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BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.
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Esofagitis Péptica , Esofagitis , Reflujo Gastroesofágico , Úlcera Péptica , Humanos , Método Doble Ciego , Esomeprazol/efectos adversos , Esofagitis Péptica/tratamiento farmacológico , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/diagnóstico , Inhibidores de la Bomba de Protones/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. METHODS: We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. RESULTS: After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. CONCLUSION: In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/inducido químicamente , Neoplasias Gástricas/epidemiología , Inhibidores de la Bomba de Protones/efectos adversos , Estudios de Cohortes , Riesgo , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Embeddingp-type gallium nitride (p-GaN) with controlled Mg out-diffusion in adjacent epitaxial layers is a key for designing various multi-junction structures with high precision and enabling more reliable bandgap engineering of III-nitride-based optoelectronics and electronics. Here, we report, for the first time, experimental evidence of how nanoporous GaN (NP GaN) can be introduced as a compensation layer for the Mg out-diffusion fromp-GaN. NP GaN onp-GaN provides anex-situformed interface with oxygen and carbon impurities, compensating for Mg out-diffusion fromp-GaN. To corroborate our findings, we used two-dimensional electron gas (2DEG) formed at the interface of AlGaN/GaN as the indicator to study the impact of the Mg out-diffusion from underlying layers. Electron concentration evaluated from the capacitance-voltage measurement shows that 9 × 1012cm-2of carriers accumulate in the AlGaN/GaN 2DEG structure grown on NP GaN, which is the almost same number of carriers as that grown with nop-GaN. In contrast, 2DEG onp-GaN without NP GaN presents 9 × 109cm-2of the electron concentration, implying the 2DEG structure is depleted by Mg out-diffusion. The results address the efficacy of NP GaN and its' role in successfully embeddingp-GaN in multi-junction structures for various state-of-the-art III-nitride-based devices.
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Semiconductor quantum well structures have been critical to the development of modern photonics and solid-state optoelectronics. Quantum level tunable structures have introduced new transformative device applications and afforded a myriad of groundbreaking studies of fundamental quantum phenomena. However, noncolloidal, III-V compound quantum well structures are limited to traditional semiconductor materials fabricated by stringent epitaxial growth processes. This report introduces artificial multiple quantum wells (MQWs) built from CsPbBr3 perovskite materials using commonly available thermal evaporator systems. These perovskite-based MQWs are spatially aligned on a large-area substrate with multiple stacking and systematic control over well/barrier thicknesses, resulting in tunable optical properties and a carrier confinement effect. The fabricated CsPbBr3 artificial MQWs can be designed to display a variety of photoluminescence (PL) characteristics, such as a PL peak shift commensurate with the well/barrier thickness, multiwavelength emissions from asymmetric quantum wells, the quantum tunneling effect, and long-lived hot-carrier states. These new artificial MQWs pave the way toward widely available semiconductor heterostructures for light-conversion applications that are not restricted by periodicity or a narrow set of dimensions.
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We report the enhanced optical and electrical properties of InGaN/GaN multiple quantum well (MQW) light-emitting diodes (LEDs) with strain-relaxing Ga-doped ZnO transparent conducting layers (TCLs). Ga-doped ZnO was epitaxially grown on p-GaN by metal-organic chemical vapor deposition. The optical output power of a LED with a 500-nm- thick-Ga-doped ZnO TCL increased by 30.9% at 100 mA, compared with that of an LED with an indium tin oxide (ITO) TCL. Raman spectroscopy measurement and the simulation of wavefunction overlap of electron and hole in MQWs revealed that the enhanced optical output power was attributed to the increased internal quantum efficiency due to the decreased compressive strain in the active region. The increase of optical output was also attributed to the increased optical transmittance of the Ga-doped ZnO TCL owing to its higher refractive index compared to that of ITO TCL. Furthermore, the forward voltage of LED with a Ga-doped ZnO TCL was lower than that of LED with an ITO TCL because of the increased carrier concentration and mobility in the Ga-doped ZnO TCL.
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The light to be trapped inside light-emitting diodes (LEDs) greatly affects the luminous efficiency and device lifetime. Abrupt difference in refractive index between the sapphire substrate and GaN-based LEDs causes light trapping by total internal reflection, however, its optical loss has been taken for granted. In this study, we demonstrate that nanoporous GaN can be used as a refractive-index-matching layer to enhance the light transmittance at the sapphire-GaN interface in InGaN/GaN flip-chip light-emitting diodes (FCLEDs). The porosity and the refractive index of the nanoporous GaN layer are controlled by electrochemical etching of n-type GaN layer. The optical output power of FCLEDs with the nanoporous GaN layer grown on flat and patterned sapphire substrates is increased by 355% and 65% at an injection current of 20 mA, respectively, compared with that of an FCLED without the nanoporous GaN layer. The remarkable enhancement of optical output is mostly attributed to the nanoporous GaN layer which drastically increases the light extraction efficiency by decreasing the reflection of light at the sapphire-GaN interface.
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BACKGROUND/AIMS: The mucosal healing process after endoscopic submucosal dissection (ESD) is mostly scarring change (flat type), but a protruded lesion is occasionally found. We investigated the factors influencing the mucosal healing process, such as the flat and protruded types. METHODS: A total of 2,096 ESD cases were performed from February 2005 to December 2013, and 1,757 underwent follow-up endoscopy after 3 months to check the healing type of the ulceration. We retrospectively reviewed the medical charts to analyze demographic, endoscopic, and pathological findings between the 2 groups. RESULTS: Forty-eight cases were of the protruded type and 1,709 were of the flat type. In univariate analysis, the protruded type was found more in the antrum, anterior wall, and greater curvature (p < 0.001). In protruded types, the Helicobacter pylori (H. pylori) infection rate was lower (p < 0.017), the mean length of ESD specimen was shorter (p < 0.012), the fibrosis rate was lower (p < 0.033), and the mean number of hot biopsy and clips during ESD were less (p < 0.008 and p < 0.001 respectively). CONCLUSIONS: The healing type of mucosal ulceration after ESD seemed to be influenced by location, specimen size, and the presence of an H. pylori infection.
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Resección Endoscópica de la Mucosa/efectos adversos , Mucosa Gástrica/patología , Gastroscopía/efectos adversos , Complicaciones Posoperatorias/patología , Neoplasias Gástricas/cirugía , Úlcera/patología , Anciano , Resección Endoscópica de la Mucosa/métodos , Femenino , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/microbiología , Mucosa Gástrica/cirugía , Gastroscopía/métodos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/microbiología , Estudios Retrospectivos , Úlcera/diagnóstico por imagen , Úlcera/etiología , Cicatrización de HeridasRESUMEN
OBJECTIVE: To propose an artificial intelligence (AI)-based decision-making rule in modified Ashworth scale (MAS) that draws maximum agreement from multiple human raters and to analyze how various biomechanical parameters affect scores in MAS. DESIGN: Prospective observational study. SETTING: Two university hospitals. PARTICIPANTS: Hemiplegic adults with elbow flexor spasticity due to acquired brain injury (N=34). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Twenty-eight rehabilitation doctors and occupational therapists examined MAS of elbow flexors in 34 subjects with hemiplegia due to acquired brain injury while the MAS score and biomechanical data (ie, joint motion and resistance) were collected. Nine biomechanical parameters that quantify spastic response described by the joint motion and resistance were calculated. An AI algorithm (or artificial neural network) was trained to predict the MAS score from the parameters. Afterwards, the contribution of each parameter for determining MAS scores was analyzed. RESULTS: The trained AI agreed with the human raters for the majority (82.2%, Cohen's kappa=0.743) of data. The MAS scores chosen by the AI and human raters showed a strong correlation (correlation coefficient=0.825). Each biomechanical parameter contributed differently to the different MAS scores. Overall, angle of catch, maximum stretching speed, and maximum resistance were the most relevant parameters that affected the AI decision. CONCLUSIONS: AI can successfully learn clinical assessment of spasticity with good agreement with multiple human raters. In addition, we could analyze which factors of spastic response are considered important by the human raters in assessing spasticity by observing how AI learns the expert decision. It should be noted that few data were collected for MAS3; the results and analysis related to MAS3 therefore have limited supporting evidence.
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Encefalopatías/fisiopatología , Articulación del Codo/fisiopatología , Hemiplejía/fisiopatología , Espasticidad Muscular/fisiopatología , Redes Neurales de la Computación , Examen Neurológico , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND AND AIM: This study aimed to investigate the effectiveness of scheduled second-look endoscopy (EGD) with endoscopic hemostasis on peptic ulcer rebleeding and to identify the risk factors related to the need for second-look EGD. METHODS: We prospectively randomized patients who had endoscopically confirmed bleeding peptic ulcer with stigmata of active bleeding, visible vessel, or adherent clot into 2 groups between August 2010 and January 2013. Hemoclip application or thermal coagulation and/or epinephrine injection were allowed for initial endoscopic therapy. The same dosage of proton pump inhibitor was injected intravenously. The study group received scheduled second-look EGD 24 to 36 hours after the initial hemostasis, and further therapy was applied if endoscopic stigmata persisted, as above. Those patients who developed rebleeding underwent operation or radiologic intervention despite the additional endoscopic therapy. Outcome measures included rebleeding, amount of transfusion, duration of hospitalization, and mortality. RESULTS: After initial endoscopic hemostasis, 319 eligible patients were randomized into 2 groups. Sixteen (10.1%) and 9 (5.6%) patients developed rebleeding (P = .132), respectively. There was also no difference in surgical intervention (0, 0% vs 1, .6%, P >.999) or radiologic intervention (3, 1.9% vs 2, 1.2%, P = .683), median duration of hospitalization (6.0 vs 5.0 days, P = .151), amount of transfusion (2.4 ± 1.7 vs 2.2 ± 1.6 units, P = .276), and mortality (2, 1.3% vs 2, 1.2%, P > .999) between the 2 groups. Multivariate analysis showed that grades 3 to 4 of endoscopists' estimation to success of initial hemostasis, history of nonsteroidal anti-inflammatory drug (NSAID) use, and larger amounts of blood transfusions (≥4 units of red blood cells) were the independent risk factors of rebleeding. CONCLUSIONS: A single EGD with endoscopic hemostasis is not inferior to scheduled second-look endoscopy in terms of reduction in rebleeding rate of peptic ulcer bleeding. Repeat endoscopy would be helpful in the patients with unsatisfactory initial endoscopic hemostasis, use of NSAIDs, and larger amounts of transfused blood. (Clinical trial registration number: KCT0000565; 4-2010-0348.).
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Úlcera Duodenal/terapia , Embolización Terapéutica , Endoscopía Gastrointestinal , Hemostasis Endoscópica , Úlcera Péptica Hemorrágica/terapia , Úlcera Gástrica/terapia , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Transfusión Sanguínea , Úlcera Duodenal/complicaciones , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Úlcera Péptica Hemorrágica/etiología , Estudios Prospectivos , Radiología Intervencionista , Recurrencia , Factores de Riesgo , Segunda Cirugía , Úlcera Gástrica/complicaciones , Factores de TiempoRESUMEN
OBJECTIVES: This study was performed to evaluate long-term outcome of indeterminate nodules detected on cirrhotic liver and to develop risk prediction model for hepatocellular carcinoma (HCC) progression of indeterminate nodules on hepatitis B virus (HBV)-related cirrhotic liver. METHODS: Indeterminate nodules up to 2 cm with uncertain malignant potential detected on computed tomography of cirrhotic liver during HCC surveillance were analyzed retrospectively. HCC risk prediction model of indeterminate nodules in HBV-related cirrhotic liver was deduced based on result of Cox regression analysis. RESULTS: A total of 494 indeterminate nodules were included. Independent risk factors of HCC progression were old age, arterial enhancement, large nodule size, low serum albumin level, high serum α-fetoprotein (AFP) level, and prior HCC history in all included subjects. In subjects with chronic hepatitis B, old age (year; hazard ratio (HR)=1.06; P<0.001), arterial enhancement (HR=2.62; P=0.005), large nodule size (>1 cm; HR=7.34; P<0.001), low serum albumin level (≤3.5 g/dl; HR=3.57; P=0.001), high serum AFP level (≥100 ng/ml; HR=6.04; P=0.006), prior HCC history (HR=4.24; P=0.001), and baseline hepatitis B e antigen positivity (HR=2.31; P=0.007) were associated with HCC progression. We developed a simple risk prediction model using these risk factors and identified patients at low, intermediate, and high risk for HCC; 5-year cumulative incidences were 1%, 14.5%, and 63.1%, respectively. The developed risk score model showed good performance with area under the curve at 0.886 at 3 years, and 0.920 at 5 years in leave-one-out cross-validation. CONCLUSIONS: We developed a useful and accurate risk score model for predicting HCC progression of indeterminate nodules detected on HBV-related cirrhotic liver.
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Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/complicaciones , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Progresión de la Enfermedad , Femenino , Hepatitis B Crónica/metabolismo , Humanos , Hipoalbuminemia/epidemiología , Incidencia , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tomografía Computarizada por Rayos X , Adulto Joven , alfa-Fetoproteínas/metabolismoRESUMEN
BACKGROUND: Although sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib. METHODS: Thirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled. Using a Luminex 200 system, 11 cytokines including interleukin-17A (IL-17A) were measured in baseline serum samples prior to sorafenib administration. Several clinical factors and the serum concentrations of the 11 cytokines were analyzed using Cox regression analysis. RESULTS: In the analysis of progression-free survival (PFS), older age (year; hazard ratio [HR]=1.07; 95% confidence interval [CI]=1.00-1.15; P=0.046) and higher baseline serum IL-17A level (>1.94pg/mL; HR=19.96; 95% CI=3.32-119.86; P=0.001) were identified as significant risk factors for early progression with good predictive power (Harrell's C=0.817, standard error estimates (se)=0.085). In the analysis of OS, higher Child-Pugh score (>5; HR=2.35, 95% CI=1.09-5.10, P=0.030) and lower serum baseline fibroblast growth factor-2 level (≤20.57pg/mL; HR=3.24, 95% CI=1.22-8.60, P=0.018) were identified as negative predictive factors for OS, even though the model did not have significant predictive power (Harrell's C=0.634, se=0.062). CONCLUSION: A higher serum IL-17A level is a potential biomarker for predicting poor PFS in patients with HBV-related advanced HCC treated with sorafenib.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis B/complicaciones , Interleucina-17/sangre , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Estudios de Cohortes , Citocinas/sangre , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , SorafenibRESUMEN
AIMS: To assess the efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, added to metformin and sulphonylurea in patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride. Participants were randomized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. RESULTS: The baseline HbA1c was 8.2% in both groups. The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo (between-group difference in adjusted mean change -0.87%, 95% confidence interval [CI] -1.09% to -0.64%). Fasting plasma glucose level was also significantly reduced with gemigliptin (-0.93 mmol/L, 95% CI -1.50 to -0.35 mmol/L), and a higher proportion of participants achieved an HbA1c level of <7% (39.3% vs 5.5%; P <.001) in the gemigliptin group than in the placebo group. Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group (-0.21 mmol/L, 95% CI -0.38 to -0.03 mmol/L for total cholesterol, -0.18 mmol/L, 95% CI -0.34 to -0.01 mmol/L for LDL cholesterol). The incidence of hypoglycaemia was 9.4% in the gemigliptin group and 2.7% in the placebo group. CONCLUSIONS: Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea. The incidence of hypoglycaemia was higher with gemigliptin than with placebo, which highlights the importance of optimal dose adjustment for sulphonylurea.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Resistencia a Medicamentos , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Piperidonas/uso terapéutico , Pirimidinas/uso terapéutico , Anciano , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Método Doble Ciego , Monitoreo de Drogas , Quimioterapia Combinada/efectos adversos , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Incidencia , Masculino , Metformina/efectos adversos , Metformina/uso terapéutico , Persona de Mediana Edad , Piperidonas/efectos adversos , Pirimidinas/efectos adversos , República de Corea/epidemiología , Riesgo , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/uso terapéuticoRESUMEN
BACKGROUND: Intestinal fibrosis is a serious complication of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. There is no specific treatment for intestinal fibrosis. Studies have indicated that peroxisome proliferator-activated receptor- γ (PPAR-γ) agonists have anti-fibrogenic properties in organs besides the gut; however, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of PPAR-γ agonists on human primary intestinal myofibroblasts (HIFs). METHODS: HIFs were isolated from normal colonic tissue of patients undergoing resection due to colorectal cancer. HIFs were treated with TGF-ß1 and co-incubated with or without one of two synthetic PPAR-γ agonists, troglitazone or rosiglitazone. mRNA and protein expression of procollagen1A1, fibronectin, and α-smooth muscle actin were determined by semiquantitative reverse transcription-polymerase chain reaction and Western blot. LY294002 (Akt inhibitor) was used to examine whether Akt phosphorylation was a downstream mechanism of TGF-ß1 induced expression of procollagen1A1, fibronectin, and α-smooth muscle actin in HIFs. The irreversible PPAR-γ antagonist GW9662 was used to investigate whether the effect of PPAR-γ agonists was PPAR-γ dependent. RESULTS: Both PPAR-γ agonists reduced the TGF-ß1-induced expression of α-smooth muscle actin which was integrated into stress fibers in HIFs, as determined by actin microfilaments fluorescent staining and α-smooth muscle actin-specific immunocytochemistry. PPAR-γ agonists also inhibited TGF-ß1-induced mRNA and protein expressions of procollagen1A1, fibronectin, and α-smooth muscle actin. TGF-ß1 stimulation increased phosphorylation of downstream signaling molecules Smad2, Akt, and ERK. TGF-ß1 induced synthesis of procollagen1A1, fibronectin, and α-smooth muscle actin through a phosphatidylinositol 3-kinase/Akt-dependent mechanism. PPAR-γ agonists down regulated fibrogenesis, as shown by inhibition of Akt and Smad2 phosphorylation. This anti-fibrogenic effect was PPAR-γ independent. CONCLUSIONS: Troglitazone and rosiglitazone suppress TGF-ß1-induced synthesis of procollagen1A1, fibronectin, and α-smooth muscle actin in HIFs and may be useful in treating intestinal fibrosis.
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Cromanos/farmacología , Intestinos/citología , Miofibroblastos/efectos de los fármacos , PPAR gamma/agonistas , Tiazolidinedionas/farmacología , Actinas/efectos de los fármacos , Actinas/genética , Células Cultivadas , Proteínas de la Matriz Extracelular/efectos de los fármacos , Proteínas de la Matriz Extracelular/genética , Fibrosis/tratamiento farmacológico , Expresión Génica , Humanos , Intestinos/patología , Fosforilación , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Rosiglitazona , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , TroglitazonaRESUMEN
PURPOSE: Cardiovascular safety alerts about rosiglitazone resulted in regulatory actions in several countries in 2010, but the Food and Drug Administration eliminated access restrictions in 2013, reflecting new evidence concerning the drug safety. We investigated the effects of safety signals and regulation shifts concerning rosiglitazone on prescribing of antidiabetic drugs (ADs). METHODS: Patient data were extracted from the Korean health insurance claims database for 2007 to 2015. Linear regression and interrupted time series analyses were performed to examine drug utilization trends and the impact of 5 milestone events regarding rosiglitazone safety on AD utilization. RESULTS: A steady growth was observed in the AD consumption, with metformin preserving its dominant market share throughout the period. Pioglitazone use has increased since 2008 in response to safety issues surrounding rosiglitazone. A significant decline in rosiglitazone use was observed after Nissen's meta-analysis and safety warnings (2007) and after restriction/suspension of access to rosiglitazone (2010), associated with a drop in prevalence by 29.5%/year and 99.5%/year, respectively. The most common AD newly started among users who discontinued rosiglitazone in 2010 was pioglitazone, followed by dipeptidyl peptidase-4 (DPP-4) inhibitors. Our concomitancy analysis showed that DPP-4 inhibitors have overtaken sulfonylureas since 2014 as the most common add-on to metformin. CONCLUSIONS: The most frequently added AD in diabetes patients who had switched off rosiglitazone in 2010 was pioglitazone, followed by DPP-4 inhibitors. Despite new evidence from a long-term clinical trial and the Food and Drug Administration's subsequent decision to eliminate access restrictions on rosiglitazone in 2013, domestic regulations were left intact; hence, its use remained negligible in Korea.
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Prescripciones de Medicamentos/estadística & datos numéricos , Hipoglucemiantes/efectos adversos , Legislación de Medicamentos/tendencias , Tiazolidinedionas/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/tendencias , Medicina Basada en la Evidencia , Humanos , Hipoglucemiantes/uso terapéutico , Análisis de Series de Tiempo Interrumpido , Metformina/efectos adversos , Metformina/uso terapéutico , Seguridad del Paciente , Farmacoepidemiología , Pioglitazona , República de Corea/epidemiología , Rosiglitazona , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/uso terapéutico , Tiazolidinedionas/uso terapéuticoRESUMEN
We report the growth of InGaN/GaN multiple quantum wells blue light-emitting diodes (LEDs) on a silicon (111) substrate with an embedded nanoporous (NP) GaN layer. The NP GaN layer is fabricated by electrochemical etching of n-type GaN on the silicon substrate. The crystalline quality of crack-free GaN grown on the NP GaN layer is remarkably improved and the residual tensile stress is also decreased. The optical output power is increased by 120% at an injection current of 20 mA compared with that of conventional LEDs without a NP GaN layer. The large enhancement of optical output power is attributed to the reduction of threading dislocation, effective scattering of light in the LED, and the suppression of light propagation into the silicon substrate by the NP GaN layer.
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OBJECTIVE: Endoscopic transpapillary gallbladder drainage using a nasocystic tube or plastic stent has been attempted as an alternative to percutaneous drainage for patients with acute cholecystitis who are not candidates for urgent cholecystectomy. We aimed to assess the efficacy of single-step endoscopic drainage of the common bile duct and gallbladder, and to evaluate which endoscopic transpapillary gallbladder drainage method is ideal as a bridge before elective cholecystectomy. MATERIALS AND METHODS: From July 2011 to December 2014, 35 patients with acute moderate-to-severe cholecystitis and a suspicion of choledocholithiasis were randomly assigned to the endoscopic naso-gallbladder drainage (ENGBD) (n = 17) or endoscopic gallbladder stenting (EGBS) (n = 18) group. RESULTS: Bile duct clearance was performed successfully in all cases. No significant differences were found between the ENGBD and EGBS groups in the technical success rates [82.4% (14/17) vs. 88.9% (16/18), p = 0.658] and clinical success rates [by intention-to-treat analysis: 70.6% (12/17) vs. 83.3% (15/18), p = 0.443; by per protocol analysis of technically feasible cases: 85.7% (12/14) vs. 93.8% (15/16), p = 0.586]. Three ENGBD patients and two EGBS patients experienced adverse events (p = 0.658). No significant differences were found in operation time or rate of conversion to open cholecystectomy. CONCLUSIONS: Single-step endoscopic transpapillary drainage of the common bile duct and gallbladder seems to be an acceptable therapeutic modality in patients with acute cholecystitis and a suspicion of choledocholithiasis. There were no significant differences in the technical and clinical outcomes between ENGBD and EGBS as a bridge before cholecystectomy.
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Colecistectomía , Colecistitis Aguda/complicaciones , Colecistitis Aguda/cirugía , Coledocolitiasis/complicaciones , Drenaje/métodos , Endoscopía del Sistema Digestivo , Vesícula Biliar/cirugía , Cuidados Preoperatorios/métodos , Stents , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nariz , Estudios ProspectivosRESUMEN
Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.
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Degeneración Hepatolenticular/complicaciones , Hipopituitarismo/diagnóstico , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/etiología , Adulto , Encéfalo/diagnóstico por imagen , Depresión/etiología , Femenino , Humanos , Hipopituitarismo/complicaciones , Hipopituitarismo/tratamiento farmacológico , Hipotiroidismo/diagnóstico , Hipotiroidismo/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Imagen por Resonancia Magnética , Esteroides/uso terapéutico , Hormona Liberadora de Tirotropina/uso terapéuticoRESUMEN
BACKGROUND AND STUDY AIMS: Endoscopists sometimes face paradoxical cases in which the endoscopic submucosal dissection (ESD) specimen reveals a non-neoplastic pathology result. The aims of the study were to determine the reasons for such results, and to compare the endoscopic characteristics of non-neoplastic and conventional neoplastic pathology groups after ESD. PATIENTS AND METHODS: A total of 1186 gastric ESDs performed between February 2005 and December 2011 were retrospectively reviewed. The ESD specimens included 52 (4.4â%) that were confirmed as negative or indefinite for neoplasia. Patient characteristics and endoscopic and pathological data were reviewed and compared. RESULTS: Non-neoplastic pathology after ESD was due to complete removal of the lesion at biopsy in 45 cases (86.5â%), pathology overestimation in 5 (9.6â%), and incorrect localization of the original tumor with subsequent ESD performed at the wrong site in 2 (3.8â%). The mean length and surface area of the non-neoplastic lesions were 9.2â±â2.6âmm and 49.6â±â23.6âmmâ(2), respectively. Mean sampling ratios were 3.0â±â1.5âmm/fragment and 16.3â±â10.0âmm(2)/fragment. Compared with 1134 cases confirmed as neoplastic on the final ESD specimen, non-neoplastic cases showed a significantly smaller tumor size and surface area, and lower sampling ratios in a logistic regression analysis adjusted for potential confounders (Pâ<â0.001 for all). CONCLUSIONS: Complete lesion removal by biopsy, pathology overestimation, and incorrect localization of the original tumor with subsequent ESD at the wrong site were the main reasons for non-neoplastic results after ESD. Small tumor size and surface area, and low sampling ratios were associated with non-neoplastic pathology results after ESD.
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Adenocarcinoma/patología , Adenoma/patología , Disección , Mucosa Gástrica/patología , Gastroscopía , Neoplasias Gástricas/patología , Adenocarcinoma/cirugía , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Disección/métodos , Femenino , Estudios de Seguimiento , Mucosa Gástrica/cirugía , Gastroscopía/métodos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: Covered self-expandable metal stents (SEMSs) are increasingly used as alternatives to uncovered SEMSs for the palliation of inoperable malignant distal biliary obstruction to counteract tumor ingrowth. We aimed to compare the outcomes of partially covered and uncovered SEMSs with identical mesh structures and anti-migration properties, such as low axial force and flared ends. MATERIALS AND METHODS: One hundred and three patients who were diagnosed with inoperable malignant distal biliary obstruction between January 2006 and August 2013 were randomly assigned to either the partially covered (n = 51) or uncovered (n = 52) SEMS group. RESULTS: There were no significant differences in the cumulative stent patency, overall patient survival, stent dysfunction-free survival and overall adverse events, including pancreatitis and cholecystitis, between the two groups. Compared to the uncovered group, stent migration (5.9% vs. 0%, p = 0.118) and tumor overgrowth (7.8% vs. 1.9%, p = 0.205) were non-significantly more frequent in the partially covered group, whereas tumor ingrowth showed a significantly higher incidence in the uncovered group (5.9% vs. 19.2%, p = 0.041). Stent migration in the partially covered group occurred only in patients with short stenosis of the utmost distal bile duct (two in ampullary cancer, one in bile duct cancer), and did not occur in any patients with pancreatic cancer. CONCLUSIONS: For the palliation of malignant distal biliary obstruction, endoscopic placement of partially covered SEMSs with anti-migration designs and identical mesh structures to uncovered SEMSs failed to prolong cumulative stent patency or reduce stent migration.
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Neoplasias de los Conductos Biliares/cirugía , Colecistitis/etiología , Cuidados Paliativos , Stents/efectos adversos , Anciano , Aleaciones , Endoscopios Gastrointestinales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pancreatitis/etiología , Complicaciones Posoperatorias/etiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , República de Corea , Stents/clasificación , Resultado del TratamientoRESUMEN
Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects' symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.