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1.
Sci Rep ; 10(1): 1952, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029785

RESUMO

Accurate prediction of non-small cell lung cancer (NSCLC) prognosis after surgery remains challenging. The Cox proportional hazard (PH) model is widely used, however, there are some limitations associated with it. In this study, we developed novel neural network models called binned time survival analysis (DeepBTS) models using 30 clinico-pathological features of surgically resected NSCLC patients (training cohort, n = 1,022; external validation cohort, n = 298). We employed the root-mean-square error (in the supervised learning model, s- DeepBTS) or negative log-likelihood (in the semi-unsupervised learning model, su-DeepBTS) as the loss function. The su-DeepBTS algorithm achieved better performance (C-index = 0.7306; AUC = 0.7677) than the other models (Cox PH: C-index = 0.7048 and AUC = 0.7390; s-DeepBTS: C-index = 0.7126 and AUC = 0.7420). The top 14 features were selected using su-DeepBTS model as a selector and could distinguish the low- and high-risk groups in the training cohort (p = 1.86 × 10-11) and validation cohort (p = 1.04 × 10-10). When trained with the optimal feature set for each model, the su-DeepBTS model could predict the prognoses of NSCLC better than the traditional model, especially in stage I patients. Follow-up studies using combined radiological, pathological imaging, and genomic data to enhance the performance of our model are ongoing.

2.
Minerva Anestesiol ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32013328

RESUMO

BACKGROUND: This study aimed to evaluate the effect of quadratus lumborum (QL) block on pain after surgeries under general or spinal anesthesia. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to compare pain scores at rest and with movement 48 h postoperatively in a QL block group and a control group both with placebo block and without block and the time to first additional analgesics. The analgesic effect of the QL block according to the type of surgery and block approach was also examined. A literature search was performed using well-known databases for articles published up to March 2019. RESULTS: Nine RCTs were included. Compared to the control group, pain scores at rest were significantly lower for 48 h postoperatively in the QL block group. QL block reduced pain scores with movement at 6, 12, and 24 h postoperatively. The QL block group exhibited the most improved numerical pain scores at 12 h postoperatively both at rest and with movement, with a mean difference (MD) of -2.16 (95% confidence interval [CI] -3.12 to - 1.20) and -2.26 [95% CI -3.54 to -0.98]), respectively. The subgroup analysis of pain scores at rest showed a statistically significant subgroup difference (P = 0.02, I2 = 75.7%), suggesting a different analgesic effect of QL block based on the approach. Time to first additional analgesics postoperatively was longer in the QL block group than in the control group (MD 333.51 minutes [95% CI 69.37 to 597.64]). CONCLUSIONS: QL block may be a good multimodal analgesic approach for pain after abdominal surgeries.

3.
Medicine (Baltimore) ; 99(5): e18913, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000397

RESUMO

The use of beta-blockers in decompensated cirrhosis accompanying ascites is still under debate. The aim of this study was to compare overall survival (OS) and incidence of cirrhotic complications between endoscopic variceal ligation (EVL) only and EVL + non-selective beta-blocker (NSBB) combination therapy in cirrhotic patients with significant ascites (≥grade 2).This retrospective study included 271 consecutive cirrhotic patients with ascites who were treated with EVL only or EVL + NSBB combination therapy as a primary prophylaxis of esophageal varices. The primary outcome was all-cause mortality. Propensity score matching was performed between the 2 groups to minimize baseline difference.Median observation period was 42.1 months (interquartile range, 18.4-75.1 months). All patients had deteriorated liver function: 81.1% Child-Pugh class B and 18.9% Child-Pugh class C. All-cause mortality was significantly higher in the EVL + NSBB group than in the EVL only group not only in non-matched cohort, but also in matched cohort (48.9% vs 31.2%; P = .039). More people died from hepatic failure in the EVL + NSBB group than that in the EVL only group (40.5% vs 20.0%; P = .020). However, the incidence of variceal bleeding, hepatorenal syndrome (HRS), or spontaneous bacterial peritonitis (SBP) was not significantly different between the 2 groups.The use of NSBB might worsen the prognosis of cirrhotic patients with significant ascites. These results suggest that EVL alone is a more appropriate treatment option for prophylaxis of esophageal varices than propranolol combination therapy when patients have significant ascites.

4.
Anticancer Res ; 40(1): 109-119, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892559

RESUMO

BACKGROUND/AIM: Although molecular targeting therapy is an attractive treatment for cancer, resistance eventually develops in most cases. Here, we evaluated chemotherapeutic efficacy on non-small cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor inhibitors mechanistically. MATERIALS AND METHODS: Antitumor effects of taxotere were evaluated using multiple models, including xenograft, and patient-derived models developed from adenocarcinoma cancer patients. Protein expressions were analyzed after drug treatment. RESULTS: Taxotere inhibited tumor growth of NSCLC cells harboring drug resistance, and reduced the expression of phosphorylated MET proto-oncogene, receptor tyrosine kinase (MET). A tumor-inhibitory effect of taxotere was also demonstrated in vivo in xenografts in mice, patient-derived primary lung tumor cells and patient-derived xenograft with concomitant repression of phosphorylated MET expression. Chemotherapeutic and MET-targeting drug exhibited a synergistic cell growth-inhibitory effect. CONCLUSION: These results suggest that the anticancer drug taxane may be an adjuvant for lung tumors exhibiting enhanced signaling of MET networks.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Cancer Res Treat ; 52(1): 309-319, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31401821

RESUMO

PURPOSE: The purpose of this study was to assess characteristics of SJ-815, a novel oncolytic vaccinia virus lacking a functional thymidine kinase-encoding TK gene, and instead, having two human transgenes: the IFNB1 that encodes interferon ß1, and the CES2 that encodes carboxylesterase 2, which metabolizes the prodrug, irinotecan, into cytotoxic SN-38. Materials and Methods: Viral replication and dissemination of SJ-815 were measured by plaque assay and comet assay, respectively, and compared to the backbone of SJ-815, a modified Western Reserve virus named WI. Tumor cytotoxicity of SJ-815 (or mSJ-815, which has the murine IFNB1 transgene for mouse cancers) was evaluated using human and mouse cancer cells. Antitumor effects of SJ-815, with/without irinotecan, were evaluated using a human pancreatic cancer-bearing mouse model and a syngeneic melanoma-bearing mouse model. The SN-38/ irinotecan ratios in mouse melanoma tissue 4 days post irinotecan treatment were compared between groups with and without SJ-815 intravenous injection. RESULTS: SJ-815 demonstrated significantly lower viral replication and dissemination, but considerably stronger in vitro tumor cytotoxicity than WI. The combination use of SJ-815 plus irinotecan generated substantial tumor regression in the human pancreatic cancer model, and significantly prolonged survival in the melanoma model (hazard ratio, 0.11; 95% confidence interval, 0.02 to 0.50; p=0.013). The tumor SN-38/irinotecan ratios were over 3-fold higher in the group with SJ-815 than those without (p < 0.001). CONCLUSION: SJ-815 demonstrates distinct characteristics gained from the inserted IFNB1 and CES2 transgenes. The potent antitumor effects of SJ-815, particularly when combined with irinotecan, against multiple solid tumors make SJ-815 an attractive candidate for further preclinical and clinical studies.

6.
Cancer Res Treat ; 52(1): 301-308, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31401823

RESUMO

PURPOSE: Prostate cancer (PCa) incidence is affected by aging phenomenon and performance of screening test. In United States, PCa incidence is affected by period effect of U.S. Preventive Services Task Force (USPSTF) recommendation. However, no study has reported the effect of USPSTF recommendation or aging phenomenon on PCa incidence in South Korea. Thus, the objective of this study was to investigate effects of age, period, and birth cohort on PCa incidence using age-period-cohort analysis. Materials and Methods: Annual report of cancer statistics between 2003 and 2013 from National Health Insurance Service (NHIS) in South Korea for the number of PCa patients and Korean Statistical Information Service (KOSIS) data between 2003 and 2013 from national statistics in South Korea for the number of Korean male population were used. Age-period-cohort models were used to investigate effects of age, period, and birth cohort on PCa incidence. RESULTS: Overall PCa incidence in South Korea was increased 8.8% in annual percentage (95% confidential interval, 6.5 to 11.2; p < 0.001). It showed an increasing pattern from 2003 to 2011 but a decreasing pattern from 2011 to 2013. Age increased the risk of PCa incidence. However, the speed of increase was slower with increasing age. PCa incidence was increased 1.4 times in 2008 compared to that in 2003 or 2013. Regarding cohort effect, the risk of PCa incidence started to increase from 1958 cohort. CONCLUSION: PCa incidence was affected by period of specific year. There was a positive cohort effect on PCa incidence associated with age structural change.

7.
J Clin Med ; 8(12)2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31771253

RESUMO

BACKGROUND: Transient elastography is now an indispensable tool for estimating liver fibrosis. Although many clinical factors other than fibrosis itself are known to affect liver stiffness (LS) values, it is still not yet clear what factors are related to improving LS values. The aim of this study was to find out how baseline histologic inflammation influences LS values and how much this inflammation affects improvement in LS values over time, regardless of actual fibrosis content. METHODS: This retrospective study included 678 consecutive patients who underwent liver biopsy and sequential LS assessment from 2006 to 2015 at six tertiary hospitals in Korea. Linear regression analysis was used to evaluate how improvement of LS value can be associated with other factors besides fibrosis content. RESULTS: Basal LS values increased with increasing inflammation in the same fibrosis stage. Degree of inflammation influenced the baseline LS value in a proportional manner (beta coefficient (BE), 6.476; 95% confidence interval (CI), 2.24-10.72; p = 0.003). Moreover, histologic inflammation affected the change in LS value significantly. Higher inflammation grade at baseline was a significant predictor for an improvement in LS value, regardless of the fibrosis stage (BE, -8.581; 95% CI, -15.715--1.447; p = 0.019). In a subgroup analysis of patients who received repeated liver biopsies, the results showed a similar tendency. CONCLUSIONS: The LS value is affected by the degree of inflammation even at a low ALT level. Furthermore, baseline histologic inflammation has a significant impact on the improvement of LS values over time. Therefore, baseline inflammation should be taken into consideration when interpreting an improvement in LS value.

8.
Gut Liver ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31533399

RESUMO

Background/Aims: Patients with an intermediate stage of hepatocellular carcinoma (HCC) represent a highly heterogeneous population; therefore, many models have been proposed to predict the survival of these patients. The aim of this study was to evaluate the prognostic performance of a novel subclassification for tumors classified as Barcelona Clinic Liver Cancer (BCLC) stage B using the Model to Estimate Survival in Ambulatory HCC patients (MESIAH). Methods: This analysis was based on 377 patients with HCC treated at Seoul National University Hospital (training cohort) and 189 patients at the Soonchunhyang University Bucheon Hospital (validation cohort). Four subclassification systems were tested: MESIAH; original BCLC B subclassification (B1, B2, B3, and B4); modified model A (B1, B2, and B3+B4); and modified model B (B1, B2+B3, and B4). Results: Median survival progressively decreased from stage B1 through stages B2 to B3 according to the new MESIAH subclassification (p<0.001). Moreover, significantly different survival among contiguous stages was observed. In the multivariable Cox regression, the MESIAH subclassification was an independent predictor of overall survival (p<0.001). In terms of discrimination and calibration, MESIAH performed better than the original BCLC B subclassification, modified model A and modified model B. Conclusions: The MESIAH model would be an effective tool for stratifying heterogeneous BCLC stage B cancer, and the ability of this model to predict survival is better than that of the other previously proposed models.

9.
J Clin Med ; 8(9)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510032

RESUMO

Pain after anterior cruciate ligament (ACL) reconstruction is usually intense in the early postoperative period, but the efficacy of a multimodal analgesia approach remains controversial. This study aimed to investigate the analgesic efficacy of pregabalin in multimodal analgesia after ACL reconstruction. Patients who underwent ACL reconstruction under spinal anesthesia and agreed to use intravenous patient-controlled analgesia (IV-PCA) were randomly administered placebo (control group, n = 47) or pregabalin 150 mg (pregabalin group, n = 46) 1 h before surgery and 12 h after initial treatment. Pain by verbal numerical rating scale (VNRS) at rest and with passive flexion of knee was assessed at postoperative 12, 24, and 36 h and 2 weeks. IV-PCA consumption, rescue analgesic use, and side effects were also evaluated. Lower scores of VNRS were obtained with passive flexion of knee in the pregabalin group than in the control group at postoperative 24 (7(4-8) vs. 8(6-9), p = 0.043) and 36 h (4(3-7) vs. 5(4-9), p = 0.042), and lower value of VNRS at rest was observed in the pregabalin group [0(0-1)] than in the control group [1(0-2)] at postoperative 2 weeks (p < 0.001). No differences were obtained for IV-PCA consumption, rescue analgesic use, and side effects except for dizziness for postoperative 12 h. Pregabalin as an adjuvant to multimodal analgesic regimen significantly reduced early postoperative pain in patients undergoing ACL reconstruction.

10.
PLoS One ; 14(8): e0220240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31442229

RESUMO

OBJECTIVE: We evaluated frequency and risk factors of delayed TSH elevation (dTSH) and investigated follow-up outcomes in the dTSH group with venous TSH (v-TSH) levels of 6-20 mU/L according to whether late preterm infants born at gestational age (GA) 35-36 weeks had risk factors. METHODS: The medical records of 810 neonates (414 boys) born at Seoul National University Hospital who had a normal neonatal screening test (NST) and underwent the first repeat venous blood test at 10-21 days post birth were reviewed. RESULTS: Seventy-three (9.0%) neonates showed dTSH, defined as a v-TSH level ≥6.0 mU/L, 12 of whom (1.5%) were started on levothyroxine medication. A multivariate-adjusted model indicated that a low birth weight (LBW <2,000 g), a congenital anomaly, and exposure to iodine contrast media (ICM) were significant predictors for dTSH (all p < 0.05). Among these 73 dTSH infants, all 5 infants with TSH levels ≥20 mU/L began levothyroxine medication, and 6 of 16 infants with v-TSH levels of 10-20 mU/L were indicated for levothyroxine, regardless of coexisting risk factors. However, only 1 of 52 infants with v-TSH levels of 6-10 mU/L who had a congenital anomaly was indicated for levothyroxine. All healthy late preterm infants, including LBW and multiple births, with v-TSH levels of 6-10 mU/L exhibited normal thyroid function. CONCLUSIONS: dTSH was detected in 9.0% and levothyroxine was indicated in 1.5% of infants born at GA 35-36 weeks, particularly those with a LBW, a congenital anomaly, or history of ICM exposure. Either levothyroxine or retesting is indicated for late preterm neonates with TSH levels ≥10 mU/L regardless of risk factors. If healthy preterm neonates show v-TSH levels of 6-10 mU/L, a second repeat test may not be necessary; however, further studies are required to set a threshold for retesting.

11.
J Youth Adolesc ; 48(8): 1494-1505, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256312

RESUMO

Adults' career choice is not an abrupt event, but an outcome of continuous development throughout childhood and adolescence. In the developmental process of one's career, personal characteristics and contextual resources come into play. The goal of the present study is to examine how family socioeconomic status, adolescents' vocational aspirations, and high school contexts affect their occupational attainment in young adulthood, using two cohorts of data from the Korean Education and Employment Panel. Cohort 1 consisted of 1535 individuals (49.3% female), and cohort 2 consisted of 1473 individuals (53.5% female). Both cohorts were surveyed during their senior year of high school (Time 1; Mage = 17.8) and followed up until young adulthood (Time 2; Mage = 25.8). The results reveal that having high vocational aspirations and attending academic high school predict attaining higher-status occupations for both cohorts. Family background has positive direct and indirect effects on occupational attainment for cohort 2, while it only has an indirect effect on occupational attainment via types of high school for cohort 1. Implications in the context of constructing social systems to support adolescents' career development are discussed.


Assuntos
Ocupações , Classe Social , Adolescente , Adulto , Escolha da Profissão , Emprego , Feminino , Humanos , Masculino , República da Coreia , Instituições Acadêmicas
12.
Tuberc Respir Dis (Seoul) ; 82(4): 341-347, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31172708

RESUMO

BACKGROUND: Information about the epidemiology of venous thromboembolism (VTE) recurrence in Korea is lacking. The purpose of this study was to investigate VTE cumulative recurrence rates and identify risk factors for VTE recurrence among Korean adults. METHODS: A retrospective cohort study was conducted on adult patients (≥18 years) admitted to a university teaching hospital for pulmonary embolism (PE) from 2005 to 2013. The main outcome of interest was a recurrence of VTE. We used Cox proportional hazard regression analyses to calculate the relative risk of VTE recurrence. RESULTS: Five-year cumulative incidence of recurrent VTE events was 21.5% (95% confidence interval [CI], 17.7-25.4) in all cases of PE; 17% after provoked and 27% after unprovoked PE. Multivariate analysis showed that body mass index (BMI) of ≥25 (hazard ratio [HR], 2.02; 95% CI, 1.17-3.46; p=0.01) and longer anticoagulation therapy duration (HR, 0.90; 95% CI, 0.84-0.96; p<0.01) were independently associated with risk of VTE recurrence. Risk factors not found to be statistically significant at the <0.05 level included history of VTE (HR, 1.81; 95% CI, 0.84-3.88; p=0.12), unprovoked PE (HR, 1.70; 95% CI, 0.89-3.25; p=0.10), symptomatic deep vein thrombosis (HR, 1.62; 95% CI, 0.89-2.94; p=0.10), and female sex (HR, 1.42; 95% CI, 0.78-2.55; p=0.24). We found that age, history of cancer, and other co-morbidities did not significantly affect the risk of VTE recurrence. CONCLUSION: Recurrence of VTE after PE is high. Patients with BMI ≥25 or reduced anticoagulation therapy duration have a higher risk of recurrent VTE.

13.
Int Urol Nephrol ; 51(9): 1459-1471, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243632

RESUMO

INTRODUCTION AND HYPOTHESIS: Anticholinergics have been established for their efficacy and safety in adults with idiopathic overactive bladder syndrome (OAB-s) but not in children and adolescents. This study was aims to investigate the efficacy and safety of anticholinergics in children and adolescents with idiopathic OAB-s. METHOD: A total of nine studies with 11 trials comprising of 1801 subjects (1116 experimental and 685 controls) were included. Inclusion criteria were idiopathic OAB-s in children or adolescents. Overall SMD of change in diurnal urge incontinence per week, change in mean voiding frequency per 24 h, change in mean voided volume, and incidence of adverse events compared with placebo were investigated. RESULTS: Overall SMD of diurnal urge incontinence per week for the anticholinergic group (experimental group) vs. the placebo group (control group) was - 0.15 (95% CI - 0.31, 0.01). Overall SMD of mean voiding frequency per 24 h was - 0.16 (95% CI - 0.33, 0.02). Overall SMD of mean voided volume was 0.49 (95% CI 0.10, 0.88). The overall incidence of any AEs of anticholinergics compared with placebo was OR = 1.06 (95% CI 0.84-1.34) (p = 0.637). Among each AEs, the only incidence of urinary tract infection showed a higher incidence rate for anticholinergics (OR = 1.92, 95% CI 1.06-3.49) than for placebo. CONCLUSIONS: Apart from oxybutynin, other anticholinergics showed efficacy including an increase in mean voided volume. Moreover, there was no significant difference in the incidence of overall adverse events between anticholinergics and placebo.

14.
Sci Rep ; 9(1): 9124, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235744

RESUMO

Anaesthesiologists are increasingly involved in nonoperating room anaesthesia (NORA) for fluoroscopic procedures. However, the radiation exposure of medical staff differs among NORA settings. Therefore, we aimed to investigate the radiation environment generated by fluoroscopic endoscopic retrograde cholangiopancreatography (ERCP) and the radiation exposure of anaesthesiologists. The dose area product (DAP), radiation entrance dose (RED), and fluoroscopy time (FT) according to the procedures and monthly cumulative radiation exposure were analysed at two sites (neck and wrist) from 363 procedures in 316 patients performed within 3 months. The total RED and DAP were 43643.1 mGy and 13681.1 Gy cm2, respectively. DAP and RED (r = 0.924) were strongly correlated and DAP and FT (r = 0.701) and RED and FT (r = 0.749) were moderately correlated. The radiation environment per procedure varied widely, DAP and RED per FT were the highest during stent insertion with esophagogastroduodenoscopy. Monthly cumulative deep dose equivalents at the wrist and neck ranged between 0.31-1.27 mSv and 0.33-0.59 mSv, respectively, but they were related to jaw thrust manipulation (r = 0.997, P = 0.047) and not to the radiation environment. The anaesthesiologists may be exposed to high dose of radiation in the ERCP room, which depends on the volume of procedures performed and perhaps the anaesthesiologists' practice patterns.

15.
PLoS One ; 14(5): e0216673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071171

RESUMO

BACKGROUND: Changes in head and neck position may significantly affect the performance of supraglottic airway devices (SADs) by altering the pharyngeal structure. PURPOSE: This systematic review and meta-analysis aimed to elucidate the effect of changes in head and neck position on performance of SADs. DATA SOURCE: Bibliographic databases, including PubMed, EMBASE, the Cochrane library, and the Web of Science. STUDY ELIGIBILITY CRITERIA: Prospective studies investigating the effects of head and neck positions on the performance of SADs. METHODS: A random effect model was applied in the all analyses. Subgroup analysis was performed according to the type of device and the age of patient. The oropharyngeal leak pressure was the primary outcome measure. Secondary outcome measures included peak inspiratory pressure, fibreoptic view, and ventilation score (PROSPERO, CRD42017076971). RESULTS: Seventeen studies met the eligibility criteria. Overall, the oropharyngeal leak pressure significantly increased (mean difference 4.07 cmH2O; 95% confidence interval 3.30 to 4.84) during neck flexion with adverse effects on ventilation and fibreoptic view. Conversely, the oropharyngeal leak pressure decreased (mean difference -4.05; 95% confidence interval -4.90 to -3.20) during neck extension with no significant effect on ventilation or fibreoptic view. Rotation of the head and neck did not significantly affect SAD performance. CONCLUSIONS: The reduced oropharyngeal leak pressure in the extended neck position was not associated with impaired ventilation except with the air-Q self-pressurizing airway. The flexed neck position significantly worsens ventilation and the alignment between the SAD and glottis despite improving the seal except with the air-Q self-pressurizing airway and LMA Proseal.

16.
Medicine (Baltimore) ; 98(7): e14601, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762814

RESUMO

There has been a marked increase in the use of low-dose computed tomography (LDCT) for lung cancer screening. However, the potential of LDCT to predict metabolic syndrome (MetS) has not been well-documented in this risk-sharing population. We assessed the reliability of epicardial fat volume (EFV) and epicardial fat area (EFA) measurements on chest LDCT for prediction of MetS.A total of 130 (mean age, 50.2 ±â€Š10.77 years) asymptomatic male who underwent nonelectrocardiography (ECG)-gated LDCT were divided into 2 groups for the main analysis (n = 75) and validation (n = 55). Each group was further divided into subgroups with or without MetS. EFV and EFA were calculated semiautomatically using commercially available software with manual assistance. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis and cutoff values to predict MetS on LDCT were then calculated and validated. Female data were not available for analysis due to small sample size in this self-referred lung cancer screening program.In the analysis group, the mean EFV was 123.12 ±â€Š42.29 and 67.30 ±â€Š20.68 cm for the MetS and non-MetS subgroups, respectively (P < .001), and the mean EFA was 7.95 ±â€Š3.10 and 4.04 ±â€Š1.73 cm, respectively (P < .001). Using 93.65 and 4.94 as the cutoffs for EFV and EFA, respectively, the sensitivity, specificity, positive and negative predictive values, and accuracy for predicting MetS were 84.2% and 84.2%, and 92.9% and 64.3% (P < .001); 80% and 44.4% (P = .01); 94.5% and 92.3%; and 90.7% and 69.3% (P < .001), respectively. The AUC for EFV and EFA for predicting MetS was 0.909 and 0.808 (95% confidence interval, 0.819-1.000 and 0.702-0.914, respectively) (P = .02). Using the same cutoff values in the analysis group, there was no significant difference in diagnostic performance using EFV and EFA between the analysis and validation sets.Although quantification of both EFA and EFV is feasible on non-ECG-gated LDCT, EFV may be used to reliably predict MetS with fairly high and better diagnostic performance in selected population.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Coração/diagnóstico por imagem , Programas de Rastreamento/métodos , Síndrome Metabólica/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico por imagem , Pessoa de Meia-Idade , Variações Dependentes do Observador , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
Fertil Steril ; 111(3): 535-546, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30611556

RESUMO

OBJECTIVE: To identify differences in the transcriptomic profiles during placentation from pregnancies conceived spontaneously vs. those with infertility using non-in vitro fertilization (IVF) fertility treatment (NIFT) or IVF. DESIGN: Cohort study. SETTING: Academic medical center. PATIENT(S): Women undergoing chorionic villus sampling at gestational age 11-13 weeks (n = 141), with pregnancies that were conceived spontaneously (n = 74), with NIFT (n = 33), or with IVF (n = 34), resulting in the delivery of viable offspring. INTERVENTION(S): Collection of chorionic villus samples from women who conceived spontaneously, with NIFT, or with IVF for gene expression analysis using RNA sequencing. MAIN OUTCOME MEASURE(S): Baseline maternal, paternal, and fetal demographics, maternal medical conditions, pregnancy complications, and outcomes. Differential gene expression of first-trimester placenta. RESULT(S): There were few differences in the transcriptome of first-trimester placenta from NIFT, IVF, and spontaneous pregnancies. There was one protein-coding differentially expressed gene (DEG) between the spontaneous and infertility groups, CACNA1I, one protein-coding DEG between the spontaneous and IVF groups, CACNA1I, and five protein-coding DEGs between the NIFT and IVF groups, SLC18A2, CCL21, FXYD2, PAEP, and DNER. CONCLUSION(S): This is the first and largest study looking at transcriptomic profiles of first-trimester placenta demonstrating similar transcriptomic profiles in pregnancies conceived using NIFT or IVF and spontaneous conceptions. Gene expression differences found to be highest in the NIFT group suggest that the underlying infertility, in addition to treatment-related factors, may contribute to the observed gene expression profiles.


Assuntos
Infertilidade/genética , Infertilidade/terapia , Placentação/genética , Técnicas de Reprodução Assistida , Transcriptoma , Adulto , Feminino , Fertilidade/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Pessoa de Meia-Idade , Gravidez , Resultado do Tratamento
18.
Otolaryngol Head Neck Surg ; 160(5): 928-934, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30668216

RESUMO

OBJECTIVES: Respiratory mechanic instability (RMI) is derived from analysis of paradoxical thoracoabdominal movements during airway obstruction. This study aimed to evaluate RMI parameters in obstructive sleep apnea (OSA) and the correlation between RMI parameters and other parameters in polysomnography. STUDY DESIGN: Retrospective review. SETTING: A university hospital. METHODS: A retrospective chart review was performed, and data from 189 adult patients who underwent an in-laboratory sleep study and were seen in our clinic during the past 8 months. The RMI parameters were measured from thoracoabdominal bands during polysomnography. RESULTS: Subjects were divided into 2 groups: control (n = 67, apnea-hypopnea index [AHI] <5) and OSA (n = 122, AHI ≥5). The OSA group was divided into 3 subgroups according to AHI: mild, 5 ≤ AHI < 15; moderate, 15 ≤ AHI < 30; severe, AHI ≥30. As AHI increased, all RMI parameters showed a significant rising pattern and difference between control and subgroups. Arousal index, lowest oxygen saturation, and oxygen desaturation index ≥3% were significantly correlated with all RMI parameters. Based on cutoff values, areas under the curves of the RMI index for predicting mild, moderate, and severe OSA were >0.85. CONCLUSION: All RMI parameters were well related to respiratory parameters of polysomnography, such as arousal index, lowest oxygen saturation, and oxygen desaturation index ≥3%. The areas under the curves of all RMI parameters for predicting OSA and subgroups showed significant diagnostic performance. These parameters may be useful to identify OSA cases from control.


Assuntos
Mecânica Respiratória/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Testes de Função Respiratória , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
J Hepatol ; 70(5): 847-854, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30630010

RESUMO

BACKGROUND & AIMS: Accurate evaluation of renal function in patients with liver cirrhosis is critical for clinical management. However, there are still discrepancies between the measured glomerular filtration rate (mGFR) and creatinine-based estimated GFR (eGFR). In this study, we compared the performance of 2 common eGFR measurements with mGFR and evaluated the impact of low muscle mass on overestimation of renal function in patients with cirrhosis. METHODS: This study included 779 consecutive cirrhotic patients who underwent 51Cr-ethylenediamine tetra acetic acid (EDTA) (as a mGFR) and abdominal computed tomography (CT). The eGFR was calculated using creatinine or cystatin C. Muscle mass was assessed in terms of the total skeletal muscle at L3 level using CT. RESULTS: Modification of diet in renal disease (MDRD)-eGFR was overestimated in 47% of patients. A multivariate analysis showed that female sex (adjusted odds ratio [aOR] 4.91), Child B and C vs. A (aOR 1.69 and 1.84) and skeletal muscle mass (aOR 0.89) were independent risk factors associated with overestimation. Interestingly, the effect of skeletal muscle mass on overestimation varied based on sex. Decreased muscle mass significantly enhanced the risk of overestimation of MDRD-eGFR in male patients, but not in female patients. Cystatin C-based eGFR showed a better correlation with mGFR than MDRD-eGFR; it was also better at predicting overall survival and the incidence of acute kidney injury than MDRD-eGFR. CONCLUSIONS: The risk factors associated with overestimation included female sex, impaired liver function, and decreased muscle mass in males. In particular, eGFR in male patients with sarcopenia should be carefully interpreted. Creatinine-based eGFR was overestimated more often than cystatin C-based eGFR, with overestimation of eGFR closely related to poor prognostic performance. LAY SUMMARY: Overestimation of renal function frequently occurs in patients with liver cirrhosis when using serum creatinine. Decreased muscle mass has a great impact on overestimation of kidney function especially in male patients with cirrhosis. Compared with creatinine, cystatin C was more closely correlated with measured glomerular filtration rate and had a higher predictive ability for renal complications and survival than creatinine.

20.
Hepatology ; 69(3): 1122-1134, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30230575

RESUMO

Regulation of the protein stability of epigenetic regulators remains ill-defined despite its potential applicability in epigenetic therapies. The histone H3-lysine 4-methyltransferase MLL4 is an epigenetic transcriptional coactivator that directs overnutrition-induced obesity and fatty liver formation, and Mll4+/- mice are resistant to both. Here we show that the E3 ubiquitin ligase UBE3A targets MLL4 for degradation, thereby suppressing high-fat diet (HFD)-induced expression of the hepatic steatosis target genes of MLL4. In contrast to Mll4+/- mice, Ube3a+/- mice are hypersensitive to HFD-induced obesity and fatty liver development. Ube3a+/-;Mll4+/- mice lose this hypersensitivity, supporting roles of increased MLL4 levels in both phenotypes of Ube3a+/- mice. Correspondingly, our comparative studies with wild-type, Ube3a+/- and Ube3a-/- and UBE3A-overexpressing transgenic mouse livers demonstrate an inverse correlation of UBE3A protein levels with MLL4 protein levels, expression of the steatosis target genes of MLL4, and their decoration by H3-lysine 4-monomethylation, a surrogate marker for the epigenetic action of MLL4. Conclusion: UBE3A indirectly exerts an epigenetic regulation of obesity and steatosis by degrading MLL4. This UBE3A-MLL4 regulatory axis provides a potential therapeutic venue for treating various MLL4-directed pathogeneses, including obesity and hepatic steatosis.

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