancer tissues from either gastrectomy or gastroscopy. Receiver Operator Characteristic (ROC) curve analysis indicated that miR-215 may be a candidate biomarker for gastric cancer diagnosis. Inhibition of miR-215 significantly suppressed gastric cancer cell proliferation possibly via G1 arrest. Further analyses indicated that miR-215 was able to target retinoblastoma tumor-suppressor gene 1 (RB1) through its 3'-UTR in gastric cancer cells. These data suggest that frequently up-regulated miR-215 in gastric cancer may influence cell proliferation by targeting RB1.