Comparative effectiveness of budesonide inhalation suspension and montelukast in children with mild asthma in Korea.

Objective: The comparative effectiveness of low-dose budesonide inhalation suspension (BIS) versus oral montelukast (MON) in managing asthma control among children with mild asthma was assessed in Korea.Methods: Claims from Korea's national health insurance database for children (2-17 years) with mild asthma (GINA 1 or 2) who initiated BIS or MON during 2015 were retrospectively analyzed. Pre- and post-index windows were 1 year each. Adherence, persistency, asthma control, asthma-related health-care resource utilization, and costs were evaluated using unadjusted descriptive statistics and propensity score-matched regression analyses.Results: The number of children identified was 26,052 for unmatched (n = 1,221 BIS; n = 24,831 MON) and 2,290 for matched populations (n = 1,145 per cohort). Medication adherence, measured by proportion of days covered, was low for both cohorts but significantly higher for MON versus BIS (13.8% vs. 4.5%; p < .001). Time to loss of persistency was longer for MON versus BIS (82.3 vs. 78.4 days, respectively; p < .001). Mean number of post-index asthma-related office visits was 6.6 for BIS versus 8.3 for MON (p < .001). However, a greater proportion of patients in the BIS cohort had an asthma exacerbation-related office visit than the MON cohort (78.3% vs. 56.1%; p < .001). Asthma-related total health-care costs were higher with MON versus BIS (₩ 190,185 vs. ₩ 167,432, respectively; p < .001), likely driven by higher pharmaceutical costs associated with MON (₩ 69,113 vs. ₩ 49,225; p < .001).Conclusions: Montelukast patients had better adherence, a longer time to loss of persistency, and were less likely to experience an exacerbation-related office visit in the post-index period than BIS patients.

The Design of CNN Architectures for Optimal Six Basic Emotion Classification Using Multiple Physiological Signals.

This study aimed to design an optimal emotion recognition method using multiple physiological signal parameters acquired by bio-signal sensors for improving the accuracy of classifying individual emotional responses. Multiple physiological signals such as respiration (RSP) and heart rate variability (HRV) were acquired in an experiment from 53 participants when six basic emotion states were induced. Two RSP parameters were acquired from a chest-band respiration sensor, and five HRV parameters were acquired from a finger-clip blood volume pulse (BVP) sensor. A newly designed deep-learning model based on a convolutional neural network (CNN) was adopted for detecting the identification accuracy of individual emotions. Additionally, the signal combination of the acquired parameters was proposed to obtain high classification accuracy. Furthermore, a dominant factor influencing the accuracy was found by comparing the relativeness of the parameters, providing a basis for supporting the results of emotion classification. The users of this proposed model will soon be able to improve the emotion recognition model further based on CNN using multimodal physiological signals and their sensors.

Effects of Topical Anti-Glaucoma Medications on Outcomes of Endoscopic Dacryocystorhinostomy: Comparison with Age- and Sex-Matched Controls.

BACKGROUND: This study analyzed the effects of topical anti-glaucoma medications on the surgical outcomes of endoscopic dacryocystorhinostomy (EDCR) in nasolacrimal duct obstruction (NLDO). METHODS: This retrospective study included patients who underwent EDCR for NLDO between September 2012 and April 2021. Thirty patients with topical anti-glaucoma medications and 90 age- and sex-matched controls were included. RESULTS: The success rate of EDCR was higher in the control group than in the anti-glaucoma group (97.8% vs. 86.7%, p = 0.034). Univariate and multivariate logistic regression analyses identified prostaglandin analogs as the most influential risk factor for EDCR success among anti-glaucoma medication ingredients (p = 0.005). The success rate of the group containing all four anti-glaucoma medication ingredients was statistically significant (p = 0.010). The success rate was significantly different in the group of patients who used anti-glaucoma medication for >24 months (p = 0.019). When multiplying the number of drug ingredients by the duration in months, the group > 69 showed a significantly decreased success rate (p = 0.022). Multivariate logistic regression analysis identified the number of anti-glaucoma medications as the most significant risk factor for EDCR success (odds ratio, 0.437; 95% confidence interval, 0.247 to 0.772; p = 0.004). CONCLUSIONS: The authors suggest that the anti-glaucoma medications might cause NLDO and increase the failure rate after EDCR. Therefore, when performing EDCR in patients using topical anti-glaucoma medications, surgeons should consider the possibility of increased recurrence after EDCR in clinical outcomes.

Towards human-scale magnetic particle imaging: development of the first system with superconductor-based selection coils.

Magnetic Particle Imaging (MPI) is an emerging tomographic modality that allows for precise three-dimensional (3D) mapping of magnetic nanoparticles (MNPs) concentration and distribution. Although significant progress has been made towards improving MPI since its introduction, scaling it up for human applications has proven challenging. High-quality images have been obtained in animal-scale MPI scanners with gradients up to 7 T/m/µ0, however, for MPI systems with bore diameters around 200 mm the gradients generated by electromagnets drop significantly to below 0.5 T/m/µ0. Given the current technological limitations in image reconstruction and the properties of available MNPs, these low gradients inherently impose limitations on improving MPI resolution for higher precision medical imaging. Utilizing superconductors stands out as a promising approach for developing a human-scale MPI system. In this study, we introduce, for the first time, a human-scale amplitude-modulated (AM) MPI system with superconductor-based selection coils. The system achieves an unprecedented magnetic field gradient of up to 2.5 T/m/µ0 within a 200 mm bore diameter, enabling large fields of view of 100 × 130 × 98 mm3 at 2.5 T/m/µ0 for 3D imaging. While obtained spatial resolution is in the order of previous animal-scale AM MPIs, incorporating superconductors for achieving such high gradients in a 200 mm bore diameter marks a major step toward clinical MPI.

Sesamolin suppresses adipocyte differentiation through Keap1-dependent Nrf2 activation in adipocytes.

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.

Butein derivatives prevent obesity and improve insulin resistance through the induction of energy expenditure in high-fat diet-fed obese mice.

Obesity is a global public health problem and is related with fatal diseases such as cancer and cardiovascular and metabolic diseases. Medical and lifestyle-related strategies to combat obesity have their limitations. White adipose tissue (WAT) browning is a promising strategy for increasing energy expenditure in individuals with obesity. Uncoupling protein 1 (UCP1) drives WAT browning. We previously screened natural products that enable induction of Ucp1 and demonstrated that these natural products induced WAT browning and increased energy expenditure in mice with diet-induced obesity. In this study, we aimed to extensively optimise the structure of compound 1, previously shown to promote WAT browning. Compound 3 s exhibited a significantly higher ability to induce Ucp1 in white and brown adipocytes than did compound 1. A daily injection of compound 3 s at 5 mg/kg prevented weight gain by 13.6 % in high-fat diet-fed mice without any toxicological observation. In addition, compound 3 s significantly improved glucose homeostasis, decreased serum triacylglycerol levels, and reduced total cholesterol and LDL cholesterol levels, without altering dietary intake or physical activity. Pharmaceutical properties such as solubility, lipophilicity, and membrane permeability as well as metabolic stability, half-life (T1/2), and blood exposure ratio of i.p to i.v were significantly improved in compound 3 s when compared with those in compound 1. Regarding the mode of action of WAT browning, the induction of Ucp1 and Prdm4 by compounds 1 and 3 s was dependent on Akt1 in mouse embryonic fibroblasts. Therefore, this study suggests the potential of compound 3 s as a therapeutic agent for individuals with obesity and related metabolic diseases, which acts through the induction of WAT browning as well as brown adipose tissue activation.

Magnetothermal-based non-invasive focused magnetic stimulation for functional recovery in chronic stroke treatment.

Magnetic heat-based brain stimulation of specific lesions could promote the restoration of impaired motor function caused by chronic stroke. We delivered localized stimulation by nanoparticle-mediated heat generation within the targeted brain area via focused magnetic stimulation. The middle cerebral artery occlusion model was prepared, and functional recovery in the chronic-phase stroke rat model was demonstrated by the therapeutic application of focused magnetic stimulation. We observed a transient increase in blood-brain barrier permeability at the target site of < 4 mm and metabolic brain activation at the target lesion. After focused magnetic stimulation, the rotarod score increased by 390 ± 28% (p < 0.05) compared to the control group. Standardized uptake value in the focused magnetic stimulation group increased by 2063 ± 748% (p < 0.01) compared to the control group. Moreover, an increase by 24 ± 5% (p < 0.05) was observed in the sham group as well. Our results show that non-invasive focused magnetic stimulation can safely modulate BBB permeability and enhance neural activation for chronic-phase stroke treatment in the targeted deep brain area.

Activation of Nrf2 by sulfuretin stimulates chondrocyte differentiation and increases bone lengths in zebrafish.

Elongation of most bones occur at the growth plate through endochondral ossification in postnatal mammals. The maturation of chondrocyte is a crucial factor in longitudinal bone growth, which is regulated by a complex network of paracrine and endocrine signaling pathways. Here, we show that a phytochemical sulfuretin can stimulate hypertrophic chondrocyte differentiation in vitro and in vivo. We found that sulfuretin stabilized nuclear factor (erythroid-derived 2)-like 2 (Nrf2), stimulated its transcriptional activity, and induced expression of its target genes. Sulfuretin treatment resulted in an increase in body length of zebrafish larvae and induced the expression of chondrocyte markers. Consistently, a clinically available Nrf2 activator, dimethyl fumarate (DMF), induced the expression of hypertrophic chondrocyte markers and increased the body length of zebrafish. Importantly, we found that chondrocyte gene expression in cell culture and skeletal growth in zebrafish stimulated by sulfuretin were significantly abrogated by Nrf2 depletion, suggesting that such stimulatory effects of sulfuretin were dependent on Nrf2, at least in part. Taken together, these data show that sulfuretin has a potential use as supporting ingredients for enhancing bone growth. [BMB Reports 2023; 56(9): 496-501].

Machine-Deep-Ensemble Learning Model for Classifying Cybersickness Caused by Virtual Reality Immersion.

This study aims to classify cybersickness (CS) caused by virtual reality (VR) immersion through a machine-deep-ensemble learning model. The heart rate variability and respiratory signal parameters of 20 subjects were measured, while watching a VR video for ∼5 minutes. After the experiment, the subjects were examined for CS and questioned to determine their CS states. Based on the results, we constructed a machine-deep-ensemble learning model that could identify and classify VR immersion CS among subjects. The ensemble model comprised four stacked machine learning models (support vector machine [SVM], k-nearest neighbor [KNN], random forest, and AdaBoost), which were used to derive prediction data, and then, classified the prediction data using a convolution neural network. This model was a multiclass classification model, allowing us to classify subjects' CS into three states (neutral, non-CS, and CS). The accuracy of SVM, KNN, random forest, and AdaBoost was 94.23 percent, 92.44 percent, 93.20 percent, and 90.33 percent, respectively, and the ensemble model could classify the three states with an accuracy of 96.48 percent. This implied that the ensemble model has a higher classification performance than when each model is used individually. Our results confirm that CS caused by VR immersion can be detected as physiological signal data with high accuracy. Moreover, our proposed model can determine the presence or absence of CS as well as the neutral state. Clinical Trial Registration Number: 20-2021-1.

Stage 2: Who Are the Best Candidates for Robotic Gait Training Rehabilitation in Hemiparetic Stroke?

We aimed to compare the effects of robotic-assisted gait training (RAGT) in patients with FAC < 2 (low initial functional ambulation category [LFAC]) and FAC ≥ 2 (high initial functional ambulation category [HFAC]) on sensorimotor and spasticity, balance and trunk stability, the number of steps and walking distance in subacute hemiparetic stroke. Fifty-seven patients with subacute hemiparetic stroke (mean age, 63.86 ± 12.72 years; 23 women) were assigned to two groups. All patients received a 30-min Walkbot-assisted gait training session, 3 times/week, for 6 weeks. Clinical outcomes included scores obtained on the Fugl-Meyer Assessment (FMA) scale, Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), trunk impairment scale (TIS), and the number of walking steps and walking distance. Analysis of covariance and analysis of variance were conducted at p < 0.05. Significant main effects of time in both groups on number of walking steps and distance (p < 0.05) were observed, but not in MAS (p> 0.05). Significant changes in FMA, BBS, and TIS scores between groups (p < 0.05) were observed. Significant main effects of time on BBS and TIS were demonstrated (p < 0.05). Our study shows that RAGT can maximize improvement in the functional score of FMA, BBS, TIS, steps, and distance during neurorehabilitation of subacute stroke patients regardless of their FAC level.

Ubiquitin Specific Protease 29 Functions as an Oncogene Promoting Tumorigenesis in Colorectal Carcinoma.

Colorectal carcinoma is the third foremost cause of cancer-related deaths and accounts for 5.8% of all deaths globally. The molecular mechanisms of colon cancer progression and metastasis control are not well studied. Ubiquitin-specific protease 29 (USP29), a deubiquitinating enzyme, is involved in the occurrence and development of wide variety of cancers. However, its clinical significance and biological roles in colorectal carcinoma (CRC) remain unexplored. In this research, we observed that the rate of USP29 overexpression was higher in colon cancer patient tissues relative to its corresponding normal tissues. CRISPR-Cas9-mediated depletion of USP29 triggered DNA double strand breaks and delayed cell-cycle progression in HCT116 cells. We also demonstrated that USP29 depletion hampers the colony formation and increases apoptosis of HCT116 cells. USP29 knockdown significantly decreased CRC cell proliferation in vitro. Depletion of USP29 in HCT116 cells substantially reduced the tumor volume of mouse xenografts. In conclusion, our study shows that elevated expression of USP29 promotes malignancy in CRC, suggesting that USP29 could be a promising target for colon cancer therapy.

Nrf2 induces Ucp1 expression in adipocytes in response to ß3-AR stimulation and enhances oxygen consumption in high-fat diet-fed obese mice.

Cold-induced norepinephrine activates ß3-adrenergic receptors (ß3-AR) to stimulate the kinase cascade and cAMP-response element-binding protein, leading to the induction of thermogenic gene expression including uncoupling protein 1 (Ucp1). Here, we showed that stimulation of the ß3-AR by its agonists isoproterenol and CL316,243 in adipocytes increased the expression of Ucp1 and Heme Oxygenase 1 (Hmox1), the principal Nrf2 target gene, suggesting the functional interaction of Nrf2 with ß3-AR signaling. The activation of Nrf2 by tert-butylhydroquinone and reactive oxygen species (ROS) production by glucose oxidase induced both Ucp1 and Hmox1 expression. The increased expression of Ucp1 and Hmox1 was significantly reduced in the presence of a Nrf2 chemical inhibitor or in Nrf2-deleted (knockout) adipocytes. Furthermore, Nrf2 directly activated the Ucp1 promoter, and this required DNA regions located at -3.7 and -2.0 kb of the transcription start site. The CL316,243- induced Ucp1 expression in adipocytes and oxygen consumption in obese mice were partly compromised in the absence of Nrf2 expression. These data provide additional insight into the role of Nrf2 in ß3-AR-mediated Ucp1 expression and energy expenditure, further highlighting the utility of Nrf2-mediated thermogenic stimulation as a therapeutic approach to diet-induced obesity. [BMB Reports 2021; 54(8): 419-424].

Butein-Enriched Fractions of Butea monosperma (Lam.) Taub. Flower Decrease Weight Gains and Increase Energy Expenditure in High-Fat Diet-Induced Obese Mice.

Butea monosperma (Lam.) Taub. has been applied to treat inflammatory, metabolic, and infectious diseases. However, the antiobesity effects of B. monosperma (Lam.) Taub. flower (BMF) and the underlying mechanisms have not been determined. In this study, we analyzed the various extraction procedures, investigated the antiobesity effects, and identified the main chemical constituents of BMF. The BMF was subjected to acid hydrolysis in 5% H2SO4 in methanol at 50°C for 48 h and partitioned with ethyl acetate. The acid-hydrolyzed BMF ethyl acetate extracts (BMFE) strongly induced the expression of uncoupling protein 1 (Ucp1) and other thermogenic genes in C3H10T1/2 adipocytes. Daily oral administration of 70 mg/kg BMFE (BMFE70) to mice with diet-induced obesity resulted in less body weight gain, increased glucose tolerance, higher rectal temperature, and increased oxygen consumption. Qualitative and quantitative analyses along with treatments in Akt1 knockout mouse embryonic fibroblasts indicate that butein is a major active ingredient of BMFE, which stimulates Ucp1 gene expression. These data show the effects of butein-containing B. monosperma flower extract on thermogenesis and energy expenditure, further suggesting the potential role of BMFE as a functional ingredient in obesity and related metabolic diseases.

Inhibition of neointimal hyperplasia after stent placement with rhenium 188-filled balloon dilation in a canine iliac artery model.

PURPOSE: To evaluate the efficacy of beta-irradiation therapy with rhenium 188 ((188)Re) mercaptoacetyltriglycine (MAG3)-filled balloon dilation to prevent neointimal hyperplasia after stent placement in a canine iliac artery model. MATERIALS AND METHODS: A total of 15 stents were implanted into the iliac arteries of eight dogs (one or two stents in each dog). Rhenium 188 MAG3-filled balloon dilation was performed immediately after placement of 10 bare stents-20 Gy in group II (n = 5) and 40 Gy in group III (n = 5)-and conventional balloon dilation was performed immediately after placement of the remaining five bare stents (group I). A follow-up angiogram was obtained 8 weeks after the procedure, and percentage of luminal stenosis was calculated for the proximal and distal ends of each stent. Neointimal thickening (expressed as the neointimal area divided by the sum of neointimal area and media area) was assessed for microscopic examination. RESULTS: All eight dogs survived until they were euthanized 8 weeks after the procedures. The mean luminal stenosis measurements at 8-week follow-up angiography in groups I, II, and III were 26.63%, -0.44%, and 10.53%, respectively. The mean neointimal thickening measurements in groups I, II, and III were 0.77, 0.21, and 0.34, respectively. The mean percentage of luminal stenosis and neointimal thickening differed significantly among the three groups (P < .05). CONCLUSIONS: beta-Irradiation with (188)Re-MAG3-filled balloon dilation has the potential to reduce neointimal hyperplasia secondary to stent placement in a canine iliac artery model. A dose of 20 Gy may be preferable versus a dose of 40 Gy to reduce neointimal hyperplasia.

Application of electrospray-scanning mobility particle sizer for the measurement of sub-10 nm chemical mechanical planarization slurry abrasive size distribution.

A scanning mobility particle sizer (SMPS) was used for measuring the size of a sub-10 nm chemical mechanical planarization slurry abrasive. An atomizer and an electrospray were used for aerosolization of slurry abrasives. It was difficult to measure the exact particle size distribution using the atomizer due to the agglomeration peak generated by the relatively large droplet size. However, the electrospray-SMPS (ES-SMPS) measurement result well matched with that of the transmission electron microscopy analysis without the agglomeration peak as ES is known to generate a relatively small droplet during aerosolization. The particle size distribution of the two sub-10 nm ceria slurries was measured using the ES-SMPS. To avoid the dispersion stability issue due to the pH change, pH adjustment was required when the sample was diluted.

The effects of functional action-observation training on gait function in patients with post-stroke hemiparesis: A randomized controlled trial.

BACKGROUND: Functional action observation (FAO) is likely to activate the corticospinal tract and is likely to increase the potential ability of a functional task. OBJECTIVE: The purpose of this study was to investigate the effects of FAO training on gait ability in patients with post-stroke hemiparesis. METHODS: Thirty-five patients with hemiparesis caused by stroke participated in this study. All subjects had suffered from stroke for more than 6 months. Subjects received either a FAO or a general action observation (GAO) training for 30 minutes each time, five times per week, for four weeks. The GAITRite was used to measure walking velocities and spatio-temporal variables. The functional gait assessment (FGA) was used to assess gait ability. The independent t-test was used to analyze whether there were significant differences of all dependent variables between groups. RESULTS: After four weeks of training, the step length, stride length, cadence, velocity, and FGA score in FAO group were statistically different from GAO group (p< 0.05). CONCLUSION: The results of this study suggest that FAO is an effective and easy method for improvement of gait ability in chronic stroke patients.

Arbitrary cross-section SEM-cathodoluminescence imaging of growth sectors and local carrier concentrations within micro-sampled semiconductor nanorods.

Future one-dimensional electronics require single-crystalline semiconductor free-standing nanorods grown with uniform electrical properties. However, this is currently unrealistic as each crystallographic plane of a nanorod grows at unique incorporation rates of environmental dopants, which forms axial and lateral growth sectors with different carrier concentrations. Here we propose a series of techniques that micro-sample a free-standing nanorod of interest, fabricate its arbitrary cross-sections by controlling focused ion beam incidence orientation, and visualize its internal carrier concentration map. ZnO nanorods are grown by selective area homoepitaxy in precursor aqueous solution, each of which has a (0001):+c top-plane and six {1-100}:m side-planes. Near-band-edge cathodoluminescence nanospectroscopy evaluates carrier concentration map within a nanorod at high spatial resolution (60 nm) and high sensitivity. It also visualizes +c and m growth sectors at arbitrary nanorod cross-section and history of local transient growth events within each growth sector. Our technique paves the way for well-defined bottom-up nanoelectronics.

Impact of geographic miss on adjacent coronary artery segments in diffuse in-stent restenosis with beta-radiation therapy: angiographic and intravascular ultrasound analysis.

BACKGROUND: The impacts of geographic miss on edge restenosis have not been sufficiently evaluated. METHODS: Beta-radiation therapy with rhenium 188-filled balloon after rotational atherectomy for diffuse in-stent restenosis was performed in 50 patients. We evaluated the impacts of geographic miss on adjacent coronary artery segments beyond the stent by angiographic (QCA) and intravascular ultrasound (IVUS) analysis in 50 irradiated lesions and 100 edges. Serial IVUS and QCA comparisons between postradiation and 6 months' follow-up were available in 44 and 47 of 50 patients, respectively. QCA measurements of minimal lumen diameter (MLD) and IVUS analysis were performed in the reference and radiation segments. Edges that were touched by the angioplasty balloon but were not adequately covered by radiation constituted the geographic miss edges. RESULTS: Geographic miss was observed in 55.6% and 52.6% in QCA and IVUS analysis, respectively. Edge restenosis after radiation therapy in 3 patients was associated with geographic miss. In contrast to uninjured edges (postradiation 2.9 +/- 0.6 mm to follow-up 2.8 +/- 0.6 mm, P =.292), MLD in the radiation segment by QCA analysis significantly decreased from 2.7 +/- 0.4 mm to 2.4 +/- 0.6 mm in geographic miss edges (P =.002). IVUS analysis showed that significant positive remodeling in the radiation segment occurred in uninjured edges (vessel area from 15.4 +/- 4.4 mm2 to 15.8 +/- 4.4 mm2, P =.001) but not in geographic miss edges (vessel area from 12.8 +/- 3.6 mm2 to 13.0 +/- 3.6 mm2, P =.119). CONCLUSION: The geographic miss might be one of the predictors, which resulted in decreased MLD at follow-up in beta-radiation therapy. Sufficient lesion coverage with radiation might be associated with positive remodeling in the radiation segment.

Extra-stent vascular remodeling in in-stent restenosis after 188Re-MAG3 radiation therapy.

BACKGROUND: The effect of beta-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received beta-radiation therapy as well as conventional therapy has also not been studied. METHODS: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a beta-radiation therapy patient group (188Re-MAG3, n=50) and a control group (n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. RESULTS: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4 +/- 3.3 mm2 post-intervention to 17.1 +/- 3.3 mm2 at follow-up, P=0.001 in the radiation therapy group, and 16.8 +/- 4.0 mm2 post-intervention to 17.4 +/- 4.1 mm2 at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Delta EEM area between the two groups: 0.7 +/- 0.4 mm2 in the radiation therapy group vs. 0.6 +/- 0.4 mm2 in the control group, P=0.389. The Delta IH area correlated with the Delta EEM area in the control group (r=0.826, P=0.022), but not in the radiation therapy group (r=0.016, P=0.919). CONCLUSIONS: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.

The Feasibility of (18)F-Fluorothymidine PET for Prediction of Tumor Response after Induction Chemotherapy Followed by Chemoradiotherapy with S-1/Oxaliplatin in Patients with Resectable Esophageal Cancer.

PURPOSE: The aim of this study was to determine whether (18)F-fluorothymidine (FLT) PET is feasible for the early prediction of tumor response to induction chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal cancer. METHODS: This study was prospectively performed as a collateral study of "randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer". (18)F-FLT positron emission tomography (PET) images were obtained before and after two cycles of induction chemotherapy, and the percent change of maximum standardized uptake value (SUVmax) was calculated. All patients underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS), computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) PET at baseline and 3-4 weeks after completion of concurrent chemoradiotherapy. Final tumor response was determined by both clinical and pathologic tumor responses after surgery. RESULTS: The 13 patients for induction chemotherapy group were enrolled until interim analysis. In a primary tumor visual analysis, the tumor detection rates of baseline (18)F-FLT and (18)F-FDG PET were 85% and 100%, respectively. The tumor uptakes on (18)F-FLT PET were lower than those of (18)F-FDG PET. Among nine patients who completed second (18)F-FLT PET, eight patients were responders and one patient was a non-responder in the assessment of final tumor response. The percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%), whereas it was 10.2% in one non-responder. CONCLUSION: The percent change of tumor uptake in (18)F-FLT PET after induction chemotherapy might be feasible for early prediction of tumor response after induction chemotherapy and concurrent chemoradiotherapy in patients with esophageal cancer.