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BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.
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Diabetes Gestacional , Hipertensión Inducida en el Embarazo , Embarazo , Femenino , Humanos , Peso al Nacer , Índice de Masa Corporal , Estudios Retrospectivos , Hipertensión Inducida en el Embarazo/epidemiología , Diabetes Gestacional/epidemiologíaRESUMEN
OBJECTIVE: To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. DESIGN: Retrospective cohort study. SETTING: Nationwide (Republic of Korea). POPULATION: All twin children delivered at term between 2007 and 2010. METHODS: The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. MAIN OUTCOME MEASURES: Long-term adverse neurodevelopmental outcome. RESULTS: Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). CONCLUSION: In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.
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Enfermedades del Recién Nacido , Complicaciones del Embarazo , Niño , Femenino , Humanos , Recién Nacido , Peso al Nacer , Enfermedades en Gemelos , Estudios Retrospectivos , Convulsiones , GemelosRESUMEN
To overcome the drawbacks of conventional drug delivery system, nanoemulsion have been developed as an advanced form for improving the delivery of active ingredients. However, safety evaluation is crucial during the development stage before the commercialization. Therefore, the aim of this study was to evaluate the cytotoxicity of two types of newly developed nanoemulsions. Turmeric extract-loaded nanoemulsion powder-10.6 (TE-NEP-10.6, high content of artificial surfactant Tween 80), which forms the optimal nanoemulsion, and the TE-NEP-8.6 made by increasing the content of natural emulsifier (lecithin) to reduce the potential toxicity of nanoemulsion were cultured with various cells (NIH3T3, H9C2, HepG2, hCPC, and hEPC) and the changes of each cell were observed followed by nanoemulsion treatment. As a result, the two nanoemulsions (TE-NEP-10.6 and TE-NEP-8.6) did not show significant difference in cell viability. In the case of cell line (NIH3T3, H9C2, and HepG2), toxicity was not observed at an experimental concentration of less than 1 mg/mL, however, the cell survival rate decreased in a concentration dependent manner in the case of primary cultured cells. These results from our study can be used as a basic data to confirm the cell type dependent toxicity of nanoemulsion.
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Curcuma/química , Emulsiones/química , Nanopartículas/química , Aceites/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Agua/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , HumanosRESUMEN
Turmeric extract (TE)-loaded oleogels (TE-OG) was fabricated by an emulsion template technique using xanthan gum (XG) and soy lecithin (SL) as oleogelators. The formulation for TE-OG was optimized using 0.32% XG, 1.2% SL, and 1.0% TE. The optimized TE-OG had a minimal particle size of 810.23 ± 10.68 nm as measured by the dynamic light scattering (DLS) method, and a high encapsulation efficiency (EE) of 96.62 ± 0.56%. Additionally, the optimized TE-OG exhibited a favorable zeta potential of -27.73 ± 0.44 mV, indicating the good stability of the TE-OG due to the electrostatic repulsion between particles. TE-OG formulated with 0.32% XG and 1.2% SL was subjected to frequency sweep testing to evaluate its solid-like rheological behavior. The oil-binding capacity (OBC) of TE-OG was consistently maintained above 99.99%. In vitro digestion of TE-OG demonstrated the potential of the emulsion template for controlled release, with less than 20% of the encapsulated curcumin being released in simulated gastric fluid (SGF), whereas nearly 70% was released in the simulated intestinal fluid (SIF). Moreover, TE-OG affected the rapid release of free fatty acids (FFAs), which have a positive effect on the digestion of triacylglycerols found in soybean oil (SO). TE-OG was further used as an alternative to commercial butter to produce pound cakes, and their rheological properties were compared to those of the pound cake prepared using commercial butter. The pound cake prepared using TE-OG showed a noticeable decrease in hardness from 10.08 ± 1.39 N to 7.88 ± 0.68 N and increased porosity, demonstrating the inherent capability of TE-OG to enhance the overall quality standards of bakery products.
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This study aimed to develop a multifunctional active composite film to extend the shelf life of minced pork. The composite film was prepared by incorporating zinc-doped grapefruit peel-derived carbon quantum dots (Zn-GFP-CD) into a cellulose nanofiber (CNF) matrix. The resulting film significantly improved UV-blocking properties from 39.0 % to 85.7 % while maintaining the film transparency. Additionally, the CNF/Zn-GFP-CD5% composite film exhibits strong antioxidant activity with ABTS and DPPH radical scavenging activities of 99.8 % and 77.4 %, respectively. The composite film also showed excellent antibacterial activity against both Gram-negative and Gram-positive bacteria. When used in minced pork packaging, the composite films effectively inhibit bacterial growth, maintaining bacterial levels below 7 Log CFU/g after 15 days and sustaining a red color over a 21-day storage period. Additionally, a significant reduction in the lipid oxidation of the minced pork was observed. These CNF/Zn-GFP-CD composite films have a great potential for active food packaging applications to extend shelf life and maintain the visual quality of packaged meat.
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Carbono , Celulosa , Citrus paradisi , Embalaje de Alimentos , Nanofibras , Puntos Cuánticos , Zinc , Puntos Cuánticos/química , Nanofibras/química , Celulosa/química , Embalaje de Alimentos/métodos , Zinc/química , Citrus paradisi/química , Carbono/química , Antioxidantes/química , Antioxidantes/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Animales , PorcinosRESUMEN
This study aimed to investigate the effect of cinnamon essential oil (CEO)-loaded metal-organic frameworks (CEO@MOF) on the properties of gelatin/pullulan (Gel/Pull)-based composite films (Gel/Pull-based films). The incorporation of CEO@MOF into Gel/Pull-based films demonstrated significant antimicrobial activity against S. aureus, S. enterica, E. coli, and L. monocytogenes. Additionally, CEO@MOF integrated film exhibited a 98.16 % ABTS radical scavenging, with no significant change in the mechanical properties of the neat Gel/Pull film. The UV blocking efficiency of the composite films increased significantly from 81.38 to 99.56 % at 280 nm with the addition of 3 wt% CEO@MOF. Additionally, Gel/Pull/CEO@MOF films effectively extended the shelf life of meat preserved at 4 °C by reducing moisture loss by 3.35 %, maintaining the pH within the threshold limit (6.2), and inhibiting bacterial growth by 99.9 %. These results propose that CEO@MOF has significant potential as an effective additive in active packaging to improve shelf life and food safety.
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Cinnamomum zeylanicum , Embalaje de Alimentos , Gelatina , Glucanos , Estructuras Metalorgánicas , Aceites Volátiles , Gelatina/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Cinnamomum zeylanicum/química , Embalaje de Alimentos/métodos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Glucanos/química , Glucanos/farmacología , Conservación de Alimentos/métodos , Antibacterianos/farmacología , Antibacterianos/química , Carne/microbiología , Animales , Pruebas de Sensibilidad MicrobianaRESUMEN
Color indicator films incorporating aronia extract powder (AEP) and biopolymers like agar, carrageenan, and cellulose nanofiber (CNF) were developed to monitor kimchi freshness. AEP-containing films showed strong UV-barrier properties, and reduced light transmittance by 99.12 % for agar, 98.86 % for carrageenan, and 98.67 % for CNF-based films. All AEP-films exhibited high sensitivity to pH changes and vapor exposure to ammonia and acetic acid. Color change notably influenced by the polymer type, particularly evident with ammonia vapor exposure, especially in the AEP/carrageenan film. The chemical structure and thermal stability of the biopolymers remained unchanged after AEP-addition. Tensile strength increased by 24.2 % for AEP/CNF but decreased by 19.4 % for AEP/agar and 24.3 % for AEP/carrageenan films. AEP-containing films displayed strong antioxidant activity, with 99 % free radical scavenging in ABTS and ~ 80 % in DPPH assays. Alkalized AEP-indicator films were more effective in detecting color changes during kimchi packaging tests. Among the labels, alkalized AEP/agar film showed the most obvious color change from green-gray (fresh kimchi, pH 5.5, acidity 0.48 %) to pale brown (optimal fermentation, pH 4.6, acidity 0.70 %), and pale violet-brown (over-fermented, pH 3.80, acidity 1.35 %). Alkalized AEP-indicator films offer promising real-time detection of packed fermented foods like kimchi.
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Agar , Carragenina , Celulosa , Colorimetría , Embalaje de Alimentos , Nanofibras , Extractos Vegetales , Carragenina/química , Nanofibras/química , Agar/química , Celulosa/química , Colorimetría/métodos , Embalaje de Alimentos/métodos , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/análisis , Resistencia a la Tracción , Color , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND: Lifestyle changes, such as those related to the COVID-19 pandemic, including alterations in physical activity and dietary habits, are known to affect pregnancy outcomes. In particular, suboptimal intrauterine conditions during pregnancy are known to influence not only fetal growth but also growth during infancy. However, research on the impact of the environmental changes caused by the COVID-19 pandemic on the growth of infants and children during their early years is lacking. To address this issue, this study evaluated the effect of the COVID-19 pandemic on obesity in infants. METHODS: This retrospective cohort study used the data collected from the Korea National Health Insurance (KNHI) claims database. The data of 1985,678 women who delivered infants between 2015 and 2021 were collected. Women who delivered during the pandemic and those who delivered during the pre-pandemic period were matched in a 1:1 frequency-matched pair procedure for factors such as age, hypertension, diabetes mellitus, preeclampsia, gestational diabetes mellitus, mode of delivery, gestational age at delivery, offspring sex, and birth weight. Finally, 197,580 women were enrolled. The weight and head circumference of infants (4-6 months of age) of the COVID-19 pandemic group were compared with those of the pre-pandemic group. RESULTS: The COVID-19 pandemic group infants exhibited significantly higher weight and prevalence of obesity at 4-6 months of age compared to infants in the pre-pandemic group. After adjustment for covariates, pandemic group infants had a higher risk of obesity (odds ratio: 1.54, 95% confidence interval: 1.51-1.57) compared to the pre-pandemic group infants. CONCLUSION: The COVID-19 pandemic has had a notable impact on the weight of infants aged 4-6 months. This suggests that pandemic conditions may influence the growth of newborns, underscoring the importance of monitoring and assessing trends in the growth of infants born during such crises.
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COVID-19 , Obesidad Infantil , Embarazo , Niño , Recién Nacido , Femenino , Humanos , Lactante , Obesidad Infantil/epidemiología , Pandemias , Estudios Retrospectivos , COVID-19/epidemiología , Resultado del EmbarazoRESUMEN
W/O/W double emulsion-based iron-solid lipid nanoparticles (Fe-SLNs) and water-soluble chitosan-coated Fe-SLNs (WSC-Fe-SLNs) were developed to increase the bioaccessibility and stability of iron. Fe-SLNs exhibited a small diameter (158.17 ± 0.72 nm) and adequate zeta potential (-34.31 ± 0.41 mV) to maintain stable dispersion. The coating with WSC resulted in an increase in particle diameter (up to 226.13 ± 1.97 nm) and change of zeta potential to positive value (+47.83 ± 1.24 mV) because of the amine groups of chitosan. The lipid peroxidation of the Fe-SLNs and WSC-Fe-SLNs was substantially lower than that of pure iron. Both Fe-SLNs and WSC-Fe-SLNs were also able to protect the encapsulated iron in simulated gastric fluid, while effectively releasing almost 80% of the iron in simulated intestinal fluid. The Fe-SLNs and WSC-Fe-SLNs showed a great potential as functional materials to apply to various food industries through enhancement of physical stability and bioaccessibility of the encapsulated iron.
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Quitosano , Nanopartículas , Portadores de Fármacos , Emulsiones , Hierro , Lípidos , Liposomas , Tamaño de la Partícula , AguaRESUMEN
Birthweight is a strong determinant of a neonate's health. The SARS-CoV-2 pandemic's impact on birthweight has not been investigated in-depth, with inconsistent conclusions from initial studies. To assess changes in preterm birth and inappropriate birthweight between the SARS-CoV-2 pandemic and pre-pandemic periods. A nationwide birth micro-data consisted with exhaustive census of all births in 2011-2020 in South Korea was accessed to examine whether the mean birthweight and rates of under/overweight births changed significantly during the SARS-CoV-2 pandemic year (2020) compared to those of the pre-pandemic period (2011-2019). A total of 3,736,447 singleton births were analyzed. Preterm birth was defined as < 37 weeks of gestation. Low birthweight (LBW) and macrosomia were defined as birthweights < 2.5 kg and ≥ 4.0 kg, respectively. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birthweights below the 10th and above 90th percentiles for sex and gestational age, respectively. Inappropriate birthweight was defined as one or more LBW, macrosomia, SGA, or LGA. Generalized linear models predicted birth outcomes and were adjusted for parental age and education level, marital status, parity, gestational age, and months from January 2011. There were 3,481,423 and 255,024 singleton births during the pre-pandemic and pandemic periods, respectively. Multivariable generalized linear models estimated negative associations between the pandemic and preterm birth (odds ratio [OR], 0.968; 95% confidence interval [CI] 0.958-0.978), LBW (OR: 0.967, 95% CI 0.956-0.979), macrosomia (OR: 0.899, 95% CI 0.886-0.912), SGA (OR: 0.974, 95% CI 0.964-0.983), LGA (OR: 0.952, 95% CI 0.945-0.959), and inappropriate birthweight (OR: 0.958, 95% CI 0.952-0.963), indicating a decline during the pandemic compared to pre-pandemic period. An 8.98 g decrease in birthweight (95% CI 7.98-9.99) was estimated during the pandemic. This is the largest and comprehensive nationwide study to date on the impact of the SARS-CoV-2 pandemic on preterm birth and inappropriate birthweight. Birth during the pandemic was associated with lower odds of being preterm, underweight, and overweight. Further studies are required to understand the dynamics underlying this phenomenon.
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COVID-19 , Nacimiento Prematuro , Peso al Nacer , COVID-19/epidemiología , Femenino , Macrosomía Fetal/epidemiología , Humanos , Recién Nacido , Sobrepeso , Pandemias , Embarazo , Nacimiento Prematuro/epidemiología , República de Corea/epidemiología , SARS-CoV-2 , Aumento de PesoRESUMEN
This study focused on improving curcumin stability in various pHs and NaCl concentrations and reducing the strong scent of turmeric by the nanoemulsions system and further coating with water-soluble chitosan (WSC). Turmeric extract-loaded nanoemulsions (TE-NEs) were firstly prepared by mixing an oil phase containing turmeric extract, MCT oil, and lecithin, and an aqueous phase containing tween 80 using an ultrasonication method. TE-NEs were further coated with WSC in the ratio of TE-NEs and WSC (1:1 to 1:10). The optimum WSC-TE-NEs exhibited an average particle size of 182 nm, a PDI of 0.317, and a zeta potential of +30.42 mV when WSC-TE-NEs were prepared in the ratio of 1:1. The stability of the WSC-TE-NEs was also assessed by determining the remained curcumin content. The remained curcumin contents of the TE-NEs and the WSC-TE-NEs were higher than that of the turmeric extract (TE) at pH 2~7 and NaCl concentrations of 100~400 mM. Fourier transform infrared (FT-IR) spectra, transmission electron microscope (TEM), and confocal laser scanning microscope (CLSM) images confirmed that the TE-NEs were successfully encapsulated with a WSC coating. As a result of GC analysis, the content of aromatic-turmerone was significantly decreased in the TE-NEs and the WSC-TE-NEs compared to the pristine TE, but there was no significant difference between the TE-NEs and the WSC-TE-NEs. These results suggest that water-soluble chitosan-coated nanoemulsions may be suitable for improving the chemical stability and masking effect of curcumin to facilitate its application in food.
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OBJECTIVE: The aim of this study was to evaluate the changes in twin pregnancy outcomes between 2007 and 2016 in a Korean population. METHODS: The data for this nationwide population-based study was obtained from the national birth registry of the Korean National Statistical Office and the Health Insurance Review & Assessment Service of Korea. Women with twin pregnancies who gave birth between 2007 and 2016 were included. RESULTS: From 2007 to 2016, the rate of twin pregnancies increased (1.37% vs. 1.91%, respectively, P<0.0001). The risk of preterm birth (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.66-1.89) also increased; however, the risk of twin growth discordance (aOR, 0.90; 95% CI, 0.82-0.99) decreased. The risks of cesarean section (aOR, 1.16; 95% CI, 1.03-1.29), gestational diabetes mellitus (aOR, 2.10; 95% CI, 1.83-2.39), and postpartum hemorrhage (aOR, 1.27; 95% CI, 1.14-1.41) all increased from 2007 to 2016. CONCLUSION: Twin pregnancy outcomes have changed significantly in Korea over a recent 10-year period.
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In this study, the authors have characterized the effect of HER-S (red ginseng, Angelicae gigantis Radix, Phyllostachys folium, and soybean extracts) on osteoporosis-associated phenomena in ovariectomized (OVX) rats by measuring body weights and bone histomorphometries in control, sham, OVX, OVX(beta-estradiol-treated), and OVX(HER-S-treated) rats. Light microscopic analyses showed a porous or eroded appearance on the femoral trabecular bone surface in OVX rats, whereas the femoral trabecular bone surfaces of the other groups (control, sham, OVX(17beta-estradiol-treated), and OVX(HER-S-treated) rats) were composed of fine particles. The femoral trabecular bone area and number were decreased in OVX rats, but these reductions were significantly prevented by the administration of HER-S for 7 weeks, similar to estrogen. In the blood biochemistry results, serum phosphorus, calcium, T(3), and T(4) remained unchanged, but blood estrogen levels were significantly increased in HER-S-treated rats, which suggests that estrogen is related to the mechanism of the HER-S-induced antiosteoporosis function in OVX rats.
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Osteoporosis/tratamiento farmacológico , Panax/química , Extractos Vegetales/farmacología , Animales , Calcio/metabolismo , Línea Celular , Estradiol/sangre , Estradiol/farmacología , Femenino , Fémur/metabolismo , Fémur/patología , Osteoporosis/sangre , Osteoporosis/patología , Ovariectomía , Fósforo/metabolismo , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Hormonas Tiroideas/sangre , Factores de TiempoRESUMEN
BACKGROUND: The idiopathic systemic capillary leak syndrome is a rare disease characterized by unexplained recurrent shock caused by capillary hyperpermeability. Because of the rarity of the disease, this disease has easily been misdiagnosed and evidence of efficacious agents used empirically is lacking. OBJECTIVE: To analyze the clinical and laboratory data, treatment modalities, and mortality rate of patients and to find contributing factors leading to mortality. METHODS: We searched MEDLINE (inception to December 2016) and reviewed reference lists of previous systematic reviews. A total of 133 case reports (161 patients) and 5 case series (102 patients) of idiopathic systemic capillary leak syndrome were included. RESULTS: Patients had hypotension (81.4%), edema (64.6%), and previous flu-like illness (34.2%). This disease was misdiagnosed as hypovolemic shock, septic shock, polycythemia vera, or angioedema. Thirty-seven patients died (23%) mainly because of systemic capillary leak syndrome itself (78.4%). There were significant differences in the survival rates between patients who were treated with prophylactic ß2 agonists, methylxanthines, and intravenous immunoglobulins and those who were not. The estimated 1-, 5-, and 10-year survival rate of patients treated with intravenous immunoglobulins was 100%, 94%, and 94%, respectively. CONCLUSIONS: We systematically analyzed in detail clinical presentations of all reported patients and identified various factors associated with mortality and effects of prophylactic treatment in idiopathic systemic capillary leak syndrome. The findings of this review will facilitate diagnostic approaches of idiopathic systemic capillary leak syndrome and aid in the selection of treatment.
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Síndrome de Fuga Capilar , Síndrome de Fuga Capilar/diagnóstico , Síndrome de Fuga Capilar/prevención & control , Síndrome de Fuga Capilar/terapia , Humanos , PronósticoRESUMEN
PURPOSE: This study aimed to determine the dose effect of smoking on the mutational frequency and spectrum of epidermal growth factor receptor (EGFR) gene in Korean non-small cell lung cancer (NSCLC). METHODS: Detailed smoking histories were obtained from 324 consecutively enrolled Korean NSCLC patients. Mutational status of EGFR (exon 18-21) was determined using nested polymerase chain reaction amplification. RESULTS: A total of 108 EGFR mutations (33.3%) were identified in 107 patients. Decreased EGFR mutation rate with increased smoking dose was observed, with 48.0% (82 of 171) in never smokers, 23.1% (15 of 65) in former smokers, and 11.4% (10 of 88) in current smokers. The incidence of EGFR mutation was significantly lower in patients who smoked for more than 25 pack-years (P < 0.0001) or who stopped smoking cigarettes less than 10 years ago (P < 0.0001). Mutations in exon 19 or 21 were associated with fewer total smoke years (5.0 vs. 25.0 years in exon 20, P = 0.024), fewer total pack-years (6.3 vs. 38.9 pack-years in exon 20, P = 0.079), and more smoke-free years (11.1 vs. 3.6 years in exon 20, P = 0.027), compared with those in exon 20. Mutations in exon 19 or 21 were associated with female (P < 0.0001), never smoker (P < 0.0001), and adenocarcinoma (P < 0.0001), whereas those in exon 20 were not. CONCLUSIONS: Smoking dosage affects the incidence of EGFR mutations. EGFR mutations in exon 19 or 21 are associated with low exposure to cigarette smoke, whereas EGFR mutation in exon 20 is more common in smokers.