Radiofrequency catheter ablation of left-sided accessory pathways via retrograde aortic approach in children

Background: We aimed to analyze the results of retrograde aortic radiofrequency catheter ablation of left-sided accessory pathways in children. Methods: Between January 2010 and September 2014, 25 children who underwent left-sided accessory pathway ablation with a retrograde aortic approach were evaluated retrospectively. Results: The mean age of the patients was 11.09 +/- 3.71 years. Seventeen patients were male (68%). The mean procedure and fluoroscopy times were 71.54 +/- 21.05 min and 31.42 +/- 19.57 min, respectively. Radiofrequency energy was delivered with 41.38 +/- 15.32 W at 52.38 +/- 5.45 degrees C. Sixteen patients (64%) presented with manifest preexcitation and, 9 had concealed accessory pathways. The location of accessory pathway was left lateral in 16 patients, posteroseptal in 5, left anterolateral in 2, and left posterolateral and left posterior in the remaining 2. The acute success rate was 96%. The patients were followed for a mean of 16.68 +/- 18.01 months. There were 2 recurrences. No major complications were observed in the periprocedural period. One patient had groin hematoma, another one had transient severe headache and vomiting. Trivial mitral regurgitation was noted in a patient, which remained the same throughout follow-up. None of the patients developed new aortic regurgitation, pericardial effusion, or thrombi at the site of ablation. Conclusions: The retrograde aortic approach can be safely employed with a high success rate for ablation of left-sided accessory pathways in children. (C) 2016 Japanese Heart Rhythm Society. Published by Elsevier B.V

Immediate and Follow-Up Results of Repeat Percutaneous Mitral Balloon Commissurotomy for Restenosis After a Succesful First Procedure

Background: The widespread use of percutaneous mitral commissurotomy (PMC) has led to an increase in restenosis cases. The data regarding follow-up results of repeat PMC are quite limited. The aim of this retrospective analysis is to evaluate the immediate and midterm results of the second PMC, in patients with symptomatic mitral restenosis after a succesful first procedure. Methods: Twenty patients (95% female, mean age 37 +/- 4 years) who have undergone a second PMC, 6.3 +/- 2.5 years after a first successful intervention built the study group. All were in sinus rhythm, with a mean Wilkins score of 8.5 +/- 1.2. Results: The valve area increased from 1.2 +/- 0.2 to 1.9 +/- 0.2 cm2 and mean gradient decreased from 10.5 +/- 3.4 to 6.1 +/- 1.1 mmHg. There were no complications except for a transient embolic event without sequela (5%) and two cases (10%) of severe mitral regurgitation. The immediate success rate was 90%. The mean follow-up was 70 +/- 29 months (36-156 months). The 5-year restenosis and intervention (repeat PMC or valve replacement) rates were 9.1 +/- 5.2% and 3.6 +/- 3.3%, respectively. The intervention free 5-year survival in good functional capacity (New York Heart Association [NYHA] I-II) was 95.1 +/- 5.5% and restenosis and intervention free 5-year survival with good functional capacity was 89.7 +/- 6.8%. Conclusions: Although from a limited number of selected patients, these findings indicate that repeat PMC is a safe and effective method, with follow-up results similar to a first intervention and should be considered as the first therapeutic option in suitable patients. (Echocardiography 2010;27:765-769)

Light-responsive microRNA molecules in human retinal organoids are differentially regulated by distinct wavelengths of light

Summary: Cells in the human retina must rapidly adapt to constantly changing visual stimuli. This fast adaptation to varying levels and wavelengths of light helps to regulate circadian rhythms and allows for adaptation to high levels of illumination, thereby enabling the rest of the visual system to remain responsive. It has been shown that retinal microRNA (miRNA) molecules play a key role in regulating these processes. However, despite extensive research using various model organisms, light-regulated miRNAs in human retinal cells remain unknown. Here, we aim to characterize these miRNAs. We generated light-responsive human retinal organoids that express miRNA families and clusters typically found in the retina. Using an in-house developed photostimulation device, we identified a subset of light-regulated miRNAs. Importantly, we found that these miRNAs are differentially regulated by distinct wavelengths of light and have a rapid turnover, highlighting the dynamic and adaptive nature of the human retina

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM+/CD133+ liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM−/CD133− non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of β-CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM−/CD133− non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM−/CD133− non-stem cells attained an in vivo tumor forming ability comparable to EpCAM+/CD133+ LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM+/CD133+ LCSCs in HuH7 HCC cells

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM(-)/CD133(-) nonStem Cells into EpCAM(+)/CD133(+) Liver Cancer Stem Cells in HCC Cell Line HuH7

The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM(+)/CD133(+) liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM(-)/CD133(-) non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of beta -CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM(-)/CD133(-) non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM(-)/CD133(-) non-stem cells attained an in vivo tumor forming ability comparable to EpCAM(+)/CD133(+) LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM(+)/CD133(+) LCSCs in HuH7 HCC cells