Radiofrequency ablation of very-early-stage hepatocellular carcinoma inconspicuous on fusion imaging with B-mode US: value of fusion imaging with contrast-enhanced US

Background/AimsTo determine the value of fusion imaging with contrast-enhanced ultrasonography (CEUS) and computed tomography (CT)/magnetic resonance (MR) images for percutaneous radiofrequency ablation (RFA) of very-early-stage hepatocellular carcinomas (HCCs) that are inconspicuous on fusion imaging with B-mode ultrasound (US) and CT/MR images.MethodsThis retrospective study was approved by our institutional review board and the requirement for informed consent was waived. Fusion imaging with CEUS using Sonazoid contrast agent and CT/MR imaging was performed on HCCs (<2 cm) that were inconspicuous on fusion imaging with B-mode US. We evaluated the number of cases that became conspicuous on fusion imaging with CEUS. Percutaneous RFA was performed under the guidance of fusion imaging with CEUS. Technical success and major complication rates were assessed.ResultsIn total, 30 patients with 30 HCCs (mean, 1.2 cm; range, 0.6-1.7 cm) were included, among which 25 (83.3%) became conspicuous on fusion imaging with CEUS at the time of the planning US and/or RFA procedure. Of those 25 HCCs, RFA was considered feasible for 23 (92.0%), which were thus treated. The technical success and major complication rates were 91.3% (21/23) and 4.3% (1/23), respectively.ConclusionsFusion imaging with CEUS and CT/MR imaging is highly effective for percutaneous RFA of very-early-stage HCCs inconspicuous on fusion imaging with B-mode US and CT/MR imaging

The effect of alpha lipoic acid in a porcine in-stent restenosis model

SummaryBackgroundThe aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model.MethodsIn protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting.ResultsProtocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2. On histopathologic analysis, the neointimal area (4.0±1.0mm2 vs. 1.5±0.7mm2, p<0.001) and histopathologic area of stenosis (66.7±10.7% vs. 24.2±9.7%, p<0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9±0.8mm2 vs. 1.0±0.4mm2, p<0.001), and the histopathologic area of stenosis (67.1±8.8% vs. 17.4±10.0%, p<0.001) were reduced in the α-LA coated stent group compared to the control stent group.Conclusionsα-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC

Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome.

An unbalanced microbial ecosystem on the human skin is closely related to skin diseases and has been associated with inflammation and immune responses. However, little is known about the role of the skin microbiome on skin aging. Here, we report that the Streptococcus species improved the skin structure and barrier function, thereby contributing to anti-aging. Metagenomic analyses showed the abundance of Streptococcus in younger individuals or those having more elastic skin. Particularly, we isolated Streptococcus pneumoniae, Streptococcus infantis, and Streptococcus thermophilus from face of young individuals. Treatment with secretions of S. pneumoniae and S. infantis induced the expression of genes associated with the formation of skin structure and the skin barrier function in human skin cells. The application of culture supernatant including Streptococcal secretions on human skin showed marked improvements on skin phenotypes such as elasticity, hydration, and desquamation. Gene Ontology analysis revealed overlaps in spermidine biosynthetic and glycogen biosynthetic processes. Streptococcus-secreted spermidine contributed to the recovery of skin structure and barrier function through the upregulation of collagen and lipid synthesis in aged cells. Overall, our data suggest the role of skin microbiome into anti-aging and clinical applications

Complications Following Outside-in and Inside-out Transobturator-Tape Procedures with Concomitant Gynecologic Operations

This study was undertaken to compare the complications of outside-in transobturator tape procedures (TOT) and inside-out transobturator tape procedures (TVT-O) with concomitant gynecologic surgery for the treatment of female stress urinary incontinence (SUI). A retrospective review of 206 consecutive patients who underwent either TOT or TVT-O with concomitant gynecologic operations between March 2008 and February 2011 was conducted. The incidence of perioperative complications was compared. For statistical analysis, chi-squared tests were used. There were no reports of intraoperative complications such as vaginal injury or bladder perforation. Postoperative complications were noted in 23 procedures (11.2%). These included 6 cases of urinary retention (2.9%), 2 cases of vulva hematoma (1.0%), 7 cases of urinary tract infection (3.4%), 4 cases of de novo urgency (2.9%), and 4 cases of vaginal erosion (2.9%). There were no significant differences in complication rates between the two groups. Our results suggest that inside-out and outside-in procedures are simple and safe techniques that may have a low rate of complications when used with a concomitant gynecologic operation

Acute and Subacute Stent Thrombosis in a Patient With Clopidogrel Resistance: A Case Report

Drug-eluting stents (DES) are considered the treatment of choice for most patients with obstructive coronary artery disease when percutaneous intervention (PCI) is feasible. However, stent thrombosis seems to occur more frequently with DES and occasionally is associated with resistance to anti-platelet drugs. We have experienced a case of recurrent stent thrombosis in a patient with clopidogrel resistance. A 63-year-old female patient suffered from acute myocardial infarction and underwent successful PCI of the left anterior descending coronary artery (LAD) with two DESs. She was found to be hyporesponsive to clopidogrel and was treated with triple anti-platelet therapy (aspirin 100 mg, clopidogrel 75 mg, and cilostazol 200 mg daily). Three days after discharge, she developed chest pain and was again taken to the cardiac catheterization laboratory, where coronary angiography (CAG) showed total occlusion of the mid-LAD where the stent had been placed. After intravenous administration of a glycoprotein IIb/IIIa inhibitor, balloon angioplasty was performed, resulting in Thrombolysis In Myocardial Infarction (TIMI) III antegrade flow. The next day, however, she complained of severe chest pain, and the electrocardiogram showed marked ST-segment elevation in V1-V6, I, and aVL with complete right bundle branch block. Emergent CAG revealed total occlusion of the proximal LAD due to stent thrombosis. She was successfully treated with balloon angioplasty and was discharged with triple anti-platelet therapy

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Inhibition of Akt activity induces the mesenchymal-to-epithelial reverting transition with restoring E-cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells

<p>Abstract</p> <p>Background</p> <p>The Akt/PKB family of kinases is frequently activated in human cancers, including oral squamous cell carcinoma (OSCC). Akt-induced epithelial-to-mesenchymal transition (EMT) involves downregulation of E-cadherin, which appears to result from upregulation of the transcription repressor Snail. Recently, it was proposed that carcinoma cells, especially in metastatic sites, could acquire the mesenchymal-to-epithelial reverting transition (MErT) in order to adapt the microenvironments and re-expression of E-cadherin be a critical indicator of MErT. However, the precise mechanism and biologic or clinical importance of the MErT in cancers have been little known. This study aimed to investigate whether Akt inhibition would restore the expression of E-cadherin and β-catenin, reduce that of Vimentin, and induce the MErT in OSCC cells with low or negative expression of E-cadherin. We also investigate whether inhibition of Akt activity would affect the E-cadherin repressors and signaling molecules like NF-κB, ERK, and p38.</p> <p>Methods</p> <p>We screened several OSCC cell lines in order to select suitable cell line models for inducing MErT, using immunoblotting and methylation specific-PCR. We examined whether Akt inhibitor phosphatidylinositol ether lipid analogues (PIA) treatment would restore the expression of E-cadherin and β-catenin, reduce that of Vimentin, and induce the MErT in KB and KOSCC-25B cells using RT-PCR, immunoblotting, immunofluorescence analysis, and <it>in vitro </it>migration assay. We also investigated whether inhibition of Akt activity would affect the E-cadherin repressors, including Snail, Twist, and SIP-1/ZEB-2 and signaling molecules like NF-κB, ERK, JNK, and p38 using RT-PCR, immunoblotting, and immunofluorescence analysis.</p> <p>Results</p> <p>Of the 7 OSCC cell lines, KB and KOSCC-25B showed constitutively activated phosphorylated Akt and low or negative expression of E-cadherin. Inhibition of Akt activity by PIA decreased NF-κB signaling, but did not affect phosphorylation of ERK, JNK, and p38 in KB and KOSCC-25B cells. Akt inhibition led to downregulation of Snail and Twist expression. In contrast, inhibition of Akt activity by PIA did not induce any changes in SIP-1/ZEB-2 expression. PIA treatment induced the expression of E-cadherin and β-catenin, reduce that of Vimentin, restored their epithelial morphology of a polygonal shape, and reduced tumor cell migration in KB and KOSCC-25B cells, which was the corresponding feature of MErT.</p> <p>Conclusion</p> <p>All of these findings suggest that Akt inhibition could induce the MErT through decreased NF-κB signaling and downregulation of Snail and Twist in OSCC cells. A strategy involving Akt inhibition might be a useful therapeutic tool in controlling cancer dissemination and metastasis in oral cancer patients.</p

Comparison of Psychological and Cognitive Characteristics between Professional Internet Game Players and Professional Baseball Players

The esports industry is increasing in popularity and is now played at the professional level. We hypothesized that esports players may have a significant advantage over the general population in terms of psychological and cognitive characteristics, which may be similar to that of professional baseball players. We recruited three participant groups: esports players (n = 55), pro-baseball players (n = 57), and age- and sex-matched healthy comparison subjects (n = 60). We assessed psychological status using the Korean versions of Temperament and Character Inventory and State and Trait Anxiety Inventory and cognitive functions using the modified Tower of London, Emotional Perception, and Mental Rotation tests. Esports players had similar psychological characteristics to pro-baseball players (higher novelty seeking [p &lt; 0.01 *, ŋ = 0.818], self-directedness [p &lt; 0.01 *, ŋ = 0.757], and self-transcendence scores [p &lt; 0.01 *, ŋ = 0.853], and decreased state anxiety scores [p &lt; 0.01 *, ŋ = 0.808]), which differed from those of the general population. However, esports players showed higher working memory [p &lt; 0.01 *, ŋ = 0.823] and slower emotional perception than pro-baseball players [p &lt; 0.01 *, ŋ = 0.812]. In conclusion, esports and pro-baseball players had similar psychological but different cognitive characteristics