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1.
Circ Cardiovasc Interv ; 13(3): e008525, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32160779

RESUMO

BACKGROUND: There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES). METHODS: This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively. RESULTS: Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference -1.4% [upper limit of 1-sided 95% CI: -3.2%]; P for noninferiority <0.001; BES versus ZES: absolute risk difference -1.7% [upper limit of 1-sided 95% CI: -3.6%]; P for noninferiority <0.001). CONCLUSIONS: The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01397175.

2.
Front Immunol ; 11: 68, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117240

RESUMO

Uncontrolled activation of transforming growth factor (TGF)-ß results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-ß signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibrosis in mice by inhibiting αv integrin-mediated activation of TGF-ß. Del-1 bound to αvß6 integrin, an important activator of TGF-ß, and inhibited the binding of αvß6 integrin to the latency-associated peptide (LAP), thereby suppressing αv integrin-mediated activation of TGF-ß. Lack of Del-1 increased colocalization of αv integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-ß activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-ß1. Del-1 supplementation improved the pathological characteristics of the mice and reduced mortality. Thus, we propose that Del-1 is a negative regulator of TGF-ß activation and a potential anti-fibrotic factor.

3.
Medicine (Baltimore) ; 99(11): e19071, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176032

RESUMO

BACKGROUND: It is important to manage inflammation after craniotomy. It may be prudent to reduce the excessive usage of antibiotics and to add supplementary treatments like acupuncture, which would be effective and safe. However, there are only a few studies available to date on the effects of acupuncture on anti-inflammatory response after craniotomy. The aim of this study was to explore the anti-inflammatory effects of acupuncture in patients after a craniotomy. METHODS: This study was a single-center, prospective, open-label, controlled trial. Forty-four subjects who underwent craniotomy for an unruptured aneurysm, facial spasm, or brain tumor were allocated to either an acupuncture group or a control group. Both groups received postoperative routine care in the Department of Neurosurgery. The subjects in the acupuncture group also received a total of 6 acupuncture treatments sessions within 8 days after craniotomy. Acupuncture treatments included acupuncture, electroacupuncture, and intradermal acupuncture. The serum interleukin (IL)-1ß and IL-6, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate levels were assessed four times within 7 days after surgery. The presence of fever, use of additional antibiotics, presence of infection including pneumonia or urinary tract infection, and safety were also reviewed. RESULTS: The IL-1ß levels of subjects who underwent aneurysmal clipping were significantly lower in the acupuncture group (P = .02). TNF-α levels of subjects who underwent aneurysmal clipping at the seventh postoperative day were also significantly lower in the acupuncture group (P = .03). Six cases of fever of unknown origin were observed in the control group, while none were seen in the acupuncture group, revealing that the incidence of fever was significantly lower in the acupuncture group (P = .02). No adverse events occurred during the trial. CONCLUSION: Acupuncture showed a possibility of alleviating inflammation by attenuating the levels of proinflammatory cytokines and significantly reduced the incidence of fever of unknown origin in patients after craniotomy. Acupuncture would be suitable as an adjunctive therapy to alleviate inflammation after craniotomy.


Assuntos
Terapia por Acupuntura/métodos , Craniotomia/efeitos adversos , Inflamação/terapia , Complicações Pós-Operatórias/terapia , Proteína C-Reativa/análise , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue
4.
Coron Artery Dis ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32168045

RESUMO

BACKGROUND: Chronic total occlusion intervention remains challenging and detailed real-world data on the safety and efficacy of which are limited. This study sought to determine whether there are differences in the 1-year clinical outcomes between chronic total occlusion patients with acute coronary syndrome and stable angina following chronic total occlusion intervention. PATIENTS AND METHODS: Data from the Korean chronic total occlusion registry were collected from May 2003 to September 2012, and a total of 3268 patients who underwent chronic total occlusion intervention were enrolled. Cardiovascular outcomes up to 12 months in the acute coronary syndrome group were compared with stable angina group. RESULTS: The acute coronary syndrome group consisted of 1657 patients, and stable angina group consisted of 1264 patients. In the acute coronary syndrome group, patients with successful chronic total occlusion intervention had a lower incidence of total death and cardiac death compared to patients with failed intervention. However, there were no significant differences in cardiovascular events in the stable angina group. The successful chronic total occlusion intervention was a significant prognostic factor for lower total death (P = 0.006, hazard ratio = 0.46) and cardiac death (P = 0.003, hazard ratio = 0.36) within acute coronary syndrome group. On the other hand, successful chronic total occlusion intervention was not a prognostic factor for cardiovascular events within stable angina group. CONCLUSIONS: Successful chronic total occlusion intervention in acute coronary syndrome patients was associated with a lower incidence of cardiovascular outcome compared to patients with failed chronic total occlusion intervention.

5.
JMIR Mhealth Uhealth ; 8(2): e16266, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32130172

RESUMO

BACKGROUND: Recent evidence of the effectiveness of mobile phone-based diabetes management systems is generally based on studies conducted in tertiary hospitals or professional diabetes clinics. OBJECTIVE: This study aimed to evaluate the clinical efficacy and applicability of a mobile phone-based glucose-monitoring and feedback system for the management of type 2 diabetes mellitus (T2DM) in multiple primary care clinic settings. METHODS: In this multicenter, cluster-randomized controlled, open trial, 13 primary care clinics in Seoul and other large cities in South Korea were voluntarily recruited. Overall, 150 (9 clinics) and 97 (4 clinics) participants with T2DM were assigned to the intervention and control groups, respectively (2:1 allocation). Every month, participants in both groups attended face-to-face physicians' consultation for the management of diabetes in the clinic. For the intervention group, participants were required to upload their daily self-monitoring of blood glucose (SMBG) results using the mobile phone app in addition to outpatient care for 3 months. The results were automatically transmitted to the main server. Physicians had to check their patients' SMBG results through an administrator's website and send a short feedback message at least once a week. At baseline and 3 months, both groups had anthropometry and blood tests, including hemoglobin A1c (HbA1c), and responded to questionnaires about treatment satisfaction and compliance. RESULTS: At 3 months, participants in the intervention group showed significantly more improvement in HbA1c (adjusted mean difference to control -0.30%, 95% CI -0.50 to -0.11; P=.003) and fasting plasma glucose (-17.29 mg/dL, 95% CI -29.33 to -5.26; P=.005) than those in the control group. In addition, there was significantly more reduction in blood pressure, and the score regarding treatment satisfaction and motivation for medication adherence increased more in the intervention group than in the control group. In the subgroup analyses, the effect on glycemic control was more significant among younger patients and higher baseline HbA1c levels. CONCLUSIONS: The mobile phone-based glucose-monitoring and feedback system was effective in glycemic control when applied in primary care clinic settings. This system could be utilized effectively with diverse institutions and patients. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) https://tinyurl.com/tgqawbz.

6.
Genes (Basel) ; 11(3)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188084

RESUMO

Non-synonymous SNPs and protein coding SNPs within the promoter region of genes (regulatory SNPs) might have a significant effect on carcass traits. Imputed sequence level data of 10,215 Hanwoo bulls, annotated and filtered to include only regulatory SNPs (450,062 SNPs), were used in a genome-wide association study (GWAS) to identify loci associated with backfat thickness (BFT), carcass weight (CWT), eye muscle area (EMA), and marbling score (MS). A total of 15, 176, and 1 SNPs were found to be significantly associated (p < 1.11 × 10-7) with BFT, CWT, and EMA, respectively. The significant loci were BTA4 (CWT), BTA6 (CWT), BTA14 (CWT and EMA), and BTA19 (BFT). BayesR estimated that 1.1%~1.9% of the SNPs contributed to more than 0.01% of the phenotypic variance. So, the GWAS was complemented by a gene-set enrichment (GSEA) and protein-protein interaction network (PPIN) analysis in identifying the pathways affecting carcass traits. At p < 0.005 (~2,261 SNPs), 25 GO and 18 KEGG categories, including calcium signaling, cell proliferation, and folate biosynthesis, were found to be enriched through GSEA. The PPIN analysis showed enrichment for 81 candidate genes involved in various pathways, including the PI3K-AKT, calcium, and FoxO signaling pathways. Our finding provides insight into the effects of regulatory SNPs on carcass traits.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32179036

RESUMO

BACKGROUND: The cyanoacrylate closure (CAC) procedure is a safe and effective modality for the treatment of an incompetent saphenous vein. Thrombus extension into the deep vein, known as endovenous glue-induced thrombosis (EGIT), may be a worrisome complication of the procedure. However, the incidence, classification, and risk factors of EGIT have not been elucidated. We report, herein, the incidence, classification, and risk factors of EGIT following the CAC procedure for an incompetent saphenous vein. METHODS: A retrospective review was performed of prospectively collected data of CAC patients. Preoperatively, the diameter, reflux time, and peak reflux velocity of the saphenous vein were measured. The CAC procedure was performed as per the instructions for use. Postoperative follow-up was conducted at 1 week, 3 months, 6 months, and 1 year after the procedure. Postoperative duplex scanning was performed to evaluate the occlusion of the target vein and presence of EGIT. Demographic data, risk factors, procedure details, and follow-up data were also obtained. A four-tier classification system and recommended treatment plan were developed based on the EGIT grade. All statistical analyses were performed using SPSS version 22.0 (IBM, Armonk, NY). A P value of <.05 was considered statistically significant. RESULTS: During the study period, the CAC procedure was performed in 191 patients (126 females [66.0%]). The mean age was 56.1 ± 11.7 years (range, 19-84) years. After the procedure, pain, the Revised Venous Clinical Severity Score, and the Aberdeen Varicose Vein Questionnaire score were significantly improved (P < .001). EGIT developed in 11 patients (5.8%). EGIT of grades I and II developed in seven (63.6%) and four (36.4%) patients, respectively. Duplex follow-up was conducted for all patients with EGIT without anticoagulation. Regarding the analysis of risk factors for the development of EGIT, the preoperative saphenous vein diameter of <5 mm was the only risk factor (P = .040). CONCLUSIONS: EGIT is not an uncommon complication of CAC. A small diameter of the saphenous vein (<5 mm) is a risk factor for the development of EGIT. A classification system and treatment protocol for EGIT based on the area of thrombus extension into the deep vein is proposed for managing patients.

8.
Korean J Intern Med ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32122114

RESUMO

Background/Aims: Recently, distal radial approach (DRA), called as snuffbox approach, has gained the interest of interventional cardiologists, but there is a lack of data about the feasibility of DRA as an alternative route for primary percutaneous coronary intervention (PCI). Methods: A total of 138 patients presenting with ST-elevation myocardial infarction (STEMI) in whom primary PCI via the DRA was attempted at three hospitals from October 2017 to September 2019 were analyzed. Results: The success rate of snuffbox puncture in the setting of STEMI was 92.8% (128/138). Successful primary PCI via the DRA was achieved in all 128 patients. The snuffbox puncture time, defined as the time interval from local anesthesia induction to successful sheath cannulation, was 2.7 ± 1.6 minutes, and snuffbox puncture was performed within 5 minutes in 95.3% of patients. Moreover, the percentage of the puncture time in the door-to-balloon time was 3.3%. The left DRA was selected in 103 patients (80.5%), and primary PCI via the DRA was performed using a 6-Fr guiding catheter in 125 patients (97.7%). There was no major bleeding; however, there were four cases (3.1%) of access-site complications, including three cases of local hematoma (≤ 5 cm diameter) and one case of local numbness, which improved 3 months later. Conclusions: In the setting of STEMI, the DRA could be a feasible alternative access route for primary PCI.

9.
J Diabetes Complications ; : 107555, 2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32019723

RESUMO

AIM: MLR-1023, called Tolimidone when evaluated unsuccessfully by Pfizer for gastric ulcer disease, has been repurposed as a novel oral insulin sensitizer with its effects mediated by selective activation of Lyn kinase. We aimed to evaluate the optimal dose, efficacy and safety of MLR-1023 in patients with type 2 diabetes. METHODS: Type 2 diabetes patients (18-75 years) on diet/exercise therapy were randomized and double-blinded to receive MLR-1023 (100-mg or 200-mg, once-daily [qd] or twice-daily [bid]) or matching placebo for 28 days. The primary endpoint was postprandial glucose (PPG) area under the curve (AUC0-3h) in a mixed meal tolerance test (MMTT) at day 29. Secondary endpoints included changes in fasting plasma glucose (FPG), insulin, HbA1c, lipids and body weight and adverse events. ANCOVA model was used for efficacy analysis. RESULTS: The placebo-corrected least-squares mean differences (ΔLSM) in MMTT PPG AUC0-3 h (mmol/L) were -5.96 and -5.6 (both p = 0.03) in the MLR-1023 100-mg qd and 100-mg bid groups, respectively. The placebo-corrected ΔLSM in FPG (mmol/L) was -2.34 (p = 0.003) in the MLR-1023 100-mg qd group. Triglycerides improved with MLR-1023 (ΔLSM, -0.56 mmol/L, p = 0.07 and -0.59 mmol/L, p = 0.05) in the 200mgqd and 200 mg bid groups, respectively. Reductions in fasting insulin, HbA1c and body weight were not statistically significant. Most common adverse events with MLR-1023 treatment were headache (4.2%) and somnolence (2.5%). CONCLUSIONS: MLR-1023 100-mg once-daily for 4 weeks was the most effective dose with significant reduction in PPG AUC following a MMTT. MLR-1023 was safe and well-tolerated in patients with type 2 diabetes. Clinical Trials Registration Number: NCT02317796.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32054155

RESUMO

Objective: The objective of this study was to characterize the number of loci affecting growth traits and the distribution of single nucleotide polymorphism (SNP) effects on growth traits, and to understand the genetic architecture for growth traits in Hanwoo (Korean cattle) using genome-wide association study (GWAS), genomic partitioning, and hierarchical Bayesian mixture models. Methods: GWAS: A single-marker regression-based mixed model was used to test the association between SNPs and causal variants. A genotype relationship matrix (GRM) was fitted as a random effect in this linear mixed model to correct the genetic structure of a sire family. Genomic restricted Maximum Likelihood (GREML) and BayesR: A priori information included setting the fixed additive genetic variance to a pre-specified value; the first mixture component was set to zero, the second to 0.0001 × σ_g^2 , the third 0.001 × σ_g^2, and the fourth to 0.01 × σ_g^2. BayesR fixed a priori information was not more than 1% of the genetic variance for each of the SNPs affecting the mixed distribution. Results: The GWAS revealed common genomic regions of 2 Mb on bovine chromosome 14 (BTA14) and 3 had a moderate effect that may contain causal variants for body weight at 6, 12, 18, and 24 months. This genomic region explained approximately 10% of the variance against total additive genetic variance and body weight heritability at 12, 18, and 24 months. BayesR identified the exact genomic region containing causal SNPs on BTA14, 3, and 22. However, the genetic variance explained by each chromosome or SNP was estimated to be very small compared to the total additive genetic variance. Causal SNPs for growth trait on BTA14 explained only 0.04-0.5% of the genetic variance. Conclusion: Segregating mutations have a moderate effect on BTA14, 3, and 19; many other loci with small effects on growth traits at different ages were also identified.

11.
Clin Transl Sci ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058642

RESUMO

The pharmacokinetic properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the pharmacokinetics of simvastatin. An open-label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for pharmacokinetic analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of microbiota considerably decreased, and the composition was altered. In particular, the relative abundance of Bacteroidetes decreased, while that of Proteobacteria increased. In addition, changes in fecal metabolites, including D-glucuronic acid, were observed. However, systemic exposure of simvastatin was not changed while that of hydroxysimvastatin showed a tendency to increase. The relationship between the change of pharmacokinetics of simvastatin and the change of gut microbiota and fecal metabolites were not clearly observed.

12.
Brain Topogr ; 33(2): 208-220, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32034577

RESUMO

Inhibitory dysfunction is closely associated to post-traumatic stress disorder (PTSD). The present study investigated the neurophysiological evidence for and the brain regions related to inhibitory dysfunction in PTSD. Fifty patients with PTSD and 63 healthy controls (HCs) participated in a Go/Nogo task combined with electroencephalographic recordings. The N2-P3 complexes of event-related potentials (ERPs) elicited during the Nogo condition were compared between groups. Participants underwent structural magnetic resonance imaging to examine cortical volumes and completed questionnaires. Correlations between altered ERPs and cortical volumes of regions of interest as well as psychological symptoms were analysed. Nogo-N2 latencies at five electrode sites (Fz, FCz, Cz, CPz, and Pz) were significantly delayed in patients with PTSD compared to HCs. Nogo-N2 latency had a significant negative correlation with the volume of gyrus in the inferior frontal cortex, orbitofrontal cortex, amygdala, and medial prefrontal cortex. Nogo-N2 latency was significantly and positively correlated with catastrophizing, anxiety, and perceived threat. These findings show inhibitory dysfunction in patients with PTSD, reflected by the delay in Nogo-N2 latencies. They also indicate that Nogo-N2 latencies are associated with smaller cortical volumes responsible for inhibition as well as with major symptoms of PTSD.

13.
Biosens Bioelectron ; 154: 112071, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056965

RESUMO

In the neuroendocrine system, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) play important roles in the regulation of the hypothalamic-pituitary-adrenal (HPA) system. Disorders of the HPA system lead to physiological problems, such as Addison's disease and Cushing's syndrome. Therefore, detection of CRH and ACTH is essential for diagnosing disorders related to the HPA system. Herein, receptors of the HPA axis were used to construct a bioelectronic sensor system for the detection of CRH and ACTH. The CRH receptor, corticotropin-releasing hormone receptor 1 (CRHR1), and the ACTH receptor, melanocortin 2 receptor (MC2R), were produced using an Escherichia coli expression system, and were reconstituted using nanodisc (ND) technology. The receptor-embedded NDs were immobilized on a floating electrode of a carbon nanotube field-effect transistor (CNT-FET). The constructed sensors sensitively detected CRH and ACTH to a concentration of 1 fM with high selectivity in real time. Furthermore, the reliable detection of CRH and ACTH in human plasma by the developed sensors demonstrated their potential in clinical and practical applications. These results indicate that CRHR1 and MC2R-based bioelectronic sensors can be applied for rapid and efficient detection of CRH and ACTH.

14.
Sci Rep ; 10(1): 2015, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029749

RESUMO

Although metallothionein-3 (MT3), a brain-enriched form of metallothioneins, has been linked to Alzheimer's disease, little is known regarding the role of MT3 in glioma. As MT3 plays a role in autophagy in astrocytes, here, we investigated its role in irradiated glioma cells. Irradiation increased autophagy flux in GL261 glioma cells as evidenced by increased levels of LC3-II but decreased levels of p62 (SQSTM1). Indicating that autophagy plays a cytoprotective role in glioma cell survival following irradiation, measures inhibiting autophagy flux at various steps decreased their clonogenic survival of irradiated GL261 as well as SF295 and U251 glioma cells. Knockdown of MT3 with siRNA in irradiated glioma cells induced arrested autophagy, and decreased cell survival. At the same time, the accumulation of labile zinc in lysosomes was markedly attenuated by MT3 knockdown. Indicating that such zinc accumulation was important in autophagy flux, chelation of zinc with tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), induced arrested autophagy in and reduced survival of GL261 cells following irradiation. Suggesting a possible mechanism for arrested autophagy, MT3 knockdown and zinc chelation were found to impair lysosomal acidification. Since autophagy flux plays a cytoprotective role in irradiated glioma cells, present results suggest that MT3 and zinc may be regarded as possible therapeutic targets to sensitize glioma cells to ionizing radiation therapy.

15.
J Microbiol Biotechnol ; 30(2): 244-247, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32066215

RESUMO

We have expressed extracellular poly(3-hydroxybutyrate) (PHB) depolymerase of Ralstonia pickettii T1 on the Escherichia coli surface using Pseudomonas OprF protein as a fusion partner by C-terminal deletion-fusion strategy. Surface display of depolymerase was confirmed by flow cytometry, immunofluorescence microscopy and whole cell hydrolase activity. For the application, depolymerase was used as an immobilized catalyst of enantioselective hydrolysis reaction for the first time. After 48 h, (R)-methyl mandelate was completely hydrolyzed, and (S)-mandelic acid was produced with over 99% enantiomeric excess. Our findings suggest that surface displayed depolymerase on E. coli can be used as an enantioselective biocatalyst.

16.
Investig Clin Urol ; 61(1): 19-27, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942459

RESUMO

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients. Materials and Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT). Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125-0.958). Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone.

17.
Sci Rep ; 10(1): 388, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31942024

RESUMO

Hormones within very low levels regulate and control the activity of specific cells and organs of the human body. Hormone imbalance can cause many diseases. Therefore, hormone detection tools have been developed, particularly over the last decade. Peptide hormones have a short half-life, so it is important to detect them within a short time. In this study, we report two types of peptide hormone sensors using human hormone receptor-carrying nanovesicles and graphene field-effect transistors (FETs). Parathyroid hormone (PTH) and glucagon (GCG) are peptide hormones present in human blood that act as ligands to G protein-coupled receptors (GPCRs). In this paper, the parathyroid hormone receptor (PTHR) and the glucagon receptor (GCGR) were expressed in human embryonic kidney-293 (HEK-293) cells, and were constructed as nanovesicles carrying the respective receptors. They were then immobilized onto graphene-based FETs. The two hormone sensors developed were able to detect each target hormone with high sensitivity (ca. 100 fM of PTH and 1 pM of GCG). Also, the sensors accurately recognized target hormones among different types of peptide hormones. In the development of hormone detection tools, this approach, using human hormone receptor-carrying nanovesicles and graphene FETs, offers the possibility of detecting very low concentrations of hormones in real-time.

19.
Otolaryngol Head Neck Surg ; 162(3): 346-352, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31959036

RESUMO

OBJECTIVE: The aim of this study was to investigate the clinical implications of diabetes for the management of idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: ISSNHL patients (N = 403) who received inpatient management between January 2015 and December 2018 were analyzed. All were managed by a uniform treatment protocol of high-dose steroid therapy and salvage intratympanic steroid injections. Treatment results were evaluated according to the American Academy of Otolaryngology-Head and Neck Surgery's criteria 3 months after the start of treatment. We compared the clinical parameters and treatment outcomes of ISSNHL with and without diabetes. We also evaluated the influence of diabetes on the prognosis of ISSNHL by propensity score matching. RESULTS: Overall, of the 403 ISSNHL patients, 94 (23.3%) had diabetes, and 11 were newly diagnosed with diabetes. The patients with diabetes were older than those without diabetes (P < .001), and their initial hearing threshold was significantly higher (P < .001). The diabetic patients were hospitalized for a longer period, and their hearing recovery rate was lower. However, when age, sex, and initial hearing level were adjusted by propensity score matching, the diabetic patients and matched controls yielded similar treatment results. CONCLUSIONS: ISSNHL with diabetes usually presents with severe hearing loss and requires longer hospitalization. However, diabetes itself may not influence the prognosis of ISSNHL. Proper management must be provided in ISSNHL with diabetes.

20.
Coron Artery Dis ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31913165

RESUMO

OBJECTIVES: Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) remains challenging because of limited success and higher target vessel failure rates. Detailed safety and efficacy data for CTO-PCI from a multicenter real-world Korean registry are limited. METHODS: Since May 2007, the Korean multicenter retrospective CTO registry has enrolled 3271 patients who underwent CTO-PCI at 26 major medical centers. Baseline clinical, angiographic, and procedural characteristics and 12-month major adverse cardiac event (MACE) rates after PCI were retrospectively collected. RESULTS: Baseline cardiovascular risk factors included: male sex, 73.8%; prior myocardial infarction (MI), 14.8%; prior PCI, 26.6%; hypertension, 62.3%; diabetes mellitus, 34.8%; dyslipidemia, 33.3%; and current smoker, 30.9%. Pre-PCI myocardial viability testing was performed in 23.6% of patients and pre-PCI cardiac computed tomography (CT) in 17.6%. CTO arterial lesions were distributed as follows: right coronary, 41.0%; left anterior descending, 40.0%; left circumflex, 22.5%; and left main, 0.4%. Unfavorable lesion morphology was detected by angiography in 38.1%. Intravascular ultrasound guidance and the retrograde approach were utilized in 23.6 and 3.1% of CTO-PCI procedures, respectively. More than 75% of patients received drug-eluting stents (sirolimus-eluting, 26.5%; paclitaxel-eluting, 23.8%; zotarolimus-eluting, 23.4%; everolimus-eluting, 11.0%; and others, 4.0%). The overall success rate was 81.6% (2672/3271 patients). Twelve-month event rates were: total mortality, 2.4%; any MI, 0.7%; target lesion revascularization, 4.4%; target vessel revascularization, 6.7%; and total MACE, 9.4%. CONCLUSIONS: Twelve-month success rates, safety profiles, and cumulative clinical outcomes of Korean CTO patients were favorable post-PCI. Long-term follow-up of larger study populations is necessary to validate our findings.

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